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Purpose: The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in neovascular age-related macular degeneration (AMD)., Methods: The study was designed as a cross-sectional case series. We collected data from already treated macular neovascularization (MNV), characterized by (I) clinically relevant recurrent exudation, (II) nonclinically relevant recurrent exudation, and (III) inactive lesion. We proposed a new OCTA metric, calculating the gap between high-resolution (HR) and high-speed (HS) OCTA samplings, hypothesizing that this gap might improve the detection of new secondary MNV branches, being also associated with exudation recurrence. Main outcome measures were the HR-HS gap-based categorization of MNV lesions and the assessment of its association with exudative, minimally exudative, and inactive lesions., Results: Our cohort (which consisted of 32 MNV eyes; 32 patients; mean disease duration 5 years) was classified as type 1 (17; 53%), type 2 (11; 34%), or mixed type (4; 13%) MNV. Subretinal fibrosis was found in 17 out of 32 eyes (53%), whereas outer retinal atrophy involved 22 of 32 eyes (69%). HR-HS MNV gap was significantly different among MNV subgroups: 18% for the exudative subgroup, 12% for the minimally exudative subgroup, and 4% for the inactive subgroup. HR-HS gap significantly correlated with best corrected visual acuity (BCVA), disease duration, fibrosis, and outer retinal atrophy., Conclusions: HR-HS gap is a novel quantitative metric to detect the secondary novel branches of AMD-related MNV. This parameter is clinically relevant because it is associated with fluid recurrence. The integration of HR-HS gap in artificial intelligence models might help to predict MNV reactivation and to optimize treatment strategies.

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., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Prof. Francesco Bandello is the Editor in Chief of EJO but he was not involved in the evaluation procedure of the present study. Francesco Bandello is consultant for Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California,USA), Farmila-Thea (Clermont-Ferrand, France), Bausch & Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), Novagali Pharma (Évry, France), Novartis (Basel, Switzerland), Bayer Shering-Pharma (Berlin, Germany), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA), Pfizer (New York, USA), Sanofi-Aventis (Paris, France), Santen (Osaka, Japan), Sifi (Aci Sant’Antonio, Italy), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA). All other authors have no financial disclosure.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

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.

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., Competing Interests: Conflict of interest: no conflict of interest exists for any author.

Purpose: To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes., Methods: Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences., Results: Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters., Conclusion: While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

Purpose: To report a case of Pigmented Paravenous Chorioretinal Atrophy (PPCRA) associated with a novel RPGRIP1 dominant variant., Methods: Case report. The patient underwent multimodal retinal imaging, including spectral-domain optical coherence tomography (OCT), OCT Angiography (OCTA), blue-light autofluorescence (BAF), and ultra-widefield pseudocolor retinography and autofluorescence. Genetic testing was performed using next-generation sequencing., Results: A 67-year-old male presented with a clinical suspicion of retinitis pigmentosa. His best-corrected visual acuity was 20/32 in the right eye and 20/200 in the left eye. On fundus examination, paravenous pigment clumping and chorioretinal atrophy were seen bilaterally, matching confluent hypoautofluorescent areas departing from the optic disc. This clinical presentation suggested a case of PPCRA. Genetic testing found a heterozygous deletion of nucleotide 631 (c.631del) in the RPGRIP1 gene, a frameshift variant that generates a premature stop codon (p.Ser211Valfs*64) and therefore results in a truncated or absent protein product. The variant was regarded as likely pathogenic (class IV)., Conclusion: In this report, we describe a case of PPCRA in association with a novel, likely pathogenic c.631del, p.Ser211Valfs*64 variant in RPGRIP1 , a gene that has been associated with Leber congenital amaurosis and cone-rod dystrophy. Our case expands the spectrum of genes associated with PPCRA and prompts further studies to ascertain the molecular etiopathogenesis of this disease.

Background: Schubert-Bornschein (SB) is the most common type of people with congenital stationary night blindness (CSNB). The aim of the study is to describe the optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) findings in patients with SB CSNB., Methods: Prospective, observational case series including three patients with genetically confirmed CSNB along with matched controls, who underwent complete ophthalmic examination and multimodal imaging., Results: On SD-OCT, a significant focal outer plexiform layer (OPL) thickening and a corresponding focal outer nuclear layer (ONL) thinning were identified in the macular area (p < 0.001). OCTA analysis overall showed decreased density of macular deep capillary plexus (mDCP) and macular choriocapillaris (mCC) (p = 0.008 and p = 0.033, respectively). DCP vessel density in the area corresponding to OPL thickening was significantly increased compared to the remaining retina (p < 0.001)., Conclusion: SB CSNB is characterized by retinal vascular impairment, as detected on OCTA.

Purpose: The development of optical coherence tomography angiography (OCTA) has radically changed the diagnostic assessment of the intraretinal vascular network. Two different OCTA acquisition modalities have recently been introduced in clinical practice, namely high-resolution (HR) and high-speed (HS) scans. HR OCTA requires more acquisition time and provides higher quality data, whereas HS OCTA is faster but furnishes lower quality data. The main aim of the present study is to gauge how much extra blood flow perfusion information can be obtained through the combined use of HR and HS OCTA., Methods: We compared HR and HS OCTA acquisitions to assess the reliability of both techniques, also putting forward a new set of quantitative metrics to measure the HR/HS OCTA gap and to highlight different perfusion information., Results: In essence, both HR and HS OCTA acquisitions proved highly feasible in detecting the intraretinal vascular flow signal, as confirmed by the stability of quantitative OCTA metrics, thus displaying their suitability for use in clinical practice. We detected an HR/HS overlapping gap of 21.6 ± 6.5% for intraretinal capillaries, and 4.3 ± 1.2% for choriocapillaris, highlighting the greater information obtained by HR OCTA., Conclusions: This novel HR/HS OCTA gap assessment might pave the way for the development of new quantitative metrics for retinal diseases that would focus on the earlier detection of perfusion impairment and relate it to the stage of the disease and its progression., Translational Relevance: This study proposes a new quantitative way to detect different perfusion signals based on OCTA. The findings presented in this paper can lay the foundations for the development of new quantitative metrics focused on the separate analysis of high flow and low flow signals, enabling very early changes in intraretinal perfusion to be detected.

Introduction: Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD., Methods: The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm)., Results: LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed., Conclusion: These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD., Trial Registration: Clinicaltrial.Gov Registration Identifier: NCT03878420., (© 2022. The Author(s).)

Purpose: This study assesses the repeatability of quantitative autofluorescence (qAF) in a multicenter setting and evaluates qAF as the end point for clinical trials in recessive Stargardt disease 1 (STGD1)., Methods: A total of 102 patients with STGD1 underwent qAF imaging as part of the Stargardt Remofuscin Treatment Trial (STARTT; EudraCT No. 2018-001496-20). For 166 eyes, we obtained qAF imaging at 2 visits, with 2 recordings per visit. The qAF8 values were independently determined by the study site and a central reading center. Intra- and inter-visit reproducibility, as well as interobserver (study site versus reading center) reproducibility were obtained using intraclass correlation (ICC), one-sample t-test, and Bland-Altman coefficient of repeatability., Results: The qAF repeatability was ± 26.1% for intra-visit, ± 40.5% for inter-visit, and ± 20.2% for the interobserver reproducibility measures. Intra-visit repeatability was good to excellent for all sites (ICC of 0.88-0.96). Variability between visits was higher with an overall ICC of 0.76 (0.69-0.81). We observed no significant difference in qAF values across sites between visits (7.06 ± 93.33, P = 0.238)., Conclusions: Real-life test-retest variability of qAF is higher in this set of data than previously reported in single center settings. With improved operator training and by selecting the better of two recordings for evaluation, qAF serves as a useful method for assessing changes in autofluorescence signal., Translational Relevance: The qAF can be adopted as a clinical trial end point, but steps to counterbalance variability should be considered.

Background: The diagnosis of inherited retinal diseases (IRDs) can only be confirmed through genetic testing. The aim of our study is to investigate the propensity of Italian patients affected by IRDs to undergo genetic testing., Materials and Methods: One hundred and thirty-two patients diagnosed with IRDs referred to Italian Retina Onlus were enrolled from 1 st January 2021 to 31 th December 2021 in this cross-sectional study to answer to a twelve-item questionnaire., Results: One hundred and four patients were aware of the possibility of taking a genetic test, and 94 of them did. Most of genetically tested patients (93.6%) had been informed about advantages and limitations of genetic investigations. The most common reason for undergoing genetic testing was to gather information for their relatives, while the most frequent reason for patients not taking the test was lack of someone who encourages them to do so. Most of genetically tested patients believed that the results could aid medical research in the search for a treatment for IRDs, while who did not undergo DNA testing often did not have a clear opinion on the topic. Almost all patients (98.9%) performed the test through the Italian National Health System., Conclusions: Our study investigated the tendency of Italian patients affected by IRDs to undergo genetic testing, highlighting the importance of educating both patients and healthcare professionals on this topic.

Purpose: To describe the multimodal imaging characteristics of benign foveal depigmentation., Methods: The study was designed as prospective observational case series. Patients with benign foveal depigmentation were prospectively investigated by means of multimodal imaging, including blue-light and near-infrared fundus autofluorescence, optical coherence tomography (OCT), OCT angiography, color testing, microperimetry, and electrophysiology. The main outcome measures were vessel density and retinal pigment epithelium (RPE)/photoreceptor complex OCT reflectivity., Results: Overall, 4 patients were identified, with bilateral and unilateral involvement in 1 case and 3 cases, respectively. Fundus autofluorescence provided variable results, showing more impairment on near-infrared fundus autofluorescence. Structural OCT revealed slight attenuation of the outer retinal bands in the area affected by benign foveal depigmentation, associated with choroidal hypertransmission, whereas enface OCT better delineated the attenuation of the reflectivity signal. The mean reflectivity intensity of RPE/photoreceptor complex was statistically significantly reduced in patients with respect to control subjects in the benign foveal depigmentation area. Optical coherence tomography angiography, color testing, microperimetry, electrooculogram, and electroretinogram findings were normal., Conclusion: Benign foveal depigmentation may represent a focal RPE disease. The limited alterations within the RPE band, as visualized on enface OCT and confirmed on near-infrared fundus autofluorescence, suggest an impairment in melanin production or distribution within the RPE cells.

Background: Vascular endothelial growth factor (VEGF) is a significant modulator of ocular angiogenesis, including that of neovascular age-related macular degeneration (nAMD). Intravitreal injection of anti-VEGF is the benchmark treatment for most retinal vascular diseases, including nAMD, diabetic maculopathy, and macular edema secondary to retinal venous occlusion. Anti-VEGF treatment is a high-frequency, time-consuming, non-cost-effective therapy, especially in countries and regions with limited resources. This treatment is easily restricted, and in practice, maintaining long-term periodic care is challenging for patients., Hypothesis: Light peripheral panretinal photocoagulation (PPRP) is applied in a mild form (barely visible mild light gray mark) anterior to the equator so as not to jeopardize the visual field. PPRP lessens the ischemia that causes neovascularization and decreases the metabolic demand in the peripheral retina. PPRP reduces serum angiopoietin-2 and VEGF levels in patients with type 2 diabetes mellitus with proliferative diabetic retinopathy. We propose using light PPRP to suppress VEGF secretion, aiming to attenuate the VEGF drive and halt choroidal neovascular growth in eyes with nAMD. Our regimen is based on two concepts: first, nAMD is a diffuse or generalized disease that affects the posterior segment; and second, PPRP is very effective in regressing diabetic retinopathy. PPRP has reportedly been successful in cases of macular edema (diabetic or following venous occlusion) resistant to VEGF antagonists. Light PPRP may be used as prophylaxis, adjunctive treatment, or monotherapy in nAMD when intravitreal injections of VEGF antagonists are not feasible., Conclusions: The established light PPRP therapy could be promising as a one-time, cost-effective therapy or prophylaxis in patients with nAMD or at high risk. This proposed modality could be suitable for patients who have injection phobia or prefer a one-time affordable therapy to the long-term monthly visits to retinologists. Future trials are necessary to verify the safety and efficacy of this proposed treatment modality in selected patients with nAMD., Competing Interests: None, (© Author(s).)

Objectives: To analyse the entity of retinal vasculitis, including frosted branch angiitis (FBA), or retina vascular occlusion in patients with familial Mediterranean fever (FMF)., Methods: Retrospective collaborative case series using invitation by email to uveitis specialists around the Mediterranean basin. This series was combined with a literature review. Exclusion criteria included infectious diseases, Behçet's disease or other autoimmune diseases., Results: A total of 16 patients (21 eyes) had FMF and retinal vasculitis (FBA 11 patients, mild retinal vasculitis 5 patients). The mean age at onset of vasculitis was 29.5 ± 13.4 (range 9-62) with a female to male ratio of 9 to 7. In 19 eyes treated with various forms of corticosteroid and/or immunosuppression, the mean initial spectacle-corrected visual acuity improved from 6/194 to 6/10.5 at the last mean follow-up of 29.0 ± 34.9 months (p < 0.001). The most common FEVR mutations were M680I and M694V. In addition, retinal vascular occlusions included one case of central retinal artery occlusion and one case of branch retinal artery occlusion., Conclusion: FBA and milder forms of retinal vasculitis are associated with FMF. Therapy involves an increase in colchicine dosage in early cases, a long period of oral corticosteroid, intravitreal dexamethasone implant or periocular corticosteroid in select cases, and combination therapy with systemic immunosuppression in severe cases. FMF needs to be included in the differential diagnosis of retinal vasculitis., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To ascertain the anatomic factors that help achieve non-surgical sealing in full thickness macular hole (FTMH)., Methods: Retrospective collaborative study of FTMH that closed without surgical intervention., Results: A total of 78 patients (mean age 57.9 years) included 18 patients with blunt ocular trauma, 18 patients that received topical or intravitreal therapies and 42 patients with idiopathic FTMH. Mean±SD of the initial corrected visual acuity (VA) in logMAR improved from 0.65±0.54 to 0.34±0.45 (p<0.001) at a mean follow-up of 33.8±37.1 months. FTMH reopened in seven eyes (9.0%) after a mean of 8.6 months. Vitreomacular traction was noted in 12 eyes (15.8%), perifoveal posterior vitreous detachment in 42 (53.8%), foveal epiretinal membrane in 10 (12.8%), cystoid macular oedema (CME) in 49 (62.8%) and subretinal fluid (SRF) in 20 (25.6%). By multivariate analysis, initial VA correlated to the height (p<0.001) and narrowest diameter of the hole (p<0.001) while final VA correlated to the basal diameter (p<0.001). Time for closure of FTMH (median 2.8 months) correlated to the narrowest diameter (p<0.001) and the presence of SRF (p=0.001). Mean time for closure (in months) was 1.6 for eyes with trauma, 4.3 for eyes without trauma but with therapy for CME, 4.4 for eyes without trauma and without therapy in less than 200 µm in size and 24.7 for more than 200 µm., Conclusion: Our data suggest an observation period in new onset FTMH for non-surgical closure, in the setting of trauma, treatment of CME and size <200 µm., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe a case of paracentral acute middle maculopathy associated with central retinal vein occlusion in a patient affected by amyloid light-chain amyloidosis., Methods: One patient with confirmed diagnosis of amyloid light-chain amyloidosis, displaying paracentral acute middle maculopathy and central retinal vein occlusion, was recruited. The patient underwent complete ophthalmologic examination and multimodal imaging, including: fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography., Results: Fundus autofluorescence showed a ferning pattern, corresponding to linear hypofluorescence in late-phase indocyanine green angiography and delayed venous filling, detected by fluorescein angiography. Structural optical coherence tomography revealed a hyper-reflective line located in the outer plexiform layer, corresponding to the prominent middle limiting membrane, along with several placoid lesions. Optical coherence tomography angiography found that the superficial capillary plexus was preserved, whereas vessel density was reduced in both the deep capillary plexus and the choriocapillaris. After 1 year of follow-up, the patient achieved an almost complete morphological recovery., Conclusion: Multimodal imaging described in depth the morphological features of a case of combined paracentral acute middle maculopathy and central retinal vein occlusion in a patient affected by amyloid light-chain amyloidosis., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts., Design: Delphi-based survey., Subjects, Participants, And/or Controls: Twenty-five retinal vascular disease and OCTA imaging experts., Methods, Intervention, or Testing: A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of "wide-field (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: "strong consensus" was defined as ≥85% agreement, "consensus" as 80% to 84%, and "near consensus" as 70% to 79%., Main Outcome Measures: Consensus and near consensus on OCTA nomenclature in retinal vascular disease., Results: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of "no-flow areas," and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round., Conclusions: This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: To analyse multimodal imaging alterations in the subclinical form of best vitelliform macular dystrophy (BVMD)., Methods: The study was designed as an observational, cross-sectional case series. Eleven eyes of 7 subclinical patients with BVMD and 12 age-matched and sex-matched controls were included. Multimodal imaging included fundus blue-light autofluorescence, near-infrared autofluorescence (NIR-AF), structural optical coherence tomography (OCT) and OCT angiography (OCTA). The quantitative analysis included the calculation of the following parameters: vessel density (VD), vessel tortuosity (VT), vessel dispersion (Vdisp), vessel rarefaction (VR), foveal avascular zone (FAZ) area, reflectivity of the outer retinal bands and choriocapillaris porosity (CCP)., Results: Mean best-corrected visual acuity was 0.0±0.0 LogMAR in both groups. The round central hypoautofluorescent alteration on NIR-AF corresponded to a significant reflectivity attenuation of the outer retinal bands on structural OCT (0.55±0.18 vs 0.75±0.08; p<0.001). VD, VT, VR and Vdisp were normal compared with controls (all p>0.05). The FAZ area turned out to be significantly restricted at the level of the deep capillary plexus in subclinical BVMD eyes (p<0.001). Furthermore, quantitative OCTA revealed a significant central increase of CCP, compared with controls (18.25±2.43 vs 4.58±1.36; p<0.001)., Conclusions: The subclinical stage of BVMD is characterised by significant alterations of the outer retinal bands and the choriocapillaris. Quantitative multimodal imaging assessment suggests that subclinical BVMD is affected by the functional impairment of the outer retinal structures, leading to an alteration in melanin and growth factor production., Competing Interests: Competing interests: FB consultant for Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Farmila-Thea (Clermont-Ferrand, France), Bayer Shering-Pharma (Berlin, Germany), Bausch and Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), NovagaliPharma (Évry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up., Methods: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models., Results: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008)., Conclusion: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.

Purpose: To differentiate acute central serous chorioretinopathy (CSC) subtypes by multimodal imaging., Methods: The research was designed as a prospective, interventional study. Naive patients with acute CSC were followed for 24 months. Overall, 96 CSC patients (96 eyes) and 210 controls (210 eyes) were included. Multimodal imaging allowed the study to classify CSC into retinal pigment epithelium-related CSC (RPE-CSC) and choroidal-related CSC (choroidal-CSC) subtypes. The RPE-CSC type was characterized by normal choroidal thickness (CT) in association with disseminated RPE alterations. The choroidal-CSC type was distinguished by identifying a pachychoroid. All the patients underwent eplerenone or verteporfin photodynamic therapy (PDT). Patients developing macular neovascularization (MNV) underwent anti-VEGF injections. Quantitative measurements included central macular thickness (CMT), choroidal thickness (CT), Sattler layer thickness (SLT) and Haller layer thickness (HLT)., Results: Considering the CSC patients as a whole, baseline BCVA was 0.18 ± 0.25 LogMAR, increasing to 0.13 ± 0.21 LogMAR after 24 months (P < 0.01), whereas baseline CMT improved from 337 ± 126 µm to 244 ± 84 µm after 24 months (P < 0.01). We found the following subdivision of CSC eyes: RPE-CSC type (45%) and choroidal-CSC type (55%). Overall, MNV were detected in 18 eyes (19%), 13 eyes (72%) in the RPE-CSC subgroup and five eyes (28%) in the choroidal-CSC subgroup. Forty eyes responded to eplerenone (57% of RPE-CSC and 47% of choroidal-CSC), whereas 38 eyes required PDT (43% of RPE-CSC and 53% of choroidal-CSC)., Conclusions: Acute CSC includes two main clinical manifestations, displaying differing features concerning retinal and choroidal involvement., Translational Relevance: This study identified two clinically different acute CSC subtypes on the basis of quantitative pachychoroid cutoff values.

Purpose: The purpose of this study was to investigate the effects of the extension of collateral vessels on the outcomes of eyes affected by central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO)., Methods: The study was designed as a cross-sectional case series. Patients affected by CRVO and BRVO were progressively recruited, along with an age- and sex-matched control group of healthy subjects. Structural optical coherence tomography (OCT) and OCT angiography (OCTA; 4.5 × 4.5 mm and 9.0 × 9.0 mm acquisitions) were performed on all participants in order to assess the relationship between the presence of collateral vessels and final anatomical outcomes - central macular thickness (CMT), foveal avascular zone - and functional outcomes - best corrected visual acuity (BCVA)., Results: Fifty-six eyes affected by CRVO and 47 eyes affected by BRVO were included. Baseline LogMAR BCVA was 0.41 ± 0.33 LogMAR in CRVO, and 0.39 ± 0.25 LogMAR in BRVO (P < 0.01), improving to 0.20 ± 0.26 LogMAR in CRVO (P < 0.01), and 0.19 ± 0.22 LogMAR in BRVO (P < 0.01). Baseline CMT was 511 ± 214 µm in CRVO and 482 ± 178 µm in BRVO (P > 0.05), decreasing to 328 ± 105 µm (P < 0.01) and 321 ± 78 µm in CRVO and BRVO, respectively (P < 0.01). Collateral vessels were detected in 16 of 56 eyes (29%) in CRVO and in 47 of 47 eyes (100%) in BRVO. Their extension was correlated with worse anatomic and visual outcomes. Remarkably, no correlation was found with peripheral capillary nonperfusion and vessel density impairment., Conclusions: The present study demonstrates that collateral vessel extension is associated with worse anatomic and functional outcomes in patients affected by CRVO and BRVO.

Purpose: To describe a clinical picture resembling classic multiple evanescent white dot syndrome (MEWDS) potentially triggered by previous or concurrent, apparently unrelated, ocular events and to provide a literature review of similar presentations., Design: Retrospective chart series and literature review., Participants: Consecutive patients diagnosed with MEWDS at the Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and the IRCCS San Raffaele Scientific Institute, Milan, Italy, between July 2019 and June 2020., Methods: Charts of patients were reviewed. Ophthalmic history, best-corrected visual acuity, spectral-domain OCT results, OCT angiography results, fundus autofluorescence results, ultra-widefield fluorescein angiography results, and indocyanine green angiography results were collected. A PubMed-based search was carried out for similar presentations using the terms MEWDS and white spot syndromes., Main Outcome Measures: An ocular history positive for previous or concurrent ocular events in patients with MEWDS was sought in our cohort and the existing literature., Results: Five eyes of 4 patients (2 females; age range, 16-81 years) were included. The first eye had a history of bilateral Best vitelliform dystrophy and unilateral choroidal neovascularization. The second eye had angioid streaks complicated by choroidal neovascularization and underwent prior thermal laser photocoagulation. The third eye had a history of high myopia and a scleral buckle procedure for retinal detachment. The fourth patient had bilateral idiopathic retinochoroiditis. We identified 16 case reports from 5 previous publications that support a MEWDS-like reaction to previous ocular insults., Conclusions: We suggest a MEWDS-like reaction may be elicited by ocular events in a subset of susceptible patients. We hypothesize that damage to the outer retina may play a role in triggering the local inflammatory response., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)