Performance of perimetric glaucoma staging systems and their preference patterns among the Indian eye care practitioners.

CONTEXT: Various systems are available to stage glaucomatous field defects into different severity grades. Still, the preference for such systems among Indian eye care practitioners (ECPs) and the consensus between them are not explored. PURPOSE: To compare the clinical performance of perimetric glaucoma staging systems and to assess their preference patterns among Indian ECPs. SETTING AND DESIGN: Retro-prospective cross-sectional study. METHODS: Three investigators stratified 400 perimetry reports using four systems: Hodapp Anderson Parrish (HAP), enhanced Glaucoma Severity Staging (eGSS), Advanced Glaucoma Intervention Study (AGIS), and Collaborative Initial Glaucoma Treatment Study (CIGTS). Their performance was compared in terms of agreement and association. Following this, 30 ECPs from across the country segregated a subset of reports (n = 20) into different stages based on their system of choice, and their preferences/perceptions about the available perimetry staging systems were enquired and documented. STATISTICAL ANALYSIS USED: Descriptive statistics, Kruskal-Wallis, Cohen's kappa, and Spearman's correlation. RESULTS: For the consolidated severity stages, substantial agreements (K ranging from 0.61 to 0.75) were found between all the systems, except for HAP-CIGTS (K = 0.58) and AGIS-CIGTS (K = 0.51). All ECPs were aware of perimetry staging systems, and a high preference was reported for HAP (97%) due to ease of implementation and interpretation. CONCLUSION: Among the four staging systems, the highest agreement was found between HAP and eGSS. A majority of ECPs proposed the need for a uniform classification system across the practices for clinical comparisons and patient education.

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.

A Study on the Candidate Gene Association and Interaction with Measures of UV Exposure in Pseudoexfoliation Patients from India.

PURPOSE: Environmental and genetic factors are associated with development of Pseudoexfoliation syndrome (XFS). Here we intended to elucidate the association of candidate genes in relevance to UV exposure in these patients. METHODS: This is a case-control study of 309 subjects (N = 219 controls and 90 XFS cases) from India. PCR based direct sequencing was performed for candidate genes (LOXL1, POMP and TMEM136) followed by genotype and haplotype analysis. The promoter methylation status was assessed by Methylation specific PCR based direct sequencing of genomic DNA for all samples. The methylation status was compared with that of primary fibroblasts cultures established from patient's Tenon's tissue samples in subset of these patients. RESULTS: SNPs rs3825942, rs41435250, rs8818 (LOXL1) and rs3737528 (POMP) showed significant association with XFS. LOXL1 gene haplotype GAGC (rs1048661- rs3825942- rs41435250-rs8818) was associated with lower risk for XFS with a p value 4.1961 × 10-6 (OR =0; 95%CI, 0.000-0.003). POMP gene haplotypes for intronic SNPs (rs1340815- rs3737528- rs913797) TCC and TTC were associated with increased risk for the disease (OR > 1.0). Significant correlation for SNPs rs3825942 of LOXL1 (ρ= -0.132) and rs3737528 of POMP (ρ = 0.12) was observed with measure of lifetime UV exposure (CUVAF value). Reduced LOXL1 gene expression was observed in cultured tenon fibroblasts from the patients that correlated with differential methylation of the Sp-1 binding sites at -253, -243bp upstream to the transcription start site of LOXL1 promoter region. CONCLUSION: Our results suggest a possible interaction for LOXL1 gene haplotype (GAGC) with the measure of ocular UV exposure in pseudoexfoliation syndrome.

Impact of Monocular and Binocular Visual Function Parameters on Vision-Related Quality of Life in Glaucoma.

PRCIS: This study describes the impact of monocular (M/O) and binocular (B/O) visual function decline, primarily the contrast sensitivity (CS) and visual field (VF) defect severity and its location, on the subjective perception of quality of life (QoL) among the Indian glaucoma population with spared central acuity. AIM: To investigate the influence of M/O and B/O visual function parameters on vision-related QoL (VRQoL) in glaucoma with spared central visual acuity. MATERIALS AND METHODS: Glaucoma subjects underwent M/O and B/O visual acuity, CS assessment, followed by the M/O perimetry from which the integrated VF was estimated (B/O summation method). VRQoL was evaluated using the Glaucoma Quality Of Life-15 (GQL-15) and Visual Function Questionnaire-Utility Index (VFQ-UI) questionnaires. The relationship between CS and VF defect (VFD) with the composite VRQoL scores was analyzed. RESULTS: A total of 154 glaucoma subjects with a median age of 61 (range: 24-83) years were enrolled. Subjects with severe VFD reported poor composite scores for GQL-15 and VFQ-UI when compared with unilateral and mild groups ( P < 0.001, Dunn post hoc). Both the composite scores were negatively correlated with M/O and B/O CS and VF mean deviation ( r range: -0.3 to -0.5, P < 0.001, Spearman rank correlation). B/O VFD in the inferior central zone contributed to poor GQL-15 score [odds ratio: 1.14 (95% CI: 1.10-1.29), P = 0.04] irrespective of sex, whereas females with increasing B/O VFD reported poor QoL score in VFQ-UI [odds ratio: 4.09 (95% CI: 1.77-9.43), p=0.003]. CONCLUSIONS: Poor GQL-15 and VFQ-UI scores were reported with increasing disease severity. B/O VFD in the inferior central region was found to contribute predominantly to the poor GQL-15 scores while both disease severity and sex influenced VFQ-UI scores.

Multifocal versus modified monovision corrections: A non-dispensing comparison of visual assessment in presbyopic neophytes.

Purpose: To compare the visual performance of two simultaneous-vision soft multifocal contact lenses and to compare multifocal contact lens and its modified monovision counterpart in presbyopic neophytes. Methods: A double-masked, prospective, comparative study was conducted on 19 participants fitted with soft PureVision2 multifocal (PVMF) and clariti multifocal (CMF) lenses in random order. High- and low-contrast distance visual acuity, near visual acuity, stereopsis, contrast sensitivity, and glare acuity were measured. The measurements were conducted using multifocal and modified monovision design with one brand and then repeated with another brand of lens. Results: High-contrast distance visual acuity showed a significant difference between CMF (0.00 [-0.10-0.04]) and PureVision2 modified monovision (PVMMV; -0.10 [-0.14-0.00]) correction (P = 0.003) and also between CMF and clariti modified monovision (CMMV; -0.10 [-0.20-0.00]) correction (P = 0.002). Both modified monovision lenses outperformed CMF. The current study did not show any statistically significant difference between contact lens corrections for low-contrast visual acuity, near visual acuity, and contrast sensitivity (P > 0.01). Stereopsis at near distance was significantly lower with both modified monovision (PVMMV: 70 [50-85]; P = 0.007, CMMV: 70 [70-100]; P = 0.006) and with CMF (50 [40-70]; P = 0.005) when compared to spectacles (50 [30-70]). Glare acuity was significantly lower with multifocal (PVMF: 0.46 [0.40-0.50]; P = 0.001, CMF: 0.40 [0.40-0.46]; P = 0.007) compared with spectacles (0.40 [0.30-0.40]), but no significant difference was noted between the multifocal contact lenses (P = 0.033). Conclusion: Modified monovision provided superior high-contrast vision compared to multifocal correction. Multifocal corrections performed better for stereopsis when compared to modified monovision. In parameters like low-contrast visual acuity, near acuity, and contrast sensitivity, both the corrections performed similarly. Both multifocal designs showed comparable visual performances.

Evaluating the impact of ocular UV exposure for the development for pseudoexfoliation syndrome in a South Indian population.

CLINICAL RELEVANCE: Pathophysiology of pseudoexfoliation syndrome (XFS) can be influenced by environmental factors such as solar exposure/occupational factors and genetic factors. BACKGROUND: The study aims to assess the association of lifetime ocular UV exposure and its impact on the risk of development of XFS. METHODS: All eligible subjects underwent a comprehensive ocular examination. XFS was defined as precipitates on the pupillary border, cornea, and angle of anterior chamber or lens in at least one eye without any clinical signs of glaucoma. A standardised questionnaire was administered to assess the lifetime UV exposure. Conjunctival ultraviolet autofluorescence (CUVAF) photography was taken to detect the conjunctival changes with exposure to UV radiation. Ascorbic acid concentration in the aqueous humour was measured. RESULTS: A total of 404 subjects of which 274 (controls) and 130 (XFS cases) were studied. There were 204 males (50.5%) and 200 females (49.5%).Lifetime UV exposure (OR: 1.14, 95% CI: 1.02-1.30, p: 0.032), CUVAF damage (OR: 1.03, 95% CI: 1.01-1.06, p: 0.008) and outdoor worker (OR: 1.87, 95% CI: 1.18-3.00, p: 0.008) were positively associated with XFS. Usage of spectacles (OR: 0.63, 95% CI: 0.39-0.95, p: 0.030) and ascorbic acid concentration in aqueous (OR: 0.47, 95% CI: 0.23-0.99, p: 0.038) were found to be protective against XFS. CONCLUSION: Besides genetic factors, environmental factors such as lifetime ocular UV exposure and outdoor work are significantly associated with the risk of XFS. CUVAF can be used as a non-invasive tool to detect preclinical sun damage in outdoor workers.

Changes in work patterns during COVID-19 lockdown and its impact on the eyes and body.

CLINICAL RELEVANCE: Greater usage of digital devices and change of work pattern as working from home have created an impact on both visual and musculoskeletal systems. Developing an understanding of these changes could assist in providing appropriate care. BACKGROUND: The current study aims to elicit the changes in work patterns due to COVID-19 lockdown and understand the impact of the usage of digital devices on the visual system and musculoskeletal system. METHODS: A survey was designed using Delphi technique and circulated through electronic communication sources using Google form to the working population and students across India, who consented to participate. The survey had components designed to develop an understanding of work patterns, digital device usage, associated visual/ocular symptoms, work-related musculoskeletal disorder (WRMSD) symptoms, and relevant information on psychological factors, and practice of yoga/exercises. RESULTS: There were 1302 valid responses. Mean age of respondents was 24 (IQR 11) years and 548 (42.1%) were male. A total of 1231 (94.5%) reported having one or many visual and ocular symptoms associated with the use of digital devices and 1140 (87.6%) responses indicated WRMSD symptoms. Of the symptomatic respondents, 561 (43.1%) had reported visual/ocular symptoms and 586 (45%) WRMSD symptoms during lockdown, which they did not experience during regular work. Risk factors for visual/ocular symptoms and WRMSD were females, spending more than 6 h on digital devices, taking breaks from digital devices after 2 h, inability to maintain a fair sleep schedule, and inability to make ergonomic modifications at home. CONCLUSIONS: A high prevalence of both visual/ocular symptoms (43.1%) and WRMSD symptoms (45%) was encountered during COVID-19 lockdown.

Assessment of knowledge, attitude, and practice of glaucoma among different cadres of optometrists.

Purpose: To assess the level of knowledge, attitude, and clinical practice of glaucoma among optometry students and optometry practitioners with different years of clinical experience and academic background. Methods: A survey with 20 questions on knowledge, attitude, and practice (KAP) of glaucoma was prepared and self-administered to optometry students and optometry practitioners practicing in an eye hospital/clinic/optical with varied years of clinical experience and education qualification. Results: Among the 558 participants, 57% were optometry practitioners and 43% were students. The knowledge scores among optometry practitioners increased significantly with an increase in the years of clinical experience (P < 0.001). Participants with master's degrees scored higher than participants with bachelor's degrees (P = 0.12). There was no statistically significant difference in knowledge scores based on the type of clinical practice - hospital, private practice, or optical (P = 0.39). Practicing optometrists who performed slit-lamp examination, gonioscopy, IOP measurements, and disc evaluation for the detection of glaucoma had significantly higher knowledge scores than those who did not perform these tests in their practice (P < 0.05). A positive attitude toward glaucoma learning through workshops and hands-on training was reported by optometrists and students. Conclusion: Knowledge about glaucoma was good among optometrists and optometry students and was better among those who handled the diagnostics. All the optometrists had a positive attitude toward enhancing their practice through proper training.

Association of metformin use among diabetics and the incidence of primary open-angle glaucoma - The Chennai Eye Disease Incidence Study.

PURPOSE: Studies have reported the usage of metformin being associated with the reduced risk of progression of glaucoma. The current study aims to determine the association of metformin usage among subjects with diabetes mellitus and the six-year incidence of primary open-angle glaucoma (POAG). METHODS: In this prospective cohort study, subjects who did not have glaucoma at the baseline and had a follow-up after a six-year interval were included. Details such as medical and drug history, applanation tonometry, gonioscopy, pachymetry, optic disc evaluation, and automated perimetry were collected. Incident POAG was defined as subjects who do not have glaucoma at baseline and developed glaucoma as classified International Society of Geographical and Epidemiological Ophthalmology Classification at the follow-up. The association between the subjects who were on metformin for treatment of diabetes mellitus and development of incident POAG was assessed. RESULTS: Among the 4302 eligible participants, 128 (3%) had incident POAG. There were 905 (21.0%) subjects who had diabetes mellitus of which 142 (15.7%) were using metformin. Of the subjects with POAG, 92 (71.9%) were nondiabetics and 36 were diabetics (28.1%). Among the diabetics, the incidence of POAG among those on metformin was 5.6% (8 participants) and those not on metformin was 3.6% (28 participants). There was no difference in the incidence of POAG in subjects with diabetes mellitus, with and without metformin use (P = 0.25). Logistic regression showed no association of metformin use with the incidence of POAG (OR: 1.33, 95 CI: 0.58-3.04, P = 0.49) after adjusting for age, gender, and place of residence. CONCLUSION: The current study did not find any association between the effects of metformin on the incidence of POAG.

Posttraumatic deep anterior lamellar keratoplasty dehiscence: Descemet's resistance.

An 18-year-old girl who had undergone deep anterior lamellar keratoplasty in her left eye for keratoconus a year back presented with inferonasal graft dehiscence with intact host Descemet's membrane and intact anterior chamber after sustaining blunt injury a week prior. The graft was sutured to the host bed, and complete resolution of graft edema was seen in 4 weeks. One year later, she underwent cataract surgery with foldable intraocular lens implantation. At her final follow-up, the best-corrected visual acuity in her left eye was 20/40 with a clear corneal graft and a stable posterior chamber intraocular lens implantation.

Visual Field Plots: A Comparison Study Between Standard Automated Perimetry and Eye Movement Perimetry.

PRéCIS:: This eye movement perimetry (EMP) study describes the development of saccadic reaction time (SRT)-based visual field plots, which could effectively display the presence, location, and extent of glaucomatous defects and support clinical decision-making. PURPOSE: EMP is capable of discriminating normal from glaucomatous visual field defects on the basis of average delays in SRTs. To classify the presence and extent of age-corrected visual field defects, it is required to create SRT-based probability maps. AIM: The aim of this study was to create visual field probability plots based on SRTs and to evaluate their clinical applicability by 2 glaucoma specialists. MATERIALS AND METHODS: The development phase included 95 controls segregated into 5 age-bins to estimate normative limits of SRT. Next, for the testing phase, a set of 28 healthy subjects and 24 glaucoma patients were recruited who underwent standard automated perimetry (SAP) and EMP visual field testing. Fifty-two SAP and EMP plots were presented to 2 glaucoma specialists to classify them as normal or abnormal and to identify the defect location and pattern as 1 or more of 7 predefined categories. RESULTS: The glaucoma specialists showed a sensitivity of 100% and a specificity of 93% and 96% for identifying normal versus abnormal visual field. For specialists 1 and 2, 85% and 92%, respectively, of EMP reports were assigned to the same category as SAP. The reports that did not agree with SAP were graded to a higher defect pattern. The intermethod agreement for specialists 1 and 2 was κ 0.92 and 0.96, respectively. CONCLUSION: SRT-based visual field probability plots provided a comprehensive summary of an individual's visual field status and showed comparable clinical applicability to that of SAP plots.

Effect of Age, Sex, Stimulus Intensity, and Eccentricity on Saccadic Reaction Time in Eye Movement Perimetry.

PURPOSE: In eye movement perimetry (EMP), the extent of the visual field is tested by assessing the saccades using an eye tracker. The aim of the present study was to determine the effects of age and sex of the subjects, the eccentricity and intensity of the peripheral stimuli on saccadic reaction time (SRT), and the interaction between these parameters in healthy participants. METHODS: Healthy participants aged between 20 to 70 years underwent a complete ophthalmic examination and an EMP test. SRT was determined from detected peripheral stimuli of four intensity levels. A multilevel mixed-model analysis was used to verify the influence of subject and stimulus characteristics on SRT within the tested visual field. RESULTS: Ninety-five subjects (mean age 43.0 [15.0] years) were included. Age, stimulus intensity, and eccentricity had a statistically significant effect on SRT, not sex. SRTs were significantly faster with increasing stimulus intensity and decreasing eccentricity (P < 0.001). At the lowest stimulus intensity of 192 cd/m2, a significant interaction was found between age and eccentricity. CONCLUSIONS: The current study demonstrated significant SRT dependence across the visual field measured up to 27°, irrespective of sex. The presented SRT values may serve as a first normative guide for EMP. TRANSLATIONAL RELEVANCE: This report of SRT interaction can aid in refining its use as a measure of visual field responsiveness.

Combination of Simple Diagnostic Tests to Detect Primary Angle Closure Disease in a Resource-constrained Region.

Purpose: To report on diagnostic accuracy of van Herick (vH) technique performed by a vision technician (VT) as well as on efficacy of a combination of vH technique and central anterior chamber depth (ACD) in detection of primary angle closure disease.Methods: Data was obtained from two cohorts; rural clinic setting (n = 111), and rural population-based research setting (n = 888). Van Herick grading was performed by a VT in first cohort and a glaucoma specialist in second cohort. A reference standard four-mirror gonioscopy was performed by a glaucoma specialist in both cohorts. We did preferential sampling. Cut-off levels for vH technique and central ACD were grade 2 and 25th percentile value, respectively. Data from one eye per participant was analyzed.Results: Three hundred and forty (34%) eyes were gonioscopically occludable. Area under receiver operating characteristic curve (95% confidence interval) for vH test was 0.83 (0.76, 0.9) and 0.81 (0.78, 0.84) in first and second cohorts, respectively. Simultaneous testing achieved sensitivity of 87.8% while sequential testing achieved specificity of 99.3%. Negative predictive value* of simultaneous testing was 98.3% compared to 96.6% of vH technique while positive predictive value* of sequential testing was 86% compared to 49.3% of vH technique. (*at 10% prevalence of gonioscopically occludable angle)Conclusions: Diagnostic accuracy of vH grading was similar when performed by a VT and a glaucoma specialist. While test combination was effective to rule in, vH technique may suffice to rule out the disease. Implications of these findings for resource-constrained regions are discussed.

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.

Prevalence of the optic disc anomalies in the adult South Indian population.

PURPOSE: To determine the prevalence of congenitally abnormal disc (all anomalies) in an adult population in southern India. METHODS: Subjects aged ≥40 years (n=6013) underwent a complete ophthalmic examination. Optic disc anomalies were diagnosed according to the definitions given in the article. RESULTS: Optic disc anomalies were found in 81 eyes of 66 (1.1%, 95% CIs 0.00834 to 0.01361) patients. The prevalence of each anomaly in the descending order was peripapillary myelinated nerve fibre (0.28%), epipapillary glial tissue on the optic disc (0.28%), peripapillary vascular loops (0.16%), tilted disc (0.09%), optic disc coloboma (0.08%), optic nerve hypoplasia (0.04%), optic disc pit (0.04%), optic disc pigmentation (0.03%), optic nerve head drusen (0.03%), Bergmeister's papilla (0.03%), optic disc pit and coloboma (0.01%). CONCLUSIONS: The prevalence of optic disc anomalies is 1.1% in the adult South Indian population.

Family-Based Genome-Wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus.

Purpose: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; ß = -0.57, 95% confidence interval [CI]: -0.78 to -0.36; P = 1.7 × 10-7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (ß = -3.94, 95% CI: -5.23 to -2.66; P = 1.7 × 10-9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.

Detecting glaucomatous progression with infrequent visual field testing.

PURPOSE: Previous work has investigated whether a significant regression slope in the first 2 years for the summary index Mean Deviation (MD) is predictive of rapid (≤-2 dB year-1 ) glaucomatous visual field progression. This work assumed six visual fields were obtained as per management guidelines, but in clinical practice commonly only two or three fields are measured. We used simulation methods to investigate how reducing test frequency influences the prediction of rapid visual field progression, along with the influence of including criteria based on regression slope. METHODS: We simulated visual field series (N = 100 000) spaced annually in the first 2 years and then biennially. We calculated positive and negative predictive values (PPV & NPV) for detecting rapid progression, based on a criterion of a significant negative regression slope of any magnitude, or of a magnitude less than a particular limit. We performed a second simulation using test frequency and disease prevalence parameters from a dataset of 255 glaucoma patients from The University of Tokyo Hospital, to check the validity of our method. RESULTS: Prediction values at 2 years were slightly less than those obtained using six visual fields. An addition of an appropriate slope based criterion materially improved PPV, with little detrimental effect on NPV. Simulated prediction values for the Tokyo dataset were similar to those determined empirically. CONCLUSION: Infrequent visual field testing does not dramatically alter predictive values at 2 years, but does substantially delay when significant progression may first be detected.

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.

Is prophylactic laser peripheral iridotomy for primary angle closure suspects a risk factor for cataract progression? The Chennai Eye Disease Incidence Study.

BACKGROUND: To report the risk of cataract progression among primary angle closure suspects (PACS) 6 years after they underwent laser peripheral iridotomy (LPI). METHODS: In the Chennai Eye Disease Incidence Study, 6 years after their baseline evaluation, 4421 subjects were examined again. As part of a detailed evaluation cataract was graded using the Lens Opacities Classification System II; progression was defined as change of cataract by two or more grades or history of cataract surgery in the 6-year period. Only bilaterally phakic subjects with less than N2 or C2 or P2 cataract at baseline with no history of any form of glaucoma, primary angle closure and pseudoexfoliation were included. RESULTS: There were 3205 eligible subjects. Of these, 190 had undergone LPI for PACS. In comparison to the study population, they were significantly older (p<0.001), female (p=0.008), urban residents (p=0.001) and patients with hypertension (p<0.001). During the intervening period, 53 subjects had undergone cataract surgery. The cataract progression rate was significantly greater (OR 1.7, 95% CI 1.3 to 2.4, p<0.001) in those who had undergone LPI. For the study population the baseline risk factors for progression of cataract were age (p<0.001), female gender (p=0.01), diabetes (p<0.001) and LPI (p<0.001). Diabetes and female gender were significant risk factors for nuclear and cortical cataract progression; LPI was a risk factor only for cortical cataract (OR 1.6, 95% CI 1.1 to 2.3, p=0.007). CONCLUSIONS: There was significant cataract progression in 6 years following LPI for PACS.