Faculty Bibliography

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: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.

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:To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage" (CBH). METHODS:Retrospective, observational, multicenter case series of eyes with CBH. Multimodal imaging features were reviewed and analyzed. RESULTS:Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6±21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with CBH displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer (HFL). Cross-sectional optical coherence tomography (OCT) showed a well-delineated round hyperreflective lesion involving the central foveal HFL/outer nuclear layer (ONL) in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented HFL were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). CONCLUSION/CONCLUSIONS:"Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with HFL hemorrhage and encountered in a spectrum of macular disease.

PURPOSE/OBJECTIVE:To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD/METHODS:From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS:From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION/CONCLUSIONS:The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) combined with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.