Adaptive Optics Ophthalmoscopy (AOO) enables high-resolution retinal imaging for clinical biomarker analysis. While existing methods automatically segment retinal bifurcations and extract vascular biomarkers, they require manual selection of high-quality arterial regions, limiting scalability and efficiency. We propose a fully automated patch-based CNN-GNN framework for vessel classification in AOO images. Our method extracts deep features from image patches, constructs graphs with cost-weighted edges capturing vessel connectivity, then applies Graph Attention Networks (GATs) for classification. This hybrid approach integrates local features with global topological information through graph processing, eliminating manual region selection requirements. We evaluate our pipeline on a dataset of 4,258 vessel patches across four CNN/Transformer backbones (ResNet-18, EfficientNet-B2, DenseNet-121, TinyViT). The backbone+GAT combination consistently outperforms backbone-only baselines, achieving up to 86.5% accuracy with improvements ranging from 1.9% to 4.4% across architectures. Our approach provides a robust, scalable foundation for automated vascular biomarker analysis in AOO imaging, supporting more efficient clinical workflows.

Purpose To describe the clinical and multimodal imaging features of a large stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) associated with midperipheral retinoschisis (MPRS) and microvascular abnormalities. Methods A single patient with no prior ocular pathology underwent spectral-domain OCT, ultra-widefield swept-source OCT with OCT-angiography (OCT-A), fluorescein angiography, ultra-widefield fundus photography, adaptive optics flood-illumination ophthalmoscopy (AO-FIO), and full-field electroretinography (ERG). Results Extensive schisis involved the henle fiber layer (HFL) in the macula and multiple retinal layers in the midperiphery. The posterior vitreous remained largely attached, without signs of pathological traction. OCT-A revealed abnormal microvasculature outside the vascular arcades without non-perfusion. Fluorescein angiography confirmed the absence of areas of non-perfusion and showed leakage from the abnormal vessels, which were confined to areas with significant inner retinal schisis. These vessels were located between the retinal nerve fiber layer and the inner limiting membrane, displaying neovascular morphological characteristics. ERG was electronegative, and genetic testing was unremarkable. AO-FIO identified hyperreflective foveal dots in the inner retina. No therapeutic intervention was initiated and the condition remained stable over more than one year of follow-up. Conclusion Extensive SNIFR with inner retinal schisis may be associated with neovascular-like changes without areas of non-perfusion on fluorescein angiography or OCT-A and can present with an electronegative ERG.

BACKGROUND AND OBJECTIVES:Cerebral small vessel disease (cSVD), characterized by pathologic changes in the structure and function of small brain vessels, is detectable on brain MRI in the absence of clinical symptoms. However, imaging cerebral small vessels themselves in vivo remains costly and challenging. There is growing interest in investigating whether retinal microvascular imaging features could be proxies for changes in the brain microvasculature. Using a multipronged approach, we explored the relation of retinal microvascular characteristics with MRI markers of cSVD (MRI-cSVD). METHODS:First, we explored this relationship in older community persons from the population-based 3C-Dijon cohort. MRI-cSVD was assessed on a 1.5-Tesla MRI at baseline, comprising white matter hyperintensity volume (WMHV), lacunes, and a composite extreme cSVD phenotype (WMHV extreme distributions and presence/absence of lacunes). At 10-year follow-up, participants underwent measurements of retinal microvascular features on fundus using the Singapore "I" Vessel Assessment software. To support 3C-Dijon findings, we conducted a comprehensive literature review up to July 2024 from PubMed/EMBASE and used 2-sample Mendelian randomization (MR) leveraging large-scale genome-wide association studies, to assess causality and directionality. RESULTS:In 670 3C-Dijon participants (median age 70.7, 65.7% women), multivariable analyses (adjusted for age, sex, axial length, and cardiovascular risk factors) showed a significant association of lower arteriolar fractal dimension (FDa) with extreme cSVD (odds ratio [OR] 1.68, 95% CI 1.20-2.34) after multiple testing correction (p < 0.0042), and at p < 0.05, associations of lower FDa and smaller arteriolar caliber with larger WMHV (β = 0.0534 [95% CI 0.0075-0.0569] and 0.0519 [95% CI 0.0045-0.0993]), and of greater venular tortuosity (TORTv) with lacunes (OR 1.45, 95% CI 1.05-2.00). Lower FDa was also associated with poorer executive function. The systematic review of the literature identified 12 studies (N = 7,796) that showed mostly consistent direction of effects for FDa (5/6 studies), TORTv (4/6), and arteriolar caliber (10/11), although statistical significance was observed in 5 individual studies only. Two-sample MR based on large genome-wide association studies (N = 5,292-52,798) showed evidence for a potentially causal association of greater TORTv with extreme cSVD and larger WMHV (p = 0.0017 and 0.049), with no evidence for reverse causation. DISCUSSION:We provide multimodal evidence that geometric characteristics of the retinal microvasculature are associated with increased burden of MRI-cSVD and possibly worse executive function.

Objective To determine the organization of normal human choroidal arteries using a combination of laser Doppler holography (LDH) and OCT. Design Cross-sectional clinical study. Subjects One hundred thirty-two eyes of 74 healthy subjects. Methods By combining images from a prototypic LDH system and from OCT, we documented the 3-dimensional disposition of choroidal arteries from their emergence from ciliary arteries to precapillary arterioles. Main Outcome Measures Distribution, diameters, and pathways of choroidal arteries. Results A notable intereye variability in the disposition of arteries was found, in which dominant patterns were identified. A short ciliary artery emerging within 1000 μm from the fovea was identified in 63% of eyes, giving rise to a horizontal submacular artery (SMA; mean diameter 119.7 ± 24.9 μm) oriented temporally. The detection rate of an SMA was inversely correlated with choroidal thickness, that is, SMAs were more often identified in thinner choroids. Among cases with a detectable SMA, its diameter positively correlated with choroidal thickness (P < 0.003). Long posterior ciliary arteries were identified in 43% of eyes and emerged at a mean distance of 4820 ± 1567 μm temporal to the fovea (mean diameter 115 ± 41 μm). Paraoptic arteries radiated from the margins of the optic nerve head, some of which perfused the macula. Disseminated axially oriented arterioles perfusing precapillary arterioles were detected from first-order arteries. Conclusions Using a combination of LDH and OCT in healthy eyes, we identified recurrent organizational patterns of choroidal arteries in normal eyes, including SMAs, long posterior ciliary arteries, paraoptic arteries, and precapillary complexes. Characterizing the physiologic variants of the disposition of choroidal arteries helps to provide a reference framework that will enable the identification of disease-related changes. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Recurrence of macular edema after intravitreal injections (IVI) may result from persistent focal microvascular abnormalities such as telangiectatic capillaries (TelCaps), which can be difficult to detect within a thickened retina. This study proposes a simple screening strategy to identify TelCaps using optical coherence tomography (OCT) thickness maps following anti-VEGF treated for diabetic macular edema (DME). This is an ancillary study from the TalaDME double-blind randomized controlled trial evaluating the benefit of adjunctive focal laser photocoagulation to anti-VEGF therapy in eyes with DME and TelCaps. OCT imaging was performed monthly and indocyanine green angiography (ICGA) quarterly over 12 months. Twenty-eight fellow eyes that had recovered from center-involved DME (CI-DME) associated with TelCaps were analyzed. TelCaps were identified as late-phase hyperfluorescent lesions on ICGA. The topography of perifoveal retinal thickening on OCT and its spatial correlation with TelCaps were assessed. Following IVI induced resolution of central DME (defined as central macular thickness < 315 µm), OCT mapping revealed 52 perifoveal thickening spots, herein referred to as islets. TelCaps were located within 100 µm of the barycenter of 47/52 (90

Purpose:To report the migration of perivascular opacities, in patients with retinal vasculopathy, with and without clinical evidence of ocular inflammation. Methods:Retrospective case series of four patients with either idiopathic retinal vasculitis or presumed retinal vascular inflammation. Patients were imaged with wide-field fundus photographs, infrared fundus images, fundus fluorescein angiography (FA), and flood-illumination adaptive optics (FIAO). Successive fundus images were registered and compared over follow-up periods ranging from 2 to 10 months. Displacement of identifiable perivascular opacities between imaging sessions was measured to estimate migration velocity. Results:Two patients presented with presumed retinal vasculopathy associated with retinal vein occlusion (RVO). Their fundus images showed disseminated perivenous opacities along veins. In both patients, time-lapse videos recapitulating several months of fundus observations revealed that most of the perivascular opacities shifted along veins with or against the flow at an estimated mean velocity of approximately 15 μm/day, calculated from displacement between imaging sessions. Two patients presented with retinal vasculopathy in the form of retinal vasculitis. Their fundus examination showed perivascular sheathing (arteritis and phlebitis). FIAO demonstrated multiple focal perivascular opacities in the same areas. All 4 patients imaged presented similar focal perivascular cell-like opacities either on infrared or FIAO fundus images. Conclusions:We describe the migration of presumed immune cell-like perivascular opacities in the human eye. The significance of this process remains to be fully explored, because evidence of ocular inflammation was clinically present in two patients. The close temporal and spatial relationship of these perivascular opacities associated with branch RVO in two of these patients suggests that they may have been involved in the occurrence of RVO.

PURPOSE:Retinal telangiectatic capillaries (TelCaps) are microvascular abnormalities associated with chronic vascular macular oedema and suboptimal response to intravitreal therapy. Targeted laser photocoagulation is beneficial but requires precise localization using indocyanine green angiography (ICG-A), the reference standard. However, ICG-A is invasive and not easily repeatable. This study evaluated OCT performance for TelCaps identification and en face localization versus ICG-A. METHODS:ICG-A and OCT images from 62 patients with TelCaps secondary to diabetic retinopathy or vein occlusion were analysed in a masked fashion. TelCaps were identified on OCT cube B-scans using predefined structural criteria and subsequently localized on co-registered infrared en face images. Sensitivity, positive predictive value (PPV) and subgroup analyses were used to assess OCT accuracy for lesion localization versus ICG-A and to evaluate the influence of anatomical factors. RESULTS:ICG-A identified 148 TelCaps, whereas OCT detected 157 lesions. ICG-stained TelCaps appeared as isolated large lesions or clustered microvascular abnormalities. OCT-identified and en face localized lesions showed 87% sensitivity (95% CI, 81%-92%) and 82% PPV (95% CI, 75%-88%). Sensitivity was higher for isolated lesions (92%) and those adjacent to hard exudates, but lower for clustered lesions (62%) and those distant from exudates. False positives were mainly lesions without retinal thickening or exudates, while false negatives predominantly involved clustered lesions. CONCLUSION:OCT represents a valuable non-invasive tool for identifying and localizing TelCaps on en face images in eyes with macular oedema and hard exudates, supporting its use for guiding focal laser photocoagulation. While it may reduce the need for systematic ICG-A in selected patients, angiography remains essential in complex equivocal cases, particularly for clustered lesions, where OCT may be less effective.

PURPOSE:To report an unusual episode of formation and spontaneous release of a thickened hyaloid and dense epiretinal membrane (ERM) complicating Stargardt disease. METHODS:Case report. RESULTS:We report the case of a 40-year-old woman who was followed in our center with a diagnosis of Stargardt. She was lost to follow-up and returned to the clinic 7 years later with recent visual loss in her left eye. Fundus examination revealed a vitreomacular adhesion with a thickened hyaloid and dense tractional ERM that was not present at the last visit. Observation was decided and the ERM underwent a spontaneous separation from the underlying retina during follow-up. CONCLUSIONS:This is a case of spontaneous release of an ERM in a patient with a known diagnostic of Stargardt disease and ongoing posterior vitreous detachment. It supports that surgical abstention and observation may be a relevant alternative in eyes with an ERM complicating Stargardt disease.

Off-axis retroillumination (known as “Retro mode”) has been shown to enhance the detection of drusen, particularly smaller lesions. Images are obtained by shifting the aperture left (DL) or right (DR), each revealing complementary aspects of drusen. This study evaluated whether combining DL and DR images could enhance drusen boundary depiction. Multimodal images from 11 patients (mean age 74.5 ± 12.1 years; 8 females) with early or intermediate age-related macular degeneration (AMD) were retrospectively analyzed. Imaging included pseudocolor photographs, Retro mode (Mirante, NIDEK), and optical coherence tomography (OCT; Cirrus 5000, Zeiss). DL and DR Retro mode images were manually aligned using vascular landmarks, and differential images (DIF) were generated with FIJI (ImageJ). DIF images appeared to facilitate lesion boundary depiction compared with individual DL or DR images. Hard drusen were barely visible on pseudocolor photographs and en face OCT but were identifiable with Retro mode; on DIF images, they appeared larger than on DL or DR images. Intermediate drusen were visible across all modalities, and Bland–Altman analysis showed a small positive bias toward larger areas on DIF compared with en face OCT (mean difference: +2.2

Purpose:To characterize structural phenotypes in intermediate and advanced non-neovascular age-related macular degeneration (AMD) using flood-illumination adaptive optics (FIAO) and to explore their relationship with established multimodal imaging biomarkers, including OCT-based atrophy classifications. Design:Prospective, cross-sectional observational study. Subjects:A total of 208 eyes from 117 patients (mean age 74 years; 63% female) with intermediate AMD (iAMD) or geographic atrophy (GA) were enrolled. Eligible participants had visual acuity ≥20/63, refractive error between -6 and +2 diopters, and sufficient media clarity for high-quality imaging. Methods:Participants underwent multimodal imaging, including color fundus photography, spectral-domain OCT, infrared reflectance, fundus autofluorescence, and FIAO. Structural phenotypes (drusen, subretinal drusenoid deposits, pigmentary changes, and GA margins) were assessed qualitatively across modalities. Flood-illumination adaptive optics features were compared with OCT-based atrophy classifications (incomplete and complete retinal pigment epithelium and outer retinal atrophy [iRORA and cRORA]) using descriptive analyses and cross-tabulation. Main Outcome Measures:Prevalence and multimodal characteristics of AMD structural phenotypes, and their correspondence with FIAO features. Results:Drusen and pigmentary abnormalities were detected in the majority of eyes across modalities, with variability in prevalence depending on imaging technique. Flood-illumination adaptive optics identified drusen in 70% of eyes revealing a consistent reflectivity pattern of hyperreflective borders and hyporeflective centers. Hyporeflective clumps corresponding to pigmentary changes were always observed on FIAO, frequently localizing to areas of atrophy or transition zones. Distinct FIAO-defined GA border phenotypes were observed, including well-demarcated and indistinct margins. In descriptive cross-tabulation, well-demarcated FIAO borders were more frequently associated with OCT-defined cRORA, whereas indistinct or hyporeflective margins were with iRORA. Conclusions:Flood-illumination adaptive optics provides high-resolution visualization of structural features in iAMD and GA, revealing distinct patterns of drusen, pigmentary changes, and atrophic margins. While certain FIAO features show qualitative correspondence with OCT-defined atrophy stages, these relationships remain descriptive. Further quantitative and longitudinal studies are needed to determine their clinical relevance and role in disease characterization. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose To investigate the hypothesis that the wall-to-lumen ratio (WLR) of retinal arteries is predictive of morbidity and mortality in patients with end-stage chronic kidney disease (CKD). Methods Prospective single center clinical study. In 83 patients with CKD (average age (±SD) 75.8 (±11.4) years), arterial metrics in the retinal vasculature were measured using adaptive optics ophthalmoscopy (AOO; rtx1, ImagineEyes, France). Multivariate analysis including vascular metrics and biological parameters was done to identify predictive risk factors of the morbidity and mortality rates at 3 years. Results At inclusion, the mean (±SD) wall-to-lumen ratio (WLR) was 0,34 (± 0,17). No correlation was found between blood pressure and the WLR. The 1, 2 and 3-year survival rates were 74.7 %, 57.3 % and 42.1 %, respectively. The 1, 2 and 3-year rates of nonfatal cardiovascular events were 25.3 %, 42.7 % and 56.5 %, respectively. Four patients were lost to follow-up. Based on a Cox model, the cumulative 3-year relative risk of death or cardiovascular event was inversely correlated to the initial WLR (RR 2.5 if WLR <0.36, 2.1 if <0.3, 4.9 if <0.27), age over 80 years (RR 1.9), and sedentarity (RR 2.3). Metabolic factors were not predictive of event-free survival. Conclusions In patients with end-stage CKD, a lower WLR is associated with a higher morbidity and mortality rate at 3 years. Retinal vascular metrics may therefore provide novel biomarkers for the prediction of event-free survival in CKD. Additional studies are necessary to elucidate the underlying relationship.

PurposeTo report an unusual case of progressive photoreceptor disruption following a herpetic labial infection.MethodCase report of a patient with severe idiopathic photoreceptoritis.ResultsA 46-year-old female patient presented with blurred vision and inferior photopsia in her right eye one week after a herpetic labial eruption. Initial examination revealed mild vitreous inflammation and focal photoreceptor alterations in the superior periphery of the right retina. Despite oral valaciclovir, the disease progressed rapidly, prompting referral to a tertiary care center. Autofluorescence and optical coherence tomography showed diffuse photoreceptor damage with impending foveal involvement. Extensive workup, including viral markers, was inconclusive. Given the temporal association with the herpetic infection and the sight-threatening progression, treatment was escalated to intravenous acyclovir and subsequently foscarnet for 2 weeks, which slowed down disease progression. The frontal margin of retinal foci stabilized with no further progression, while ellipsoid zone restoration was achieved following systemic corticosteroids and interferon alpha-2a.ConclusionThe term "photoreceptoritis" describes conditions involving diffuse photoreceptor damage, predominantly unilateral, without primary choriocapillaritis. This case highlights a severe form of photoreceptoritis with diffuse photoreceptors loss, likely triggered by a herpetic labial infection. The disease was stabilized with antiviral therapy, while structural recovery of the photoreceptors was achieved through anti-inflammatory and immunosuppressive treatments. This report underscores the importance of a multidisciplinary approach to managing atypical retinal inflammatory disorders.

PURPOSE:To report an unusual episode of acute bilateral retinal and choroidal detachment. METHODS:Case report. RESULTS:We report the case of a fifty-seven-year-old male referred to the emergency department for an acute bilateral retinal detachment. He had experienced profound visual loss three weeks earlier while hospitalized for sepsis of unknown cause. Fundoscopy revealed bilateral annular retinal and choroidal detachment, confirmed by echography. An extensive work-up was negative, and the patient was given steroid boluses for suspected uveal effusion syndrome, although the axial length was normal. After five days of steroid treatment, minimal improvement was observed. The treatment was discontinued, and new multimodal imaging revealed a hyperfluorescent spot on fluorescein angiography (FA) in the right eye with subretinal hyperreflective material on corresponding optical coherence tomography suggesting fibrin and adjacent serous detachment. The spot was treated with laser photocoagulation, and the retinal detachment started to decrease two days later. Additional hyperfluorescent spots were later found and treated with laser photocoagulation. Over a few weeks, both functional and anatomical improvements were observed. Over the course of seven months, the central serous retinal detachment slowly and completely resolved while vision progressively and dramatically improved. This very slow and dramatic anatomical and functional improvement was atypical for both uveal effusion syndrome and central serous chorioretinopathy. CONCLUSIONS:This atypical case of type-3 uveal effusion syndrome presented as acute bilateral retinal and choroidal detachment with central serous chorioretinopathy-like features. Multifocal laser photocoagulation may have improved both functional and anatomical outcomes, with dramatic recovery after seven months.

Rod-cone dystrophy (RCD) comprises genetic conditions where rod photoreceptor degeneration leads to cone loss, causing progressive vision loss. We investigated the phototransduction cascade in degenerating cones using two RCD mouse models and found that opsin and arrestin expression continues in the cell body during outer segment degeneration. Based on this observation, we explored reactivating cones through G-protein-coupled inwardly rectifying K (GIRK) channel expression. Using adeno-associated viral delivery of GIRK channels, we achieved improved visual function in both mouse models. Additionally, we examined human tissue from late-stage RCD patients and confirmed the presence of cone opsin and cone arrestin expression, supporting the potential therapeutic application of this approach. This GIRK-channel-based strategy offers a promising method to preserve high-quality vision in RCD patients, regardless of their specific genetic mutation.

PURPOSE:The identification of telangiectatic capillaries (TelCaps) in chronic macular oedema (ME) resistant to conventional intravitreal injections (IVIs) has renewed interest in focal laser treatment. However, the indications and modalities of this laser treatment remain to be clarified. METHODS:A modified Delphi approach was used to establish a consensus among French macular laser specialists regarding recommendations on assessment of TelCaps, indications for laser treatment, treatment procedures and follow-up. RESULTS:Presence of TelCaps should be considered in cases of recurrent vascular oedema that do not respond, or partially respond, to IVIs. A strong consensus has emerged on treating TelCaps with laser when they are located ≥1000 μm from the fovea and associated with thickening of the surrounding retina, usually in combination with IVIs. For TelCaps located <1000 μm from the centre, IVIs alone were preferred. ICG-guided laser treatment was advised to target TelCaps but was not considered mandatory if TelCaps were visible on fundus photography or OCT. Assessment of the effectiveness of laser treatment should be based on reduction in macular thickness on OCT after 3 months, before a second laser session may be considered. Although experts have recommended the use of small, short-duration impacts allowing greying of the lesion, no consensus has been reached on the optimal numerical parameters for the laser procedure. CONCLUSION:This study provides precise guidelines on laser treatment for vascular ME in cases of TelCaps, and emphasizes the need for standardized lesion selection and laser parameters to ensure safe and effective ME management.

Neurovascular coupling (NVC) regulates local blood flow in response to neuronal activity, yet its precise characterization at the capillary level has been hindered by the lack of a noninvasive, high-resolution imaging method. Here, we introduce the adaptive optics rolling slit ophthalmoscope, a unique noninvasive, label-free, high-speed, cellular-resolution clinical imaging system for assessing retinal NVC in the living human eye. Using an off-axis phase contrast approach combined with camera-based confocal slit gating, our method provides large field-of-view imaging of arterial and venular walls, enabling the study of vascular dynamics with unprecedented spatiotemporal precision. Our findings highlight that this level of precision is essential for accurately distinguishing NVC-driven vasodilation from spontaneous fluctuations, such as vasomotion and the cardiac cycle. By bridging the gap between fundamental neurovascular research and clinical applications, this approach offers a powerful tool for neuroscience research and early disease detection and monitoring of neurodegenerative and vascular disorders.

Structured illumination microscopy (SIM) is one of the most versatile super-resolution techniques. Yet, its application to high-resolution live imaging has been mainly limited to fluorescent and stationary specimens. Here, we present advancements in SIM to jointly tackle all the challenges of imaging living samples, i.e., obtaining super-resolution over an undistorted wide-field while dealing with sample motion, multiple scattering, sample-induced optical aberrations, and low signal-to-noise ratio. By using adaptive optics to compensate for optical aberrations and a reconstruction algorithm tailored for moving and thick tissue, we successfully apply SIM to in vivo retinal imaging and demonstrate structured illumination ophthalmoscopy with optical sectioning and resolution improvement for in vivo imaging of the human retina.