Intraretinal Hyper-Reflective Foci Are Almost Universally Present and Co-Localize With Intraretinal Fluid in Diabetic Macular Edema.

Purpose: In diabetic macular edema (DME), hyper-reflective foci (HRF) has been linked to disease severity and progression. Using an automated approach, we aimed to investigate the baseline distribution of HRF in DME and their co-localization with cystoid intraretinal fluid (IRF). Methods: Baseline spectral-domain optical coherence tomography (SD-OCT) volume scans (N = 1527) from phase III clinical trials YOSEMITE (NCT03622580) and RHINE (NCT03622593) were segmented using a deep-learning-based algorithm (developed using B-scans from BOULEVARD NCT02699450) to detect HRF. The HRF count and volume were assessed. HRF distributions were analyzed in relation to best-corrected visual acuity (BCVA), central subfield thickness (CST), and IRF volume in quartiles, and Diabetic Retinopathy Severity Scores (DRSS) in groups. Co-localization of HRF with IRF was calculated in the central 3-mm diameter using the en face projection. Results: HRF were present in most patients (up to 99.7%). Median (interquartile range [IQR]) HRF volume within the 3-mm diameter Early Treatment Diabetic Retinopathy Study ring was 1964.3 (3325.2) pL, and median count was 64.0 (IQR = 96.0). Median HRF volumes were greater with decreasing BCVA (nominal P = 0.0109), and increasing CST (nominal P < 0.0001), IRF (nominal P < 0.0001), and DRSS up to very severe nonproliferative diabetic retinopathy (nominal P < 0.0001). HRF co-localized with IRF in the en face projection. Conclusions: Using automated HRF segmentation of full SD-OCT volumes, we observed that HRF are a ubiquitous feature in DME and exhibit relationships with BCVA, CST, IRF, and DRSS, supporting a potential link to disease severity. The spatial distribution of HRF closely followed that of IRF.

Morphological changes of macular neovascularization during long-term anti-VEGF-therapy in neovascular age-related macular degeneration.

PURPOSE: To analyze the morphological changes of macular neovascularization (MNV) in exudative neovascular age-related macular degeneration under long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy in a retrospective cohort study. METHODS AND PATIENTS: We evaluated 143 nAMD eyes of 94 patients (31 male, 63 female; initial age 55-97 y, mean age 75.9 ± 7.5 y), who started anti-VEGF therapy (IVAN pro re nata (PRN) protocol) between 2009-2018 and received ongoing therapy until the last recorded visit (mean follow-up 5.3 ± 2.9 y, range 1-14 y). The mean total number of injections was 33.3 ± 19.8 with 7.0 ± 2.3 injections/year. MNV size and, if present, associated complete retinal pigment epithelium (RPE) and outer retina atrophy (cRORA) size were measured on optical coherence tomography (OCT) volume scans at the initial visit and for each year of follow-up. MNV and cRORA were identified on B-scans and their respective borders were manually transposed onto the en-face near infrared image and measured in mm2. RESULTS: MNV enlarged through follow-up, with a mean growth rate of 1.24 mm2 / year. The mean growth in MNV size was independent of initial MNV size, age, gender, MNV subtypes or number of injections per year. Nevertheless, a great interindividual variation in size and growth was observed. cRORA developed in association with increasing MNV size and its incidence increased linearly over follow-up. cRORA lesions also showed continuous growth by a rate of 1.22 mm2 / year. CONCLUSIONS: Despite frequent long-term anti-VEGF therapy, we observed ongoing MNV growth. This is consistent with the concept that the development of MNV may be a physiological biological repair mechanism to preserve RPE and photoreceptor function, provided hyperpermeability and fluid exudation are controlled. Whether recurring low VEGF levels or other factors are responsible for MNV growth remains controversial.

Hyperreflective Material Boundary Remodeling in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the AVENUE Trial.

OBJECTIVE: To describe the spatial and temporal characteristics of hyperreflective material (HRM) on spectral-domain OCT (SD-OCT) in neovascular age-related macular degeneration (nAMD) during antiangiogenic treatment and explore associations with best-corrected visual acuity (BCVA) and macular atrophy (MA). DESIGN: Retrospective regrading of SD-OCT-images from the multicenter, randomized controlled AVENUE trial (NCT02484690, conducted from August 2015 to September 2017). PARTICIPANTS: Treatment-naive nAMD patients enrolled from 50 sites in the US. METHODS: Retrospective regrading and secondary analysis. MAIN OUTCOME MEASURES: Spectral-domain OCT images from 207 study eyes that fit criteria for the present analysis were graded for HRM features, its evolution, and associated hypertransmission into choroid (HTC), a proxy for MA. The appearance of a well-defined hyperreflective inner boundary that separated persistent HRM from the neurosensory retina continuous with the adjacent retinal pigment epithelium layer was defined as hyperreflective material boundary remodeling (HRM-BR). Patterns of HRM composition/evolution were defined as follows: (1) no subretinal HRM at baseline, (2) fully resolved, (3) persistent with complete HRM-BR, or (4) partial/absent HRM-BR. Associations of HRM patterns with BCVA and HTC were analyzed. Predictive factors for complete HRM-BR were explored. RESULTS: Of 207 included eyes, subretinal HRM was present in 159 (76.8%) at baseline and persisted until month 9 in 118 (57.0%) eyes. Of these 118 eyes, 44.9% developed complete HRM-BR and had similar BCVA outcomes by month 9 compared with no/fully resolved subretinal HRM. Partial/absent HRM-BR had a strong negative association with BCVA outcome (-6.1 ETDRS letters; P = 0.016) and a higher frequency of intralesional HTC (69.2%) compared with eyes with complete HRM-BR (20.8%) at month 9. Older age (odds ratio [OR], 0.96; P = 0.054) and presence of intralesional HTC (OR, 0.06; P = 0.010) at baseline were associated with lower odds of complete HRM-BR at month 9. CONCLUSIONS: In nAMD eyes under antiangiogenic treatment, complete HRM-BR occurred frequently and was associated with better BCVA than when HRM-BR was only partial/absent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Fibrosis in neovascular age-related macular degeneration: A review of definitions based on clinical imaging.

Despite the success of antiangiogenic therapy in controlling exudation in neovascular age-related macular degeneration (nAMD), the involvement of the outer retina in fibrosis results in gradual vision loss over time. The development of drugs that prevent or ameliorate fibrosis in nAMD requires that it is accurately detected and quantified with reliable endpoints and identification of robust biomarkers. Achievement of such an aim is currently challenging due to the lack of a consensus definition of fibrosis in nAMD. As a first step towards the establishment of a clear definition of fibrosis, we provide an extensive overview of the imaging modalities and criteria used to characterize fibrosis in nAMD. We observed variety in the selection of individual and combinations of imaging modalities, and criteria for detection. We also observed heterogeneity in classification systems and severity scales for fibrosis. The most commonly used imaging modalities were color fundus photography, fluorescein angiography and optical coherence tomography (OCT). A multimodal approach was frequently utilized. Our review suggests that OCT offers a more detailed, objective and sensitive characterization than color fundus photography/fluorescein angiography. Thus, we recommend it as a primary modality for fibrosis evaluation. This review provides a basis for future discussions to reach a consensus definition using standardized terms based on a detailed characterization of fibrosis, its presence and evolution, and taking into consideration impact on visual function. Achieving this goal is of paramount importance for the development of antifibrotic therapies.

[Maculopathy in sickle cell disease]. / Makulopathie bei Sichelzellerkrankung.

BACKGROUND: Sickle cell disease (SCD) is a hereditary hemoglobinopathy, which leads to microcirculatory disturbances of various organ systems through recurrent vaso-occlusive episodes, with a possibly fatal outcome. Sickle cell retinopathy (SCR) is the best described ocular manifestation of SCD. Irrespective of the presence of peripheral SCR, sickle cell maculopathy (SCM) can occur early in the course of the disease. METHODS: Review of the international and German literature on ocular involvement in SCD with a focus on SCR and SCM and an overview of current systemic therapeutic approaches in SCD on the occasion of the presentation of two patients with HbSS SCD. RESULTS AND CONCLUSION: In contrast to SCR, SCM with temporal thinning of the inner retinal layers has only been increasingly described in the literature in the last 5 years, with the advent of SD-OCT and OCTA. Irrespective of the presence of SCR, as many as about half of the patients may develop SCM early in the course of the disease. As a result of progress in systemic therapeutic options and due to migration, the clinical picture will occur more often also in Germany. By knowing about this complication of SCD an early diagnosis can be made and unnecessary diagnostics can be avoided.