No abstract

Diabetic retinopathy (DR) is the most common complication of diabetes and has been historically regarded as a microangiopathic disease. Now, the paradigm is shifting toward a more comprehensive view of diabetic retinal disease (DRD) as a tissue-specific neurovascular complication, in which persistently high glycemia causes not only microvascular damage and ischemia but also intraretinal inflammation and neuronal degeneration. Despite the increasing knowledge on the pathogenic pathways involved in DR, currently approved treatments are focused only on its late-stage vasculopathic complications, and a single molecular target, vascular endothelial growth factor (VEGF), has been extensively studied, leading to drug development and approval. In this review, we discuss the state of the art of research on neuroinflammation and neurodegeneration in diabetes, with a focus on pathophysiological studies on human subjects, in vivo imaging biomarkers, and clinical trials on novel therapeutic options.

The aim of the study was to characterize macular edema (ME) in retinitis pigmentosa (RP) by means of quantitative optical coherence tomography (OCT)-based imaging. The study was designed as observational, prospective case series, with 1-year follow-up. All RP patients underwent complete ophthalmologic assessment, including structural OCT, OCT angiography, and microperimetry (MP). The primary outcome was the characterization through quantitative OCT-based imaging of RP eyes complicated by ME. A total of 68 RP patients’ eyes (68 patients) and 68 eyes of 68 healthy controls were recruited. Mean BCVA was 0.14 ± 0.17 LogMAR at baseline and 0.18 ± 0.23 LogMAR at 1-year follow-up (p > 0.05). Thirty-four eyes (17 patients; 25%) showed ME, with a mean ME duration of 8 ± 2 months. Most of the eyes were characterized by recurrent ME. The ME was mainly localized in the inner nuclear layer in all eyes. LogMAR BCVA was similar in all RP eyes, whether with or without ME, although those with ME were associated with higher vessel density values, as well as thicker choroidal layers, than those without ME. In conclusion, the inner retina is closely involved in the pathogenesis of ME. The impairment of retinal-choroidal exchanges and Müller cell disruption might be a major pathogenic factor leading to the onset of ME in RP.

Purpose To investigate the clinical and imaging features associated with retinal sensitivity in Best vitelliform macular dystrophy (BVMD). Methods This was a cross-sectional, single-center, observational study. Each patient underwent optical coherence tomography (OCT), near-infrared fundus autofluorescence, and OCT angiography. Macular integrity assessment microperimetry under mesopic conditions was performed to obtain retinal sensitivity thresholds from 68 testing points in the central macula. Structural OCT was used to classify BVMD lesions into four types according to their composition: vitelliform, mixed, subretinal fluid, and atrophy. Multilevel, mixed-effects linear regression was used to determine the factors associated with retinal sensitivity. Results The study included 57 eyes of 30 patients with BVMD, 48 of which (84%) were in a clinical stage. Mean retinal sensitivity varied according to the composition of the lesion: the vitelliform type registering the highest (22 ± 4.1 dB), followed by mixed (18.73 ± 2.7 dB), subretinal fluid (15.68 ± 4.2 dB), and atrophy types (11.85 ± 4.6 dB). The factors most strongly associated with mean retinal sensitivity in BVMD proved to be the OCT lesion type and outer nuclear layer thickness. Conclusions Retinal sensitivity in BVMD is influenced by lesion composition and outer nuclear layer thickness. Further studies with long-term follow-up are warranted to examine retinal sensitivity over time and to validate retinal sensitivity changes as biomarkers for BVMD. Translational Relevance Assessing retinal sensitivity in BVMD provides a new instrument in the clinical characterization of the disease and offers the opportunity to identify imaging biomarkers for use as outcome measures in future clinical trials.

In this study, we described multimodal imaging findings occurring before the onset of macular neovascularization in angioid streaks. Our imaging findings suggest that intraretinal hyperreflective foci concentration and migration may represent the early alterations preceding macular neovascularization complication.

Purpose Bietti crystalline dystrophy (BCD) is a rare autosomal recessive retinal dystrophy caused by pathogenic variants of CYP4V2 gene and characterized by shiny yellow deposits in the retina and progressive atrophy of the retinal pigment epithelium (RPE) and choriocapillaris. The main aim of the present study is to describe the optical coherence tomography angiography (OCTA) characteristics of a patient affected by BCD. Methods A 59-years-old female with genetically confirmed BCD underwent an ophthalmological examination complete of OCTA performed in the atrophic retina, the junctional zone and the apparently normal retina. The area of choriocapillaris (CC) atrophy was compared to the area of RPE atrophy on fundus autofluorescence (FAF) imaging. Results A severe vessel density (VD) deficit at the level of superficial and deep capillary plexa as well as CC was registered in atrophic areas, which resulted deeper with respect to the junctional area, whereas the apparently preserved retina revealed VD values similar to that of control eyes. The area of RPE atrophy on FAF was larger (55.90 mm2 in right eye and 48.76 mm2 in left eye) than the area of CC atrophy on OCTA imaging (51.86 mm2 and 42.44 mm2 respectively in right and left eye). Conclusions Our findings suggest that VD impairment of retinal plexa and CC follows the degeneration of RPE as demonstrated by the greater size of the area of RPE atrophy compared to CC atrophy. Further investigations based on OCTA imaging are necessary to enhance our knowledge of this rare disease.

Best Vitelliform Macular Dystrophy (BVMD) is a dominantly inherited retinal disease caused by dominant variants in the BEST1 gene. The original classification of BVMD is based on biomicroscopy and color fundus photography (CFP); however, advancements in retinal imaging provided unique structural, vascular, and functional data and novel insights on disease pathogenesis. Quantitative fundus autofluorescence studies informed us that lipofuscin accumulation, the hallmark of BVMD, is unlikely to be a primary effect of the genetic defect. It could be due to a lack of apposition between photoreceptors and retinal pigment epithelium in the macula with subsequent accumulation of shed outer segments over time. Optical Coherence Tomography (OCT) and adaptive optics imaging revealed that vitelliform lesions are characterized by progressive changes in the cone mosaic corresponding to a thinning of the outer nuclear layer and then disruption of the ellipsoid zone, which are associated with a decreased sensitivity and visual acuity. Therefore, an OCT staging system based on lesion composition, thus reflecting disease evolution, has been recently developed. Lastly, the emerging role of OCT Angiography proved a greater prevalence of macular neovascularization, the majority of which are non-exudative and develop in late disease stages. In conclusion, effective diagnosis, staging, and clinical management of BVMD will likely require a deep understanding of the multimodal imaging features of this disease.

ImportanceABCA4-associated retinopathy is a common inherited retinal disease, and its phenotype spans from late-onset macular dystrophy to extensive cone-rod degeneration. Over 2000 disease-causing variants in the ABCA4 gene have been identified.ObjectiveTo investigate genotype-phenotype correlations in ABCA4-associated retinopathy.Design, Setting, and ParticipantsThis cohort study took place at a single referral center for inherited retinal diseases in Italy. Data were prospectively acquired from January 2015 to June 2022. Patients diagnosed with an inherited retinal disease related to biallelic ABCA4 variants were included for analysis.ExposureGenotype, classified into 4 groups according to the presence of the (1) p.Gly1961Glu allele, (2) a hypomorphic allele, (3) at least 1 moderate variant (moderate genotypes), or (4) 2 biallelic severe variants (severe genotypes).Main Outcomes and MeasuresTotal decreased autofluorescence (TDAF) and definitely decreased autofluorescence (DDAF) areas, inner and outer retinal volumes, and the respective progression rate.ResultsA total of 71 patients (median [IQR] age, 34 [22.4-47.2] years; 40 [56%] female) were included in the study, and 54 (76%) were followed up for a median (IQR) of 3.5 (1.6-4.7) years. Compared with moderate genotypes, those with the p.Gly1961Glu allele had smaller TDAF lesions by 61% (95% CI, −78% to −33%; P < .001) and DDAF lesions by 77% (95% CI, −93% to −18%; P = .02), along with slower growth rates for both TDAF (0.05 mm/y; 95% CI, 0.01-0.07; P < .001) and DDAF (0.06 mm/y; 95% CI, 0-0.12; P = .004). Hypomorphic alleles were associated with a thicker inner (+0.19 mm3; 95% CI, +0.02 to +0.36; P = .03) and outer retinal volume (+0.16 mm3; 95% CI, +0.03 to +0.28; P = .01) compared with moderate genotypes as well as a slower TDAF growth rate (0.05 mm/y; 95% CI, 0.01-0.08; P = .007). Severe genotypes had a 7-fold larger TDAF area (95% CI, 3.4-14.7; P < .001) and 11-fold larger DDAF area (95% CI, 2.9-42.1; P < .001) compared with moderate genotypes, along with faster growth rates estimated at 0.16 mm/y for TDAF (95% CI, 0.12-0.20; P < .001) and 0.17 mm/y for DDAF (95% CI, 0.12-0.23; P < .001).Conclusions and RelevanceIn this study of ABCA4-associated retinopathy, a 4-tier classification of genotypes was found to capture substantial variation in disease phenotype severity. These findings could prove beneficial for the prognostication of patients and warrant consideration of genotype in the design of future clinical trials.