Publications by authors named "Rohit Shetty"

324 Publications

Intensive topical interferon therapy in uveitic macular edema.

Indian J Ophthalmol 2022 Aug;70(8):2986-2989

Department of Cornea and Refractive, Narayana Nethralaya, Bangalore, Karnataka, India.

Purpose: To evaluate the efficacy of intensive topical interferon alfa-2b (IFN) therapy in uveitic macular edema (UME).

Methods: This is a prospective, interventional case study of eyes with UME. Commercially available injection IFN for subcutaneous use was reconstituted to form eye drops and a dose of 6 times/day for 2 weeks, 5 times/day for next 2 weeks, followed by 4, 3, 2, 1 taper per month was prescribed. Optical coherence tomography (OCT) and clinical examination was done at 0, 2, 4, 8 weeks, and further as required.

Results: Nine eyes of 9 patients with UME were studied. Mean central macular thickness (CMT) at presentation was 522.2 μm (range: 408-803 μm). At 2-week, 1-month, and 2-month follow-up, mean CMT decreased to 451.6 μm (range: 322-524 μm), 375.8 μm (range: 287-480 μm), and 360.3 μm (range: 260-485 μm), respectively. Four eyes which showed inadequate response to previous topical IFN therapy (4 times/day) showed significant improvement with intensive therapy at 1 month follow-up. In 4 eyes, UME resolved completely with mean CMT 285.5 μm (range: 260-312 μm) at 7.5 weeks (range: 4-12 weeks). Study exit was seen in 2 cases due to inadequate response and relapse of uveitis. Mean follow up was 3.38 months (range: 1-5 months).

Conclusion: Intensive topical IFN therapy can be an alternative therapeutic option in the treatment of UME. Study of intraocular penetration, combination with other drugs, and the efficacy of IFN separately for different uveitic entities may explore new avenues in treatment of UME.
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http://dx.doi.org/10.4103/ijo.IJO_3210_21DOI Listing
August 2022

Commentary: Predictors of outcomes after corneal collagen cross linking: Present, and future directions.

Indian J Ophthalmol 2022 Aug;70(8):2937-2938

Department of Cornea and Refractive Surgery, Narayana Nethralaya Eye Hospital, Bangalore, Karnataka, India.

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http://dx.doi.org/10.4103/ijo.IJO_882_22DOI Listing
August 2022

Commentary: Evaluation of meibomian gland morphology and anterior segment parameters by Sirius topography systems in polycystic ovary syndrome.

Indian J Ophthalmol 2022 Aug;70(8):2928-2929

Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India.

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http://dx.doi.org/10.4103/ijo.IJO_960_22DOI Listing
August 2022

Unilateral recurrent central serous chorioretinopathy (CSCR) following COVID-19 vaccination- A multimodal imaging study.

Am J Ophthalmol Case Rep 2022 Sep 6;27:101644. Epub 2022 Jul 6.

Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India.

Corona virus disease-19 (COVID-19) vaccines have been approved for emergency use. Ocular adverse effects following the vaccines have been reported.

Purpose: To report an unique case of recurrent central serous chorioretinopathy following both doses of COVID-19 vaccine.

Observations: A 40-year-old male presented with blurring of vision in the left eye during 2 days following COVISHIELD™ (Serum Institute of India). He had a previous history of central serous chorioretinopathy in the right eye 2 years back and was treated with micropulse laser. Ocular examination showed a best corrected visual acuity of 20/20 right eye and 20/60 left eye. Fundus evaluation of left eye showed central serous chorioretinopathy. Spectral domain optical coherence tomography of the left eye revealed neurosensory detachment. Fundus fluorescein angiography of the left eye showed multiple window defects and ink-blot appearance in the macula. Oral eplerenone 50mg once a day for a month showed significant reduction in the subretinal fluid. Patient developed central serous chorioretinopathy in the left eye 3 days after 2nd dose of COVISHIELD™.

Conclusion And Importance: CSCR following vaccination may be a temporal event. In our patient it occurred following the vaccination. This is the first case of a recurrent CSCR after either dose of COVID-19 vaccination. Ocular symptoms after vaccination warrant a thorough eye evaluation.
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http://dx.doi.org/10.1016/j.ajoc.2022.101644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258414PMC
September 2022

Commentary: Dexamethasone intravitreal implant therapy in Vogt-Koyanagi-Harada disease.

Indian J Ophthalmol 2022 Jul;70(7):2470-2471

Department of Cornea and Refractive, Narayana Nethralaya, Bangalore, Karnataka, India.

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http://dx.doi.org/10.4103/ijo.IJO_1207_22DOI Listing
July 2022

Trials and tribulations of rare eye diseases.

Indian J Ophthalmol 2022 Jul;70(7):2216-2217

Department of Ophthalmology, Narayana Nethralaya Eye Institute, Bengaluru, Karnataka, India.

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http://dx.doi.org/10.4103/ijo.IJO_782_22DOI Listing
July 2022

Topographic changes in contralateral eye of a case of Terrien's marginal degeneration.

BMJ Case Rep 2022 Jul 4;15(7). Epub 2022 Jul 4.

Refractive Surgery, Narayana Nethralaya, Bangalore, Karnataka, India.

A woman in her late twenties presented with blurring of vision in the right eye for 6 years. Retinoscopy showed a scissoring reflex in the right eye with best spectacle-corrected visual acuity of 20/40 in the right eye and 20/20 in the left eye. Slit-lamp examination of the right eye showed superior crescentic thinning with conjunctivalisation and lipid deposition while the left eye was normal. Corneal topography of the right eye showed inverse crab-claw pattern suggestive of Terrien's marginal degeneration (TMD) and the left eye showed inferior steepening with posterior elevation and thinning suggestive of keratoconus-like topography. This case shows that evaluation of the other apparently normal eye with 20/20 vision might show changes on topography in cases of unilateral TMD and needs follow-up to assess any further progression.
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http://dx.doi.org/10.1136/bcr-2022-249493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255395PMC
July 2022

Visual Fields in Epidemic Retinitis.

Ocul Immunol Inflamm 2022 Jun 16:1-6. Epub 2022 Jun 16.

Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India.

Aim: The aim of the study is to analyze visual fields defects (VFDs) in epidemic retinitis (ER).

Methods: Patients with ER and Humphrey's visual field (HFA) 30-2 performed after resolution were studied. VFD severity grading was performed. Patients treated with oral doxycycline (Group-A) versus doxycycline-steroids (group-B) were compared.

Results: Thirty-five eyes of 25 patients were studied. Nasal, inferior, temporal and central VFD were seen in 19 (54.2%), 13 (37.1%), 7 (20%) and 6 (17.1%) eyes, respectively. Grade 0, 1, 2 and 3 VFDs were seen in 4 (11.4%), 15 (42.8%), 12 (34.2%) and 4 (11.4%) eyes respectively. Seven eyes with ≥1 year of follow-up post-resolution also showed grade 0-3 scotomas. Mean severity of scotoma was grade 1.15 (Median: 1) and 1.42 (Median: 1.5) in groups A (n = 13) and B (n = 14), respectively (p = .637).

Conclusion: ER can cause VFD persisting long after resolution. Treatment with oral doxycycline without steroids was non-inferior to combined treatment with respect to VFD.
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http://dx.doi.org/10.1080/09273948.2022.2084422DOI Listing
June 2022

Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors.

Cells 2022 05 18;11(10). Epub 2022 May 18.

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India.

Retinoblastoma (Rb) is a pediatric intraocular malignancy that is proposed to originate from maturing cone cell precursors in the developing retina. The molecular mechanisms underlying the biological and clinical behaviors are important to understand in order to improve the management of advanced-stage tumors. While the genetic causes of Rb are known, an integrated understanding of the gene expression and metabolic processes in tumors of human eyes is deficient. By integrating transcriptomic profiling from tumor tissues and metabolomics from tumorous eye vitreous humor samples (with healthy, age-matched pediatric retinae and vitreous samples as controls), we uncover unique functional associations between genes and metabolites. We found distinct gene expression patterns between clinically advanced and non-advanced Rb. Global metabolomic analysis of the vitreous humor of the same Rb eyes revealed distinctly altered metabolites, indicating how tumor metabolism has diverged from healthy pediatric retina. Several key enzymes that are related to cellular energy production, such as hexokinase 1, were found to be reduced in a manner corresponding to altered metabolites; notably, a reduction in pyruvate levels. Similarly, E2F2 was the most significantly elevated E2F family member in our cohort that is part of the cell cycle regulatory circuit. Ectopic expression of the wild-type gene in the Rb-null Y79 and WERI-Rb1 cells rescued hexokinase 1 expression, while E2F2 levels were repressed. In an additional set of Rb tumor samples and pediatric healthy controls, we further validated differences in the expression of HK1 and E2F2. Through an integrated omics analysis of the transcriptomics and metabolomics of Rb, we uncovered a significantly altered tumor-specific metabolic circuit that reduces its dependence on glycolytic pathways and is governed by Rb1 and HK1.
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http://dx.doi.org/10.3390/cells11101668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139581PMC
May 2022

Altered Ocular Surface Health Status and Tear Film Immune Profile Due to Prolonged Daily Mask Wear in Health Care Workers.

Biomedicines 2022 May 18;10(5). Epub 2022 May 18.

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India.

Prolonged daily face mask wearing over several months might affect health of the ocular surface and is reported to be associated with complaints of discomfort and dry-eye-like symptoms. We studied the ocular surface clinical parameters, tear soluble factors and immune cell proportions in ophthalmologists practicing within similar environmental conditions ( = 17) at two time points: pre-face-mask period (Pre-FM; end of 2019) and post-face-mask-wearing period (Post-FM; during 2020 COVID-19 pandemic), with continuous (~8 h/day) mask wear. A significant increase in ocular surface disease index (OSDI) scores without changes in tear breakup time (TBUT), Schirmer's test 1 (ST1) and objective scatter index (OSI) was observed Post-FM. Tear soluble factors (increased-IL-1β, IL-33, IFNβ, NGF, BDNF, LIF and TSLP; decreased-IL-12, IL-13, HGF and VEGF-A) and mucins (MUC5AC) were significantly altered Post-FM. Ex vivo, human donor and corneoscleral explant cultures under elevated CO stress revealed that the molecular profile, particularly mucin expression, was similar to the Post-FM tear molecular profile, suggesting hypercapnia is a potential contributor to ocular surface discomfort. Among the immune cell subsets determined from ocular surface wash samples, significantly higher proportions of leukocytes and natural killer T cells were observed in Post-FM compared to Pre-FM. Therefore, it is important to note that the clinical parameters, tear film quality, tear molecular factors and immune cells profile observed in prolonged mask-wear-associated ocular surface discomfort were distinct from dry eye disease or other common ocular surface conditions. These observations are important for differential diagnosis as well as selection of appropriate ocular surface treatment in such subjects.
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http://dx.doi.org/10.3390/biomedicines10051160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139140PMC
May 2022

Non-arteritic anterior ischaemic optic neuropathy (NA-AION) and COVID-19 vaccination.

BMJ Case Rep 2022 May 13;15(5). Epub 2022 May 13.

Neuro-Ophthalmology, Narayana Nethralaya, Bangalore, Karnataka, India.

A woman in her 50s presented with diminution of vision in her left eye (OS) 4 days after COVISHIELD vaccination. She had been diagnosed with non-arteritic anterior ischaemic optic neuropathy (NA-AION) of right eye (OD) 8 months earlier. The present episode revealed a best-corrected visual acuity (BCVA) of 20/50 in OD and 20/20 in OS with grade 1 relative afferent pupillary defect. Fundus evaluation showed pale disc in OD and temporal disc oedema in OS. Humphrey's visual field analysis showed incomplete inferior altitudinal defect in OD and a centro-caecal scotoma in OS. Systemic investigations were normal. OS was diagnosed with NA-AION. She was started on oral aspirin 75 mg. At 1-month follow-up, disc oedema of OS had resolved with BCVA maintaining at 20/20. The patient was lost to follow-up later. The relationship between the vaccine and the ocular event is temporal with no causal association.
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http://dx.doi.org/10.1136/bcr-2021-248415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109041PMC
May 2022

Corneal Confocal Microscopy Features and Tear Molecular Profile in Study Participants with Discordance between Ocular Surface Disease Clinical Signs and Discomfort.

J Clin Med 2022 Apr 25;11(9). Epub 2022 Apr 25.

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India.

Various ocular surface conditions such as dry eye disease can present with severe discomfort and pain. However, it is clinically challenging to establish etiology and prescribe correct treatment in patients who have a lot of discordance between symptoms and signs. To understand the basis of such discordance, we stratified subjects with ocular surface pain based on concordance between the severity of signs and symptoms and evaluated corneal structural features and tear molecular factors. All subjects underwent slit lamp examination, dry eye evaluation, and ocular surface disease index (OSDI) scoring. Subjects were stratified into group 1-without symptoms or clinical signs; group 2-without symptoms but with signs; group 3-with similar severity of symptoms and signs; and group 4-with symptom severity greater than that of the signs. Laser scanning in vivo confocal microscopy (IVCM) and tear fluid analysis for soluble factors by multiplex ELISA was performed for all subjects. Patients with a higher grade of symptoms and signs showed increased corneal dendritic cell (cDC) density ( < 0.05) which was more pronounced in subjects with discordance between the symptoms and signs (group 4). A significantly higher proportion of microneuroma-like structures and cDC were observed in group 4. IL-17A levels were significantly elevated in the tears of subjects with more discomfort. Our results demonstrate that corneal IVCM and the measurement of tear film factors can help clinicians improve diagnosis and treatment choice. Stratifying patients with ocular surface discomfort on the basis of discordance between symptoms and clinical signs may help identify patients who need additional adjunctive targeted therapy to resolve their condition.
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http://dx.doi.org/10.3390/jcm11092407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099769PMC
April 2022

A case of acute endothelial corneal transplant rejection following immunization with ChAdOx1 nCoV-19 coronavirus vaccine.

Indian J Ophthalmol 2022 05;70(5):1817-1818

Department of Cornea and External Diseases of the Eye, Narayana Nethralaya, Bengaluru, Karnataka, India.

A 28-year-old female who underwent an uneventful femtosecond laser enabled keratoplasty (FLEK) in her left eye presented with pain, redness, and blurring of vision in the operated eye two weeks after getting immunized with COVID-19 vector vaccine (ChAdOx1 nCoV19 Vaccine Recombinant COVISHIELD, AstraZeneca). Slit-lamp examination showed donor stromal edema with Descemet's membrane folds and Khodadoust line (KP's on endothelium) with anterior chamber cells and flare. The patient was diagnosed with acute corneal graft rejection and advised hourly topical steroids with cycloplegics and oral steroids. The patient responded to treatment and there was progressive reversal of graft rejection with the patient achieving best spectacle-corrected visual acuity (BSCVA) of 20/30 after five weeks of treatment. Our case highlights possible immune corneal graft rejection after COVID19 vaccination and the need to step up topical steroids before vaccination.
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http://dx.doi.org/10.4103/ijo.IJO_66_22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332947PMC
May 2022

Psychosocial assessment among ophthalmic patients attending tertiary eye care centre during the lockdown in times of COVID-19 pandemic.

Indian J Ophthalmol 2022 05;70(5):1767-1772

Cornea and Refractive Services, Narayana Nethralaya, Bengaluru, Karnataka, India.

Purpose: The coronavirus disease (COVID-19) pandemic continues to play havoc in our lives. During the first " lockdown" in 2020, we were keen on assessing the anxiety levels of patients who sought ophthalmic care despite the lockdown. Public health actions, such as social distancing, were necessary to reduce the spread of COVID-19. As a result, most people felt isolated and lonely, thereby causing increased levels of stress and anxiety in them. We aimed to assess the anxiety levels using the Hamilton Anxiety Scale and personality assessment using the 57-point Eysenck's Personality Inventory (EPI) questionnaire among patients visiting a tertiary eye care hospital during the lockdown period.

Methods: Consecutive patients attending an ophthalmic tertiary care hospital during the COVID-19 pandemic and lockdown were approached to be a part of this prospective cross-sectional survey.

Results: In total, 1,088 responses were analyzed during the 2-month study period with the mean age being 45.7 + 16.9 years. The majority had completed graduation (78%) with 15 years or more of formal education. The purpose of the visit was an emergency consultation in 42% (n = 455), a review appointment in 42% (n = 457), and the remaining (16%, n = 176) came for a routine consultation. The majority of the patients (>90%) did not report experiencing any of the 14 sets of symptoms. A mild level of anxiety was noted in 1,086 (>99%) respondents, whereas only 2 (<1%) respondents showed mild-moderate levels of anxiety. Financial concerns such as affordability of medications (6% vs. 3%, P = 0.05) and fear of losing their job (16% vs. 11%, P = 0.02) were significantly more in those experiencing any anxiety compared to those with no anxiety.

Conclusion: Our study revealed that patients visiting a tertiary ophthalmic center during lockdown were graduates, sought eye consultation primarily for emergency or a review, and had no major anxiety symptoms. In those with anxiety, the affordability of medicines and loss of jobs were the main concerns.
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http://dx.doi.org/10.4103/ijo.IJO_3074_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332942PMC
May 2022

Reactivation of juvenile idiopathic arthritis associated uveitis with posterior segment manifestations following anti-SARS-CoV-2 vaccination.

J Ophthalmic Inflamm Infect 2022 Apr 27;12(1):15. Epub 2022 Apr 27.

Department of Rheumatology, Vikram Hospital, Bangalore, India.

Background/purpose: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in the pediatric population and anterior uveitis is its commonest extra-articular manifestation. Typically the uveitis presents as chronic anterior uveitis and there is limited literature of the posterior segment manifestations of the disease. Similar to other vaccines, anti-SARS-CoV-2 vaccination that began as an urgent measure to control the spread of the SARS-CoV-2 pandemic has not been without adverse events. We are reporting a 19-year-old Asian Indian female who was diagnosed and treated for JIA associated anterior uveitis that was unilateral and was under anti-inflammatory control but showed worsening of uveitis with posterior segment inflammation in both eyes following anti-SARS-CoV-2 vaccination.

Case Report: A 19-year-old Asian Indian female with a history of juvenile idiopathic arthritis on treatment with methotrexate, presented with right eye chronic anterior uveitis with peripheral subclinical retinal vasculitis and macular edema which was brought under control following administration of adalimumab. She was inflammation free for 6 months until she received anti-SARS-CoV-2 vaccination and developed new onset floaters in both eyes that were initially noted after the first dose and increased after the second dose. Clinical examination revealed presence of keratic precipitates and grade 1+ anterior chamber inflammation along with vitiritis in both eyes. Fundus fluorescein angiography revealed angiographically active retinal vasculitis without the presence of macular edema in both eyes. This was managed with a short course of topical difluprednate and continuation of systemic immunosuppressive therapy with adalimumab and methotrexate.

Conclusion: JIA associated uveitis results from an autoimmune process which can be controlled with timely immunosuppressive treatment. It is important to be aware of the potential risk of flare up of uveitis with posterior segment manifestations following anti- SARS-CoV-2 vaccination.
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http://dx.doi.org/10.1186/s12348-022-00294-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043884PMC
April 2022

Generation of iPSC line (GLNNFi001-A) from peripheral blood mononuclear cells of a patient with macular corneal dystrophy.

Stem Cell Res 2022 07 22;62:102789. Epub 2022 Apr 22.

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, Karnataka, India.

Macular corneal dystrophy (MCD) an autosomal recessive disorder leading to severe visual impairment is caused by mutations in the carbohydrate sulfotransferase 6 (CHST6) gene. Here, we describe generation of a iPSC line from peripheral blood mononuclear cells (PBMCs) from a 38 year old MCD patient harboring a homozygous mutation, p.V172L in the CHST6 gene. The iPSC line GLNNFi001-A was generated using an integration-free Sendai virus containing (KLF4, c-MYC, OCT4 and SOX2).
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http://dx.doi.org/10.1016/j.scr.2022.102789DOI Listing
July 2022

Herpes Simplex Virus 1 Anterior Uveitis following Coronavirus Disease 2019 (COVID-19) Vaccination in an Asian Indian Female.

Ocul Immunol Inflamm 2022 Apr 11:1-5. Epub 2022 Apr 11.

Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India.

Purpose: To describe a case of herpes simplex virus 1 (HSV 1) infection following coronavirus disease 2019 (COVID-19) vaccination in an Asian Indian female.

Methods: Retrospective case report.

Result: A 40-year-old female presented with decreased vision, pain, and photophobia of 2 weeks duration. She reported receiving the second dose of COVISHIELD (ChAdOx1-S [recombinant]) 1 week prior to the onset of ocular symptoms. Left eye examination revealed granulomatous anterior uveitis. Aqueous sample from the left eye tested positive for HSV1 by polymerase chain reaction(PCR) method. She was managed with oral antiviral therapy, topical steroids, and cycloplegic agent and showed significant improvement of inflammation within 1 week and resolved within 3 weeks.

Conclusion: This report demonstrates a potential association of HSV 1 anterior uveitis with COVID-19 vaccination. A high index of suspicion of viral etiology is warranted when uveitis presents with reduced corneal sensations and pigmented keratic precipitates, following a recent history of COVID-19 vaccination.
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http://dx.doi.org/10.1080/09273948.2022.2055580DOI Listing
April 2022

Serial ERG monitoring of response to therapy in vitamin A deficiency related night blindness.

BMJ Case Rep 2022 Mar 29;15(3). Epub 2022 Mar 29.

Vitreoretina Services, Narayana Nethralaya Eye Institute, Bangalore, India.

Two male patients with known systemic disorders who presented with complaints of nyctalopia underwent a complete ophthalmic examination including electrophysiological evaluation and serum vitamin A (retinol) levels. A significant vitamin A deficiency was detected, supplementation started and repeat electroretinogram (ERG) testing was carried out to monitor the timeline of recovery. Restoration of rod and generalised cone function was rapid within the first week of receiving treatment and near normal recovery was seen after 1 month of supplementation. Serial monitoring of ERG changes in vitamin A deficiency (VAD) associated night blindness plays an important role to demonstrate functional recovery post-treatment. The different effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptors. We report the serial ERG changes in VAD related night blindness secondary to intestinal lipofuscinosis and liver cirrhosis in two patients.
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http://dx.doi.org/10.1136/bcr-2021-247856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966552PMC
March 2022

Corneal Biomechanics and Intraocular Pressure Following Scleral Lens Wear in Penetrating Keratoplasty and Keratoconus.

Eye Contact Lens 2022 May 24;48(5):206-209. Epub 2022 Mar 24.

Narayana Nethralaya (M.K., R.S., V.G.L., A.S.R., P.K.), Bangalore, India; and Centre for Vision and Eye Research (S.J.V.), School of Optometry & Vision Science, Queensland University of Technology, Brisbane, Australia.

Objective: To compare corneal biomechanics and intraocular pressure (IOP) in keratoconus and penetrating keratoplasty eyes before and after nonfenestrated scleral lens wear.

Methods: Twenty-three participants were enrolled, and 37 eyes were included in the analysis (11 penetrating keratoplasty and 26 keratoconus). A range of corneal biomechanical parameters and IOP were measured using the CORVIS ST before and after 8 hr of nonfenestrated scleral lens wear (Keracare, Acculens, Denver, CO).

Results: Before lens wear, penetrating keratoplasty eyes displayed significantly greater median values for central corneal thickness (97 μm thicker, P=0.02), IOP (3.89 mm Hg higher, P=0.01), and biomechanical parameter A2 length (0.48 mm longer, P=0.003) compared with keratoconic eyes. No significant changes in corneal biomechanical parameters or IOP were observed after scleral lens wear in either group (all P>0.05).

Conclusion: Although nonfenestrated scleral contact lenses can induce a subatmospheric pressure after lens settling and compress tissue surrounding the limbus, no significant changes were detected in the corneal biomechanical parameters studied using CORVIS ST after scleral lens wear in eyes with penetrating keratoplasty and keratoconus.
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http://dx.doi.org/10.1097/ICL.0000000000000886DOI Listing
May 2022

Ocular Surface Infection Mediated Molecular Stress Responses: A Review.

Int J Mol Sci 2022 Mar 14;23(6). Epub 2022 Mar 14.

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560 099, India.

Infection mediated ocular surface stress responses are activated as early defense mechanisms in response to host cell damage. Integrated stress responses initiate the host response to different types of infections and modulate the transcription of key genes and translation of proteins. The crosstalk between host and pathogen results in profound alterations in cellular and molecular homeostasis triggering specific stress responses in the infected tissues. The amplitude and variations of such responses are partly responsible for the disease severity and clinical sequelae. Understanding the etiology and pathogenesis of ocular infections is important for early diagnosis and effective treatment. This review considers the molecular status of infection mediated ocular surface stress responses which may shed light on the importance of the host stress-signaling pathways. In this review, we collated literature on the molecular studies of all ocular surface infections and summarize the results from such studies systematically. Identification of important mediators involved in the crosstalk between the stress response and activation of diverse signaling molecules in host ocular surface infection may provide novel molecular targets for maintaining the cellular homeostasis during infection. These targets can be then explored and validated for diagnostic and therapeutic purposes.
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http://dx.doi.org/10.3390/ijms23063111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952005PMC
March 2022

Impact of tear optics on the repeatability of Pentacam AXL wave and iTrace in measuring anterior segment parameters and aberrations.

Indian J Ophthalmol 2022 04;70(4):1150-1157

Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India.

Purpose: To assess impact of tear optics on repeatability of a Scheimpflug device with a Hartmann Shack aberrometer and a ray tracing aberrometer.

Methods: One hundred healthy and 100 postrefractive surgery eyes underwent dry eye evaluation including Schirmer's test and tear film break-up time (TBUT). They underwent optical quality analyzer (OQAS, Visio metrics S.L, Terrassa, Spain) to assess objective scatter index (OSI), three scans each on Pentacam AXL wave (OCULUS Optikgerate Gmbh, Wetzlar, Germany), iTrace (Tracey™ Technologies, Texas, USA) for flat, steep keratometry, thinnest corneal thickness, root mean square higher-order aberrations (RMS HOA), RMS lower-order aberrations (LOA), spherical aberrations, RMS COMA. Repeatability of Pentacam AXL wave and iTrace in healthy and postrefractive eyes (OSI >1 vs OSI <1) was studied using within-subject standard deviation (Sw) test-retest repeatability (TRT), coefficient of variation (COV).

Results: OSI showed an inverse association with TBUT (P < 0.001). All measurements with Pentacam AXL wave with OSI < 1 had excellent repeatability, intraclass correlation coefficient (ICC) ranging from 0.88 for HOA, to 0.92 for LOA. The Sw, TRT, and COV of all aberration measurements were significantly lower (better) than those of iTrace. In eyes with OSI ≥1, the repeatability with Pentacam AXL wave dropped with ICC ranging from 0.77 for HOA, to 0.84 for LOA with lower Sw, TRT, and COV of all aberration measurements as compared to iTrace. Maximum variation was seen with HOA and minimum with LOA.

Conclusion: Tear optics affected repeatability of Pentacam wave and iTrace. Pentacam wave had better repeatability in eyes with a poor tear film as compared to iTrace. Thus, the tear film can impact repeatability of an instrument and it is important to assess the tear film prior to imaging patients, which can change the way we interpret and image these patients.
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http://dx.doi.org/10.4103/ijo.IJO_2153_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240491PMC
April 2022

Repeatability and Agreement of a New Scheimpflug Device and a Hartmann-Shack Aberrometer With a Ray-Tracing Aberrometer in Normal, Keratoconus, and CXL Groups.

J Refract Surg 2022 Mar 1;38(3):201-208. Epub 2022 Mar 1.

Purpose: To assess repeatability and agreement of a Scheimpflug topographer and a Hartmann-Shack aberrometer with a ray-tracing aberrometer in normal, keratoconus, and corneal cross-linking (CXL) groups.

Methods: In this cross-sectional, observational study, normal, keratoconus, and CXL groups with 125 eyes in each of the three groups were included. All eyes underwent three sets of measurements, at a single visit, using the Pentacam AXL Wave (Oculus Optikgeräte GmbH) and iTrace (Tracey Technologies). Keratometry, pachymetry, objective refraction, and total ocular aberrations including root mean square (RMS) lower order aberrations (LOAs), RMS higher order aberrations (HOAs), RMS coma, and spherical aberrations (SA) were analyzed. Objective assessment of haze after CXL was done using the Pentacam AXL Wave. Repeatability was assessed using within-subject standard deviation (Sw), test-retest variability, within-subject coefficient of variation (COV), and intraclass correlation coefficient (ICC). Bland-Altman analysis assessed 95% limits of agreement and correlation coefficient () determined the strength of the relationship between measurements.

Results: The Pentacam AXL Wave had Sw for keratometry of 0.12 in the normal group and 0.15 in the keratoconus group and lower (poorer) Sw of 0.17 in the CXL group. For pachymetry, Sw was 9.18, 9.53, and 10.11 in the normal, keratoconus, and CXL groups, respectively. Total aberrations had ICCs ranging from 0.88 for RMS HOAs to 0.95 for SA in the normal group, 0.86 for RMS HOAs to 0.92 for SA in the keratoconus group, and 0.72 for RMS HOAs to 0.82 for SA (poorer) in the CXL group. In the normal group, mean differences between the two devices were nonsignificant for all parameters except SA (0.011 ± 0.038 μm, < .01; limits of agreement = -0.09 to 0.07; = 0.87). In the keratoconus group, mean differences were significant in all aberrations except RMS LOAs (-0.27 ± 0.85 μm, = .10; limits of agreement = -3.3 to 3.8; = 0.92). In the CXL group, all parameters varied significantly ( < .006).

Conclusions: The Pentacam AXL Wave showed comparable repeatability in the normal and keratoconus groups, but was poorer in the CXL group, more so with increasing corneal haze. Both devices can be used interchangeably in normal eyes, except for SA, but not in eyes with keratoconus or CXL for aberration measurements. .
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http://dx.doi.org/10.3928/1081597X-20220110-01DOI Listing
March 2022

Quantitative Proteomics Reveals Molecular Network Driving Stromal Cell Differentiation: Implications for Corneal Wound Healing.

Int J Mol Sci 2022 Feb 25;23(5). Epub 2022 Feb 25.

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India.

The differentiation of keratocytes to fibroblasts and myofibroblasts is an essential requisite during corneal wound closure. The aim of this study is to uncover factors involved in differentiation-dependent alteration in the protein profile of human corneal stromal cells using quantitative proteomics. Human corneal fibroblasts were cultured and differentiated into keratocytes in serum-free media and myofibroblasts through treatment with TGF-β. The protein cell lysates from the donors were tryptic and were digested and labeled using a 3-plex iTRAQ kit. The labeled peptides were subjected to LCMS analysis. Biological functional analysis revealed a set of crucial proteins involved in the differentiation of human corneal stromal cells which were found to be significantly enriched. The selected proteins were further validated by immunohistochemistry. Quantitative proteomics identified key differentially expressed proteins which are involved in cellular signaling pathways. Proteins involved in integrin signaling (Ras-RAP1b, TLN and FN) and SLIT-ROBO pathways (PFN1, CAPR1, PSMA5) as well as extracellular matrix proteins (SERPINH1, SPARC, ITGβ1, CRTAP) showed enhanced expression in corneal fibroblasts and myofibroblasts compared to keratocytes, indicating their possible role in wound healing. Corneal stromal cell differentiation is associated with the activation of diverse molecular pathways critical for the repair of fibroblasts and myofibroblasts. Identified proteins such as profilin 1 and talin could play a tentative role in corneal healing and serve as a potential target to treat corneal fibrosis.
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http://dx.doi.org/10.3390/ijms23052572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910342PMC
February 2022

"Acute Bilateral Neuroretinitis and Panuveitis in A Patient with Coronavirus Disease 2019: A Case Report"- Few Comments.

Ocul Immunol Inflamm 2022 Mar 8:1-2. Epub 2022 Mar 8.

Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India.

During the Coronavirus Disease 2019 (COVID-19) pandemic, we have witnessed increase in number of reports of a known uveitic entity being associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Causal relation is yet to be proven for many reports. Perhaps, occurrence of a previously known region-specific endemic disease or closely resembling manifestations of a known disease in a non-endemic region during the COVID-19 pandemic might suggest a causal relationship. Epidemic retinitis (ER) or post fever retinitis is such condition with geographic variation. Occurrence of ER or ER-like manifestations in a non-endemic country during the pandemic should instigate further studies to consider SARS-CoV-2 as a causative organism.
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http://dx.doi.org/10.1080/09273948.2022.2039212DOI Listing
March 2022

Trends in teleconsultations for uveitis during the COVID-19 lockdown.

Indian J Ophthalmol 2022 03;70(3):1007-1012

Cataract and Refractive Lens Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India.

Purpose: To study the use of teleophthalmology as a tool to manage patients with uveitis and to describe the experience of teleconsultation for uveitis at a tertiary eye care hospital in India during the two waves of the COVID-19 pandemic.

Methods: A prospective observational case series of uveitis patients seeking teleconsultations during the first (March 25-May 2020) and second lockdown (April 27 to June 21, 2021) in a tertiary eye care center were analyzed.

Results: There were 79 teleconsultations in the first and 89 teleconsultations in the second lockdown. A majority of the patients presented in the age group of 41-60 years in both the lockdowns. There were both new or primary consultations and follow-up patients (6% vs. 94%) in the first lockdown, and similarly in the second lockdown (8% new vs. 92% follow-up). The majority of patients resided in Bengaluru city (78% in the first and 76% in the second lockdown). After evaluation through video consultation, only 15% required a hospital referral in the first lockdown, whereas in the second lockdown, 21.3% were referred to the hospital. During the second lockdown, 20% presented with COVID-19 infection-related ailments.

Conclusion: Based on our preliminary experience using a customized smartphone-based application for teleconsultation, we found it to be an alternative option to provide continuation of ophthalmic care to uveitis patients. Given the current COVID-19 situation, it can help avoid physical visits of uveitis patients to the hospital.
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http://dx.doi.org/10.4103/ijo.IJO_1759_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114533PMC
March 2022

Upregulated NOTCH Signaling in the Lens of Patients With Pseudoexfoliation Syndrome Compared With Pseudoexfoliation Glaucoma Suggests Protective Role.

J Glaucoma 2022 Mar;31(3):e1-e9

Stem Cell Lab, GROW Labs, Narayana Nethralaya Foundation, Bangalore, Karnataka, India.

Prcis: NOTCH signaling is significantly upregulated in the lens capsules of eyes with pseudoexfoliation syndrome (PXF) but not in those with pseudoexfoliation glaucoma (PXG) when compared with healthy controls.

Purpose: NOTCH signaling has neuroprotective functions and altered NOTCH signaling is associated with neurodegenerative diseases with protein aggregation such as Alzheimer disease. As PXG is also a protein aggregate disease associated with neural degeneration, NOTCH molecular expression was explored in the lens capsules of patients with PXF, PXG, primary open-angle glaucoma (POAG), and healthy controls.

Methods: Anterior lens capsules were collected from 106 patients (27 PXF, 24 PXG, 22 POAG, and 33 controls) undergoing cataract surgery. Gene expression profiling for NOTCH pathway molecules (ligands, receptors, and downstream target genes) was performed on the tissue using a quantitative reverse transcription-polymerase chain reaction. The results were confirmed by protein analysis using dot-blot or immunostaining techniques.

Results: There was no difference in the demographic characteristics between the groups. There was an increase in NOTCH4 receptor expression (>14-fold) in the PXF group as compared with the controls. Similarly, the Delta-like 3 and Delta-like 4 ligands were significantly elevated in the PXF group compared with controls (P<0.05). Downstream targets HES3, HES5, and HEY1 expression were significantly elevated (P<0.005) in PXF lens capsules, confirming a higher activity of NOTCH signaling in this cohort. Immunostaining also corroborated the gene expression profile.

Conclusion: The finding that NOTCH signaling is significantly upregulated in the lens capsule of eyes with PXF and not in PXG or POAG patients suggests a possible protective role in the development of glaucoma.
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http://dx.doi.org/10.1097/IJG.0000000000001975DOI Listing
March 2022

Systemic Markers in Ophthalmic Manifestations of Post Corona Virus Disease-19 (COVID-19).

Ocul Immunol Inflamm 2022 Feb 9:1-6. Epub 2022 Feb 9.

Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India.

Introduction: Corona virus disease (COVID-19) has been associated with ophthalmic manifestations which can occur during or following the infection.

Purpose: To explore the systemic status in ophthalmic patients who had a recent history of COVID-19 or those with positive COVID-19 antibody status.

Methods: Retrospective case series.

Results: 30 patients with history of COVID-19 infection and positive COVID-19 antibodies were included in the study. The median age was 49 years (mean 48.7 ± 13.7 years), 20 were males (66.7%) and 10 (33.3%) were females. Patients with VA>/= 6/60 were included in group 1 and those with VA<6/60 were included in group 2. D-dimer/serum Ferritin levels were raised in group 2 compared to group 1with / respectively.

Conclusion: Serum D-dimer and ferritin levels were statistically significant and were higher in patients with sight threatening ocular manifestations. ESR and CRP were raised even after recovery from COVID-19 although they were not statistically significant.
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http://dx.doi.org/10.1080/09273948.2021.2025253DOI Listing
February 2022

Nodular scleritis-a rare presentation of COVID-19& variation with testing.

Am J Ophthalmol Case Rep 2022 Mar 3;25:101396. Epub 2022 Feb 3.

Narayana Nethralaya Eye Institute, 121/C, Chord Road, Rajajinagar, 1st R block, Bangalore, Karnataka, India.

Purpose: - To report a rare case of patient presenting with nodular scleritis and SARS-CoV2.

Observations: This case highlights a unique presentation of SARS-CoV2 positive patient with nodular scleritis as a presenting feature. Patient initially had ocular symptoms and developed only mild systemic features subsequently which did not require hospitalization. COVID testing done at different time points showed variable results which correlated with the ocular features. This patient was followed up during quarantine using tele-ophthalmology.

Conclusion And Importance: This case highlights a possible rare presentation of a SARS-CoV2 patient with nodular scleritis and also importance of tele medicine during these unprecedented times.
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http://dx.doi.org/10.1016/j.ajoc.2022.101396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810438PMC
March 2022

Corneal scarring following collagen cross-linking: evidence of increased lysyl oxidase activity.

Eur J Ophthalmol 2022 Feb 7:11206721221078152. Epub 2022 Feb 7.

Vitreo- Retina Services, Eye Life, Mumbai, India.

Purpose: To report a case of corneal scarring following collagen cross linking in a young female.

Methods: A 24-year-old female presented to us with complaints of decreased vision and a white spot in her left eye following collagen cross linking (CXL) performed elsewhere, four years prior. We diagnosed her as a case of left eye leucomatous corneal opacity for which she underwent optical penetrating keratoplasty under local anaesthesia. The excised corneal tissue was evaluated by routine histopathology and immunohistochemistry.

Results: At the final follow up visit, one year following corneal transplantation, her visual acuity improved to 20/20, J1 with a clear graft.

Conclusion: Vision threatening corneal scarring may be rarely noted following CXL.
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http://dx.doi.org/10.1177/11206721221078152DOI Listing
February 2022

Mapping of corneal birefringence in thin and asymmetric keratoconus corneas with ultrahigh-resolution polarization-sensitive OCT.

J Cataract Refract Surg 2022 08;48(8):929-936

From the Imaging, Biomechanics and Mathematical Modelling Solutions Lab, Narayana Nethralaya Foundation, Bangalore, India (Patil, Narasimhan, Patel, Roy); Department of Cataract Surgery, Narayana Nethralaya, Bangalore, India (Shetty, Khamar); Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India (Shetty, Khamar); Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria (Pircher, Hitzenberger); University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands (Nuijts).

Purpose: To evaluate phase retardation (PR) across healthy eyes and eyes with thin corneas (<500 μm) and with asymmetric and bilateral keratoconus (KC).

Setting: Narayana Nethralaya Eye Hospital, Bangalore, India.

Design: Observational cross-sectional.

Methods: There were 4 eye groups: healthy eyes (Group 1; n = 10 eyes), eyes with thin corneas and no clinical disease (Group 2; n = 10 eyes), eyes with asymmetric KC (Group 3; n = 5 eyes), and eyes with clinical KC (Group 4; n = 15 eyes). All eyes were imaged with polarization-sensitive optical coherence tomography (PS-OCT), MS-39, and Corvis-ST. Using PS-OCT, PR was analyzed in annular regions. The anterior (A-E) and Bowman (E-B) wavefront aberrations, epithelial Zernike indices (EZI), total corneal thickness, Corvis biomechanical index (CBI), total biomechanical index (TBI), and Belin-Ambrósio overall deviation index (BAD-D) were analyzed.

Results: Only CBI, TBI, BAD-D, A-E and E-B aberrations, EZI, and total corneal thickness distributions of Groups 1 (n =10), 2 (n =10), and 3 (n =5) were similar ( P > .05) but not CCT ( P < .05). PR distributions clearly showed that the eyes in Groups 1, 2, and 3 had a normal corneal birefringence unlike Group 4 (n = 10) eyes ( P < .05). The PR map was similar to the preferred orientations of collagen fibers seen in X-ray diffraction ex vivo studies of corneal stroma.

Conclusions: PR distributions may eliminate the uncertainty associated with the stromal status of thin and asymmetric KC corneas. Group 2 and 3 eyes appeared as healthy because of normal corneal birefringence at the time of imaging, but a longitudinal follow-up of these eyes with PS-OCT may assist in early detection of onset of disease.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000898DOI Listing
August 2022
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