Faculty Bibliography

PURPOSE/OBJECTIVE:To explore the impact of home optical coherence tomography (OCT)-guided treatment personalization for type 3 macular neovascularization (MNV) in age-related macular degeneration (AMD). METHODS:A prospective home OCT trial of a patient with a one-month history of type 3 MNV under anti-angiogenic treatment (two "loading" injections). During the 23.4-week study period, the patient's treatment regimen was managed through regular self-imaging, enabling continuous monitoring of retinal fluid dynamics. RESULTS:Over the observation period, the patient performed 143 home OCT measurements (mean 6.1 per week, standard deviation 1), which prompted three in-office visits where three anti-angiogenic injections were delivered at the discretion of the investigator. The mean individualized treatment intervals established through home OCT were 8 weeks, with the patient maintaining stable visual acuity at 20/20 Snellen. Complete resolution of intraretinal fluid was noted between injection. Notably, home OCT revealed unexpected fluctuations in retinal fluid measured as hyporeflective spaces in the absence of treatment. Two out of three injections were administered after the retinal fluid volume had decreased by more than half within two, and eight days following an initial transient spike. CONCLUSION/CONCLUSIONS:The neovascular subtype as defined by the Consensus Nomenclature for Reporting Neovascular AMD Data (CONAN) may serve as a useful management framework when approaching home OCT guided treatment decisions. In type 3 disease, home OCT-guided management demonstrates significant potential for optimizing treatment. Further research is warranted to elucidate the dynamics of retinal fluid variations in different MNV subtypes.

The retinal pigment epithelium (RPE) is the metabolic gatekeeper to the photoreceptors, thus playing many essential roles in healthy vision. Under certain conditions, RPE cells may transdifferentiate and migrate from the RPE layer. Ectopic RPE cells are potential signal sources for hyperreflective foci, prominent clinically visible biomarkers in age-related macular degeneration, which causes central vision loss globally. Applying multiple imaging modalities including ex vivo optical coherence tomography, autofluorescence microscopy, and imaging mass spectrometry (IMS) to human retina tissue, we compared lipid profiles in ectopic and orthotopic RPE cells. Our results showed that ectopic RPE cells share some molecular signatures with normal RPE cells as revealed through autofluorescence imaging and IMS. In both orthotopic and ectopic RPE cells, IMS detected phosphatidylglycerol, PG 36:2, and several triacylglycerols containing long-chain fatty acids. GM3 gangliosides (40:1, 42:1, and 42:2) were also detected in ectopic RPE cells with differences in abundance in different populations of ectopic RPE cells. Lactosylceramide (LacCer 44:5) and glucosylceramide (GlcCer 44:5) were found exclusively in ectopic RPE cells. In contrast, ectopic RPE did not exhibit signals of phosphatidylinositols (PI) (PI32:0, PI32:1, PI34:1, and PI34:2) normally detected in RPE cells. Near-single-cell resolution IMS results suggest that RPE transdifferentiation, with loss of normal functions and gain of new functions like migration, may be linked to altered metabolism of glycosphingolipids and PIs.

BACKGROUND:Posterior segment pathology can be challenging to diagnose and may lead to irreversible vision loss. Ocular imaging modalities are limited in the emergency department (ED) where many posterior segment emergencies present. Automated fundus-OCT cameras are emerging as a rapid, user-friendly and cost-effective tool in the ED. METHODS:Fundus and OCT images were taken by residents as needed for patients undergoing ophthalmology consultation in an academic ED in 2023. Image type and quality were graded on a scale of 1 to 3 (poor, adequate, good). Medical records were reviewed to record relevant patient characteristics. Statistical analysis was performed using unequal variances T-test to compare patients with poor and at least adequate photo quality. RESULTS:288 patients were imaged with the fundus-OCT camera over 12 months. Camera utilization increased at the start of the academic year, then decreased towards the end of the academic year. Adequate diagnostic quality images were taken in 92% of color photos and 94% of OCT images. The odds of poor image quality were significantly higher in patients presenting with logMAR > 1.0 (OR 8.07, 95% CI 3.28-19.86, p < 0.001) and age > 65 (OR 4.69, 95% CI 1.94-11.34, p < 0.001). CONCLUSIONS:Fundus photography and OCT are emerging as viable imaging modalities in the ED where access to ophthalmic expertise and equipment has traditionally been limited. Automated fundus-OCT cameras can offer high quality images that may facilitate rapid and accurate diagnosis of posterior segment pathology.

PURPOSE/UNASSIGNED:To compare genetic associations of rod- and cone-driven vision with those previously defined for delayed rod-mediated dark adaptation (RMDA), a functional risk indicator for incident age-related macular degeneration (AMD). METHODS/UNASSIGNED:In adults aged ≥60 years with two normal eyes (per the Age-Related Eye Disease Study 9-step scale) or with AMD in one or both eyes, we measured RMDA at 5° superior retina, photopic vision (acuity, contrast sensitivity, light sensitivity), and mesopic vision (low luminance acuity and deficit). Vision associations of risk-conferring single-nucleotide polymorphisms in CFH and ARMS2 genes were adjusted for age and smoking and stratified for the presence of subretinal drusenoid deposit (SDD). RESULTS/UNASSIGNED:Of 608 participants, 462 had normal maculas and 146 had AMD. Neither ARMS2 nor CFH was significantly associated with AMD stage. Across all eyes, RMDA worsened significantly in association with ARMS2 (P = 0.0005). Associations were stronger in normal eyes than in AMD (P = 0.0012 vs. 0.0580) and in normal eyes lacking SDD (n = 384, P < 0.0024). Across all eyes, RMDA was significantly associated with CFH (P = 0.0023) but not in normal and AMD eyes separately (P = 0.270 vs. 0.0596). RMDA was significantly associated with the number of risk alleles in normal and AMD eyes (P < 0.0001). Low luminance deficit was associated with gene dose for AMD eyes only (P = 0.477). CONCLUSIONS/UNASSIGNED:Of six vision tests, only RMDA was consistently associated with major risk alleles, including ARMS2 (not CFH) in normal eyes, with or without SDD. RMDA assesses dynamic retinoid resupply from the circulation, perhaps presaging SDD. Results are interpreted considering localization of key proteins in Bruch's membrane.

PURPOSE/OBJECTIVE:To investigate the corneal endothelial integrity in patients who underwent corneal cross-linking (CXL) with the Sub400 protocol, which treats progressive ectasia not eligible for standard CXL due to a stromal thickness of less than 400 µm. METHODS:This was an investigator-initiated, retrospective, single-center study conducted at the Department of Ophthalmology at the University Hospital Zurich in collaboration with the ELZA Institute in Zurich, Switzerland. Confocal endothelial measurements were performed before and up to 24 months after CXL. We applied a linear mixed-effect model to compare endothelial cell density (ECD) differences depending on time and treatment. At the 1-month follow-up visit, the demarcation line (DL) depth was assessed using anterior segment optical coherence tomography. RESULTS:= .09). CONCLUSIONS:.

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.

OBJECTIVE:To develop a consensus nomenclature for Optical Coherence Tomography Angiography (OCTA) findings in retinal vascular diseases (RVD). DESIGN/METHODS:Expert consensus using standardized online surveys with modified Likert scale. PARTICIPANTS/METHODS:RVD imaging experts, OCT biomedical engineers and the members of the International Retinal Imaging Society (IntRIS) METHODS: A PubMed literature review identified quantitative and qualitative terms forming the basis for a consensus-building process using a modified Delphi method. Agreement levels were categorized as "Accepted" (median ≥ 6), "Considerable Consensus" (median 6-7, IQR ≤ 3), "Strong Consensus" (median ≥ 8, IQR ≤ 2), and "Refined Strong Consensus" (median ≥ 8, IQR ≤ 2, with ≥ 70% responses in the 8-10 range). A multidisciplinary expert panel refined the terminology through three survey rounds, leading to a final survey conducted by IntRIS members. MAIN OUTCOME MEASURES/METHODS:Consensus on OCTA nomenclature in RVD RESULTS: The literature review identified 58 relevant papers, yielding 51 quantitative and 108 qualitative terms. A series of three surveys was used to refine the nomenclature framework for describing OCTA findings. The selected framework includes a generic term ("OCTA signal"), adjective terms ("presence/absence", "decreased/increased", "normal/abnormal"), and descriptive/etiologic terms ("of unknown cause", "due to blockage", "due to non-perfusion"). In the final survey among 44 IntRIS members, the framework achieved strong consensus for overall acceptance (median: 8.0, IQR: 7.0-9.0). The term "OCTA signal" met refined strong consensus criteria (median: 8.0, IQR: 8.0-9.0, with ≥ 70% of responses in the 8-10 range). Adjective terms, including "absence/presence" and "increased/decreased," were also rated with strong consensus (median: 8.0, IQR: 7.0-9.0). Similarly, descriptive/etiologic terms achieved strong consensus (median: 8.0, IQR: 7.0-9.0). Adoption of the framework for clinical practice and scientific reporting was rated with strong consensus (clinical: median 8.0, IQR: 7.0-9.0; scientific: median 9.0, IQR: 8.5-10.0). CONCLUSIONS:This study establishes a strong consensus framework for reporting OCTA findings in RVD for clinical and scientific contexts.