In depth understanding of retinitis pigmentosa pathogenesis through optical coherence tomography angiography analysis: a narrative review

Retinitis pigmentosa (RP) is the most recognized inherited retinal disorder involving progressive photoreceptors degeneration which eventually causes blindness. However, the pathogenesis of RP is still unclear, making it difficult to establish satisfying treatments. Evidence have been found to support the theory that vascular dysfunction is associated with the progression of RP. Optical coherence tomography angiography (OCTA) is a newly developed technology that enables visualization as well as quantitative assessment of retinal and choroidal vasculature non-invasively. Advances in OCTA have opened a window for in-depth understanding of RP pathogenesis. Here, we propose a hypothesis of RP pathogenesis based on the current OCTA findings in RP, which includes four stages and two important key factors, vascular dysfunction and microglia activation. Further, we discuss the future animal experiments needed and how advanced OCTA technology can help to further verity the hypothesis. The final goal is to explore potential treatment options with enhanced understanding of RP pathogenesis.

Associations Between the Choroidal Vascularity Index and Malignant Glaucoma After Trabeculectomy for Primary Angle Closure Glaucoma

Purpose: To compare the choroidal vasculature characteristics by using the choroidal vascularity index (CVI) in eyes with malignant glaucoma (MG), fellow eyes with non-MG, and eyes with uncomplicated primary angle-closure glaucoma (PACG) after trabeculectomy by spectral-domain optical coherence tomography (SD-OCT).Methods: This case–control study included 53 patients diagnosed with MG after trabeculectomy. Eyes with MG (n = 53) and the fellow eyes with non-MG (n = 50) were included. Eyes with PACG without MG after trabeculectomy (n = 60) were also enrolled as controls. The choroidal parameters, including CVI and the subfoveal choroidal thickness (SFCT), were measured by using SD-OCT images.Results: Eyes with MG and the fellow eyes showed a significantly lower CVI than eyes with PACG controls (p < 0.001). After adjusting for age, sex, axial length (AL), and intraocular pressure (IOP), eyes with the greater CVI [odds ratio (OR), 0.44] were significantly related to MG. The area under the receiver operating characteristic curve of the CVI was greater than that of the SFCT in the diagnosis of MG (0.911 vs. 0.840, p = 0.034).Conclusion: Eyes with MG showed a significantly lower macular CVI than eyes with PACG controls. A higher macular CVI was an associated factor of eyes with MG. The CVI serves as a more stable and sensitive indicator for MG than the SFCT in this group of patients with PACG.

Clinical applications of OCTA in ocular oncology: pearls and pitfalls

Background: Optical Coherence Tomography Angiography (OCTA) is a valuable imaging tool for the diagnosis of several retinal and choroidal diseases. Its role in ocular oncology is clinically promising but still controversial. In this review we report the main applications and limits of the use of OCTA for the study of intraocular tumors. Summary: OCTA allows a rapid, safe, low-cost and high-resolution visualization of the retinal and choroidal vasculature. Attempts have been made to use this technology in ocular oncology to differentiate benign and malignant lesions and to assist physicians in the evaluation and monitoring of post-treatment complications. Main limitations include failure in correct segmentation due to tumor inner profile or thickness, poor penetration of laser into the lesion, masking effect from overlying fluid and media opacities and poor fixation. Key messages: The main applications of OCTA in ocular oncology consist in the documentation of tumor-associated choroidal neovascularizations and the study of vascular changes following tumor treatments. In particular, the diffusion of wide-field protocols makes OCTA suitable for the diagnosis and follow-up of radiation chorio-retinopathy allowing a detailed visualoization of both macular and peripheral ischemic changes. Optimistically, future innovations in OCTA technology may offer new perspectives in the diagnosis and follow-up of intraocular tumors.

Choroidal Vascularity Index in Adult-Onset Foveomacular Vitelliform Dystrophy: A Pilot Study

This pilot study aims to investigate choroidal vascular status in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD), early age-related macular degeneration (AMD), and age-matched controls. In this retrospective study, choroidal thickness (CT) was measured manually using spectral domain optical coherence tomography images of the fovea, and 500 and 1500 µm from the nasal and temporal regions in the fovea. The horizontal B-scan was imported into Fiji software. Choroidal vascularity index (CVI) and luminal and stromal areas were calculated. A total of 36 eyes from 36 patients, including 18 eyes with AOFVD and 18 eyes with CD, and 16 eyes of healthy subjects were included. CVI was significantly different among subgroups (ANOVA, p = 0.004). Eyes with AOFVD presented a higher CVI (+0.03 ± 0.01, p = 0.001) than eyes with CD and controls (p = 0.03). No differences in CVI were detected between controls and eyes with CD (p = 0.25). AOFVD eyes accounted for the greatest luminal area, particularly significant in comparison with healthy controls (+0.27 ± 0.11, p = 0.02). AOFVD eyes present a greater CVI than eyes with CD and controls. The major choroidal involvement is on the luminal component, further corroborating a possible role of the choroidal vasculature in the pathological manifestations of AOFVD disease.

Role of the choroidal vascularity index in branch retinal vein occlusion (BRVO) with macular edema

Purpose To assess choroidal vasculature changes in eyes with branch retinal vein occlusion (BRVO) and macular edema (ME) using the choroidal vascularity index (CVI) and evaluate the effectiveness of CVI as a prognostic biomarker. Methods 35 patients with monocular BRVO and ME were analyzed retrospectively. Luminal and stromal areas in choroids of swept-source optical coherence tomography were calculated using the image binarization technique. The CVI was calculated as the ratio of the luminal to total choroidal area. The CVI of BRVO and ME eyes were compared with that of the unaffected fellow and post anti-vascular endothelial growth factor (VEGF) injected eyes. A regression analysis was performed on the choroidal parameters, logMAR visual acuity (VA) two years post disease onset and central macula thickness (CMT). Results The CVI of BRVO and ME eyes was significantly lower than the fellow and post-injected eyes (p<0.05). The regression analysis showed a strong association between two years after logMAR VA and the CVI of fellow eyes (R2 = 0.433, p<0.001). Remarkable correlations were observed in the CVI and subfoveal choroidal thickness of BRVO and ME eyes (R2 = 0.189, 0.155, respectively, p<0.05). The CMT of diseased eyes were also significantly associated with the CVI of unaffected fellow eyes (R2 = 0.113, p<0.05). Conclusions The alteration of CVI in BRVO and ME suggests that choroidal vasculature might be affected by extracellular fluid shift and VEGF changes. The fellow eye CVI could be a useful supplementary prognostic biomarker.

COVID-19 Associated Choroidopathy

The aim of the study is to report on the indocyanine green angiography (ICGA) and OCT findings in patients hospitalized for severe COVID infection. In this observational prospective monocentric cohort study, we included patients hospitalized for severe COVID infection. The main outcomes were ICGA and OCT findings. A total of 14 patients with a mean age of 58.2 ± 11.4 years and a male predominance (9/14 patients; 64%) were included. The main ICGA findings included hypofluorescent spots in 19 eyes (68%), intervortex shunts in 10 eyes (36%), and characteristic “hemangioma-like” lesions in five eyes (18%). “Hemangioma-like” lesions were both unique and unilateral, and showed no washout on the late phase of the angiogram. The main OCT findings included focal choroidal thickening in seven eyes (25%), caverns in six eyes (21%) and paracentral acute middle maculopathy lesions in one eye (4%). All patients hospitalized for severe COVID infection had anomalies on ICGA and OCT. Lesions to both retinal and choroidal vasculature were found. These anomalies could be secondary to vascular involvement related directly or indirectly to the SARS-CoV2 virus.

MR pathway in retinal health and diseases

In the retina, mineralocorticoid receptor (MR), expressed in vessels, glial and neuronal cells, is mainly activated by glucocorticoids. Under pathological conditions, ocular MR expression and corticoids change, leading in most cases to MR overactivation. Experimental models using MR agonists or antagonists, administered systemically or intraocularly, acutely or chronically and transgenic models, allowed to identify the deleterious consequences of MR pathway overactivation. Among them, oxidative stress, inflammation, deregulation of hydro-ionic channels, alteration of choroidal vasculature, angiogenesis and cell death, are common to major retinal diseases. Specific MR antagonists showed efficacy in models of diabetic retinopathy, ischaemia, retinal and choroidal angiogenesis and in models of glaucoma. It is highly likely that MR antagonists will find a place in the therapeutic arsenal of age-related macular degeneration, diabetic retinopathy, glaucoma and in pachychoroid associated diseases. Their use in humans is still limited by the need of biomarkers of MR activation and specific ocular formulations.

Optical coherence tomography angiography in amblyopia: A critical update on current understandings and future perspectives

Optical coherence tomography angiography (OCTA) is a non-invasive tool to assess the retino-choroidal vasculature in vivo. It tracks the red blood cell movement and maps the vasculature in quick succession. In routine, diabetic retinopathy, age related macular degeneration, central serous chorioretinopathy, and others are commonly being studied to unveil its clinic role. On the other hand, amblyopia is a condition where the visual acuity is subnormal due to non-organic causes in the eye. But the OCTA studies till now have shown variable changes along retino-choroidal vasculature. Hence, to comprehend the existing literature knowledge, a systematic literature search was carried out and the original works describing novel findings in amblyopic eyes on OCTA were included. Upon detailed assessment, firstly, the disturbed vasculature along superficial retinal plexus, deeper retinal plexus, and choroidal plexus were evident in most untreated amblyopic eyes. However, such changes were not uniform, which is due to noted heterogenic patient profile, small sample size, biometric biases, non-uniform algorithms, and other factors. And to note, even in presence of such diverse changes, almost all the authors stated a plausible explanation for their notable changes. Secondly, the utility of OCTA in identifying vascular changes with standard treatments and segregation of visual beneficiaries from non-beneficiaries were possible. Hence, to conclude, OCTA is a valuable tool which can provide valuable useful insights into the amblyopic eyes during pre and post treatment periods. However, to gather more concrete evidence for clinical benefits, systematic, homogenous, and better structured clinical studies are mandated.