Search Results (128)

Background/Objectives: Genetic testing is important for diagnosing inherited retinal diseases (IRDs), but further evidence is needed on the utility of singleton genetic testing in an Australian cohort. Methods: A consecutive series of individuals with clinically diagnosed IRDs without prior genetic testing underwent commercial panel-based sequencing (Invitae or Blueprint Genetics), clinical assessment, and multimodal imaging. Retinal images were graded using the Human Phenotype Ontology terms. Binary logistic regression was used to evaluate clinical predictors of a positive molecular diagnosis. Results: Among 140 participants (mean age 49 ± 19 years), genetic testing was undertaken, on average, 23 ± 17 years after the initial clinical IRD diagnosis. Of the 60% who received a probable molecular diagnosis, 40% require further phase testing, highlighting the limitations of singleton genetic testing. USH2A, ABCA4, and RPGR were the most common encountered genes; 67% of the probably solved participants had causative genes with targeted experimental treatments in ongoing human clinical trials. Symptom onset before the age of 30 (OR = 3.06 [95% CI: 1.34–7.18]) and a positive IRD family history (OR = 2.87 [95% CI: 1.27–6.78]) were each associated with higher odds of receiving a molecular diagnosis. Diagnostic rates were comparable across retinal imaging phenotypes (atrophy and autofluorescence patterns in widespread IRD, and the extent of dystrophy in macular IRDs). Conclusions: In an Australian IRD population without prior genetic testing, commercial panels yielded higher diagnostic rates in individuals with IRD onset before the age of 30 and those with an IRD family history. Further research is needed to understand the genetic basis of IRDs, especially isolated and late-onset cases, to improve diagnosis and access to emerging therapies. Full article

Background and Clinical Significance: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome characterized by bilateral uveal melanocyte proliferation and progressive visual disturbance. While most commonly associated with solid tumors, its occurrence in hematologic malignancies is exceedingly rare. Case Presentation: We report a case of BDUMP in a 64-year-old male recently diagnosed with chronic myelomonocytic leukemia (CMML), who presented with subacute, painless bilateral blurred vision. Multimodal imaging revealed suggestive features of BDUMP, including orange-red subretinal patches, retinal pigment epithelium mottling, and diffuse choroidal thickening, consistent with early structural involvement despite preserved central vision. No intraocular mass or signs of inflammation were observed. The patient did not receive specific treatment for BDUMP, and visual acuity remained stable during follow-up. Conclusions: This case underscores the importance of considering BDUMP in the differential diagnosis of bilateral visual symptoms in patients with hematologic malignancies. Although rare, BDUMP may occur in the context of CMML. Recognition through multimodal imaging and interdisciplinary collaboration is essential, and further research is needed to clarify its pathogenesis and improve management strategies. Full article

Ocular diseases can significantly affect vision and overall quality of life, with diagnosis often being time-consuming and dependent on expert interpretation. While previous computer-aided diagnostic systems have focused primarily on medical imaging, this paper proposes VisionTrack, a multi-modal AI system for predicting multiple retinal diseases, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), drusen, Central Serous Retinopathy (CSR), and Macular Hole (MH), as well as normal cases. The proposed framework integrates a Convolutional Neural Network (CNN) for image-based feature extraction, a Graph Neural Network (GNN) to model complex relationships among clinical risk factors, and a Large Language Model (LLM) to process patient medical reports. By leveraging diverse data sources, VisionTrack improves prediction accuracy and offers a more comprehensive assessment of retinal health. Experimental results demonstrate the effectiveness of this hybrid system, highlighting its potential for early detection, risk assessment, and personalized ophthalmic care. Experiments were conducted using two publicly available datasets, RetinalOCT and RFMID, which provide diverse retinal imaging modalities: OCT images and fundus images, respectively. The proposed multi-modal AI system demonstrated strong performance in multi-label disease prediction. On the RetinalOCT dataset, the model achieved an accuracy of 0.980, F1-score of 0.979, recall of 0.978, and precision of 0.979. Similarly, on the RFMID dataset, it reached an accuracy of 0.989, F1-score of 0.881, recall of 0.866, and precision of 0.897. These results confirm the robustness, reliability, and generalization capability of the proposed approach across different imaging modalities. Full article

To compare the clinical characteristics of inherited retinal diseases (IRDs) caused by biallelic versus monoallelic variants in the RP1, BEST1, and PROM1 genes. A total of 52 patients (26 female) with genetically confirmed IRDs were retrospectively selected from the records of the Harkness Eye Institute Clinical Coordinating Center at Columbia University Irving Medical Center. In RP1, 3 individuals with biallelic variants and 22 patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. In BEST1, eight individuals with biallelic variants and nine individuals with monoallelic variants classified as either pathogenic or likely pathogenic were included. In PROM1, four individuals with biallelic variants and six patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. All patients underwent multimodal retinal imaging and, when available, full-field electroretinography (ffERG). In all three genes, individuals with biallelic variants had markedly earlier disease onset and more severe phenotypes. In RP1, on SD-OCT, foveal involvement was observed in all biallelic cases (3/3, 100%) and in 4/22 (18%) monoallelic cases. In BEST1, the average age of onset in the biallelic cohort was 7.12 years, and the average age was 32.7 years in the monoallelic cohort. Four of eight (50%) patients in the biallelic group were additionally found to have widespread serous lesions outside of the central macula. This finding was not observed in the monoallelic group. Three of eight (38%) biallelic BEST1 patients had moderate reductions in their photopic flicker. All monoallelic BEST1 patients had photopic responses within the normal range. PROM1 biallelic cases showed severe functional impairment on ffERG, while most monoallelic cases retained normal responses. In the biallelic cohort, four of four (100%) of patients had severely attenuated or extinguished photopic responses. In the monoallelic PROM1 group, four of five (80%) monoallelic PROM1 patients had normal photopic responses, and P2-2 had mildly attenuated photopic responses. Individuals with biallelic variants exhibited earlier disease onset, more severe retinal degeneration, and significantly reduced retinal function compared with those with monoallelic variants. These observations highlight the role of loss-of-function mechanisms in more aggressive disease courses and underscore the importance of considering zygosity when determining prognosis and planning gene-based therapies. Full article

Background/Objectives: To investigate the role of multimodal imaging, specifically optical coherence tomography angiography (OCTA) and adaptive optics (AO), in the diagnosis and monitoring of diabetic retinopathy. Methods: Our study represents an observational, cross-sectional analysis including sixty-nine patients from four distinct groups: a control group (17 patients), diabetic patients without diabetic retinopathy (no DR) (14 patients), diabetic patients with non-proliferative diabetic retinopathy (NPDR) (18 patients), and diabetic patients with proliferative diabetic retinopathy (PDR patients). A comprehensive ophthalmological evaluation, along with high-resolution imaging using OCTA and AO, was performed. OCTA images of the superficial capillary plexus, acquired with the OCT Angio Topcon, were analyzed using a custom-developed MATLAB algorithm, while AO retinal vascular images were evaluated with the manufacturer’s software of the Adaptive Optics Retinal Camera rtx1™. Results: Our findings demonstrated statistically significant reductions in foveal avascular zone circularity, superficial capillary plexus density, vessel length density, and fractal dimension, correlating with the severity of diabetic retinopathy, particularly in the PDR. Additionally, mean wall thickness and wall-to-lumen ratio were significantly increased in patients with diabetic retinopathy, notably in PDR. Conclusions: In conclusion, our findings demonstrate that the combined use of OCTA and AO imaging offers complementary insights into the microvascular alterations associated with diabetic retinopathy progression and severity. These high-resolution modalities together reveal both perfusion deficits and structural vascular changes, underscoring their utility as essential tools for early detection, staging, monitoring, and informed management of DR. Full article

Objectives: This study aims to describe the clinical features and genetic findings of nine Vietnamese patients with autosomal recessive bestrophinopathy. Methods: This retrospective and cross-sectional study included individuals diagnosed with autosomal recessive bestrophinopathy at the Eye Clinic, Vietnam National Geriatric Hospital between May 2024 and April 2025. The patients underwent a visual acuity assessment, retinal multimodal imaging, and molecular testing through BEST1 gene sequencing. Results: Nine patients from seven unrelated families were included. The mean age was 38.6 years (range: 14.1–79.6). Visual acuity ranged from 20/20 to 20/125. All patients showed vitelliform lesions, subretinal deposits, and both intraretinal and subretinal fluid. Other main features included diffuse macular hyperfluorescence and hyperopia. Less common clinical features encompassed glaucoma, retinoschisis, outer retinal thinning, serous retinal detachment, retinal thickening, and thinning of the retinal pigment epithelium. Compound heterozygous or homozygous variants were detected in all patients. Among the five identified BEST1 variants, the most frequent were p.(A195V) and p.(R200*). One novel variant, p.(K289*), was detected. Conclusions: The main clinical retinal features of nine Vietnamese patients with autosomal recessive bestrophinopathy included vitelliform lesions, subretinal deposits, retinal fluid, and diffuse macular hyperfluorescence. The most common variants were p.(A195V) and p.(R200*). Additionally, the identification of various compound heterozygotes and a novel BEST1 variant expands the mutation spectrum of the disease. Full article

Background: Age-related macular degeneration (AMD) is one of the leading causes of permanent vision loss in the elderly, particularly in higher-income countries. Fundus autofluorescence (FAF) imaging is a widely used, non-invasive technique that complements structural imaging in the assessment of retinal pigment epithelium (RPE) integrity. While optical coherence tomography (OCT) remains the gold standard for retinal imaging due to its high-resolution cross-sectional visualization, FAF offers unique metabolic insights. Among the FAF modalities, blue light FAF (B-FAF) is more commonly employed, whereas green light FAF (G-FAF) provides subtly different image characteristics, particularly improved visualization and contrast in the central macula. Despite identical acquisition times and nearly indistinguishable workflows, G-FAF is notably underutilized in clinical practice. Objectives: This narrative review critically compares green and blue FAF in terms of their diagnostic utility relative to OCT, with a focus on lesion detectability, macular pigment interference, and clinical decision-making in retinal disorders. Methods: A comprehensive literature search was performed using the PubMed database for studies published prior to February 2025. The search utilized the keywords fundus autofluorescence and age-related macular degeneration. The primary focus was on short-wavelength FAF and its clinical utility in AMD, considering three aspects: diagnosis, follow-up, and prognosis. The OCT findings served as the reference standard for anatomical correlation and diagnostic accuracy. Results: Both FAF modalities correlated well with OCT in detecting RPE abnormalities. G-FAF demonstrated improved visibility of central lesions due to reduced masking by macular pigment and enhanced contrast in the macula. However, clinical preference remained skewed toward B-FAF, driven more by tradition and device default settings than by evidence-based superiority. G-FAF’s diagnostic potential remains underrecognized despite its comparable practicality and subtle imaging advantages specifically for AMD patients. AMD stages were accurately characterized, and relevant images were used to highlight the significance of G-FAF and B-FAF in the examination of AMD patients. Conclusions: While OCT remains the gold standard, FAF provides complementary information that can guide management strategy. Since G-FAF is functionally equivalent in acquisition, it offers slight advantages. Broader awareness and more frequent integration of G-FAF that could optimize multimodal imaging strategies, particularly in the intermediate stage, should be developed. Full article

Progression independent of relapse activity (PIRA) is increasingly recognized as a key driver of disability in multiple sclerosis (MS). However, the concept of PIRA remains elusive, with uncertainty surrounding its definition, underlying mechanisms, and methods of quantification. This review examines the current landscape of biomarkers used to predict and measure PIRA, focusing on clinical, imaging, and body fluid biomarkers. Clinical disability scores such as the Expanded Disability Status Scale (EDSS) are widely used, but may lack sensitivity in capturing subtle relapse-independent progression. Imaging biomarkers, including MRI-derived metrics (brain and spinal cord volume loss, chronic active lesions) and optical coherence tomography (OCT) parameters (retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning), offer valuable insights, but often reflect both inflammatory and neurodegenerative processes. Body fluid biomarkers, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), are promising indicators of axonal damage and glial activation, but their specificity for PIRA remains limited. This review emphasizes the distinction between predicting PIRA—identifying individuals at risk of future progression—and measuring ongoing PIRA-related disability in real time. We highlight the limitations of current biomarkers in differentiating PIRA from relapse-associated activity and call for a clearer conceptual framework to guide future research. Advancing the precision and utility of PIRA biomarkers will require multimodal approaches, longitudinal studies, and standardized protocols to enable their clinical integration and to improve personalized MS management. Full article

Background/Objectives: The aim of this study was to investigate the potential contribution of microaneurysms (MAs) and retinal cysts to the pathogenesis of macular non-perfusion in patients with diabetic macular edema (DME) using multimodal imaging. Methods: In this cross-sectional study, 42 eyes with DME were analyzed using color fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT). Macular non-perfusion within the central 3000 µm was categorized by location and extent into foveal avascular zone enlargement (FAZE), focal non-perfusion (FNP) and diffuse non-perfusion (DNP). A custom-developed software was used to assess the colocalization of retinal cysts on OCT with areas of non-perfusion on the corresponding FA images. Also, the presence of leaky MAs adjacent to retinal cysts on FA was verified. Results: Colocalization between retinal cysts and non-perfusion was observed in 32 of 42 (76%) eyes: 19 of 23 (83%) eyes with FAZE and 13 of 16 (81%) eyes with FAZE+FNP. No cysts colocalization was found in all three eyes (100%) presenting with DNP. None of the eyes presented with FNP alone. In the remaining seven eyes (four eyes with FAZE and three eyes with FAZE+FNP), no colocalization was noticed. At least one leaky MA adjacent to retinal cysts was identified in all eyes presented with colocalization. Conclusions: Retinal cysts may contribute to the development of limited non-perfusion in DME. Leaky MAs appear to be the primary source of cyst formation, which may lead to localized capillary occlusion in the macula. Full article

Stem cell therapy has emerged as a promising approach for treating various retinal diseases, particularly degenerative retinal diseases such as geographic atrophy in age-related macular degeneration (AMD), retinitis pigmentosa (RP), and Stargardt disease. A wide variety of imaging techniques have been employed in both preclinical and clinical settings to assess the efficacy and safety of stem cell therapy for retinal diseases. These techniques can be classified into two categories: methods for imaging stem cells and those for the overall morphology and function of the retina. The techniques employed for stem cell imaging include optical imaging, magnetic resonance imaging (MRI), and radionuclide imaging. Additional imaging techniques include fundus photography, fluorescein angiography, and fundus autofluorescence. Each technique has its own advantages and disadvantages, and thus, the use of multimodal imaging can help to overcome the shortcomings and achieve a more comprehensive evaluation of stem cell therapy in retinal disease. This review discusses the characteristics of the main techniques and cell-labeling techniques applied in stem cell therapy, with a particular focus on the applications of multimodal imaging. Furthermore, this review discusses the challenges and prospects of multimodal imaging in stem cell therapy for retinal disease. Full article

Background and Objectives: Uveitis-masked syndromes or masquerade syndromes (UMSs) are a group of ocular conditions with several systemic underlying causes, malignant or nonmalignant, that mimic the inflammatory status of the uvea. They are often difficult to detect and diagnose with traditional techniques, such as ophthalmic exams. Ocular B (bidimensional)-ultrasound (OBU) is a non-invasive, repeatable, rapid ultrasound method effective in indirect signs that lead back to systemic diseases. It is comparable in effectiveness with other imaging tools. The cause of UMSs can often be serious, and therefore early diagnosis and prompt treatment are critical. This study aimed to identify the sonographic signs of these forms, which can help physicians discover the cause underlying UMS. Materials and Methods: This was a consecutive, retrospective, nonrandomized study. This study was conducted at the University Hospital Polyclinic of Bari, Italy, from January 2022 to December 2024. A total of 186 patients were included, from 10 to 85 years old. They all underwent B-scan ultrasonography (Quantel Medical ABSolu Ocular Ultrasound). Results: All patients reported blurred vision, which could be accompanied by visual reduction (<20/40, Snellen charts), photophobia, floaters, flashes, proptosis, and redness. In all cases, we noted peculiar ultrasonographic signs, which allowed us to discriminate the underlying systemic diagnosis, such as vitreous corpuscles, choroid thickening, and primitive or metastatic solid tumors. Finally, we identified different diseases, such as primary intraocular lymphoma (PIOL), other lymphoproliferative conditions, orbital plasmacytoma, uveal melanoma, metastasis, endogenous endophthalmitis, retinal detachment, central serous retinopathy, metallic foreign bodies, ocular amyloidosis, and drug-induced UMSs. The sensitivity and specificity of ocular ultrasound compared to multimodal ocular imaging in UMSs were as follows: for primary intraocular lymphoma (PIOL) and other lymphoproliferative conditions, 0.98 (95% CI, 0.80–1) and 0.68 (90% CI, 0.40–0.92), respectively; for orbital plasmacytoma, 0.64 (92% CI, 0.52–0.86) and 0.66 (93% CI, 0.48–0.89), respectively; uveal melanoma, 1.00 (98% CI, 0.88–1.00) and 0.98 (95% CI, 0.86–0.98), respectively; metastasis, 0.75 (95% CI, 0.53–0.85) and 0.85 (95% CI, 0.48–0.98), respectively; endogenous endophthalmitis, 1.00 (95% CI, 0.50–1.00) and 0.83 (95% CI, 0.48–0.98), respectively; retinal detachment, both were 1.00 (95% CI, 0.87–1.00 and 0.84–0.97, respectively); central serous retinopathy, 0.60 (80% CI, 0.41–0.88) and 0.85 (95% CI, 0.52–0.98), respectively; metallic foreign bodies, 1.00 (95% CI, 0.78–1.00) and 0.99 (95% CI, 0.99–1.00), respectively; ocular amyloidosis, 0.77 (82% CI, 0.52–0.90) and 0.83 (80% CI, 0.49–0.88), respectively; and drug-induced UMSs, 0.64 (95% CI, 0.49–0.88) and 0.85 (95% CI, 0.52–0.98), respectively. Conclusions: Diagnosing UMS accurately can be quite challenging, and many of its different types frequently go undetected. This complexity in identification often leads to underdiagnosis, meaning it is essential to improve awareness and understanding of the condition in order to achieve better recognition and treatment. Early detection of these forms is imperative. The use of OBU can help diagnose indirect signs of these forms early and treat them promptly. It compares well with other diagnostic imaging techniques, such as MRI, but this does not mean that it replaces them; it can offer added value in multimodal imaging. Full article

Macular Telangiectasia (MacTel) is a rare retinal vascular disorder, with Type 3a MacTel being a distinct form characterized by retinal ischemia with the classical findings of MacTel, such as juxtafoveal telangiectasis, right-angled venules, and deep capillary plexus involvement without central nervous system findings. This case presents a novel X-shaped lesion pattern and ischemic features, expanding the known imaging spectrum of MacTel. A 53-year-old male with diabetes and a history of aripiprazole use presented with persistent blurred vision, a black curtain sensation, and metamorphopsia in the right eye. Visual acuity was 0.8 in the right eye and 1.0 in the left. A multimodal imaging approach, including fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FFA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), was used to evaluate structural and vascular abnormalities. Fundus examination revealed an X-shaped hypopigmented lesion with central pigmentation. FAF showed hypoautofluorescence, indicating chronic RPE loss, and no loss of foveal autofluorescence was observed. FFA demonstrated progressive hyperfluorescence with perifoveal aneurysmal and telangiectatic vessels, along with a slightly enlarged foveal avascular zone (FAZ), suggesting ischemic involvement. OCT revealed intraretinal cysts, a disruption of the ellipsoid zone and external limiting membrane, pigment epithelial detachment, and increased choroidal backscattering. OCTA confirmed right-angled venules, aneurysmal telangiectatic vessels, and localized ischemia predominantly affecting the deep capillary plexus. This case highlights a rare variant of Type 3a MacTel with a unique X-shaped lesion. The presence of juxtafoveal telangiectasis, vascular occlusion, right-angled venules, and deep capillary plexus changes supports the diagnosis. Multimodal imaging played a critical role in characterizing the disease and differentiating it from other macular disorders, contributing to an expanded understanding of the clinical and imaging spectrum of MacTel. Full article

Background/Objectives: Diabetic retinopathy (DR) remains a leading cause of preventable blindness, with its global prevalence projected to rise sharply as diabetes incidence increases. Early detection and timely management are critical to reducing DR-related vision loss. Optical Coherence Tomography Angiography (OCTA) now enables non-invasive, layer-specific visualization of the retinal vasculature, facilitating more precise identification of early microvascular changes. Concurrently, advancements in artificial intelligence (AI), particularly deep learning (DL) architectures such as convolutional neural networks (CNNs), attention-based models, and Vision Transformers (ViTs), have revolutionized image analysis. These AI-driven tools substantially enhance the sensitivity, specificity, and interpretability of DR screening. Methods: A systematic review of PubMed, Scopus, WOS, and Embase databases, including quality assessment of published studies, investigating the result of different AI algorithms with OCTA parameters in DR patients was conducted. The variables of interest comprised training databases, type of image, imaging modality, number of images, outcomes, algorithm/model used, and performance metrics. Results: A total of 32 studies were included in this systematic review. In comparison to conventional ML techniques, our results indicated that DL algorithms significantly improve the accuracy, sensitivity, and specificity of DR screening. Multi-branch CNNs, ensemble architectures, and ViTs were among the sophisticated models with remarkable performance metrics. Several studies reported that accuracy and area under the curve (AUC) values were higher than 99%. Conclusions: This systematic review underscores the transformative potential of integrating advanced DL and machine learning (ML) algorithms with OCTA imaging for DR screening. By synthesizing evidence from 32 studies, we highlight the unique capabilities of AI-OCTA systems in improving diagnostic accuracy, enabling early detection, and streamlining clinical workflows. These advancements promise to enhance patient management by facilitating timely interventions and reducing the burden of DR-related vision loss. Furthermore, this review provides critical recommendations for clinical practice, emphasizing the need for robust validation, ethical considerations, and equitable implementation to ensure the widespread adoption of AI-OCTA technologies. Future research should focus on multicenter studies, multimodal integration, and real-world validation to maximize the clinical impact of these innovative tools. Full article

Sphingolipidoses are a class of inherited lysosomal storage diseases, characterized by enzymatic deficiencies that impair sphingolipid degradation. This enzymatic malfunction results in the pathological accumulation of sphingolipids within lysosomes, leading to tissue damage across multiple organ systems. Among the various organs involved, the eye and particularly the retina, can be affected and this will be the primary focus of this study. This article will explore the various subtypes of sphingolipidoses, detailing their associated retinal abnormalities, with an emphasis on multimodal imaging findings and clinical recognition of these rare disorders. Full article

Objectives: To assess the association between clinical outcomes and the multimodal imaging-based classification of central serous chorioretinopathy (CSC). Methods: This retrospective study included 207 eyes from 155 treatment-naïve patients with CSC. The eyes were categorized into two groups, including the simple CSC group (n = 164) and the complex CSC group (n = 43), based on the presence of retinal pigment epithelial atrophy spanning two or more disc areas. All patients were initially observed without treatment for 3–6 months. For cases with persistent subretinal fluid after this observation period, treatment modalities, including continued observation, photocoagulation (PC), or photodynamic therapy (PDT), were selected. Results: Patients in the complex CSC group were more likely to be older (p = 0.01) and male (p = 0.01) than those in the simple group and to exhibit a higher prevalence of bilateral involvement (p < 0.001) and previous CSC episodes (p < 0.001) than those exhibited by patients in the simple group. Eyes with complex CSC exhibited a comparable incidence of spontaneous resolution within 6 months and a higher incidence of recurrence after spontaneous resolution within 6 months than eyes with simple CSC. In both the simple and complex CSC groups, the PDT subgroup exhibited a lower recurrence rate than that of the PC subgroup (simple CSC: p < 0.001, complex CSC: p = 0.03). Conclusions: Although CSC is typically a self-limiting disease often managed conservatively, patients with complex CSC, characterized by bilateral involvement or a history of previous episodes, are at a higher risk of subretinal fluid recurrence and may benefit from early interventions without a period of observation, such as PDT. Full article