Multifocal vitelliform lesions associated with mitochondrial retinopathy.

Purpose: To report a case of multifocal vitelliform lesions in a patient affected by metabolic encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) with the m.3243A>G variant. Observations: A 37-year-old woman affected by MELAS was referred to our center for progressive vision deterioration. On fundus examination, she presented bilateral macular atrophy associated in the left eye with neurosensory detachment, along with several bilateral vitelliform lesions close to the vascular arcades. We describe the dynamic evolution of the vitelliform lesions, which could either enlarge and coalesce or undergo atrophic evolution. Conclusions: Mitochondrial retinopathy due to the m.3243A>G variant can be associated with multifocal vitelliform lesions.

New observations on rare and threatened saproxylic hoverflies in North-Western Italy with ecological notes.

Background: The knowledge on the distribution of saproxylic hoverflies in the Piedmont region has always been incomplete, despite the large wooded areas present in the territory. We know of a few scattered specimens collected in the 19th century, often with a generic or incomplete locality on the label such as "surrounding Turin" or "Alps". The recent publication of the first European Red List on hoverflies highlights some threatened species including some saproxylics. To fill this knowledge gap we report here unpublished data and establish new ecological note on threatened or nationally scarce saproxylic species actually present in the region. New information: In this study, we present new findings concerning rare saproxylic hoverflies. These include the rediscovery of Hammerschmidtiaferruginea (Fallen), 1817, marking its first recorded occurrence in the Italian fauna since the middle of 19th century. Additionally, we report novel observations of the "Chimera fly" Dorosdestillatorius Mik, 1885, along with further observations on endangered or vulnerable species such as Callicera spp. and Brachypalpuschrysites Egger 1859. Moreover, we document the rediscovery of Criorhinapachymera Egger, 1858, within the Piedmont region, and the first record of Brachyopagrunewaldensis Kassebeer, 2000, within Italy. Comprehensive data detailing these observations are provided herein.

Prevalence, Features, and Outcomes of Type 1 Neovascularization in Eyes with Angioid Streaks.

PURPOSE: This study aimed to delineate the characteristics, prevalence, and outcomes of neovascularization (NV), particularly aneurysmal type 1 NV, in patients with angioid streaks (AS) secondary to pseudoxanthoma elasticum (PXE), and to introduce a clinical classification based on multimodal imaging. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Eighty-five patients (168 eyes) with AS secondary to PXE at 2 tertiary referral centers. METHODS: Data collection included demographic, medical, and ocular histories. Diagnostic methods comprised fundus photography, autofluorescence, indocyanine green angiography, OCT, and OCT angiography. MAIN OUTCOME MEASURES: Prevalence of type 1 NV, visual acuity (VA), risk of exudation. RESULTS: Type 1 NV was identified in 127 eyes (76%), with 85 of these (67%) showing exclusively type 1 NV. These lesions often originated around the disc, at sites of Bruch membrane dehiscences, and followed the path of AS, extending to the macula in 101 eyes (80%). Despite 65% of type 1 NV remaining nonexudative, 35% evolved into exudative over 5 years, and 11 eyes experienced midperipheral subretinal hemorrhages. Aneurysmal dilations, observed in 57% of eyes, substantially increased exudation risk (hazard ratio = 3.86, P = 0.02). Despite treatment, VA significantly deteriorated in exudative type 1 NV (P = 0.02). Type 2 NV, detected in 42 eyes (33%), often coexisted with type 1 NV and was associated with poorer visual outcomes and higher rates of macular atrophy. A classification of AS was developed, ranging from empty AS (stage 0, no NV) to advanced NV (stage 3, both type 1 and type 2 NV). CONCLUSIONS: Type 1 NV predominates in AS. Although predominantly nonexudative, its progression correlates with substantial visual impairment, similar to the deficits observed with type 2 NV. Aneurysmal type 1 NV poses a significant exudation risk, underscoring the need for vigilant monitoring. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

RDH5 and RLBP1-Associated Inherited Retinal Diseases: Refining the Spectrum of Stationary and Progressive Phenotypes.

PURPOSE: To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations. DESIGN: Retrospective single-center cohort study. METHODS: Twenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing. RESULTS: The median (interquartile ranges) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy (MA) was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm3 (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm3/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference between the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of MA. CONCLUSIONS: Progressive MA in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with MA. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Extensive Macular Atrophy with Pseudodrusen-like appearance: Progression Kinetics and Late-Stage Findings.

PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. MAIN OUTCOME MEASURES: The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. RESULTS: At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical coherence tomography (OCT) and OCT-angiography in syndromic versus non-syndromic USH2A-associated retinopathy.

PURPOSE: To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA). METHODS: Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA + OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy. RESULTS: Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p = 0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p = 0.775 and p = 0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups. CONCLUSIONS: Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.

Multimodal Imaging of Vitreo-Retinal Lymphoma: A Comprehensive Review.

PURPOSE: Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL. METHODS: We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions. RESULTS: The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination. CONCLUSION: Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.

Inner retinal thickness in Stargardt disease.

PURPOSE: To analyze the alterations at the level of the inner retina in patients affected by Stargardt disease (STGD1). METHODS: Cross-sectional investigation involving STGD1 patients with genetically confirmed diagnosis, who underwent optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and microperimetry. RESULTS: Overall, 31 patients (62 eyes) with genetically confirmed STGD1 were included in the study. Mean inner retinal thickness, vessel density of plexa, and retinal sensitivity resulted significantly reduced in STGD patients, compared with healthy controls (p < 0.05), both in the outer and in the inner ETDRS rings. Overall, 43% of eyes revealed an inner retinal thinning, whereas 21% and 35% showed a thicker or within normal range inner retina. CONCLUSIONS: Inner retina is irregularly altered in STGD1, showing variable quantitative alterations as detected on OCT. Inner retinal status might represent a useful biomarker to better characterize STGD1 and to ascertain the effects of new treatment approaches.

Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy.

PURPOSE: Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent. METHODS: Genome, targeted next-generation, and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants' pathogenicity was accessed using 3D-modeling and/or ROs. RESULTS: Here, we identified a novel gene defect with three distinct pathogenic variants in UBAP1L in 4 independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein. CONCLUSION: Biallelic UBAP1L variants are a novel cause of IRDs, most likely enriched in the North African population.

Multimodal imaging in Best Vitelliform Macular Dystrophy: Literature review and novel insights.

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.

New insights in the multimodal imaging of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited rod-cone dystrophies, noted for a high genotypical and phenotypical heterogeneity.Traditionally, VA, visual field, and electroretinography have been used to assess RP progression. However, visual acuity and visual field tests are essentially subjective and, especially in the late stages of the disease, are unable to confidently reveal minor progression. Therefore, there is a need for novel examination modalities that rely on quantitative, structural measurements. In this regard, several non-invasive imaging techniques have been studied, including spectral-domain optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. By correlating surrogate biomarkers with functional measurements of the disease, these techniques may be able to develop reliable outcome meters that can be used to gain a deeper understanding of the underlying causes of the disease and to assess the effectiveness of therapy even before an actual loss of vision occurs.In this review, we will summarize the recent imaging findings and biomarkers that have been identified in RP patients. Our goal is to provide information that can promptly aid in selecting patients for clinical trials and new gene therapies, monitoring the disease progression, and evaluating treatment outcomes.

Non-vasogenic cystoid maculopathy in autosomal recessive bestrophinopathy: novel insights from NIR-FAF and OCTA imaging.

BACKGROUND: Autosomal Recessive Bestrophinopathy (ARB) is an inherited retinal disease caused by biallelic mutations in the BEST1 gene. Herein, we report the multimodal imaging findings of ARB presenting with cystoid maculopathy and investigate the short-term response to combined systemic and topical carbonic anhydrase inhibitors (CAIs). MATERIAL AND METHODS: An observational, prospective, case series on two siblings affected by ARB is presented. Patients underwent genetic testing and optical coherence tomography (OCT), blue-light fundus autofluorescence (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), fluorescein angiography (FA), MultiColor imaging, and OCT angiography (OCTA). RESULTS: Two male siblings, aged 22 and 16, affected by ARB resulting from c.598C>T, p.(Arg200*) and c.728C>A, p.(Ala243Glu) BEST1 compound heterozygous variants, presented with bilateral multifocal yellowish pigment deposits scattered through the posterior pole that corresponded to hyperautofluorescent deposits on BL-FAF. Vice versa, NIR-FAF mainly disclosed wide hypoautofluorescent areas in the macula. A cystoid maculopathy and shallow subretinal fluid were evident on structural OCT, albeit without evidence of dye leakage or pooling on FA. OCTA demonstrated disruption of the choriocapillaris throughout the posterior pole and sparing of intraretinal capillary plexuses. Six months of combined therapy with oral acetazolamide and topical brinzolamide resulted in limited clinical benefit. CONCLUSIONS: We reported two siblings affected by ARB, presenting as non-vasogenic cystoid maculopathy. Prominent alteration of NIR-FAF signal and concomitant choriocapillaris rarefaction on OCTA were noted in the macula. The limited short-term response to combined systemic and topical CAIs might be explained by the impairment of the RPE-CC complex.

The Retinal Phenotype Associated with the p.Pro101Thr BEST1 Variant.

PURPOSE: To describe the retinal phenotype associated with the p.Pro101Thr BEST1 variant. DESIGN: Retrospective, observational case series. PARTICIPANTS: Patients diagnosed with bestrophinopathies in which molecular genetic testing identified the p.Pro101Thr BEST1 as well as healthy carriers among their first-degree relatives. METHODS: Medical records were reviewed to obtain data on family history and ophthalmic examinations, including retinal imaging. The imaging protocol included OCT and fundus autofluorescence using Spectralis HRA + OCT (Heidelberg Engineering). Genetic analysis was performed by next-generation sequencing. MAIN OUTCOME MEASURES: Results of ophthalmic examinations and multimodal imaging features of retinal phenotypes. RESULTS: The c.301C>A, p.Pro101Thr BEST1 missense variant was identified as the causative variant in 8 individuals (all men) from 5 families, accounting for 13% of cases (8/61) and 10% of pathogenic alleles (9/93) in our cohort of patients affected by bestrophinopathies. Seven individuals (14 eyes) had the variant in heterozygous status: all eyes had a hyperopic refractive error (median spherical equivalent of + 3.75 diopters [D]) and 4 individuals had a macular dystrophy with mildly reduced visual acuity (median of 20/25 Snellen), whereas the other 3 were asymptomatic carriers. On multimodal retinal imaging, 5 (36%) out of 14 eyes had subclinical bestrophinopathy, 4 (29%) had typical findings of adult-onset foveomacular vitelliform dystrophy (AOFVD), and the remaining 5 (36%) displayed a pattern dystrophy-like phenotype. Follow-up data were available for 6 subjects, demonstrating clinical stability up to 11 years, in both subclinical and clinical forms. An additional patient with autosomal recessive bestrophinopathy was found to harbor the p.Pro101Thr variant in homozygosity. CONCLUSIONS: The p.Pro101Thr BEST1 variant is likely a frequent cause of bestrophinopathy in the Italian population and can result in autosomal dominant macular dystrophies with incomplete penetrance and mild clinical manifestations as well as autosomal recessive bestrophinopathy. The spectrum of autosomal dominant maculopathy includes the typical AOFVD and a pattern dystrophy-like phenotype. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Non-perfusion severity correlates with central macular thickness and microvascular impairment in branch retinal vein occlusions.

PURPOSE: To study peripheral capillary non-perfusion (PCN-P) in branch retinal vein occlusion (BRVO) by means of ultra wide-field fluorescein angiography (UWFFA), and to correlate its extent and severity with optical coherence tomography (OCT) and OCT-angiography (OCTA) parameters and best corrected visual acuity (BCVA). METHODS: Prospective case series with 2 years of planned follow-up. We recruited patients from June 2019 to December 2019. Ophthalmologic examination included BCVA, UWFFA, OCT and OCTA. Partial (p) and complete (c) ischemic index (ISI) were evaluated on UWFFA images. Vessel density (VD) in both the macular region and the optic nerve head (ONH) was calculated. RESULTS: Twelve BRVO subjects and 12 healthy controls were recruited. Mean age was 63.8 ± 8.74 years. Mean BCVA improved from 0.43 ± 0.25 logMAR to 0.15 ± 0.18 after two years (p < 0.01), while mean central macular thickness (CMT) decreased from 463.83 ± 200.85 µm to 353.17 ± 108.85 µm (p > 0.05). Mean cISI, pISI and total ISI were 25.2 ± 13.0%, 6.3 ± 5.0% and 31.5 ± 12.0%, respectively. Except for VDs of the superficial capillary plexus and choriocapillaris in the macular region, all VDs were lower in the BRVO group (p < 0.01). cISI and tISI negatively correlated with mDCP (p < 0.01), whereas only pISI correlated with CMT at baseline (p < 0.05). Additionally, cISI also negatively correlated with VD at the ONH (p < 0.05). CONCLUSION: The amount of complete and partial ischemia may have different implications in BRVO, with the former being more associated with microvascular impairment and the latter with macular edema.

Acute atrophic evolution of drusenoid pigment epithelium detachment after photobiomodulation.

PURPOSE: To report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration (AMD). METHODS: Optical coherence tomography (OCT) was performed in the study eye before and after PBM. RESULTS: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM the D-PED collapsed, resulting in incomplete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening. CONCLUSION: Thinning of the outer retinal layers over a D-PED and posterior hypertrasmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history towards atrophic evolution.

Association of Circulating Antiretinal Antibodies With Clinical Outcomes in Retinitis Pigmentosa.

Purpose: To determine if circulating antiretinal antibodies (ARAs) differ between patients affected by retinitis pigmentosa (RP) and control participants and to assess whether ARAs are associated with clinical outcomes in patients with RP. Methods: Cross-sectional study involving a group of patients clinically diagnosed with RP and a control group of healthy participants. Serum autoantibodies against enolase, heat shock protein 70 (HSP70), and carbonic anhydrase II (CAII) were tested in all participants using Jess capillary Western blot. We compared ARA prevalence between the RP and control groups and investigated the association of serum ARA positivity with macular edema and vitreomacular disorders in patients affected by RP. Results: Thirty-six patients affected by RP and a control group of 39 healthy individuals were included. Overall, at least one ARA positivity was detected in 89% and 80% of participants in the RP and control groups, respectively. We observed a similar prevalence of anti-CAII and anti-enolase ARA between patients and controls (P = 0.87 and P = 0.35, respectively). Sera from patients with RP tested positive for anti-HSP70 ARAs more frequently than those from controls (53% vs. 36%), albeit without reaching statistical significance (P = 0.29). Among the 72 eyes with RP, 25% presented with macular edema (most often bilateral) and 33% with epiretinal membrane and/or lamellar macular hole. None of the three ARAs was associated with an increased risk of any macular complications in eyes affected by RP (all P > 0.05). Conclusions: The prevalence of circulating ARAs against enolase, HSP70, and CAII is similar between patients affected by RP and healthy individuals. Our results provide evidence against the association of ARAs with macular edema and vitreomacular interface disorders in RP.

Pigmented paravenous chorioretinal atrophy: Updated scenario.

Pigmented paravenous chorioretinal atrophy (PPCRA) is an uncommon form of chorioretinal atrophy characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinal pigment epithelial atrophy that are distributed along the retinal veins. Most patients are asymptomatic, and evidence suggest that PPCRA is slowly progressing. Unless macular involvement is present, the majority of patients usually retain a normal visual function. Our ability to diagnose PPCRA has recently improved thanks to multimodal imaging, especially with the advent of ultra-widefield (UWF) imaging. Blood tests and functional and genetic testing can help with the correct differential diagnosis of pseudo-PPCRA or other disorders with similar characteristics. Although the cause of PPCRA is unknown, it is possible that it has a genetic basis. In this review we provide a summary of the multimodal imaging characteristics of PPCRA, and discuss its possible pathogenesis, based on the genes that have been associated with this disease.

Hyperautofluorescent Ring Pattern in Retinitis Pigmentosa: Clinical Implications and Modifications Over Time.

Purpose: The purpose of this study was to investigate the relation among hyperautofluorescent ring patterns, visual acuity (VA), and optical coherence tomography (OCT) features in patients with retinitis pigmentosa (RP), and to describe its modifications over time. Methods: This was a retrospective, longitudinal, and observational study. Clinical and imaging data from the first and last available visits of patients with a clinical diagnosis of RP were reviewed. The ellipsoid zone (EZ) width was measured on OCT acquisitions. Short-wavelength autofluorescence (SW-AF) images were classified based on the hyperautofluorescent ring pattern as absent, regular, and irregular, and their modifications over the follow-up were described. The VA, EZ width, and progression rate were compared among the three groups. Results: One hundred eight eyes from 54 subjects were included in the study. The hyperautofluorescent ring was not present in 28 eyes (25.9%), appeared regular in 45 eyes (41.7%), and had an irregular pattern in 35 eyes (32.4%). The three groups differed in terms of age, VA, and EZ width (all P < 0.05). Additionally, the absence of a hyperautofluorescent ring indicated a faster rate of progression (P < 0.001). Throughout the follow-up period, 17 eyes (15.7%) experienced a change in the AF pattern, with irregular rings being more commonly affected. Conclusions: The hyperautofluorescent ring is a useful tool to frame patients based on their EZ width and VA. We described its possible modifications over time, the knowledge of which can aid clinicians in the interpretation of imaging finding changes of their patients.

The Clinical Role of the Choroidal Assessment in High Myopia: Characteristics and Association With Neovascular and Atrophic Complications.

Purpose: To investigate the clinical utility of choroidal quantitative assessment associated with the presence of macular neovascularization (MNV) or atrophy in high myopia. Methods: The study was designed as a retrospective case series with two-year follow-up. We measured choroidal thickness (CT) and the presence and subtype of dome-shaped macula (DSM). In DSM eyes we also calculated the presence and type of choroidal deepening (CD). The eyes were categorized as Subgroup 1 (high myopia without complications), Subgroup 2 (high myopia complicated by MNV), and Subgroup 3 (high myopia complicated by macular or posterior pole atrophy). Main outcome measures were the detection of significant CT cutoffs associated with the three subgroups of eyes and the clinical impact of DSM and CD subtypes. Results: Our cohort (190 eyes affected by high myopia) was categorized as Subgroup 1 (66 eyes), Subgroup 2 (72 eyes) and Subgroup 3 (52 eyes). Baseline CT values allowed to separate the subgroups with myopic-related complications (area under the curve = 0.85; P < 0.05). In Subgroup 1, vertical DSM was the most frequent (54%), with CD absence characterizing the 46% of cases. Round DSM was the most represented subtype in Subgroup 2 (49%), with 55% of sub-dome CD subtypes; in these cases, MNV resulted always localized in the fovea. Subgroup 3 equally shown horizontal or vertical DSM (53% and 47%, respectively), with 80% of cases showing peri-dome CD. Conclusions: Choroidal quantitative assessment can categorize three high myopia subgroups. MNV subgroup is characterized by intermediate choroidal thinning and higher prevalence of round DSM with sub-dome CD.