Prevalence of diabetic retinopathy (DR) in the United States is estimated at 34.6% (93 million people), and 10.2% (28 million) have vision threatening complications.1,2 The presence of diabetic macular edema (DME) increases risk of visual impairment; therefore, treatment is often indicated to reduce risk of central vision loss.3
Anti-vascular endothelial growth factor (VEGF) injections are first-line therapy for center-involving DME. The anti-VEGF therapies available at study enrollment included Food and Drug Administration-approved ranibizumab (Lucentis; Genentech, South San Francisco, CA) and aflibercept (Eylea; Regeneron, Tarrytown, NY) as well as off-label bevacizumab (Avastin; Genentech, South San Francisco, CA). Although all anti-VEGF medications are effective in improving best-corrected visual acuity (BCVA) and reducing central subfield thickness (CST), the Diabetic Retinopathy Clinical Research Network Protocol I and T studies both reported persistent DME despite treatment.4 In subsequent case reports, patients with recalcitrant DME despite treatment with bevacizumab or ranibizumab exhibited further treatment response after transition to intravitreal aflibercept injection (IAI).5–10 Aflibercept also reduced rates of persistent DME when following a specified treatment protocol.11
Several studies, however, have reported a lack of statistically significant vision improvement despite significant anatomical improvements after either continued ranibizumab or switch to aflibercept; this discrepancy was thought to be secondary to permanent functional damage from chronic DME.12,13 A degree of vision loss may stem from structural microvascular damage as seen on optical coherence tomography angiography (OCTA), which has been reported in patients with DR.14–16 It is currently unknown whether this damage stabilizes or progresses following adequate treatment of DME.
Although some studies report no change from baseline in capillary perfusion density (CPD) and foveal avascular zone (FAZ) in patients undergoing anti-VEGF treatment for DME,17–19 long-term follow-ups have not been reported. The aim of this study was to examine the effect of transition to fixed-dosing IAI in patients with DME previously treated with other anti-VEGF agents by assessing the mean CST and BCVA change from baseline, and to evaluate perfusion changes by OCTA overtime; participants were then followed prospectively over 24 months. Herein, we report significant changes in CST, BCVA, and retinal perfusion in study participants at 24 months.
Patients and Methods
Study Design and Participants
This study is a prospective, interventional, single-arm study performed at the Cole Eye Institute in Cleveland, Ohio. The study received approval from the Cleveland Clinic Investigational Review Board and followed the tenants of the Health Insurance Portability and Accountability Act. Written informed consent was obtained from each patient prior to enrollment.
Eligible eyes exhibited persistent center-involved DME with CST of 325 µm or greater on spectral-domain optical coherence tomography (SD-OCT) who required ongoing anti-VEGF therapy despite prior treatment with at least four injections of either bevacizumab or ranibizumab during the 6 months leading up to the baseline visit. Each visit included a comprehensive eye exam and fovea-centered Cirrus SD-OCT (Zeiss, Dublin, CA). A 3 mm × 3 mm en face retinal map using Avanti RTVue XR OCTA (Optovue, Fremont, CA) was performed at baseline, 6, 12, and 24 months. DME severity and distribution were also graded by investigators at each visit according to location: extrafoveal versus foveal with or without foveal depression disruption.20
ReVue software (version 2017.1.0.129; Optovue, Fremont, CA) performed automated segmentation of retinal vascular plexuses, delineated FAZ borders, and calculated CPD in addition to discriminating foveal (central 1-mm Early Treatment Diabetic Retinopathy Study [ETDRS] grid) and parafoveal (3-mm ETDRS grid, excluding central 1-mm) areas. The automated software algorithm auto-segmented retinal slabs with the superficial vascular complex starting at the level of the internal limiting membrane spanning to a −10 µm offset from the inner plexiform layer (IPL). The deep vascular plexus' upper border spanned from −10 µm offset from the IPL ending at a +10 µm offset from the outer plexiform layer. The software also measured CPD using a binary system, followed by calculation of vascular density based on space occupied by vessels. Angiographic analysis was performed by a single trained reader, and manual corrections were made as errors were identified. Additional design details have been previously reported.20
Patients were treated with monthly 2 mg IAI until SD-OCT demonstrated fluid resolution. Fluid resolution was defined as lack of subretinal fluid, CST less than 320 µm, or central edema without disruption of the foveal contour.20 Patients exhibiting resolution were extended to a fixed 8-week interval. IAI was supplied by Regeneron Pharmaceuticals.
The primary outcome measured was mean change in CST from baseline to 24 months; secondary outcomes included mean change from baseline in cube average thickness (CAT), cube volume (CV), BCVA, macular CPD, and FAZ area. Participants were also stratified according to baseline BCVA as either poor vision (PV), defined as 20/50 vision or worse, or good vision (GV), defined as 20/40 vision or better, and evaluated within groups at 24 months. A sub-analysis was also performed to evaluate correlation between BCVA and various parameters at 24 months including foveal, parafoveal, and foveal + parafoveal (“whole”) superficial and deep CPD.
All adverse events (AEs), ocular and non-ocular, were reported by both investigators and participants. They were categorized according to severity, and as either related or unrelated to the study drug.
Measures were summarized using mean values. Normality of measurements was assessed at each time point using Shapiro-Wilk tests. Changes from baseline to 24 months were estimated with 95% confidence intervals. To assess key changes in measurements among the poor- and good-vision groups, baseline comparisons were made using two-sample t-tests, whereas changes over time were made using mixed effect models. Missing data were accounted for using a linear mixed effect model. In our sub-analysis, Pearson correlations were fit to assess the linear associations between VA and other measures at baseline, 24-months and change between baseline and 24-months. All analyses were calculated using SAS Software (version 9.4; SAS Institute, Cary, NC). A significance level of .05 was assumed for all tests.
A total of 20 participants were enrolled; 16 completed the study. Those who exited early (n = 4; 20%) did so for different reasons (death = 1; relocation = 1; subject withdrawal = 1; dismissal = 1). Data from early withdrawal patients were not factored into 24-month outcomes. The mean age of all 20 participants was 63.7 years (range: 45 to 78 years); the majority were female (65%). All participants had history of anti-VEGF therapy: 95% bevacizumab and 5% ranibizumab. No participant had received more than one type of anti-VEGF medication. The average number of prior injections was 4.25 per eye, and the average washout time between prior treatment and study enrollment was 44.5 (± 21.2) days. Five patients had a history of focal laser therapy; two carried a diagnosis of epiretinal membrane with no vitreomacular traction.
Of the 16 eyes followed through 24 months, baseline severity of DR was as follows: zero mild, nine (56%) moderate, two (12.5%) severe, and 5 (31.3%) quiescent proliferative DR, all status post-panretinal photocoagulation. At baseline, seven (35%) exhibited PV, whereas the other 13 (65%) had GV. A baseline comparison between the two groups revealed no statistically significant difference between CST (422.6 µm ± 92.2 [PV] vs. 418.2 µm ± 95.7 [GV]; P = .92), whole superficial CPD (46.3% ± 3.2 [PV] vs. 45.8% ± 4.6 [GV]; P = .83), whole deep CPD (51.3% ± 3.3 [PV] vs. 50.5% ± 4.7 [GV]; P = .70), or FAZ area (0.34 mm3 ± 0.16 [PV] vs. 0.27 mm3 ± 0.11 [GV]; P = .31). Not surprisingly, ETDRS reported vision was the only statistically significant difference between the two groups (61.6 letters ± 1.9 letters [PV] vs. 74.5 letters ± 4.0 letters [GV]; P < .001).
The mean number of IAI received prior to extension was 8.3. Seventy percent (n = 14) extended to fixed 8-week IAI, whereas 10% (n = 2) required monthly IAI.
Mean CST at baseline was 420 µm ± 34 µm and improved to 251 µm ± 38 µm (P < .001) at 24 months. Mean CV improved from 11.5 mm3 ± 5 mm3 to 10.03 mm3 ± 0.4 mm3, and mean CAT improved from 321 µm ± 16 µm to 280 µm ± 16 µm (P < .001).
When analyzed in PV and GV groups, both groups exhibited a statistically significant mean decrease in CST from baseline (−178.4 µm; P < .001 [PV] vs. −164.5 µm; P < .001 [GV]; however, the mean difference in decreased CST between the two groups was not statistically significant (−13.9 µm; P = .77).
The mean BCVA at baseline was 70 letters, which improved +5.5 letters at 24 months (P = .042). The PV group showed a statistically significant improvement in BCVA from baseline (+7.97 ± 7.7 letters; P = .043), whereas the GV group did not (+3.48 ± 5.39 letters; P = .2). The difference in mean visual acuity change between the two groups was not statistically significant (difference of 4.49; P = .34).
OCTA Capillary Perfusion Density
Twenty-four-month OCTA images were available for 15 out of 16 eyes (Table 1). Baseline whole superficial CPD was 45.98% ± 2.22% and deep CPD was 50.82% ± 2.19%. Baseline FAZ area was 0.30 mm3 ± 0.7 mm3. At 24 months, superficial and deep CPD decreased, whereas the FAZ enlarged. Whole superficial CPD decreased by 5.3% ± 3.1% from baseline (P = .001); deep CPD decreased by 4.4% ± 3.3% (P = .009). Mean FAZ area enlarged by 0.11 mm3 ± 0.07 mm3 (P = .006). When subdivided into foveal and parafoveal CPD, each measurement also showed statistically significant decreases in CPD except for deep foveal CPD. Mean superficial foveal CPD decreased by 12.63% ± 4.62% (P < .001) and superficial parafoveal CPD decreased by 4.41% ± 2.59% (P = .001). Mean deep parafoveal CPD decreased by 4.87% ± 3.52% (P = .008). Mean deep foveal CPD decreased by 0.87% ± 6.18%, which was not statistically significant (P = .78).
Overall Changes Over Time
When comparing CPD measurements between PV and GV groups, significant mean decreases occurred in most categories (Table 2). Baseline whole superficial CPD was 46.3% ± 3.2% in the PV group and 45.8% ± 4.6% in the GV group (P = .83). Baseline whole deep CPD was 51.3% ± 3.3% in the PV group and 50.5% ± 4.7% in the GV group; this difference was also not significant (P = .70). At 24 months, both groups experienced a statistically significant decrease in CPD. The PV's whole superficial CPD decreased by 6.44% ± 5.66% (P = .026); the GV's CPD decreased by 4.88% ± 3.68% (P = .01). The PV group exhibited a statistically significant decrease in whole deep CPD (−6.45% ± 5.99%; P = .036), whereas the GV group did not (−3.60% ± 3.92%; P = .07). There was no significant difference in mean change between the groups for either whole superficial CPD (P = .64) or deep CPD (P = .43).
Vision Group Comparison: 24 Months
Mean baseline FAZ area was larger in the PV group (0.34 mm3 ± 0.16 mm3) when compared to GV (0.24 mm3 ± 0.11 mm3); this baseline difference, however, was not statistically significant (P = .31). Each group exhibited FAZ enlargement at 24 months, which was statistically significant for PV participants (+0.23 mm3 ± 0.12 mm3; P < .001) and not for GV participants (+0.06 mm3 ± 0.08 mm3; P = .13). The mean difference between FAZ enlargement between the groups at 24 months was statistically significant (0.17 mm3 ± 0.14 mm3; P = .31).
At baseline, there was no statistically significant correlation between BCVA and any of the OCT and OCTA measurements (Table 3). Better final BCVA was negatively correlated with decreased CAT (r= −0.58 [–0.84 to −0.10]; P = .021) and decreased CV [r= −0.59 (−0.84 to −0.14). There was no significant correlation between BCVA and CST (P = .13). Better final BCVA positively correlated with less CPD loss within the superficial parafovea (r= +0.66 [0.23 to 0.88]; P = .006) and superficial whole (r= +0.60 [0.12 to 0.85]; P = .017) areas. There was no statistically significant correlation between final BCVA and the following mean CPD values: superficial foveal; deep foveal; deep parafoveal and deep whole macular (Table 4).
Pearson Correlations With BCVA at Baseline
Pearson Correlations With BCVA at 24 Months
Four severe, non-ocular AEs occurred. Three of the four AEs arose within the first 6 months and included a participant with dehydration, hypertension, and hyperglycemia requiring hospitalization; a participant with chest pain requiring cardiac catherization; and a participant hospitalized for bilateral lower limb cellulitis treatment. At Month 14, one patient exited the study due to death. AEs were categorized as unrelated to the study drug.
Our results suggest that FAZ enlargement and macular CPD loss continues to progress in eyes with DME despite fixed-interval IAI therapy; this loss also impacts visual outcomes. Statistically significant FAZ enlargement along with superficial and deep whole macular CPD loss occurred at 24 months (Figure 1). This study also identified a significant positive correlation between better final BCVA and less superficial parafoveal and whole macular CPD loss. Although many studies have not found statistically significant changes in FAZ and CPD in eyes treated with anti-VEGF for DME,17–19,21–22 our study is the first to offer a fixed treatment regimen and a notably longer follow-up time.
Optical coherence tomography angiography (OCTA), optical coherence tomography (OCT), and capillary perfusion density (CPD) analysis in a single study eye with center-involved diabetic macular edema (DME). (A1) Baseline foveal avascular zone (FAZ) area analysis; FAZ area = 0.592 mm2. (A2) Baseline OCT. (A3) Baseline CPD analysis. (B1) FAZ area analysis at Month 6; FAZ area = 0.635 mm2. (B2) Month 6 OCT. (B3) Month 6 CPD analysis. (C1) FAZ area analysis at Month 24, which depicts enlargement of FAZ from baseline; FAZ area = 0.685 mm2. (C2) Month 24 OCT with resolution of DME. (C3) Month 24 CPD analysis showing loss of perfusion density from baseline.
Like previous reports,5–10 our participants exhibited significant improvement in anatomic measurements and BCVA when switched from other anti-VEGF medications to fixed-interval IAI. The EARLY study23 offers additional support of early switch in anti-VEGF therapy; their analysis of Protocol I reported that long-term response to anti-VEGF therapy could be predicted by degree of BCVA improvement following three injections and concluded that if eyes did not show early (initial 3 to 6 months) improvement in BCVA, a different anti-VEGF or intraocular corticosteroid should be trialed. Protocol T also noted that eyes with 20/50 vision or worse showed greater visual and anatomical outcomes with IAI at year 1, which promoted some physicians to initiate IAI therapy earlier in eyes with poor vision; these vision outcomes, however, were not upheld at year 2.11 Although these switch studies showed greater anatomic improvement results with aflibercept, it is worth mentioning that non-switched controls have demonstrated continued improvement in CST and BCVA with chronic therapy.13 Both groups in the Demircan et al. study13 exhibited statistically significant decreases in CST, with the switch group's improvement being significantly greater; however, BCVA improvement between the groups was not significant. Although our authors can only speculate, anatomical improvement on OCT alone may not adequately reflect permanent structural damage, specifically small losses in capillary structure over time, which could explain these mixed visual outcomes.
FAZ enlargement is a known complication of DR and is detected by OCTA before other retinal abnormalities become apparent.14,15 Significantly larger FAZ areas in DR patients with DME in comparison to those without edema are reported.16 Some studies suggest that anti-VEGF therapy is protective and slows CPD and FAZ loss,24,25 whereas others argue that continuous anti-VEGF therapy may have detrimental effects, possibly secondary to promotion of retinal nonperfusion,26 retinal capillary vasoconstriction,27 or disruption of VEGF molecules necessary for retinal health.28 Prior results evaluating CPD and FAZ by OCTA in anti-VEGF-treated DME patients are contradictory with limited follow-up durations. Several studies found no significant change in CPD or FAZ following anywhere from a single anti-VEGF injection17 up to five total injections.21,22 Other studies that strictly used IAI either as needed19 or on fixed-interval18 showed no significant change in OCTA measurements at 8.5 months and 12 months, respectively. In contrast, Gill et al.29 reported decreased FAZ area as DME improved. Recently, Elnahry et al.30 reported statistically significant FAZ enlargement and capillary perfusion loss in both superficial and deep plexuses on 6 mm × 6 mm scans following 3 monthly bevacizumab injections; 3 mm × 3 mm scans were similar but not all measurements were found to be statistically significant. In this study, IAI dosing occurred at more frequent intervals than the studies above, with standardized IAI treatment for all participants, and this study provides a significantly longer treatment period than prior studies assessing OCTA outcomes. Despite adequate treatment of DME in 70% of our participants, significant superficial and deep CPD loss still occurred and was correlated with vision decline at 24 months. These findings suggest that alterations in macular capillary structure may occur more slowly, over years rather than months. Although it is not known whether or how much the initiation of anti-VEGF therapy slows this process, longer follow-up than the studies noted above is warranted.
Strengths of this paper include its prospective design, standardization of anti-VEGF regimen across all patients, and 24-month treatment period. Limitations of this study include its small sample size, lack of non-transitioned comparison group, and lack of standardization of other anti-VEGF therapies prior to trial initiation. This study did not control for additional factors that alter CPD and FAZ as follows — increasing age, which has been linked to decreased superficial and deep capillary vessel density;31 higher degrees of myopia associated with decreased superficial plexus density;31 hypertension that, when poorly controlled, results in reduced deep vascular plexus density32 and FAZ enlargement;33 and increasing severity of DR that is correlated with decrease in macular vascular parameters in all layers.34 Lastly, OCTA measurements are affected by artifacts from macular edema35 and weak signal strength indices;36 although a single trained reader manually segmented scans and qualitatively accessed image quality to increase reliability of measurements, we did not standardize OCTA image signal strength. Further investigation with standardization of the above limitations is necessary to determine if CPD loss continues over years with anti-VEGF treatment and if this loss differs greatly between eyes treated with different anti-VEGF medications.
In summary, the use of a fixed-interval IAI regimen for DME demonstrated statistically significant improvements in CST and BCVA at 24 months. Statistically significant CPD and FAZ loss occurred despite adequate treatment of DME through 24 months. Less superficial foveal and parafoveal CPD loss were correlated with better final BCVA. Although CPD is a relatively new biomarker for monitoring diabetic retinopathy, the findings from this study suggest that patients with diabetic macular edema undergoing anti-VEGF treatment may still demonstrate alterations in macular capillary structure despite adequate treatment of diabetic macular edema. Further studies enrolling larger cohorts for longer durations are needed to assess clinical correlation of CPD changes in this setting.
- Kempen JH, O'Colmain BJ, Leske MC, et al. Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004;122(4):552–563. doi:10.1001/archopht.122.4.552 [CrossRef] PMID:15078674
- Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA. 2010;304(6):649–656. doi:10.1001/jama.2010.1111 [CrossRef] PMID:20699456
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- Bahrami B, Hong T, Schlub TE, Chang AA. Aflibercept for Persistent Diabetic Macular Edema: Forty-Eight-Week Outcomes. Retina. 2019;39(1):61–68. doi:10.1097/IAE.0000000000002253 [CrossRef] PMID:30015767
- Lim LS, Ng WY, Mathur R, et al. Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab. Clin Ophthalmol. 2015;9:1715–1718. doi:10.2147/OPTH.S81523 [CrossRef] PMID:26396494
- Klein KA, Cleary TS, Reichel E. Effect of intravitreal aflibercept on recalcitrant diabetic macular edema. Int J Retina Vitreous. 2017;3(1):16. doi:10.1186/s40942-017-0064-0 [CrossRef] PMID:28373914
- Laiginhas R, Silva MI, Rosas V, et al. Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success. Graefes Arch Clin Exp Ophthalmol. 2018;256(1):83–89. doi:10.1007/s00417-017-3836-1 [CrossRef] PMID:29082448
- Mira F, Paulo M, Henriques F, Figueira J. Switch to aflibercept in diabetic macular edema patients unresponsive to previous anti-VEGF therapy. J Ophthalmol. 2017;2017:5632634. doi:10.1155/2017/5632634 [CrossRef] PMID:28348885
- Do DV, Nguyen QD, Vitti R, et al. Intravitreal Aflibercept Injection in Diabetic Macular Edema Patients With and Without Prior Anti-Vascular Endothelial Growth Factor Treatment Outcomes From The Phase 3 Program. Ophthalmology. 2016;123(4):850–857. doi:10.1016/j.ophtha.2015.11.008 [CrossRef] PMID:26832658
- Wells JA, Glassman AR, Ayala AR, et al. Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123(6):1351–1359. doi:10.1016/j.ophtha.2016.02.022 [CrossRef] PMID:26935357
- Rahimy E, Shahlaee A, Khan MA, et al. Conversion to aflibercept after prior anti-VEGF therapy for persistent diabetic macular edema. Am J Ophthalmol. 2016;164:118–27.e2. doi:10.1016/j.ajo.2015.12.030 [CrossRef] PMID:26748058
- Demircan A, Alkin Z, Yesilkaya C, Demir G, Kemer B. Comparison of intravitreal aflibercept and ranibizumab following initial treatment with ranibizumab in persistent diabetic macular edema. J Ophthalmol. 2018;2018:4171628. doi:10.1155/2018/4171628 [CrossRef] PMID:29850202
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Overall Changes Over Time
|Measurement||Mean Estimates By Time||Change at 24 Months|
|Baseline Mean (95% CI)||Month 24 Mean (95% CI)||Difference (95% CI)||P Value|
|ETDRS||70 (66–74)||75 (71–80)||5.5 (0.2–10.7)||.042|
|CST||420 (386–454)||251 (213–288)||−169 (−213 to −125)||< .001|
|CV||11.5 (11.0–12.1)||10.1 (9.5–10.7)||−1.47 (−1.89 to −1.04)||< .001|
|CAT||321 (305–336)||280 (264–296)||−41 (−53 to −28)||< .001|
|Super: Whole||45.98 (43.76–48.21)||40.68 (38.17–43.19)||−5.30 (−8.40 to −2.21)||.001|
|Super: Fovea||31.15 (28.03–34.26)||18.51 (14.94–22.08)||−12.63 (−17.26 to −8.01)||< .001|
|Super: Parafovea||47.34 (44.89–49.80)||42.93 (40.24–45.61)||−4.41 (−7.01 to −1.82)||.001|
|Deep: Whole||50.82 (48.63–53.01)||46.40 (43.88–48.92)||−4.42 (−7.71 to −1.14)||.009|
|Deep: Fovea||24.56 (20.34–28.77)||23.69 (18.87–28.50)||−0.87 (−7.05 to 5.30)||.78|
|Deep: Parafovea||53.71 (51.30–56.11)||48.83 (46.08–51.58)||−4.87 (−8.40 to −1.35)||.008|
|FAZ Area||0.30 (0.22–0.37)||0.40 (0.33–0.48)||0.11 (0.03–0.18)||.006|
Vision Group Comparison: 24 Months
|Poor Vision (20/50 or Worse)||Good Vision (20/40 or Better)||Difference|
|Measurement||Mean (95% CI)||P Value||Mean (95% CI)||P Value||Difference (95% CI)||P Value|
|ETDRS||7.97 (0.27 to 15.67)||.043||3.48 (−1.91 to 8.87)||.20||−4.49 (−13.88 to 4.91)||.34|
|CST||−178.4 (−255.6 to −101.3)||< .001||−164.5 (−218.5 to −110.6)||< .001||13.9 (−80.2 to 108.0)||.77|
|Super: Whole||−6.44 (−12.10 to −0.79)||.026||−4.88 (−8.56 to −1.20)||.010||1.56 (−5.19 to 8.31)||.64|
|Deep: Whole||−6.45 (−12.44 to −0.45)||.036||−3.60 (−7.52 to 0.31)||.070||2.84 (−4.31 to 10.00)||.43|
|FAZ Area||0.23 (0.10 to 0.35)||< .001||0.06 (−0.02 to 0.14)||.13||−0.17 (−0.31 to −0.02)||.031|
Pearson Correlations With BCVA at Baseline
|Measurement||N||rho (95% CI)||P Value|
|CAT: Baseline||20||−0.12 (−0.53 to 0.34)||.62|
|CST: Baseline||20||−0.19 (−0.58 to 0.28)||.43|
|CV: Baseline||20||−0.12 (−0.53 to 0.34)||.62|
|Whole Deep Density: Baseline||20||0.04 (−0.41 to 0.48)||.85|
|FAZ Area: Baseline||20||−0.12 (−0.53 to 0.34)||.63|
|Fovea Deep Density: Baseline||20||−0.05 (−0.48 to 0.40)||.84|
|Fovea Superficial Density: Baseline||20||0.11 (−0.35 to 0.53)||.65|
|Parafovea Deep Density: Baseline||20||0.12 (−0.34 to 0.53)||.63|
|Parafovea Superficial Density: Baseline||20||0.16 (−0.31 to 0.56)||.51|
|Whole Superficial Density: Baseline||20||0.14 (−0.32 to 0.55)||.56|
Pearson Correlations With BCVA at 24 Months
|Measurement||N||rho (95% CI)||P Value|
|CAT: 24 months||15||−0.58 (−0.84 to −0.10)||.021|
|CST: 24 months||16||−0.40 (−0.75 to 0.12)||.13|
|CV: 24 months||16||−0.59 (−0.84 to 0.14)||.014|
|Whole Deep Density: 24 months||15||0.46 (−0.06 to 0.79)||.081|
|FAZ Area: 24 months||15||−0.48 −–0.80 to 0.04)||.068|
|Fovea Deep Density: 24 months||15||0.25 (−0.30 to 0.68)||.37|
|Fovea Superficial Density: 24 months||15||0.41 (−0.13 to 0.76)||.13|
|Parafovea Deep Density: 24 months||15||0.46 (−0.07 to 0.79)||.084|
|Parafovea Superficial Density: 24 months||15||0.66 (0.23–0.88)||.006|
|Whole Superficial Density: 24 months||15||0.60 (0.12–0.85)||.017|