Faculty Bibliography

This prospective single-center study aims to identify biomarkers that predict improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6 months, in 76 eyes with diabetic macular edema (DME) treated monthly with intravitreal aflibercept. At baseline, all patients underwent standardized imaging with color photography, optical coherence tomography (OCT), fluorescein angiography (FA) and OCT angiography (OCTA). Glycosylated hemoglobin, renal function, dyslipidemia, hypertension, cardiovascular disease and smoking were recorded. Retinal images were graded in a masked fashion. Baseline imaging, systemic and demographic variables were investigated to detect associations to BCVA and CRT change post aflibercept. Predictors of BCVA improvement included greater macular vessel density quantified using OCTA (p = 0.001) and low-density lipoprotein (LDL) ≥ 2.6 mmol/L (p = 0.017). Lower macular vessel density eyes showed a significant reduction in CRT but no BCVA improvement. Predictors of CRT reduction included peripheral non-perfusion seen on ultrawide-field FA (p = 0.005) and LDL ≥ 2.6 mmol/L (p < 0.001). Retinal angiographic biomarkers derived from OCTA and ultrawide-field FA may help predict functional and anatomic response to anti-vascular endothelial growth factor (VEGF) therapy in patients with DME. Elevated LDL is associated with treatment response in DME. These results may be used to better-select patients who will benefit from intravitreal aflibercept for treatment of DME.

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.

OBJECTIVE:To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration. METHODS:A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG). RESULTS:Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients. CONCLUSION/CONCLUSIONS:Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera.

PURPOSE/OBJECTIVE:To investigate whether non-invasive en face ultra-widefield (UWF) optical coherence tomography (OCT) can demonstrate salient features of the choroidal vasculature in eyes with central serous chorioretinopathy (CSC). DESIGN/METHODS:Retrospective observational case series. PARTICIPANTS/METHODS:Patients diagnosed with CSC who underwent UWF indocyanine green angiography (ICGA) and widefield OCT imaging were included. METHODS:Widefield OCT imaging was performed with a horizontal 23 mm x vertical 20 mm field of view of 5 visual fixations (1 central and 4 peripheral fixations) to compose structural en face UWF OCT montage images and UWF choroidal thickness maps. Automated image alignment was performed prior to grading. MAIN OUTCOME MEASURES/METHODS:A comparison of choroidal vascular findings seen with UWF ICGA and en face UWF OCT images including size and distribution of choroidal venous drainage areas and identification of dilated choroidal veins ("pachyvessels") crossing the physiological choroidal watershed zones. Spatial correlation between choroidal vascular hyperpermeability (CVH) on UWF ICGA images and areas of choroidal thickening (ACT) on UWF choroidal thickness maps was determined. RESULTS:Forty-two eyes from 27 CSC patients with a mean age of 56 ±12 years (range, 31 to 77 years) were included. Quantitative measures of vortex vein drainage areas on en face UWF OCT images were significantly and positively correlated with those obtained with UWF ICGA (mean Pearson r=0.825, P < 0.01). Identification of pachyvessels crossing the choroidal watershed zones showed an excellent correlation between UWF ICGA and en face UWF OCT images (mean Spearman ρ= 0.873, P < 0,01). In all cases, CVH observed on UWF ICGA spatially co-localized with ACT on the UWF choroidal thickness map. Congestion within the entire drainage area of the dominant vortex systems was observed on UWF choroidal thickness maps. CONCLUSIONS:In eyes with CSC, non-invasive en face UWF OCT imaging can show distinctive features of choroidal venous insufficiency previously identified with UWF ICGA. UWF OCT choroidal thickness maps enable quantitative assessment of choroidal congestion.

PURPOSE/OBJECTIVE:To analyze the urinary metabolomic profile of central serous chorioretinopathy (CSC) cases. METHODS:In a cross-sectional study, 80 participants with CSC were compared with 80 age- and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4TM platform. RESULTS:Of 1031 metabolites total that were measured in urine samples, 53 were up-regulated and 27 down-regulated in CSC participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid sub-pathway. The down-regulated metabolites are unrelated to the identified corticosteroid sub-pathway. CONCLUSION/CONCLUSIONS:The upregulation of urinary tetrahydrocortisol sulfate in CSC cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.

PURPOSE/UNASSIGNED:To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. METHODS/UNASSIGNED:A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. RESULTS/UNASSIGNED:The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). CONCLUSIONS/UNASSIGNED:The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.