Electronic Early Treatment Diabetic Retinopathy Research Articles

SCORE2 Report 24: Nonlinear Relationship of Retinal Thickness and Visual Acuity in Central Retinal and Hemiretinal Vein Occlusion

To investigate whether a nonlinear association between central subfield thickness (CST) on spectral-domain OCT and concurrent visual acuity letter score (VALS) exists in eyes treated initially with aflibercept or bevacizumab for macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Long-term follow-up after a randomized clinical trial from 64 centers in the United States. Participants were followed up to 60 months and treated at investigator discretion after completing the 12-month treatment protocol. Two-segment linear regression models were compared with simple linear regression models of VALS on CST. Pearson correlation coefficients were calculated to assess strength of CST and VALS associations. Central subfield thickness was measured by OCT and VALS by the electronic Early Treatment Diabetic Retinopathy Study methodology. Estimated inflection points, reflecting turning points at which the CST and VALS association changes from positive to negative, calculated at 7 postbaseline visits, range from 217 to 256 μm. A strongly positive correlation exists to the left of each estimated inflection point, ranging from 0.29 (P < 0.01 at month 60) to 0.50 (P < 0.01 at month 12), and a strongly negative correlation exists to the right of each estimated inflection point, ranging from -0.43 (P < 0.01 at month 1) to -0.74 (P < 0.01 at month 24). Randomization statistical tests showed that 2-segment models are favored over 1-segment models for all postbaseline months (P < 0.001 for all tests performed). The relationship between CST and VALS in eyes with CRVO or HRVO after treatment with anti-vascular endothelial growth factor (VEGF) therapy is not simply linear. The usually modest correlations between OCT-measured CST and visual acuity belie strong left and right correlations present in 2-segment models. Post-treatment CST close to the estimated inflection points showed the best expected VALS. The SCORE2 participants with a post-treatment CST after treatment close to the estimated inflection points of 217 to 256 μm showed the best VALS. In patients treated with anti-VEGF for macular edema associated with CRVO or HRVO, a thinner retina is not always associated with better VALS. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of Snellen Visual Acuity Measurements in Retinal Clinical Practice to Electronic ETDRS Protocol Visual Acuity Assessment

Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic Early Treatment Diabetic Retinopathy Study (eETDRS) protocol VA measurements and factors affecting the size of the differences. Retrospective chart review. Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (nonproliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. Differences and their association with patient and ocular factors were evaluated using linear mixed models with random effects for correlations within sites and participants. Difference between VA letter scores measured by eETDRS during a study visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation [SD]) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA ≤ 20/50 (n= 376), and 5.8 (6.6) letters in eyes with clinical VA ≥ 20/40 (n= 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (P < 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole, and 9.8 (9.3) letters without correction (P= 0.06). On average, clinical Snellen VA is 1 to 2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision. Proprietary or commercial disclosure may be found after the references.

Psychophysical Validation of a Novel Active Learning Approach for Measuring the Visual Acuity Behavioral Function.

PurposeTo evaluate the performance of the quantitative visual acuity (qVA) method in measuring the visual acuity (VA) behavioral function.MethodsWe evaluated qVA performance in terms of the accuracy, precision, and efficiency of the estimated VA threshold and range in Monte Carlo simulations and a psychophysical experiment. We also compared the estimated VA threshold from the qVA method with that from the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) and Freiburg Visual Acuity Text (FrACT) methods. Four repeated measures with all three methods were conducted in four Bangerter foil conditions in 14 eyes.ResultsIn both simulations and psychophysical experiment, the qVA method quantified the full acuity behavioral function with two psychometric parameters (VA threshold and VA range) with virtually no bias and with high precision and efficiency. There was a significant correlation between qVA estimates of VA threshold and range in the psychophysical experiment. In addition, qVA threshold estimates were highly correlated with those from the E-ETDRS and FrACT methods.ConclusionsThe qVA method can provide an accurate, precise, and efficient assessment of the full acuity behavioral function with both VA threshold and range.Translational RelevanceThe qVA method can accurately, precisely, and efficiently assess the full VA behavioral function. Further research will evaluate the potential value of these rich measures for both clinical research and patient care.

Long-term Effect of Intraocular Lens vs Contact Lens Correction on Visual Acuity After Cataract Surgery During Infancy

Although intraocular lenses (IOLs) are often implanted in children, little is known whether primary IOL implantation or aphakia and contact lens correction results in better long-term visual outcomes after unilateral cataract surgery during infancy. To compare long-term visual outcomes with contact lens vs IOL correction following unilateral cataract surgery during infancy. This multicenter randomized clinical trial enrolled 114 infants with a unilateral congenital cataract who underwent cataract surgery with or without primary IOL implantation between 1 and 6 months of age. Data on long-term visual outcomes were collected when the children were age 10.5 years (July 14, 2015, to July 12, 2019) and analyzed from March 30 through August 6, 2019. Intraocular lens implantation at the time of cataract surgery. Best-corrected visual acuity using the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) testing protocol. Analysis was performed on an intention-to-treat basis. Best-corrected visual acuity was measured at age 10.5 years for 110 of the 114 patients (96%) enrolled as infants. The participants included 58 girls (53%) and 52 boys (47%). Overall, 27 of the children (25%) had good (logMAR 0.30 [Snellen equivalent, 20/40] or better) visual acuity in the treated eye (12 [22%] in the IOL group and 15 [27%] in the aphakia group), but 50 children (44%) had a visual acuity of logMAR 1.00 (Snellen equivalent, 20/200) or worse (25 [44%] in the IOL group and 25 [44%] in the aphakia group). The median logMAR acuity in the treated eye was similar in children randomized to receive an IOL at the time of cataract extraction (0.89; interquartile range [IQR], 0.33-1.43 [Snellen equivalent, 20/159]) and those who remained aphakic (0.86; IQR, 0.30-1.46 [Snellen equivalent, 20/145]) (IQR, 0.30-1.46; P = .82). Although the overall difference in median visual acuity between the 2 groups was small, the estimate was imprecise (99% CI for the difference in medians was -0.54 to 0.47). As in previous phases of the study, visual acuity outcomes were highly variable with only 27 children (25%) achieving excellent visual acuity in their treated eye and 50 children (44%) having poor vision in the treated eye. Implanting an IOL at the time of cataract extraction was neither beneficial nor detrimental to the visual outcome. ClinicalTrials.gov Identifier: NCT00212134.

Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema

ImportanceSome eyes have persistent diabetic macular edema (DME) following anti–vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone.ObjectiveTo compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME.Design, Setting, and ParticipantsPhase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat.InterventionsFollowing the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol.Main Outcomes and MeasuresThe primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography.ResultsOf the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9% were female and 60.3% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of –0.5 letters (95% CI, −3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was –110 (86) μm compared with –62 (97) μm for the ranibizumab group (adjusted difference, –52; 95% CI, −82 to −22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001).Conclusions and RelevanceAlthough its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy.Trial Registrationclinicaltrials.gov Identifier: NCT01945866

Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion

ImportanceStudies have established the efficacy and safety of aflibercept for the treatment of macular edema due to central retinal vein occlusion. Bevacizumab is used off-label to treat this condition despite the absence of supporting data.ObjectiveTo investigate whether bevacizumab is noninferior to aflibercept for the treatment of macular edema secondary to central retinal or hemiretinal vein occlusion.Design, Setting, and ParticipantsThe SCORE2 randomized noninferiority clinical trial was conducted at 66 private practice or academic centers in the United States, and included 362 patients with macular edema due to central retinal or hemiretinal vein occlusion who were randomized 1:1 to receive aflibercept or bevacizumab. The first participant was randomized on September 17, 2014, and the last month 6 visit occurred on May 6, 2016. Analyses included data available as of December 30, 2016.InterventionsEyes were randomized to receive intravitreal injection of bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg; n = 180) every 4 weeks through month 6.Main Outcomes and MeasuresThe primary outcome was mean change in visual acuity (VA) letter score (VALS) from the randomization visit to the 6-month follow-up visit, based on the best-corrected electronic Early Treatment Diabetic Retinopathy Study VALS (scores range from 0-100; higher scores indicate better VA). The noninferiority margin was 5 letters, and statistical testing for noninferiority was based on a 1-sided 97.5% confidence interval.ResultsAmong 362 randomized participants (mean [SD] age, 69 [12] years; 157 [43.4%] women; mean [SD] VALS at baseline, 50.3 [15.2] [approximate Snellen VA 20/100]), 348 (96.1%) completed the month 6 follow-up visit. At month 6, the mean VALS was 69.3 (a mean increase from baseline of 18.6) in the bevacizumab group and 69.3 (a mean increase from baseline of 18.9) in the aflibercept group (model-based estimate of between-group difference, −0.14; 97.5% CI, −3.07 to ∞; P = .001 for noninferiority), meeting criteria for noninferiority. Ocular adverse events in the aflibercept group included 4 participants with intraocular pressure (IOP) more than 10 mm Hg greater than baseline; ocular adverse events in the bevacizumab group included 1 participant with endophthalmitis (culture negative), 9 with IOP more than 10 mm Hg greater than baseline, 2 with IOP higher than 35 mm Hg, and 1 with angle-closure glaucoma not attributed to the study drug or procedure.Conclusions and RelevanceAmong patients with macular edema due to central retinal or hemiretinal vein occlusion, intravitreal bevacizumab was noninferior to aflibercept with respect to visual acuity after 6 months of treatment.

A 24-Month Evaluation of Aflibercept for Wet Age-Related Macular Degeneration in Patients Previously Receiving Ranibizumab or Bevacizumab

To report the 24-month results and predictive factors for outcomes in patients transitioned from other anti-vascular endothelial growth factor agents to aflibercept for the treatment of exudative age-related macular degeneration (AMD). A prospective, single arm, investigator-initiated study. A total of 24 patients participated in the study and 87.5% (n= 21) completed the 24 month assessments. Patients were included if they had an active exudative AMD confirmed by fluorescein angiography, presence of fluid on spectral-domain optical coherence tomography (OCT) or new hemorrhage on clinical examination, Electronic Early Treatment Diabetic Retinopathy Study vision of 25 to 80 letters (Snellen equivalent of approximately 20/25-20/320), prior bevacizumab or ranibizumab injections within 3 months of enrollment, and an initial response on OCT defined as a decrease of retinal edema and/or subretinal fluid to anti-vascular endothelial growth factor injections. Patients were treated the first 3 months with 2 mg of intravitreal aflibercept monthly, followed by a fixed bimonthly schedule for 24 months. At each study visit, visual acuity and a spectral-domain OCT scanning of both eyes were performed. The mean absolute change from baseline in central subfield thickness at month 24, mean change from baseline in best-corrected visual acuity (BCVA) score, change from baseline in macular volume, and cube average thickness by spectral-domain OCT. Additionally, predictive factors associated with final visual and anatomic outcomes at month24. A mean decrease in central subfield thickness of-41 μm (P= 0.004) was observed with a mean increase in ETDRS BCVA of+10.4 letters (P < 0.001). At study entry, BCVA was a significant predictive factor for BCVA change at month 24 (rho=-0.59; P= 0.003). Also, the duration between AMD diagnosis and study entry was a significant factor for central subfield thickness change at month 24 (rho=-0.51; P= 0.011). In nonnaïve patients with active exudative AMD, treatment with a fixed intravitreal aflibercept dosing regimen for 24 months demonstrated sustained improvements in anatomy and vision in patients transitioned from other anti-vascular endothelial growth factor agents and stability when compared with 12-month outcomes. Patients who benefited most were those with worse vision at entry and longer duration of disease.

Descemet Stripping Endothelial Keratoplasty for Fuchs' Endothelial Corneal Dystrophy: Five-Year Results of a Prospective Study

To determine 5-year outcomes of Descemet stripping endothelial keratoplasty (DSEK) for Fuchs' endothelial corneal dystrophy (FECD). Prospective cohort study. Fifty-two eyes of 45 subjects with FECD undergoing primary DSEK. Subjects were examined before and at fixed intervals through 60 months after DSEK. At each visit, graft survival was determined by slit-lamp examination; best spectacle-corrected visual acuity (BSCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study (ETDRS) protocol; total anterior corneal higher-order aberrations (HOAs) were derived from corneal topography; and corneal backscatter, corneal thickness, and endothelial cell density were measured from confocal microscopy images. Corneal thickness also was measured by ultrasonic pachymetry. Changes after DSEK were analyzed using generalized estimating equation models. Best-corrected visual acuity, HOAs, endothelial cell loss, corneal thickness, and corneal backscatter. Complete 60-month follow-up was possible in 34 eyes. Mean BSCVA±standard deviation improved from 0.45±0.19 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent, 20/56) before DSEK to0.09±0.13 logMAR (Snellen equivalent, 20/25) at 5 years (P < 0.001). Between 1 and 5 years, BSCVA improved by 0.06 logMAR (or 3 ETDRS letters; 95% confidence interval, 0.05-0.07 logMAR) per year (P < 0.001), and 56% of eyes were 0.1 logMAR (20/25) or better at 5 years. Graft thickness (approximately 155 μm) and corneal thickness (approximately 700 μm) did not change after surgery. Anterior corneal HOAs and backscatter decreased between 1 and 5 years (P ≤ 0.002). Six grafts failed, of which 4 were primary (iatrogenic); mean endothelial cell loss±standard deviation was 55±15% at 5 years. Between 1 and 5 years after DSEK, BSCVA continues to improve such that at 5 years, more than half of eyes see better than 20/25 with a mean total corneal thickness of 700 μm. Improvement in vision is accompanied by continued reduction in corneal haze and aberrations, suggesting ongoing remodeling of the cornea after restoration of endothelial function.

Visual Acuity Testing Using Autorefraction or Pinhole Occluder Compared with a Manual Protocol Refraction in Individuals with Diabetes

To compare visual acuity (VA) scores obtained after autorefraction or using a pinhole occluder to scores obtained after refraction according to a standard clinical research protocol. Prospective, comparative case series. One hundred ten study participants (209 eyes) with diabetes mellitus and a broad range of diabetic retinopathy severity and VA. We measured VA after autorefraction by a Topcon KR-8000 autorefractor as well as after a Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction. The order of testing was randomized and examiners were masked to the source of each refraction. A second VA measurement, utilizing an identical DRCR.net manual refraction, was made in a subset of eyes (n = 144; 69%) to establish test-retest variability for comparison purposes. All eyes underwent VA testing using a pinhole occluder. Best corrected VA as measured by the Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Test (E-ETDRS). In all eyes, the median E-ETDRS VA letter score (EVA) obtained after manual refraction (MR-EVA) was 69 (Snellen equivalent 20/40), ranging from 4 to 93 (20/800 to 20/16). The median MR-EVA was slightly better than the median EVA obtained after autorefraction (AR-EVA), with a median difference (AR-EVA - MR-EVA) of -1 letter (25th, 75th percentiles, -4, 2 letters). The absolute difference between AR-EVA and MR-EVA was similar to the test-retest variability of MR-EVA alone. In contrast, MR-EVA was better than EVA obtained using a pinhole occluder (PH-EVA; median PH-EVA - MR-EVA, -4 letters [-9, 0]), and had significantly less test-retest variability (P<0.001). Generally, the spherical equivalent of autorefraction was slightly more hyperopic (or less myopic) than the spherical equivalent of manual refraction (median difference, +0.25 diopters [0, +0.63]). Given the substantial time and effort required for training and certification of study protocol refractionists, and the similarity between AR-EVA and MR-EVA, further evaluation of autorefraction, but not pinhole occluder testing, as an alternative to the current clinical research gold standard of ETDRS protocol manual refraction in study participants with diabetic retinopathy is warranted.

Baseline Predictors of Visual Acuity and Retinal Thickness Outcomes in Patients with Retinal Vein Occlusion: Standard Care versus COrticosteroid for REtinal Vein Occlusion Study Report 10

To investigate baseline factors associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study. Two multicenter, randomized clinical trials: one evaluating participants with central retinal vein occlusion (CRVO) and one evaluating participants with branch retinal vein occlusion (BRVO). Participants with follow-up data of 1 year or more, including 238 with CRVO and 367 with BRVO. Visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method, and central retinal thickness was measured by optical coherence tomography (OCT). Regression analysis related these outcomes to 20 baseline measures. Multiple P values were adjusted to control the false discovery rate. Outcome measures of visual acuity letter score included absolute change from baseline, a gain of ≥ 15 from baseline, and a loss of ≥ 15 from baseline. Outcome measures of center point thickness included absolute change from baseline, a measurement of ≤ 250 μm, and a measurement of ≥ 500 μm. Outcomes were assessed at 1 and 2 years. For CRVO and BRVO, younger age was associated with improved visual acuity and central retinal thickness outcomes. For CRVO, triamcinolone treatment and less severe anatomic abnormalities of the retina (center point thickness and areas of retinal hemorrhage, thickening, and fluorescein leakage) were predictive of better visual acuity outcomes. For BRVO, no history of coronary artery disease was predictive of improved visual acuity outcomes. For center point thickness outcomes, shorter duration of macular edema was associated with improvement in both disease entities. For CRVO, higher baseline visual acuity letter score was predictive of favorable OCT outcomes. For BRVO, lower baseline visual acuity letter score, presence of dense macular hemorrhage, and no prior grid photocoagulation were predictive of favorable OCT outcomes. Several factors were predictive of better visual acuity outcomes and more favorable OCT outcomes, including younger age and shorter duration of macular edema, respectively. These factors may assist clinicians in predicting disease course for patients with CRVO and BRVO.

Host and Graft Thickness after Descemet Stripping Endothelial Keratoplasty for Fuchs Endothelial Dystrophy

To determine relationships between vision, forward scatter, and total corneal and graft thicknesses after Descemet stripping endothelial keratoplasty (DSEK). Prospective, cohort study. Forty-four eyes with Fuchs endothelial dystrophy were examined before and at 1, 3, 6, and 12 months after DSEK; all eyes were pseudophakic after surgery. Central total corneal and graft thicknesses were measured using confocal microscopy. Best-corrected high-contrast visual acuity (BCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study protocol, and forward light scatter was measured using a straylight meter. Total corneal thickness was 610 ± 50 μm (mean ± standard deviation) before DSEK, increased to 680 ± 74 μm by 1 month after DSEK (P < .001), and stabilized at 660 ± 68 μm by 3 months after DSEK (P = .03 vs 1 month). Graft thickness was 170 ± 57 μm at 1 month, decreased to 157 ± 49 μm by 3 months (P = .004), and then remained stable through 12 months (156 ± 51 μm; P = .99 vs 3 months). BCVA was 0.44 ± 0.21 logarithm of the minimal angle of resolution (logMAR) units (Snellen equivalent, 20/55) before DSEK, improved to 0.26 ± 0.20 logMAR units (Snellen equivalent, 20/36) by 3 months (P < .001), and improved to 0.16 ± 0.16 logMAR units (Snellen equivalent, 20/29) at 12 months (P < .001 vs 3 months). BCVA and forward light scatter did not correlate with corneal or graft thickness after DSEK. Stromal edema resolves by 3 months after DSEK for Fuchs dystrophy, whereas visual acuity continues to improve through 12 months. Thicker corneas and grafts are not associated with worse visual acuity or increased forward scatter.

Factors Associated with Improvement and Worsening of Visual Acuity 2 Years after Focal/Grid Photocoagulation for Diabetic Macular Edema

To identify factors associated with the visual acuity outcome after focal/grid photocoagulation for diabetic macular edema (DME) among eyes randomized to the focal/grid photocoagulation treatment group within the Diabetic Retinopathy Clinical Research Network (DRCR.net) trial comparing triamcinolone with focal/grid laser. Multicenter, randomized, clinical trial. Three hundred thirty eyes with DME assigned to the focal/grid photocoagulation group, visual acuity 20/40 to 20/320, and optical coherence tomography (OCT) central subfield thickness > or =250 microns. Eyes were treated with a protocol-defined photocoagulation technique, which was repeated at 4-month intervals for persistent or recurrent edema. Separate logistic regression models were used to evaluate the associations of demographic, clinical, OCT, and fundus photographic variables with visual acuity improvement or worsening of > or =10 letters from baseline to 2 years. The association of the initial visual acuity outcome after treatment with the subsequent visual acuity course also was evaluated. Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method. Worse baseline visual acuity was the only factor found to be associated with more frequent visual acuity improvement (P<0.001), and both greater baseline OCT-measured retinal volume (P = 0.001) and better baseline visual acuity (P = 0.009) were found to be associated with more frequent visual acuity worsening. Visual acuity outcomes were similar in eyes with and without prior macular or panretinal photocoagulation. The initial visual acuity outcome at 4 months was not generally predictive of the subsequent course. Many eyes that worsened > or =10 letters from baseline to 4 months subsequently improved, and many eyes that initially improved, subsequently worsened. At this time, focal/grid photocoagulation remains the standard management for DME and these results do not alter this paradigm.

Patching vs Atropine to Treat Amblyopia in Children Aged 7 to 12 Years

To compare patching with atropine eyedrops in the treatment of moderate amblyopia (visual acuity, 20/40-20/100) in children aged 7 to 12 years. In a randomized, multicenter clinical trial, 193 children with amblyopia were assigned to receive weekend atropine or patching of the sound eye 2 hours per day. Main Outcome Measure Masked assessment of visual acuity in the amblyopic eye using the electronic Early Treatment Diabetic Retinopathy Study testing protocol at 17 weeks. At 17 weeks, visual acuity had improved from baseline by an average of 7.6 letters in the atropine group and 8.6 letters in the patching group. The mean difference between groups (patching - atropine) adjusted for baseline acuity was 1.2 letters (ends of complementary 1-sided 95% confidence intervals for noninferiority, -0.7, 3.1 letters). This difference met the prespecified definition for equivalence (confidence interval <5 letters). Visual acuity in the amblyopic eye was 20/25 or better in 15 participants in the atropine group (17%) and 20 in the patching group (24%; difference, 7%; 95% confidence interval, -3% to 17%). Treatment with atropine or patching led to similar degrees of improvement among 7- to 12-year-olds with moderate amblyopia. About 1 in 5 achieved visual acuity of 20/25 or better in the amblyopic eye. Atropine and patching achieve similar results among older children with unilateral amblyopia. (clinicaltrials.gov) Identifier: NCT00315328.

A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Focal/Grid Photocoagulation for Diabetic Macular Edema

To evaluate the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone in comparison with focal/grid photocoagulation for the treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. Eight hundred forty study eyes of 693 subjects with DME involving the fovea and with visual acuity of 20/40 to 20/320. Eyes were randomized to focal/grid photocoagulation (n = 330), 1 mg intravitreal triamcinolone (n = 256), or 4 mg intravitreal triamcinolone (n = 254). Retreatment was given for persistent or new edema at 4-month intervals. The primary outcome was evaluated at 2 years. Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method (primary), optical coherence tomography-measured retinal thickness (secondary), and safety. At 4 months, mean visual acuity was better in the 4-mg triamcinolone group than in either the laser group (P<0.001) or the 1-mg triamcinolone group (P = 0.001). By 1 year, there were no significant differences among groups in mean visual acuity. At the 16-month visit and extending through the primary outcome visit at 2 years, mean visual acuity was better in the laser group than in the other 2 groups (at 2 years, P = 0.02 comparing the laser and 1-mg groups, P = 0.002 comparing the laser and 4-mg groups, and P = 0.49 comparing the 1-mg and 4-mg groups). Treatment group differences in the visual acuity outcome could not be attributed solely to cataract formation. Optical coherence tomography results generally paralleled the visual acuity results. Intraocular pressure increased from baseline by 10 mmHg or more at any visit in 4%, 16%, and 33% of eyes in the 3 treatment groups, respectively, and cataract surgery was performed in 13%, 23%, and 51% of eyes in the 3 treatment groups, respectively. Over a 2-year period, focal/grid photocoagulation is more effective and has fewer side effects than 1-mg or 4-mg doses of preservative-free intravitreal triamcinolone for most patients with DME who have characteristics similar to the cohort in this clinical trial. The results of this study also support that focal/grid photocoagulation currently should be the benchmark against which other treatments are compared in clinical trials of DME.

Reliability of the electronic early treatment diabetic retinopathy study testing protocol in children 7 to

Purpose To assess the test-retest reliability of the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity algorithm using the computerized Electronic Visual Acuity (EVA) tester in children 7 to <13 years old. Design Test-retest reliability study. Methods This multicenter study involved 245 subjects at four clinical sites. As the main outcome measure, visual acuity was measured twice using the E-ETDRS testing protocol on the EVA system, which uses a programmed handheld device to communicate with a personal computer and a 17-inch monitor at a 3-m test distance. Results Test–retest reliability was high ( r = .94 for right eyes and 0.96 for left eyes) and for both right and left eyes, 89% of retest scores were within 0.1 logarithm of the minimal angle of resolution (logMAR) (five letters) of the initial test score and 99% of retests were within 0.2 logMAR (10 letters). Reliability was high across the age range of 7 to <13 years. Based on 95% confidence level estimates, a change in visual acuity of 0.2 logMAR (10 letters) from a previous acuity measure is unlikely to result from measurement variability. Conclusions The E-ETDRS protocol using the EVA has high test–retest reliability in children 7 to <13 years of age. Potential advantages include better standardization across multiple sites, the ability to directly capture data electronically with an automatic acuity score calculation, the reduction of potential bias by limiting the tester’s role, and the requirement of only a single testing distance for measurements from 20/800 to 20/12. This computerized testing method should be considered when visual acuity is used as an outcome measure in eye research involving children 7 to <13 years old.