To assess the outcomes of teleophthalmology-based diabetic retinopathy (DR) screening in individuals over 70 years within the OPHDIAT network and to compare them with those of patients aged 18-69 years. A cohort of 16,459 diabetic patients, without known DR or with mild non-proliferative DR (NPDR), screened in 2024 in 32 OPHDIAT centers, was included and divided into two groups: < 70 years (n = 13,639) and ≥ 70 years (n = 2,820). Two non-mydriatic retinal photographs per eye were analyzed by certified ophthalmologists. Among patients aged ≥70 years, 21.3% (95% CI: 19.8-22.8) had any DR, and 6.1% (95% CI: 5.2-6.9) were referred to an ophthalmologist for moderate NPDR or a more severe form of the disease, including suspected macular edema. These proportions did not significantly differ from those found in patients < 70 years: 21.9% (95% CI: 21.2-22.6) and 6.1% (95% CI:5.6-6.5), respectively. Severe NPDR or proliferative DR were rare in both groups (1.0%, 95% CI: 0.6-1.4% vs. 1.7%, 95% CI: 1.5-1.9%, P < 0.001). The proportion of ungradable images was higher in the group ≥70 year (14.4%, 95% CI:13.1-15.7% vs. 6.1%, 95% CI: 5.7-6.5%, P < 0.001), particularly in phakic eyes, although 80% of patients had interpretable images for both eyes. Pupil dilation significantly improved image quality in this group. Screening also allowed detecting other ocular disorders, including age-related macular degeneration and glaucoma, which were more common in the group ≥ 70 years (2.1%, 95% CI: 1.5-2.6% vs. 0.6%, 95% CI: 0.4-0.7% P < 0.001). Teleophthalmology-based DR screening appeared feasible and clinically relevant in patients aged ≥70 years, allowing identifying patients requiring ophthalmologic evaluation, while also detecting other age-related ocular diseases. Pupil dilation is recommended to optimize image quality in this population.

This systematic review aims to evaluate and synthesize the existing literature on the interventions used for submacular haemorrhage (SMH), highlighting the controversies and differences in clinical practice. A systematic review was conducted following the PRISMA guidelines. A comprehensive search was performed across multiple databases, including MEDLINE, EMBASE and Cochrane Library, to identify studies on SMH treatment. Inclusion criteria encompassed randomized controlled trials, cohort studies and case series that focused on different therapeutic interventions. Data on functional outcomes, efficacy and safety of the interventions were extracted and analysed. The review included 150 studies, of which 38 were included in the network meta-analysis. The analysis of best corrected visual acuity (BCVA) Included 26 studies, 20 interventions and 2125 eyes. Heterogeneity was moderate (I2 = 28.9%). Non-vitrectomy therapies showed better BCVA outcomes and fewer complications (e.g. retinal detachment, vitreous haemorrhage), while vitrectomy-based treatments achieved better anatomical results. According to P-score ranking, "Observation" had the highest probability of being most effective for BCVA (P-score = 0.8051), followed by anti-VEGF monotherapy and non-vitrectomy combinations. However, this result should be interpreted cautiously, as the "Observation" group was based on only two studies (26 eyes) with clinical heterogeneity. No publication bias was detected (Egger's test p = 0.582). There is no consensus on a standard evidence-based treatment for SMH. Minimally invasive strategies are promising, but factors such as timing, lesion size and anti-VEGF use remain critical. Further large-scale randomised trials are needed to define optimal management.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The alternative pathway (AP) of complement has been linked to the pathogenesis of AMD. In particular, rare variants (RVs) in the complement factor I (CFI) gene encoding the Factor I (FI) protein confer increased AMD risk. The prevalence of CFI RVs are well characterised in European AMD, however little is known about other populations. The Finnish population underwent genetic restriction events which have skewed allele frequencies in unexpected ways. A series of novel or enriched CFI RVs were identified in individuals with dry AMD from the Finnish Biobank Cooperative (FINBB), but the relationship between these genotypes and contribution to disease was unclear. Understanding how RVs impact the ability of FI to regulate the complement system is important to inform mechanistic understanding for how different genotypes contribute to disease development. To explore this a series of in vitro assays were used to functionally characterise the protein products of 3 CFI RVs enriched in FINBB dry AMD, where no prior data were available. The G547R variant resulted in almost complete loss of both classical pathway and AP regulatory potential. The c.982 g>a variant encoding G328R FI perturbed an exon splice enhancer site which resulted in exon skipping and a premature stop codon in vitro and low levels of FI in vivo. Despite detailed analysis no defect in levels or function was demonstrated in T107A. Functional characterization of all Finnish CFI RVs in the cohort allowed us to demonstrate that in Finnish dry AMD, collectively the type 1 CFI RVs (associated with FI haploinsufficiency) were significantly enriched with odds ratio (ORs) of 72.6 (95% confidence interval; CI 16.92 to 382.1). Meanwhile, type 2 CFI RVs (associated with FI dysfunction) collectively conferred a significant OR of 4.97 (95% CI 1.522 to 15.74), and non-impaired or normal CFI RV collectively conferred an of OR 3.19 (95% CI 2.410 to 4.191) although this was driven primarily by G261D. Overall, this study for the first time determined the ORs and functional effect for all CFI RVs within a Geographic Atrophy (GA) cohort, enabling calculations of combined risk scores that underline the risk conferred by type 1 and 2 CFI RVs in GA/AMD.

Background/Objectives: Inherited retinal diseases (IRDs) are a heterogeneous group of rare eye disorders characterized by progressive photoreceptor degeneration, leading to severe visual impairment or even blindness. This study aims to investigate the prevalence, types, and clinical significance of ophthalmic comorbidities in Portuguese patients with IRDs. Methods: This nationwide Portuguese population-based retrospective study was based on the IRD-PT registry (retina.com.pt). Statistical analysis was conducted using Microsoft® Excel® for Microsoft 365 and IBM SPSS Statistics version 29.0.2.0. Informed consent was obtained from all participants. Results: A total of 1531 patients (1254 families) from six centers were enrolled. The cohort consisted of 51% males, with a mean age of 45.8 ± 19.3 years and a mean age at diagnosis of 39.4 ± 19.5 years. Overall, ocular comorbidities were reported in 644 patients (42.1%). In 176 individuals (11.5%), multiple concurrent comorbidities were found. Cataract was the most common comorbidity (21.3%), followed by amblyopia (6.3%) and high myopia (5.9%). Statistically significant associations with ocular comorbidities were observed in isolated progressive IRDs. Specifically, AR RP was associated with cataract (p < 0.001), and gene analysis revealed several significant associations. CRB1 was statistically linked to epiretinal membrane (ERM) (p = 0.003), EYS with cataract (p = 0.001), PROM1 with choroidal neovascularization (CNV) (p = 0.0026), and USH2A with macular hole (p = 0.01). Patients with the RPE65 mutation in Leber congenital amaurosis were associated with ERM (p = 0.019). There was also a significant association between X-linked RP and high myopia (p < 0.001) and CNV in Best disease (p < 0.001); in syndromic IRDs, cataract, cystoid macular edema, and ERM were observed in Usher syndrome, p = 0.002, p = 0.002, and p = 0.005, respectively, and the MYO7A gene was linked to cataract (p = 0.041) and strabismus (p = 0.013); pseudoxanthoma elasticum was significantly associated with CNV (p = 0.002); and foveal hypoplasia was associated with anterior segment dysgenesis (p < 0.001). Conclusions: This study enhances the current understanding of ocular comorbidities in IRDs in Portuguese patients. Common findings were cataract, refractive error, and CME. Stationary IRDs and pattern dystrophies showed fewer concomitant comorbidities, supporting their classification as non-progressive or benign conditions. The significance of registries like IRD-PT cannot be overstated, particularly in the context of rare diseases. These databases serve multiple crucial functions in enabling detailed documentation of disease characteristics and long-term monitoring of disease progression.

Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.