Retinal Vessel Analysis and Microvascular Abnormalities in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

Background: Philadelphia-negative chronic myeloproliferative neoplasms are a group of clonal hematopoietic disorders including polycythemia vera, essential thrombocythemia, and primary myelofi-brosis. These neoplasms are characterized by an increased risk of thrombotic complications. Several studies have highlighted that the study of vessels of the retina offers the opportunity to visualize, in vivo, the damage to microcirculation that is common in various systemic pathologies. Methods: in our study, forty patients underwent an ophthalmological examination, using non-invasive imaging tech-niques, for analyses of their retinal vascularization. The objective was to correlate the findings ob-tained from this study of the retina with different markers of thrombotic risk, to demonstrate the usefulness of studying retinal vessels as a possible new prognostic biomarker of thrombotic risk in patients affected by Philadelphia-negative chronic myeloproliferative neoplasms. Results: retinal imaging demonstrated changes in the microcirculation, with a reduced vascular density of the deep and superficial capillary plexuses with respect to a normal group, and a correlation between retinal changes and blood parameters. Conclusions: additional research will allow us to determine whether retinal changes in individuals with chronic myeloproliferative neoplasms could be predictive of the development of thrombotic events in these subjects.

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.

Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.

INTRODUCTION: Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. METHODS: This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. RESULTS: We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). CONCLUSIONS: We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020.

BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Estimates are age-standardized using the GBD standard population. RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%). CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.

Linear streaks associated with retinitis pigmentosa.

PURPOSE: To describe a phenotypical manifestation characterized by the identification of peripheral linear streaks associated with retinitis pigmentosa (RP). METHODS: Study design is a prospective observational case series. All consecutive patients affected by RP underwent a complete ophthalmological examination. The diagnosis of peripheral linear streaks was based on the identification of curvilinear atrophic streaks in the periphery of the retina. RESULTS: Overall, six out of 140 patients (4.2%) were affected by peripheral linear streaks associated with RP. A single patient showed also punched out chorioretinal lesions at the posterior pole, with macular neovascularization development over the follow-up, treated with ranibizumab injections. CONCLUSIONS: RP phenotypical manifestation characterized by peripheral linear streaks is infrequent and may provide additional evidence to support the contribution of inflammation in the pathogenesis of RP.

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.

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.

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.

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.

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.

Smartphone Eye Examination: Artificial Intelligence and Telemedicine.

Background: The current medical scenario is closely linked to recent progress in telecommunications, photodocumentation, and artificial intelligence (AI). Smartphone eye examination may represent a promising tool in the technological spectrum, with special interest for primary health care services. Obtaining fundus imaging with this technique has improved and democratized the teaching of fundoscopy, but in particular, it contributes greatly to screening diseases with high rates of blindness. Eye examination using smartphones essentially represents a cheap and safe method, thus contributing to public policies on population screening. This review aims to provide an update on the use of this resource and its future prospects, especially as a screening and ophthalmic diagnostic tool. Methods: In this review, we surveyed major published advances in retinal and anterior segment analysis using AI. We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for published literature without a deadline. We included studies that compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting prevalent diseases with an accurate or commonly employed reference standard. Results: There are few databases with complete metadata, providing demographic data, and few databases with sufficient images involving current or new therapies. It should be taken into consideration that these are databases containing images captured using different systems and formats, with information often being excluded without essential detailing of the reasons for exclusion, which further distances them from real-life conditions. The safety, portability, low cost, and reproducibility of smartphone eye images are discussed in several studies, with encouraging results. Conclusions: The high level of agreement between conventional and a smartphone method shows a powerful arsenal for screening and early diagnosis of the main causes of blindness, such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. In addition to streamlining the medical workflow and bringing benefits for public health policies, smartphone eye examination can make safe and quality assessment available to the population.

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.

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.

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.

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.

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.

The Localization of Intraretinal Cysts Has a Clinical Role on the 2-Year Outcome of Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the relationship between ≥ 1 localizations of intraretinal fluid (IRF) within retinal layers and the 2-year outcome in a cohort of neovascular age-related macular degeneration (AMD) eyes. DESIGN: Retrospective case series. PARTICIPANTS: Two hundred forty-three eyes of 243 AMD patients affected by type 1 and type 2 macular neovascularization (MNV). METHODS: We analyzed data considering MNV onset, 1-year, and 2-year timepoints. Optical coherence tomography images were used to classify MNV types, distinguish different types of fluids and assess IRF localization within retinal layers. A subcohort of eyes were also analyzed by OCT angiography. MAIN OUTCOME MEASURES: The association between IRF cyst localization and both visual outcome and onset of outer retinal atrophy at 2-year follow-up. RESULTS: Macular neovascularizations were distributed as type 1 (69%) and type 2 (31%). The mean number of intravitreal injections was 7 ± 2 at 1-year follow-up and 5 ± 2 at 2-year follow-up. Baseline best-corrected visual acuity was 0.4 ± 0.3 logarithm of the minimum angle of resolution, improving to 0.3 ± 0.4 at 2-year follow-up (P < 0.01). Outer retinal atrophy occurred in 24% of cases at 1 year and 39% of cases at 2-year follow-up. Intraretinal fluid localizations at the level of IPL-INL and OPL-ONL at baseline were associated with the worst functional and anatomical outcome. Moreover, the presence of IRF at baseline was associated with greater impairment of the intraretinal vascular network. CONCLUSIONS: The localization of IRF at the level of IPL-INL and OPL-ONL retinal layers represents a negative prognostic biomarker for the morphologic and functional outcomes of neovascular AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association Between Genotype and Phenotype Severity in ABCA4-Associated Retinopathy.

Importance: ABCA4-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. Objective: To investigate genotype-phenotype correlations in ABCA4-associated retinopathy. Design, Setting, and Participants: This 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. Exposure: Genotype, 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 Measures: Total decreased autofluorescence (TDAF) and definitely decreased autofluorescence (DDAF) areas, inner and outer retinal volumes, and the respective progression rate. Results: A 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 Relevance: In 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.

Ocular surface in posterior segment surgery.

Nowadays, the technological breakthroughs of mini-invasive vitreo-retinal surgery improved the perioperative management and the outcomes of millions of patients. The most common procedures include pars plana vitrectomy, episcleral surgery, intravitreal injections, and laser photocoagulation. Potential sight and non-sight-threatening side effects have been reported during the follow-up period. Ocular surface disbalance can be induced by the aforementioned procedures, resulting in mild to severe ocular discomfort symptoms. This condition may recognize different causes such as pre-existing or concomitant diseases of the external eye, the surgical procedure damage of the anatomical or physiological structures of the ocular surface, the prolonged side effects induced by the chronic topical treatment that may be toxic to the external eye.In addition to the most frequent dry eye-related signs and symptoms, subconjunctival haemorrhages, corneal epithelium damage, partial loss of corneal sensitivity or changes in corneal nerve density could postoperatively affect our patients.In conclusion, any surgical trauma directed to the posterior segment of the eye may cause the loss of the ocular surface homeostasis. Ophthalmologists should not only recognise and treat, but possibly prevent, all patients' symptoms that could manifest in the postoperative time.