DJO Jan- Mar -2022 Volume 32 No (3)

DJO Vol. 32, No. 3, January-March 2022

pressure from latanoprost to bimatoprost in eyes with open and meta-analysis. Br J Ophthalmol. 2016; 100:86-93.
angle glaucoma: implication to the changes of central corneal 38. Bohn RL, Gurwitz JH, Yeomans SM, Glynn RJ, Pasquale LR,
thickness. Jpn J Ophthalmol. 2014; 58: 423-8.
17. Cheng JW, Wei RL. Meta-analysis of 13 randomized controlled Walker AM, et al. Which patients are treated for glaucoma? An
trials comparing bimatoprost with latanoprost in patients with observational analysis. J Glaucoma. 2000; 9:38-44.
elevated intraocular pressure. Clin Ther. 2008; 30: 622-32. 39. Baudouin C. Allergic reaction to topical eye drops. Curr Opin
18. Park KH, Simonyi S, Kim CY, Sohn YH, Kook MS. Bimatoprost Allergy Clin Immunol. 2005; 5:459-63.
0.01% in treatment-naïve patients with open-angle glaucoma 40. Stewart WC, Stewart JA, Nelson LA. Ocular surface disease in
or ocular hypertension: an observational study in the Korean patients with ocular hypertension and glaucoma. Curr Eye Res.
clinical setting. BMC Ophthalmol. 2014; 14: 1-9. 2011; 36: 391-8.
19. Shimazaki J, Hanada K, Yagi Y, Yamagami J, Ishioka M, 41. Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular
Shimmura S, et al. Changes in ocular surface caused by symptoms and signs with preserved and preservative free
antiglaucomatous eyedrops: prospective, randomised study glaucoma medication. Br J Ophthalmol. 2002; 86: 418-23.
for the comparison of 0.5% timolol v 0. 12% unoprostone. Br J 42. Becquet F, Goldschild M, Moldovan MS, Ettaiche M, Gastaud
Ophthalmol. 2000; 84: 1250-4. P, Baudouin C. Histopathological effects of topical ophthalmic
20. Bhatti A, Singh G. Efficacy of three different formulations of preservatives on rat corneoconjunctival surface. Curr Eye Res.
brimonidine for control of intraocular pressure in primary 1998; 17: 419-25.
open-angle glaucoma: A 6-week randomized trial. Oman J 43. Paimela T, Ryhanen T, Kauppinen A, Marttila L, Salminen A,
Ophthalmol. 2018; 11: 140-3. Kaarniranta K. The preservative polyquaternium-1 increases
21. Katz LJ. Twelve-month evaluation of brimonidine-purite versus cytoxicity and NF-kappaB linked inflammation in human
brimonidine in patients with glaucoma or ocular hypertension. corneal epithelial cells. Mol Vis. 2012; 18: 1189-96.
J Glaucoma. 2002; 11: 119-26. 44. Valente C, Iester M, Corsi E, Rolando M. Symptoms and signs
22. Mundorf T, Williams R, Whitcup S, Felix C, Batoosingh A. A of tear film dysfunction in glaucomatous patients. Journal of
3-month comparison of efficacy and safety of brimonidine- Ocular Pharmacology and Therapeutics. 2011; 27:281-5.
purite 0.15% and brimonidine 0.2% in patients with glaucoma 45. Pérez-Bartolomé F, Martínez-de-la-Casa JM, Arriola-Villalobos
or ocular hypertension. J Ocul Pharmacol Ther. 2003; 19: 37-44. P, Fernández-Pérez C, Polo V, García-Feijoó J. Ocular surface
23. Kadambi SV, George R. Newer drugs in glaucoma management. disease in patients under topical treatment for glaucoma. Eur J
TNOA J Ophthalmic Sci Res. 2017; 55: 134-9. Ophthalmol. 2017; 27:694-704.
24. Ramli N, Supramaniam G, Samsudin A, Juana A, Zahari 46. Mathews PM, Ramulu PY, Friedman DS, Utine CA, Akpek EK.
M, Choo MM. Ocular surface disease in glaucoma: effect of Evaluation of ocular surface disease in patients with glaucoma.
polypharmacy and preservatives. Optometry and Vision Ophthalmology. 2013; 120: 2241-8.
Science 2015; 92: e222-6. 47. Ghosh S, O'Hare F, Lamoureux E, Vajpayee RB, Crowston JG.
25. Van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Prevalence of signs and symptoms of ocular surface disease in
Arch. Ophthalmol. 1969; 82: 10-4. individuals treated and not treated with glaucoma medication.
26. Cvenkel B, Štunf S, Kirbiš IS, Fležar MS. Symptoms and signs of Clin Exp Ophthalmol. 2012; 40: 675-81.
ocular surface disease related to topical medication in patients
with glaucoma. Clin Ophthalmol. 2015: 9; 625-31. Cite This Article as: Aparajita Richhariya, Anshu Sahai,
27. Nelson JD. Impression cytology. Cornea 1988; 7: 71-81. Mohammad Abid Shamshad, Pukhrambam Ratan Kumar, Maryem
28. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular Ansari. Retrobulbar Amphotericin B in Mucormycosis: A Ray of
surface disease in glaucoma patients. J Glaucoma 2008; 17: 350- Hope. Delhi Journal of Ophthalmology.2022; Vol 32, No (3): 45- 49.
5.
29. Servat JJ, Bernardino CR. Effects of common topical Acknowledgments: Nil
antiglaucoma medications on the ocular surface, eyelids and
periorbital tissue. Drugs & Aging 2011; 28: 267-82. Conflict of interest: None
30. Asbell PA, Potapova N. Effects of topical antiglaucoma
medications on the ocular surface. Ocul Surf. 2005; 3:27-40. Source of Funding: None
31. Ouyang PB, Duan XC. Ocular surface injury resulted from
topical anti-glaucoma medications prevention and cure. Date of Submission: 02 Jan 2022
Zhonghua Yan Ke Za Zhi. 2012; 48: 557-61. Date of Acceptance: 24 Mar 2022
32. Thirunavukkarasu A, Karunakaran R. A study on evaluation of
ocular surface disease in patients with glaucoma. Int J Sci Stud. Address for correspondence
2019; 7:48-52.
33. Saini M, Vanathi M, Dada T, Agarwal T, Dhiman R, Khokhar Aparajita Richhariya
S. Ocular surface evaluation in eyes with chronic glaucoma
on long term topical antiglaucoma therapy. Int J Ophthalmol. DOMS, DNB Resident
2017; 10:931-8.
34. Zhu W, Kong X, Xu J, Sun X. Effects of Long-Term Antiglaucoma Department of Ophthalmology, Sahai
Eye Drops on Conjunctival Structures: An In Vivo Confocal Hospital and Research Centre, Jaipur,
Microscopy Study. J Ophthalmol. 2015; 2015: 165475. Rajasthan, India.
35. Chen J, Dinh T, Woodward DF, Holland M, Yuan YD, Lin Email : [email protected]
TH, Wheeler LA. Bimatoprost: mechanism of ocular surface
hyperemia associated with topical therapy. Cardiovasc Drug Quick Response Code
Rev. 2005; 23: 231-46.
36. Kim YK, Choi HJ, Jeoung JW, Park KH, Kim DM. Five-
year incidence of primary open-angle glaucoma and rate of
progression in health center-based Korean population: The
Gangnam eye study. PLoS ONE. 2014; 9: e114058.
37. Kapetanakis VV, Chan MPY, Foster PJ, Cook DG, Owen CG,
Rudnicka A. Global variations and time trends in the prevalence
of primary open angle glaucoma (POAG): a systematic review

E-ISSN: 2454-2784  P-ISSN: 0972-0200 49 Delhi Journal of Ophthalmology

DJO Vol. 32, No. 3, January-March 2022

Original Article

Health Literacy on Cataract and Its Treatment Options Among
Patients with Operable Cataract: A Cross Sectional
Study from Moradabad (India)

Richa Gupta, Akansha Gupta, Mossab Omair, Lokesh Chauhan, Pradeep Agarwal, Ashi Khurana

Department of Ophthalmology, CL Gupta Eye Institute, Ram Ganga Vihar, Phase 2(Ext) Moradabad, Uttar Pradesh, India.

Purpose: To investigate the awareness of cataract disease and treatment options among patients with operable cataract.

Methods: Participants were selected by means of eye disease screenings throughout Moradabad district. A pre-tested structured,
content-validated questionnaire, translated in Hindi, was used for seeking study-related information and consisted of three
sections: 1) Socio-demographic characteristics, 2) Knowledge and 3) Attitude of patients regarding cataract and its treatment.
Questionnaire was administered by a trained interviewer after it was determined that the patient needed cataract surgery.

Results: A total of 192 participants were interviewed. Of all, 98.5% patients were aware of their condition. Surgery as a

Abstract treatment for cataract was known to 57.6% respondents. 50.2% patients knew that during surgery, natural lens was replaced
with an artificial lens. 89.2% believed that the cost of cataract surgery prevented people from seeking interventions, while 31.5%

deemed it unaffordable. An acquaintance getting operated was the motivating factor for 47.3% patients. The principal barriers

in seeking cataract treatment were found to be lack of accessibility and fear of pain in by 98% and 65.5% of patients respectively.

Conclusion: Our study highlighted that majority of the respondents were aware of cataract as a disease, but the potential
barriers preventing them from seeking treatment were accessibility, cost of surgery and personal belief. This study emphasizes
the need for increasing the uptake of cataract services in the North Indian community. We apprehend that focused propagation
of knowledge and communication will successfully enhance demand for cataract surgical services.

Delhi J Ophthalmol 2022;32; 50-54; Doi http://dx.doi.org/10.7869/djo.741
Keywords: Awareness, Cataract surgery, Knowledge, Barrier, Affordability

Introduction Methods

Worldwide, over 300 million people are visually impaired This population based cross-sectional study was designed
and 45 million are blind.1 Cataract is the leading cause of and conducted by a tertiary eye care institute in Moradabad
non-refractive reversible blindness. Studies have also shown district of Uttar Pradesh (India) during August 2019
that even though the visual function can recovered by to January 2020. It was reviewed and approved by the
cataract surgery, still the uptake of cataract surgery is low Institutional Ethics Committee and was conducted in
in developing countries. The barriers for uptake of cataract accordance to the tenets of Declaration of Helsinki. Informed
surgery ranged from economic and socio-cultural influencing consent was taken from every patient before enrollment.
factors such as beliefs, values, and the individual's attitudes
and perceptions, to fear, lack of confidence, and insecurity.2,3 Study enrollment was done at community eye screening
Lack of knowledge about the disease, its surgical procedure camps by convenient sampling technique. Inclusion criteria
and occasionally, unrealistic expectations about the visual were- patients diagnosed with senile cataract with sub-
outcomes have also been identified as contributing factors.4,5 optimal best corrected visual acuity (BCVA), and counselled
Globally, in the last two decades, the number of blind and for cataract surgery. Eyes with congenital cataract and
visually impaired due to cataract have decreased by 11.4% secondary causes of cataract like trauma, uveitis etc. were
and 20.2% respectively.6 excluded from the study. A comprehensive eye examination
of all patients was done according to community eye
Though, India has been successfully raising its cataract screening camp protocol.10
surgical rate,7,8 which is defined as the number of cataract
operations performed per year per million people of an A total of 192 participants were interviewed. A content-
area,4 the burden of cataract remains a major public health validated questionnaire was used during interview,
concern. According to the State Census 2011, the most which was developed by performing literature review
populated state in India, Uttar Pradesh (UP) has a population of previously published studies and was pretested by
of 199.6 million,9 out of which 0.7 million people are visually interviewing 30 cataract patients identified at our institute.
impaired.9 Such a high degree of disability necessitates an Content validation was done by subject matter experts.
extensive effort towards increasing the uptake of cataract Pre-testing was done to improve its reliability and ease
surgeries. While reviewing the data of our community eye of implementation. The resultant data generated was not
screening camps, a significant number of patients were included in the final analysis. As Hindi is the local language;
identified to have opted out of cataract surgery. This study all questions were asked verbally in Hindi accordingly by
was planned to identify the potential barriers to the uptake an independent trained interviewer. Apart from socio-
of cataract surgery. demographic characteristics, questionnaire consisted of
two sections comprising of knowledge and attitude of
participants regarding cataract and its treatment. Socio-

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DJO Vol. 32, No. 3, January-March 2022

demographic section contained five questions on age, considered it as a treatable disease. A total of 110 (57.3%;
gender, education, occupation and duration of symptoms. 95% CI: 50-64%) were well informed about its basic surgical
A patient who has completed at least primary education was procedure, like availability of different types of cataract
considered as literate. Nine questions were included in the surgeries {by 113 subjects (58.9%; 95% CI: 51.5-65.9%)} and
knowledge and attitude sections each. (Annexure 1) that natural lens was replaced with an artificial lens during
surgery {by 99 participants (51.6%; 95% CI: 44.3-58.8%)}. Less
Statistical Analysis than half of the patients, {60 (31.3%; 95% CI: 24.8-38.3%)}
deemed cataract surgery affordable. An acquaintance
Statistical analysis was performed using Statistical software already operated for cataract surgery was the most frequent
IBM SPSS Statistics version 20. Descriptive statistics were source of information, as responded by 91 (47.4%; 95% CI:
obtained to determine the frequency and proportions. 40.2-54.7%) participants. The frequency distributions of
Mean and standard deviation was calculated for continuous responses to all questions asked in this section are presented
variables. Summaries of descriptive statistics and group in (Table 2).
comparisons were provided, which were made using the
unpaired t-test for continuous data and the chi square test Table 2: Knowledge of respondent as regards to cataract and its surgery
for proportions. (n=192)

Findings Questions Options Response
(N %)
[A] Demographics: Of all participants, 90 (46.9%) were male Q1: Previous knowledge about cataract Yes
and 102 (53.1%) were female (p=0.42; One sample binomial 189 (98.4)
test). Average age of participants was 60.7±9.5 (Range: 40-
86) years (males: 60.5±9.7 and females 60.8±9.3 years {p=0.85; No 3 (1.6)
independent t test}). The average duration of symptoms was
9.8±8.7 months. The average duration of symptom of male Aging 90 (46.9)
participants was 8.7±0.9 and of female participants was
8.8±0.8 months (p=0.7; independent t test). The frequency Malnutrition 18 (9.4)
distribution of education and occupation of participants are
presented in (Table 1). Q2: What cause cataract Smoking 25 (13.0)
17 (8.9)
Prolong
physical/
Outdoor
activity

[B] Knowledge: A total of 189 (98.4%; 95% CI: 95.5-99.7%) Don't know 42 (21.9)
participants were aware of the term cataract. Of all 90 (46.9%;
95% CI: 39.1-54.2%) knew that aging caused cataract, 183 Yes 146 (76.0)
(95.3%; 95% CI: 91.3-97.8%) were conscious of blindness as
its possible complication and 146 (76%; 95% CI: 69.4-81.9%) Q3: Is cataract treatable/or preventable No 46 (24.0)
Yes 183 (95.3)

Table 1: Frequency distribution of respondents as regards to socio- No 9 (4.7)
demographics characteristics (n=192)
Medication 5 (2.6)
Variable Categoryn Female Male Total P-Value Q5:Whatistheeffectitreatmentforcataract Spiritual 18 (9.4)
n (%) n (%) 30 0.97
Age 40-50 Years 58 Don't know 59 (30.7)
16 14 104 0.00
Occupation 51-60 Years (53.3%) (46.7%) 31 0.66 Eye is 37 (19.3)
104 0.82 removed
Education >60 Years 30 28 33
Duration (51.7%) (48.3%) 24 Q6: How cataract is operated in hospital Lens is 99 (51.6)
Farmer 89 removed
of eye House wife 56 48 103
problem (53.8%) (46.2%) 162 and replaced
Service 31 (100%) 22
Not 0 (0.0%) 0 (0.0%) 8 Don't know 34 (17.7)

working 104 33 (100%) Others 22 (11.5)
Illiterate (100%) 24 (100%)
Affordable 60 (31.3)
Literate 0 (0.0%) 40 46 (24.0)
(44.9%) Q7: Are all cataract surgeries the same Not
1-12 0 (0.0%) affordable 37 (19.3)
50
13-24 49 (48.5%) It should be 49 (25.5)
(55.1%) free 41 (21.4)
>24 77 91 (47.4)
53 (47.5%) Can`t say
(51.5%) 9 (40.9%) 27 (14.1)
Media
85 4 (50%) 33 (17.2)
(52.5%) Q9: Sources of information that motivates Someone
people to go for cataract intervention operated
13
(59.1%) Family/
community
4 (50%)
None

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DJO Vol. 32, No. 3, January-March 2022

[C] Attitude: A total of 150 (78.1%; 95% CI: 71.6-83.8%) Gender and the level of literacy did not affect the frequency
patients had consulted a doctor previously for diminution of responses for any question in any section.
of vision. In our study, the most common reason preventing
people from seeking treatment for cataract was found to Discussion
be lack of accessibility by 188 (97.9%; 95% CI: 94.8-99.4%)
subjects, followed by the cost of cataract surgery and fear of In this study, majority of the respondents belonged to more
surgical outcome by 173 (90.1%; 95% CI: 85-93.9%) subjects than sixty years of age group. This is a typical reflection that
each, the personal belief of a person by 145 (75.5%; 95% CI: cataract is a disease of ageing, and also has been reported
68.8-81.4%) participants and fear of pain during surgery by Soundarssanane et al and Chatterjee et al.11,12 Also, we
by 126 (65.6%; 95% CI: 58.4-72.3%) participants. A total of found more number of female respondents as compared
137 (71.4%; 95% CI: 64.4-77.6%) subjects knew that cataract to males, although the difference was not significant. The
did not recur after surgery, 187 (97.4%; 95% CI: 94-99.1%) study population was gender matched in terms of age and
agreed that a person with poor vision should visit an eye education level of participants. This validates the finding
hospital for treatment. For their ailments, 40 (20.8%; 95% of this study as the responses of the participants had not
CI: 15.3-27.3%) participants agreed that urban population been gender biased. Many previous studies had reported
sought treatment more frequently than rural population. gender inequalities in case of cataract and other eye diseases
The frequency distributions of responses to all questions in developing countries.13-17 Dhaliwal et al reported female
asked in this section are presented in (Table 3). gender as an attitudinal barrier to uptake of cataract surgery.18
Almost all participants of our study were aware of the word
Table 3: Attitude of respondent regarding cataract and its surgery (n=192) cataract (98.4%) (Commonly termed as “Motiabind” in the
study area). This data is in concordance with international
Questions Options Response studies including the Australian Blue Mountain Eye Studies
(N %) (98%),19 Hong Kong Study (92.9%)20 and Australian Visual
Q10: Do you ever attended hospital for Yes Impairment Study (92%).21
150 (78.1)
treatment No 42 (21.8) Most of the respondents knew that cataract was treatable
145 (75.5) and the natural lens was replaced during cataract surgery.
Q11: Personal belief can prevent people Agree 15 (7.8) Almost half of the participants considered ageing as its
from cataract treatment Disagree 32 (16.7) main cause. Many of the study participants were illiterate or
Neutral 173 (90.1) educated only up to primary level; still the level of literacy
0 (0.0) did not seem to have an impact in the disease awareness
Q12: Cost of cataract surgery can prevent Agree 19 (9.9) amongst the subjects, and was high in the study area. This
people from seeking treatment Disagree 126 (65.6) may be due to the extensive media campaigns about cataract
Neutral 27 (14.1) conducted; both at the government as well as nonprofit
39 (20.3) organization level. Most of the study participants had had
Q13: Fear of pain can prevent people from Agree 173 (90.1) a previous history of hospital for treatment; and could be
seeking treatment Disagree 1 (0.5) another possible reason behind this high awareness.
Neutral 18 (9.4)
188 (97.9) The study had been conducted in the proximity (within 30
Q14: Fear of surgical outcome can prevent Agree 1 (0.5) kilometer) of a tertiary eye care institution. A previous study
people from seeking treatment Disagree 3 (1.6) reported that the health service availability had an impact
Neutral 3 (1.6) on health seeking behavior.22 However, direct relation to
137 (71.4) knowledge level about a disease of community residing in
Q15:Lack of accessibility can prevent people Agree 52 (27.1) proximity of a health care institution has not been studied.
from seeking treatment Disagree 187 (97.4)
Neutral 0 (0.0) Personal belief, cost of cataract surgery, fear of surgical
5 (2.6) outcome and associated pain and lack of accessibility
Q16: Cataract will recur after surgery Agree 192 (100.0) have been identified as potential barriers for the uptake of
Disagree 0 (0.0) cataract surgery by majority of study participants. This is
0 (0.0) in conformity with previous study by Dhaliwal et al18 who
Neutral 40 (20.8) reported that patients opted to undergo cataract surgery only
87 (45.3) when they were unable to see anything, and this decision
Q17: Person with poor vision should go to Agree 64 (33.3) was irrespective of their knowledge and awareness level.
hospital for treatment Disagree Cost of cataract surgery and better vision in other eye have
Neutral been published as the major barriers to uptake of cataract
surgery by Rabiu et al.23 This corroborates with our findings
Q18: Cataract extraction restore sight Agree regarding cost of surgery, however the better vision of other
Disagree eye has not been studied by us.

Neutral

Q19:People from cities go to hospital for Agree
intervention than those in rural areas Disagree
Neutral

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DJO Vol. 32, No. 3, January-March 2022

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cataract services in the Indian context. Community Eye Health.
2014;27(85):4‐5.

9. Census 2011/Disabled persons in India. A statistical profile

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DJO Vol. 32, No. 3, January-March 2022

Cite This Article as: Richa Gupta, Akansha Gupta, Mossab
Omair, Lokesh Chauhan, Pradeep Agarwal, Ashi Khurana. Health
literacy on cataract and its treatment options among patients with
operable cataract: A cross sectional study from Moradabad (India).
Delhi Journal of Ophthalmology.2022; Vol 32, No (3): 50- 54.

Acknowledgments: Nil

Conflict of interest: None

Source of Funding: None

Date of Submission: 12 Dec 2021
Date of Acceptance: 25 Mar 2022

Address for correspondence
Richa Gupta, MS Ophthalmology

Department of Ophthalmology, CL
Gupta Eye Institute, Ram Ganga Vihar,
Phase 2(Ext) Moradabad,
Uttar Pradesh, India.
Email : [email protected]

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DJO Vol. 32, No. 3, January-March 2022

Case Report

A Misleading Orbital Cystic Lesion

Shruthi Tara, Shraddha Shah

Department of Orbit and Oculoplasty, Sankara Eye Hospital, Coimbatore, Tamil nadu, India.

Abstract Orbital schwannomas are rare and arise from the Schwann cells of sensory nerves. Cystic degeneration has been known to
occur with orbital schwannomas but those occurring intra-ocularly have not been reported till date. Authors here report a rare
case of a 24 year old woman, blind in the right eye, presenting with right sided headache and progressive proptosis since four
years. Computer tomography (CT) of right eye showed presence of a well-demarcated, retro-orbital cystic lesion with a solid
component causing displacement of the globe-like structure and bony remodelling. From the clinical and radiological features
a pre-operative diagnosis of a right congenital cystic eyeball and a left microphthalmos with cyst was made. The patient
underwent enucleation of the right eye along with the cystic lesion as a whole. Based on histopathology, a final diagnosis of an
orbital schwannoma with extensive cystic degeneration and intra-ocular extension was made

Delhi J Ophthalmol 2021; 32; 55-57; Doi http://dx.doi.org/10.7869/djo.742

Keywords: Bilateral, Cystic degeneration, Intra-ocular extension, Orbital, Schwannoma

Introduction perception of light and presence of a shrunken globe with

Schwannomas are benign tumours arising from schwann cells rudimentary cornea was seen. Left eye (LE) showed features

of sensory nerves, often seen in head and neck region. Orbital of microphthalmos with microcornea. Diminution of vision

schwannomas are rare.1 Few cases of cystic schwannomas in the LE occurred after 15 years of age, which deteriorated

have been reported in the brainstem, intracranial nerves, to perception of light.

adrenals and orbit1 but to our knowledge, no cases of cystic RE Computed Tomography (CT) of orbit with contrast
showed a well-demarcated, complex lesion predominantly
orbital schwannoma with intra-ocular extension have been cystic with a small solid component, measuring 3.2 x 2.8
x 2.4cm in size. This was located retro-orbital and infero-
documented till date. There are no pathognomonic clinical nasal to the globe-like structure causing medial bowing
of the lamina papyracea (Figure 2a). The solid component
or radiological features and definitive diagnosis is based on with calcification measured 1.4 x 1.2cm and was seen on the
anterolateral aspect of the cystic lesion (Figure 2b). Shrunken
histopathology. Case History globe-like structure, hyperdense and mildly enhancing,
measuring 1.3 x 1.3cm with absent crystalline lens and foci
A 24 year old woman, presented to us with headache of calcification within, was noted (Figure 2c). CT findings

and progressive proptosis in the right eye (RE) since

four years which gradually increased causing horizontal

dystopia (Figure 1). Neonatal history revealed a full term

forceps delivery. On examination, the visual acuity was no

of LE showed an eyeball measuring 2.1 x 2.3 x 2.7cm with

intact lens. Similar smaller cystic lesions were seen on the

sclera, superior to the optic nerve. On T2 weighted Magnetic

resonance imaging (MRI) of RE, the cyst was hyper-intense

with a hypo-intense solid component (Fig.3b). Post contrast

showed greater enhancement of the cystic lesion (Figure

3c). Anteriorly, the cystic component was seen attached to

the globe-like structure (Figure 3d). LE showed multiple

hyper-intense cysts projecting posteriorly from the globe

(Figure 3a). Imaging of the superior and inferior orbital

fissures, sinuses and brain were unremarkable. No systemic

Figure 1: Clinical picture showing proptosis and horizontal dystopia of the malformations were present. Probable diagnosis of a right
right eye. congenital cystic eyeball and left microphthalmos with cyst
was made.

Figure 2: Orbital Computed tomography (CT) scan of the right eye (a) Axial view showing a well-defined cystic lesion (asterisk) located in the retro-orbital plane.
(b) Coronal view showing presence of a solid component (black arrow) within the lesion with calcifications (c) Sagittal view demonstrating enhancement of the

calcifications (red arrow) within the shrunken globe.

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DJO Vol. 32, No. 3, January-March 2022

Figure 3: Magnetic Resonance Imaging (MRI) scan of the orbit (a) Left eye, T2 weighted image (axial view) showing small multiple hyper-intense cystic lesions

behind the posterior sclera (red arrow head). (b) Right eye, T2 weighted image (coronal view) showing a hyper-intense cystic lesion (asterisk) with a hypo-intense

solid component (white arrow). (c) Right eye, post contrast scan showing enhancement of the lesion as well as the eyeball. (d) Right eye (coronal view) showing

anterior attachment of the cystic lesion to the globe (black arrow).

RE cystic mass was aspirated and sclerosing agent was body (Figure 4a)(Figure 5). In some areas, fewer cells with

injected elsewhere. However, it recurred with no further oval nuclei arranged haphazardly within loose myxomatous

improvement in symptoms. RE enucleation with cyst tissue descriptive of Antoni B pattern, with hyalinised blood

removal into was performed. Gross specimen showed a vessels were seen (Figure 4b)(Figure 5). Cystic spaces with

globe-like structure measuring 2 x 1.8 x 1.7cm filled with extensive degeneration were a characteristic feature noted

soft greyish-white solid material with no evidence of on histopathological examination (Figure 4c)(Figure 5). No

crystalline lens. Another encapsulated solid-cystic mass of signs of mitosis, necrosis and nuclear atypia were noted.

3 x 2.5 x 2cm was found adherent to the globe-like structure, With the confirmatory histopathology findings, a diagnosis

infero-nasally. Optic nerve was not seen separately from of Orbital Schwannoma with cystic degeneration and intra-

this lesion but was found attached at some points. On light ocular extension was made.

microscopy, sections of gross specimen of both components Discussion
consisted of closely packed fusiform cells with eosinophilic
cytoplasm suggestive of Antoni A pattern. The nuclei were Orbital schwannomas are seen commonly in females
arranged in a typical palisade pattern known as a verocay occurring in second to fifth decade.2 In the orbit, specific
origin of the tumor cannot be identified owing to complexity

Figure 4: (Hematoxylin-eosin stain, 10x). Photomicrograph of intra-ocular mass showing (a) Antoni A pattern with typical verocay bodies (black arrow) (b) Antoni
B pattern (arrow heads) with hyalinised blood vessels (black arrow) and (c) Areas of extensive cystic degeneration (black arrow).

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DJO Vol. 32, No. 3, January-March 2022

Figure 5: (Hematoxylin-eosin stain, 10x).Photomicrograph of orbital mass Rarely, calcifications can be seen within the schwannoma.
showing typical features of a cystic Schwannoma. Cystic degeneration (black Our patient showed characteristic features of a cystic
arrow); Antoni A pattern with verocay bodies (red arrow); Antoni B areas with schwannoma with intraocular extension probably via optic
nerve, explaining locally aggressive nature of the tumor.6
hyalinised blood vessels (arrow heads) Similar cystic lesions were seen in LE but since the patient
was asymptomatic, we decided against any intervention.
of nerves traversing it. However, tumor often arises from the Presence of these retro-orbital cystic lesions speculates
supratrochlear or supraorbital branches of trigeminal nerve.2 the possibility of a bilateral schwannoma, which is not
They present with proptosis, decreased vision, diplopia, pain reported in literature till date and can be confirmed only on
or numbness along the nerve of origin.2 Schwannomas are histopathology. These varied presentations of schwannoma
usually unilateral.2 Although, in our patient, MRI showed make it challenging for the physician to come to a conclusive
retro-orbital cystic lesions in the LE, nature of which cannot diagnosis. Thus, schwannoma must be borne in mind as a
be determined without biopsy. differential for an orbital cystic lesion.

Long standing tumours can undergo cystic degeneration References
which has been reported in a few cases of orbital
schwannomas,3 but none have demonstrated its intra- 1. Lam DS, Joan SK, To KF, Abdulah V, Liew CT, Tso MO. Cystic
ocular presence. Cystic areas are secondary to coalescence schwannoma of the orbit. Eye. 1997 Nov;11(6):798-800.
of microcysts within the Antoni B tissue. It is hypothesized
that alteration in the vascular supply resulting in necrosis 2. Subramanian N, Rambhatia S, Mahesh L, Menon SV,
and haemorrhage within the tumor or hyaline degeneration Krishnakumar S, Biswas J et al. Cystic schwannoma of the
causes cyst formation.1 Diagnostic difficulty in our case orbit—a case series. Orbit. 2005 Jan 1;24(2):125-9.
stemmed from the cystic nature of the lesion seen bilaterally
on MRI, long standing duration and past history of cyst 3. Kashyap S, Pushker N, Meel R, Sen S, Bajaj MS, Khuriajam N
aspiration which misled us to a diagnosis of a right sided et al. Orbital schwannoma with cystic degeneration. Clinical &
congenital cystic eye, which is known to occur either in experimental ophthalmology. 2009 Apr;37(3):293-8.
isolation or with malformations such as contralateral
microphthalmos with cyst.4 4. Gupta R, Seith A, Guglani B, Jain TP. Congenital cystic
eye: features on MRI. The British journal of radiology. 2007
MRI is the imaging of choice in suspected cases of orbital Jul;80(955):e137-40.
schwannoma, due to its high sensitivity especially with the
use of contrast agents.5 On MRI, they appear hyper-intense 5. Kim KS, Jung JW, Yoon KC, Kwon YJ, Hwang JH, Lee SY.
similar to cerebrospinal fluid on T2 weighted images and Schwannoma of the Orbit. Archives of Craniofacial Surgery.
hypo-intense on T1 weighted images with homogenous or 2015 Aug;16(2):67.
heterogeneous enhancement on contrast. This heterogeneity
is seen in cases of cystic degeneration. Although, imaging 6. You JY, Finger PT, Iacob C, McCormick SA, Milman T. Intraocular
is helpful in diagnosing orbital schwannomas, there are no schwannoma. Survey of Ophthalmology. 2013 Jan 1;58(1):77-85.
pathognomonic diagnostic features and histopathological
confirmation is needed. Gross appearance of schwannoma is Cite This Article as: Shruthi Tara, Shraddha A Misleading
characteristic with a smooth homogenous yellow-grey well- Orbital Cystic Lesion Delhi J Ophthalmol 2021; 32 (3): 55- 57.
encapsulated mass, the capsule derived from perineurium
of the nerve of origin. Microscopically, biphasic cellular Acknowledgments: We thank Dr. Nilesh T (K.J Somaiya
arrangements are seen: a densely cellular Antoni A pattern Medical College) , Dr. A. Anbarasu (Aran Diagnostic Centre)
with picket-fence-like palisaded nuclei (verocay bodies) and and Dr Murthy (Lakshmiram Biopsy Centre) for their valuable
less cellular Antoni B pattern distributed in myxoid tissue. radiological and pathological inputs.

Conflict of interest: None declared

Source of Funding: None

Date of Submission: 12 Mar 2021
Date of Acceptance: 26 Jan 2022

Address for correspondence

Shruthi Tara, DO

Deparment of Orbit and Oculoplasty,
Sankara Eye Hospital,Coimbatore,
Tamil nadu, India.
E-mail: [email protected]

Quick Response Code

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DJO Vol. 32, No. 3, January-March 2022

Case Report

Congenital Combined Eyelid Imbrication with Congenital
Floppy Eyelid Syndrome- A Rare Case Report

Anuradha, Param Harsh, Jeevitha Periyakaruppan, Divya Dhiman

Department of Ophthalmology, 167 Military Hospital, Pathankot, Punjab, India.

Abstract A healthy male term neonate born by a normal vaginal delivery was referred with severe bilateral eyelid edema and erythema
at birth. On evaluation he was found to have eyelid imbrication with floppy eyelids bilaterally. The patient was managed
conservatively and showed complete recovery of symptoms and signs over a period of ten days. This rare clinical entity can
be a cause of concern to parents and clinicians but can be satisfactorily managed by conservative measures. This is the fourth
case of congenital combined eyelid imbrication (CEI) with congenital floppy eyelid syndrome (CFES) reported worldwide, to our
knowledge.

Delhi J Ophthalmol 2021; 32; 58-60; Doi http://dx.doi.org/10.7869/djo.743

Keywords: Congenital eyelid imbrication syndrome, floppy eyelid syndrome, eyelid laxity, eyelid eversion, Down syndrome

Introduction

Congenital eyelid imbrication syndrome (CEIS) is a rare
clinical entity which is characterized by over-riding of
upper eyelids over the lower eyelids.1 It is observed at or
shortly after birth and is generally bilateral in nature. It is
essentially self-resolving with conservative1 management,
in contrast to adult-onset eyelid imbrication and floppy
eyelids, which is acquired in nature and requires surgical
intervention. In very rare cases, CEIS is associated with
congenital floppy eyelid syndrome (CFES).2 We report such
a case of congenital combined eyelid imbrication with floppy
eyelid syndrome, which was managed conservatively at our
center. To our knowledge, this is the sixth case of congenital
eyelid imbrication reported worldwide, and fourth reported
case with an associated congenital floppy eyelid component
till date. An informed consent has been obtained from the
parents for submission of this case report.

Case Report Figure 1: Patient photo at presentation showing bulky upper eyelids over-
riding lower eyelids
A three-hour old male neonate was referred for gradually
increasing bilateral swelling and redness of the eyelids, with
failure to open both eyes, since birth. The baby was born by
a normal vaginal delivery at term and had no comorbidities
or syndromic associations. There was no history of
consanguinity among parents or in the family.

On evaluation, the baby was found to have bilateral bulky, Figure 2: Spontaneous eversion of eyelid with gentle traction on skin, with
edematous and erythematous eyelids, with over-riding of erythema of tarsal conjunctiva
the upper eyelids over the lower eyelids by 6mm (Figure
1). The horizontal length of the upper eyelids was 23mm,
while the mid-point of their vertical height was measured
at 10mm. There was no spontaneous opening of the eyes.
No other facial anomaly was noted. On applying gentle
traction to open the eyes, the upper eyelids were found to
evert spontaneously, and the tarsal conjunctiva was seen
severely erythematous (Figure 2). The lower eyelids were
folded inward bilaterally and when gently pulled down,
they were also found to evert on minimal traction and the
underlying conjunctiva was inflamed. There was mild
mucoid discharge from the eyes. The globes were bilaterally
normal on gross evaluation.2

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DJO Vol. 32, No. 3, January-March 2022

Figure 1: Follow-up picture at four days post-partum with reduced bulkiness (Tobramycin 0.3% eye drops) and lubricating agent
of upper eyelids (Carboxymethylcellulose 0.5% eye drops). The baby was
routinely followed up and parents were counselled to
Figure 4: Follow-up picture at four days post-partum showing eversion of alleviate anxiety regarding the clinical appearance. Over
upper eyelids a period of ten days with conservative management, all
symptoms and signs were resolved completely, and the
Figure 5: Follow-up picture at ten days post-partum showing normal eye baby achieved normal eye opening with reduction in eyelid
opening laxity (Figures 3, 4, 5). Subsequent ophthalmic examination
including fundoscopy was normal in both eyes.
Based on the over-riding of upper eyelids over lower, eyelid
laxity and eversion of eyelids, with inflammation of tarsal Discussion
conjunctiva of both eyes, the patient was diagnosed as a case
of congenital combined eyelid imbrication with congenital Congenital eyelid imbrication syndrome (CEIS) is a rare,
floppy iris syndrome. self-resolving condition of unknown etiology, which may
Swabs were sent from upper and lower tarsal conjunctivae also be associated with congenital floppy eyelid syndrome
of both eyes for culture and were reported negative. The (CFES). This essentially self-resolving entity can be a
baby was managed conservatively with topical antibiotic matter of anxiety among parents and healthcare staff at
initial presentation, due to its clinical picture. The baby is
characteristically found to have bulky, erythematous, over-
riding upper eyelids, with mild to severe discharge from
the eyes, at or shortly after birth. There is spontaneous lid
eversion on gentle pull over the eyelid skin, and even on
forceful crying in many cases.3

The etiopathogenesis of this condition is poorly understood
and still under research. Many theories have been
hypothesized to describe the course of events that occur
from the onset to resolution of the clinical features. The over-
riding of eyelids is said to be due to lid laxity and poor tone
of the medial and lateral canthal tendons.4 Irritation of upper
tarsal conjunctiva by lower lid eyelashes may set up a vicious
cycle of the irritation-spasm-over riding phenomenon.3,5 The
spontaneous eversion of eyelids is hypothesized to be due to
persistent spasm of orbicularis oculi subsequent to irritation,
which is probably aggravated as the eyelid skin is pulled to
open the eyes, or when the baby is crying.3,5 The management
of these cases, hence, is based on alleviating irritation,
thereby breaking the cycle. Topical lubricating agents like
carboxymethylcellulose play a crucial role in reducing
irritation, while topical antibiotics like tobramycin give
prophylaxis against secondary infection. Sometimes there
may be simultaneously existing ophthalmia neonatorum
at presentation, and these cases need to be managed more
aggressively depending on etiology. Hence, early reporting
of cases and a reliable laboratory diagnostic facility are very
important in satisfactory management of these cases. CEIS
is said to spontaneously resolve due to tightening of medial
and lateral canthal tendons with growth of bony orbit.2,4 It
has also been hypothesized that involution of upper eyelid
structures in the first week after birth under yet unidentified
influence may result in tightening of the canthal tendons and
reduction in eyelid laxity.6

To this day, the etiology of this condition is largely unknown.
CEIS has no proven syndromic associations. Congenital
floppy eyelid syndrome has been associated with Down
syndrome, however, our patient did not exhibit any features
of Down syndrome or any other syndromic association.7
Further research is needed to identify the etiopathogenesis
of this condition.

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DJO Vol. 32, No. 3, January-March 2022

It is 4impeded to some extent, by the rare nature of the entity. Cite This Article as: Anuradha, Param Harsh, Jeevitha
However, it may be noted that many cases with very mild Periyakaruppan, Divya Dhiman. Congenital combined
symptoms may go unreported, where the clinical picture eyelid imbrication with congenital floppy eyelid
may not be as dramatic and may resolve completely before it syndrome- a rare case report 2022; 32 (3): 58 - 60
attracts the attention of the clinician. Acknowledgments: Nil
Conflict of interest: None declared
References Source of Funding: None
Date of Submission: 8 April 2021
1. Karesh JW, Nirankari VS, Hameroff SB. Eyelid imbrication. An Date of Acceptance: 13 Dec 2021
unrecognized cause of chronic ocular irritation. Ophthalmology
1993;100:883-9. Address for correspondence
Anuradha MS, DNB
2. Odat TA, Hina SJ. Congenital combined eyelid imbrication and
floppy eyelid syndrome. J Optom 2010;3:91-3 Department of Ophthalmology,
Dept of Ophthalmology,
3. De Silva DJ, Fielder AR, Ramkissoon YD. Congenital eyelid 167 Military Hospital, Dhangu road,
imbrication syndrome. Eye (Lond). 2006 Sep;20(9):1103-4. doi: Pathankot, Punjab, India.
10.1038/sj.eye.6702141. Epub 2006 Mar 24. PMID: 16557289. E-mail: [email protected]

4. Rumelt S, Kassif Y, Rehany U. Congenital eyelid imbrication
syndrome. Am J Ophthalmol. 2004 Sep;138(3):499-501. doi:
10.1016/j.ajo.2004.04.023. PMID: 15364246.(5)

5. Kaur M, Singh S, Singh M. Congenital bilateral eyelid imbrication
in a neonate: A rare case. J Clin Neonatol 2016;5:137-9

6. Chandravanshi SL, Rathore MK, Tirkey ER. Congenital combined
eyelid imbrication and floppy eyelid syndrome: Case report and
review of literature. Indian J Ophthalmol 2013;61:5936

7. Rao LG, Bhandary SV, Devi AR, Gangadharan S. Floppy eyelid
syndrome in an infant. Indian J Ophthalmol. 2006 Sep;54(3):217-
8. doi: 10.4103/0301-4738.27090. PMID: 16921233.

Quick Response Code

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DJO Vol. 32, No. 3, January-March 2022

Case Report

Stage 3 Retinopathy of Prematurity in a Child with
Lipemia Retinalis

Ritesh Verma, Manisha Rathi, Sumit Sachdeva, Jitender Phogat, Sakshi Lochab

Department of Ophthalmology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.

Abstract We report a case of four month old child with low birth weight presenting with raised serum triglyceride (2793mg/dl) and
serum cholesterol levels (1200mg/dl) with zone 2 stage 3 retinopathy of prematurity with lipemia retinalis. Though the
regression of lipemia retinalis has been reported but there are no guidelines regarding treatment of ROP in such cases as
this is an unusual finding.

Delhi J Ophthalmol 2021; 32; 61-62; Doi http://dx.doi.org/10.7869/djo.744

Keywords: Lipemia Retinalis; Retinopathy of Prematurity; Triglycerides

Introduction discharged ass condition after stable from the NICU and

Lipemia retinalis is a known manifestation of raised referred to PGIMS for further management. The baby
triglyceride level in infants. The fundus becomes salmon- presented to ROP clinic at postmenstrual age of 45 weeks
colored, with creamy arteries and veins that can be and weight of 2050gms. The patient had a history of very
distinguished by calibre only.1 Hypertriglyceridemia can poor weight gain and was not accepting feeds properly.

occur as a primary metabolic disorder or secondary to Anterior segment examination of both eyes was normal.
other diseases. Lipemia retinalis does not affect visual Fundus examination revealed salmon coloured vessels in
acuity; however, ERG changes have been described by Lu both eyes and the distinction between arteries and veins
et al.1 Retinopathy of prematurity is still a leading cause of could only be made on the basis of calibre of vessel. The
childhood blindness in developing countries. We present a patient also had stage 3 ROP in zone II in both the eyes with
case of lipemia retinalis with stage 3 retinopathy which has no plus disease. Lab investigations revealed raised serum

not been described in literature till date. triglyceride (2793mg/dl; normal reference value <150mg/dl)
and raised serum cholesterol (1200mg/dl; normal reference
Case History value <200mg/dl). The ocular examination of the parents was

A four month old child presented to the retinopathy of normal and there was no history of consanguineous marriage

prematurity (ROP) clinic of our institute from a nearby in the family. The patient was referred to paediatrician and

district after neonatal intensive care unit (NICU) stay for was switched to low fat skimmed milk and started on lipid

3 months. The female baby was born preterm at 30 weeks lowering agents. The patient was being followed up closely

gestation at a rural hospital with birth weight of 540gms. meanwhile the Stage 3 ROP and lipemia retinalis did not

The baby had respiratory distress and was kept on ventilator regress even 6 weeks after starting the therapy. This child

for 7 days followed by hood oxygen for 28 days in NICU. could not survive unfortunately as the parents did not have

The patient also developed sepsis for which intravenous enough financial support for the treatment of the child.

antibiotics were administered for 7 days. The patient was

Figure 1: Fundus photo of right eye showing salmon pink appearance of Figure 2: Fundus photo of temporal periphery of right eye showing fibro
retinal blood vessels with a dark background suggesting lipemia retinalis vascular proliferation at the edge of vascular and avascular retina suggestive

of stage 3 retinopathy in zone 2 with salmon pink vessels

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DJO Vol. 32, No. 3, January-March 2022

Figure 3: Fundus photo of right and left eye (respectively) showing salmon Figure 4: Fundus photo of left peripheral fundus showing lipemia retinalis but
pink appearance of retinal blood vessels with a dark background suggesting stage 3 could not be captured because of its presence in anterior zone 2
Nutritional practices in the neonatal intensive care unit: analysis
lipemia retinalis of a 2006 neonatal nutrition survey. Pediatrics 2009;123:51-7.
4. Jain A, Mochi TB, Braganza SD, Agrawal S, Shetty BK,
Discussion Pachiyappan B. Lipemia retinalis in an infant treated for
retinopathy of prematurity. J AAPOS. 2017;21:254–7.
Lipemia retinalis is non vision threatening manifestation 5. Vinger PF, Sachs BA. Ocular manifestations of
of a lipid metabolism disorder. Multiple reports of lipemia hyperlipoproteinemia. Am J Ophthalmol. 1970;70:563–7. 569-73.
retinalis have been published. In almost all cases lipemia 6. Ju R-H, Zhang J-Q, Ke X-Y, et al. Spontaneous regression of
retinalis resolves once the triglyceride levels return to retinopathy of prematurity: incidence and predictive factors. Int
normal.2-4 Three grades of lipemia retinalis have been J Ophthalmol. 2013;6(4):475–480.
described according to which our patient had grade III
lipemia retinalis.5 Cite This Article as: Ritesh Verma, Manisha Rathi, Sumit
Sachdeva, Jitender Phogat, Sakshi Lochab. Stage 3 Retinopathy of
As per our literature search, very few cases of lipemia Prematurity in a child with Lipemia Retinalis Delhi J Ophthalmol
retinalis have been reported in premature infants. A case 2022; 32 (3): 61 - 62.
of laser treated threshold ROP which later on developed
lipemia retinalis has been reported.4 No case of lipemia Acknowledgments: Nil
retinalis with concurrent stage 3 ROP has been reported
till date. There are no guidelines regarding management of Conflict of interest: None declared
these cases in the present literature.
Source of Funding: None
Late presentation for ROP screening is still a major concern
in developing countries due to lack of trained health care Date of Submission: 12 Mar 2021
providers in rural areas who can visit NICU and screen Date of Acceptance: 26 Jan 2022
babies. Our patient presented four months after birth with
stage 3 ROP which also makes this case interesting as most Address for correspondence
of the ROP cases regress spontaneously by this time.6 This Ritesh Verma, MBBS, MS, FICO,
also emphasizes on the fact that early screening for ROP will
lead to early diagnosis and management of these metabolic MRCSed (Assistant professor)
disorders. Although no retinal neuronal and vascular toxicity
has been described in acute hypertriglyceridemia but in long Department of Ophthalmology,
standing cases like ours there might be some changes in the Dayanand Medical College and Hospital,
vascular morphology which makes diagnosis of plus disease Ludhiana, Punjab, India
and management of ROP challenging. E-mail: [email protected]

References Quick Response Code

1. Lu CK, Chen SJ, Niu DM, et al. Electrophysiological changes in
lipaemia retinalis. Am J Ophthalmol 2005;139:1142-5.

2. Cypel M, Manzano R, Dos Reis FA, Ishida N, Ayhara T. Lipemia
retinalis in a 35-dayold infant with hyperlipoproteinemia: case
report. Arq Bras Oftalmol 2008;71:254-6.

3. Hans DM, Pylipow M, Long JD, Thureen PJ, Georgieff MK.

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DJO Vol. 32, No. 3, January-March 2022

Case Report

Vascular Occlusions triggered post Covid-19 infection

Dhaivat Shah, Manan Solanki, Shams Tabrez, Rinal Pandit, Devanshi Dalal

Abstract Choithram Netralaya, Shriram Talawadi, Dhar Road, Indore, Madhya Pradesh, India.
One of the ophthalmic complications seen following Covid19 infection is occlusive retinopathy. This occurs due to
increased coagulopathy and inflammation which in turn is triggering the vascular events. Since end vessels are
involved here, vision loss is significant. We report five such cases seen in our setup within a span of one month with
varied presentations and deranged systemic parameters.

Delhi J Ophthalmol 2022; 32; 63-66; Doi http://dx.doi.org/10.7869/djo.745
Keywords: Covid 19 Infection, Retinal Vascular Occlusion, Central Retinal Artery Occlusion, Central Retinal Vein Occlusion, Ophthalmic Artery Occlusion,

Paracentral Acute Middle Maculopathy

Introduction view of these findings, we suspected right eye Ophthalmic

COVID-19 infection which is known to be caused by the severe Artery Occlusion (OAO), advised him an occlusion profile

acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and explained the visual prognosis. He was referred to a

has been linked to inflammation-induced homeostatic cardiologist on urgent basis. His investigation revealed

alterations that result in a severe coagulopathy with raised D-Dimer levels (2.5 μg/ml) and he was started on oral

multi-organ involvement.1 The pathophysiology of retinal dual anti platelet therapy by the cardiologist.

vascular occlusions (RVO) is a multifactorial process where Case 2
inflammation and hypercoagulation state are known risk
factors.2 There have been reports of conjunctivitis3, or retinal An 80-year-old hypertensive male presented with sudden
microvascular alterations such as retinal microangiopathy4, painless vision loss in his right eye (Visual Acuity: PL+)
cotton wool spots and haemorrhages5, acute middle since 4 hours. He was diagnosed COVID-19 positive 3 weeks
maculopathy and acute macular neuroretinopathy6, and back and underwent home isolation and treatment for the
papillophlebitis7 in COVID-19 patients. Here we present a same. His right eye fundus revealed pale central retina with
case series of five patients who developed vascular occlusion attenuated vessels and cherry red spot at the macula (Figure
post Covid-19 infection (moderate to severe category) with 2) suggestive of Central Retinal Artery Occlusion (CRAO).
myriad of presentations. Since it was an early presentation, right eye paracentesis was
done. He was urgently referred to a cardiology unit where

Case 1 they found a plaque at common carotid artery with 50%
lumen narrowing on carotid doppler examination. He was
A 62-year-old hypertensive male who experienced sudden started on oral anticoagulants and dual anti platelet drugs.
decrease in vision in his right eye associated with mild At 6-weeks follow-up, he presented with mild ocular pain
ocular pain 2 days ago, presented to us with no perception of and was noted to have Neovascularisation of Iris (NVI)
light. He had been admitted for COVID-19 infection 2 weeks suggesting early stage of neovascular glaucoma. Thus, an
back and had recovered from the same. On examination, aggressive pan retinal photo coagulation laser was done. On
right eye fundus findings included pale disc, pale retina, further follow up patient symptomatically got better.
cherry red spot at the macula and multiple areas of cattle

tracking (Figure 1). Left eye was within normal limits. In

Figure 1: Fundus photo of right eye showing pale retina, cherry red spot at Figure 2: Fundus photo of right eye showing pale central retina with
macula and vascular area of cattle tracking. attenuated vessels.

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DJO Vol. 32, No. 3, January-March 2022

Case 3 VEGF injection, his BCVA improved to 6/60 with macular
thinning noted on the optical coherence tomography (OCT).
A 44-year-old diabetic male presented with sudden painless
loss of vision in left eye since 3 days. He had history of Case 4
hospital admission for COVID-19 and got discharged 10
days ago. He presented to us with best corrected visual A 35-year-old diabetic male had history of hospital
acuity (BCVA) of 2/60 in left eye. Left eye fundus showed admission for COVID-19 six weeks ago. 1 week after the
disc edema, dilated and tortous retinal veins, multiple discharge, he was diagnosed with left sided Mucormycosis
superficial and deep haemorrhages with macular thickening of the sinuses (Stage 3 ROCM) and underwent Functional
(Figure 3) denoting central retinal vein occlusion (CRVO) Endoscopic Sinus Surgery (FESS). He was then referred to
with cystoid macular edema. He was investigated further the ophthalmology department for ocular evaluation. He
and found to have raised D-Dimer (3 μg/ml) and altered presented to us with history of dimness of vision (BCVA:
serum homocysteine (34 mcmol/L). He was treated with PL) in left eye with mild ptosis, mild proptosis (Figure 4a)
intravitreal Anti-VEGF injection (Ranibizumab) after strict and ophthalmoplegia since 1 week. His fundus showed
control of systemic condition. Post 3 loading doses of Anti- pale retina with cherry red spot at the macula (Figure 4b)
suggestive of CRAO. He was advised to continue oral anti-
Figure 3: Fundus photo of left eye showing 360 degree multiple superficial platelet and systemic antifungal medication as advised by
and deep hemorrhages with macular thickening. the physician. Poor visual prognosis was explained.

Case 5

A 32-year-old male presented with complaint of sudden
appearance of black spot in front of the left eye (BCVA: Right
eye: 6/6, Left eye 6/9). He had history of hospital admission
for COVID-19 3 weeks back and got recovered from the same.
His fundus in the left eye showed area of retinal whitening
in the nasal half (Figure 5a) which was appeared like
isolated branch retinal arterial occlusion on the OCT (Figure
5b). He was further investigated and found to have raised
serum homocysteine (28 mcmol/L) and altered lipid profile
(triglycerides 277 mg/dL). He was referred to a cardiologist
where he was started on oral anti platelet therapy.

Discussion

COVID-19 infection has been shown to cause inflammation-
induced homeostatic abnormalities in the venous and arterial
circulation, predisposing to thrombotic disease [1]. The
incidence of thromboembolic events in COVID-19 patients
is now being investigated, with early findings revealing that
patients with more severe illness had considerably longer

Figure 4: (4a) Photo showing left eye mild proptosis with yellow fundal glow. (4b) Fundus showing pale retina and cherry red spot at fovea

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DJO Vol. 32, No. 3, January-March 2022

Figure 5: (5a) Fundus photo of left eye showing small area of retinal whitening near fovea (white arrow). (5b) OCT left eye passing through macula shows
hyper-reflectivity in inner retinal layers nasal to the fovea.

prothrombin times, higher D-dimer and Homocysteine We underline the need of a thorough posterior segment
levels, and higher concentrations of proinflammatory examination in COVID-19 positive cases and lookout
cytokines and biomarkers of inflammation like C-reactive for acute visual complaints and indicators of thrombotic

protein and Interleukin-6. This clearly indicates the consequences such as vascular occlusions. Before initiating

possibility of disseminated intravascular coagulation or treatment in such cases, it is imperative to get a thorough

thrombotic microangiopathy.8 systemic check-up done, especially the coagulation profile.

The potential influence of COVID-19 illness on retinal In all our cases, we could find an abnormality either in the
vascular circulation and the formation of retinal vascular coagulation pathway or in the systemic circulation. Hence,
disease might be explained by three mechanisms: simultaneous systemic therapy with anti-coagulants or anti
platelets in accordance with a physician is extremely crucial
1. A pseudo-vasculitis state as a result of viral infiltration in treatment of these cases.
of endothelial cells.9
Conclusion
2. A hypercoagulable condition triggered by
disseminated intravascular coagulation-like events.10 A thorough systemic evaluation is must before initiating
ophthalmic treatment; especially in post COVID occlusive
3. Posterior compressive retinopathy secondary to retinopathies. A multidisciplinary approach in cases of
fungal inflammation and invasion. vascular occlusions is the way to go ahead.

A summary of all 5 cases has been listed in Table 1.

Table 1: A summary of all 5 cases has been listed below

SR. Age/ Duration Eye Symptoms Time since Systemic Vision IOP Diagnosis Deranged
No. Sex since involved onset of history mmHg Investigations
Covid ocular

positivity symptoms

1 62/M 2 weeks Left Ocular pain & 2 days Hypertension No PL 16 Ophthalmic d-Dimer, lipid

dimness of vision artery occlusion profile

2 80/M 3 weeks Right sudden painless 4 hrs Hypertension PL 24 Central retinal Carotid
vision loss artery occlusion Doppler,d-

Dimer

3 44/M 4 weeks Left sudden painless 3 days Diabetes 2/60 14 Central retinal HbA1c,
vision loss vein occlusion d-Dimer, blood
pressure

4 35/M 6 weeks Left dimness of vision, 7 days Diabetes PL 16 Central retinal HbA1c,
mild ptosis, artery occlusion d-Dimer, Lipid
mild proptosis,
ophthalmoplegia profile

5 32/M 3 weeks Left sudden 7 days Nil 6/9 12 Branch retinal Homocysteine,
appearance of artery occlusion lipid profile
black spot

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DJO Vol. 32, No. 3, January-March 2022

References Cite This Article as: Dhaivat Shah, Manan Solani, Shams
Tabrez. Vascular Occlusions triggered post Covid-19 infection.
1. Levi, M., Thachil, J., Iba, T., and Levy, J. H. (2020). Coagulation Delhi J Ophthalmol 2022; 32 (3): 63 - 66.
abnormalities and thrombosis in patients with COVID-19. Lancet. Acknowledgments: Nil
Haematol. 7, e438–e440. doi:10.1016/S2352-3026(20)30145-9 Conflict of interest: None declared
Source of Funding: None
2. Flaxel, C. J., Adelman, R. A., Bailey, S. T., Fawzi, A., Lim, J. I., Date of Submission:24 Sep 2020
Vemulakonda, G. A., et al. (2020). Retinal and ophthalmic artery Date of Acceptance: 26 Jan 2022
occlusions preferred practice Pattern®. Ophthalmology 127,
P259–P287. doi:10.1016/j.ophtha.2019.09.028 Address for correspondence
Dhaivat Shah MS DNB
3. S. Khavandi, E. Tabibzadeh, M. Naderan, S. Shoar Corona virus
disease-19 (COVID-19) presenting as conjunctivitis: atypically Department of Ophthalmology
high-risk during a pandemic Contact Lens Anterior Eye (2020), Choithram Netralaya, Shriram
10.1016/j.clae.2020.04.010 Talawadi, Dhar Road, Indore
Madhya Pradesh, India.
4. M.F. Landecho, J.R. Yuste, E. Gándara, et al. COVID‐19 retinal E-mail: [email protected]
microangiopathy as an in vivo biomarker of systemic vascular
disease? J Intern Med (July 2020), p. 13156

5. P.M. Marinho, A.A.A. Marcos, A.C. Romano, H. Nascimento, R.
Belfort Retinal findings in patients with COVID-19 Lancet, 395
(10237) (2020), p. 1610, 10.1016/S0140-6736(20)31014-X

6. J. Virgo, M. Mohamed. Paracentral acute middle maculopathy
and acute macular neuroretinopathy following SARS-CoV-2
infection Eye (July 2020), pp. 1-2, 10.1038/s41433-020-1069-8

7. A. Insausti-García, J.A. Reche-Sainz, C. Ruiz-Arranz, Á. López
Vázquez, M. Ferro-Osuna Papillophlebitis in a COVID-19 patient:
inflammation and hypercoagulable state Eur J Ophthalmol (July
2020), 10.1177/1120672120947591112067212094759

8. Connors, J. M., and Levy, J. H. (2020). COVID-19 and its
implications for thrombosis and anticoagulation. Blood 135,
2033–2040. doi:10.1182/blood.2020006000

9. Z. Varga, A.J. Flammer, P. Steiger, et al. Endothelial cell infection
and endotheliitis in COVID-19 Lancet, 395 (10234) (2020), pp.
1417-1418, 10.1016/S0140-6736(20)30937-5

10. N. Tang, D. Li, X. Wang, Z. Sun Abnormal coagulation
parameters are associated with poor prognosis in patients with
novel coronavirus pneumonia J Thromb Haemostasis, 18 (4)
(2020), pp. 844-847, 10.1111/jth.14768

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DJO Vol. 32, No. 3, January-March 2022

Photo Essay

Cryopreserved Amniotic Membrane in The Management of
Persistent Epithelial Defect

Rajiv Garg1, Siddharth Madan2

Department of Ophthalmology, Lady Hardinge Medical college and Associated Hospitals, University of Delhi, New Delhi, India.
Department of Ophthalmology, University College of Medical Sciences and Associated GTB Hospital, University of Delhi, Delhi, India.

Amniotic membrane has anti-inflammatory, anti-scarring and anti-angiogenic properties. Preclinical and clinical

Abstract evidence support the successful use of cryopreserved amniotic membrane in treating corneal epithelial defects and
ulcers caused by neurotrophic keratitis and the ulcers which are unresponsive to prior treatment. The case describes

one such use of amniotic membrane in the treatment of a persistent epithelial defect.

Delhi J Ophthalmol 2022; 32; 67-68; Doi http://dx.doi.org/10.7869/djo.746

Keywords: Cryopreserved Amniotic Membrane, Persistent Epithelial Defect, Neurotrophic Keratitis, Dry Eye Disease

Photo Essay autoimmune disorder, trauma, previous ocular surgery OD
or similar complaints in the past. His presenting visual acuity
The safety and effectiveness of cryopreserved amniotic OD was finger counting close to face. Fundus could not be
membrane (AM) in expediting restoration of corneal visualized however a B-scan ultrasound demonstrated no
epithelial health and eventually alleviating patient posterior segment echoes. Although the basal schirmer
symptoms is known.1 Amniotic membrane can successfully value was 10 mm but the tear film break up time (TBUT) was
treat persistent epithelial defect (PED) in the cornea.2 An decreased. He was managed on the lines of neurotrophic
unattended PED may result in Dellen’s ulcer, corneal keratitis (NK) possibly due to herpetic keratitis. Over
melting, descemetocele, and corneal perforation that can one month of treatment with topical preservative free
be potentially devastating leading to blindness. Amniotic antibiotics, cycloplegics, topical diluted steroids, antivirals
membrane transplantation (AMT) prevented these events and lubricants, resulted in non-resolution of clinical signs.
in an 80-year-old gentleman suffering from coronary artery He maintained normal intraocular pressures throughout.
disease. He developed a non-healing epithelial defect in his Eventually a cryopreserved AM was transplanted using an
right eye (OD) measuring 7.8 x 6 mm having ill- defined overlay technique and fixing with 10-0 nylon sutures (Figure
borders (Figure 1A). Corneal thinning upto one third of the 1C-D). The defect started to heal by two weeks (Figure 2A-
corneal thickness was seen with stromal haze. Hypopyon B) and the healing (Figure 2C) was complete by 35 days
was absent. The epithelial defect stained with fluorescein with a vascularized corneal opacity (Figure 2D). His corneal
dye (Figure 1B). Moreover, the corneal sensations were sensitivity improved as so did the TBUT.
diminished. The patient denied cataract surgery OD that Traditional treatment for PED includes addressing the
was advised to him a year back as he had reasonably mobile primary underlying pathology along-with suppression of
vision of 6/9 in his left eye that had a posterior chamber inflammation. Lubricants, fibronectin, growth factors, serum
pseudophakia. He had constant complaints of redness,
watering, foreign body sensation and photophobia OD
for last four months. There was no history suggestive of

Figure 1(A-D): Patient on presentation with a large epithelial defect (1A) that Figure 2(A-D): Two weeks after AMT the staining became faint (2A) and
stained deeply with fluorescein dye (1B). Amniotic membrane transplantation reduced as healing ensued (2B). Vascularization started and the ulcer reduced

(AMT) was performed using overlay technique (1C) fixed with sutures (1D). in size (2C) to heal completely with a vascularized corneal opacity (2D).

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DJO Vol. 32, No. 3, January-March 2022

drops and substance P are alternatives.2 A few of these agents Cite This Article as: Rajiv Garg, Siddharth Madan.
may not be readily accessible and may not always suffice. Cryopreserved amniotic membrane in the management of
Surgical options may then be tried which include tissue persistent epithelial defect. Delhi Journal of Ophthalmology.2022;
adhesive, contact lens, conjunctival flap, tarsorrhaphy or Vol 32, No (3): 67- 68.
eventually a penetrating keratoplasty.2,3 Nevertheless, these
options come with problems. A short surgical procedure of Acknowledgments: Nil
placing a cryopreserved AM fixed with sutures may prove
beneficial in augmenting ulcer healing in difficult cases Conflict of interest: None declared
that require anesthetic monitoring as described. After its
placement the membrane gradually becomes transparent Source of Funding: None
and the healing area becomes clearer. Although AM limits
corneal vascularization but it may not always be possible in Date of Submission: 14 Sep 2020
such large PEDs.2 Ocular surface inflammation is markedly Date of Acceptance: 20 Nov 2020
reduced after AMT, which has been reported by several
investigators.4 AMT has brought a paradigm shift in ocular Address for correspondence
surface reconstructive surgery. The growing popularity of Siddharth Madan, M.S, D.N.B, F.I.C.O,
AMTs in recent years has been modulated by the increasing
knowledge about growth factors, cytokines and demographic FAICO (Retina), MNAMS, Assistant Professor,
changes that enhance AM usage.
Assistant Professor, Department of
References Ophthalmology, University College of
Medical Sciences and Associated GTB
1. Mead OG, Tighe S, Tseng SCG. Amniotic membrane Hospital, University of Delhi,
transplantation for managing dry eye and neurotrophic keratitis. Delhi India
Taiwan J Ophthalmol. 2020 Mar 4;10(1):13-21. doi: 10.4103/tjo. Email : [email protected]
tjo_5_20. PMID: 32309119; PMCID: PMC7158925.

2. Prabhasawat P, Tesavibul N, Komolsuradej W. Single and
multilayer amniotic membrane transplantation for persistent
corneal epithelial defect with and without stromal thinning
and perforation. Br J Ophthalmol. 2001 Dec;85(12):1455-63. doi:
10.1136/bjo.85.12.1455. PMID: 11734521; PMCID: PMC1723817.

3. Feldman ST. The effect of epidermal growth factor on corneal
wound healing: practical considerations for therapeutic use.
Refract Corneal Surg. 1991 May-Jun;7(3):232-9. PMID: 2069916.

4. Chen HJ, Pires RT, Tseng SC. Amniotic membrane transplantation
for severe neurotrophic corneal ulcers. Br J Ophthalmol. 2000
Aug;84(8):826-33. doi: 10.1136/bjo.84.8.826. PMID: 10906085;
PMCID: PMC1723607.

5. Seitz B, Das S, Sauer R, Mena D, Hofmann-Rummelt C. Amniotic
membrane transplantation for persistent corneal epithelial
defects in eyes after penetrating keratoplasty. Eye (Lond). 2009
Apr;23(4):840-8. doi: 10.1038/eye.2008.140. Epub 2008 Jun 6.
PMID: 18535612.

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DJO Vol. 32, No. 3, January-March 2022

Photo Essay

Corneal Laceration Repair!

Prateek Jain1, Anshuman Pattnaik2

Department of Community Ophthalmology ,Global Hospital Institute of Ophthalmology, Abu Road, Sirohi, Rajasthan, India.

Abstract Ocular trauma is an emergency which should be addressed immediately. Injury to cornea is a preventable cause of blindness.
A meticulous corneal tear repair is essential for optimal visual outcome.This photo essay aims to brief postgraduate
residents with an insight on principles of full thickness corneal tear repair.Two cases of severe penetrating corneal injury
are presented here who were operated with satisfactory restoration of ocular integrity

Delhi J Ophthalmol 2022; 32; 69-70; Doi http://dx.doi.org/10.7869/djo.747
Keywords: Ocular Trauma, Full Thickness Corneal Tear, Corneal Laceration

Photo-essay noted. Self-sealed corneal wound by iris incarceration was
noted.Visual acuity examination showed accurate Perception
Ocular trauma is an emergency which should be addressed of light(PL) andprojection of rays(PR)in all quadrants.
immediately. Injury to cornea is a preventable cause of
blindness. A meticulous corneal tear repair is essential for The second case involves a 27 year-old male whoseleft eye
optimal outcome.Two cases of penetrating corneal injury was injured by a sharp iron particle while working 2 days
are presented here who were operated with satisfactory back.On examination, a limbus-to-limbus full-thickness
restoration of ocular integrity. This photo essay aims to brief corneal tear without iris incarceration was observed but with
postgraduate residents with an insight on principles of full flat AC.(Figure 2) Traumatic mydriasis, sphincter tear and
thickness corneal tear repair. traumatic cataract were noted.Visual acuity was HMCF with
accurate PL,PR in all quadrants.
The first case involves a five year-old school-going girl.Her
left eye was injured by goat’s horn while playing one day Orbital CT scan did not reveal any intraocular foreign
prior. On examination,a limbus-to-limbus full thickness body in either case.The mainstay of treatment involved
corneal tear with 2mm extension into sclera (Figure 1) on assessment of wound extent followed by primary repair
either side was noted along with iris incarceration. Anterior along with tackling traumatic cataract either in same
chamber(AC) was shallow.Pupil was irregular, sluggishly sitting(in first case)or as staged procedure(in second case)
reacting to light(No RAPD).Presence of posterior synechiae under suitable anaesthesia. Post-op B-scan in the first case
and traumatic cataract without vitreous herniation was revealed vitreous haemorrhage with no retinal detachment
while it was unremarkable in the second case.

Figure 1 : (1a)Pre-Op image of Case 1 -Limbus-to-limbus full thickness Figure 2 : (a)Pre-Op image of Case 2 showing limbus-to-limbus full thickness
corneal tearwith scleral extension,iris incarceration and traumatic cataract; corneal tear with flat AC and traumatic cataract;
(b)Intra-Op image showing multiple interrupted 10-0 nylon corneal sutures
(b)Magnified view showing stellate shaped wound edges;
after abscission of incarcerated iris tissue. Red pupillary reflex and intact (c)POD1 image showing properly placed sutures with layer-to-layer apposition
posterior capsule visible after traumatic cataract extraction.
of wound edges,dilated pupil revealing traumatic cataract;
(c)Intra-Op image showing optimally sutured corneal wound with buried (d)POD7 image showing healthy and intact sutures with buried knots.
suture knots

(d)POD1 image showing well formed AC with air bubble

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DJO Vol. 32, No. 3, January-March 2022

Figure 3 : Effects of suture placement for corneal lacerations. Principles of corneal tear repair4,5
(a) For sharp perpendicular wounds, deep suture placement equidistant
1. Place the first suture at limbus when it is involved.It
from the wound margins gives excellent wound approximation. provides anatomic stability to wound edges.
(b) Shallow sutures create internal wound gape.
2. Place suture perpendicular and equidistant to the cut
(c) Full-thickness sutures may create a conduit for microbial invasion. edge at 85-90% depth to ensure optimum tension for
(d) Sutures of unequal depth create wound override. layer-to-layer approximation.Equal amount of tissue
(e) Sutures of unequal length create wound override. should be incorporated on each side of the wound.
(Figure 3A)
(f)For shelved lacerations, sutures should be placed equidistant with respect
to the internal aspect of the wound to achieve good wound apposition. 3. In shelved/oblique lacerations, sutures to be placed
(Acknowledgement:Hersh P S et al.Surgical Management of Anterior equidistant with respect to the internal aspect of the
wound(Figure 3F).
Segment Trauma. In Duane's Clinical Ophthalmology 2006.Vol6 Chapter39).
4. Apply long tight compressive suture at the periphery.
Central sutures should be minimally compressive and
short.This results in peripheral flattening and central
steepening of the cornea.(Figure 4)

5. Bury suture knots in corneal stroma to lessen post-op
inflammation and infection.

6. Revise any loose or too tight sutures to achieve regular
corneal contour. Cornea flattens adjacent to tight sutures
and steepens adjacent to loose sutures, hence affecting
astigmatism significantly.

References

1. Krachmer, Mannis and Holland: Book of Cornea; Second
Edition 2005:Volume1; Section 8-Corneal Trauma; Chapter 100:
Mechanical Injury. 1245.

2. Macewen CJ. Glasgow eye infirmary, eye injuries a prospective
survey of 5671 cases. Br J Ophthalmol.1989; 73: 888-894.

3. Premchander A, Channabasappa S, Balakrishna N, Nargis N. An
evaluation of visual outcome of corneal injuries in a tertiary care
hospital. Int J Clin Exp Ophthalmol. 2019; 3: 020-029

4. John B, Raghavan C. Open Globe Injuries-Primary Repair
of Corneoscleral Injuries. Kerala Journal of Ophthalmology.
2010;22(3):225-234

Cite This Article as: Prateek Jain, Anshuman Pattnaik. Corneal
Laceration Repair! Delhi J Ophthalmol 2022;32; (3) 69 - 70.

Acknowledgments: Department of General Medicine

Conflict of interest: None declared

Source of Funding: None

Date of Submission: 29 Oct 2020
Date of Acceptance: 19 Feb 2022

Figure 4: Long, deep, and relatively tight peripheral sutures and shorter, Address for correspondence
shallower, appositional sutures near the central cornea may restore the normal Prateek Jain MS, DNB, MNAMS
corneal dome.(Acknowledgement:Hersh P S et al.Surgical Management of
Anterior Segment Trauma. In Duane's Clinical Ophthalmology 2006.Vol6 Department of Community
Ophthalmology ,Global Hospital
Chapter39). Institute of Ophthalmology, Abu Road,
Sirohi, Rajasthan India.
Cornea forms the major refracting surface;any change in Email: [email protected]
corneal contour, clarity,thickness can result in significant
visual disturbance.[1]Studies found that corneal injuries Quick Response Code
were more in most active period of life(15-50 years)and
15% of them were among children.This has a considerable
socioeconomic impact since people of this age group form
the bulwark of workforce.Literature search revealed full
thickness corneal laceration asmost important cause of
corneal blindness followed by infectious keratitis.2,3

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DJO Vol. 32, No. 3, January-March 2022

Photo essay

Isolated Co-Existence of Cerulean and Sutural Cataract
Cheau Wei, Chin

Department of Ophthalmology, Hospital Sultanah Aminah, Jalan Mahmoodiah, Johor Bahru, Malaysia.

Cerulean and sutural cataracts are developmental cataracts that are relatively rare. In this photo essay we will discuss the nature
Abstract of cerulean and sutural cataract. Usually no surgery will be needed until adulthood as their visual acuity is usually well-preserved.

Delhi J Ophthalmol 2022; 32; 71 Doi http://dx.doi.org/10.7869/djo.748
Keywords: Cerulean Cataract; Sutural Cataract; Developmental Cataract

A 39-year old lady presented to Our clinic with progressive an autosomal-dominant trait.1,3
blurring of vision of her left eye for 2 years. She had history
of trauma over her right eye during childhood resulting Cerulean cataract is associated with mutation in beta-
in white cataract, and phacoemulsification surgery was B2-crystallin, gamma-D-crystallin, V-MAF avian
performed. The best corrected visual acuity was 20/20 in musculoaponeurotic fibrosarcoma oncogene homolog.1,4
the Right eye and 20/70 in the left eye, respectively. Slit- whereas both cerulean and sutural cataracts are associated
lamp examination of her right eye revealed pseudophakia, with mutation in the major intrinsic protein genes of the lens
while that of her left eye showed dispersed bluish opacities fibre cell membranes.4
throughout the lens cortex with opacified central suture Visual acuity is usually well-preserved in patients with
(Figure 1). cerulean and sutural cataract, therefore cataract extraction is
rarely required before adulthood.2
Her intraocular pressure was 14 in both eyes, and the posterior
segment was unremarkable. Left eye phacoemulsification References
surgery was planned in view of decrease in vision.
1. Francis P, Berry V, Bhattacharya S and Moore A. The genetics of
Cerulean cataract is a developmental cataract, where in its childhood cataract. Journal of medical genetics. 2000; 37: 481-8.
distinct blue-white opacities are distributed throughout the
lens, forming large wedge shapes in the mid-periphery.1,2 2. Ionides A, Francis P, Berry V, et al. Clinical and genetic
heterogeneity in autosomal dominant cataract. British journal of
On the other hand, sutural cataract is an opacity affecting ophthalmology. 1999; 83: 802-8.
the anterior or posterior suture, usually visible as a Y-shaped
opacity.3 Both cerulean and sutural cataracts are inherited as 3. Zhang Q, Guo X, Xiao X, Yi J, Jia X and Hejtmancik JF. Clinical
description and genome wide linkage study of Y-sutural cataract
and myopia in a Chinese family. Mol Vis. 2004; 10: 890-900.

4. Xiao X, Li W, Wang P, et al. Cerulean cataract mapped to 12q13
and associated with a novel initiation codon mutation in MIP.
Molecular Vision. 2011; 17: 2049.

Cite This Article as: Cheau Wei Chin. Isolated co-existence
of cerulean and sutural cataract” for publication as a photo
essay Delhi J Ophthalmol 2021; 32 (3) 71.

Acknowledgments: Nil

Conflict of interest: Nil

Source of Funding: None

Date of Submission: 17 Aug 2020
Date of Acceptance: 23 Nov 2020

Address for correspondence
Cheau Wei Chin MBBS

Department of Ophthalmology
Hospital Sultanah Aminah
Jalan Mahmoodiah,
Johor Bahru Malaysia
Email: [email protected]

Figure 1: Diffuse light examination on slit lamp showing dispersed bluish Quick Response Code
opacities throughout the lens cortex with opacified central suture on the left eye Delhi Journal of Ophthalmology

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DJO Vol. 32, No. 3, January-March 2022

Photo essay

Leber’s Hereditary Optic Neuropathy: A Case Misinterpreted
As Optic Neuritis

Abstract Dhaivat Shah, Tina Damani, Shirali Gokharu, Akshar Soni

Choithram Netralaya, Shriram Talawadi, Dhar Road, Indore, Madhya Pradesh, India.

A 38 year old male presented with bilateral complete loss of vision over 1 year, left followed by right eye. He was diagnosed
to have optic neuritis and was given treatment accordingly, with no improvement in vision. After clinical examination and MRI
testing, we diagnosed him to have LHON, explained him the guarded course and nature of the disease and advised gene testing.
LHON is a diagnosis of exclusion, and often confused with other optic neuropathies. A sound history, astute clinical examination
and appropriate testing can diagnose this rare condition.

Delhi J Ophthalmol 2022; 32; 72-73; Doi http://dx.doi.org/10.7869/djo.749

Keywords: Leber's Optic Neuropathy; Hereditary; Fundus Photo; Telangiectatic Vessels

Case Description and ruling out other causes, the patient was diagnosed to
have Leber’s hereditary optic neuropathy (LHON). Gene
A young 38 year old male presented in our OPD complaining testing was advised to confirm LHON and patient was
of complete painless loss of vision in both eyes (no perception referred for genetic counseling. The patient and his family
of light). Patient said that the loss started in left eye first were explained regarding the poor visual prognosis and the
before 1 year, for which he was diagnosed to have optic course and nature of the disease.
neuritis and was given intravenous Methylprednisolone
(IVMP) pulse dosage. The vision did not improve post LHON is a rare mitochondrial disease often misinterpreted
IVMP and eventually there was complete loss of vision. as or confused with other optic neuropathies. A sound
Two months back, the patient began to have a similar loss history, astute clinical examination and appropriate testing
of vision in right eye, and he was diagnosed to have optic can aid in diagnosis.1 Usually these patients tend to present
neuritis and advised IVMP again. The patient came to us in the second-forth decade. Family history is extremely
for a second opinion. On fundus examination, the right important to elicit. One eye is commonly involved initially.
eye showed mild blurring of disc margin (pseudoedema) The optic nerve might show pseudo edema along with fine
with fine peripapillary telangiectatic vessels (yellow arrow) peripapillary telangiectatic vessels with or without tortuosity
(Figure a). Left eye showed optic disc pallor along with of retinal arterioles. FFA will show no evidence of leak at
mild tortuosity of retinal arterioles (red arrow) (Figure b). optic disc. In today’s era, treatment modalities for LHON
FFA showed no leakage at the optic disc, which ruled out an include nutritional supplements, activators of mitochondrial
inflammatory etiology. On further digging into the family biogenesis, brimonidine, idebenone and gene and stem cell
history, it was noted that the patient’s maternal aunt had a therapy.2
similar problem in her late thirties, and she passed away due
to a heart problem when she was 42 years of age. Orbital fat- Declaration Of Patient Consent
suppressed contrast enhanced MRI showed mild optic nerve
enhancement in both eyes. On basis of all these findings The authors certify that they have obtained all appropriate
patient consent forms. In the form the patient(s) has/have

Figure 1: (1a) Right eye fundus photo showing mild blurring of disc margin (pseudoedema) with fine peripapillary telangiectic vessels (yellow arrow) (1b)Left eye
fundus photo showing optic disc pallor along with mild tortuosity of retinal arterioles (red arrow)

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DJO Vol. 32, No. 3, January-March 2022

Figure 2: Orbital fat-suppressed contrast enhanced MRI showing mild optic Cite This Article as: Dhaivat Shah, Tina Damani, Shirali
nerve enhancement in both eyes. Gokharu, Akshar Soni. Leber’s hereditary optic neuropathy:
A case misinterpreted as optic neuritis . Delhi J Ophthalmol
given his/her/their consent for his/her/their images and 2022; 32 (3): 72 - 73.
other clinical information to be reported in the journal. The Acknowledgments: Nil
patients understand that their names and initials will not Conflict of interest: None declared
be published and due efforts will be made to conceal their Source of Funding: None
identity, but anonymity cannot be guaranteed. Date of Submission:24 Sep 2020
Date of Acceptance: 26 Jan 2022
References
Address for correspondence
1. Bi R, Logan I, Yao YG. Leber hereditary optic neuropathy: Dhaivat Shah MS DNB
a mitochondrial disease unique in many ways. Handb Exp
Pharmacol. 2017;240:309–36 Deppartment of Opthalmology
Choithram Netralaya, Shriram
2. Theodorou-Kanakari, A., Karampitianis, S., Karageorgou, V. Talawadi, Dhar Road, Indore
et al. Current and Emerging Treatment Modalities for Leber’s Madhya Pradesh, India.
Hereditary Optic Neuropathy: A Review of the Literature. Adv E-mail: [email protected]
Ther 35, 1510–1518 (2018)
Quick Response Code

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DJO Vol. 32, No. 3, January-March 2022

Abstract PG Snippet

A Brief About Hess and Lees Charting

Aakanksha Raghuvanshi, Rishabh Sah, Deepanshu, Subhash Dadeya

Department of ophthalmology, Guru Nanak Eye Centre, Maharana Ranjit Singh Marg, New Delhi, India.

Hess chart detects the amount of underaction and overaction of muscles therefore it helps in diagnosis of ocular motility defects.
Further by comparing subsequent Hess charts, one can find out improvement or deterioration of a condition. This test can give
us repeated and reliable results. Modification of the Hess screen is a Lees screen which uses double sided mirror instead of color
dissociation method used by Hess chart. This pg snippet manuscript demonstrates various conditions where Hess or Lees chart
can be used and help in diagnosis along with decision making in the management of various ocular motility defects.

Delhi J Ophthalmol 2022; 32; 74-78; Doi http://dx.doi.org/10.7869/djo.750
Keywords: Hess Chart, Less Screen, Underaction, Overaction Of Muscles, Ocular Motility Defects

HESS Charting Introduction immobile. The lights of the examination room are dimmed
to remove fusional background cues and further dissociate
Hess chart underwent various modifications in the past. the eyes. The patient is then asked to project green line on
The modern Hess screen is a gray board on which there is a the screen to bisect each red dot with the green line. Plotting
square meter tangent scale and small red lights are mounted of each dot is first done for inner field and then the outer one.
which can be illuminated in turn by bulbs behind the screen. Once this task is completed, the goggles are reversed while
Also there is a movable illuminated green indicator.1 The the patient still projects a green line, and the test is repeated.
examiner switches on a specific target while the patient
bisects the red dot by projecting the green light. For opposite Indications
field the goggles are reversed as the red lights are an integral
part of the Hess screen. The Hess screen consists of a central Patients complaining of diplopia should be tested on Hess
dot, an inner square of 8 dots, and an outer square of 16 chart. Specific indications are
dots (15 degrees and 30 degrees from the primary position,
respectively) (Figure 1). Atleast 33 cm distance is necessary 1. All patients of incomitant strabismus with normal
to be maintained to avoid accommodative or convergence retinal correspondence (NRC).
factors.
2. Patients of esotropia to rule out 6th nerve palsy.
Principles of HESS screen 3. To provide a baseline in conditions likely to develop

Hess screen follows haploscopic principle which involves defective ocular movements e.g. thyroid-related
foveal projection and dissociation of eyes.1 This test can be orbitopathy.
called as a fovea-to-fovea (maculo-macular) test as each
fovea was looking at the point on the screen to which it is Interpretation
deviated (Figure 2)1
Basic Rules for Interpretation of a Hess Plot
Hess chart plotting • Small field belongs to eye having defect.
• Neurogenic paresis will show the muscle sequelae to
Hering’s and Sherrington’s law of innervation are used a greater or lesser extent (dependent on the duration
of underlying condition and which eye is used for
to plot the chart.2 The patient wears Armstrong goggles fixation).
• The largest underaction is normally in the direction of
during the test. The eye with red glass is the fixing eye. The action of the paretic muscle and the largest overaction
is normally of the contralateral synergist.3
distance between the screen and patient is kept at 0.5 m with

the patient in sitting position keeping his head erect and

Figure 1: Hess chart Figure 2: Fovea-to-fovea projection used to dissociate the eyes.

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DJO Vol. 32, No. 3, January-March 2022

Hess Chart in Various Case scenarios antagonist (inferior oblique) versus the contralateral
(Figure 3 - Figure 9) synergist (opposite inferior rectus) in deciding which
Uses of Hess chart muscle should be weakened, or weakened first if two-
staged surgery is planned.
• In Duane’s or Brown’s syndrome, an obvious restriction
in the affected gaze position does not produce the usual • Other disorders - Most restrictive conditions (e.g.
overaction of ipsilateral antagonist as it would be in case orbital fractures with entrapment of muscles) or thyroid
of palsy. restrictive disease can be differentiated from muscle
palsy by the different patterns seen in these diseases on
• Useful in planning surgery In conditions like superior Hess chart.
oblique muscle palsy, Hess chart is useful in planning
surgery by comparing the overaction of the ipsilateral

Figure 3: Hess charts demonstrating bilateral fourth nerve palsies showing superior oblique underaction, contralateral inferior rectus overaction and extorsion
of both the fields suggestive of bilateral fourth nerve paralyses.

Figure 4: Hess chart demonstrating smaller field of right eye suggestive of underacting right lateral rectus, mild overaction of right medial rectus, marked
overaction of left medial rectus and also fixation spot of right eye is shifted nasally showing right esotropia. All these features are suggestive of a right lateral

rectus palsy.

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Figure 5: Hess chart demonstrating restriction on both up and down-gaze in the left eye due to mild entrapment as the outer chart is close to inner chart
superiorly and inferiorly. Also, central dot in left eye is shifted down showing hypotropia. Right eye has overaction of muscles superiorly and inferiorly suggestive

of left orbital floor fracture.

Figure 6: Hess chart demonstrating vertically compressed field in left eye and also the central dot is shifted nasally suggestive of left Duane’s retraction type A
(Brown’s classification) as there is limitation of abduction and also adduction to lesser extent.

LEES Screen bisects the screens such that the virtual image of one screen
is superimposed on the other.4
Lees designed a new test that would resolve the problems
like color separation and difficulty in retaining sufficient Plotting of LEES chart
color contrast and would be more comfortable to use by the
patients, by retaining tangential screen. The deviating eye projects a virtual image on the blank
screen which is seen by the fixing eye. The patient is handed
Principles a pointer with a small ring at the distal end. As the examiner
indicates which object has to be fixated on the illuminated
It consists of two screens which are independently screen, the patient is asked to place the pointer on each of the
illuminated and are positioned at 90° to each other. These similar positions which are seen by them on another screen
screens have identical tangent screens printed in back. A and that screen will appear blank to the examiner.
double-sided plane mirror is used for dissociation as it

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DJO Vol. 32, No. 3, January-March 2022

Figure 7: Hess chart shows a smaller right eye field and a larger left eye field where right eye is hypotropic and exotropic as the central dot is shifted down and
out suggestive of right eye third nerve palsy.

Figure 8: Hess chart shows small superior field and normal inferior field in right eye as there in underaction of right inferior oblique and overaction of left superior
rectus suggestive of right eye Brown’s syndrome.

This blank screen is illuminated by means of a foot pedal Uses of a Lee's Screen
pressed long enough for the observer to plot the apparent
object position on the chart. The test is repeated using the • Similar to Hess chart
other eye for fixation. This requires the patient to turn the The Lees test is easier to perform by majority of
chin rest and face towards the other screen. The illumination patients including young (5-6 years)children provided
is switched and the opposite screen becomes the one used they are able to maintain central fixation.
for fixation. (Figure 10)
Interpretation Of Lee's Chart Same as Hess chart.


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Figure 9: Hess chart shows left eye hypotropic as central dot is shifted down. There is underaction of left superior rectus which may be due to entrapment of left
inferior rectus along with inward displacement of left lateral rectus suggestive of left thyroid eye disease.

Cite This Article as: Aakanksha Raghuvanshi, Rishabh Sah,

Deepanshu, Subhash Dadeya. A Brief About Hess And Lees

Charting 2022; 32 (3): 74 - 78.

Acknowledgments: Nil

Conflict of interest: None declared

Source of Funding: None

Date of Submission: 05 Jan 2022
Date of Acceptance: 25 Feb 2022

Figure 10: The Lees screen Address for correspondence

References Aakanksha Raghuvanshi

1. Roper-Hall G. The hess screen test. American Orthoptic Journal. MBBS, DOMS, DNB
2006 Jan 1;56(1):166-74.
Department of ophthalmology,
2. Pritchard C, Ellis GS. Approach to visual acuity assessment Guru Nanak Eye Centre,
and strabismus evaluation of the pediatric patient. InPractical Maharana Ranjit singh marg,
Management of Pediatric Ocular Disorders and Strabismus 2016 New Delhi, India.
(pp. 3-23). Springer, New York, NY. Email: docaakanksha.raghuvanshi@
gmail.com
3. Fung TH, Amoaku WM. Viva and OSCE Exams in
Ophthalmology. Springer International Publishing; 2020.

4. Timms C. The Lees screen test. American Orthoptic Journal. 2006
Jan 1;56(1):180-3.

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DJO Vol. 32, No. 3, January-March 2022

Omnibus Humanus (Masters, Change Makers, Out of Box Thoughts)

Through The Eyes of An Ophthalmologist.....

Anju Sharma

Delhi J Ophthalmol 2022;32; 79-80; Doi http://dx.doi.org/10.7869/djo.751

Since times immemorial, medicine has been considered a most noble profession and practicing medicine has been a
prestigious career. Doctors alone know that practicing medicine has been an art of a quintessential balance of initially
learning then unlearning and thereafter relearning, over several years of focused efforts.

I am reminded of a David Lean classic I watched while in medical school. In a particular scene, Alec Guinness, was playing
the role of a distinguished war hero, yet, for me, his presence paled in comparison to a doctor who was seen percussing a
patient. I didn’t recognize the actor but was impressed by his impeccable percussion skills. In those days I was in the initial
stages of picking up the technique myself. By the time I graduated, to my great sorrow, percussion had become an outdated
skill. Technology in the form of ultrasonography by then was considered a more significant tool.

Practicing medicine is a beautiful balancing act between opposites. While one needs to be brief one still needs to have all the
relevant details. There is no time for idle chit chat yet one needs to build a rapport with one’s patients. One hopes to give
each patient quality time but is acutely aware of the many waiting outside in a jam packed OPD. When the description
of symptoms and the statements of patients are repetitive one really needs to be patient. However, you yourself need to
be repetitive in explanations about disease and treatment, especially with inattentive or less educated patients who have
difficulty reading prescriptions. One will require technology to differentiate between diseases or to narrow down the
differentials and yet needs the clinical acumen to decide what technological parameter to really ask for. Bedside manners
are the sound foundation on which the clinical practice should proceed
.
The Hippocratic oath mentions the word ‘art’ several times but the word ‘science’ not even once in reference to medicine.
This is astute, for the cure of the patient lies in efficient team work between patient and physician more than the patient
obeying a` know it all` doctor. Many nervous patients are visibly put at ease if a doctor knows what to say as well as what
to do medically. A patient, an old grandmother from the village was acutely conscious of her illiterate status. I simply
commiserated with her about the unavailability of schools in her village. This ice-breaker had a magical effect. Visibly at
ease she air drew English alphabets from Snellen’s chart and not only listened attentively but felt safe enough to ask me a
barrage of questions too. It was gratifying when she blessed me by touching my head before leaving.

Illustrative language can help the patient firm up their decisions. Cars and driving are well-used metaphors. We let the
patient know that all cars can take you from destination A to B (the crux) but some have a better pick up and some plush
leather seats. Lenses, similarly, help you reach 6/6 vision (other factors being in place) but the expensive ones may have
additional features. The car allegory also helps when explaining a complication in a surgery. A high-end car with a careful
driver on a good road cannot guarantee that there will never be an accident – for a child may dart across or the road
may cave in a bit (on a rainy day in Delhi this is not unusual!). I recall how there was a patient with mature cataract who
needed immediate surgery but was keen to postpone it to the ‘winter months’. When I painted the geographical picture of
how several warm places in South India have a winter ‘in name only’, yet have centers of excellence with very high surgical
numbers, it helped him make up his mind to go ahead with the surgery.

When working in the OT, loose words are as impermissible as loose hair. An air of calm and quiet is highly desirable with the
occasional murmurs of encouragement or just some pleasant music. In the OPD, an electronic hospital information system
has now become an important tool of modern medicine. One needs to juggle one’s time between patients in first talking,
diagnosing and then noting the details and management. One has to toggle one’s gaze between the patient and the computer
screen. Listing ICD codes, generic names of drugs, investigations and all steps of surgery does become fairly time consuming.

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DJO Vol. 32, No. 3, January-March 2022

Several published studies have brought out the strong link between physician burn-out and electronic medical records, even
to the tune of over 40% in some of the studies. The doctors feel this is insurance driven ‘clerical work’ which reduces the
efficient use of their time. Patients can feel that the doctor is not engaging directly with them when they repeatedly look at
the screen. All this underlines to us that while technology shows us the way into the future, we can never automate the human
touch.

The importance of this was starkly demonstrated during the Covid Pandemic. With little knowledge of the disease, treatment
was more trial and error. With distancing being an important facet, the sufferers were at the mercy of strangers whose faces
they couldn’t even see and voices that were at best, muffled. Yet compassionate medical staff came up with innovative ideas
to recreate the ‘human touch’ and boost well-being. One such method was to fill gloves with saline and put in in the hands
of semi-conscious patients on ventilators who felt they were holding a human hand. This must have been a tremendous
psychological boost.

This sacred connection, the intangible thread of healing between doctor and patient sometimes undergoes various trials and
tribulations. When the outcome of a surgery or treatment goes wrong, one should not try to avoid or even slightly abandon
one’s patient. That’s the time the worried patient needs us the most. The patient should be robustly hand-held through the
temporary state of discomfort that he is undergoing. His fear and depression should be empathized with. There was wisdom
when we were told that each patient maybe thought of as if he were a family member.

Outside the twosome of doctor and patient, we have supporting players. It can sometimes be jarring when medical
representatives appear after you have just finished with a hectic OPD. But for a weary bike traveler highlighting his products
at every doctor’s door, it can give a very pleasant edge to a dull, repetitive job when a doctor looks beyond the eye drops at
the person itself and engages warmly and possibly remembers his name or his products.

The golden rule to be followed in medical practice is not to take one’s compliments too seriously and to learn to take brick
bats in your stride. Time and again I have witnessed how the particular patient who screams loudest in OPD has some
underlying depression. It has always paid to swallow one’s anger and pacify a quarrelling one. He will then be in a better
position to hear you out as well.

Finally, what does one do on a day when one loses one’s own cool? The answer is ridiculously simple - drink a glass of
cold water and feel the anger dissipate in the fluid wave (God knows we have been dealing with bigger waves of late) going
down your throat. Our technical knowledge helps patients heal physically but it is our small personal gestures that makes
the world around the patient truly peaceful.

Dr Anju Sharma
MBBS, MS (Ophthalmology) AFMC
Deputy Medical Superintendent
Chaudhary Eye Centre & Laser Vision, Darya Ganj New Delhi, India.
(My sincere thanks to Dr Anjali Mehta and Ms Shabana for their inputs)

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DJO Vol. 32, No. 3, January-March 2022

Letter to Editor

A battle within the war - Mucormycosis: The Black fungus
disease in India during COVID -19

Sujeeth Modaboyina, Mandeep S Bajaj, Sahil Agrawal, Deepsekhar Das

Department Of Ophthalmology, Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences,New Delhi, India.

Delhi J Ophthalmol 2022; 32; 81-82; Doi http://dx.doi.org/10.7869/djo.752

Keywords: COVID-19, India, Mucormycosis, Black Fungus, Rhino-Orbito-Cerebral Disease

Dear Editor, 15 patients cases where orbital spread of mucormycosis
The second wave of COVID 19 infection hit India in the were mostly found in non-COVID uncontrolled diabetics.6
mid of March 2021, with a sudden exponential surge in the However, both these reports were from the first wave of
number of active cases. The newly reported cases, which COVID 19, and with the exponential rise in the number of
were approximately 17000 per day between the months of COVID 19 cases, the number of mucor cases had also gone
January and March, catapulted to 1.5 lakhs per day in the up. In the present day senario, a tertiary care hospital in
mid of April and reached a record peak of 4.1 lakhs per north India receives nearly ten new cases of rhino-orbito-
day in the first week of May 2021.1 As the nation gasped for cranial mucormycosis every day. At this juncture, there is an
oxygen and the healthcare system was stretched to its limit, epidemic amidst the ongoing pandemic.
an unanticipated problem emerged. Mucormycosis, a life-
threatening fungal infection now commonly referred to as The management of rhino-orbito-cerebral mucormycosis
'Black fungus', which typically infects immunocompromised requires a multidisciplinary approach involving oto-rhino
and diabetic individuals, found its ideal environment for laryngology, ophthalmology, neurosurgery, endocrinology,
growth in patients recovering from COVID 19. The fungi and even the medicine department. The conventional
usually gets transmitted by traumatic inoculation. management options revolve around aggressive usage
of intravenous, Amphotericin B coupled with surgical
COVID-19 patients with Acute Respiratory Distress debridement and, at times, exenteration of the orbit. Apart
Syndrome in severe forms require high doses of steroids from the conventional amphotericin B deoxycholate,
with oxygen supplementation. The steroids compromise three lipid formulations, namely amphotericin B lipid
the immune system making it a suitable habitat, and the complex (ABLC), liposomal amphotericin B (L-AmB),
improperly sanitised oxygen delivery systems and hospital and amphotericin B colloidal dispersion (ABCtD), are also
linens act as a vehicle for the transmission of the fungi.2 available. All three drugs have different pharmacokinetics
due to difference in the composition of lipids. Recommended
Although the incidence of rhino-orbito-cerebral therapeutic dosage for ABLC is 5 mg/kg/day, L-AmB is
mucormycosis amongst COVID 19 affected patients remain 3-6mg/kg/day and ABCtD is 3-4 mg/kg/day. Posaconazole is
unknown, there are few studies related to mucormycosis a triazole antifungal, given at a dose of 800mg daily in two to
in COVID 19 individuals from India. One is a multicentric, four divided doses. To enhance its rate of absorption, it has to
retrospective, interventional study conducted between be given along with high fatty meals. Though Posaconazole
August 2020 and December 2020, where the authors reported has a lesser side effect profile, its efficacy is comparable
six patients with simultaneous COVID 19 and mucormycosis with Amphotericin B.5 Moreover, low dose amphotericin B
infection. The mean duration between diagnosis of COVID combined with Posaconazole had similar efficacy compared
19 and development of the symptoms of fungal infection was with standard-dose amphotericin B alone. Isavuconazole
15.6 ± 9.6 (3-42) days. All the patients underwent endoscopic is a water-soluble second-generation triazole with broad-
sinus surgery; two required exenteration, and no deaths spectrum antifungal activity; for both intravenous and oral
were reported.3 Sarkar et al. reported a cluster of 10 cases of administration recommended dose is 200 mg every 8th hourly
mucormycosis with COVID 19 infection between November for 48 hours followed by a maintenance dose of 200mg once
and December 2020. All were treated with intravenous daily. Major advantage of azole over amphotericin B is lesser
dexamethasone for COVID-19 and liposomal amphotericin toxicity and availability for oral administration. Intraorbital
B for mucormycosis. Four patients died within a month, injections of Amphotericin B has yet to be proven by large
and five patients had satisfactory systemic outcomes with scale randomised studies.
irreversible vision loss, while only one patient had both
ocular and systemic favourable outcomes.4 A multi centric The rise in the number of rhino-orbito-cerebral mucormycosis
collaborative retrospective, observational study by Sen has also led to an unprecedented increase in the demand
et al of 2826 patients revealed that corticosteroids and for antifungal medications, and many tertiary centres are
Diabetes mellitus (DM) (78% cases) are the most important running out of supplies, and the country is facing an acute
predisposing factors in the development of COVID-19- shortage of antifungal drugs.
associated mucormycosis.5
As more and more cases reach the hospital, oculoplasty
This was noted in another study, where authors presented surgeons and otorhinolaryngologist are busy performing

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DJO Vol. 32, No. 3, January-March 2022

repeated surgical debridements and exenterations every Cite This Article as: Sujeeth Modaboyina, Mandeep S Bajaj,
day. screening and stringent management guidelines before Sahil Agrawal, Deepsekhar Das. A battle within the war -
the deadly fungus causes further damage. The formulation Mucormycosis: the black fungus disease in India during COVID
of high-risk group criteria and screening protocols are the -19 Delhi Journal of Ophthalmology.2022; Vol 32, No (3): 81 - 82
need of the hour.
Acknowledgments: none
References
Conflict of interest: None declared
1. Second Covid wave to peak in mid-April, to see 25 lakh cases’:
SBI report. The Tribune - Voice of the people web site. https:// Source of Funding: None
www.tribuneindia.com/news/nation/second-covid-wave-
to-peak-in-mid-april-to-see-25-lakh-cases-sbi-report-230411. Date of Submission: 27 Jan 2022
Accessed 13 May 2021. Date of Acceptance: 10 Feb 2022

2. Alexander J Sundermann, Cornelius J Clancy, A William Address for correspondence
Pasculleet al. How Clean Is the Linen at My Hospital? The Deepsekhar Das MD
Mucorales on Unclean Linen Discovery Study of Large United
States Transplant and Cancer Centers. Clinical Infectious Senior Resident
Diseases. 2019 Mar; 68(5):850-3. https://doi.org/10.1093/cid/
ciy669 Oculoplasty and Ocular,Oncology
Services,Dr. Rajendra Prasad
3. Sen M, Lahane S, Lahane TP, Parekh R, Honavar SG. Mucor in a Centre for Ophthalmic Sciences, All
Viral Land: A Tale of Two Pathogens. Indian J Ophthalmol. 2021 India Institute of Medical Sciences
Feb;69(2):244-252. doi: 10.4103/ijo.IJO_3774_20. PMID: 33463566; New Delhi, India
PMCID: PMC7933891. Email : [email protected]

4. Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19 and
orbital mucormycosis. Indian J Ophthalmol. 2021 Apr;69(4):1002-
1004. doi: 10.4103/ijo.IJO_3763_20. PMID: 33727483; PMCID:
PMC8012924.

5. Sen M, Honavar SG, Bansal R et al.; members of the Collaborative
OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC)
Study Group. Epidemiology, clinical profile, management,
and outcome of COVID-19-associated rhino-orbital-cerebral
mucormycosis in 2826 patients in India - Collaborative OPAI-
IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.
Indian J Ophthalmol. 2021 Jul;69(7):1670-1692. doi: 10.4103/ijo.
IJO_1565_21. PMID: 34156034; PMCID: PMC8374756.

6. Saluja G, Bhari A, Pushker N et al. Experience on Rhino-Orbital
Mucormycosis from a Tertiary Care Hospital in the First Wave of
COVID-19: An Indian Perspective. Med J Armed Forces India. In
Press

7. Van Burik, J., R. S. Hare, H. F. Solomon, M. L. Corrado, and D. P.
Kontoyiannis. 2006. Posaconazole is effective as salvage therapy
in zygomycosis: a retrospective summary of 91 cases. Clin.
Infect. Dis. 42:61–65.47: 1831-8.

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DJO Vol. 32, No. 3, January-March 2022

Theme Article

Drugs Used in Ocular Local Anaesthesia: An Overview
Anam Ansari, Priyanka Gupta, Siddharth Madan

Department of Ophthalmology, University College of Medical Sciences and Associated GTB Hospital, University of Delhi, Delhi, India.

Ocular local anaesthetics are the drugs which are used for various ocular procedures including examination of cases of

Abstract ocular trauma, removal of superficial foreign bodies, intraocular pressure assessment and in ocular surgery. Various
drugs used for ocular local anaesthesia are summarised.

Delhi J Ophthalmol 2022; 32; 83-86; Doi http://dx.doi.org/10.7869/djo.753
Keywords: Drugs, Ocular anaesthesia, lignocaine, bupivacaine, proparacaine

Classification Name of the drug Mechanism of action Route of Dose/toxic dose Site of action Onset of Duration Complications/
administration action of action side effects
and concentration Peak blood Topical-naked (DOA)
of the drug used levels of nerve endings
Solutions 1) Lidocaine Reversible inhibition (Percentage) lidocaine may in cornea & Topical- Topical-lasts Burning-due to
Amide hydrochloride1,2 of nerve impulse occur as early conjunctiva, Action for 15 – 20 acidic nature
linked generation and Topical-2 – 4% as 5 minutes penetrate begins minutes of solution (ph
anaesthetics Trade names- conduction at free (preferably- 2%) and as late as 30 through within Retro/ 6- 6.5), alteration
(LOX 2% nerve endings of Peri/retrobulbar minutes cornea into 2-5 mins peribulbar- of tear film
XYLOCAINE cornea (topical) block- 1 – 2% Max dose with the anterior Retro/ lasts for temporarily
LIGNOX 2 % and nerves within Intracameral- 1%1 epinephrine chamber & peribulbar- 60-120 mins Crosses corneal
ADR the cornea (retro/ Sub-tenon- 2% -7mg/kg & not acts on iris & begins epithelium
GESICAINE peribulbar) lignocaine >500mg. ciliary body within 10 & may cause
WITH Due to blockage of with 150 IU neurons mins epithelial &
ADRENALINE) sodium channels hyaluronidase2 Regional- stromal edema
branches Drowsiness
of the & mental
ophthalmic clouding-
division of after systemic
trigeminal absorption
nerve as they
pass through
supraorbital /
infraorbital
fissure &
annulus of
zinn

2) Bupivacaine Most lipid soluble. Topical-0.75% The maximum Topical-naked Topical- Topical-lasts Same as
hydrochloride Excellent corneal Retrobulbar/ recommended nerve endings starts for 20-30 lidocaine
Trade names- penetration & peribulbar-0.25- dose for in cornea & within 5-10 mins
(SENSORCAINE entry into anterior 0.75% bupivacaine conjunctiva mins Regional-
BUPIVAN) chamber. Higher Sub-tenon- 0.5% without Peribulbar/ Regional- lasts for 180-
lipid solubility & bupivacaine with epinephrine is retrobulbar- starts 360 mins
protein binding than 2% lignocaine 1 to 2 mg/kg, branches of within 10
mepivacaine, more and 150 IU increasing to 2 ophthalmic mins
potent & has longer hyaluronidase2 to 3 mg/kg when division of
duration of action. epinephrine is trigeminal
Blocks sodium added nerve,
channels in nerve branches of
endings of cornea, oculomotor,
blocking nerve abducent
impulse generation & trochlear
when used topically. nerves
Retro/peribulbar-
blocks motor nerves
supplying the
extraocular muscles,
orbicularis oculi &
sensory neurons
from cornea and
conjunctiva-blocking
impulse generation

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DJO Vol. 32, No. 3, January-March 2022

3) Mepivacaine Amide linked Retrobulbar/ - Same as Topical-starts Topical- lasts 10- Used Intracamerally
hydrochloride anesthetic peribulbar- lidocaine within 1-3 15 minutes as 0.4 ml of 2%
Poor corneal 0.25-0.75% mins Retro/peribulbar- unpreserved solution
penetration- Retro/ lasts -80-160 mins Causes more burning
not preferred peribulbar- DOA of 2% because of pH 5-5.6
topically starts in 10 mepivacaine is
mins 50%longer than
lidocaine-lesser
vasodilator
property

4) Etidocaine Amide linked 1% - Same as Slightly rapid Slightly longer -
hydrochloride anaesthetic lidocaine onset
duration of action

5) Ropivacaine1 Amide linked Topical- 0.2% Ropivacaine With 2 drops Duration of action Minimal cardiological
anaesthetic Peribulbar- elicits equivalent (reappearance of and neurological toxic
0.5% regional to 375 μg of corneal reflex) is events. This action is
Intracameral- anaesthetic ropivacaine 48 min. potentiated by dose-
0.1% that, like all dose, the onset dependent inhibition
amide-type of action (loss of potassium-
anaesthetic- of corneal when used in high
nerve reflex) is 5 concentrations.3
block via minutes.
6) Prilocaine Amide linked 3 % prilocaine - reversible --
anaesthetic injection for inhibition -
peribulbar of sodium
anaesthesia. ion influx in
In 1994, a nerve fibres
sub-Tenon’s
injection of -
prilocaine
chlorhydrate
using an
atraumatic
curved
cannula,
without
the use of
the needle,
in order to
avoid the
risk of globe
perforation
or intraocular
structures got
popularised
as “No-
needle
anaesthesia
technique
uses
atraumatic
cannula for
infiltration.”
Not routinely
used now.

7) Amide linked Peribulbar/ Maximum 12 ± 2.6 Duration of Hypotension
Levobupivacaine4 anaesthetic Retrobulbar: single dose of minutes peribulbar block Lower chances
(CHIROCAINE) levobupivacaine was similar of neurotoxicity
5mg/ml for peribulbar between racemic and cardiotoxicity
administration is bupivacaine and compared to
112.5 mg (15 mL levobupivacaine bupivacaine5
in 0.5% solution) (188 ± 35.7minutes
versus 185 ± 33.2
minutes5

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DJO Vol. 32, No. 3, January-March 2022

8)Oxybuprocaine6 Amide linked Topical: 0.4% Overdose Reversibly One drop Corneal Dose dependent
anaesthetic following the blocks the instilled sensitivity is adverse effects which
Topical- 0.5% recommended use propagation into the normal after include severe allergic
Topical- 0.5- is unlikely and conjunctival about one hour. reactions, burning
1% conduction sac – sufficient sensations, iritis,
1 drop every 5-10 of nerve to anaesthetise moderate corneal
minutes for 5-7 impulses the ocular swelling, pulmonary
applications for along nerve surface edema and certain
deep anaesthesia. axons. to allow effects on CNS.
1 or 2 drops 2 to tonometry Burning or stinging
3 minutes before - after one sensation subsides
a short procedure minute. within 30 seconds of
like suture A further instillation. Frequent
removal, foreign drop after or chronic use may
body removal. 90 seconds result in tolerance
-adequate to its beneficial
Maximum doze- anaesthesia for effects, severe
1.5-3mg/kg the fitting of corneal damage,
contact lenses. disciform keratitis,
Three drops peripheral corneal
at 90 second ring formation, and
intervals- infiltration of the
sufficient for a corneal stroma.
foreign body
removal from Contraindicated
cornea or for in patients with
incision and hypersensitivity to
curettage of the any component of the
chalazion. preparation.
No adverse safety
9)Proxymetacaine6 Reversibly issues reported
blocks
initiation and Circumoral
conduction numbness,
of nerve tinnitus, blurry
impulses by vision, dizziness,
decreasing hyperexcitability/
permeability seizures, increase in
of the PR and QRS interval7
neuronal Discouraged due to
membrane to corneal toxicity. Also
sodium ions. toxic in patients with
esterase deficiency.
Ester linked 1)Tetracaine 1st of ester -- Not used nowadays
compounds linked
compound Not degraded to
PABA so safer than
2) Proparacaine Ester linked Used as 0.5% - As other Duration of Lasts 5-10 other ester linked
(PARACAINE) anaesthetic. concentration agents action-starts minutes anesthetics.
Sodium topically within 0.25 Certain side effects
channel minutes include: blurred
blocker, vision, redness of
hydrolysed eyes, sensitivity
by plasmatic to light, tearing,
& tissue stinging in the eye or
esterases. a change in vision.
Excessive instillation
may cause epithelial
corneal haze and
punctate keratopathy
as the drug has
toxic effect on
stromal keratocytes.
Proparacaine
inhibits epithelial
cell migration and
adhesion.
Less irritating
and painful than
benoxinate

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DJO Vol. 32, No. 3, January-March 2022

3)Benoxinate - - -- - It is more toxic to
Benzdon 0.4% cornea hence to be used
eye drops High dose cautiously. Caution to be
lignocaine observed in patients with
Gels 1)Lignocaine Preservative 3.5 % One drop of As lignocaine might protect history of allergy, heart
free gel gel followed from bacterial disease, hyperthyroidism
formulation by cleaning infections and and open wounds.
of high with betadine hydroxypropyl
concentration after 2-3 cellulose aids in Most common adverse
lignocaine minutes, preserving corneal effect is corneal staining
reapplication epithelium. which usually resolves
of another gel within 24 hours.
drop

References Cite This Article as: Anam Ansari, Priyanka Gupta, Siddharth
Madan. Drugs Used in Ocular Local Anaesthesia: An Overview.
1. Sharma AK, Singh S, Hansraj S, Gupta AK, Agrawal S, Katiyar V, et al. Delhi Journal of Ophthalmology.2022; Vol 32, No (3): 83- 86.
Comparative clinical trial of intracameral ropivacaine vs. lignocaine
in subjects undergoing phacoemulsification under augmented Acknowledgments: Nil
topical anesthesia. Indian Journal of Ophthalmology 2020; 68 (4):
577-582. doi: 10.4103/ijo.IJO_1388_19. Conflict of interest: None declared

2. Guise P. Sub-Tenon's anesthesia: an update. Local Reg Anesth. Source of Funding: None
2012;5:35-46. doi:10.2147/LRA.S16314.
Date of Submission: 25 Mar 2022
3. Simpson D, Curran MP, Oldfield V, Keating GM. Ropivacaine: a review Date of Acceptance: 01 April 2022
of its use in regional anaesthesia and acute pain management. Drugs.
2005;65(18):2675-717. doi: 10.2165/00003495-200565180-00013. Address for correspondence
PMID: 16392884. Siddharth Madan, M.S, D.N.B, F.I.C.O,

4. Sanford M, Keating GM. Levobupivacaine: a review of its use FAICO (Retina), MNAMS, Assistant Professor,
in regional anaesthesia and pain management. Drugs. 2010 Apr
16;70(6):761-91. doi: 10.2165/11203250-000000000-00000. PMID: Assistant Professor, Department of
20394458. Ophthalmology, University College of
Medical Sciences and Associated GTB
5. Pacella E, Pacella F, Troisi F, Dell'edera D, Tuchetti P, Lenzi T,et al. Hospital, University of Delhi,
Efficacy and safety of 0.5% levobupivacaine versus 0.5% bupivacaine Delhi India
for peribulbar anesthesia. Clin Ophthalmol. 2013;7:927-32. doi: Email : [email protected]
10.2147/OPTH.S43553. Epub 2013 May 21. PMID: 23723684; PMCID:
PMC3665566.

6. Pelosini L, Treffene S, Hollick EJ. Antibacterial activity of
preservative-free topical anesthetic drops in current use in
ophthalmology departments. Cornea. 2009 Jan;28(1):58-61. doi:
10.1097/ICO.0b013e318182ecf9. PMID: 19092407.

7. Stringer CM, Lopez MJ, Maani CV. Tetracaine. [Updated 2021
Aug 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.
gov/books/NBK535437/

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DJO Vol. 32, No. 3, January-March 2022

Theme Article

Ocular Effects of Systemic Medications
Divya Jain

Department of Ophthalmology Postgraduate Institute of Child Health,Sector 30, Noida, India.

Abstract Systemic medications can give rise to ocular toxicity due to rich ocular blood supply and small ocular mass. These side
effects can range from dry eye, keratitis, corneal deposits, glaucoma, cataract to blinding complications as a result of
retinal toxicity and optic neuropathy. This review focuses on commonly used drugs, their ocular side effects, some newer
drugs and their toxicity. Baseline examination and follow up at regular intervals is necessary for timely recognition of
toxicity and discontinuation of these side effects. Recommendations for monitoring for medications with frequent and/
or severe adverse ocular effects are discussed.

Delhi J Ophthalmol 2022; 32; 87-92; Doi http://dx.doi.org/10.7869/djo.754

Keywords: Drug Toxicity, Ocular Side Effects,Drug Safety

Introduction patients with allergic tendencies. Prior exposure to the drug

Eyes are prone to harmful effects of systemic medications leads to sensitization of the patient and subsequent drug
due to a rich blood supply and a small mass.1 exposures may result in different types of allergic reactions.
Sometimes adverse drug reactions may be idiopathic. (Table

The drug molecules from the systemic circulation can reach 1) shows commonly used drugs causing ocular side effects.

the ocular structures by the uveal or retinal vasculature. Specific Drug Groups and Their Side Effects
Thin fenestrated walls of the choroid, sclera and ciliary body Anticholinergic Drugs
acts as a gateway for small lipid molecules which can pass

freely across into the aqueous humour and also diffuse into Drugs with anticholinergic effects such as antihistamines,
the avascular structures such as the lens, the cornea, or the antidepressants, anticholinergics, diuretics, ß-blockers and
trabecular meshwork. The common sites of accumulation of antipsychotics are used to treat various systemic disorders
these drugs in the eye are the cornea, lens, and retina. like urinary incontinence, overactive bladder, chronic

The drug molecules bind to stromal glycosaminoglycans obstructive pulmonary disorder and organophosphate
leading to edema and can reduce the transparency of cornea. poisoning. These drugs can lead to ocular surface dryness
The drug molecules can bind to the lens proteins leading to and may require artificial tear supplementation, punctal
its opacification and cataract formation. plugs, or administration of topical cyclosporine for the
treatment depending on the severity.

Drug deposits in the retina manifest as a loss of pigmentation Angle-closure glaucoma might be induced in predisposed
and accumulation of pigment-laden cells in the outer retinal patients due to pupillary dilatation induced by the
layers, leading to damage to the photoreceptors and the anticholinergic effect. Oxybutynin and other drugs used in
ganglion cell layer. the treatment of overactive bladder have resulted in the rise
of intraocular pressure (IOP) in individuals with shallow
Adverse drug reactions can be dose-related, allergic or angles, the majority being adult females.2 These drugs are
idiopathic. Dose-related effects are predictable and common also used for the treatment of bedwetting in children and for
with drugs having a narrow therapeutic index. These are the prevention of catheter induced spasms after hypospadias
commoner in patients with impaired renal, hepatic function, surgery.3 Rare cases of acute rise in IOP have been reported
or polypharmacy leading to drug-to-drug interactions. in children after oxybutynin use.
Allergic aetiology may not be dose-related, commoner in

Table 1: Common drugs implicated for causing various ocular adverse (Figure 1) shows a child with anterior synechiae post
effects keratoplasty who presented with acutely raised IOP after
oxybutynin usage. Therefore, a high index of suspicion and
SNo Drug group Ocular side effects prompt referral to an ophthalmologist by the paediatrician
1. Anticholinergic Dry eye, Angle closure glaucoma is required to prevent a sight-threatening rise in IOP in
2. Alpha 1a agonist predisposed patients. (Table 2) shows some commonly used
3. Anti arrhythmias Floppy Iris syndrome drugs which can cause glaucoma in predisposed individuals.
4. Anti coagulants Corneal deposits
5. Anti malarials Ocular bleed Alpha 1 blocker
6. Anti epileptics Retinal toxicity
Alpha 1 blocker can be selective α1 blockers (Tamsulosin),
7. Corticosteroids Visual field constriction, and non-selective α1 blockers e.g. terazosin and doxazosin
8. Anti tubercular drugs nystagmus are used for the treatment of benign prostatic hypertrophy
9. (BPH) in men and bladder problems in women. This drug
Anti psychotics Cataract, Glaucoma relaxes the bladder and prostatic smooth muscle making it
10. Toxic optic neuropathy easier to urinate.
Anti neoplastic Corneal and lenticular
The alpha 1 blocker has a weakening effect on pupillary
pigmentation dilator muscles. This weakening effect along with the strong
Retinal haemorrhages

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Table 2: Shows drugs causing glaucoma Amiodarone

Class of Drug Example of drug Mechanism of It is used to treat serious cardiac arrhythmias. The patient
action complains of green halos and also reports a reduction in
Adrenergic agonist Ephedrine visual acuity. It can cause vortex keratopathy or cornea
Non catecholamine Naphazoline, Pupillary block verticillata seen as a whorl-like pattern on the cornea. These
adrenergic agonist Salbutamol Pupillary block corneal opacities are not visually significant.
Ipratropium
Anti cholinergics Pupillary block Anterior capsular lens opacities can also be seen and it can
bromide, lead to multiple chalazia and dry eye. Amiodarone can cause
Tricyclic Promethazine Pupillary block optic neuropathy leading to decreased vision. It appears in
antidepressants Imipramine 1-2% of the cases and can manifest within a week or two
(with anticholinergic Pupillary block after a patient consumes Amiodarone.
Fluoxetine
side effects) Ciliochoroidal Other drugs that are known to cause vortex keratopathy
Serotonin reuptake Topiramate and effusion leading include chloroquine, Hydroxychloroquine, Amiodarone,
Acetazolamide Indomethacin, and Tamoxifen.
inhibitor (with to forward
anticholinergic side displacement of lens Anticoagulants

effects) Iris diaphragm These are used to reduce the incidence of strokes and heart
Sulfa based drugs disease. This class of drugs may lead to intraocular and
extraocular haemorrhage therefore are usually discontinued
Figure 1: Showing shallow anterior chamber with synechiae post PK in a child prior to surgery. Anticoagulants can also cause retinal
predisposing him to angle closure post oxybutynin (Reproduced from Jain haemorrhages. Angle-closure glaucoma due to massive
D, Dhua A, Ravisankar V, Chellam L, Joshi M. Acute angle closure glaucoma suprachoroidal haemorrhage has been reported post-
after hypospadias surgery: A vision-threatening complication of oxybutynin. J Warfarin use, so a high index of suspicion is warranted in
predisposed individuals.7
Indian Assoc Pediatr Surg 2015 ;20:161-2)
Antimalarials
effect of the constrictor muscle prevents full pupillary
dilatation for cataract surgery. In addition, iris billows due They belong to aminoquinolines group e.g., chloroquine
to the effect of fluid during irrigation and the atonic muscle and Hydroxychloroquine (HCQ). These are used for the
tend to prolapse through the main or side port leading to treatment of rheumatologic conditions, malaria etc. With
intraoperative floppy iris syndrome (IFIS).4 It can be graded the surgence of coronavirus disease (COVID-19),oral HCQ
into mild (only iris billowing), moderate (iris billowing with was administered as a prophylaxis for COVID-19 in the first
intraoperative miosis), and severe (moderate IFIS along with wave. The retinal toxicity results due to cumulative dosage
iris prolapse). IFIS has also been reported with non-selective and concurrent presence of renal disorders and Tamoxifen
agents5 and has even been reported in patients who have use.8 The starting dosage is 400 milligrams to 600 milligrams,
a single dose or twice a day. The action of HCQ being
discontinued tamsulosin 1 year back.6 cumulative, may require weeks to months, for maximum
therapeutic effect for a given patient.

The maximum recommended daily dose of HCQ is ≤ 5.0 mg/
kg real weight. For Chloroquine maximum recommended
dose is ≤ 2.3 mg/kg real weight.

The risk of toxicity till 5 years is less than 1% and under 2%
up to 10 years, but is almost 20% after 20 years. Those who
do not manifest toxicity after 20 years have a 4 % risk of
toxicity in the subsequent year.

A baseline fundus examination should be done to rule out
pre-existing maculopathy. Thereafter annual screening is
recommended every 5 years.

Primary screening is performed with automated visual fields
plus spectral-domain optical coherence tomography (SD-
OCT). Fundus autofluorescence (FAF) can show damage
topographically and multifocal electroretinogram (mfERG)
provides objective corroboration with visual fields. Modern
screening should detect retinopathy before it is visible in the
fundus. Retinopathy induced due to antimalarial toxicity is
irreversible. Timely recognition and cessation of therapy at
an early stage (before any retinal pigment epithelial loss) are
important to prevent central visual loss.

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DJO Vol. 32, No. 3, January-March 2022

Antiepileptic drugs In family members of patients with primary open-angle
glaucoma (POAG)and glaucoma suspects risk of ocular
These are used for the treatment of seizures, as mood- side effects increases with chronic use. (Figure 2) shows
stabilizing agents and treatment of migraine headaches. corticosteroid-induced posterior capsular cataract. (Figure
Vigabatrin irreversibly inhibits Gamma-aminobutyric acid 3&4) Optical coherence Tomography (OCT) and Fluorescein
(GABA)-transaminase and is used for refractory seizures in angiography (FA) of steroid-induced CSR.
adults and infantile spasms. It can lead to bilateral peripheral
visual field constriction Figure 2: Corticosteroid induced posterior capsular cataract

The ocular effects are asymptomatic, the defects may lead Figure 3: Showing CSR induced by corticosteroid use (Photo courtesy: Dr Devesh
Kumawat, Assistant Professor, Lady Hardinge Medical College, New Delhi)
to tunnel vision, are largely irreversible and can occur in
Figure 4: Multiple leaks seen in a patient of corticosteroid-induced CSR on
30% to 50% of patients after 6 to 24 months of treatment. fluorescein angiography (Photo courtesy: Dr Devesh Kumawat, Assistant

The recommended safest dose of Vigabatrin is up to 3 g per Professor, Lady Hardinge Medical College, New Delhi)

day in adults, or 50 to 100 mg/kg/day in children. Baseline

screening and follow up every 3-6 months is recommended

for patients on Vigabatrin. For children under 9 years and

who are not cooperative for a visual field examination,

follow-up evaluation can be done by means of a fundus

examination. Fundus examination in these cases reveals

nasal disc atrophy and macular pigmentation. OCT shows

thinning of average retinal nerve fibre layer thickness

in patients taking Vigabatrin as compared to controls.10

Electroretinogram (ERG)11 and Visual evoked potential

(VEP)12 findings may add on to fundus examination for

toxicity evaluation. Topiramate toxicity can present with

acute myopia, acute angle-closure glaucoma due to anterior

chamber shallowing, suprachoroidal effusion, scleritis.13

Table 3 depicts ocular effects of commonly used antiepileptic

drugs Corticosteroids

Systemic corticosteroids are given orally, nasally, topically,
intravenous, intramuscular, and also intraarticular into
joints. Oral corticosteroids are the mainstay of treatment
of rheumatological disorders, hematopoietic malignancies,
bone marrow transplantation, autoimmune disorders,
dermatological disease etc.14

Corticosteroids can cause posterior subcapsular cataracts,
glaucoma15 and also central serous chorioretinopathy (CSR).
Some factors postulated in the development of open-angle
glaucoma post corticosteroid therapy are

a) Stabilization of lysosomal membranes leading to
accumulation of polymerized glycosaminoglycans
(GAGs) in the trabecular meshwork which on
hydration increase outflow resistance.16

b) Increased expression of extracellular matrix protein
fibronectin, laminin, GAG within the trabecular
meshwork cells leading to increased trabecular
meshwork resistance.17

c) Alteration in trabecular meshwork cell morphology by
causing an increase in nuclear size and DNA content

The steroid response has classically been described by
Armaly and Becker depending on IOP rise.

• High responders (4 to 6% population) – IOP > 31 mm
Hg or a rise >15 mm Hg from baseline

• Moderate responders (1/3rd of the population)-
developed an IOP between 25-31 mm Hg or rise of
6-15 mm Hg from baseline

• Non-responders (2/3rd of the population) – found to
have an IOP <20 mm Hg or a rise of less than 6 mm Hg
from baseline

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Digoxin Transient amplifying cells (TACs) located within the basal
cell layer of epithelium
Digoxin is used for the treatment of congestive heart failure Usually occurs with high-dose intravenous therapy >1 g/m2
and cardiac arrhythmias. Patients with this medication occurring after 5–7 days of treatment and can be prevented
complain of flickering or flashing of light, they can see by using topical corticosteroids. (Table 3) depicts ocular
coloured spots, blue/yellow vision defects and entoptic toxicity of commonly used anti neoplastic agents.
phenomenon. It is known to cause retrobulbar neuritis. The
visual changes due to digoxin are reversible if the drug is Biological therapy is recently being used for cancer
discontinued. treatment. These compromise of four groups, molecularly
targeted therapies e.g. BRAF inhibitors and MEK inhibitors,
Anti-psychotic drugs Immune checkpoint inhibitors e.g. Ipilimumab, Cytotoxic
T-lymphocyte antigen e.g. EGFR inhibitor and others like
These belong to the phenothiazine group e.g. Thioridazine Bacillus Calmette-Guerin, Ibrutinib etc. Ocular side effects of
and Chlorpromazine and are used for the treatment of immunotherapy are uncommon and occur in approximately
anxiety, depression, and behavioural disorders. These can 1% of patients. The most commonly reported ocular side
cause pigmentation of the eyelids, conjunctiva, and even effects dry eye occurring in 1–24%, inflammatory uveitis in
cornea in large doses. Retinal pigmentary degeneration 1%, and myasthenia gravis with ocular involvement.16
can occur with long term use. It presents as salt/pepper
retinopathy leading to widespread loss of retinal pigment Table 3: Ocular Toxicity of Anti Neoplastic Agents
epithelium and also choriocapillaris. Drug-induced cataracts
can also be induced by antipsychotics. (Figure 5) shows Cyclophosphamide Blurring of vision and dry eye
antipsychotic-induced cataract.
Cytarabine Conjunctivitis, keratitis
Figure 5: Chlorpromazine induced cataract (Reproduced from Anterior
Segment Involvement in Antipsychotics-An Unusual Presentation. The Official Fluorouracil Epiphora, blepharitis, conjunctivitis,
cicatricial ectropion
Scientific Journal of Delhi Ophthalmological Society .2018;29 (1), 68-69
Methotrexate Epiphora, blepharitis, conjunctivitis,
Anti-Neoplastic drugs cataracts

Skin hyperpigmentation, epiphora are some common ocular Tamoxifen Retinopathy, corneal opacity,
side effects associated with antineoplastic drugs. Interferon decreased vision
A is used for the treatment of hepatitis C and also for the
treatment of malignancies, it can lead to retinal ischemia Vinblastine Extraocular muscle paralysis,
and/or non-perfusion.18 It can also manifest as optic neuritis diplopia, ptosis
and also the dry eye.
Vincristine Optic atrophy
Tamoxifen is used for treatment for metastatic breast cancer
in postmenopausal women can cause crystalline retinopathy. Cisplatin and Nitorsoureas Retinal toxicity and Optic nerve
Methotrexate can lead to peri-orbital edema, blurred vision, toxicity
photophobia, conjunctivitis, blepharitis, non-arteritic
ischemic optic neuropathy. Folate supplementation along Bisphosphonates
with methotrexate, minimizes its adverse effects and may
therefore prevent the development of optic neuropathy. Bisphosphonates are prescribed in postmenopausal women
Cytosine arabinoside causes keratitis, especially in high to prevent calcium bone loss, these can cause uveitis, orbital
doses. It is said to affect inflammation, and scleritis.

Tetracyclines

Tetracyclines, used to treat acne and rosacea can cause
idiopathic intracranial hypertension /pseudotumour
cerebri, especially with long term use. It can lead to scleral
pigmentation in this 3 to 5 mm band starting at the limbus.
The skin pigmentations caused by tetracyclines are reversible
on discontinuation of the drug. But the eye pigmentation,
though less common, is irreversible. (Figure 6) shows
papilledema in a patient with pseudotumor cerebri.

Fingolimod

This is used for the treatment of multiple sclerosis. It is
known to cause Fingolimod-associated macular edema,
commonly known as FAME, sometimes can present
with retinal haemorrhages and retinal vein occlusions.
Fingolimod-associated macular edema usually occurs within
four months of starting treatment. A baseline eye exam and
follow up eye exam is required three to four months after
starting Fingolimod.

Antiretroviral agents

Cidofovir, is used for treatment for Cytomegalovirus
retinitis in AIDS and also as an antiherpetic agent. It can

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DJO Vol. 32, No. 3, January-March 2022

Figure 6: Papilledema in a patient of tetracycline induced Even at the “safe” daily dosage of 15 mg/kg, the incidence
Pseudotumour cerebri of ocular toxicity is 1% to 2%. The risk is increased with
impaired renal function or diabetes.19 Bilateral retrobulbar
cause anterior uveitis and can also result in macular folds, optic neuropathy usually is noted at 3 to 6 months of use,
retinal or even choroidal detachment, and can permanently rarely at the start of therapy.20
impair vision.
The patient presents with decreased vision and
Toxic optic neuropathy dyschromatopsia. In a study done by Garg et al,21 the visual
loss has been reported in 9.4% of eyes, defective colour
An important drug-induced ocular side effect is Toxic optic vision in 12.3%, 4.7% had optic disc abnormalities and visual
neuropathy (TON). field defects were present in 6.3%. Cecocentral scotoma22 is
the commonest visual field defect, but bitemporal defects
The presenting symptom of the patient in toxic optic or peripheral field constriction23 may also be present.
neuropathy (TON) is bilateral painless loss of vision. TON is Dyschromatopsia mainly blue yellow, sometimes red-green
dependent on the dose and duration of the offending drug. It defects can be the initial symptom in some patients.
has been reported with antituberculosis drugs (Ethambutol
and Isoniazid), Antiepileptic Drugs (Vigabatrin), OCT show the loss of retinal nerve fibres from the optic
Antimicrobial Agents (Linezolid, Ciprofloxacin, Cimetidine nerves, as a sign of early toxicity before fundal findings
And Chloramphenicol), Disulfiram (in Association with become manifest. In conjunction with visual field testing this
Chronic Alcoholism), Halogenated Hydroquinolones can be used to objectively monitor patients on ethambutol.
(Amoebicidal Medications), Antimetabolites (e.g. The majority of defects reverse on timely discontinuation,24
Methotrexate, Cisplatin, Carboplatin, Vincristine And some reports have noted the persistence of defects due to
Cyclosporin), Tamoxifen And Sildenafil. ethambutol toxicity even after prompt discontinuation of the
drug.25,26
Screening for toxic optic neuropathy includes visual
acuity evaluation, color vision, contrast sensitivity and Reports have pointed out that ethambutol toxicity can even
central visual field testing. On Visual fields examination, occur with intermittent DOTS therapy27,21 and complacency
centroceacal scotoma can be seen, colour vision is impaired. in monitoring ocular toxicity can lead to significant ocular
RAPD may not be present; on examination, the disc pallor toxicity.
and optic atrophy ensues.
Dietary Supplements
Ethambutol
Methylsulfonylmethane (MSM) is used as a dietary and
Ethambutol chelates metal ions involved in prokaryotic detox supplement.28. Its use is being recommended due
ribosomes. It inhibits arabinosyl transferase, an enzyme in to its anti-inflammatory and antioxidant properties and
mycobacterial cell wall synthesis. is currently under trial for effects in arthritis, reduction of
seasonal allergies and as an anti-cancer supplement. This
The ethambutol optic nerve toxicity (EMB) is dose related being a sulphur compound can lead to angle closure in
seen in predisposed individuals secondary to ciliary body effusion.

• 18% in patients receiving >35 mg/kg/day Conclusion
• 5-6% with 25 mg/kg/day
• <1% with 15 mg/kg/day of EMB, more than two Systemic drug therapy can have devastating ocular effects
if not timely detected. Awareness among physicians and
months paediatricians prescribing these medications and timely
• 4 to 12 months after initiating EMB, but rarely have referral to ophthalmologists is the need of the hour.

been reported within a few days of the start of therapy References
• Sooner -concurrent renal disease
1. Bartlett J, Jaanus S, eds. Ocular Effects of Systemic Drugs.
Clinical Ocular Pharmacology 4th Ed. Woburn, MA:
Butterworth-Heinemann, 2001:903-48. 37.

2. Ritchie RW, Lindfield DM, Lockyer CR, Adamson A. Ocular
side-effects of urological pharmacy. BJU Int 2008; 101:1336-8.

3. Jain D, Dhua A, Ravisankar V, Chellam L, Joshi M. Acute
angle closure glaucoma after hypospadias surgery: A vision-
threatening complication of oxybutynin. J Indian Assoc Pediatr
Surg 2015; 20:161-2.

4. ChangDF,OsherRH,WangL,KochDD.Prospectivemulticen- ter
evaluation of cataract surgery in patients taking tamsulosin
(Flomax). Ophthalmology 2007; 114:957–964

5. Venkatesh R, Veena K, Gupta S, Ravindran RD. Intraoperative
floppy-iris syndrome associated with terazosin [letter]. Indian
J Ophthalmol 2007; 55:395–396.

6. Chang DF, Campbell JR. Intraoperative floppy-iris syndrome

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DJO Vol. 32, No. 3, January-March 2022

associated with tamsulosin. J Cataract Refract Surg 2005; Cite This Article as: Divya Jain. Ocular effects of
systemic medications. Delhi J Ophthalmol 2022 32 (3) 87-92.
31:664–673. Acknowledgments: Nil
Conflict of interest: None declared
7. Chandra A, Barsam A, Hugkulstone C. A spontaneous Source of Funding: None
Date of Submission 10 Mar 2022
suprachoroidal haemorrhage: a case report. Cases J. 2009; Date of Acceptance: 26 Mar 2022

2:185. Address for correspondence
Divya Jain, MBBS(Gold Medalist),
8. Tehrani R, Ostrowski RA, Hariman R, Jay WM. Ocular toxicity
MS,DNB,FAICO(Glaucoma),FICO,MNAMS
of hydroxychloroquine. Semin Ophthalmol 2008;23(3):201-209.
Associate Professor,
9. Camposano S, Major P, Halpern E, Thiele E. Vigabatrin in the Department of Ophthalmology
Postgraduate Institute of Child Health,
treatment of childhood epilepsy: A retrospective chart review Sector 30,Noida India.
Email: [email protected]
of efficacy and safety profile. Epilepsia 2008; 49:1186-91.
Quick Response Code
10. Wild JM, Robson CR, Jones AL, Cunliffe IA, Smith PE.

Detecting vigabatrin toxicity by imaging of the retinal nerve

fiber layer. Invest Ophthalmol Vis Sci 2006; 47:917-24.

11. Miller NR, Johnson MA, Paul SR, Girkin CA, Perry JD, Endres

M, Krauss GL. Visual dysfunction in patients receiving

vigabatrin: clinical and electrophysiologic findings. Neurology.

1999 ;53(9):2082-7.

12. Harding GFA, Spencer EL, Wild JM, Conway M, Bohn RL.

Field-specific visual evoked potentials: Identifying field defects

in vigabatrin-treated children. Neurology 2002; 58(8):1261-

1265.

13. Ozturk BT, Genc E, Tokgoz M, Kerimoglu H, Genc BO.

Ocular changes associated with topiramate. Curr Eye Res

2011;36(1):47-52.

14. Suda K, Akagi T, Ikeda HO, Kameda T, Hasegawa T, Miyake

M, Kido A, Nakano E, Tsujikawa A. Atopic dermatitis as a

risk factor for severe visual field loss in youth-a retrospective

cohort study of glaucoma under steroid treatment. Graefes

Arch Clin Exp Ophthalmol. 2021 Jan;259(1):129-136.

15. McLean JM. Use of ACTH and cortisone. Trans Am Ophthalmol

Soc. 1950;48:293–296.

16. Dalvin LA, Shields CL, Orloff M, Sato T, Shields JA.

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic

Indications and Ophthalmic Side Effects. Retina. 2018

Jun;38(6):1063-1078.

17. François F, Victoria-Troncoso V. Mukopolysaccharide und

Pathogenese kortisonbedingter Augendrucksteigerung

[Mucopolysaccharides and pathogenesis of cortisone glaucoma

(author's transl)]. Klin Monbl Augenheilkd. 1974 ;165(1):5-10.

18. O'Day R, Gillies MC, Ahlenstiel G. Ophthalmologic

complications of antiviral therapy in hepatitis C treatment.

World J Gastroenterol. 2013 Dec 7;19(45):8227-37.

19. Talbert Estin KA, Sadun AA. Risk factors for ethambutol optic

toxicity. Int Ophthalmol 2010; 30:63-72.

20. Schild HS, Fox BC. Rapid-onset reversible ocular toxicity from

ethambutol therapy. Am J Med. 1991 Mar;90(3):404-6.

21. Garg P, Garg R, Prasad R, Mishra AK. A prospective study of

ocular toxicity in patients receiving ethambutol as a part of

directly observed treatment strategy therapy. Lung India. 2015

Jan-Feb;32(1):16-9.

22. Melamud A, Kosmorsky GS, Lee MS. Ocular ethambutol

toxicity. Mayo Clin Proc. 2003 ;78(11):1409-11.

23. Kwok A. Ocular toxicity of ethambutol. The Hong Kong

Medical Diary. 2006; 11:27–9

24. Ezer N, Benedetti A, Darvish-Zargar M, Menzies D. Incidence

of ethambutol-related visual impairment during treatment of

active tuberculosis. Int J Tuberc Lung Dis. 2013; 17:447–55.

25. Kumar A, Sandramouli S, Verma L, Tewari HK, Khosla

PK. Ocular ethambutol toxicity: is it reversible?.J Clin

Neuroophthalmol. 1993; 13: 15-17

26. Tsai RK, Lee YH. Reversibility of ethambutol optic neuropathy.

J Ocul Pharmacol Ther. 1997; 13: 473-477.

27. Kandel H, Adhikari P, Shrestha GS, Ruokonen EL, Shah DN.

Visual function in patients on ethambutol therapy for

tuberculosis. J Ocul Pharmacol Ther. 2012 Apr;28(2):174-8.

28. Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane:

Applications and Safety of a Novel Dietary Supplement.

Nutrients. 2017 Mar 16;9(3): 290.

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DJO Vol. 32, No. 3, January-March 2022

Theme Article

Anti VEFG Agents In Retinal Diseases
Khushboo Chawla

Department of Ophthalmology, Guru Nanak Eye Centre, New Delhi, India.

Abstract Anti-vascular endothelial growth factor (Anti VEGF) agents are emerging as the most vital tool in the prevention of
blindness due to ocular neovascularization in modern medicine. VEGFs are glycoproteins specific to endothelial cells,
acting as key regulators of angiogenesis, vasculogenesis, and increasing vascular permeability. These are indicated
in conditions such as diabetic macular edema (DME), vascular occlusions (RVO), Retinopathy of prematurity (ROP),
neovascular age-related macular degeneration (nAMD), etc. The cost effect, need for frequent dosage, and side effects
of increased IOP, infection, and cataract adds to the economic and disease burden. The newer research is now focused
beyond anti-VEGF such as Angiopoietin and tyrosine kinase for vasculogenesis. This article reviews various anti-VEGF
and angiogenic agents available in clinical practices.

Delhi J Ophthalmol 2022; 32; 93-96; Doi http://dx.doi.org/10.7869/djo.755

Introduction Keywords: Anti Vegf , Antiangiogemic Agents
In humans, the VEGF family consists of 7 components

A diffusible glycoprotein” factor X” was identified by namely, VEGF A to F and Placental growth factors (PIGF).

Michelson I.C. in 1980 which showed angiogenic properties Each member has certain functions as stated in (Table 1).2

resulting in proliferation and increased permeability of the VEGF bind to specific Tyrosine kinase (TKR) VEGF receptors
vascular endothelium.1 Decades later, this 40kDa molecule to initiate vasculogenesis and angiogenesis. These are

was recognized as VEGF. VEGF is released in response VEGFR1 (Flt1), VEGFR2 (KDR), VEGFR3 (Flt4). The receptors

to hypoxia of the retinal vasculature. It is released by the consist of an ecto-domain and an endo-domain. The VEGF

retinal endothelial cells, Muller cells, and retinal pigment Fab portion binds to the ecto-domain which in turn activates

epithelium. the endo-domain and initiates the vasculogenic cascade via

Abnormal angiogenesis may occur in a plethora of conditions associated tyrosine kinase activity.

such as diabetic retinopathy, hypertensive retinopathy, VEGF A has numerous isoforms which result from alternate
retinopathy of prematurity, Coat’s disease, macular edema splicing and processing of the VEGF gene. These are
secondary to vascular occlusions, wet age-related macular classified based on the number of amino acids present such
degeneration (AMD). The development of anti-VEGFs as VEGF A121, A145, A165, A189, and A206. VEGF A165 is
has made a breakthrough in the treatment of retinal and the most abundant form (Table 1).
choroidal pathologies.
Indications3
Table 1: Receptors and Functions of various VEGF released intraocular.
1. Diabetic macular edema
VEGF Receptors Function 2. Retinal vascular occlusions
VEGF A 3. Neovascular age-related macular degeneration/ choroidal
A121 VEGFR1 Angiogenesis and chemotaxis
VEGFR2 neovascular membrane
Endothelial cell proliferation 4. Retinopathy of prematurity
Sequestered in the extracellular 5. Vasculitis such as Eale’s disease
matrix due to the presence of a
heparin-binding domain

A145 cell migration, angiogenesis, and 6. Myopic Choroidal neovascularization
A165 increases vascular permeability 7.Ocular tumor, Neovascular glaucoma
A189 Fibroblast proliferation 8.Preoperative- in diabetic, vasculitic Vitreous haemorrhage,
A206 Sequestered in the extracellular
matrix due to presence of a heparin- Tractional retinal detachment
binding domain
Anti-VEGF Agents

VEGF B VEGFR1 Specific to myocardial tissue The first anti-VEGF agent Pegaptinib sodium was approved
Helps in embryonic angiogenesis by FDA in 2004 for its use in colon cancer.

VEGF C VEGFR3, Lymphangiogenesis The introduction of anti-VEGF in ophthalmology has set
a weak high expectation in treating all neovascular conditions.
VEGF D affinity for Lymphatic development, Specific to Pegaptanib was the first FDA-approved anti-VEGF agent
VEGFR2 the pulmonary system used to treat ocular neovascularization. Currently, the
VEGF E ( orf commonly available anti VEGFs in ophthalmology are
Viral gene) VEGFR3, Angiogenesis, usually not found in Pegaptanib sodium, Ranibizumab, aflibercept. Bevacizumab
a weak humans is used “off-label” in ophthalmic conditions. Bevacizumab
affinity for and aflibercept are the two anti-VEGF available as systemic
VEGFR2 therapy also. Direct drug delivery into the vitreous helps

VEGFR 2

VEGF F VEGFR1 Inflammation and vasculogenesis in increased efficacy of the drug with a reduced burden of
PIGF systemic adverse effects.

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DJO Vol. 32, No. 3, January-March 2022

Anti-angiogenic effect can be brought by blocking the VEGF Side effects: Uncontrolled hypertension, proteinuria,

receptors by antibodies against the VEGF molecule, VEGF thromboembolism, gastrointestinal bleeding, and

receptors and decoy proteins that compete with VEGF perforation. It has been discontinued due to these side

binding to the VEGF receptors, inhibitors specific to tyrosine effects.6

kinase. Ranibizumab

Humanized monoclonal Immunoglobulin G antibodies (LucentisTM By Genentech/Roche, Usa)

consist of Fc and Fab parts. The Fab portion binds to the It is made up of Fab moiety of monoclonal human

target while the Fc portion carries out the effector function immunoglobulin IgG1 produced from E. coli by insertion

by activation or deactivation of the intrinsic cascade.4 of complementary determining sequences (CDR) of murine

Pegaptanib Sodium (MacugenTM): approved by FDA in anti-VEGF A molecule with amino acid sequence alteration
December 2004 for use in neovascular AMD. It is a highly for its stability and immunogenicity. It has more affinity
selective oligonucleotide ligand (RNA aptamer) having an to the receptors as compared to bevacizumab and more
affinity to the VEGF A165 isoform.5 It is the first Anti-VEGF diffusion into the retina and choroid. Ranibizumab avoids
drug approved for ocular use. binding of VEGF A to VEGR receptors 1 and 2 present on the
endothelial cell surface and thus inhibited vasculogenesis

Efficacy: VEGF inhibition Study in Ocular Neovascularization and inflammation.7

(VISION) AFLIBERCEPT/ VEGF Trap (Eyelea/Zaltraptm
Regeneron, New York)
Bevacizumab
(AvastinTM by Genentech, San Francisco) Fully humanized fusion protein Ig of 115 kDa approved for

Full-length humanized IgG1 monoclonal antibody of AMD in 2011 and retinal vein occlusions in 2012. It blocks

145kDa (Figure1) molecular weight blocks all the isoforms VEGF A, VEGF B, Placental growth factor (PIGF) 1 and 2. 8

of anti-VEGF. It is cost-effective and thus used off-label in It binds to VEGF from both sides of the VEGF molecule,

nAMD and DR. unlike bevacizumab and Ranibizumab which binds from

Table 2: molecular structure and pharmacodynamics of commercially available Anti VEGF agents

S.NO. Anti- VEGF Commercially FDA Structure Molecular T1/2 Dose Mechanism Pharmacokinetics
1 Available as Approval Aptamer Weight of action Slow metabolism
2 December 10 0.3mg, Excretion: Kidney
3 PEGAPTANIB MACUGEN 50kDa Days 6weekly Angiogenesis
4 SODIUM Single prefilled 2004 injections and increased Clearance faster
20 1.25mg IN X100 times
syringes June 2006 Days 0.05ml vascular
permeability
BEVACIZUMAB AVASTIN 2011 Humanized 148kDa 9
monoclonal 48kDa Days
RANIBIZUMAB LUCENTIS 115kDa 0.5mg in
antibody 0.05ml

AFLIBERCEPT EYELEA Monoclonal 2mg in
antibody 0.5ml
fragment

Recombinant
fusion
protein

Figure 1: Diagram showing structures of the various anti-VEGF molecules one single side. However, single molecule bevacizumab
can bind to multiple VEGF molecules (Figure1). Aflibercept
was considered superior to the other two drugs considering
improvement of visual acuity in Protocol T of DRCR.network
study for DME.9

Summary Of Pharmacology of AntiVEGF
Biosimilars

These are biotherapeutic products that are similar to the
pre-existing generic molecule with comparable efficacy,
pharmacodynamics, immunogenicity, and safety profiles.
The biosimilars are however not the same as the originator
generic drug. These are larger molecules with a different
structure and a chemical formula not predefined by the
original fixed formulated molecule. Stability and its efficacy
is difficult to attain due to a different molecular structure as
compared to the generic drug.10
At present, Mvasi (Amgen) and Zirabev (Pfizer) are
commercially available biosimilars for Bevacizumab, and
ONS-5010 (Outlook Therapeutics) is under research.

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DJO Vol. 32, No. 3, January-March 2022

Razumab (Intas Pharmaceuticals Ltd., Ahmedabad, India) study). REACH study gave comparative results between
was approved in India in 2015 after a clinically registered Ranibizumab and different doses of Abicipar. Phase III
trial on 104 patients of wet AMD. RE-ENACT (REal life SEQUOIA ad CEDAR study has shown non-inferiority to
assessmENt of safety And effectiveness of Razumab) Ranibizumab in treating nAMD with a lesser frequency of
study showed similar results in DME, nAMD, RVO, and intravitreal injection advised.16 The drug is under regulatory
myopic CNVM. Another retrospective analysis to evaluate review by FDA at present.
the “Clinical Efficacy and Safety of Razumab” (CESAR)
showed equivalent results in vision improvement as Faricimab
shown in RE-ENACT along with no ocular side effects and
immunogenicity.11 A bispecific intravitreal anti-VEGF binds and neutralizes
Ang 2 and VEGF A. Angiopoietin 1 and 2, angiopoietin-like
Other biosimilars under study are: Ranizurel (Reliance life proteins, and tyrosine kinase (Ang 2-Tie) help in mediating
science, India), FYB201, SB11 Byooviz and CKD-701(South vascular growth and inflammation. Faricimab targets
Korea), LUBT010 (Lupin India).12 this alternative biological pathway of Ang 2-Tie complex
thus, inhibiting this pathway provides a better long-term
Newer Anti-VEGF prognosis.17 (Figire 1)
Patients with DME (BOULEVARD study)18 and nAMD
CONBERCEPT (Lumitin, Sichuan) (AVENUE and STAIRWAY study)19 6mg of Faricimab
A recombinant human fusion protein of extracellular showed significant visual improvement, was considered
(Ig) domains of VEGFR1, the third and fourth domain of equally safe and efficacious compared to Ranibizumab. It is
VEGFR2, and a portion of Fc IgG1. Conbercept 0.5 mg varies indicated in cases of DME and nAMD. Ongoing trials in eyes
from aflibercept with the addition of VEGFR2 domain 4, with DME (YOSEMITE and RHINE) and nAMD (TENAYA
which allows for tighter binding to VEGFA, VEGFB, and and LUCERNE) are aimed at assessing the safety durability
PGF. and effect of the drug.20

In a phase III prospective PHOENIX trial conducted in China, Port Delivery System
the Conbercept group showed a significant improvement in
visual acuity compared to sham groups in wet AMD.13 PDS is surgically fitted drug delivery system fitted in
The phase III trials PANDA-1 and PANDA-2 were quadruple- the sclera or at the pars plana level. In Phase III trial of
blinded multicentric randomized trials evaluating the BCVA Ranibizumab (ARCHWAY study) permanent implant with
at the end of 36weeks, with 0.5 mg and 1 mg Conbercept, refill of 100mg/ml every 24 weeks at fixed dose interval was
and 2 mg Aflibercept.14 given in eyes with nAMD. These reservoir implants helped in
delaying the need for repeated injection with the advantage
Brolucizumab of continued drug delivery into the eye by passive diffusion
along the concentration gradient into the vitreous cavity.
It is a humanized monoclonal antibody fragment that LADDER study employed an additional step of ablation of
acts against VEGF A. It has a molecular weight of 26kDa the choroid at the pars plana dissection site which helped
(Figure1). It is highly stable and soluble thus allowing it to be decrease the risk of haemorrhage.15
available at 120mg/ml concentration. The dose of 6mg/0.5ml
is considered 10 times more effective than the routing dose Other Drugs
of aflibercept and 20 times more effective than Bevacizumab
and Ranibizumab. Being the smallest of all anti-VEGF it has 1. OPT-302: 2mg drug injected intravitreal, targets VEGF
a better penetrance, faster clearance, and lower systemic side C and D.
effects.
2. KSI-301: Antibody biopolymer conjugate (abc)
Efficacy and safety of Broculizumab were found to be non- indicated in retinal vascular disease and nAMD.
inferior to aflibercept in nAMD was analysed by a 2year
multicentric randomized trial HAWK and HARRIER. 3. X-82: Tyrogenex: Oral route of delivery, binds and
Another similar study OSPREY is in its Phase II trial.15 inhibits VEGF A and PDGF. Ongoing APEX trial is
Occlusive vasculitis and vitreous inflammation are the major testing 50mg, 100mg and 200mg of the drug.
side effects noted.
4. ICON-1 is a recombinant factor VIIIa modified protein
Abicipar Pegol with Fc portion of a human Ig G1.

Abicipar (Allergan) is a designed ankyrin repeat protein, Adverse Effects Of Intravitreal Injection
directed to all VEGF A isoforms similar to Ranibizumab
(Figure 1). However, it differs from Ranibizumab in its 1. Sub conjunctival hemorrhage,
higher affinity to bind to the receptors and also in t1/2 being 2. ocular pain,
longer thus, less frequent dosing is required. 3. short-term and long-term increase in ocular pressure
4. Floaters
Various study groups have found longer effects with 1mg 5. Endophthalmitis
and 2mg Abicipar in nAMD (BAMBOO and CYPRESS 6. Vitreous hemorrhage
7. Retinal detachment
8. Systemic side effects are rare such as thromboembolic

events.21

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DJO Vol. 32, No. 3, January-March 2022

Contraindications 18. Simultaneous Inhibition of Angiopoietin-2 and Vascular
Endothelial Growth Factor-A with Faricimab in Diabetic
1. Ocular/periocular infection Macular Edema: BOULEVARD Phase 2 Randomized Trial. Sahni
2. High intraocular pressure J, Patel SS, Dugel PU, Khanani AM, Jhaveri CD, Wykoff CC,
3. Hypersensitivity Hershberger VS, Pauly-Evers M, Sadikhov S, Szczesny P, Schwab
4. Tachyphylaxis 21 D, Nogoceke E, Osborne A, Weikert R, Fauser S Ophthalmology.
2019 Aug; 126(8):1155-117.
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Acknowledgments: Nil
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Rich RM, Rosenfeld PJ, Puliafito CA, Dubovy SR, Davis JL, Flynn Date of Submission 02 Mar 2022
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Macular Degeneration in 2020. Asia Pac J Ophthalmol (Phila).
2020;9(3):250-259.

17. Khan M, Aziz AA, Shafi NA, Abbas T, Khanani AM. Targeting
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and Summary of Clinical Trials Involving Faricimab. Cells.
2020;9(8):1869. Published 2020 Aug 10. doi:10.3390/cells9081869

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DJO Vol. 32, No. 3, January-March 2022

Theme Article

Vital Stains in Retina and Vitreous
Shreyangshi Dipta, Shruti Bhattacharya, Khushboo Chawla
Department of Ophthalmology, Guru Nanak Eye Centre, New Delhi, India.

Abstract Dyes used to stain living tissues are known as vital dyes and these have become an effective surgical aid in ocular tissue
identification and visualization in ophthalmology. “Chromovitrectomy” is a phrase used for describing the use of vital
dyes to stain these transparent tissues and facilitate their manipulation during vitreo-retinal surgery.1 Common vital
dyes used in the posterior segment are indocyanine green (ICG) and brilliant blue (BB); and dyes which are still under
research include patent blue, bromophenol blue, light green, and Evans’s blue.

Delhi J Ophthalmol 2022; 32; 97-99; Doi http://dx.doi.org/10.7869/djo.756

Keywords: Vital Stains, Chromomvitrectomy, Trypan Blue, Indocyanine Green

Dyes used to stain living tissues are known as vital dyes Uses:
and these have become an effective surgical aid in ocular • To peel the ILM for macular hole treatment
tissue identification and visualization in ophthalmology. • To help ILM peeling in other diseases, such as diabetic
“Chromovitrectomy” is a phrase used for describing the use macular edema
of vital dyes to stain these transparent tissues and facilitate • for better visualization of epiretinal membranes (ERMs)
their manipulation during vitreo-retinal surgery.1 in vitrectomy for proliferative diabetic vitreoretinopathy,
idiopathic ERMs, and proliferative vitreoretinopathy.2
Common Vital Stains
Disadvantages
These may be classified according to the chemical
composition: (1) azo dyes like trypan blue; (2) arylmethane • ICG has been found to be associated with the risk
dyes like brilliant blue; (3) cyanine dyes like Indocyanine of damage to the photoreceptors and RPE cells, RPE
green; (4) xanthene dyes like Fluorescein; and (5) colored atrophy, visual field defect, loss of epiretinal cellular
corticosteroids like Triamcinolone acetonide.2 integrity, and optic nerve damage. However, in low
doses, it is considered safe.
1. Trypan Blue (TB)
• For use in anterior capsule staining in cataract surgery,
Concentration: 1.2mg/ml (0.15%) the dye has to be reconstituted and diluted. This has to
be folowed by filtration to prevent undissolved particles
Brand Name: Membrane Blue (DORC International, from entering the eye before use.
Zuidland, Netherlands).
• Use in intraocular surgery is not approved by the FDA.
Mechanism: TB has high affinity for cellular-proliferative
tissues, hence, it stains the ERM very well but not the ILM.1 4. Infracyanine Green (IfCG)
To augment staining property, it can be injected after air-
fluid exchange or mixed with 5-10% glucose. It may cause Concentration: 5 mg (0.5%) and 25 mg (2.5%) of infracyanine
chronic retinal toxicity by inducing arrest of the cell cycle at green
G0–G1 via increased expression of p21.2 Brand Name: Infracyanine (Laboratoires SERB, Paris,
France).
2. Brilliant Blue (BB)
Mechanism: IfCG also binds with high affinity to the acellular
Concentration: 0.025% ILM and facilitates its visualization and peeling similar
Brand Name: Brilliant Peel (Geuder, Heidelberg, Germany) to ICG.5 Its advantage over ICG is that it is synthesized
Mechanism: BB markedly stains ILM without staining the without sodium iodine, as it is believed that iodine damages
epiretinal membrane or the vitreous.3 the retina. However, IfCG can be phagocytosed by RPE
It is hydrosoluble; it would thus penetrate less into the cells cells, remaining in the interior of these cells for long periods,
and be more easily washed away, leaving less residues with a risk of inducing chronic toxicity. The downside of
after surgery.2 It is hence considered to have to have lower being iodine free is that it is not water soluble and has to be
toxicity. dissolved in a 5% glucose solvent.

3. Indocyanine Green4 5. Sodium Fluorescein

Concentration: 5 mg (0.5%); 25 mg (2.5%); 50 mg (5.0%) 5-25% of fluorescein dye is commonly used during
Brand Names: ICG (Pulsion Medical Systems, Munich, fluorescein angiography. The clear vitreous can be stained
Germany) ICV Indocianina Verde (Ophthalmos, São Paulo, markedly green by SF administered 12–16 h before surgery
Brazil), Diagnogreen (Daiichi Pharmaceutical, Tokyo, and new research involves the use of intraoperative three-
Japan), and IC-Green (Akorn, Buffalo Grove, USA). dimensional fluorescein angiography (3D-FA)-guided pars
plana vitrectomy.6
Mechanism: It has a maximum affinity for laminin and
collagen type 4 (which is found in the basement membrane) 6. Triamcinolone Acetonide (TA)
of the internal limiting membrane (ILM), due to which it
was most widely used to stain the ILM during vitreoretinal Concentration: 0.1- 0.3ml of 40mg/ml (4%)
surgeries. Mechanism: Triamcinolone acetonide (TA) is a synthetic

E-ISSN: 2454-2784  P-ISSN: 0972-0200 97 Delhi Journal of Ophthalmology

DJO Vol. 32, No. 3, January-March 2022

insoluble corticosteroid.1 Its crystals have an affinity for dye containing trypan blue 0.15%, BBG 0.025%, and
acellular tissues such as vitreous and internal limiting 4% polyethylene glycol. It is suitable for ILM, ERM,
membrane – they deposit on the vitreous gel and helps in and PVR membrane staining. 12
easy differentiation between vitreous free area from an • Lutein: lutein + zeaxanthin 0.3% + BBG 0.025%.13
area where vitreous is still present, facilitating complete It is another heavy dye that also helps in better
vitrectomy. view of vitreous and posterior hyaloid. Lutein and
xanthin do not affect the staining property of BBG
Uses: During vitrectomy, it facilitates removal of posterior on the ILM, and protect the retina by filtering blue
• hyaloid from retina and decreases proliferative light.
vitreoretinopathy.
• Injecting this steroid during vitrectomy for the Dye injection techniques
management of retinal detachment may prevent
• fibrin reaction and PVR postoperatively • The “dry method” or “air-filled technique” – in
Other than as a dye, intravitreal triamcinolone is which the fluid in the vitreous cavity is removed by
FDA approved (Triesence) for treatment of macular a fluid-gas exchange before dye injection. This has the
edema and uveitis.7 advantage of concentrating the dye in the posterior
pole and avoiding contact at the posterior capsule
Disadvantages of the lens, but it may expose the retinal surface to a
higher concentration of dye. 2
• It may remain in the vitreous cavity even upto 40
days after injection. • The “wet method” or “fluid-filled technique.” - In this
approach, the intravitreal fluid (usually BSS) is left
• Risk of formation of cataract. inside, while the dye is injected. The amount of dye in
• Risk of IOP spike contact with the retinal surface becomes much lower
• The commonly used formulation of TA, kenalog, because it is immediately washed out by the fluid in
the vitreous cavity. Hence this method is safer and
is not formulated for the eye, for this reason, there faster during surgery than dry method.2
is a risk of pseudoendothalmitis and retina toxicity
when injected intravitreally.2 • Double staining – It is used for peeling of ERM and
ILM. After vitrectomy, the ERM is first stained with
7. Fluoromethonolone Acetate BBG, and then peeled. BBG stain is then reapplied,
and the residual ILM was peeled.
Studies have shown that FMA can be used as an alternate to
TA as it doesn’t show any abnormal changes in ERG as well as Other Uses Of The Vital Stains In Ophthalmology
no histological changes. However, not enough studies have
been conducted to compare advantages and disadvantages 1. Fluorescein
of newly discovered vital dyes and their long-term effects.8 • Endothelial cell viability
• To see extent of epithelial defect in the cornea,
Dyes Under Research
especially in ulcers
1. Bromophenol Blue: It is a novel adjunct used in • Anterior capsule lens identification during cataract
Concentration of 0.13% to 0.2% and stains the epiretinal
membrane, internal limiting membrane and vitreous well. surgery
Literature differs regarding toxicity of the dye, but it is still 2. Trypan Blue
not FDA approved for intraocular use.3 • Endothelial cell viability (0.001-0.1%)
• Identify anterior lens capsule during cataract
2. Patent Blue: Patent Blue (0.25%) has recently been
discovered that to stain the glial ERM noticeably with poor surgery (0.06%)
staining of ILM. It causes retinal toxicity at higher doses, and • Keratoplasty (0.02% - to stain DM of donor and
is not FDA approved for intra-ocular use.9
recipient cornea)
3. Anthocyanins: it is a natural dye derived from • Conjunctival cyst capsule identification
the acai fruit. It is seen to stain posterior hyaloid and ILM • To identify clear corneal incision with dye coated
in studies conducted with animals, with no toxicity to the
retina.10 blade
4. Trisodium, Orangell and Methyl Violet – novel • Visualization of drainage function during cataract
dyes to stain vitreous and preretinal tissues without major
toxicity concerns.11 surgery in a operated trabeculectomy eye (0.06%)
• Staining of SO in strabismus surgery
Commercial Combinations • Enucleation- to stain tenon’s capsule

• ILM Blue (DORC) - BBG (0.25 mg/ml) with 4% 3. Triamcinolone
polyethylene glycol. It is a heavy dye facilitating If a posterior capsular rent occurs during cataract surgery,
sedimentation on the retina.12 triamcinolone can be used to know if any vitreous strands
are left in AC [anterior chamber] after anterior vitrectomy.
• MembraneBlue-Dual (DORC) - Another heavy
4. ICG
• Endothelial cell viability (0.5% for 3 min)
• Conjunctival cyst capsule identification
• Anterior lens capsule in cataract surgery (0.125-

0.5%)

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