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Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

Background: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration., Methods: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes., Results: Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells., Conclusion: Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.

Objectives: To investigate the correlation between the AI-measured area of the lacquer cracks (LC) at their first detection and the occurrence of a choroidal neovascularization (CNV) during the follow-up in patients affected by pathologic myopia. Secondary outcome was the detection of a correlation between the time to onset of CNV with both baseline LC area and LC area increase during follow-up., Methods: Optical coherence tomography (OCT) acquisitions of patients diagnosed with LC were retrospectively analysed. The study population was divided in a CNV group (showing the documented onset of a CNV) and a n-CNV group (no CNV development during follow-up). LC area was measured using MatLab software after the application of a customized method for LC segmentation on infrared (IR) enface images., Results: Forty-five (45) patients with a mean follow-up of 4.9 ± 1.5 years were included. LC area at baseline was 2.82 ± 0.54 mm 2 and 1.70 ± 0.49 mm 2 in CNV (20 patients) and n-CNV group (25 patients) group respectively (p < 0.001). LC area increase was significantly higher in CNV group (p < 0.001). Time to onset of CNV was linearly correlated with both LC area at baseline (p = 0.006) and LC area increase (p < 0.001)., Conclusions: Myopic CNV development is associated with lager LC areas and higher LC area increase during time. Earlier CNV onset is inversely correlated with LC area and LC area increase., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To describe the steps leading to the development and progression of macular neovascularization (MNV) in angioid streaks., Methods: The study was designed as retrospective, longitudinal case series. Patients with angioid streaks were investigated by means of multimodal imaging, including fundus autofluorescence and structural optical coherence tomography. Main outcome measures were hyperreflective foci and MNV progression steps., Results: Overall, 40 eyes (20 patients) affected by angioid streaks were evaluated. Over the follow-up, five eyes of five patients developed MNV. The mean follow-up was of 1.6 years. The mean number of anti-vascular endothelial growth factor injections was 4.35 ± 1.4. Mean best-corrected visual acuity was 0.53 ± 0.38 LogMAR at the MNV onset, improving to 0.42 ± 0.40 LogMAR at the end of the follow-up ( P > 0.05). Intraretinal hyperreflective foci onset and coalescence represented the first alterations occurring before the onset of the MNV. Anti-vascular endothelial growth factor treatment was associated with exudation relapsing and remitting, with still present intraretinal hyperreflective foci and pigment accumulation. The longitudinal analysis of our cohort of eyes outlined the event timeline: 1.2 months to find concentrated hyperreflective foci, 4.5 months to observe pigment organization through the outer nuclear layer, and 1.5 years to detect MNV., Conclusion: Hyperreflective foci formation, concentration, and migration represent early alterations occurring before the onset of the MNV in angioid streaks.

In recent years, optical coherence tomography (OCT) biomarkers for specific retinal diseases have been found to be associated with treatment outcome and disease recurrence. The main purposes of this study were to identify OCT biomarkers for myopic choroidal neovascularization (mCNV) treated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF). OCT features in 43 eyes of 39 patients with mCNV treated with anti-VEGF with at least 1 year of follow-up were retrospectively analyzed. Eyes with subretinal hyperreflective material (SHM) in baseline spectral-domain OCT (SD-OCT) had significantly more visual improvement than eyes without SHM at month 6 (p = 0.007) and had a trend of more visual improvement than eyes without SHM (p = 0.058) at month 12. Eyes with subretinal fluid (SRF) at baseline had significantly more central retinal thickness (CRT) decrease than patients without SRF at month 6 and 12 (p = 0.012 and 0.006 respectively). In univariate regression analysis, dome-shaped macula (DSM), SRF in baseline OCT image and fuzzy border of mCNV when entering pro re nata (PRN) injection protocol tended to have higher risk of disease recurrence in 1 year (odds ratio: 14.86 (p = 0.003), 3.75 (p = 0.049) and 22.92 (p < 0.001) respectively). However, they were not significant in multivariate regression analysis. OCT biomarkers at baseline could provide prognostic information for mCNV management., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background/objectives: To assess systemic associations of angioid streaks (AS) using a large US healthcare database., Subjects/methods: A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV)., Results: One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p < 0.001), connective tissue disease (1.0% vs 0.3%, p < 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p < 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis., Conclusions: In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Clinicopathologic correlation of two optical coherence tomography (OCT) features in neovascular age-related macular degeneration., Methods: Case report, clinicopathologic correlation., Results: A patient in her 90s was diagnosed with Type 3 macular neovascularization secondary to age-related macular degeneration in the index right eye and underwent intravitreal antivascular endothelial growth factor treatment for 5 years. A double-layer sign on in vivo OCT was correlated to calcified drusen on histology. Furthermore, hyperfluorescence on fluorescein angiography corresponded on histology to choroidal hypertransmission on OCT and retinal pigment epithelium atrophy above calcified drusen., Conclusion: A double-layer sign on OCT can represent nonneovascular subretinal pigment epithelium material including wide and flat calcific nodules. Furthermore, hyperfluorescence on FA, among different origins, can be due to a window defect corresponding to retinal pigment epithelium atrophy, which can be confirmed with OCT. Clinicopathological correlation using high-resolution histology can demonstrate the fine details available to clinical decision making through currently available in vivo OCT imaging.

Purpose: To investigate the quantitative characteristics of anastomoses of macular neovascularization (MNV) in neovascular age-related macular degeneration using optical coherence tomography angiography according to the frequency of intravitreal injections., Methods: Eighty-six eyes of 86 patients treated for neovascular age-related macular degeneration were classified into two groups based on the number of intravitreal injections administered over 12 months: stable (<3) and unstable (≥3). Anastomotic areas were defined as areas surrounded by neighboring vessels in the MNV; their total number, mean area, maximal and minimal diameters (i.e., maximal and minimum Feret diameters), and ratio (Feret aspect ratio) were analyzed in the inner and outer areas of the MNV., Results: Forty-four and 42 eyes were classified into the stable and unstable groups, respectively. The eyes in the unstable group had larger anastomotic areas with longer minimum Feret diameters and longer perimeters in the outer MNV. In the logistic regression analysis, instability was associated with a larger anastomotic area and a longer minimum Feret diameter in the outer MNV. Multivariate analysis revealed that a longer minimum Feret diameter in the outer MNV was the most significant factor ( P = 0.03)., Conclusion: The quantitative characteristics of the anastomotic areas in the MNV might indicate the need for intravitreal injections in patients with neovascular age-related macular degeneration.

Purpose: To report a case of sequential retinal pigment epithelium (RPE) tears following intravitreal Ranibizumab injections for neovascular age-related macular degeneration (AMD)., Methods: Retrospective, observational case., Case Description: A 75-year-old hypertensive male was diagnosed with active neovascular AMD and pre-existing RPE tear in the left eye. His presenting best-corrected visual acuity was counting finger @ 1 metre,

Purpose: Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are sister diseases and have several similar clinical features and still have few genetic differences. The association of HERPUD1 (homocysteine inducible ER protein with ubiquitin like domain 1) gene variant rs2217332 with PCV is known; however, such association with AMD has not been reported in the Indian population. We analyzed the association of rs2217332 with PCV and AMD to identify the preferential association of this variant with these diseases., Methods: This is a population-based case-control study consisting of 422 patients (129 AMD cases; 101 PCV cases, 192 healthy controls) recruited from the vitreoretinal clinic Sankara Nethralaya. The sample size for the study was calculated using appropriate power calculation methods. Genotype was determined using PCR-based Sanger sequencing. The SPSS V23.0 statistical package tool was used to calculate chi-square and ROC to determine the association of rs2217332 with control, AMD, and PCV., Results: Here, we report for the first time the association of this genetic variant (rs2217332) with AMD and PCV in the Indian population. The case-control study shows a significant association of this SNP with PCV (P value = 0.002); however, this variant is not significantly associated with AMD (P value = 0.602). Comparison between AMD (as control) and PCV (as case) also showed significant association of the SNP with PCV (P value = 0.02). Minor allele A conferred to increase the risk of PCV., Conclusions: The study concludes that the genetic variant rs2217332 in HERPUD1 gene is highly significantly associated with PCV and not with AMD in Indian populations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To report the long-term outcomes of anti-vascular endothelial growth factor (VEGF) treatment in eyes with peripapillary choroidal neovascularisation (PPCNV) associated with age-related macular degeneration (AMD)., Methods: A retrospective cohort study included patients with AMD-related PPCNV. Eyes were treated with anti-VEGF according to pro re nata regimen. Inactivation index was calculated as the proportion of disease inactivity from the total follow up time., Results: Sixty-seven eyes of 66 consecutive patients were included in the study; mean follow-up time was 53.2 months. Best corrected visual acuity (BCVA) remained stable for the first four years of follow up, with a significant deterioration in BCVA thereafter. Baseline BCVA was a significant predictor of final BCVA (p < 0.001). The mean inactivation index was 0.38 ± 0.23. Subretinal fluid (SRF) at presentation was significantly associated with decreased inactivation index (p < 0.05). Worse baseline BCVA, SRF and pigment epithelium detachment (PED), male sex, and younger patient age were associated with increased risk for recurrence after first inactivation (p < 0.05)., Conclusion: The use of anti-VEGF agents in the treatment of AMD-related PPCNV managed to preserve BCVA in the first four years of follow-up. Male sex, SRF and PED at presentation and baseline BCVA are associated with increased risk for PPCNV recurrence after the first inactivation, and should prompt careful follow-up in these patients., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To assess 5-year cumulative incidence and risk factors of fellow eye involvement in Asian neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy., Methods: In a prospective cohort study of Asian nAMD and polypoidal choroidal vasculopathy, the fellow eyes were evaluated for exudation. The 5-year incidence of exudation was compared between nAMD and polypoidal choroidal vasculopathy., Results: A total of 488 patients were studied. The 5-year incidence of exudation in fellow eyes was 16.2% (95% confidence interval: 12.0-20.2). Polypoidal choroidal vasculopathy compared with nAMD in the first eye was associated with lower fellow eye progression (9.8% [95% confidence interval: 5.1-14.3]) vs. 22.9% [95% confidence interval: 15.8-29.3], P < 0.01). Drusen (hazards ratio 2.11 [95% confidence interval: 1.10-4.06]), shallow irregular retinal pigment epithelium elevation (2.86 [1.58-5.18]), and pigment epithelial detachment (3.01 [1.27-7.17]) were associated with greater progression. A combination of soft drusens and subretinal drusenoid deposits, and specific pigment epithelial detachment subtypes (multilobular, and sharp peaked) were associated with progression. Pigment epithelial detachment, shallow irregular retinal pigment epithelium elevation, and new subretinal hyperreflective material occurred at 10.4 ± 4.2 months, 11.1 ± 6.0 months, and 6.9 ± 4.3 months, respectively, before exudation., Conclusion: The 5-year incidence of fellow eye involvement in Asian nAMD is lower than among Caucasians because of a higher polypoidal choroidal vasculopathy prevalence. Drusens, shallow irregular retinal pigment epithelium elevation, and pigment epithelial detachment are risk factors for fellow eye progression.

This study aimed to investigate the longitudinal change in the reticular pseudodrusen (RPD) area in the fundus and its association with late age-related macular degeneration (AMD). 91 RPD eyes (55 patients; age 67.9 ± 7.3 years) with > 5 years' follow-up (6.8 ± 0.9 years) from a single medical center were enrolled. Ultrawide-field photography images were analyzed using the concentric rings method, and the RPD area was semi-quantitatively classified according to the affected segment number into central, intermediate, and extensive types. Correlations of longitudinal changes in the RPD area and late AMD risk were investigated. RPD area increased significantly during the follow-up (p < 0.001). The increase rate correlated with age (r = 0.207; p = 0.048), RPD area at first visit (r = - 0.222; p = 0.035), and the decrease rate of subfoveal choroidal thickness (SFCT) (r = 0.217; p = 0.039). Many central (18/49, 36.7%) and intermediate (15/23, 65.2%) types switched to the more advanced type during the follow-up. Macular neovascularization and geographic atrophy developed in 12.3% and 18.7% of patients by 7 years. Late AMD incidence was significantly higher in eyes with large than in those with small RPD areas (p = 0.002). Larger RPD area at baseline, faster increase in RPD area, thinner SFCT, rapid decrease in SFCT, and the presence of late AMD on fellow eye were associated with late AMD. All RPD areas progressively increase over time. The regular assessment of RPD area may help to predict late AMD risk in RPD eyes., (© 2022. The Author(s).)

Purpose: To determine potential factors associated with the long-term visual prognoses in patients with choroidal osteoma undergoing anti-vascular endothelial growth factor (VEGF) treatment., Design: Retrospective case series., Methods: Patients diagnosed at tertiary high-volume hospitals between January 2000 and December 2020 were evaluated. The primary outcome measure was visual acuity at 5-year follow-up. The secondary outcome measures included factors associated with favorable vision, defined as loss of <1 line and >20/200 vision., Results: Of 38 eyes from 36 patients (22 female, 61%; mean age 38 years) with choroidal osteoma, 23 eyes (61%) received anti-VEGF treatment (bevacizumab 1.25mg/0.05 cc, monthly or treat-and-extend) and 65% completed the 5 years of follow-up. All treated eyes had associated chorioretinal comorbidities (subretinal fluid 91%; choroidal neovascularization 74%; subretinal hemorrhage 30%). Although there was significant vision loss by 5 years (P = .002), 12 eyes (44%) had favorable outcomes. Only tumor thickness was significantly associated with unfavorable visual outcomes (OR 917.1, 95% CI 1.0-5687.7; P = .049). The optimal cut-off point predictive of visual outcomes was 1.4 mm, and tumor thickness ≥ 1.4 mm was associated with unfavorable vision (OR 27.0, 95% CI 2.0-368.4; P = .013)., Conclusions: Among patients with choroidal osteoma undergoing anti-VEGF therapy, a particular patient subset presented with divergent outcomes with very poor vision. Tumor thickness appeared to be the differentiating factor and is thus a potential prognostic indicator for long-term visual prognoses., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To analyze the relationship between a focal increase of choroidal thickness (ChT) and exudative activity of macular neovascularization (MNV) secondary to pathologic myopia., Methods: Retrospective analysis including eyes with pathologic myopia presenting with a focally increased ChT underneath active MNV. All patients included were treated, and ChT was measured before and after each intravitreal injection by two experienced ophthalmologists., Results: Fifty-two eyes of 52 patients with myopic MNV (19 men and 33 women) were included in this analysis. ChT at T-1 averaged 51.09 ± 33.56 μ m, whereas at the time of MNV activation (T0), ChT was significantly thicker: 85.11 ± 43.99 μ m ( P < 0.001). After a single intravitreal injection, the ChT significantly decreased to 53.23 ± 34.15 μ m ( P < 0.001)., Conclusion: This study showed that focal ChT variations may be considered an interesting corollary sign of MNV in high myopic patients, indicating the activity of myopic neovascularization.

Purpose: The aim of this study was to compare intraocular cytokines among different types of pigment epithelial detachments (PEDs) in patients with chronic central serous chorioretinopathy (CSC) and to investigate the association of cytokine levels and PED types with response to anti-vascular endothelial growth factor (VEGF) therapy., Methods: We included 88 patients with chronic CSC and 30 controls. The anti-VEGF agent conbercept was given intravitreally to chronic CSC patients. Cytokines VEGF, interleukin-6 (IL-6), IL-8, IL-10, interferon-inducible protein-10 and monocyte chemoattractant protein-1 in aqueous humour were measured. Treatment efficacy, cytokine levels, changes in best-corrected visual acuity (BCVA) and optical coherence tomography parameters were assessed at baseline and 1 month after treatment., Results: Patients were divided into three groups: flat irregular PED (FIPED) with choroidal neovascularization (CNV), FIPED without CNV and focal PED. Vascular endothelial growth factor (VEGF) was the only cytokine significantly higher in chronic CSC FIPED patients. There were no significant differences in VEGF between FIPED patients with or without CNV (p = 0.234). At 1 month after conbercept injection, treatment effective rates in FIPED patients with or without CNV were significantly higher than in patients with focal PED (p < 0.05). Best-corrected visual acuity (BCVA) was improved in both FIPED groups (p < 0.05), but not in the focal PED group (p = 0.180). All three groups had significant decreases in central macular thickness (p < 0.05), and PED heights in FIPED patients were reduced (p < 0.05)., Conclusions: Patients with FIPED in chronic CSC had elevated intraocular VEGF levels and responded favourably to conbercept. Anti-VEGF treatment may be an option for FIPED CSC patients with or without secondary CNV., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC)., Design: Genome-wide survival analysis using a longitudinal cohort study., Participants: We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography., Methods: We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values < 1.0 × 10 -5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis., Main Outcome Measures: The association between SNPs and MNV development in patients with CSC., Results: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR] meta , 3.63; P meta  = 5.76 × 10 -9 ). Among previously reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR, 0.39, P = 2.55 × 10 -4 ), COL4A3 rs4276018 (HR, 0.26, P = 1.56 × 10 -3 ), and B3GALTL rs9564692 (HR, 0.56, P = 8.30 × 10 -3 ) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of 8 pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport., Conclusions: ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: Case report of choroidal neovascularization (CNV) detection in patient who was treated for bilateral retinoblastoma in early childhood., Material and Methods: Patient at 1.5 years of age treated for endophytic retinoblastoma stage 4 (according to the Reese-Ellsworth classification) bilaterally, with a positive mutation in the Rb1 gene. After undergoing bilateral retinal laser treatment and 6 cycles of systemic chemotherapy, the tumor remained inactive without other complications. At the age of 14, the boy developed visual impairment in his left eye with metamorphosis. Based on a local finding and other auxiliary examinations, he was diagnosed with CNV in the macular area at the interface of the tumor scar and the healthy retina of the left eye., Results: After three applications of anti-VEGF (antibodies blocking vascular endothelial growth factor) substance intravitreally (bevacizumab 1.2 mg), there was a reduction in CNV and also an improvement in visual function.

Purpose: To identify baseline morphological predictors of lesion shrinkage in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor., Methods: This retrospective study included 46 eyes (41 consecutive patients) with active mCNV receiving anti-vascular endothelial growth factor treatment. Optical coherence tomography angiography was performed at baseline and 1 year after treatment. Quantitative features were obtained from optical coherence tomography angiography images using AngioTool software. Eyes were classified as "high shrinkage" or "low shrinkage" according to the median relative change in lesion area. Baseline quantitative morphological features associated with mCNV shrinkage were identified in univariate and multivariate analyses., Results: The mCNV area was significantly smaller after 1 year ( P = 0.013), with a median relative change of -16.5%. The relative change in mCNV area was -48.3% in high-shrinkage eyes (n = 23) and -5.2% in low-shrinkage eyes (n = 23). High-shrinkage eyes had a smaller mCNV area ( P = 0.013), shorter total vessel length ( P = 0.023), and higher end point density ( P < 0.001). Multivariate analysis showed significant associations of high shrinkage with end point density (β = -0.037, P = 0.043) and previous anti-vascular endothelial growth factor treatment (β = 0.216, P = 0.029)., Conclusion: Morphological features of neovascularization detected by optical coherence tomography angiography can predict lesion shrinkage in eyes with mCNV receiving anti-vascular endothelial growth factor therapy. Higher end point density contributed to shrinkage, particularly of treatment-naive lesions.

Objective: To investigate the evolution of treatment-naive type 3 macular neovascularization (MNV) undergoing anti-vascular endothelial growth factor (VEGF) treatment through volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA)., Design: Retrospective observational study., Participants: Patients with type 3 MNV and age-related macular degeneration (AMD)., Methods: Included subjects had three loading injections of an anti-VEGF agent. The OCTA volume data at baseline and follow-up were processed with a previously published algorithm in order to obtain a volume-rendered representation of type 3 MNV. Progressive changes in type 3 lesions were analyzed via 3D OCTA volume rendering., Results: A total of 14 treatment-naive eyes with type 3 MNV from 11 AMD patients (7 females) were included. At both baseline and follow-up visits, a type 3 MNV complex was identifiable. Each complex was composed of a mean number of 2.5 ± 0.7 vascular branches at baseline and 1.4 ± 0.6 at the follow-up visit (p < 0.0001). The mean changes in central macular thickness and visual acuity were significantly correlated with modifications in the number of type 3 MNV branches (ρ = -0.533, p = 0.049, and ρ = -0.581, and p = 0.040, respectively)., Conclusions: This study demonstrated that type 3 lesions do not disappear completely after loading treatment, as indicated previously by histopathologic studies. Importantly, quantitative volume changes in type 3 lesions are directly associated with treatment response., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: We sought to investigate the chorioretinal thickness and retinal pigment epithelial (RPE) degenerative features of eyes with early age-related macular degeneration (AMD) and subretinal drusenoid deposits (SDDs) according to the presence of macular neovascularization (MNV) in the fellow eyes., Methods: We classified 70 eyes into two groups of 47 eyes with non-neovascular AMD and 23 eyes with neovascular AMD, respectively, according to the presence of MNV in the fellow eyes. The mean macular retinal, ganglion cell-inner plexiform layer (GCIPL), and choroidal thickness values and RPE features of the 6-mm-diameter zone were compared. RPE degeneration was defined as a lesion with an incomplete RPE and outer retinal atrophy (iRORA) or attenuated RPE reflectivity with diffuse basal laminar deposits, which was defined as when the eye showed an attenuated RPE line with granular features and mixed reflectivity in combination with sub-RPE deposits with a lesion ≥ 1,000 µm in length., Results: Mean retinal, GCIPL, and choroidal thickness values (286.69 ± 15.02 µm, 64.36 ± 4.21 µm, and 156.11 ± 33.10 µm) of the neovascular AMD group were greater than those (278.61 ± 13.96 µm, 61.44 ± 4.63 µm, and 133.59 ± 34.33 µm) of the non-neovascular AMD group (all P < 0.05). RPE degeneration was more prevalent in the neovascular AMD group (65.2%) than the non-neovascular AMD group (38.3%; P = 0.034). Greater mean GCIPL and choroidal thickness values and the presence of RPE degeneration were associated with type 3 MNV in fellow eyes (all P < 0.05)., Conclusions: Different degenerative features according to MNV in fellow eyes of patients with AMD and SDDs suggest that variable degenerative features might be present during disease progression and have an association with the phenotype., (© 2022. The Author(s).)

Competing Interests: The authors have no conflicts of interest to declare.

Tilted disc syndrome (TDS) is considered a congenital anomaly due to a delayed closure of the embryonic fissure. It is characterized by an oblique orientation of the axis of the optic disc, associated with other posterior pole anomalies such as inferior crescent, situs inversus and inferior staphyloma. The aim of this review was to summarize the data supporting the current hypotheses for the pathogenesis of TDS, and its anatomical and functional clinical consequences. Recent imaging techniques, such as magnetic resonance imaging, wide-field fundus imaging, and 2- and 3-D optical coherence tomography have provided a new perspective on TDS and its complications. Different abnormalities have previously been reported, both in the anterior and posterior segments. The focus was on vision-threatening chorioretinal changes or complications, including choroidal neovascularization and serous retinal detachments and their therapeutic options. Based on clinical observations, assumptions were proposed to understand the occurrence of complications such as chorioretinal degenerative changes, choroidal neovascularization and polypoidal choroidal vasculopathy, macular serous retinal detachment, myopic foveoschisis and chorioretinal folds. These hypotheses could be referred to as the curvature "breaking point" hypothesis, the uneven growth "tractional" hypothesis, the "container-content" imbalance hypothesis, and the "choroidal funnel" hypothesis. Because these complications could also occur in other contexts, understanding the pathogenesis of TDS complications could help to understand their pathophysiology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Age-related macular degeneration (AMD) shares many of the same risk factors with atherosclerosis. There is a postulated role of lipid-lowering agents in preventing AMD. This meta-analysis investigates the possible role of statins in the prevention of AMD onset and progression., Methods: MEDLINE, EMBASE, Cochrane CENTRAL, and the reference lists of included studies were systematically searched from inception to September 2020. Studies were included if they measured the risk of AMD development or progression with statin use. The primary outcomes assessed were AMD incidence and progression. Secondary outcomes were the incidence of early AMD, late AMD, choroidal neovascularization, and geographic atrophy., Results: Twenty-one articles (1 randomized control trial and 20 observational studies) collectively reporting on 1,460,989 participants were included. The pooled risk ratios (95% confidence interval) for statin use on any, early, and late AMD incidence were 1.05 (0.85-1.29) (P = 0.44), 0.99 (0.88-1.11) (P = 0.86), and 1.15 (0.90-1.47) (P = 0.27), respectively. In patients with existing AMD, the respective risk ratios for statin use on incidence of AMD progression, choroidal neovascularization, and geographic atrophy were 1.04 (0.70-1.53) (P = 0.85), 0.99 (0.66-1.48) (P = 0.95), and 0.84 (0.58-1.22) (P = 0.36)., Conclusion: This meta-analysis found that there was no significant difference in the incidence or progression of AMD based on statin use.

A woman in her 70s who was being followed up for neovascular age-related macular degeneration (nAMD) in both eyes for 2 years with recalcitrant choroidal neovascularisation (CNV) and had an episode of acute endophthalmitis in one eye was identified. After treatment of postinjection culture-negative right eye (RE) endophthalmitis with intravitreal vancomycin and tazobactam, the patient had complete regression of treatment-resistant CNV in RE to date with postinfection follow-up of 2 years. In contrast, the fellow eye continued showing activity in the choroidal neovascular membrane that required antivascular endothelial growth factor injections on a pro re nata basis to date. Prolonged regression of nAMD for 3 years in the affected eye and continued activity in the fellow eye support the hypothesis that inflammation accompanying endophthalmitis or the drugs used for the treatment can have a role in the regression of nAMD., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Pigment epithelial detachment (PED) is common in eyes with central serous chorioretinopathy (CSC), and choroidal neovascularisation (CNV), which is almost always associated with PED, is found in a higher proportion than previously expected. Using en-face optical coherence tomography, this retrospective study aimed to investigate the PED location in relation to various geometric landmarks including the foveal centre (FC), greatest choroidal thickness (GCT) point and optic disc centre. In a total of 98 eyes, the distance from the FC to PED centroid was correlated with the ratio of GCT to subfoveal choroidal thickness (r = 0.278, P = 0.006) and the distance from the FC to GCT point (r = 0.371, P < 0.001). Eyes with CNV had a shorter distance between the PED centroid and FC (700 ± 439 μm) than those without (1191 ± 964 μm, P = 0.001). Analysis of covariance showed that the distance from the FC to the PED centroid was significantly correlated with the distance from the FC to the GCT point (P = 0.009) and the PED group with and without CNV (P = 0.020). This result suggests that the development of complicated PED with CNV can be related to both choroidal vascular abnormalities and retinal pigment epithelial insufficiency., (© 2022. The Author(s).)

Purpose: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential., Design: Multicenter, open-label, single- and multiple-dose phase 1 study., Methods: Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm 2 , best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, and 15 mg) or received 2 doses of NGM621 (15 mg) 4 weeks apart in the multidose phase and were monitored for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low-luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments., Results: All 15 participants completed the 12-week study. There were no serious adverse events, no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points., Conclusions: In this small, open-labeled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the 24-month outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in predominantly Caucasian eyes in routine clinical practice., Methods: Retrospective analysis of treatment-naïve eyes starting intravitreal injection of VEGF inhibitors of either bevacizumab (1.25 mg) or ranibizumab (0.5 mg) for mCNV from 1 January 2006 to 31 May 2018 that were tracked in the Fight Retinal Blindness! registry., Results: We identified 203 eyes (bevacizumab-85 and ranibizumab-118) of 189 patients. The estimated mean (95% CI) change in VA over 24 months for all eyes using longitudinal models was +8 (5, 11) letters with a median (Q1, Q3) of 3 (2, 5) injections given mostly during the first year. The estimated mean change in VA at 24 months was similar between bevacizumab and ranibizumab [+9 (5, 13) letters for bevacizumab versus +9 (6, 13) letters for ranibizumab; p = 0.37]. Both agents were also similar in the mCNV activity outcomes, treatment frequency and visit frequency., Conclusions: The 24-month treatment outcomes of VEGF inhibitors for mCNV were favourable in this largest series yet reported of predominantly Caucasian eyes in routine clinical practice, with approximately two lines of visual gain and a median of three injections given mostly during the first year. These outcomes are similar to those reported for predominantly Asian eyes. Bevacizumab appeared to be as safe and effective as ranibizumab., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Melanotic cells with large spherical melanosomes, thought to originate from retinal pigment epithelium (RPE), are found in eyes with neovascular age-related macular degeneration (nvAMD). To generate hypotheses about RPE participation in fibrosis, we correlate histology to clinical imaging in an eye with prominent black pigment in fibrotic scar secondary to nvAMD., Methods: Macular findings in a white woman with untreated inactive subretinal fibrosis due to nvAMD in her right eye were documented over 9 years with color fundus photography (CFP), fundus autofluorescence (FAF) imaging, and optical coherence tomography (OCT). After death (age 90 years), this index eye was prepared for light and electron microscopy to analyze 7 discrete zones of pigmentation in the fibrotic scar. In additional donor eyes with nvAMD, we determined the frequency of black pigment (n = 36 eyes) and immuno-labeled for retinoid, immunologic, and microglial markers (RPE65, CD68, Iba1, TMEM119; n = 3 eyes)., Results: During follow-up of the index eye, black pigment appeared and expanded within a hypoautofluorescent fibrotic scar. The blackest areas correlated to melanotic cells (containing large spherical melanosomes), some in multiple layers. Pale areas had sparse pigmented cells. Gray areas correlated to cells with RPE organelles entombed in the scar and multinucleate cells containing sparse large spherical melanosomes. In 94% of nvAMD donor eyes, hyperpigmentation was visible. Certain melanotic cells expressed some RPE65 and mostly CD68. Iba1 and TMEM119 immunoreactivity, found both in retina and scar, did not co-localize with melanotic cells., Conclusion: Hyperpigmentation in CFP results from both organelle content and optical superimposition effects. Black fundus pigment in nvAMD is common and corresponds to cells containing numerous large spherical melanosomes and superimposition of cells containing sparse large melanosomes, respectively. Melanotic cells are molecularly distinct from RPE, consistent with a process of transdifferentiation. The subcellular source of spherical melanosomes remains to be determined. Detailed histology of nvAMD eyes will inform future studies using technologies for spatially resolved molecular discovery to generate new therapies for fibrosis. The potential of black pigment as a biomarker for fibrosis can be investigated in clinical multimodal imaging datasets., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Subretinal fibrosis is a key pathological feature in neovascular age-related macular degeneration (nAMD). Previously, we identified soluble very low-density lipoprotein receptor (sVLDLR) as an endogenous Wnt signaling inhibitor. This study investigates whether sVLDLR plays an anti-fibrogenic role in nAMD models, including Vldlr -/- mice and laser-induced choroidal neovascularization (CNV). We found that fibrosis factors including P-Smad2/3, α-SMA, and CTGF were upregulated in the subretinal area of Vldlr -/- mice and the laser-induced CNV model. The antibody blocking Wnt co-receptor LRP6 significantly attenuated the overexpression of fibrotic factors in these two models. Moreover, there was a significant reduction of sVLDLR in the interphotoreceptor matrix (IPM) in the laser-induced CNV model. A transgenic strain (sVLDLR-Tg) with sVLDLR overexpression in the IPM was generated. Overexpression of sVLDLR ameliorated the profibrotic changes in the subretinal area of the laser-induced CNV model. In addition, Wnt and TGF-β signaling synergistically promoted fibrogenesis in human primary retinal pigment epithelium (RPE) cells. CRISPR/Cas9-mediated LRP6 gene knockout (KO) attenuated this synergistic effect. The disruption of VLDLR expression promoted, while the overexpression of sVLDLR inhibited TGF-β-induced fibrosis. These findings suggest that overactivated Wnt signaling enhances the TGF-β pathway in subretinal fibrosis. sVLDLR confers an antifibrotic effect, at least partially, through the inhibition of Wnt signaling and thus, has therapeutic potential for fibrosis., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Although choriocapillaris flow deficit (CFD) around choroidal neovascularization (CNV) is less associated with CNV activity in myopic eyes, no reports are investigating its size as an indicator of CNV activity. We investigated the relationship between CFD and high myopia-related CNV. In this retrospective, observational study, patients underwent optical coherence tomography angiography (OCTA) with split-spectrum amplitude-decorrelation angiography for diagnosing pathological myopic CNV (mCNV); CFD features around CNV margins were evaluated. Of the 33 eyes (30 patients), 11 (33.3%) had active mCNV, and 22 (66.7%) had inactive CNV. Six eyes (18.2%) were treatment-naïve, while the remainder previously underwent anti-vascular endothelial growth factor therapy. On OCTA, blood flow signals were detected in CNV in the outer retinal layer in 28 (84.8%) eyes, including all active cases (11 cases) and 17 (77.3%) of 22 inactive cases. CNV flow signal size correlated significantly with activity (P < 0.001). CFD around CNV was observed in 24 eyes (72.7%), including all active cases (11 cases) and 13 (59.1%) of 22 inactive cases. CFD size correlated significantly with CNV activity (P < 0.001). The size of both the CFD area around CNV and CNV flow signal area are useful indicators of CNV activity in eyes with mCNV, which may help determine treatment timing., (© 2021. The Author(s).)

To investigate the association between clinical features of chronic central serous chorioretinopathy (CSC) and subsequent development of polypoidal choroidal vasculopathy (PCV). Characteristics and treatment response of PCV secondary to CSC were described. This retrospective observational study included 18 patients with chronic CSC (18 eyes) with subsequent PCV and 36 controls (36 eyes) with chronic CSC without PCV development during follow-up. Clinical features were compared between the two groups. A logistic regression model was used to evaluate the risk factor of PCV formation. Treatments for PCV included anti-vascular endothelial growth factor (VEGF) monotherapy, photodynamic therapy (PDT), or PDT and anti-VEGF combination treatment. Subretinal fluid on optical coherence tomography images were assessed after treatments. Significant between-group differences were observed in best-corrected visual acuity after disease resolution and presence of pachyvessels (P = .001 and P = .003, respectively). The presence of pachyvessels in chronic CSC was associated with subsequent PCV (odds ratio = 6.00; 95% CI, 1.74-20.68; P = .005). CSC recurrence and subfoveal choroidal thickness (SFCT) were not significantly associated with subsequent PCV development (P = .393 and P = .911, respectively). The mean age of PCV diagnosis was 51 years, and the mean time from CSC diagnosis to PCV confirmation was 77.8 months. The mean (range) SFCT of PCV was 327.7 (134-599) μm. Nine patients received anti-VEGF monotherapy and 5 had disease remission. Four patients received PDT and anti-VEGF combination treatment and all of the 4 had disease remission. In chronic CSC, pachyvessel characteristics are associated with subsequent PCV development. This result will assist clinicians to evaluate CSC in clinical practice and provide insights into the pathogenesis of PCV.

Purpose: To report the morphological and clinical features of a case of pachychoroid disease with focal choroidal excavation and large choroidal excavation complicated by choroidal neovascularization., Methods: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity assessment, anterior segment and dilated fundus examination, fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography., Results: During the previous follow-up, the 57-year-old man received a diagnosis of central serous chorioretinopathy in the right eye with a late appearance of a choroidal neovascularization. The best-corrected visual acuity was 20/125 and 20/20 in the right and left eye, respectively. Dilated fundus examination, fluorescein angiography, and indocyanine green angiography confirmed a large subretinal fibrosis corresponding to the evolution of the choroidal neovascularization in the right eye. Spectral-domain optical coherence tomography clearly demonstrated in the right eye a large choroidal excavation below the fibrotic neovascular lesion with multiple hyperreflective foci inside the cavity, and in the left eye, a conforming focal choroidal excavation, bowl-shape type, associated with increased choroidal thickness with pachyvessels., Conclusion: Large choroidal excavation has been rarely reported. Although the pathogenetic mechanisms leading to the formation of large choroidal excavation are still only hypotheses, a combination of primary degenerative inflammatory factors sustaining the focal choroidal excavation formation and disruptive process of the choroidal neovascularization could be retained responsible for the large choroidal excavation.

Abstract: Optical coherence tomography angiography is one of the latest noninvasive imaging modalities for visualizing the vasculature of retina and choroid. We describe its application in the diagnosis, treatment, and monitoring of a patient with peripapillary choroidal neovascular membrane in the setting of idiopathic intracranial hypertension, who responded well to a course of ranibizumab intravitreal injections., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

A 44-year-old woman presented with decreased vision in both eyes. The retina in both eyes had drusen distributed along vascular arcades, central macula and in peripapillary region. Macula had pigmented scarring and exudation. Fundus autofluorescence showed drusen. Optical coherence tomography showed drusen, subretinal and intraretinal fluid. Fundus fluorescein and indocyanine green angiography showed drusen, retinal pigment epithelial atrophy and vascular network. Younger age at presentation, bilateral symmetry, typical distribution of drusen along the arcades in a radiating pattern, peripapillary involvement, scarring and atrophy at macula were suggestive of doyne honeycomb retinal dystrophy. The reduced vision was due to macular atrophy and an active choroidal neovascular membrane. The patient was treated with antivascular endothelial growth factor injections for choroidal neovascular membrane. Our case highlights the importance of pattern recognition and multimodal imaging for diagnosing the type of macular dystrophy as doyne honeycomb retinal dystrophy, while simultaneously managing choroidal neovascular membrane., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the case of a 19-year-old patient with symptomatic unilateral serous maculopathy associated with an optic nerve coloboma. Fluorescein angiography detected a focal late leak at the temporal edge of the coloboma which was later found to correspond with an area of choroidal neovascularisation on optical coherence tomography angiography. A course of intravitreal ranibizumab achieved good clinical and structural response. This report contributes to the evidence that maculopathies associated with cavitary optic nerve anomalies may in some instances result from choroidal neovascularisation. It also highlights the importance of angiography to identify potential choroidal neovascular membranes, particularly in the absence of haemorrhages and neovascular membranes on fundus examination and conventional optical coherence tomography., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)