Sub-retinal Pigment Epithelium Fluid Research Articles

Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER

ObjectiveTo compare the efficacy of brolucizumab and aflibercept treatment in reducing maximum thickness of pigment epithelial detachments (PED) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration (nAMD) in the HAWK and HARRIER studies. DesignHAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies Subjects, participants, and/or controls1,775 patients across 11 countries were included in the HAWK study and 1,048 patients across 29 countries were included in the HARRIER study. Method and interventionsAfter three monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks (q12w) or q8w if disease activity (DA) was detected. Aflibercept-treated eyes received fixed q8w dosing. Main outcomes measuresMaximum thickness of PED and sub-RPE fluid across the macula were assessed at baseline through Week 96 in the brolucizumab- and aflibercept-treated patients, and in the patient subgroups with DA at Week 16 (matched in terms of injection number and treatment interval). ResultsAt Week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PED and sub-RPE fluid in brolucizumab-treated patients versus aflibercept-treated patients (PED: 19.7% [n=336] vs 11.9% [n=335] in HAWK; 29.5% [n=364] vs 18.3% [n=361] in HARRIER. Sub-RPE fluid: 75.4% vs 57.3% in HAWK; 86.0% vs 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at Week 16. ConclusionsThis analysis shows that brolucizumab achieved greater reductions in PED and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER.

Данные о распределении патологической ретинальной жидкости у пациентов с неоваскулярной возрастной макулярной дегенерацией, получавших антиангиогенную терапию в течение 5 лет в условиях реальной клинической практики

Purpose. To analyze the distribution of pathological retinal fluids according to optical coherence tomography (OCT) over time in patients with neovascular age-related macular degeneration (nAMD) who received anti-angiogenic therapy for 5 years. Material and methods. A retrospective analysis of OCT data of patients treated with anti-VEGF therapy (ranibizumab, aflibercept) in the 3+PRN regimen was performed. The study group consisted of 24 patients (79.2 % women, mean age 70.5 years). Results. Best corrected visual acuity increased from the initial 0.31 0.42 0.52 to 0.40 0.50 0.60 (p = 0.00028) by the 60th month. Central retinal thickness decreased from initial 304.0 343.4 382.7 µm to 190.6 209.8 229.1 µm (p < 0.00001). Significant correlation indicators according to Spearman (p < 0.05) were established in relation to an increase in the proportion of patients who had a «dry» retina and cases of subretinal fluid (SRF) resolution. Using the method of proportions, a significant (p < 0.05) increase in the proportion of patients without pathological fluid was determined, as well as a decrease in the percentage of patients with SRF and sub-retinal pigment epithelium fluid, which were achieved in the first year of therapy and maintained until the end of the study, as well as a decrease in the proportion of patients with intraretinal fluid, which achieved a statistical significance (p < 0.05) by the 60th month. Conclusion. One of the indicators confirming the high efficiency of long-term (60 months) anti-VEGF therapy for nAMD was a decrease in the proportion of patients with all compartments of the pathological retinal fluid. Keywords: age-related macular degeneration, anti-VEGF therapy, optical coherence tomography, retinal fluid, biomarkers

Artifact-Removed Quantitative Analysis of Choriocapillaris Flow Voids.

To investigate choriocapillaris flow voids (FV) with a new optical coherence tomography angiography (OCTA) image processing strategy that can eliminate artifacts caused by vitreous opacities, sub-retinal pigment epithelium fluid and deposits, and subretinal fluid (SRF) by thresholding the en-face OCT image of the outer retina. We retrospectively reviewed medical records of patients with drusen and patients with active central serous chorioretinopathy (CSC). FV number (FVn), average area (FVav), and maximum area (FVmax) and the percentage of nonperfused choriocapillaris area (PNPCA) obtained using the proposed strategy were compared with those obtained by removing only artifacts caused by the superficial capillary plexus (SCP). The SRF group included 21 eyes with active CSC and the drusen group included 29 eyes with nonexudative age-related macular degeneration. FVav, FVmax, FVn, and PNPCA obtained using the algorithm were significantly lower than those obtained by removing only SCP-related artefacts in both groups (all p<0.05). The algorithm was also able to remove 96.9% of artifacts secondary to vitreous opacities and all artifacts secondary to serous pigment epithelial detachments. Choriocapillaris nonperfusion areas on OCTA images may be overestimated in eyes with RPE abnormalities and SRF due to artifacts. These artifact areas on choriocapillaris OCTA images can be removed using thresholded images of the outer retina en-face OCT scans. Our new artifact-removal strategy is useful in the assessment of choriocapillaris FV in eyes with SRF, drusen, drusen-like deposits, and pigment epithelial detachment.

Prevalence of Polypoidal Choroidal Vasculopathy in Eyes with Neovascular Age-Related Macular Degeneration Resistant to Intravitreal Anti-VEGF Treatment.

To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in intravitreal (IV) anti-vascular endothelial growth factor (anti-VEGF)-resistant neovascular age-related macular degeneration (nvAMD) cases. Eyes that were diagnosed as having active and treatment-naive nvAMD in the Ege University Ophthalmology Department, Retina Unit in 2011-2018, were non-responsive to IV anti-VEGF treatment, and for which indocyanine angiography (ICGA) could be obtained were included in the study. Active nvAMD was defined as the presence of fresh hemorrhage on clinical examination or findings of subretinal, intraretinal, or sub-retinal pigment epithelial fluid on spectral domain optical coherence tomography and accompanying fluorescein dye leakage in fluorescein angiography. Eyes that had activation findings despite at least 6 consecutive intravitreal anti-VEGF injections were defined as non-responders and underwent ICGA to assess for PCV. The diagnosis of PCV was based on the Everest II study criterion. A total of 97 eyes of 88 patients were included in the study. Of 88 patients, 44 (50%) were female, 44 (50%) were male, and the mean age was 75.9±8.3 years (range: 59-93). The mean number of anti-VEGF injections until the time of ICGA was 7.3±2.2 (range: 6-15). PCV was detected in 62 eyes (63.9%) on ICGA. The prevalence of PCV is quite high among eyes with IV anti-VEGF treatment-resistant nvAMD in Turkey (63.9%). ICGA evaluation for PCV should be conducted for all nvAMD cases that are non-responsive to IV anti-VEGF treatment, both to shed light on the reason for resistance and to modify treatment as necessary.

The Role of Retinal Plasticity in the Formation of Irreversible Retinal Deformations in Age-Related Macular Degeneration

Purpose To construct a realistic physical model of viscoelastic retinal stretching and, on its basis, derive a universal quantitative criterion of irreversible retinal deformations during age-related macular degeneration. Methods In this work, standard methods of nonlinear fracture mechanics of ductile and viscoelastic materials were applied to study the evolution of retinal deformation progress in patients with neovascular age-related macular degeneration in the area of large druses or subretinal or sub-retinal pigment epithelium fluid accumulation. A two-dimensional rhombic model of viscoelastic Kelvin-Feucht primitives was used to reconstruct the parameters included in the approximation of the creep strain growth rate. A clinical case of a patient with age-related macular degeneration and retinal pigment epithelium detachment in the macula was taken as a basis for theoretical research. The patient underwent retinal optical coherent tomography on DRI Swept-Source OCT. Results A closed realistic theoretical model of retinal stretching in the projection of retinal pigment epithelium elevation due to its detachment or drusen based on a two-dimensional rhombic Kelvin-Feucht primitives model was constructed. The calculation of stress in the retinal tissue with consistent consideration of creep effects was performed. Conclusions The time of critical retinal loading – a new quantitative criterion for the irreversibility of retinal stretching in age-related macular degeneration is proposed. This criterion allows the prediction of the functional outcome of antiangiogenic therapy in patients with age-related macular degeneration with identical initial retinal morphometric parameters.

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials

BackgroundThiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration...

Difference Between the Incidence of Retinal Fluid Subtypes and Their Association with Visual Outcomes According to the Types of Macular Neovascularization in a Korean Population.

Purpose: To investigate differences in the incidence of retinal fluid subtypes among different subtypes of macular neovascularization (MNV) and evaluate the influence of the presence of retinal fluid subtypes on visual outcome in each subtype of MNV. Methods: This retrospective study included 248 patients (248 eyes) diagnosed with treatment-naive neovascular age-related macular degeneration and polypoidal choroidal vasculopathy (PCV). The incidence of retinal fluid subtypes at diagnosis and during the 24-month follow-up was compared among the different subtypes of MNV. In addition, visual acuity was compared between patients with and without the retinal fluid subtypes. Results: At diagnosis, there was a significant difference in the incidence of subretinal fluid (SRF), intraretinal fluid (IRF), and subretinal pigment epithelial fluid among type 1 MNV, type 2 MNV, type 3 MNV, and PCV (P < 0.001). The incidence of SRF (P < 0.001) during follow-up also differed among the 4 groups. In patients with type 1 MNV and IRF, the visual acuity at diagnosis (P = 0.004) and at 24 months (P < 0.001) were significantly worse. However, the presence of SRF was not associated with poor visual acuity. In type 3 MNV, there was no significant difference in visual acuity between patients with and without SRF/IRF. Conclusion: The results of this study indicate that the clinical significance of retinal fluid subtypes may differ in different subtypes of MNV, suggesting the need for analysis in isolation of each MNV subtype in fluid-based prognostication.

IMPACT OF FLUID COMPARTMENTS ON FUNCTIONAL OUTCOMES FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Systematic Literature Review.

Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment. Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible. Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status. To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.

Intraretinal, sub-retinal, and sub-retinal pigmented epithelium fluid in non-exudative age-related macular degeneration: follow-up with OCT imaging.

To evaluate the presence and evolution of fluid in non-exudative age-related macular degeneration (AMD) through serial OCT. A retrospective analysis of eyes with non-exudative AMD with a minimum of 4 year follow-up was done. Parameters including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid (SRPEF); subfoveal choroidal thickness (SFCT) and type of drusen were evaluated using optical coherence tomography (OCT) scans at baseline and follow up visits. Seventy-two eyes (in 63 patients) were followed up for an average of 5.83 ± 2.17 years. A total of 26/72 (36%) and 29/65 (52%) of the non-exudative eyes had fluid during baseline and the last visit. Seven eyes (10%) out of 72 eyes converted into exudative AMD or neo-vascular AMD (nAMD) during the study period. SRPEF at baseline was most common fluid location for non-exudative eyes that eventually converted to nAMD. Non-exudative fluid including IRF, SRF, and SRPEF is seen in patients with non-exudative AMD with increasing incidence during long term follow-up.

Resident physician concordance in tomographic fluid detection in näive patients with neovascular age-related macular degeneration (AMD)

Abstract Purpose To analyze the presence of subretinal fluid (SRF), intraretinal fluid (IRF) and subretinal pigment epithelial fluid (SRPEF) in naive patients with exudative neovascular AMD at baseline and at one year follow-up and treatment, in clinical practice, and perform a concordance analysis between resident physicians. Methods A retrospective analysis of the naive patients who attended our service for 6 months between 2016–2017 by neovascular AMD was performed. Optical coherence tomography (OCT), at baseline and at one year follow-up, were analyzed from independently by two resident doctors, determined the presence or not of SRF, IRF, SRPEF. A retina specialist ophthalmologist intervened in cases where there was no consensus among resident physicians. A descriptive and interobserver concordance analysis was performed. Results 27 eyes of 24 patients were evaluated, 20.8% being men and 79.16% women, with a mean age of 78.57 ± 8 years. 32.14% of the eyes presented the three types of fluid before the start of treatment and the frequency of the different fluids at the beginning and at the end of the follow-up were respectively: SRF, 82.1% and 50%; IRF, 57.1% and 41.7%, and SRPEF, 67.9% and 79.2%). The Kappa analysis of interobserver concordance in the evaluation of the different fluids at the beginning and at the end of the follow-up were respectively: SRF, 0.88 and 0.67; IRF, 0.86 and 0.91, and SRPEF, 0.65 and 0.78. Conclusions The presence of SRF, IRF, RPEF in clinical practice, in the debut of neovascular AMD has a similar distribution to that presented in international clinical trials. The agreement between resident physicians is very good for SRF and IRF and good for SRPEF in the debut of the disease and good for SRF and IRF and very good for SRPEF at one year of treatment.

ASSESSMENT OF EARLY CHANGES IN SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY AFTER INITIATION OF TREATMENT WITH INTRAVITREAL AFLIBERCEPT (EYLEA) OVER A 12-WEEK PERIOD FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Multicenter French Study (START).

To assess early changes in spectral-domain optical coherence tomography during the loading phase with intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration. In this prospective, open-label, single-arm, multicenter study, patients with neovascular age-related macular degeneration, who were antivascular endothelial growth factor treatment-naïve, received three monthly initial doses of intravitreal aflibercept 2 mg. The primary outcome was the proportion of patients with dry spectral-domain optical coherence tomography at 12 weeks, defined as an absence of intraretinal edema, intraretinal cysts, subretinal fluid, and subretinal pigment epithelium fluid. Fifty eyes of 50 patients were investigated. At 12 weeks, 34.0% (17/50) had dry spectral-domain optical coherence tomography. Marked reductions were observed for all other spectral-domain optical coherence tomography parameters. The mean macular central thickness fell significantly from 463.2 ± 184.3 µm at baseline to 288.9 ± 76.8 µm at Week 12 (P < 0.0001). The mean best-corrected visual acuity also improved significantly from 61.0 ± 16.0 letters at baseline to 66.6 ± 19.0 letters at Week 12 (P = 0.0006). The anatomic and functional outcomes improved over the 12-week study period. All outcome variables peaked after the third aflibercept injection, confirming the benefit of three initial doses.

Transient accumulation of subretinal fluid after half-fluence photodynamic therapy in neovascular age-related macular degeneration

BackgroundPhotodynamic therapy (PDT) is known to occlude choroidal neovascularisation selectively, and there have been several reports on its adverse effects on the normal choroid and retinal pigment epithelium, resulting in decreased vision.MethodsThis retrospective interventional case series aimed to investigate the changes in visual acuity and retinal thickness in the immediate post-treatment period after half-fluence PDT, administered alone or with anti-vascular endothelial growth factor and steroids, in 29 eyes (26 patients) with neovascular age-related macular degeneration. The patients’ best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography images were measured 1 day, 1 week, and 1 month post-treatment.ResultsCompared to the pre-treatment CFT (270.38 μm), the mean CFT was significantly increased 1 day post-treatment (387.07 μm, P = 0.001), which then started to decrease, with a mean CFT of 269.32 μm (P = 0.516) at 1 week, and of 240.66 μm (P = 0.066) at 1 month post-treatment. All CFT increases were due to the accumulation of subretinal fluid (SRF), rather than the intraretinal or subretinal pigment epithelium fluid. Relative to the pre-treatment BCVA (0.59 logMAR), the mean BCVA at 1 day (0.74 logMAR, P = 0.005) and 1 week (0.75 logMAR, P = 0.002) post-treatment was significantly deteriorated; however, it recovered to 0.62 logMAR at 1 month. The patterns of change in CFT and BCVA did not differ according to treatment modality.ConclusionsHalf-fluence PDT resulted in accumulation of SRF in the immediate post-treatment period; this damage mostly recovered within a week, and the BCVA was restored within a month.

Estudio del fluido tomográfico y concordancia en su detección entre médicos residentes en pacientes näive con degeneración macular asociada a la edad (DMAE) neovascular

PurposeTo analyze the presence of subretinal fluid (SRF), intraretinal fluid (IRF) and subretinal pigment epithelial fluid (SRPEF) in näive patients with exudative neovascular AMD at baseline and at one year follow-up and treatment, in clinical practice, and perform a concordance analysis between resident physicians. MethodsA retrospective analysis of the näive patients who attended our service for 6months between 2016-2017 by neovascular AMD was performed. Optical coherence tomography (OCT), at baseline and at one year follow-up, were analyzed from independently by two resident doctors, determined the presence or not of SRF, IRF, SRPEF. A retina specialist ophthalmologist intervened in cases where there was no consensus among resident physicians. A descriptive and interobserver concordance analysis was performed. Results27 eyes of 24 patients were evaluated, 20.8% being men and 79.16% women, with a mean age of 78.57±8years. 32.14% of the eyes presented the three types of fluid before the start of treatment and the frequency of the different fluids at the beginning and at the end of the follow-up were respectively: SRF, 82.1% and 50%; IRF, 57.1% and 41.7%, and SRPEF, 67.9% and 79.2%). The Kappa analysis of interobserver concordance in the evaluation of the different fluids at the beginning and at the end of the follow-up were respectively: SRF, 0.88 and 0.67; IRF, 0.86 and 0.91, and SRPEF, 0.65 and 0.78. ConclusionsThe presence of SRF, IRF, RPEF in clinical practice, in the debut of neovascular AMD has a similar distribution to that presented in international clinical trials. The agreement between resident physicians is very good for SRF and IRF and good for SRPEF in the debut of the disease and good for SRF and IRF and very good for SRPEF at one year of treatment.

Localized Optical Coherence Tomography Precursors of Macular Atrophy and Fibrotic Scar in the Comparison of Age-Related Macular Degeneration Treatments Trials

To identify precursors of macular atrophy (MA) and of fibrotic scar (FS) in eyes treated with anti-vascular endothelial growth factor through pixel-mapping analysis of baseline optical coherence tomography (OCT). Design: Cross-sectional analysis. Multicenter clinical trial. 68 eyes from the Comparison of Age-Related Macular Degeneration Treatments Trials. Treatment with anti-vascular endothelial growth factor agents. The percentage of MA or FS pixels with each OCT feature at baseline, and the odds ratio for baseline pixels with an OCT feature to develop MA or FS. Retinal pigment epithelium atrophy and photoreceptor loss on OCT were highly predictive of MA at that location at years 2 and 5 (P < .0001), but accounted for only 22.5% of the ensuing atrophy at year 2 and less at year 5. Among pixels of MA at year 2, 78% were preceded by thick drusen, 54% by subretinal macular neovascularization (MNV), and 22.5% by no detectable OCT features. MNV, subretinal hyperreflective material, pigment epithelial detachment, intraretinal fluid, and sub-retinal pigment epithelium fluid were predictive of FS at that location (P values <.05). More than 75% of the pixels of FS at years 2 and 5 were preceded by pixels of baseline MNV. Most pixels of FS were preceded by components of neovascularization. Although one-quarter of MA was accounted for by pre-existing evidence of atrophy on OCT alone, the development of MA in areas of thick drusen, areas with and without subretinal MNV lesion, and areas without detectable OCT precursors argues that the development of MA is multifactorial and may follow, in part, a non-neovascular pathway.

Five-Year Follow-up of Nonfibrotic Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials

To describe changes in visual acuity (VA) and macular morphologic features at 5 years in eyes with nonfibrotic scar (NFS) identified at 1 year in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a randomized clinical trial. Participants in CATT. Participants assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens were released from the clinical trial protocol after 2 years and recalled at 5 years. Nonfibrotic scar was identified on color images at year 1 as flat, small, well-circumscribed areas of pigmentation with varying degrees of central hypopigmentation without exposure of underlying choroidal vessels at the site of baseline choroidal neovascularization. Follow-up images were assessed for changes in and around NFS. Pigmentation changes, VA, development of fibrotic scar (FS), nongeographic atrophy (NGA), geographic atrophy (GA), retinal fluid on OCT, and fluorescein leakage. Among 474 eyes with images obtained at 1, 2, and 5 years, 39 (8.2%) showed NFS at 1 year with a mean VA of 80 letters (Snellen equivalent, 20/25). Among these eyes, FS developed in 5% at 2 years and 28% at 5 years. Nongeographic atrophy was observed in 34%, 47%, and 65% of eyes at 1, 2, and 5 years, respectively. Geographic atrophy developed in 5% of eyes at 2 years and 21% at 5 years. Among eyes with NFS, FS, or no scar at 1 year, mean VA at 5 years was 73 letters (20/32), 48 letters (20/100), and 62 letters (20/63), respectively. At 5 years, NFS eyes demonstrated less GA, less intraretinal fluid, more subretinal fluid, and less subretinal pigment epithelium fluid (all P < 0.01). Among NFS eyes, mean thickness of the retina, subretinal tissue complex, and total retina did not change across years 1 to 5 (P > 0.50). The proportion of eyes with fluid on OCT also did not change (P= 0.36). Subretinal hyperreflective material disappeared by 5 years in 40% of eyes with NFS. These results indicate that, on average, eyes with NFS after anti-VEGF treatment have good VA not only at 1 and 2 years, but also through 5 years.

Macular Fluid Reduces Reproducibility of Choroidal Thickness Measurements on Enhanced Depth Optical Coherence Tomography

To determine if different types of retinal fluid in the central macula affect the reproducibility of choroidal thickness (CT) measurements on enhanced depth imaging optical coherence tomography (EDI-OCT). Retrospective reliability analysis. EDI-OCT images were obtained and the choroidal-scleral junction was analyzed through semiautomated segmentation. CT was measured at the fovea and averaged across the central 3-mm horizontal segment. Demographic data, central macular thickness, and type of fluid present were recorded. Intragrader and intergrader repeatability were assessed using the intraclass correlation coefficient (ICC) and coefficient of repeatability (CR). Of 124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had neovascular age-related macular degeneration, and 32 (25.8%) had other causes of fluid. Intergrader ICC (CR) was 0.95 (74.1μm) and 0.96 (63.9μm) for subfoveal and average CT, respectively. CR was similar across various causes of retinal fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal pigment epithelial fluid. CR also worsened with increasing choroidal thickness, but was not affected by retinal thickness. Intragrader repeatability was generally greater than intergrader values, and followed the same trend. The presence of macular fluid reduces CT measurement reproducibility, particularly in eyes with subretinal fluid and greater choroidal thickness. A difference of 74.1μm in subfoveal CT or 63.9μm in average CT may be necessary to detect true clinical change in eyes with macular fluid.

Automatic Subretinal Fluid Segmentation of Retinal SD-OCT Images With Neurosensory Retinal Detachment Guided by Enface Fundus Imaging.

Accurate segmentation of neurosensory retinal detachment (NRD) associated subretinal fluid in spectral domain optical coherence tomography (SD-OCT) is vital for the assessment of central serous chorioretinopathy (CSC). A novel two-stage segmentation algorithm was proposed, guided by Enface fundus imaging. In the first stage, Enface fundus image was segmented using thickness map prior to detecting the fluid-associated abnormalities with diffuse boundaries. In the second stage, the locations of the abnormalities were used to restrict the spatial extent of the fluid region, and a fuzzy level set method with a spatial smoothness constraint was applied to subretinal fluid segmentation in the SD-OCT scans. Experimental results from 31 retinal SD-OCT volumes with CSC demonstrate that our method can achieve a true positive volume fraction (TPVF), false positive volume fraction (FPVF), and positive predicative value (PPV) of 94.3%, 0.97%, and 93.6%, respectively, for NRD regions. Our approach can also discriminate NRD-associated subretinal fluid from subretinal pigment epithelium fluid associated with pigment epithelial detachment with a TPVF, FPVF, and PPV of 93.8%, 0.40%, and 90.5%, respectively. We report a fully automatic method for the segmentation of subretinal fluid. Our method shows the potential to improve clinical therapy for CSC.

Incidence and Growth of Geographic Atrophy during 5 Years of Comparison of Age-Related Macular Degeneration Treatments Trials

To estimate the incidence, size, and growth rate of geographic atrophy (GA) during 5 years of follow-up among participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Cohort within a clinical trial. Participants included in CATT. A total of 1185 CATT participants were randomly assigned to ranibizumab or bevacizumab treatment and to 3 treatment regimens. Participants were released from protocol treatment at 2 years and examined at approximately 5 years (N= 647). Two masked graders assessed the presence and size of GA in digital color photographs (CPs) and fluorescein angiograms (FAs) taken at baseline and years 1, 2, and 5. Cox proportional hazard models were used to identify risk factors for incidence of GA. Annual change in the square root of the total area of GA was the measure of growth. Multivariate linear mixed models including baseline demographic, treatment, and ocular characteristics on CP/FA and optical coherence tomography (OCT) as candidate risk factors were used to estimate adjusted growth rates, standard errors (SEs), and 95% confidence intervals (CIs). Geographic atrophy incidence and growth rate. Among the 1011 participants who did not have GA at baseline and had follow-up images gradable for GA, the cumulative incidence was 12% at 1 year, 17% at 2 years, and 38% at 5 years. At baseline, older age, hypercholesterolemia, worse visual acuity, larger choroidal neovascularization (CNV) area, retinal angiomatous proliferation (RAP) lesion, GA in the fellow eye, and intraretinal fluid were associated with a higher risk of incident GA. Thicker subretinal tissue complex and presence of subretinal fluid were associated with less GA development. The overall GA growth rate was 0.33 mm/year (SE, 0.02 mm/year). Eyes treated with ranibizumab in the first 2 years of the clinical trial had a higher growth rate than eyes treated with bevacizumab (adjusted growth rate, 0.38 vs. 0.28 mm/year; P= 0.009). Geographic atrophy in the fellow eye, hemorrhage, and absence of sub-retinal pigment epithelium fluid at baseline were associated with a higher growth rate. Development of GA is common 5 years after initiating therapy. Several risk factors identified at 2 years of follow-up persist at 5 years of follow-up.

Single-Nucleotide Polymorphisms Associated With Age-Related Macular Degeneration and Lesion Phenotypes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

Single-nucleotide polymorphisms (SNPs) associated with the CFH, ARMS2, C3, LIPC, CFB, and C2 genes are associated with age-related macular degeneration (AMD); however, the association of these SNPs with angiographic features of neovascular AMD has been inconsistent in previous studies, and to date, no studies have addressed their association with features on optical coherence tomography. To evaluate the influence of genotype of SNPs previously associated with AMD on the phenotype of neovascular lesions. Participants for this cross-sectional study were recruited from the 1185 patients enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), a randomized clinical trial. Eligibility criteria for CATT specified that eyes have choroidal neovascularization and visual acuity between 20/25 and 20/320. A subgroup of 835 patients provided blood samples from July 2010 through September 2011 and were genotyped for the SNPs rs1061170 (CFH), rs10490924 (ARMS2),rs2230199 (C3), rs10468017 (LIPC), rs4151667 (CFB), rs547154 (C2) using TaqMan SNP genotyping assays. Data analysis was initiated in November 2013 and completed in January 2016. Pretreatment ocular characteristics on fluorescein angiography (lesion type, area of neovascularization and total lesion, retinal angiomatous proliferation) and on time-domain optical coherence tomography (presence of intraretinal, subretinal, and subretinal pigment epithelium fluid; thickness at the foveal center of the retina, subretinal fluid, and subretinal tissue complex), visual acuity, and age. A total of 835 (73%) of 1150 CATT patients were genotyped. Mean age decreased with the number of risk alleles for CFH (P < .001), ARMS2 (P < .001), and C3 (P = .005). The following results were found as the number of risk alleles increased from 0 to 1 to 2. For CFH, mean total thickness decreased from 476 to 476 to 434 µm (P = .01; adjusted for age, sex, and smoking status). For ARMS2, the mean area of the total lesion increased from 2.0 to 2.8 to 2.4 mm2 (P = .03), the proportion with retinal angiomatous proliferation lesions increased from 8% to 10% to 12% (P = .05), and the proportion with intraretinal fluid increased from 72% to 71% to 82% (P = .008). For C3, the proportion with intraretinal fluid decreased from 78% to 69% to 64% (P = .001), and the mean retinal thickness decreased from 225 to 207 to 197 µm (P = .02). CFH, ARMS2, and C3 were associated with specific features of neovascularization at the time patients were enrolled in CATT. Previously identified associations of ARMS2 and CFH with type of choroidal neovascularization on fluorescein angiography were not confirmed. New associations with OCT features identified in CATT need confirmation to establish whether a true association exists. clinicaltrials.gov Identifier: NCT00593450.

Automated Identification of Lesion Activity in Neovascular Age-Related Macular Degeneration

The objective of the study was to evaluate the accuracy of the Notal OCT Analyzer (NOA) versus that of a retina specialist (RS) in the automated detection of fluid on optical coherence tomography (OCT). A study of the performance of the NOA compared with the results from 3 RSs. A selection of 155 anonymized OCT scans (Zeiss Cirrus; Carl Zeiss Meditec, Dublin, CA) from an image repository at a single tertiary referral retina center (Belfast Health and Social Care Trust, Belfast, United Kingdom) after approval from the local data guardian of the clinical site. One hundred fifty-five OCT cube scans were stripped of all clinical identifiers and exported. The NOA and 3 independent RSs analyzed all 128 B-scans of each cube scan for the presence of intraretinal fluid, subretinal fluid, and sub-retinal pigment epithelium fluid. The NOA also ranked individual B-scans of each volume scan for likelihood of CNV activity, which was subjected to a second grading session by the 3 RSs. The NOA's sensitivity and specificity versus the RS grading and the NOA's performance in ranking B-scans for activity. One hundred forty-two cube scans met the inclusion criteria for the primary analysis. On testing the RS grading versus the NOA, the accuracy was 91% (95% confidence interval [CI], ±7%), sensitivity was 92% (95% CI, ±6%), and specificity was 91% (95% CI, ±6%), meeting the primary outcome. The graders' accuracy when compared with the majority of the other graders (including a fourth grader) was 93%. On average, the 3graders could identify fluid in 95% of scans by just reviewing a single cross-section with the highest NOA score and 99.5% of scans with fluid by viewing the top 3 cross-sections. Concordance between the NOA and the RS determination of lesion activity was extremely high. The level of discrepancy between the RS and the NOA results was similar to the NOA's mismatches. Our results show that automated delineation of the retinal contours combined with interpretation of disease activity is feasible and has the potential to become a powerful tool in terms of its clinical applications.