Acute macular neuroretinopathy secondary to central retinal artery occlusion.

Purpose: Acute Macular Neuroretinopathy (AMN) may be the result of deep retinal capillary plexus (DCP) impairment, but its mechanism remains elusive. A recent study has described simultaneous onset of Paracentral Acute Middle Maculopathy (PAMM) and AMN, suggesting a related pathogenic pathway. In this report, we analyze and describe the imaging characteristics of patients with concomitant Central Retinal Artery Occlusion (CRAO) and AMN and suggest a mechanistic pathway to explain this relationship. Observations: A total of 2 cases of CRAO, arteritic and non arteritic, were included in this report. At initial presentation, outer retinal layers were intact. At the two-week follow-up visit, both cases displayed Henle fiber layer hyperreflectivity and ellipsoid zone disruption consistent with AMN. Conclusions: Secondary development of AMN in CRAO is a new finding. DCP ischemia secondary to CRAO may lead to Henle fiber layer disruption, leading to the characteristic findings of AMN.

Macular Telangiectasia Type 2: A Classification System Using MultiModal Imaging MacTel Project Report Number 10.

Purpose: To develop a severity classification for macular telangiectasia type 2 (MacTel) disease using multimodal imaging. Design: An algorithm was used on data from a prospective natural history study of MacTel for classification development. Subjects: A total of 1733 participants enrolled in an international natural history study of MacTel. Methods: The Classification and Regression Trees (CART), a predictive nonparametric algorithm used in machine learning, analyzed the features of the multimodal imaging important for the development of a classification, including reading center gradings of the following digital images: stereoscopic color and red-free fundus photographs, fluorescein angiographic images, fundus autofluorescence images, and spectral-domain (SD)-OCT images. Regression models that used least square method created a decision tree using features of the ocular images into different categories of disease severity. Main Outcome Measures: The primary target of interest for the algorithm development by CART was the change in best-corrected visual acuity (BCVA) at baseline for the right and left eyes. These analyses using the algorithm were repeated for the BCVA obtained at the last study visit of the natural history study for the right and left eyes. Results: The CART analyses demonstrated 3 important features from the multimodal imaging for the classification: OCT hyper-reflectivity, pigment, and ellipsoid zone loss. By combining these 3 features (as absent, present, noncentral involvement, and central involvement of the macula), a 7-step scale was created, ranging from excellent to poor visual acuity. At grade 0, 3 features are not present. At the most severe grade, pigment and exudative neovascularization are present. To further validate the classification, using the Generalized Estimating Equation regression models, analyses for the annual relative risk of progression over a period of 5 years for vision loss and for progression along the scale were performed. Conclusions: This analysis using the data from current imaging modalities in participants followed in the MacTel natural history study informed a classification for MacTel disease severity featuring variables from SD-OCT. This classification is designed to provide better communications to other clinicians, researchers, and patients. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Retinal Thickness and Morphology Changes on OCT in Youth with Type 2 Diabetes: Findings from the TODAY Study.

Objective: To evaluate changes in retinal thickness and morphology using OCT in youth with type 2 diabetes (T2D) and to identify systemic biomarkers correlating with these changes. Design: Retrospective subgroup analysis of a prospective study. Participants: Participants who underwent OCT imaging in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial and its follow-up study TODAY2. Methods: In 2010-2011 (TODAY) and 2017-2018 (TODAY2), 6 × 6-mm macular volume OCT scans were acquired, segmented, and analyzed to generate total retinal thickness, inner retinal thickness, and outer retinal thickness. The main retinal morphologies graded were intraretinal cystoid spaces, subretinal fluid, and posterior vitreous detachment (PVD). Main Outcome Measures: Changes in total and individual retinal layer thickness and development of abnormal vitreomacular morphology between TODAY and TODAY2. Results: Participants had a mean age of 17.9 ± 2.4 years and glycated hemoglobin (HbA1c) of 8.2 ± 2.8% in TODAY and a mean age of 25.0 ± 2.4 years and mean HbA1c of 9.5 ± 2.8% in TODAY2. Longitudinally between assessments, there were overall decreases in outer retinal thickness from 167.2 ± 11.5 microns to 158.4 ± 12.8 microns (P < 0.001) and in photoreceptor thickness from 30.3 ± 2.9 microns to 29.8 ± 4.1 microns (P = 0.04) in the central subfield, while in the inner subfield, we noted a decrease in outer retinal thickness from 150.5 ± 10.1 microns to 144.9 ± 10.5 microns (P < 0.001) and an increase in inner retinal thickness from 136.9 ± 11.5 microns to 137.4 ± 12.6 microns (P = 0.01). Multivariate analysis showed that in the center subfield, HbA1c increases were associated with increases in total retinal thickness (r: 0.67, P = 0.001), whereas fasting glucose was positively correlated with inner retinal thickness (r: 0.02, P = 0.02). In the inner subfield, both systolic (r: -0.22, P < 0.001) and diastolic (r: -0.22, P = 0.003) blood pressures were negatively correlated with total retinal thickness. There was an increase in PVD (18.9%) and cystoid spaces (4.2%). Conclusions: Youth with T2D develop retinal thickness changes on OCT, including increases in total retinal and inner retinal thickness in the center subfield that correlate with HbA1c and fasting glucose, respectively. Taken together with the increased prevalence of abnormal vitreomacular morphology in this cohort at risk, these findings emphasize the importance of controlling risk factors to prevent the development of sight-threatening retinal complications.

Physiology of retinal reattachment in humans: Swept source optical coherence tomography imaging data supporting a novel staging system.

This article presents high-resolution swept source optical coherence tomography (SS-OCT) imaging data used to describe the physiology of retinal reattachment in humans. SS-OCT imaging was performed at baseline and every 2 h for the first 6 h and at frequent intervals thereafter up to 6 weeks following the injection of intravitreal gas in eyes undergoing pneumatic retinopexy for rhegmatogenous retinal detachment. Imaging data presented in this article is related to the research paper titled "Real-Time in Vivo Assessment of Retinal Reattachment in Humans using Swept-Source Optical Coherence Tomography" (Bansal et al., 2021). SS-OCT images were assessed longitudinally and used to devise a novel staging system that describes the physiology of retinal reattachment. Multiple examples of each stage and the transition from one stage to the next are provided. SS-OCT images were also assessed to determine the timing associated with each stage, and the anatomic abnormalities, such as outer retinal folds and subretinal fluid blebs that occured as a result of delayed progression through certain stages.

Reliability of Subjective Assessment of Spectral-Domain OCT Pathologic Features by Multiple Raters in Retinal Vein Occlusion.

Purpose: To examine the interrater and intrarater reliability of qualitatively and quantitatively assessed disorganization of retinal inner layers (DRIL) and disorganization of retinal outer layers (DROL) by multiple raters. Subjectively assessing these surrogate biomarkers can be challenging in daily routine, despite the high resolution of spectral-domain (SD) OCT scans. Design: Retrospective trial. Participants: Three hundred six pooled SD OCT scans of 34 patients treated for macular edema caused by retinal vein occlusion (RVO) between January 2016 and December 2017. Methods: SD OCT scans were assessed by 6 raters regarding presence of cystoid macular edema, subretinal fluid (SRF), vitreoretinal traction, and epiretinal membrane and extent of DRIL and DROL. Main Outcome Measures: Interrater and intrarater reliability were calculated applying κ statistics for qualitative assessment regarding each pathologic feature's presence in all evaluated OCT scans, and for quantified horizontal DRIL and DROL extent within each OCT cross-section. Results: Cystoid macular edema and SRF assessments revealed excellent inter- and intrarater reliability with almost perfect strength of agreement, whereas subjective DRIL and DROL evaluations yielded low κ statistics with slight to moderate strength of agreement. Furthermore, the presence of SRF remarkably compromised the reliability of DROL detection. Conclusions: Our data highlight the limited subjective assessibility of DRIL and DROL, underscoring the need for automated image analysis to improve the reliability of OCT biomarkers for clinical studies and daily practice.

Deep Learning-Based Automatic Detection of Ellipsoid Zone Loss in Spectral-Domain OCT for Hydroxychloroquine Retinal Toxicity Screening.

Purpose: Retinal toxicity resulting from hydroxychloroquine use manifests photoreceptor loss and disruption of the ellipsoid zone (EZ) reflectivity band detectable on spectral-domain (SD) OCT imaging. This study investigated whether an automatic deep learning-based algorithm can detect and quantitate EZ loss on SD OCT images with an accuracy comparable with that of human annotations. Design: Retrospective analysis of data acquired in a prospective, single-center, case-control study. Participants: Eighty-five patients (168 eyes) who were long-term hydroxychloroquine users (average exposure time, 14 ± 7.2 years). Methods: A mask region-based convolutional neural network (M-RCNN) was implemented and trained on individual OCT B-scans. Scan-by-scan detections were aggregated to produce an en face map of EZ loss per 3-dimensional SD OCT volume image. To improve the accuracy and robustness of the EZ loss map, a dual network architecture was proposed that learns to detect EZ loss in parallel using horizontal (horizontal mask region-based convolutional neural network [M-RCNNH]) and vertical (vertical mask region-based convolutional neural network [M-RCNNV]) B-scans independently. To quantify accuracy, 10-fold cross-validation was performed. Main Outcome Measures: Precision, recall, intersection over union (IOU), F1-score metrics, and measured total EZ loss area were compared against human grader annotations and with the determination of toxicity based on the recommended screening guidelines. Results: The combined projection network demonstrated the best overall performance: precision, 0.90 ± 0.09; recall, 0.88 ± 0.08; and F1 score, 0.89 ± 0.07. The combined model performed superiorly to the M-RCNNH only model (precision, 0.79 ± 0.17; recall, 0.96 ± 0.04; IOU, 0.78 ± 0.15; and F1 score, 0.86 ± 0.12) and M-RCNNV only model (precision, 0.71 ± 0.21; recall, 0.94 ± 0.06; IOU, 0.69 ± 0.21; and F1 score, 0.79 ± 0.16). The accuracy was comparable with the variability of human experts: precision, 0.85 ± 0.09; recall, 0.98 ± 0.01; IOU, 0.82 ± 0.12; and F1 score, 0.91 ± 0.06. Automatically generated en face EZ loss maps provide quantitative SD OCT metrics for accurate toxicity determination combined with other functional testing. Conclusions: The algorithm can provide a fast, objective, automatic method for measuring areas with EZ loss and can serve as a quantitative assistance tool to screen patients for the presence and extent of toxicity.

Retinitis Punctata Albescens and RLBP1-Allied Phenotypes: Phenotype-Genotype Correlation and Natural History in the Aim of Gene Therapy.

Purpose: To identify relevant criteria for gene therapy based on clinical and genetic characteristics of rod-cone dystrophy associated with RLBP1 pathogenic variants in a large cohort comprising children and adults. Design: Retrospective cohort study. Participants: Patients with pathogenic variants in RLBP1 registered in a single French reference center specialized in inherited retinal dystrophies. Methods: Clinical, multimodal imaging, and genetic findings were reviewed. Main Outcome Measures: Age of onset; visual acuity; ellipsoid line length; nasal, temporal, and foveal retinal thickness; and pathogenic variants and related phenotypes, including Newfoundland rod-cone and Bothnia dystrophies (NFRCDs), were reappraised. Results: Twenty-one patients (15 families) were included. The most frequent form was NFRCD with 12 patients (8 families) homozygous for the recurrent deletion of exons 7 through 9 in RLBP1 and 5 patients (4 families) with biallelic protein-truncating variants (2 novel: p.Gln16∗ and p.Tyr251∗). A novel combination of the p.Arg234Trp Bothnia variant with a nonsense variant in trans led to Bothnia dystrophy in 2 sisters. One proband carrying the p.Met266Lys Bothnia variant and in trans p.Arg121Trp and a second, with the p.Arg9Cys and p.Tyr111∗ combination, both demonstrated mild retinitis punctata albescens. Independently of genotype, all patients showed a visual acuity of worse than 20/200, an ellipsoid line width of less than 1000 µm, and a mean foveal thickness of less than 130 to 150 µm, with loss of both the interdigitation and ellipsoid lines. Conclusions: The eligibility for RLBP1 gene therapy first should be determined according to the biallelic variant combination using a robust classification as proposed herein. An ellipsoid line width of more than 1200 µm and a central thickness of more than 130 to 150 µm with detectable ellipsoid and interdigitation lines should be 2 prerequisite imaging indicators for gene therapy.

Spectral optical coherence tomography findings in patients with ocular toxoplasmosis: A case series study.

PURPOSE: Ocular toxoplasmosis is the most common cause of infectious uveitis worldwide. The diagnosis of ocular toxoplasmosis is primarily clinical when it is a typical presentation.With an atypical presentation in the fundus, parasitological diagnosis is a decisive contribution, as well as multimodal imaging. The aim of this study was to investigate vitreal, retinal, and choroidal morphologic changes in active and scarred toxoplasmosis lesions using swept source optical coherence tomography. To our knowledge, it is the first study in Tunisia which describes with precision the retinochoroidal lesions caused by Toxoplasma Gondi by means of the optical coherence tomography (OCT). METHODS: A retrospective analysis of fifteen patients diagnosed with ocular toxoplasmosis was conducted. The patients were examined at ophthalmology service of Farhat Hached Hospital in Sousse Tunisia between January 2002 and December 2019. Complete ophthalmologic examination including best-corrected visual acuity, slit lamp biomicroscopy, dilated biomicroscopic and fundus examinations, colour fundus photography as well as fluorescein angiography and OCT were done at the initial visit and during follow-up. RESULT: In the acute phase, thickening, hyper-reflectivity of the neurosensory retina, posterior shading, bumping of the RPE, hyporeflectivity and thickening of choroid were found in 86,6% of patients. During follow-up, neurosensory retinal layers thinning and disorganization, interrupting ofthe ellipsoid zone (EZ), and RPE hyper reflective were noticed in 73% of patients. The choroid became thin and more hyperreflective in 73% of patients. Multiple hyperreflective dots in the vitreous cavity and posterior hyaloid thickening were demonstrated in the acute phase in 60% of patients, with complete resolution and detachment of the posterior hyaloid in the scarred lesions. CONCLUSION: The SS-OCT is an important adjunctive imaging modality in the diagnosis and follow-up of patients with ocular toxoplasmosis.