The clinical utility of a glaucoma polygenic risk score in four population-based European-ancestry cohorts.

OBJECTIVE: We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts. DESIGN: Secondary analysis of four prospective population-based studies. PARTICIPANTS: We included four European-ancestry cohorts: the United States (US) based Nurses' Health Study (NHS), NHS2, and the Health Professionals Follow-up Study, and the Rotterdam Study (RS) in the Netherlands. The US cohorts included female nurses and male health professionals aged 55+ years. The RS included residents aged 45 years or older living in Rotterdam, the Netherlands. METHODS: PRS weights were estimated by applying the Lassosum method on imputed genotype and phenotype data from the UK-Biobank. This resulted in 144,020 variants, single nucleotide polymorphism (SNPs) and indels, with non-zero betas that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C-statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits. MAIN OUTCOME MEASURES: The relative risk for POAG and Harrell's C-statistic (the equivalent of an area-under-the-curve for longitudinal models). RESULTS: Among 1,046 cases and 38,809‬ controls, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08, 5.18) in the US cohorts, and 4.89 (2.93, 8.17) in the Rotterdam Study, compared with participants with median genetic risk (3rd quintile). In restricted cubic spline analyses, the relation between continuous PRS and POAG risk increased exponentially in the US and Rotterdam cohorts (Pspline<0.05). Combining age, sex, intraocular pressure >25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (0.73, 0.75). Adding the PRS to this model improved the concordance to 0.82 (0.80, 0.84). In a meta-analysis of all cohorts, cases in the highest tertile had a larger cup-disc ratio at diagnosis, by 0.11 (0.07, 0.15), and a 2.07-fold increased risk of requiring glaucoma surgery (1.19, 3.60). CONCLUSIONS: Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

Transformer-Based Deep Learning Prediction of 10-Degree Humphrey Visual Field Tests From 24-Degree Data.

Purpose: To predict 10-2 Humphrey visual fields (VFs) from 24-2 VFs and associated non-total deviation features using deep learning. Methods: We included 5189 reliable 24-2 and 10-2 VF pairs from 2236 patients, and 28,409 reliable pairs of macular OCT scans and 24-2 VF from 19,527 eyes of 11,560 patients. We developed a transformer-based deep learning model using 52 total deviation values and nine VF test features to predict 68 10-2 total deviation values. The mean absolute error, root mean square error, and the R2 were evaluation metrics. We further evaluated whether the predicted 10-2 VFs can improve the structure-function relationship between macular thinning and paracentral VF loss in glaucoma. Results: The average mean absolute error and R2 for 68 10-2 VF test points were 3.30 ± 0.52 dB and 0.70 ± 0.11, respectively. The accuracy was lower in the inferior temporal region. The model placed greater emphasis on 24-2 VF points near the central fixation point when predicting the 10-2 VFs. The inclusion of nine VF test features improved the mean absolute error and R2 up to 0.17 ± 0.06 dB and 0.01 ± 0.01, respectively. Age was the most important 24-2 VF test parameter for 10-2 VF prediction. The predicted 10-2 VFs achieved an improved structure-function relationship between macular thinning and paracentral VF loss, with the R2 at the central 4, 12, and 16 locations of 24-2 VFs increased by 0.04, 0.05 and 0.05, respectively (P < 0.001). Conclusions: The 10-2 VFs may be predicted from 24-2 data. Translational Relevance: The predicted 10-2 VF has the potential to improve glaucoma diagnosis.

Impact of Demographics on Regional Visual Field Loss and Deterioration in Glaucoma.

Purpose: To elucidate the impact of demographics, including gender, race, ethnicity, and preferred language, on regional visual field (VF) loss and progression in glaucoma. Methods: Multivariable linear mixed regressions were performed to determine the impact of race, ethnicity, and preferred language on regional VF loss with adjustment for age and gender. Regional VF loss was defined by pointwise total deviation values and VF loss patterns quantified by an unsupervised machine learning method termed archetypal analysis. All cross-sectional and longitudinal analyses were performed both without and with adjustment for VF mean deviation, which represented overall VF loss severity. P values were corrected for multiple comparisons. Results: All results mentioned had corrected P values less than 0.05. Asian and Black patients showed worse pointwise VF loss than White patients with superior hemifield more affected. Patients with a preferred language other than English demonstrated worse pointwise VF loss than patients with English as their preferred language. Longitudinal analyses revealed Black patients showed worse VF loss/year compared to White patients. Patients with a preferred language other than English demonstrated worse VF loss/year compared to patients preferring English. Conclusions: Blacks and non-English speakers have more severe VF loss, with superior hemifield being more affected and faster VF worsening. Translational Relevance: This study furthered our understanding of racial, ethnic, and socioeconomic disparities in glaucoma outcomes. Understanding the VF loss burden in different racial, ethnic, and socioeconomic groups may guide more effective glaucoma screening and community outreach efforts. This research could help reduce vision loss and improve quality of life in disproportionately affected populations by guiding public health efforts to promote glaucoma awareness and access to care.

Cross-sectional study of cognitive impairment and visual impairment among the elderly population in residential care in India: the Hyderabad Ocular Morbidity in Elderly Study (HOMES).

OBJECTIVE: To report the relationship between visual impairment (VI) and cognitive impairment (CI) among the older population living in residential care homes in Hyderabad, India. STUDY DESIGN: Cross-sectional study. SETTING: 41 homes for the aged centres in the Hyderabad region. PARTICIPANTS: 965 participants aged ≥60 years from homes for the aged centres. PRIMARY OUTCOME MEASURES: Visual impairment and cognitive impairment. METHODS: The Hindi mini-Mental Status Examination (HMSE) questionnaire was used to assess the cognitive function. The final HMSE score was calculated after excluding vision-dependent tasks (HMSE-VI). A detailed eye examination was conducted, including visual acuity (VA) measurement for distance and near vision, using a standard logarithm of the minimum angle of resolution chart under good illumination. CI was defined as having a HMSE-VI score of ≤17. VI was defined as presenting VA worse than 6/12 in the better-seeing eye. Near VI (NVI) was defined as binocular presenting near vision worse than N8 and distance VA of 6/18 or better in the better-seeing eye. Multiple logistic regression was done to assess the association between VI and CI. RESULTS: The mean age (±SD) was 74.3 (±8.3) years (range: 60-97 years). There were 612 (63.4%) women, and 593 (61.5%) had a school education. In total, 260 (26.9%; 95% confidence intervals: 24.2 to 29.9) participants had CI. The prevalence of CI among those with VI was 40.5% compared with 14.6% among those without VI (p<0.01). The logistic regression analysis showed that the participants with VI for distance vision had three times higher odds of having CI (OR 3.09; 95% confidence intervals: 2.13 to 4.47; p<0.01). Similarly, participants with NVI had two times higher odds of having CI (OR 2.11; 95% confidence intervals: 1.36 to 3.29; p<0.01) after adjusting for other covariates. CONCLUSIONS: CI was highly prevalent among those with distance and near VI. VI was independently and positively associated with CI after adjusting for potential confounders. Interventions can be planned to address VI in this vulnerable population which could have a ripple effect in preventing cognitive decline.

Use of Diagnostic Codes for Primary Open-Angle Glaucoma Polygenic Risk Score Construction in Electronic Health Record-Linked Biobanks.

PURPOSE: Polygenic risk scores (PRSs) likely predict risk and prognosis of glaucoma. We compared the PRS performance for primary open-angle glaucoma (POAG), defined using International Classification of Diseases (ICD) codes vs manual medical record review. DESIGN: Retrospective cohort study. METHODS: We identified POAG cases in the Mount Sinai BioMe and Mass General Brigham (MGB) biobanks using ICD codes. We confirmed POAG based on optical coherence tomograms and visual fields. In a separate 5% sample, the absence of POAG was confirmed with intraocular pressure and cup-disc ratio criteria. We used genotype data and either self-reported glaucoma diagnoses or ICD-10 codes for glaucoma diagnoses from the UK Biobank and the lassosum method to compute a genome-wide POAG PRS. We compared the area under the curve (AUC) for POAG prediction based on ICD codes vs medical records. RESULTS: We reviewed 804 of 996 BioMe and 367 of 1006 MGB ICD-identified cases. In BioMe and MGB, respectively, positive predictive value was 53% and 55%; negative predictive value was 96% and 97%; sensitivity was 97% and 97%; and specificity was 44% and 53%. Adjusted PRS AUCs for POAG using ICD codes vs manual record review in BioMe were not statistically different (P ≥.21) by ancestry: 0.77 vs 0.75 for African, 0.80 vs 0.80 for Hispanic, and 0.81 vs 0.81 for European. Results were similar in MGB (P ≥.18): 0.72 vs 0.80 for African, 0.83 vs 0.86 for Hispanic, and 0.74 vs 0.73 for European. CONCLUSIONS: A POAG PRS performed similarly using either manual review or ICD codes in 2 electronic health record-linked biobanks; manual assessment of glaucoma status might not be necessary for some PRS studies. However, caution should be exercised when using ICD codes for glaucoma diagnosis given their low specificity (44%-53%) for manually confirmed cases of glaucoma.

Cross-sectional study of prevalence and correlates of fear of falling in the older people in residential care in India: the Hyderabad Ocular Morbidity in Elderly Study (HOMES).

OBJECTIVE: To report the prevalence and risk factors for the fear of falling (FOF) among older individuals living in residential care facilities in India. DESIGN: Cross-sectional study. SETTING: Homes for the aged centres in Hyderabad, India. PARTICIPANTS: The study included individuals aged ≥60 years from homes for the aged centres. The participants underwent a comprehensive eye examination in make-shift clinics setup in homes. Trained investigators collected the personal and demographic information of the participants and administered the Patient Health Questionnaire-9 and Hearing Handicap Inventory for Elderly questionnaire in the vernacular language. FOF was assessed using the Short Falls Efficacy Scale. The presence of hearing and visual impairment in the same individual was considered dual sensory impairment (DSI). A multiple logistic regression analysis was done to assess the factors associated with FOF. PRIMARY OUTCOME MEASURE: FOF. RESULTS: In total, 867 participants were included from 41 homes for the aged centres in the analyses. The mean (±SD) age of the participants was 74.2 (±8.3) years (range 60-96 years). The prevalence of FOF was 56.1% (95% CI 52.7% to 59.4%; n=486). The multivariate analysis showed that those with DSI had eleven times higher odds of reporting FOF than those with no impairment (OR 11.14; 95% CI 3.15 to 41.4.) Similarly, those with moderate depression had seven times higher odds (OR 6.85; 95% CI 3.70 to 12.70), and those with severe depression had eight times higher odds (OR 8.13; 95% CI 3.50 to 18.90) of reporting FOF. A history of falls in the last year was also associated with increased odds for FOF (OR 1.52; 95% CI 1.03 to 2.26). CONCLUSION: FOF is common among older individuals in residential care in India. Depression, falling in the previous year and DSI were strongly associated with FOF. A cross-disciplinary approach may be required to address FOF among the older people in residential care in India.

Manhattan Vision Screening and Follow-up Study (NYC-SIGHT): a nested cross-sectional assessment of falls risk within a cluster randomised trial.

BACKGROUND: To investigate the feasibility of using the Stopping Elderly Accidents, Deaths and Injuries (STEADI) Falls Risk Tool Kit during community-based eye health screenings to assess falls risk of participants enrolled in the Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT). METHODS: Cross-sectional analysis of data from a 5-year prospective, cluster-randomised clinical trial conducted in affordable housing developments in New York City in adults age 40 years and older. Prescreening questions determined whether participants were at risk of falling. STEADI tests classified participants at low, moderate or high risk of falling. Multivariate logistic regression determined odds of falls risk of all enrolled participants. RESULTS: 708 participants completed the eye health screening; 351 (49.6%) performed STEADI tests; mean age: 71.0 years (SD±11.3); 72.1% female; 53.6% Black, non-Hispanic, 37.6% Hispanic/Latino. Level of falls risk: 32 (9.1%) low, 188 (53.6%) moderate and 131 (37.3%) high. Individuals age >80 (OR 5.921, 95% CI (2.383 to 14.708), p=0.000), had blurry vision (OR 1.978, 95% CI (1.186 to 3.300), p=0.009), high blood pressure (OR 2.131, 95% CI (1.252 to 3.628), p=0.005), arthritis (OR 2.29876, 95% CI (1.362 to 3.875), p=0.002) or foot problems (OR 5.239, 95% CI (2.947 to 9.314), p=0.000) had significantly higher odds of falling, emergency department visits or hospitalisation due to falling. CONCLUSION: This study detected a significant amount of falls risk in an underserved population. The STEADI Falls Risk screening questions were easy for eye care providers to ask, were highly predictive of falls risk and may be adequate for referral to occupational health and/or physical therapy.

Natural History and Risk Factors for Glaucoma Progression in Chinese Patients With Normal-Tension Glaucoma.

Purpose: To characterize the natural history of normal-tension glaucoma (NTG) in Chinese patients. Methods: The prospective observational cohort study included patients with untreated NTG with a minimum follow-up of 2 years. Functional progression was defined by visual field (VF) deterioration, while structural progression was characterized by thinning of the retinal nerve fiber layer (RNFL) or ganglion cell inner plexiform layer (GCIPL). Results: Among 84 participants (mean age, 60.5 years; mean deviation, -5.01 decibels [dB]) with newly diagnosed NTG followed for an average of 69.7 months, 63.1% progressed during the observation period. Specifically, 29.8% progressed by VF, and 48.8% progressed by either RNFL or GCIPL. In Cox proportional hazards analysis, disc hemorrhage (hazard ratio [HR], 2.82; 95% confidence interval [CI], 1.48-5.35), female gender (HR, 1.98; 95% CI, 1.08-3.62), and mean IOP during the follow-up period (HR, 1.14 per mm Hg; 95% CI, 1.00-1.31) were significant predictors of glaucomatous progression. Additionally, longer axial length (AL; HR, 0.57 per millimeter; 95% CI, 0.35-0.94) was protective against VF progression faster than -0.50 dB/y, and higher minimum diastolic blood pressure (DBP; HR, 0.96 per mm Hg; 95% CI, 0.92-1.00) was protective against structural progression. Conclusions: Nearly two-thirds of untreated Chinese patients with NTG progressed over an average follow-up of 70 months by VF, RNFL, or GCIPL. Disc hemorrhage, female gender, higher mean IOP, shorter AL, and lower minimum DBP were significant predictors for disease progression.

Visual Impairment and Real-World Home Physical Activity With Home Environment in an Older Population.

Importance: Physical activity levels are lower in visual impairment. However, additional factors, such as home environmental features, which can modify physical activity in this group, are unknown. Objective: To investigate the association between home environment features and home physical activity in patients with visual impairment. Design, Setting, and Participants: This cross-sectional study of clinical patients included participants with glaucoma suspect and primary glaucoma who were 60 years or older with varying degrees of visual field damage. Study participants were recruited from the Johns Hopkins Wilmer Eye Institute Glaucoma Clinic, Baltimore, Maryland, from September 2013 through March 2015. Data were analyzed from December 19, 2022, through December 25, 2022. Main Outcomes and Measures: Total in-home steps taken per day was the primary outcome measure; time in daily home physical activity and nonsedentary activity were secondary outcomes. Results: A total of 153 participants were included in analyses with mean age of 71 (SD, 7.8) years and 71 were female (46%). Sixty percent had more than 1 comorbid illness, about one-third took 5 or more prescription drugs, and median daily home steps were 1137. Median integrated visual field sensitivity was 28 dB. Better-eye median visual acuity in logMAR was 0.05 (20/22 Snellen equivalent). For every 0.1-log unit increment in average measured home lighting, participants took 5% more daily steps (rate ratio [RR], 1.05; 95% CI, 1.00-1.10; P = .04) and had a 3% faster average daily peak cadence (RR, 1.03; 95% CI, 1.01-1.05; P = .01). The average number of nonsedentary activity minutes (RR, 1.04; 95% CI, 1.00-1.07; P = .06), average bout duration (ß = 0.03; 95% CI, 0.00-.07; P = .06), and activity fragmentation (ß = -0.06; 95% CI, -0.13 to 0.00; P = .06) showed associations with home lighting. The number of hazards was not associated with any activity metric (steps: RR, 1.14; 95% CI, 0.96-1.34; P = .13; peak cadence: RR, 1.00; 95% CI, 0.93-1.08; P = .98; and nonsedentary time: RR, 1.11; 95% CI, 0.98-1.26; P = .11), nor was the frequency of hazards. Conclusions and Relevance: In this study, results demonstrated that home environment features, particularly lighting, may influence home activity metrics in older adults with visual impairment. Further prospective studies would be needed to confirm if home modifications can improve at-home activity.

Long-Term Risk and Prediction of Progression in Primary Angle Closure Suspect.

Importance: Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS. Objective: To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC). Design, Setting, and Participants: This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up. Results: The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 µm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 µm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 µm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance. Conclusions and Relevance: This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 µm and light-room ARA at 750 µm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.

Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT): Subanalysis of Referral to Ophthalmology.

PURPOSE: The Manhattan Vision Screening and Follow-up Study aims to provide access to eye care for underserved populations, detect native rates of ocular pathology, and refer participants with eye disease to ophthalmology. This subanalysis describes the reasons for referral to ophthalmology and identifies risk factors associated with being referred. METHODS: Enrolled participants were aged ≥40 years, living independently in public housing developments and able to provide consent for eye health screenings. Those with habitual visual acuity 20/40 or worse, intraocular pressure (IOP) 23-29 mmHg, or an unreadable fundus image failed and were scheduled with the on-site optometrist. The optometric exam determined whether further referral to ophthalmology for a clinic exam was warranted. Those with an abnormal image or IOP ≥30 mmHg were referred directly to ophthalmology. Main outcome was factors associated with referral to ophthalmology. RESULTS: A total of 708 individuals completed the eye health screening over 15 months. A total of 468 participants were referred to ophthalmology (250 had an abnormal image and 218 were referred by the optometrist). Those referred were predominantly older adults (mean age 70.0 ± 11.4 years), female (66.7%), African American (55.1%) and Hispanic (39.5%). Seventy percent of participants had not had a recent eye exam. Stepwise multivariate logistic regression analysis showed that participants with pre-existing glaucoma (OR 3.14, 95% CI 1.62 to 6.08, p = 0.001), an IOP ≥23 mmHg (OR 5.04, 95% 1.91 to 13.28, p = 0.001), or vision impairment (mild) (OR 2.51, 95% CI 1.68 to 3.77, p = 0.001) had significantly higher odds of being referred to ophthalmology. CONCLUSION: This targeted community-based study in Upper Manhattan provided access to eye care and detected a significant amount of ocular pathology requiring referral to ophthalmology in this high-risk population.

Comparison of Structural and Functional Features in Primary Angle Closure and Open Angle Glaucomas.

PRCIS: Using a large data set, we showed structural and functional differences between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG). Primary angle closure glaucoma has relative structural preservation and worse functional loss inferiorly. PURPOSE: To identify structural and functional differences in PACG and POAG. MATERIALS AND METHODS: In this large cross-sectional study, differences in structural and functional damage were assessed among patients with POAG and PACG with optical coherence tomography and reliable visual field testing. RESULTS: In all, 283 patients with PACG and 4110 patients with POAG were included. Despite similar mean deviation on visual fields (mean [SD] -7.73 [7.92] vs. -7.53 [6.90] dB, P =0.72), patients with PACG had thicker global retinal nerve fiber layer (RNFL), smaller cup volume, smaller cup-to-disc ratio, and larger rim area than POAG (77 [20] vs. 71 [14] µm, 0.32 [0.28] vs. 0.40 [0.29] mm 3 , 0.6 [0.2] vs. 0.7 [0.1], 1.07 [0.40] vs. 0.89 [0.30] mm 2 , P <0.001 for all), while patients with POAG had more pronounced inferior RNFL thinning (82 [24] vs. 95 [35] µm, P <0.001). In a multivariable analysis, hyperopia [odds ratio (OR): 1.24, confidence interval (CI): 1.13-1.37], smaller cup-to-disc ratio (OR: 0.69, CI: 0.61-0.78), thicker inferior RNFL (OR: 1.15, CI: 1.06-1.26) and worse mean deviation (OR: 0.95, CI: 0.92-0.98) were associated with PACG. Functionally, POAG was associated with superior paracentral loss and PACG with inferior field loss. After adjusting for average RNFL thickness, PACG was associated with more diffuse loss than POAG (total deviation differences 1.26-3.2 dB). CONCLUSIONS: Patients with PACG had less structural damage than patients with POAG despite similar degrees of functional loss. Regional differences in patterns of functional and structural loss between POAG and PACG may improve disease monitoring for these glaucoma subtypes.

Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study.

PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. METHODS: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. RESULTS: A total of 19 of 125 eyes (15%, CI, 9%-24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%). CONCLUSIONS: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over 6 months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

MNREAD Reading Vision in Adults With Glaucoma Under Mesopic and Photopic Conditions.

Purpose: Despite good photopic visual acuity, glaucoma patients report difficulty performing daily activities under dim light such as reading. Here we investigated the impact of mesopic lighting conditions on reading vision of glaucoma patients. Methods: The study design included 39 patients with glaucoma and 40 healthy controls. Reading vision was assessed with MNREAD charts under mesopic (2 cd/m2) and photopic (220 cd/m2) conditions. Four reading indexes: maximum reading speed (MRS), critical print size (CPS), reading acuity (RA), and reading accessibility index (ACC) were obtained from the MNREAD test yielding a plot of reading speed versus print size. Results: Compared to photopic conditions, reading vision of both healthy controls and glaucoma patients significantly decreased under mesopic conditions (P < 0.05). For glaucoma patients (85% with mild or moderate glaucoma), MRS and ACC decreased by six words per minute and 0.1, respectively under mesopic conditions; CPS and RA increased by 0.25 and 0.18 logMAR, respectively. Moreover, under both photopic and mesopic conditions, reading vision of glaucoma patients was significantly worse than that of healthy controls, but the difference was greater under mesopic conditions (P < 0.05) even after controlling for age and visual acuity. Conclusions: Mesopic conditions make reading more challenging for both healthy controls and glaucoma patients. However, reading in dim light appears to be more burdensome for glaucoma patients. Mesopic reading tests mediated by both cone and rod photoreceptor systems likely provide a more sensitive and comprehensive assessment of a patient's reading impairment than testing under photopic conditions.

Glaucoma: now and beyond.

The glaucomas are a group of conditions leading to irreversible sight loss and characterised by progressive loss of retinal ganglion cells. Although not always elevated, intraocular pressure is the only modifiable risk factor demonstrated by large clinical trials. It remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing the rate of vision loss from glaucoma. Methods for lowering intraocular pressure include laser treatments, topical medications, and surgery. Although modern surgical innovations aim to be less invasive, many have been introduced with little supporting evidence from randomised controlled trials. Many cases remain undiagnosed until the advanced stages of disease due to the limitations of screening and poor access to opportunistic case finding. Future research aims to generate evidence for intraocular pressure-independent neuroprotective treatments, personalised treatment through genetic risk profiling, and exploration of potential advanced cellular and gene therapies.

Participant Experience Using Novel Perimetry Tests to Monitor Glaucoma Progression.

PRCIS: Participant surveys taken after using tablet-based and smart visual function analyzer (SVFA) perimetry tests suggest that patients may prefer novel perimetry tests over traditional visual field machines. PURPOSE: Compare patient experience using the IMOvifa SVFA and the tablet-based Melbourne Rapid Fields visual field (VF) tests to the Humphrey Field 24-2 Swedish Interactive Threshold Algorithm Standard. PATIENTS AND METHODS: Prospective observational cohort study on adult participants with diagnoses of glaucoma suspect, ocular hypertension, or glaucoma. Participants attended 2 study visits ~3 months apart. During the first visit, participants were trained to use the 2 novel perimeters, took 1 test on both new devices and the Humphrey Field Analyzer, then were surveyed. Participants received tablets and performed weekly tablet VF tests at home between study visits. At the final study visit, participants re-took the VF tests and completed the same surveys. RESULTS: Eighty-one participants were surveyed twice. At the baseline survey, participants preferred the SVFA (71.7%) and tablet tests (69.2%) over the Humphrey VF. Most were willing to perform weekly monitoring at home on the SVFA (69.1%) and tablet (75.4%). Participants generally had a "very good" overall experience when testing on the SVFA (71.6%) and tablet (90.1%). At the final visit, fewer participants were willing to test on the tablet daily (23.5% to 9.9%; P = 0.02 for change) and more were willing to test monthly (18.5% to 33.3%; P = 0.03 for change). CONCLUSION: Users reported a preference for novel VF devices. Overall participant experience using these devices was positive, supporting the feasibility of home monitoring of VFs from an experience perspective.

Treatment Outcomes for Juvenile Open Angle Glaucoma in Thailand.

PRCIS: Juvenile open angle glaucoma (JOAG) patients with thick central corneas and negative family history were more likely to undergo surgery, mainly trabeculectomy with half requiring additional surgery within 10 years. PURPOSE: To assess the characteristics and treatment outcomes of patients with JOAG in Thailand. PATIENTS AND METHODS: This retrospective, multicenter study included all patients diagnosed with JOAG over 12 years from 2 tertiary hospitals in Bangkok, Thailand. RESULTS: A total of 200 eyes from 104 patients were included in this study. The mean age of onset was 24.0±10.1 years (range: 5-40 y), with male predominance (60.5%). Over 90% of patients had bilateral JOAG and 25% had a positive family history. Negative family history (adjusted odds ratio=4.59, P =0.02) and thick central corneal thickness were surgical predictors (every 10 µm adjusted odds ratio=1.29, P =0.01). Over 70% of cases needed glaucoma surgery. Trabeculectomy with Mitomycin-C was performed on 131 eyes (65.5%) with a cumulative probability of complete success of 71.0%, 57.8%, 39.2%, and 26.9% and qualified success of 86.3%, 73.6%, 64.8%, and 45.7% at 1, 3, 5, and 10 years, respectively. The mean follow-up after surgery was 94.9 ± 69.8 months (range: 13-153 mo). There were no serious postoperative complications. Myopia and the number of baseline glaucoma medications were significantly associated with surgical failure. CONCLUSIONS: Trabeculectomy with mitomycin C was the most common primary surgery performed in Thai patients with JOAG, and successfully reduced intraocular pressure without significant complications. Patients with thicker corneas were more likely to undergo surgery. By 10 years, half of the patients required additional surgery and risk factors for failure included myopia and the number of medications.

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden.

Importance: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. Objective: To evaluate phenotypic features across genetic burden for POAG. Design, Setting, and Participants: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. Main Outcomes and Measures: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. Results: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 µm and macular ganglion cell complex (GCC) of 0.26 µm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). Conclusion and Relevance: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.

Role of Static and Dynamic Ocular Biometrics Measured in the Dark and Light as Risk Factors for Angle Closure Progression.

PURPOSE: To assess the role of static and dynamic ocular biometric parameters measured in the dark and light for predicting progression of primary angle closure suspect (PACS) to primary angle closure (PAC). DESIGN: Retrospective cohort study using prospective randomized controlled trial data from untreated, control eyes. METHODS: Zhongshan Angle Closure Prevention Trial subjects underwent anterior segment optical coherence tomography (AS-OCT) imaging in the dark and light. Static biometric parameters were measured, consisting of angle, iris, lens, and anterior chamber parameters. Dynamic change parameters were calculated by subtracting light measurements from dark measurements. Cox proportional hazards regression models were developed to assess risk factors for PACD progression. RESULTS: A total of 861 eyes of 861 participants were analyzed (36 progressors). On univariable analysis, TISA500 measurements in the light and dark were associated with progression (P < .001), whereas dynamic change parameters were not (P ≥ .08). In the primary multivariable model, older age (hazard ratio [HR] = 1.09 per year), higher intraocular pressure (IOP) (HR = 1.13 per mm Hg), and smaller TISA500 in the light (HR = 1.28 per 0.01 mm2) were significantly associated with greater risk of progression (P ≤ .04). Dark TISA500 had similar significance (HR = 1.28, P = .002) when replacing light TISA500. Risk of progression was more predictive among eyes in the lowest quartile of light TISA500 measurements (HR = 4.56, P < .001) compared to dark measurements (HR = 2.89, P = .003). CONCLUSION: Static parameters measured in the light are as predictive, and possibly more so, of angle closure progression as those measured in the dark. Ocular biometrics measured under light and dark conditions may provide additional information for risk-stratifying patients for angle closure progression.

Artifact-Tolerant Clustering-Guided Contrastive Embedding Learning for Ophthalmic Images in Glaucoma.

Ophthalmic images, along with their derivatives like retinal nerve fiber layer (RNFL) thickness maps, play a crucial role in detecting and monitoring eye diseases such as glaucoma. For computer-aided diagnosis of eye diseases, the key technique is to automatically extract meaningful features from ophthalmic images that can reveal the biomarkers (e.g., RNFL thinning patterns) associated with functional vision loss. However, representation learning from ophthalmic images that links structural retinal damage with human vision loss is non-trivial mostly due to large anatomical variations between patients. This challenge is further amplified by the presence of image artifacts, commonly resulting from image acquisition and automated segmentation issues. In this paper, we present an artifact-tolerant unsupervised learning framework called EyeLearn for learning ophthalmic image representations in glaucoma cases. EyeLearn includes an artifact correction module to learn representations that optimally predict artifact-free images. In addition, EyeLearn adopts a clustering-guided contrastive learning strategy to explicitly capture the affinities within and between images. During training, images are dynamically organized into clusters to form contrastive samples, which encourage learning similar or dissimilar representations for images in the same or different clusters, respectively. To evaluate EyeLearn, we use the learned representations for visual field prediction and glaucoma detection with a real-world dataset of glaucoma patient ophthalmic images. Extensive experiments and comparisons with state-of-the-art methods confirm the effectiveness of EyeLearn in learning optimal feature representations from ophthalmic images.