Faculty Bibliography

PURPOSE/OBJECTIVE:To demonstrate the relationship between alternating hypointense signal bands on OCT angiography (OCTA), real-time fluorescein angiography (FA), and structural OCT findings in patients with retinal vascular occlusive disease (RVOD). DESIGN/METHODS:Retrospective, consecutive case series. SUBJECTS/METHODS:Consecutive patients with a clinical diagnosis of acute RVOD and alternating bands of hypointense OCTA flow signal on en face projections. METHODS:Complete ophthalmic examination and multimodal imaging, including color fundus photography, real-time FA, spectral-domain OCT, and OCTA performed with different instruments having different scan speeds and acquisition protocols. MAIN OUTCOME MEASURES/METHODS:The primary outcomes were: hypointense OCTA band characteristics (number, width, orientation, and location), OCTA acquisition characteristics (speed and scan direction), and FA findings including delayed arteriovenous (AV) transit and pulsatile flow. Secondary outcomes were: structural OCT changes including retinal fluid, paracentral acute middle maculopathy (PAMM) lesion, and a prominent middle limiting membrane (p-MLM) sign. RESULTS:OCT angiography hypointense bands were detected in the superficial and deep vascular plexuses in 9 eyes of 9 patients with either partial central retinal vein occlusion (RVO) or nonischemic RVO. When obtained on the same device, hypointense bands were thinner and more numerous at lower (100 kHz) scan speeds compared with higher (200 kHz) scan speeds. Band orientation was parallel to the OCTA scan direction, and their extent correlated with the area of delayed AV transit on FA. Structural OCT showed multiple PAMM lesions in 78% of cases and a p-MLM sign centered in the fovea in 44% of cases. CONCLUSIONS:OCT hypointense bands are a novel biomarker in RVOD indicating delayed AV transit and pulsatile filling without the need for dye angiography. Structural OCT often shows PAMM in these eyes and, less commonly, a p-MLM sign. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE/OBJECTIVE:To describe a new retinal phenotype characterized by bilateral, multifocal, subretinal vitelliform lesions along the vascular arcades that we refer to as multifocal vitelliform paravascular retinopathy (MVPR). DESIGN/METHODS:Observational case series. METHODS:Multimodal retinal imaging including color fundus photography, fundus autofluorescence and cross sectional and en-face optical coherence tomography was performed to evaluate and characterize the lesions of MVPR. RESULTS:Thirteen asymptomatic patients aged 10 to 78 [mean 49±24, 49% under 50] were evaluated for bilateral retinal lesions. Initial visual acuity was 20/30 or better in 22 (85%) eyes. Of the 20 eyes with follow-up, 14 (70%) exhibited visual acuity 20/30 or better at final follow-up. Multifocal small round yellow lesions with distinct borders were identified along the vascular arcades in all patients. The vitelliform lesions were brightly hyperautofluorescent and consisted of focal areas of subretinal hyperreflective material on optical coherence tomography (OCT) that in some cases evolved to hyporeflective spaces (or retinal pigment epithelium atrophy) with associated hypoautofluorescence. When performed, electroretinography (ERG) and electrooculography (EOG) testing were normal and genetic testing was negative for variants in BEST1 and other genes associated with vitelliform retinopathies. CONCLUSIONS:MVPR may represent a novel entity of vitelliform disorders with a distinct clinical presentation and phenotype and generally favorable prognosis.

PURPOSE/OBJECTIVE:To describe remarkable choroidal thickness fluctuations corresponding to episodes of recurrent anterior uveitis with subretinal fluid development when exceeding a choroidal thickness threshold. METHODS:A patient with pachychoroid pigment epitheliopathy and unilateral acute anterior uveitis of the left eye was evaluated over a period of 3 years with multimodal retinal imaging including optical coherence tomography (OCT). Longitudinal changes in subfoveal choroidal thickness (CT) were measured and correlated with episodes of recurrent inflammation. RESULTS:Over the course of 5 recurrent episodes of inflammation in the left eye treated with oral antiviral and topical steroid therapy, subfoveal CT increased as much as 200 um or more. Subfoveal CT in the fellow quiescent right eye by contrast, was within normal limits and minimally changed throughout the follow up. Increased CT occurred with each episode of anterior uveitis and decreased by 200 µm or more during periods of quiescence in the affected left eye. Subretinal fluid and macular edema developed with a maximum CT of 468 um and spontaneously resolved when CT decreased after treatment. CONCLUSION/CONCLUSIONS:In eyes with pachychoroid disease, anterior segment inflammation may lead to marked increases in subfoveal CT and the development of subretinal fluid at a threshold thickness value.

PURPOSE/OBJECTIVE:The purpose of this study was to report the multimodal imaging features of a cavitary choroidal nevus showing thickness fluctuations that mirrored the response of diabetic macular edema (DME) to intravitreal antivascular endothelial growth factor (VEGF) therapy. METHODS:This is a retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), fluorescein and indocyanine green angiography, OCT-angiography (OCTA), and B-scan ultrasonography were analyzed. RESULTS:A woman in her 80s with a cavitary choroidal nevus and DME was treated with intravitreal anti-VEGF therapy using a pro re nata regimen over 5 years. The choroidal nevus showed thickness fluctuations paralleling the response of DME to anti-VEGF therapy. Worsening of the DME was associated with marked increased choroidal lesion thickness on OCT. Conversely, resolution of DME after intravitreal anti-VEGF injections was followed by choroidal lesion flattening on OCT. Variations of the choroidal lesion thickness were mainly dependent on changes of intralesional hyporeflective caverns on OCT. CONCLUSION/CONCLUSIONS:Our report shows thickness variations of a cavitary choroidal nevus that paralleled the clinical course of DME treated with intravitreal anti-VEGF therapy. To the best of our knowledge, this is the first report on volume variations of a cavitary choroidal nevus after anti-VEGF therapy.

PURPOSE/OBJECTIVE:In this study, we identify risk factors that predict the progression of acquired vitelliform lesions (AVLs) over time. DESIGN/METHODS:Retrospective cohort study. SUBJECTS/METHODS:One hundred sixty-three eyes of 132 patients with a diagnosis of intermediate age-related macular degeneration (iAMD) with AVL. METHODS:This retrospective study evaluated consecutive eyes with AMD from a retina clinic population and included 1181 patients and 2362 eyes. After excluding cases with associated geographic atrophy, macular neovascularization (MNV), vitreomacular traction, and those with <2 years of follow-up data, the final analysis cohort consisted of 163 eyes (132 patients) with ≥1 AVL. The first available visit in which an AVL was evident was considered the baseline visit, and follow-up data were collected from a visit 2 years (± 3 months) later. Progression outcomes at the follow-up visit were classified into 6 categories: resorbed, collapsed, MNV, stable, increasing, and decreasing. Subsequently, we analyzed the baseline characteristics for each category and calculated odds ratios (ORs) to predict these various outcomes. MAIN OUTCOME MEASURES/METHODS:The study focused on identifying predictive factors influencing the evolution of AVL in iAMD eyes. RESULTS:In total, 163 eyes with AVL had follow-up data at 2 years. The collapsed group demonstrated a significantly greater baseline AVL height and width compared with other groups (P < 0.001). With regard to qualitative parameters, subretinal drusenoid deposits (SDDs) and intraretinal hyperreflective foci (IHRF) at the eye level, AVL located over drusen, and IHRF and external limiting membrane disruption over AVL were significantly more prevalent in the collapsed group compared with other groups (P < 0.05 for all comparisons). Odds ratios for progressing to atrophy after 2 years of follow-up, compared with the resorbed group, were significant for SDD (OR, 2.82; P = 0.048) and AVL height (OR, 1.016; P = 0.006). CONCLUSIONS:The presence of SDDs and greater AVL height significantly increases the risk of developing atrophy at the location of AVL after 2 years of follow-up. These findings may be of value in risk prognostication and defining patient populations for inclusion in future early intervention trials aimed at preventing progression to atrophy. FINANCIAL DISCLOSURES/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE/OBJECTIVE:This study aims to define the characteristics of acquired vitelliform lesions (AVLs) in patients with intermediate age-related macular degeneration (iAMD). DESIGN/METHODS:Retrospective, observational, cross sectional study. SUBJECTS/METHODS:This study included 217 eyes with AVLs associated with iAMD, and an equivalent number of control patients. METHODS:OCT scans were evaluated for qualitative and quantitative parameters at both the eye and lesion level. Eye-level parameters included the presence of: hyporeflective core drusen, intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits, macular pachyvessels, central retinal thickness, and central choroidal thickness. Lesion-level qualitative parameters included the presence of ellipsoid zone (EZ) and external limiting membrane disruption overlying the AVL, IHRF overlying the AVL, AVL overlying drusen, pachyvessels under the AVL, a solid core within AVL, and AVL location. Lesion-level quantitative characteristics included AVL height and width, AVL distance from the fovea, and sub-AVL choroidal thickness. MAIN OUTCOME MEASURES/METHODS:The primary outcomes assessed included the frequency of IHRF, the presence of macular pachyvessels, central choroidal thickness, and the dimensions (both height and width) of AVLs. RESULTS:Comparing the AVL and control groups, the frequency of IHRF (AVL: 49.3% vs. control: 26.3%) and macular pachyvessels (37.3% vs. 6.9%) was significantly higher in the AVL case group, and the central choroidal thickness (256.8 ± 88 μm vs. 207.1± 45 μm) was thicker in the AVL group. Acquired vitelliform lesions located over drusen, with overlying IHRF, or situated subfoveally, and AVL lesions with EZ disruption were found to have a greater lesion height and width compared with AVL lesions lacking these characteristics (P value < 0.001 for all). Additionally, a significant negative correlation was observed between the distance from the fovea and AVL height (Spearman rho: -0.19, P = 0.002) and width (Spearman rho: -0.30, P = 0.001). CONCLUSIONS:This study represents the largest reported cohort of AVL lesions associated with iAMD. Novel findings include the higher frequency of pachyvessels in addition to the presence of a thicker choroid in these eyes, as well as the greater height and width of AVL closer to the foveal center. These findings may offer insights into pathophysiologic mechanisms underlying the development of AVL. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

IMPORTANCE/UNASSIGNED:Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications. OBJECTIVE/UNASSIGNED:To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022. INTERVENTIONS/UNASSIGNED:Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks. MAIN OUTCOMES AND MEASURES/UNASSIGNED:IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection. RESULTS/UNASSIGNED:Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.

PURPOSE/OBJECTIVE:Enface OCT may disclose a distinct "fingerprint-like' pattern within the HFL in various macular disorders. This study aims to investigate the frequency and characteristics of this pattern in healthy eyes and identify potential factors influencing its visibility. METHODS:Two, independent masked reading center graders evaluated for the presence and prominence of a fingerprint pattern in the Henle fiber layer (HFL) on enface OCT images from 33 healthy subjects (66 eyes). The prominence of the pattern was rated qualitatively using a 0-3 scale, with 3 indicating the strongest prominence. Tilt angles (relative to the normal/perpendicular at the center) of the retina were measured on horizontal and vertical B-scans, and the retinal curvature was assessed using ImageJ, in order to determine the impact of the incident light angle on the visibility and prominence of the fingerprint pattern. Inter-grader agreement using Cohen's kappa and the frequency and percentage of patterns in the entire enface image and in each quadrant were calculated and compared using the Friedman test with Dunn's post-test. A generalized estimating equation (GEE) was used to analyze the association between these metrics and fingerprint prominence. RESULTS:Substantial inter-grader agreement was observed (Cohen's kappa = 0.71) for assessing the prominence of the fingerprint pattern. Over 70% of eyes exhibited some evidence of the pattern (score ≥1). Significant difference in pattern prominence across quadrants was detected (p < 0.05), with lowest prominence in the temporal quadrant (p < 0.001 for pairwise comparisons against all other quadrants). The GEE analysis to account for the extent of the effect of scan tilt angle and RPE curvature was not able to predict the prominence of the fingerprint pattern, highlighting that angle of incidence (of the scanning laser light) alone could not explain the pattern. CONCLUSIONS:This study confirms that a fingerprint-like pattern within the HFL can also be observed in healthy eyes, challenging the notion that this finding is only manifest in the setting of disease. In addition, the lack of correlation with angle of incident light suggests that the pattern may be related to other intrinsic characteristics of the HFL.

PURPOSE/OBJECTIVE:To report the long-term (23 years) clinical and multimodal imaging features of acquired vitelliform lesions (AVLs) associated with non-neovascular age-related macular degeneration (AMD). METHODS:Retrospective case report. Color and red free fundus photographs, high-resolution optical coherence tomography (High-Res OCT), fluorescein (FA) and indocyanine green angiography (ICGA), and OCT-angiography (OCTA) were performed. RESULTS:A 58-year-old man presented with bilateral AVLs in the setting of non-neovascular AMD. At baseline, his best-corrected visual acuity (BCVA) was 20/30 in his right eye and 20/20 in his left eye. Red free fundus photographs showed AVLs with cuticular drusen in both eyes corresponding to a "stars-in-the-sky" pattern on FA. ICGA showed no evidence of macular neovascularization (MNV). Throughout the 23-year follow-up, the patient reported consuming 20mg/day of lutein supplement. At the end of follow-up, his BCVA was 20/20 in both eyes. Color fundus photographs showed resorption of the AVLs in both eyes and High-Res OCT showed relative preservation of the outer retinal bands in the fovea. OCTA confirmed the absence of MNV. CONCLUSION/CONCLUSIONS:In non-neovascular AMD, spontaneous resorption of AVLs may be associated with long-term maintenance of visual acuity and relative preservation of the outer retinal morphology.