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

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

An incipient late-onset retinal degeneration with a C1QTNF5 mutation: a case report with an 11-year follow-up.

PURPOSE: The purpose of this study was to describe and diagnose the difficulty in a long-term follow-up (eleven years) patient with a very early presentation of late-onset retinal degeneration (L-ORD) and the significance of electrophysiological examinations and follow-up in assessing undiagnosed inherited retinal diseases. METHODS: This is an observational case report of a 56-year-old woman, with scattered multiple yellow-white retinal dots firstly diagnosed as fundus albipunctatus. Ten years after presentation, a deterioration in rod and cone responses in ff-ERG was detected, which allowed us to discard the first diagnostic hypothesis and proceed with a genetic testing. RESULTS: Ten years after presentation, she presented a clear progression of the abnormal photoreceptor response with a cone and rod involvement in ff-ERG, which was not compatible with the previous suspicion of fundus albipunctatus. Six months later, genetic testing results together with the typical progression of atrophic patchy lesions in multimodal imaging allowed a certain diagnosis of L-ORD, caused by an already reported pathogenic variant in the C1QTNF5 gene (c.563C > T; p. Pro188 Leu). CONCLUSIONS: We demonstrate the importance of the ff-ERG examination and the follow-up (or ERG and imaging repetition) in the differential diagnosis of an incipient L-ORD, which can be easily misdiagnosed in the early stages, before the appearance of the characteristic chorioretinal atrophy seen with the progression of this rare disease.

Effect of Pro Re Nata Regimen with Anti-VEGF on Type 3 Macular Neovascularization: Long-Term Outcomes.

INTRODUCTION: The purpose of this study was to investigate long-term outcomes of intravitreal injections (IVI) of antivascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV). METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and a PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT), and macular atrophy (MA) were assessed at baseline (T0) and during follow-up (T1, post-loading phase; T2, 1 year; T3, 2 years; T4 >2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analyzed. MA differences at T4 were assessed for pseudodrusen presence. RESULTS: BCVA improved significantly during follow-up (p = 0.013) particularly increasing from baseline to post-loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward an increase in the post-loading phase that was not statistically significant (p = 0.082) and CT decreased significantly during follow-up (p < 0.001). MA changed significantly during follow-up (p < 0.001) with a significant increase from T0 to T3 and from T0 to T4 (p < 0.010). A Cochran-Armitage test for trend showed a significant reduction (p = 0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p = 0.040) and CT (p = 0.020). Indeed, the number of injections did not influence the change over time of MA (p = 0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p = 0.497). CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.

Electrophysiological findings in extensive macular atrophy with pseudodrusen.

PURPOSE: To present electroretinogram findings in extensive macular atrophy with pseudodrusen (EMAP) and describe associated systemic factors. DESIGN: Retrospective case series. METHODS: Data on medical history, visual symptoms, multimodal imaging findings, and visual field were collected from the medical records of patients with extensive macular atrophy with pseudodrusen who attended a visual electrophysiology laboratory. Electrophysiological tests, including full-field electroretinogram, multifocal electroretinogram and photopic negative response, were performed. RESULTS: Eighteen patients (10 [56%] females, age 49-66 years) were included. Of these, 17 (94%) had a history of rheumatic fever in childhood and/or adolescence, 7 (39%) had cardiovascular disease, 4 (22%) had autoimmune disease, and 10 (56%) had inflammatory conditions. The primary visual complaints were nyctalopia (95%), followed by visual field loss (67%) and dyschromatopsia (67%). The key retinal findings included retinal pigmented epithelium atrophy in the macular region and subretinal drusenoid deposits. Regarding electrophysiological results, 100% of patients had abnormalities on multifocal electroretinogram, 94% displayed alterations in photopic negative response, and 78% showed changes in the full-field electroretinogram. CONCLUSIONS: In this cohort, electrophysiologic evaluation demonstrated diffuse retinal dysfunction affecting all layers of the retina in patients with EMAP. The disease is associated with immune-mediated systemic conditions, chiefly rheumatic fever.

Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes.

PURPOSE: Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD). METHODS: This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA. RESULTS: MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study's follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (p < 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4 years, nAMD eyes had an average MA progression rate of 0.275 mm/year versus 0.110 mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p < 0.001), eye (p = 0.003), and time-eye interaction (p < 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295 mm/year vs. nAMD: 0.176 mm/year) with a significant time-eye interaction (p = 0.015). CONCLUSIONS: In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.

Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.

PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA. METHODS: This longitudinal, observational study included 63 treatment-naïve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea. RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20 ± 0.24 to 0.29 ± 0.45 over 7 years. BCVA improved significantly after years 1 and 2 (P = 0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P = 0.007, ß = 0.35). CONCLUSIONS: BCVA was maintained for 7 years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.

Geographic Atrophy in AMD: Prognostic Factors Based on Long-Term Follow-Up.

INTRODUCTION: The aim of this large-scale long-term retrospective study was to show the enlargement rate (ER) of geographic atrophy (GA) in age-related macular degeneration (AMD), defined as complete retinal pigment epithelium and outer retinal atrophy (cRORA), to find predictors of progression in a clinical routine setting and to compare GA evaluation methods. METHODS: All patients available in our database with follow-up of at least 24 months and cRORA in at least one eye, regardless of neovascular AMD being present, were included. SD-OCT and fundus autofluorescence (FAF) evaluations were performed according to a standardized protocol. The cRORA area ER, the cRORA square root area ER, the FAF GA area, and the condition of the outer retina (inner-/outer-segment [IS/OS] line and external limiting membrane [ELM] disruption scores) were determined. RESULTS: 204 eyes of 129 patients were included. Mean follow-up time was 4.2 ± 2.2 (range 2-10) years. 109 of 204 (53.4%) eyes were classified as MNV-associated GA in AMD (initially or during follow-up); 95 of 204 (46.6%) eyes were classified as pure GA in AMD. The primary lesion was unifocal in 146 (72%) eyes and multifocal in 58 (28%) eyes. A strong correlation was observed between the area of cRORA (SD-OCT) and the FAF GA area (r = 0.924; p < 0.001). Mean ER was 1.44 ± 1.2 mm2/year, mean square root ER 0.29 ± 0.19 mm/year. There was no significant difference in mean ER between eyes without (pure GA) and with intravitreal anti-VEGF injections (MNV-associated GA) (0.30 ± 0.19 mm/year vs. 0.28 ± 0.20 mm/year; p = 0.466). Eyes with multifocal atrophy pattern at baseline had a significantly higher mean ER compared to eyes with unifocal pattern (0.34 ± 0.19 mm/year vs. 0.27 ± 1.19 mm/year; p = 0.008). There were moderate significant correlations between ELM and IS/OS disruption scores and visual acuity at baseline, 5 and 7 years (all r values ca. -0.5; p < 0.001). In multivariate regression analysis, a multifocal cRORA pattern at baseline (p = 0.022) and a smaller baseline lesion size (p = 0.036) were associated with a higher mean ER. CONCLUSION: SD-OCT-evaluated cRORA area might serve as a GA parameter comparable to traditional FAF measurement in clinical routine. The dispersion pattern and baseline lesion size might be predictors of ER, whereas anti-VEGF treatment seems not to be associated with ER.

Real-Life Experience and Predictors of Visual Outcomes with Intravitreal Brolucizumab Switch for Treatment of Neovascular Age-Related Macular Degeneration.

INTRODUCTION: To analyze visual and anatomical outcomes after switch to intravitreal brolucizumab therapy in eyes affected by neovascular age-related macular degeneration (nAMD) previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Retrospective study of eyes with nAMD that underwent intravitreal brolucizumab at San Raffaele Hospital (Milan, Italy) or San Rocco Clinical Institute (Ome, Italy) between January 2021 and July 2022. All study eyes had persistent residual retinal fluid after receiving at least 3 intravitreal injections of other anti-VEGF agents prior to switch to brolucizumab. RESULTS: Among 66 eyes from 60 patients (35 males; mean age 76.5 ± 7.4 years) with nAMD, 43 (65.2%) eyes received a complete loading dose of 3 brolucizumab injections, while 15 (22.7%) and 8 (12.1%) eyes were treated with 2 or 1 brolucizumab injections, respectively. The average number of brolucizumab injections was 2.5 during 4.0 ± 2.0 months (mean interval between two injections of 51.2 days). Lower letter gains (<5 letter improvement from baseline) were found in eyes that did not complete a loading dose, after a greater number of previous anti-VEGF injections, after a longer duration of disease, and in eyes with a greater rate of macular atrophy at baseline. No serious ocular or systemic adverse events were found after switch to brolucizumab. CONCLUSION: nAMD eyes with persistent residual retinal fluid despite frequent anti-VEGF treatment can still gain functional and anatomical improvements after switch to brolucizumab therapy. Despite a relevant heterogeneity in patients' response to brolucizumab, we identified potential biomarkers for functional and anatomical improvement.

[Prognostic factors and a customized approach to anti-VEGF therapy for exudative age-related macular degeneration. Analysis of the risk of macular atrophy development]. / Prognosticheskie faktory i kastomizirovannyi podkhod k anti-VEGF-terapii pri ekssudativnoi forme vozrastnoi makulyarnoi degeneratsii. Analiz riska vozniknoveniya makulyarnoi atrofii.

Age-related macular degeneration (AMD) is a chronic progressive multifactorial disease characterized by a degenerative process in the retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris of the fovea with secondary neuroepithelial (NE) damage. Intravitreal administration of drugs that inhibit VEGF is recognized as the only treatment for exudative form of AMD. Literature data is limited, and do not allow drawing conclusions about the influence of various factors (identified using OCT in the EDI mode) on the development of various subtypes of atrophy and their progression, so we decided to conduct our own study and research the possible timing and risks of developing various subtypes of macular atrophy in patients with exudative AMD receiving anti-VEGF therapy. As a result of the study, it was revealed that general macular atrophy (p=0.005) has a predominant effect on BCVA in the first year of the follow-up, while subtypes of atrophy anatomically less pronounced at one year of the follow-up manifest themselves only in the second year of the follow-up (p<0.05). Although color photography and autofluorescence are currently the only approved methods for assessing the degree of atrophy, the use of OCT may reveal reliable precursor endpoints that will facilitate and allow earlier and more accurate assessment of neurosensory tissue loss resulting from the atrophy. Thus, the development of macular atrophy is influenced by such parameters of disease activity as intraretinal fluid (p=0.006952), RPE detachment (p=0.001530) and the type of neovascularization (p=0.028860), as well as neurodenegerative changes in the form of drusen (p=0.011259) and cysts (p=0.042023). The new classification of atrophy according to the degree and localization of the lesion allows more differentiated conclusions about the effect of anti-VEGF drugs on the development of certain types of atrophy, which can be a decisive factor in determining the treatment tactics.

Choroidal vascularity index in eyes with central macular atrophy secondary to age-related macular degeneration and Stargardt disease.

PURPOSE: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI). METHODS: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 µm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts. RESULTS: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 µm vs 353 ± 105 µm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old. CONCLUSION: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response.

Development of Macular Atrophy in Patients with Wet Age-Related Macular Degeneration Receiving Anti-VEGF Treatment.

Age-related macular degeneration (AMD) is a leading cause of blindness. Late AMD can be classified into exudative (commonly known as wet AMD [wAMD]) or dry AMD, both of which may progress to macular atrophy (MA). MA causes irreversible vision loss and currently has no approved pharmacological treatment. The standard of care for wAMD is treatment with anti-vascular endothelial growth factors (VEGFs). However, recent evidence suggests that anti-VEGF treatment may play a role in the development of MA. Therefore, it is important to identify risk factors for the development of MA in patients with wAMD. For example, excessive blockade of VEGF through intense use of anti-VEGF agents may accelerate the development of MA. Patients with type III macular neovascularization (retinal angiomatous proliferation) have a particularly high risk of MA. These patients are characterized as having a pre-existing thin choroid (age-related choroidopathy), suggesting that the choroidal circulation is unable to respond to increased VEGF expression. Evidence suggests that subretinal fluid (possibly indicative of residual VEGF activity) may play a protective role. Patients receiving anti-VEGF agents must be assessed for overall risk of MA, and there is an unmet medical need to prevent the development of MA without undertreating wAMD.

Progression of Macular Atrophy in Patients Receiving Long-Term Anti-VEGF Therapy for Age-Related Macular Degeneration: Real-Life Data.

PURPOSE: This study aimed to evaluate the progression of macular atrophy (MA) based on near-infrared reflectance (NIR) and optical coherence tomography (OCT) images, in patients with age-related macular degeneration (AMD), receiving anti-vascular endothelial growth factor (anti-VEGF) treatment for at least a 6-year period. MATERIALS AND METHODS: This retrospective study included 53 naïve patients (53 eyes) with neovascular AMD from 2 centers, who were treated with anti-VEGF intravitreal injections and had no MA at baseline. MA was evaluated in an annual basis using NIR images, while all available OCT images were used to confirm that the atrophic area fulfilled the criteria proposed by the Classification of Atrophy Meetings (CAM) group for complete retinal pigment epithelium and outer retinal atrophy. Incidence and progression of MA were evaluated. Associations with best-corrected visual acuity (BCVA) and total number of injections were also studied. RESULTS: Treatment duration of our patients was 7.34 ± 1.54 years. The mean number of anti-VEGF injections was 24.4 ± 13.6. BCVA at baseline was 0.38 ± 0.27 logMAR, while at the final visit, it was 0.60 ± 0.35 logMAR (p = 0.731). The cumulative incidence of new MA at years 1, 2, 3, 4, 5, and 6 was 1.89%, 18.87%, 32.08%, 39.62%, 49.06%, and 50.94%, respectively. In patients who developed MA, mean MA area increased from zero at baseline to 5.66 ± 7.18 mm2 at the final visit. The estimated annual enlargement of MA was 0.45 mm/year based on square root transformation (1.12 mm2/year, untransformed data). MA progression does not appear to be significantly associated with age (R = 0.055; p = 0.784), gender (R = 0.113; p = 0.576), BCVA (R = 0.168; p = 0.404), and total number of injections (R = 0.133; p = 0.255). CONCLUSION: In this real-life setting, half of the neovascular AMD patients under anti-VEGF treatment, without MA at therapy initiation, developed MA over a period of at least 6 years. In this work, the number of injections did not seem to have a significant association with MA progression.

Morphological differences between two types of Bruch's membrane defects in pathologic myopia.

PURPOSE: To investigate morphological differences between two types of Bruch's membrane (BM) defects-patchy atrophy (PA) and CNV-related macular atrophy (CNV-MA) METHODS: Eyes presenting with PA or CNV-MA were included. Scleral thickness (ST), choroidal thickness (CT), and scleral morphological characteristics were obtained by swept-source optical coherence tomography (SS-OCT). Fundus photographs were performed to measure the size of PA and CNV-MA lesions. RESULTS: Among a total of 167 eyes evaluated, 106 eyes had PA and 61 eyes had CNV-MA. In addition, dome-shaped macula (DSM) was identified in 20 (18.87%) and 10 (16.39%) eyes among PA and CNV-MA, respectively. The eyes of CNV-MA without DSM showed a thicker subfoveal ST (278.61 ± 56.17 vs 231.58 ± 66.09 mm, P < 0.001), a thinner subfoveal CT, and a higher rate of scleral perforating vessels (70.6% vs 50.0%, P = 0.021) when compared with those of PA without DSM. The size of PA/CNV-MA lesions was associated with CT in eyes without DSM. However, it was only associated with bulge height in eyes with DSM (r = 0.5, P = 0.013). CONCLUSIONS: The eyes with CNV-MA had a thicker sclera than those with PA, which add another evidence to indicate the absence of the progressive relationship between two types of BM defects. The enlargement of lesions in BM defects between eyes with and without DSM may be caused by different mechanical forces. SS-OCT, which focuses on scleral and choroid morphology, may be necessary for more accurate classification of pathologic myopia.

Optical coherence tomography angiography for detection of macular neovascularization associated with atrophy in age-related macular degeneration.

PURPOSE: To evaluate the ability of optical coherence tomography angiography (OCTA) to detect macular neovascularization (MNV) in eyes with atrophy compared with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). METHODS: In this prospective study, eyes with MNV and atrophy (termed macular atrophy or MA) secondary to age-related macular degeneration (AMD), and AMD eyes with geographic atrophy (GA) without MNV underwent multimodal imaging with FA, ICGA, structural OCT, and OCTA. The presence of MNV was determined using all imaging modalities by senior retina specialists and was considered the gold standard reference. Each individual imaging modality was then evaluated independently by two expert readers for the presence of MNV in a masked fashion. Morphologic characteristics of the MNV were evaluated on the custom OCTA slab. RESULTS: Twenty-one patients with MA+MNV and 21 with GA only were enrolled. Manual segmentation on OCTA allowed detection of the MNV in 95.2% of eyes with MA+MNV and in 4.7% of eyes with GA, showing high specificity (95.2%) and sensitivity (95.2%). FA, ICGA, and OCT detected MNV in 57.1%, 52.3%, and 66.7% of eyes with MA+MNV and in 14.2%, 9.5%, and 42.8% with GA. Sensitivity and specificity were 85.7% and 57.1% for FA, 90.5% and 52.4% for ICGA, and 66.7% and 57.1% for OCT. CONCLUSIONS: OCTA appears to be superior to other imaging modalities for identification of MNV in eyes with macular atrophy. OCTA should be considered as part of the multimodal imaging evaluation of eyes with atrophy, particularly in the context of clinical trials.

Serous Retinal Detachment in Dome-Shaped Macula Is Associated with Greater Central Choroidal Blood Flow Measured by Optical Coherence Tomography Angiography.

PURPOSE: Dome-shaped macula (DSM) is characterized by an inward bulge in the macula, often associated with a myopic staphyloma. One complication of DSM is particularly studied: foveolar serous retinal detachment (SRD). This study analyzed the variations of optical coherence tomography angiography (OCT-A) decorrelation signal in cases of DSM with and without SRD. METHODS: This was a retrospective study including twenty height eyes presenting with DSM. OCT-A scans were recorded, and the intensity of the choroidal decorrelation signal was quantified to analyze choroidal blood flow (CBF) in central, temporal, and nasal macular areas. The size of retinal pigment epithelium (RPE) atrophy was evaluated. RESULTS: CBF in the central area was significantly greater in the SRD group than in the no-SRD group (7.00 × 105 vs. 2.58 × 105) (p = 0.0049). CBF appeared decreased in the subfoveal area compared with the periphery for patients without SRD (p = 0.0107). The size of RPE atrophy was 0.762 optic disc area ±0.87. RPE atrophy correlated very significantly with CBF (p = 0.0012). CONCLUSION: A greater retrofoveolar CBF intensity is associated with the presence of SRD. These changes could reflect variations of CBF, and may represent a potential explanation for the pathogenesis of SRD in DSM.

Effect of intravitreal injection of aflibercept or ranibizumab on chorioretinal atrophy in myopic choroidal neovascularization.

PURPOSE: To compare chorioretinal atrophy (CRA) progression in myopic choroidal neovascularization (mCNV) between intravitreal injections of ranibizumab (IVR) and aflibercept (IVA) in the eyes with mCNV. METHODS: Thirty eyes (28 patients) with treatment-naïve mCNV were included in this study. IVR or IVA was administered for up to 1 year. The best-corrected visual acuity (BCVA) was measured, and fundus photographs and fundus autofluorescence were obtained before and 1, 3, 6, and 12 months after the initial treatment. The clinical characteristics including the macular choroidal thickness in various areas and CRA progression were compared between the drugs. The clinical characteristics and macular choroidal thicknesses were compared between eyes with and without CRA progression. RESULTS: The BCVA improved significantly (p < 0.05 for all comparisons) from 0.44 to 0.26, 0.19, 0.20, and 0.17 after 1, 3, 6, and 12 months, respectively. CRA progressed in 12 (40%) eyes over 1 year. The CRA progression did not differ significantly between aflibercept and ranibizumab. The foveal choroid was significantly (p = 0.0043) thinner in aflibercept-treated eyes compared with ranibizumab-treated eyes at 1 year. Subfoveal CNV tended to cause CRA progression more frequently at 1 year, although this did not reach significance. CONCLUSIONS: IVA to treat mCNV caused more severe thinning of the foveal choroid than ranibizumab; however, no significant difference was seen in CRA progression between the drugs and the choroidal thickness should not be associated with CRA progression. The CNV location may predict CRA progression after anti-vascular endothelial growth factor therapy for mCNV.

Five-year treatment outcomes following intravitreal ranibizumab injections for neovascular age-related macular degeneration in Japanese patients.

PURPOSE: To assess the real-world 5-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration (AMD). METHODS: This was a retrospective, observational, and open-label effectiveness study that included 295 eyes. The participants were patients with treatment-naïve neovascular AMD who received intravitreal ranibizumab (IVR) monthly injection at least three times as the loading phase, followed by further injections as needed (pro re nata (PRN)) and follow-up assessments for 5 years. Outcomes were determined at least 5 years after the first ranibizumab injection. RESULTS: Mean logMAR best-corrected visual acuity (BCVA) at baseline was 0.52. The mean BCVA significantly improved after three loading injections; however, it declined gradually. The BCVA at 1 year was significantly better than the baseline BCVA, whereas the 3-year, 4-year, and 5-year BCVA values were significantly lower than the baseline values. The average central foveal thickness improved significantly from 366 ± 125 µm to 268 ± 134 µm (p < 0.0001). Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization (CNV) than in cases with other AMD (p = 0.01). CONCLUSIONS: IVR is well tolerated in eyes with AMD. However, a PRN regimen for AMD may have limited real-world effectiveness for long-term maintenance of improved visual acuity. Macular atrophy may occur more frequently in classic CNV. To maintain good vision, IVR treatment should be started earlier and performed continuously.

Subfoveal choroidal thickness predicts macular atrophy in age-related macular degeneration: results from the TREX-AMD trial.

BACKGROUND: Our purpose was to evaluate the relationship between subfoveal choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with age-related macular degeneration (AMD). METHODS: This was a prospective, multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial (NCT01648292) with treatment-naïve neovascular AMD (NVAMD) in at least one eye were included. SCT was measured by certified reading center graders at baseline using spectral domain optical coherence tomography (SDOCT). The baseline SCT was correlated with the presence of MA at baseline and development of incident MA by month 18. Generalized estimating equations were used to account for information from both eyes. RESULTS: Baseline SCT in eyes with MA was statistically significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04) and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and non-MA developers revealed a statistically significant difference (P = 0.03). Receiver operating characteristic curve (ROC) analysis showed the cut-off threshold of SCT for predicting the development of MA in cases without MA at baseline was 124 µm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among eyes without MA at baseline, those with baseline SCT ≤124 µm were 4.3 times more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P = 0.005) than those with baseline SCT >124 µm. CONCLUSIONS: Eyes with AMD and MA had less SCT than those without MA. Eyes with less baseline SCT also appear to be at higher risk to develop MA within 18 months.

Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe retinal dystrophy, typically manifesting in the first year of life. Mutations in more than 18 genes have been reported to date. In recent studies, biallelic mutations in NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 have been found to cause LCA. PURPOSE: To broaden the knowledge regarding the phenotype of NMNAT1-associated LCA. METHODS: Clinical ophthalmologic examinations were performed in two sisters with LCA. Whole exome sequencing was performed in one of the affected girls, with subsequent segregation analysis in the affected sister and unaffected parents. The literature was reviewed for reports of NMNAT1-associated LCA. RESULTS: Exome sequencing revealed the known NMNAT1 mutation c.25G>A (p.Val9Met) in a homozygous state. Segregation analysis showed the same homozygous mutation in the affected younger sister. Both parents were found to be heterozygous carriers of the mutation. The two girls both presented with severe visual impairment, nystagmus, central atrophy of the pigment epithelium, and pigment clumping in the periphery before the age of 6 months. Retinal vessels were attenuated. Both children were hyperopic. In the older sister, differential diagnosis included an inflammatory origin, but electrophysiology in her as well as her sister confirmed a diagnosis of LCA. Pallor of the optic nerve head was not present at birth but developed progressively. CONCLUSIONS: We confirmed a diagnosis of NMNAT1-associated LCA in two siblings through identification of the mutation (c.25G>A [p. Val9Met]) in a homozygous state. In infants with non-detectable electroretinogram (ERG), along with severe congenital visual dysfunction or blindness and central pigment epithelium atrophy with pigment clumping resembling scarring due to chorioretinitis, LCA due to NMNAT1 mutations should be considered.