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.

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.

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.

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.

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).

Manhattan Vision Screening and Follow-Up Study: (NYC-SIGHT)Tele-Retinal Image Findings and Importance of Photography.

Purpose: To describe tele-retinal abnormality image findings from the Manhattan Vision Screening and Follow-up Study (NYC-SIGHT), which aims to investigate whether community-based eye health outreach strategies using telemedicine can improve visual outcomes among at-risk populations in Upper Manhattan. Methods: A 5-year prospective, cluster-randomized clinical trial was conducted. Eligible individuals aged 40 years and older were recruited from affordable housing developments and senior centers in New York City. Participants underwent on-site eye health screening (best-corrected visual acuity, intraocular pressure [IOP] measurements, and fundus photography). Fundus images were graded via telemedicine by a retina specialist. Multivariate logistic regression modeling was used to assess the factors associated with abnormal retinal findings requiring referral to ophthalmology. Results: Participants with a retinal abnormality on fundus photography (n = 157) were predominantly older adults, with a mean age of 68.4 ± 11.1 years, female (63.7%), African American (50.3%), and Hispanic (43.3%). A total of 32 participants in our study passed the vision and IOP screening but had an abnormal retinal image and ocular pathology that would have been missed without fundus photography. Individuals who self-identified as having preexisting glaucoma (odds ratio [OR] = 3.749, 95% confidence interval [CI] = 1.741-8.074, p = 0.0001) and had severe vision impairment (OR = 4.1034, 95% CI = 2.0740-8.1186, p = 0.000) at the screening had significantly higher odds of having an abnormal retinal image. Conclusion: This community-based study targeted populations at-risk for eye disease, improved access to eye care, detected a significant number of retinal image abnormalities requiring follow-up by using telemedicine, and provided evidence of the importance of fundus photography during eye health screenings. CTR number: NCT04271709.

Identifying Rapid Glaucoma Progression Using Hemifield Rates of Progression.

PRCIS: Hemifield rates of progression are more sensitive to focal progression (or faster progression) than global rates. This can aid in tailoring management and treatment decisions. PURPOSE: To determine if the rate of progression (ROP) of each hemifield of the 24-2 visual field (VF) aids in the detection of rapidly progressing eyes. METHODS: In this retrospective longitudinal study, we evaluated 1658 eyes of 1658 consecutive glaucoma patients with global mean deviation (MD) VF loss between -3 and -15 dB at baseline and ≥8 reliable VF tests (Swedish Interactive Thresholding Algorithm 24-2) with over ≥3 years of follow-up. The ROP (dB/year) based on global MD, superior hemifield MD, and inferior hemifield MD was calculated. The worst hemifield ROP (ROPworst) and hemifield ROP absolute difference (ROPdiff) were determined for each eye. Eyes were categorized based on the ROP from each metric as slow (-0.5 dB/year or better), rapid (worse than -0.5 dB/year), very rapid (worse than -1.0 dB/year), and catastrophic (worse than -2.0 dB/year) progression. The rate of significant asymmetric hemifield progression rate (ROPdiff ≥0.5 dB/year) was also evaluated. RESULTS: On average, ROPworst was faster than ROPglobal by 0.25±0.3 dB/year ( P <0.001). Based on ROPworst, 422 eyes (25%) were classified as progressing more rapidly than the ROPglobal classification. Over 40% (153/339) of the eyes classified as rapid progressors by ROPglobal were classified as very rapid or catastrophic progressors based on ROPworst. Eyes that progressed more rapidly based on ROPworst also had a higher rate of asymmetric progression. CONCLUSION: Hemifield ROPs are more sensitive to focal progression (or faster progression) than global rates and can aid in tailoring management and treatment decisions.

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.

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.

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.

A Model of Progression to Help Identify Macular Damage Due to Glaucoma.

The central macula contains a thick donut shaped region of the ganglion cell layer (GCL) that surrounds the fovea. This region, which is about 12 degrees (3.5 mm) in diameter, is essential for everyday functions such as driving, reading, and face recognition. Here, we describe a model of progression of glaucomatous damage to this GCL donut. This model is based upon assumptions supported by the literature, and it predicts the patterns of glaucomatous damage to the GCL donut, as seen with optical coherence tomography (OCT). After describing the assumptions and predictions of this model, we test the model against data from our laboratory, as well as from the literature. Finally, three uses of the model are illustrated. One, it provides an aid to help clinicians focus on the essential central macula and to alert them to look for other, non-glaucomatous causes, when the GCL damage does not fit the pattern predicted by the model. Second, the patterns of progression predicted by the model suggest alternative end points for clinical trials. Finally, the model provides a heuristic for future research concerning the anatomic basis of glaucomatous damage.

Extracting decision-making features from the unstructured eye movements of clinicians on glaucoma OCT reports and developing AI models to classify expertise.

This study aimed to investigate the eye movement patterns of ophthalmologists with varying expertise levels during the assessment of optical coherence tomography (OCT) reports for glaucoma detection. Objectives included evaluating eye gaze metrics and patterns as a function of ophthalmic education, deriving novel features from eye-tracking, and developing binary classification models for disease detection and expertise differentiation. Thirteen ophthalmology residents, fellows, and clinicians specializing in glaucoma participated in the study. Junior residents had less than 1 year of experience, while senior residents had 2-3 years of experience. The expert group consisted of fellows and faculty with over 3 to 30+ years of experience. Each participant was presented with a set of 20 Topcon OCT reports (10 healthy and 10 glaucomatous) and was asked to determine the presence or absence of glaucoma and rate their confidence of diagnosis. The eye movements of each participant were recorded as they diagnosed the reports using a Pupil Labs Core eye tracker. Expert ophthalmologists exhibited more refined and focused eye fixations, particularly on specific regions of the OCT reports, such as the retinal nerve fiber layer (RNFL) probability map and circumpapillary RNFL b-scan. The binary classification models developed using the derived features demonstrated high accuracy up to 94.0% in differentiating between expert and novice clinicians. The derived features and trained binary classification models hold promise for improving the accuracy of glaucoma detection and distinguishing between expert and novice ophthalmologists. These findings have implications for enhancing ophthalmic education and for the development of effective diagnostic tools.

What is the Optimal Frequency of Visual Field Testing to Detect Rapid Progression Among Hypertensive Eyes?

PRCIS: We evaluated 16,351 visual field (VF) tests from Ocular Hypertension Treatment Study (OHTS) database and showed that more frequent testing resulted in a shorter time to detect glaucoma progression, with the best trade-off being the 6-month intervals for high-risk and 12 months for low-risk patients. PURPOSE: To investigate the effect of different testing intervals on time to detect visual field progression in eyes with ocular hypertension. METHODS: A total of 16,351 reliable 30-2 VF tests from 1575 eyes of the OHTS-1 observation arm with a mean (95% CI) follow-up of 4.8 (4.7-4.8) years were analyzed. Computer simulations (n = 10,000 eyes) based on mean deviation values and the residuals of risk groups (according to their baseline 5 y risk of developing primary open angle glaucoma: low, medium, and high risk) were performed to estimate time to detect progression with testing intervals of 4, 6, 12, and 24 months using linear regression. The time to detect VF progression ( P < 5%) at 80% power was calculated based on the mean deviation slope of -0.42 dB/year. We assessed the time to detect a -3 dB loss as an estimate of clinically meaningful perimetric loss. RESULTS: At 80% power, based on the progression of -0.42 dB/year, the best trade-off to detect significant rates of VF change to clinically meaningful perimetric loss in high, medium, and low-risk patients was 6, 6, and 12-month intervals, respectively. CONCLUSION: Given the importance of not missing the conversion to glaucoma, the frequency of testing used in OHTS (6 mo) was optimal for the detection of progression in high-risk patients. Low-risk patients could potentially be tested every 12 months to optimize resource utilization.

Risk Calculation in the Medication Arm of the Ocular Hypertension Treatment Study.

PURPOSE: Risk assessment is integral to the management of individuals with ocular hypertension (OHTN). This study aims to determine the predictive accuracy of the Ocular Hypertension Treatment Study 5-year risk calculator (OHTS calculator) among treated patients with OHTN by applying it to patients randomized to the Ocular Hypertension Treatment Study (OHTS) medication arm. DESIGN: Post hoc secondary analysis of a randomized clinical trial. SUBJECTS: Individuals participating in the OHTS who were randomized to the medication arm. Only participants with complete baseline data in both eyes were included (n = 726). METHODS: The hazard ratios (HRs) of the medication group in OHTS were compared to the HR used for the OHTS calculator using the z-test statistic to establish the OHTS calculator's generalizability to the OHTS medication arm. The performance of the OHTS calculator among the OHTS medication group was evaluated twice, using both untreated baseline intraocular pressure (IOP) and average treated IOP during the first 24 months for the IOP variable. MAIN OUTCOME MEASURES: The performance was determined based on the model's accuracy in estimating the risk of reaching an OHTS primary open-angle glaucoma (POAG) end point using calibration chi-square and discriminating between participants who did or did not develop POAG. RESULTS: The HRs for the OHTS medication arm were not significantly different from those used in the OHTS calculator for untreated OHTN derived from observation arm data (P > 0.1). Based on the calibration chi-square test for the medication group, the OHTS calculator prediction model had good predictive accuracy when using the mean treated IOP and poorer predictive accuracy with the untreated baseline IOP (chi-square 10 and 29, respectively). The model had good discrimination with treated IOP (c-statistic = 0.77), comparable to what has been reported for the OHTS calculator in the OHTS observation group. CONCLUSIONS: The OHTS calculator can be applied to treated patients with OHTN, and repeat risk calculation after initiating IOP reduction may provide useful information that can aid in disease management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Progression of Early Glaucomatous Damage: Performance of Summary Statistics From Optical Coherence Tomography and Perimetry.

Purpose: Performance comparison of optical coherence tomography (OCT) and visual field (VF) summary metrics for detecting glaucomatous progression. Methods: Thirty healthy control eyes (mean deviation [MD], -1.25 ± 2.03; pattern standard deviation [PSD] , 1.78 ± 0.77) and 91 patient eyes comprised of 54 glaucoma patients and 37 glaucoma suspects (MD, -1.58 ± 1.96; PSD, 2.82 ± 1.92) with a follow-up of at least 1 year formed a group to evaluate progression with event analyses (P-Event). A subset of eyes with an additional criterion of a minimum of four tests was used for trend analyses (P-Trend) (30 healthy controls and 73 patients). For P-Event analysis, test-retest variability thresholds (lower 5th percentile) were estimated with repeat tests within a 4-month period. A P-Event eye was considered a "progressor" if the difference between follow-up and baseline tests exceeded the variability thresholds. For the P-Trend analysis, rates of change were calculated based on least-squares regression. Negative rates with significant (P < 0.05) values were considered progressing. For a reference standard, 17 patient eyes were classified as definitely progressing based on clear evidence of structural and corresponding functional progression. Results: Isolated OCT and VF summary metrics were either inadequately sensitive or not too specific. Combinations of OCT-OCT and OCT-VF metrics markedly improved specificity to nearly 100%. A novel combination of OCT metrics (circumpapillary retinal nerve fiber layer and ganglion cell layer) showed high precision, with 13 of the 15 statistical progressors confirmed as true positives. Conclusions: Although relying solely on metrics is not recommended for clinical purposes, in situations requiring very high specificity and precision, combinations of OCT-OCT metrics can be used. Translational Relevance: All available OCT and VF metrics can miss eyes with progressive glaucomatous damage and/or can falsely identify progression in stable eyes.

Manhattan Vision Screening and Follow-up Study (NYC-SIGHT): Baseline Results and Costs of a Cluster-Randomized Trial.

PURPOSE: To describe the 15-month baseline results and costs of the Manhattan Vision Screening and Follow-up Study, which aims to investigate whether innovative community-based eye health screening can improve early detection and management of glaucoma and other eye diseases among high-risk populations. DESIGN: Five-year prospective, cluster-randomized controlled trial. METHODS: Individuals aged 40+ years were recruited from public housing buildings in New York City for an eye health screening (visual acuity (VA) with correction, intraocular pressure measurements (IOP), and fundus photography). Participants with VA 20/40 or worse, IOP 23-29 mm Hg, or an unreadable fundus image failed the screening and were scheduled for an optometric examination at the same location; those with an abnormal image were referred to ophthalmology. A cost analysis was conducted alongside the study. RESULTS: A total of 708 participants were screened; mean age 68.6±11.9 years, female (65.1%), African American (51.8%) and Hispanic (42%). 78.4% (n = 555) failed the eye health screening; 35% (n= 250) had an abnormal image and were also referred to ophthalmology. 308 participants attended the optometric exam; 218 were referred to ophthalmology. Overall, 66.1% were referred to ophthalmology. The cost per participant to deliver the eye health screening and optometric examination was $180.88. The cost per case of eye disease detected was $273.64. CONCLUSIONS: This innovative study in public housing developments targeted high-risk populations, provided access to eye-care, and improved early detection of ocular diseases in New York City. The study has identified strategies to overcoming barriers to eye care to reduce eye health disparities.