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To use multimodal assessment (fluorescein angiography [FA], color fundus photography [CFP], and/or spectral domain OCT [SD-OCT]) to reevaluate macular atrophy (MA) and macular neovascularization (MNV) type in the HARBOR trial according to the Consensus on Neovascular AMD Nomenclature criteria; and to determine if there are any associations between baseline demographic factors, ocular characteristics, and/or treatment for neovascular age-related macular degeneration (nAMD) and the development of MA by month 24.Post hoc analysis of the phase 3, randomized, multicenter, double-masked, controlled HARBOR trial (NCT00891735).Nine hundred twenty-two study eyes and 919 fellow eyes from the HARBOR trial.This post hoc analysis included patients with multimodal assessments on FA, CFP, and SD-OCT at baseline. A risk analysis for the development of MA was performed by multimodal assessment and SD-OCT on study eyes without MA at baseline that had completed SD-OCT assessments for MA at month 24.Development of MA in study eyes at month 24 and a risk analysis for developing MA at month 24 in study eyes that had no MA at baseline, as assessed by multimodal assessment.Of 1097 patients in the HARBOR trial with nAMD and active subfoveal MNV, a total of 922 study eyes and 919 fellow eyes were included in the multimodal analysis of MNV. MA assessment was performed on SD-OCT. Of these, 593 had no baseline MA and were included in the risk analysis for developing MA. In eyes with no detectable MA at baseline, a larger proportion of eyes with any MNV type 3 (including mixed type) at baseline developed new MA at month 24 (49.2%) than eyes with MNV type 1 (26.5%), type 2 (29.1%), or mixed type 1 and 2 (34.6%). MNV type 3 and fellow eye MA were identified as risk factors for new MA development at month 24.MNV type 3 was a strong risk factor for new MA development at month 24, with fellow eye MA also being identified as a predictor. No other variables, including ranibizumab treatment, were identified as risk factors for new MA development.

To describe the presence of specific morphological characteristics of idiopathic, full-thickness macular hole (MH) potentially influencing postoperative best corrected visual acuity (BCVA) and surgical outcomes.Retrospective, multicenter and interventional case series.Clinical charts and multimodal imaging pictures of 149 eyes of 143 consecutive patients diagnosed with MH, treated surgically and with a minimum follow-up of 12 months, were reviewed.Supra-retinal pigment epithelium (RPE) granular deposits were diagnosed in 121 of 149 eyes (81.2%). A smooth morphology was identified in 58 of 149 eyes (38.9%), whereas a bumpy border was present 91 of 149 eyes (61.1%). Photoreceptor disruption was mainly located close to the MH aperture. In 8% of the included cases, preoperative anatomical progression from smooth to bumpy morphology was noted. The presence of supra-RPE granular deposits was a significant predictor of lower postoperative BCVA only in univariate analysis (P.001). The presence of a bumpy border was significantly correlated with lower postoperative BCVA in both univariate and multivariate analysis (P.001). BCVA gain was significantly lower in MH with bumpy borders (P.001). A bumpy border was also significantly associated with poor postoperative anatomical restoration (P.001).Supra RPE-granular deposits and a bumpy morphology may be indicators of photoreceptor disruption in MH. A bumpy morphology may suggest deeper and potentially irreversible photoreceptor damage, and may negatively influence both functional and anatomical recovery.

To describe a case of choroidal nevus with intralesional cavitations detected with enhanced depth imaging optical coherence tomography and to show its changes during an 8-year follow-up.A case report.A 55-year-old male patient was found to have a pigmented lesion at the posterior pole of his right eye, just temporal to the fovea. A complete multiimaging examination was obtained and showed a lesion of about 4 mm of diameter with a small amount of subretinal fluid and chronic changes in the retina overlying the lesion. Based on clinical examination, a diagnosis of choroidal nevus was made, but interestingly the enhanced depth imaging optical coherence tomography revealed the presence of intralesional cavitations. Close follow-up with no intervention was planned, and over 8 years of observation, the lesion remained stable in size, with a gradual increase of the central necrosis.Benign pigmented choroidal lesions can show internal cavitations likely secondary to internal necrosis. This feature does not represent a sign of malignancy of the lesion. Enhanced depth imaging optical coherence tomography is a feasible imaging tool for the visualization of the internal cavitations and to follow their evolution over time.

To compare the enlargement rates of geographic atrophy (GA) over 5 years of follow-up with those of macular atrophy (MA) associated with macular neovascularization (MNV).Retrospective, longitudinal, comparative case series.Consecutive series of patients with age-related macular degeneration and GA (dry) or with MA and MNV.Atrophic regions detected on serial registered fundus autofluorescence images were semiautomatically delineated, and the measurements of these areas were recorded every 6 ± 3 months for the first 2 years of follow-up and at yearly intervals for up to 5 years.Annual raw and square root-transformed rates of atrophy growth.The study included 117 eyes of 95 patients (61 in the GA cohort and 56 in the MA cohort); 100% and 38.5% of the eyes completed 2 and 5 years of follow-up, respectively. The mean size of lesions at baseline was similar between the 2 groups (raw: 1.74 vs. 1.53 mmThe presence of MNV was associated with a slower rate of expansion, resulting in overall smaller areas of atrophy over time. These findings support the hypothesis that MNV may protect against the progression of atrophy.

To report imaging findings, including optical coherence tomography (OCT), of a case of endogenous Aspergillus endophthalmitis in a patient with newly diagnosed acquired immunodeficiency syndrome.Observational case report.A 38-year-old patient presented with acute painful vision loss in his right eye (RE). Examination of the RE revealed anterior inflammation, vitritis and a fluffy macular infiltrate; OCT showed preretinal hyperreflective aggregates extending into the vitreous cavity with no evidence of subretinal and/or choroidal involvement. Lab tests showed leukopenia with lymphocyte T CD4+ count of 13 cells/μL and positive HIV serology. Vitreous biopsy was positive forOCT findings of this case show that ocular aspergillosis may present with disruption of the inner retinal layers and sparing of the outer retina and choroid, suggesting that

To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment5 years or daily HCQ dose5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAFThirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAFThese results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.

To investigate choroidal granulomas visualized by indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in response to treatment.Ten eyes of eight patients with tubercular, sarcoid, or Vogt-Koyanagi-Harada-associated choroidal granulomas were evaluated in this multicentric study. All patients underwent ICGA and OCTA at baseline, 1, and 3 months after treatment onset. Granulomas were identified as hypofluorescent lesions on intermediate ICGA phases. Late ICGA behavior and OCTA visualization were assessed.On baseline intermediate ICGA, 222 choroidal granulomas were detected. Overall, 174/222 granulomas were detected on baseline OCTA images. At 1 month, 28% of lesions were healed and 48 late ICGA hyperfluorescent lesions were identified. At 3 months, 63% of baseline lesions were healed, with 33 persistent late hyperfluorescent lesions. Optical coherence tomography angiography sensitivity was reduced at 1 and 3 months compared with baseline. Some flow-voids detected on OCTA at 1 and 3 months did not correspond to any visible lesion on ICGA.Different healing behaviors of choroidal granulomas were identified combining ICGA and OCTA analysis. Late ICGA hyper-fluorescent lesions may be the consequence of a possible fibrotic shift. Structural changes in the choroid may persist after active granulomas resolution resulting in persistent flow voids on OCTA.

PURPOSE: To evaluate the occurrence of retinal micro-vasculopathy in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developed coronavirus disease (COVID-19). DESIGN: Systematic review and meta-analysis. METHODS: The Pubmed and Embase databases were comprehensively searched to identify studies that reported retina vascular changes in eyes with COVID-19. Two independent reviewers selected papers and extracted data for analysis. Data of interest were extracted and analysed in RevMan Web versions 3.3. Quality of evidence was assessed using the National institute of health (NIH) quality assessment tool of case-control study. RESULTS: Thirty one studies reporting on 1373 subjects (972 COVID-19 and 401 controls) were included. Only case control studies were included in the pooled analysis. There was a significantly higher likelihood of retinal micro-vasculopathy in subjects with COVID-19 compared to controls. (odds ratio [95% confidence interval], 8.86 [2.54-27.53], p

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

To compare multimodal imaging findings in patients with choroidal lymphoma (CL).Multicenter retrospective observational case series. Multimodal imaging features of patients with CL were reviewed with particular attention to the patterns of choroidal infiltration on indocyanine green angiography (ICGA) and optical coherence tomography (OCT).Eighteen eyes of 15 patients were included in this study. Average tumor thickness on ultrasonography was 2.6 mm (range, 1.2-5.7 mm). Choroidal infiltration on ICGA was characterized by multifocal, round areas (300-500 microns diameter) of hypocyanescence in all cases, whereas OCT at the same region disclosed diffuse choroidal infiltration. By OCT, the tumor surface contour was primarily placid (22%), dome-shaped (11%), or undulating (67%).In this analysis of eyes with CL, ICGA demonstrated multifocal sub-millimeter regions of choroidal hypocyanescence whereas OCT documented diffuse choroidal infiltration. This incongruence could be a distinctive diagnostic feature of choroidal lymphoma, assisting with differentiation from other pathological entities.

PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 μm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 μm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.

PURPOSE To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

Purpose To assess changes in outer retinal layer (ORL) thickness before the development of exudative macular neovascularization (MNV) in eyes with age-related macular degeneration. Design Retrospective observational case series. Methods Eyes with age-related macular degeneration that eventually developed exudative MNV followed with sequential optical coherence tomography for ≥2 years before the exudation occurred were enrolled. The ORL thickness was automatically calculated by the optical coherence tomography software for each sector of the early treatment diabetic retinopathy study map at each follow-up visit. The ORL thickness change from baseline to the day when the exudative MNV developed was compared between sectors that eventually developed exudative MNV and those that did not. Results Forty-seven eyes (47 patients) were included. At baseline (24 ± 3 months before exudative MNV), mean (standard deviation) ORL thickness of sectors that eventually developed exudative MNV was similar to that of sectors that did not (85.2 [8.2] µm vs 86.8 [5.7] µm, P = .08). ORL thickness significantly increased in sectors that developed exudative MNV compared with those that did not (+5.8 [10.4] µm vs −2.8 [3.6] µm, P Conclusion Thickening of the ORL begins in the area where exudative MNV will develop long before the exudation, accelerating significantly in the last 2 months. The occurrence of exudative MNV could be predicted by 2 months using this simple analysis.

Purpose The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch’s membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). Methods In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity. Results Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P Conclusion Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

Purpose To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural OCT. Design Consensus meeting. Participants International group that included those with expertise in imaging and AMD basic science and histology, and those with Reading Center experience in AMD clinical trials. Methods As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA, risk of progression to GA, or both. Attendees undertook premeeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histologic features. Each of these different features were then discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees to refine the consensus definitions and descriptions further. Results Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypotransmission or hypertransmission), features frequently seen in eyes with atrophy (e.g., refractile drusen), and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits). Conclusions An international consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.

To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial.Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).Patients with GA secondary to age-related macular degeneration (AMD), n = 246.Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period.Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity.Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy.Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria.

Purpose To document by optical coherence tomography angiography the presence of a choroidal neovascularization (CNV) secondary to unilateral retinal pigment epithelium dysgenesis and describe its changes after treatment with intravitreal bevacizumab. Methods Case report. Results A 51-year-old woman referred to our ocular oncology service for a possible choroidal osteoma in her left eye was found to have a unilateral retinal pigment epithelium dysgenesis complicated by CNV. Best-corrected visual acuity at baseline was 20/200. A complete ophthalmological evaluation including color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography was performed. The CNV appeared as a tangled vascular network on optical coherence tomography angiography. After 2 intravitreal injections of bevacizumab, the best-corrected visual acuity improved to 20/50, and optical coherence tomography angiography showed a progressive contraction of the CNV. Unilateral retinal pigment epithelium dysgenesis margins remained stable at consecutive follow-up. Conclusion Optical coherence tomography angiography is a useful imaging technique for the diagnosis and follow-up of CNVs secondary to unilateral retinal pigment epithelium dysgenesis. Anti-vascular endothelial growth factor agents represent an effective therapy for the treatment of CNV in patients with this disease.

Purpose To describe a case of congenital retinal macrovessel complicated by cystoid macular edema associated with contralateral myelinated retinal nerve fibers and retinal vascular abnormalities studied with optical coherence tomography angiography (OCTA). Methods Case report. Results A healthy 25-year-old woman with decreased vision in her right eye was found to have a congenital retinal venous macrovessel in the macula associated with cystoid edema. In the contralateral amblyopic eye, the examination revealed a tuft of myelinated retinal nerve fibers along the superotemporal vascular arcade associated with superficial vascular abnormalities. A complete multi-imaging examination was obtained, including fundus color photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), and optical coherence tomography angiography. At 1-week follow-up, the optical coherence tomography displayed spontaneous resolution of the edema that remained stable at consecutive 1-month follow-up. Conclusion Congenital retinal macrovessels can be associated with other ocular developmental anomalies. Vascular complications can occur, leading to macular edema and retinal ischemia. Optical coherence tomography angiography can be useful for the diagnosis and follow-up of this condition.

Purpose To report a case of acute idiopathic maculopathy complicated by choroidal neovascularization (CNV) in which multimodal imaging was used to confirm the presence of CNV and follow the response to anti-vascular endothelial growth factor treatment. Methods A 39-year-old man was referred to our clinic for the evaluation of maculopathy in the right eye. Multimodal imaging was performed including fundus photography, fundus autofluorescence, infrared fundus reflectance (IR), optical coherence tomography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography. Results On the first examination, best-corrected visual acuity was 20/63 in the right eye and 20/20 in the left eye. A diagnosis of acute idiopathic maculopathy in the right eye was made on the basis of clinical presentation and multimodal imaging. After 3 months, best-corrected visual acuity had decreased to 20/100. Fluorescein angiography and indocyanine green angiography suggested the presence of a CNV. Optical coherence tomography angiography confirmed the presence of the CNV and well outlined the extension of the neovascular network. The patient underwent 2 monthly bevacizumab intravitreal injections. One month after the second injection, best-corrected visual acuity improved to 20/25, and optical coherence tomography angiography showed regression of the neovascular network. Best-corrected visual acuity remained stable during 20 months of follow-up. Conclusion Our case reports the uncommon association of acute idiopathic maculopathy complicated by CNV. Multiimaging approach allowed to document the features observed in this disease. Optical coherence tomography angiography was particularly useful in showing the extension of the neovascular network and response to treatment.

Background/rationaleArtificial intelligence (AI)-based clinical decision support tools, being developed across multiple fields in medicine, need to be evaluated for their impact on the treatment and outcomes of patients as well as optimisation of the clinical workflow. TheRAZORBILLstudy will investigate the impact of advanced AI segmentation algorithms on the disease activity assessment in patients with neovascular age-related macular degeneration (nAMD) by enriching three-dimensional (3D) retinal optical coherence tomography (OCT) scans with automated fluid and layer quantification measurements.MethodsRAZORBILLis an observational, multicentre, multinational, open-label study, comprising two phases: (a) clinical data collection (phase I): an observational study design, which enforces neither strict visit schedule nor mandated treatment regimen was chosen as an appropriate design to collect data in a real-world clinical setting to enable evaluation inphase IIand (b) OCT enrichment analysis (phase II): de-identified 3D OCT scans will be evaluated for disease activity. Within this evaluation, investigators will review the scans once enriched with segmentation results (i.e., highlighted and quantified pathological fluid volumes) and once in its original (i.e., non-enriched) state. This review will be performed using an integrated crossover design, where investigators are used as their own controls allowing the analysis to account for differences in expertise and individual disease activity definitions.ConclusionsIn order to apply novel AI tools to routine clinical care, their benefit as well as operational feasibility need to be carefully investigated.RAZORBILLwill inform on the value of AI-based clinical decision support tools. It will clarify if these can be implemented in clinical treatment of patients with nAMD and whether it allows for optimisation of individualised treatment in routine clinical care.

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). 1 , 2 , 3 , 4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment. 1 , 2 , 3 , 4 , 5 , 6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms “optical coherence tomography angiography” or “OCT angiography” or “OCT-A”, AND “neovascular macular degeneration” or “neovascular age-related macular degeneration” or “neovascular AMD” or “nAMD” or “wet age-related macular degeneration” or “wet AMD” or “wet ARMD”. A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.

To investigate the influence of age on the thickness of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex and the quantitative autofluorescence (qAF) and to study the possible correlation existing between these 2 parameters in a healthy White population.Cross-sectional, observational study.Healthy White volunteers aged 18 to 65 years.All subjects underwent spectral domain OCT (SD-OCT) and qAF imaging with the Heidelberg HRA-Spectralis (Heidelberg Engineering, Heidelberg, Germany). Spectral domain OCT images were analyzed using the in-built graph-based automatic segmentation algorithm for single retinal layer identification to assess RPE/BM complex thickness in vivo. The thickness values of both inner and outer rings of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, generated by the software using the "RPE" segmentation, were averaged to obtain a single RPE/BM complex thickness value in each eye. Quantitative autofluorescence images were also evaluated using a dedicated software. The qAF values of 8 subfields forming a ring centered onto the fovea were collected and averaged to obtain a single qAF value (qAFThe in vivo correlation between RPE/BM complex thickness and qAF.A total of 105 eyes from 105 subjects (mean age, 42.1 ± 13.9 years; range, 18-65) were included in the analysis. The mean RPE/BM complex thickness significantly increased with age (r = 0.33, P = 0.0006). The values of qAF also positively increased with age (P0.0001). A significant correlation was found between qAF and RPE/BM complex thickness (r = 0.27, P = 0.004). After adjusting for age, iris color, and gender, the correlation remained significant only for subjects aged less than 40 years (P = 0.009).BM complex thickness was significantly co/BM complex thickness increased with age in a healthy White population. A similar increase was found for qAF values. After adjusting for age and iris color, qAF and RPE/BM complex thickness were still correlated in subjects aged less than 40 years. The RPE/BM complex thickness could reflect the lipofuscin/melanolipofuscin accumulation in normal subjects, adding great interest in RPE cell biology.

Purpose To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV), and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiograph (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photograph findings. Design Evaluation of diagnostic test Participants Panel of retina specialists. Methods As part of the Asia-Pacific Ocular Imaging Society (APOIS), an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV and proposed an updated consensus nomenclature, which reflects our latest understanding based on imaging and histology reports. The workgroup evaluated a set of diagnostic features based on OCT and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria which does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. Main Outcome Measures A consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. Results The workgroup recommended the terms ‘polypoidal lesion’ and ‘branching neovascular network’ for the two key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based ‘major criteria’ (sub-RPE ring-like lesion, enface OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 110 eyes achieved an accuracy of 82%. Conclusions We propose updated terminology for PCV lesion components which better reflect the nature of these lesions which was based on international consensus. A set of practical diagnostic criteria that are easily applied to SD-OCT can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not routinely performed.

Purpose To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro-re-nata (PRN) regimen over 4-years in a real-life setting. Design 4-year, multicenter, retrospective comparative study PARTICIPANTS: 264 patients with treatment-naive nAMD. Methods Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n=163) or PRN (n=101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4-years and had annual fundus autofluorescence (FAF) and optical coherence tomography (OCT) imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. Main outcomes measures MA incidence and progression over 4-years, association between treatment strategy, and number of injections. Results At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (p=0.32). At year-4, 27% (34/124) and 25% (20/81) eyes without baseline MA had detectable MA, in the T&E and PRN groups respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4±0.2 and 0.4±0.1mm/year in the T&E and PRN groups, respectively (p=0. 23). Multivariate analysis for baseline predictors of MA growth demonstrated older age, poorer baseline VA and presence of RAP, had a higher risk of greater MA progression (P=0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of developing new MA during the four years of follow-up or the progression of pre-existing MA at year-4 (p=0.692). Conclusion Over four years, neither incidence nor progression of macular atrophy in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and had better visual outcomes compared to those treated with a PRN approach.

Comparing two different sutureless scleral fixation techniques. A retrospective study of patients who underwent sutureless scleral fixation IOL from October 2013 to May 2018 at “Luigi Sacco Hospital”, University of Milan. Comparison between two groups: Group 1 implanted with a 3-piece ALCON-MA60AC and group 2 implanted with a newly developed single-piece foldable IOL SOLEKO FIL-SSF. Patients underwent a complete preoperative ophthalmic assessment and post-operative evaluation at 1, 3, and 6 months. Vitrectomy was performed in all cases. The two groups were compared for age, axial length, and lens status at baseline. Visual acuity, refractive results, surgical time, and post-operative complications were recorded. Thirty-one eyes were included: group 1, 15 eyes of 15 patients, and group 2, 16 eyes of 14 patients. No difference was found in visual acuity. Mean refractive error was 1D in both groups (group 1 1.01D, group 2 1.09D), but spherical equivalent was more often moved toward negative values and induced astigmatism was greater in the 3-piece group (group 1 1.91D [SD ± 2.07], group 2 0.67D [SD ± 0.88] P = 0.04). Surgical procedure was faster in group 2 (mean time difference 21′, P = 0.01*). New displacement occurred in 5 cases (33%) of group 1 and in no cases of group 2 (P = 0.01*). Post-operative bleeding was registered only in group 1 (20%), but the difference was not statistically significant. The group 2 IOL gives in our sample better results due to less post-operative astigmatism and reducing dislocation and bleeding during follow-up. Surgical technique appeared easier and faster: the specifically designed IOL seems to be a feasible solution for sutureless scleral fixation.

Purpose To calculate the measures of accuracy of different imaging modalities in patients with early/intermediate age-related macular degeneration (AMD). Design Prospective, observational, cross-sectional study. Participants Patients with early or intermediate AMD. Methods All participants underwent a complete multimodal imaging assessment with a confocal scanning laser ophthalmoscope, including near-infrared reflectance (NIR), green fundus autofluorescence (G-FAF), confocal pseudocolor, and retromode deviated to right (DR) and left (DL). Drusen were topographically divided as small and medium (≤125 μ diameter) and large (>125 μ diameter), whereas subretinal drusenoid deposits (SDDs) were divided into dot and ribbon phenotypes. Multimodal imaging was considered the reference standard for detecting different subtypes of drusen and SDDs. Cohen’s kappa (k) was used to test interobserver agreement for each imaging modality. Main Outcome Measures Capability to differentiate subtypes of drusen and SDDs with different imaging modalities. Results A total of 100 eyes (62% were female participants) were evaluated. The inter-rate reliability between 2 readers for each imaging modality ranged between 0.76 and 0.95. Overall, large drusen were better identified with confocal pseudocolor imaging (96.6% sensitivity; 77.8% specificity). Smaller drusen were better detected with retromode modalities DR or DL (92% sensitivity; 58.3% specificity and 85.2% sensitivity; 83.3% specificity, respectively). Ribbon SDDs were better detected by color imaging (80.5% sensitivity; 98.3% specificity). Dot SDDs were well identified with NIR (83.1% sensitivity; 91.4% specificity) and G-FAF (84.6% sensitivity; 77.1% specificity). Conclusions Near-infrared reflectance and G-FAF should be considered for classification of dot SDDs, and confocal pseudocolor is optimal for characterizing ribbon SDDs. Among all imaging modalities, retromode technology DR and DL may be a potential supplementary modality to detect even smaller drusen.