The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1).

BACKGROUND/AIMS: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. METHODS: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. RESULTS: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36-10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. CONCLUSIONS: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.

7-Hexagon Multifocal Electroretinography for an Objective Functional Assessment of the Macula in 14 Seconds.

PURPOSE: We present the multifocal electroretinogram (mfERG) with a 7-hexagon array as an objective test of macular function that can be recorded in 14 s. We provide normal values and investigate its reproducibility and validity. METHODS: Healthy participants underwent mfERG testing according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards using the Espion Profile/D310 multifocal ERG system (Diagnosys, LLC, Lowell, MA, USA). One standard recording of a 61-hexagon array and 2 repeated recordings of a custom 7-hexagon array were obtained. RESULTS: A total of 13 subjects (mean age 46.9 years) were included. The median response densities were 12.5 nV/deg2 in the center and 5.2 nV/deg2 in the periphery. Intereye correlations were strong in both the center (ρCenter = 0.821; p < 0.0001) and the periphery (ρPeriphery = 0.862; p < 0.0001). Intraeye correlations were even stronger: ρCenter = 0.904 with p < 0.0001 and ρPeriphery = 0.955 with p < 0.0001. Bland-Altman plots demonstrated an acceptable retest mean difference in both the center and periphery, and narrow limits of agreement. We found strong correlations of the center (ρCenter = 0.826; p < 0.0001) and periphery (ρPeriphery = 0.848; p < 0.0001), with recordings obtained by the 61-hexagon method. CONCLUSIONS: The 7-hexagon mfERG provides reproducible results in agreement with results obtained according to the ISCEV standard.

Evidence of macular pigment in the central macula in albinism.

PURPOSE: Albinism represents a spectrum of disorders with diminished to absent amounts of melanin pigmentation including the posterior segment of the eye. Macular pigment (MP) consists of two main carotenoids, lutein and zeaxanthin, concentrated in the macula. MP serves as blue light absorbent, antioxidant, and may reduce chromatic aberration and glare. It remains unclear if albinos have detectable MP. The purpose was to investigate the distribution of MP in albino patients with psychophysical and imaging techniques. METHODS: MP was measured at the eccentricity of 0.5° by heterochromatic flicker perimetry (QuantifEye(®); Tinsley Precision Instruments Ltd.) or by scanning laser ophthalmoscopy (MPOD module, MultiColor Spectralis(®), Heidelberg Engineering, Heidelberg, Germany) in four albino patients, who were also investigated with multimodal ophthalmic imaging. RESULTS: Visual acuity ranged from 20/32 to 20/125, nystagmus was present in three patients, and all patients showed typical foveal hypoplasia on fundus exam and optical coherence tomography. Fundus autofluorescence (FAF) demonstrated various degrees of central FAF signal attenuation. Genetic testing was available in three patients and confirmed the diagnosis. Measurable amounts of MP were detected in all four patients and ranged from 0.05 to 0.24, which is below the normal range. CONCLUSIONS: We conclude that MP can be demonstrated and measured in albinos. Further studies are needed to investigate MP accumulation following carotenoid supplementation and its impact on visual performance.

COMPARISON OF MANUAL AND SEMIAUTOMATED FUNDUS AUTOFLUORESCENCE ANALYSIS OF MACULAR ATROPHY IN STARGARDT DISEASE PHENOTYPE.

PURPOSE: To evaluate manual and semiautomated grading techniques for assessing decreased fundus autofluorescence (DAF) in patients with Stargardt disease phenotype. METHODS: Certified reading center graders performed manual and semiautomated (region finder-based) grading of confocal scanning laser ophthalmoscopy (cSLO) fundus autofluorescence (FAF) images for 41 eyes of 22 patients. Lesion types were defined based on the black level and sharpness of the border: definite decreased autofluorescence (DDAF), well, and poorly demarcated questionably decreased autofluorescence (WDQDAF, PDQDAF). Agreement in grading between the two methods and inter- and intra-grader agreement was assessed by kappa coefficients (κ) and intraclass correlation coefficients (ICC). RESULTS: The mean ± standard deviation (SD) area was 3.07 ± 3.02 mm for DDAF (n = 31), 1.53 ± 1.52 mm for WDQDAF (n = 9), and 6.94 ± 10.06 mm for PDQDAF (n = 17). The mean ± SD absolute difference in area between manual and semiautomated grading was 0.26 ± 0.28 mm for DDAF, 0.20 ± 0.26 mm for WDQDAF, and 4.05 ± 8.32 mm for PDQDAF. The ICC (95% confidence interval) for method comparison was 0.992 (0.984-0.996) for DDAF, 0.976 (0.922-0.993) for WDQDAF, and 0.648 (0.306-0.842) for PDQDAF. Inter- and intra-grader agreement in manual and semiautomated quantitative grading was better for DDAF (0.981-0.996) and WDQDAF (0.995-0.999) than for PDQDAF (0.715-0.993). CONCLUSION: Manual and semiautomated grading methods showed similar levels of reproducibility for assessing areas of decreased autofluorescence in patients with Stargardt disease phenotype. Excellent agreement and reproducibility were observed for well demarcated lesions.

Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration.

BACKGROUND: The use of intravitreal anti-VEGF agents in general, and of bevacizumab (Avastin) in particular, has become the common first-line treatment of neovascular age-related macular degeneration (AMD). Several reports addressed the possible elevation of intraocular pressure (IOP) following intravitreal injection of anti-VEGF. The aim of this study was to determine the prevalence of sustained IOP elevation following intravitreal bevacizumab injections for neovascular AMD and identify possible risk factors for the development of increased IOP. METHODS: This retrospective cohort study included 174 consecutive patients (201 eyes) receiving intravitreal bevacizumab (1.25 mg/0.05 ml) as treatment for neovascular AMD. The records of the study patients were reviewed for age, gender, history of glaucoma, phakic status, IOP levels, length of follow-up, total number of injections, intervals between injections, and IOP management in eyes that exhibited IOP elevation. Sustained IOP elevation was defined as IOP ≥22 mmHg and a change from baseline of ≥6 mmHg recorded on at least two consecutive visits and lasting ≥30 days. Risk factors for an IOP increase were identified from the association between the studied variables and IOP elevations. RESULTS: Sustained IOP elevation was found in 22 of 201 eyes (11%). The increased IOP was controlled with topical medications in all eyes. Among the variables studied, only male gender [OR = 3.1, 95% CI (1.1, 8.5) p = 0.029] and length of interval between injections <8 weeks [OR = 3.0, 95%CI (1.1, 7.9), p = 0.028] emerged as risk factors for IOP elevation in a multivariable model. The prevalence of IOP elevation was significantly higher when the interval between injections was <8 weeks than ≥8 weeks (17.6 and 6%, respectively, p = 0.009). Pre-existing glaucoma was not associated with IOP elevation (p = 0.9). CONCLUSIONS: Sustained IOP elevations can occur in normotensive eyes undergoing intravitreal bevacizumab treatment for neovascular AMD. This phenomenon was related to shorter intervals between injections, with 8 weeks being taken as the cut-off point. AMD eyes that receive intravitreal bevacizumab injections need to be monitored for IOP changes, especially those in which the intervals between injections are <8 weeks.

Longitudinal Microperimetric Changes of Macular Sensitivity in Stargardt Disease After 12 Months: ProgStar Report No. 13.

Importance: Functional end points for clinical trials investigating the efficacy of emerging treatments for Stargardt disease type 1 (STGD1) are needed. Objective: To assess the yearly rate of change of macular function in patients with STGD1 using microperimetry. Design, Setting, and Participants: This multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. The study included participants with ABCA4-related STGD1 who were enrolled in the Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study at baseline. Data were analyzed from February 16, 2017, to December 1, 2019. Exposure: ABCA4-related STGD1 with a minimum lesion size on fundus autofluorescence and a minimum visual acuity. Main Outcomes and Measures: Changes in overall macular sensitivity (MS), deep scotoma count, number of points that tested normal, and location-specific sensitivity changes. Results: Among the 359 eyes from 200 patients (87 [43.5%] men; mean [SD] age, 33.3 [15.2] years) who underwent microperimetry examination graded at baseline and month 12, the mean (SD) yearly change in MS was -0.68 (2.04) dB (95% CI, -0.89 to -0.47 dB; P < .001), and deep scotoma points increased by a mean (SD) of 1.56 (5.74) points per year. The points with sensitivity of 12 dB or higher decreased in sensitivity by a mean (SD) of -3.01 (9.84) dB (95% CI, -4.03 to -1.99 dB; P < .001). The mean (SD) yearly change in MS was not significantly different between the eyes with a grading of good or fair pattern placement at both visits (-0.67 [2.1] dB) and the eyes with a poor pattern placement during at least 1 visit (-0.64 [2.2] dB) (P = .91). Conclusions and Relevance: This study showed that MS and the number of deep scotoma points had measurably changed after follow-up of approximately 1 year. Microperimetry may serve as a useful functional outcome parameter for clinical trials aimed at slowing the progression of STGD1.

A Novel Mutation in the Choroideremia Gene in a Turkish Family.

Choroideremia is an X-linked recessive genetic disorder caused by mutations in the CHM gene. It is a rare retinal dystrophy that manifests as nyctalopia and vision loss, progressing to blindness in later stages. We report a 21-year Turkish man who presented with nyctalopia for the past 4-5 years. His mother and maternal grandmother had similar, but less pronounced complaints. Fundus examination revealed pigmentary changes and retinal atrophy in both eyes. Optical coherence tomography showed outer retinal loss, with central island of preserved autofluorescence surrounded by absent autofluorescence on fundus autofluorescence examination. Goldmann visual fields were constricted. Microperimetry detected retinal sensitivity losses, and full-field electroretinogram demonstrated extinguished cone responses. Genetic analysis revealed a novel nonsense mutation in the CHM gene, namely p.E480X: c.1438G >T. The mutation causes a premature stop codon in exon 12. This is the first report of a G1438T mutation resulting in an E480X premature stop in the CHM gene.

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 (ß = -0.18; P < .001), with a lower number of normal test points (ß = -0.71; P < .001), and with a higher number of deep scotoma points (ß = -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.

Comparison of Prevalence of Diabetic Macular Edema Based on Monocular Fundus Photography vs Optical Coherence Tomography.

IMPORTANCE: Diagnosing diabetic macular edema (DME) from monocular fundus photography vs optical coherence tomography (OCT) central subfield thickness (CST) can yield different prevalence rates for DME. Epidemiologic studies and telemedicine screening typically use monocular fundus photography, while treatment of DME uses OCT CST. OBJECTIVE: To compare DME prevalence from monocular fundus photography and OCT. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cross-sectional study of DME grading based on monocular fundus photographs and OCT images obtained from patients with diabetic retinopathy at a single visit between July 1, 2011, and June 30, 2014, at a university-based practice and analyzed between July 30, 2014, and May 29, 2015. Presence of DME, including clinically significant macular edema (CSME), on monocular fundus photographs used definitions from the Multi-Ethnic Study of Atherosclerosis (MESA) and the National Health and Nutrition Examination Survey (NHANES). Presence of DME on OCT used Diabetic Retinopathy Clinical Research Network eligibility criteria thresholds of CST for trials evaluating anti-vascular endothelial growth factor treatments. MAIN OUTCOMES AND MEASURES: Prevalence of DME based on monocular fundus photographs or OCT. RESULTS: A total of 246 eyes of 158 participants (mean [SD] age, 65.0 [11.9] years; 48.7% women; 60.8% white) were included. Among the 246 eyes, the prevalences of DME (61.4%) and CSME (48.5%) based on MESA definitions for monocular fundus photographs were greater than the DME prevalence based on OCT (21.1%) by 40.2% (95% CI, 32.8%-47.7%; P < .001) and 27.2% (95% CI, 19.2%-35.3%; P < .001), respectively. Using NHANES definitions, DME and CSME prevalences from monocular fundus photographs (28.5% and 21.0%, respectively) approximated the DME prevalence from OCT (21.1%). However, among eyes without DME on OCT, 58.2% (95% CI, 51.0%-65.3%) and 18.0% (95% CI, 12.9%-24.2%) were diagnosed as having DME on monocular fundus photographs using MESA and NHANES definitions, respectively, including 47.0% (95% CI, 39.7%-54.5%) and 10.3% (95% CI, 6.3%-15.7%), respectively, with CSME. Among eyes with DME on OCT, 26.9% (95% CI, 15.6%-41.0%) and 32.7% (95% CI, 20.3%-47.1%) were not diagnosed as having either DME or CSME on monocular fundus photographs using MESA and NHANES definitions, respectively. CONCLUSIONS AND RELEVANCE: These data suggest that many eyes diagnosed as having DME or CSME on monocular fundus photographs have no DME based on OCT CST, while many eyes diagnosed as not having DME or CSME on monocular fundus photographs have DME on OCT. While limited to 1 clinical practice, caution is suggested when extrapolating prevalence of eyes that may benefit from anti-vascular endothelial growth factor therapy based on epidemiologic surveys using photographs to diagnose DME.

Assessment of estimated retinal atrophy progression in Stargardt macular dystrophy using spectral-domain optical coherence tomography.

AIMS: To estimate disease progression based on analysis of macular volume measured by spectral-domain optical coherence tomography (SD-OCT) in patients affected by Stargardt macular dystrophy (STGD1) and to evaluate the influence of software errors on these measurements. METHODS: 58 eyes of 29 STGD1 patients were included. Numbers and types of algorithm errors were recorded and manually corrected. In a subgroup of 36 eyes of 18 patients with at least two examinations over time, total macular volume (TMV) and volumes of all nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields were obtained. Random effects models were used to estimate the rate of change per year for the population, and empirical Bayes slopes were used to estimate yearly decline in TMV for individual eyes. RESULTS: 6958 single B-scans from 190 macular cube scans were analysed. 2360 (33.9%) showed algorithm errors. Mean observation period for follow-up data was 15 months (range 3-40). The median (IQR) change in TMV using the empirical Bayes estimates for the individual eyes was -0.103 (-0.145, -0.059) mm3 per year. The mean (±SD) TMV was 6.321±1.000 mm3 at baseline, and rate of decline was -0.118 mm3 per year (p=0.003). Yearly mean volume change was -0.004 mm3 in the central subfield (mean baseline=0.128 mm3), -0.032 mm3 in the inner (mean baseline=1.484 mm3) and -0.079 mm3 in the outer ETDRS subfields (mean baseline=5.206 mm3). CONCLUSIONS: SD-OCT measurements allow monitoring the decline in retinal volume in STGD1; however, they require significant manual correction of software errors.

Comparison of Short-Wavelength Reduced-Illuminance and Conventional Autofluorescence Imaging in Stargardt Macular Dystrophy.

PURPOSE: To compare grading results between short-wavelength reduced-illuminance and conventional autofluorescence imaging in Stargardt macular dystrophy. DESIGN: Reliability study. METHODS: setting: Moorfields Eye Hospital, London (United Kingdom). PATIENTS: Eighteen patients (18 eyes) with Stargardt macular dystrophy. OBSERVATION PROCEDURES: A series of 3 fundus autofluorescence images using 3 different acquisition parameters on a custom-patched device were obtained: (1) 25% laser power and total sensitivity 87; (2) 25% laser power and freely adjusted sensitivity; and (3) 100% laser power and freely adjusted total sensitivity (conventional). The total area of 2 hypoautofluorescent lesion types (definitely decreased autofluorescence and poorly demarcated questionably decreased autofluorescence) was measured. MAIN OUTCOME MEASURES: Agreement in grading between the 3 imaging methods was assessed by kappa coefficients (κ) and intraclass correlation coefficients. RESULTS: The mean ± standard deviation area for images acquired with 25% laser power and freely adjusted total sensitivity was 2.04 ± 1.87 mm(2) for definitely decreased autofluorescence (n = 15) and 1.86 ± 2.14 mm(2) for poorly demarcated questionably decreased autofluorescence (n = 12). The intraclass correlation coefficient (95% confidence interval) was 0.964 (0.929, 0.999) for definitely decreased autofluorescence and 0.268 (0.000, 0.730) for poorly demarcated questionably decreased autofluorescence. CONCLUSIONS: Short-wavelength reduced-illuminance and conventional fundus autofluorescence imaging showed good concordance in assessing areas of definitely decreased autofluorescence. However, there was significantly higher variability between imaging modalities for assessing areas of poorly demarcated questionably decreased autofluorescence.

Qualifying to Use a Home Monitoring Device for Detection of Neovascular Age-Related Macular Degeneration.

IMPORTANCE: Patients with intermediate age-related macular degeneration (AMD) using a home monitoring device have less loss of visual acuity, on average, at detection of choroidal neovascularization than do individuals using standard care monitoring techniques. Understanding the frequency with which patients are likely to initiate using a home monitoring device successfully is important in planning implementation of the device into practice. OBJECTIVES: To determine the frequency with which patients with intermediate AMD qualify to use a home monitoring device and to establish a reliable baseline reference value with the device to monitor their AMD for progression to choroidal neovascularization. DESIGN, SETTING, AND PARTICIPANTS: Between October 8, 2010, and May 20, 2011, a total of 131 eligible participants within a university-based retina practice with intermediate AMD in the study eye and visual acuity of 20/63 or better completed an in-clinic qualification test for the home device. Intermediate AMD was defined as multiple intermediate-sized drusen or at least 1 large druse. If both eyes were eligible, the eye with better visual acuity was selected as the study eye. If both eyes had the same visual acuity, the patient used the eye with subjectively better vision. Analysis was performed between August 1, 2011, and January 11, 2014. MAIN OUTCOMES AND MEASURES: The proportion of patients with reliable qualification test results and a test score predictive of successful home use of a monitoring device for detecting neovascular AMD, and the proportion who established a baseline reference value at home. RESULTS: A total of 129 participants (98.5%; 95% CI, 96.4%-99.9%) had reliable qualification test results; 91 participants (69.5%; 95% CI, 61.6%-77.4%) who completed this test attained a score that suggested they would be able to successfully use the home device. Among the 91 participants who could initiate home testing, 83 did so, including 80 participants (87.9%; 95% CI, 81.2%-94.6%) who established a baseline value that could be used as a reference for future monitoring. Younger participants were more likely to qualify for home testing (mean [SD] age, 73.1 [8.4] vs 81.1 [7.1] years; P < .001). Visual acuity at study enrollment did not appear to be associated with successful qualification (mean visual acuity for those who did and did not qualify was 20/28 and 20/31, respectively; P = .10). CONCLUSIONS AND RELEVANCE: These data suggest that the in-office qualification test is a useful screening tool to identify patients who may benefit from the home device. In any given retina practice, our data suggest an estimated 61.6% to 77.4% of patients with intermediate AMD should be able to produce reliable initial test results in the office test using the home monitoring device and pass a qualification test to initiate home monitoring. Subsequently, 81.2% to 94.6% of patients should be able to establish a home baseline reference value for future monitoring.

Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?

Retinitis pigmentosa (RP) is a group of diseases in which a mutation in one of the large variety of genes causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. Studies in animal models of RP have demonstrated that oxidative damage is a major contributor to cone cell death. In this study, we extended those findings to patients with RP, because compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione (GSH/GSSG) ratio in aqueous humor and a significant increase in aqueous protein carbonyl content. In contrast, there was no significant decrease in the serum GSH/GSSG ratio or increase in carbonyl content of serum proteins. These data indicate that patients with RP have ocular oxidative stress and damage in the absence of manifestations of systemic oxidative stress and/or damage indicating that demonstrations of oxidative damage-induced cone cell death in animal models of RP may translate to human RP. These observations lead to the hypothesis that potent antioxidants will promote cone survival and function in patients with RP and that the aqueous GSH/GSSG ratio and carbonyl content on proteins may provide useful biomarkers. Antioxid. Redox Signal. 23, 643-648.

Comparison of time- and spectral-domain optical coherence tomography in management of diabetic macular edema.

PURPOSE: Some clinical trials that proved the benefits of anti-VEGF therapy for diabetic macular edema (DME) based retreatment decisions on visual acuity and time-domain ocular coherence tomography (TD-OCT) central subfield thickness changes since the last treatment. This study assessed the impact of TD-OCT followed by spectral domain (SD)-OCT on as needed treatment decision-making in the management of DME with anti-VEGF medications. METHODS: Patients previously treated for DME with anti-VEGF medications in the Retina Division of the Wilmer Eye Institute, following an institutional review board-approved informed consent process, underwent clinical examination, TD-, and SD-OCT imaging. Their retina specialists recorded whether additional anti-VEGF therapy was recommended and their level of certainty in the decision after performing a clinical examination and reviewing a TD-OCT, and then again after reviewing a SD-OCT. RESULTS: Data were collected for 129 treatment decision pairs involving 67 eyes from 46 subjects. Nonconcordant decisions occurred in 9 (7%) treatment decision pairs. In 7 of these (5%, 95% confidence interval [CI]: 2%-11%), the addition of SD-OCT changed the retina specialist's decision from not recommending to recommending retreatment. The addition of SD-OCT increased the certainty of the retina specialist in 36% (95% CI: 27%-45%) of all treatment decision pairs. CONCLUSIONS: Spectral-domain OCT does not appear to change the ultimate treatment decision or increase the level of certainty of the retina specialist relative to TD-OCT in most cases of DME under anti-VEGF management in clinical practice. The few nonconcordant decisions appear to trend toward recommending more anti-VEGF therapy following SD-OCT.

Automated classification of severity of age-related macular degeneration from fundus photographs.

PURPOSE: To evaluate an automated analysis of retinal fundus photographs to detect and classify severity of age-related macular degeneration compared with grading by the Age-Related Eye Disease Study (AREDS) protocol. METHODS: Following approval by the Johns Hopkins University School of Medicine's Institution Review Board, digitized images (downloaded AT http://www.ncbi.nlm.nih.gov/gap/) of field 2 (macular) fundus photographs from AREDS obtained over a 12-year longitudinal study were classified automatically using a visual words method to compare with severity by expert graders. RESULTS: Sensitivities and specificities, respectively, of automated imaging, when compared with expert fundus grading of 468 patients and 2145 fundus images are: 98.6% and 96.3% when classifying categories 1 and 2 versus categories 3 and 4; 96.1% and 96.1% when classifying categories 1 and 2 versus category 3; 98.6% and 95.7% when classifying category 1 versus category 3; and 96.0% and 94.7% when classifying category 1 versus categories 3 and 4; CONCLUSIONS: Development of an automated analysis for classification of age-related macular degeneration from digitized fundus photographs has high sensitivity and specificity when compared with expert graders and may have a role in screening or monitoring.