DEFINING "STRONG" VERSUS "WEAK" RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR CENTER-INVOLVED DIABETIC MACULAR EDEMA.

BACKGROUND/PURPOSE: To define "strong" versus "weak" antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME). METHODS: Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25-20/32, 20/40-20/63, or 20/80-20/320, respectively. Thresholds of 50, 100, or 200- µ m reduction defined strong anatomical response when baseline central subfield thickness (CST) was <75, ≥75 to <175, or ≥175- µ m above standard thresholds. Additional thresholds from regression equations were calculated. RESULTS: At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50%) for VA and 505 eyes (53%) for CST. At 104 weeks among the 32% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69%) maintained strong VA and CST response, whereas 20 (7%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations. CONCLUSION: These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.

Improving Access to Eye Care: A Systematic Review of the Literature.

PURPOSE: The goals were to develop a working and inclusive definition of access to eye care, identify gaps in the current system that preclude access, and highlight recommendations that have been identified in prior studies. This manuscript serves as a narrative summary of the literature. CLINICAL RELEVANCE: Health care disparities continue to plague the nation's well-being, and eye care is no exception. Inequities in eye care negatively affect disease processes (i.e., glaucoma, cataracts, diabetic retinopathy), interventions (surgical treatment, prescription of glasses, referrals), and populations (gender, race and ethnicity, geography, age). METHODS: A systematic review of the existing literature included all study designs, editorials, and opinion pieces and initially yielded nearly 2500 reports. To be included in full-text review, an article had to be US-based, be written in English, and address 1 or more of the key terms "barriers and facilitators to health care," "access," and "disparities in general and sub-specialty eye care." Both patient and health care professional perspectives were included. One hundred ninety-six reports met the inclusion criteria. RESULTS: Four key themes regarding access to eye care from both patient and eye care professional perspectives emerged in the literature: (1) barriers and facilitators to access, (2) utilization, (3) compliance and adherence, and (4) recommendations to improve access. Common barriers and facilitators included many factors identified as social determinants of health (i.e., transportation, insurance, language, education). Utilization of eye care was largely attributable to having coverage for eye care, recommendations from primary care professionals, and improved health status. Geographic proximity, age, and lack of transportation surfaced as factors for compliance and adherence. There were a variety of recommendations to improve access to eye care, including improving presence in community health clinics, reimbursement for physicians, and funding of community-based programs such as DRIVE and REACH. CONCLUSIONS: The eye care profession has abundant evidence of the disparities that continue to affect marginalized communities. Improving community-based programs and clinics, addressing social determinants of health, and acknowledging the effects of discrimination and bias on eye care serve as ways to improve equity in this field.

Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration? A Prospective, Randomized, Pilot Study.

PURPOSE: To report findings when dilated fundus examination (DFE) is omitted from follow-up of patients receiving anti-VEGF injections for neovascular age-related macular degeneration (NVAMD). DESIGN: Randomized pilot study. PARTICIPANTS: NVAMD patients with two or more injections of anti-VEGF within prior six months who were expected to require treatment for at least eight more months. METHODS AND INTERVENTIONS: Participants were assigned to either retinal imaging and DFE or retinal imaging without a DFE except at 16 weeks and 32 weeks and at study completion. OUTCOMES: Primary safety outcomes were change in usual-corrected visual acuity (UCVA) and central subfield thickness (CST). Primary efficacy outcomes included time spent in clinic and patient satisfaction with clinic visits. RESULTS: The 66 participants had mean baseline UCVA of 20/50 in the study eye. Median change in UCVA from baseline to each clinic visit in each arm was "no change". Mean change in CST was less than 15 microns from baseline to any follow-up clinic visit. Time spent in the clinic at follow-up visits averaged 20 minutes less for participants in the Imaging Only group than those in the Full Exam group. More participants in the Imaging Only group were satisfied with the time spent in clinic and with the clinic visits overall than participants in the Full Exam group: means of 71 vs 91 minutes, respectively, per clinic visit. CONCLUSION: Based on findings from this randomized pilot study, follow-up retina clinic visits for established patients who have NVAMD and are under treatment with intravitreous injection of anti-VEGF agents could be streamlined by implementing longer intervals between DFE and by relying on imaging alone to make most decisions regarding the need for retreatment, thereby reducing the time spent by patients in clinic and increasing their satisfaction with care received, without excess adverse events. TRIAL REGISTRATION: NCT02251366.

Prevalence and causes of clinically detectable uveitic serous retinal detachment.

PURPOSE: To describe the prevalence and causes of clinically detectable uveitic serous retinal detachment (SRD). METHODS: Retrospective chart review of a large clinic-based series. RESULTS: Serous retinal detachment was present in 78 of the 2761 (2.8%) patients. Vogt-Koyanagi-Harada (VKH) disease was the most commonly identified cause (38/78, 48.7%). Less common associated etiologies included toxoplasmic retinochoroiditis (8/78, 10.3%), sarcoidosis (5/78, 6.4%), intraocular lymphoma (4/78, 5.1%), presumed tuberculosis (3/78, 3.8%), and posterior scleritis (2/78, 2.6%). Fifteen patients (19.2%) with uveitic SRD at presentation had no identifiable etiology and were labeled idiopathic or indeterminant. Thirty of the 38 patients with VKH disease (78.9%) had positive neurological and/or integumentary findings, and therefore constituted either complete or incomplete subtypes of the disease. The remaining eight (21.1%) had presumed/ocular VKH disease limited to the eye. CONCLUSION: While VKH disease by far is the most common cause of clinically detectable uveitic SRD, a number of other non-infectious and infectious inflammatory disorders were also associated with this distinctive clinical finding.

Structured layer surface segmentation for retina OCT using fully convolutional regression networks.

Optical coherence tomography (OCT) is a noninvasive imaging modality with micrometer resolution which has been widely used for scanning the retina. Retinal layers are important biomarkers for many diseases. Accurate automated algorithms for segmenting smooth continuous layer surfaces with correct hierarchy (topology) are important for automated retinal thickness and surface shape analysis. State-of-the-art methods typically use a two step process. Firstly, a trained classifier is used to label each pixel into either background and layers or boundaries and non-boundaries. Secondly, the desired smooth surfaces with the correct topology are extracted by graph methods (e.g., graph cut). Data driven methods like deep networks have shown great ability for the pixel classification step, but to date have not been able to extract structured smooth continuous surfaces with topological constraints in the second step. In this paper, we combine these two steps into a unified deep learning framework by directly modeling the distribution of the surface positions. Smooth, continuous, and topologically correct surfaces are obtained in a single feed forward operation. The proposed method was evaluated on two publicly available data sets of healthy controls and subjects with either multiple sclerosis or diabetic macular edema, and is shown to achieve state-of-the art performance with sub-pixel accuracy.

Fully Convolutional Boundary Regression for Retina OCT Segmentation.

A major goal of analyzing retinal optical coherence tomography (OCT) images is retinal layer segmentation. Accurate automated algorithms for segmenting smooth continuous layer surfaces, with correct hierarchy (topology) are desired for monitoring disease progression. State-of-the-art methods use a trained classifier to label each pixel into background, layer, or surface pixels. The final step of extracting the desired smooth surfaces with correct topology are mostly performed by graph methods (e.g. shortest path, graph cut). However, manually building a graph with varying constraints by retinal region and pathology and solving the minimization with specialized algorithms will degrade the flexibility and time efficiency of the whole framework. In this paper, we directly model the distribution of surface positions using a deep network with a fully differentiable soft argmax to obtain smooth, continuous surfaces in a single feed forward operation. A special topology module is used in the deep network both in the training and testing stages to guarantee the surface topology. An extra deep network output branch is also used for predicting lesion and layers in a pixel-wise labeling scheme. The proposed method was evaluated on two publicly available data sets of healthy controls, subjects with multiple sclerosis, and diabetic macular edema; it achieves state-of-the art sub-pixel results.

Deep learning based topology guaranteed surface and MME segmentation of multiple sclerosis subjects from retinal OCT.

Optical coherence tomography (OCT) is a noninvasive imaging modality that can be used to obtain depth images of the retina. Patients with multiple sclerosis (MS) have thinning retinal nerve fiber and ganglion cell layers, and approximately 5% of MS patients will develop microcystic macular edema (MME) within the retina. Segmentation of both the retinal layers and MME can provide important information to help monitor MS progression. Graph-based segmentation with machine learning preprocessing is the leading method for retinal layer segmentation, providing accurate surface delineations with the correct topological ordering. However, graph methods are time-consuming and they do not optimally incorporate joint MME segmentation. This paper presents a deep network that extracts continuous, smooth, and topology-guaranteed surfaces and MMEs. The network learns shape priors automatically during training rather than being hard-coded as in graph methods. In this new approach, retinal surfaces and MMEs are segmented together with two cascaded deep networks in a single feed forward propagation. The proposed framework obtains retinal surfaces (separating the layers) with sub-pixel surface accuracy comparable to the best existing graph methods and MMEs with better accuracy than the state-of-the-art method. The full segmentation operation takes only ten seconds for a 3D volume.

ETDRS Grading of Diabetic Retinopathy: Still the Gold Standard?

This article aims to provide a narrative history of the evolution, modification, and legacy of the Early Treatment Diabetic Retinopathy Study classification system.

Loss of Peak Vision in Retinal Vein Occlusion Patients Treated for Macular Edema.

PURPOSE: To evaluate long-term visual and anatomic outcomes in patients with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (VEGF) agents. DESIGN: Prospective, interventional case series. PARTICIPANTS: Patients with central RVO (CRVO) or branch RVO (BRVO). METHODS: Number of anti-VEGF injections and improvement from baseline best-corrected visual acuity (BCVA) and central subfield thickness (CST) were prospectively recorded in 40 eyes of 39 CRVO patients and 50 eyes of 47 BRVO patients. RESULTS: Mean follow-up was 58 months for BRVO and 78 months for CRVO. Within 6 months of last follow-up, 58% of BRVO patients and 75% of CRVO patients required anti-VEGF injections to control edema. Analysis of the course of each patient over time showed that for BRVO patients, BCVA letter score increased by a mean of 24, from baseline of 52 (20/100) to peak of 76 (20/32), and subsequently decreased by 13, to 63 (20/50), at final visit; and for CRVO patients, BCVA letter score increased by a mean of 26, from baseline of 48 (20/100) to peak of 74 (20/32), and subsequently decreased by 18, to 56 (20/80), at last follow-up. Loss from peak BCVA occurred primarily owing to persistent/recurrent edema and related foveal damage. CONCLUSIONS: Patients with RVO showed large improvements in BCVA after initiation of anti-VEGF injections, but in many patients some visual gains were lost over time owing to bouts of recurrent edema. Sustained suppression of VEGF may help to provide optimal outcomes in RVO and reduce treatment burden.

Layer boundary evolution method for macular OCT layer segmentation.

Optical coherence tomography (OCT) is used to produce high resolution depth images of the retina and is now the standard of care for in-vivo ophthalmological assessment. It is also increasingly being used for evaluation of neurological disorders such as multiple sclerosis (MS). Automatic segmentation methods identify the retinal layers of the macular cube providing consistent results without intra- and inter-rater variation and is faster than manual segmentation. In this paper, we propose a fast multi-layer macular OCT segmentation method based on a fast level set method. Our framework uses contours in an optimized approach specifically for OCT layer segmentation over the whole macular cube. Our algorithm takes boundary probability maps from a trained random forest and iteratively refines the prediction to subvoxel precision. Evaluation on both healthy and multiple sclerosis subjects shows that our method is statistically better than a state-of-the-art graph-based method.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to AMD accounts for most cases of AMD-related severe vision loss. Intravitreous injection of anti-vascular endothelial growth factor (anti-VEGF) agents aims to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, to improve vision. OBJECTIVES: • To investigate ocular and systemic effects of, and quality of life associated with, intravitreous injection of three anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) versus no anti-VEGF treatment for patients with neovascular AMD• To compare the relative effects of one of these anti-VEGF agents versus another when administered in comparable dosages and regimens SEARCH METHODS: To identify eligible studies for this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (searched January 31, 2018); MEDLINE Ovid (1946 to January 31, 2018); Embase Ovid (1947 to January 31, 2018); the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 31, 2018); the International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com/editAdvancedSearch - searched January 31, 2018); ClinicalTrials.gov (www.clinicaltrials.gov - searched November 28, 2018); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en - searched January 31, 2018). We did not impose any date or language restrictions in electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or versus a control treatment (e.g. sham treatment, photodynamic therapy), in which participants were followed for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We compared outcomes using risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial. Six trials compared anti-VEGF treatment (pegaptanib, ranibizumab, or bevacizumab) versus control, and 10 trials compared bevacizumab versus ranibizumab. Pharmaceutical companies conducted or sponsored four trials but funded none of the studies that evaluated bevacizumab. Researchers conducted these trials at various centers across five continents (North and South America, Europe, Asia, and Australia). The overall certainty of the evidence was moderate to high, and most trials had an overall low risk of bias. All but one trial had been registered prospectively.When compared with those who received control treatment, more participants who received intravitreous injection of any of the three anti-VEGF agents had gained 15 letters or more of visual acuity (risk ratio [RR] 4.19, 95% confidence interval [CI] 2.32 to 7.55; moderate-certainty evidence), had lost fewer than 15 letters of visual acuity (RR 1.40, 95% CI 1.27 to 1.55; high-certainty evidence), and showed mean improvement in visual acuity (mean difference 6.7 letters, 95% CI 4.4 to 9.0 in one pegaptanib trial; mean difference 17.8 letters, 95% CI 16.0 to 19.7 in three ranibizumab trials; moderate-certainty evidence) after one year of follow-up. Participants treated with anti-VEGF agents showed improvement in morphologic outcomes (e.g. size of CNV, central retinal thickness) compared with participants not treated with anti-VEGF agents (moderate-certainty evidence). No trial directly compared pegaptanib versus another anti-VEGF agent and followed participants for one year; however, when compared with control treatments, ranibizumab and bevacizumab each yielded larger improvements in visual acuity outcomes than pegaptanib.Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence); results showed similar mean improvement in visual acuity (mean difference [MD] -0.5 letters, 95% CI -1.5 to 0.5; high-certainty evidence) after one year of follow-up, despite the substantially lower cost of bevacizumab compared with ranibizumab. Reduction in central retinal thickness was less among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -11.6 µm, 95% CI -21.6 to -1.7; high-certainty evidence); however, this difference is within the range of measurement error, and we did not interpret it to be clinically meaningful.Ocular inflammation and increased intraocular pressure (IOP) after intravitreal injection were the most frequently reported serious ocular adverse events. Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to show a meaningful difference between groups (evidence of low- to moderate-certainty). Investigators rarely measured and reported data on visual function, quality of life, or economic outcomes. AUTHORS' CONCLUSIONS: Results of this review show the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; studies show that ranibizumab and bevacizumab improved visual acuity in some eyes that received these agents and were equally effective. Available information on the adverse effects of each medication does not suggest a higher incidence of potentially vision-threatening complications with intravitreous injection of anti-VEGF agents compared with control interventions; however, clinical trial sample sizes were not sufficient to estimate differences in rare safety outcomes. Future Cochrane Reviews should incorporate research evaluating variable dosing regimens of anti-VEGF agents, effects of long-term use, use of combination therapies (e.g. anti-VEGF treatment plus photodynamic therapy), and other methods of delivering these agents.

Factors Associated With Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema With Anti-Vascular Endothelial Growth Factor Therapy: An Exploratory Analysis of the Protocol T Randomized Clinical Trial.

Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial , Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95% CI, -3.0 to -1.2; P < .001) in the VA and 1.9 letters (95% CI, -2.4 to -1.3; P < .001) in the VA AUC analyses. For each 1% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95% CI, -1.5 to -0.5; P < .001) and 0.5 letters (95% CI, -0.9 to -0.2; P < .001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95% CI, 0.9-5.4; P = .007) and VA AUC (95% CI, 1.3-4.2; P < .001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 µm, P = .01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 µm, P = .01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.

Retinal layer parcellation of optical coherence tomography images: Data resource for multiple sclerosis and healthy controls.

This paper presents optical coherence tomography (OCT) images of the human retina and manual delineations of eight retinal layers. The data includes 35 human retina scans acquired on a Spectralis OCT system (Heidelberg Engineering, Heidelberg, Germany), 14 of which are healthy controls (HC) and 21 have a diagnosis of multiple sclerosis (MS). The provided data includes manually delineation of eight retina layers, which were independently reviewed and edited. The data presented in this article was used to validate automatic segmentation algorithms (Lang et al., 2013).

Shortest Distance From Fovea to Subfoveal Hemorrhage Border Is Important in Patients With Neovascular Age-related Macular Degeneration.

PURPOSE: To identify factors influencing visual outcome in patients with neovascular age-related macular degeneration (NVAMD) and subfoveal hemorrhage (SFH) treated with anti-vascular endothelial growth factor (VEGF) agents. DESIGN: Retrospective case series. METHODS: Anti-VEGF-treated eyes with SFH > 1 disc area (DA) were identified (n = 16) and changes in visual acuity (VA) and central subfield thickness (CST) from baseline to last follow-up, along with SFH area, thickness, minimum distance from fovea to SFH border, and time to resolution, were determined. RESULTS: At baseline, mean (± standard error of the mean) size and thickness of SFH were 14.9 ± 2.8 DA and 386.6 ± 46.9 µm, and mean Snellen VA and CST were 20/250 and 591.7 ± 57.0 µm. Median follow-up was 47.6 months. While more than 50% of patients had VA ≤ 20/200 at baseline and all time points through week 48, the percentage of patients with VA ≥ 20/50 increased to 30%-40% at months 6 and 12 and remained stable through month 48. Spearman rank correlation demonstrated 2 independent variables that correlated with good visual outcome, smaller area of SFH at baseline (r = -0.630; P = .009), and high frequency of anti-VEGF injections (r = 0.646; P = .007). In exceptional patients with good visual outcome despite large baseline SFH, shortest distance between the fovea and hemorrhage border significantly correlated with baseline VA (r = -0.503, P = .047) and final VA (r = -0.575, P = .02). CONCLUSIONS: Patients with NVAMD and thick SFH, but short distance between fovea and uninvolved retina, can have good visual outcomes when given frequent anti-VEGF injections.

Multi-layer Fast Level Set Segmentation for Macular OCT.

Segmenting optical coherence tomography (OCT) images of the retina is important in the diagnosis, staging, and tracking of ophthalmological diseases. Whereas automatic segmentation methods are typically much faster than manual segmentation, they may still take several minutes to segment a three-dimensional macular scan, and this can be prohibitive for routine clinical application. In this paper, we propose a fast, multi-layer macular OCT segmentation method based on a fast level set method. In our framework, the boundary evolution operations are computationally fast, are specific to each boundary between retinal layers, guarantee proper layer ordering, and avoid level set computation during evolution. Subvoxel resolution is achieved by reconstructing the level set functions after convergence. Experiments demonstrate that our method reduces the computation expense by 90% compared to graph-based methods and produces comparable accuracy to both graph-based and level set retinal OCT segmentation methods.

Intensity inhomogeneity correction of SD-OCT data using macular flatspace.

Images of the retina acquired using optical coherence tomography (OCT) often suffer from intensity inhomogeneity problems that degrade both the quality of the images and the performance of automated algorithms utilized to measure structural changes. This intensity variation has many causes, including off-axis acquisition, signal attenuation, multi-frame averaging, and vignetting, making it difficult to correct the data in a fundamental way. This paper presents a method for inhomogeneity correction by acting to reduce the variability of intensities within each layer. In particular, the N3 algorithm, which is popular in neuroimage analysis, is adapted to work for OCT data. N3 works by sharpening the intensity histogram, which reduces the variation of intensities within different classes. To apply it here, the data are first converted to a standardized space called macular flat space (MFS). MFS allows the intensities within each layer to be more easily normalized by removing the natural curvature of the retina. N3 is then run on the MFS data using a modified smoothing model, which improves the efficiency of the original algorithm. We show that our method more accurately corrects gain fields on synthetic OCT data when compared to running N3 on non-flattened data. It also reduces the overall variability of the intensities within each layer, without sacrificing contrast between layers, and improves the performance of registration between OCT images.

A proteomic approach to understanding the pathogenesis of idiopathic macular hole formation.

Idiopathic macular holes (IMH) are full-thickness defects of retinal tissue that cause severe vision loss due to disruption of the anatomic fovea. Abnormal vitreous traction is involved in the formation of macular holes. Both glial cells and hyalocytes contribute to epiretinal membrane formation in IMH. In order to gain further insight into the pathophysiology of IMH, we conducted a discovery phase investigation of the vitreous proteome in four patients with macular holes and six controls using one-dimensional gel fractionation and liquid chromatography-tandem mass spectrometry analyses on an Orbitrap Elite mass spectrometer. Of a total of 5912 vitreous proteins, 32 proteins had increased and 39 proteins had decreased expression in IMH compared with controls, using a false discovery rate approach with p value < 0.001 and q value < 0.05. IMH was associated with increased expression of proteins in the complement pathway, α-2-macroglobulin, a major inducer of Müller glial cell migration, fibrinogen, and extracellular matrix proteins, and decreased expression of proteins involved in protein folding and actin filament binding. A proteomic approach revealed proteins and biological pathways that may be involved in the pathogenesis of IMH and could be targeted for future studies.