Acute macular neuroretinopathy following Valsalva manoeuvre: an insight into the pathophysiology.

Acute macular neuroretinopathy (AMN) affects the outer retina and is most likely induced by non-inflammatory ischaemia of the retinal deep capillary plexus and choriocapillaris. A man in his early 20s developed Valsalva retinopathy following weightlifting at the gym and presented with blurring of vision in the left eye 1 month after the initial retinal haemorrhages had resolved. A diffuse, purplish, donut-shaped, perifoveal lesion was seen on funduscopy and was well defined by an optical coherence tomography angiography (OCTA) en face image in the left eye. Outer retinal changes on optical coherence tomography (OCT) and a dense co-localised scotoma on a visual field (VF) examination confirmed the diagnosis of AMN, and the patient was started on a tapering dose of oral steroids. Improvement was seen in OCT, OCTA and VF during the 6-month follow-up visit. The use of OCTA en face imaging enabled the accurate identification of the lesion in the affected layers of the retina.

Diagnostic Role of Oral Fluorescein Angiography in Pediatric Ambulatory Clinics.

Oral ingestion of fluorescein can be done in ambulatory pediatric clinics. We show that oral ultra-widefield fluorescein angiography is a non-invasive approach to rapidly diagnose and manage a diverse set of pediatric retinal vascular diseases.

Quantifying Putative Retinal Gliosis in Preclinical Alzheimer's Disease.

Purpose: Neuroinflammation plays a significant role in the pathology of Alzheimer's disease (AD). Mouse models of AD and postmortem biopsy of patients with AD reveal retinal glial activation comparable to central nervous system immunoreactivity. We hypothesized that the surface area of putative retinal gliosis observed in vivo using en face optical coherence tomography (OCT) imaging will be larger in patients with preclinical AD versus controls. Methods: The Spectralis II instrument was used to acquire macular centered 20 × 20 and 30 × 25-degrees spectral domain OCT images of 76 participants (132 eyes). A cohort of 22 patients with preclinical AD (40 eyes, mean age = 69 years, range = 60-80 years) and 20 control participants (32 eyes, mean age = 66 years, range = 58-82 years, P = 0.11) were included for the assessment of difference in surface area of putative retinal gliosis and retinal nerve fiber layer (RNFL) thickness. The surface area of putative retinal gliosis and RNFL thickness for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map were compared between groups using generalized linear mixed models. Results: The surface area of putative retinal gliosis was significantly greater in the preclinical AD group (0.97 ± 0.55 mm2) compared to controls (0.68 ± 0.40 mm2); F(1,70) = 4.41, P = 0.039; Cohen's d = 0.61. There was no significant difference between groups for RNFL thickness in the 9 ETDRS sectors, P > 0.05. Conclusions: Our analysis shows greater putative retinal gliosis in preclinical AD compared to controls. This demonstrates putative retinal gliosis as a potential biomarker for AD-related neuroinflammation.

Retinal Ischemic Perivascular Lesion Reflects Cerebral Small Vessel Disease Burden in Single Subcortical Infarction.

BACKGROUND: Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. METHODS AND RESULTS: In this case-control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept-source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept-source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365-1.662], P<0.001). Eyes with RIPLs showed lower deep vascular complex density (P=0.035) compared with eyes without RIPLs in patients with SSI. After adjusting for vascular risk factors, the presence of RIPLs in patients with SSI was associated with an increased periventricular white matter hyperintensity burden (ß=0.414 [95% CI, 0.181-0.647], P<0.001) and perivascular spaces-basal ganglia (ß=0.296 [95% CI, 0.079-0.512], P=0.008). CONCLUSIONS: RIPLs are associated with SSI independent of underlying risk factors. The relationship between the presence of RIPLs and small vessel disease markers provides evidence that RIPLs might be an additional indicator of cerebral ischemic changes.

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

OBJECTIVE: Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. METHODS: A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. RESULTS: All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. CONCLUSION: Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

Posterior segment manifestations of Takayasu arteritis: A narrative review.

Ocular symptoms can be the presenting manifestation of Takayasu arteritis (TA) or could be indicative of disease reactivation. A review of published literature related to posterior segment manifestations of TA by using the keywords "Takayasu arteritis," "ophthalmic manifestations," "retina," "retinopathy," "ocular," "optic nerve," and "optic neuropathy" was performed. In total, 62 case reports and 12 case series were included. The majority of the articles were from Asia (n = 47, 64%). Females outnumbered males in the ratio of 7:1. The mean age of patients was 33 years (range: 8-78 years, SD: 13.5 years). In 58% (n = 41 out of 71) cases, ocular symptoms were the presenting manifestation of the underlying disease. Hypotensive retinopathy was found in 70% of eyes, and hypertensive retinopathy was found in 27%. The mean presenting visual acuity (VA) was +1.03 logMAR (range: -0.12 to 3, SD: 1.07), and at the final follow-up was +1.02 logMAR (range: -0.12 to 3, SD 1.17). VA improved in 34% (n = 29/86), remained stable in 45% (39/86), and worsened in 21% (18/86). The mean follow-up was 9 months (range: 0.5-204, SD: 16 months).

Diagnosis of retinal damage using Resnet rescaling and support vector machine (Resnet-RS-SVM): a case study from an Indian hospital.

PURPOSE: This study aims to address the challenge of identifying retinal damage in medical applications through a computer-aided diagnosis (CAD) approach. Data was collected from four prominent eye hospitals in India for analysis and model development. METHODS: Data was collected from Silchar Medical College and Hospital (SMCH), Aravind Eye Hospital (Tamil Nadu), LV Prasad Eye Hospital (Hyderabad), and Medanta (Gurugram). A modified version of the ResNet-101 architecture, named ResNet-RS, was utilized for retinal damage identification. In this modified architecture, the last layer's softmax function was replaced with a support vector machine (SVM). The resulting model, termed ResNet-RS-SVM, was trained and evaluated on each hospital's dataset individually and collectively. RESULTS: The proposed ResNet-RS-SVM model achieved high accuracies across the datasets from the different hospitals: 99.17% for Aravind, 98.53% for LV Prasad, 98.33% for Medanta, and 100% for SMCH. When considering all hospitals collectively, the model attained an accuracy of 97.19%. CONCLUSION: The findings demonstrate the effectiveness of the ResNet-RS-SVM model in accurately identifying retinal damage in diverse datasets collected from multiple eye hospitals in India. This approach presents a promising advancement in computer-aided diagnosis for improving the detection and management of retinal diseases.

Clinical, electrophysiologic and serologic evidence of cancer associated retinopathy preceding a diagnosis of breast cancer.

We report the case of a woman in her 50s who presented headaches, blurred vision, diplopia and loss of peripheral vision. She was treated for normal tension glaucoma based on optic nerve cupping prior to the development of diplopia. Records demonstrated visual field constriction over 4 months despite well-controlled intraocular pressures. Examination revealed decreased visual acuity and visual field constriction. The multifocal electroretinogram was abnormal. After a thorough review of her medical and family history, a concern for cancer-associated retinopathy developed. Blood samples were positive for antiretinal antibodies against 23 kDA and 46 kDA proteins. Cancer screening was recommended as the aetiology for retinopathy was unknown and revealed a left breast lump. Following lumpectomy with adjuvant chemoradiation, her visual acuity normalised and visual field defects completely resolved. This case serves to provide an example that distant systemic symptoms may be a manifestation of the underlying malignancy and the importance of clinical suspicion with prompt evaluation.

Atypical multiple evanescent white dot syndrome presenting with peripheral retinal lesions.

Multiple evanescent white dot syndrome (MEWDS) is a rare inflammatory eye condition. We report an atypical case of MEWDS in a man in his 30s who presented with blurred vision (visual acuity 6/9), floaters and photopsia in his left eye. Funduscopy examination showed mild peripheral nasal vascular sheathing with subtle grey-white dots highlighted on fundus autofluorescence. As far as the authors are aware, this is the first case presentation whereby areas affected by MEWDS started in the peripheral retina and migrated centrally. Fluorescein angiography showed hyperfluorescent areas in wreath-like patterns nasally. Optical coherence tomography showed disruption of the ellipsoid zone and hyperreflective projections into the outer nuclear layer. The size of the involved area increased over 3 weeks and subsequently resolved over 4 months. Simultaneously, the patient's symptoms also resolved, without treatment. This case highlights the importance of multimodal imaging, especially ultrawidefield imaging in diagnosing MEWDS.

Bilateral Takayasu's retinopathy as the initial presentation of Takayasu's arteritis.

We present a case of Takayasu's arteritis in a woman in her 30s, who exhibited visual symptoms and ophthalmic manifestations of the disease, specifically Takayasu's retinopathy stage 4, in both eyes. Despite severe narrowing of all branches of the aortic arch and compromised perfusion in both upper limbs, she had no history of intermittent claudication. Doppler study and CT angiography revealed diffuse circumferential wall thickening of bilateral common carotid, subclavian and axillary arteries. Treatment involved retinal laser photocoagulation and immune suppression. This case underscores that advanced Takayasu's retinopathy can be an initial presentation of Takayasu's arteritis even in a state of severely compromised peripheral limb circulation.

Artificial Intelligence (AI) for Early Diagnosis of Retinal Diseases.

Artificial intelligence (AI) has emerged as a transformative tool in the field of ophthalmology, revolutionizing disease diagnosis and management. This paper provides a comprehensive overview of AI applications in various retinal diseases, highlighting its potential to enhance screening efficiency, facilitate early diagnosis, and improve patient outcomes. Herein, we elucidate the fundamental concepts of AI, including machine learning (ML) and deep learning (DL), and their application in ophthalmology, underscoring the significance of AI-driven solutions in addressing the complexity and variability of retinal diseases. Furthermore, we delve into the specific applications of AI in retinal diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), Macular Neovascularization, retinopathy of prematurity (ROP), retinal vein occlusion (RVO), hypertensive retinopathy (HR), Retinitis Pigmentosa, Stargardt disease, best vitelliform macular dystrophy, and sickle cell retinopathy. We focus on the current landscape of AI technologies, including various AI models, their performance metrics, and clinical implications. Furthermore, we aim to address challenges and pitfalls associated with the integration of AI in clinical practice, including the "black box phenomenon", biases in data representation, and limitations in comprehensive patient assessment. In conclusion, this review emphasizes the collaborative role of AI alongside healthcare professionals, advocating for a synergistic approach to healthcare delivery. It highlights the importance of leveraging AI to augment, rather than replace, human expertise, thereby maximizing its potential to revolutionize healthcare delivery, mitigate healthcare disparities, and improve patient outcomes in the evolving landscape of medicine.

Trends in the Prevalence of Common Retinal and Optic Nerve Diseases in China: An Artificial Intelligence Based National Screening.

Purpose: Retinal and optic nerve diseases have become the primary cause of irreversible vision loss and blindness. However, there is still a lack of thorough evaluation regarding their prevalence in China. Methods: This artificial intelligence-based national screening study applied a previously developed deep learning algorithm, named the Retinal Artificial Intelligence Diagnosis System (RAIDS). De-identified personal medical records from January 2019 to December 2021 were extracted from 65 examination centers in 19 provinces of China. Crude prevalence and age-sex-adjusted prevalence were calculated by mapping to the standard population in the seventh national census. Results: In 2021, adjusted referral possible glaucoma (63.29, 95% confidence interval [CI] = 57.12-68.90 cases per 1000), epiretinal macular membrane (21.84, 95% CI = 15.64-29.22), age-related macular degeneration (13.93, 95% CI = 11.09-17.17), and diabetic retinopathy (11.33, 95% CI = 8.89-13.77) ranked the highest among 10 diseases. Female participants had significantly higher adjusted prevalence of pathologic myopia, yet a lower adjusted prevalence of diabetic retinopathy, referral possible glaucoma, and hypertensive retinopathy than male participants. From 2019 to 2021, the adjusted prevalence of retinal vein occlusion (0.99, 95% CI = 0.73-1.26 to 1.88, 95% CI = 1.42-2.44), macular hole (0.59, 95% CI = 0.41-0.82 to 1.12, 95% CI = 0.76-1.51), and hypertensive retinopathy (0.53, 95% CI = 0.40-0.67 to 0.77, 95% CI = 0.60-0.95) significantly increased. The prevalence of diabetic retinopathy in participants under 50 years old significant increased. Conclusions: Retinal and optic nerve diseases are an important public health concern in China. Further well-conceived epidemiological studies are required to validate the observed increased prevalence of diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion, and macular hole nationwide. Translational Relevance: This artificial intelligence system can be a potential tool to monitor the prevalence of major retinal and optic nerve diseases over a wide geographic area.

Using a smartphone-based digital fundus camera for screening of retinal and optic nerve diseases in veterinary medicine: A preliminary investigation.

BACKGROUND: Ophthalmoscopy is a valuable tool in clinical practice. We report the use of a novel smartphone-based handheld device for visualisation and photo-documentation of the ocular fundus in veterinary medicine. METHODS: Selected veterinary patients of a referral ophthalmology service were included if one or both eyes had clear ocular media, allowing for examination of the fundus. Following pharmacological mydriasis, fundic images were obtained with a handheld fundus camera (Volk VistaView). For comparison, the fundus of a subset of animals was also imaged with a veterinary-specific fundus camera (Optomed Smartscope VET2). RESULTS: The large field of view achieved by the Volk VistaView allowed for rapid and thorough observation of the ocular fundus in animals, providing a tool to visualise and record common pathologies of the posterior segment. Captured fundic images were sometimes overexposed, with the tapetal fundus artificially appearing hyperreflective when using the Volk VistaView camera, a finding that was less frequent when activating a 'veterinary mode' that reduced the sensitivity of the camera's sensor. The Volk VistaView compared well with the Optomed Smartscope VET2. LIMITATION: The main study limitation was the small sample size. CONCLUSIONS: The Volk VistaView camera was easy to use and provided good-quality fundic images in veterinary patients with healthy or diseased eyes, offering a wide field of view that was ideal for screening purposes.

The Use of the RETeval Portable Electroretinography Device for Low-Cost Screening: A Mini-Review.

Electroretinography (ERG) provides crucial insights into retinal function and the integrity of the visual pathways. However, ERG assessments classically require a complicated technical background with costly equipment. In addition, the placement of corneal or conjunctival electrodes is not always tolerated by the patients, which restricts the measurement for pediatric evaluations. In this short review, we give an overview of the use of the RETeval portable ERG device (LKC Technologies, Inc., Gaithersburg, MD, USA), a modern portable ERG device that can facilitate screening for diseases involving the retina and the optic nerve. We also review its potential to provide ocular biomarkers in systemic pathologies, such as Alzheimer's disease and central nervous system alterations, within the framework of oculomics.

PdmIRD: missense variants pathogenicity prediction for inherited retinal diseases in a disease-specific manner.

Accurate discrimination of pathogenic and nonpathogenic variation remains an enormous challenge in clinical genetic testing of inherited retinal diseases (IRDs) patients. Computational methods for predicting variant pathogenicity are the main solutions for this dilemma. The majority of the state-of-the-art variant pathogenicity prediction tools disregard the differences in characteristics among different genes and treat all types of mutations equally. Since missense variants are the most common type of variation in the coding region of the human genome, we developed a novel missense mutation pathogenicity prediction tool, named Prediction of Deleterious Missense Mutation for IRDs (PdmIRD) in this study. PdmIRD was tailored for IRDs-related genes and constructed with the conditional random forest model. Population frequencies and a newly available prediction tool were incorporated into PdmIRD to improve the performance of the model. The evaluation of PdmIRD demonstrated its superior performance over nonspecific tools (areas under the curves, 0.984 and 0.910) and an existing eye abnormalities-specific tool (areas under the curves, 0.975 and 0.891). We also demonstrated the submodel that used a smaller gene panel further slightly improved performance. Our study provides evidence that a disease-specific model can enhance the prediction of missense mutation pathogenicity, especially when new and important features are considered. Additionally, this study provides guidance for exploring the characteristics and functions of the mutated proteins in a greater number of Mendelian disorders.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.