Whole-genome sequencing unravels novel genetic determinants and regulatory pathways associated with triamcinolone acetonide-induced ocular hypertension.

Glucocorticosteroids commonly used to treat certain ocular inflammatory conditions cause an unwarranted elevation in intraocular pressure (IOP) leading to steroid-induced ocular hypertension (OHT). This study aims to identify novel genetic variants in the Indian population associated with steroid responsiveness, specifically to that of intravitreal Triamcinolone acetonide (TA) injections, which leads to OHT in 27% of the TA-treated Indian subjects. Genetic determinants and pathways regulating TA-OHT progression were investigated by applying whole-genome sequencing (WGS) on DNA extracted from 53 blood samples that included TA responders and non-responders. Sequencing analysis yielded 45 intronic and 49 exonic variants to be associated with TA-OHT, which are known to play a vital role in eye, heart, brain, and bone deformities. Of these, the most significant genetic variant associated with TA-OHT was further considered for molecular dynamics (MD) simulation studies. Variants in the CRPPA, PLOD1, ARHGAP1, TIMELESS and TNFSF4 genes were found to be directly implicating TA-OHT. Furthermore, these genes were enriched in pathways associated with cardiomyopathy, focal adhesion, extracellular matrix, and actin cytoskeleton reorganization. MD simulation studies revealed that the top significant variant (rs141625803) in the CRPPA gene possesses a high pathogenic and structurally destabilizing effect. Thus, novel genetic variants that could be significantly associated with the TA-OHT progression were identified in this study. Validation of these targets in a larger cohort of patients along with their functional analysis would inform on the disease, thereby adding to the existing knowledge on the pathophysiology of TA-OHT.

Copper, Lysyl Oxidase Activity, and Collagen in Aqueous Humour of Primary Glaucoma: An Association with Clinical Parameters.

INTRODUCTION: To measure copper (Cu), lysyl oxidase (LOX) activity, and collagen levels in aqueous humour (AH) of primary glaucoma patients and correlate with clinical parameters. METHODS: 120 patients with 40 each of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and cataract controls were recruited in this case-control study. AH samples were collected during the trabeculectomy and cataract surgeries. Cu levels were measured using an atomic absorption spectrophotometer. LOX unit activity was determined by Amplex Red assay and collagen concentration by Sirius red assay. RESULTS: Significantly higher levels of Cu expressed as median (IQR) µmol/L were observed in POAG (p = 0.008) and PACG (p = 0.005) compared to controls. The LOX activity was increased in POAG and PACG (p = 0.04) compared to controls represented as median (IQR) µmol/min. The collagen levels given as median (IQR) mg/ml showed an insignificant increase in POAG and PACG compared to controls (p = 0.78). The LOX unit activity was correlated with visual field index (VFI), which showed a significant increase with the progression of the diseases (p < 0.05), whereas Cu levels were negatively correlated with LOX activity in AH. Cu and LOX activity showed weak correlation with YAG peripheral iridotomy (YAGPI), duration of anti-glaucoma medications, and highest preoperative intraocular pressure. CONCLUSION: Elevated Cu and LOX activity was observed in both POAG and PACG groups compared to controls. LOX activity showed notable increase with VFI as the severity of the disease. Although Cu levels are increased in glaucoma, it's insufficient to significantly increase the activity of LOX.

Anti-glaucoma medications lowered decorin and altered profibrotic proteins in human tenon's fibroblasts.

Long term exposure to anti-glaucoma medications (AGMs) leads to an increase in extracellular matrix (ECM) accumulation in primary glaucoma patients. This study aims to evaluate the effect of topical AGMs in primary human tenon's fibroblasts (HTFs) and analyze the expression of profibrotic and anti-fibrotic proteins. Primary HTFs were cultured from patients undergoing cataract (control) and trabeculectomy. The different types of AGMs in single/multiple combinations (BB, PG, AA, CAI, CH, combinations of 3- PG + AA + CAI, 4A- BB + PG + AA + CAI, 4B- BB + PG + CAI + CH and 5- BB + PG + AA + CAI + CH) on chronic exposure were tested for cell viability using MTT assay and morphological alterations. Profibrotic proteins mainly SPARC, LOXL2, COL1A1 and anti-fibrotic DCN were analyzed in treated HTFs using q-PCR and ELISA. Sirius red staining and collagen gel contraction (CGC) assay were performed to assess collagen synthesis and the contractility of HTFs, respectively. Except for AA and CH, the other AGMs at a higher concentration were found to decrease the cell viability of HTFs. The morphology of HTFs were altered on exposure to BB, CH and AA; Profibrotic proteins i.e., SPARC, LOXL2 and COL1A1 were significantly increased (p < 0.05) on exposure to a combination of AGMs with TGF-ß1, whereas the anti-fibrotic DCN expression was significantly lowered (p < 0.05) in single/multiple AGM exposure. Sirius red staining showed increased collagen synthesis with combinations of AGMs with TGF-ß1. Meanwhile, HTFs showed increased collagen gel contraction with TGF-ß1, CAI and CH. This study reveals that altered profibrotic proteins, with significantly lowered DCN on chronic exposure of AGMs in HTFs.

Incidence, Risk Factors, Treatment, and Outcome of Ocular Hypertension following Intravitreal Steroid Injections: A Comparative Study.

PURPOSE: To compare the incidence, risk factors, treatment, and outcomes associated with intravitreal triamcinolone-acetonide (TA) and dexamethasone-implant (Dex)-induced ocular hypertension (OHT). METHODS: This retrospective study reviewed 1,549 TA and Dex administrations in 1,075 eyes of 897 patients. Intraocular pressure (IOP) values were monitored for a period of 6 months following intravitreal injection(s) and patients were categorized as steroid-responders (SR): IOP≥21 mm Hg, and steroid non-responders (NR): IOP≤20 mm Hg. Glaucoma patients, glaucoma suspects, uveitis, trauma, and less than 1 month of IOP follow-up cases were excluded from the study. The incidence of IOP rise, time and magnitude of IOP rise, and its management procedures were studied. Ocular and systemic associations with OHT incidence were investigated. Statistical analysis was performed using SPSS.23 and p < 0.05 was considered significant. RESULT: Twenty-eight percent of TA and 17% of Dex administered eyes developed OHT. Male subjects and elderly people (greater than 40 years of age) are at higher risk for OHT following steroid treatment. A high percentage of IOP rise was observed on day 1 (41%) for TA-SR, and after 1 month (50%) for Dex-SR. IOP rise was found to be more severe (>30 mm Hg) for TA-SR compared to Dex-SR (p = 0.006). 6% TA-SR required trabeculectomy with medically uncontrollable IOP. Myopia is a risk factor for secondary OHT, whereas diabetes mellitus and hypercholesterolemia are protective of it. CONCLUSION: Twenty-eight percent of TA and 17% of Dex administrations developed OHT. Early and severe IOP rises were more common in TA than among Dex administrations. Myopia is a risk for Dex-OHT.

INTRAOCULAR PRESSURE OUTCOMES AFTER SURGERY FOR RHEGMATOGENOUS RETINAL DETACHMENT IN SCHWARTZ SYNDROME.

PURPOSE: To study intraocular pressure (IOP) outcomes after surgery for rhegmatogenous retinal detachment in Schwartz syndrome. METHODS: We reviewed records of 32 eyes of 32 patients with Schwartz syndrome (patients with rhegmatogenous retinal detachment, IOP above 21 mmHg, and open angles without angle recession, chronic steroid use or other secondary causes of increased IOP) who had undergone surgical treatment consisting of scleral buckling or vitrectomy. Intraocular pressure, number of medication, best-corrected visual acuity were compared at baseline and postsurgery visits and also studied association of various factors on long-term IOP. RESULTS: The median duration of rhegmatogenous retinal detachment was 2 months, and the inter quartile range was 1 to 12 months. Follow-up was 15 months (inter quartile range: 7-33 months). Sixteen (50%) had prior ocular trauma. Baseline IOP was 35 ± 8 mmHg, and 12% (4/32) of patients were on IOP-lowering medication at presentation. At the final visit, mean IOP was 17 ± 6 mmHg and 59% patients (19/32) required additional IOP-lowering medication or surgery for IOP control. CONCLUSION: Surgical management of rhegmatogenous retinal detachment resulted in significant reduction in IOP. At the final visit, 41% did not require any IOP-lowering medication or surgical intervention for IOP control.

Eye Movement Perimetry and Frequency Doubling Perimetry: clinical performance and patient preference during glaucoma screening.

PURPOSE: To evaluate the screening accuracy of an Eye Movement Perimetry (EMP) in comparison with Frequency Doubling Perimetry (FDP) and to investigate the patient preference and perception towards these visual field screening methods. METHODS: A total of 104 healthy subjects (mean age (SD) of 48 (14) years) and 73 glaucoma patients (mean age (SD) of 52 (13) years) were recruited. All the participants underwent a comprehensive ophthalmic evaluation including the 24-2 SITA standard protocol on the Humphrey Field Analyzer (HFA). This was followed by the 26-point protocol in EMP and the C-20-1 protocol in FDP. During EMP, all subjects were instructed to fixate a central target and to look at the detected peripheral target, followed by refixation of the central target and Saccadic Reaction Time (SRT) towards each of the "seen" stimuli was calculated. Next, a questionnaire was administered to evaluate the patient preference and perception towards the perimetry techniques. Mean SRTs and Robin scores were used to plot Receiver Operating Characteristics (ROC) curves to determine the screening accuracies. From the questionnaire survey, the frequency distributions of the responses were calculated. RESULTS: Robin score and SRT were significantly increased in glaucoma patients in comparison with the age-matched healthy subjects (p < 0.001). The ROC analysis revealed comparable Area Under the Curve (AUC) values (0.95, p = 0.81) with a specificity of 95.2% for FDP and 96.2% for EMP with a sensitivity of 87.7%. Thirty-seven percent of the older age group (≥ 40 years) and 65% of severe glaucoma patients showed preference for EMP over FDP. CONCLUSIONS: This study results indicate that the customized protocol in EMP provides efficient and rapid means of screening visual field defects in glaucoma, which compared well with FDP. Elderly healthy participants and patients with moderate and severe glaucomatous defects preferred EMP as it permitted natural reflexive eye movements thereby resembling a real-life test setting.

INTRAOCULAR PRESSURE CHANGES AFTER DEXAMETHASONE IMPLANT IN PATIENTS WITH GLAUCOMA AND STEROID RESPONDERS.

PURPOSE: To assess the changes in intraocular pressure (IOP) after dexamethasone (DEX) implant in patients with glaucoma or history of steroid responders. METHODS: A retrospective study of patients who received DEX implant was conducted in a tertiary care center in India. Demographic details and IOP measurements at preinjection and postinjection were collected. The proportion of patients with and without IOP rise after DEX implant was noted, and the number of antiglaucoma medications to control the IOP was analyzed. The changes in IOP were also compared in the group with no glaucoma/steroid responder. RESULTS: A total of 815 patients, 767 patients in the nonglaucoma group and 48 patients in the glaucoma referral group, who underwent DEX implant were included in this study. The overall mean (SD) age of study participants was 56.3 (SD = 12.6) years. The overall mean (SD) IOP at baseline and at follow-up after injection for both nonglaucoma and glaucoma referral groups was found to be significant (P < 0.001). The differences in IOP measurements across follow-ups after DEX implant were found to be significant in both nonglaucoma (P < 0.001) and glaucoma referral groups (P < 0.001). Among the study patients in the IOP-rise group, 46.43% had maximum IOP rise in 1-week follow-up and 39% in 2-week follow-up, where 78.6% showed IOP controlled with 1 antiglaucoma medication. CONCLUSION: The rise in IOP after DEX implant was noted within first 2 weeks, which can be managed with topical antiglaucoma medications. Hence, with a close early follow-up monitoring of IOP, and timely medical intervention, DEX implant can be performed in patients with glaucoma.

Can Corneal Biomechanical Properties Explain Difference in Tonometric Measurement in Normal Eyes?

SIGNIFICANCE: Corneal biomechanical parameters can affect intraocular pressure (IOP) measurements by different tonometers compared with Goldmann applanation tonometer. This study implies that corneal hysteresis (CH) and corneal resistance factor (CRF) better explain variability in IOP measurements. PURPOSE: The aim of this study was to evaluate the effect of corneal properties on the difference in IOP measured by the Ocular Response Analyzer (ORA), Rebound Tonometer (RBT), Dynamic Contour Tonometer (DCT), and Tono-Pen from the Goldmann applanation tonometer (GAT). METHODS: An observational study was done on healthy participants in a tertiary eye care center. Corneal curvature was measured with a manual keratometer prior to IOP measurements. Intraocular pressure was measured by a single trained examiner with ORA, RBT, DCT, GAT, and Tono-Pen. CH and CRF were measured using the ORA. Central corneal thickness was measured using the ultrasonic pachymeter. Only the right eye was included for analysis. One-way analysis of variance was performed to compare variables, Bland-Altman plots to assess agreement, and regression analyses to study associated factors. RESULTS: We included 82 eyes of 82 participants with a mean age of 40.9 (14.3) years. Mean ± SD DCT IOP (15.22 ± 1.98) mmHg was significantly higher than GAT IOP (13.73 ± 2.42) (P = .01) and ORA Goldmann correlated IOP (13.66 ± 3.16) (P = .003). The limits of agreement between GAT and other tonometers measurements ranged between -5.0 and 2.1 mmHg. With multiple linear regression analyses, CH and CRF were found to be associated with the measured IOP differences between GAT and ORA (corneal compensated IOP and Goldmann correlated IOP) (P < .001) and DCT (P = .014, <.001) whereas differences between GAT and RBT measurements were independently explained by corneal curvature (P = .035) and central corneal thickness (P = .045). CONCLUSIONS: There was good agreement between GAT and other tonometers, but was not good enough for them to be used interchangeably. A combination of CH and CRF may better explain the variability between GAT and tonometers.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Six-year incidence of visually significant age-related cataract: the Chennai eye disease incidence study.

BACKGROUND: The aim of this study is to report the 6-year incidence of age-related cataract in a population-based study. DESIGN: The design used is a population-based cohort study. PARTICIPANTS: A cohort of 2484 phakic subjects, aged 40 years and above at baseline, from a south Indian population was included in the study. METHODS: Bilateral phakics with visual acuity of 6/12 or better and cataract less than N2, C2 and P2 on the Lens Opacities Classification System II at baseline were included. Subjects with glaucoma and corneal or retinal diseases were excluded. Incident visually significant cataract was defined as visual acuity of less than 6/18 with a corresponding one grade or greater change in Lens Opacities Classification System II or history of having undergone cataract surgery with evidence of pseudophakia or aphakia at the 6-year follow-up. MAIN OUTCOME MEASURES: Six-year incidence of visually significant cataract and associated risk factors data were collected. RESULTS: Incident visually significant cataract at 6 years was seen in 158 subjects (6.36%, 95% CI: 5.40-7.32, phakics:pseudophakics/aphakics 70:88). Incidence was higher in the rural cohort as compared with the urban cohort (P < 0.001). Incidence increased with age and was highest in the ≥70 years age group (odds ratio (OR):31.23, 95% CI: 15.20-64.16, P < 0.001). Other associated risk factors included illiteracy (OR 1.75, 95% CI: 1.17-2.61, P = 0.007) and smoking (OR 1.77, 95% CI: 1.08-2.88, P = 0.02). CONCLUSIONS: A significant proportion of the population developed visually significant age-related cataract at 6 years. Incident visually significant cataract was significantly greater for the rural cohort between 50 and 69 years old.

Six-Year Incidence and Baseline Risk Factors for Pseudoexfoliation in a South Indian Population: The Chennai Eye Disease Incidence Study.

OBJECTIVE: To estimate the 6-year incidence of pseudoexfoliation and its risk factors in a South Indian population. DESIGN: Longitudinal population-based study. PARTICIPANTS: Subjects 40 years of age or older without pseudoexfoliation at baseline. METHODS: Participants were examined at baseline and after a 6-year interval. The presence of pseudoexfoliation was looked for after pupillary dilation in either or both eyes at 1 or more locations. Glaucoma was defined using the International Society of Geographical and Epidemiological Ophthalmology Classification. Logistic regression was performed to identify the baseline risk factors that could predict the incident pseudoexfoliation. MAIN OUTCOME MEASURES: Six-year incidence, associated risk factors, and rural-versus-urban differences. RESULTS: From the study cohort of 4228 subjects, 87 subjects (male-to-female ratio, 48:39; rural-to-urban ratio, 69:18) demonstrated incident pseudoexfoliation (2.03%; 95% confidence interval [CI], 1.6-2.5; rural: -2.86%; 95% CI, 1.6-2.5; urban: 0.96%; 95% CI, 0.5-1.4). Pseudoexfoliation was associated with glaucoma in 1 subject (1.1%), with primary angle-closure suspicion in 10 subjects (11.5%), and with ocular hypertension in 2 subjects (2.2%). Significant predictive baseline risk factors were older age (P < 0.001), rural residence (P < 0.001), illiteracy (P = 0.02), pseudophakia (P = 0.04), and nuclear cataract (P = 0.05). With reference to the 40-to-49-year age group, the risk of incidence increased from 4.7 (95% CI, 2.4-9.4) for the 50-to-59-year age group to 12.9 (95% CI, 6.1-27.2) for 70 years of age and older group. CONCLUSIONS: In 6 years, pseudoexfoliation developed in 2.03% of the population. Rural and urban incidence was significantly different.

Predictors for incidence of primary open-angle glaucoma in a South Indian population: the Chennai eye disease incidence study.

OBJECTIVE: To determine the 6-year incidence of primary open-angle glaucoma (POAG) and its associated predictors. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 4316 subjects without POAG at baseline who were 40 years of age and older from a south Indian population. METHODS: Participants were examined at baseline and after a 6-year interval. Detailed ophthalmic examination included applanation tonometry, gonioscopy, pachymetry, optic disc evaluation, and automated perimetry. Glaucoma was defined using the International Society of Geographical and Epidemiological Ophthalmology Classification. Multivariable logistic regression was performed to identify the baseline risk factors that could predict the incident POAG. MAIN OUTCOME MEASURES: Six-year incidence of POAG and its associated risk factors. RESULTS: In 6 years, incident POAG developed in 129 subjects (2.9%; 95% confidence interval [CI], 2.4-3.4; male-to-female ratio, 65:64). Baseline age was a risk factor. In reference to the group 40 to 49 years of age, the incidence increased from 2.3 (95% CI, 1.4-3.7) for the group 50 to 59 years of age to 3.5 (95% CI, 2.2-5.7) for the group 60 to 69 years of age (P<0.001). Other baseline risk predictors were urban residence (odds ratio [OR], 1.6; 95% CI, 1.1-2.2; P = 0.01), higher intraocular pressure (IOP; OR, 2.0; 95% CI, 1.5-2.6 per 10 mmHg; P<0.001), myopia (OR, 1.7; 95%, CI, 1.1-2.5; P<0.001), and axial length (OR, 1.5; 95% CI, 1.0-2.2 per millimeter; P = 0.03). Thinner corneas with higher IOP at baseline had the highest incidence of POAG. In 80% of the urban population and 100% of the rural population, incident glaucoma was previously undetected. CONCLUSIONS: A significant proportion of this population demonstrated incident POAG. The baseline risk factors could help in identifying those at highest risk of disease.

To identify risk factors for central visual field progression in moderate to advanced glaucoma.

PURPOSE: To identify the risk factors for central visual field progression in moderate to advanced glaucoma. METHODS: We included patients with moderate to advanced primary glaucoma who had undergone at least five reliable Humphrey visual field (HVF) 10-2 tests with follow-up of at least 2 years. Regression slopes for each threshold location on the 10-2 plot were calculated. A test location with a regression slope worsening more than -1 dB/year with P < 0.01 was labeled as a progressing point on point-wise linear regression (PLR) analysis. We compared point-wise progression with progression on the 10-2 mean deviation (defined as a negative MD slope P < 0.05). RESULTS: Ninety-six eyes of 74 patients with a median follow-up of 4 years (±1.97) were included. The median mean deviation 10-2 (MD) at inclusion was -19.01 dB (interquartile range [IQR] -13.2 to -24.14). Eighteen eyes (18.75%) had moderate glaucoma and 78 eyes (81.25%) had advanced glaucoma. The baseline median 24-2 MD in moderate glaucoma was -10.35 dB (IQR -11.35 to -9.25) and in advanced glaucoma was -24.96 dB (IQR -28.48 to -18.26). Based on 10-2 PLR, 27 eyes (28%) showed progression. On multivariate logistics regression analysis, the rate of change for 10-2 MD was a risk factor for progression based on 10-2 PLR analysis: odds ratio (OR) 0.04 (95% confidence interval [CI]: 0.006-0.323), P = 0.002, and for progression based on 10-2 MD analysis: OR 0.03 (95% CI: 0.002-0.602), P = 0.02. In addition, average MD 24-2 (OR 1.343 [95% CI: 1.006-1.793], P = 0.04) and visual field index (OR 0.787 [95% CI: 0.649-0.954], P = 0.01) were found to be risk factors based on 10-2 PLR. CONCLUSION: Rate of change for 10-2 mean deviation and baseline damage were predictors of point-wise progression.

Understanding the treatment paradigm and the sequencing of antiglaucoma fixed-dose combinations in a tertiary center in South India.

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India. METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications (AGMs) after 5 years. RESULTS: Three hundred and seventy eyes (198 patients) were analyzed; 84% of them had POAG. Prostaglandin analogs (PGAs) were the most common (66.2%). FDCs were started in 48 eyes (12.9%), with brimonidine + timolol combination being the most common. FDC usage at subsequent modifications was 10.1%, 24.04%, and 30.0%. Beta-blockers and PGAs were the most frequently prescribed AGMs in our practice pattern, with ß-blockers being the most consistent one. CONCLUSION: This study is a fairly large study with a minimum of a 5-year follow-up of patients with POAG and OHT and gives insights into the treatment patterns, use of FDCs, and the need for multiple medications over time.

Barriers and Potential Solutions to Glaucoma Screening in the Developing World: A Review.

PURPOSE: Glaucoma is a leading public health concern globally and its detection and management are way more complex and challenging in the developing world. This review article discusses barriers to glaucoma screening in developing countries from the perspective of different key stakeholders and proposes solutions. METHODS/RESULTS: A literature search was carried out in the electronic catalogs of PubMed, Medline, and Cochrane database of systematic reviews to find studies that focused on barriers and enablers to glaucoma screening. The authors' interpretations were tabulated as descriptive and qualitative data and presented concisely from the point of view of key stakeholders such as the patients and their relatives, care providers, and system/governing bodies. Key barriers to glaucoma care identified are lack of awareness, poor accessibility to ophthalmic centers, inadequately trained human resources, unsatisfactory infrastructure, and nonavailability of financially viable screening programs. Educating care providers, as well as the public, providing care closer to where people live, and developing cost-effective screening strategies are needed to ensure proper identification of glaucoma patients in developing countries. CONCLUSIONS: The logistics of glaucoma detection and management are complex. Hence, glaucoma detection programs should be implemented only when facilities for glaucoma management are in place. Understanding the importance of glaucoma screening and its future implications, addressing the various roadblocks, empowering and efficiently implementing the existing strategies, and incorporating novel ones using Artificial Intelligence (AI) and deep learning (DL) will help in establishing a robust glaucoma screening program in developing countries.

Characterization of Gaze Metrics and Visual Search Pattern Among Glaucoma Patients While Viewing real-world Images.

PRCIS: We quantified and compared the gaze metrics during target-oriented visual search tasks between glaucoma and healthy controls. Based on a mathematical concept we showed that due to glaucoma, focal search becomes prominent over global search. PURPOSE: Visual Search (VS) which is essential for target identification and navigation is significantly impacted by glaucoma. VS metrics can be influenced by differences in cultural exposure or coping strategies, leading to varying VS patterns. The aim of this study was to explore and label the pattern of VS based on gaze metrics quantified using eye-tracking technology. METHODS: Twenty-seven glaucoma subjects and thirty healthy controls (median age 51 (14) and 54 (19) years respectively) underwent a VS experiment during which they had to identify specific targets from real-world images. Eye movements were recorded using a remote eye-tracker and gaze metrics - Fixation Count (FC), Fixation Duration (FD), Saccade Amplitude (SA), and VS Time (VST) were computed and compared between the study groups. A Z-score-based coefficient 'K' was derived to label the search patterns as global (K ≤ - 0.1: short FD with long SA), focal (K ≥ +0.1: long FD with short SA), or a combination (K between +/-0.1). RESULTS: Similar to other ethnicities, Indian glaucoma subjects also exhibited statistically significantly increased FC, FD, and VST (P=0.01). Healthy controls presented a comparable proportion of focal (47%) and global (42%) search patterns while glaucoma subjects exhibited predominantly focal (56%) than global search patterns (26%, P=0.008). CONCLUSIONS: This study suggests that glaucoma subjects perform more focal search during active gaze scanning. This change in viewing behavior reflects underlying compensatory strategies adapted for coping with their visual impairments. These search patterns can be influenced by factors such as saliency which requires further investigation.

Effect of beta blockers on optical coherence tomography angiography in normal, suspect, and glaucomatous eyes: A prospective study.

PURPOSE: The study aimed to assess the effect of hypertension, and use of systemic beta blockers (BB) and other antihypertensives on ocular perfusion by optical coherence tomography angiography (OCTA) in normal, suspect, and glaucomatous eyes. METHODS: Cross-sectional study in tertiary eye care center. Prospectively recruited consenting subjects between 18 and 90 years with or without glaucoma. Measured the optic nerve peripapillary perfusion and flux and macular vessel density (MVD: 6 × 6 and 3 × 3 mm) in the superficial retinal layer using OCTA. RESULTS: Included 200 eyes (112 patients). Compared to nonhypertensives or those on non-BB antihypertensives (NBB), hypertensives on BB had lower peripapillary perfusion (43.45,43.40, 42.05%, P = 0.003), and MVD (6 × 6 mm: 16.65, 16.70,15.75 mm/mm 2 , P = 0.002; 3 × 3 mm: 18.70, 18.50, 18.00 mm/mm 2 , P = 0.025). Those on systemic BB with vasodilatory properties had similar perfusion parameters as nonhypertensives and NBB. Those on systemic BB without vasodilating properties had significantly lower peripapillary perfusion (42.05 vs 43.30%, P = 0.011) and MVD (6 × 6 mm: 15.15 vs 16.60 mm/mm 2 , P < 0.001; 3 × 3 mm: 17.40 vs 18.70 mm/mm 2 , P = 0.005) compared to nonhypertensives. On multivariate analysis, peripapillary perfusion increased with increase in diastolic blood pressure (ß:0.051, p: 0.04) and increasing age was the only factor found to be significantly associated with decreased peripapillary and macular perfusion parameters. CONCLUSION: Systemic BB users have worse ocular perfusion parameters compared to those on other medications or nonhypertensives on univariate analysis but similar perfusion on multivariate analysis. Those on BB with vasodilation have better ocular perfusion parameters. All BB cannot be considered equally detrimental to ocular perfusion. Further well-controlled prospective studies are needed to reassess the effects of BB with or without vasodilation on ocular perfusion.

Omidenepag Isopropyl 0.002% versus Latanoprost 0.005% in Open-Angle Glaucoma/Ocular Hypertension: The Randomized Phase III PEONY Trial.

Purpose: To compare the efficacy and safety of omidenepag isopropyl (OMDI) 0.002% with latanoprost 0.005% once daily in Asian subjects with open-angle glaucoma (OAG)/ocular hypertension (OHT). Methods: In this Phase III randomized, observer-masked, active-controlled, multinational trial (NCT02981446), subjects aged ≥18 years with OAG/OHT in both eyes and baseline intraocular pressure (IOP) ≥22 mmHg and ≤34 mmHg were randomized 1:1 to OMDI or latanoprost. IOP was measured at 9AM, 1PM, and 5PM at baseline, 1 week, 6 weeks, and 3 months. Adverse events (AEs) were recorded. Non-inferiority of OMDI to latanoprost was tested for primary and key secondary endpoints. Results: Each group included 185 subjects. Mean diurnal IOP from baseline to month 3 was reduced 7.1 mmHg (28.8%) with OMDI and 7.8 mmHg (31.3%) with latanoprost, with the least-squares mean difference (OMDI minus latanoprost) being 0.6 mmHg (95% CI: 0.0, 1.2 mmHg; p = 0.0366), indicating non-inferiority. Mean IOP reductions at the nine timepoints were -5.8 to -7.3 mmHg (23.5-29.5%) for OMDI and -6.1 to -7.9 mmHg (24.3-31.7%) for latanoprost. Non-inferiority per FDA criteria was also met. Rates of all AEs, ocular AEs, and ocular AEs associated with treatment were 40.0%, 36.8%, and 23.2%, respectively, for OMDI and 29.7%, 21.1%, and 11.9%, respectively, for latanoprost. Conjunctival hyperemia rates were higher with OMDI than latanoprost (11.9% vs 5.4%). Most AEs were mild, with no serious ocular AEs. Conclusion: OMDI safely and effectively reduces IOP in Asian subjects with OAG/OHT, with mean diurnal IOP at Month 3 and per-timepoint IOP reductions non-inferior to those of latanoprost.

PEONY Study: Testing How Well and How Safely Omidenepag Isopropyl Eye Drops Treat People with Glaucoma or Ocular Hypertension Compared with Latanoprost. Who took part in the study? Three hundred and seventy participants average age of 57 years, from 34 centers across four Asian countries who had glaucoma or high pressure in both eyes were randomly divided into two groups. One group (185 people; 50%) was given OMDI, and the other group (185 people; 50%) latanoprost for 3 months. The intraocular pressure of both eyes was measured in all participants at three time points (9 AM, 1 PM, and 5 PM) after 1 week, 6 weeks, and 3 months of treatment. The primary endpoint was the average of the daily eye pressure after 3 months of treatment. The safety of OMDI was also assessed. Study results. After 3 months of treatment, OMDI decreased the eye pressure by 29%. This was similar to latanoprost, which decreased the eye pressure by 31% over the same time period. OMDI was safe and well tolerated by those participants who received it. The most common side-effect in people receiving OMDI or latanoprost was conjunctival hyperemia (red eye) (experienced by 22 people receiving OMDI, and 10 people receiving latanoprost). Conclusions After 3 months of use, OMDI was found to safely reduce high eye pressure to a similar level as latanoprost in Asian people with glaucoma or high eye pressure.

Effect of ethnic diversity on the saccadic reaction time among healthy Indian and Dutch adults.

Eye movement perimetry (EMP) expresses the decline in visual field (VF) responsiveness based on the deviation in saccadic reaction times (SRTs) from their expected age-similar responses (normative database). Since ethnic dissimilarities tend to affect saccade parameters, we evaluated the effect of such a factor on SRT and its interaction with age, stimulus eccentricity, and intensity. 149 healthy adults, spread into five age groups, drawn from Indian and Dutch ethnicities underwent a customized EMP protocol integrated with a saccade task from which the SRTs to 'seen' visual stimuli were computed. The EMP test had a total of 54 coordinates (five stimulus eccentricities) tested using Goldmann size III visual stimuli presented at four stimulus intensity (SI) levels against a constant background. Considering SRT as a dependent variable, a Generalized Linear Mixed Model analysis was conducted that revealed a statistically significant (p < 0.001) influence of ethnicity and interaction between the tested factors (ethnicity × age × stimulus eccentricity × intensity). However, during the post hoc analysis, out of the 100 possible pair-wise comparisons, only 6% (minor proportion) of the estimates showed statistical significance. Hence, the ethnic-specific differences need not be accounted for while implementing EMP in a diverse set of populations instead a collective database might serve the purpose.

Stereoacuity in mild, moderate and severe glaucoma.

PURPOSE: To determine the association between stereoacuity and severity of glaucoma. METHODS: Stereoacuity was measured using the Titmus stereo test for 97 glaucoma subjects with visual acuity better than 0.3 logMAR (6/12, 20/40 Snellen) and reliable Humphrey visual fields (24-2 SITA standard). The severity of visual fields was graded with the Hodapp-Anderson-Parrish (HAP) classification and visual fields index (VFI) score and the stereoacuities for different grades were compared. Presence of a significant field defect (p < 1%) in any one of the paracentral points in 10-2 SITA standard/Macular threshold was considered as a threat to fixation. RESULTS: Mean ± SD age of the subjects was 57.28 ± 14.0 years. The median [inter-quartile range, (IQR)] stereoacuity of the 97 subjects was 50 (40-100) arc sec with 13 subjects having stereoacuity of >3000 arc sec. Median (IQR) stereoacuity of 97 subjects classified with HAP as mild, moderate and severe were 40 (40-40), 50 (40-60) and 60 (40-400) arc sec; similarly median (IQR) stereoacuity of the subjects classified using VFI as mild, moderate and severe were 40 (40-55), 60 (40-100) and 120 (50-3000) s of arc and the difference between groups were significant (p < 0.001). Median (IQR) stereoacuity in subjects with no threat to fixation (45) and threat to fixation in at least one eye (52) were 40 (40-60) and 70 (40-800) arc sec (p < 0.001). CONCLUSIONS: Decreased stereoacuity was associated with greater glaucomatous visual field loss, although it was normal with early visual field defects. Relatively moderate defects can be associated with decreased stereoacuity and it is more pronounced in the severe stages of the disease when there is a threat to fixation.