Lajos Csincsik

Objective: To examine the prognostic significance of intraretinal hyperreflective foci (HRF) and subretinal drusenoid deposits (SDD) as predictors of atrophy presence and progression to exudative macular neovascularisation (eMNV) in the unaffected second eye of participants with eMNV in the first eye. Methods: Post hoc prognostic analysis on iAMD eyes from the prospective EDNA cohort. SD-OCT scans of 459 study eyes were graded for presence of HRF, SDD, and their characteristics, including location within retina (inner, outer, or both), proximity to irregular elevation of RPE (adjacent, remote or both), and SDD load (mild or moderate to severe). The cohort was subdivided in four follow up groups, iAMD without focal regions of atrophy (FoA), persistent or new onset FoA, eMNV alone and eMNV with FoA. Results: Of the 459 included eyes, 234 (51.0%) had HRF and 273 (60.0%) had SDD at baseline. Persistent or new onset FoA was seen in 83, 66 progressed to eMNV alone and 38 to eMNV with FoA, and 272 had no worsening of iAMD status. Presence of HRF and especially a higher SDD load were associated with a significantly faster progression to exudation. A higher SDD load doubled the hazard of progression to any eMNV compared to eyes with a mild load or without SDD. This hazard was highest in eyes with the presence of both HRF and SDD. HRF were associated with a lower BCVA. Conclusions: HRF and SDD are consistently observed in high risk AMD eyes and characterising their distribution and load might allow differentiation of their contributions to risk of progression to late stage features of atrophy and exudation.

Introduction: There is a need for early, non-invasive and inexpensive biomarkers for Alzheimer’s disease (AD), which could serve as a proxy measure in prevention and intervention trials that might eventually be suitable for mass screening. People with Down syndrome (DS) are the largest patient group whose condition is associated with a genetically determined increased risk of AD. The REVEAL study aims to examine changes in the structure and function of the eye in individuals with DS compared with those with mild cognitive impairment (MCI) and cognitively healthy control (HC) individuals. REVEAL will also explore whether these changes are connected to inflammatory markers previously associated with AD. Methods and analysis: The protocol describes a cross-sectional, non-interventional, single-centre study recruiting three cohorts, including (1) participants with DS (target n=50; age range, 6–60 years), (2) participants with MCI (target n=50; age range, 50–80 years) and (3) HC participants (target n=50; age range, 50–80 years). The primary research objective is to profile retinal, choroidal and lenticular status using a variety of eye imaging modalities and retinal functional testing to determine potential associations with cognitive status. The REVEAL study will also measure and compare established blood markers for AD and proteomic and transcriptomic marker profiles between DS, MCI and HC groups. Between-group differences will be assessed with an independent sample t-test and χ ² tests for normally distributed or binary measures, respectively. Multivariate regression analysis will be used to analyse parameters across all three cohorts. Data collection began in October 2023 and is expected to end in October 2025. Ethics and dissemination: The study gained a favourable opinion from Health and Social Care Research Ethics Committee A (REC reference 22/NI/0158; approved on 2 December 2022; Amendment 22/0064 Amend 1, 5 April 2023; Amendment 22/0064 Amend 2; 23 May 2024; Amendment 22/0064 Amend 3; 25 June 2024; Amendment 22/0064 Amend 4; 16 January 2025; Amendment 22.0064 Amend 5; 9 May 2025; Amendment 22.0064 Amend 6; 9 June 2025). The study has also been reviewed and approved by the School of Biomedical Sciences Research Ethics Filter Committee within Ulster University. Findings from the REVEAL study will be presented to academic audiences at international conferences and peer-reviewed publications in targeted high-impact journals after data collection and analysis are complete. Dissemination activities will also include presentations at public events.

INTRODUCTION: Retinal and choroidal vascular changes have been proposed as a non‐invasive central nervous system (CNS) proxy for clinical trials in Alzheimer's disease (AD). However, their role in Down syndrome (DS), the largest genetically predisposed group for AD, remains unclear.METHODS: We conducted ultra‐widefield and optical coherence tomography imaging on 24 individuals with DS and 17 controls and extracted various vascular parameters. Data were analyzed using logistic and linear regression models.RESULTS: The DS retinae exhibited supernumerary vessels that were wider and thinned more rapidly along their paths (p = 0.01). There was a more complex central retinal (p = 0.047) and a less complex peripheral retinal vascular tree (p = 0.001), with increased numbers of peripheral microvascular abnormalities (p = 0.038) and reduced choroid vascularity index in DS (p < 0.001).DISCUSSION: We found that retinal and choroidal vascular changes are present in DS adults before the clinical onset of AD and might become early surrogates for cerebral vascular abnormalities.Highlights: Eye imaging in DS showed retinal and choroidal changes seen in AD. Far peripheral retinal microaneurysms and hemorrhages associated to DS. Wider and faster thinning vessels associated to DS. Reduced vascular tree complexity in the peripheral retina linked to DS. Lower choroidal vascularity associated with DS.

Background: Visual impairment is a global problem and, regardless of the cause, it substantially impacts people’s daily lives. Navigating towns and cities can be one of the most difficult tasks for someone with a visual impairment. This is because our streetscapes are often inaccessible for navigating safely and independently by people with a visual impairment. Barriers include street clutter, bollards, pavement parking, and shared spaces. Methodology: Participants with varying levels of diabetic retinopathy (DR) and retinitis pigmentosa (RP) were recruited. Each participant completed a clinical visit and a 1-mile walk. Participants discussed confidence, anxiety, difficulty, and any barriers encountered while completing the walkaround. Participants completed quality of life (RetDQol), diabetes distress scales, and a study questionnaire. They also underwent retinal imaging and visual function testing. Retinal imaging and visual function results were compared with confidence, difficulty, and anxiety levels during the walkaround using Spearman’s correlation. Results: Thirty-three participants took part in the study, 22 with diabetes and 11 with RP. Results showed that average confidence was correlated with visual acuity, RetDQol, mean visual fields, and vertical peripheral diameter visual fields. Average difficulty was associated with visual acuity, RetDQol, dark adaptation, mean visual fields, percentage of the retina, and both horizontal and vertical diameter visual fields. In addition, some of the barriers discussed were pavement issues, bollards, parked cars, uneven pavements, alfresco dining, light levels, and street features such as tree roots, poles, A-boards, and street clutter. Conclusions: People with RP and treated DR faced common barriers while navigating the walkaround. The removal of these common barriers would make our streetscapes more accessible for all and will allow for more independence in those with visual impairments.

Background: Changes of choroidal vasculature in the eye have been reported in Alzheimer’s disease (AD) and this is positively correlated with declining cognitive status. Patients with Down’s syndrome (DS) are at a high risk of developing AD and also show signs of premature ageing. Both AD and ageing have been associated with thinner choroid, measured on optical coherence tomography (OCT) scans, however, there are currently no studies in the literature to evidence whether choroidal thinning occurs in DS. Our study, for the first time, investigated choroidal thickness (CT) in DS using OCT imaging.Method: 21 DS and 9 controls (Ctrl) were imaged using Enhanced Depth Imaging Spectral Domain OCT (Heidelberg). The choroid was manually segmented, and thickness values calculated using conventional grading grid (ETDRS). Statistical analysis was conducted in SPPS using only the right eye. The analysis was controlled for age, image quality, refractive error and time of the scan as covariates.Result: OCT imaging in DS proved to be challenging due to some participants having difficulties maintaining the fixation for an extended period. In this preliminary cohort the DS group was older than the Ctrl group (39.5±6.9 vs 31.2±6.0 years, p=.004) but there was no difference in gender (χ2=0.7, df=1, p=.376). Sub‐foveal (SF) and Superior‐inner (SI) CT was significantly increased in DS compared to Ctrl (SF: 363.2µm±25.9µm vs 237.3µm±45.8µm, p=.046; SI: 381.8µm±26.2µm vs 253.6µm±46.3µm, p=.044) but no differences were found in other sectors of the ETDRS grid. Increase in SF CT showed a moderate, positive correlation with cognitive status in the 14 participants whose cognitive score was available (ρ=.539, p=.047). Suprachoroidal space (SCS) as a hypo‐reflective band at the choroidal scleral interface, was only visible in DS in 13 (61.9%) out of the 21 participants. Those with SCS were older than those without (41.9±1.7 vs 35.6±2.2 years, p=.040).Conclusion: In this study we found that there is an increase in choroidal thickness in DS which is in contrast to the thinning observed in AD; this might be an anatomical feature of DS or may reflect inflammation. The increased prevalence of SCS in DS is likely to be associated with the accelerated ageing.