Time to glaucoma progression detection by optical coherence tomography and visual field in glaucoma individuals of African descent.

PURPOSE: To examine the time to glaucoma progression detection by retinal nerve fiber layer thickness (RNFLT) and visual field (VF) among African descent (AD) individuals. DESIGN: Retrospective cohort study. METHODS: Setting: Multi-center. STUDY POPULATION: We included AD glaucoma eyes from DIGS/ADAGES with ≥2-year/5-visits of optic nerve head RNFLT and 24-2 VF examinations. Intervention or Observation Procedure: Rates of VF mean deviation (MD) and RNFLT worsening were analyzed using linear mixed-effects models, and longitudinal data was simulated using the variability estimates. MAIN OUTCOME MEASURE: The simulated time to detect trend-based glaucoma progression was assessed with assumed rates of VF MD and RNFLT change derived from the cohort (25th, 50th, 75th percentile [p25, median, p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 AD subjects (mean baseline age: 63.4 years; VF MD: -4.2 dB, RNFLT: 80.2 µm). The p25, median, mean and p75 rates of change were -0.43, -1.01, -1.15 and -1.64 µm/year for RNFLT, and 0.00, -0.21, -0.30 and -0.51 dB/year for VF MD, respectively. Compared to VF MD, RNFLT showed an overall shorter mean time to progression detection (time difference: 0.4-1.7 years), with the mean rates showing the largest difference (RNFLT: 5.2 years vs. VF MD: 6.9 years). Similarly, we found an overall shorter time to detect RNFLT progression, compared to that of VF MD progression, in mild glaucoma eyes (≥1 year earlier) and in moderate-advanced glaucoma eyes (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed potentially shorter time to detect RNFLT progression than VF MD progression in AD eyes. Our findings support the importance of using RNFLT to detect progressive glaucoma in AD individuals.

Glaucoma and the Human Microbiome.

PURPOSE OF REVIEW: To explore a view of the human microbiome as an interconnected, functional, dynamic system that may be linked to the pathogenesis and progression of glaucoma. METHOD: A literature review was undertaken that included publications from 1966 to 2023. RESULTS: Bacterial lipopolysaccharides (LPS) activate toll-like receptors (TLR) and mediate the human immune response. The LPS-TLR4 pathway is a potential avenue for the ocular, gut, and oral microbiomes to interface and/or influence ocular disease. Studies of gut dysbiosis have shown that alterations on the healthy microbiota can predispose the host to immune-mediated inflammatory and neurodegenerative conditions, while oral and ocular surface dysbiosis have been correlated with glaucoma. While developmental exposure to commensal microflora has shown to be necessary for the autoimmune and neurodegenerative responses to elevated intraocular pressure to take place, commensal bacterial products like short chain fatty acids have regulatory effects protective against glaucoma. SUMMARY: Alterations to human microbiotas have been associated with changes in intestinal permeability, gene regulation, immune cell differentiation, and neural functioning, which may predispose the host to glaucoma. Select microbes have been highlighted for their potential contributions to glaucoma disease progression or protection, raising the potential for microbiota-based treatment modalities. Current topical glaucoma treatments may disrupt the ocular surface microbiota, potentially having ramifications on host health. Further study of the relationships between human microbiome and glaucoma is needed.

Racial Differences in Diagnostic Accuracy of Retinal Nerve Fiber Layer Thickness in Primary Open-Angle Glaucoma.

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC: 0.86 and 0.90 in AD and ED, respectively, P =0.33). Adjustments for age, central corneal thickness, axial length, disc area, visual field mean deviation, and intraocular pressure yielded similar results. Conclusions: OCT-RNFLT has lower diagnostic accuracy in eyes of AD compared to those of ED. This finding was generally robust across two OCT instruments and remained after adjustment for many potential confounders. Further studies are needed to explore the potential sources of this difference.

Association of Long-Term Intraocular Pressure Variability and Rate of Ganglion Complex Thinning in Patients With Glaucoma.

PURPOSE: To evaluate the association of mean intraocular pressure (IOP) and IOP variability (IOP fluctuation [SD of IOP] and the IOP range) with the rate of ganglion cell complex (GCC) layer thinning over time in patients with glaucoma. DESIGN: Prospective cohort study. METHODS: Participants with at least 4 visits and 2 years of follow-up of optical coherence tomography tests were included. A linear mixed-effect model was used to investigate the association of IOP parameters with the rates of GCC thinning. Subgroup analyses were conducted for eyes with early (MD ≥ -6 dB), and moderate to advanced stage (MD < -6 dB) at baseline. RESULTS: The cohort consisted of 369 eyes of 249 glaucoma patients (282 early glaucoma and 87 moderate to advanced glaucoma) with mean (standard deviation [SD]) age of 68.2 (10.7) years over 5.1 years of follow-up. The mean rate of GCC change was -0.59 (95% confidence interval [CI], -0.67 to -0.52) µm per year. In multivariable models, faster annual rate of GCC thinning was associated with a higher IOP fluctuation (-0.17 [95% CI, -0.23 to -0.11] µm per 1-mmHg higher, P < .001) or higher IOP range (-0.07 [95% CI, -0.09 to -0.05] µm per 1-mmHg higher, P < .001) after adjustment for mean IOP and other confounding factors. Similar results were found for early and moderate to advanced stages of glaucoma. CONCLUSIONS: IOP variability showed an independent association with macular change in patients with glaucoma regardless of severity at baseline, even after adjustment for mean IOP, supporting its potential value as a therapeutic target for clinical decision-making.

Understanding Patterns of Preserved Retinal Ganglion Cell Layer in Advanced Glaucoma as seen with OCT.

PRECIS: Using OCT, eyes with advanced glaucoma were found to have a wide range of patterns of damage that were consistent with the natural history of progression based upon a model of macular progression. PURPOSE: To understand the patterns of preserved retinal ganglion cells in eyes with advanced glaucoma using OCT and a model of progression of the central macula. METHODS: OCT GCL thickness was measured in 94 eyes with advanced glaucoma, defined as glaucomatous eyes with a 24-2 MD (mean deviation) worse than -12 dB. A commercial report supplied the GCL thickness in 6 sectors of the thick, donut-shaped GCL region around the fovea. For each eye, the 6 sectors were coded as green (within normal limits, WNL), yellow (≤5th, ≥1st percentile), or red (<1st percentile). RESULTS: In all 94 eyes, one or more of the 6 sectors of the donut were abnormal (red or yellow), while all 6 sectors were red in 52 (55%) of the eyes. On the other hand, 33 eyes had one or more sectors WNL (green). While the pattern of donut damage varied widely across these 33 eyes, 61 of the 66 hemiretinas were consistent with a temporal-to-nasal progression of damage within each hemiretina as predicted by our model. CONCLUSION: All eyes with advanced glaucoma had damage to the critically important central, donut-shaped GCL region. This region showed a wide range of patterns of damage, but these patterns were consistent with the natural history of progression based upon a model of macular progression. These results have implications for the clinical identification of macular progression, as well as for inclusion criteria for clinical trials seeking to preserve central macular function.

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.

Drug-Induced Liver Injury During a Glaucoma Neuroprotection Clinical Trial.

There are several ongoing, worldwide clinical trials with a cumulative target enrollment of over 1300 participants on the role of nicotinamide (a specific form of vitamin B3) as a therapeutic neuroprotective treatment for glaucoma. We describe a serious adverse event of drug-induced liver injury (DILI) likely related to the use of 3 grams/day nicotinamide in a glaucoma clinical trial (clinicaltrials.gov identifier: NCT05695027) based in the United States. This report is important to share with the medical community, as other participants in glaucoma nicotinamide trials globally may have similar adverse events and many patients are using nicotinamide as a health supplement without medical supervision. We recommend that investigators, physicians, and patients remain vigilant about DILI as they seek novel vision-preserving neuroprotective therapies.

Manhattan Vision Screening and Follow-up Study (NYC-SIGHT): Vision and refractive error results.

CLINICAL RELEVANCE: Optometrists can play a key role in providing access to eye care in underserved populations by organising community-based eye health screenings that include optometric exams to detect vision impairment and uncorrected refractive error. BACKGROUND: Community-based eye health screenings and optometric exams were conducted in the NYC-SIGHT Study. METHODS: A sub-analysis of vision impairment and refractive error results within a 5-year prospective, cluster-randomised clinical trial. Eligible individuals (age ≥40 years) were recruited from 10 affordable housing developments in Upper Manhattan. Developments were randomised into usual care (received glasses prescription only) and intervention (free glasses) groups. Participants with 6/12 visual acuity or worse, intraocular pressure 23-29 mmHg, or an unreadable fundus image were scheduled with the study optometrist for refraction and a non-dilated exam. Visual improvement data were obtained by comparing the presenting acuity at screening compared to the best corrected acuity after refraction by the optometrist. Chi-square, two-sample t-tests, and a stepwise multivariate logistic regression model were used to determined factors associated with improvable visual impairment. RESULTS: Seven hundred and eight participants completed screening, 308 received an optometric exam. Those with improvable vision impairment (n = 251), mean age: 69.8 years, 70.5% female, 53% African American, 39.8% Hispanic, >95% had health insurance. Refractive error diagnosed in 87.8% of the participants; lines of improvement: 2 lines (n = 59), 3 to 5 lines (n = 120), and ≥6 lines (n = 72). Stepwise multivariate logistic regression analysis showed that participants with visual acuity 6/12 or worse (odds ratio 16.041, 95% confidence interval 6.009 to 42.822, p = 0.000) or a normal fundus image (odds ratio 2.783, 95% confidence interval 1.001 to 7.740, p = 0.05) had significantly higher odds of improvable vision impairment. CONCLUSION: This innovative, targeted community-based study included an optometrist who detected high rates of refractive error and improvable vision impairment in an underserved population living in New York City.

Association of Psychosocial Factors with Activation Among Patients with Glaucoma.

OBJECTIVE: To investigate the association of psychosocial factors with health self-management behaviors and beliefs among patients with primary open-angle glaucoma (POAG). DESIGN: Prospective cross-sectional cohort study. PARTICIPANTS: Patients (n = 202) with mild, moderate, or advanced bilateral POAG. METHODS: Patients (N = 1164) were identified from electronic medical records at a single academic medical center. Letters soliciting participation were mailed to 591 randomly selected potential participants. Psychometric measures and a social determinants of health questionnaire were administered by phone to 202 study participants. MAIN OUTCOME MEASURES: The National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ), the Multidimensional Health Locus of Control (MHLC), the Perceived Medical Condition Self-Management Scale-4, the Patient Health Questionnaire-9 (PHQ), the Patient Activation Measure-13 (PAM), a health literacy question, and a social determinants of health questionnaire. RESULTS: For each increase in level of POAG severity, there was a decrease in mean NEI-VFQ score (P < 0.001). For each unit increase in NEI-VFQ item 1, self-rated vision, mean PAM score increased (R2 = 5.3%; P = 0.001; 95% confidence interval [CI], 0.077-0.276). For each unit increase in "Internal" on the MHLC, mean PAM score increased (R2 = 19.3%; 95% CI, 0.649-1.166; P < 0.001). For each unit increase in "Doctors" on the MHLC, mean PAM score increased (R2 = 11.0%; 95% CI, 1.555-3.606; P < 0.001). For each unit increase in "Chance" on the MHLC, mean PAM score decreased (R2 = 2.6%; 95% CI, -0.664 to -0.051; P = 0.023). On multivariate analysis, adjusting for age, sex and race, for each unit increase in PHQ, mean PAM score decreased (95% CI, 0.061-1.35; P = 0.032); for each unit increase in MHLC "Doctors", mean PAM score increased (95% CI, -1.448 to 3.453; P < 0.001); for each unit increase in MHLC "Internal", mean PAM score increased (95% CI, 0.639-1.137; P < 0.001); for each unit increase in MHLC "Chance", mean PAM score decreased (95% CI, -0.685 to -0.098; P = 0.009). CONCLUSIONS: We identified modifiable behavioral factors that could increase patients' self-perceived ability and confidence to manage their own eye care. Locus of control (MHLC), level of depression (PHQ), and self-rated functional vision (NEI-VFQ) were each associated with patient behaviors, attitudes, and beliefs needed for health self-management (activation, assessed by the PAM) and may be important determinants of adherence behaviors. Targeting change in patients' care beliefs and behaviors may improve activation and treatment outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging. The ML models were trained to predict surgical interventions and evaluated on independent data collected at a separate study site. The models were evaluated based on their ability to predict surgeries at varying lengths of time prior to surgical intervention. The highest performing predictions achieved an AUC of 0.93, 0.92, and 0.93 in predicting surgical intervention at 1 year, 2 years, and 3 years, respectively. The models were also able to achieve high sensitivity (0.89, 0.77, 0.86 at 1, 2, and 3 years, respectively) and specificity (0.85, 0.90, and 0.91 at 1, 2, and 3 years, respectively) at an 0.80 level of precision. The multi-modal models trained on a combination of data types predicted surgical interventions with high accuracy up to three years prior to surgery and could provide an important tool to predict the need for glaucoma intervention.

Visual field progression patterns in the ocular hypertension treatment study correspond to vulnerability regions of the disc.

OBJECTIVES: To determine the locations on the 24-2 visual field (VF) testing grid that are most likely to progress in patients with ocular hypertension (OHTN). Based on a structural model of superior and inferior areas of relative vulnerability at the optic disc, we hypothesized that the nasal and paracentral regions are more prone to show a reduction in sensitivity. METHODS: Posthoc analysis of data collected in phases 1 and 2 of the Ocular Hypertension Treatment Study (OHTS). A pointwise analysis was applied to determine the progression patterns in the early and delayed treatment groups. Each group's progression rate and frequency were calculated for each of the 52 locations corresponding to the 24-2 VF strategy, using trend- and event-based analyses, respectively. RESULTS: For the event-based analysis, the events were most commonly found in the nasal and paracentral regions. The same regions, with some modest variation, were found to have the fastest rates of progression (ROP) measured with trend analysis. A similar pattern of progression was observed in both the early and delayed treatment groups. The difference in event rates and ROP between the early and delayed treatment groups was also greatest in the nasal and paracentral regions. CONCLUSIONS: Development of VF loss in ocular hypertensive eyes appears to be consistent with the vulnerability zones previously described in glaucomatous eyes with established VF loss. Ocular hypotensive treatment likely helps to slow the rate of progression in these regions. This suggests that careful monitoring of these locations may be useful.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents.

BACKGROUND: To examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma. METHODS: This retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races. RESULTS: There were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p<0.05). In both races, intervening CE was most strongly correlated with higher RNFLT variability (ß: 0.24-0.92, p<0.05). After excluding eyes with intervening CE, RNFLT variability was reduced and the small racial difference was no longer significant (AD: 1.40 (1.31, 1.48) µm vs ED: 1.34 (1.27, 1.40) µm; p=0.280). CONCLUSIONS: Although some predictors were identified, long-term RNFLT variability appeared small for both AD and ED eyes. Moreover, the racial difference did not remain once intervening CE, the strongest predictor of variability, was eliminated. Our findings inform on strategies to optimise structural assessment and suggest that, when accounting for relevant factors, RNFLT is reliable across races.

Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT): optometric exam improves access and utilization of eye care services.

PURPOSE: To describe the benefits of optometric evaluation for detection of vision-affecting conditions in the context of community-based eye health screenings and identify factors associated with having a recent dilated eye exam. METHODS: Enrolled participants were age 40 and older, living independently in affordable housing developments in New York City. Eye health screening failure and criteria for seeing the on-site study optometrist were defined as visual acuity 20/40 or worse in either eye, intraocular pressure 23-29 mmHg, or an unreadable fundus image. The optometrist conducted a manifest refraction using loose lenses and used a portable slit lamp and ophthalmoscope to perform a non-dilated anterior and posterior segment ocular health evaluation. Demographics, social determinants of health, eye health screening results, and rates of suspected ophthalmic conditions were recorded. To determine factors associated with having a recent dilated eye exam, which was the main outcome for this statistical analysis, a stepwise multivariate logistic regression was performed. RESULTS: A total of 708 participants were screened, 308 attended the optometric exam; mean age 70.7 ± 11.7 [standard deviation (SD)] years. Among this subgroup, 70.1% identified as female, 54.9% self-identified as African American, 39% as Hispanic/Latino, and 26.6% Dominican ethnicity; 78.2% (241/308) had not undergone a dilated eye exam within the last year, 71.4% reported they did not have an eye care provider. Stepwise multivariate logistic regression analysis indicated that participants who self-reported having cataracts (odds ratio (OR) 2.15; 95% confidence interval (CI) 1.03-4.47; p = 0.041), self-reported having glaucoma/glaucoma suspect (OR 5.60; 95% CI 2.02-15.43; p = 0.001), or spoke Spanish as their primary language (OR 3.25; 95% CI 1.48-7.11; p = 0.003) had higher odds of having a recent dilated eye exam. CONCLUSIONS: This community-based screening initiative demonstrated the effectiveness of optometric exams in detecting vision-affecting conditions and identified factors associated with having a recent dilated eye exam. Optometrists play a vital role in increasing access to eye care for high-risk, underserved populations. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04271709).

Deep Learning Identifies High-Quality Fundus Photographs and Increases Accuracy in Automated Primary Open Angle Glaucoma Detection.

Purpose: To develop and evaluate a deep learning (DL) model to assess fundus photograph quality, and quantitatively measure its impact on automated POAG detection in independent study populations. Methods: Image quality ground truth was determined by manual review of 2815 fundus photographs of healthy and POAG eyes from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study (DIGS/ADAGES), as well as 11,350 from the Ocular Hypertension Treatment Study (OHTS). Human experts assessed a photograph as high quality if of sufficient quality to determine POAG status and poor quality if not. A DL quality model was trained on photographs from DIGS/ADAGES and tested on OHTS. The effect of DL quality assessment on DL POAG detection was measured using area under the receiver operating characteristic (AUROC). Results: The DL quality model yielded an AUROC of 0.97 for differentiating between high- and low-quality photographs; qualitative human review affirmed high model performance. Diagnostic accuracy of the DL POAG model was significantly greater (P < 0.001) in good (AUROC, 0.87; 95% CI, 0.80-0.92) compared with poor quality photographs (AUROC, 0.77; 95% CI, 0.67-0.88). Conclusions: The DL quality model was able to accurately assess fundus photograph quality. Using automated quality assessment to filter out low-quality photographs increased the accuracy of a DL POAG detection model. Translational Relevance: Incorporating DL quality assessment into automated review of fundus photographs can help to decrease the burden of manual review and improve accuracy for automated DL POAG detection.

Detecting Established Glaucoma Using OCT Alone: Utilizing an OCT Reading Center in a Real-World Clinical Setting.

Purpose: We evaluated the ability of an optical coherence tomography (OCT)-based reading center for glaucoma (ORG) to detect established glaucoma using OCT alone. Methods: This study included eyes from 70 consecutive patients with established glaucoma (i.e. moderate or severe glaucoma according to the International Classification of Diseases [ICD]-10 guidelines) and 20 consecutive healthy subjects, who had no evidence of glaucomatous optic neuropathy (GON) or visual field (VF) loss in either eye. Using a standardized ORG quality assessment, 33 eyes were excluded due to media opacity (12), poor image quality (13), or epiretinal membrane (8). Of the remaining 147 eyes, 86 had established glaucoma and 36 were from healthy controls (total n = 122). Based on the OCT report alone and applying a previously described evaluation method, the presence of GON in each eye was determined by two masked ORG graders. The main outcome measures were sensitivity and specificity for detection of eyes with established glaucoma. Results: Of the 86 eyes with established glaucoma (average mean deviation [MD] = -10.9 ± 7.7 dB, range = -0.5 to -31.5 dB), only one eye (MD = -0.46) was missed (sensitivity = 98.8%). However, the other eye of this patient was correctly classified as GON. Therefore, at a patient level, sensitivity was 100%. None of the 36 healthy eyes was classified as GON by the ORG (specificity = 100%). Conclusions: An OCT-based reading center is able to identify eyes with established glaucoma using OCT alone with high sensitivity and specificity. Translational Relevance: Our study validates the use of a systematic OCT-based approach for glaucoma detection in a real-world setting.

Improving glaucoma staging in clinical practice by combining the ICD-10 glaucoma severity classification system and optical coherence tomography.

OBJECTIVE: The International Classification of Disease, 10th revision (ICD-10) codes used for glaucoma severity classification are based on the 24-2 visual-field (VF) test. This study aim was to assess the added value of providing clinicians with optical coherence tomography (OCT) data, in addition to functional data, for glaucoma staging in clinical practice. EXPOSURE: Disease classification was determined for 54 glaucoma eyes, according to the principles of the ICD-10 guidelines. Eyes were independently graded in a masked fashion using the 24-2 VF test and 10-2 VF test, with and without OCT information. The reference standard (RS) for severity was determined using a previously published automated structure-function topographic agreement for glaucomatous damage using all available information. RESULTS: The RS classified eyes as mild, moderate and advanced in 3, 16 and 35 cases, respectively. Individual and combined 24-2 and 10-2 based gradings were significantly different from the RS (all P < 0.005), with Kappa agreements of 0.26, 0.45 and 0.42 respectively (P < 0.001). Classifications using OCT combined with either of the VF were not-significantly different from the RS (P > 0.3) with Kappa agreements of 0.56 and 0.57 respectively (P < 0.001). Combining 24-2 with OCT had less severity overestimations while 10-2 with OCT had fewer underestimations. CONCLUSION: Combining OCT and VF data provides better staging of glaucoma severity than VF data alone. The 24-2 and OCT combination seems most appropriate given the high concordance with the RS and less overestimation of severity. Incorporating structural information into disease stages allows clinicians to set more appropriate severity-based treatment targets for individual patients.

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.

Glaucoma Detection Using Optical Coherence Tomography: Reviewing the Pitfalls of Comparison to Normative Data.

PRCIS: Optical coherence tomography is essential in managing glaucoma. This review describes various artifacts that originate from using a normative database to compare the individual's scans. This is a review paper regarding artifacts in optical coherence tomography imaging for glaucoma arising from using a normative database as a reference for healthy retinal nerve fiber layer and ganglion cell layer.