Age-related macular degeneration (AMD) degrades central vision in older adults worldwide. To enable precision prevention and early intervention, the longitudinal Alabama Study of Age-related Macular Degeneration 2 (ALSTAR2) seeks functional and imaging outcomes at the aging-AMD interface. ALSTAR2 relies on accurate two-dimensional maps of photoreceptor and retinal pigment epithelium (RPE) distributions and a histology-informed, deposit-driven progression sequence involving dysregulated bi-directional transport between photoreceptors and circulation. This transport is globally assessed by rod-mediated dark adaptation (RMDA), a dynamic measure of rod sensitivity recovery after exposure to a bright light. RMDA measured at the rim of the high-risk macula lutea is affected earlier and is more predictive of AMD onset and progression than steady-state functional measures of rods, cones, and neural circuitry, in both tested and fellow eyes. Delayed RMDA incorporates the Oil Spill hypothesis of drusen formation, which posits that lipoprotein particles constitutively released by RPE are trapped by aged Bruch's membrane and choriocapillaris. Subretinal drusenoid deposit, associated with poor RMDA and risk for advanced AMD, may represent a late-appearing barrier to transport at the level of the RPE. Although RMDA slowing is already underway before routinely visible AMD pathology, some structural and metabolic imaging technologies may assist early detection.

Purpose:The purpose of this study was to evaluate change in visual functions over 3 years in normal macular health, and early and intermediate age-related macular degeneration (AMD) including tests of rod-, cone-, and mixed rod-cone-mediated visions; and to evaluate whether visual function change over 3 years meets the minimal clinically important difference (MCID), defined as meaningful to patients in everyday life. Methods:Eight visual functions were evaluated at baseline and 3-year follow-up (acuity, low luminance acuity, photopic and mesopic contrast sensitivity, mesopic and scotopic light sensitivity, and rod-mediated dark adaptation [RMDA] at 5 degrees and 12 degrees). The Age-Related Eye Disease Study (AREDS) 9-step classification system defined AMD severity. Results:In normal aging and intermediate AMD, 6 of 8 visual functions had statistically significant worsening over 3 years; mesopic contrast sensitivity and mesopic light sensitivity, respectively, showed no change. In early AMD, five of eight visual functions showed worsening over time, with photopic and mesopic contrast sensitivity and scotopic sensitivity unchanged. The largest percentage of eyes in each group meeting MCID was RMDA at 5 degrees or 12 degrees (38%-55%). The lowest percentage of eyes meeting MCID was visual acuity and photopic contrast sensitivity (0%-10%). Conclusions:Whereas most visual functions evaluated have statistically significant worsening over 3 years in normal aging to intermediate eyes, the percentage of eyes reaching MCID was low for most visual functions except RMDA, which met MCID for almost half the eyes. Translational Relevance:The natural history of change in visual function over time in normal aging to intermediate AMD should be characterized in terms of MCID, not only statistical significance.

Purpose:To cross-sectionally compare parameters from the quick contrast sensitivity function (qCSF)-area under the log CSF (AULCSF) and sensitivity at each spatial frequency-in older eyes with normal macular health and early, intermediate, and late AMD. Our purpose was to determine whether qCSF could be a promising functional outcome measure in interventions designed to slow AMD progression from aging to late AMD. Methods:qCSF contrast sensitivity was measured at 1.0 to 18 cycles per degree (cyc/deg). Models evaluated the impact of diagnostic group on the AULCSF and individual spatial frequencies, adjusting for age and lens status. The AREDS nine-step classification system defined AMD presence and severity. Results:Eight hundred twenty-three eyes were studied: 383 normal macular health, 203 early AMD, 208 intermediate AMD, and 29 late AMD (23 geographic atrophy, six neovascular AMD). AULCSF decreased with increasing AMD severity; this was mostly attributable to the late AMD eyes having lower AULCSF than other groups. Late AMD eyes had significantly worse sensitivity at 1 and 1.5 cyc/deg compared to all other groups, with other groups having similar sensitivity. At frequencies near or just beyond the CSF peak (3-12 cyc/deg), late AMD eyes again had the worst sensitivity, with intermediate AMD eyes having slightly worse sensitivity than early AMD eyes. There were no group differences at 18 cyc/deg. Conclusions:The qCSF will be most useful in trials studying the transition from intermediate AMD to late-stage AMD, rather than in studying the transition from aging to early and intermediate AMD.

PURPOSE:To highlight the role of en face OCT in the measurement of choroidal hypertransmission defects (hyperTDs) in complete retinal pigment epithelial and outer retinal atrophy (cRORA), and to refine the definition of retinal pigment epithelium (RPE)-related alterations associated with cRORA. DESIGN:Consensus meeting. PARTICIPANTS:Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. METHODS:As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed the role of en face OCT in the assessment of cRORA. A structured study was conducted, consisting of an exercise to assess en face OCT cases, reviewed jointly during the eighth CAM meeting, and to explore the utility of this advanced tool for disease staging and progression. Additionally, definitions previously applied to RPE abnormalities were discussed and refined leading to modifications. The current report summarizes the methods used during the consensus meeting and the outcomes achieved as pertains to the application of en face OCT for cRORA grading and simplification of the RPE assessment criteria. MAIN OUTCOME MEASURES:Defining the role of en face OCT in the detection and quantification of hyperTDs, improving classification of cRORA, and refining the terminology related to RPE alterations to enhance grading consistency. RESULTS:During the consensus case discussions, high levels of agreement were achieved for hyperTD detection using en face OCT. The CAM group affirmed the role of en face OCT as a critical adjunct to traditional B-scan analysis, for more precise measurement of the area of cRORA lesions and for distinguishing threshold cRORA from smaller incomplete retinal pigment epithelial and outer retinal atrophy lesions. Additionally, merger of RPE attenuation and RPE disruption into a unified category termed "abnormal RPE band" significantly reduced interreader variability, leading to greater consistency among graders. CONCLUSIONS:The integration of en face OCT with cross sectional B-scan imaging enhances the accurate classification and area measurement of early atrophic alterations in age-related macular degeneration, improving diagnostic consistency and lesion assessment. The consensus panel's adoption of the abnormal RPE band term as a unified category for RPE abnormalities may reduce confusion regarding the definition of RPE degeneration and has the potential to improve interreader variability. FINANCIAL DISCLOSURE(S):The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose To evaluate patient satisfaction and preferences for portable versus table-mounted visual field (VF) devices in a rural telemedicine setting and identify influencing factors. Methods We conducted a sequential explanatory mixed methods study at three Federally Qualified Health Centers (FQHCs) within the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine (AL-SIGHT) study. Participants completed VF testing with table-mounted Humphrey Field Analyzer (HFA), tablet-based Melbourne Rapid Fields (MRF), and virtual reality (VR)-based VisuALL perimeters. Participants rated satisfaction, comfort, ease of use, and future testing preference. Chi-square tests assessed differences in device preferences. Twelve participants completed semi-structured interviews to explore reasons underlying preferences. Qualitative data were analyzed in NVivo 14 using reflexive thematic analysis. Results Among 271 respondents (mean age 60.4 years; 62.4% women), 50.6% preferred VR-based, 35.1% tablet-based, and 14.4% table-mounted for future testing (χ2 (2) = 53.52, p<0.001, Cramér’s V = 0.31). Satisfaction was highest for VR-based (56.9% very satisfied), followed by tablet-based (49.4%), and HFA (38.0%). VR-based perimeter was most frequently selected as the most comfortable (55.7%; χ2 (2) = 63.33, p<0.001, V = 0.34) and easiest to use (54.6%; χ2 (2) = 71.96, p<0.001, V = 0.36). Preferences did not vary significantly across demographic variables (all p>0.05). Qualitative themes identified four key drivers: comfort and physical experience, visual experience, ease of use and interaction, and psychological and motivational factors. Portability and community suitability were valued. Conclusion Rural underserved patients strongly preferred portable visual field devices, particularly VR-based, over table-mounted HFA. Comfort, ergonomic flexibility, immersive visual experience, and simplicity of interaction were central determinants of preference. Portable perimetry may enhance patient-centered glaucoma monitoring within telemedicine programs and access in resource-limited settings. ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following disclosures: E.K. Antwi-Adjei, None S. Datta, None C.A. Girkin, Heidelberg Engineering (F), Topcon (F) C. Owsley, Johnson & Johnson (C), Sanofi (C) L.A. Rhodes, IdentifEye Health (C) M. Fifolt, None L. Racette, Olleyes, Inc. (C). These relationships do not alter our adherence to PLOS ONE policies on sharing data and materials. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol was approved by the Institutional Review Board of the University of Alabama at Birmingham, and all procedures adhered to the tenets of the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.

Purpose:To compare visual field (VF) outcomes from tablet-based (Melbourne Rapid Fields [MRF]) and table-mounted (Humphrey Visual Field Analyzer [HFA]) devices in a telemedicine program in underserved rural areas. Methods:Participants from the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine (AL-SIGHT) study completed VF testing using both HFA and MRF in counterbalanced order. Outcome measures included reliability indices, mean deviation (MD), pattern standard deviation (for HFA/PD for MRF), and VF index (for HFA)/visual capacity (VC for MRF). Analyses were conducted by eye, assessing agreement using intraclass correlation coefficients and Bland-Altman plots. Results:Of the 253 eligible participants (mean age, 56.7 ± 12.2 years; 67.6% female; 60.1% White), 174 right eyes and 180 left eyes had reliable results on both devices. Fixation losses were higher with HFA (P < 0.001); however, no significant differences were observed for false positives and false negatives between the devices. For right eyes, agreement between tests was moderate (intraclass correlation coefficient, 0.55 for MD, 0.56 for PD, and 0.65 for VC). No significant differences were observed in MD. The MRF yielded higher PD (mean difference, 0.88 dB; 95% limits of agreement, -5.01 to 3.25 dB) and lower VC (mean difference, 3.01%; 95% limits of agreement, -10.87 to 16.90%). Similar left eyes trends were observed. Conclusions:The MRF showed moderate agreement with the HFA across selected VF indices. These findings represent an initial step toward feasibility for telemedicine integration, with additional studies needed to determine reliability and clinical utility. Translational Relevance:Tablet-based perimetry shows potential for rural telemedicine settings.

Laboratory and patient-oriented research on photoreceptors and vision in ageing and early and intermediate age-related macular degeneration (AMD) were conducted in parallel starting in the 1990s by Christine Curcio and Cynthia Owsley, respectively. They joined forces in two longitudinal observation studies, the Alabama Study on Age-related Macular Degeneration (ALSTAR) in 2009 and in ALSTAR2 in 2019, together involving >1100 participants. These studies established rod-mediated dark adaptation (RMDA) measured close to the fovea as the first functional biomarker for incident early AMD and the progression of AMD. These studies used standardised grading of colour fundus photography and prioritised large samples for statistical power. RMDA is a global measure of dysregulated transport between the circulation and photoreceptors, involving at least seven different steps in a retinoid re-supply route especially needed by rods, and a surrogate for the delivery of other essentials across this route. The choice of functional and imaging outcome measures was informed by a model of AMD pathophysiology based on drusen biology, as discovered in the laboratory using high-quality human donor eyes. Specifically, high-risk drusen in the central retina were thought to result from large lipoproteins constitutively made by the retinal pigment epithelium and impaired in transit to circulation by ageing changes in Bruch’s membrane and choriocapillaris. Imaging studies in ALSTAR/2 thus included optical coherence tomography (OCT) angiography assessments of choriocapillaris flow signal and OCT assessments of outer bands involved in intercellular transfer (interdigitation zone). Of seven vision tests utilised in ALSTAR2, only RMDA achieved a Minimum Clinically Important Difference at 3 years follow-up. This research highlights the importance of developing functionally valid structural endpoints for use in early and intermediate AMD intervention trials. Research to date supports the idea that functional changes emerge earlier than structural changes in early and intermediate AMD. Clinicaltrials.gov # NCT04112667 (registration date October 7, 2019)

Introduction and Objective: The ability to understand and affect the course of complex, multi-system diseases like diabetes has been limited by a lack of well-designed, high-quality and large multimodal datasets. The NIH Bridge2AI AI-READI project (aireadi.org) aims to address this shortfall by generating an AI-ready dataset to support AI discoveries in type 2 diabetes mellitus (T2DM). Methods: Our goal is to recruit 4000 persons ≥ 40 years of age balanced for 4 categories of T2DM: non-diabetic, prediabetes/lifestyle-controlled, controlled by oral-medications/non-insulin injectables and insulin-dependent. Data collection sites are located in Birmingham AL, San Diego CA, and Seattle WA. The variable domains of the dataset encompass many biomedical and behavioral aspects of health often impacted in T2DM (Figure 1). Blood derivatives, including serum, plasma, RNA and Peripheral Blood Mononuclear Cells, are available to researchers for future research. Results: As of November 2025, data from 2280 participants has been released that is standardized and optimized for AI/ML research. The current release includes 358,999 files (3.87 TB) of data and is available to researchers through a registered public access or a controlled access database, depending on the variables requested. A final dataset release from ~4000 participants is scheduled by November, 2026. Conclusion: This flagship dataset may enable new AI discoveries in T2DM. Disclosure D. Matthies: None. J. Owen: None. G. McGwin: None. C. Owsley: Consultant; Current; Johnson & Johnson. Research Support; Current; Boehringer Ingelheim International GmbH, Roche Pharmaceuticals. Consultant; Current; Sanofi. S. Baxter: Consultant; Ended; Topcon Healthcare. L.M. Zangwill: Research Support; Current; Heidelberg Engineering, Carl Zeiss Meditec, Topcon Medical Systems, Optovue Inc, iCare Inc, Optomed, EssilorLuxotica. Other - Travel; Current; AISight Health. C. Lee: None. A. Lee: Research Support; Current; Regeneron Pharmaceuticals Inc. Research Support; Ended; Topcon Healthcare. Consultant; Current; Sanofi-Aventis U.S. Consultant; Ended; Boehringer Ingelheim International GmbH. Consultant; Current; Johnson & Johnson, Sanofi, Genentech, Inc. Research Support; Ended; Zeiss. Consultant; Current; Gyroscope. Research Support; Current; Santen. Funding National Institutes of Health (OT2OD032644)

Purpose:The purpose of this study was to determine cross-sectional associations among intake of xanthophyll carotenoids lutein and zeaxanthin (L&Z), plasma L&Z, and two wavelength autofluorescence (2WAF) retinal imaging in aging and age-related macular degeneration (AMD). Methods:Adults ≥63 years old from a comprehensive ophthalmology clinic underwent assessments: macular health (Age-Related Eye Disease Study [AREDS] 9-step); self-reported L&Z intake from diet (LZQ Food Frequency Questionnaire) and supplements; total intake; macular pigment optical volume (MPOV; in 2WAF); non-fasting plasma L&Z; and HDL and LDL cholesterol. Associations were adjusted for age and HDL/LDL. Results:We studied 369 persons (74 ± 5.8 years, 60% women, 89% White, 62% never-smoker, and 23% supplement use) and 369 eyes (48.4% healthy, 26.0% early AMD [eAMD], and 25.2% intermediate AMD [iAMD]). Diagnostic groups differed in supplement users (10%, 17%, and 56%), total L&Z intake (5.3 ± 6.4, 5.5 ± 5.4, and 11.0 ± 8.3 mg/d, P < 0.01), and MPOV (1.04 ± 0.46, 1.02 ± 0.52, and 1.33 ± 0.61). Groups did not differ in dietary intake (3.8 ± 4.5, 3.4 ± 3.2, and 3.7 ± 3.8 mg/d), plasma HDL, or HDL/LDL. Associations were strong between plasma L&Z and MPOV (r = 0.41-0.67, P < 0.01); moderate between total intake and plasma L&Z (Spearman r = 0.29-0.50, P < 0.01); weaker but significant for L&Z intake, and MPOV (r = 0.22-0.30, P < 0.01) of 3-mm-diameter macula lutea only, for eAMD and iAMD. Conclusions:In a large US sample, we assess for the first time L&Z intake from diet and supplements and determined the relative strength of correlations among intake, plasma, and retinal xanthophylls. We replicate our earlier finding of elevated retinal and plasma L&Z in iAMD. LZQ and 2WAF are suitable outcome measures for future interventions that directly test the impact of L&Z on AMD onset and progression.

Purpose:To determine if a baseline choriocapillaris flow signal deficits (CCFD%), as a marker of impaired transport, is associated with age-related macular degeneration (AMD) onset and progression at the 3-year follow-up. Methods:Participants ≥ 60 years old with normal macular health, early AMD (eAMD), and intermediate AMD (iAMD) were staged at baseline and follow-up with the Age-Related Eye Disease Study (AREDS) 9-step classification system and were then classified as stable and progressing based on whether their stage advanced. Spectral-domain optical coherence tomography angiography (OCTA) quantified baseline CCFD% across the Early Treatment Diabetic Retinopathy Study (ETDRS) central subfield (CS), inner ring (IR), and an outer area (OA, extending superiorly). Adjusted baseline CCFD% values were compared between stable and progressing eyes. Results:Of 332 included eyes at baseline (mean age, 71.1 ± 5.8 years), 173 eyes were normal, 101 were eAMD, and 58 were iAMD. Over 3 years, 284 eyes remained stable (85.5%), and 48 eyes progressed (14.5%). In the overall cohort, progressing eyes demonstrated significantly higher baseline CCFD% than stable eyes in the CS (57.7% vs. 53.5%; P = 0.007) and IR (56.1% vs. 53.9%; P = 0.045), but not in the OA. When stratified by baseline AMD stage, stable versus progressor differences were exclusively observed in eAMD (51.4% vs. 60.7% and 52.6 vs. 58.0% for CS and IR, respectively) but not in OA or in normal eyes (all P > 0.05). Conclusions:CCFD% in the CS and IR, one aspect of impaired transport between circulation and photoreceptors, is associated with AMD progression in early-stage disease; this spatial specificity implicates the fovea.

The ability to understand and affect the course of complex, multi-system diseases like diabetes has been limited by a lack of well-designed, high-quality and large multimodal datasets. The NIH Bridge2AI AI-READI project (aireadi.org) aims to address this shortfall by generating an AI-ready dataset to support AI discoveries in type 2 diabetes mellitus (T2DM). This manual of procedures provides a detailed description of the AI-READI protocol.

BackgroundCognitive processing speed is integral to everyday activities and can be improved with training in persons with mild cognitive impairment (MCI). However, whether this training maintains everyday abilities is not known.ObjectiveWe aimed to determine whether everyday functions key to independence could be preserved with two years of processing speed training.MethodsIn a randomized controlled trial, we objectively evaluated a processing speed training protocol compared to a control training protocol, in 103 persons with MCI (n = 90) or very mild dementia (n = 13) due to Alzheimer's disease (AD). Each protocol involved serial assessments, laboratory training, and home training over a two-year period. We accounted for APOE ε4 carrier status and MRI-based neurodegeneration conducted at baseline. Outcomes were longitudinal changes in performance-based Instrumental Activities of Daily Living (IADLs), community mobility, and on-road driving. We used linear mixed models to evaluate changes in these outcomes over time.ResultsChanges in IADL function, driving, and community mobility did not differ by training assignment. Greater baseline neurodegeneration predicted larger declines in all functional outcomes (p values < 0.001).ConclusionsIn persons with MCI or very mild dementia, processing speed training was no more effective for maintaining everyday functions than training involving common computer activities and games that do not target processing speed. Greater baseline neurodegeneration predicted worse performance over time on all measures of function.

PURPOSE:To examine whether delayed rod-mediated dark adaptation (RMDA) in healthy older eyes and those with early age-related macular degeneration (AMD) is associated with AMD incidence and progression at follow-up, as compared with other visual functions reliant on rods, cones, or mixed rod-cone mediation. DESIGN:Longitudinal study over 3 years. PARTICIPANTS:Eyes from adults ≥60 years of age with normal macular health or with early AMD at baseline. METHODS:At baseline, eyes underwent fundus photography to establish AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step classification system. The following visual functions were tested in 1 eye at baseline (the study eye): RMDA, scotopic sensitivity, low-luminance acuity, mesopic contrast sensitivity, mesopic light sensitivity, visual acuity, and contrast sensitivity. Three years later at follow-up, fundus photography and the AREDS classification were repeated. Age-adjusted relative risks and 95% confidence intervals measured the association between visual functions and AMD incidence and progression for the study eye and the fellow eye at follow-up. MAIN OUTCOME MEASURES:Presence and severity of AMD at the 3-year follow-up visit in the study and fellow eyes. RESULTS:Healthy older eyes at baseline with delayed RMDA were 3.54 or 3.40 times more likely to have incident AMD at the 3-year follow-up in the study eye and the fellow eye, respectively, compared with eyes without delays. No other visual functions were associated with AMD incidence, except for low-luminance visual acuity in the study eye. Eyes with early AMD at baseline with delayed RMDA were 3.89 or 2.65 times more likely to have progressed at follow-up for the study and fellow eye, respectively. No other visual functions were associated with AMD progression at follow-up. CONCLUSIONS:Rod-mediated dark adaptation is the only visual function of those tested that was associated with AMD incidence and progression over 3 years in healthy eyes or those with early AMD at baseline. Our results suggest that other visual functions are not useful for understanding AMD incidence and early progression risk. Interventions that eventually are designed to arrest early AMD progression or preventative measures in those at risk should consider RMDA a functional outcome measure. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Age-related macular degeneration (AMD), a neurodegenerative disease, is the leading cause of visual impairment in industrialized countries. Challenges in defining structural/functional relationships at various stages of disease especially with non-neovascular AMD, have slowed therapeutic development. Development of such sensitive and specific markers associated with AMD progression could provide the basis necessary for future regulatory outcome variables that will be useful in assessing new, innovative AMD therapies. Advanced imaging technologies such as high-resolution optical coherence tomography, fundus autofluorescence and near infrared imaging; and functional tests including rod-mediated dark adaptation, microperimetry, fluorescence lifetime imaging ophthalmoscopy and others will be important in the evaluation of these structure/function correlations. Development of more advanced methods to study structure such as high-resolution OCT and en face OCT offer further opportunities to better correlate structure and function in clinical trials, and to better define useful biomarkers of visual outcome endpoints. Dark adaptation, although correlated with AMD stage, is difficult to incorporate as endpoint in clinical trials because dark adaptation changes slowly and the technique is time consuming. Microperimetry has become a useful outcome variable in many clinical trials and new methodology may improve its utility in structure-function correlation. These and other newer techniques will require further prospective studies to determine their clinical utility in early AMD detection, prediction of disease progression from intermediate to late stages, and the ability to monitor the advancement of non-neovascular AMD.

Purpose:Eyes with age-related macular degeneration (AMD) and some healthy aged eyes exhibit risk-indicating delays in rod-mediated dark adaptation (RMDA) and prolonged long spectral channel (LSC) lifetimes by fluorescence lifetime imaging ophthalmoscopy (FLIO) in the Early Treatment Diabetic Retinopathy Study (ETDRS) outer ring, especially nasally. To learn FLIO's potential for AMD detection, we correlate FLIO to RMDA. Methods:The ALSTAR2 follow-up cohort underwent FLIO, color fundus photography, two-wavelength autofluorescence (for macular pigment optical density [MPOD]), visual function testing, including RMDA (rod intercept time [RIT]). AMD was staged by the Age-Related Eye Disease Study (AREDS) 9-step at baseline and follow-up. In pseudophakic eyes with high-quality FLIO, mean intensity maps and meridian plots were created. Vision data were analyzed using linear regression and Spearman's r. Results:Of 155 eyes (155 participants [75 ± 5.0 years; 60.7% female participants]), 67 eyes were healthy, 38 had early (e)AMD, and 50 had intermediate (i)AMD (P = 0.02). LSC lifetimes were longest in iAMD in all ETDRS regions (P < 0.01) and short spectral channel (SSC) lifetimes in inner and outer rings (P < 0.01). The LSC pattern manifested in 65 of 88 AMD eyes and 30 of 67 healthy eyes. Lifetimes were longest on the nasal meridian and shortest on temporal. LSC lifetimes in the inner and outer rings correlated strongly with RIT (r = 0.68). A stable subgroup had short LSC lifetimes and short RIT. SSC correlated weakly with MPOD. Conclusions:Prolonged lifetimes in AMD exhibit spatial asymmetry, suggesting mechanisms beyond retinal cells and including choroid. Lifetimes correlate with delayed RMDA, potentially indicating risk for AMD onset and early progression. Further research into SSC signal sources is warranted.

PURPOSE:To report eye disease detection referral rates for in-office eye care across the Screening and Intervention for Glaucoma and eye Health through Telemedicine (SIGHT) Studies conducted in Alabama (AL-SIGHT), Michigan (MI-SIGHT), and New York City (NYC-SIGHT). METHODS:Individuals age ≥40 years who completed eye health screenings in federally qualified health centers, a free clinic, and affordable housing developments were included in the analysis. Visual acuity, intraocular pressure (IOP), and fundus photography were conducted across all sites and detection of eye diseases and referral rates are reported. Two-sample t-test and chi-square test (or Fisher's exact test) were used to compare continuous and categorical variables, respectively, between those referred and not referred. RESULTS:Of the 838 participants screened in AL-SIGHT, 2970 in MI-SIGHT, and 708 in NYC-SIGHT, referral rates for in-office eye care were 47.3%, 42.8%, and 66.1% respectively. Detection rates of glaucoma and glaucoma suspect in AL-SIGHT were 18.6%, MI-SIGHT were 24%, and NYC-SIGHT were 26.7%. Among those referred there were significantly more participants who identified as Black race, had high school or less education, were single/divorced/separated/widowed, retired or unable to work/disabled, insured with Medicare, or reported having diabetes, hypertension, or glaucoma (p < 0.05). CONCLUSION:The SIGHT Studies provide evidence that reaching underserved individuals at high-risk for eye diseases and providing telehealth-based eye health screenings in trusted community-based settings, led to high rates of eye disease detection and referral for in-office eye care.

PurposeFinancial incentives have proven successful in addressing health behaviors associated with several chronic diseases and may represent a potential method to improve adherence to follow-up eye examinations from vision screening programs. The study was conducted to determine the effect of financial incentives on follow-up adherence in the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine.MethodsThis study enrolled eligible patients receiving care at three Federally Qualified Health Centers to undergo screening for refractive error and ocular diseases. Follow-up appointments for continued care were made for patients suspected to have uncorrected refractive error or ocular disease. A subset of patients (n = 187) received a financial incentive while a control group did not (n = 234). Follow-up attendance within 6 months was compared with Poisson's models between incentivized and non-incentivized groups for all referrals and across specific disease states.ResultsAmong 187 patients with and 234 without incentive, there was a significantly higher rates of follow-up in the incentivized group (83.4% incentivized vs. 74.4% non-incentivized, p = .05) overall. There was a significantly higher rate of attendance for patients referred for diabetic retinopathy (p = .02) and refractive error (p = .02), but not glaucoma (p = .46), glaucoma suspect (p = .70), ocular hypertension (p = .22), and cataract (p = .29). After matching across groups, these differences were less pronounced and only remained significant for diabetic retinopathy (p = .04).ConclusionPatients receiving financial incentive had a higher follow-up rate within 6 months. These differences where primarily driven by patients referred for refractive error and diabetic retinopathy. However, once matched for baseline covariates, this improvement was not seen in the overall group. This suggests that incentives may not be an effective method to improve adherence to vision screening in this setting especially for glaucoma screening.

Purpose:To advance metabolic imaging of the high-risk macula lutea by quantifying the topography of macular pigment optical density (MPOD), measured with two-wavelength autofluorescence (2WAF), and quantitative (short-wavelength) autofluorescence (qAF) intensity, which share the same signal source and cross-retinal light path, in aging, early (e), and intermediate (i) age-related macular degeneration (AMD). Methods:2WAF and qAF images of 384 pseudophakic eyes of 230 persons (mean age, 74.2 ± 5.7 years; 145 female) from ALSTAR2 (AREDS 9-step classification: 170, normal; 118, eAMD; 96 iAMD) were shown as maps (intensity, z-score) and meridian plots. Correlations were determined in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Results:MPOD was higher in the central subfield (P < 0.01) in iAMD compared to eAMD and normal eyes, and qAF was lower in the central subfield and inner ring (both P < 0.01) in AMD compared to normal eyes. MPOD differed along horizontal versus vertical meridians, depending on disease stage. Pixel-level z-score maps and meridian plots showed distinct annuli of alternating levels of MPOD anchored on the foveal center, unrelated to qAF. Across the central subfield, high 2WAF was associated with low qAF in all disease stages (r = -0.47, r = -0.47, r = -0.42; all P < 0.001). In the inner ring, correlations were significant for normal and eAMD only (r = -0.31, P = 0.004 and r = -0.22, P ≤ 0.001, respectively). Conclusions:New analytics support previously reported higher MPOD in AMD compared to normal eyes, especially central subfield and inner ring. MPOD and qAF differ by disease-stage-related topography and correlations, supporting independent use in metabolic imaging of the macula lutea.

PURPOSE:Both retinal changes and age-related macular degeneration (AMD) have been shown to be associated with Alzheimer's disease and related dementias (ADRD). In AMD, the outer retina is impacted significantly and early, but little is known about its association with cognition or changes in brain morphometry. This study investigates the relationship between retinal and brain morphometry in older adults with early and intermediate AMD. DESIGN:Cross-sectional study. METHODS:Adults ≥70 years with normal, early, and intermediate AMD were recruited from Callahan Eye Hospital Clinics at the University of Alabama at Birmingham. Participants underwent cognitive testing, optical coherence tomography, and magnetic resonance imaging. Associations of retinal layer thickness with brain volume and thickness of specific brain regions were evaluated utilizing multivariable linear regression. The relevance of retinal thickness variables in brain volumetrics was quantified using least absolute shrinkage and selection operator regression models. Correlations between demographic variables, cognitive scores, and brain morphometry were evaluated. RESULTS:Participants with thinner outer retina had significantly smaller hippocampus (β = 0.019, P = .022), lower occipital cortex regions of interest (occipital ROIs) thickness (β = 5.68, P = .020), and lower cortical thickness in ADRD-related brain regions (β = 7.72, P = .006). People with thinner total retina had significantly lower occipital ROIs (β = 3.19, P = .009) and ADRD-related brain region (β = 3.94, P = .005) thickness. Outer retinal thickness in the outer Early Treatment of Diabetic Retinopathy Study ring was the most frequently reported retinal variable associated with brain morphometry on least absolute shrinkage and selection operator regression. Total gray matter volume showed positive correlations with education (Pearson's r = 0.30, P = .022). CONCLUSIONS:In older adults with normal retinal aging and early and intermediate AMD, thinner outer retina had specific associations with brain regions primarily involved in vision and cognition, such as lower hippocampal volume and lower thickness of the occipital ROIs and brain regions known to show early structural changes in dementia.

Introduction Artificial Intelligence Ready and Equitable for Diabetes Insights (AI-READI) is a data collection project on type 2 diabetes mellitus (T2DM) to facilitate the widespread use of artificial intelligence and machine learning (AI/ML) approaches to study salutogenesis (transitioning from T2DM to health resilience). The fundamental rationale for promoting health resilience in T2DM stems from its high prevalence of 10.5% of the world’s adult population and its contribution to many adverse health events.Methods AI-READI is a cross-sectional study whose target enrollment is 4000 people aged 40 and older, triple-balanced by self-reported race/ethnicity (Asian, black, Hispanic, white), T2DM (no diabetes, pre-diabetes and lifestyle-controlled diabetes, diabetes treated with oral medications or non-insulin injections and insulin-controlled diabetes) and biological sex (male, female) (Clinicaltrials.org approval number STUDY00016228). Data are collected in a multivariable protocol containing over 10 domains, including vitals, retinal imaging, electrocardiogram, cognitive function, continuous glucose monitoring, physical activity, home air quality, blood and urine collection for laboratory testing and psychosocial variables including social determinants of health. There are three study sites: Birmingham, Alabama; San Diego, California; and Seattle, Washington.Ethics and dissemination AI-READI aims to establish standards, best practices and guidelines for collection, preparation and sharing of the data for the purposes of AI/ML, including guidance from bioethicists. Following Findable, Accessible, Interoperable, Reusable principles, AI-READI can be viewed as a model for future efforts to develop other medical/health data sets targeted for AI/ML. AI-READI opens the door for novel insights in understanding T2DM salutogenesis. The AI-READI Consortium are disseminating the principles and processes of designing and implementing the AI-READI data set through publications. Those who download and use AI-READI data are encouraged to publish their results in the scientific literature.