Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments

Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts

Changes in activity impairment and work productivity after treatment for vitreous hemorrhage due to proliferative diabetic retinopathy: Secondary outcomes from a randomized controlled trial (DRCR Retina Network Protocol AB).

BackgroundVitreous hemorrhage from proliferative diabetic retinopathy can cause severe vision loss. DRCR Retina Network Protocol AB was a randomized clinical trial comparing intravitreal aflibercept versus vitrectomy with panretinal photocoagulation and found no difference in the average rate of visual recovery over 104 weeks. Herein, we describe patient-reported outcome measures from Protocol AB.MethodsSecondary analysis of a multicenter (39 sites) randomized clinical trial. The Work Productivity and Activity Impairment Questionnaire was administered at 4, 12, 24, 36, 52, 68, 84, and 104 weeks. Main outcomes were mean change in activity impairment and work productivity loss over 24 and 104 weeks (area under the curve).ResultsMean (SD) activity impairment at baseline was 58% (27%) in the aflibercept group (N = 99) and 56% (30%) in the vitrectomy group (N = 105). The mean reduction in activity impairment from baseline over 24 weeks was 21% (25%) in the aflibercept group and 27% (31%) in the vitrectomy group (adjusted difference = -6.8% [95% CI, -12.7% to -0.9%], P = .02); over 104 weeks, the adjusted mean difference was -3.1% (95% CI, -9.2% to 3.0%, P = .31). Mean work productivity loss at baseline was 51% (28%) in the aflibercept group (N = 44) and 58% (30%) in the vitrectomy group (N = 43). The mean reduction in work productivity loss from baseline over 24 weeks (area under the curve) was 19% (23%) in the aflibercept group and 31% (24%) in the vitrectomy group (adjusted difference = -8.3% [95% CI, -16.8% to 0.2%], P = .06); over 104 weeks, the adjusted mean difference was -9.1% (95% CI, -18.4% to 0.2%, P = .05).ConclusionsParticipants with vitreous hemorrhage from proliferative diabetic retinopathy had less activity impairment over 24 weeks when treated initially with vitrectomy and panretinal photocoagulation versus intravitreal aflibercept. The trend was similar for work productivity but not statistically significant. By 104 weeks, the improvements were similar in the two treatment groups.Trial registrationClinicalTrials.gov NCT02858076

Defining “Strong” versus “Weak” Response to Anti-VEGF Treatment for Center-Involved Diabetic Macular Edema

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

Lapses in Care Among Patients Assigned to Ranibizumab for Proliferative Diabetic Retinopathy: A Post Hoc Analysis of a Randomized Clinical Trial

The follow-up schedule for individuals with eyes treated with anti-vascular endothelial growth factor agents for proliferative diabetic retinopathy (PDR) requires that patients return frequently for monitoring and repeated treatment. The likelihood that a patient will comply should be a consideration in choosing a treatment approach. To describe completion of scheduled examinations among participants assigned to intravitreous injections of ranibizumab for PDR in a multicenter randomized clinical trial. This post hoc analysis evaluates data from a randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012. Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. Data were analyzed from April 2019 to July 2021. Ranibizumab injections for PDR or macular edema. A long lapse in care of 8 or more weeks past a scheduled examination, dropout from follow-up, visual acuity at 5 years. Among 170 participants, the median age was 51 years, and 44.7% were female. Through 5 years of follow-up, 94 of 170 participants (55.3%) had 1 or more long lapse in care. Median time to the first long lapse was 210 weeks, and 69 of 94 participants (73.4%) returned for examination after the first long lapse. Fifty of 170 participants (29.4%) dropped out of follow-up by 5 years. Among the 120 participants who completed the 5-year examination, median change from baseline in visual acuity was -2 letters for participants who had 1 or more long lapse compared with +5 letters for those without a long lapse (P = .02). After multivariable adjustment, the odds ratio (95% CI) for baseline associations with 1 or more long lapse was 1.21 (1.03-1.43) for each 5-letter decrement in visual acuity score, 2.19 (1.09-4.38) for neovascularization of the disc and elsewhere, and 3.48 (1.38-8.78) for no prior laser treatment for diabetic macular edema. Over 5 years, approximately half of the participants assigned to ranibizumab for PDR had a long lapse in care despite substantial effort by the DRCR Retina Network to facilitate timely completion of examinations. The likelihood of a long lapse in care during long-term follow-up needs to be considered when choosing treatment for PDR. ClinicalTrials.gov Identifier: NCT01489189

Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial

Importance: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. Objective: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. Design, setting, and participants: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. Interventions: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. Main outcomes and measures: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. Results: Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50; P < .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs 33.2% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs 14.8% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5% CI, -1.0 to 1.9 letters]; P = .47). Conclusions and relevance: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes

A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE)

PurposeTo determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision.DesignPhase 2 randomized clinical trial.ParticipantsParticipants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States.MethodsOne eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months.Main outcome measuresChange in CST on spectral-domain OCT at 4 months.ResultsFrom April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n&nbsp;= 69) or placebo (n&nbsp;= 66); median age was 62 years, 37% were women, and 82% were White. The median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes, with the mean difference (95% confidence interval [CI]) being&nbsp;-2 (-20 to 16) μm (P&nbsp;= 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI]&nbsp;= 1.30 (0.44-3.83); P&nbsp;= 0.63). VA decreased by a mean (SD) of&nbsp;-0.2 (5.5) letters and&nbsp;-0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95% CI]&nbsp;= 0.4 (-1.3 to 2.0) letters; P&nbsp;= 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious.ConclusionsPBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision