CONTENTS
PAGE NO. TITLE
07 From the President’s DESK
08 From the DESK of Chief Editor
09 From the DESK of Managing Editor
Subspecialty Article PG Corner
10 An atypical presentation of right sided infra 67 Clinical Signs of Corneal Ulcer
orbital region foreign body with no signs of
external entry wound Basic Ophthalmology
12 Sarcoidosis presenting as bilateral lacrimal gland 71 Addressing the Spectacle Lens Related
enlargement: Eyes speak the truth Problems of a Myope
15 Comparative study of efficacy of pupillary Beyond Ophthalmology
dilatation using preoperative topical mydriatics
versus the use of intracameral adrenaline in 74 Humorous one liners
phacoemulsification: A prospective randomised
control study Article Review
22 A rare case of snow flake opacification of three 75 Management of Recalcitrant Corneal Hydrops
piece polymethyl methacrylate intraocular lens
Monthly Meeting
24 Trifocal and EDOF IOLs : A New Era of Multifocal
IOL 80 Tackling the posterior capsule in pediatric
cataract surgery for prevention of visual axis
31 Postoperative corneal morphological changes opacification
in senile cataract: Small incision cataract surgery
versus Phacoemulsification 88 SD - OCT Imaging in high myopia and
glaucoma detection
36 Diabetic Retinopathy - The Recent Insights
43 A rare case of Serratia marcescens
endophthalmitis post optical penetrating
keratoplasty with missed foreign body in inferior
temporal quadrant of posterior segment
46 Recent Advances in Perimetry
58 Newer perspectives and recent advances in
Amblyopia
Surgical Techniques
62 Intraoperative OCT Guided Bleb Sparing Epithelial
Exchange for Avascular Thin Cystic Blebs
Photo Essay
66 Carancular Dermoid Cyst
DOS EXECUTIVE MEMBERS (2021-2023)
DOS Office Bearers
Dr. Pawan Goyal Dr. Jatinder Singh Bhalla Dr. Alkesh Chaudhary
President Secretary Treasurer
Dr. Rajendra Prasad Dr. Sandhya Makhija Prof. Kirti Singh Dr. Jatinder Bali
Vice President Joint Secretary Editor Library Officer
Executive Members
Dr. Om Prakash Anand Dr. Gagan Bhatia Dr. Vivek Gupta Dr. Vivek Kumar Jain
Dr. Prafulla Kumar Maharana Dr. Amar Pujari Dr. Bhupesh Singh Dr. Pankaj Varshney
DOS Representative to AIOS Ex-Officio Members
Prof. Jeewan S. Titiyal Prof. M. Vanathi Prof. Subhash C. Dadeya Prof. Namrata Sharma
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03
DOS Times - Volume 28, Number 2, March-April 2022
Know Your Editor
Dr. Jatinder Singh Bhalla
MS, DNB, MNAMS
Hony. General Secretary
Delhi Ophthalmological Society
DDU Hospital, Hari Nagar
Chief Editor DOS Times
Dr. Prafulla Kumar Maharana, MD
Associate Professor of Ophthalmology
Dr. Rajendra Prasad Centre for Ophthalmic
Sciences, AIIMS, New Delhi
Managing Editor DOS Times
Prof. (Col) Sanjay Kumar Mishra, Dr. Raghav Malik, MS Dr. Deepankur Mahajan
HOD, Dept of Ophthalmology Fellowship Cataract & MBBS, MD (AIIMS), FICO, FAICO
(vitreo retina surgeon), Army Refractive Surgery (Retina and Vitreous)
Hospital (R&R) Associate Consultant Consultant Ophthalmologist and
Dept of Cataract, Cornea & Vitreoretina Specialist, New Delhi
Section Editor - Retina & Uvea Refractive Services, CFS, New Delhi
Section Editors - Retina & Uvea
Section Editor - Retina & Uvea
Dr. Rushil Kumar Saxena Dr. Ankur Singh Dr. Abhishek Jain
Dept of Vitreoretina Assistant professor D.O., D.N.B., FAICO
Dr. Shroff’s Charity Eye Hospital, Dept of Ophthalmology RBM Eye Institute, Delhi
New Delhi University College of Medical ADK Jain eye hospital, Bhagpat
Sciences and GTB Hospital, Delhi
Section Editor - Retina & Uvea Section Editor - Retina & Uvea
Section Editor - Retina & Uvea
Dr. Naginder Vashisht Dr. Prateek Kakkar Dr. Aman Kumar
MD, FRCS, FICO (Retina Specialist), MD MD, Senior Resident
Director & Senior Consultant Ex-Senior Resident (Vitreo-retina, Vitreo-Retina, Uvea, ROP services
Ophthalmology, Kailash Eye Care, AIIMS, New Delhi) Dr. R P Centre for Ophthalmic Sciences
Patel Nagar, New Delhi AIIMS, New Delhi
Senior Consultant Ophthalmology, Section Editor - Uvea & Ocular
Artemis Hospitals, Gurugram Inflammatory Disorders Section Editor - Uvea & Ocular
Inflammatory Disorders
Section Editor - Uvea & Ocular
Inflammatory Disorders Dr. Ritu Nagpal
MD, Senior Research Associate
Dr. Sameer Kaushal Dr. Abha Gour Dr. R P Centre for Ophthalmic Sciences,
Senior Consultant & Head Senior Consultant Cornea and AIIMS, New Delhi
(Ophthalmology) Anterior Segment
Artemis Hospital and PL Memorial Dr. Shroffs Charity Eye Hospital, Section Editor - Cornea & External
Eye Clinic, Gurgaon New Delhi Eye Disease
Section Editor - Cornea & External Section Editor - Cornea & External
Eye Disease Eye Disease
DOS Times - Volume 28, Number 2, March-April 2022 04 www.dosonline.org/dos-times
Dr. Parul Jain Dr. Rajat Jain Dr. Jaya Gupta
MBBS, MS, FICO, FAICO, MRCSEd MBBS, MS (Gold Medalist), FICO (UK) Consultant Cornea Cataract &
Associate Professor Fellow- Cornea and Anterior Refractive Surgery
GNEC, Maulana Azad Medical College Segment- LVPEI Hyderabad The Healing Touch Eye Care
Centre, New Delhi
Section Editor - Cornea & External Section Editor - Ocular Surface Section Editor - Ocular Surface
Eye Disease
Dr. Neeraj Verma Dr. Amrita Joshi
Dr. Abhishek Dave MS (Ophthal) Assistant Professor
Consultant Cornea, Cataract & Senior Consultant Department of Ophthalmology
Refractive Surgery - CFS, New Delhi Centre For Eye Care Army Hospital (R&R)
Kirti Nagar, New Delhi
Section Editor - Ocular Surface Section Editor - Ocular Surface Section Editor - Ocular Surface
Dr. Ritin Goyal Dr. Wangchuk Doma Dr. Amit Mehtani
Director & Cornea, Cataract and Venu Eye Institute and Research MBBS, MS, DNB
LASIK surgeon at Goyal Eye Group Centre DDU HOSPITAL
of Eye Centers.
Section Editor - Cataract & Section Editor - Cataract & Section Editor - Cataract &
Comprehensive Ophthalmology Comprehensive Ophthalmology Comprehensive Ophthalmology
Dr. Manpreet Kaur Dr. Pranita Sahay, MD Dr. Rwituja Thomas Grover
MD, Assistant Professor (AIIMS), FRCS (Glasgow), Consultant Oculoplastics, Orbit,
Cornea, Cataract & Refractive Surgery DNB, FICO, FICO (Cornea), Ocular Oncology and Aesthetics
Services FAICO (Ref Sx) services, Vision Eye Centres,
Dr. R P Centre for Ophthalmic Sciences Consultant, CFS, New Delhi New Delhi
AIIMS, New Delhi
Section Editor - Oculoplasty & Asthetics
Section Editor - Refractive Surgery Section Editor - Refractive Surgery
Dr. Jyoti Batra Dr. Anuj mehta Dr. Kiran Bhanot
Consultant, Oculoplasty and Consultant and Professor MS, DNB
Ocular Oncology, ICARE Eye Vardhman Mahavir Medical College Senior Consultant & Hod GGS
Hospital and Post graduate and Safdarjung Hospital Hospital & Indira Gandhi Hospital,
Institute, Noida Dwarka, New Delhi
Section Editor - Oculoplasty & Asthetics Section Editor - Oculoplasty & Asthetics Section Editor - Glaucoma
Dr. Suneeta Dubey Dr. Kanika Jain Dr. Shweta Tripathi
Head - Glaucoma Services MBBS, MS, DNB DNB, MNAMS, FMRF
Medical Superintendent Senior Resident, Dept of Ophthalmology, Senior Consultant Glaucoma
Chairperson - Quality Assurance DDU Hospital, Hari Nagar, New Delhi. Services
Dr. Shroff’s Charity Eye Hospital Indira Gandhi Eye Hospital and
New Delhi, India Research Centre, Lucknow
Section Editor - Glaucoma Section Editor - Glaucoma Section Editor - Glaucoma
Dr. Prathama Sarkar Dr. Kavita Bhatnagar Dr. Simi Gulati
Consultant in Eye7 Professor & Head, Dept of I/C and Specialist
Chaudhary Eye Centre Ophthalmology, AIIMS, Basani Charak palika hospital (ndmc)
Phase-2, Jodhpur Moti bagh, New Delhi
Section Editor - Glaucoma
Section Editor - Glaucoma Section Editor - Glaucoma
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DOS Times - Volume 28, Number 2, March-April 2022
Dr. Rebika Dhiman Dr. Amar Pujari Dr. Sumit Monga,
Assistant Professor Assistant Professor Senior Consultant. Pediatric,
Strabismus and Neuro- Dr. R P Centre for Ophthalmic Strabismus and Neuro-Ophthal-
Ophthalmology services, Sciences, AIIMS, New Delhi mology Services, CFS group of Eye
Dr. R P Centre, AIIMS, New Delhi Hospitals, Delhi-NCR
Section Editor - Neuro-Ophthalmology
Section Editor - Neuro-Ophthalmology Section Editor - Neuro-Ophthalmology
Dr. Paromita Dutta Prof. Swati Phuljhale Dr. Gunjan Saluja
Associate Professor Dr. R P Centre for Ophthalmic Ex SR Strabismus, Oculoplasty and
Guru Nanak Eye Centre Sciences, AIIMS, New Delhi Neuro-Ophthalmology services,
Maharaja Ranjit Singh Marg Dr. R P Centre, AIIMS, New Delhi
New Delhi Section Editor - Strabismus
Section Editor - Strabismus
Section Editor - Strabismus
Dr. Suraj Singh Senjam Dr. V Rajshekhar Prof. Bhavna Chawla
Community Ophthalmology MS, FICO Professor of Ophthalmology
Dr. R P Centre for Ophthalmic Professor & Consultant Dr. R P Centre, AIIMS, New Delhi
Sciences, AIIMS, New Delhi Dept of Ophthalmology
VMMC & Safdarjung Hospital, Section Editor - Ocular Oncology
Section Editor - Community Ophthalmology New Delhi
Section Editor - Community Ophthalmology
Dr. Sima Das Dr. Vineet Sehgal Dr. Digvijay Singh
Head, Oculoplasty and Ocular MBBS, MD Affiliation, Noble Eye Care,
Oncology Services Fellowship in Glaucoma Gurugram
Incharge, Medical Education Senior Consultant & Incharge
Dr. Shroff’s Charity Eye Hospital Glaucoma Sharp Sight Eye Hospitals Section Editor - Residents Corner
New Delhi
Section Editor - Residents Corner
Section Editor - Ocular Oncology
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DOS Times - Volume 28, Number 2, March-April 2022 06 www.dosonline.org/dos-times
DOS TIMES
From the
President’s DESK
Dr. Pawan Goyal Dear All
Our previous issue on Recent Advances and Innovations was very well received. Our
MBBS, MS Editorial team under guidance of Secretary Dr. Jatinder Singh Bhalla has brought out
extremely useful issue on General Ophthalmology. You shall find interesting amalgamation
of Practically useful & Academic articles.
I take this opportunity to invite you all to Grand Academic extravaganza of Annual DOS
Conference scheduled to be held on 7th-9th October.
Your feedback is very important to us.
Please write your suggestions to us .
Dr. Pawan Goyal
President, DOS
Chairman Goyal Eye Institute, Delhi
www.dosonline.org/dos-times 07
DOS Times - Volume 28, Number 2, March-April 2022
DOS TIMES
From the DESK of
Chief Editor
Dr. J S Bhalla, I feel honoured to write the editorial for yet another exciting issue of DOS Times. The response
& Feedback that we received from inaugural issue was very encouraging. We are bringing for you
MS, DNB, MNAMS compilation of nicely written articles on Pan Ophthalmology that would be of interest to General
Secretary Ophthalmologists. The article in PG Corner & Case Report shall arouse Academic interest of
one & all.
Delhi Ophthalmological Society Tremendous response to DOS VT (Video teaching programme) and DOS Quiz has buoyed
us. Shift to Physical DOS monthly meeting has brought back the joy of one to one interaction.
With the support of Executive committee, we have been able to organise highly successful DOS
Midterm Conference on 2nd-3rd April 2022. Cautious optimism to organise physical conference
was reciprocated by enthusiastic response of you all. DOS Midterm Conference recorded highest
ever attendance of around 1100 delegates. Live surgery, Scientific session, Free paper, wet labs,
Poster presentation, Quiz & active participation by Trade were the hallmarks of this Academic
extravaganza.
With the commitment to set a new yardstick in terms of dissemination of scientific knowledge,
networking & trade, we extend invitation to you all to Annual DOS Conference, scheduled to be
held from 7th-9th Oct, 2022.
The section of Beyond Ophthalmology will bring smile to your faces by highlighting that there is
place for humour too in Ophthalmology.
I thank our Editorial team, our honourable readers and esteemed contributors.
A writer only begins a book
A Reader finishes it.
We wish you all a pleasant and enjoyable reading from beginning to finish.
Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS
Chief Editor - DOS Times,
Consultant & Academic Incharge (Ophthalmology)
DDU Hospital, Hari Nagar
DOS Times - Volume 28, Number 2, March-April 2022 08 www.dosonline.org/dos-times
DOS TIMES
From the DESK of
Managing Editor
Dr. Prafulla Kumar It’s a great pleasure to bring out this edition of DOS Times. In our previous edition we had
Maharana, MD focused on recent advances. This edition is a general edition including a conglomeration of
various subspecialty articles.
The articles on phacoemulsification, multifocal IOL, amblyopia, spectacles in myopia and
diabetic retinopathy would help the readers in their day to day practice. The case reports would
highlight some interesting clinical scenarios. The article on beyond ophthalmology would bring
out the humor component hidden by the burden of day to day clinical practice.
The article under the PG corner section would help the residents and practitioners in
understanding microbial keratitis. The articles on usefulness of modern imaging techniques in
recalcitrant cases of corneal hydrops and trabeculectomy blebs would update the readers about
the recent advances.
In the end I would like to repeat my previous words. Change is an essential part of improvement
over time. In spite of all our efforts there will definitely be scope for improvement in future. I
would request the readers of this edition to convey us through whatever possible means their
valuable suggestions and help us improve further.
Dr. Prafulla Kumar Maharana, MD
Managing Editor DOS Times,
Associate Professor of Ophthalmology
Cornea Cataract & Refractive Services
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi
Email : prafulmaharana@gmail.com
www.dosonline.org/dos-times 09
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Oculoplasty
An atypical presentation of right sided
infra orbital region foreign body with no
signs of external entry wound
Devanshi Mehta[1], MBBS, Donika Patel[2], MBBS, Avani Chudasma[3], MBBS, Samir Bhavsar[4], MS, Chaitali Patel[5], DNB
1. 3rd year resident, M.S Ophthalmology, Pramukh Swami Medical College, Bhaikaka University, Shree Krishna Hospital.
2. Consultant Ophthalmologist at Adarsh Multispeciality Hospital, Kalol.
3. 2nd year resident, M.S Ophthalmology, Pramukh Swami Medical College, Bhaikaka University, Shree Krishna Hospital.
4. Head of Department of Ophthalmology, Pramukh Swami Medical College, Bhaikaka University, Shree Krishna Hospital.
5. Associate Professor, Ophthalmology department, Pramukh Swami Medical College, Bhaikaka University, Shree Krishna Hospital.
Abstract: Intra ocular and extra ocular foreign bodies usually have a preceding history of source of origin. The
authors reported an unusual a case of subcutaneous foreign body which did not correlate with the history of patient.
Thus, early recognition of foreign body around eye needs a routine xray irrespective of a kind of injury. This will allow
for early diagnosis and an improved outcome.
Case Report wound or inflammation or scar was present. So, the authors
made a differential diagnosis of hematoma, dermoid / lipoma.
A 54 year male presented in the Eye OPD in a Tertiary Care Initially patient was given Oral antibiotic (Tablet Augmentin
Hospital, Gujarat with chief complaints of Right eye pain, foreign 625mg TDS), oral antacid (Tablet ranitidine 150mg OD), oral
body sensation, and a swelling below the lower lid since 2days. analgesic (Tablet Combiflam BD) for 7 days along with Tetanus
Patient had a history of fall on road due to road traffic accident toxoid Intra muscular injection stat as he had abrasions over
5 days back. He was a known case of hypertension since 2 years, forehead.
on treatment. On presentation, best corrected visual acuity of When the swelling did not reduce over a period of 5 days, right
patient for distance recorded on Snellen’s chart was 6/6 in both eye x-ray orbit was advised.
eyes and for near recorded on Roman’s chart was N6 in both Right eye orbit x-ray AP and lateral view (Figure 2 & 3) showed
eyes. very small, elongated, biconvex, rice like opacity seen in the
On examination patient had superficial abrasions over fore head right cheek region overlying the inferior margin of right orbit
and a firm mobile non tender swelling of around 3 mm in size suggesting the possibility of foreign body. On the basis of the
was present over the infra orbital margin as shown in Figure 1. above findings, diagnosis of right eye infra orbital subcutaneous
Rest ocular examination was normal in right eye. Ocular exam- foreign body was made.
ination in left eye was absolutely within normal limits.
At the infra orbital region of swelling, no signs of any entry
Figure 1 : Appearance of infra orbital area on presentation. Figure 2 : Right eye orbit x-ray AP view.
DOS Times - Volume 28, Number 2, March-April 2022 10
www.dosonline.org/dos-times
Subspecialty - Oculoplasty
Conclusion
It was an atypical presentation of subcutaneous infra orbital
foreign body with no visible external entry wound, so all cases
of ocular trauma should undergo radiological investigations to
rule out presence of any foreign body.
Figure 3 : Right eye orbit x-ray lateral view.
Management
Surgical removal of foreign body under local anesthesia was
planned. 1 cm horizontal incision was put. On exploring, a
hard foreign body measuring about 3 mm, partly embedded in
muscle layer was found and removed. Wound closure was done
with sutures. On examining the foreign body, it was a piece of
granite as shown in Figure 4. Post operatively patient was seen
after 2 days, incision site sutures were in place with no localized
edema.
Corresponding Author:
Dr. Devanshi Mehta, MBBS
3rd year resident, M.S Ophthalmology, Pramukh Swami Medical College,
Bhaikaka University, Shree Krishna Hospital
Figure 4 : Appearance of foreign body.
www.dosonline.org/dos-times 11
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Oculoplasty
Sarcoidosis presenting as bilateral lacrimal
gland enlargement: Eyes speak the truth
Indu Dhiman[1], MS, Rajneesh K. Thakur[2], MD
1. Senior Resident, Department of Ophthalmolog, Dr. RPGMC Kangra at Tanda (HP).
2. Senior Resident, Department of Pathology, Dr. RPGMC Kangra at Tanda (HP).
Sarcoidosis is an idiopathic, multisystem disorder and is neutrophil cytoplasmic antibodies (c-ANCA) and serum IgG4
mainly characterised by pulmonary, dermatologic and ocular levels were also found to be negative. On imaging, computed
involvement. The prevalence of ocular involvement in this tomography (CT) of the orbit revealed bilateral lacrimal gland
condition has been reported by different studies to range enlargement (Figure 2). CT of the brain was normal. X-ray chest
between 25-60%.[1,2] Uveitis is the most common manifestation showed bilateral hilar lymph node prominence with reticular
of ocular sarcoidosis followed by conjunctival nodules, lacrimal opacities in the lungs. High resolution CT (HRCT) of the chest
gland enlargement, dry eye, chronic dacryocystitis and retinal revealed multiple bilateral parahilar nodes with peribroncho-
vasculitis.[3] Diagnosing sarcoidosis is a challenge both for the vascular thickening and perifissural nodules (Figure 3). These
clinician and for a radiologist and requires a detailed background findings were strongly suggestive of pulmonary sarcoidosis. A
knowledge of various diseases considered in the differential negative Mantoux test strengthened the diagnosis. A confirma-
diagnosis. We present a case of ocular sarcoidosis with bilateral tion of the diagnosis was carried out with lacrimal gland biopsy
enlargement of the lacrimal glands as the initial manifestation of which revealed epitheloid cells with non-necrotizing granulo-
systemic sarcoidosis. mas diagnostic of sarcoid granulomas (Figure 4). Oral prednis-
Case Report olone in a daily dose of 50mg/day (based on the body weight)
A 31 years old female presented with complaints of swellings was initiated for two weeks and then tapered by 10mg every
in the outer aspects of both eyes. The swelling developed two weeks until two months were completed. The patient was
over 4 months and there were no other ocular or systemic then advised to continue oral prednisolone 10 mg for the next
complaints. General physical examination was normal. On three months and a further five mg for next three months. The
ocular examination, there were nodular swellings over the swelling subsided after one month of treatment and the patient
lateral part of both upper eyelids (Figure 1). Visual acuity was on three monthly follow ups for one year after treatment
(uncorrected visual acuity) was 6/6 and colour vision was with no recurrence noted till the last follow up.
within normal limits in both eyes. Pupil reacted briskly to light
and the intraocular pressure and ocular motility were normal in
both eyes. On slit lamp examination, the anterior and posterior
segment were found to be normal. The result of the Schirmer test
without topical anaesthesia was 17 mm/5minutes for both eyes.
Keeping in mind the bilateral and symmetrical enlargement of
the lacrimal glands, differential diagnoses of systemic conditions
such as lymph proliferative disorder, Sjogren syndrome, ocular
tuberculosis, ocular sarcoidosis and Wegener’s granulomatosis
with polyangiitis (GPA) were considered.
Figure 1 : Shows nodular swelling over lateral aspects of both the eyelids.
Routine blood investigations were within normal limits and the Figure 2 : Computed Tomography orbit shows enlargement of lacrimal
Mantoux test was negative. Serum calcium level and angioten- glands both eyes.
sin converting enzyme level were within normal limits. Anti-
DOS Times - Volume 28, Number 2, March-April 2022 12 www.dosonline.org/dos-times
Subspecialty - Oculoplasty
Figure 3 : HRCT chest shows multiple bilateral parahilar peribronchovas- In lymphoproliferative disease, the spectrum can vary from
cular thickening and perifissural nodules. lymphoid hyperplasia to lymphoma.[5] Lymphoproliferative
disorders can also manifest as bilateral lacrimal gland
Figure 4 : Lacrimal gland biopsy shows epitheloid cells with discrete non- enlargement, which may be primary or secondary to systemic
caseating granulomas. lymphoma. Although mediastinal and hilar lymphadenopathy
are common in lymphoma, but lacrimal gland biopsy findings
Discussion were not compatible with a diagnosis of lymphoproliferative
Ocular sarcoidosis can involve any part of the eye and its disorder in our case.
adnexal tissues. Two large studies have reported lacrimal gland Tuberculosis may rarely present with bilateral lacrimal gland
involvement at rates of 7% and 15.8%.[2,4] Because the disease enlargement.[6] Pulmonary tuberculosis shows upper lobe
shares features with tuberculosis and lymphoproliferative predominance with branching nodules, areas of consolidation
disorders, Sjögren’s syndrome, immunoglobulin G4 (Ig-G4)- and necrosis. On histopathology Caseating granulomas are
related disease and granulomatosis with polyangiitis (GPA), typical of tuberculosis. In our case, the respiratory imaging was
differential diagnosis of these systemic diseases should also be classical of pulmonary sarcoidosis with a negative Mantoux test.
considered. In Sjögren’s syndrome, bilateral lacrimal gland enlargement
may be seen occasionally. In this disease, lacrimal gland biopsy
shows periductal and focal inflammatory aggregates and
atrophy of acini and fibrosis in histopathology.
GPA is a multisystem disease. Orbital involvement is seen in
40%–50% cases and is usually accompanied by paranasal sinus
disease.[7] In GPA, pulmonary nodules are larger and cavitatory
with involvement of the upper respiratory tract and elevated
c-ANCA levels.
Immunoglobulin G4-related (Ig-G4) disease is an inflammatory,
multisystem disease characterized by infiltration of one or more
organs with Ig-G4 positive cells. It may also involve the ocular
adenexa, typically leading to lacrimal gland enlargement.[8]
Serum IgG4 levels are raised, and histopathological findings
shows lymphoplasmacytic infiltration and storiform fibrosis.
In our case Serum IgG4 levels were normal and biopsy findings
were characterstic of sarcoidosis.
Sarcoidosis is a grossly under-reported condition in the tuber-
culosis-endemic regions and the true burden of the disease is
difficult to estimate as there is insufficient epidemiological data.
The clinical course varies from being completely asymptomatic
to a severe disease. The diagnosis of sarcoidosis is based on clin-
ical, laboratory and radiological findings and is confirmed by
histopathological examination. In this case, the only symptom
was a swelling on the lateral aspect of both upper eyelids with no
history of any other ocular or systemic complaints. Evaluation
of a case of bilateral lacrimal gland enlargement is important as
it may be tell-tale sign of an undiagnosed systemic disease. It is
necessary to screen all systems, and the final line of management
should be based on organ and system involvement. A multi-dis-
ciplinary approach is required to achieve the best treatment out-
comes for both ocular and systemic manifestations. With appro-
priate treatment, prognosis is generally good.
References
1. Prabhakaran VC, Saeed P, Esmaeli B, Sullivan TJ, McNab A, Da-
vis G,Valenzuela A, Leibovitch I, Kesler A, Sivak-Callcott J, Hoya-
ma E, Selva D.Orbital and adnexal sarcoidosis. Arch Ophthalmol.
2007;125:1657-1662.
2. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J
Ophthalmol. 1986;102:297-301.
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Oculoplasty
3. Usui Y, Kaiser ED, See RF, Rao NA, Sharma OP. Update of ocular Corresponding Author:
manifestations in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis
2002;19:167‑75. Dr. Indu Dhiman, MS
Senior Resident, Department of Ophthalmology, Dr. RPGMC Kangra at Tanda (HP).
4. Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and
its ophthalmic manifestations. Am J Ophthalmol. 1978;86:648-655.
5. Farmer JP, Lamba M, Lamba WR, Jordan DR, Gilberg S, Sengar DP,
et al. Lymphoproliferative lesions of the lacrimal gland: Clinicopatho-
logical, immunohistochemical and molecular genetic analysis. Can J
Ophthalmol. 2005;40:151–60.
6. Bansal RK, Malhotra C, Bhatia R, Chhabra S, Sood S. Tubercular da-
cryoadenitis – A case report and review of literature. Indian J Pathol
Microbiol. 2006;49:385–7.
7. Vaidhyanath R, Kirke R, Brown L, Sampath R. Lacrimal fossa lesions:
Pictorial review of CT and MRI features. Orbit. 2008;27:410–8.
8. Yu WK, Tsai CC, Kao SC, Liu CJ. Immunoglobulin G4-related oph-
thalmic disease. Taiwan J Ophthalmol. 2018;8:9–14.
DOS Times - Volume 28, Number 2, March-April 2022 14 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
Comparative study of efficacy of pupillary
dilatation using preoperative topical
mydriatics versus the use of intracameral
adrenaline in phacoemulsification: A
prospective randomised control study
Kirti Kaim[1], MBBS, MS, L. Sarkar[2], MBBS, MS, Ashok Kumar Ahirwar[3], MBBS, MD, DNB
1. Insurance Medical Officer (IMO), ESI Hospital, Rohini, New Delhi.
2. Professor & Head, Department of Ophthalmology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi.
3. Assistant Professor, Department of Biochemistry, University College of Medical Sciences, New Delhi.
Abstract: Purpose: comparative study of efficacy of pupil dilatation using preoperative topical mydriatics tropicamide
and phenylephrine and intracameral adrenaline tartrate during phacoemulsification surgery.
Materials and Methods: The study population consisted of 72 patients with senile cataract who underwent phacoemul-
sification with PCIOL implantation. They were randomly assigned into two groups based on the method of pupillary
dilation, first group consisted of 36 patients in which topical tropicamide and phenylephrine combination was used
preoperatively and second group consisted of 36 patient in which only intracameral adrenaline tartrate in 1:10,000
(epitrate injection, Sunways (I) Pvt. Ltd.) was used for pupil dilation. Patients did not know which method was used
for pupil dilatation (Blinding). Pupil size was measured at 1 hour prior to surgery, and then 1 minute, 5 minutes, 10
minutes and 15 minutes after incision at the starting of surgery.
Results: The mean age, sex, cataract density, baseline horizontal pupil diameter, and mean duration of the surgery
were the same between the topical group and intracameral group. Although there is statistical significant difference
between the two groups (P=0.023) but clinically there is no significant difference (average pupil diameter of 8.4 mm in
tropical group as compared to 8.1 mm in the intracameral group) in phacoemulsification surgery.
Conclusion: Intracameral adrenaline acts as an effective and efficacious drug which can be used as an alternative to
preoperative topical tropicamide and phenylephrine for pupillary dilatation.
Keywords: Pupillary dilatation, Tropicamide and Phenylephrine combination, Intracameral Adrenaline, Phacoemul-
sification.
Introduction Various methods are used for pupillary dilation out of which the
Phacoemulsification is a modern day cataract surgery which re- most commonly used is through topical mydriatic agents like
quires a well-dilated pupil throughout surgery for its successful phenylephrine, cyclopentolate, and tropicamide which act by
surgical outcome. If the pupil becomes constricted during sur- paralysing the parasympathetic constrictor drive, allowing the
gery, there is an increased risk of complications, which range sympathetic input to the dilator to dominate. Combinations of
from incomplete removal of cortical material to posterior cap- two topical synergistic mydriatic agents (a sympathomimetic
sule tear and loss of lens nucleus into the vitreous cavity.[1] A agent and a parasympatholytic agent) are commonly employed
small pupil affects all steps of surgery, from capsulorrhexis to for preoperative mydriasis.[5] Tropicamide and phenylephrine
IOL insertion. Difficult maneuvering can cause iris damage, is a popular combination. Tropicamide (muscarinic receptor
sphincter tears, zonular dialysis, bleeding and further compli- antagonist) and phenylephrine (α-adrenergic receptor agonist)
cations. Poor exposure through a small pupil forces the surgeon are commonly used and act synergistically to dilate the pupils by
to make a smaller capsulorhexis, adding further to the difficulty topical application.
and frequently leading to capsular dehiscence and nucleus drop. Topical regimen suffers from disadvantages like slow penetra-
The prolonged surgical time takes its toll thereafter.[2,3] Corne- tion through cornea which leads to delayed mydriasis, limited
al edema, uveitis, secondary glaucoma, cystoid macular edema, bioavailability of topically administered substances with signif-
distorted pupil are late complications.[4] icant systemic absorption which increases the cardiovascular
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
side effects. Also, topical mydriatic effect, even if good initial- these drugs are also responsible for corneal endothelial and ep-
ly, tends to wear off during surgery. Tropicamide has failed to ithelial toxicity. Also, they are contraindicated in persons with
produce satisfactory mydriasis when given alone. Prominent primary glaucoma or a tendency toward glaucoma (e.g. narrow
cardiovascular effects of phenylephrine include a rise in systolic anterior chamber angle).[7]
and diastolic blood pressure and reflex bradycardia. More than Several solutions to this problem have been suggested including
80% of the active ingredient that actually penetrates into the eye preoperative treatment with diclofenac, viscous phenylephrine,
passes through the cornea, producing adverse effects.[6] Both intraoperative intracameral epinephrine.[8]
Assessed for eligibility
Enrollment Excluded (n= 163)
• Not meeting inclusion criteria (n=91)
• Declined to participate (n=19 )
• Complicated Cataract (n= 10 )
• Nuclear Sclerosis grade ≥ 4(n=3)
• Associated ocular co-morbidity (n= 15)
• Past History of ocular trauma (n=5)
• High degree of refractive trauma (n=10)
Randomized (n=76)
Allocated to intervention Group 1 (n=36) Allocation Allocated to intervention Group 2 (n=36)
• Received topical Mydriatic (n=36) • Received intracameral adrenalin (n=36)
Analysed (n= 36) Follow-Up and Analysis Analysed (n=36)
Figure 1 : Flow diagram showing recruitment of study population during the course of study.
Intracameral regimen offers an alternative which helps to avoid Sample size
some disadvantages as there is no preoperative waiting time and 72 eyes of 72 patients with the diagnosis of immature senile
the dose of mydriatic agents is reduced, lowering the risk for sys- cataract in either eye were enrolled and were allocated to one of
temic side effects.[9] the two groups (36 patients each) through simple randomization
The purpose of our study is to compare the efficacy of pupil di- as shown in Figure 1. In one group, topical mydriatics (0.8%
lation using topical mydriatics tropicamide and phenylephrine tropicamide and 5% phenylephrine) were used at 15 minutes
preoperatively and adrenaline tartrate intracamerally during interval (3 times) starting 1 hour prior to surgery to dilate the
phacoemulsification surgery. pupil and in the other group, only intracameral epinephrine
Materials and Methods tartrate, available as Epitrate injection (0.1 ml adrenaline in 1 ml
of solution, that is, 1:10,000 dilution) was used for pupil dilation.
Study design Inclusion criteria
Our study was a prospective randomized control study that
compared efficacy of pupillary dilatation of two different The inclusion criteria for enrolment into the study included
mydriatic agents by studying intraoperative findings. It was patients of senile mature cataract (grade 1, 2 and 3 only) using
conducted in the Department of Ophthalmology, Vardhaman slit lamp assessment.
Medical College and Safdarjung Hospital, New Delhi from
2011-2013 (22 months). Study was approved by the ethical Exclusion criteria
committee of VMMC & SJH, New Delhi. The research protocol Exclusion criteria included age>75 years and age<45 years, com-
was in accordance with the Helsinki Declaration of studying plicated cataract (white cataract, cataract with subluxated lens,
human subjects. Informed and written consent was taken from associated uveitis, associated glaucoma, cataract with posterior
the study population. synechiae), Nuclear sclerosis ≥ grade 4, associated co-morbidity
DOS Times - Volume 28, Number 2, March-April 2022 16 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
such as cardiac disease, diabetes, hypertension and patients on Postoperatively, patients were examined when detailed anterior
topical or systemic steroids, past history of ocular trauma, high segment evaluation was done using slit lamp microscope, Intra-
degree of refractive errors, intraoperative or postoperative com- ocular pressure measurement using non-contact tonometry, en-
plications which can independently affect pupil dilation, endo- dothelial cell count of central cornea, morphology of endothelial
thelial cell count < 1500 cells/mm square. cells. Refraction was done at day 42.
Statistical analysis
Surgical technique used was common for both the groups and
2 operating surgeons performed all the cases included in the Variables measured were expressed as mean ± standard de-
study. viation. Comparisons of mean between two groups were per-
Pupil size was measured at 1 hour prior to surgery, 1 minute, formed using independent-sample t tests (Student’s t test). Data
5 minutes, 10 minutes and 15 minutes after incision. Coaxial considered statistically significant when the P-value was below
phacoemulsification was done: A 2.8 mm clear corneal incision 0.05. The analysis was performed using statistical programme
was made superiorly using disposable keratome followed by (SPSS Version 20.0, SPSS Inc, Chicago, USA) and and GraphPad
making a side port entry and injecting adrenaline in group 2 Prism version 5 (GraphPad Software, Inc. CA, USA).The power
patients followed by capsular staining with trypan blue. Side port of the study is 80%, alpha is 5%, effect size is 0.6.
incision was made about 2 o’clock left of entry wound in clear Results
cornea with 15° angled knife or 20 G MVR blade. Viscoelastic
substances like hydroxymethylcellulose (appavisc) and sodium Our study included patients suffering from immature senile
hyaluronate (Hyal 2000) were used to maintain the anterior cataract. The age and sex distribution of study population is
chamber and for endothelial protection. Continous curvilinear shown in Table 1 & 2. The age of the patients ranged from 45-75
capsulorrhexis was performed with bent 26 G needle (cystitome) years and mean age was 56 years. Maximum no. of patients were
or capsulorrhexis forces (Utrata’s forceps). Triplanar corneal in age group 56-60.
tunnel was dissected and anterior chamber was entered using As shown in Table 3 and Figure 2, the comparison of pupil di-
2.8 mm keratome. Hydroprocedure was performed. “In the bag ameters showed that there was no significant difference at 1 hour
phacoemulsification” was performed. Phaco machines used were prior to surgery in horizontal (P=0.453) or vertical (P=0.281)
Oertli machines (Oertli Instrument AG, Berneck, Switzeland). axis. Hence, neither of the 2 groups had any difference in pupil
For phacoemulsification, a standard stop and chop technique size before the use of any drug.
was employed and the parameters used during different stages At 1 minute, combination of tropicamide and phenylephrine
of surgery were a power of 50-55%, pulse mode, a vacuum of was more efficacious statistically in pupillary dilatation as com-
50-400 mmHg, and an aspiration flow rate of 25-30 cc/min. pared to intracameral adrenaline. (P=0.029 that is P<0.05).
Care was taken to perform phacoemulsification at the posterior The average pupil diameter in group 1 was 8.3 mm and that in
plane. Constant anterior chamber depth was maintained with group 2 was 8 mm. At 5 minutes, combination of tropicamide
viscoelastics (methylcellulose) before removing any instrument and phenylephrine was more efficacious statistically in pupillary
from the eye. Bimanual irrigation/aspiration was performed for dilatation as compared to intracameral adrenaline (P=0.023).
cortex removal. A foldable PCIOL was implanted in capsular Group 1 had average pupil diameter of 8.5 mm and group 2 had
bag using an injector cartridge and IOL was dialed. The residual average diameter 8.2 mm. However at 10 minutes, there was
viscoelastic was removed with bimanual irrigation/aspiration. no significant difference between the two groups statistically
Stromal hydration was done and surgery was completed after (P=0.06). There was no significant difference between the aver-
making sure that no wound leakage was there. All surgeries were age pupil diameters of the two groups i.e. 8.5 mm and 8.2 mm.
uncomplicated and hence, were included in the study. Also at 15 minutes, there was no significant difference between
the two groups (P=0.19) i.e. pupil diameter of 8.2 mm (group 1)
Method of pupillary dilation measurement and 7.97 mm (group 2) does not make any significant difference.
All surgeries were performed under sterile conditions. The sur- Although there was statistical difference between the two groups
geon was not masked and knew the type of mydriatic that was but clinically there was no significant difference (average pupil
being used for each patient. The following parameters were not- diameter of 8.4 mm in group 1 as compared to 8.1 mm in group
ed intraoperatively: pupil size (measured by placing a caliper 2) in phacoemulsification surgery. Surgical clock time varied in
horizontally and vertically at midpoint of pupil as close to the group 1 from 11 to 20 minutes with most of the surgeries being
eye) 1 hour prior to surgery, and 1 minute, 5 minutes, 10 min- done in 15 to 18 minutes, group 2 clock time also varied from
utes and 15 minutes after incision, surgical clock time. In case of 11 minutes to 16 minutes, the difference between the two groups
non dilation of pupil, iris hooks were used, but the patient was being statistically insignificant (P=0.452) as shown in Table 4
excluded from this study. and Figure 3.
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
AGE & SEX WISE DISTRIBUTION OF STUDY SUBJECTS
Parameters Group 1 Group 2 P value
(Mean ± SD) (Mean ± SD) 0.898
Age (years) 56.9 ± 6.9 56.7 ± 7.6 P value
0.238
Table 1 : shows that distribution of Age in study population.
P value
Sex Group 1 Group 2 0.453
Male 21 15 0.281
Female 15 21 0.029*
0.029*
Table 2 : shows that distribution of sex in study population. 0.023*
0.029*
Pupillary Diameter (cm) Group 1( N=36) Group 2 (N=36) 0.062
(Mean ± SD) (Mean ± SD) 0.110
2.5 ± 0.37 0.200
Horizontal diameter 1 hour 2.45 ± 0.38 2.54 ± 0.38 0.200
before surgery 2.47 ± 0.39 8.03 ± 0.71
Vertical diameter 1 hour before 8.39 ± 0.67 8.03 ± 0.71 P value
surgery 8.39 ± 0.67 8.20 ± 0.50 0.452
Horizontal diameter 1 8.56 ± 0.74 8.22 ± 0.51
minute after incision 8.56 ± 0.73 8.20 ± 0.55 www.dosonline.org/dos-times
Vertical diameter 1 minute 8.50 ± 0.74 8.22 ± 0.56
after incision 8.49 ± 0.80
Horizontal diameter 5 8.0 ± 0.44
minute after surgery 8.0 ± 0.44
Vertical diameter 5 minute
after surgery
Horizontal diameter 10
minute after surgery
Vertical diameter 10 minute
after surgery
Horizontal diameter 15 8.25 ± 0.73
minute after surgery 8.25 ± 0.73
Vertical diameter 15 minute
after surgery
*p value≤0.05 is considered statistically significant.
Table 3 : Parameters observed pre operatively and intraoperatively.
Parameter Group 1 (N=36) Group 2 (N=36)
Clock time (minutes) (Mean ± SD) (Mean ± SD)
15.9 ± 3.5 15 ± 3.1
Table 4 : Comparison of surgical clock time of study population.
DOS Times - Volume 28, Number 2, March-April 2022 18
Subspecialty - Lens & Cataract
Horizontal diameter one hour before surgeryHprizontal diameter (mm)Vertical diameter (mm)Vertical diameter one hour before surgeryHprizontal diameter (mm)Horizontal diameter one minute after incision
4.0 Group 1 Group 14.0 Group 111 P = 0.029*
Group 2 Group 2 Group 210
Non significant Non significant
9
3.5 3.5 8
3.0 3.0 7
2.5 2.5 6
2.0 2.0 5
1.5 1.5
Study population
Study population Study population
Vertical diameter 5 minute after surgery
Vertical diameter one minute after incision Horizontal diameter 5 minute after surgery 12
11 P = 0.029* 12
10 P = 0.029*
P = 0.023*
9 10
8 10
7 8
6 8
5 6
Vertical diameter (mm) 6
Group 1 Hprizontal diameter (mm) Vertical diameter (mm)
Group 2 Group 1 Group 1
Group 2 Group 2
Study population Study population Study population
Vertical diameter 10 minute after surgery Horizontal diameter 15 minute after surgery Vertical diameter 15 minute after surgery
12 11 11
P = 0.110 P = 0.200 P = 0.200
10 10 10
8 9 9
8
6 7 8
6
Hprizontal diameter (mm) 7
Group 1 6
Vertical diameter (mm) Group 2 Vertical diameter (mm)
Group 1 Group 1
Group 2 Group 2
Study population Study population Study population
Figure 2 : Dot plot of papillary diameters one hour before surgery and after surgery.
Clock time (minutes) Clock time Discussion
Group 1
Group 230 Majority of studies have used adrenaline tartarate as an adjunct
P = 0.452 to some other method of preoperative dilatation. Our study is
different as no comparison is available till date between preoper-
20 ative tropicamide and phenylephrine as compared to intraoper-
ative adrenaline tartarate only used intracamerally.
10 Preoperative pupillary dilatation is achieved most commonly
by topical mydriatic agents like combination of Tropicamide
0 0.8% and Phenylephrine Hydrochloride 5% which comprises
of Tropicamide 0.8% (w/v), Phenylephrine hydrochloride 5%
Study population (w/v), Benzalkonium chloride (as preservative-0.01% w/v) and
sterile aqueous vehicle. Phenylephrine/tropicamide is a com-
Figure 3 : Dot plot showing Clock time of surgery. bination of a mydriatic/cycloplegic drug.[5] Tropicamide is a
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
synthetic muscarinic agent, cholinergic antagonist, parasym- surgically this is not of much significance as far as phacoemul-
patholytic drug which is derived from tropic acid. It inhibits the sification surgery is concerned. Hence, it can be a promising al-
contraction of the circular muscle and also paralyses the ciliary ternative to preoperative topical mydriatics and can be used in
muscle. Side effects reported with tropicamide are transient patients with no systemic contraindications (excluding hyper-
stinging, blurred vision, photophobia & superficial punctate tension) as it proves to be a time saving option.
keratitis, dryness of mouth, tachycardia, headache, allergic re- In conclusion, in phacoemuslification surgery, intracameral
actions, nausea, vomiting, central nervous system disturbances adrenaline tartrate is almost equally efficacious for pupil dila-
& muscle rigidity.[10] It is contraindicated in case of hypersensi- tation as compared to preoperative combination of tropicamide
tivity to any of the components, narrow angles or narrow angle and phenylephrine. Good pupillary dilatation is attained with
glaucoma. both drugs i.e. tropicamide and phenylephrine combination and
Phenylephrine is a synthetic sympathomimetic which acts selec- intracameral adrenaline. The difference between the sizes of the
tively on alpha-1 adrenergic receptors following topical applica- pupil is of 0.3 mm which is statistically significant (P=0.023)
tion. Phenylephrine brings about contraction of the radial mus- but clinically this difference is not of much significance as the
cle thereby bringing about dilatation of the pupil.[11] Side effects surgeon did not find any difficulty while doing phacoemulsifica-
reported with phenylephrine are decrease in intraocular pres- tion. These findings suggest that intracameral adrenaline acts as
sure due to vasoconstriction of the ciliary blood vessels, reduced an effective and efficacious drug which can be used as an alterna-
aqueous humor formation, allergic blepharoconjunctivitis, lid tive to preoperative tropicamide and phenylephrine.
retraction, rise in systolic and diastolic blood pressure, tachy- Strength of our study was 1) Randomised control study, well
cardia, reflex bradycardia, ventricular arrythmia, myocardial standardized method to determine the study variables, char-
infarction, occipital headache & subarachnoid haemorrhage, acterized and diverse study population, 2) data appropriately
hence it is used with caution in elderly patients.[12] collected from study populations. 3) age and sex matched study
Adrenaline is a sympathomimetic and maintains mydriasis by populations.
a direct action on the dilator pupillae and is relatively not toxic Limitations
to the corneal endothelium.[13] It is also the drug of choice for
pupillary dilatation in patients who are allergic to mydriatics like Our study was hospital based cross sectional study so that we
tropicamide or phenylephrine. Adrenaline being a sympathomi- cannot predict cause effect relationship. Our study had small
metic is contraindicated in patients with cardiac disease. Intraca- sample size.
meral Epinephrine Tartrate (available as Epitrate injection) - 1.8 Conflict of Interest
mg Equivalent to Adrenaline base Sodium Metabisulphite (as
antioxidant-0.1%) preservative free, is used in 1:10000 dilution No conflict of interest to declare.
intraoperatively by injecting into the anterior chamber directly. References
As concluded by Lundberg, Behndig, intracameral mydriatics
are a rapid, effective, and safe alternative to topical mydriatics 1. Lundberg B, Behndig A. Intracameralmydriatics in phacoemulsifi-
in phacoemulsification[8] but they have studied on 60 study cation surgery obviate the need for epinephrine irrigation. ActaOph-
subjects as compare to present study where the study population thalmologicaScandinavica. 2007 Aug 1;85(5):546-51.
consisted of 72 patients. Their use can simplify preoperative
routines and in certain high-risk groups, may reduce the risk 2. Lindsay Ong-Tone, Ali Bell Pupil size with and without adrenaline
for cardiovascular side effects which concurs with the findings with diclofenac use before cataract surgery, J Cat and Ref Surg -vol.
in our study that intracameral injection of adrenaline tartrate 35,august 2009; 1396-1400
is an effective and time saving option as compared to topical
mydriatics. 3. Bartlett JD, Miller KM. Phacoemulsification techniques for patients
As concluded by Shiow-Wen Liou and Chun-Chen Chen, one with small pupils. ComprOphthalmol Update. 2003;4:171–176.
bolus of an extremely dilute concentration of epinephrine (i.e.,
1:400,000) injection might be effective in maintaining mydriasis 4. Malyugin B. Complications of small-pupil cataract surgery. Cataract
during cataract surgery without systemic side effects which is RefrSurg Today Europe. 2013;26-30
confirmed by our study in phacoemulsification surgery.[14] How-
ever, the concentration used in the above mentioned study is 5. Lam PT, Poon B, Wu WK, Chi SC, Lam DS. Randomized clinical
1:400,000 dilution of epinephrine whereas we have used a more trial of the efficacy and safety of tropicamide and phenylephrine in
concentrated epinephrine solution (1:10,000) which is proved to preoperative mydriasis for phacoemulsification, Cl. & Exp. Ophthal.
be effective and time saving alternative. 2003 Feb 1;31(1):52–56.
The present study has shown preoperative topical mydriatics are
slightly more efficacious as compared to intracameral adrena- 6. McGhee CN. An overview of topical ophthalmic drugs and the thera-
line intraoperatively (Average size of pupil 8.4 mm in group 1 peutics of ocular infection. CNJ McGhee: Ocular Therapeutics. 2012.
compared to average pupil diameter of 8.1 mm in group 2). But
7. Razeghinejad MR, Myers JS, Katz LJ. Iatrogenic glaucoma second-
ary to medications. The American journal of medicine. 2011 Jan
31;124(1):20-5.
8. Lundberg B, Behndig A. Intracameralmydriatics in phacoemulsifica-
tion cataract surgery. Journal of Cataract & Refractive Surgery. 2003
Dec 31;29(12):2366-71.
9. Nikeghbali A, Falavarjani KG, Kheirkhah A. Pupil dilation with
intracameral lidocaine during phacoemulsification: benefits for the
DOS Times - Volume 28, Number 2, March-April 2022 20 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
patient and surgeon. Indian journal of ophthalmology. 2008 Jan Corresponding Author:
1;56(1):63.
Dr. Kirti Kaim, MBBS, MS
10. Ukai M, Okuda A, Mamiya T. Effects of anticholinergic drugs selec- Insurance Medical Officer (IMO), ESI Hospital, Rohini, New Delhi.
tive for muscarinic receptor subtypes on prepulse inhibition in mice.
European journal of pharmacology. 2004 May 25;492(2):183-7.
11. Apt L, Henrick A. Pupillary dilatation with single eyedropmydri-
atic combinations. American journal of ophthalmology. 1980 Apr
1;89(4):553-559.
12. Fraunfelder FT, Scafidi AF. Possible adverse effects from topical ocular
10% phenylephrine. American journal of ophthalmology. 1978 Apr
1;85(4):447-453.
13. Corbett MC, Richards AB. Intraocular adrenaline maintains mydri-
asis during cataract surgery. British journal of ophthalmology. 1994
Feb 1;78(2):95-98.
14. Liou and Chun-Chen Chen. Maintenance of Mydriasis with One Bo-
lus of Epinephrine Injection During Phacoemulsification. J Ocul Phar
and Ther. June 2001, 17(3):249-253.
www.dosonline.org/dos-times 21
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
A rare case of snow flake opacification of
three piece polymethyl methacrylate
intraocular lens
Divya Ramraika[1], DOMS, DNB, Bithi Chowdhury[2], MS, FRCS
1. Senior Resident, Department of Ophthalmology, Hindu Rao Hospital, New Delhi.
2. Senior Consultant and Head of Department, Department of Ophthalmology, Hindurao Hospital, New Delhi
Abstract: We report a case of 60 year old female with complaint of gradual diminution of vision in left eye. She had
history of cataract surgery almost a decade ago in both eyes, left eye operated earlier than right eye with three piece
polymethyl methacrylate (PMMA) intraocular lens implantation. On examination we found snow flake opacification
of three piece intraocular lens which involved the optic and hence visual axis was involved. Patient had no history
of any systemic illness. Hence, the intraocular lens opacification is extremely rare but an important complication of
uneventful cataract surgery which usually requires explantation.
Introduction normal in both the eyes by Ishihara plates. Iris had few atrophic
An uncommon but serious complication post cataract surgery patches which were probably due to trauma sustained during
is opacification of intraocular lens (IOL) which may cause the cataract surgery. Intraocular pressure, pupils, anterior
significant loss of vision and an IOL explantation may be chamber and vitreous were normal. Fundus examination was
required.[1] Snowflake opacification is a slowly progressive unremarkable in both the eyes. The patient was kept under
opacification of polymethyl methacrylate (PMMA) IOLs due follow up as the patient refused to give consent for explantation
to prolonged exposure of ultraviolet radiation and had been of intraocular lens.
observed in PMMA IOL implanted in 80s and 90s.[2] Leading Discussion
causes of clinically significant IOL opacification are calcification Variable patterns of opacification observed in various IOL
and snow flake degeneration.[3] biomaterials such as snowflake opacification in PMMA IOLs,
Case Report discolouration in silicon IOLs, calcification in hydrophilic
A 60 year old female, housewife by occupation presented with acrylic IOLs and glistening in hydrophobic acrylic IOLs.[4,5] A
chief complaint of gradual diminution of vision in left eye since clinicopathologic classification of snowflake degeneration of
1 year. She had history of cataract surgery in right eye in 2001 PMMA IOL optic given by Apple DJ et al.[2] who had divided
and in left eye in 1998. Patient had no history of any systemic the snowflake opacification into four groups based on the lesion
illness. Her best corrected visual acuity was 20/30 and 20/60 in morphology and severity, along with the number of opacities
right and left eye respectively. On slit lamp examination, both in each optic determining the classification in which grade I
the eyes of the patients were pseudophakic with scattered white included minimal opacities in IOL causing mild scattering of
deposits in the central region with a clear periphery of the three light and opacities were faintly visible in visual axis, grade II
piece intraocular lens in left eye (Figure 1). Colour vision was included mild opacities with increased number of visible leisons
and rare overlapping of opacities, grade III included moderate
Figure 1 : (A): Slit lamp photograph showing snow flake opacities in three opacities with further increase in visible leisons with significant
piece PMMA IOL in undilated pupil involving visual axis (B): Image overlapping of opacities, grade IV included maximal opacities
showing snow flake opacities in three piece PMMA IOL involving centre with numerous leisons overlapping and presence of multiple
of IOL in dilated pupil with uninvolved periphery. layer of opacities, leisons were examined using slit lamp . As
per this classification our patient had grade IV opacities i.e
numerous overlapping opacities in visual axis and multiple layers
of opacification. The term “Snowflake” was based on clinical and
low power microscopic appearance of each lesion. Apple DJ et
al.[2] under high–power examination revealed that snow flake
opacifications were spherical or stellate shaped depending on
the contour of the surrounding pseudocapsule, they found that
interior of the sphere did not contain fluid. They added that each
DOS Times - Volume 28, Number 2, March-April 2022 22 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
IOL optic had characteristic spherical inclusion within PMMA 4. Grzybowski A, Markeviciute A, Zemaitiene R. A narrative review
optic. Our case showed unilateral snow flake opacification of of intraocular lens opacifications: update 2020. Ann Transl Med
three piece PMMA IOL implanted more than 10 years ago in 2020;8:1547.
patient without any systemic illness.
Conclusion 5. Walker NJ, Saldanha MJ, Sharp JA, Porooshani H, McDonald BM,
Ferguson DJ, et al. Calcification of hydrophilic acrylic intraocular
There may be snowflake opacification of three piece PMMA IOL lenses in combined phacovitrectomy surgery. J Cataract Refract Surg
implanted ten or more years ago, hence we should have a wide 2010;36:1427-31.
overlook of the opacitites of IOL and cognizance of this rare
and delayed complication as India being a developing country Corresponding Author of the Article:
where PMMA IOL are still used in cataract surgeries and people
had exposure to ultraviolet radiation as more than half of the Dr. Divya Ramraika, DOMS, DNB
population is engaged in agriculture. Senior Resident, Department of Ophthalmology,
References Hindu Rao Hospital, New Delhi
1. Szigiato A-A, Schlenker MB, Ahmed IIK. Population based analy-
sis of intraocular lens exchange and repositioning. J CataractRefract
Surg. 2017;43(6):754-760.
2. Apple DJ, Peng Q, Arthur SN, Werner L, Merritt JH, Vargas LG, et al.
Snowflake degeneration of polymethyl methacrylate posterior cham-
ber intraocular lens optic material: A newly described clinical condi-
tion caused by unexpected late opacification of polymethyl methacry-
late. Ophthalmology 2002;109:1666‑75.
3. Werner L. Causes of intraocular lens opacification or discoloration. J
Cataract Refract Surg. 2007 Apr;33(4):713-26.
www.dosonline.org/dos-times 23
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
Trifocal and EDOF IOLs : A New Era of Multi-
focal IOL
Deepali Singhal, MD
Centre For Sight Eye Hospital, Bhubaneswar, India.
Introduction Types and Optical Properties of Different Multifocal IOLs
Based on the two basic optical phenomena (refraction and
In this new era of refractive cataract surgery, the biggest aim of diffraction of light), multifocal IOLs can be divided into[2]:
the surgeon and the biggest desire of patients is to achieve spec-
tacle independence after cataract surgery. The ideal situation 1. Refractive
would be to provide a continuous range of vision at all distances a) Zonal refractive IOL
or restoration of accommodation without any disturbance in the b) Aspheric IOLs
quality of vision just like a natural lens in a young human eye.
However, still with the ongoing research we are yet to fulfill this 2. Diffractive
desire. The trifocal and EDOF IOLs have reached very close to a) Bifocal diffractive
achieving this desire. b) EDOF Diffractive
Patients have become less tolerant of their visual disability c) Trifocal diffractive IOLs
for near and intermediate distances and often overestimate
the outcomes of refractive cataract procedures. The constant 3. Combined
evolution in multifocal IOLs to overcome these visual disabilities
by using various non-physiological optical methods is most 1. Refractive
accepted in the community.
Older Generation Multifocal IOLs and their Disadvantages a) Zonal refractive IOLs
These lenses have different zones with different power through
The principle behind the design of Multifocal IOLs is division which light undergoes refraction leading to different focal
or distribution of light entering the eye into different foci. This points.
however is not physiological since the light follows a different The first design of MFIOL granted FDA investigation status was
focal performance at the level of retina. Therefore, the success a bifocal bull’s eye PMMA IOL manufactured by Precision Cos-
of simultaneous vision relies on the ability of the human brain met with two zones. The central segment had a near add sur-
to select amongst the superimposed images, a primary in-focus rounded by a distance optical segment. Major disadvantages
image, whilst suppressing the blurred out-of-focus images, also were pupil dependency leading to a loss of distance vision in
known as neuroadaptation. Also, adaptation to the changes bright light due to pupil constriction and halos in dim light. The
induced in the quality of the retinal image by dispersion of light transition between the zones was blended and a third zone was
is required. Moreover, it causes a loss of contrast sensitivity and introduced to provide intermediate vision. Thereafter multiple
scattering of light at the edge of different zones. These are the zones were introduced in refractive foldable IOLs like AMO Ar-
main challenges with multifocal IOLs. All the recent advances in ray silicone IOL with 5 concentric alternate zones and central
this technology are aimed to smoothen and to make the division distance zones. The light distribution in this IOL was 50% for
of light more physiological thereby providing a continuous range distance, 37% for near and 15% for intermediate vision at a pu-
of vision. It is important to deliver the best possible subjective pil size of 3-3.5 mm. Major drawbacks included loss of contrast,
quality of vision along with visual acuity. pupil dependency, glare, and halos. The Rezoom lens was mod-
This concept of multifocality was patented by Hoffer in ified by expanding the distance zones and increasing near add
November 1982 after observing a patient with decentered IOL with a light distribution of 60% for distance and 40% for inter-
(50% in pupillary area) experiencing clear 6/6 best corrected mediate and near zones. This also had an aspheric transition be-
vision.[1] He gave the concept of split bifocal IOL with a split line tween the 5 zones leading to reduced pupil dependency, better
parallel to the axis of the haptic loops. Following this, the first distance, and intermediate vision for both day and night. Glare
bifocal IOL (bull’s eye design) was implanted by Dr John Pierce and halos were also reduced. The triple edge design minimized
in 1986. Thereafter, a 3 M diffractive bifocal IOL was developed the rate of posterior capsular opacification (PCO).
with multiple annular rings. These designs had various problems
and were modified later. b) Aspheric refractive IOLs
These lenses are EDOF aspheric IOLs that have an aspheric
design meant to increase the depth of focus rather than
neutralizing corneal spherical aberrations like in monofocal
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Subspecialty - Lens & Cataract
IOLs. In this design, the negative asphericity is increased depth of focus is increased from far to intermediate distance
generating a more negative spherical aberration. Thus, the by increasing the proximity of the main foci leading to a steady
paraxial incoming rays are focused farther away from the central optical performance. This lens also has an achromatic profile and
rays leading to an increase in the depth of focus within a range minimizes the chromatic aberration induced by the diffractive
of 1 to 1.5D providing a better intermediate vision. A commonly design by increasing the height of the steps.
used IOL based on this principle is the Tecnis Eyhance (Johnson
& Johnson, New Brunswick/USA). c) Trifocal diffractive IOL
Another recent addition is the Vivity IOL by Alcon laboratories. Trifocal IOL technology is the latest advancement in the field
This is also an EDOF IOL with non-diffractive aspheric profile. towards achieving spectacle independence. With increasing
Thus, it uses a negative spherical aberration and blended zones use of computers, tablets and smart phones in recent years,
to form a no zone IOL. It has an aspheric, wavefront-shaping more patients desire better intermediate vision at all distances.
optic that uses Alcon’s proprietary X-Wave technology. This has The main difference with the previous MFIOLs is that trifocal
a disruptive technology and does not cause splitting of light as IOLs also provides an excellent intermediate vision along with
in multifocals. The central optical element has a change in the distance and near. Thus, moving one step forward towards
elevation and curvature leading to a delayed central wavefront restoration of accommodation. Intermediate vision is also
while the peripheral rays reach the retinal first. Thus, the depth important for cooking, gardening, and viewing the speedometer
of focus is extended till up to -1.5 to -2D providing a good and maps while driving. These lenses also dispel the myth that
intermediate and a functional near vision as well. distance vision might be compromised. In addition, the loss of
light and the contrast is also minimized providing a clear vision
2. Diffractive IOLs at all distances regardless of light conditions.
These IOLs are based upon diffraction of light that utilizes The first trifocal diffractive IOL, FineVision lens (Physiol,
the wave nature of light. They create regions of constructive Liège, Belgium), was released in 2010.[2,4] This trifocal IOL is
interference for the light waves propagating to the retina, a combination of two bifocal diffractive elements. The first
by selectively delaying the optical path (altering the phase element has an add power of 3.5D and the second has 1.75D
relationships between the incoming light waves) in selected add for intermediate vision. The second order of the second
areas.[2] The concentric annular zones form an asymmetric diffractive element is such that the amount of lost light energy is
saw-tooth profile. The step height is of the same order as the reduced from 20% in bifocal diffractive IOL to 14%. Apodization
wavelength of the incoming light. These diffractive elements of the optic results in uniform distribution of light energy and
create a finite number of non-contiguous focal points for the superimposed intermediate diffractive profile. Other IOLs based
same wavelength of incident light. Depending on these focal on the same optical design are the RayOne trifocal IOL (Rayner,
points diffractive IOLs can be: Sussex, UK) which has a diffractive zone limited to central
4.5mm and AT LISA tri 839 MP IOL (Carl Zeiss Meditech
a) Bifocal diffractive IOL AG Jena, Germany) which has a non-apodized optic with a
The Pharmacia 808,811E and 3M diffractive PMMA IOL are bi- diffractive zone limited to central 4.5mm.
focal diffractive lenses. 3M diffractive MFIOL had an anterior The Acrysof IQ PanOptix (Alcon Laboratories, Fort Worth,
aspheric surface and a posterior diffractive surface with mul- TX) is a quadrifocal IOL manipulated to behave as trifocal. The
tiple annular rings. The light gets diffracted from this surface extended intermediate focal point (120 cm) is redistributed to
and there was a loss of 20% of the incoming light leading to loss the distance focal point for amplified performance and results
of contrast. Thus, 40% light was focused for distance and near in the creation of 3 foci: distance, intermediate at 60 cm, and
focus each. The advantage was that it was pupil independent. near at 40 cm. This is called as ENLIGHTEN (Enhanced LIGHT
However, loss of contrast and glare and halos due to rings were Energy) optical technology. This IOL can transmit 88% of light
major concerns. In addition, the surgical results were compro- energy at 3 mm pupil diameter and has a near add of 3.25D and
mised due to high astigmatism and decentration with rigid IOLs intermediate power of 2.17D.
in the pre-phacoemulsification era. Another recent addition among trifocal diffractive IOLs is the
Foldable bifocal diffractive MFIOL with a more advanced Technis Synergy IOL (Johnson & Johnson, New Brunswick/
technology is the AMO Technis multifocal Zm900 IOL. This has USA). It has a novel, hybrid design with a combination of
a wavefront designed, modified prolate, anterior aspheric surface EDOF echelette and achromatic technology of Symfony IOL
to neutralize the corneal spherical aberration. The posterior along with the diffractive multifocal optics for near vision. In
surface had a diffractive multifocal surface with 32 concentric the Symfony IOL, diffractive echelette technology provides
rings. This was pupil independent and significantly improved continuous vision from distance to about 60 to 65 cm; in the
near vision and reading speed in both bright and dim light. Synergy IOL, the EDOF portion of the lens is in the near to
intermediate range, from about 33 to 80 cm.
b) EDOF Diffractive IOL
These IOLs have a reduced near add power leading to reduced The lens is based on a feature called as InteliLight, which includes
number of concentric diffractive zones called as “echelettes”. a high-definition laser lathing process that minimizes scatter
This is the Symfony IOL (Technis, Santa Ana, California). The
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
and halo intensity. The contrast and night vision are improved by • Any other systemic history
achromatic technology and by blocking the high energy violet • Any facial abnormality that can prevent the patient from
and ultra-violet wavelengths. Blocking the violet wavelengths
can reduce light scatter, improve contrast sensitivity, and reduce wearing glasses should be noted
halo intensity for easier driving and digital device use, without
blocking the healthy blue light that is needed to maintain Examination
circadian rhythm and low light vision. It provides a continuous • Complete ocular evaluation
range of vision due to EDOF mechanism and improved contrast • Eyelids and adnexal abnormality should be ruled out that
acuity with minimal night vision disturbances.
3. Combined Bifocal diffractive and refractive IOL can affect tear film distribution
Acrysof ReSTOR IOL by Alcon is a combination of both • Ocular motility and squint evaluation
technologies. This IOL has 2 optical regions. A central apodized • Ocular surface and dry eye workup
bifocal diffractive region 3.6 mm wide has 12 concentric steps • Slit lamp examination to rule out any anterior segment
with gradually decreasing step height (1.3 to 0.2 microns)
providing a good range of vision at all distances. Apodization pathology other than cataract
a special feature of this IOL means a gradual reduction of step • Pupil reactions and optic nerve function
height leading to a gradual bending of light rays at different • Retina evaluation and macular function tests
steps. Lower steps send more light to distance and higher steps
send more light to near. This provides a uniform distribution of Investigations
light for distance and near, independent of the lighting. When • Dry eye assessment and meibography if available
the pupil is small (when reading), the lens maximizes near
vision. In dim-light conditions when the pupil is enlarged, the (aggressively treat meibomian gland dysfunction and dry
lens becomes a distant-dominant lens. The second outer region eye before surgery)
has a refractive optics and directs the light at a distant focal point • Corneal topography for ruling out irregular astigmatism
at a larger pupil diameter in dim light condition. There is also a • Posterior corneal astigmatism evaluation if available
reduction in glare and halos. otherwise predicted PCA available with newer generations
Advantages of EDOF and trifocal over other multifocal IOLs formulas can be used in patients with normal corneas. Koch
Trifocal IOLs also provides an excellent intermediate vision et at suggested that 0.5D should be subtracted in with-the-
along with distance and near. Also, the loss of light and the rule astigmatism and 0.3D should be added for against-the-
contrast is minimized providing a clear vision at all distances rule astigmatism when total astigmatism is calculated with
regardless of light conditions as compared to bifocal and anterior corneal measurements.
older generation multifocal IOLs. EDOF IOLs provide a good • Accurate biometry is very important to achieve spectacle
distance and intermediate vision with minimal dysphotopsias. independence. Using optical methods along with the latest
Thus, extending the depth of vision and reducing night vision formulas like Barrett’s or Hill RBF or SRKT can be useful to
symptoms come at the expense of some near vision. hit the refractive target.
Workup of a patient • Angle kappa and pupil diameter: Chang-Waring chord
(chord mu) less than 0.5mm and mesopic pupil should be
History taking within. Chord mu is the 2-dimensional displacement of the
• Assessing the patient’s needs and personality during entrance pupil center from the subject- fixated coaxially
sighted corneal light reflex. Since the pupil center can shift
history taking, that is to identify which distances are most with miosis and mydriasis, this should be described with the
important to him or her for daily functioning is essential. state of the pupil (photopic or scotopic). The cut-off value
This can be done using a questionnaire also. (Figure 1) A will also depend upon the radius of the central most zone of
detailed history of their daily routine, work, hobbies, and diffractive rings in the MFIOL.
lifestyle should be taken. Whether they are dependent on • Rule out any pupil or iris abnormality and zonular weakness
night driving a lot or reading very fine prints or jeweler that might lead to decentration later
work. • Aberrometry: Corneal HOA’s should be within normal
• History of any other ocular symptoms like dryness, watering, limits (<0.3 microns) to minimize visual symptoms after
redness, or irritation. Rule out any other ocular pathology MFIOL implantation.
than cataract. • Posterior segment OCT macula to rule out any macular
• Rule out type A personality by talking to the patient and pathology like ERM, macular hole or thinning.
assess if he or she has unrealistic expectations. Patient counseling
• Any history of vision loss since childhood and ruling out
amblyopia is important Meticulous planning and selecting an appropriate patient are the
most important factors for success in refractive cataract surgery
practice. It becomes essential for the surgeon and counsellor to
detect patients who will not be satisfied with these multifocal
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Subspecialty - Lens & Cataract
IOLs. Assessing the patient’s needs and personality during discouraging potential patients since the benefits are also
counseling that is to identify which distances are most important much greater. Most patients experience problems of depth
to him or her for daily functioning is essential. This can be done perception and falling while using bifocal spectacles and might
using a questionnaire.[5] (Figure 1) A detailed history of their have problems with progressive spectacles also. Thus, trifocal
daily routine, work, hobbies, and lifestyle should be taken. In and EDOF IOLs are much safer and forgiving alternatives. The
patients who are dependent on night driving a lot or need to read surgeons should discuss about the possible side-effects, night
very fine prints or are jewelers, the possible visual symptoms vision issues as well as neuroadaptation in detail. Patients should
and possible need of glasses should be explained. Always under be open to the idea of enhancement by laser correction for any
promise and overdeliver is the rule to be followed. residual error as well as the probable need of glasses for some
The most important factor to keep in mind is that even with the activities. It is very important not to leave any astigmatism for a
latest advancement any multifocal IOL can cause dysphotopsias satisfied patient.
mainly during night. However, this cannot be the reason for
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DOS Times - Volume 28, Number 2, March-April 2022
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Preference of types or her for daily functioning. Various factors to consider for IOL
All patients always desire good vision at all distances and in selection are defined by Chang et al.[6] (Table 1) Ten key points
all lighting conditions. However, such an ideal situation might to keep in mind before advising trifocal IOL’s are mentioned in
be difficult to achieve. The first step while deciding the type of table 2.
MFIOL is to identify which distances are most important to him
Subjective
Interest in spectacle independence
Concern about night vision symptoms
Occupation
Hobbies
Personality
Expectations
Satisfaction with first eye
Objective
Preoperative visual acuity
Preoperative refraction
Astigmatism—degree and regular versus irregular
Ocular surface health
Severity and type of cataracts (nuclear, cortical, or subcapsular)
• Comorbidities
• Height/armlength
Table 1 : Factors to consider for Multifocal IOL selection[3]
Always under-promise and overdeliver
Proper patient selection
Patient expectations, occupation, and hobbies
Good ocular surface
Patient education and counselling
Explain about neuroadaptation
Accurate IOL power calculation
Minimal residual astigmatism
Minimal corneal aberrations
Good surgical planning to hit the refractive target
Table 2 : Ten key-points to keep in mind while advising trifocals
Trifocals are the best choice for patients with bilateral cataracts provide better refractive forgiveness and issues like dry eye,
who desire spectacle independence. Trifocal IOLs perform much missing the refractive target and PCO can be better tolerated.
better in near vision with a similar distance and intermediate Both IOLs have minimal level of photic phenomenon as well
vision. EDOF IOL like Symfony provides a good distance which are slightly less with EDOF IOLs. Other than the EDOF
and intermediate vision and has minimal dysphotopsias. design, reasons of reduced dysphotopsias include achromatic
Thus, extending the depth of vision and reducing night vision profile and lower refractive index of 1.47 as compared to trifocal
symptoms comes at the expense of some near vision. These lenses IOLs like Panoptix.
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The first category of patients would be those patients who are The use of femtosecond laser can help to improve precision and
very active, and need daily driving, computer, tablet, or mobile consistency. This also contributes by managing the astigmatism
phone use, prefer a better intermediate vision with minimal using limbal relaxing incisions or arcuate incisions. Toric IOLs
distortions. Or those who are willing to use minimal add for are the most preferred modality for WTR astigmatism equal to
small print and cannot compromise on night vision, it is better or more than 1.0 or 1.5D or ATR astigmatism 0.5D or 0.75D.
to prefer EDOF lenses like Symfony and Vivity IOL. These are Residual astigmatism should be less than 0.5D for a good
suitable for those patients who are intolerant for dysphotopsias. outcome.
Vivity and Eyhance IOLs are also the best choice for non-pristine Secondly centration of MFIOL is also essential for preventing
eyes like those with mild irregular astigmatism, mild dryness, dysphotopsias. The MFIOL implanted in the bag will get
mild ARMD, early glaucoma or DR and mild ERM. These IOLs centered at the center of the bag or the pupil. Thus, eyes with a
work best with mini-monovision that is targeting the dominant large angle kappa can lead to decentration of the central ring and
eye for plano and the nondominant eye for -0.5D. visual symptoms. Melki et al proposed the coaxially sighted IOL
Second category of patients would be those who read a lot and do light reflex (CSILR) as a landmark to allow consistent centration
not drive at night or who want complete spectacle independence of MFIOL on visual axis.[8] During the procedure, the patient
and who don’t have much astigmatism will benefit maximally is asked to fixate between the two rectangle coaxial microscope
from trifocal IOLs like Synergy or Panoptix IOL. However, if all lights. The surgeon can then identify the CSILR as the position
the above activities are equally important then, it will be better of these two coaxial light reflections on the anterior capsule that
to implant trifocal IOLs with minimal halos and glare. Another is nasal to the pupil center. After IOL placement, the IOL can be
important factor is the corneal astigmatism. Toric IOLs should then gently moved to position the 2 coaxial light reflexes within
be considered for WTR astigmatism equal to or more than the central ring of the multifocal IOL. This method can be used
1.5D or ATR astigmatism 0.75D to prevent significant residual for optimal centration of the IOL. Holladay et al. reported that
refractive error. decentration more than 0.5mm and tilt of more than 7 degree is
Conventional MFIOLs with a lower add power have a smaller significant for all aspheric IOLs.[8]
number of concentric zones or rings such as low add Technis In-the-bag IOL placement is the goal in all MFIOL patients
MFIOLs, ZKB00 (+2.75D add) and ZLB00 (+3.25D add), can because it offers maximum stability and centration. However,
also provide a better intermediate vision along with reduction in cases of posterior capsular rupture (PCR) this might not
in glare and halos. Bilateral implantation of +2.75D add be possible. In case of a small, central PCR converting it into
provides a good functional vision to most of the patients.[3] posterior continuous curvilinear capsulorhexis (CCC) can allow
Liu et al. evaluated the safety and efficacy of EDOF Symfony in the bag placement of MFIOL. Some surgeons also prefer
IOL in a review and meta-analysis and concluded that reverse optic capture (the haptics are placed in the bag and the
compared to monofocals, EDOFs provided better intermediate optic is prolapsed into sulcus) in PCR cases. However, in larger
and near visual acuity, but more contrast reduction and more and peripheral PCR it is wise to use a monofocal IOL in sulcus
frequent halos.[7] However, compared to trifocals, EDOFs after completing anterior vitrectomy.
had better contrast sensitivity and comparable incidence Postoperative considerations
of halos.[7]
Contraindications of MFIOL It is important to identify all unhappy patients and follow them up.
The cause of vision problem should be identified and corrected.
Contraindications include any other ophthalmic pathology like This will help to improve the results in the future patients.
macular degeneration or macular scar, diabetic retinopathy Some changes can also be made in the existing nomograms
or its increased risk, optic nerve pathology, large angle kappa, and A constants depending upon postoperative refraction.
advanced glaucoma, compromised capsular and zonular support. If the patient is only experiencing photic phenomenon, then
Any other ophthalmic pathology involving the macula, optic explaining about neuroadaptation is important. Patients with
nerve or cornea should be excluded. Relative contraindications any residual ametropia should be offered laser vision correction.
include severe dry eye, Fuch’s endothelial corneal dystrophy, Thus, tracking results and modifying preoperative processes,
glaucoma, type A personality, high occupational visual demands accordingly, would help to accurately identify true red flags and
like pilots, and drivers. deliver superior results.
Surgical planning Complications
Intraoperative considerations Defective vision due to ametropia, poor ocular surface or
posterior capsular opacification might cause significant patient
Surgical planning should start from preoperative workup as dissatisfaction. Ametropia can occur due to inaccurate biometric
well. Intraoperatively incision construction should be aimed analysis, limitations of IOL power calculation, and errors in
towards minimal astigmatism. Some surgeons also prefer an IOL positioning.[9–11] Rehabilitation options include spectacles,
on-axis incision for less than 0.75D astigmatism. A properly contact lenses, or surgical intervention in the form of laser
sized, capsulorhexis centered on the visual axis and covering the correction, piggyback IOLs, or IOL exchange.
optic equally 360 degrees is most important for IOL function.
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
New concept of hybrid vision 2. Rampat R, Gatinel D. Multifocal and Extended Depth-of-Focus
The most physiological and ideal situation would be a continuous Intraocular Lenses in 2020. Ophthalmology 2021;128(11):e164–85.
range of vision with no dysphotopsias. We are not quite there yet,
however, we can move slightly closer by combining EDOF and 3. Developments in Multifocal IOLs Good for Patients [Internet].
multifocal IOLs (mix and match cataract surgery) or combining CRSToday [cited 2022 Feb 10];Available from: https://crstoday.com/
two IOLs with different near add (blended vision). This would articles/2015-oct/developments-in-multifocal-iols-good-for-patients/
be particularly beneficial in patients opting for refractive lens
exchange (RLE). 4. Gatinel D, Pagnoulle C, Houbrechts Y, Gobin L. Design and
A combination of EDOF IOL like Symfony in dominant eye and qualification of a diffractive trifocal optical profile for intraocular
a multifocal or trifocal in the other eye can be used for a good lenses. J Cataract Refract Surg 2011;37(11):2060–7.
outcome. Lee et al. evaluated the outcomes of mix and match with
Symfony IOL (ZXR00) in dominant eye and Technis multifocal 5. Patient-Questionaire.pdf [Internet]. [cited 2022 Feb 10];Available
3.25D add (ZLB00) in non-dominant eye in a prospective study from: https://www.changcataract.com/wp-content/uploads/2018/09/
involving 37 patients.[12] 81.1% patients were more than satisfied Patient-Questionaire.pdf
with near vision and 91.1% achieved spectacle independence for
near vision. Stereopsis was better than 50 seconds of arc in 83.8% 6. Extended Range-of-Vision or Low-Add Multifocal IOL? [Internet].
patients. 21% patients complained of glare and halos. Thus, this CRSToday [cited 2022 Feb 10];Available from: https://crstoday.com/
can provide good outcome with minimal symptoms. Similarly articles/2017-jan/extended-range-of-vision-or-low-add-multifocal-
trifocal IOLs can be combined with EDOF IOLs as well. iol/
Hybrid monovision means combining monofocal IOL in
dominant eye with a multifocal or EDOF IOL in another eye. 7. Liu J, Dong Y, Wang Y. Efficacy and safety of extended depth of focus
Brar et al. evaluated the outcomes of monofocal IOL (Technis intraocular lenses in cataract surgery: a systematic review and meta-
1 IOL) in dominant eye and EDOF IOL (Symfony) in non- analysis. BMC Ophthalmol 2019;19(1):198.
dominant eye with a target myopia of -0.75D for a better
near vision in a prospective clinical study involving 25 8. Melki SA, Harissi-Dagher M. Coaxially sighted intraocular lens light
patients.[13] They reported that spectacle independence reflex for centration of the multifocal single piece intraocular lens.
satisfaction scores were 96%, 100% and 88% for distance, Can J Ophthalmol J Can Ophtalmol 2011;46(4):319–21.
intermediate, and near respectively. At 6 months, only 12% (3
patients) reported mild halos. Contrast sensitivity was similar 9. Sachdev GS, Sachdev M. Optimizing outcomes with multifocal
in monofocal and MFIOL group. Thus, this method provided a intraocular lenses. Indian J Ophthalmol 2017;65(12):1294–300.
continuous range of vision with minimal symptoms.
Other options include blended vision with a +2.5D add MFIOL 10. Pierro L, Modorati G, Brancato R. Clinical variability in keratometry,
in dominant eye for a better intermediate and distance vision in ultrasound biometry measurements, and emmetropic intraocular lens
combination with a +3.5D add MFIOL in non-dominant eye for power calculation. J Cataract Refract Surg 1991;17(1):91–4.
a better near vision.
In an active patient, it is best to implant EDOF IOL in dominant 11. Erickson P. Effects of intraocular lens position errors on postoperative
eye and observe the satisfaction for all distances along with night refractive error. J Cataract Refract Surg 1990;16(3):305–11.
vision symptoms to decide the other eye IOL. If these patients
desire a better near vision, then in the other eye you can implant 12. Lee JH, Chung HS, Moon SY, Park SY, Lee H, Kim JY, et al. Clinical
a trifocal with +3.25 or +3.5D near add. Outcomes after Mix-and-Match Implantation of Extended Depth of
Conclusion Focus and Diffractive Multifocal Intraocular Lenses. J Ophthalmol
To summarize, trifocal IOLs provide a good distance and near 2021;2021:8881794.
vision along with filling the gap of intermediate vision by older
generation multifocal or bifocal IOLs. EDOF lenses provide 13. Brar S, Ganesh S, Arra RR, Sute SS. Visual and Refractive Outcomes
the least near vision and best intermediate vision with minimal and Patient Satisfaction Following Implantation of Monofocal
photic phenomenon. The aberration profile of the cornea mainly IOL in One Eye and ERV IOL in the Contralateral Eye with Mini-
spherical aberration and coma should be matched with aspheric Monovision. Clin Ophthalmol Auckl NZ 2021;15:1839–49.
trifocal IOLs and keeping minimal residual astigmatism for best
outcomes. Corresponding Author:
References Dr. Deepali Singhal, MD
Associate Consultant
1. Alió JL, Pikkel J. Multifocal Intraocular Lenses: The Art and the Ophthalmology (Cornea, Cataract and Refractive surgery Department)
Practice. Springer Nature; 2019. Centre For Sight Eye Hospital, Bhubaneswar, India.
DOS Times - Volume 28, Number 2, March-April 2022 30 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
Postoperative corneal morphological chang-
es in senile cataract: Small incision cataract
surgery versus Phacoemulsification
Shreya Singh, MS, Manisha Gupta, MS, Vatsala Vats, MS, Priyanka Gupta, MS
Department of Ophthalmology, Shri Mahant Indresh Hospital, Dehradun, Uttarakhand.
Abstract: Aim: To assess the postoperative corneal morphological changes in senile cataract.
Settings and Design: Hospital-based and observational prospective study.
Methods and Material: 101 study subjects aged 40-70 years were taken in the study. A complete ocular examination
was done, including non-contact specular microscopy preoperatively and postoperatively at Day1, 1st, 2nd and 4th
week. SICS (GroupI) and PHACO (GroupII) were performed using a single method and a single experienced surgeon
each with inclusion criteria – NS2-3 with LOCS III classification system and excluded complicated cataracts and
ocular diseases.
Statistical analysis: SPSS 21version (SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows.
Results: GroupI and GroupII has NS2-51% and 52%, NS3-49% and 48% respectively. Preoperative parameters were
statistically insignificant between both Groups. On postoperative day1, 1st, 2nd and 4th week Mean Endothelial cell
count (cells/mm2) in GroupI- 2541.39, 2430res.47, 2337.12 and 2227.29, GroupII- 2543.92, 2437.56, 2350.40 and
2263.44; Mean Coefficient of variation in GroupI- 41.63, 45.29, 50.04 and 53.49, in GroupII- 42.38, 45.42, 50.60
and 54.81; Mean Hexagonality (%) in GroupI- 53.10, 48.86, 43.47 and 40.94 whereas in GroupII- 53.37, 49.58, 45.42
and 42.19; Mean Central corneal thickness (µm) in GroupI- 558.47, 544.41, 535.88 and 530.53 whereas in GroupII-
565.98, 549.23, 542.35 and 538.40 respectively was insignificant. Mean Best-corrected visual acuity (logMAR) was
statistically significant at PO4th week between both Groups.
Conclusions: Both surgical techniques are equally efficacious and cost-effective for postoperative outcomes in soft
cataracts with their own merits/demerits.
Keywords: Corneal endothelium; Specular microscopy; Small incision cataract surgery; Phacoemulsification; Senile
cataract.
Introduction Institutional Ethics Committee. The procedures followed were
in accordance with the Helsinki Declaration of 1975, as revised
Cataract is the leading cause of visual impairment. Surgical in 2000. Informed written consent was sought from each
management only definitive treatment has evolved through subject in their vernacular language and the type of surgery
increased finesse and precision into a promising outcome for was a subject’s discretion as per his or her financial stability and
the patient and an encouraging response to the surgeon in general understanding.
developing countries. Still, the endothelial loss is inevitable after Subjects selected were the patients admitted in the eye ward
uneventful surgery.[1] for elective cataract surgery and were enrolled in the study as
Previous studies done on similar topics showed varied results per the inclusion criteria i.e. age group 40 – 70 years, senile
because of effect modifiers which were the limiting factors in cataract including Nuclear Sclerosis (NS) grade 2 and 3 and
those studies.[2,3,4,5,6,7] uneventful surgeries. The exclusion criteria included cataracts
Our study tried to eliminate the effect modifiers and; have other than NS grade 2 or 3, complicated cataracts, traumatic or
compared almost entire specular parameters and visual outcomes post-trauma cataracts, structural and/or organic ocular disease
between Small incision cataract surgery and Phacoemulsification involving the cornea, anterior chamber, lens, vitreous or retina,
in comparison to most of the previous studies. previous ocular surgery, history of drugs/laser or injection,
Materials and Methods eventful surgeries and co-morbidities.
All the subjects underwent baseline ocular examination which
This was an observational prospective study conducted at the included Best-corrected visual acuity (BCVA) determined by
Department of Ophthalmology over a period from December refraction using logMAR vision chart, Intraocular pressure
2019 to August 2021, after securing due approval from the
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
measurement with Goldman’s Applanation Tonometry, Anterior Pre-operative characteristics
segment evaluation by the slit-lamp biomicroscopic examination The ECC (cells/mm2) in GroupI was 2684.27 ± 217.40 and
and Grading of cataract according to Lens Opacity Classification GroupII was 2664.87 ± 251.81. The CV in GroupI was 37.41 ±
System III (LOCS III), Posterior segment evaluation with 5.87 and GroupII was 38.25 ± 5.91. The HEX (%) in GroupI was
+90D lens and indirect ophthalmoscopy and; Endothelial cell 57.22 ± 5.49 and GroupII was 57.23 ± 4.28. The CCT (µm) in
evaluation with non-contact Specular biomicroscope (NIDEK GroupI was 527.84 ± 38.58 and in GroupII was 536.48 ± 27.59.
CME-530 SPECULAR MICROSCOPE JAPAN) for parameters The BCVA in GroupI was 0.64 ± 0.22 and GroupII was 0.63 ±
- Endothelial cell count (ECC), Coefficient of variation (CV), 0.24. There was statistically no significant difference between the
Hexagonality (HEX) and Central corneal thickness (CCT) in preoperative characteristics between both Groups.
which average of five readings was taken by the same examiner.
Post-operative characteristics
Each surgical technique was performed by a separate individual
surgeon each having experience of more than five years ECC Group P-value
respectively, using standardized techniques and operating
conditions. The procedure done was SICS by viscoexpression POD1 GroupI GroupII 0.957
technique with polymethyl methacrylate hydrophilic non- PO 1st week 0.872
foldable posterior-chamber intraocular lens (PCIOL) PO 2nd week 2541.39 ± 221.06 2543.92 ± 252.10 0.766
implantation in the capsular bag in GroupI and PHACO by PO 4th week 2430.47 ± 196.62 2437.56 ± 241.16 0.401
modified phaco-chop technique (CENTURION VISION 2337.12 ± 189.50 2350.40 ± 251.53
SYSTEM ALCON USA machine – Torsional mode) with Acrylic 2227.29 ± 166.37 2263.44 ± 252.49
hydrophobic foldable PCIOL implantation in the capsular bag
in GroupII. The phaco parameters were kept the same for all the Table 1 : Comparison of ECC of study subjects between both the groups.
subjects of grade 2 and grade 3 nuclear cataracts. The viscoelastic
hydroxypropyl methylcellulose 2% was used in both Groups. CV Group P-value
Postoperative (PO) medications were started in the operated eye, POD1 GroupI GroupII 0.548
which included eyedrop antibiotic 2 hourly and eyedrop steroid PO 1st week 0.917
with a tapering dose weekly for both Groups. Each subject PO 2nd week 41.63 ± 6.05 42.38 ± 6.47 0.664
was followed up for BCVA, detailed slit lamp examination and PO 4th week 45.29 ± 6.89 45.42 ± 6.32 0.310
specular biomicroscopy in both the groups at POD1, PO1st 50.04 ± 6.69 50.60 ± 6.13
week, PO2nd week and PO4th week. 53.49 ± 6.57 54.81 ± 6.39
Data management and Statistical Analysis Table 2 : Comparison of CV of study subjects between both the groups.
Data were described in terms of range, mean ± standard deviation
(Mean ± SD), frequencies (number of cases), and relative HEX Group P-value
frequencies (percentages) as appropriate. To determine whether
the data were normally distributed, a Kolmogorov-Smirnov test GroupI GroupII 0.807
was used. Comparison of quantitative variables between the 0.549
study groups was done using Student t-test and Mann Whitney U POD1 53.10 ± 6.12 53.37 ± 4.61 0.116
test for independent samples for parametric and non-parametric PO 1st week 0.372
data respectively. Comparison of quantitative variables within PO 2nd week 48.86 ± 6.23 49.58 ± 5.80
the study groups was done using paired t-test. For comparing PO 4th week 43.47 ± 6.58 45.42 ± 5.81
categorical data, Chi-square (χ2) test was performed and the 40.94 ± 7.93 42.19 ± 6.02
exact test was used when the expected frequency is less than
5. A probability value (p-value) less than 0.05 was considered Table 3 : Comparison of HEX of study subjects between both the groups.
statistically significant with a 95% Confidence interval. All
statistical calculations were done using (Statistical Package for CCT Group P-value
the Social Science) SPSS 21version (SPSS Inc., Chicago, IL,
USA) statistical program for Microsoft Windows. GroupI GroupII
Observation and Results
Total 101 eyes of 101 patients were operated in which GroupI POD1 558.47 ± 40.38 565.98 ± 28.64 0.281
had 49 eyes and GroupII had 52 eyes. The mean age for GroupI PO 1st week 0.475
was 62.02 ± 6.37 years and GroupII was 60.60 ± 7.62 years. PO 2nd week 544.41 ± 37.53 549.23 ± 29.79 0.327
GroupI had 22 (45%) females and 27 (55%) males and; GroupII PO 4th week 535.88 ± 37.38 542.35 ± 28.29 0.242
had 24(46%) females and 28 (54%) males. 530.53 ± 38.18 538.40 ± 28.58
Table 4 : Comparison of CCT of study subjects between both the groups.
BCVA Group P-value
POD1 0.000
GroupI GroupII
0.23 ± 0.12 0.12 ± 0.10
DOS Times - Volume 28, Number 2, March-April 2022 32 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
BCVA Group P-value tainer and high-density viscoelastic.[10,32] In our study, the per-
centage endothelial loss in GroupI was 5.32% at POD1, 9.48%
GroupI GroupII 0.000 at PO1st week, 12.93% at PO2nd week and 17.02% at PO4th week;
0.000 while in GroupII it was 4.53% at POD1, 8.52% PO1st week,
PO 1st week 0.11 ± 0.06 0.04 ± 0.05 0.000 11.80% PO2nd week and 15.06% PO4th week. The mean ECC re-
PO 2nd week 0.10 ± 0.01 0.01 ± 0.03 duction was statistically insignificant between both Groups at
PO 4th week 0.10 ± 0.02 0.01 ± 0.03 each follow-up visit. Stump et al study concluded the endothelial
loss to be 34.77% in PHACO which included only hard cata-
Table 5 : Comparison of BCVA of study subjects between both the groups. racts.[33] Gupta M et al included NS1-4 cataracts in their study
and; reported highly statistically significant mean endothelial
Discussion loss between SICS and PHACO at 1 week and 6 week postoper-
With an ever-evolving technique, and remarkable inputs of atively (p<0.001).[10]
technology from time to time, cataract surgery has shaped into The health of corneal endothelium is also interpreted by the
a cost-related refractive procedure of minimum duration. In the Coefficient of Variation of cell area (Polymegathism), which
present study, we have compared the SICS and PHACO on the is the most sensitive index of endothelial dysfunction.[34,35] In
basis of changes in the corneal morphology and visual outcome. the present study, the mean CV in SICS was shown to increase
from 37.41 ± 5.87% preoperatively to 53.49 ± 6.57% at 4 weeks
Demographic profile post-surgery; while in PHACO, it was noted to increase from
A total of 101 eyes of 101 study subjects were included in the 38.25 ± 5.91% to 54.81 ± 6.39% on the same occasions respec-
study that fit the inclusion criteria. The sample size was similar tively. On comparing the increase of CV in SICS against PHA-
to several studies conducted in the past having the same study CO, it was statistically insignificant on each occasion and both
design.[8,9] Groups had almost similar polymegathism. Zhu N et al reported
There is a higher prevalence of cataracts as age advances.[10] In a significant difference in CV between diabetic and non-diabetic
our study, the age-wise distribution was such that there was no patients at preoperative and postoperative periods.[36]
statistically significant difference seen in the mean age of the The hexagonality is an index of endothelial healing and a devia-
study subjects between both Groups. Hence, no age-related bias tion from it is called Pleomorphism.[34,35] In our study, the mean
influenced the final outcome of the study. % of HEX in GroupI decreased from 57.22 ± 5.49% prior to sur-
Females do not receive cataract surgery at the same rate as gery to 40.94 ± 7.93% after surgery at 4th week and; in GroupII
males,[11] even when they are shown to have a slightly increased from 57.23 ± 4.28% to 42.19 ± 6.02% at similar intervals respec-
age-adjusted risk of cataract.[12] It could be attributed to gender- tively. The decrease in hexagonality was similar in SICS and
defined social roles and gender-related differences in self- PHACO; and was found to be statistically insignificant between
assessment visual function, women do not demand surgery both Groups on each given interval. Zhu N et al mentioned a
earlier than men. In our study, a male predominance was seen significant difference in HEX preoperatively and postoperatively
among the study subjects but the association was statistically between diabetic and non-diabetic groups.[36] This is because the
insignificant. A study by Noronha D et al[8] and Adepoju et al[13] time taken for HEX recovery in the diabetic cornea is longer
also observed a higher rate of cataracts in males than females. than 3 months.
Relatively harder cataract densities can be vulnerable to more Post-operative corneal thickness and edema are indirect ways
endothelial loss after cataract surgery, affecting the outcome of to predict endothelial changes.[37] The reliable measure of tran-
the surgery.[14] In our study, both Groups showed that NS2 was sient corneal edema is considered to be CCT.[38] In our study, the
more than NS3 but the distribution of study subjects on the basis mean CCT in both Groups depicted a decreasing trend to near-
of the grade of cataract was found to be statistically insignificant. by baseline values over a period of 4 weeks and was found to be
Hence, cataract grades did not affect the final outcome of the insignificant on every occasion post-surgery. The mean change
present study. in CCT in GroupI was 30.63 ± 14.49 at POD1, 16.57 ± 15.52
PO1st week, 8.04 ± 15.76 PO2nd week and 2.69 ± 13.04 PO4th
Postoperative corneal morphology week. In GroupII was 29.50 ± 11.91 POD1, 12.75 ± 12.84 PO1st
Endothelial loss after cataract surgery varies from 4% to 25% week, 5.87 ± 7.83 PO2nd week and 1.92 ± 7.80 PO4th week. The
in the literature.[10] The important causes for which during change was slightly more in SICS but the difference on every
PHACO are reported to be advance cataract,[10,15,16,17] irrigating occasion post-surgery when compared was found to be insignif-
fluid turbulence,[18,19,20] ultrasonic power fluctuation,[20] bub- icant between both Groups. Kongap P et al showed significantly
ble and free-radical formation,[20,21,22,23,24] thermal and mechan- higher CCT in PHACO group than those who underwent SICS
ical injury from sonic waves,[25,26,27] mechanical trauma from (p<0.008) in patients with white cataract.[15]
instruments,[27,28] presence of lens fragments[20,21,22,29,30] and
IOLs.[21,22,29,31] In SICS, the endothelial loss could be attributed to Postoperative visual outcome
the nucleus and endothelial contact during delivery, irrigating Good, fast and stable visual recovery is the main goal of cataract
vectis, viscoexpression of the nucleus, anterior chamber main- surgery. BCVA is one of the best parameters to evaluate the ef-
www.dosonline.org/dos-times 33
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Lens & Cataract
ficacy of surgery and quality of life. In our study, on POD1 43% quer versus phaco-chop technique. Journal of Cataract and Refractive
attained logMAR 0.1 or better in GroupI and in GroupII 79% Surgery. 2008 Jun;34(6):996-1000.
attained the same. On PO1st week, logMAR 0.1 or better was
seen in 92% of study subjects in GroupI and 100% in GroupII. 5. O’Brien PD, Fitzpatrick P, Kilmartin DJ, Beatty S. Risk factors for en-
On PO2nd week in GroupI, 96% had BCVA logMAR 0.1 and 4% dothelial cell loss after phacoemulsification surgery by a junior resi-
BCVA logMAR 0.0, while in GroupII 13% BCVA logMAR 0.1 dent. Journal of Cataract and Refractive Surgery. 2004 Apr;30(4):839-
and 87% BCVA logMAR 0.0. On PO4th week in GroupI 94% 43.
had BCVA logMAR 0.1 and 6% BCVA logMAR 0.0, while in
GroupII 12% BCVA logMAR 0.1 and 88% BCVA logMAR 0.0. 6. Ganesan N, Srinivasan R, Babu KR, Vallinayagam M. Risk factors for
The association between both Groups was statistically significant endothelial cell damage in diabetics after phacoemulsification. Oman
at each interval. It was due to a higher astigmatic shift in GroupI J Ophthalmol. 2019 May-Aug;12(2):94-8.
as compared to GroupII. Thus, indicating a better postoperative
visual recovery in GroupII. On account of a smaller incision (2.2 7. Bigar F, Witmer R. Corneal endothelial changes in primary acute an-
mm), early wound healing and early stabilization of refraction gle-closure glaucoma. Ophthalmology. 1982 Jun;89(6):596-9.
PHACO was more precise but SICS is not lagging behind as 96%
achieved the visual status of logMAR 0.1. Gupta M et al study 8. Noronha D, D’souza M. Changes in Central corneal thickness before
showed that there was a statistically insignificant difference in and after phacoemulsification cataract surgery. J Clin Ophthalmol.
BCVA between SICS and PHACO at 6 weeks postoperatively 2020 Aug 25;4(4):300-2.
which may be due to the 2.8mm incision used in the PHACO
group.[10] According to the study done by Kamonporn N et al, 9. Bhan C, Chaudhary A, Kumar S, Rana J. Comparison of endothelial
BCVA≥6/18 was present in 86.33% and 72.12% of patients in cell loss by specular microscopy between phacoemulsification versus
the PHACO and MSICS group respectively.[39] Their authors small incision cataract surgery. IJCEO. 2020 Jun 28;6(2):176-9.
concluded that poor visual outcome was due to the presence of
associated ocular pathology. 10. Gupta M, BH M, Shedole SS. Comparison of Morphological and
Conclusion Functional Corneal Endothelial Changes after Cataract Surgery un-
der DBCS Program at a Tertiary Care Centre. J Clin Exp Ophthal.
On comparing each technique of SICS and PHACO the present 2020;11(1):823.
study concluded that firstly, there was a difference in corneal
morphology but was statistically insignificant postoperatively at 11. Anjum KM, Qureshi MB, Khan MA, Jan N, Ali A, Ahmad K, et al.
4th week as the density of cataracts in both Groups were similar. Cataract blindness and visual outcome of cataract surgery in a tribal
Thus, inferring that both of the surgeries are equally safe and area in Pakistan. Br J Ophthalmol. 2006 Feb;90(2):135-8.
efficacious for corneal morphology in soft cataracts with their
own merits/demerits. Secondly, PHACO gave statistically 12. Lewallen S, Courtright P. Gender and use of cataract surgical services
significant better visual outcome than SICS at 4th week post- in developing countries. Bull World Health Organ. 2002;80(4):300-3.
surgery as the latter led to a higher astigmatic shift.
Both the techniques have their utility, with no signs of redun- 13. Adepoju FG, Owoeye JF, Ademola-popoola DS. Assesment of one-year
dancy seen in SICS, as the learning curve for PHACO is longer, follow up of patients with Ecce-pciol surgery at University of Ilorin
with additional issues like the cost of surgery. Therefore, SICS teaching hospital, Kwara State, Nigeria. Nigerian Journal of Ophthal-
may be a promising surgical procedure to advanced phacoemul- mology. 2005 Sep 15;12(2):65-9.
sification technique where the latter is still not available.
References 14. Hwang HB, Lyu B, Yim HB, Lee NY. Endothelial Cell Loss af-
ter Phacoemulsification according to Different Anterior Chamber
1. Liesegang TJ, Bourne WM, Ilstrup DM. Short- and long-term endo- Depths. J Ophthalmol. 2015;2015:210716.
thelial cell loss associated with cataract extraction and intraocular
lens implantation. Am J Ophthalmol. 1984 Jan;97(1):32-9. 15. Kongsap P. Central corneal thickness changes following manual small
incision cataract surgery versus phacoemulsification for white cata-
2. Ray-Chaudhuri N, Voros G, Sutherland S, Figueiredo F. Comparison ract. Rom J Ophthalmol. 2019 Jan-Mar;63(1):61-7.
of the Effect of Sodium Hyaluronate (Ophthalin®) and Hydroxypro-
pylmethylcellulose (HPMC-Ophtal®) on Corneal Endothelium, Cen- 16. Mehra DP, Verma DRK. Evaluation of corneal endothelial cell loss in
tral Corneal Thickness, and Intraocular Pressure after Phacoemulsifi- different grades of nucleus during phacoemulsification. Int J Med Res
cation. European Journal of Ophthalmology. 2006 Mar;16(2):239-46. Rev. 2015 Nov 30;3(10):1128-32.
3. Kristianslund O, Pathak M, Østern AE, Drolsum L. Corneal endo- 17. Orski M, Synder A, Pałenga-Pydyn D, Omulecki W, Wilczyński M.
thelial cell loss following cataract surgery in patients with pseudo- The effect of the selected factors on corneal endothelial cell loss follow-
exfoliation syndrome: a 2‐year prospective comparative study. Acta ing phacoemulsification. Klin Oczna. 2014;116(2):94-9.
Ophthalmol. 2020 Jun;98(4):337-42.
18. Edelhauser HF, Van Horn DL, Hyndiuk RA, Schultz RO. Intraocu-
4. Storr-Paulsen A, Norregaard JC, Ahmed S, Storr-Paulsen T, Pedersen lar irrigating solutions. Their effect on the corneal endothelium. Arch
TH. Endothelial cell damage after cataract surgery: Divide-and-con- Ophthalmol. 1975 Aug;93(8):648-57.
19. Joussen AM, Barth U, Çubuk H, Koch H. Effect of irrigating solu-
tion and irrigation temperature on the cornea and pupil during
phacoemulsification. Journal of Cataract and Refractive Surgery.
2000 Mar;26(3):392-7
20. Sorrentino FS, Bonifazzi C, Parmeggiani F, Perri P. A Pilot Study to
Propose a “Harm Scale”, a New Method to Predict Risk of Harm to the
Corneal Endothelium Caused by Longitudinal Phacoemulsification,
and the Subsequent Effect of Endothelial Damage on Post Operative
Visual Acuity. PLoS One. 2016 Jan 13;11(1):e0146580.
21. Bourne RR, Minassian DC, Dart JK, Rosen P, Kaushal S, Wingate
N. Effect of cataract surgery on the corneal endothelium: Modern
DOS Times - Volume 28, Number 2, March-April 2022 34 www.dosonline.org/dos-times
Subspecialty - Lens & Cataract
phacoemulsification compared with extracapsular cataract surgery. 34. Chaurasia S, Vanathi M. Specular microscopy in clinical practice. In-
Ophthalmology. 2004 Apr;111(4):679-85. dian J Ophthalmol. 2021 03;69(3):517-24.
22. Cameron MD, Poyer JF, Aust SD. Identification of free radicals pro- 35. Nishida T, Saiko S, Morishige N. Cornea and sclera: Anatomy and
duced during phacoemulsification. J Cataract Refract Surg. 2001 physiology. In: Mannis MJ, Holland EJ, editors. Cornea. 4th ed. Mos-
Mar;27(3):463-70. by: Elsevier Health Sciences; 2017. p. 1–22.
23. Craig MT, Olson RJ, Mamalis N, Olson RJ. Air bubble endothelial 36. Zhu N, Zhang ZC & Hao XL. Influence of phacoemulsification on
damage during phacoemulsification in human eye bank eyes: the pro- corneal endothelial cell of cataract patients with diabetes or hyperten-
tective effects of Healon and Viscoat. J Cataract Refract Surg. 1990 sion. International Eye Science. 2014;14:480-3.
Sep;16(5):597-602.
37. Ventura AC, Wälti R, Böhnke M. Corneal thickness and endotheli-
24. Holzer MP, Tetz MR, Auffarth GU, Welt R, Völcker H. Effect of heal- al density before and after cataract surgery. Br J Ophthalmol. 2001
on5 and 4 other viscoelastic substances on intraocular pressure and Jan;85(1):18-20.
endothelium after cataract surgery. Journal of Cataract and Refrac-
tive Surgery. 2001 Feb;27(2):213-8. 38. Kuerten D, Plange N, Koch EC, Koutsonas A, Walter P, Fuest M.
Central corneal thickness determination in corneal edema using ul-
25. Beesley RD, Olson RJ, Brady SE. The effects of prolonged phacoemul- trasound pachymetry, a Scheimpflug camera, and anterior segment
sification time on the corneal endothelium. Ann Ophthalmol. 1986 OCT. Graefes Arch Clin Exp Ophthalmol. 2015 Jul;253(7):1105-9.
Jun;18(6):216-9, 222.
39. Kamonporn N, Pipat K. The visual outcomes and complications of
26. Walkow T, Anders N, Klebe S. Endothelial cell loss after phacoemul- manual small incision cataract surgery and phacoemulsification: long
sification: Relation to preoperative and intraoperative parameters. term results. Rom J Ophthalmol. 2021 Jan-Mar;65(1):31-7.
Journal of Cataract and Refractive Surgery. 2000 May;26(5):727-32
Corresponding Author:
27. Behndig A, Lundberg B. Transient corneal edema after phacoemul-
sification: comparison of 3 viscoelastic regimens. J Cataract Refract Dr. Manisha Gupta,
Surg. 2002 Sep;28(9):1551-6. Department of Ophthalmology,
Shri Mahant Indresh Hospital, Dehradun, Uttarakhand.
28. McCarey BE, Polack FM, Marshall W. The phacoemulsification pro-
cedure. I. The effect of intraocular irrigating solutions on the corneal
endothelium. Invest Ophthalmol. 1976 Jun;15(6):449-57.
29. Roper-Hall MJ, Wilson RS. Reduction in endothelial cell density fol-
lowing cataract extraction and intraocular lens implantation. Br J
Ophthalmol. 1982 Aug;66(8):516-7.
30. Davis EA, Lindstrom RL. Corneal thickness and visual acuity after
phacoemulsification with 3 viscoelastic materials. J Cataract Refract
Surg. 2000 Oct;26(10):1505-9.
31. Hayashi K, Hayashi H, Nakao F, Hayashi F. Risk factors for corneal
endothelial injury during phacoemulsification. Journal of Cataract
and Refractive Surgery. 1996 Oct;22(8):1079-84.
32. Gunjan Verma, Minal Patel, Pina Soni, Deepika Singhal, Mayur Da-
mor. Comparative Study of Corneal Endothelial Changes: Manual
Sics Vs Phacoemulsification. INTERNATIONAL JOURNAL OF SCI-
ENTIFIC RESEARCH. 2016 Apr; 5(4):159-161.
33. Stumpf S, Nose W. Endothelial damage after planned extra-capsular
cataract extraction and phacoemulsification of hard cataracts. Arq
Bras Oftalmol. 2006;69(4):491-96.
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Retina
Diabetic Retinopathy - The Recent Insights
Ankur Singh, MS, Isha Sharma, MS, Shimpa kundan, MS
Department of Ophthalmology, University college of Medical Sciences, New Delhi, India.
Introduction vascular disease with the earliest clinical sign of DR being the
appearance of micro aneurysms and the earliest microscopic
Diabetes is a group of metabolic diseases characterized by hy- sign being pericyte loss. However, recent studies have suggested
perglycaemia caused by defects in insulin secretion, insulin ac- that neuro-degenerative changes that includes glial activation,
tion, or both. In last few decades, it has become a global health or gliosis precede the vascular manifestations of diabetic
problem affecting low-and middle-income countries with in- retinopathy.[5] Retinal glial cells including Müller glial cells
creasing severity.[1] With India ranking second in the prevalence (MGCs) and astrocytes are not only responsible for providing
of diabetes globally, diabetes mellitus and consequent diabetic structural support, but are also involved in maintaining the
retinopathy, which is among the leading causes of preventable complex homeostasis of the retina by regulating the metabolism,
blindness, is of a serious concern.[2] the phagocytosis of debris and the cycling of neurotransmitters
Diabetic retinopathy is classically considered as a microvascular and trophic factors.[6] Metabolic derangement seen in diabetes
disease of the retina. However, growing evidence suggests that is associated with activation of these glial cells and eventual
retinal neurodegeneration is an early event in the pathogenesis gliosis. Activation of these resident immune cells produce pro-
of diabetic retinopathy and contributes to the development inflammatory mediators, which sets in the inflammatory cascade
of microvascular abnormalities. Thus, it would be prudent to responsible for retinal damage at later stages of the disease.[7]
acknowledge that DR is a neuro-vascular disorder of the retina Structural changes like neural apoptosis, ganglion cell loss, gli-
caused by metabolic dysfunction affecting the entire retina osis, and inner retinal thinning occuring in diabetc retinopa-
causing neurodegeneration and neuro-apoptosis of the retinal thy form the integral part of neuro-degeneration seen in DR.
ganglion cells as well as micro-angiopathy.[3] Various local Diagnostic modalities to assess neuro-degenerative includes
and systemic biomarkers based on the pathogenic mechanism OCT electroretinogram, microperimetry etc. On OCT neu-
involved in the development of DR i.e., advanced glycation ro-degenerative changes are visualized as ganglion cell/nerve fi-
end products (AGEs), molecules reflecting basal membrane ber layer thinning, disorganization of the inner retinal as well as
turnover, oxidative stress, inflammation, and angiogenesis have photoreceptor layer of the outer retina.[7-9] Functional alterations
been identified which aid in detecting population at risk of such as altered dark adaptation, color and contrast sensitivity
developing DR, patients with subclinical disease or the ones in and deficits pointing to ganglion cells such as altered pattern
whom the disease will progress. It also helps in monitoring the electroretinogram, microperimetry complement the structural
response of treatment. changes taking place diabetic retinal neuropathy. Above obser-
Methods of screening diabetic retinopathy used commonly in- vations strongly suggest that diabetes directly affects the neu-
clude dilated fundus examination, fundus fluorescein angiogra- roretina rather than being solely secondary to the breakdown of
phy, optical coherence tomography. Optical coherence tomog- the blood-retinal barrier (BRB).[6] These new insights into reti-
raphy (OCTA) is a rapidly emerging diagnostic modality owing nal physiology have led to the emergence of the concept that the
to its ability to screen the fundus for vascular changes in a rapid, retinal dysfunction associated with diabetes may be viewed as a
non-invasive yet reliable manner which gives it an edge above change in the retinal neurovascular unit.[7]
the fundus fluorescein angiography in terms of screening. Diabetic retinopathy - role of inflammation
The management of diabetic retinopathy at present is based on
its presentation and severity. The currently available treatment Various studies have suggested that inflammation is a critical
modalities for DR are laser photocoagulation, intravitreal contributor to the development of Diabetic Retinopathy.[10,11]
injections of corticosteroids or anti-VEGF agents and lastly Glial cell activation is associated production of adhesion mol-
vitreoretinal surgery which are applicable only at advanced ecules ICAM-1 and the neutrophil chemotactic MCP-2 mole-
stages of the disease and are associated with few adverse cules, involved in leukostasis, observed early in DR pathology.
effects.[4] Despite the availability of a wide variety of treatment With low grade, persistent leukocyte activation occurring in
modalities, a need for early interventions that could prevent or early stages of DR leads to repeated episodes of capillary occlu-
retard or halt the progression of diabetic retinopathy is palpable. sion and, progressive, attritional retinal ischemia and the subse-
Diabetic retinal neurodegeneration/diabetic retinal quent spectrum of microvascular complications associated with
neuropathy - what we know by far? DR.[11,12]
Murine models have suggested have shown that 4 weeks after
Diabetic retinopathy has been perceived so far as a micro- diabetes induction, before any vascular defects can be recorded,
DOS Times - Volume 28, Number 2, March-April 2022 36 www.dosonline.org/dos-times
Subspecialty - Retina
leukocytes start to adhere to the retinal capillaries with subse- ers like Angiopoietin-2 (Ang-2), VEGF and ICAM-1, TNF-α
quent migration into the retina.[13,14] This follows diminution of have been studied in DME.[26]
vascular wall integrity leading to increased vascular permeabil- A new concept of “imaging biomarkers” has emerged. These
ity which allows extravasation of vascular fluid and migration include a variety of morphological changes that can be detect-
of additional immune cells (neutrophils, monocytes) into the ed using imaging modalities like Optical coherence tomogra-
tissue. Concurrently, loss of capillary pericytes causes endothe- phy (OCT) and Optical coherence tomography angiography
lial cell degeneration, which leads to accumulation of vacuoles (OCTA). Which includes DRIL (disorganization of inner retinal
and debris in the basement membrane resulting in its thicken- layers), hyper-reflective foci, intraretinal cystoid spaces, bridg-
ing, and ultimately vascular lumen occlusion.[15,16] The retinal ing retinal processes, retinal thickness, sub-foveal choroidal
ischemia thus resulted are strong stimulus for endothelial and thickness, sub-foveal neurosensory detachment, hard exudates,
glial cells for production of VEGF and other pro-inflammato- photoreceptor outer segment, taut posterior hyaloid, etc.[27]
ry cytokines such as TNF-α, IL-6, and IL-1β. TNF-α and IL-6 OCTA is an emerging diagnostic imaging modality which is
and other inflammatory cytokines and growth factors thus being used to diagnose diabetic retinopathy in patients with
produced stimulate further release of MCP-1, IL-6 and VEGF no clinically apparent diabetic retinopathy by detecting foveal
by endothelial cells, potentially resulting in increased vascular vessel density in a 300µm wide region around FAZ which can
permeability as seen in non-proliferative DR (NPDR) and di- act as a sensitive biomarker for detecting microvascular changes
abetic macular edema (DME).[17] Inflammatory cytokines and in diabetic patients before the clinical sign of DR.[28] Extrafoveal
growth factors regulate angiogenic responses of endothelial avascular area (EEA) that is avascular area outside of a 1-mm-
cells resulting in the development of new vessel in PDR. Murine diameter circle in superficial capillary plexus segmentation
model of choroidal neovascularization has shown that inhibi- is a sensitive biomarker to discriminate No-DR from NPDR
tion of monocyte recruitment by deleting MCP-1 or deletion eyes.[29] Vessel density in the deep capillary plexus segmentation
of ICAM-1 or CD18 led to significant inhibition of neovascu- is the most sensitive parameter to distinguish eyes with NPDR
larization.[18,19] The understanding of the role of inflammation from those with PDR. Thus “imaging biomarkers” are of great
in pathogenesis of DR thus developed supports the hypothesis, diagnostic as well as prognostic significance. The discussion of
that blocking of inflammatory cascade may cause the possible individual biomarker is beyond the scope of this article.
reduction of neovascularization, neurodegeneration and subse- Diagnosis of diabetic retinopathy - what’s is new
quent tissue destruction and may also have therapeutic role.
Diabetic retinopathy - biomarkers Early detection of DR is of utmost important in diabetic
Diabetes Control and Complications Trial/Epidemiology of retinopathy as in subclinical cases of DR, where neural
Diabetes Interventions and Complications Research Group retinal damage and microvascular changes may occur but
showed that HbA1c values only explained up to 11% of the be asymptomatic to patients. The need of hour is to detect
risk of DR, and that the unexplained 89% of variation in risk these early changes so that the progression of disease could
is due to elements of the diabetic milieu not attributable to al- be halted or delayed. Advances in imaging technology have
tered HbA1c. This led to search for other systemic or local de- provided ophthalmologists with adjunctive diagnostic tools
terminants associated with the development or progression of for better management of DR. Neural retinal damage lead
DR. Human fluids are represented by a complex mixture of cells, to functional changes which could be picked up as deficits in
electrolytes, organic solutes, and proteins of different molec- pattern electroretinogram (pattern ERG), increased implicit
ular weight, such as growth factors, cytokines, and additional times in the multifocal ERG (mf-ERG), changes in oscillatory
proteins whose main function is to provide the metabolic re- potentials, abnormal dark adaptation, abnormal contrast
quirements to the ocular tissues.[10] A biomarker is usually a ob- sensitivity, abnormal color vision, and altered micro perimetric
jectively measurable characteristic which act as an indicator of and perimetric psychophysical testing. Generally, central visual
normal biological processes, pathogenic processes, or pharma- acuity is not affected in early DR and is normal before the
cologic responses to a therapeutic intervention. Currently there vascular lesions of clinical DR develop.[30-32] Form early 2000
are no accepted biomarkers to monitor DR severity or efficiently OCT has remain an important diagnostic tool in management
assess the treatment efficacy, but reports indicate, that VEGF, of diabetic macular edema. With bettered understanding of
HGF, IL-6 and MCP-1 intravitreal concentration increase with pathophysiology of DR, OCT has also come out as a rapid
the progression of DR from the non-proliferative form to active non-invasive tool in picking up early DR neuro-degenerative
PDR.[20,21] Furthermore, IL-6 levels have been shown to have a changes. A recent study has observed that birefringence of
positively correlation with retinal macular thickness.[22] Retinal the peripapillary RNFL was significantly reduced in eyes of
glial cells when activated under chronic metabolic stress act as diabetics even without any clinically detectable signs of DR
a source for cytokines (IL-1β, IL-3, IL-6, IL-8, TNF-α, MIP- and with normal RNFL thickness which could act as important
1, MCP-1), cytotoxic molecules and growth factors (VEGF) parameter for early DR assessment.[33] OCTA is another
which play a key role in perpetuating vascular dysfunction and imaging modality that is relatively new, providing non-invasive
neurodegeneration.[23-25] Role of various inflammatory biomark- visualization of the retinal and choroidal vasculature. OCTA
may serve as a useful tool in the diagnosis and monitoring of
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Retina
diabetic retinopathy and maculopathy by not only aiding in stages of diabetic retinal disease have been limited to strict con-
detection of morphological changes such as microaneurysms trol of modifiable DR risk factors particularly hyperglycemia,
(MAs), intraretinal microvascular abnormalities (IRMAs), blood pressure and lipid profile. The advent of anti-VEGF agents,
nonperfusion areas and neovascularization’s (NVs) but by also it has revolutionized the treatment of diabetic retinopathy (DR)
providing for quantitative measurements indices which can and the severe complications associated with it. Clinical trials
allow for objective identification and staging of NPDR - mild, like RISE/RIDE and VIVID/VISTA have established the critical
moderate and severe, with significant diagnostic accuracy and role of anti-VEGF (vascular endothelial growth factor) intrav-
predictability of DR progression. These indices can also pave itreal injections in the treatment of DME.[40,41] While Protocol
the path for Artificial Intelligence (AI) based non-invasive rapid S has demonstrated the Anti-VEGFs, as an effective alternative
diagnostics and monitoring. to pan retinal photocoagulation (PRP) in cases with PDR and
Other advances are in form of ultra-widefield (UWF) imaging also found lower rates of vision-impairing DME in Anti-VEGFs
technology. Even though early treatment diabetic retinopathy arm.[42] Recent evidences have also suggested the role An-
study seven standard field is able to visualise central posterior ti-VEGFs in treatment of patients with moderate to severe
90° of the retina, which equates to about 30% of the entire NPDR.[43,44] The feared complications associated with increased
retina surface, it is seen in some cases, peripheral pathology number of Anti-VEGFs injections is of endophthalmitis. But
is associated with greater disease severity and higher risk now with the availability of longer acting Anti-VEGFs like brol-
of disease progression. Studies have also demonstrated the icizumab and Port Delivery System for Anti-VEGFs the dreaded
agreement and possible superiority of UWF photographs and complication of endophthalmitis can be reduced further.[45]
fluorescein angiography (FA) in grading DR severity compared However, in the study by Aiello et al. 36% of diabetic patients
to the ETDRS 7-field protocol.[34-37] Predominantly peripheral with PDR had undetectable levels of VEGF in the vitreous fluid.
lesions (PPLs) in eyes with NPDR at baseline in any peripheral This finding explains why intravitreal anti-VEGF treatments fail
field indicated a 3.2-fold increased risk of a two-step worsening in a significant proportion of patients and reveals that VEGF-
of Diabetic Retinopathy Severity Scale (DRSS) grade and a 4.7- independent pathways play a primary role in these patients.
fold increased risk of developing PDR over 4 years compared to As discussed previously inflammation is a critical contributor
eyes with NPDR and no PPLs. As for eyes with no DR activity to the development of Diabetic Retinopathy. Intravitreal
on seven-field imaging, eyes with PPLs present at baseline had a steroid seems effective therapeutic alternative, due to its broad-
2.5-fold greater risk of developing DR within the posterior pole spectrum anti-inflammatory cascade whereby it inhibits
over 4 years.[35] leukostasis, inhibits VEGF gene transcription and translation,
A recent update in AI technology is of FDA approval for IDx- reduces vascular permeability and breakdown of the blood
DR (IDx Technologies), a device designed to detect DR with- retinal barrier. However, its utility is limited to a second line
out requiring specialized clinician review. Fundus photographs treatment option due to its potential side effects of inducing
taken by this device which are uploaded to a server, where an cataract and glaucoma. To overcomes these potential side effects
Artificial Intelligence (AI) program can identify the eyes with alternative corticosteroid delivery strategies have been under
worse than mild DR. In the pilot observational study, the IDx- investigation. One of the recent technological advancements
DR AI program shown to have the sensitivity of 87.2%, specific- includes suprachoroidal drug delivery, which can achieve up
ity of 90.7% and an imageability rate of 96.1%.[38] This allows for to 10 times greater chorioretinal concentration compared to
DR screening to be performed without a human assistant and intavitreous route.[46] In conclusion it could be deduced that
in areas where specialized clinician in unviable. in real world scenarios anti-VEGFs are one of the most viable
Another arena of recent interest is “liquid biopsy” which refers therapeutic options when it comes in treating the complications
to the use of direct aqueous or vitreous sample to study, in vivo associated with DR eg. DME, PDR. However in cases that are
the presence and changes of specific molecules concentration non responsive to anti-VEGFs, steroids are a decent alternatives.
defining phenotypic profiles of diabetic retinopathy and diabetic Emerging therapeutic options
macular edema. The application of liquid biopsy to the structur-
al retinal analysis may allow a broad application to a wide range Researchers are on a continuous lookout for strategies that
of settings, from diagnosis (including screening) prognosis and could alter the course of DR at an earlier stage. Prolonged
the prediction of response or resistance to treatments. More- hyperglycemia and oxidative stress along with other molecular
over, it would allow a personalized, cost effective approach to mediators drive chronic inflammation and inhibition or
each patient, both in terms of therapeutic choice and follow-up modulation of such pro-inflammatory mediators could act as an
timing.[39] important target to prevent early neuronal damage in DR.
The most effective therapeutic option In preclinical murine trials, neuroprotective factors like EPO
have yielded positive results in animal models of diabetic reti-
Treatment of DR is an actively evolving space. Early pharmaco- nopathy. Cibinetide (ARA 290), an erythropoietin 9 (EPO)- de-
logic intervention can play an important role in maintaining and rived peptide, has been shown to reduce retinal thinning and
improving visual function. Therapeutic approaches in the early inflammation.[47] A Phase II Clinical Trial of Cibinetide for the
DOS Times - Volume 28, Number 2, March-April 2022 38 www.dosonline.org/dos-times
Subspecialty - Retina
Treatment of DME is currently ongoing. Another such mole- to polyethylene glycol, which targets VEGF-A. It has several
cule is lutein, a naturally occurring carotenoid and a potent therapeutic advantages including high affinity, stability, high
antioxidant that has been shown to inhibit oxidative stress and molar concentration, longer half-life and higher affinity than
maintain the thickness of the retinal neural layer. Muller glial ranibizumab makes it an interesting therapeutic agent for DME
cells (MGC) has been shown to play an important role in ini- with a potentially lower frequency of intravitreal injection. The
tiation and amplification of inflammatory response secondary recent Phase II trial, PALM study has demonstrated that over a
to metabolic insult in DR. Lutein treatment has shown to re- period of 28 weeks, 2 mg of intravitreal Abicipar pegol has both
duce gliosis and reduce production of pro-inflammatory factors functional and anatomical benefits with fewer intravitreal injec-
from the Müller cells.[48] Although recent clinical trial has failed tions compared with novel concept of neurodegeneration, re-
to show any significant improvement in visual acuity but have cent developments in diagnostics, novel therapeutic agents, and
yielded improvements in contrast sensitivity suggesting some the emerging therapies that have the potential to revolutionize
neuroprotective role.[49] RGD (arginylglycylaspartic acid) inte- the management of DR and DME.
grin antagonist like THR-687 has the potential to amend the Anti-VEGF therapy has significantly improved the care and
course of DR, independent of anti-VEGF responsiveness. Pre- prognosis of DR patients. How-ever like any therapeutic agent,
clinical animal trials have shown positive results as THR-687 anti-VEGFs also have several limitations such as the cost factor,
inhibited vascular leakage in a mice model and neovasculariza- need for frequent injections, possible treatment resistance and
tion-induced leakage in a monkey.[50] Another integrin inhibitor potential side effects. On-going research molecules like long-
ALG-1001 (Luminate, Allegro Ophthalmic) has been investi- acting anti-angiogenic agents targeting VEGF as well as VEGF-
gated as sequential therapy to a single anti-VEGF injection in independent pathways have shown promising results. The utility
DME patients compared to anti-VEGF monotherapy. In DEL of these molecules to be used as an independent as well as part
MAR phase II trial ALG-1001 has shown potential, to be an combination therapy needs further research to determine their
alternative for the DME treatment with fewer intravitreal long-term efficacy and cost-benefit ratio. Corticosteroids are an
injections and could provide hope for patients unresponsive alternative therapeutic option for patients with refractory DME
to anti-VEGF therapy.[51] or insufficient response to anti-VEGF.
DME and PDR is the major cause of blinding complications as- The discovery of the role of inflammation and neurodegenera-
sociated with DR. Anti-VEGFs still remain the most effective tion in DR pathogenesis has revealed several molecules that can
therapeutic option for center involving DME along with PRP act as potential therapeutic targets. However, the translation of
for PDR. The need for patient compliance for monthly injec- many novel therapeutic strategies from experimental studies to
tions, the cost and dreaded side effects that is endophthalmitis clinical trials has failed to show any significant promising re-
has always shadowed the therapeutic efficacy of Anti-VEGFs. sults. Thus, further studies are still needed to better understand
Trials have been underway to improve its therapeutic half-life the exact molecular mechanisms underlying their role in DR.
and to look for a suitable alternative for patients refractory to In this 21 century with rapidly evolving diagnostics and ther-
Anti-VEGFs. Conbercept may be one such alternative. Conber- apeutics for DR, the way forward is to screen for DR changes
cept is a recombinant human VEGF receptor-Fc fusion protein earliest using advanced screening techniques, strict control over
that is being evaluated for DME.[52] Conbercept has shown to modifiable risk factors, to treat DR at an earlier stage to prevent
have a much more potent affinity to VEGF compared to bevaci- its sight-threatening complications.
zumab and ranibizumab and also blocks VEGF-A/B/C isoforms To increase awareness of DR and incorporation of AI-based
and PGF. Phase III SAILING studies has suggests that the use screening tools to increase the outreach of screening in DR
of Conbercept is safe and effective for the treatment of DME. seems a plausible step.
Abicipar pegol is another such molecule. Abicipar pegol is a re-
combinant designed ankyrin repeat protein (DARPin) coupled
Drugs Mechanism of action Ophthalmic outcomes Associated side effects
Bevacizumab Anti-VEGF
Superior in reducing in CRT and Rise in IOP Vitreous hemorrhage
Ranibizumab Anti-VEGF improving visual acuity compared Inflammation
to laser
Superior BCVA improvement Rise in IOP Vitreous hemorrhage
and greater reduction in CRT Inflammation
compared to laser in treating
DME
Non-inferior to PRP in treating
PDR DR improvement in patients
with NPDR
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Retina
Drugs Mechanism of action Ophthalmic outcomes Associated side effects
Aflibercept Anti-VEGF Superior in improving BCVA vs. Rise in IOP Vitreous hemorrhage
laser in treating DME and PDR Inflammation
Brolucizumab Long -Anti-VEGF Significantly improves BCVA Rise in IOP
compared to baseline in treating Vitreous hemorrhage
Conbercept Long -Anti-VEGF DME Inflammation
Abicipar pegol Long -Anti-VEGF Non-inferior to ranibizumab in
treating DME Rise in IOP Conjunctival
Greater resolution of intra- and hemorrhage
subretinal fluid
Inflammation Vitreous/
Significantly improves BCVA Conjunctival hemorrhage
compared to baseline in treating Vitreous floaters
DME
Non-inferior to ranibizumab in
treating DME
Functional and anatomical
benefits with fewer intravitreal
injections compared with
ranibizumab in patients with
DME
Table 1 : Antiangiogenic agents for treatment of DR and DME
Figure 1 : Multimodal imaging of PDR patients. Colour fundus picture (A) Figure 2 : Multimodal imaging of the right eye of a patient with
on conventional fundus camera visualises 50 degree of fundus revealing proliferative diabetic retinopathy (A-D). A Optical coherence tomography
with few NVE along superior arcade and a haemorrhage temporal to angiography (OCTA) (vitreous frames) shows neovascularization of
fovea. Ultra-wide field image (B) provides for single 200 degreed of retinal the optic disc. B Cross-sectional OCTA showing NVD complex over
details on single image, with visualisation laser scars and signs of PDR, the disc. C Fundus photograph NVD, laser scar marks inferiorly and
while the dotted circle represents 50 degree of posterior pole. haemorrhages. D Fluorescein angiogram (FA) montage shows NVD along
with multiple NVEs, temporal and superior avascular retina, laser scar
marks and blocked fluoresce due to haemorrhage.
References Mullins RF, Kuehn MH, Schlingemann RO, Sonka M, Verbraak FD,
Abràmoff MD. Retinal neurodegeneration may precede microvascu-
1. Dunachie S, Chamnan P. The double burden of diabetes and global lar changes characteristic of diabetic retinopathy in diabetes mellitus.
infection in low and middle-income countries. Trans R Soc Trop Med Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2655-64.
Hyg. 2019 Feb 1;113(2):56-64.
5. Rübsam A, Parikh S, Fort PE. Role of Inflammation in Diabetic
2. Burton MJ, Ramke J, Marques AP, Bourne RRA, Congdon N, Jones Retinopathy. Int J Mol Sci. 2018 Mar 22;19(4):942. doi: 10.3390/
I et al. The Lancet Global Health Commission on Global Eye Health: ijms19040942. PMID: 29565290; PMCID: PMC5979417.
vision beyond 2020. Lancet Glob Health. 2021 Apr;9(4):e489-e551.
6. Antonetti, D.A.; Klein, R.; Gardner, T.W. Diabetic retinopathy. N.
3. Barber AJ, Baccouche B. Neurodegeneration in diabetic retinopathy: Engl. J. Med. 2012, 366, 1227–1239.
Potential for novel therapies. Vision Res. 2017 Oct;139:82-92. doi:
10.1016/j.visres.2017.06.014. Epub 2017 Oct 16. 7. Sun, J.K.; Lin, M.M.; Lammer, J.; Prager, S.; Sarangi, R.; Silva, P.S.;
Aiello, L.P. Disorganization of the retinal inner layers as a predictor
3. Romero-Aroca P, Reyes-Torres J, Baget-Bernaldiz M, Blasco-Suñe C. of visual acuity in eyes with center-involved diabetic macular edema.
Laser treatment for diabetic macular edema in the 21st century. Curr JAMA Ophthalmol. 2014, 132, 1309–1316. [CrossRef] [PubMed]
Diabetes Rev. 2014 Mar;10(2):100-12.
8. Bonnin, S.; Tadayoni, R.; Erginay, A.; Massin, P.; Dupas, B. Correlation
4. Sohn EH, van Dijk HW, Jiao C, Kok PH, Jeong W, Demirkaya N, Gar- between ganglion cell layer thinning and poor visual function after
mager A, Wit F, Kucukevcilioglu M, van Velthoven ME, DeVries JH,
DOS Times - Volume 28, Number 2, March-April 2022 40 www.dosonline.org/dos-times
Subspecialty - Retina
resolution of diabetic macular edema. Investig. Ophthalmol. Vis. Sci. sin,A.T.;Allen,D.M.;Cardona, A.E. The role of microglia in diabetic
2015, 56, 978–982. [CrossRef] [PubMed] retinopathy. J. Ophthalmol. 2014, 2014, 705783.
9. Adamis AP. Is diabetic retinopathy an inflammatory disease? Br J 25. Funatsu, H.; Noma, H.; Mimura, T.; Eguchi, S.; Hori, S. Association
Ophthalmol 2002;86:363-5. of vitreous inflammatory factors with diabetic macular edema. Oph-
thalmology 2009, 116, 73–79.
10. Kern, T.S. Contributions of inflammatory processes to the development
of the early stages of diabetic retinopathy. Exp. Diabetes Res. 2007, 26. Markan A, Agarwal A, Arora A, Bazgain K, Rana V, Gupta V. Nov-
2007, 95103 el imaging biomarkers in diabetic retinopathy and diabetic macular
edema. Ther Adv Ophthalmol. 2020 Sep 4;12:2515841420950513.
11. Joussen AM, Poulaki V, Le ML, et al. A central role for inflammation doi: 10.1177/2515841420950513. PMID: 32954207; PMCID:
in the pathogenesis of diabetic retinopathy. FASEB J 2004;18:1450-2. PMC7475787.
12. Joussen A.M., Poulaki V., Le M.L., Koizumi K., Esser C., Janicki H., 27. Ragkousis A, Kozobolis V, Kabanarou S, Bontzos G, Mangouritsas
Schraermeyer U., Kociok N., Fauser S., Kirchhof B., et al. A central G, Heliopoulos I, Chatziralli I. Vessel Density around Foveal Avas-
role for inflammation in the pathogenesis of diabetic retinopathy. cular Zone as a Potential Imaging Biomarker for Detecting Preclin-
FASEB J. 2004;18:1450–1452. doi: 10.1096/fj.03-1476fje. ical Diabetic Retinopathy: An Optical Coherence Tomography An-
giography Study. Semin Ophthalmol. 2020 Aug 17;35(5-6):316-323.
13. 103. Miyamoto K., Khosrof S., Bursell S.E., Rohan R., Murata T., doi: 10.1080/08820538.2020.1845386. Epub 2020 Dec 1. PMID:
Clermont A.C., Aiello L.P., Ogura Y., Adamis A.P. Prevention of 33258720.
leukostasis and vascular leakage in streptozotocin-induced diabetic
retinopathy via intercellular adhesion molecule-1 inhibition. Proc. 28. Yansha Lu, Joseph M. Simonett, Jie Wang, Miao Zhang, Thomas
Natl. Acad. Sci. USA. 1999;96:10836–10841. Hwang, Ahmed M. Hagag, David Huang, Dengwang Li, Yali Jia;
Evaluation of Automatically Quantified Foveal Avascular Zone
14. 104. Stitt A.W., Curtis T.M., Chen M., Medina R.J., McKay G.J., Metrics for Diagnosis of Diabetic Retinopathy Using Optical Co-
Jenkins A., Gardiner T.A., Lyons T.J., Hammes H.P., Simo R., herence Tomography Angiography. Invest. Ophthalmol. Vis. Sci.
et al. The progress in understanding and treatment of diabetic 2018;59(6):2212-2221. doi: https://doi.org/10.1167/iovs.17-23498
retinopathy. Prog. Retin. Eye Res. 2016;51:156–186. doi: 10.1016/j.
preteyeres.2015.08.001. 29. Van der Torren, K.; van Lith, G. Oscillatory potentials in early dia-
betic retinopathy. Doc. Ophthalmol. 1989, 71, 375–379. [CrossRef]
15. 105. Durham J.T., Herman I.M. Microvascular modifications in [PubMed]
diabetic retinopathy. Curr. Diabetes Rep. 2011;11:253–264.
30. Sokol, S.; Moskowitz, A.; Skarf, B.; Evans, R.; Molitch, M.; Senior, B.
16. Yoshida S., Yoshida A., Ishibashi T. Induction of IL-8, MCP-1, and Contrast sensitivity in diabetics with and without background retin-
BFGF by TNF-alpha in retinal glial cells: Implications for retinal opathy. Arch. Ophthalmol. 1985, 103, 51–54.
neovascularization during post-ischemic inflammation. Graefes
Arch. Clin. Exp. Ophthalmol. 2004;242:409–413. 31. Roy, M.S.; Gunkel, R.D.; Podgor, M.J. Color vision defects in early
diabetic retinopathy. Arch. Ophthalmol. 1986, 104, 225–228.
17. Tsutsumi C., Sonoda K.H., Egashira K., Qiao H., Hisatomi T., Nakao
S., Ishibashi M., Charo I.F., Sakamoto T., Murata T., et al. The 32. Pollreisz A, Desissaire S, Sedova A, Hajdu D, Datlinger F,
critical role of ocular-infiltrating macrophages in the development of Schwarzhans F, Steiner S, Steiner I, Vass C, Hitzenberger CK, Pircher
choroidal neovascularization. J. Leukoc. Biol. 2003;74:25–32. M, Schmidt-Erfurth U. Early Identification of Retinal Neuropathy in
Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapil-
18. 112. Sakurai E., Taguchi H., Anand A., Ambati B.K., Gragoudas E.S., lary Retinal Nerve Fiber Layer. Invest Ophthalmol Vis Sci. 2021 Apr
Miller J.W., Adamis A.P., Ambati J. Targeted disruption of the CD18 1;62(4):24.
or ICAM-1 gene inhibits choroidal neovascularization. Investig.
Ophthalmol. Vis. Sci. 2003;44:2743–2749. 33. Silva PS, Cavallerano JD, Sun JK, et al. Peripheral lesions identified
by mydriatic ultrawide field imaging: distribution and potential im-
19. Rusnak, S.; Vrzalova, J.; Sobotova, M.; Hecova, L.; Ricarova, R.; pact on diabetic retinopathy severity. Ophthalmology. 2013;120:2587-
Topolcan, O. The measurement of intraocular biomarkers in various 2595.
stages of proliferative diabetic retinopathy using multiplex xmap
technology. J. Ophthalmol. 2015, 2015, 424783. 34. Silva PS, Cavallerano JD, Haddad NMN, et al. Peripheral lesions
identified on ultrawide field imaging predict increased risk of diabetic
20. Doganay, S.; Evereklioglu, C.; Er, H.; Turkoz, Y.; Sevinc, A.; Mehmet, retinopathy progression over 4 years. Ophthalmology. 2015;122:949-
N.; Savli, H. Comparison of serum no, TNF-alpha, IL-1beta, SIL- 956.
2r, IL-6 and il-8 levels with grades of retinopathy in patients with
diabetes mellitus. Eye (London) 2002, 16, 163–170. 35. Aiello LP, Odia I, Glassman AR, et al. Comparison of early treatment
diabetic retinopathy study standard 7-field imaging with ultraw-
21. Dong N, Xu B, Chu L, Tang X. Study of 27 Aqueous Humor Cytokines ide-field imaging for determining severity of diabetic retinopathy.
in Type 2 Diabetic Patients with or without Macular Edema. PLoS JAMA Ophthalmol. 2019;137:65-73.
One. 2015 Apr 29;10(4):e0125329.
36. Wessel MM, Aaker GD, Parlitsis G, et al. Ultra-wide-field angiogra-
22. Yang, L.P.; Sun, H.L.; Wu, L.M.; Guo, X.J.; Dou, H.L.; Tso, M.O.; phy improves the detection and classification of diabetic retinopathy.
Zhao, L.; Li, S.M. Baicalein reduces inflammatory process in a rodent Retina. 2012;32:785-791.
model of diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 2009,
50, 2319–2327. 37. Abràmoff MD, Lavin PT, Birch M, Shah N, Folk JC. Pivotal trial of
an autonomous AI-based diagnostic system for detection of diabetic
23. Zeng,H.Y.;Green,W.R.;Tso,M.O.Microglialactivationinhumandi- retinopathy in primary care offices. Npj Digit Med. 2018;1:39.
abeticretinopathy.Arch.Ophthalmol. 2008, 126, 227–232.
38. Midena E, Frizziero L, Midena G, Pilotto E. Intraocular fluid bio-
24. Grigsby,J.G.;Cardona,S.M.;Pouw,C.E.;Muniz,A.;Mendiola,A.S.;T-
www.dosonline.org/dos-times 41
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Retina
markers (liquid biopsy) in human diabetic retinopathy. Graefes Arch 49. Hu,T.;Vanhove,M.;Porcu,M.;VanHove,I.;VanBergen,T.;Jonckx,B.;
Clin Exp Ophthalmol. 2021 Dec;259(12):3549-3560. doi: 10.1007/ Barbeaux,P.;Vermassen,E.;Feyen,J.H.M.Thepotent small molecule in-
s00417-021-05285-y. tegrin antagonist THR-687 is a promising next-generation therapy for
retinal vascular disorders. Exp. Eye Res. 2019, 180, 43–52
39. Brown DM, Nguyen QD, Marcus DM, et al. Long-term outcomes
of ranibizumab therapy for diabetic macular edema: the 36-month 50. QuirozMercado,H.;Boyer,D.S.;Campochiaro,P.A.;Heier,J.S.;Kai-
results from two phase III trials: RISE and RIDE. Ophthalmolo- ser,P.K.;Kornfield,J.;Kupperman,B.D.;Karageozian,V.H.;Karageo-
gy.2013;120(10):2013-2022. zian, H.L.; Karageozian, L.; et al. Randomized, prospective, dou-
ble-masked, controlled phase 2b trial to evaluate the safety & efficacy
40. Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal aflibercept for of ALG-1001 (L,uminate®) in diabetic macular edema. Investig. Oph-
diabetic macular edema: 148-week results from the VISTA and VIV- thalmol. Vis. Sci. 2018, 59, 1960.
ID studies. Ophthalmology. 2016;123(11):2376-2385.
51. Zhang, M.; Zhang, J.; Yan, M.; Luo, D.; Zhu, W.; Kaiser, P.K.; Yu,
41. Gross JG, Glassman AR, Liu D, et al; Writing Committee for the Di- D.C.; KH902 Phase 1 Study Group. A phase 1 study of KH902, a vas-
abetic Retinopathy Clinical Research Network. Five-year outcomes of cular endothelial growth factor receptor decoy, for exudative age-re-
panretinal photocoagulation vs intravitreous ranibizumab for prolif- lated macular degeneration. Ophthalmology 2011, 118, 672–678.
erative diabetic retinopathy: a randomized clinical trial. JAMA Oph-
thalmology.2018;136(10):1138-1148. Corresponding Author:
42. Lim JI. Intravitreal aflibercept injection for nonproliferative diabetic Ankur Singh, MS, FAICO (Vitreo-Retina)
retinopathy: year 2 results from the PANORAMA study. Invest Oph- Assistant Professor, Department of Ophthalmology
thalmol Vis Sci. 2020;61(7):1381-1381. University college of Medical Sciences, New Delhi, India.
43. Maturi RK, Glassman AR, Josic K, et al. Effect of intravitreous an-
ti-vascular endothelial growth factor vs sham treatment for pre-
vention of vision-threatening complications of diabetic retinopa-
thy: the Protocol W randomized clinical trial. JAMA Ophthalmol.
2021;139(7):701-712.
44. Campochiaro PA, Marcus DM, Awh CC, Regillo C, Adamis AP,
Bantseev V, Chiang Y, Ehrlich JS, Erickson S, Hanley WD, Horvath
J, Maass KF, Singh N, Tang F, Barteselli G. The Port Delivery System
with Ranibizumab for Neovascular Age-Related Macular Degener-
ation: Results from the Randomized Phase 2 Ladder Clinical Trial.
Ophthalmology. 2019 Aug;126(8):1141-1154
45. Wykoff,C.C. Suprachoroidal triamcinolone acetonide with and with-
out intravitreal aflibercept for diabetic maculare dema: Phase 1/2
HULK study. Am. Acad. Ophthalmol. Retin. Subspecialty Day 2017,
10–11.
46. Canning,P.;O’Lear y,O.;Allen,L.;Brines,M.;Cerami,A.;Stit-
t,A.W.ARA290(cibinetide)treatmentconfersneuroprotective effects in
diabetic retinopathy, through modulation of inflammatory mediators.
Investig. Ophthalmol. Vis. Sci. 2019, 60, 2720.
47. Moschos, M.M.; Dettoraki, M.; Tsatsos, M.; Kitsos, G.; Kalogeropou-
los, C. Effect of carotenoids dietary supplementation on macular func-
tion in diabetic patients. Eye Visión 2017, 4, 1–6
48. Zhang, P.; Wu, C.; Wang, Z.; Wang, L.; Han, Y.; Sun, S.; Li, Q.; Ma, L.
Effect of lutein supplementation on visual function in nonproliferative
diabetic retinopathy. Asia Pac. J. Clin. Nutr. 2017, 26, 406–411.
DOS Times - Volume 28, Number 2, March-April 2022 42 www.dosonline.org/dos-times
Subspecialty - Retina
A rare case of Serratia marcescens
endophthalmitis post optical penetrating
keratoplasty with missed foreign body in
inferior temporal quadrant of posterior
segment
Pendyala Yashaswi[1], MBBS, MS, FIOL, Jain nidhee[2], MBBS, MS, FVR, Ahuja Nisha[3], MBBS, DOMS, FCRS
1. IOL Fellow, Sankara Eye Hospital, Mogar, Anand, Gujarat.
2. Consultant Vitreoretina, Sankara Eye Hospital, Mogar, Anand, Gujarat.
3. Chief Medical Officer, Sankara Eye Hospital, Mogar, Anand, Gujarat.
Introduction Figure 1 : Pre-operative photo of right eye showing near total pigmented
Serratia marcescens is an aerobic rod shaped gram negative leucomatous corneal opacity with peripheral thinning.
bacillus commonly associated with nosocomial infections of
respiratory and urogenital tract.[1,2] Depending on the source On 3rd POD, corneal graft had few descemet membrane folds
of infection s.marcescens endophhalmitis is either exogenous along with 3+ cells in AC. Pinkish-white hypopyon was noted
or endogenous but usually exogenous with its source being in AC measuring 2.5 mm (Figure 2) though there were no graft
damp environment such as bathroom, tile grout shower corner infiltrates. Fundal details were hazily seen. B Scan revealed
and dirt.[3] Post keratoplasty endophthalmitis is rare but serious multiple dot echoes in vitreous with moderate reflectivity
complication associated with poor visual and structural outcome suggesting vitreous haemorrhage and IOFB. Retina choroid
and gram positive organisms are the major source of infection.[4] sclera (RCS) complex was normal.
Case History On 4 th POD, pinkish-white hypopyon was around half of the
A 63 years old male patient came at tertiary eye care center located AC (Figure 3) along with lid edema and conjunctival chemosis.
in Gujarat state of west India with complaints of diminution of Vision dropped to PL+, PR inaccurate. B-Scan showed vitreous
vision in the Right Eye (RE) since 6 months following ocular haemmorrhage filling the entire vireous cavity or vitritis with
trauma, treated primarily elsewhere. He is a known hypertensive RCS thickening and an early T- sign and a hyperreflective echo
since 8 years. with after shadowing in the infero-temporal quadrant (ITQ).
Vision in RE was counting fingers close to face and 6/18 in Left
Eye (LE) which improved to 6/6 with refraction. RE anterior
segment examination revealed corneal opacity with peripheral
thinning (Figure 1). AC could only be seen from periphery
which revealed posterior chamber intraocular lens (PCIOL)
implanted in AC. Fundus details could not be ascertained.
Screening ultrasound B-scan revealed an anechoic vitreous
cavity. Retina appeared attached. LE had pseudophakia and rest
was within normal limit. Patient was planned for penetrating
keratoplasty (PK) with IOL explantation and secondary iris
claw lens implantation. Intra-opearatively IOL was found to
be adherent to the Iris. After synechial release the IOL was
explanted and anterior vitrectomy was done. Post explantation
diffuse iris atrophy was noted and hence iris claw lens could
not be implanted. Patient was left aphakic and planned for
scleral fixated IOL later. Donor Corneal button was sent for
microbiological examination which revealed no growth.
www.dosonline.org/dos-times 43
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Retina
Culture report revealed Serratia marcescens. Patient was taken
up for 23G pars plana vitrectom (PPV) and the IOFB was noted
to be embedded in the retina in the ITQ. A metallic IOFB of
about 3x1mm was removed by extending the superotemporal
incision. Intraoperatively, retina showed siderotic changes along
with optic disc pallor. Intravitreal moxifloxacin and gentamicin
were injected. Antifungal were discontinued. Patient was started
on fortified Gentamycin eye drops and topical as well as oral
Ciprofloxacin was started.
Figure 2 : 3nd post operative day photo showing 2.5 mm pinkish white Figure 4 : 5th post operative day B-scan photo showing moderate reflective
hypopyon. multiple dot echoes in vitreous (large white arrow) suggestive of vitritis
and single hyperreflective echo with after shadowing (small black arrow)
suggestive of intra ocular foreign body in the infero-temporal quadrant.
On first day following IOFB removal, there was little graft edema
along with 3+ AC reaction (Figure 5a). He was continued on
medications. On subsequent visits, patient showed clinical and
symptomatic improvement. At 1 month follow up, vision was
PL+, PR inaccurate. There was little graft edema along with deep
vascularization and few pigments on endothelium. AC cells 1+.
No view of fundus. B-scan revealed retina on and moderate
vitritis (Figure 5b).
Figure 3 : 4th post operative day photo showing around half anterior
chamber pinkish white hypopyon.
AC tap was done and sent for microbiological examination on Figure 5 : (a) On first day following IOFB removal, there was little graft
the 4th POD along with intracameral injection of Vancomycin, edema along with AC reaction.
amphotericin B and Ceftazidime. Topical treatment was
continued.
On 5th POD, corneal graft was clear but AC had exudates.
Fundus was not visible. B-scan showed a similar picture of 4th
POD suggestive of a FB in the ITQ (Figure 4).
DOS Times - Volume 28, Number 2, March-April 2022 44 www.dosonline.org/dos-times
Subspecialty - Retina
Figure 6 : B- scan (after IOFB removal) showing retina on and peripheral given his/her/their consent for his/her/their images and other
uncut vitreous with moderate vitritis. clinical information to be reported in the journal. The patients
understand that their names and initials will not be published
Discussion and due efforts will be made to conceal their identity, but
To our knowledge this is the first reported case of an early onset anonymity cannot be guaranteed.
s.marcescens endophthalmitis after optical PK, with a past References
history of ocular trauma with metallic object. Cohen SM et al 1. Marinella MA, Warwar R. Endogenous endophthalmitis due to Ser-
reported s.marcescens endophhalmitis after cataract extraction,
glaucoma procedures, PK, sclera buckle procedures[3], ratia marcescens. South Med J. 1998; 91: 388–391.
pterygium surgery with adjuvant mitomycin-C application[5] 2. Hejazi A, Falkiner FR. Serratia marcescens. J Med Microbiol. 1997;
and intravitreal bevacizumab injection[6] but it has not yet been
reported in association with ocular trauma with a metallic object. 46: 903–912.
Endogenous s.marcescens endophthalmitis account for 5-10% of 3. Derek Y kunimoto, William Tasman, Christopher Rapuano, Franco
the cases. The predisposing risk factors include diabetes mellitus,
renal failure on dialysis, Hepatitis-C, HIV and intravenous drug Recchia, Brandon Busbee, Robert Pearlman et al. Endophthalmitis
use.[7, 8] But in our patient, IOFB and hypertension were the after penetrating keratoplasty: microbiologic spectrum and suscepti-
plausible risk factors for endophthalmitis. bility of isolates. American journal of ophthalmology.2004; 137: 343-
Due to its ability to produce reddish-orange tripyrrole pigment, 345.
s.marcescens endophthalmitis can present with hypopyon 4. Cohen SM, Flynn HW, Miller D. Endophthalmitis caused by Serratia
varying between dark pink and tan hues.[9] R A Equi et al reported Marcescens. Ophthalmic Surg Lasers Imaging Retina. 1997; 28:195–
a single case of endogenous s.marcescens endophthalmitis with 200.
dark hypopon.[10] Hypopyon in our study varied pinkish-white. 5. Yi, M.Y., Chung, J.K. & Choi, K.S. Serratia marcescens endoph-
Cohen SM et al assessed the treatment outcomes of 10 patients thalmitis after pterygium surgery: a case report. BMC Ophthalmol.
with culture proven s.marcescens endophthalmitis and noted 2017; 17: 197.
that eyes with s.marcescens endophthalmitis have poor 6. Lee, S., Woo, S., Park, K. et al. Serratia marcescens endophthalmi-
visual prognosis despite appropriate intravitreal and systemic tis associated with intravitreal injections of bevacizumab.2010;
antibiotic therapy.[3] Our case also had poor visual outcome Eye 24, 226–232.
after appropriate antibiotic therapy but showed clinical and 7. Kernt M., Kampik A. Endophthalmitis: pathogenesis, clinical pre-
symptomatic improvement after PPV and IOFB removal. sentation, management, and perspectives. Clin Ophthalmol. 2010; 4:
Limitation of our case report was using an AC tap and culture 121–135.
for diagnosis, but not using vitreous tap and PCR technique for 8. Breazzano M.P., Day H.R., Jr., Bloch K.C. Utility of ophthalmolog-
diagnosis which is more sensitive and an initial missed finding ic screening for Candida bloodstream infections: a systematic re-
of iofb in B-scan. view. JAMA Ophthalmol. 2019; Apr 18; 137: 698–710.
Conclusion 9. Fineran PC, Slater H, Everson L, Hughes K, Salmond GP. Biosynthesis
S.marcescens is a rare cause of endophthalmitis which can have of tripyrrole and beta-lactam secondary metabolites in Serratia: inte-
devastating consequence despite appropriate treatment and to gration of quorum sensing with multiple new regulatory components
our knowledge this is the first reported case associated with past in the control of prodigiosin and carbapenem antibiotic production.
history ocular trauma with a metallic object. Mol Microbiol. 2005 Jun; 56:1495–1517.
Declaration of patient consent 10. Equi RA, Green WR. Endogenous Serratia marcescens endophthal-
The authors certify that they have obtained all appropriate mitis with dark hypopyon: case report and review. Surv Ophthalmol.
patient consent forms. In the form the patient(s) has/have 2001; 46: 259–268.
Corresponding Author:
Dr. Pendyala Yashaswi,
IOL fellow, Sankara eye hospital, mogar, Anand, Gujarat.
www.dosonline.org/dos-times 45
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Glaucoma
Recent Advances in Perimetry
Jatinder Singh Bhalla[1], MBBS, MS, DNB, MNAMS, Kanika Jain[2], MBBS, MS, DNB, Yogesh Bathla[3], MBBS, Neha Yadav[3], MBBS,
Thory Prakash[3], MBBS, DO, Ashwini Kulkarni[3], MBBS
1. Senior Consultant & Academic Incharge, Department of Ophthalmology, DDU Hospital, New Delhi.
2. Senior Resident, Department of Ophthalmology, Deen Dayal Upadhyay Hospital, Hari Nagar, New Delhi.
3. Junior Residents, Department of Ophthalmology, Deen Dayal Upadhyay Hospital, Hari Nagar, New Delhi.
Visual field (VF) testing is an integral part of glaucoma man- 1. Starting stimulus intensities: Like the original Full Thresh-
agement. It is a standard method to detect functional damage in old strategy, SS and SF programs begin each examination
glaucoma and to monitor progression over follow up examina- by presenting 25 dB stimuli at each of 4 primary test points.
tions which helps in management of these patients. Most widely A primary point is the first tested point in each quadrant.
used technique of VF testing in glaucoma is the standard auto- Twenty-five dB is considerably brighter than the threshold
mated perimetry (SAP) with Humphrey Field Analyser and the in normal eyes, and most of the time several stimuli must be
most widely used VF testing strategy is the SITA Standard (SS) presented before the visual threshold is reached. In SFR, the
algorithm which replaced Full Threshold strategy. Visual field test sequence begins at the age-corrected normal threshold
testing with SS takes about 6 minutes per eye i.e 50% time re- level, therefore reducing the number of stimulus presenta-
duction as compared to Full Threshold. SITA Fast (SF) has 50% tions for most eyes.
time reduction as compared to Fastpac which it replaced. These
strategies identified atleast as much glaucomatous field loss as 2. Reversals at primary test points: In older test programs,
the algorithms they replaced without worsening inter-test var- 2 staircase test sequences were performed at each primary
iability. However, threshold sensitivity values were higher with point. In SFR, only 1 staircase test reversal is required but
shorter tests because increased visual fatigue with earlier algo- step sizes are unchanged.
rithms tends to decrease threshold values with increasing test
duration.[1] 3. Prior models: The legacy SITA tests and SITA Faster all
Most challenging aspect in perimetry is to establish a reliable use iterative maximum posterior probability calculations of
baseline and test-retest reliability. Frequent examinations are threshold levels in real time to determine when testing can
required to establish a baseline and to differentiate true progres- stop at each point location. Visual field models of thresholds
sion from noise.[1] Longer duration of VF testing induced fatigue at each test location are important for the efficiency of this
in glaucoma patients who are generally senile and thus preclude process. SF and SITA SS visual field models were based on
generation of reliable tests. distributions of normal threshold levels obtained using the
There have been many recent advances to perimetry in the re- original Full Threshold program because normal values for
cent past. They have been directed towards improving accuracy, SITA were not yet available when those SITA tests were under
efficiency and isolating subsets of visual mechanisms with the development. SFR’s visual field model uses the distribution
hope of detecting functional losses earlier. The newer approach- of SITA Fast normal values, leading to more time-efficient
es are predominantly directed towards developing new test types testing.
or new test algorithms. However most of these procedures are
still in research settings, and would require further improve- 4. Retesting at perimetrically blind points: In older strate-
ments/applications in clinics before they can be considered as gies, test points where the test subject has not responded
an alternative to SAP in a routine clinical setting. to the maximum stimulus intensity of the perimeter (0
SITA Faster (SFR) dB/10,000 apostilb) have been confirmed by presenting a
second maximum intensity stimulus. In SFR, this second
It is a new addition to the SITA family of testing strategies for check is not performed.
the Humphrey Field Analyzer (HFA3) perimeter whose clinical
development began in 2011. It takes about half the time required 5. False negative catch trials: Test reliability was assessed us-
by SITA Standard (SS) test and two-thirds of the time required ing several “reliability parameters”—blind spot catch trials,
by SITA Fast (SF). Test time reductions are largest in eyes with false negative (FN) responses and false positive (FP) re-
severe field loss. It is available only for 24-2. Many patients are sponses. In SITA Faster, FN catch trials are no longer per-
able to complete SFR 24-2 testing in about 2 minutes. A signifi- formed.
cantly faster testing strategy may facilitate more frequent visual
field testing, thus bringing clinical practice more in line with 6. Blind spot catch trials: In SITA Faster, the earlier method
current recommendations. Seven modifications were made to of checking fixation by projecting stimuli into the blind spot
SF to produce SFR which are as follows[2]: has been replaced by use of the Humphrey gaze tracker.
7. Stimulus timing: SITA tests have a rather advanced tim-
ing algorithm that is sensitive to each patient’s individual
reaction time and to how that reaction time may change as
DOS Times - Volume 28, Number 2, March-April 2022 46 www.dosonline.org/dos-times
Subspecialty - Glaucoma
testing proceeds. In earlier SITA programs, an extra 300-ms • Virtual reality based visual field testing strategies-Googles
delay was added after non-seen stimuli at the end of the re- with inbuilt display or googles with smart phones. Uses a
sponse time window before a new stimulus was presented. wired or wireless connection to a computer. Simulates a
This extra delay was eliminated in SFR. standard visual field testing by presenting a sequential light
Clinical testing has shown that SFR produces results that are stimulus to a patient and feedback is given using a clicker.
clinically equivalent to SF with no loss of repeatability. Pham et
al evaluated effect of transitioning from SS to SFR in 766 glau- Visual field easy (VFE) (Figure 2)
comatous eyes (421 patients) and found that mean deviation
showed no significant change when transitioned from SS to Figure 1 : Test times vs stage of glaucoma. Test times were shortest in
SFR (average difference -0.23dB) in eyes with mild disease (MD normal fields and fields with early glaucomatous field loss with all
≤6dB). In moderate disease (MD -6 to -12 dB) and severe dis- strategies. SITA [Swedish Interactive Threshold Algorithm; VFI [visual
ease (MD worse than -12dB), MD showed a mean improvement field index].
of 0.87 Db and 1.49Db respectively when transitioned from SS • Cost effective tablet based visual field assessment tool
to SFR. They concluded that transitioning from SS to SFR in pa- • Help clinicians in developing countries to screen patients
tients with moderate to advanced glaucoma may conceal disease
progression.[3] with increased efficiency and effectiveness
SFR test times were approximately 36.1% shorter than SF and • Can perform in remote areas of world where access to bulky
60.7% shorter than SS (Figure 1). MD values were lower with
SFR compared with SF and SS. Mean PSD and VFI showed no medical equipment is limited and also for non ambulatory
significant differences between algorithms. Mean foveal thresh- or debilitated elderly patients
old was higher for SFR compared to SF and SS. Number of points • I pad application with suprathreshold method of visual field
depressed at p<0.5% was less in SFR than in both SF and SS. testing
Bland Altmann plots showed considerable variability between • 96 test locations are tested within central 30 degrees with a
algorithms. Thus, SFR provides benefits in shorter test time and size V target when placed at 33cm test distance and 16db su-
shows similar VF indices compared to SF and SS, however de- prathreshold static perimetry target for screening purposes
tection of early cases of glaucoma with SFR is questionable and • Takes about 3 minutes on average per eye
algorithms cannot be used interchangeably for same patient on • Before performing VFE, Ipad requires calibration and per-
different test sessions.[4] form test in a dimly lit room to avoid reflections
HFA’s Guided Progression Analysis (GPA) has been improvised • Limitations associated with using VFE
to allow mixing of SITA test strategies: SS, SF and SFR allowing Touching the screen repeatedly created smudges leading to
ophthalmologists to switch over to SFR without having to re-es- decreased quality and contrast sensitivity of target
tablish baseline. Requirement of manual dexterity for accurate dot tracking
on screen
SITA Faster 24-2c No gaze/head tracking (inability to control fixation and dis-
tance from eye to screen)
It is a new SITA test pattern that adds 10 central test points which Inability to retest spots with bracketing
are tested at the end of SITA Faster 24-2 test thus combining Need of manual processing of printouts with a companion
10-2 and 24-2 test patterns. It is available on HFA3 model 860 program to get parametric information
perimeter (Zeiss, Dublin, CA). It has faster test duration than SF Cannot substitute Humphrey Field analyzer in clinic owing
24-2 or SF 10-2 and it offers the advantage of earlier detection of to its suboptimal sensitivity and specificity to detect early/
central visual field loss without the need to run a supplementary moderate glaucoma[5]
10-2 test. It has the potential of early detection of glaucoma.
Tablet based and virtual reality headset based visual field
testing strategies
• Desktop based- Visual Field Easy and Peristat; home based
applications with suprathreshold testing. Can be used at
homes by patients for screening purposes only.
• Tablet based visual field testing strategies- Melbourne rapid
fields (MRF) and eye tracker. Web based in clinic visual field
testing, supported by IOS, windows and android. Uniocu-
lar testing is done wearing full refractive correction. Held
at 33cm in dim light in a silent room. It is fast thresholding
tests with 8 step ZEST algorithms and takes about 2-3 min-
utes each eye. Gaze based or touch based feedback systems.
www.dosonline.org/dos-times 47
DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Glaucoma
Figure 2 : Visual field easy printout showing perimetry results as compared to Humphrey Field Analyser SITA Standard 24-2.
Melbourne Rapid Fields (MRF) (Figure 3,4) • This would facilitate monitoring of presumed stable or
controlled glaucoma patients/suspects to reduce the overall
• GLANCE Optical Pvt Ltd., Melbourne, Australia number of office visits per year.
• The software uses the zippy estimation by sequential testing
• Disadvantage- If portable visual field data were relied upon
(ZEST) algorithm, which is an adaptive Bayesian method, to detect progression, diagnosis might come too late and
for determining retinal sensitivity measures. glaucoma is an irreversible pathology. Identification of
• Each eye is tested separately and with patient wearing near progression on structural evaluation prior to functional loss
spectacle correction if required. is optimal.[11]
• Fixation is maintained with a central fixation target, which
can move to the peripheries of the tablet to further test the Figure 3 : Melbourne Rapid Fields is an iPad app that uses a moving
extremities of the field.[6] A computed voice prompt guides fixation target to test up to 30 degrees of field.
patients throughout the test and voice reminder given at
regular intervals to remind patients to maintain focus on
fixation target.
• At the end of the test, the software generates a 24-2 visual
field printout map that has good reliability and similarity
with Humphrey visual field (HVF) testing (Fig. 4).[7,8]
• When independently evaluated, global indices were highly
correlated between MRF and HVF: MD r2 = 0.80, PSD
r2 = 0.77, VFI r2 = 0.85 (all p < 0.0001). The ROC analysis of
global indices showed reasonable sensitivity/specificity with
AUC values of 0.89 (MD), 0.85 (PSD), and 0.88 (VFI). The
MRF retest variability was low with ICC values at 0.95 (MD
and VFI) and 0.94 (PSD).[9]
• Speed similar to SF (4.6±0.1 min as compared to 4.3±0.2
min of SF), significantly faster than SS (6.2±0.1 min).[10]
DOS Times - Volume 28, Number 2, March-April 2022 48 www.dosonline.org/dos-times
Subspecialty - Glaucoma
Figure 4 : Melbourne Rapid Field result (a,b) as compared to Humphrey Field Analyser SITA Standard 24-2.
Moorfields Motion Displacement Test (MMDT)[11] Cambridge Glaucoma Visual Function Test (CGVFT)
(Figure 5)
• Accessible multilocation perimetry • Patients with worsening glaucoma have increasing difficulty
• Presented on a laptop/desktop
• Windows based software program with light/dark adaptation, contrast discrimination, and
• Enhanced suprathreshold algorithm (ESTA) peripheral vision-dependent activities.[12] This can impact
• Takes 90-120 seconds per eye walking, driving, venturing from home, seeing at night,
• Test distance of 30cm reading, adjusting to different levels of illumination,
• Presents 31 lines of stimulus in a location format that fits a judging distances, and seeing peripheral objects and
moving objects coming from the side, resulting in falls or
15 inch laptop screen motor vehicle accidents.[13-15] Progressive vision impairment
• Each location corresponds to a location on the Humphrey from glaucoma may adversely affect one’s ability to perform
daily activities, physical and psychological well-being, and
24-2 program health-related quality of life (QoL).
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DOS Times - Volume 28, Number 2, March-April 2022
Subspecialty - Glaucoma
• Functional loss by perimetry may not reflect real-world interfere with patients’ daily life; it could be an important
visual function. For instance, in real life, patients can be educational intervention for patients.[19]
distracted, or be multitasking, and are able to move their • Virtual reality based CGVRT- The image on the smartphone
head and use saccades to compensate for loss of peripheral is duplicated on two halves of the smartphone, one for
vision.[16] Questionnaires—also known as patient-reported each viewing eyepiece, as the smartphone is inserted into
outcomes (PROs)—allow patients to self-evaluate their the VR viewing headpiece (Figure 6). The user was able to
ability to perform visually related tasks. However, recall “look around” the VR world, as the phone detects any head
bias, psychological factors, and personality may influence movement and alters the displayed field of view accordingly.
patients’ responses. Two patients with the same degree of This is virtual reality glaucoma function test which was
clinically measured vision loss may rate their disability evaluated to assess the daily quality of life in glaucoma
differently on a questionnaire, or may alter their responses patients. The items of this test were grouped into three
on different days depending on mood or other factors.[17-18] categories—stationary tasks, moving ball tasks, and driving
tasks. Only the stationary test correlated with glaucoma
• These are objective computer simulated functional visual severity, albeit weakly (R = 0.244; p = 0.018). The widescreen
ability activities designed to reflect daily life activities. CGVFT projector is more similar in nature to VF testing
and this may be the reason for the greater correlation.
• This comprised of 63 image-based tasks projected on a large Furthermore, the widescreen CGVFT had a form of fixation
screen, subtending 120° horizontally of binocular vision. control to challenge peripheral vision use, which the VR-
The images were designed to reflect peripherally visually headset test did not.[20]
challenging tasks of varying difficulty levels, and patients’
ability to complete the tasks was timed. Each task began
with the patient looking at a central, spinning yellow star,
which was a form of initial fixation to challenge their vision
peripherally.
• Such testing may help bridge the gap in understanding
between patients and clinicians as to how glaucoma may
Figure 5 : (A to D): Items from the Cambridge glaucoma visual function Figure 6 : (A,B): (A) Google Goggles viewing binocular system allowing
test (CGVFT). The CGVFT comprises timed visually challenging tasks a simulated virtual reality (VR) environment; (B) Testing strategy with
projected onto a wide screen and designed to reflect daily living. For patients wearing the VR headset. Their view can be tracked on the
each task, the participant is required to begin gaze at a centrally rotating invigilators’ computer screen on the desk.
gold star and then find a target. For example, participants are asked to
find a raspberry among the cherries, match a sock, identify camouflaged • 6-inch display smartphone, and a software that evaluates the
animals, and find items on a street scene. central 24° of the visual field using a fast-threshold 3 dB step
staircase algorithm. The 52 testing points are all on each of
Virtual reality based perimetry (Figure 7,8) the two halves of the smartphone, to stimulate either eye. The
• Adjustable fixation using gaze tracking (no matter where software automatically locates the blind spot and accordingly
adjusts the location of the test points. The display’s gamma
the patient looks, stimulus can be shown relative to fixation level (luminosity per pixel), contrast, and brightness can
at that moment) be tightly controlled for optimal testing settings. Lens rim
• Can easily test individual eyes without one needing to be artifact can be a problem, with manual calibration required
patched prior to test commencing to ensure all points are visible by the
user. [21]
• Inexpensive
• Light weight
• Either available or in development
• Examples[11]
Vivid Vision
BioFormatix’s virtual eye perimeter
Micro medical device’s palm scan VF 2000
Elisar’s eCloud perimeter
Kasha visual field system
Virtual eye
Imo system (CREWT medical systems, Tokyo Japan)
visuAll
oculus quest
DOS Times - Volume 28, Number 2, March-April 2022 50 www.dosonline.org/dos-times