Association of imaging factors derived from convolutional neural network with visual outcomes in age-related macular degeneration and polypoidal choroidal vasculopathy.
ABSTRACT: We investigated the association of visual outcome in typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) with or without pachychoroid with lesion areas on optical coherence tomography (OCT) quantified by convolutional neural network (CNN) analysis. Treatment-naïve 132 nAMD and 45 PCV eyes treated with ranibizumab or aflibercept for at least 12 months were retrospectively reviewed. Significant factors, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED) and subretinal hyperreflective material (SHRM) area quantified by CNN at baseline and 12 months, were analyzed by logistic regression analyses for 3-line visual gain or maintenance of 20/30 Snellen vision. Visual gain at the final visit in nAMD was associated with a smaller SHRM at baseline (OR 0.167, P?=?0.03), greater decrease in SRF and SHRM from baseline to month 12 (OR 1.564, P?=?0.02; OR 12.877, P?=?0.01, respectively). Visual gain in nAMD without pachychoroid was associated with a greater decrease in SRF and SHRM (OR 1.574, P?=?0.03, OR 1.775, P?=?0.04). No association was found in nAMD with pachychoroid and any type of PCV. Greater decrease in SRF and SHRM from baseline to month 12 was associated with favorable visual outcomes in nAMD without pachychoroid but not in nAMD with pachychoroid and PCV.
Project description:PURPOSE:To evaluate associations of morphologic features with 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). DESIGN:Cohort study within a randomized clinical trial. PARTICIPANTS:Participants in CATT. METHODS:Eyes with age-related macular degeneration-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists' discretion thereafter. MAIN OUTCOME MEASURES:Visual acuity, thickness and morphologic features on OCT, and lesion size and foveal composition on fundus photography (FP) and fluorescein angiography (FA). RESULTS:Visual acuity and image gradings were available for 523 of 914 participants (57%) alive at 5 years. At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid (SRF), 36% had subretinal pigment epithelium (RPE) fluid, and 66% had subretinal hyper-reflective material (SHRM). Mean (standard deviation) foveal center thickness was 148 ?m (99) for retina, 5 ?m (21) for SRF, 125 ?m (107) for subretinal tissue complex, 11 ?m (33) for SHRM, and 103 ?m (95) for RPE + RPE elevation. The SHRM, thinner retina, greater CNV lesion area, and foveal center pathology (all P < 0.001) and IRF (P < 0.05) were independently associated with worse VA. Adjusted mean VA letters were 62 for no pathology in the foveal center; 61 for CNV, fluid, or hemorrhage; 65 for non-geographic atrophy (GA); 64 for nonfibrotic scar; 53 for GA; and 56 for fibrotic scar. Incidence or worsening of 8 pathologic features (foveal GA, foveal scar, foveal CNV, SHRM, foveal IRF, retinal thinning, CNV lesion area, and GA area) between years 2 and 5 was independently associated with greater loss of VA from years 2 to 5 and VA loss from baseline to year 5. CONCLUSIONS:Associations between VA and morphologic features previously identified through year 1 were maintained or strengthened at year 5. New foveal scar, CNV, intraretinal fluid, SHRM and retinal thinning, development or worsening of foveal GA, and increased lesion size are important contributors to the VA decline from years 2 to 5. A significant need to develop therapies to address these adverse pathologic features remains.
Project description:BACKGROUND/OBJECTIVES:To investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians' decision to retreat with anti-VEGFs. SUBJECTS/METHODS:Retrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses. RESULTS:In 321 eyes, absence of IRF or SRF at ?2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p?=?0.006) or SRF (p?=?0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits. CONCLUSIONS:Retreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.
Project description:IMPORTANCE:It is important to identify features of polypoidal choroidal vasculopathy (PCV) that differentiate it from typical neovascular age-related macular degeneration (nAMD) on various imaging modalities, including fluorescein angiography (FA). BACKGROUND:PCV was thought to be indistinguishable from nAMD using FA alone. In real-world practice, indocyanine-green angiography may often be unavailable or contraindicated. DESIGN:Analysis of FA images from a prospective, multicentre study. PARTICIPANTS:Study images of both PCV and nAMD patients from the EVEREST study. METHODS:FA features at baseline were independently graded by masked graders (fellowship-trained ophthalmologists) using standardized diagnostic algorithms. MAIN OUTCOME MEASURES:Predictive indicators (sensitivity, specificity, positive and negative predictive values) for PCV. RESULTS:Of the 95 patients screened, 61 had PCV. Of the 34 screening failures, 15 were diagnosed as nAMD. Hyperfluorescent nodules on FA were observed in 80% of patients with PCV vs 20% with nAMD (P < 0.001). Blocked fluorescence on FA, which corresponded to the presence of subretinal haemorrhage, occurred more frequently among patients with PCV vs nAMD (61.7% vs 13.3%, P = 0.001). Similarly, the leakage characteristic of occult choroidal neovascularization occurred more frequently among patients with PCV vs nAMD (95.0% vs 73.3%, P = 0.026). The positive predictive value for PCV was 94.1% for hyperfluorescent nodules, 94.9% for blocked fluorescence, 83.8% for occult choroidal neovascularization and 82.0% for pigment epithelial detachment. CONCLUSIONS AND RELEVANCE:This study demonstrated that certain FA features can be predictive of PCV and may be considered as an indication for retina specialists to perform indocyanine green angiography as confirmatory test.
Project description:Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with clinical features distinct from neovascular age-related macular degeneration (nAMD) which is the leading cause of irreversible blindness in the elderly. Our studies focused on the genetic background and function of a novel gene HERPUD1 in PCV. HERPUD1 has been reported to increase the level of amyloid ? (A?), which is a component of drusen deposits underlying the retinal pigment epithelium (RPE) layer. To verify the genetic functional associations of HERPUD1 with PCV, exome sequencing of HERPUD1 was performed in unrelated Chinese individuals, including nAMD patients, PCV patients and control subjects. Immunohistochemistry assays for HERPUD1 were performed in the subretinal membranes of PCV patients. The relationship between HERPUD1 and amyloid beta precursor was determined using real-time PCR in HERPUD1-overexpressing RPE cells. The gene expression patterns of angiogenesis cytokines and chemokines in both A?-treated RPE cells and in Brown Norway rats that received A? subretinal injections were determined. We showed that HERPUD1 rs2217332 is significant associated with Chinese PCV, and HERPUD1 was expressed in PCV subretinal membranes. Besides, Plasma A?42 protein was significantly higher in PCV patients compared to nAMD and control subjects. A? could upregulate angiogenic factors, chemokines and matrix metalloproteinases both in RPE cells and in a rat model of subretinal A? injection. The imbalance of the cytokines may be one of the mechanisms for the formation and development of PCV. Our results strongly suggest that HERPUD1 is highly associated with PCV patients.
Project description:Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) and fibrosis. In the current study, we aimed to investigate the effect of blockade for platelet derived growth factor receptor-? (PDGFR-?) on the formation of choroidal neovascularization and fibrosis in the laser-induced CNV model in mice. Firstly, the presence of PDGFR-? in CNV lesions were confirmed. Intravitreal injection of PDGFR-? neutralizing antibody significantly reduced the size of CNV and subretinal fibrosis. Additionally, subretinal hyperreflective material (SHRM), a landmark feature on OCT as a risk factor for subretinal fibrosis formation in nAMD patients was also suppressed by PDGFR-? blockade. Furthermore, pericytes were abundantly recruited to the CNV lesions during CNV formation, however, blockade of PDGFR-? significantly reduced pericyte recruitment. In addition, PDGF-BB stimulation increased the migration of the rat retinal pericyte cell line, R-rPCT1, which was abrogated by the neutralization of PDGFR-?. These results indicate that blockade of PDGFR-? attenuates laser-induced CNV and fibrosis through the inhibition of pericyte migration.
Project description:Polypoidal choroidal vasculopathy (PCV) is a retinal disorder commonly found in Asians presenting as neovascular age-related macular degeneration and is characterized by serous macular detachment, serous or hemorrhagic pigment epithelial detachment, subretinal hemorrhage, and occasionally visible orange-red subretinal nodular lesions. PCV is diagnosed using indocyanine green angiography (ICGA), and the lesions appear as polypoidal aneurysmal vascular lesions with or without abnormal branching vascular network. Although ICGA remains the gold standard for the diagnosis of PCV, various imaging modalities have also facilitated the diagnosis and monitoring of PCV. Recent advances in imaging technology including the use of high resolution spectral domain optical coherence tomography (OCT) and OCT angiography have provided new insights on the pathogenesis of PCV, suggesting a link between PCV and pachychoroid spectrum of macular disorders. With the evolving understanding on the pathogenesis and clinical characteristics of PCV, different therapeutic options have been proposed. These include intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy, combination therapy with anti-VEGF and verteporfin photodynamic therapy, and thermal laser photocoagulation. In recent years, major multi-center randomized clinical trials such as EVEREST, EVEREST II, and PLANET studies have been conducted to compare the efficacy and safety of various treatment options for PCV. This review aims to summarize the results of recent literature, clinical trials and studies to provide an update on the management options of PCV. An overall management strategy for PCV will also be proposed.
Project description:To describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).Prospective cohort study within a randomized clinical trial.Patients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).Eyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation.Scar formation.Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4-3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1-1.8), foveal retinal thickness >212 ?m (aHR, 2.4; CI, 1.7-3.6) versus <120 ?m, foveal subretinal tissue complex thickness >275 ?m (aHR, 2.4; CI, 1.7-3.6) versus ?75 ?m, foveal subretinal fluid (aHR, 1.5; CI, 1.1-2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3-2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5-0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars.Approximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar.
Project description:Age-related macular degeneration (AMD) is the main cause of visual impairment and legal blindness in older individuals. COL8A1 rs13095226 variants have recently been implicated associated with neovascular age-related macular degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV) in American studies. The aim of this study was to investigate the association between the COL8A1 rs13095226 Polymorphism and neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese people.900 Chinese subjects-300 cases with nAMD, 300 cases with PCV and 300 controls, were enrolled in a cross-sectional observational study. The diagnoses of nAMD and PCV were confirmed by Fundus photography, Fluorescence Fundus Angiography (FFA) and Indocyanine Green Angiography (ICGA). Genomic DNA was extracted from venous blood leukocytes and genotypes of rs13095226 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Differences in allele distribution between cases and controls were tested by chi-square tests, with age and gender adjusted by logistic regression analysis.The COL8A1 rs13095226 polymorphism was not statistically significantly different from the nAMD or PCV to the normal controls (P>0.05) in Chinese Population. The association remained insignificant after adjustment for age and gender differences (P>0.05).This case-control study indicated that the COL8A1 rs13095226 polymorphism is not associated with nAMD or PCV, which suggesting this gene maybe not a susceptibility gene locus for nAMD or PCV in Chinese subjects.
Project description:To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a randomized clinical trial.The 1185 CATT participants.Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Presence of SHRM, as well as location and size, and associations with VA, scar, and GA.Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 ?m, 120 ?m, and 122 ?m, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05).In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.
Project description:BACKGROUND:Polypoidal choroidal vasculopathy (PCV) is one of the disorders within the pachychoroid spectrum diseases. The presence of pachyvessels is one of the characteristics of pachychoroid disorders. However, the relationship between the presence of pachyvessels and the clinical characteristics of PCV eyes has not been determined. The purpose of this study was to determine the relationship between the presence of choroidal pachyvessels and the clinical characteristics of eyes with PCV. METHODS:The medical records of patients who were diagnosed with PCV and were treatment-naïve were reviewed. Fluorescein and indocyanine green angiography, fundus photography, spectral domain optical coherence tomography (SD-OCT), and enhanced depth imaging OCT (EDI-OCT) were used to obtain images of the choroid. The presence of pathologically dilated outer choroidal vessels, pachyvessels, was determined by ICGA images. These pachyvessels were confirmed to correspond with the large choroidal vessels in the EDI OCT images. The PCV eyes were divided into two groups based on the presence or absence of pachyvessels and clinical features and subfoveal choroidal thickness (SFCT) were evaluated between the two groups. RESULTS:Eighty-six eyes of 84 patients with PCV were evaluated. Pachyvessels were detected in 48 eyes (55.8%). The mean SFCT was 203.9?±?83.9??m in all 86 eyes, and it was significantly thinner in eyes with pachyvessels (+) than without pachyvessels (-) (183.2?±?58.4??m vs 230.2?±?103.1??m; P =?0.01). The differences in the incidence of subretinal fluid, pigment epithelial detachments, and hemorrhages between the two groups were not significant. However, the PCV eyes in pachyvessels (+) group with hemorrhage had the thinnest choroid (P =?0.047). The choroidal features of the fellow eyes were similar to those of the PCV affected eyes, that is, the fellow eyes in pachyvessels (+) group had pachyvessels and the fellow eyes in pachyvessels (-) group did not have pachyvessels. CONCLUSIONS:Pachyvessels were presented 55.8% in eyes with PCV, and these eyes had the thin SFCT. The presence of pachyvessels and attenuation of the inner choroid were probably due to the pathological changes in the eyes with PCV.