Biomechanical changes of tree shrew posterior sclera during experimental myopia, after retrobulbar vehicle injections, and crosslinking using genipin.

Myopia is a common ocular condition characterized by biomechanical weakening revealed by increasing creep rate, cyclic softening scleral thinning, change of collagen fibril crimping, and excessive elongation of the posterior sclera resulting in blurred vision. Animal studies support scleral crosslinking as a potential treatment for myopia control by strengthening the weakened sclera and slowing scleral expansion. While multiple studies investigated aspects of the biomechanical weakening and strengthening effects in myopia and after scleral crosslinking, a comprehensive analysis of the underlying mechanical changes including the effect of vehicle injections is still missing. The purpose of this study was to provide a comprehensive analysis of biomechanical changes by scleral inflation testing in experimental myopia, after retrobulbar vehicle injections and scleral crosslinking using genipin in tree shrews. Our results suggest that biomechanical weakening in myopia involves an increased creep rate and higher strain levels at which collagen fibers uncrimp. Both weakening effects were reduced after scleral crosslinking using genipin at doses that were effective in slowing myopia progression. Vehicle injections increased mechanical hysteresis and had a small but significant effect on slowing myopia progression. Also, our results support scleral crosslinking as a potential treatment modality that can prevent or counteract scleral weakening effects in myopia. Furthermore, vehicle solutions may cause independent biomechanical effects, which should be considered when developing and evaluating scleral crosslinking procedures.

Acute ocular hypertension in the living human eye: Model description and initial cellular responses to elevated intraocular pressure.

This initial methods study presents the initial immunohistochemical and transcriptomic changes in the optic nerve head and retina from three research-consented brain-dead organ donors following prolonged and transient intraocular pressure (IOP) elevation. In this initial study, research-consented brain-dead organ donors were exposed to unilateral elevation of IOP for 7.5 h (Donor 1), 30 h (Donor 2), and 1 h (Donor 3) prior to organ procurement. Optic nerve tissue and retinal tissue was obtained following organ procurement for immunohistological and transcriptomic analysis. Optic nerve sections in Donor 1 exposed to 7.5-hours of unilateral sub-ischemic IOP elevation demonstrated higher levels of protein expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), within the lamina cribrosa with greatest expression inferior temporally in the treated eye compared to control. Spatial transcriptomic analysis performed on optic nerve head tissues from Donor 2 exposed to 30 h of unilateral IOP elevation demonstrated differential transcription of mRNA across laminar and scleral regions. Immunohistochemistry of retinal sections from Donor 2 exhibited higher GFAP and IBA1 expression in the treated eye compared with control, but this was not observed in Donor 3, which was exposed to only 1-hour of IOP elevation. While there were no differences in GFAP protein expression in the retina following the 1-hour IOP elevation in Donor 3, there were higher levels of transcription of GFAP in the inner nuclear layer, and CD44 in the retinal ganglion cell layer, indicative of astrocytic and Müller glial reactivity as well as an early inflammatory response, respectively. We found that transcriptomic differences can be observed across treated and control eyes following unilateral elevation of IOP in brain dead organ donors. The continued development of this model affords the unique opportunity to define the acute mechanotranscriptomic response of the optic nerve head, evaluate the injury and repair mechanisms in the retina in response to IOP elevation, and enable correlation of in vivo imaging and functional testing with ex vivo cellular responses for the first time in the living human eye.

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 individuals of African descent (AD). DESIGN: Retrospective cohort study. METHODS: This multicenter study included eyes with glaucoma from individuals of AD from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study with ≥2 years/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 were 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, and 75th percentile [as p25, median, and p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 subjects of AD (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 per year for RNFLT, and 0.00, -0.21, -0.30, and -0.51 dB per year for VF MD, respectively. Compared with 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 with that of VF MD progression, in eyes with mild glaucoma (≥1 year earlier) and in eyes with moderate to advanced glaucoma (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed a potentially shorter time to detect RNFLT progression than VF MD progression in eyes from individuals of AD. Our findings support the importance of using RNFLT to detect progressive glaucoma in individuals of AD.

Comparison of Glaucoma Diagnosis by Telemedicine, In-Person Ophthalmologist, and Optometrist.

PRCIS: Diagnosis of glaucoma through telemedicine demonstrates moderate agreement with in-person ophthalmologist (MD) and in-person optometrist (OD) diagnosis, providing evidence that telemedicine is a timely, accurate screening method in settings where an in-person visit may not be feasible. OBJECTIVE: To compare diagnostic agreement of glaucoma between in-person MD, in-person OD, and a simulated telemedicine program. PATIENTS AND METHODS: A cross-sectional study of patients with normal optic nerve structural and functional imaging and new patients referred for glaucoma evaluation examined in-person by an MD for glaucoma with a dilated examination and structural and functional optic nerve testing (optical coherence tomography, photos, and visual field); examined in person by an OD with a dilated examination and optic nerve testing; and structural and functional optic nerve testing reviewed separately by 2 ophthalmologists [telemedicine ophthalmologist reviewer 1 (TMD1), telemedicine ophthalmologist reviewer 2 (TMD2)] with masking of prior MD and OD diagnoses. Interrater agreement between each diagnostic method (MD, OD, TMD1, and TMD2) of normal versus disease (open angle glaucoma, normal tension glaucoma, other types of glaucoma, other optic nerve disorders, ocular hypertension, and glaucoma suspect) for each eye was calculated (Cohen unweighted kappa). RESULTS: A total of 100 patients with a median age of 66 years (interquartile range: 59-72), male (40%) and white (62%) were analyzed. There was moderate agreement between MD and telemedicine [TMD1 kappa 0.49 (95% CI: 0.37-0.61), TMD2 kappa 0.44 (95% CI: 0.32-0.56)] and between MD and OD diagnosis [0.41 (95% CI: 0.28-0.54)] and fair-moderate agreement between OD and telemedicine [TMD1: 0.46 (95% CI: 0.34-0.58), TMD2: 0.61 (95% CI: 0.50-0.72)]. CONCLUSIONS: The simulated telemedicine approach had comparable levels of agreement in glaucoma diagnosis with in-person fellowship-trained ophthalmologists, presenting a crucial complementary role in screening and increasing access to care, particularly in rural or underserved settings.

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.

Social Determinants of Health and Glaucoma Screening and Detection in the SIGHT Studies.

PRCIS: Targeted glaucoma screenings in populations with high levels of poverty and high proportions of people who identify as African American or Hispanic/Latino identified a 27% rate of glaucoma and suspected glaucoma, which is 3 times the national average. PURPOSE: To describe the neighborhood-level social risk factors across the 3 SIGHT Study sites and assess potential characteristics of these populations to help other researchers effectively design and implement targeted glaucoma community-based screening and follow-up programs in high-risk groups. METHODS/RESULTS: In 2019, Columbia University, the University of Michigan, and the University of Alabama at Birmingham each received 5 years of CDC funding to test a wide spectrum of targeted telehealth delivery methods to detect glaucoma in community-based health delivery settings among high-risk populations. This collaborative initiative supported innovative strategies to better engage populations most at risk and least likely to have access to eye care to detect and manage glaucoma and other eye diseases in community-based settings. Among the initial 2379 participants enrolled in all 3 SIGHT Studies; 27% screened positive for glaucoma/glaucoma suspect. Of all SIGHT Study participants, 91% were 40 years of age and older, 64% identified as female, 60% identified as African-American, 32% identified as White, 19% identified as Hispanic/Latino, 53% had a high school education or less, 15% had no health insurance, and 38% had Medicaid insurance. Targeted glaucoma screenings in populations with high levels of poverty and high proportions of people who identify as African American or Hispanic/Latino identified a 27% rate of glaucoma and suspected glaucoma, three times the national average. CONCLUSION: These findings were consistent across each of the SIGHT Studies, which are located in 3 geographically distinct US locations in rural Alabama, small urban locations in Michigan, and urban New York City.

Telemedicine Screening for Eye Disorders in Federally Qualified Health Centers: Relationship to Vision-Targeted Health-Related Quality of Life.

Introduction: Federally Qualified Health Centers (FQHCs) play a crucial role as safety-net primary health care clinics in the United States, serving medically underserved areas and populations. However, eye services are rarely offered at FQHCs. We examined how telemedicine-generated ocular diagnoses impacted vision-targeted health-related quality of life at FQHCs in rural Alabama. Methods: We focused on patients who are at risk for glaucoma. Both visual function and retinal imaging were assessed. The telemedicine vision screening protocol performed by a remote ophthalmologist evaluated eyes for glaucoma, diabetic retinopathy, cataract, age-related macular degeneration, and a measurement of habitual visual acuity. The National Eye Institute Visual Function Questionnaire-9 (VFQ-9) was administered. Results: Using stepwise regression, the best-fitting model for predicting VFQ-9 scores incorporated visual acuity 20/40 or worse, a diabetic retinopathy diagnosis, and sociodemographic variables (gender, transportation, insurance type/status, and employment status). Conclusion: Vision-targeted, health-related quality of life in our FQHC settings was related to the visual acuity impairment and the diagnosis of diabetic retinopathy but was also influenced by a variety of sociodemographic factors.

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.

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.

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.

Feasibility of Glaucoma Detection Programs for At-Risk Populations Using Existing Health Care Infrastructure.

PRCIS: Targeted glaucoma screening strategies performed within retail care-based clinics and Federally Qualified Health Centers (FQHCs) uncover a high prevalence of glaucoma. OBJECTIVE: To summarize the glaucoma detection and maintenance programs that utilize existing health care infrastructure to promote up-scalable programs. METHODS: Health care infrastructure that already exists may facilitate glaucoma detection. This infrastructure includes retail-based optometry practices and FQHC. Persons who are at risk for glaucoma are disproportionately represented within the patient populations served by much of this infrastructure, thus suggesting that it could be useful for deploying glaucoma screening programs. Glaucoma screening within FQHCs reveals a very high prevalence of glaucoma and related disease in the patients seeking care at these facilities. RESULTS: These telemetric-based care delivery programs have a high patient acceptance. A simulated telemedicine program modeled after a telemedicine program based in Walmart Vision Centers for the diagnosis of glaucoma indicated that there was moderate diagnostic agreement between an ophthalmologist's telemedicine diagnosis and an ophthalmologist's in-person diagnosis. There was also moderate agreement between an optometrist's telemedicine diagnosis and the ophthalmologist's in-person diagnosis. CONCLUSION: Telemetric care delivery programs that capitalize on existing infrastructure within a retail-based care setting or FQHCs may provide a promising setting to cost-effectively screen for glaucoma and other eye diseases that are potentially expandable nationwide.

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.

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.

Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents.

PURPOSE: To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED). DESIGN: Retrospective cohort study. METHODS: AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort-specific RNFLT baseline/thinning rates). RESULTS: We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively. In standardized scenarios, the time to detect RNFLT progression appeared to be similar (difference, <0.2 years) for AD and ED across different assumed RNFLT thinning rates/baseline. In real-world scenarios, compared to ED, AD had a faster RNFLT thinning rate (-0.8 vs -0.6 µm/y) and thicker baseline RNFLT (84.6 vs 81.8 µm). With a faster thinning rate, the mean (SD) time to progression detection was shorter in AD (4.8 [2.0] vs ED: 5.4 [2.4] years), and the 5-year progression rate appeared to be higher (AD: 59% vs ED: 47%). CONCLUSIONS: Time to progression detection was similar for both races when assuming identical RNFLT baseline/thinning rates, and shorter in AD eyes under real-world simulation when AD had faster RNFLT thinning. In contrast to prior results on VF, which detected progression later in AD eyes than in ED eyes, OCT may detect progression more consistently across these races.

Optical Coherence Tomographic Optic Nerve Head Morphology in Myopia III: The Exposed Neural Canal Region in Healthy Eyes-Implications for High Myopia.

PURPOSE: To determine the prevalence and magnitude of optical coherence tomography (OCT) exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT), and exposed scleral flange (ESF) regions in 362 non-highly myopic (spherical equivalent -6.00 to 5.75 diopters) eyes of 362 healthy subjects. DESIGN: Cross-sectional study. METHODS: After OCT optic nerve head (ONH) imaging, Bruch membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented. BMO, ASCO, and SFO points were projected to the BMO reference plane. The direction and magnitude of BMO/ASCO offset as well as the magnitude of ENC, EOCBT, and ESF was calculated within 30° sectors relative to the foveal-BMO axis. Hi-ESF eyes demonstrated an ESF ≥100 µm in at least 1 sector. Sectoral peri-neural canal choroidal thickness (pNC-CT) was measured and correlations between the magnitude of sectoral ESF and proportional pNC-CT were assessed. RESULTS: Seventy-three Hi-ESF (20.2%) and 289 non-Hi-ESF eyes (79.8%) were identified. BMO/ASCO offset as well as ENC, EOCBT, and ESF prevalence and magnitude were greatest inferior temporally where the pNC-CT was thinnest. Among Hi-ESF eyes, the magnitude of each ENC region correlated with the BMO/ASCO offset magnitude, and the sectors with the longest ESF correlated with the sectors with proportionally thinnest pNC-CT. CONCLUSIONS: ONH BMO/ASCO offset, either as a cause or result of ONH neural canal remodeling, corresponds with the sectoral location of maximum ESF and minimum pNC-CT in non-highly myopic eyes. Longitudinal studies to characterize the development and clinical implications of ENC Hi-ESF regions in non-highly myopic and highly myopic eyes are indicated.

Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT): Baseline Results.

PURPOSE: To describe baseline results of the Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT) for patients at federally qualified health centers (FQHCs). Candidates were persons at risk for glaucoma-associated diseases (GAD) based on age, race/ethnicity, current diagnosis of GAD, family history, and diabetes. DESIGN: Baseline screening visit followed by remote diagnosis and referral for follow-up examinations. METHODS: Patients presenting to FQHCs who were at least 18 years of age were enrolled and underwent screening for acuity, autorefraction, intraocular pressure, visual field testing, and fundus imaging. Results were transmitted to an ophthalmologist at University of Alabama at Birmingham for diagnosis who made referrals for follow-up; follow-up attendance was noted. Questionnaires assessed participants' perspectives on screening. Primary outcomes were rates of disease detection, referral for follow-up, follow-up attendance, and participant satisfaction. RESULTS: Of the 500 participants enrolled (mean age 58 years), 45.6% were African American and 51.6% White. Remote diagnostic evaluation of ocular screening by ophthalmologist revealed 30% GAD, 6.8% diabetic retinopathy, 37.6% cataract, 68.4% refractive error, 9.2% other eye conditions. In all, 47.2% of the participants were referred for follow-up examination and for acuity 20/40 or worse or IOP ≥23 mm Hg in one or both eyes. Follow-up examination attendance was 76.7% for those referred. Participants reported being very satisfied with screening (85.8%) and with the convenience of screening in their primary care clinic (92.2%). CONCLUSIONS: The high percentage of patients diagnosed with treatable eye conditions at telemedicine screening suggest these programs in FQHCs can be effective and scalable nationwide. Attendance when referred for follow-up examination was high. Participants welcomed screenings in their communities.

Displacement of the Lamina Cribrosa With Acute Intraocular Pressure Increase in Brain-Dead Organ Donors.

Purpose: To examine deformations of the optic nerve head (ONH) deep tissues in response to acute elevation of intraocular pressure (IOP). Methods: Research-consented brain-dead organ donors underwent imaging by spectral domain optical coherence tomography (OCT). OCT imaging was repeated while the eye was sequentially maintained at manometric pressures of 10, 30, and 50 mm Hg. Radial scans of the ONH were automatically segmented by deep learning and quantified in three dimensions by a custom algorithm. Change in lamina cribrosa (LC) depth and choroidal thickness was correlated with IOP and age by linear mixed-effect models. LC depth was computed against commonly utilized reference planes. Results: Twenty-six eyes from 20 brain-dead organ donors (age range, 22-62 years; median age, 43 years) were imaged and quantified. LC depth measured against a reference plane based on Bruch's membrane (BM), BM opening, and an anterior sclera canal opening plane showed both a reduction and an increase in LC depth with IOP elevation. LC depth universally increased in depth when measured against a sclera reference plane. Choroidal (-0.5222 µm/mm Hg, P < 0.001) and retinal nerve fiber layer thickness (-0.0717 µm/mm Hg, P < 0.001) significantly thinned with increasing IOP. The magnitude of LC depth change with IOP was significantly smaller with increasing age (P < 0.03 for all reference planes). Conclusions: LC depth changes with IOP reduce with age and are significantly affected by the reference plane of choice, which highlights a need for standardizing LC metrics to properly follow progressive remodeling of the loadbearing tissues of the ONH by OCT imaging and for the definition of a reference database.

Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study.

OBJECTIVES: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma. DESIGN: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). SETTING: Three tertiary glaucoma centres in the USA. PARTICIPANTS: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies. OUTCOME MEASURES: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time. RESULTS: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years). CONCLUSION: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people. TRIAL REGISTRATION NUMBER: NCT00221897 and NCT00221923.

Clinical Factors Associated With Long-Term OCT Variability in Glaucoma.

PURPOSE: To examine clinical factors associated with long-term optical coherence tomography (OCT)-measured retinal nerve fiber layer thickness (RNFLT) variability in glaucoma. STUDY DESIGN: Retrospective cohort study. METHODS: Glaucoma eyes from Diagnostic Innovations in Glaucoma Study (DIGS)/the African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2-years and 4-visit follow-up were included. RNFLT variability was calculated per visit as the absolute error of optic nerve head RNFLT residuals across longitudinal follow-up. Clinical factors examined included general demographics, baseline ocular measurements, prior and intervening cataract extraction (CE) or glaucoma surgery, scan quality, baseline RNFLT and RNFLT thinning rate, follow-up duration, and visit/testing frequency. Three multivariable linear mixed models (full model, baseline model, and parsimonious model) were fit to evaluate the effects of clinical factors on RNFLT variability, with 10-fold cross-validation to estimate real-world model performance. RESULTS: A total of 1140 eyes (634 patients) were included. The overall mean (95% CI) RNFLT variability was 1.51(1.45, 1.58) µm. Across different models, African American race (ß [standard error {SE} = 0.18 [0.06]), intervening CE (ß [SE] = 0.52 [0.07]), intervening glaucoma surgeries (ß [SE] = 0.15 [0.03]), and more positive RNFLT thinning rate (ß [SE] = 0.06 [0.02] per 1 µm/y more positive) showed consistent association with greater RNFLT variability, whereas more frequent visits/testing (ß [SE] = -0.11[0.05] per 1 visit/y higher) was associated with smaller RNFLT variability (P < .05 for all). CONCLUSIONS: Relevant clinical factors affecting long-term RNFLT variability in glaucoma were identified. These data enhance the evaluation of longitudinal structural change. Increasing the testing frequency, especially in eyes at risk for higher measurement variability, and resetting of baseline imaging after intervening procedures may help to more reliably detect OCT progression.

Progressive Visual Field Loss and Subsequent Quality of Life Outcomes in Glaucoma.

PURPOSE: To evaluate the association between baseline severity of visual field (VF) damage and the initial rates of VF progression with quality of life (QOL) outcomes over an extended follow-up in glaucoma. DESIGN: Retrospective cohort study. METHODS: Both eyes of 167 glaucoma or suspected glaucoma patients were followed for 10.0±0.3 years. The National Eye Institute Visual Function Questionnaire (NEI-VFQ)-25 was performed at the end of the follow-up. Separate linear regression models included the VF parameters of the better eye, the worse eye, and the central and peripheral points of the integrated binocular VF to evaluate the association of baseline and initial rates of change of VF parameters (first half of the follow-up) with NEI-VFQ-25 Rasch-calibrated disability scores over an extended follow-up. RESULTS: All models demonstrated association of worse baseline severity of VF damage with worse subsequent NEI-VFQ-25 scores. Faster rates of decline in VF mean deviation of the better eye and the mean sensitivity of the central and peripheral test locations of the integrated binocular VF were significantly associated with worse subsequent NEI-VFQ-25 scores. VF parameters of the better eye performed better than those of the worse eye (R2 of 0.21, and 0.15, respectively), and the VF parameters of the central test locations performed better than those of the peripheral test locations (R2 of 0.25, and 0.20, respectively). CONCLUSIONS: Baseline severity and initial rates of change of VF damage are associated with QOL outcomes over an extended follow-up. Assessment of longitudinal VF changes, especially in better eye, provides prognostic utility to identify glaucoma patients at a higher risk for developing disease-related disability.