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The purpose of this study was to explore the age-related change in choroidal thickness (ChT) and test the hypothesis that baseline ChT is predictive of refractive error change in healthy young adults.Participants underwent spectral-domain optical coherence tomography (SD-OCT) imaging and autorefraction at 20 (baseline) and 28 years old. The enhanced depth imaging mode on the SD-OCT was used to obtain images of the choroid. Scans were exported from the SD-OCT and analyzed with a custom software that automatically measures the central ChT. The longitudinal change in subfoveal ChT and association between baseline subfoveal ChT and 8-year change in refractive error (spherical equivalent) were determined using linear mixed models.In total, 395 eyes of 198 participants (44% men; 18-22 years at baseline) were included. Over 8 years, mean spherical equivalent decreased by 0.25 diopters (D) and axial length increased by 0.09 mm. Subfoveal choroid thickened by 1.3 µm/year (95% confidence interval [CI] = 0.6-2.0), but this was reduced by 0.9 µm/year (95% CI = 1.6-0.2) for every 1 mm increase in axial length. For every 10 µm increase in baseline ChT, average annual change in spherical equivalent and axial length reduced by 0.006 D/year and 0.003 mm/year, respectively.In a community-based cohort of young adults, the choroid continued to change during early adulthood. Choroidal thickening was less in eyes that were longer at baseline, and the choroid thinned in eyes that showed myopia progression. The association between baseline ChT and longitudinal changes in spherical equivalent and axial length supports the hypothesis that ChT may be predictive of refractive error development and/or myopia progression.

Purpose : To determine the influence of choroidal boundary morphology on the accuracy of automated measurements of subfoveal choroidal thickness (SFCT) in swept source optical coherence tomography (SSOCT). Methods : A retrospective image analysis of foveal-centered horizontal line scans from normal and diseased eyes using the Topcon DRI OCT-1 Atlantis SSOCT was conducted. Subfoveal choroid-scleral junction (CSJ) and retina-choroidal junction (RCJ) morphologies were graded by two observers. Automated SFCT (A-SFCT) was compared with manual SFCT (M-SFCT) measurements from Bruch's membrane to the posterior limits of choroidal vessel, hyperreflective stroma, and hyporeflective lamina fusca. Agreement in boundary grading was assessed by Cohen's kappa. A-SFCT and M-SFCT were compared using Bland-Altman analysis and paired t-tests. Results : A total of 200 eyes of 100 patients with a mean (SD) age of 62 (18) years were included. The choroidal vessel, stromal, and lamina fusca boundaries were visible in 100%, 58%, and 38% of the eyes, respectively. Interobserver agreement in RCJ and CSJ grading was high (kappa = 0.974 and 0.851). Mean A-SFCT differed from M-SFCT by only 2 μm at posterior choroidal vessel boundary (P = 0.801). A-SFCT overestimated SFCT at the posterior vessel wall boundary by 17 μm (P = 0.026) and 23 μm (P = 0.001) in the presence of a visible posterior choroidal stroma and lamina fusca, respectively. Conclusions : Automated outer choroidal boundary segmentation tends to identify the posterior limit of the choroidal vessel. Agreement between A-SFCT and M-SFCT is reduced by the presence of posterior stromal layer and lamina fusca. A-SFCT should be interpreted with RCJ and CSJ boundary grading.

To evaluate the impact of image magnification correction on superficial retinal vessel density (SRVD) and foveal avascular zone area (FAZA) measurements using optical coherence tomography angiography (OCTA).Participants with healthy retinas were recruited for ocular biometry, refraction, and RTVue XR Avanti OCTA imaging with the 3 × 3-mm protocol. The foveal and parafoveal SRVD and FAZA were quantified with custom software before and after correction for magnification error using the Littman and the modified Bennett formulae. Relative changes between corrected and uncorrected SRVD and FAZA were calculated.Forty subjects were enrolled and the median (range) age of the participants was 30 (18-74) years. The mean (range) spherical equivalent refractive error was -1.65 (-8.00 to +4.88) diopters and mean (range) axial length was 24.42 mm (21.27-28.85). Images from 13 eyes were excluded due to poor image quality leaving 67 for analysis. Relative changes in foveal and parafoveal SRVD and FAZA after correction ranged from -20% to +10%, -3% to +2%, and -20% to +51%, respectively. Image size correction in measurements of foveal SRVD and FAZA was greater than 5% in 51% and 74% of eyes, respectively. In contrast, 100% of eyes had less than 5% correction in measurements of parafoveal SRVD.Ocular biometry should be performed with OCTA to correct image magnification error induced by axial length variation. We advise caution when interpreting interocular and interindividual comparisons of SRVD and FAZA derived from OCTA without image size correction.

PURPOSE. Cultured retinal pigment epithelium (RPE) may become a therapeutic option for transplantation in retinal disease. However maintaining a native RPE phenotype in vitro has proven challenging. The human RPE cell-line ARPE-19 is used widely as an alternative to primary RPE. It is grown in DMEM/F12 medium as standard, but its phenotype is dependent on culture conditions, and many differentiation markers are usually absent. The purpose of this study was to examine how this sensitive phenotype of ARPE-19 can be modulated by growth media with or without the metabolite pyruvate to elucidate better RPE growth conditions.METHODS. ARPE-19 cells at passages p22 to p28 were cultured on filters for up to 3 months in DMEM/F12 or DMEM media with or without pyruvate and 1% fetal calf serum. Assessment of differentiation was performed using pigmentation, immunocytochemistry, protein/mRNA expression, transepithelial resistance, VEGF secretion, and ultrastructure.RESULTS. Pyruvate, in combination with DMEM, induced dark pigmentation and promoted differentiation markers such as CRALBP and MerTK. Importantly, RPE65 protein was detected by Western blotting and was enhanced by pyruvate, high glucose, and DMEM. ARPE-19 cells maintained in this medium could also phagocytose human photoreceptor outer segments (POS). VEGF secretion was greater in DMEM cultures and was affected by glucose but not by pyruvate. Pigmentation never occurred in DMEM/F12.CONCLUSIONS. This study demonstrated important differentiation markers, including pigmentation and Western blots of RPE65 protein, and showed human POS phagocytosis in ARPE-19 cultures using a simple differentiation protocol. The results favor the use of high-glucose DMEM with pyruvate for future RPE differentiation studies. (Invest Ophthalmol Vis Sci. 2011;52:7148-7159) DOI:10.1167/iovs.10-6374

PURPOSE. To determine the test-retest variability of reading ability using the MNREAD charts in patients with stable age-related macular degeneration (AMD).METHODS. In this prospective study, reading ability was measured at two visits in 124 nontreated eyes of 124 patients with AMD, who were enrolled in an ongoing clinical trial using a standardized MNREAD protocol. Only patients with stable AMD who could perform the reading test at 40 cm at both visits were included in the analysis. Different scoring rules were applied to calculate critical print size and maximum reading speed.RESULTS. Data from the 59 patients with a mean (SD) age of 78 (7.6) years who met the study criteria were analyzed at a mean (SD) interval of 43 (6) days between measurements. The 95% coefficient of repeatability (CR) was 0.30 logMAR for reading acuity. The CR for critical print size and maximum reading speed varied depending on the analysis method applied.CONCLUSIONS. This is a report of estimates of the intersession test-retest variability of reading performance metrics in patients with stable AMD. The results are helpful both in defining end points in clinical trials for AMD and in distinguishing clinical change from measurement variability in clinical practice. (Invest Ophthalmol Vis Sci. 2011; 52: 3854-3859) DOI: 10.1167/iovs.10-6601

In recent years, the treatment of neovascular age-related macular degeneration (AMD) has been revolutionized by the introduction of antiangiogenic therapies such as ranibizumab (Lucentis), and bevacizumab (Avastin; both from Genentech, Inc., South San Francisco, CA).1–3 Optical coherence tomography (OCT), an imaging modality that provides cross-sectional images of the neurosensory retina, plays a critical role in this treatment by allowing noninvasive monitoring of disease activity.4,5 Although it is presumed that anatomic improvements demonstrated by OCT will ultimately result in clinical benefits, many studies have failed to show a consistent correlation between reduction in OCT-derived retinal thickness and improvement in visual function.3,6 Such failures may be due, at least in part, to the limitations of the automated image-analysis software provided by current OCT systems.7,8 In addition, however, the structurally heterogeneous nature of the disorder and the reliance on high-contrast distance visual acuity as the primary measure of visual function in these studies may play a role.9,10 CNV, the hallmark of neovascular AMD, results in a wide range of alterations in retinal morphology, with intraretinal, subretinal, and RPE components.11,12 CNV lesions also vary widely, both in size, and in location relative to the fovea. Although high-contrast distance visual acuity is largely a function of foveal integrity, other visual parameters, such as reading ability and contrast sensitivity, may be more reflective of alterations in macular structure as a whole.10,13–15 Thus, evaluation of contrast sensitivity and reading ability may allow detection of stronger and more consistent correlations with OCT-derived retinal parameters. The detection of any such robust relationship is of interest for clinical trials, where the use of validated morphologic parameters as surrogate endpoints could lead to increased accuracy, reduced costs, and shortened duration.16–18 Furthermore, in clinical practice, measurement of reading ability and contrast sensitivity may also allow the clinician to better assess individual visual performance. Contrast sensitivity, for example, is closely linked with both orientation and mobility and, in patients with macular disease, may be markedly reduced despite near-normal distance visual acuity.19 To address these questions and others, we have developed a software tool (OCTOR) that allows the user to manually quantify any retinal structure of interest.20 Using this tool, we have identified novel OCT parameters that show modest correlations with Snellen visual acuity in neovascular AMD.6,9 In the current report, we evaluate the effect of changes in retinal morphology on reading ability and contrast sensitivity, using OCTOR, in a recently completed phase III/IV clinical trial: the Avastin (bevacizumab) for choroidal neovascularization (ABC) Trial.21

PURPOSE To investigate the interobserver agreement for the detection of optical coherence tomography (OCT) features of disease activity in patients with neovascular age-related macular degeneration (nAMD). METHODS This was a cross-sectional agreement study in which grading of OCT line scans from patients with nAMD was conducted by two retinal specialists before the patients received treatment. Scans were graded for the presence of features of nAMD disease activity (intraretinal cysts [IRC], subretinal fluid [SRF], diffuse retinal edema [DRE], retinal pigment epithelial detachment [PED], and subretinal tissue [SRT]). RESULTS Although scans from 78 patients were available for analysis, five patients were excluded because of a mean signal strength of

PURPOSE: To describe the rate of automated segmentation error in Stratus optical coherence tomography (OCT) scans in consecutive patients with neovascular age-related macular degeneration (nAMD) receiving treatment and to investigate the effect of the segmentation error on automated retinal thickness measures and whether further imaging reduces the rate of segmentation error. METHODS: A retrospective analysis of fast macular thickness map (FMTM) protocol OCT scans of 50 eyes of 50 consecutive patients with nAMD. Each line scan was analyzed for segmentation error with manual measurement of the center-point retinal thickness allowing calculation of the percentage error in automated thickness. OCT scanning was repeated to overcome segmentation error. RESULTS: Segmentation error was detected in 45 (90%) of the 50 patients with 37 (74%) patients having an error affecting the central 1-mm subfield. Scan sets with a high central segmentation error score (two or more line scans affected of six) had a significantly greater error in automated center-point retinal thickness than scan sets with a low error score (20% compared with 3%, P < 0.000005). Central subfield segmentation error persisted in 30 (60%) patients despite repeat scanning. CONCLUSIONS: There is a high rate of segmentation error in OCT scans of patients with nAMD who are undergoing treatment, leading to errors in automated central retinal thickness measurement. The authors recommend manual measurement of central macular thickness when two or more line scans are affected by segmentation error in the central 1-mm subfield. Repeated scanning reduced the rate of error but did not eliminate the problem.

PURPOSE: To determine the repeatability of Stratus optical coherence tomography (OCT) measures of retinal thickness and volume in patients with neovascular age-related macular degeneration (nAMD) METHOD: Fifty-one eyes of 51 consecutive patients with nAMD underwent an OCT imaging session in which two fast macular thickness map (FMTM) protocol scans sets were acquired by a single experienced operator certified for clinical trials work. Coefficients of repeatability for each of nine Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions, foveolar center-point retinal thickness (CPT) and total macular volume (TMV), were calculated. Scans were analyzed retrospectively for errors in retinal boundary placement by two observers, with revised coefficients of repeatability calculated after excluding any scan sets with significant segmentation error. RESULTS: The coefficient of repeatability for the central 1-mm macular subfield was 67 mum (23%) and was less than 75 mum for all macular subfields. There was much larger variability in the center-point thickness measure, with a coefficient of repeatability of 88 mum (32%) for the automated center-point thickness (ACPT). After excluding nine scan set pairs with significant segmentation error, the coefficient of repeatability for the central 1-mm macular subfield was reduced to 50 mum (19%). CONCLUSIONS: OCT-derived retinal thickness measurements are subject to considerable measurement variability in patients with nAMD. Changes in central macular thickness of more than 50 mum may better reflect true clinical change in scan sets without significant segmentation error and may be used to guide the retreatment of patients with nAMD in clinical trials and clinical practice.