Faculty Bibliography

PURPOSE/OBJECTIVE:To assess whether slit-scanning specular microscopy (CellChek C; Konan Medical) can repeatedly image the same corneal location using anatomic landmarks (posterior corneal rings and corneal undulations) and unique cells identified during imaging. METHODS:A total of 203 eyes (113 patients) with and without corneal pathology were imaged to assess the prevalence of anatomic landmarks. A subcohort of 20 healthy eyes was used to identify unique cells adjacent to anatomic landmarks. Landmarks were then used to locate the same cells on repeat imaging approximately 1 week later. Endothelial cell density (ECD), coefficient of variation, and percent hexagonality were calculated. Intraclass correlation coefficient and 95% limits of agreement were used to measure variability and reproducibility of imaging. RESULTS:Approximately 91% of eyes had either posterior corneal rings or undulations present. Undulations were more common than posterior corneal rings in both healthy and diseased corneas. Among subcohort eyes, unique cells were found adjacent to anatomic landmarks in 100% of eyes. Landmarks were used to reimage the same cells in 75% of eyes. There was minimal variation in ECD, coefficient of variation, and hexagonality; intraclass correlation coefficient and 95% confidence intervals were 0.891 [0.715-0.962], 0.612 [0.179-0.849], and 0.793 [0.499-0.925], respectively. The 95% limits of agreement for ECD was -359.9-260.98. CONCLUSIONS:Landmarks identified with slit-scanning specular microscopy allowed reliable reimaging of the same endothelial location, providing a powerful tool to better understand the role of the peripheral endothelium in health and disease.

PURPOSE/UNASSIGNED:The purpose of this study was to assess the utility of artificial intelligence (AI) assisted analysis of anterior segment optical coherence tomography (AS-OCT) imaging of the device-cornea joint in predicting outcomes of an intrastromal synthetic cornea device in a rabbit model. METHODS/UNASSIGNED:Sixteen rabbits underwent intrastromal synthetic cornea implantation. Baseline anterior lamellar thickness was established using AS-OCT intraoperatively. Monthly postoperative clinical examinations and AS-OCT imaging were performed, focusing on the peri-optic zone. A convolutional neural network was trained using a subset of manually marked images to automatically detect anterior lamellar tissue. Images were aligned manually using reference coordinates. The tissue volume data were evaluated as both absolute volume and percentage change from baseline using AI. RESULTS/UNASSIGNED:Sixteen rabbits were observed for 6 (n = 8) and 12 (n = 8) months. Mild focal anterior lamella thinning without retraction was seen near tight sutures in 2 rabbits (2/8) in the 6-month cohort, whereas 2 rabbits (2/8) in the 12-month cohort showed mild focal retraction from the optic stem with thinning. AI-assisted AS-OCT image analyses detected tissue volume reduction up to 3 months before clinical examination, with a reliable threshold of 5% change in tissue volume. CONCLUSIONS/UNASSIGNED:AI-assisted AS-OCT can detect peri-prosthetic tissue loss and predicting postoperative complications following an intrastromal synthetic cornea implantation in a rabbit model. Further studies are warranted to explore its clinical utility in human patients. TRANSLATIONAL RELEVANCE/UNASSIGNED:AI-assisted monitoring of peri-optic corneal tissue volume may be a useful screening modality to detect subclinical thinning after artificial corneal implantation and inform clinical decision making.

PURPOSE/OBJECTIVE:To develop consensus nomenclature amongst international retinal specialists for the distinctive optical coherence tomography (OCT) finding of a lesion originating from the retinal capillary bed, measuring ≥100 µm in size, and characterized by a hyperreflective wall with a hyporeflective lumen. METHODS:A comprehensive literature search was performed from inception to January 2024 on three databases to elicit publications reporting on relevant vascular abnormalities and corresponding nomenclature. A panel of retinal specialists with expertise in this topic reviewed the list of candidate terms and proposed other names for the lesion of interest. A refined list was then incorporated into a Delphi survey, which was distributed to the general membership of the International Retinal Imaging Society (IntRIS). Consensus was defined as at least 70% agreement amongst participants. RESULTS:An expert panel (n=11) reviewed candidate names for the lesion, with poor agreement noted amongst panel members regarding the relevant nomenclature. In the first Delphi survey, (n=70 IntRIS members), the need for a unified nomenclature was highlighted and two leading candidate names were established: large retinal capillary aneurysm (LRCA, n=38, 54.3%) and retinal capillary macroaneurysm (n=14, 20.0%). A second follow-up survey (n=54 IntRIS members) established LRCA (n=44, 81.5%) as the consensus term to identify the OCT vascular abnormality. CONCLUSION/CONCLUSIONS:This Delphi project reached consensus on a unifying term, large retinal capillary aneurysm, for a specific and signature OCT lesion. Identification of this characteristic OCT finding and adoption of this term may facilitate diagnosis, guide therapeutic decisions, and improve clinical and scientific communication.

PURPOSE/OBJECTIVE:To evaluate anti-vascular endothelial growth factor (VEGF) treatment patterns and long-term visual acuity (VA) outcomes in retinal vein occlusion (RVO) in routine clinical practice. DESIGN/METHODS:Retrospective observational study of the Vestrum Health Retina database. SUBJECTS/METHODS:Treatment-naïve eyes with a diagnosis of macular edema secondary to branch RVO (BRVO) or central RVO (CRVO) between January 2014 and November 2021. METHODS:Patient eyes were identified in the database using International Classification of Diseases, Clinical Modification codes, and free text searches of Vestrum's 'Exam Findings' field for macular edema. Eyes included for analysis were required to have ≥ 1 intravitreal anti-VEGF injection and ≥ 3 months of follow-up. MAIN OUTCOME MEASURES/METHODS:Treatment patterns and VA outcomes up to 60 months (5 years) of follow-up. Mean VA change stratified by the tertile of the number of anti-VEGF injections received over 60 months. RESULTS:22 365 BRVO and 18 064 CRVO eyes were included in the analysis; ∼70% had ≥ 12 months follow-up and ∼10% had ≥ 60 months follow-up. The mean number of anti-VEGF injections for BRVO and CRVO, respectively, were 6.9 and 7.0 in year 1 and 3.7 and 3.9 in year 5. Mean VA gains from baseline for BRVO and CRVO, respectively, were 11.5 and 9.7 Early Treatment Diabetic Retinopathy Study letters at month 12 and 8.2 and 5.3 letters at month 60. BRVO and CRVO eyes with fewer injections (tertile 1) tended to have lower VA gains compared with eyes that received more injections (tertile 3). Of available eyes at 60 months, 68% of BRVO and 71% of CRVO eyes had received ≥ 1 anti-VEGF injection in year 5 of follow-up. Overall, 24% of BRVO and 5% of CRVO eyes received focal/grid-pattern laser, whereas 14% of both BRVO and CRVO eyes received intravitreal corticosteroids at any time during follow-up over 60 months. CONCLUSIONS:In this retrospective analysis of the Vestrum database, VA gains were observed after anti-VEGF treatment. These were lower in patients with longer follow-up times and higher in patients who received a higher number of injections, suggesting a need for long-term monitoring of eyes with RVO.

PURPOSE/OBJECTIVE:To describe the clinical features, multimodal imaging findings, natural history, and treatment outcomes of acute outer retinopathy (AOR), which represents an expanded spectrum of acute annular outer retinopathy (AAOR). DESIGN/METHODS:Retrospective, observational, longitudinal, multicenter case series. PARTICIPANTS/METHODS:Twenty-three patients (15 female, 8 male) with a mean age of 41.8 ± 18.6 years (range: 14-86 years) and a mean follow-up duration of 3.7 ± 1.5 years (range: 1-12 years). METHODS:Clinical characteristics, multimodal imaging findings, laboratory evaluations, genetic testing, natural history, therapeutic management, and outcomes were reviewed and analyzed. MAIN OUTCOMES MEASURES/METHODS:Specific multimodal imaging signatures of AOR were identified, including findings from ophthalmoscopy, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Humphrey visual field testing, full-field electroretinography (ERG), and multifocal ERG were analyzed. Baseline features and the natural course of the disease were delineated. RESULTS:Thirty-eight eyes from 23 patients were analyzed. Presenting symptoms included photopsia (87%), blurred vision (57%), and scotoma (57%). On ophthalmoscopy, AOR was acutely characterized by yellow-greyish outer retinal lesions corresponding to hyperautofluorescent changes on FAF and the angular sign of Henle fiber layer hyperreflectivity (ASHH) on OCT. FAF imaging revealed ring-like hyperautofluorescent lesions surrounding the optic disc in 18% of eyes. Additional lesion patterns on FAF included perivenular (53%), sectoral (16%), and spot-like distributions (13%). FA and ICGA findings were mostly unremarkable. Lesion progression primarily occurred within the initial weeks following presentation and stabilized in size beyond this period in the majority of eyes. Over time, affected areas progressed to outer retinal atrophy with pigmentary changes. Foveal sparing was observed in 68% of the eyes. None of the therapeutic interventions appeared effective in halting the progression to complete outer retinal atrophy or preventing lesion enlargement. CONCLUSIONS:AOR is characterized by early photoreceptor disruption, evidenced by ASHH on OCT, leading to rapid outer retinal atrophy and subsequent degeneration of the retinal pigment epithelium within the damaged zones. Although distinct patterns of lesion distribution were observed, their consistent features on multimodal imaging support their inclusion within a unified disease spectrum termed acute outer retinopathy.

Targeted cancer therapies have transformed the landscape of cancer treatments but are often associated with off-target adverse drug reactions due to overlapping molecular pathways in healthy tissues, including those in the eye. Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. AEs across clinical trials are graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), which may not completely capture the ocular sequelae resulting from the use of emerging therapies. As CTCAE grading is mainly through the description of symptoms and their impact on visual acuity, it is imperative to use a tool that relies more on objective findings from ophthalmologic evaluations. The novel ocular adverse reaction severity grading scale developed by Amgen in collaboration with expert ophthalmologists, accounts for the anatomical regions impacted by ocular adverse reactions and anchors each severity grade to objective observable criteria from ophthalmologic evaluations. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care.

BACKGROUND:The number of pediatric ophthalmology and strabismus (PO&S) fellowship positions filled each year remains consistently lower compared with other subspecialities. It is unclear where along the recruitment pathway trainees interested in pediatrics decide to select other subspecialities. This study assesses for differences in the competitiveness of ophthalmology residency applicants based on interest in PO&S, which may impact their ability to matriculate into residency. METHODS:and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. RESULTS:Of the 631 applications reviewed, 125 (19.8%) of applicants stated a subspeciality interest. Among those who stated an interest, 34 (27.2%) were interested in PO&S. When compared to all other applicants (with or without a stated subspecialty interest), applicants interested in PO&S were more likely to be female (P < 0.001). No significant difference was found in academic, research, or extracurricular variables based on subspeciality interest in PO&S. The same was true when applicants interested in PO&S were compared to those interested in competitive subspecialities (cornea, glaucoma, retina, or oculoplastics). CONCLUSIONS:Applicants interested in PO&S were observed to be as competitive as other applicants. Among students who expressed a fellowship interest, there was a high proportion interested in pediatrics. Recruitment efforts can be targeted toward encouraging medical students interested in pediatrics to apply into ophthalmology.

PURPOSE/OBJECTIVE:To characterize the clinical and multimodal imaging features of central bouquet hemorrhage (CBH) with Henle fiber layer (HFL) involvement in highly myopic eyes, and to investigate the relationships between hemorrhage characteristics, reabsorption time, and visual outcomes. METHODS:Multicenter, retrospective analysis of highly myopic eyes with CBH involving the HFL, confirmed by optical coherence tomography (OCT). RESULTS:Eighteen eyes from 18 subjects were included for analysis. The mean age of the cohort was 39 ± 13.7 years (range: 17-69) and 61% of subjects were female. Mean refractive error was -14.8 ± 3.14 diopters (range: -9 D to -22 D). All eyes demonstrated a combined CBH with HFL component, while a subretinal component was present in 83.3% of cases. Myopic choroidal neovascularization (CNV) was excluded in all eyes using optical coherence tomography angiography (OCTA) or dye-based angiography (fluorescein or indocyanine green). No correlation was observed between hemorrhage size and visual outcomes or reabsorption time. Hemorrhage cleared after a mean of 2.63 months, and the radial HFL hemorrhage component resolved first. All eyes showed improvement in visual acuity from baseline. Persistent OCT alternations after resolution of hemorrhage included ellipsoid zone disruption (88.9%) and hyperreflective changes in HFL (77.8%). Anti-VEGF injections were administered to 6 eyes (33.3%) and did not correlate with a significant visual or anatomical benefit. CONCLUSION/CONCLUSIONS:CBH with HFL involvement in high myopia was associated with significantly improved visual outcomes from baseline but structural alterations can persist after clinical resolution. The size of the hemorrhage did not correlate with resorption time, and anti-VEGF treatment did not affect outcome. These findings provide new insights into the natural history and management of nonneovascular CBH in highly myopic eyes.

PURPOSE/OBJECTIVE:We describe a case of secondary multiple evanescent white dot syndrome (MEWDS) with optic disc pit as the underlying triggering pathology. METHODS:Observational case report. RESULTS:A 41-year-old well man with a background of right optic disc pit presented with right eye loss of vision and photopsia. Visual acuity at presentation was 20/100. He was found to have clinical and multimodal imaging features consistent with right unilateral MEWDS, and the spatial distribution of lesions made it likely that the optic disc pit was the trigger. Fundus autofluorescence revealed hyperautofluorescent 'spots' that gradually faded over serial imaging, with the complete absence of hyperautofluorescent 'dots'. Over three months of follow-up visual acuity recovered to 20/25. CONCLUSION/CONCLUSIONS:Optic disc pit may act as a trigger for secondary MEWDS, which is an increasingly recognized epiphenomenon. Secondary MEWDS may present as 'spots without dots', and we hypothesize that this feature may differentiate it from primary MEWDS.