Muneeswar Gupta Nittala

Accuracy and reproducibility of automated drusen segmentation in eyes with non-neovascular age-related macular degeneration.

PURPOSE To evaluate the accuracy and reproducibility of drusen quantification by an automated drusen segmentation algorithm in spectral domain optical coherence tomography (SD-OCT) images of eyes with non-neovascular age-related macular degeneration (AMD). METHODS Drusen segmentation was performed using both a commercial automated algorithm (Cirrus OCT RPE analysis tool) and manual segmentation in 44 eyes of 30 subjects with dry AMD who underwent volume OCT scanning. The drusen (space between outer RPE layer and Bruchs membrane) was segmented automatically using an automated RPE tool and manually by 3D-OCTOR software. Drusen area and volume were calculated in all eyes. Age and visual acuity data were also collected. Reproducibility of manual and automated measurements was assessed by intraclass correlation (ICC). RESULTS The mean age of subjects was 78.24 (± 9.4; range, 56-97 years). The mean logMAR (logarithm of the minimum angle of resolution) visual acuity was 0.4 (Snellen equivalent, ~20/50) (standard deviation, 0.40; range, 0-1.3). The mean (standard deviation) drusen area was 5.05 (3.67) mm(2) with manual segmentation and 4.66 (3.51) mm(2) with the automated RPE tool; the absolute difference was 2.63 (2.5) mm(2). The mean drusen volume was 1.49 (0.42) mm(3) with manual segmentation and 1.42 (0.43) mm(3) with the automated RPE tool; the absolute difference was 1.42 (0.43) mm(3). The agreement between manual and automated measurements of drusen volume (highest ICC = 0.95) was better than the agreement for drusen area (ICC = 0.65). CONCLUSIONS The quantification of drusen area and volume using an automated RPE yielded better agreement for volume than for area when compared with human expert manual segmentation. Using this software, drusen volume measurements may be a useful tool for quantifying drusen burden in clinical trials and clinical practice.

Measuring retinal sensitivity with the microperimeter in patients with diabetes.

Purpose: To evaluate the retinal sensitivity and fixation characteristics in participants with diabetes mellitus, using the microperimeter (MP-1) and to correlate the MP-1 values with the severity of diabetic retinopathy (DR). Methods: We performed complete ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, indirect ophthalmoscopy, and microperimetry (central 20° of macula) on 210 eyes of 160 participants. Participants included healthy individuals, individuals with diabetes but no retinopathy, and individuals with different stages of DR. Results: The mean age of participants was (mean ± SD) 49.83 ± 7.43 years for healthy individuals, 53.20 ± 5.7 years for participants with diabetes but no retinopathy, and 55.39 ± 7.81 years for participants with DR. Retinal sensitivity was significantly (P = 0.001) decreased with severity of DR. The mean foveal sensitivity (retinal sensitivity in the central 2°) was 16.68 ± 2.13 dB in healthy individuals, 14.73 ± 3.64 dB in participants with diabetes but no DR, and 11.60 ± 5.76 dB in participants with DR. There was significant loss of retinal sensitivity in participants with diabetes but no retinopathy when compared with healthy individuals. Participants with severe nonproliferative DR showed more significant loss of retinal sensitivity in the central 20° than those with other stages of DR. Conclusion: The MP-1 is a useful tool to quantify retinal sensitivity in DR. Using the MP-1, we can detect early loss of retinal sensitivity in patients with diabetes but no retinopathy. Patients with severe nonproliferative DR will have less retinal sensitivity than those with other stages of DR. Scotoma mapping using the MP-1 provides details of functional vision in patients with DR.

Risk factors for proliferative diabetic retinopathy in a Latino American population.

Purpose: To assess the personal and demographic risk factors for proliferative diabetic retinopathy in Latino Americans in Los Angeles County. Methods: In this prospective, non-interventional, cross-sectional case control study, seven hundred and twenty-nine subjects from Los Angeles County University of Southern California Medical Center (LAC + USC), Los Angeles, CA, were enrolled. All patients were recruited prospectively from the LAC + USC Medical Center and affiliated clinics between June 2008 and June 2011. Complete personal data and results from systemic and ophthalmic examinations were collected for all enrolled subjects. Laboratory tests such as glycosylated hemoglobin, creatinine levels, and cholesterol levels were collected prospectively by drawing blood at the time of each patients clinic visit. The main outcome measures were age, gender, type of diabetes mellitus (DM I or II) duration of diabetes mellitus, history of hypertension, history of insulin use, height, weight, and body mass index, smoking history, glycosylated hemoglobin, creatinine levels, and cholesterol levels. Results: The mean age of subjects with no diabetic retinopathy was 56.38 years (SD, 10.16), whereas that of patients with proliferative diabetic retinopathy was 57.43 years (SD, 9.63). Parameters that conferred a statistically significant increased risk for proliferative diabetic retinopathy in the multivariate model included gender (men were at higher risk: odds ratio [OR], 4.11; 95% confidence interval [CI], 2.56–6.58), insulin use (OR, 1.85; 95% CI, 1.13–3.03), history of hypertension (OR, 1.64; 95% CI, 1.02–2.63), and duration (>25 years vs. 10–15 years) of diabetes (OR, 22.00; 95% CI, 9.76–49.60). Conclusion: In this case–control study in a Latino population, duration of diabetes and male gender were the strongest risk factor for the development of proliferative diabetic retinopathy followed by insulin use and hypertension. Interestingly, smoking and glycosylated hemoglobin levels did not confer additional significant risk in this cohort.

Measurement of retinal blood flow in normal Chinese-American subjects by doppler fourier-domain optical coherence tomography

PURPOSE To measure total retinal blood flow (TRBF) in normal, healthy Chinese Americans by using semi-automated analysis of Doppler Fourier-domain optical coherence tomography (FD-OCT) scans. METHODS Two hundred sixty-six normal, healthy Chinese-American participants (266 eyes) were enrolled from The Chinese American Eye Study. All participants underwent complete ophthalmic examination, including best-corrected visual acuity, indirect ophthalmoscopy, and Doppler FD-OCT imaging, using the circumpapillary double circular scan protocol. Total retinal blood flow and other vascular parameters (e.g., venous and arterial cross-sectional area and their velocities) were calculated by using Doppler OCT of Retinal Circulation software. Associations between TRBF and other clinical parameters were assessed by using bivariate correlations and linear regression. RESULTS The mean age of study participants was 57.40 ± 5.60 (range, 50-82) years. The mean TRBF was 49.34 ± 10.08 (range, 27.17-78.08, 95% confidence interval: 25.98-69.10) μL/min. The mean venous area was 0.0548 (±0.0084) mm(2). Superior retinal hemispheric blood flow (25.50 ± 6.62 μL/min) was slightly greater than inferior retinal hemispheric blood flow (23.84 ± 7.19 μL/min, P = 0.008). The mean flow velocity was 15.16 ± 3.12 mm/s. There was a weak but significant negative correlation between TRBF and age (r = -0.15, P = 0.012). No significant correlation was found between TRBF and axial length (r = 0.11, P = 0.08). Retinal blood flow was not significantly correlated with any other clinical parameters, including body mass index, systolic blood pressure, diastolic blood pressure, and intraocular pressure. CONCLUSIONS Normal Doppler OCT-derived total retinal blood values in a Chinese-American population showed considerable variability, some of which was explained by age. These observations should help design future studies evaluating TRBF in populations with eye disease.

Effect of angle of incidence on macular thickness and volume measurements obtained by spectral-domain optical coherence tomography.

PURPOSE Evaluation of the effect of angle of incidence on macular thickness and volume measurements obtained by spectral-domain optical coherence tomography (OCT). METHODS A total of 30 eyes from 15 healthy young subjects underwent macular cube volume scans (512 × 128 protocol) following dilation using the Cirrus spectral domain OCT. For each eye, scans were obtained by positioning the scanning beam in the center of the dilated pupil, as well as in four eccentric positions (approximately 3 mm from the center), superior, inferior, nasal, and temporal to the pupillary center, to create oblique angles of incidence between the light beam and retina. In all cases, the region scanned by the volume cube was centered on the fovea. Macular thickness and volume measurements were computed for volume scan acquisitions, and differences in values between eccentric scans and the central scan were analyzed. RESULTS Retinal thickness and volume values were observed to increase significantly in all subfields for all eccentrically-obtained scans compared to scans obtained through the center of the pupil. The mean increase in thickness for the various scan positions and subfields ranged from 3.76 to 11.38. Scans that were displaced temporally consistently showed the greatest increase in thickness and volume, whereas nasally positioned scans showed the least increase. The increase in retinal thickness for all subfields correlated significantly with angle of inclination or tilting of the retina. CONCLUSIONS Macular thickness and volume measurement results may be affected significantly by positioning of the scanning beam in the pupil and resultant angle of incidence on the retina. These findings suggest that care should be taken to position the scanning beam consistently in the center of the pupil to achieve reliable measurements.

Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 5

Importance Outcome measures that are sensitive to disease progression are needed as clinical end points for future treatment trials in Stargardt disease. Objective To examine the incidence of atrophic lesions of the retinal pigment epithelium in patients with Stargardt disease as determined by fundus autofluorescence imaging. Design, Setting, and Participants In this retrospective multicenter cohort study, 217 patients 6 years and older at baseline at tertiary referral centers in Europe, the United States, and the United Kingdom who were harboring disease-causing variants in the adenosine triphosphate (ATP)–binding cassette subfamily A member 4 (ABCA4) gene and who met the following criteria were enrolled: (1) at least 1 well-demarcated area of atrophy with a minimum diameter of 300 µm, with the total area of all atrophic lesions being less than or equal to 12 mm2 in at least 1 eye at the most recent visit, and (2) fundus autofluorescence images for at least 2 visits with a minimum of 6 months between at least 2 visits. Data were collected between August 22, 2013, and December 12, 2014. Data analysis was performed from March 15, 2015, through January 31, 2017. Exposures Images were evaluated by staff at a central reading center. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) were outlined and quantified. Lesion-free survival rates were estimated using Kaplan-Meier survival curves. Main Outcomes and Measures Incidence of atrophic lesions as determined by fundus autofluorescence. Results The 217 patients (mean [SD] age, 21.8 [13.3] years; 127 female [57.5%]; 148 white [68.2%]) contributed 390 eyes for which the mean (SD) follow-up time was 3.9 (1.6) years (range, 0.7-12.1 years). Among eyes without DDAF at first visit, the median time to develop a DDAF lesion was 4.9 years (95% CI, 4.3-5.6 years). Among eyes without QDAF, the median time to develop a QDAF lesion was 6.3 years (95% CI, 5.6-9.7 years). Eyes with a lesion of DDAF at the first visit were less likely to develop a QDAF lesion compared with eyes without a lesion of DDAF (hazard ratio, 0.19; 95% CI, 0.05-0.70; P = .01). Conclusions and Relevance An estimated 50% of the eyes without DDAF at first visit will develop the lesion in less than 5 years, suggesting that incidence of DDAF could serve as an outcome measure for treatment trials.

Macular sensitivity measured with microperimetry in stargardt disease in the progression of atrophy secondary to stargardt disease (ProgStar) study report No. 7

Importance New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity. Objective To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry). Design, Setting, and Participants This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as “normal,” “relative,” or “deep” scotoma. Main Outcomes and Measures Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas. Results Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, −0.13 to −0.041; P < .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, −0.28 to −0.14; P < .001). Longer duration of STGD1 was associated with worse MS (&bgr; = −0.18; P < .001), with a lower number of normal test points (&bgr; = −0.71; P < .001), and with a higher number of deep scotoma points (&bgr; = −0.70; P < .001). We found 11 eyes with low MS (<6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent). Conclusions and Relevance We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.

Automated Diabetic Retinopathy Screening and Monitoring Using Retinal Fundus Image Analysis

Background: Diabetic retinopathy (DR)—a common complication of diabetes—is the leading cause of vision loss among the working-age population in the western world. DR is largely asymptomatic, but if detected at early stages the progression to vision loss can be significantly slowed. With the increasing diabetic population there is an urgent need for automated DR screening and monitoring. To address this growing need, in this article we discuss an automated DR screening tool and extend it for automated estimation of microaneurysm (MA) turnover, a potential biomarker for DR risk. Methods: The DR screening tool automatically analyzes color retinal fundus images from a patient encounter for the various DR pathologies and collates the information from all the images belonging to a patient encounter to generate a patient-level screening recommendation. The MA turnover estimation tool aligns retinal images from multiple encounters of a patient, localizes MAs, and performs MA dynamics analysis to evaluate new, persistent, and disappeared lesion maps and estimate MA turnover rates. Results: The DR screening tool achieves 90% sensitivity at 63.2% specificity on a data set of 40 542 images from 5084 patient encounters obtained from the EyePACS telescreening system. On a subset of 7 longitudinal pairs the MA turnover estimation tool identifies new and disappeared MAs with 100% sensitivity and average false positives of 0.43 and 1.6 respectively. Conclusions: The presented automated tools have the potential to address the growing need for DR screening and monitoring, thereby saving vision of millions of diabetic patients worldwide.

Reproducibility of anterior segment angle metrics measurements derived from Cirrus spectral domain optical coherence tomography.

Purpose:To investigate the reproducibility of anterior segment angle (ACA) metrics measurements in normal subjects on Cirrus spectral domain optical coherence tomography (SD-OCT). Methods:40 eyes from 20 healthy, normal subjects underwent anterior segment imaging using a Cirrus SD-OCT. For each eye, 2 acquisitions of 5-line raster scans were performed perpendicularly on the inferior (270 degrees) angle. The Schwalbe’s line-angle opening distance (SL-AOD) and Schwalbe’s line-trabecular-iris space area (SL-TISA) measurements were performed by masked certified reading center graders using customized grading software. Intra-acquisition, intergrader, and intragrader reproducibility of SL-AOD and SL-TISA measurements were evaluated by intraclass correlation coefficients (ICC), Bland-Altman plots, and computation of mean percent difference (MPD) and coefficient of variability (CV). Results:The mean SL-AOD (average of 2 acquisitions) was 0.75 mm (range, 0.32 mm to 1.39 mm); SL-TISA was 0.28 mm2 (range, 0.082 mm2 to 0.569 mm2). The repeatability of Cirrus SD-OCT was excellent for both SL-AOD (MPD 4.74%, CV=0.92, ICC=0.99) and SL-TISA (MPD 9.4%, CV=0.8, ICC=0.99). The intragrader reproducibility was high for SL-AOD (MPD 4.28%, CV=0.94, ICC=0.995) and SL-TISA (MPD 6.05%, CV=0.89, ICC=0.993). The inter-grader reproducibility was not as good but still excellent for both SL-AOD (MPD 15.47%, CV=0.95, ICC=0.94) and SL-TISA (MPD 19.43%, CV=0.99, ICC=0.93). Bland-Altman plots of all comparisons did not demonstrate any apparent bias, with similar repeatability at various SL-AOD and SL-TISA values. Conclusions:In our population of young healthy adults with normal eyes, there was excellent intra-acquisition, intragrader, and intergrader reproducibility for Schwalbe’s line-based ACA metrics obtained from Cirrus SD-OCT images. These SD-OCT-derived measures may serve as reliable descriptors of angle morphometry for use in clinical trials and clinical practice.

Comparison of Retinal Layer Intensity Profiles From Different OCT Devices

BACKGROUND AND OBJECTIVE The purpose of this study is to use automated multiple retinal layer segmentation to compare retinal layer intensity profiles between different spectral-domain optical coherence tomography (SD-OCT) devices with and without normalization. PATIENTS AND METHODS A graph-based multistage segmentation approach was used to identify 11 boundaries in horizontal SD-OCT B-scans passing through the foveal center. Four acquisition protocols from two different SD-OCT devices were applied on 34 eyes from 17 healthy participants. The mean intensity of the 11 layers was compared within each device and between the two devices. In addition, the intensity of the various layers was normalized against the vitreous and retinal pigment epithelium band, and the normalized intensity profiles were also compared. RESULTS Within each OCT device, the mean intensity of the 11 retinal layers did not show significant difference (P values of paired t test ranging between 0.15 and 0.30). For the two different devices, before normalization, the mean intensity of the 11 retinal layers differed significantly (P = .02 to .03). After normalization, the mean intensity no longer differed significantly (P = .26 to .51). Linear regression demonstrated an average R(2) of 0.94 (P < .001) before normalization and 0.98 (P < .001) after normalization between the two devices. CONCLUSION The morphology of the intensity profiles was found to be similar within each SD-OCT device. Comparing intensity profiles from the two different devices, significant differences in unnormalized layer intensity were observed. Following normalization, the differences between OCT devices were no longer significant.