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

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.

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

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.

Significance of non-intraocular pressure (IOP)-related factors particularly in normal tension glaucoma: Looking beyond IOP.

PURPOSE: To study the relationship between intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) in patients with POAG and NTG. The secondary objective was to identify other contributory ischemic factors. METHODS: This was an observational cross-sectional study from a tertiary eye hospital in patients who underwent full-day diurnal variation of tension (DVT). Blood pressure (BP) and IOP measurements were done every 3 h over 24 h. Mean arterial pressure (MAP) and MOPP were calculated. The nocturnal dip in BP was assessed; patients were classified as non-dippers, dippers, and over-dippers. The circadian MOPP fluctuation (CMF) was calculated using the Kruskal-Wallis test, and its relationship with type and severity of visual field was assessed. RESULTS: In total, 149 patients were evaluated; 109 were classified as NTG, and 40 were classified as POAG. A nocturnal dip in BP was noted in 20% of NTG and 17.5% of POAG. The MAP was found to be lower in patients with NTG than POAG. In the NTG subgroup, we found that 20% of patients were over-dippers, 32% were dippers, and 48% were non-dippers. The CMF showed a greater fluctuation for over-dippers (P = 0.004 for the RE and 0.003 for the LE) than dippers and non-dippers. A weak positive correlation of CMF with the severity of fields was found. CONCLUSION: A 24-h monitoring of IOP, BP, MOPP, and assessment of systemic risk factors for primary glaucoma acts as an invaluable tool for the comprehensive management of NTG despite the limitations posed by DVT and BP recording.

Ophthatome™: an integrated knowledgebase of ophthalmic diseases for translating vision research into the clinic.

BACKGROUND: Medical big data analytics has revolutionized the human healthcare system by introducing processes that facilitate rationale clinical decision making, predictive or prognostic modelling of the disease progression and management, disease surveillance, overall impact on public health and research. Although, the electronic medical records (EMR) system is the digital storehouse of rich medical data of a large patient cohort collected over many years, the data lack sufficient structure to be of clinical value for applying deep learning methods and advanced analytics to improve disease management at an individual patient level or for the discipline in general. Ophthatome™ captures data contained in retrospective electronic medical records between September 2012 and January 2018 to facilitate translational vision research through a knowledgebase of ophthalmic diseases. METHODS: The electronic medical records data from Narayana Nethralaya ophthalmic hospital recorded in the MS-SQL database was mapped and programmatically transferred to MySQL. The captured data was manually curated to preserve data integrity and accuracy. The data was stored in MySQL database management system for ease of visualization, advanced search functions and other knowledgebase applications. RESULTS: Ophthatome™ is a comprehensive and accurate knowledgebase of ophthalmic diseases containing curated clinical, treatment and imaging data of 581,466 ophthalmic subjects from the Indian population, recorded between September 2012 and January 2018. Ophthatome™ provides filters and Boolean searches with operators and modifiers that allow selection of specific cohorts covering 524 distinct ophthalmic disease types and 1800 disease sub-types across 35 different anatomical regions of the eye. The availability of longitudinal data for about 300,000 subjects provides additional opportunity to perform clinical research on disease progression and management including drug responses and management outcomes. The knowledgebase captures ophthalmic diseases in a genetically diverse population providing opportunity to study genetic and environmental factors contributing to or influencing ophthalmic diseases. CONCLUSION: Ophthatome™ will accelerate clinical, genomic, pharmacogenomic and advanced translational research in ophthalmology and vision sciences.

Preferred practice guidelines for glaucoma management during COVID-19 pandemic.

The COVID-19 pandemic has threatened the humanity at a global level to a large extent by the burden of the disease with significant mortality and to a certain extent as a byproduct of the necessary efforts to contain the same. There is a significant impact on the health care system, as we not only have to contain pandemic, but continue to treat our non-COVID-19 patients in a safe and responsible manner. Ophthalmology practice in general and glaucoma in particular needs certain modifications and additional precautions while examining as well as managing these patients keeping their and our safety in mind. As the lockdown relaxations are in vogue we need to learn how to deal with our regular patients as well in addition to emergency care. This paper presents the consensus-based guidelines by an expert panel on how to restart glaucoma practice during this COVID-19 time. These guidelines will be applicable across the country and should help ophthalmologists and glaucoma specialist to restart their practices while safeguarding the patients and their own selves from getting infected.

Treatment of glaucoma by prostaglandin agonists and beta-blockers in combination directly reduces pro-fibrotic gene expression in trabecular meshwork.

Prostaglandin analogues (PG), beta-blockers (BB) or their combination (PG+BB) are used primarily to reduce the intraocular pressure (IOP) pathologically associated with glaucoma. Since, fibrosis of the trabecular meshwork (TM) is a major aetiological factor in glaucoma, we studied the effect of these drugs on fibrosis-associated gene expression in TM of primary glaucoma patients. In the present study, TM and iris of primary open-angle (n = 32) and angle-closure (n = 37) glaucoma patients were obtained surgically during trabeculectomy and categorized based on the type of IOP-lowering medications use as PG, BB or PG+BB. mRNA expression of pro-fibrotic and anti-fibrotic genes was quantified using qPCR in these tissues. The gene expression levels of pro-fibrotic genes were significantly lower in PG+BB as compared to other groups. These observations and underlying signalling validated in vitro in human TM cells also showed reduced fibrotic gene and protein expression levels following PG+BB treatment. In conclusion, it is observed that PG+BB combination rather than their lone use renders a reduced fibrotic status in TM. This further suggests that IOP-lowering medications, in combination, would also modulate fibrosis-associated molecular changes in the TM, which may be beneficial for maintaining aqueous out-flow mechanisms over the clinical treatment duration.

Influence of Anterior Biometry on Corneal Biomechanical Stiffness of Glaucomatous Eyes Treated With Chronic Medication or Filtration Surgery.

PRéCIS:: Anterior chamber depth, IOP, and thickness confounded the assessment of corneal biomechanical properties with noncontact applanation in glaucoma eyes. Compared with normal eyes, glaucoma eyes, which underwent long-term treatment or filtration surgery, had similar properties. PURPOSE: The purpose of this study was to evaluate corneal stiffness in primary angle-closure (PACG) and primary open-angle (POAG) glaucoma eyes that were subgrouped on the basis of the type of topical medication and filtration surgery using noncontact applanation. METHODS: All eyes were retrospectively reviewed for intraocular pressure (IOP) with Corvis-ST (OCULUS Optikgerate Gmbh, Germany). Nonglaucoma (n=140), PACG (n=102 under medication), and POAG (n=154 under medication) eyes were included. Corneal stiffness was calculated using deformation amplitude and a biomechanical model. Multivariate analyses were performed, which evaluated the effect of systemic conditions (diabetes and hypertension), the effect of medication (prostaglandins or beta blockers or combined), and the effect of filtration surgery (PACG: n=23; POAG: n=26). Age, IOP, central corneal thickness (CCT), refractive error, and anterior chamber depth (ACD) were covariates. RESULTS: Diabetes and hypertension did not alter corneal stiffness of glaucoma eyes compared with nonglaucoma eyes (P>0.05). Corneal stiffness of POAG and nonglaucoma eyes was similar but significantly different from the stiffness of PACG eyes (P=0.002), irrespective of the type of topical medication. This difference was strongly correlated with ACD (P=0.003) in addition to IOP and CCT. In eyes treated with filtration surgery, ACD (P=0.04) again impacted the trends between nonglaucoma and glaucoma eyes. CONCLUSIONS: Medication or filtration surgery did not affect the corneal biomechanical parameters differentially from nonglaucoma eyes. However, IOP, CCT, and ACD strongly affected corneal biomechanical parameters in the same glaucoma eyes.

Small lens for a big eye: Successful management of anterior megalophthalmos.

We report a case of anterior megalophthalmos and complicated cataract, with apparently smaller lens in both eyes. The right eye had spontaneous retinal detachment. The child underwent cataract surgery in both the eyes with retinal detachment surgery in the right eye. Due to small size of the lenticular bag, a downsized customized intraocular lens (IOL) was implanted. Postoperatively, the IOL was well centered with ambulatory vision till 3 years of follow-up. This case describes this rare disorder and its association with apparently small-sized lens and discusses the course of its management, highlighting the visual rehabilitation with customization of IOLs.

Role of Age and Myopia in Simultaneous Assessment of Corneal and Extraocular Tissue Stiffness by Air-Puff Applanation.

PURPOSE: To assess the correlation of age and myopia with corneal and extraocular tissue stiffness derived from air-puff applanation using a composite viscoelastic model. METHODS: This retrospective, cross-sectional study evaluated 155 normal eyes (age range: 5 to 50 years) measured on Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany). Manifest refraction spherical equivalent was also analyzed. A linear viscoelastic model that segregated corneal and extraocular tissue stiffness from the applanation deformation waveform was implemented. Corvis ST measured the total deformation (deformation amplitude waveform), which was simply the sum of corneal and extraocular tissue deformation. Age- and myopia-based multivariate analyses of variance between deformation parameters were performed after adjusting for intraocular pressure and central corneal thickness. Corvis ST corneal hysteresis was also calculated from the corneal deformation waveform. RESULTS: All myopia and age groups were matched for intraocular pressure and central corneal thickness. Extraocular tissue stiffness significantly increased with age (P = .03). Some other extraocular tissue deformation parameters also correlated with age, indicating age-related stiffening (P < .05). Corneal and extraocular tissue stiffness decreased with increasing myopia, but the trend was not significant (P = .10). Corvis ST corneal hysteresis increased with increasing age (P = .01) but not with increasing myopia (P = .61). CONCLUSIONS: Extraocular deformation parameters indicated stiffening of the extraocular tissues with age. Corneal deformation parameters were unaffected by age and myopia. Further studies with larger sample sizes are needed to clearly understand the effect of myopia on corneal and extraocular tissue stiffness. [J Refract Surg. 2016;32(7):486-493.].

Diagnostic Efficacy of Normalization of Corneal Deformation Variables by the Intraocular Pressure in Glaucomatous Eyes.

PURPOSE: To analyze the diagnostic efficacy of normalization of corneal deformation variables by the IOP in healthy, primary-angle closure (PACG), and primary open angle glaucoma (POAG) patients. METHODS: Fifty-nine healthy, 83 POAG, and 57 PACG eyes, matched for age and pachymetry, were included in a prospective, observational, cross-sectional study. Goldmann applanation tonometry (GAT-IOP), Corvis-ST IOP, IOPg (Goldmann correlated), and IOPcc (cornea compensated) from the ocular response analyzer were acquired. Corneal hysteresis (CH) and corneal resistance factor (CRF) from the ORA, and deformation amplitude (DA) from Corvis-ST were analyzed. Further, ratios of CH, CRF, and DA to IOP were assessed among the groups and defined as new variables (e.g., ratio [CH, IOPcc] was the ratio of CH to IOPcc). RESULTS: Goldmann applanation tonometry-IOP, IOPcc, and IOPg of PACG and POAG eyes were significantly higher than normal (P < 0.05). Corvis-ST IOP of healthy eyes was similar to POAG (P > 0.05) but lower than PACG (P = 0.02). Corneal hysteresis and CRF of PACG and POAG were significantly lower than normal (P < 0.0001). The ratio (CH, IOPcc), ratio (CRF, IOPcc), and ratio (DA, IOPcc) of healthy eyes were significantly higher than those of PACG and POAG eyes (P < 0.0001). The sensitivity and specificity of ratio (CRF, IOPcc) and ratio (DA, IOPcc) was significantly better than CRF and DA alone in PACG eyes (P < 0.001). However in POAG, only the sensitivity and specificity of ratio (DA, IOPcc) was significantly better than DA alone (P < 0.001). CONCLUSIONS: Presence of glaucoma may be indicated better by ratio variables than by CH, CRF, or DA alone.

A cross-sectional study to compare intraocular pressure measurement by sequential use of Goldman applanation tonometry, dynamic contour tonometry, ocular response analyzer, and Corvis ST.

OBJECTIVE: To study the correlation and effect of sequential measurement of intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), ocular response analyzer (ORA), dynamic contour tonometer (DCT), and Corvis ST. SETTING AND DESIGN: Observational cross-sectional series from the comprehensive clinic of a tertiary eye care center seen during December 2012. METHODS: One hundred and twenty-five study eyes of 125 patients with normal IOP and biomechanical properties underwent IOP measurement on GAT, DCT, ORA, and Corvis ST; in four different sequences. Patients with high refractive errors, recent surgeries, glaucoma, and corneal disorders were excluded so as to rule out patients with evident altered corneal biomechanics. STATISTICAL ANALYSIS: Linear regression and Bland-Altman using MedCalc software. RESULTS: Multivariate analysis of variance with repeated measures showed no influence of sequence of device use on IOP (P = 0.85). Linear regression r2 between GAT and Corvis ST, Corvis ST and Goldmann-correlated IOP (IOPg), and DCT and Corvis ST were 0.37 (P = 0.675), 0.63 (P = 0.607), and 0.19 (P = 0.708), respectively. The Bland-Altman agreement of Corvis ST with GAT, corneal compensated IOP, and IOPg was 2 mmHg (-5.0 to + 10.3), -0.5 mmHg (-8.1 to 7.1), and 0.5 mmHg (-6.2 to 7.1), respectively. Intraclass correlation coefficient for repeatability ranged from 0.81 to 0.96. CONCLUSIONS: Correlation between Corvis ST and ORA was found to be good and not so with GAT. However, agreement between the devices was statistically insignificant, and no influence of sequence was observed.

Biomechanics of the cornea evaluated by spectral analysis of waveforms from ocular response analyzer and Corvis-ST.

PURPOSE: In this study, spectral analysis of the deformation signal from Corvis-ST (CoST) and reflected light intensity from ocular response analyzer (ORA) was performed to evaluate biomechanical concordance with each other. METHODS: The study was non-interventional, observational, cross-sectional and involved 188 eyes from 94 normal subjects. Three measurements were made on each eye with ORA and CoST each and then averaged for each device. The deformation signal from CoST and reflected light intensity (applanation) signal from ORA was compiled for all the eyes. The ORA signal was inverted about a line joining the two applanation peaks. All the signals were analyzed with Fourier series. The area under the signal curves (AUC), root mean square (RMS) of all the harmonics, lower order (LO included 1st and 2nd order harmonic), higher order (HO up to 6th harmonic), CoST deformation amplitude (DA), corneal hysteresis (CH) and corneal resistance factor (CRF) were analyzed. RESULTS: The device variables and those calculated by Fourier transform were statistically significantly different between CoST and ORA. These variables also differed between the eyes of the same subject. There was also statistically significant influence of eyes (left vs. right) on the differences in a sub-set of RMS variables only. CH and CRF differed statistically significantly between the eyes of subject (p<0.001) but not DA (p = 0.65). CONCLUSIONS: CoST was statistically significantly different from ORA. CoST may be useful in delineating true biomechanical differences between the eyes of a subject as it reports deformation.

Mutational screening of Indian families with hereditary congenital cataract.

PURPOSE: To screen for pathogenic mutations in ten candidate genes in Indian families diagnosed with autosomal recessive and autosomal dominant cataracts. METHODS: Families with two or more affected individuals with bilateral familial congenital/developmental cataract were ophthalmically evaluated, and blood samples were obtained. Genomic DNA extracted from the blood leukocytes was screened with PCR amplification of the exons and the flanking intronic regions of various genes selected for analysis. The amplified products were subjected to single strand conformation polymorphism (SSCP) analysis. The variants in SSCP analysis were subjected to bidirectional sequencing by automated methods. RESULTS: We identified four novel sequence changes that cosegregated with the disease phenotype in each family and were absent in at least 50 ethnically matched unrelated normal controls. These changes include a homozygous missense change of c.649G>A (Val196Met) in GJA8/connexin 50 (Cx50) in a family with autosomal recessive cataract, two heterozygous missense changes, c.658C>T (Pro199Ser) in GJA8/Cx50 and c.589C>T (Pro197Ser) in GJA3/connexin 46 (Cx46) in two separate families with autosomal dominant cataract, and a silent change ( c.84G>A/p.Val28Val, predicted to result in the creation of a new potential branch point) in GJA8 one family with an autosomal dominant inheritance of cataract. Of the four novel mutations identified, three mutations, Val196Met (GJA8), Pro199Ser (GJA8), and Pro197Ser (GJA3), are predicted to be in the second extracellular domain of the respective connexin proteins. CONCLUSIONS: Our report extends the mutation spectrum of connexin genes GJA8 and GJA3 and confirms that connexin genes are among the most frequently mutated genes in hereditary cataracts. Our results suggest that connexin gene (GJA8 and GJA3) mutations occur in approximately 10% (4/40 families) of families with congenital hereditary cataracts in a population from southern India.

Impact of a month-long training program on the clinical skills of ophthalmology residents and practitioners.

A cohort study was performed to assess the impact of an intensive, hands-on, supervised training program in ophthalmic clinical evaluation, for ophthalmology residents and private practitioners. All students underwent one-month training in comprehensive ophthalmology examination and investigations at a tertiary care center between January 2004 and January 2006. The training methodology included didactic lectures, video-demonstrations and hands-on training. The participants completed a self-assessment with a set of 23 questions designed to assess the level of confidence in various skills on the first and last day of the training. Of a total of 118 students, 67 (56.8%) were residents and 51 (43.2%) were practitioners. The mean score pre-training was 38.3 out of 92 (S.D. +/-16.9), and was 70.6 out of 92 (S.D.+/- 10.1) post-training. The mean increase in the scores was 32.3 (P value < 0.001). We concluded that intensive, short-term training programs could improve the self-perceived level of confidence of ophthalmology residents and practitioners.

Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract.

GJA8 encodes connexin-50, a gap junction protein in the eye lens. Mutations in GJA8 have been reported in families with autosomal dominant cataract. The objective of this report was to identify the disease gene in a family with congenital cataract of autosomal recessive inheritance. Eight candidate genes were screened for pathogenic alterations in affected and unaffected family members and in normal unrelated controls. A single base insertion leading to frameshift at codon 203 of connexin 50 was found to co-segregate with disease in the family. These results confirm involvement of GJA8 in autosomal recessive cataract.

A missense mutation in LIM2 causes autosomal recessive congenital cataract.

PURPOSE: To identify mutations in the LIM2 gene in families with hereditary congenital or juvenile-onset cataract. METHODS: Forty families (total of 100 affected and 84 unaffected individuals) were recruited for the study. Probands were screened for pathogenic alterations in 10 different candidate genes including the lens intrinsic membrane protein-2 (LIM2) gene. Exons and flanking regions were screened by polymerase chain reaction (PCR) amplification, single-strand conformation polymorphism, and sequencing. Sequence changes were evaluated in 75 unrelated normal controls. RESULTS: A missense mutation, Gly154Glu, was found in LIM2 in one family with four individuals diagnosed with autosomal recessive cataract from two generations. An evaluation of seven individuals (four affected and three unaffected) showed that the mutation was homozygous in the affected members and heterozygous in unaffected members tested. It was absent in 75 unrelated ethnically matched normal controls. All affected individuals had a severe phenotype of congenital cataracts and visual impairment. CONCLUSIONS: The Gly154Glu mutation involves a non-conservative change that presumably results in loss of function of the MP19 protein. This study shows the involvement of LIM2 in human congenital cataract.

Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract.

BACKGROUND: GJA8 encodes connexin-50, a gap junction protein in the eye lens. Mutations in GJA8 have been reported in families with autosomal dominant cataract. OBJECTIVE: To identify the disease gene in a family with congenital cataract of autosomal recessive inheritance. METHODS: Eight candidate genes were screened for pathogenic alterations in affected and unaffected family members and in normal unrelated controls. RESULTS: A single base insertion leading to frameshift at codon 203 of connexin 50 was found to co-segregate with disease in the family. CONCLUSIONS: These results confirm involvement of GJA8 in autosomal recessive cataract.