DOS Times Vol. 26 No. 2

DVolume 26, No. 2 SSeptember-October 2020 For Private Ciruculation Only
TIMES

Highlights
Oculoplasty Issue

Ocular Stevens-Johnson
Syndrome
Targeted Therapy in Orbital
and Periorbital Lesions
Navigation Guided Orbital Surgery:
Better Planning and Greater Control
Retinoblastoma Management - Whats New?
Ocular Plaque Brachytherapy

Official Bulletin Magazine of

DELHI
OPHTHALMOLOGICAL
SOCIETY

Contents

Editorial 38 Entropion and Ectropion: Evaluation and
Management
05 Prof. (Dr.) Namrata Sharma
Hony. General Secretary 45 Contracted Socket
54 Orbital Trauma
06 Dr. Subhash C Dadeya 58 Animal Bites in Periocular Areas
President 61 Recent Updates in the Staging of Ocular and Orbital

07 Dr. Neelam Pushker Tumors
Professor of Ophthalmology 71 Classification Systems in Thyroid Ophthalmopathy
76 Pathology of Intraocular Tumours
Oculoplasty 80 Orbital Implants: An Overview
85 Orbital Fungal Infections
8 Ocular Stevens-Johnson Syndrome 90 Tarsorrhaphy
94 Botulinum Toxin- Therapeutic Uses
Focus
98 Oculoplasty basics: Clinical work up proformas
13 Diagnosis & Management of Acute Bacterial Orbital
Cellulitis

Subspecialities PG Corner

Oculoplasty 105 Orbital Emphysema

15 Targeted Therapy in Orbital and Periorbital Lesions DOS Quiz

20 Navigation Guided Orbital Surgery: Better Planning 108
and Greater Control

24 Retinoblastoma Management - Whats New? Tearsheet
28 Ocular Plaque Brachytherapy
34 Proximal Lacrimal System Obstructions 109 Antibiotics in Orbital cellulitis

02 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

DOS Executive Members 2019-21

DOS Office Bearers

Dr. Subhash C Dadeya Dr. Pawan Goyal Dr. Namrata Sharma Dr. Hardeep Singh
President Vice President Secretary Joint Secretary

Dr. Jatinder S Bhalla Dr. Vinod Kumar Dr. Manav Deep Singh
Treasurer Editor Library Officer

Executive Members

Dr. Dewang Angmo Dr. Jatinder Bali Dr. Shantanu Gupta Dr. C. P. Khandelwal

Dr. Rahul Mayor Dr. Vipul Nayar Dr. Rajendra Prasad Dr. Kirti Singh

DOS Representative to AIOS Ex-Officio Members

Dr. Jeewan S. Titiyal Dr. M. Vanathi Dr. Rakesh Mahajan Dr. Arun Baweja

Volume 26 No. 2, September-October, 2020

DOS Times Editorial Board

Editor In Chief Editorial Board National Board
Namrata Sharma
Dr. Atul Kumar Dr. Parul Icchpujani
Editor Dr. Aniruddha Maiti Dr. Ronnie George
Prafulla Kumar Maharana Dr. Apporva Ayachit Dr. Sushmita Kaushik
Dr. Jitendra Jethani Dr. Gopal Pillai
Assistant Editors Dr. Mita Joshi Dr. Usha Singh
Dr. P. Dutta Majumdar Dr. Subhendu Boral
Dr. Noopur Gupta Dr. Meena Chakrabarti
Dr. Brijesh Kakkar Dr. Raksha Rao
Dr. Digvijay Singh Dr. Kumudini Verma
Dr. Ritika Sachdev Dr. Rashmin Gandhi
Dr. Dewang Angmo Dr. Siddharth Kesarwani
Dr. Rebika Dr. Chaitra Jayadev
Dr. Saurabh Sawhney Dr. Bibhuti P. Sinha
Dr. Reena Sharma Dr. Amit Porwal
Dr. Rajat Jain Dr. Prashant Bawankule
Dr. Jaya Gupta Dr. Arvind Kumar Morya
Dr. Anita Ganger
Ritu Nagpal Sahil Agarwal Dr. Umang Mathur
Dr. Neera Agarwal
Gunjan Saluja Deepali Singhal Dr. Poonam Jain
Dr. Manisha Agarwal
Dr. Hardeep Singh
Dr. Anita Sethi
Dr. Tushar Agarwal
Dr. Rohit Saxena
Dr. Swati Phuljhele
Dr. Vivek Dave
Dr. Mohita Sharma
Dr. Rajesh Sinha
Dr. Ritu Arora
Dr. P.K. Pandey
Dr. H.K. Yaduvanshi
Dr. O.P. Anand

Mohamed Ibrahime Asif Rahul Kumar Bafna

Sohini Mandal Prakhyat Roop

04 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Editorial

From the
Editor’s Desk

Respected Seniors & Dear Friends Prof. (Dr.) Namrata Sharma

Oculoplasty Perspective In Ophthalmology (MD, DNB, MNAMS)

Ophthalmology has been a continuously growing specialty, last few decades Hony. General Secretary
have completely changed the subject with the introduction of microsurgical Delhi Ophthalmological Society
techniques, technological infusion in diagnostics and therapeutics, and division of
subspecialties in ophthalmology. Each of these distinct subspecialties are now on Cornea, Cataract & Refractive Surgery Services
their own trajectory of further evolution. Dr. R.P. Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences (AIIMS)
Oculoplasty is one such sub-specialty that has emerged as a rapidly evolving branch New Delhi
in ophthalmology. Meticulous work is being done in the field to refine the defined
surgical techniques, with an inclination towards non-invasive and simpler methods.

The wide range of oculoplastic surgeries encompasses both emergency surgeries
for trauma and infectious disorders as well as functional and cosmetic eyelid and
facial surgery, nasolacrimal surgery, and complex orbitotomy. The increasing
understanding of the molecular pathways involved in the occurrence and
progression of periocular tumors has given rise to the targeted therapy which has
been found to drastically change the outcomes of the orbital tumors. Similarly,
image-guided surgeries have helped surgeons to overcome the challenges of orbital
surgeries by aiding in real-time monitoring and high-resolution visualization. The
eyelids and periocular area being an important part of the face plays an essential
role in the development of one’s personality, and any facial disfigurement can
cause functional and psychological distress to the patient. New approaches in the
management of patients with congenital disorders such as micro/ anophthalmos
and contracted socket not only improve patient’s appearance but also helps to
solve their functional deficit. Moreover, with evolving times, the paradigm of
management of intraocular malignancies like retinoblastoma is shifting towards
the globe salvage procedures.

Facial aesthetics is another growing field in oculoplasty, the indications of
botulinum toxin have rapidly expanded for a large number of ocular conditions
ranging from facial dystonia to its cosmetic applications.

With the innovations coming up in the field we hope to soon have more cost-
effective, predictable, and non-invasive procedures in the near future.

Prof. (Dr.) Namrata Sharma

(MD, DNB, MNAMS)

Hony. General Secretary
Delhi Ophthalmological Society

www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 05

President’s Editorial

From the
President’s Desk

Respected Seniors & Dear Friends Prof. Subhash C Dadeya

In continuation of our sub-specialty DOS times series with great pleasure we President
introduce this oculoplasty issue of DOS times, which touches all the aspects of the
subject.

DOS times has become an integral part of ophthalmology in Delhi, providing
knowledge, information and updates about the subject in a comprehensive way.

The aim of DOS times is to give a platform for the residents, and authors as well as
to provide rich scientific content to our readers.

The issue covers expert opinions, PG corner, review articles, recent trends, and DOS
times quiz, a complete package for keeping everyone update.

I would like to congratulate our dynamic secretary and editor in chief Prof. Namrata
Sharma, and the editorial team for coming up with this concept of sub-specialty
series of DOS times and for continuing the work with zeal.

Happy reading

Thank you

Prof. Subhash Dadeya
President, DOS

06 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Guest Editorial

From the
Guest’s Desk

Respected Seniors & Dear Friends Dr. Neelam Pushker

It gives me immense pleasure to write this guest editorial for the DOS Times issue on Professor of Ophthalmology
‘Oculoplasty’. In our constant endeavor to share knowledge, skills and innovations
with our fraternity, this issue brings out some important and newer aspects in the
field of oculoplasty and ocular oncology. Over the past few decades, there have
been rapid advancements in both surgical and non-surgical methods of treatment
of orbital, periorbital diseases and tumors. In-depth research at a molecular level
has led to better understanding of diseases i.e., the specific molecular structure,
the ‘target’ which implicates in development and progression of a disease. Targeted
therapies have been showing promising results in difficult and challenging areas of
orbital disorders and tumors such as thyroid eye disease, IgG4-related ophthalmic
disease, neurofibromatosis, melanoma and lymphoma. 3D-image reconstruction
and navigation-assisted surgery have gained popularity in orbital surgeries.
This issue also provides the readers insight into the globe salvage treatment
in retinoblastoma and melanoma, updates on staging and treatment of eyelid
malignancies, management of orbital cellulitis and pathology of ocular tumors.
Therapeutic role of botulinum toxin injection, types of orbital implants, eyelid
disorders and other common orbital and adnexal disorders have been discussed.
Complete basic work-up proformas for major oculoplasty-related areas would help
residents in enlisting the differentials and understand the management strategies.
As is evident from the editorial this issue has a variety of multifaceted articles and
one can choose to read as per their field of interest.

Wish you all a happy reading.

Dr. Neelam Pushker,
Professor of Ophthalmology,
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences
New Delhi –110 029, India

www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 07

Subspeciality-Oculoplasty

Ocular Stevens-Johnson Syndrome

Renu Venugopal PhD1, Gunjan Saluja MD2, Rahul Bafna MD2, Praful Maharana MD3, Namrata Sharma MD3
1. Department of Ocular Pathology, 2. Oculoplasty, Tumor & Pediatric Ophthalmology Services, 3. Cornea & Refractive Surgery Services
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences, New Delhi-110029, India

Stevens-Johnson syndrome (SJS) is an the systemic condition of the patient severe dryness of the eye continue
acute exfoliative blistering disorder and ocular management strategies lifelong as ocular sequelae4,5.
of the skin and mucous membranes. aimed at preventing cicatrizing
First described by Lyell (1979) as an sequelae. Aggressive management Clinical Investigations
extraordinary, generalized epidermal to control inflammation in the acute A thorough clinical examination and
eruption, it is accompanied by fever, stage helps in reducing chronic ocular detailed documentation of the onset
inflammation of the buccal mucosa, complications. of the disease is required. The detailed
and severe purulent conjunctivitis in history of onset including the causative
the acute stage1. SJS involves less than OCULAR COMPLICATIONS OF agent (drugs/ infections(antivirals),
10% body surface area involvement STEVENS JOHNSON SYNDROME duration of systemic presentations, time
with at least two mucous membranes. to presentation to the ophthalmologist.
Although SJS is milder compared to Acute stage ocular SJS Assessment of ocular presentation and
its severe variant, Toxic Epidermal During an acute episode of SJS, response to the advised treatment in
Necrolysis (TEN), the etiology, genetic ocular surface inflammation and cases of acute SJS can be done using a
susceptibility and patho-mechanism acute conjunctivitis occur before, or grading scale (Table 1).
are similar for both the SJS and TEN2. SJS simultaneously with skin eruptions4.
and TEN represent two clinical entities Extensive inflammation of the Management in acute stage
within a spectrum of adverse cutaneous ocular surface is accompanied by During the acute stage, widespread
drug reactions. corneal and/or conjunctival epithelial apoptosis on the ocular surface
The condition is mostly triggered defects. In the acute stage, the ocular leads to severe inflammation and a
by drugs; however, this may also be examination reveals the presence of ‘cytokine storm’ in the deep layers
incited by infections and there is also persistent epithelial defects, ulceration, of the epithelium. Controlling the
a genetic susceptibility in some ethnic and perforation. Further, there may destructive inflammation at the
populations. Identification of the be corneal, conjunctival, and eyelid height of the acute phase can prevent
cause of the onset of SJS plays an cicatricial changes which may lead difficult long-term ocular problems. A
important role for patients as in cases to neovascularization, opacification, combination of a topical corticosteroid
of drug-induced disease withdrawal of keratinization and symblepharon and preservative-free lubricant is
the inducing drug have an impact on the formation. Visual impairment and required to protect the ocular surface
patient’s systemic and long term visual
prognosis. Supportive management Table 1: Ophthalmic grading criteria and treatment recommendation for acute SJS6
is crucial to improve the patient’s
state, in addition to specific immune-
modulating treatments. Mortality is
high and increases with disease severity,
patients’ age, and underlying medical
conditions. Survivors may suffer from
long-term sequelae such as strictures
of mucous membranes and severe
eye problems3. Ocular complications
as long-term sequelae of systemic SJS
account for 50 -81% of complications.
The management of SJS/TEN consists of
general measures aimed at improving

08 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Subspeciality-Oculoplasty

in the acute-stage. As lacrimal functions and inflamed. The fusion between the Impression cytology for monitoring
get disrupted in the acute stage due bulbar and fornical surfaces due to limbal stem cell deficiency.
to underlying innate immunological conjunctival ulcerations or conjunctival Ocular Surface Analyser (OSA) /
reaction, it leads to tear film disruption. membrane formation acutely, or Lipiview to monitor the meibomian
This dryness causes patient discomfort persistent inflammation later, causes gland obstruction and lipid layer
and increases photophobia. Adjoining permanent symblepharon and thickness in the tear film.
cicatricial eyelid inflammation disturbs ankyloblepharon. Chronic conjunctival Pentacam helps in the early detection
the corneal surface which is aggravated cicatrization leads to the deformation of of corneal ectasia in SJS.16
due to dryness. Preservative-free the lid margins, which causes entropion, ASOCT in cases with pannus or corneal
lubricants provide symptomatic relief trichiasis, and distichiasis. Scarring scarring assists in monitoring surgical
and also aid in the epithelization of the in fornices and lacrimal gland ducts outcomes.
ocular surface. SJS eyes harbor altered leads to severe aqueous tear deficiency Thirty to 50% of patients with acute SJS
ocular microbial flora which makes increases the risk of corneal damage. go on to develop chronic ocular sequelae,
them more prone to several microbial Chronic meibomitis also disrupts including progressive symblepharon,
infections during this stage7. Topical eyelid hygiene in these cases. Resultant lid margin keratinization, trichiasis,
steroids have a role in the management corneal blindness due to the absence entropion, dry eye syndrome, corneal
of ocular surface inflammation in SJS, of tears, eyelid malpositions, and tarsal pannus, and persistent corneal
but they alone may not be sufficient conjunctival keratinization is the most epithelial defects. Management of
in treating severe cases. Combination dreaded long-term complication among chronic SJS requires routine patient
therapy using immunosuppressants SJS/TEN survivors. follow-ups with a detailed examination
like topical cyclosporine in addition of the position of the eyelids relative
to corticosteroids helps attenuate the Clinical Investigations to the globe, patency of the lacrimal
inflammation and discomfort. Close Cases presenting at chronic stage puncta, the direction of the eyelashes,
monitoring of such cases for corneal require detailed documentation of the status of the meibomian glands, the
infections using Fluorescein staining is history and clinical investigations height of the tear meniscus, quality of
imperative in determining the long-term to evaluate the patient response to the tear film, depth of the fornices and
visual outcome. Systemic steroids also treatment advised. A detailed history presence of symblepharon and presence
help in managing acute cases of SJS by of acute onset of the disease, time to or absence of lid margin and ocular
lowering the immunological pathway. presentation, h/o of infections, any surface keratinization.
Multiple studies have suggested that prior surgery is important to decide on Management also includes long-
amniotic membrane transplantation the way onwards. Assessment of best- term use of lubricating eye drops for
(AMT) is a successful therapy in corrected visual acuity (from Snellen’s dryness and topical steroids depending
the acute phase of SJS which may chart to finger countings calculations), on the state of the ocular surface.
prevent severe scarring of the ocular Schirmer’s test, clinical photograph Scleral contact lenses provide a unique
surface that leads to long-term visual from the first presentation form the environment that ensures an adequate
morbidity.8,9,10,12,13 Sharma et al, basic investigations for chronic SJS supply of oxygen to the ocular surface
advocate that AMT is a useful adjuvant patients. Based on multiple ocular required for the epithelial surface
in addition to conventional medical surface grading systems available, a to heal and repair. Additionally, it
treatment in maintaining visual acuity severity score can be generated which provides the constant presence of fluid
and a stable ocular surface in cases helps objective evaluation in these at the interface and prevents shearing
of acute ocular SJS in a randomized cases (Figure 1,2).5,15 activity between lids and the ocular
control trial.14 surface.17,18,19,20
Other investigations that can be useful
Management in chronic stage in chronic SJS cases include: Surgical management of chronic
In chronic stages, severe dry eye SJS cases
occurs due to abnormality in the Conjunctival swab to identify The consequences of chronic SJS
tear film components and extensive the presence of any unusual like eyelid margin keratinisation,
ocular surface scarring, leading to microorganism7 trichiasis, and metaplastic eyelashes,
a combination of symblepharon posterior lamella shortening, cicatricial
formation, limbal stem cell deficiency, Tear osmolarity helps assess the entropion, symblepharon formation,
and persistent corneal epithelial extent of dryness by detecting tear and limbal stem cell deficiency need to
defects. Keratinization of the posterior concentration indicative of evaporative be managed surgically.
lid margin and the subsequently dry eye in SJS
repeated microtrauma of the cornea
makes it more damaged, vascularized, Tear MMP9 assay (Inflammadry)
to detect the levels of MMP9, an
inflammatory protein in tear.

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Subspeciality-Oculoplasty

Figure 1 Representative images showing the multistep grading system for clinical scoring of corneal complications in chronic ocular sequelae
in Stevens-Johnson syndrome eyes showing corneal parameters. POV [ palisades of Vogt; SPK/CED [ superficial punctate keratitis/corneal
epithelial defect].15

Figure 2. Representative images showing the multistep grading system for clinical scoring for mucocutaneous junction involvement and
conjunctival complications in chronic ocular sequelae in Stevens-Johnson syndrome eyes.15

10 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Subspeciality-Oculoplasty

Management of eyelid margin Symblepharon release sutures and fibrin glue with cardinal
keratinisation A symblepharon is an abnormal sutures have been found to have similar
adhesion between the palpebral and post-operative results. Placement of
A keratinised lid margin can continue bulbar conjunctiva and is predisposed a symblepharon ring keeps the graft
to rub against the corneal surface, by a bare conjunctival surface. In stretched and prevents the recurrence.
leading to further corneal damage and mild grades of anterior symblepharon, Minor salivary gland transplantation
persistent epithelial defects. Therefore, amniotic membrane graft can suffice, (direct oral sub-mandibular parotid
lid margin rotation surgery should be however, in patients with total and gland transplantation) and mucous
planned. The surgical options of various recurrent symblepharon mucous membrane grafting (MMG) (direct oral
lid margin rotation surgeries include membrane graft can be added. mucosal epithelium transplantation)22,23
have both shown to provide long-term
Rotation of terminal tarsus Mucous membrane graft benefits to SJS cases by reducing dryness
In this procedure, the tarsus is cut and Mucous membrane graft (MMG) on the ocular surface and providing
the lower portion is rotated by 180 prevents the recurrence of comfort to the patient.13,24,25
degrees, the posterior lamella is further symblepharon by providing epithelial
advanced, forming a new lid margin. basement membrane support for the Limbal stem cell transplant
growing cells. The labial mucosa is the Limbal stem cell transplantation (LSCT)
Tarsal fracture ideal site for harvesting the graft, due to is used for effective ocular surface
In tarsal fracture, the tarsus is fractured its easy access and simple harvesting. reconstruction after symblepharon,
horizontally and hinged with the and conjunctivalized pannus excision
everting sutures. Full-thickness mucous membrane grafts to allow corneal epithelialization.21
have less post-operative contracture and Cultivated and conventional LSCTs
A horizontal incision is made in the are commonly performed. The first step have both been attempted in SJS but the
whole width of the tarsus just below is to dissect the scar tissue, following results obtained have not been able to
its center, and to expose the pretarsal which fornix-forming sutures are show sufficient improvement in visual
muscle. The anterior tarsal surface is passed with the help of 4-0 silk suture. acuity due to persistent dryness. Basu
freed from the pre-tarsal muscle, and The size of the defect is then measured et al reported that timely surgical and
three 4-0 double-armed silk sutures are with the help of blotting paper to get an conservative treatment in children with
passed, from the lower fragment of the approximate size of the graft. The donor severe ocular presentations improves
tarsus and then returning through the site is cleaned with povidone-iodine, visual acuity.26
skin, below the lash line. The everting the size of the graft is marked with the
sutures are tied to overcorrect, allowing help of the blotting paper. The donor Cultivated oral mucosal epithelial
the tarsus to heal, granulate and site is infiltrated with lignocaine which transplantation (COMET) involves the
contract. Thus, pulling the lid margin also helps to create a plane of dissection. transplantation of cultivated autologous
against the globe. The incision is made along the marking excised oral mucosal epithelium
with the help of 15 no. blade, and the over 2 weeks. The autologous nature
Wedge resection dissection is performed with the help of this procedure removes the need
Wedge resection can be planned in of conjunctival scissors. Care must be for immuno-modulatory topical
patients without posterior lamella taken to avoid damage to the frenulum, medications in cases of SJS. COMET has
shortening and lagophthalmos. and the vermilion lid margin, similarly been regarded as one of the most useful
while harvesting the graft from the methods of surgical management of
In patients with entropion associated buccal mucosa Stenson’s duct must chronic SJS cases so far.27,28,29
with shortening of the posterior lamella, not be damaged. The graft should be
as evident on lagophthalmos, mucous harvested as thin as possible. The donor Allogenic Simple epithelial stem cell
membrane graft should be added along site is then cauterized and in the post- transplant (SLET) has been described in
with excision of the keratinised margin operative period patient is advised patients with SJS syndrome.30
strip and rotation sutures. betadine gargles along with systemic
antibiotics, patient can also be asked to Cataract surgery in SJS
Management of trichiasis and metaplastic opt for a liquid diet till the wound heals. Prolonged use of steroids in SJS patients,
eyelashes After harvesting, the graft can be placed predispose them for the development
Trichiasis eyelashes, can be managed on the index finger to carefully dissect of cataract, further deteriorating the
to be electrolysis or by anterior lamella the sub-mucosal fat from the graft with vision. Post-cataract surgery persistent
excision. Metaplastic eyelashes are the help of Westcott scissors. The graft epithelial defects, corneal abscess
managed by electrolysis of the lid is placed on the bed and can be either formation, poor intra-operative
margin position is normal. But in sutured with a 6-0 polyglactin suture or visibility due to the corneal opacities are
patients with abnormal lid margin fixed with the help of fibrin glue. Both some of the challenges in performing
position, entropion surgery is combined the cataract surgery of SJS patients.
with electrolysis.

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Subspeciality-Oculoplasty

Trichiasis eyelashes, entropion, and 11. Ciralsky J.B., Sippel K.C., Gregory D.G. Freitas D, Gomes JÁ. Minor salivary
keratinised lid margins must be taken Current ophthalmologic treatment glands and labial mucous membrane
care of before the surgery.31 strategies for acute and chronic Stevens- graft in the treatment of severe
Keratoprosthesis has been used as the Johnson syndrome and toxic epidermal symblepharon and dry eye in patients
last resort in end-stage corneal blindness necrolysis. Curr Opin Ophthalmol. 2012,
in SJS chronic ocular sequelae. 24:321-8. with Stevens-Johnson syndrome. Br J
Ophthalmol. 2012 Feb;96(2):234-9.
References 12. Ma K.N., Thanos A., Chodosh J. et
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2016 Aug;123:1653-1658. et al. Clinical Outcome of Autologous
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Center. Cornea. 2016 ;35:1117-21. et al. Boston ocular surface prosthesis: an 30. Shanbhag SS, Patel CN, Goyal R,
8. Shammas M.C., Lai E.C., Sarkar J.S. Indian experience. Indian J Ophthalmol. Donthineni PR, Singh V, Basu S. Simple
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membrane: a review of 10 consecutive Medical applications of scleral contact Stevens-Johnson syndrome: aspects
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10. Hsu M, Jayaram A, Verner R. Indications cases. Cornea.1995, 14:121e9 Nov;100(11):1542-1546.
and outcomes of amniotic membrane
transplantation in the management 21. Tsai RJ, Tseng SC. Human allograft Corresponding Author:
of acute stevens-johnson syndrome
and toxic epidermal necrolysis: a case- limbal transplantation for corneal Prof. (Dr.) Namrata Sharma, MD
control study. Cornea. 2012, 31:1394- surface reconstruction. Cornea. 1994;13: Cornea & Refractive Surgery Services
402. 389-400. Dr. Rajendra Prasad Centre for Ophthalmic
22. McCord CD Jr, Chen WP. Tarsal polishing Sciences, All India Institute of Medical
and mucous membrane grafting for Sciences, New Delhi-110029,India
cicatricial entropion, trichiasis and
epidermalization. Ophthalmic Surg.
1983;14(12):1021-5.
23. Iyer G, Pillai VS, Srinivasan B, et al.
Mucous membrane grafting for lid
margin keratinization in Stevens–
Johnson syndrome: results. Cornea. 2010
Feb;29(2):146-51
24. Sant’ Anna AE, Hazarbassanov RM, de

12 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Focus

Focus
Diagnosis & Management of
Acute Bacterial Orbital Cellulitis

Prof. M.S. Bajaj Prof. M.S. Bajaj, Professor of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of
Prof. A.K. Grover Medical Science, New Delhi, India.
Dr. A K Grover, MD (AIIMS), MNAMS, FICO, FAICO, FRCS (Glasgow) - Oculoplasty (Awarded Padma Shri)
Consultant, Sir Ganga Ram Hospital (SGRH), Delhi
Chairman at Vision Eye Center and chairman for the department of Ophthalmology
Sir Ganga Ram Hospital in Delhi

Q1. What would you like to emphasize in basic workup of a case of orbital cellulitis?
M.S. Bajaj : A meticulous ophthalmic examination, including visual function, should be carried out.
The patient may present with severe eyelid oedema, decreased visual acuity, pain on ocular movement
with decreased extraocular motility, proptosis and posterior segment venous congestion. There may be
a history of acute sinusitis or upper respiratory tract infection or trauma preceding the development of
oedema. Samples of conjunctival discharge, eyelid lesions, and lacrimal sac material should be sent for
culture and sensitivity.
The evaluation should encompass systemic examination, including an assessment of routine vital
signs, complete hemogram, blood sugars, liver and renal function tests should be performed. In case of a
suspected systemic infection, blood and urine cultures should be obtained. In case of non-responders to
medical management, a workup for the immunocompromised state should be done.
Sinorbital imaging, usually by a CT scan, provide imaging of the orbital contents and paranasal
sinuses, any extension of disease posteriorly, identification of concurrent sinus or intracranial disease,
and detection of the presence of orbital and subperiosteal abscesses. However, its use should be limited
and not routinely used to differentiate preseptal from orbital cellulitis.
A.K. Grover: It is vital to examine for any of the earliest signs of visual compromise. It is also essential
to monitor for any clues for etiology (sinus infection/systemic infection / immune-compromised status).
Imaging may be necessary where an abscess is suspected.

Q2. What is your antibiotic of choice for such patients?
M.S. Bajaj : In cases of mild preseptal cellulitis, treatment is typically rendered on an outpatient basis
with oral antibiotics like moxicillin-clavulanic acid to cover both Gram-negative and Gram-positive
organisms.
Patients showing no response or clinical deterioration should be promptly transitioned to intravenous
antibiotics; ceftriaxone and vancomycin. For better anaerobic coverage, metronidazole is typically
concurrently administered especially in a macerated wound or crush injuries, contaminated foreign
bodies and suspected, dental source of infection. Where available, consultation with the infectious
disease service may be valuable.
A.K. Grover : Antibiotics are chosen to cover a broad spectrum of micro organisms-Gram positive,
Gram negative and anaerobic organisms. A special attention is also given to ensure coverage of MRSA. A
common combination is intravenous Clindamycin / Vancomycin + 3rd generation cephalosporin (Such
as Ceftriaxone (Monocef) + Metronidazole.

Q3. How doyou monitor for the clinical response and adverse effectsto intravenous drugs?
M.S. Bajaj : Patients with severe orbital cellulitis often follow a protracted course, and careful
monitoring of clinical response is crucial. Patients are ideally monitored by an ophthalmologist, ENT
specialist, and infectious disease specialist until symptoms, fever, blood count, and imaging confirm that
antibiotics can be discontinued.

www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 13

Focus

Depending of which intravenous responding or deteriorating on medical proptosis and ptosis are also frequently
antibiotics have been prescribed, liver therapy (displaying worsening of seen.
and renal function test every third day visual function/pupillary changes)
is performed. or developing an orbital abscess, Q7. How has attending and
especially in those cases with orbital managing such patients in
A.K. Grover : Most important is the apex, cavernous sinus involvement or COVID19 era been different?
monitoring of clinical signs- especially intracranial extension. In older patients
if no clinical response is noted in with completely opacified sinuses, M.S. Bajaj : In addition to the
2-3days. One also needs to be constantly surgical drainage may be considered to standard operating procedures
looking for any systemic deterioration. facilitate the resolution of infection. prescribed for attending to patients
Children older than 9 years of age during the pandemic, emphasis
with a subperiosteal abscess need to A.K. Grover : A surgical should be given to maintaining strict
be watched carefully, to see if they intervention is needed if patient fails hand hygiene, changing of bed sheets
would need a surgical intervention. to respond in 48 hours, deteriorates after every course of intravenous
Paediatric patients need to be under clinically, afferent papillary defect administration etc., helping both
the supervision of a physician to look appears, visual acuity shows a sign of patients (hospitalized as well as day-
both at the systemic condition and any compromise or develops an abscess. care) and health care professionals
possible antibiotic toxicity. However, most cases of abscess, to prevent any unwanted spread of
especially in children < 9 years, can COVID-19, especially as these patients
Q4. What, by your experience, often be treated conservatively. may be immunocompromised.
are the indications for oral steroids
in a case of orbital cellulitis? Q6. What are the possible During the early course of infection,
complications in bacterial orbital the appearance of fever in such patients
M.S. Bajaj- : The use of oral steroid cellulitis that you have come has been a challenge to differentiate and
in the setting of orbital cellulitis is across in your practice? get their evaluation done including RT
somewhat controversial. It may possibly PCR for SARS CoV2, where adequate
worsen the disease process. However, M.S. Bajaj: Orbital cellulitis can evidence of exposure was found.
with adequately controlled infection, its result in orbital and intracranial
use, in conjunction with an antibiotic, complications. Subperiosteal or orbital For patients with a positive RT PCR
may prove to be beneficial in sight- abscess formation may occur, while for COVID-19, found prior to or during
threatening situations. Traditionally permanent vision loss may result from the course of treatment, a separate
systemic steroids are not initiated until corneal damage secondary to exposure isolation ward was formed at the centre
the patient improves with antibiotic or neurotrophic keratitis, destruction for the provision of inpatient medical/
or surgical intervention. It decreases of intraocular tissues, secondary surgical management.
periorbital congestion and mucosal glaucoma, optic neuritis, or central
oedema and levels of inflammatory retinal artery occlusion. Blindness A.K. Grover : A COVID test, usually
cytokines in the sinus mucosa of also may occur secondary to elevated RT-PCR is carried out in all hospitalized
patients. In cases of a subperiosteal intraorbital pressure or the direct patients as a routine, otherwise the
abscess, decreasing the inflammatory extension of infection to the optic nerve management of orbital cellulitis in
component may facilitate draining and from the sphenoid sinus. COVID 19 era has been essentially the
resolution of sinusitis. same. Surgical intervention, where
At our centre we have seen cases of needed, is an emergency and must be
A.K. Grover : Adjuvant systemic orbital cellulitis presenting late with done.
steroid are used after observing the loss of vision, subperiosteal or orbital
initial response to antibiotics. They abscess, cavernous sinus thrombosis, Corresponding Author:
help hasten resolution of inflammation meningitis, frontal abscess and
and recovery with reduced chance of osteomyelitis, and systemic sepsis. Dr. Sahil Agrawal, MD
residual ptosis, proptosis or ocular Oculoplasty, Tumor & Pediatric
motility restriction. A.K. Grover : Orbital cellulitis Ophthalmology Services,
can never be taken lightly. I have seen Dr. R. P. Centre for Ophthalmic Sciences,
Q5. When would you like to cases which developed loss of vision All India Institute of Medical Sciences,
drain an orbital abscess and do a due to exposure keratopathy or optic New Delhi, India
sinus debridement? nerve compression, or an intracranial
infection with a fatal result. Residual
M.S. Bajaj : Surgical intervention problems of ocular motility restriction,
should be considered in patients not

14 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Subspeciality-Oculoplasty

Targeted Therapy in Orbital and
Periorbital Lesions

Neelam Pushker MD, Sujeeth Modaboyina MD
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Over the past few decades, there has for TED generally depend on disease and specificity to IGF-1R, inducing
been a significant improvement in the activity and severity. Intravenous internalization and degradation of the
understanding of molecular aspects and methyl prednisolone is used as the first- antibody-receptor complexes. In vitro
pathways involved in occurrence and line treatment for active moderate – studies showed that teprotumumab
progression of autoimmune diseases very severe TED which reduces edema attenuates TSH-mediated cytokine
and cancers. With advancement and orbital inflammation but does not production by reducing IGF-1R and
and challenges of chemotherapy modify the disease course. Coupling TSH-R cell surface expression.1 Further, it
and immunotherapy, the emerging of steroids with immunomodulators, attenuates IGF-1R and TSH-R–mediated
treatment landscape of targeted azathioprine or mycophenolate mofetil signaling, hence reduces hyaluronan
therapies has been identified as novel is indicated in resistant cases or patients production and cytokine stimulation
targets and development of targeted intolerant to steroids. by orbital fibroblasts, reducing orbital
therapies. Molecularly targeted or hyaluronan accumulation and muscle
targeted therapy is one of the major Targeted Therapy: expansion and also adipogenesis.
modalities that use drug designed to
aim the specific molecular structure, Various studies conducted at the In January, 2020, the U.S. Food and
the ‘target’, implicated in development molecular level have demonstrated Drug Administration (FDA) approved
and progression of a disease without over-expression of thyroid-stimulating teprotumumab (brand name Tepezza)
affecting normal cells. Targeted therapy hormone (TSH) receptors and insulin- for the treatment of adults with
has high specificity for the molecules like growth factor – 1 receptors (IGF-1R) active moderate to severe thyroid eye
involved in key molecular events that by orbital fibroblasts (key target cells) disease. Approval of this breakthrough
is responsible for phenotypic changes that act as autoantigens, stimulated by therapy was based on randomized,
such as abnormal cell growth, survival, the pathogenic autoantibodies known as double-masked, placebo-controlled,
invasion, metastasis, apoptosis, cell- thyroid-stimulating immunoglobulins. multicenter trials conducted in United
cycle progression, inflammation, These autoantibodies can be detected in States and Europe, on patients with
and angiogenesis. The mechanism most persons who have Graves’ disease active moderate – severe TED. These
of action of targeted therapy is more with or without ophthalmopathy. studies concluded that teprotumumab
effective, less toxic and better tolerated Orbital fibroblasts start the cascade for resulted in better outcomes with
than the traditional therapy. Use of production of cytokines (IL-6, IL-12, IL- respect to proptosis, clinical activity
targeted therapy has markedly changed 17, IFN-c, and TNF-a), and hyaluronan score, diplopia, and quality of life than
outcomes of some of the orbital (gylcosaminogylcan), which leads to soft placebo. Serious adverse events were
inflammatory diseases and tumors. tissue inflammation and thickening of uncommon.2,3 Patients received eight
extraocular muscles. Orbital fibroblasts intravenous infusions, one every 3
Thyroid Eye Disease also have varied phenotypic properties weeks starting with an initial dose of
and can differentiate into adipocytes 10 mg per kilogram of body weight,
Thyroid eye disease (TED) is a complex and myofibroblasts resulting in followed by 20 mg per kilogram for the
autoimmune disease characterized by adipogenesis and fibrosis, respectively remaining seven infusions. In the study
orbital inflammation, enlargement of in TED. published in 2017, Smith et al reported
extraocular muscles and fat, and fibrosis that 29/ 42 patients who received
of tissues. It is a sight-threatening Teprotumumab: teprotumumab (69%), as compared to 9/
condition that markedly affects the 45 patients who received placebo (20%),
quality of life also. Treatment options Teprotumumab, an IGF-1R inhibitory had a statistically significant response
antibody, binds with high affinity

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Subspeciality-Oculoplasty

at week 24. Also, 69% of the patients group (58%).7 Common side effects Targeted therapy:
who received teprotumumab had a noticed were headaches and infections.
clinical activity score of 0 or 1 at week Infliximab and adalimumab, anti-tumor Rituximab is a monoclonal therapeutic
24, as compared to 21% of the patients necrosis alpha agents have been used as antibody against CD20 B cell
who received placebo. Forty percent an off label drugs in sight threating and lymphocytes, and appears to be an
patients who received the drug had a inflammatory stage TED.8,9 There was effective agent as both induction and
reduction of 4 mm or more in proptosis improvement in CAS, vision, diplopia maintenance therapy.12 The mechanism
as compared with 0 % in placebo group. and pain in the patients (60% showed behind re-activation of IgG4-RD
The only drug mechanism-related reduction in inflammatory score) on has been hypothesized to be active
adverse event was hyperglycemia in adalimumab.9 antigen presentation of B lymphocytes.
patients with diabetes.2 In another Rituximab is effective in part because
study published in 2020, Douglas et al IgG4-Related Ophthalmic it depletes B lymphocytes, preventing
reported, reduction of 2 mm or more in plasma cells from producing IgG4. It is
proptosis was seen in 83% (34 patients) Disease (IgG4-ROD) initiated as a second or third line therapy
in the study group as compared to 10% and clinical response is seen in 87.5%
(4 patients) in placebo. All secondary IgG4-related disease (IgG4-RD) cases of IgG4-ROD and 97% in systemic
outcomes i.e., clinical activity score, is a chronic fibro-inflammatory diseases.11,13 With limited available data,
diplopia response and quality of life disorder characterized by elevated it is suggested that 2 doses of rituximab
score were significantly better with concentrations of serum IgG4 and (1 g for two doses, 2 weeks apart), is
teprotumumab than with placebo. infiltration of IgG4-expressing followed by the maintenance therapy
Two serious events occurred in the plasma cells in the affected organs. at 6 months interval (3 -4 times). This
teprotumumab group, of which one Though the exact patho-mechanism can be considered to prevent relapses.14
(an infusion reaction) led to treatment is still not clear but it seems to result Compared to other treatments
discontinuation.3 Other side effects due to immunomodulation. It can modalities, rituximab is an efficient
observed were muscle spasms, nausea, affect a wide range of organs and has therapy for patients with refractive
alopecia (hair loss), diarrhea, fatigue, a propensity to involve glandular IgG4 RD.12
hyperglycemia (high blood sugar), structures such as lacrimal gland,
hearing loss, dry skin, dysgeusia (altered salivary gland and pancreas. Orbital Infliximab, a chimeric monoclonal
sense of taste) and headache.2 involvement constitutes about 5 % antibody against TNF-α, has been
of non-thyroid orbital inflammatory reported to be successful in cases
Other Targeted Therapies: diseases.10 Systemic corticosteroids resistant to standard treatment.15
Rituximab, a humanized chimeric remain the first line of therapy.
monoclonal antibody that targets Induction therapy is given in the form Abatacept, a cytotoxic T lymphocyte-
CD20 on B cells has been considered of oral prednisolone, 0.5 – 1.0 mg/kg associated antigen fusion protein,
as a potential treatment for TED. or equivalent for 2 -4 weeks followed which acts as a negative regulator of
Role of rituximab (1gm biweekly by tapering the dose by 10% every 2 CD28-mediated T cell activation, is also
for 2 infusions) alone seems to be weeks up to a final maintenance dose emerging as steroid sparing therapy for
controversial, as observed in two of 5-10 mg per day for 3 – 6 months. IgG4-RD.16
different randomized controlled trials The relapse rate on tapering or
where no therapeutic benefit was found discontinuation of steroids is seen in Other treatment modalities:
in one study, whereas the other study two-third patients.11 In patients with
showed 100% response.4,5 In a recent relapse or those intolerant to steroids, In single organ involvement, surgical
study, authors reported limited and disease modifying anti-rheumatic excision or resection of involved part
partial improvement with rituximab. drugs (DMARDs), or steroid sparing along with short course of oral steroids
Disease inactivation was found in 50% drugs are preferred for 1 – 2 years, in can be considered.12 Radiotherapy
of patients with moderate to severe consultation with rheumatologist, to has also shown satisfactory results
Graves’ orbitopathy.6 Tocilizumab, prevent relapses. An initial short course in limited number of patients with
an interleukin-6 (IL-6) receptor of low dose steroids might be needed refractory disease. Spontaneous
monoclonal antibody, have been found along with immunosuppressant to resolution has been documented in
to reduce inflammation in patients control the inflammation. DMARDs about 30% of IgG4-RD.17
unable to tolerate glucocorticoids. A used are immunosuppressants
recent randomized controlled trial such as azathioprine (2 mg/kg/day), Orbital & Conjunctival
showed toclizumab to be effective in mycophenolate mofetil, (1 g twice a day Lymphomas
reducing CAS by ≥2 points at week 16 in up to a maximum dose of 2.5 g/day),
93.3% patients compared to the placebo or methotrexate (15mg – 25 mg per Rituximab:
week).12
Majority of orbital and conjunctival
lymphomas are of B-cell origin (~ 95%),

16 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Subspeciality-Oculoplasty

of which extranodal marginal zone Melanoma: Dabrafenib and trametinib is the first
BRAF and MEK inhibitor combination
B-cell lymphoma or mucosa-associated The standard treatment of conjunctival which got the FDA approval (2018) for
melanoma (CM) is wide-surgical treatment of patients with advanced
lymphoid tissue (MALT) conjunctival excision with cryotherapy of BRAFV600 mutated melanoma. Till
conjunctival margins and base. date, the clinical trials have been
lymphoma is the most common subtype, Incisional biopsy and excision without on cutaneous melanomas in which
adjuvant therapy are associated conjunctival melanomas were not
followed by follicular lymphoma, with poor outcomes in patients with included. There are few reports on the
CM. Genetic studies on CMs have efficacy of BRAF/MEK inhibitors for
diffuse large B-cell lymphoma, and shown mutation of BRAF (of which BRAF mutated advanced (unresectable/
~ 90% were V600E) in 29%-50%, and metasatatic) CMs with encouraging
mantle cell lymphoma.18 The low grade NRAS in ~ 20%.22,23 Though rates are results.24,25
similar to those found in cutaneous
lymphomas are MALT and follicular melanoma but seem to be distinct from Neurofibromatosis
uveal melanomas, in which somatic Neurofibromatosis type-1 is an
lymphomas and high grade lymphomas mutations in GNAQ or GNA11 are autosomal dominant genetic disorder.
frequently detected. BRAF mutated CMs There is mutation of a gene on
are diffuse large B-cell lymphoma, and are commoner in younger population, chromosome 17 that is responsible
bulbar location, and have been found for the production of a protein, called
mantle cell lymphoma. For unilateral to be associated with more distant neurofibromin, a tumor suppressor
metastasis despite a more favorable protein. Dysfunction in neurofibromin
low grade lymphomas, low dose bulbar location. protein leads to over expression of RAS
pathway. RAS-RAF-MEK-ERK signaling
external beam radiotherapy is given as The mitogen-activated protein kinase pathway is an oncogenic pathway
(MAPK) pathway, consisting of RAS/ (MAPK) that plays a significant role
it results in excellent response. Over RAF/MEK/ERK is a RAS-RAF-MEK- in mediating cellular physiological
ERK oncogenic signaling pathway activities, such as proliferation,
the past two decades, for patients with that can transfer extracellular signals, differentiation, apoptosis, and
including hormones, cytokines, and senescence. Its activation is known to
bilateral orbital involvement and/ or growth factors, to the nucleus, thus cause uncontrolled cell proliferation
changing gene expression in the cell and and tumorogenesis. MEK is a MAPK
associated systemic lymphomas or mediating proliferation, differentiation, (mitogen activated protein kinase)
survival, and apoptosis. BRAF, a proto‐ that activates a MAPK (ERK), the
high grade lymphomas, a combination oncogene, is one of the three members final kinase in the RAS-RAF-MEK-
of the RAF family. BRAF mutations ERK signaling pathway in several
of Rituximab, the most common anti- enhance the expression of the MAPK tumors. Oral selumetinib, is a MEK 1/
signaling pathway and are thus related 2 inhibitor, that got FDA approval in
CD20 monoclonal antibody, with CHOP to the occurrence and development April 2020 for the treatment of pediatric
of various malignant tumors. NF-1 inoperable patients with age
(cyclophosphamide, doxorubicin, Vemurafenib, is the first molecularly more than 2 years.26 It is given as oral
targeted (BRAF inhibitor) therapy to be medication in dose of 25mg per square
vincristine, and prednisone) or rarely licensed (2011) in the US and Europe meter of surface area twice a day in a
for the treatment of advanced BRAF 28-day cycle on a continuous dosing
CVP (cyclophosphamide, vincristine, V600E mutation-positive cutaneous schedule. In the initial phase-1 trial,
melanomas. A combination of BRAF 71% of patients showed partial clinical
and prednisone) regimen is used for inhibitor plus MEK inhibitor has shrinkage (> 20%) of the lesion.27 A
demonstrated advantage over BRAF similar response (70%) was seen on
better response and overall survival than inhibitors alone, especially in terms subsequent phase-2 study, where the
of development of resistance with treatment was given for a median of
chemotherapy alone. Radiotherapy is BRAF inhibitors alone. BRAF and 36 cycles.28 A recent, prospective case
MEK inhibitors block the activity series on oral selumetinib, showed
given, if indicated. Two pilot studies of the V600E and V600K mutations, more than 20% reduction in size of
respectively, and its combination is plexiform neurofibroma in16/17 (94%)
have reported the successful treatment now standard of care for advanced/ tumors. Minor side-effects such as acne,
metastasized cutaneous melanomas.
of intralesional injection of Rituximab

in primary conjunctival MALT

lymphoma; however, its long-term

effects are not yet known.19.20 A recent

retrospective study on intralesional

rituximab (50mg in 5ml) in low-grade

conjunctival mostly MALT lymphomas,

has shown complete and partial

response in 73% and 27%, respectively

(n=15). At monthly intervals, 2-3

injections were given subconjunctivally

around the tumor. The mean follow-up

was 37 months. Only one patient who

had mantle cell lymphoma developed

recurrence four years later.21

Depending on the clinical and
histological type and staging, age of the
patient and relapses, there are multitude
of other molecular drugs that have
been used, in patients with systemic
lymphoma such as bendamustine
(alkylating agent), copanlisib (P13
kinase inhibitor) and lenalidomide
(immunomodulatory drug).

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Subspeciality-Oculoplasty

mucositis, diarrhoea, etc were reported. Thompson EHZ, Perdok R, Fleming disease in the eye and ocular adnexa. Curr
Selumetinib should be withheld, dosage JC, Fowler BT, Marcocci C, Marinò M, Opin Ophthalmol. 2017 Nov;28(6):617-
reduced, or permanently discontinued Antonelli A, Dailey R, Harris GJ, Eckstein 622.
based on the severity of adverse A, Schiffman J, Tang R, Nelson C, Salvi
reactions.29 M, Wester S, Sherman JW, Vescio T, 13. Carruthers MN, Topazian MD,
Holt RJ, Smith TJ. Teprotumumab Khosroshahi A, et al. Rituximab for
Orbital Necrobiotic for the Treatment of Active Thyroid IgG4-related disease: a prospective,
Xanthogranuloma Eye Disease. N Engl J Med. 2020 Jan open-label trial. Ann Rheum Dis. 2015
Necrobiotic xanthogranuloma is 23;382(4):341-352. Jun;74(6):1171-7.
a rare sub-type of non-Langerhans
cell histiocytosis seen in adults. 4. Stan MN, Garrity JA, Carranza Leon 14. Campochiaro C, Della-Torre E,
Histopathologically, it is characterized BG, Prabin T, Bradley EA, Bahn RS. Lanzillotta M, et al. Long-term efficacy
by foamy histiocytes (xanthoma cell), Randomized controlled trial of of maintenance therapy with Rituximab
B lymphocytes, giant cells, necrobiosis rituximab in patients with Graves’ for IgG4-related disease. Eur J Intern
(collagen degeneration). Few case orbitopathy. J Clin Endocrinol Metab. Med. 2020 Apr;74:92-98.
reports are available on successful 2015;100(2):432–441.
outcome of Rituximab in patients with 15. Karim F, Paridaens D, Westenberg LEH,
xanthogranuloma showing strong 5. Salvi M, Vannucchi G, Curro N, et Guenoun J, et al. Infliximab for IgG4-
expression of CD-20 positive B cells on al. Efficacy of B-cell targeted therapy Related Orbital Disease. Ophthalmic
immunohistochemistry.30 with rituximab in patients with active Plast Reconstr Surg. 2017 May/Jun;33(3S
moderate to severe Graves’ orbitopathy: Suppl 1):S162-S165.
In conclusion, advancement in a randomized controlled study. J Clin
technology and ongoing molecular- Endocrinol Metab. 2015;100(2):422–431. 16. Akiyama M & Takeuchi T (2018): IgG4-
based research have led to better related disease: beyond glucocorticoids.
understanding of the cellular 6. Eid L, Coste-Verdier V, Longueville Drugs Aging 35: 275–287.
mechanisms that control the tumor/ E, Ribeiro E, Nicolescu-Catargi B,
disease development and progression. Korobelnik JF. The effects of Rituximab 17. Lokdarshi G, Pushker N, Bajaj MS.
This has further helped in the on Graves’orbitopathy: A retrospective Sclerosing Lesions of the Orbit: A
development of newer and better study of 14 patients. Eur J Ophthalmol. Review. Middle East Afr J Ophthalmol.
targeted drugs, when administered 2020 Sep;30(5):1008-1013. 2015 Oct-Dec;22(4):447-51.
either solely or in combination with
established therapy leads to better 7. Perez-Moreiras JV, Gomez-Reino JJ, 18. Olsen TG, Heegaard S. Orbital
clinical response and overall survival. lymphoma. Surv Ophthalmol. 2019 Jan-
High cost and unavailability of some Maneiro JR, et al. Efficacy of tocilizumab Feb;64(1):45-66.
of these drugs are major limitations.
Administration of targeted therapy in patients with moderate-to-severe 19. Savino G., Battendieri R., Balia L., et
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Patients need regular monitoring and orbitopathy: a randomized clinical trial. Cancer Science. 2011;102(8):1565–1567.
follow-up for the response and side-
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BRAF Mutant Metastatic Conjunctival 2020 Apr 9;382(15):1430-1442. Dr. R. P. Centre for Ophthalmic Sciences,
Melanoma. Front Oncol. 2019;9:232. All India Institute of Medical Sciences,
29. Baldo F, Grasso AG, Cortellazzo Wiel New Delhi, India
25. Dagi Glass LR, Lawrence DP, Jakobiec L, et al. Selumetinib in the Treatment
FA, Freitag SK. Conjunctival melanoma of Symptomatic Intractable Plexiform
responsive to combined systemic BRAF/ Neurofibromas in Neurofibromatosis
MEK inhibitors. Ophthalmic Plast Type 1: A Prospective Case Series with
Reconstr Surg. (2017) 33:e114–6. Emphasis on Side Effects. Paediatr
Drugs. 2020 Aug;22(4):417-423.
26. 1. Markham A, Keam SJ. Selumetinib:
First Approval. Drugs. 2020 30. Sagiv O, Thakar SD, Morrell G,
Jun;80(9):931-937. Tetzlaff MT, Esmaeli B. Rituximab
Monotherapy Is Effective in Treating
27. Dombi E, Baldwin A, Marcus LJ, Orbital Necrobiotic Xanthogranuloma.

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Subspeciality-Oculoplasty

Navigation Guided Orbital
Surgery: Better Planning and
Greater Control

Kasturi Bhattacharjee1 MS, DNB, FRCSEd, FRCS (Glasg), Mohit Garg1, Ankit Ahir1, Harsha Bhattacharjee2
1. Departments of Orbit, Ophthalmic Plastic and Reconstructive Surgery, 2. Ocular Trauma and Vitreo Retina Surgery
Sri Sankaradeva Nethralaya, Guwahati, Assam, India

Surgical management in case of process by enabling accurate planning, stereotactic surgery by David Roberts in
orbital pathologies is difficult owing evolving safer and less invasive 1990s. The current technology involves
to confined and crowded space and procedures and enabling more daring either electromagnetic system or an
poor visualisation1. Even though approaches. The synergy between the optical system which is highly accurate.
conventional surgical techniques have surgeon and the machine has unlocked It helps the surgeon in thorough
borne good results, the surgeons face tremendous potential. planning, find a specific anatomical
a myriad of problems while operating target, avoid risky locations and have a
in many complex scenarios. With In order to understand anything better intra-operative orientation of the
the advent of Image guided surgery, completely we have to delve a little into instrument.
the surgeon can now overcome a history and understand its evolution.
number of these challenges. Extensive The discovery of X-rays by William The use of Image Guided Surgery (IGS)
planning, real time monitoring and Roentgen in 1895 enabled us, for the has spilled over from neurosurgery to
high-resolution visualisation has first time, to see inside the human other specialities and Ophthalmology
improved surgical outcomes and body without opening it. However, is one branch where this technology
decreased operating time. Many X-rays being 2D images could not help has found a suitable role. Orbital
questions in a surgeons mind such as localise the area of interest precisely. surgeries are challenging due to limited
“Where (anatomical location) do I have With the growth in the computational space, crowded vital structures and
to go?”, “how to go there?”, “Where is power it became possible to create 3D difficult illumination. In cases where
my instrument presently”, “What lies reconstruct from 2D images. In 1970’s, the anatomy is distorted due to trauma,
ahead” etc can be answered using this Sir Hounsfield introduced the world the surgical complexity is further
technology2. In this article we attempt to “computerised axial tomography.” compounded. In such cases, the use of
to explain, in brief, the technology, This machine was able to take multiple image guided surgical systems has the
it’s history, it’s need and the principle axial scans of the human body in order potential to deliver better results. With
behind it along with its potential use in to create a 3D construct. This along real time tracking, the surgeon can be
ophthalmology. with the development of computer sure of the anatomical location and
vision lead to a significant leap in the operate with a greater confidence and
The History evolution of a stereotactic system for lead to lesser number of complications.
navigation during surgery.
Technology has been the greatest driver The Hardware
of progress of the human civilisation Initially sought after by neurosurgeons,
in the recent past. It has completely various attempts were made in order Armamentarium for IGS includes:
transformed the way we live our to access the intracranial space and
lives. Medicine and surgery have also accurately tag the target tissue during 1. Imaging modality
greatly benefited from technological surgery. The journey was long and
advances leading to better patient care began with the advent of a fixed 2. Software for planning
and improved therapeutic outcomes. frame stereotactic surgery. But this
Navigation in surgery is one of the technology suffered from a number of 3. Navigation guided surgical
examples of how surgery has benefitted drawbacks such as limited field of view, workstation: either optical or
from scientific advancement. It has patient’s discomfort etc. which were electromagnetic
continued to transform the surgical addressed by introduction of frameless
The Process3:

1. Imaging: A multislice CT or MRI

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Subspeciality-Oculoplasty
Figure 1: This image is showing planning being done for navigation guided optic nerve decompression surgery. Star
shows the 3D rendition from the scan of the patient. Arrow shows the planning pane where targets are set.

Figure 2: Intraoperative screen view of Medtronic Stealth station, a navigation guided surgery workstation showing
4 four views 1. Coronal, 2. Saggital 3. Axial 4.Surgical field. The position of the instrument is depicted by the arrow.

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Subspeciality-Oculoplasty

scan is obtained preoperatively. the coordinates in relation to the space also the makes novice surgeons
This data is transferred to satellites in space. Meanwhile an more confident by increasing the
the planning laptop and the image guiding system works on appreciation of the anatomy.
workstation via either Digital the same principle by continuously
Imaging Communication (DICOM) tracking the surgeon’s instrument’s Some modern workstations also offer the
or by using external storage devices. location with respect to patient’s ability to mirror the scan images.[6] In this
anatomical landmarks. feature the software mirrors the scan
2. Planning: Each case to be reviewed of the orbit of one side on to the other
on a soft copy workstation as per 5. Visualisation: Image guiding systems side. This helps the surgeon to orient
the requirement of the procedure. have a high-resolution monitor himself in cases where the anatomy of
The software tools allow the images to display the surgeon’s location. one side is distorted and operate even
to be viewed in surface rendering, Software offers all traditional views in the absence of normal anatomical
volume rendering and in 3D the such as sagittal, coronal, axial as landmarks.
surgeon can decide the surgical standard but certain advanced
approach, anticipate the challenges system have the capability to Significant advantages of IGS have
and tactically rehearse the surgical offer 3D rendition, guidance view, been documented in both primary
steps in the mind. This helps in tracking view etc. also (Figure 1) and secondary orbital and facial
decreasing the operating time, (Figure 2). reconstructions[7]. The modality has also
reducing intra-operative surprises proven to be effective in maintaining
and improving the outcomes by The Utility: post-operative globe volume and
enabling targeted approach. projection after orbital repair.
Navigation guided surgery has found
3. Registration: It is the process of great utility in various orbital surgeries Navigation guided localisation and
achieving synergy between the such as orbital reconstructions, mid biopsy technique has greatly increased
coordinate system in real space facial corrections, foreign body removal, safety while dealing with the closed
(operating theatre) and digital optic nerve decompression, orbital wall space of the orbital apex[8]. It has been
space (preoperative imaging). This repair etc. documented to have reduced post-
achieved by using preselected operative complications and decreased
points (fiducials) on the patient’s When it comes to the orbital space the number of repeat procedures
preoperative scan and marking and surgery of the orbital apex, it is a required[9].
them in real time on the patient. complex situation that presents before
A mobile probe is used marked the surgeon a myriad of challenges. Traumatic optic neuropathy is a serious
with reflectors. A camera present Firstly, the orbit is a compact space complication of crania-facial injury
in the workstation emits infrared with distal parts of the space with whose management has no set protocol.
rays reflected by the probe and poor visualisation. Secondly, the Optic canal decompression is one of the
detected by a detector. The probe space is packed with vital nerves and methods employed to treat any optic
is sequentially placed on fiducials vessels, a damage to which can lead nerve compression. There are various
in order to register the probe. This to complete and irreversible loss of methods to perform decompression
can be performed using either soft visual potential[4]. Any such procedure of the optic canal such as intracranial,
tissue surface anatomy such as carries huge amount of risk and a trans-ethmoidal, trans-caruncular,
in Medtronic Stealth System or high complication potential[5]. The use endonasal, and sublabial approaches
using registration mask such as in of navigation guided surgery in this , done either via open surgery or by an
Stryker Nav3® system, Brainlab. domain has revolutionised the way endoscopic approach.[10] In a small case
Post-registration the accuracy of orbital pathologies are approached series, the authors have demonstrated
the system is verified by touching surgically. The ability to accurately promising results, both in visual
various bony landmarks and localise the lesion within 1-2mm of recovery and precision of surgery by
verifying the probe position on the the 3-dimensional space enables us to using Navigation guided surgery for
screen. delineate the approach trajectory pre- optic canal decompression.
operatively. The ability to “look-ahead”
4. Tracking: The workstation tracks the or see what lies beyond helps avoid While the advantages are plenty, there
probe in real-time using a principle intra-operative surprises. The ability are some disadvantages too. Increased
which is similar to modern day to plan better enables the surgeon to cost can hamper affordability. The
geo-positioning systems. In a GPS make more daring choices. The ability preparation required to be done
system the location of any object to extensively plan and monitor your increases the overall Operation theatre
is determined by triangulating movements in real time in the 3D time. An untrained surgeon might find

22 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Subspeciality-Oculoplasty

it more difficult than conventional open in orbitofacial surgery. Indian J 9. Cai EZ, Koh YP, Hing ECH, Low JR, Shen
surgery[11]. Users have also reported Ophthalmol 2019;67(7):995. JY, Wong HC, et al. Computer-assisted
difficulties in achieving accurate navigational surgery improves outcomes
registration[12]. 5. Decompression of the Orbital Apex: in orbital reconstructive surgery. J
An Alternate Approach to Surgical Craniofac Surg 2012;23(5):1567–73.
Conclusion Excision for Radiographically Benign
Orbital Apex Tumors | Ophthalmology 10. Traumatic Optic Neuropathy: A Review
Navigation based surgery has opened | JAMA Otolaryngology–Head & Neck [Internet]. [cited 2020 Nov 28];Available
up a whole sea of opportunities and Surgery | JAMA Network [Internet]. from: https://www.ncbi.nlm.nih.gov/
unlocked huge potentials when it [cited 2020 Nov 28];Available from: pmc/articles/PMC4329032/
comes to surgical management of https://jamanetwork.com/journals/
complex orbital cases. There is a need to jamaotolaryngology/fullarticle/410567 11. Image guided navigation system-a new
pursue a scientific randomised control technology for complex endoscopic
trial and increase training opportunities 6. Terzic A, Scolozzi P. Image guided endonasal surgery - PubMed [Internet].
for young surgeons enabling us to fully surgical navigation integrating [cited 2020 Nov 28];Available from:
utilise its potential. “mirroring” computational planning https://pubmed.ncbi.nlm.nih.
based on intra-operative cone-beam CT gov/14707243/
References imaging: a promising new approach
for management of primary bilateral 12. Paydarfar JA, Wu X, Halter RJ. Initial
1. Bhattacharjee K, Serasiya S, Kapoor D, midfacial fractures. Comput Aided experience with image-guided surgical
Bhattacharjee H. Navigation-guided Surg Off J Int Soc Comput Aided Surg navigation in trans-oral surgery. Head
optic canal decompression for traumatic 2011;16(4):170–80. Neck 2019;41(1):E1–10.
optic neuropathy: Two case reports.
Indian J Ophthalmol 2018;66(6):879. 7. Schramm A, Suarez-Cunqueiro MM, Corresponding Author:
Rücker M, Kokemueller H, Bormann
2. Mezger U, Jendrewski C, Bartels M. K-H, Metzger MC, et al. Computer- Dr. Kasturi Bhattacharjee
Navigation in surgery. Langenbecks assisted therapy in orbital and mid-facial MS, DNB, FRCSEd, FRCS (Glasg)
Arch Surg 2013;398(4):501–14. reconstructions. Int J Med Robot Comput Ocular Trauma and Vitreo Retina Surgery
Assist Surg MRCAS 2009;5(2):111–24. Sri Sankaradeva Nethralaya, Guwahati,
3. Haller J, Ryken T, Gallagher T, Vannier Assam, India.
M. Infrastructure for Image Guided 8. Interactive image guidance for surgical
Surgery. 2001; localization of orbital apical tumors:
Orbit: Vol 21, No 3 [Internet]. [cited
4. Udhay P, Bhattacharjee K, 2020 Nov 28];Available from: https://
www.tandfonline.com/doi/abs/10.1076/
Ananthnarayanan P, Sundar G. orbi.21.3.199.7180

Computer-assisted navigation

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Subspeciality-Oculoplasty

Retinoblastoma Management -
Whats New?

Rachna Meel, MS
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Treatment of retinoblastoma Fig 1: Fundus photo showing (a) dense vitreous seed cloud in a case of retinoblastoma
underwent a revolutionary change (arrow) (b) Complete regression of retinal tumours and vitreous seeds following systemic
from external beam radiotherapy chemotherapy and ivc with melphalan.
(EBRT) to systemic chemotherapy
in the 1990s, resulting in extensive refractory or recurrent vitreous seeds. detachment increases the risk of drug
benefits in globe survival and life Response is directly related to vitreous getting concentrated close to retina
salvage. Systemic chemotherapy thus seed morphology. Hence dose is thus increasing risk of retinal toxicity.[4]
became the standard of care. However, modified based on seed morphology. Risk of extra ocular extension is less
tumour seeds remained a hurdle in Most common side effect is mild to than 0.04% according to a published
achieving 100% globe salvage. In the moderate salt and pepper retinopathy.[2] meta-analysis.[5] Limited studies
last decade, some targeted treatments Few ERG studies in treated eyes have from literature and our experience
were revisited and new ones explored shown permanent non-progressive (unpublished data) has also shown
in an effort to tackle retinoblastoma deterioration of retinal functions. A that use of ivc in combination with
seeds. The outcomes of these targeted recently published study documented intravenous chemotherapy, may be
treatments were significantly better that on an average each intravitreal associated with increased toxicity.[6,7]
than systemic chemotherapy with injection of melphalan is associated
focal treatment in management of witha5.3 μVdecreaseinERGamplitude. Topotecan is the second most tried drug
advanced retinoblastoma and hence In this study, concurrent intra-arterial for ivc. It can be used in combination
these became very popular. chemotherapy and a greater ocular with melphalan or alone. Treatment
pigmentation were also significantly with melphalan/ combination of
In this article, I intend to highlight associated with a deterioration in ERG melphalan and topotecan is more likely
recent studies on the most advanced while concomitant focal treatment to cause retinal function deterioration
retinoblastoma management options. and duration between injections did than topotecan alone. Recent study
not augment the toxicity.[3] Other side shows that intravitreal topotecan
What is new in intravitreal effects include vitreous haemorrhage, injections at doses of 20 μg or 30 μg are
not associated with retinal toxicity in
chemotherapy? cataract formation, conjunctival retinoblastoma patients.[8]

The history of use of intravitreal hemorrhage and uveitis. Vitreous
chemotherapy (ivc) in retinoblastoma
dates back to the 1960s, when Ericson
and Rosengren used thiotepa, only
to abandon it later because of a high
incidence of extraocular extension.
Currently, with the safety enhanced
technique, ivc has shown to be safe
and very effective for treatment
of retinoblastoma seeds (Fig1).[1]
Melphalan (20-30micrograms/0.1ml) is
the most tried and tested drug for ivc.
It is most popularly used for residual

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Subspeciality-Oculoplasty

Whether intravitreal chemotherapy intravitreal chemotherapy further laser fluence and irradiance threshold
can also treat retinal tumor and improves globe salvage in group D and in TTT photocoagulation properties.[20]
subretinal seeds is doubtful as reports E eyes with retinoblastoma seeds.[17]
from literature show contradictory Two mechanisms were postulated
results.[9,10] Recently precision ivc was Intra-arterial chemotherapy can be explaining the improved treatment
described and found to be effective in technically challenging in infants. outcomes: direct cytotoxicity due to
treating focal vs with decreased side Shields et al reported outcomes with thermal effect of the laser treatment,
effects. In this modified technique, the iac in infants weighing less than and the photodynamic effect, which
ivc is administered focally around the 10 kg.[18] They found that although generated reactive oxygen. More
focal vitreous seeds making it more patients weighing ≤10 kg had greater studies are needed to select the optimal
targeted and less toxic.[11] number of aborted procedures (12 dye dosage, duration between ICG and
[5.4%] versus 7 [1.6%]; P = .01), on TTT, laser parameters and the long-
Intra- arterial chemotherapy multivariate analysis, weight ≤10 kg term control after this treatment.[21]
was not an independent predictor of
The pioneering work by Kaneko et complications or procedure failure. Aqueous humor sampling for
al in 1998 led to the introduction Infact Patients weighing ≤10 kg had a tumor prognostication
of intraarterial chemotherapy (iac) greater frequency of complete tumor
as a safe and effective treatment of regression (82.6% versus 60.9%; P Retinoblastoma is initiated by a
advanced retinoblastoma after the = .02), and a reduced frequency of mutation in RB1 tumor suppressor
failed historical attempts in 1958 by enucleation (16 [21.6%] versus 52 gene located on chromosome 13q
Reese and another one by Kiribuchi in [39.1%]; P = .01). in 98% of cases, the remaining are
1968.[12,13,14] initiated by MYCN amplification
In a case report, published recently, on chromosome 2p.[22-25] Studies on
Today iac is used both as primary and authors have documented some tumor DNA in retinoblastoma have
secondary treatment of intraocular therapeutic effect of iac on the opposite also revealed somatic copy-number
retinoblastoma. There is no universal eye.[19] alteration (SCNA) profiles with highly
consensus regarding drugs and dosage recurrent chromosomal gains on 1q,
for iac. In their systematic review, All said and done, it remains a costly 2p, 6p and losses on13q, 16q, apart from
Yousef et al reported melphalan as the procedure out of reach for the poor and focal MYCN amplification on 2p.[22,26,27]
most common single agent employed. economically constrained. It is useful
As protocols evolve, iac is preferably as primary treatment for unilateral Access to tumour DNA in
administered every 4 weeks for three retinoblastoma . However, it should retinoblastoma is limited to tumor
sessions by many centres.[15] be avoided in bilateral retinoblastoma tissue harvested from enucleated eyes.
and those with high risk of metastasis, Tissue biopsy of retinoblastoma from
Recently, a meta-analysis compared both of which require systemic salvageable eyes is contraindicated for
the clinical efficacy of intravenous chemotherapy. fear of extraocular tumor spread. Hence,
chemotherapy versus iac and found till a few years back there was no way
iac to be more effective overall in ICG enhanced TTT to access tumor DNA from cases that
treatment of retinoblastoma (75.7% do not undergo enucleation. However,
vs. 69.5%). The globe salvage was ICG enhancement with TTT is not a after Francis Munier introduced
higher with iac than with intravenous very recent development but there the safe technique for intravitreal
chemotherapy in group D eyes (79.5% are only a few studies reporting chemotherapy in 2012, aqueous tap
vs 55.1%), but not in group B. C and E, the outcome of this therapeutic became a feasible option for harvesting
where iac and systemic chemotherapy modality in retinoblastoma eyes. It tumor DNA from salvageable eyes.[1,28]
did not differ significantly with regard has been shown to cause a measurable Liquid biopsies based on circulating
to the recurrence and metastasis rates tumor regression in lesions that had tumor cells and cell free DNA (cfDNA)
(15.0% vs. 15.4%,and 2.7% vs. 0.6%, previously not been responsive to within the blood or other fluids have
respectively).[16] traditional chemothermotherapy or been explored for other cancers to
isolated TTT and therefore needs to be prognosticate therapeutic outcome,
When used as primary treatment explored further in more studies.[20] thus precluding the need for invasive
in unilateral retinoblastoma it has tissue biopsy. Aqueous humor has
been found to achieve 100% salvage In one study, ICG dye (0.6 mg/kg) was recently been explored as the liquid
in groups B and C retinoblastoma, delivered intravenously 30 s before source of tumor-derived cfDNA.[29]
80 % in group D and 79% in group E laser treatment. It has been postulated This can allow us to improve our
retinoblastoma. Addition of adjuvant that ICG dye possibly decreases the understanding of genes that contribute
to retinoblastoma tumorigenesis, and

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Subspeciality-Oculoplasty

hence identify biomarkers that portend 5. Smith SJ, Smith BD. Evaluating the 14. Kiribuchi M. [Radiation therapy for
more aggressive disease activity. risk of extraocular tumour spread malignant intraocular tumors] Ganka.
following intravitreal injection 1966;8:268–303.
A study by Berry et al identified a therapy for retinoblastoma: a
corroborative pattern between the systematic review. Br J Ophthalmol. 15. Yousef YA, Soliman SE, Astudillo PP,
chromosomal copy number variation 2013 Oct;97(10):1231-6. Durairaj P, Dimaras H, Chan HSL, et
(CNV) profiles of the aqueous humor al. Intra-arterial chemotherapy for
cell-free DNA(cfDNA) and tumor- 6. Lee JH, Han JW, Hahn SM, Lyu CJ, retinoblastoma: A systematic review.
derived DNA from the enucleated Kim DJ, Lee SC. Combined intravitreal JAMA Ophthalmol 2016;134:584-91
samples. This study demonstrated that melphalan and intravenous/
there are quantifiable levels of cfDNA intra-arterial chemotherapy for 16. Chen Q, Zhang B, Dong Y, Mo X, Zhang
in the aqueous humor of treated and retinoblastoma with vitreous seeds. L, Huang W, Jiang H, Xia J, Zhang S.
untreated retinoblastoma eyes.[29] In a Graefes Arch Clin Exp Ophthalmol. Comparison between intravenous
subsequent study, Berry et al reported 2016 Feb;254(2):391-4. doi: 10.1007/ chemotherapy and intra-arterial
correlation between presence of s00417-015-3202-0. Epub 2015 Oct 29. chemotherapy for retinoblastoma: a
aqueous humor SCNAs and eye salvage, PMID: 26511530. meta-analysis. BMC Cancer. 2018 Apr
specifically 6p gain. The study indicated 27;18(1):486
that 6p gain in the aqueous humor may 7. Berry J, L, Shah S, Kim F, Jubran
be a potential prognostic biomarker for R, Kim J, W: Integrated Treatment 17. Shields CL, Alset AE, Say EA, Caywood
poor clinical response to therapy.[30] during the Intravitreal Melphalan Era: E, Jabbour P, Shields JA. Retinoblastoma
Concurrent Intravitreal Melphalan Control With Primary Intra-arterial
References and Systemic Chemoreduction. Ocul Chemotherapy: Outcomes Before and
Oncol Pathol 2018;4:335-340. doi: During the Intravitreal Chemotherapy
1. Munier FL, Gaillard MC, Balmer A, 10.1159/000486098 Era. J Pediatr Ophthalmol Strabismus.
Soliman S, Podilsky G, Moulin AP, et al. 2016 Sep 1;53(5):275-84
Intravitreal chemotherapy for vitreous 8. Nadelmann J, Francis JH, Brodie
disease in retinoblastoma revisited: SE, Muca E, Abramson DH. Is 18. Sweid A, Hammoud B, Weinberg JH,
From prohibition to conditional intravitreal topotecan toxic to retinal et al. Intra-Arterial Chemotherapy
indications. Br J Ophthalmol function? Br J Ophthalmol. 2020 Jul for Retinoblastoma in Infants ≤10
2012;96:1078-83. 14:bjophthalmol-2020-316588. kg: 74 Treated Eyes with 222 IAC
Sessions. AJNR Am J Neuroradiol. 2020
2. Francis JH, Abramson DH, Gaillard 9. Abramson DH, Ji X, Francis JH, Jul;41(7):1286-1292.
MC, Marr BP, Beck-Popovic M, Catalanotti F, Brodie SE, Habib
Munier FL. The classification of L. Intravitreal chemotherapy in 19. Su GL, Lim LS, Welch RJ, Shields CL.
vitreous seeds in retinoblastoma and retinoblastoma: expanded use beyond Retinoblastoma regression following
response to intravitreal melphalan. intravitreal seeds. Br J Ophthalmol. intra-arterial chemotherapy to the
Ophthalmology. 2015 Jun;122(6):1173- 2019 Apr;103(4):488-493. doi: 10.1136/ contralateral eye. Saudi J Ophthalmol.
9. doi: 10.1016/j.ophtha.2015.01.017. bjophthalmol-2018-312037. Epub 2019;33(3):291-293
Epub 2015 Mar 18. PMID: 25795478. 2018 Jun 6. PMID: 29875233.
20. Al-Haddad CE, Abdulaal M, Saab
3. Francis JH, Brodie SE, Marr B, Zabor EC, 10. Mohanan, A., Meel, R., Venkatesh, P. et RH, Bashshur ZF. Indocyanine
Mondesire-Crump I, Abramson DH. al. Retinal tumour outcome with IVC Green-Enhanced Thermotherapy for
Efficacy and Toxicity of Intravitreous in retinoblastoma. Eye (2020). https:// Retinoblastoma. Ocul Oncol Pathol.
Chemotherapy for Retinoblastoma: doi.org/10.1038/s41433-020-1076-9 2015;1(2):77-82.
Four-Year Experience. Ophthalmology.
2017 Apr;124(4):488-495. doi: 10.1016/j. 11. Yu M, D, Dalvin L, A, Welch R, J, 21. Francis JH, Abramson DH, Brodie SE,
ophtha.2016.12.015. Epub 2017 Jan 12. Shields C, L: Precision Intravitreal Marr BP. Indocyanine green enhanced
PMID: 28089679; PMCID: PMC5441308. Chemotherapy for Localized Vitreous transpupillary thermotherapy in
Seeding of Retinoblastoma. Ocul combination with ophthalmic artery
4. Aziz HA, Kim JW, Munier FL, Berry Oncol Pathol 2019;5:284-289. chemosurgery for retinoblastoma. Br J
JL. Acute Hemorrhagic Retinopathy Ophthalmol. 2013;97:164–168.
following Intravitreal Melphalan 12. Yamane T, Kaneko A, Mohri M. The
Injection for Retinoblastoma: A technique of ophthalmic arterial 22. RushloRushlow DE, Mol BM,
Report of Two Cases and Technical infusion therapy for patients with Kennett JY, et al. Characterisation
Modifications to Enhance the intraocular retinoblastoma. Int J Clin of retinoblastomas without RB1
Prevention of Retinal Toxicity. Ocul Oncol. 2004;9:69–73 mutations: genomic, gene expression,
Oncol Pathol. 2017 Jan;3(1):34-40. doi: and clinical studies. Lancet
10.1159/000448718. Epub 2016 Sep 14. 13. Reese AB, Hyman GA, Tapley Oncol.2013;14(4):327-334.
PMID: 28275601; PMCID: PMC5318931. ND, Forrest AW. The treatment
of retinoblastoma by x ray and 23. Li WB, Buckley J; Sanchez-Lara, PA,
triethylene melamine. AMA Arch et al. A Rapid and Sensitive Next
Ophthalmol. 1958;60:897–906. Generation Sequencing Method to
Detect RB1 Mutations Improves Care

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for Retinoblastoma Patients and Their of retinoblastoma: a review. Clin Exp Biopsy for Retinoblastoma. Mol
Families. J Mol Diagn. 2016. Ophthalmol 2014;42:33–52. Cancer Res. 2018;16(11):1701-1712.
doi:10.1158/1541-7786.MCR-18-0369
24. Murphree AL, Benedict WF. 28. Munier FL, Soliman S, Moulin AP,
Retinoblastoma: clues to human Gaillard MC, Balmer A, Beck-Popovic Corresponding Author:
oncogenesis. Science. 1984;223 M.Profiling safety of intravitreal
(4640):1028-1033. injections for retinoblastoma using an Dr. Rachna Meel, MS Ophthalmology
anti-reflux procedure and sterilisation Associate Professor
25. Sparkes RS, Murphree AL, Lingua of the needle track. Br J Ophthalmol. Oculoplasty, Tumor & Pediatric
RW, et al. Gene for hereditary 2012;96(8):1084-1087. Ophthalmology Services,
retinoblastoma assigned to human Dr. R. P. Centre for Ophthalmic Sciences,
chromosome 13 by linkage to esterase 29. Berry JL, Xu L, Murphree A, et al. All India Institute of Medical Sciences,
D. Science. 1983;219(4587):971-973. Potential of Aqueous Humor as a New Delhi, India
Surrogate. Biopsy for Retinoblastoma.
26. Kooi IE, Mol BM, Massink MP et JAMA Ophthalmol. 2017; 135:1221-
al. Somatic genomic alterations in 1230.
retinoblastoma beyond RB1 are rare and
limited to copy number changes. Sci Rep 30. Berry JL, Xu L, Kooi I, et al. Genomic
2016;6:25264. cfDNA Analysis of Aqueous Humor
in Retinoblastoma Predicts Eye
27. Theriault BL, Dimaras H, Gallie BL, Salvage: The Surrogate Tumor
Corson TW. The genomic landscape

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Ocular Plaque Brachytherapy

Neiwete Lomi, MD, Alisha Kishore, MD, Suresh Azimeera, MD.
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Introduction sec) which emits beta with a maximum the prescribed dose at the tumor apex
energy of 3.54MeV and Mean Energy is delivered.
Brachytherapy has gained popularity of 1.42 MeV. The parent 106Ru For the success of treatment in terms of
in the recent years as an important radionuclide has a half-life of 373.6 tumor control as well as normal tissue
therapeutic modality in ocular days. toxicity, the accurate calculation of
tumours. There are various ways of treatment time is very crucial. 106Ru
giving radiotherapy to the ocular Dosimetry calculations and plaque brachytherapy has been used for
or orbital tumours. It can be given surgical procedure: morethanfivedecades,butintheabsence
as external beam radiotherapy, Ocular plaque brachytherapy is a of dedicated suitable commercial
stereotactic radiosurgery, particle challenging job for both medical dosimeters and phantoms and still-
radiation therapy, brachytherapy.1 physicist and radiation oncologist evolving protocols, the dosimetry of
Brachytherapy involves placing because of steep dose gradient, high plaques remains a challenging task and
a radioactive material surgically spatial resolution, tumor dimension further improvement is required due
adjacent to required site of therapy and location. Dose distribution is to the high uncertainty reported in the
thereby allowing higher and specific calculated by medical physicist after literature.
dose of radiation to reach the tumour noting the requisite information
site while causing minimal exposure from ocular oncologist like clinical
to other normal ocular structures.2,3 diagnosis, tumour dimension, location,
The various sources described are measurement of tumour distant
60Co, 106Ru,125I, 103Pd, 90Sr, and 131Cs25,31. from optic nerve and fovea and also
Modern plaques include assemblies prescribe dosage rate from radiation
of gold shells with low-energy photon oncologist. The plaque is sutured on
seeds (125I, 103Pd, and 131Cs) or solid beta the sclera after confirming the position
(106Ru and 90Sr) plaques.4 106Ru based using indirect ophthalmoscope,
plaque brachytherapy is an effective ultrasound or transillumination optic
treatment of small to medium-sized fibres while maintains coverage of
ocular malignancies for the local atleast 2 mm free edge of tumour mass.
control and disease-free survival. Based on the pre-calculated treatment
106Ru is a pure beta emitter (in secular time, the plaque remains in situ for
equilibrium with its daughter 106Rh specific time followed by removal after
with a half-life of approximately 30

Figure 1: RU-106 Plaques with different sizes and shapes Figure 2: Plaque insertion and confirming
the plaque position using ultrasound B scan
28 DOS Times - Volume 26, Number 2, September-October 2020 intra-operatively.

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Indications of Brachytherapy: retinal capillary hemangiomas (RCH), modalities like systemic or intra-
The most common indication for vasoproliferative tumors (VPTs) and arterial chemotherapy, cryotherapy
brachytherapy in ocular malignant choroidal neovascularization in age- or transpupillary thermotherapy fail
tumours are retinoblastoma5,6 and related macular degeneration (AMD).9 to regress the tumour.12 It also serves
uveal melanoma7,8. Even though Ocular as a secondary treatment modality for
brachytherapy started with treatment Retinoblastoma(RB): residual and recurrent tumours. The
of cancers, such as retinoblastoma, Brachytherapy is less commonly used usual tumour dose prescribe at the
uveal melanoma and ocular surface as a primary treatment for RB.10,11 apex is 3000 to 4500cGy. The presence
squamous neoplasia, but it has now The ideal RB tumours for primary of anterior segment involvement
been expanded to benign ocular brachytherapy are unilateral tumours and juxta papillary location are the
conditions that cause deterioration ideally located anterior to the equator, exclusion criteria for brachytherapy
of vision. It can be used for various with apical thickness <6mm and as it is anatomically difficult location
vascular tumours where traditional basal diameter < 16 mm. Plaque for plaque placement and also higher
methods of treatment have failed and brachytherapy is more commonly risk of radiation-induced optic
the various lesions which fall into this used as a secondary treatment option neuropathy.13
category are choroidal hemangiomas, when the conservative treatment Sample Case: Figure 3.

Pre-Brachytherapy Post-Brachytherapy 1 Month

Apical Height 5.8mm Basal diameter 12.1mm Apical Height 2.1mm Basal diameter 6.0mm

Figure 3: 5years old girl diagnosed retinoblastoma, RE enucleated for Group E RB and LE Recurrent Group C RB after receiving total 12
cycle of standard protocol VEC chemotherapy. Pre and Post- Brachytherapy follow-up at 1 month.

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Uveal melanoma: and those patient with limited size uveal melanoma insufficient
extrascleral extension.14 radiation dose delivered at the apex
Brachytherapy is an effective method Brachytherapy exclusion criteria could jeopardise local tumour control
for treating small to medium size according to ABS-OOTF (The American and increase the risk of recurrence as
uveal melanoma. Indications for Brachytherapy Society - Ophthalmic well as metastasis and mortality, hence
brachytherapy in uveal melanoma have Oncology Task Force) recommendation case based multimodality approach
expanded since 2003 ABS (American includes no perception of light, tumour need to be considered.
Brachytherapy Society) guidance, this size >5mm size, gross extrascleral
includes, iris, ciliary body, choroid, sub extension, painful blind eye.14 In large Sample Case: Figure 4
foveal, circumpapillary, peripapillary

Pre-op 6 Months Post Brachytherapy

Apical Height 7.4mm Basal diameter 15.4mm Apical Height 5.1mm Basal diameter 10.5mm

Figure 4: 45 years old male with Right eye choroidal melanoma treated with plaque brachytherapy

Ocular surface Tumours: Incomplete excision of primary tumors plaque brachytherapy as an adjuvant
with margin positive on histopathology treatment for vision and globe salvage.
Ocular surface malignancies including is a significant risk factor for recurrence Anterior segment OCT or Ultrasound
conjunctival melanoma (CM) and and regional spreads. Currently in biomicroscopy (UBM) is done to
squamous cell carcinoma (SCC) are cases with residual tumor growth measure the scleral or intraocular
potentially sight- and life-threatening with scleral invasion and intraocular involvement. The radiation dose at the
conditions usually managed by topical involvement diagnosed on imaging apex may range from 50-80Gy. Some
chemotherapy or wide surgical excision and histopathology are subjected to associated complications includes
and superficial keratectomy. However,

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cataract, transient corneal epithelial carcinoma (SCC) patients treated by none experienced recurrence at the
defect, iris telangiectasia, corneal surgical excision followed by Iodine -125 treatment site. Plaque brachytherapy
oedema and glaucoma. A Retrospective, plaque brachytherapy for primary or has been shown to be a safe and reliable
non-comparative, interventional case recurrent ocular surface malignancies treatment alternative to enucleation for
series by Conway et al.15 describe an with evidence of deep margin (corneo- scleral and intraocular involvement of
excellent outcome of 5 conjunctival scleral) invasion. At mean follow up squamous neoplasia.25
melanoma(CM) or 6 squamous cell of 23.4 months (range 12–36 months) Sample Case: Figure 5

Figure 5: A) Conjunctival squamous cell carcinoma B) Post mass excision with cryotherapy and AMG C) Anterior segment OCT showing
scleral invasion D) Episcleral plaque brachytherapy in-situ E) Regressed tumor control one month post brachytherapy F) Regressed lesion
two months post brachytherapy

Choroidal hemangioma: candidates for laser and cryotherapy Retinal capillary
Role of radiotherapy has been due to subfoveal location or presence of
described in the management of both extensive subretinal fluid; this has come hemangioma(RCH):
Circumscribed choroidal hemangioma up due to the potential for radiation-
(CCH) and Diffuse choroidal induced complications such as cataract, Radiotherapy was one of the first
hemangiomas (DCHs).16 Mac Lean and retinopathy and papillopathy.18 treatment modalities for retinal
associates probably used brachytherapy angiomas.20 In 1935, Moore sutured
for the first time for the treatment of Brachytherapy has also been used in the radon seeds to the sclera over the tumour
choroidal haemangioma.17 They used management of DCH in selected cases site in two patients and successful
trans scleral diathermy with scleral where the diffuse area can be covered regression was noted in both the
suturing of radon seeds and presently by brachytherapy plaque. Murthy et al. patients.21 Radiation therapy failed to
Episcleral plaque brachytherapy is have used Ru-106 brachytherapy in the come up as a better treatment modality
considered an effective treatment treatment of a 10-year-old child with as compared to laser photocoagulation
option for large circumscribed choroidal DCH and secondary total exudative due to wrong case selection and limited
hemangiomas with sub retinal fluid. retinal detachment.19 They observed a experience. But recently radiotherapy is
50% reduction in tumour thickness, emerging as a new approach for patients
Plaque brachytherapy should be resolution of subretinal fluid and which are not responding to laser,
considered only for choroidal improvement of Visual acuity from 6/60 cryotherapy and have large exudative
hemangiomas which have history of to 6/9 at the end of one month without retinal detachments. Kreusel et al.22
treatment failure, especially in larger any radiation-related complications. reported a series of 25 RCH treated with
lesions which are not amenable to ruthenium-106 (Ru-106) plaques in
laser photocoagulation or PDT, or not Sample Case: Figure 6 1998. The various reports suggest
brachytherapy to be a safe option for

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Subspeciality-Oculoplasty 5 Months Post-op
Pre-op

Regression of tumour mass and settled exudative RD

Figure 6: 24years male with LE choroidal hemangioma with exudative retinal detachment successfully treated with brachytherapy

managing challenging cases of RCH a decrease in mean tumor thickness radiation side effects are minimized
as well as those cases in which other from 2.8-mm to 1.5 mm. 11% did not due to the peripheral location of these
treatment options have failed. However, respond to treatment out of which tumours.
it requires larger case series with longer three had secondary glaucoma prior to
follow-up periods a to provide long- brachytherapy thus making glaucoma Conclusion:
term safety and efficacy data to support as a significant cause of treatment Brachytherapy is now a widely
the use of brachytherapy in managing failure. They did not report any case accepted treatment modality in ocular
large RCHs. of Radiation-induced retinopathy or tumours. With proper case selection
optic neuropathy. Another case series and experience, plaque brachytherapy
Vasoproliferative retinal tumors by Cohen et al. reported 30 eyes with has gained a promising modalities for
(VPT): VPT treated with I-125 brachytherapy.24 an effective eye and vision sparing
The VPT is a benign vascular tumor alternative to enucleation for patients
of the sensory retina. It can be either They observed tumor regression in of intraocular tumors.
primary (idiopathic) or secondary to 97% cases and complete resolution of
other ocular disease. Brachytherapy retinal detachment in 65% cases after References:
is being seen as a newer treatment brachytherapy. Brachytherapy appears 1. Paul T. Finger. Radiation Therapy for
modality for larger VPTs (greater than to be superior to conventional treatment
2 mm in thickness). In 2006, a case modalities like laser or cryotherapy Orbital Tumors: Concepts, Current
series of 35 VPTs treated withRu-106 as in the high-dose radiation emitted Use, and Ophthalmic Radiation Side
plaques was published by Anastassiou by plaques are delivered to a well- Effects. Surv Ophthalmol. 2009 Sep-
and co-workers.23 They documented defined area, allowing larger tumors Oct;54(5):545-68
to be treated more effectively. Also the 2. Nag S, Martinez-Monge R, Ruymann FB,

32 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times

Subspeciality-Oculoplasty

Bauer CJ. Feasibility of intraoperative Hilton NE, Rodriguez-Galindo C, Haik in treatment of retinal angiomas. Int
high-dose rate brachytherapy to boost BG. Episcleral plaque brachytherapy for Ophthalmol Clin 1997;37(4):159-70
low dose external beam radiation therapy retinoblastoma. Pediatr Blood Cancer 21. Raja D, Benz MS, Murray TG, Escalona-
to treat pediatric soft tissue sarcomas. 2004;43: 134e139. Benz EM, Markoe A. Salvage external
Med Pediatr Oncol. 1998;31(2):79—85 beam radiotherapy of retinal capillary
12. Shields JA, Shields CL, De Potter P, hemangiomas secondary to von
3. Nag S, Tippin D, Ruymann FB. Hernandez JC , Brady LW .Plaque Hippel-Lindau disease: visual and
radiotherapy for residual or recurrent anatomic outcomes. Ophthalmology
Intraoperative high-doserate retinoblastoma in 91 cases. J Pediatr 2004;111(1):150-3
brachytherapy for the treatment of Ophthalmol Strabismus 1994; 22. Kreusel KM, Bornfeld N, Lommatzsch A,
pediatric tumors: The Ohio State 31:242e245. Wessing A, Foerster MH. Ruthenium-106
brachytherapy for peripheral retinal
University experience. Int J Radiat Oncol 13. Stannard C, Maree G, Munro R, Lecuona capillary hemangioma. Ophthalmology
Biol Phys. 2001;51(3):729—35 K , Sauerwein W .Iodine-125 orbital 1998;105(8):1386-92
brachytherapy with a prosthetic 23. Anastassiou G, Bornfeld N, Schueler
4. Chiu-Tsao ST, Astrahan MA, Finger PT, implant in situ. Strahlenther Onkol AO, Schilling H, Weber S, Fluehs D et al.
Followill DS, Meigooni AS, Melhus CS et 2011; 187:322e327. Ruthenium-106 plaque brachytherapy
al. Dosimetry of 125I and 103Pd COMS for symptomatic vasoproliferative
eye plaques for intraocular tumors: 14. Nag S, Quivey JM, Earle JD, Followill tumours of the retina. Br J Ophthalmol
Report of Task Group 129 by the AAPM D, Fontanesi J, Finger PT. The 2006;90(4): 447-50
and ABS. Med Phys 2012; 39:6161e6184. American Brachytherapy Society 24. Cohen VM, Shields CL, Demirci
recommendations for brachytherapy of H, Shields JA. Iodine I 125 plaque
5. Stallard HB. Retinoblastoma treated uveal melanomas. Int J Radiat Oncol Biol radiotherapy for vasoproliferative
with radioactive applicators. In: Acta Phys 2003; 56:544e555. tumors of the retina in 30 eyes. Arch
XVIII Concilium Ophthalmologicum. Ophthalmol 2008;126(9):1245-51
1958. 2): 1360-9 15. Natalie Walsh-Conway et al. Plaque 25. Sruthi Arepalli, Swathi Kaliki, Carol
brachytherapy for the management L. Shields et al. Plaque radiotherapy in
6. Shields CL, Shields JA, De Potter P, of ocular surface malignancies with the management of scleral- invasive
Minelli S, Hernandez C, Brady LW et al. corneoscleral invasion. Clin Exp conjunctival squamous cell carcinoma.
Plaque radiotherapy in the management Ophthalmol. 2009 Aug;37(6):577-83. JAMA Ophthalmol.2014;132(6):691-696.
of retinoblastoma. Use as a primary and
secondary treatment. Ophthalmology 16. Hannouche D, Frau E, Desjardins L, Corresponding Author:
1993; 100(2):216-24 Cassoux N, Habrand JL, Offret H. Efficacy
of proton therapy in circumscribed Dr. Neiwete Lomi, MD
7. Stallard HB. Radiotherapy for malignant choroidal hemangiomas associated Assistant Professor,
melanoma of the choroid. Br J with serious retinal detachment. Oculoplasty, Tumor & Pediatric
Ophthalmol 1966;50(3):147-55 Ophthalmology1997;104(11):1780-4 Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences,
8. Diener-West M, Earle JD, Fine SL, 17. Mac Lean AL, Maumenee E. All India Institute of Medical Sciences,
Hawkins BS, Moy CS, Reynolds SM Hemangioma of the choroid. Am J New Delhi, India
et al.The COMS randomized trial of Ophthalmol 1960; 50:3-11.
iodine 125 brachytherapy for choroidal
melanoma, III: initial mortality findings. 18. Shields CL, Honavar SG, Shields JA,
COMS Report No. 18. Arch Ophthalmol Cater J, Demirci H. Circumscribed
2001;119(7):969-82 choroidal hemangioma: clinical
manifestations and factors predictive of
9. Manjit S Mehat,Timothy L Jackson visual outcome in 200 consecutive cases.
and Mandeep S Sagoo. Brachytherapy Ophthalmology 2001;108(12):2237-48
for benign fundus lesions. Expert Rev.
Ophthalmol. 9(4), 275–284 19. Murthy R, Honavar SG, Naik M, Gopi
S, Reddy VP. Ruthenium-106 plaque
10. Schueler AO, Fl€uehs D, Anastassiou brachytherapy for the treatment of
G, Jurklies C, Sauerwein W, Bornfeld diffuse choroidal haemangioma in
N. Beta-ray brachytherapy of Sturge-Weber syndrome. Indian J
retinoblastoma: Feasibility of a new Ophthalmol 2005; 53(4):274-5
small-sized ruthenium- 106 plaque.
Ophthalmic Res 2006; 38:8e12. 20. Palmer JD, Gragoudas ES. Advances

11. Merchant TE, Gould CJ, Wilson MW,

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Subspeciality-Oculoplasty

Proximal Lacrimal System
Obstructions

Vikas Menon, DNB, FLVPEI
Centre for Sight, New Delhi, India.

Keywords: Canalicular block, Bicanalicular block, Punctal agenesis, Punctal steno-sis, Botulinum toxin, Canalicular
trephination

The proximal lacrimal system Table 1
comprises of the puncta and canaliculi. 1. Involutional or age related.
Any obstruc-tion in this part of lacrimal 2. Infections (HSV, HPV, chlamydial).
drainage system is far more complex to 3. Topical medications toxicity (timolol, latanoprost).
manage, com-pared to an obstruction in 4. Systemic medications (5- uorouracil, paclitaxel).
the distal part of lacrimal system. 5. Lid malpositions.
Puncta and canaliculi may be non 6. Trauma (thermal).
functional from birth (congenital) or 7. Chronic cicatricial disorders (Steven-Johnson syndrome).
develop a closure subsequently in life 8. Peri-punctal tumors.
(acquired). Agenesis of one or both 9. Systemic disorders (porphyrias, acrodermatitis, lichen planus).
lacrimal canaliculi is rare, diagnosed 10. Radiotherapy.
in about 4% of the patients attending
a lacrimal clinic1. Most of the acquired Figure 1: Absence of punctal papilla and is difficult. Patients with agenesis
punctal / canalicular obstructions are presence of eyelashes medial to normal involving single punctum may not
either idiopathic or result of some sort anatomical site of punctum. need any intervention unless there
of allergic or inflammatory process, is an associated nasolacrimal duct
either to some topical medications medial to normal anatomical site of obstruction which can be managed with
or environmental factors2,3. Common punctum (Figure 1). probing or dacryocystorhinostomy
causes of acquired proximal lacrimal Punctal agenesis has been found (DCR). Patients with both puncta
system pathway stenosis and to be associated with other ocular missing can be kept under observation
obstruction are enumerated in (Table abnormalities like lacrimal fistula, if the symptoms are minimal, whereas
1). absent caruncle, distichiasis, eyelid tags those with significant epiphora need
and divergent strabis-mus. to be managed with conjunctivo-DCR
Punctal Agenesis Management of punctal agenesis with Lester-Jones tube or Gladstone-
Congenital obstruction of the proximal Putterman tube.
pathway can rarely be in the form of
isolated punctal atresia, but most often Other punctal pathologies include
it is seen in association with canalicular punctal membranes, also termed as
agenesis as well, which makes this ‘Incomplete Punctal Canalization’ by Ali
problem complex to manage. The basic et al.4 This could represent persistence
defect lies in failure of outbudding of epithelium over the normally formed
of canaliculi from the upper end of canaliculi. Management is simple
lacrimal cord during embryogenesis. membranotomy using a punctal dilator.
Severity of symptoms depend on
whether the dysgenesis involves Punctal Stenosis
single punctum or both. Examination Punctal Stenosis is a fairly common
reveals an absence of punctal papilla cause of epiphora. The common causes
and occasionally presence of eyelashes

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Subspeciality-Oculoplasty

Figure 3: Sisler’s canalicular trephine. (BV International).

Figure 2: Proximal canalicular, mid
canalicular or distal canalicular
obstructions.

of ac-quired stenosis are mentioned Figure 4: Mini monoka stent. (FCI ophthalmics).
in (Table 1). The basic underlying
mechanism in-volves inflammation Diagnosis can be easily made with a edge of trephine advanced through
leading to fibrosis and stenosis5. carefully done gentle probing which the ob-struction along the anatomical
shows a typical ‘soft’ stop as the probe direction of canaliculus till the time
Management options include punctal encounters soft tissue obstruction obstruction is bypassed. Syringing is
snip procedures, Perforated punctal within the cana-liculus, compared to then performed and if found patent, a
plugs or punctal dilatation with self a ‘hard’ stop seen in nasolacrimal duct self-retaining mono-canalicular mini
retaining mini monoka stents. The obstructions. A thin probe, preferably monoka stent (Figure 4) is passed
authors prefer the at-raumatic technique not larger than 00 should be used gently through the canaliculus. Since the
of using mini monoka stent after and never forced inside the canaliculus advancing edge of the trephine is very
appropriate dilatation of the punctum to avoid creating a false passage. sharp, the surgeon must be very careful
instead of the snip procedures6. The Fluorescein dye disappearance test can to avoid creating a false passage.
problems with snip procedures are also be used as an adjunct for evaluation Success with trephination has been
inadequate symptomatic relief owing of epiphora. variably reported, and depends on site
to lacrimal pump injury and restenosis of ob-struction. More distal the block,
follow-ing cicatrization which can be Management of canalicular higher is the likelihood of success.
even more difficult to manage than obstruction However, a de-layed re-closure of a
primary punctal stenosis itself. Canalicular Trephination: Sisler successfully opened canaliculus always
and Allarakhia first described a remains a possibility even after an ‘on-
Disorders of Canaliculi transcanalicular trephine in 19907. table’ successful surgical procedure.
Canalicular obstruction and stenosis Canalicular trephine (Figure 3) has a Conjunctivodacryocystorhinostomy:
can be either congenital or more sharp metallic end which is advanced This technique is considered to be the
commonly acquired. Management of carefully through the canaliculus after gold standard for managing epiphora
congenital canalicular obstruction has appropriately dilating the punctum. associated with bicanalicular blocks
been described in the previous section While advancing initially a blunt and true con-genital canalicular
along with punctal abnormalities. ended stillet that protrudes beyond the agenesis patients. In this procedure, a
trephine’s sharp end is kept inside the specially designed Lester Jones pyrex
Anatomically, the canalicular lumen of trephine till the soft tissue glass tube is passed directly from the
obstructions can be proximal obstruction is en-countered within medial fornix into the nose8 (Figure
canalicular (first 2-3mm of canaliculus), the canaliculus. Once the obstruction 5). Pyrex glass is chosen due to its
mid canalicular (3-6mm) or distal has been reached, then the blunt
canalicular (beyond 6-8mm of normal stillet is withdrawn and the sharp
canaliculus) (Figure 2).

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Figure 5: Lester Jones pyrex glass tube at the Endocanalicular laser surgery: Management depends on the severity
medial fornix. Holmium, erbium or KTP (potassium- of the symp-toms and asymptomatic
titanium phos-phate) laser have patients can be observed. Obstructions
excellent capillary action. The proximal been described for treatment of focal at the level of puncta are managed
end remains at medial canthus after stenoses (approximately 2mm or less) by dilatation or snip procedures and
removing caruncle, and the distal end within the canaliculi. Success of laser insertion of stents. Whereas, canalicular
should ideally project 2mm in the nose. canaliculoplasty is varied, symptomatic obstructions require procedures like
Some surgeons prefer to perform a DCR success at 12 months has been reported conjunctivo-dacryocystorhinostomy
surgery with mucosal flaps, and the to be around 43 – 84%12,13. or canalicular trephination. Botulinum
tube is inserted between the anterior toxin is a non-invasive measure and
and posterior sac-nasal mucosal flap Retrograde intubation can be used for providing symptomatic
anastomosis, but it is not mandatory to dacryocystorhinostomy: relief to these, other-wise often
do so. Under endoscopic visualisation, intractable problems.
direct tube insertion has been reported This technique involves performing
to be as successful even with-out an a DCR, and then retrograde probing References
accompanying routine DCR. There are of the canalicular system from the
different varieties of tubes available, common canalicular side. Mid or 1. Lyons CJ, Rosser PM, Welham RA. The
straight, bent, frosted, covered with proximal canalicular obstruction is management of punctal agenesis. Oph-
PMMA, tubes with a hole for fixing bypassed, a pseudo-punctum is created, thalmology 1993; 100:1851–1855.
suture. Basi-cally, different methods to and silicone intubation tube is passed.
ensure that the tube remains in place. Success rate of 73% of patients with 2. Esmaeli B, Valero V, Ahmadi MA, et al.
Even with best of techniques, long term proximal or midcanalicular disease has Canalicular stenosis secondary to docet-
tube displacement and extrusion can be been reported. Postoperative failure axel (taxotere): a newly recognized side
as high as 50%9,10. occurs in a higher proportion of cases effect. Ophthalmology 2001; 108:994 –
Canaliculodacryocystorhinostomy: This with midcanalicular obstruction (39%) 995.
technique is indicated in cases of distal compared with proximal canalicular
canalicular or common canalicular obstruction (23%)14. 3. McCartney E, Valluri S, Rushing D, et al.
obstruction, when at least 8 mm of the Upper and lower system nasolacrimal
lateral canaliculi are patent. In this Botulinum Toxin: Botulinum toxin duct stenosis secondary to paclitaxel.
procedure, an anastomosis is made injection into lacrimal gland is an Ophthal Plast Reconstr Surg 2007;
between the patent medial ends of the office-based procedure performed 23:170 – 171.
canaliculi or the common canaliculus under topical anesthesia. A dose of
and the nasal mucosa, after excision of 2.5 or 5 units of Botulinum toxin A is 4. Ali MJ, Mohapatra S, Mulay K, et al.
the obstructed part. Reported success usually sufficient. Published studies Incomplete punctal canalization:
rate is approximately 80% when the have preferred transconjunctival route the external and internal punctal
procedure is performed for common over transcutaneous route15. Transient membranes. Outcomes of
canalicular obstruction and 60% partial or complete ptosis can occur membranotomy and adjunctive pro-
when it is performed for more lateral following injection into lacrimal gland cedures. Br J Ophthalmol. 2013;97:92–5.
obstructions11. Owing to technical as the drug sometimes diffuses and
complexity involved in performing this affects Levator aponeurosis function. 5. Port AD, Chen YT, Lelli GJ.
procedure, it has never gained much To prevent this potential complication, Histopathological changes in punctal
popularity. the patient is advised not to massage stenosis. Oph-thal Plast Reconstr Surg.
eyelids post-injection. The injections 2013;29:201–4.
can be repeated at 3–6 monthly
intervals depending upon the response. 6. Mathew RG, Olver JM. Mini-monoka
The response is highly variable and made easy: a simple technique for mini-
subjective16. It is often useful for monoka insertion in acquired punctal
symptomatic relief in patients who are stenosis. Ophthal Plast Reconstr Surg.
not will-ing for an invasive procedure. 2011;27:293–4.

Summary 7. Sisler HA, Allarakhia L. New
Disorders of proximal lacrimal system minitrephine makes lacrimal
include obstructions at the level of canalicular rehabilitation an office
puncta or the canaliculi. Irrespective of procedure. Ophthal Plast Reconstr Surg
the level of the obstruction, epiphora is 1990; 6:203 – 206.
the most common presenting symptom.
8. Olver J. Colour atlas of lacrimal
surgery. Oxford, Boston: Butterworth-
Heinemann; 2002. pp. 164.

9. Devoto MH, Bernardini FP, de Conciliis
C. Minimally invasive conjunctivoda-
cry-ocystorhinostomy with Jones tube.
Ophthal Plast Reconstr Surg 2006;
22:253 – 255.

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Subspeciality-Oculoplasty

10. Mombaerts I, Colla B. Modified Jones’ presaccal canalicular obstruction. Br J palliative treatment of epiphora in a
lacrimal bypass surgery with an angled Ophthalmol 1999; 83:443–447. patient with canalicular obstruction.
extended Jones’ tube. Ophthalmology Ophthalmology 2005;112:1469–1471.
2007; 114:1403–1408. 14 Wearne MJ, Beigi B, Davis G,
et al. Retrograde intubation Corresponding Author:
11 Doucet TW, Hurwitz JJ. dacryocystorhi- nos-tomy for proximal
Canaliculodacryocystorhinostomy and midcanalicular obstruction. Dr. Vikas Menon, DNB, FLVPEI
in the manage- ment of unsuccessful Ophthalmology 1999; 106:2325–2328; Centre for Sight,
lacrimal surgery. Arch Ophthalmol discussion 2328–2329. New Delhi, India.
1982; 100:619– 621.
15. Falzon K, Galea M, Cunniffe G, Logan
12. Steinhauer J, Norda A, Emmerich KH, P. Transconjunctival botulinum toxin
et al. Laser canaliculoplasty. Ophthal- offers an effective, safe and repeatable
mologe 2000; 97:692–695. method to treat gustatory lacrimation.
Br J Ophthalmol 2010; 94:379–380.
13 Kuchar A, Novak P, Pieh S, et al.
Endoscopic laser recanalisation of 16. Tu AH, Chang EL. Botulinum toxin for

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Subspeciality-Oculoplasty

Entropion and Ectropion:
Evaluation and Management

Urmil Chawla1, Monika Dahiya2 , Bhawna P Khurana3
1 Professor, Strabismus and Oculoplasty Unit, RIO, PGIMS, Rohtak
2 Senior Resident, RIO, PGIMS, Rohtak
3 Consultant, Strabismus and Oculoplasty Services, Khurana Eye Centre, Rohtak

Abstract: Entropion and ectropion are common eyelid malpositions, consequences of which can range from mild discomfort
to potential threat to ocular surface. The goal in treating these eyelid malpositions is to reposition the eyelid so that the new
healing forces will overcome the pathologic forces leading to them. This article reviews the types, etiology and management of
entropion and ectropion which are commonly encountered in clinical practice.
Keywords: Ectropion, entropion, orbicularis, canthal tendon.

Introduction Anatomical aspect Suspensory system of eyelids
Eyelids are mobile tissue curtains placed Each eyelid is divided into two lamellae: (Figure 3)
in front of eyeball which act as shutters anterior and posterior. Anterior lamella
and protect eyeball from injuries and comprising of skin and orbicularis • Whitnall’s ligament
helps in spreading the tear film over muscle and posterior lamella
the ocular surface. Eyelid malpositions comprising of tarsus and conjunctiva. • Lockwood ligament
are the result of forces acting upon the Besides being aware of the anatomy
eyelid margin. Eyelid margin become of eyelid one needs to understand the • Lateral canthal ligament/
unstable due to tendon laxity at medial significance of lower lid retractors Tendon: Superior crux from
and lateral canthi making it susceptible and the suspensory system of eyelids superior tarsus and an inferior
to contractile forces resulting into that keep the eyelids in their normal crux from inferior tarsus fuse at the
entropion, ectropion. position.1 (Figure 1,2). lateral border of tarsal plates to join
lateral retinaculum, a condensation
of several anatomic structures that

Figure 1: Anatomy of upper eyelid. Figure 2: Anatomy of Lower Lid.

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Subspeciality-Oculoplasty

inserts onto lateral orbital tubercle Kemp and Collin2 Grading of Entropion
of Whitnall.
Kemp and Collin2 Grading of Entropion
• Medial canthal ligament/
Tendon: Anterior limb is a broad Degree of Entropion Clinical signs
fibrous structure which attaches
eyelids to frontal process of Minimal Apparent migration of meibomian glands
maxillary bone and to lacrimal Conjunctivalization of lid margin
crest. Posterior limb of MCL inserts Lash-globe contact on upgaze
on posterior lacrimal crest and
lacrimal fascia. It aids in lacrimal Moderate Apparent migration of meibomian glands
pump function. Conjunctivalization of lid margin
Lash-globe contact in primary position
• Eyelid margin Thickening of tarsal plate
Lid retraction
Frequently, tendon laxity at the medial
and lateral canthi will render the eyelid Severe Lid retraction causing incomplete closure
margin unstable making it susceptible Gross lid distortion
to contractile forces. Based on the Metaplastic lashes
contractile forces either entropion, Presence of keratin plaques
ectropion might occur.
Classification Congenital Entropion
Entropion 1. Congenital entropion
• Epiblepharon Epiblepharon
It is a common eyelid malposition • True congenital entropion It is more commonly seen in Asian
characterized by inward turning of lid 2. Acquired entropion races. Hypertrophic changes in skin and
margin against the globe Lower eyelid • Involutional underlying orbicularis muscle in the
entropion (usually involutional) is • Cicatricial medial part push eyelashes upwards
much more common than upper eyelid • Acute spastic and inwards. (Figure 4) It often resolves
entropion (usually cicatricial). with age and should be treated only in
case of recurrent attack of conjunctivitis
and corneal abrasion. A simple suture
correction is done by passing sutures
from below the tarsal plate and tied on
to the apex of epiblepharon fold.3

Figure 3: Suspensory system of eyelids. Figure 4: Epiblepharon.
True congenital entropion
www.dosonline.org/dos-times Upper eyelid entropion occurs
secondary to the mechanical effects of
microphthalmos and enophthalmos
while lower eyelid entropion is caused
by lower lid retractor dysgenesis,
structural defects in tarsal plate
and shortened posterior lamella.2
(Figure5) Clinically, to differentiate
true congenital entropion from
epiblepharon, patient is asked to
look upwards, epiblepharon resolves

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Subspeciality-Oculoplasty

whereas true congenital entropion does Signs 2. Sutures
not resolve. 1. Horizontal lid laxity They offer temporary cure up to 18
A. Pinch test: manually pulling the
Figure 5: Congenital entropion. eyelid away from the eyeball. months and passed to correct the
Differential diagnosis: lamellar dissociation as follows:(a)
1. Tarsal kink: a rare congenital If lid can be pulled down >6mm away transverse sutures prevent upward
from globe, lid is lax. movement of preseptal muscle and
eyelid anomaly manifesting with (b) everting sutures tighten the
severe entropion, which may lead B. Snap back test: Central part of lower eyelid retractors and evert
to corneal opacity and consequent eyelid is pulled 8mm or more away the eyelid.6
amblyopia.2 from the globe, failure of lid to snap 3. Lateral tarsal strip (LTS)
Treatment: back to normal position on release, Lateral canthotomy is followed
1. Temporary correction by fillers in without patients first blinking , denotes by lysis of inferior crus of lateral
eyelid like Hyaluronic acid. horizontal lid laxity. canthal tendon. A thin strip is
2. Hotz procedure: involves excision fashioned from the lateral end of
of a strip of skin and muscle and Normal: lid returns to normal position tarsus by removing the overlying
fixation of the skin crease to the immediately on release skin, orbicularis and conjunctiva.
tarsal plate.4 Grade 1: lid return to normal position Depending on the amount of eyelid
Acquired Entropion approximately 2-3 second laxity, excessive redundant tarsus
Involutional entropion Grade 2: lid return to normal position is excised (Figure 6). Lateral edge
Most common type and commonly approximately in 4-5 second of the tarsus is then anchored to
seen in elderly.5 Grade 3: lid return to normal position in the periorbita lining the inner
Predisposing factors: > 5second part of lateral orbital wall with
1. Horizontal eyelid laxity Grade 4: lid continues to hang down a nonabsorbable suture-like 6-0
2. Vertical eyelid laxity due to weak prolene.7
lower eyelid retractor/ disinsertion C.Medial canthal tendon laxity test:
of lower eyelid retractors. eyelid is pulled laterally and position of Figure 6: Diagrammatic representation of
3. Overriding of preseptal over inferior punctum is observed. Laxity is LTS
pretarsal orbicularis muscle graded as: 4. Jones Procedure
4. Involution of the soft tissues of the Indicated as a primary entropion
orbit due to orbital septum laxity. Normal: Punctum is not displaced more
Clinical approach than 1-2 mm procedure. Horizontal skin incision
Symptoms Mild: Punctum reaches limbus is made at lower border of tarsal
The presenting symptoms can be Severe: Punctum reaches pupil plate and dissection done. LL
sagging skin around the eye, pain, retractors are identified by feeling a
redness, epiphora and decreased vision, D. Lateral canthal tendon laxity test: ‘tug’ as patient look upwards. Then
especially if the cornea is damaged. identified grossly by: interrupted sutures are passed
Corneal abrasion, microbial keratitis, Rounded contour of the lateral canthus. through lower skin edge, lower lid
corneal vascularisation and visual loss Lateral part of the eyelid is moved retractors, lower border of tarsal
may occur.5 medially and >2 mm displacement of plate and out through upper skin
the lateral canthus is significant. edge. LL retractors are shortened
2. Test for orbicularis overriding: and strengthened and sutures
create a barrier for overriding of
Entropic eyelid is placed in its orbicularis oculi.8
normal position and patient is
asked to squeeze, a hump is seen in
lower lid.
3. Disinsertion of retractors: Deep
inferior fornix, white band in
inferior fornix and little or absent
lower lid retraction in downgaze.
4. Slit lamp examination to look for
keratopathy and corneal infections

Management
1. Lid Taping and Lubricating eye

drops

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5. Weis Operation (Transverse posterior lamella using mucous Figure 7: Congenital Ectropion
eyelid split + everting sutures) membrane grafts.12
Indicated for long term cure in exposed conjunctiva with antibiotic
patients with little horizontal Ectropion ointment. Rarely, inverting sutures
laxity. Eyelid is split transversely have to be applied.5,6
to create fibrous tissue scar barrier Ectropion refers to out rolling or
which prevents the upward outward turning of lid margin. Acquired Ectropion
movement of preseptal muscle and Depending upon degree of out rolling, Involutional ectropion:
everting sutures shorten the lower ectropion is divided into 3 grades .5 Most frequent eyelid malposition more
eyelid retractors.9 common in the lower eyelid.
Grade I: Only punctal eversion
6. Quickert Procedure (Transverse Grade II: Lid margin is everted and Predisposing Factors
eyelid split + everting sutures + palpebral conjunctiva is visible Abnormal laxity of eyelid support
horizontal eyelid shortening) Grade III: The fornix is also visible system. It is usually secondary to :
1. Horizontal lid laxity,
Indicated for mild entropion with Classification 2. Lower lid retractor weakness and
horizontal laxity, spastic entropion 3. Lamellar dissociation.
and debilitated patients. It basically A. Congenital ectropion
combines horizontal lid shortening Primary Clinical Approach
with Weis procedure.10 Secondary Symptoms:
Epiphora is the main symptom in
Spastic Entropion B. Acquired ectropion ectropion of lower lid. Symptoms due
Spastic closure of the eyelids allows the Involutional to associated chronic conjunctivitis
orbicularis oculi muscle to overwhelm Cicatricial such as irritation, discomfort and mild
the oppositional action of the lower Mechanical photophobia may be present.
eyelid retractors, resulting in an inward Paralytic
turning of the eyelid margin and Signs:
further irritation of the ocular surface. Congenital Ectropion 1. Horizontal lid laxity:is
It can be essential blepharospasm
or reflex blepharospasm, secondary It is rare entity and usually associated demonstrated by Pinch test, Snap
to acute inflammatory episode or with euryblepharon, ptosis, epicanthus back test, Medial canthal tendon
ocular irritation. It can be managed inversus and blepharophimosis laxity test and lateral canthal
by injection Botox (botulinum) or syndrome. Based on etiology, it can be tendon laxity.
Quickert procedure. classified into-

Cicatricial Entropion Primary congenital ectropion -
It is caused by cicatricial contraction of occurs due to congenital absence or
palpebral conjunctiva, with or without atrophy of tarsus. (Figure 7)
associated distortion of tarsal plate.
It can occur secondary to previous Secondary congenital ectropion
eyelid surgery, chronic allergy, trauma, - occurs secondary to birth trauma,
chemical burns, infection, trachoma, skin retraction, lamellar icthyosis,
Stevens-Johnson syndrome, ocular Down syndrome and acute eversion
cicatricial pemphigoid, radiation of lid secondary to orbicularis muscle
exposure and Sjogren’s syndrome.11 spasm.

Examination of the tarsus and palpebral Primary congenital ectropion can
conjunctiva usually points to its result in exposure keratitis which can
diagnosis. be managed conservatively in form of
lubricating eye drops in mild cases, while
Treatment : Lengthening of the moderate and severe cases are managed
posterior lamella surgically by horizontal lid shortening
1. Mild – tarsal fracture operation is or auricular cartilage graft. Secondary
congenital ectropion on the other hand
done requires careful identification of the
2. Moderate to severe – lysis of the cause. Orbicularis spasm is managed
by gently repositioning the everted
scar tissue and lengthening of the lid with a finger and lubricating the

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Subspeciality-Oculoplasty

2. Punctal eversion: examined under Figure 8: Medial canthoplasty Lazy T operation:full thickness
slit lamp. pentagonal lid resection followed by
Generalized Lid Laxity excision of diamond of tarsoconjunctiva
3. Lower eyelid retractor disinsertion/ Bick’s procedure: Full-thickness and repair of coloboma is done in three
laxity: eyelid is completely everted excision of the eyelid is done just medial layers.
to the lateral canthal angle. Resection of
4. Superior lid laxity the eyelid in this location may cause Tarsal ectropion repair with
rounding and medial displacement of reattachment of lower lid retractors:for
5. Presence of scleral show the lateral canthal angle.16 LL ectropion with partial or total LL
retractor weakness.
8. Orbicularis tone: tested by forced Kuhnt–Szymanowski procedure:
closure of eyes, compared with This procedure is useful when there is Cicatricial Ectropion
other side also. excess of lower eyelid skin in addition
to the horizontal laxity. Full-thickness Cicatricial ectropion of the upper or
Management pentagon excision is combined with lower eyelid occurs following loss of
excision of redundant skin.17 skin secondary to thermal or chemical
1. Mild punctal ectropion without Lid burns, mechanical trauma, surgical
laxity 3. Ectropion with Lower lid retractor trauma or chronic actinic skin damage
weakness
Excision of diamond of tarsus and
conjunctiva.

2. Ectropion with horizontal lid
laxity without lower lid retractor
weakness

Lateral canthal tendon (LCT) laxity
a. Mild
LCT sutures/ plication: suturing of
lateral most edge of lower tarsal plate
and adjoining lateral canthal tendon
to periosteum just posterior to lateral
orbital rim by 5-0 prolene.13

b. Severe
Lateral tarsal strip : To tighten the
lateral canthus and to shorten the eyelid
horizontally.

Medial canthal tendon (MCT) laxity
a. Mild
MCT sutures/ plication :
The canalicular part of medial
canthal tendon is shortened by
suturing the medial end of lower
tarsal plate to the main part of
medial canthal tendon with a buried
nonabsorbable suture.14 (Figure
8)

b. Severe
MCT resection: for marked medial
canthal laxity with severe medial
ectropion. Full thickness vertical
resection of medial lid structures
including punctum is done followed
by marsupialization of remaining
canaliculus on medial side is done.
Lateral cut edge of tarsal plate is then
anchored to exposed periosteum of
posterior lacrimal crest.15

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Subspeciality-Oculoplasty

leading to shortening of anterior
lamella, chronic inflammation of the
eyelid from dermatologic conditions
such as rosacea, atopic dermatitis,
eczematoid dermatitis or herpes zoster
infections.Cicatricial changes of varying
degree are characteristic features and
may be associated with symblepharon
and ankyloblepharon. (Figure 9)

Figure 10: Z plasty.

Figure 9: Post traumatic cicatricial ectropion original scar and kept for 48 hours are frequently seen in clinical
postoperatively (Figure 10). practice. Proper diagnosis and timely
Management management can prevent further
3. Skin grafting: it is indicated if there complications like recurrent corneal
Conservative management : Antiscar is shortage of skin, using a pedicle abrasions and exposure keratopathy.
creams flap or graft. Role of antifibrotic
agents like 5FU and Mitomycin References
Occlusive dressings: silicone gel sheet – C has also been documented to
decrease periorbital scarring and 1. Rook A. The skin and the eyes. In: Rook
Surgical management: thereby has a role in treatment of A, Wilkinson DS (eds). Textbook of
1. VY operation:indicated in mild cicatricial ectropion. Dermatology.

degree ectropion. V shaped incision Mechanical Ectropion 2. Kemp EG, Collin JR. Surgical
is given , skin is undermined and management of upper lid entropion. Br
sutured in Y shaped pattern after It occurs secondary to bulky tumors, J Ophthalmol 1986;70:575-9.
excising underlying scar tissue. proptosis and chronic inflammatory
disorders. Cause of mechanical 3. Aziz S, Bhatt PR, Lavy T, Dutton G. A
2. Z plasty/ Elschnig’s operation:after ectropion needs to be treated and if lid simple correction for congenital tarsal
marking the line of the scar, from laxity is there, it should be appropriately kink associated with distichiasis. J
each end two other lines of same corrected surgically. AAPOS 2006;10:281-3.
length angled at 60o are drawn;
forming a Z shape. The skin flaps are Paralytic Ectropion 4. Kakizaki H, Selva D, Leibovitch I. Cilial
cut and deep scar tissue is excised. entropion: Surgical outcome with a new
The flaps are transposed and sutured It results due to paralysis of the seventh modification of the Hotz procedure.
with 6-0 nonabsorbable suture. A cranial nerve. Common causes of facial Ophthalmology 2009;116:2224-9.
4-0 silk traction suture should be nerve palsy are Bell’s palsy, head injury
passed through lid margin in line of and otitis media.18 5. Khurana AK. Disorders of Eyelids,
Lacrimal System, Orbit and Oculoplastic
Treatment surgery. 2nd edition. India:MSO;2018.

1. Self resolution: it often resolves 6. Quickert MH, Rathbun E. Suture
spontaneously within 6 months repair of entropion. Arch Ophthalmol
specially in Bell’s palsy cases. 1971;85:304-5.

2. Temporary measures like frequent 7. 13.Anderson RL, Gordy DD. The tarsal
lubrication and lid taping at night. strip procedure. Arch Ophthalmol
1979;97:2192-6.
3. Tarsorrhaphy to manage exposure
keratitis. 8. Jones LT. The anatomy of the lower
eyelid and its relation to the cause and
Conclusion cure of entropion. Am J Ophthalmol
1960;49:29-36.
Ectropion and entropion are
common eyelid malpositions which 9. Lance SE, Wilkins RB. Involutional
entropion: A retrospective analysis of
the Wies procedure alone or combined
with a horizontal shortening procedure.

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Subspeciality-Oculoplasty

OphthalPlastReconstrSurg 1991;7:273- 13. Fox SA. A medical ectropion procedure. 18. Jelks GW, Smith B, Bosniak S. The
7. Arch Ophthalmol 1968;80:494-5. evaluation and management of eye in
facial palsy. Clin PlastSurg 1979;6:397.
10. Ahuero AE, Hatton MP. Eyelid 14. Jones LT. An anatomical approach
malposition after cataract and Corresponding Author:
refractive surgery. Int Ophthalmol Clin to problems of eyelids and lacrimal
2010;50:25-36. Dr.Urmil Chawla
apparatus. Arch Ophthalmol Professor
11. Kersten RC, Kleiner FP, Kulwin DR. Strabismus and Oculoplasty Unit
Tarsotomy for the treatment of 1961;66:137-50. Pt.BD Sharma, PGIMS, Rohtak
cicatricial entropion with trichiasis.
Arch Ophthalmol 1992;110:714-7. 15. McCord CD. Canalicular resection with
canaliculostomy. Ophthalmic surgery
12. Sodhi PK, Yadava U, Mehta DK. Efficacy 1980;11:440-5.
of lamellar division for correcting
cicatricial lid entropion and its 16. Leone CR Jr. Repair of ectropion using
associated features unrectified by the Bick procedure. Am J Ophthalmol
the tarsal fracture technique. Orbit 1970;70:233-5.
2002;21:9-17.
17. Choi SJ, Park SH. Surgical treatment
of facial paralysis by using static

ancillary procedures. J Korean Soc

PlastReconstrSurg 1998;25:1531-9.

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Subspeciality-Oculoplasty

Contracted Socket

Nitish Arora MS, Sweety Tiple MS, Sima Das MS
Dr Shroff’s Charity Eye Hospital, Drayaganj, New Delhi, India

The loss of an eye leading to Table 1: Ideal Anophthalmic socket
anophthalmic socket causes functional
and psychological morbidity to the Implant • Centrally placed
patient and poses a challenge for both • Well Covered
the ophthalmologist and ocularist. • Adequate volume
This article provides an overview of the • Stable Material
etiology, classification, evaluation and
management algorithms for contracted Conjunctiva • Healthy
socket. • Well-formed and deep fornices

Anophthalmic socket can present as: Eyelids • Normal tone and position of the eyelid margin

1. Post enucleation socket syndrome- Prosthesis • Satisfactory movements of prosthesis over the surface
It encompasses features like-
a. Enophthalmos Table 2: Etiology of Contracted Socket
b. Ptosis
c. Lower lid laxity Congenital • Congenital anophthalmia
d. Orbital implant exposure • Microphthalmos
• Cystic ocular remnants
2. Contracted Socket- It is defined as a
complicated anophthalmic socket Acquired • Conjunctival scarring due to trauma
with inadequacy of surface area of • Chronic inflammation
the conjunctiva or orbital volume • Poor surgical techniques during previous surgeries with
or both leading to instability and/or extensive dissection of the orbital tissues
inability to support the prosthesis. • Poor vascular supply
• Prior severe ischemic ocular disease
Ideal anophthalmic socket • Alkali/acid burns
The salient features of an ideal • Cicatrizing conjunctival diseases
anophthalmic socket conducive for • Radiation therapy (plaque or external beam)
good cosmetic rehabilitation and • Implant migration
outcome is provided in Table 1. A • Implant exposure or extrusion
well centered implant, adequate • Inadequate orbital implant size
conjunctival surface and normally • Infection
functioning and positioned eyelid are • Not wearing a conformer or prosthesis
essential for achieving good cosmetic • A poor-fitting prosthesis
outcome.
most widely used system for contracted prosthesis stability.
Etiology of contracted socket socket. Contracted socket is divided b. Volume of the socket: It is assessed
Contracted socket could be congenital into five grades as per this classification
or acquired following trauma, surgery, and is provided in Table 3. by noting the relative depth of the
radiation etc. The various causes of Evaluation of contracted socket socket compared to the fellow eye.
contracted socket are outlined in Table a. Area of the Socket: The depth of The depth of the superior sulcus
2. and presence of ptosis are also
the fornices helps in assessment indicators of volume loss.
Contracted socket -classification of area. The inferior fornix is c. Dry / Wet socket: Presence of active
most important as it supports the discharge from the socket signifies
Gopal Krishna1 classification is the prosthesis. The other fornices also infection. Dry fibrosed conjunctiva
need to be adequate to ensure the indicates a poorly vascularised
socket.

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Subspeciality-Oculoplasty

Table 3: Classification of Contracted Socket cases can usually difficult to treat.
Any orbital fractures, if present
Grade I Shortening of the inferior fornix should be noted and corrected
simultaneously wherever possible.
Grade II Shortening of both superior and inferior fornices Prevention of contracted socket

Grade III Shortening of all four fornices The following precautions taken during
surgery or following surgery can help
Grade IV Grade III + reduced vertical and horizontal palpebral aperture in prevention of surface contraction to
dimensions some extent.

Grade V Recurrence of contracture after repeated trial of reconstruction 1. During surgery: Careful handling of
Tenon’s and conjunctival tissue is
Table 4: Algorithm of Congenital Contracted Socket Management of utmost importance. Conjunctival
peritomy during evisceration or
Serially • It is the mainstay of treatment enucleation surgery should be
enlarging • Started in first few weeks of life done flush to the limbus to prevent
conformer • Act by stretching the eyelids as well as the conjunctival and unwanted excision of healthy
fornices conjunctiva. Surgery in an inflamed
• Conformer is replaced with the next bigger size, once the socket should be avoided. Use of
socket outgrows a particular sized appropriate and adequate sized
implant can prevent complications
Hydrogel • Are in form of spheres or pellets like post enucleation socket
hemispherical • They are injected in their dry anhydrous state, and once syndrome (PESS). An appropriately
expanders placed, imbibe water and expand up to 30 times their volume wrapped implant especially in
(for spheres) and 10 times (for pellets) enucleation can prevent implant
• Once they reach equilibrium with surrounding structures, related complications.
further expansion ceases and may need to be exchanged (for
spheres) or require re-injections (for pellets) 2. Conformer: A conformer should
• Adverse effects are migration, uncontrolled expansion, alwaysbe placed at the end of
foreign body reaction and infection the surgery to maintain the
• Placed in the conjunctival fornix followed by a tarsorrhaphy conjunctival surface and fornices
which aid in forniceal expansion and is replaced by the prosthetic
• Tarsorrhaphy is released after 2–3 months, which is followed eye after 4-6 weeks.
by the placement of an acrylic conformer for further socket
expansion2,5 3. Radiotherapy: Orbital radiation
whenever required should be
Orbital tissue • Consists of an inflatable balloon attached to a titanium used with fractionation of dose to
expander (OTE) fixation plate6-8 reduce the chances of socket and
conjunctival scarring and fibrosis.
• The titanium plate can be fixed to lateral orbital rim with
screws ensuring unidirectional expansion unlike other Management of contracted socket
inflatable expanders
• It is provided with an injection port through which a 30G The primary goal of management is
needle is connected to a 1 cc syringe can be inserted to inflate to identify and correct the underlying
the expander. The ports seals after removal of the needle etiology so that patient is able to
Thus, it eliminates the use of any conjunctival or soft tissue comfortably wear prosthesis, and
incision achieve the best motility and cosmesis
• In addition to orbital growth stimulation, this device induces possible.
the growth of surrounding bones like the maxilla and
zygoma and provided better eyebrow position, facial fullness In advanced cases of socket contracture,
and symmetry primarily the ability of the patient
to wear a stable prosthesis forms
d. Movements: Presence of intact e. Eyelid: Abnormalities of eyelid like the primary goal, with motility and
extraocular muscles is essential for lid laxity, notching, eyelid closure symmetry to the contralateral side are
the final prosthesis movement. In and lagophthalmos should be of secondary consideration.
case of intrascleral shell implant looked for.
the movements are better. Also in
dermis fat grafting, suturing the f. Associated bony contracture seen in
muscles to the graft ensures better cases with insult in early childhood,
survival. post radiotherapy or congenital

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Subspeciality-Oculoplasty

Congenital socket contracture

Features

a. Patients present with both soft
tissue as well as bony contracture.

b. There is narrowing of palpebral
fissure, both horizontal and vertical,
with deficiency of the palpebral and
bulbar conjunctiva. The growth of
the orbit, lids and also surrounding
facial skeleton and the sinuses is
stimulated by the growth of the
eyeball. The eye grows fastest in
the first year of life with 70% of its
adult size attained by 4 years, 90%
by 7 years and completed by 14
years of age2-4.

c. Patients with congenital
anophthalmos can have associated
systemic anomalies and needs to
be screened by the pediatrician
for the same. The child should be
assessed for any vision potential in
the involved eye by the pediatric
ophthalmologist before planning
for socket rehabilitation.
Figure 1: Grades of Contracted Socket; A. Grade 1: shelving of the inferior fornix with
A stepwise algorithm to be followed increased laxity of the lower lid; B. Grade 2: Loss of the upper and lower fornices; C. Grade
for the management of congenital 3: Loss of overall depth of the fornix due to obliteration of all the four fornices with severe
anophthalmos is provided in Table 4. volume loss; D. Grade 4: complete obliteration of inferior, lateral and medial fornices with
The management steps involve: shallowing of the superior fornix thereby causing reduction of the dimension of the palpebral
aperture.
1. Expansion of lids/phimosis
2. Expansion of fornices anteriorly displaced implant also and irradiated sockets are also
3. Expansion of bone fall in this category (Figure 1A). included in this category (Figure
Acquired socket contracture 1D).
2. Grade 2: Mild contracture of Management of Acquired
Acquired socket contracture could be the inferior and/or the superior Contracted Socket
following surgery, chemical, thermal fornix. Patient either complains The management algorithm for acquired
or mechanical trauma to the socket, of inability to wear the prosthesis socket contracture is provided in Table
radiation etc, It is important to identify or may complain of a cosmetic 5. Both the surface contracture and
the cause of the contracture, and treat disfigurement due to rolling-in of volume loss needs to be addressed along
it accordingly. Socket contracture is the upper and lower eyelid margin with management of other associated
classified into four grades (Figure 1) (Figure 1B). conditions like eyelid abnormalities etc
for the management point of view as to achieve an adequate socket for a well
follows: 3. Grade 3: More advanced scarring fitted prosthesis
than grade 2. Cicatrization
1. Grade 1: Minimal or no actual generally involving the entire Management of volume deficiency
contraction. Patients usually upper and lower fornices. Wearing
complain of inability to retain the prosthesis is impossible (Figure Orbital implants are used for correction
the prosthesis for a long time. 1C). of volume deficit. Primary volume
Horizontal lid laxity is usually replacement is preferred unless it is
observed, with subsequent prolapse 4. Grade 4: Severe phimosis of the contraindicated as in cases of severe
or retraction of the inferior fornix. palpebral fissures both vertically ocular trauma or infection (inhibiting
Patients with an unusually large or and horizontally. Recurrent cases

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Subspeciality-Oculoplasty

Table 5: Management of Acquired Contracted Socket

Table 5: Management of Acquired Contracted Socket a) Autologous implants
Management of Socket contracture
• Dermis fat graft (DFG) (Figure 2).
Management of volume deficit Management of deficient surface
DFG is a widely preferred live graft as it
Autologous Implants Synthetic Orbital Implants Mucous Membrane Graft (MMG) an autologous graft and is known to grow
Amniotic Membrane Graft (AMG) with age. It is preferred both in children
Dermis Fat Graft Non integrated and adults in managing anopthalmia
Split thickness skin Graft following implant migration/exposure
Micro Fat Graft Semi integrated and also as a primary implant following
Integrated enucleation. DFG is indicated in cases
(Porous with both surface as well as volume
implants) loss, as the dermis replaces the surface
and allows conjunctival growth and the
Figure 2: Dermis Fat Graft; A: Spindle shaped incision marked in the upper outer fat replaces the volume lost.
quadrant of the buttock area; B. Epidermis over the donor area is removed with a #15 blade.
Presence of multiple pin-point hemorrhages on the surface indicates adequate removal of Surgical technique
the epidermis. Graft surface area has to be 25% excess of the recipient bed; C. The graft is
obtained by giving vertical incision with depth of approx. 25mm to obtain a thick chunk of o The graft is taken from patient’s
fat; D. 2 months post –op socket photo after DFG. Complete epithelization of the graft noted own body – upper outer quadrant
with adequate fornices. of the gluteal region, non-hair
bearing area of anterior abdominal
closure of the wound)12. In such cases, methods used for volume replacement wall is the most preferred sites. A
secondary implantation or a dermis fat for the anophthalmic socket are as horizontal incision is given on the
graft should be considered. The various follows: conjunctival surface from caruncle
to the lateral canthus and the
subconjunctival tissue is dissected
to remove all the scar tissues.
After passing the Fornix formation
sutures, the size of the bed is
calculated taking into account
the length, width and the depth.
An excess of 30% of the bed size
is calculated while harvesting the
graft.

o A spindle shaped skin incision is
marked with the desired dimensions
(Figure 2A). The epidermis is shaved
off using a # 15 blade (Figure 2B).
Multiple pin-point hemorrhages
can be visualized on the dermis
surface. Care should be taken to
remove all the visible hair follicles
from the graft surface. The graft is
harvested as a conical graft with a
#11 blade taking a depth of 25mm
to get a large bulk of fat (Figure 2C).
The fat can be trimmed according
to the depth of the socket. The graft
is then placed on the host bed and
pressed into the socket and secured
with absorbable 6-0 vicryl sutures
to the edges of the conjunctiva
(Figure 2D). Extra-ocular muscles
whenever identified can be attached
to the DFG as it helps in early

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Subspeciality-Oculoplasty

Table 6: Advantages and Disadvantages of DFG uptake of the graft. This is followed
Advantages by placement of the conformer and
• Replaces both volume and surface deficiency, so these are good for severely tightening of the FFS.
o The advantages and disadvantages
contracted sockets with severe forniceal shortening of DFG are discussed in Table 6.
• Preferred for growing children as it has a tendency to expand with growth of b) Synthetic orbital implant

the child As proposed by Kaltrieder et al13,14,
• Does not need a wrapping material for implantation the size of the implant is calculated
• Nil chances of extrusion/migration by subtracting 1 mm from the axial
Disadvantages length of the normal contralateral
• Graft can undergo central ulceration, necrosis and melt. eye, if the implant is to be wrapped.
• Donor site morbidity Implants can be placed directly within
• Can undergo fat atrophy and lead to suboptimal volume replacement or the scleral coat (if sclera is available
after the previous evisceration surgery)
excessive fat proliferation if the patient gains weight or can be placed directly in the
• Chances of graft failure is high if the socket is ischemic/dry (post radiotherapy intraconal space following enucleation.
Integrated implants need to be wrapped
patients with repeated socket surgeries as the chance of bed vascularity is in materials such as sclera, dura,
compromised) pericardium, fascia lata, temporalis
fascia, alloderm or vicryl mesh to attach
Figure 3: Fornix Formation Sutures with Mucosal membrane graft; A. Socket the extraocular muscles15. Three types
is prepared by giving a horizontal incision and fibrous tissue excised by undermining the of synthetic implant been described in
conjunctiva till the fornices. Three double armed 4-0 silk sutures (FFS) are passed through the Table 7.
conjunctival edges taking a bite through periosteum of the superior and inferior orbital rim to
form the fornices.; B. MMG placed over the recipient bed and sutured to the conjunctival edges o Non-integrated: silicon or acrylic
with 6-0 Vicryl sutures; C. FFS are tightened over the bolsters after inserting a conformer and (PMMA).
suture tarsorrhaphy done; D. Oral mucosal wound 1 week post op. The amniotic membrane
graft over the donor area has started to disintegrate and the wound is healing. o Semi-integrated: Allen implant,
Iowa implant, Medpor quad
implant.

o Integrated: hydroxyapatite (HA)-
natural coralline or synthetic,
Porous polyethylene (Medpor),
Aluminium oxide (Bioceramic
implants).

Management of surface deficiency

Contracted socket syndrome is
characterized by fibrosis of the
anophthalmic socket including
conjunctival cicatrisation and fornix
shortening. Various techniques
and adjuvant measures such as
fornix deepening sutures, topical
application of Mitomycin C and
the use of conformers shells to
optimise the outcome of conjunctival
reconstruction and to minimize the
risk of recurrent fornix shortening and
socket contraction can be considered in
surgical reconstruction.

a. Fornix formation sutures (FFS)

Primary FFS without surface

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Subspeciality-Oculoplasty

Table7: Types of Implants

Non- • Made of inert material like silicon or acrylic spherical in shape
integrated • No connection with the overlying prosthesis
(non- • Inert and lack ingrowths of fibrovascular tissue
porous) • Higher rates of migration but lower chances of implant exposure.
• Implanted using the myoconjunctival technique
• A 18 mm diameter, sphere typically gives a volume of 3.1 mL,
while a 20 mm sphere gives a volume of 4.2 mL
Advantages:-
• Motility of the custom ocular prosthesis is better
• Used in cases where exchange of implant may be required later
and are generally inexpensive

Semi- • Can be porous or non-porous
integrated • Implants remain buried under the conjunctiva and do not have
a peg system. Instead they have a rough anterior surface which
provides indirect coupling of the prosthesis resulting in better
motility
• Risk of exposure is high
• Examples are Allen Implant, Iowa Implant and Medpor Quad
Implant

Integrated • Have a regular system of interconnecting pores which allow
implants fibrovascular ingrowth which reduces the chances of migration
(porous and extrusion of the implant
implants) • Time for fibrovascular ingrowth varies between 4 and 12 months
• Motility peg can be inserted usually at 6 months to 1 year
• Risk of thinning and erosion of the Tenon’s and conjunctiva Figure 4: Pre and Postop picture; A &B
is very high and may be associated with formation of pyogenic Pre-op photo showing grade 1 anophthalmic
granulomas or orbital infection socket with severe volume loss, Superior
• Examples are Hydroxyapatite (HA)- natural coralline or sulcus deformity and shelving of the inferior
synthetic, Porous polyethylene (Medpor), Aluminium oxide fornixl C. 8 weeks Post op photo of the patient
(Bioceramic implants) after undergoing secondary implant MMG
and FFS. The superior sulcus deformity and
augmentation with a graft is indicated membrane graft (Figure 3C) to deepen volume loss is corrected with stable retention
in grade 1 contracted socket when the the respective fornices when there is of the customized prosthesis.
surface is adequate, but due to shelving associated surface contracture.
or stretching of the inferior fornix, there The medial and lateral fornices are
is failure to retain the prosthesis. Under b. Mucous membrane graft formed only if shallow. The area of the
local infiltration, 2 or 3 double armed central defect is then measured. 30-40 %
4-0 silk sutures are passed through the Mucosa can be taken from any of the excess mucosal graft (especially in the
respective fornix and brought out on following sites: Buccal cavity (lip or vertical dimension) is harvested allow
the skin surface (Figure 3A) taking a cheek), rectum or vagina. The buccal for some shrinkage. The graft is sutured
deep bite through the periosteum of cavity is preferred as it is easy to access onto the bed with absorbable 6-0 vicryl
the adjacent orbital rim in order to (Figure 3D). sutures to the conjunctival edges. A
cause adhesion of the subconjunctival well fitting conformer is placed on the
tissues to the periosteum and thereby Surgical technique graft and the FFS sutures tightened after
causing deepening of the respective placing a suture tarsorrhaphy.
fornix. They sutures are brought out The host bed is prepared as follows.
through a rubber peg/ bolster to prevent A horizontal linear incision is Retrieval of graft
cheese - wiring of the skin (Figure 3B). placed in the centre of the socket, The mucosal graft may be taken from
A conformer is then placed into the extending from the medial to the the lip or from the cheek. Split thickness
socket and the FFS are tied after doing lateral canthus. Dissection is done in
a temporary suture tarsorrhaphy. These the subconjunctival plane and all the
sutures are removed after 2-3 weeks. scar tissue is excised and fibrous septa
FFS can be combined with a mucus broken. Three fornix formation sutures
are passed through both the fornices.

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