Key Points
Question
What are the associations between changes in visual acuity and changes in optical coherence tomographic central subfield thickness across 3 anti–vascular endothelial growth factor medications used for diabetic macular edema?
Findings
In a post hoc analysis of 652 participants in a randomized clinical trial, changes in central subfield thickness were compared with changes in visual acuity. Analysis showed that changes in central subfield thickness accounted for only a small proportion of the total variation in changes in visual acuity.
Meaning
These findings do not support using changes in optical coherence tomography central subfield thickness as a surrogate for changes in visual acuity in phase 3 trials evaluating anti–vascular endothelial growth factor for diabetic macular edema or to guide physicians or patients about changes in visual acuity with anti–vascular endothelial growth factor treatment.
Abstract
Importance
The determination of optical coherence tomography (OCT) central subfield thickness (CST) is an objective measure, and visual acuity (VA) is a subjective measure. Therefore, using OCT CST changes as a surrogate for VA changes in diabetic macular edema seems reasonable. However, studies suggest that change in OCT CST following anti–vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema is correlated with changes in VA but varies substantially among individuals, and so may not be a good surrogate for changes in VA.
Objective
To determine associations between changes in VA and changes in OCT CST across 3 anti-VEGF agents (aflibercept, bevacizumab, or ranibizumab) used in a randomized clinical trial for diabetic macular edema.
Design, Setting, and Participants
Post hoc analyses were conducted of DRCR Retina Network Protocol T among 652 of 660 participants (98.8%) meeting inclusion criteria for this investigation. The study was conducted between August 22, 2012, and September 23, 2015. The post hoc data collection and analysis were performed from May 29 to July 11, 2018.
Interventions
Six monthly intravitreous anti-VEGF injections (unless success was achieved after 3-5 months) were administered; subsequent injections or focal/grid laser photocoagulation treatments were given as needed per protocol to achieve stability.
Main Outcomes and Measures
Association between changes in VA letter score with changes in CST at 12, 52, and 104 weeks after randomization to aflibercept, bevacizumab, or ranibizumab.
Results
Of the 652 participants, 304 were women (46.6%); median age was 61 years (interquartile range, 54-67 years). The correlation between CST and VA at the follow-up visits was 0.24 (95% CI, 0.16-0.31) in 616 patients at 12 weeks, 0.31 (95% CI, 0.24-0.38) in 609 patients at 52 weeks, and 0.23 (95% CI, 0.15-0.31) in 566 patients at 104 weeks. The correlation coefficients of change in VA vs change in OCT CST for these time intervals were 0.36 (95% CI, 0.29-0.43) at 12 weeks, 0.36 (95% CI, 0.29-0.43) at 52 weeks, and 0.33 (95% CI, 0.26-0.41) at 104 weeks.
Conclusions and Relevance
Changes in CST appear to account for only a small proportion of the total variation in changes in VA. These findings do not support using changes in OCT CST as a surrogate for changes in VA in phase 3 clinical trials evaluating anti-VEGF for diabetic macular edema or as a guide to inform the physician or patient about changes in VA after anti-VEGF treatment.
Trial Registration
ClinicalTrials.gov identifier: NCT01627249
This post hoc analysis of a randomized clinical trial compared the changes in visual acuity vs the changes in optical coherence tomographic central subfield thickness measures in evaluation of the outcomes of anti–vascular endothelial growth factor therapy in patients with diabetic macular edema.
Introduction
Phase 3 randomized clinical trials evaluating anti–vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) have used visual acuity (VA) as the primary outcome.1,2,3,4 These trials also have used optical coherence tomography (OCT) central subfield thickness (CST) measures as a secondary outcome. Previous publications have reported that CST is the preferred OCT measurement for the central macula in DME because of its higher reproducibility and correlation with other measurements of the central macula.5 Some 2-year trials with 1-year extensions have used fixed dosing of anti-VEGF either monthly for 3 years or monthly for 5 months followed by every other month through 3 years,2,4 regardless of anatomic or functional outcomes. The DRCR Retina Network trials use a treatment algorithm based on changes in either OCT CST or best-corrected VA at each follow-up visit to determine whether retreatment is indicated after 4 to 6 initial monthly injections.6
It seems reasonable to use OCT CST changes as a surrogate for VA changes in DME because the objective determination of OCT CST is faster to obtain and less prone to subjective aspects of VA measurement. However, in the DRCR Retina Network Protocol I in eyes treated with focal/grid laser for DME, OCT CST correlated only moderately with VA.7 Furthermore, in the DRCR Retina Network Protocol T, change in OCT CST after 3 anti-VEGF injections was a weak determinant of a patient’s subsequent VA outcome at 2 years when following the DRCR Retina Network anti-VEGF treatment regimen for DME.8 Among eyes with less than 10% vs 20% or greater CST reduction from baseline at 12 weeks, the percentage of eyes gaining 10 or more letters from baseline at 2 years appeared similar when using aflibercept, 2.0 mg, or ranibizumab, 0.3 mg, although not necessarily with bevacizumab, 1.25 mg.8 Furthermore, after 6 monthly injections of anti–VEGF therapy with 1 of these 3 agents, changes in VA between baseline and 2 years among eyes with persistent DME based on OCT CST were similar to changes in VA among eyes without persistent DME based on OCT CST.9 To extend our knowledge regarding the association of OCT CST and VA following anti-VEGF therapy for DME, this present investigation is a post hoc analysis of data from the DRCR Retina Network Protocol T trial to determine the association between changes in VA and changes in OCT CST across 3 different anti-VEGF agents evaluated in a randomized clinical trial for DME.3
Methods
Between August 22, 2012, and September 23, 2015, 660 participants were enrolled at 89 clinical sites in the United States. The study adhered to the tenets of the Declaration of Helsinki.10 Study participants provided written informed consent. The protocol and Health Insurance Portability and Accountability Act–compliant consent forms were approved by the institutional review board associated with each participating center. The institutional review boards at all sites approved the study, including collection of data for this analysis, which was performed from May 29 to July 11, 2018.
A detailed description of the methods for Protocol T has been published elsewhere3 and the complete protocol is available online.11 In brief, participants were adults (≥18 years) with type 1 or type 2 diabetes, had at least 1 eye with best-corrected Electronic Early Treatment Diabetic Retinopathy Study VA letter score of 78 through 24 (approximate Snellen equivalent, 20/32-20/320) and center-involved DME on clinical examination and OCT according to instrument-specific cutoffs for CST. Each participant had 1 study eye randomly assigned to aflibercept, 2.0 mg; bevacizumab, 1.25 mg (repackaged or compounded at 1 central site); or ranibizumab, 0.3 mg.
Protocol visits were every 4 weeks through the 52-week visit and every 4, 8, or 16 weeks through the 104-week visit, depending on the course of the disease. Retreatment with intravitreous anti-VEGF through follow-up was based on protocol-specified criteria. Subsequent focal/grid laser also was given as needed per protocol starting as early as the 24-week visit.
All eyes with complete VA and OCT CST measurements at baseline were included in this analysis. To minimize the potential influence of outliers on the results, changes in VA (n = 1, 8, and 16) and changes in CST (n = 4, 8, and 12) measurements at 12, 52, and 104 weeks, respectively, were truncated to ±3 SDs from the mean using the 52-week distribution (protocol T primary outcome). The association between changes in VA letter score with changes in CST at 12, 52, and 104 weeks was summarized using the Pearson correlation coefficient. The association between changes in VA and changes in measures of fluid on OCT (subretinal fluid and cystoid spaces, defined as improved, no change, or worsened) was evaluated at 52 and 104 weeks with the nonparametric Spearman correlation coefficient. The 95% CIs of the correlation coefficients were estimated using Fisher z transformation and the magnitude of the correlation was described using Cohen terminology (r): 0.10, small; 0.30, moderate; and 0.50, large.12,13 Generalized linear regression models were used to calculate the slope of the regression line for change in CST and the coefficient of determination (R2), adjusting for treatment group, for each visit. At 104 weeks, previously identified baseline factors (VA, treatment group interaction with VA, age, hemoglobin A1c level, and prior panretinal photocoagulation and diabetic retinopathy severity) associated with VA changes and additional factors were included in the model.14 Additional factors included presence of subretinal fluid within 500 μm of the macula center or cystoid spaces on OCT, as well as hard exudates within 1800 μm of the macula center or hemorrhages and microaneurysms within 1800 μm of the macula center on fundus photographs. A backward stepwise procedure with entry selection criterion set at P ≤ .10 and stay criterion set at P ≤ .05 were used to select the final model. Residuals from the final models were evaluated to verify assumptions of normality and equal variance. No adjustments were made for multiplicity. All reported P values are 2-sided and all analyses were performed in SAS, version 9.4 (SAS Institute Inc).
Results
A total of 652 eyes were included in this analysis, among which 221 eyes (33.9%) were in the aflibercept group, 216 eyes (33.1%) were in the bevacizumab group, and 215 eyes (33.0%) were in the ranibizumab group. Baseline characteristics are summarized in Table 1; 304 of 652 participants were women (46.6%), median age was 61 years (interquartile range, 54-67 years), 424 of 649 participants were white (65.3%), and 590 of 639 individuals had type 2 diabetes (92.3%).
Table 1. Selected Baseline Characteristics for Eyes Included in the Study.
| Characteristic | Eyes Included, No. (%) |
|---|---|
| No. | 652 |
| Women | 304 (46.6) |
| Age, median (IQR) | 61 (54-67) |
| Racea | |
| White | 424 (65.3) |
| Black/African American | 104 (16.0) |
| Hispanic/Latino | 102 (15.7) |
| Other (Asian/American Indian/Alaskan Native /Native Hawaiian/other Pacific Islander)b | 19 (2.9) |
| Type of diabetesa | |
| 1 | 49 (7.7) |
| 2 | 590 (92.3) |
| Insulin used | |
| No | 207 (31.7) |
| Yes | 445 (68.3) |
| Duration of diabetes, median (IQR) | 16 (10-23) |
| HbA1c, % median (IQR)a | 7.7 (6.8-9.0) |
| Prior treatment for DME | 268 (41.1) |
| Prior laser treatment for DME | 240 (36.8) |
| Prior anti-VEGF for DME | 83 (12.7) |
| Lens status | |
| Pseudophakic | 157 (24.1) |
| Phakic | 495 (75.9) |
| VA letter score, median (IQR) | 69 (59-73) |
| VA (approximate Snellen equivalent), median (IQR) | 20/40 (20/40-20/63) |
| Diabetic retinopathy severity based on reading center grading | |
| NPDR | |
| Absent or mild | 18 (2.8) |
| Mild to moderately severe | 422 (65.7) |
| Severe | 49 (7.6) |
| Prior PRP without active PDR | 55 (8.6) |
| Mild to moderate PDR | 80 (12.5) |
| High risk PDR | 18 (2.8) |
| Type of DME as judged by the investigator | |
| Predominantly focal | 209 (32.1) |
| Neither predominantly focal nor diffuse | 106 (16.3) |
| Predominantly diffuse | 337 (51.7) |
| OCT CST, median (IQR), μma | 387 (308-479) |
| Cystoid spaces | |
| No | 9 (1.4) |
| Yes | 635 (98.6) |
| Subretinal fluid within 500 μm of the macula centera | |
| No | 441 (68.8) |
| Yes | 200 (31.2) |
| Epiretinal membrane within 500 μm of the macula centera | |
| No | 500 (78.4) |
| Yes | 138 (21.6) |
| Hard exudates within 1800 μm of the macula centera | |
| None | 162 (25.2) |
| Questionable or definite (complete hard exudate grid) | 481 (74.8) |
| Hemorrhages and microaneurysms within 1800 μm of the macula center | |
| None/questionable/less than standard ETDRS photo 1 | 115 (17.9) |
| Standard ETDRS photo 1 to less than standard ETDRS photo 2A | 423 (65.8) |
| ≥ Standard ETDRS photo 2A | 105 (16.3) |
Abbreviations: CST, central subfield thickness; DME, diabetic macular edema; DR, diabetic retinopathy; ETDRS, Early Treatment Diabetic Retinopathy Study; HbA1c, hemoglobin A1c; IQR, interquartile range; NPDR, nonproliferative diabetic retinopathy; OCT, optical coherence tomography; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation; VA, visual acuity; VEGF, vascular endothelial growth factor.
Eyes with missing/unknown data: race/ethnicity (n = 3), diabetes type (n = 13), HbA1c (n = 6), subretinal fluid (n = 11), epiretinal membrane (n = 14), hard exudates (n = 9), cystoid spaces (n = 8), and hemorrhages and microaneurysms (n = 9).
Other race/ethnicity distribution: Asian (n = 8), Pacific Islander (n = 4), American Indian/Alaskan Native (n = 1), and more than 1 race (n = 6).
Association Between VA and OCT CST
At baseline (N = 652), the mean (SD) (approximate Snellen equivalent) VA letter score was 65.0 (11.1) (20/50) letters and the mean (SD) CST was 459 (128) μm. The Pearson correlation coefficient for the association between VA and OCT CST at baseline (Figure 1) was 0.36 (95% CI, 0.30-0.43). The correlation coefficient was similar among the 3 treatment groups (eFigure 1 in the Supplement; Table 2). The slope of the regression line indicated 3.2 letters (95% CI, 2.5-3.8 letters) increased VA for every 100-μm decrease in OCT CST. Central subfield thickness accounted for 13% of the total variation in VA observed. The association between VA and CST was similar (3.3 letters; 95% CI, 2.7-3.9 letters) after accounting for the hemoglobin A1c level, which was the only other previously identified baseline variable significantly related to VA.14
Figure 1. Visual Acuity (VA) by Central Subfield Thickness (CST) at Baseline.
Total of 652 patients. The solid line indicates the line of best fit; r = 0.36.
Table 2. Correlation Between Visual Acuity and Central Subfield Thickness by Treatment Group.
| Visit | All | Aflibercept | Bevacizumab | Ranibizumab | ||||
|---|---|---|---|---|---|---|---|---|
| No. | r (95% CI) | No. | r (95% CI) | No. | r (95% CI) | No. | r (95% CI) | |
| Correlation Between Visual Acuity and Central Subfield Thickness | ||||||||
| Baseline | 652 | 0.36 (0.30-0.43) | 221 | 0.39 (0.28-0.50) | 216 | 0.44 (0.33-0.54) | 215 | 0.25 (0.12-0.38) |
| 12 wk | 616 | 0.24 (0.16-0.31) | 209 | 0.19 (0.06-0.32) | 207 | 0.31 (0.18-0.42) | 200 | 0.16 (0.03-0.30) |
| 52 wk | 609 | 0.31 (0.24-0.38) | 205 | 0.24 (0.10-0.36) | 203 | 0.42 (0.30-0.53) | 201 | 0.14 (0.00-0.27) |
| 104 wk | 566 | 0.23 (0.15-0.31) | 198 | 0.17 (0.03-0.30) | 182 | 0.28 (0.14-0.41) | 186 | 0.19 (0.05-0.33) |
| Correlation Between Changes in Visual Acuity and Changes in Central Subfield Thickness | ||||||||
| 12 wk | 616 | 0.36 (0.29-0.43) | 209 | 0.31 (0.18-0.43) | 207 | 0.39 (0.26-0.50) | 200 | 0.36 (0.24-0.48) |
| 52 wk | 609 | 0.36 (0.29-0.43) | 205 | 0.40 (0.28-0.51) | 203 | 0.37 (0.24-0.48) | 201 | 0.25 (0.12-0.38) |
| 104 wk | 566 | 0.33 (0.26-0.41) | 198 | 0.33 (0.20-0.45) | 182 | 0.38 (0.25-0.50) | 186 | 0.27 (0.13-0.39) |
Of the 652 eyes analyzed at baseline, the numbers evaluable for follow-up were 616 at 12 weeks, 609 at 52 weeks, and 566 at 104 weeks. The correlation between CST and VA was 0.24 (95% CI, 0.16-0.31) at the 12-week visit, 0.31 (95% CI, 0.24-0.38) at the 52-week visit, and 0.23 (95% CI, 0.15-0.31) at the 104-week visit (Table 2).
Association Between Changes in VA and Changes in CST
eTable 1 in the Supplement provides the mean (SD) of the distributions of changes in VA and changes in CST by treatment group for each follow-up visit. At 12, 52, and 104 weeks, combining all treatment groups, the mean (SD) changes in OCT CST were −115.1 (121.2) μm at 12 weeks, −137.7 (129.4) μm at 52 weeks, and −147.5 (136.7) μm at 104 weeks, and mean (SD) VA letter score changes were 8.3 (8.7) letters at 12 weeks, 11.3 (10.2) letters at 52 weeks, and 11.7 (11.5) letters at 104 weeks. The correlation coefficients of change in VA vs change in OCT CST for these time intervals were 0.36 (95% CI, 0.29-0.43) at 12 weeks, 0.36 (95% CI. 0.29-0.43) at 52 weeks, and 0.33 (95% CI, 0.26-0.41) at 104 weeks (Table 2, Figure 2; eFigure 2 in the Supplement). The correlation coefficients of change in VA vs change in OCT CST at 12 weeks among eyes with baseline CST were 0.21 with less than 450 μm (n = 351), 0.37 with 450 to less than 650 μm (n = 211), and 0.47 with 650 μm and above (n = 54) (Figure 2). Correlation coefficients were similar across all treatment groups (range, 0.25-0.40) (eFigure 3 in the Supplement).
Figure 2. Change in Visual Acuity (VA) by Change in Central Subfield Thickness (CST) at 12 Weeks.
Total of 612 patients; r = 0.36.
After adjusting for treatment group, the slope of the regression line for changes in VA vs changes in CST (for better VA letter score for every 100-μm lower OCT CST) was 2.5 (95% CI, 2.0-3.1) at 12 weeks, 2.7 (95% CI, 2.1-3.3) at 52 weeks, and 2.7 (95% CI, 2.1-3.4) at 104 weeks. The R2 values for these models were 14% at 12 and 52 weeks and 12% at 104 weeks (eTable 2 in the Supplement). For the analysis of data at 104 weeks, previously identified baseline factors associated with VA changes (VA, treatment group, VA and treatment group interaction, hemoglobin A1c level, age, and prior panretinal photocoagulation and diabetic retinopathy severity) were included in the model and this inclusion increased the R2 to 29% (Table 3). There were no statistically significant interactions between treatment group and changes in CST at each visit identified (eTable 2 in the Supplement).
Table 3. Linear Regression Analysis of Change in Visual Acuity and Change in Central Subfield Thickness at 2 Years, Adjusting for Baseline Factorsa,b.
| Factor | No. | Model Estimate (95% CI) Difference in Letter Scorec | P Value (R2 = 29%)c |
|---|---|---|---|
| Changes in central subfield thickness (per 100-μm increase) | 553 | −1.3 (−1.9 to −0.6) | <.001 |
| Age (each 10-y increment) | 553 | −1.9 (−2.8 to −1.0) | <.001 |
| HbA1c (each 1% increment) | 553 | −0.8 (−1.3 to −0.3) | .002 |
| PRP and DR severity | .03 | ||
| No prior PRP and at most moderately severe NPDR (levels 10-47) | 377 | 3.1 (0.8 to 5.3) | NA |
| No prior PRP and severe NPDR through high-risk PDR (levels 53-75, excluding 60) | 84 | 2.2 (−0.8 to 5.2) | |
| Prior PRP and inactive PDR (level 60) or at least mild PDR (levels 61-75) | 92 | 1 [Reference] |
Abbreviations: DR, diabetic retinopathy; HbA1c, hemoglobin A1c; NA, not applicable; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation.
Additional factors not significantly associated with visual acuity in the final model were cystoid spaces, hard exudates, hemorrhages and microaneurysms, and subretinal fluid.
The R2 for the model without changes in central subfield thickness was 28%.
Adjusted for baseline visual acuity, treatment, and their interaction. Changes in visual acuity (n = 16) and changes in central subfield thickness (n = 12) were truncated to ±3 SD of the mean.
At the 12-, 52-, and 104-week visits, a small percentage of eyes showed presumably paradoxical improvement in VA with increased OCT CST (12 weeks, 5.7%; 52 weeks, 5.4%; 104 weeks, 5.1%) or paradoxical worsening of VA with a decrease in OCT CST (12 weeks, 9.1%; 52 weeks, 7.4%; 104 weeks, 7.6%). The correlation between changes in VA and changes in cystoid spaces (n = 594) was −0.10 at 52 weeks; the correlation of changes in VA with changes in subretinal fluid (n = 588) was −0.21 at 52 weeks (eFigure 4 and eFigure 5 in the Supplement).
Discussion
Among eyes with DME in Protocol T at baseline, small to moderate correlations were observed between VA and OCT CST at baseline and follow-up times. A moderate correlation was observed between changes in VA and changes in CST after the DRCR Retina Network anti-VEGF retreatment regimen for DME was applied with aflibercept, bevacizumab, or ranibizumab. However, changes in CST accounted only for a small proportion (12%-14%) of the total variation in changes in VA at each follow-up visit. For any given change in OCT CST from baseline, there was a broad range of changes in VA from baseline at 12, 52, and 104 weeks. Similarly, for any given change in VA from baseline, there was a broad range of changes in OCT CST from baseline at 12, 52, and 104 weeks. The data suggested that the correlation coefficients of change in VA vs change in OCT CST at 12 weeks were greater when the baseline CST was 650 μm or more compared with greater than 350 μm but less than 450 μm. However, the correlation between change in OCT CST and change in VA was still no better than moderate (0.47) in eyes with the most pronounced thickening.
The findings in this analysis are similar to those observed when evaluating the correlation between VA and OCT CST when laser treatment was used to treat DME.7 The results also are consistent with findings reported regarding this association when anti-VEGF therapy was used to treat choroidal neovascularization secondary to age-related macular degeneration.15 Thus, the preponderance of data to date suggests that one should not use change in OCT CST over time as a definitive surrogate for VA changes over time. Because there is a general correlation, though, between changes in OCT CST and changes in VA that has been found consistently across study cohorts, using changes in OCT CST as a surrogate outcome for generating hypotheses regarding potential VA benefits or risks of treatments for DME in phase 1 or phase 2 trials seems reasonable.
Strengths and Limitations
Strengths of this analysis included limitation of the potential for selection bias with greater than 90% retention of living study participants through 2 years, masked VA examiners at annual visits, objective OCT data, and a protocol-mandated anti-VEGF retreatment algorithm. Given the post hoc nature of this investigation, the results should be viewed as exploratory and potentially applicable only to the DRCR Retina Network treatment regimen for DME. Nevertheless, the consistency of these findings across other treatments for DME, such as laser,7 or other macular diseases, such as neovascular age-related macular degeneration treated with anti-VEGF,15 increase the likelihood that these findings generalize to other treatment regimens for DME.
There are several limitations to this study. It is unknown if changes over time of other OCT measures, which have been correlated with VA at baseline or at follow-up in cross-sectional evaluations, also could be considered as a surrogate for changes in VA over time. For example, the height of intraretinal cystoid spaces at baseline has been shown to correlate with subsequent change in VA.16 However, that finding does not indicate that change in the height of intraretinal cystoid spaces correlates with change in VA such that this structural change could serve as a surrogate for change in VA. Similarly, there are cross-sectional studies showing that measures on OCT angiography, such as the size of the foveal avascular zone, correlate with VA.17 These cross-sectional studies do not necessarily mean that changes in the size of the foveal avascular zone over time on OCT angiography are a good surrogate for changes in VA. The DRCR Retina Network also has not yet evaluated whether other OCT features, such as changes in the disorganization of the retinal inner layers, correlate with changes in VA over time. Also, the data from this investigation do not allow us to speculate why the correlation of change in OCT CST with change in VA during anti-VEGF treatment is relatively poor, although others have speculated recently on some possibilities.18
Conclusions
These results support findings from previous studies of laser photocoagulation for DME or anti-VEGF treatment for other macular diseases, wherein there is at best a moderate correlation between changes in VA and changes in CST after anti-VEGF therapy. However, these changes in CST account for only a small proportion of the total variation in changes in VA at each follow-up visit. For any given change in OCT CST from baseline, there was a broad range of changes in VA from baseline at 12, 52, and 104 weeks. These findings do not support using changes in OCT CST in lieu of changes in VA in phase 3 clinical trials evaluating anti-VEGF treatments for DME and suggest that OCT CST changes are not typically a reliable guide to informing a physician or patient about changes in VA with anti-VEGF treatment for an individual eye.
eTable 1. Visual Acuity and Central Subfield Thickness Distribution by Treatment Group
eTable 2. Linear Regression Analysis of Change in Visual Acuity With Change in Central Subfield Thickness by Treatment Group
eFigure 1. Scatterplots of Visual Acuity by Central Subfield Thickness Stratified by Treatment Group at Baseline
eFigure 2. Scatterplots of Changes in Visual Acuity by Changes in Central Subfield Thickness at 52 and 104 Weeks
eFigure 3. Scatterplots of Changes in Visual Acuity by Changes in Central Subfield Thickness Stratified by Treatment Group at 12 Weeks
eFigure 4. Correlation Between Changes in Visual Acuity and Changes in Cystoid Spaces at 52 and 104 Weeks
eFigure 5. Correlation Between Changes in Visual Acuity and Changes in Subretinal Fluid at 52 and 104 Weeks
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Associated Data
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Supplementary Materials
eTable 1. Visual Acuity and Central Subfield Thickness Distribution by Treatment Group
eTable 2. Linear Regression Analysis of Change in Visual Acuity With Change in Central Subfield Thickness by Treatment Group
eFigure 1. Scatterplots of Visual Acuity by Central Subfield Thickness Stratified by Treatment Group at Baseline
eFigure 2. Scatterplots of Changes in Visual Acuity by Changes in Central Subfield Thickness at 52 and 104 Weeks
eFigure 3. Scatterplots of Changes in Visual Acuity by Changes in Central Subfield Thickness Stratified by Treatment Group at 12 Weeks
eFigure 4. Correlation Between Changes in Visual Acuity and Changes in Cystoid Spaces at 52 and 104 Weeks
eFigure 5. Correlation Between Changes in Visual Acuity and Changes in Subretinal Fluid at 52 and 104 Weeks