PRÉCIS:In this prospective multicenter study, eyes with primary congenital glaucoma exhibited lower retinal vascular parameters compared to healthy controls, as assessed by optical coherence tomography angiography fractal dimension analysis. PURPOSE:To study the retino-choroidal peripapillary microvascular pattern in primary congenital glaucoma (PCG) using fractal dimension (FD) analysis and compare it to healthy controls. METHODS:This was a prospective multicenter comparative study. We obtained peripapillary optical coherence tomography angiography (OCTA) scans (Optovue Inc) and computed FD at the vitreous/retina (large retinal vessels), inner limiting membrane/nerve fiber layer (ILM-NFL) (radial peripapillary capillary plexus, RPC), and the choroid. Other peripapillary OCTA parameters, including the whole image inside the disk and peripapillary superior and inferior vascular density (VD) parameters, were also collected. 1 eye per patient was included in the analysis. RESULTS:We included a total of 17 PCG eyes and 24 control eyes. The mean age at the time of enrollment was 8.24±0.75 years in the PCG group compared to 8.33±1.09 in controls ( P =0.74). Eight patients (47%) in the PCG group and 14 (58.3%) in the control group were male. Among the PCG group, the mean vitreo-retina (large retinal vessels) FD (1.79) and ILM-NFL (RPC) FD (1.75) were significantly reduced compared to controls [vitreo-retina FD (1.85), ILM-NFL FD (1.82), P -value 0.011 and 0.014, respectively]. There was no statistically significant difference in the averaged choroidal FD between both groups (1.89 vs. 1.88, P =0.29). All optic nerve VD parameters (whole image, inside disc, superior, and inferior-hemi) were also significantly reduced in the PCG group. CONCLUSIONS:PCG was associated with lower vascular parameters in the vitreo-retina (large retinal vessels) and ILM-NFL (RPC) layers as detected by OCTA FD.

Interpretability is crucial to enhance trust in machine learning models for medical diagnostics. However, most state-of-the-art image classifiers based on neural networks are not interpretable. As a result, clinicians often resort to known biomarkers for diagnosis, although biomarker-based classification typically performs worse than large neural networks. This work proposes a method that surpasses the performance of established machine learning models while simultaneously improving prediction interpretability for diabetic retinopathy staging from optical coherence tomography angiography (OCTA) images. Our method is based on a novel biology-informed heterogeneous graph representation that models retinal vessel segments, intercapillary areas, and the foveal avascular zone (FAZ) in a human-interpretable way. This graph representation allows us to frame diabetic retinopathy staging as a graph-level classification task, which we solve using an efficient graph neural network. We benchmark our method against well-established baselines, including classical biomarker-based classifiers, convolutional neural networks (CNNs), and vision transformers. Our model outperforms all baselines on two datasets. Crucially, we use our biology-informed graph to provide explanations of unprecedented detail. Our approach surpasses existing methods in precisely localizing and identifying critical vessels or intercapillary areas. In addition, we give informative and human-interpretable attributions to critical characteristics. Our work contributes to the development of clinical decision-support tools in ophthalmology.

Purpose The aim of this study was to investigate the correlation between glaucoma and retinal vein occlusion (RVO) using quantitative metrics of vascular stasis on optical coherence tomography angiography (OCTA). Patients and methods This is a prospective observational, cross-sectional, case–control study that evaluated the retinal peripapillary venous tortuosity index (VTI), as a sign of vascular stasis, by using OCTA images. The study included 45 eyes of 45 patients who were equally distributed among three study groups: healthy controls (15 eyes), glaucomatous eyes with no RVO (15 eyes), and glaucomatous eyes with unilateral RVO (15 eyes). The OCTA scans were also evaluated to obtain the vessel density of the peripapillary and macular capillary plexuses for evidence of capillary nonperfusion. Results There was a statistically significant difference in the VTI among the three groups (P<0.001). The highest VTI was in the glaucoma with RVO group (1.13±0.02, 1.16±0.02) followed by the glaucoma without RVO group (1.06±0.01, 1.07±0.01) and the healthy control group (1.04±0.01, 1.05±0.01). The vessel density was significantly less (P=0.002) in the macular superficial capillary plexus in the glaucomatous eyes with RVO (39.8±5.5%), and in the eyes without RVO (40.1±4.3%) compared to the nonglaucomatous eyes (47.6±3.2%). On the other hand, the deep capillary plexus showed no statistically significant differences between the three groups. Conclusions Primary glaucomas contributed to higher peripapillary vascular stasis, manifested by increased venous tortuosity, associated with the precipitation of RVO. Larger longitudinal studies may be required to evaluate the peripapillary VTI as a prognostic marker for developing RVO in glaucoma.

PURPOSE:To investigate the prevalence, patterns, and topographic distribution of peripheral retinal neovascularization in treatment-naïve patients with proliferative diabetic retinopathy (PDR) using ultra-widefield fluorescein angiography. METHODS:A retrospective cross-sectional observational study conducted in a single center. An overlay grid outlining the 7-field ETDRS and five peripheral fields was applied on ultra-widefield fluorescein angiography images. Neovascular lesions were classified as neovascularization of the disk within one disk diameter of the optic disc, neovascularization elsewhere within the ETDRS 7-field area, and peripheral neovascularization (PNV) within the five peripheral fields. The study evaluated the prevalence and distribution of PNV in the extended ETDRS fields and examined its associations with other forms of retinal neovascularization. RESULTS:Ninety seven eyes of 61 patients with were included. PNV was identified in 56 eyes (57.7%) and solely present in only three eyes (3.1%). PNV was most associated with both neovascularization of the disk and neovascularization elsewhere in 34 eyes (35.1%), followed by its coassociation with neovascularization elsewhere only in 17 eyes (17.5%) and was observed alongside neovascularization of the disk alone in two eyes (2.1%). PNV demonstrated the highest prevalence in Extended Field 6 (43.3%) and showed a significant association with younger patients (50 years and younger; P = 0.012). CONCLUSION:Retinal neovascularization frequently develops outside the ETDRS 7-field area in treatment-naïve eyes with PDR, particularly among younger patients, underscoring the need for vigilant monitoring and tailored management. Nevertheless, peripheral neovascularization (PNV) often coexists with posterior neovascularization, reinforcing the continued relevance of standard ETDRS 7-field imaging for PDR grading.

OBJECTIVE:To evaluate the role of retinal and choriocapillaris blood flow in the development of diabetic foveal neovascularization (DFN) using optical coherence tomography angiography (OCTA). METHODS:Eyes with proliferative diabetic retinopathy (PDR) and DFN underwent OCTA imaging; defined as surface retinal neovascularization within the central foveal 1 mm diameter circle. 3 × 3 and 6 × 6 mm2 choriocapillaris and superficial and deep retinal capillary plexus (SCP and DCP) slabs were extracted to evaluate adjusted flow index (AFI) as a surrogate for blood flow. For choriocapillaris flow; total, subfoveal and extrafoveal AFI were assessed, while only total AFI was calculated for SCP and DCP. These findings were compared to healthy controls and eyes with PDR with no DFN. RESULTS:18 eyes of 18 patients were included in each of the 3 groups: healthy controls, PDR with and without DFN. Choriocapillaris AFI was significantly lower in PDR with DFN than healthy controls in all but the 6 × 6 mm2 extrafoveal AFI (p < 0.01). PDR with DFN also showed a lower AFI compared to eyes without DFN, but only in the 3 × 3 mm2 total and subfoveal AFI (p = 0.01). SCP and DCP AFI were not statistically significant. CONCLUSIONS:Our findings suggest that choroidal hypoperfusion may be a potential driving factor for the development of DFN. The detection of these changes in the smaller scans of the total and subfoveal areas suggests a rather exaggerated and localized subfoveal distribution of ischaemia. Larger longitudinal studies are needed to explore the use of subfoveal choroidal AFI as a prognostic sign for DFN.

OBJECTIVES:To study the changes in vessel densities (VD) stratified by vessel diameter in the retinal superficial and deep vascular complexes (SVC/DVC) using optical coherence tomography angiography (OCTA) images obtained from people with diabetes and age-matched healthy controls. METHODS:We quantified the VD based on vessel diameter categorized as <10, 10-20 and >20 μm in the SVC/DVC obtained on 3 × 3 mm2 OCTA scans using a deep learning-based segmentation and vascular graph extraction tool in people with diabetes and age-matched healthy controls. RESULTS:OCTA images obtained from 854 eyes of 854 subjects were divided into 5 groups: healthy controls (n = 555); people with diabetes with no diabetic retinopathy (DR, n = 90), mild and moderate non-proliferative DR (NPDR) (n = 96), severe NPDR (n = 42) and proliferative DR (PDR) (n = 71). Both SVC and DVC showed significant decrease in VD with increasing DR severity (p < 0.001). The largest difference was observed in the <10 μm vessels of the SVC between healthy controls and no DR (13.9% lower in no DR, p < 0.001). Progressive decrease in <10 μm vessels of the SVC and DVC was seen with increasing DR severity (p < 0.001). However, 10-20 μm vessels only showed decline in the DVC, but not the SVC (p < 0.001) and there was no change observed in the >20 μm vessels in either plexus. CONCLUSIONS:Our findings suggest that OCTA is able to demonstrate a distinct vulnerability of the smallest retinal vessels in both plexuses that worsens with increasing severity of DR.

BACKGROUND:Acute exudative polymorphous vitelliform maculopathy is a presumed retinal pigment epithelium abnormality that has been reported in patients with neoplasms and under certain classes of drugs. The pathophysiology remains unclear, despite the typical clinical features.PURPOSE:To report two cases of acute exudative polymorphous vitelliform maculopathy occurring after vaccination with a COVID-19 vaccine.CASE REPORTS:Two adult patients presented with visual disturbance after inoculation with a COVID-19 vaccine. The patients were otherwise healthy and have no family history of retinal dystrophies. Both cases exhibited the following features on multimodal imaging: multifocal hyporeflective lesions involving the macula, elongated photoreceptors, accumulated vitelliform material exhibiting autofluorescence, and lack of fluorescein dye leakage. Evidence of retinal pigment epithelium dysfunction was confirmed by electrooculography.CONCLUSION:Two cases of acute exudative polymorphous vitelliform maculopathy occurring after COVID-19 vaccination were reported. A relationship between the vaccine and the retinal pigment epithelial abnormality development that led to acute exudative polymorphous vitelliform maculopathy was postulate, possibly through autoantibodies against the severe acute respiratory syndrome coronavirus 2 virus structural surface glycoprotein antigens that cross react with the normal retinal pigment epithelial cells.

Introduction: We aim to explore the safety and efficacy of episcleral brachytherapy as a primary management option for eyes with retinal pigment epithelial (RPE) adenoma. Methods: Retrospective chart review of the demographic, clinical, ancillary, and postoperative outcome data of patients with RPE adenoma in 2 tertiary referral centers. Tumor regression, final visual acuity, and complications were assessed. Results: Five patients (3 females and 2 males) were included. Four of the 5 eyes had peripheral and mid-peripheral lesions, while one tumor was juxtapapillary. Three eyes were treated with ruthenium-106 (100 Gray), and 2 received iodine-125 episcleral plaques (85 Gray). All eyes showed clinical and imaging-based evidence of regression. Four eyes had stable or improved visual acuity, while 1 eye exhibited one line loss of visual acuity due to radiation retinopathy. Local recurrence was not observed in any eye over a median follow-up of 24 (range 6–112) months. Conclusions: Episcleral brachytherapy is an effective management option for select cases of RPE adenoma that is capable of achieving tumor regression while maintaining favorable visual acuity. The initial safety profile of brachytherapy is good without significant vision-compromising complications.

Introduction: We aim to report the anatomical and functional outcomes of ruthenium-106 brachytherapy in the management of circumscribed choroidal hemangiomas (CCH). Methods: This is a single-center, retrospective case series including patients with unilateral symptomatic CCH treated with ruthenium-106 brachytherapy at the Cairo University Ocular Oncology Service. Patient records were analyzed for patients’ demographics, best corrected visual acuity (BCVA), tumor dimensions (thickness and largest base diameter), foveal subretinal fluid, radiation-related complications, and recurrence. Results: Seven patients were included in the study (including 6 males) with a mean age of 39.3 ± 15.4 years; ruthenium-106 plaque was used to deliver 50 Gray to the tumor apex. After a mean follow-up duration of 12.5 months, all patients had significant improvement in BCVA after treatment, mean tumor height decreased significantly from 4.76 ± 1.76 mm to 1.70 ± 1.2 mm (p value 0.01). The largest tumor base diameter also decreased significantly from 9.13 ± 2.68 mm to 4.65 ± 3.75 mm (p value 0.05). Subretinal fluid and exudative retinal detachment resolved in all patients, and no significant radiation-related complications were observed in any patient. None of the patients needed any further treatment or experienced recurrence within the follow-up period. Conclusion: Ruthenium-106 brachytherapy is an effective tool in the management of symptomatic CCH with a good visual prognosis and safety profile.

Introduction:We aimed to report the demographic data, clinical features, and management outcomes of patients with uveal melanoma (UM) in a single tertiary center in Egypt. Methods:This is a single-center retrospective case series. Patients with UM who were managed at Cairo University Ocular Oncology Service between January 2019 and December 2023 were included. Records were analyzed for patients' demographics, clinical features and different management options. Outcomes included changes in best corrected visual acuity and tumor dimensions (thickness and largest base diameter), perioperative complications, globe salvage, and recurrence rates. Results:A total of 93 eyes of 93 patients with UM were treated in our service over a period of 5 years. The mean age of patients was 52.18 ± 13.30 years, and 91.4% of tumors were choroidal or ciliochoroidal. 52 eyes (55.91%) were managed with ruthenium-106 episcleral brachytherapy, of which two eyes required additional brachytherapy, 8 eyes ended with secondary enucleation, and the globe was salvaged in 84.62% of eyes. 8 eyes (8.60%) were managed by gamma knife radiosurgery with or without endoresection. One eye with an iridociliary tumor was managed with partial lamellar sclerouvectomy, and the remaining 32 eyes (34.41%) were primarily enucleated. Conclusion:Timely referral channels and accurate assessment of cases with UM are invaluable for achievement of higher success rates in tumor regression, as well as globe and/or vision salvage in eyes managed with brachytherapy. Patients with more advanced tumors should be counseled on the importance of more invasive options such as enucleation in achieving lower metastasis and mortality rates.

Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can acquire high-resolution volumes of the retinal vasculature and aid the diagnosis of ocular, neurological and cardiac diseases. Segmenting the visible blood vessels is a common first step when extracting quantitative biomarkers from these images. Classical segmentation algorithms based on thresholding are strongly affected by image artifacts and limited signal-to-noise ratio. The use of modern, deep learning-based segmentation methods has been inhibited by a lack of large datasets with detailed annotations of the blood vessels. To address this issue, recent work has employed transfer learning, where a segmentation network is trained on synthetic OCTA images and is then applied to real data. However, the previously proposed simulations fail to faithfully model the retinal vasculature and do not provide effective domain adaptation. Because of this, current methods are unable to fully segment the retinal vasculature, in particular the smallest capillaries. In this work, we present a lightweight simulation of the retinal vascular network based on space colonization for faster and more realistic OCTA synthesis. We then introduce three contrast adaptation pipelines to decrease the domain gap between real and artificial images. We demonstrate the superior segmentation performance of our approach in extensive quantitative and qualitative experiments on three public datasets that compare our method to traditional computer vision algorithms and supervised training using human annotations. Finally, we make our entire pipeline publicly available, including the source code, pretrained models, and a large dataset of synthetic OCTA images.

SIGNIFICANCEBrown syndrome, or superior oblique tendon sheath syndrome, is characterized by limitation of elevation on adduction. The disorder is thought to involve the trochlea/superior oblique tendon complex through traumatic, surgical, and inflammatory mechanisms. It could be an indication of multiple underlying immunological or rheumatological disorders.PURPOSEThis study aimed to report an unusual strabismus after receiving the first dose of a live attenuated coronavirus disease 2019 (COVID-19) vaccine.CASE REPORTA 31-year-old female patient presented with painful vertical diplopia and tenderness of the left trochlear area 3 days after the first dose of COVID-19 vaccination. She had a compensatory chin elevation and face turn to the right, as well as a left 10-prism-diopter hypotropia in the primary position, which increased to 15 prism diopters in the right gaze and disappeared in the left gaze. Ocular motility revealed the limitation of elevation on adduction. The patient denied any history of ocular trauma and was consequently investigated for dysthyroid disease and various immunological and rheumatological disorders, which were excluded. A Hess chart was obtained to document the motility disorder.CONCLUSIONSWe report a case of acquired Brown syndrome in a 31-year-old otherwise healthy woman shortly after COVID-19 vaccination. It is possible that the patient may have developed trochleitis and/or superior oblique tenosynovitis brought on by cross-reacting antibodies generated by the immune response to the vaccine. In the age of the widest vaccination campaign in human history, it is highly likely that we will continue to observe many unexpected potential adverse effects of these vaccines in our clinical practice.

Purpose The aim of this study was to compare choroidal adjusted flow index (AFI) in healthy, hypertensive & preeclamptic pregnancies using optical coherence tomography angiography (OCTA). Methods In this prospective study, healthy, hypertensive & preeclamptic third trimester pregnant women underwent OCTA imaging. 3x3 & 6x6 mm choriocapillaris slabs were exported and the parafoveal area was marked by two concentric ETDRS circles at 1 & 3 mm, centered on the foveal avascular zone. Parafoveal AFI was calculated as a parameter of choroidal blood flow. Results Fifteen eyes of fifteen women per group were recruited (45 eyes). AFI was significantly lower in the preeclamptic compared to the healthy & hypertensive groups (Tukey HSD: <0.001 in both groups on 3x3 mm, and 0.02 & 0.04 in 6x6 mm scans), and in the hypertensive compared to the healthy group (0.005 & 0.03 in 3x3 & 6x6 mm scans respectively). Conclusions Pregnancies complicated with preeclampsia revealed the lowest choroidal blood flow on OCTA followed by pregnancies with systemic hypertension compared to healthy pregnancies. We provide in-vivo documentation of choroidal ischemia, highlighting its culpability in hypertensive and preeclamptic retinochoroidal pathology, and the possibility of utilizing choroidal blood flow on OCTA as a precursor for disease progression.

PURPOSE:The purpose of this study was to determine whether subretinal hyperreflective material (SHRM) may mask the detection of macular neovascular membranes (MNV) on optical coherence tomography angiography (OCTA).METHODS:In this observational study, eyes with active neovascular age-related macular degeneration (nAMD), co-existing SHRM & intraretinal or subretinal fluid or hemorrhage on structural OCT, underwent OCTA & fundus fluorescein angiography (FFA) imaging. 6 × 6 mm choriocapillaris and outer retinal slabs on OCTA were examined to determine the presence of MNV underneath the SHRM. The corresponding area on FFA was used as a reference arm to confirm activity.RESULTS:Thirty eyes of thirty patients with SHRM and active nAMD were recruited. All eyes failed to show a MNV in the choriocapillaris & avascular slabs of the OCTA underneath the SHRM, but showed active hyperfluorescent MNVs that increased in size and intensity in the late stages of FFA. In one eye, parts of a MNV under the SHRM were undetectable due to signal attenuation, while parts extending beyond the SHRM were detected on the choriocapillaris en face slab with flow on the B scan.CONCLUSIONS:SHRM may act as a reflecting surface that limits the passage of light waves in OCTA, creating areas of signal attenuation and diminishing its ability to detect underlying MNVs.

Background In this report, we present a case of a 12-year-old boy with Best vitelliform macular dystrophy (BVMD) complicated by macular neovascularization (MNV) and treated with two intravitreal ranibizumab injections. We document an unusual temporary regression of his vitelliform deposits and describe a 2-year follow-up course through multimodal imaging. Case Presentation A 12-year-old boy complaining of metamorphopsia presented with bilateral yellowish subfoveal deposits, suggestive of BVMD, which was confirmed by fundus autofluorescence and electrooculography. The left eye showed an inferior juxtafoveal complicating MNV, for which the patient was treated with two intravitreal ranibizumab injections. In addition to demonstrating a remarkable response to injection, both clinically and through various multimodal imaging modalities, optical coherence tomography (OCT) showed a surprising temporary resolution of the subfoveal hypopreflective space denoting a regression in the lipofuscin deposits accumulating at the RPE and the subfoveal space. Within 2 months, there was a subsequent build-up of the subfoveal space and lipofuscin reaccumulation through serial imaging despite the clear regression of the MNV. The patient remained stable over a course of 2 years. Conclusion Our findings cast light on a rather unusual response to intravitreal anti-VEGF injections that has not been previously reported in literature in the form of a temporary disappearance of the subfoveal vitelliform deposits, which later began to reaccumulate. This process may reflect a temporary relief of the RPE dysfunction or decreased photoreceptor damage with regression of the complicating MNV, leading to decreased vitelliform deposition. Adding to other reports, our findings also provide a 2-year-long follow-up with serial multimodal documentation of the response to injection and suggest a favorable long-term prognosis for intravitreal anti-VEGF injections in eyes with BVMD presenting with early complicating MNVs.

We present two ICU-hospitalized patients with coronavirus disease-19 (COVID-19) presenting with endogenous endophthalmitis in one eye and variable manifestations of chorioretinitis in the fellow eye. Two diabetic patients (57 and 62 years old) showed anterior uveitis and yellowish-white subretinal infiltrations. The fellow eye of one patient showed patches of choroiditis, while the other showed full retinal thickness infiltrations. A workup yielded high serum titers of galactomannan, diagnostic of aspergillosis. The widespread use of high doses of corticosteroids in the management of COVID-19 may predispose to various secondary fungal opportunistic infections and may manifest in different forms of chorioretinal infiltration.

We demonstrated a paradoxical decrease in choroidal thickness and increase in blood flow in remitting Vogt–Koyanagi–Harada syndrome on optical coherence tomography angiography. This may represent resolution of granulomatous infiltration of the thickened intercapillary spaces affecting choroidal circulation during activity. Larger studies are needed to assess adjusted flow index as a predictor of disease activity. Purpose: To assess changes in choroidal thickness and blood flow in active Vogt–Koyanagi–Harada syndrome and after remission using optical coherence tomography angiography. Methods: This was a prospective study of patients with active early uveitis secondary to Vogt–Koyanagi–Harada syndrome. They underwent optical coherence tomography angiography imaging twice: at baseline and after remission on treatment. 3- × 3- and 6- × 6-mm choriocapillaris slabs were used to evaluate parafoveal adjusted flow index as a marker for choroidal blood flow. Mean choroidal thickness of 3 points (subfoveally and 2 points 300 µm parafoveally) was also measured. Results: Thirty-nine eyes of 25 patients were initially recruited. After excluding eyes with media opacity, submacular fibrosis, and choroidal neovascularization, 23 eyes of 14 patients were included. The mean follow-up period was 8.7 ± 2.5 months. Mean choroidal thickness in activity and remission was 581.65 ± 108.29 µm and 318.34 ± 72.85 µm respectively (P < 0.01). Mean adjusted flow index in the 3- × 3-mm slabs activity and remission were 0.495 ± 0.027 and 0.519 ± 0.0336 (P = 0.011), and the 6- × 6-mm slabs were 0.487 ± 0.037 and 0.517 ± 0.052 respectively (P = 0.025). Conclusion: We demonstrate decreasing choroidal thickness with paradoxically increasing choroidal flow on optical coherence tomography angiography in remitting Vogt–Koyanagi–Harada syndrome. This may reflect inflammatory infiltrations or granulomas increasing choroidal thickness during activity and causing sluggish circulation of the choriocapillaris, and a reversal of this process with remission. These findings shed more light on the relationship between Vogt Koyanagi Harada syndrome and its underlying choroidal disturbances. Larger studies are needed to evaluate the efficacy of adjusted flow index in evaluating and predicting disease activity.

The retina is supplied by two circulations: the choroidal circulation via the choroidal vessels and the retinal circulation via the central retinal artery (Jakobiec 1982). In up to 32% of the eyes (Justice and Lehmann 1976), an additional branch, the cilioretinal artery, may extend from the choroidal circulation to supply a portion of the inner retina, mainly in the macular region.