Faculty Bibliography

PURPOSE/UNASSIGNED:To describe a rare case of severe anterior and posterior scleritis that led to a diagnosis of high-risk myelodysplastic syndrome. METHODS/UNASSIGNED:We present a case report along with a literature review on cases of paraneoplastic scleritis to highlight commonalities in etiology, presentation, treatment response, and outcomes. RESULTS/UNASSIGNED:A 59-year-old male presented with a severe case of unilateral anterior and posterior scleritis with ciliochoroidal detachment and secondary angle closure. His workup revealed severe macrocytic anemia and thrombocytopenia. A subsequent bone marrow biopsy demonstrated cytogenetic analysis consistent with high-risk myelodysplastic syndrome (MDS). The patient was started on high-dose prednisone but was unable to be tapered below 30 mg without recurrence. Rituximab infusions were initiated followed by resolution of ocular symptoms and a successful taper of prednisone. He initiated chemotherapy and was to receive allogenic bone marrow transplantation. However, while on chemotherapy, he clinically deteriorated and passed away. CONCLUSION/UNASSIGNED:This case of severe scleritis was suspected to be a paraneoplastic syndrome secondary to myelodysplastic syndrome. Paraneoplastic syndromes represent a rare etiology of scleritis. Patients with hematologic abnormalities such as unexplained cytopenias, severe manifestations at presentation, or steroid refractory scleritis may warrant comprehensive evaluation for malignancy, expedited systemic workup with attention to blood counts, and interdisciplinary collaboration between ophthalmology, hematology, and internal medicine. If an underlying malignancy is identified, definitive treatment of the scleritis involves treatment of the cancer.

OBJECTIVE:or Purpose: To investigate the potential association of semaglutide and neovascular age-related macular degeneration (NVAMD) DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network during the study period from 12/1/2017-12/31/2024 SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Adults with type 2 diabetes (T2D) on semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs) (dulaglutide, exenatide), or non-GLP-1RAs (empagliflozin, sitagliptin, glipizide) METHODS, INTERVENTION OR TESTING: The association between semaglutide and NVAMD was assessed using two approaches: an active-comparator cohort design and a self-controlled case-series (SCCS) analysis. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates. MAIN OUTCOME MEASURES/METHODS:Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) or condition codes and procedures (NVAMD-CP). RESULTS:A total of 227,971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to users of dulaglutide (NVAMD-C HR 0.57, 95% CI 0.21 to 1.57, P=.28; NVAMD-CP HR 0.25, 95% CI 0.05 to 1.27, P=.10), empagliflozin (NVAMD-C HR 0.98, 95% CI 0.54 to 1.79, P=.94; NVAMD-CP HR 0.79, 95% CI 0.38 to 1.64, P=.52), sitagliptin (NVAMD-C HR 2.08, 95% CI 0.90 to 4.83, P=.09; NVAMD-CP HR 1.80, 95% CI 0.55 to 5.86, P=.33), and glipizide (NVAMD-C HR 0.83, 95% CI 0.35 to 2.02, P=0.69; NVAMD-CP HR 0.50, 95% CI 0.21 to 1.19, P=.12). There was no evidence of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: incidence rate ratio [IRR] 0.92, 95% CI 0.67 to 1.26, P=.60; NVAMD-CP IRR 1.02, 95% CI 0.76 to 1.36, P=.92) nor any of the other GLP-1RA or non-GLP-1RAs. CONCLUSIONS:We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D.

PURPOSE/UNASSIGNED:We aim to study a case of pathologic myopia with visible light OCT. DESIGN/UNASSIGNED:Case report. SUBJECTS/UNASSIGNED:We recruit 1 patient with pathologic myopia presenting with an acute lacquer crack with submacular hemorrhage (SMH) in the right eye and a chronic lacquer crack in the left eye. METHODS/UNASSIGNED:We acquire visible light OCT images with 1 μm axial resolution. Images are processed to depict spectral centroid shift, and spectral fitting is performed to determine oxygen saturation. Results are compared to clinical imaging. MAIN OUTCOME MEASURES/UNASSIGNED:Visible light OCT images, spectral centroid shift (redshift), oximetry, and spectral fitting. RESULTS/UNASSIGNED:with spectral evidence of an overlying RPE deficit (deficient red shift) and photoreceptor abnormalities. CONCLUSIONS/UNASSIGNED:As visible light OCT technology advances, its application toward well-characterized human retinal pathology can clarify its utility. We describe the first case of visible light OCT applied to pathologic myopia, a primary RPE-BM-choriocapillaris interface disease. We confirm that extravascular hemoglobin can be subject to spectral fitting, and we quantify the oxygen saturation of acute SMH. We further show that structural changes in chronic lacquer cracks can be characterized with this new technology. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BACKGROUND AND OBJECTIVE/UNASSIGNED:This study aimed to develop machine learning algorithms to predict visual and anatomic outcomes and treatment frequency in patients with macular edema following central retinal vein occlusion (MEfCRVO) after intravitreal aflibercept injections (IAI). PATIENTS AND METHODS/UNASSIGNED:= 91) trials treated with monthly IAI 2 mg for 24 weeks then pro re nata (PRN) through week 52 were used to develop machine learning algorithms. RESULTS/UNASSIGNED:= 0.76). PRN injection frequency from week 24 to 52 was predicted with high accuracy (AUC = 0.83). Univariate analyses confirmed all predictive factors. CONCLUSION/UNASSIGNED:Machine learning algorithms predicted outcomes and dosing frequency with high accuracy and may help inform patients' and clinicians' expectations during MEfCRVO management.

OBJECTIVE:Macular retinal nerve fibre layer (mRNFL) and ganglion cell-inner plexiform layer thickness (GC-IPL) measurements are important markers of diabetic retinal neurodegeneration (DRN). In this cross-sectional study, we aimed to quantify the contribution of total retinal thickness (TRT) and other factors in the variation of mRNFL and GC-IPL thickness among participants with diabetes. METHODS AND ANALYSIS/METHODS:We used macular-centred spectral domain-optical coherence tomography scans from participants with diabetes in the UK Biobank. Two multiple linear regression models (prior to and after adjusting for TRT) were used to determine factors associated with mRNFL and GC-IPL thicknesses. A p value of less than 0.05 was considered statistically significant. RESULTS:A total of 3832 eyes from 3832 participants with diabetes were analysed. Factors that explained the greatest variation in thickness were TRT (20.9% for mRNFL and 57.2% for GC-IPL), followed by spherical equivalent (8.0% for mRNFL only), gender (2.2% for mRNFL only) and age (1.4% for GC-IPL only). Other factors significantly associated with mRNFL and/or GC-IPL thickness explained less than 1% of the variation in their thicknesses. Self-reported ancestral background was not significantly associated with mRNFL thickness after accounting for TRT. CONCLUSIONS:Although many factors were significantly associated with mRNFL and GC-IPL thickness in participants with diabetes, they accounted for a fraction of the variation in the thickness of both layers. TRT explained most of the variation in these measurements, hence accounting for TRT is needed when using these metrics to evaluate DRN.

The availability of big data can transform the studies in biomedical research to generate greater scientific insights if expert labeling is available to facilitate supervised learning. However, data annotation can be labor-intensive and cost-prohibitive if pixel-level precision is required. Weakly supervised semantic segmentation (WSSS) with image-level labeling has emerged as a promising solution in medical imaging. However, most existing WSSS methods in the medical domain are designed for single-class segmentation per image, overlooking the complexities arising from the co-existence of multiple classes in a single image. Additionally, the multi-class WSSS methods from the natural image domain cannot produce comparable accuracy for medical images, given the challenge of substantial variation in lesion scales and occurrences. To address this issue, we propose a novel anomaly-guided mechanism (AGM) for multi-class segmentation in a single image on retinal optical coherence tomography (OCT) using only image-level labels. AGM leverages the anomaly detection and self-attention approach to integrate weak abnormal signals with global contextual information into the training process. Furthermore, we include an iterative refinement stage to guide the model to focus more on the potential lesions while suppressing less relevant regions. We validate the performance of our model with two public datasets and one challenging private dataset. Experimental results show that our approach achieves a new state-of-the-art performance in WSSS for lesion segmentation on OCT images.

PURPOSE:To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. METHODS:Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. RESULTS:Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. CONCLUSIONS:Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. TRANSLATIONAL RELEVANCE:Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.

PURPOSE/UNASSIGNED:To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. METHODS/UNASSIGNED:67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. RESULTS/UNASSIGNED:Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. CONCLUSIONS/UNASSIGNED:Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.