Aqueous and Plasma Levels of Phosphorylated Tau 181 in Individuals with Normal Cognition.

Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer's disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between aqueous concentrations, plasma concentrations, and MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p = 0.005 and p = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights.

Analysis of the Retinal and Choroidal Vasculature Using Ultrawidefield Fundus Imaging in Mild Cognitive Impairment and Normal Cognition.

Purpose: To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with that of controls with normal cognition. Design: Prospective cross sectional study. Participants: One hundred thirty-one eyes of 82 MCI patients and 230 eyes of 133 cognitively normal participants from the Eye Multimodal Imaging in Neurodegenerative Disease Study. Methods: A scanning laser ophthalmoscope (California, Optos Inc) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina UWF (VAMPIRE-UWF 2.0, Universities of Edinburgh and Dundee) software. Main outcome measures: Imaging parameters included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension. Results: Both retinal artery and vein width gradients were less negative in MCI patients compared with controls, demonstrating decreased rates of vessel thinning at the periphery (P < 0.001; P = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates the width of the vessel at the center of the optic disc, were smaller in MCI patients compared with that of controls (P < 0.001; P = 0.017). The large vessel choroidal vascular density, which quantifies the vascular area versus the total choroidal area, was greater in MCI patients compared with controls (P = 0.025). Conclusions: When compared with controls with normal cognition, MCI patients had thinner retinal vasculature manifested in both the retinal arteries and the veins. In MCI, these thinner arteries and veins attenuated at a lower rate when traveling toward the periphery. MCI patients also had increased choroidal vascular density. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Performance of Automated Machine Learning in Predicting Outcomes of Pneumatic Retinopexy.

Purpose: Automated machine learning (AutoML) has emerged as a novel tool for medical professionals lacking coding experience, enabling them to develop predictive models for treatment outcomes. This study evaluated the performance of AutoML tools in developing models predicting the success of pneumatic retinopexy (PR) in treatment of rhegmatogenous retinal detachment (RRD). These models were then compared with custom models created by machine learning (ML) experts. Design: Retrospective multicenter study. Participants: Five hundred and thirty nine consecutive patients with primary RRD that underwent PR by a vitreoretinal fellow at 6 training hospitals between 2002 and 2022. Methods: We used 2 AutoML platforms: MATLAB Classification Learner and Google Cloud AutoML. Additional models were developed by computer scientists. We included patient demographics and baseline characteristics, including lens and macula status, RRD size, number and location of breaks, presence of vitreous hemorrhage and lattice degeneration, and physicians' experience. The dataset was split into a training (n = 483) and test set (n = 56). The training set, with a 2:1 success-to-failure ratio, was used to train the MATLAB models. Because Google Cloud AutoML requires a minimum of 1000 samples, the training set was tripled to create a new set with 1449 datapoints. Additionally, balanced datasets with a 1:1 success-to-failure ratio were created using Python. Main Outcome Measures: Single-procedure anatomic success rate, as predicted by the ML models. F2 scores and area under the receiver operating curve (AUROC) were used as primary metrics to compare models. Results: The best performing AutoML model (F2 score: 0.85; AUROC: 0.90; MATLAB), showed comparable performance to the custom model (0.92, 0.86) when trained on the balanced datasets. However, training the AutoML model with imbalanced data yielded misleadingly high AUROC (0.81) despite low F2-score (0.2) and sensitivity (0.17). Conclusions: We demonstrated the feasibility of using AutoML as an accessible tool for medical professionals to develop models from clinical data. Such models can ultimately aid in the clinical decision-making, contributing to better patient outcomes. However, outcomes can be misleading or unreliable if used naively. Limitations exist, particularly if datasets contain missing variables or are highly imbalanced. Proper model selection and data preprocessing can improve the reliability of AutoML tools. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evolution of Autoimmune Retinopathy in Stiff Person Syndrome: A Case Report.

PURPOSE: To report a case of autoimmune retinopathy (AIR) as the presenting feature of Stiff Person Syndrome (SPS) and assess its evolution. OBSERVATIONS: A 35-year-old man presented with progressive, chronic, vision loss. On initial examination, visual acuity measured 20/20 OD and 20/50 OS. Humphrey Visual Field testing (HVF) demonstrated decreased foveal threshold OU. Mild subfoveal ellipsoid zone loss was noted on Optical Coherence Tomography (OCT). Five years later the patient presented with painful lower extremity muscle spasms and stiffness and complained of increasing vision loss with difficulty distinguishing colors. OCT showed marked progression of ellipsoid zone loss. Scotoma were demonstrated on HVF and electroretinography demonstrated reduced responses consistent with bilateral severe maculopathy. Serum testing showed autoantibodies to the glutamic acid decarboxylase 65-kilodalton isoform (GAD65) at a high titer and a diagnosis of AIR in the setting of SPS was made. A systemic workup for malignancy was negative. The patient was treated with IVIG and transitioned to rituximab with improvement in systemic symptoms. CONCLUSIONS: and Importance: Unlike previous cases of AIR in the setting of SPS, vision symptoms and OCT changes presented years before the onset of muscle spasms. Etiologies such as SPS should be on the differential of unexplained retinopathy, even in the absence of systemic symptoms, especially when paraneoplastic etiologies are ruled out.

Longitudinal Retinal and Choroidal Image Analysis in a Set of Monozygotic Twins.

We analyzed multimodal retinal and choroidal imaging, including optical coherence tomography (OCT) and OCT angiography (OCTA), to assess differences and characterize variations in the retinal and choroidal structure and microvasculature between healthy monozygotic twins without ocular or systemic pathology over a five-year period. Retinal imaging of both subjects revealed normal age-related changes. There was up to an 11% difference in OCT and OCTA variables within the subjects, both at baseline and at five years, and there was up to an 18% difference in OCT and OCTA parameters between the subjects for both time points. Larger changes in subfoveal choroidal thickness and foveal avascular zone area were observed. Our observations suggest that the parafoveal superficial capillary plexus, choroidal vascularity index, central subfield thickness, retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness may be more heavily influenced by genetic, rather than environmental, factors. In contrast, subfoveal choroidal thickness and the foveal avascular zone area may be more heavily influenced by environmental factors. The environmental impact on retinal and choroidal structure and microvasculature is increasingly important to characterize, as such imaging parameters are being explored as potential biomarkers of systemic disease. These differences, as seen in these identical twin subjects, may be important considerations in supporting the security of biometric identifiers.

Peripapillary Optical Coherence Tomography Angiography in Alzheimer's Disease, Mild Cognitive Impairment, and Normal Cognition.

OBJECTIVE: This study aimed to identify peripapillary microvascular changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: In this prospective study, 66 eyes of 36 subjects with AD, 119 eyes of 63 with MCI, and 513 eyes of 265 controls with normal cognition were enrolled. Peripapillary capillary perfusion density (CPD), capillary flux index (CFI), and retinal nerve fiber layer (RNFL) thickness were determined. RESULTS: Average CPD differed significantly between all three groups (P = 0.001), being significantly greater in AD vs controls (0.446 ± 0.015 vs 0.439 ± 0.017, P = 0.001) and MCI vs controls (0.443 ± 0.020 vs 0.439 ± 0.017, P = 0.007) but not AD vs MCI (P = 0.69). CFI and average RNFL thickness did not significantly differ among groups (all P > 0.05). CONCLUSION: Peripapillary CPD is increased in eyes with AD or MCI compared to controls despite similar RNFL thickness. [Ophthalmic Surg Lasers Imaging Retina 2024;55:78-84.].

Ultra-Widefield Imaging of the Retinal Macrovasculature in Parkinson Disease Versus Controls With Normal Cognition Using Alpha-Shapes Analysis.

Purpose: To investigate retinal vascular characteristics using ultra-widefield (UWF) scanning laser ophthalmoscopy in Parkinson disease (PD). Methods: Individuals with an expert-confirmed clinical diagnosis of PD and controls with normal cognition without PD underwent Optos California UWF imaging. Patients with diabetes, uncontrolled hypertension, glaucoma, dementia, other movement disorders, or known retinal or optic nerve pathology were excluded. Images were analyzed using Vasculature Assessment and Measurement Platform for Images of the Retina (VAMPIRE-UWF) software, which describes retinal vessel width gradient and tortuosity, provides vascular network fractal dimensions, and conducts alpha-shape analysis to further characterize vascular morphology (complexity, Opαmin; spread, OpA). Results: In the PD cohort, 53 eyes of 38 subjects were assessed; in the control cohort, 51 eyes of 33 subjects were assessed. Eyes with PD had more tortuous retinal arteries in the superotemporal quadrant (P = 0.043). In eyes with PD, alpha-shape analysis revealed decreased OpA, indicating less retinal vasculature spread compared to controls (P = 0.032). Opαmin was decreased in PD (P = 0.044), suggesting increased vascular network complexity. No differences were observed in fractal dimension in any region of interest. Conclusions: This pilot study suggests that retinal vasculature assessment on UWF images using alpha-shape analysis reveals differences in retinal vascular network spread and complexity in PD and may be a more sensitive metric compared to fractal dimension. Translational Relevance: Retinal vasculature assessment using these novel methods may be useful in understanding ocular manifestations of PD and the development of retinal biomarkers.

Characterizing differences in retinal and choroidal microvasculature and structure in individuals with Huntington's Disease compared to healthy controls: A cross-sectional prospective study.

OBJECTIVE: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD). METHODS: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation. RESULTS: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups. CONCLUSIONS: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD.

Differences in Retinal and Choroidal Microvasculature and Structure in Dementia With Lewy Bodies Compared With Normal Cognition.

Purpose: To evaluate the retinal and choroidal microvasculature and structure in individuals with dementia with Lewy bodies (DLB) compared with controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: An institutional review board-approved cross-sectional comparison of patients with DLB and cognitively normal controls was performed. The Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec) was used to obtain OCT and OCTA images. Results: Thirty-four eyes of 18 patients with DLB and 85 eyes of 48 cognitively normal patients were analyzed. The average capillary perfusion density (CPD) was higher in the DLB group than in the control group (P = .005). The average capillary flux index (CFI) and ganglion cell inner-plexiform layer (GC-IPL) thickness were lower in the DLB group than in the control group (P = .016 and P = .040, respectively). Conclusions: Patients with DLB had an increased peripapillary CPD, decreased peripapillary CFI, and attenuated GC-IPL thickness compared with those with normal cognition.

Incident glaucoma and ocular hypertension after periocular and intravitreal steroid injections: a claims-based analysis.

BACKGROUND/AIMS: This study aims to determine the incidence and risk of open-angle glaucoma or ocular hypertension (OHT) following ocular steroid injections using healthcare claims data. METHODS: We retrospectively reviewed deidentified insurance claims data from the IBM MarketScan Database to identify 19 156 adult patients with no prior history of glaucoma who received ocular steroid injections between 2011 and 2020. Patient demographics and steroid treatment characteristics were collected. Postinjection glaucoma/OHT development was defined as a new diagnosis of glaucoma/OHT, initiation of glaucoma drops, and/or surgical or laser glaucoma treatment. Cox proportional hazards models were used to determine the risk of glaucoma/OHT development within 5 years after first steroid injection. RESULTS: Overall, 3932 (20.5%) patients were diagnosed with new glaucoma/OHT, 3345 (17.5%) started glaucoma drops and 435 (2.27%) required a laser or surgical glaucoma procedure within 5 years of first steroid injection. Triamcinolone subconjunctival injections were associated with a lower risk of glaucoma/OHT development than retrobulbar or intravitreal steroid injections (p<0.001, HR 0.68, 95% CI 0.59 to 0.79), whereas the 0.59 mg fluocinolone acetonide intravitreal implant had the highest risk of glaucoma/OHT development (p=0.001, HR 2.01, 95% CI 1.34 to 3.02). The risk of glaucoma/OHT development was also higher for patients receiving multiple steroid injections (p<0.001), with the largest increase in risk occurring after three total steroid injections. CONCLUSION: Patients receiving ocular steroid injections are at risk of developing glaucoma/OHT, even with no prior glaucoma/OHT diagnosis or treatment. Patients should be closely monitored for the development of glaucoma following ocular steroid injections, particularly in the setting of intravitreal and/or repeated steroid administration.

Herpetic anterior uveitis following COVID-19 vaccines: a case series.

Purpose: To report a case series of herpetic uveitis following COVID-19 vaccinations. Methods: Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well. Results: Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2. Conclusion: This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing.

Bilateral Panuveitis in an Adolescent with Autoimmune Lymphoproliferative Syndrome Due to CTLA4 Haploinsufficiency.

PURPOSE: To describe a case of bilateral panuveitis in an 11-year-old girl with autoimmune lymphoproliferative syndrome (ALPS) due to CTLA4 haploinsufficiency. CASE DESCRIPTION: A 5-year-old girl developed cervical adenopathy, and autoimmune hemolytic anemia and thrombocytopenia consistent with Evan's Syndrome. She was subsequently diagnosed with autosomal dominant CTLA4 haploinsuffciency and treated with immunosuppressants. Ocular symptoms developed 6 years later when she complained of blurry vision and photophobia. There were 3+ anterior chamber cells and 1+ flare, stellate keratic precipitates, and 3+ vitreous cells in both eyes. On fluorescein angiography, there was staining along the arcades and peripheral perivascular leakage in both eyes. On indocyanine green angiography, there were hypofluorescent spots throughout the posterior pole. The inflammation was partially responsive to topical and oral corticosteroids. CONCLUSION: Panuveitis may be associated with ALPS due to CTLA4 haploinsufficiency. Retinal and choroidal involvement should be assessed when anterior chamber inflammation is the presenting sign.

VISUAL AND ANATOMICAL CHANGES AFTER DRUG CESSATION IN PENTOSAN POLYSULFATE SODIUM-ASSOCIATED MACULOPATHY.

PURPOSE: The purpose of this study was to describe a case of development of pentosan polysulfate sodium (PPS)-related maculopathy that exhibited potential improvement in imaging findings after drug cessation. METHODS: This study is a case report. RESULTS: A 66-year-old woman presented with progressive pigmentary maculopathy associated with long-term PPS usage, including development of a choroidal neovascular membrane in her right eye. After discontinuation of PPS, her clinical course was notable for partial subjective and objective improvement in visual acuity, as well as partial improvement in outer retinal architecture on ocular coherence tomography, but persistence of retinal pigment epithelium atrophy and autofluorescence changes. CONCLUSION: The course of retinopathy after discontinuation of PPS has yet to be fully determined and has so far been suggested to be progressive. Anatomical improvements seen in our case suggest that further investigations are warranted to determine whether there is potential for partial reversal of some changes in PPS maculopathy.

Autoimmune Inflammatory Eye Disease: Demystifying Clinical Presentations for the Internist.

PURPOSE OF REVIEW: Provide a framework for recognizing key symptoms and clinical findings in patients with autoimmune inflammatory eye disease. RECENT FINDINGS: The most common manifestations of autoimmune inflammatory eye disease are episcleritis, scleritis, uveitis (anterior, intermediate, posterior, and panuveitis), and keratoconjunctivitis sicca. Etiologies can be idiopathic or in association with a systemic autoimmune condition. Referral of patients who may have scleritis is critical for patients presenting with red eyes. Referral of patients who may have uveitis is critical for patients presenting often with floaters and vision complaints. Attention should also be directed to aspects of the history that might suggest a diagnosis of a systemic autoimmune condition, immunosuppression, drug-induced uveitis, or the possibility of a masquerade condition. Infectious etiologies should be ruled out in all cases. Patients with autoimmune inflammatory eye disease may present with ocular or systemic symptoms alone, or in combination. Collaboration with ophthalmologists and other relevant specialists is vital to optimal long-term medical care.

GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes mellitus. Recent research suggests that GLP-1 RAs may influence diabetic retinopathy (DR). We searched ClinicalTrials.gov for trials comparing FDA-approved GLP-1 RAs to placebo, insulin, or oral antidiabetic medicine. Rates of DR, ocular adverse events, demographics, and clinical characteristics were compared amongst cohorts on 93 trials. GLP-1 RA use was significantly associated with increased risk of early-stage DR (risk ratio (RR) = 1.31, 95% confidence interval (CI) [1.01, 1.68]) and early-stage retinal adverse events (RR = 1.29, 95% CI [1.01, 1.66]) compared to placebo. Compared to insulin, GLP-1 RA use protected against late-stage DR (RR = 0.38, 95% CI [0.15, 0.98]). Analysis of individual GLP-1 RAs showed that albiglutide is responsible for these trends, as it is significantly associated with a higher risk of early-stage DR (RR = 2.18, 95% CI [1.01, 4.67]) compared to placebo and a lower risk of late-stage DR (RR = 0.25, 95% CI [0.09, 0.70]) compared to insulin. Albiglutide similarly affected retinal and ocular adverse events. Demographic analysis revealed significant differences between GLP-1 RA and comparator groups for age, HbA1c, body weight, BMI, duration of diabetes, sex, race, and ethnicity. The influence of GLP-1 RAs on DR and the eye may depend on the specific GLP-1 RA and patient demographic and clinical characteristics.

Convolutional Neural Network-Based Automated Quality Assessment of OCT and OCT Angiography Image Maps in Individuals With Neurodegenerative Disease.

Purpose: To train and test convolutional neural networks (CNNs) to automate quality assessment of optical coherence tomography (OCT) and OCT angiography (OCTA) images in patients with neurodegenerative disease. Methods: Patients with neurodegenerative disease were enrolled in the Duke Eye Multimodal Imaging in Neurodegenerative Disease Study. Image inputs were ganglion cell-inner plexiform layer (GC-IPL) thickness maps and fovea-centered 6-mm × 6-mm OCTA scans of the superficial capillary plexus (SCP). Two trained graders manually labeled all images for quality (good versus poor). Interrater reliability (IRR) of manual quality assessment was calculated for a subset of each image type. Images were split into train, validation, and test sets in a 70%/15%/15% split. An AlexNet-based CNN was trained using these labels and evaluated with area under the receiver operating characteristic (AUC) and summaries of the confusion matrix. Results: A total of 1465 GC-IPL thickness maps (1217 good and 248 poor quality) and 2689 OCTA scans of the SCP (1797 good and 892 poor quality) served as model inputs. The IRR of quality assessment agreement by two graders was 97% and 90% for the GC-IPL maps and OCTA scans, respectively. The AlexNet-based CNNs trained to assess quality of the GC-IPL images and OCTA scans achieved AUCs of 0.990 and 0.832, respectively. Conclusions: CNNs can be trained to accurately differentiate good- from poor-quality GC-IPL thickness maps and OCTA scans of the macular SCP. Translational Relevance: Since good-quality retinal images are critical for the accurate assessment of microvasculature and structure, incorporating an automated image quality sorter may obviate the need for manual image review.

Rapid regression of idiopathic multifocal choroiditis with intravitreal methotrexate-wide-field optical coherence tomography angiography-based study.

Wide-field optical coherence tomography angiography (OCTA) results in a patient of idiopathic multifocal choroiditis successfully treated with intravitreal methotrexate injections.

Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease.

Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), and normal cognition (NC). Design: Cross sectional study. Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis. Methods Intervention or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay. Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging. Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49-0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67-0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease. Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Stepwise approach for fundus imaging in the diagnosis and management of posterior uveitis.

An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a 'multimodal' approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.

Biosimilars for retinal diseases: United States-Europe awareness survey (Bio-USER - survey).

PURPOSE: To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. METHODS: A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. RESULTS: The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). CONCLUSIONS: The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.