Table 1.
Summary of Clinical Trials Investigating Predictors of Visual Outcomes in Anti-VEGF Treated Patients
| Study | Treatment | Duration (Years) | Findings and Significant Factors | Non-Significant Factors |
|---|---|---|---|---|
| ANCHOR45 | RBZ 0.3/0.5mg, q1m or PDT prn | 1 | ● RBZ treated arms gained more VA than the PDT group ● Lower baseline VA, smaller baseline CNV lesion size and younger age associated with better VA gains |
● Gender ● CNV type ● Duration between diagnosis and treatment |
| MARINA26 | RBZ 0.3/0.5mg vs sham | 2 | ● Lower baseline VA, smaller baseline CNV lesion size and younger age associated with better VA gains | ● Gender ● CNV type ● Duration between diagnosis and treatment |
| MARINA & ANCHOR122 | RBZ | 1 | ● Fellow eye visual acuity was not predictive of study eye response | ● Fellow eye visual acuity |
| PrONTO123 | RBZ prn | 2 | ● Larger reductions in CRT after 1 month associated with better VA gains | ● # of injections |
| PIER124 | RBZ 0.3/0.5mg q3m | 2 | ● Lesion inactivity determined by FFA at 3 months associated with better 1 year VA gains ● Lesion inactivity on determined by OCT at 5 or 8 months associated with better 2 year VA gains |
● RBZ dose |
| CATT46,67 | RBZ or BVZ, prn or q1m | 1 | ● Factors associated with worse final VA were older age, worse baseline VA, larger CNV size, predominantly or minimally classic lesions, presence of GA, thicker foveal thickness and the presence of RPE elevation ● Factors associated with less VA gains were older age, better baseline VA (≥20/40), larger CNV size, absence of RAP lesions and presence of RPE elevation ● Factors associated with a decreased likelihood of VA gains ≥15 letters were better baseline VA, worse VA in the fellow eye, larger CNV size, absence of RAP lesions, thinner foveal thickness and the presence of RPE elevation ● PRN treatment group was less likely to gain ≥15 letters compared to fixed monthly dosing |
● SNPs of CFH, ARMS2, HTRA1 & C3 ● No interactions between treatment groups and predictors |
| CATT40,106 | RBZ or BVZ, prn or q1m | 2 | ● Older age, baseline VA of 20/40 or better, larger CNV area, presence of GA in the study eye, thicker (≥425 µm) or thinner (≤325 µm) CRT, and presence of RPE elevation were associated with less VA gain ● VA gains at 12 months (R2=0.30) more predictive of 2 year VA gains than baseline VA (R2=0.13) ● Baseline non-foveal GA (OR: 2.86), larger CNV area (OR: 3.91, 4 DA vs ≤1 DA), and BVZ treatment (OR: 1.83) were associated with a VA loss of 15 or more letters by weeks 88 and 104 ● Scars, GA, persistent IRF and SRHM were more common in eyes with VA loss |
● Treatment group ● # of treatments or visits |
| CATT49 | RBZ or BVZ, prn or q1m | 5 | ● Better baseline VA associated with better final VA but less VA gains ● Smaller CNV lesion size presence of SRF associated with better final VA and better VA gains ● Absence of RPE elevation (OR: 3.85), female gender (OR: 1.79) and BVZ use during first 2 years of treatment (OR: 1.62) more likely to gain ≥3 lines ● Current (OR: 2.61) and former smokers (OR: 1.21) more likely to have final VA 20/200 or worse |
● Various SNPs ● Hypertension, diabetes ● Treatment group ● IRF ● Various RT measures |
| HARBOR48 | RBZ 0.5/2mg, prn or q1m | 1 | ● Baseline predictors of better VA gains and/or percentage of 3-line gainers included lower VA, younger age, smaller CNV leakage area, smaller area of occult CNV, and presence of SRF ● Baseline predictors of final VA better than 20/40 included higher VA, smaller CNV leakage area, and presence of SRF |
● Gender, ethnicity, smoking status ● Treatment regimen ● CNV type ● Other baseline morphologies |
| HARBOR125,126 | RBZ 0.5/2mg, prn or q1m | 2 | ● Those in the lowest quartile for BCVA-LLVA gap at baseline (≤ 17 letters) gained more VA than those in the highest quartile (≥ 33 letters) and were more likely to gain ≥ 15 letters as well as lose ≥15 letters ● Patients who achieved peak BCVA after 6 months of treatment, had better VA gains and final VA than those who peaked during the first 6 months |
● Treatment group ● Baseline morphology |
| VIEW47,97 | RBZ q4w, AFL q4w/q8w | 1 | ● Younger age, lower VA and smaller CNV size more likely to have ≥15 letter VA gains ● Older age, larger CNV size and pre-dominantly classic CNV lesions likely to lose ≥1 and ≥15 letter VA ● Younger age, better baseline VA and smaller CNV size more likely to have final VA better than 20/40 ● Older age, lower baseline VA, larger CNV size and predominantly classic CNV lesions more likely to have final VA worse than 20/200 ● Higher baseline VA associated with less VA gain (−0.25 letters per letter increase) ● IRF and PED at baseline associated with less VA gains (−2.77 and −1.88 letters respectively) ● SRF at baseline associated with better VA gains (+2.11 letters) |
● Gender ● Ethnicity ● Lesion location |
| EXCITE99 | RBZ 0.3mg q1m or 0.3/0.5mg q3m | 1 | ● Baseline IRF and infrequent treatment associated with less VA gains (−3.6 and −4.4 letters respectively) ● PVD and SRF at baseline associated with better VA gains (+3.5 and +2.8 letters respectively) ● Interaction between SRF, PVD and treatment frequency, where those without SRF and/or PVD at baseline requiring frequent dosing for better VA gains |
● CRT, PED ● RBZ dose |
| OSPREY102 | Brolucizumab or AFL | 1 | ● Decreased SHRM correlated with better VA gains ● Improved ellipsoid zone integrity was associated with better VA gains |
● Sub RPE volume |
| AREDS111 | Any anti-VEGF | 2 | ● Patients with final VA of 20/200 or worse were more likely to be non-White, have lower baseline VA, have macular atrophy or macular hemorrhage at baseline and fewer anti-VEGF injections in total | - |
Abbreviations: AFL, aflibercept; RBZ, ranibizumab; BVZ, bevacizumab; PRN, pro re nata; VA, visual acuity; BCVA, best-corrected visual acuity; LLVA, low-luminance visual acuity; PDT, photodynamic therapy; CNV, choroidal neovascularization; RT, retinal thickness CRT, central retinal thickness; FFA, fundus fluorescein angiography; OCT, optical coherence tomography; GA, geographic atrophy; RPE, retinal pigment epithelium; RAP, retinal anomalous proliferation; SNP, single nucleotide polymorphism; IRF, intraretinal fluid; SRF, subretinal fluid; SHRM, subretinal hyper-reflective material; PED, pigment epithelial detachment; PVD, posterior vitreous detachment.