Table 1.
Summary of studies examining anti-vascular endothelial growth factor drugs for the treatment of non-proliferative phase of MacTel
| Author, year | Study design, evidence level | Eyes (patients) | F/U (m) | Regimen; protocol | No. of injections | Functional outcomes | Structural outcomes | Support for intervention |
|---|---|---|---|---|---|---|---|---|
| Lira, 2010 [22] | Case series, IV | 3 (3) | 6 |
0.5 mg IVR; a single dose injection |
1 | BCVA: 20/200, 20/100, and 20/400 improved to 20/60, 20/60, and 20/80 in the study eyes, respectively | CMT: reduced – 11, – 130, and − 126 µm from baseline of 253,287, and 331 µm in the study eyes, respectively | ++ |
| Matt, 2010 [23] | Retrospective cohort, IV | 23 (13) | 32 ± 5 |
1 mg IVB (7 eyes) vs. untreated (16 eyes) Baseline injection in patients with recent visual loss, then re-injection as needed (based on OCT changes or reduced VA) |
2.3 ± 1.3 |
BCVA in logMAR at the last visit: improved logMAR (0.47 ± 0.32 to 0.33 ± 0.31; p = 0.21) in the TG and deteriorated logMAR (0.25 ± 0.39–0.30 ± 0.40; p = 0.17) in the CG Stabilization or improvement in vision on Snellen testing in TG (p = 0.04) |
CMT at the last visit: 260 ± 83 and 201 ± 32 µm at baseline were reduced to 237 ± 69 and 199 ± 29 µm in the TG and CG, respectively (p = 0.23 and 0.77) FA staining size: smaller at month 3 (p = 0.004) in TG,but not different after 30 months (p = 0.11) compared with the CG |
+ |
| Roller, 2011 [31] | Case series, IV | 5 (4) | 17 ± 7 |
1.25 mg IVB Baseline injection, then re-injection every 6–8 weeks until no fluid seen on the OCT |
2.2 |
BCVA at 6 weeks: 1.7 ± 2 lines gained BCVA at final visit: 0.5 ± 1 lines lost |
At 6 weeks: mean CMT change of +13 ± 34 and mean TPT change of +8 ± 19 µm At final visit: mean CMT change of +29 ± 27 and mean TPT change of +8 ± 32 µm |
|
| Charbel, 2011 [28] | Prospective cohort, IIb | 20 (10) | 12–18 |
0.5 mg IVR vs. untreated fellow eyes 12 monthly unilateral injections |
12 | BCVA change after the last treatment: no significant change compared with the baseline or compared with the CG (study eyes: +3.5 ± 5.4 letters and fellow eyes: +3.7 ± 5.9 letters; p = 0.08) |
At 4 months: transient reduction in telangiectatic-appearing capillaries and late-phase leakage in FA and significant reduction in macular thickness − 53 ± 26.8 µm from a baseline average of 333 µm in OCT At 3–5 months after the last injection: FA and OCT were similar to baseline |
|
| Toy, 2012 [27] | Non-randomized clinical trial, IIb | 10 (5) | 14 |
0.5 mg IVR vs. untreated fellow eyes 12 monthly unilateral injections |
12 |
BCVA change after 1 year: no significant change compared with the CG (study eyes: 0.0 ± 7.5 letters and fellow eyes: +2.2 ± 1.9 letters; p > 0.05) * BCVA change at any visit time point: p > 0.05 |
CMT after 1 year: greater decrease compared with the CG (− 11.7 ± 7.0% for study eyes and − 2.9 ± 3.5% for fellow eyes) FA leakage: greater decrease in the area of late-phase FA leakage (− 33 ± 20% for study eyes, + 1 ± 8% for fellow eyes) |
+ |
| Meyer, 2013 [24] | Retrospective cohort, IV | 35 (19) | 81 (15–188) |
1.25 mg IVB (6 eyes) vs. untreated (29 eyes) Baseline injection, then re-injection as needed (based on OCT changes or reduced VA) |
1.6 | * BCVA change after 3 years: -1.2 ± 1.5 lines for untreated eyes and -1.0 ± 1.8 lines for IVB eyes (no significant difference) |
No significant difference in structural changes in OCT compared with the CG Transient reduction in FA leakage for 3 to 5 months after the last injection |
|
| Sigler, 2013 [25] | Case series, IV | 48 | 24 ± 13 |
2.5 mg IVB (15 eyes) vs. untreated (33 eyes) Baseline injection, then re-injection every 4–6 weeks until no fluid seen on the OCT |
2.5 ± 3.5 | BCVA change at final visit: 0.02 ± 0.10 logMAR in TG compared with 0.09 ± 0.29 logMAR in CG (p = 0.49). | Transient decreased leakage in FA for 1 to 3.5 months after the last injection | |
| Veloso, 2013 [32] | Case series, IV | 10 (5) | 15 |
1.25 mg IVB 3 monthly injections |
3 | No BCVA improvement during the study | Initial improvement in FA leakage and CMT, but returned to the baseline levels after 12 months | |
| Do, 2014 [26] | Randomized clinical trial without control group, IIb | 20 (10) | 6 |
Randomized to either 0.3 mg or 0.5 mg IVR unilateral injection at month 1 and 2 with optional retreatment at 3–5 months. |
4 (0.3) vs 4.4 (0.5) |
* BCVA change at 3 months: 4 letters in both 0.3 mg and 0.5 mg IVR groups vs. 3 letters in fellow eyes (no intergroup difference) BCVA change at 6 months: 4, 8, and 5 letters in 0.3, 0.5 mg, and fellow eye groups (no intergroup difference) |
CMT change at 3 months: +1, – 11, and 0 µm in 0.3, 0.5 mg, and fellow eye groups, respectively. * CMT change at 6 months: – 6, – 26, and – 6 µm, respectively. Decreased CMT compared with the baseline in 0.5 mg group at month 3, but no difference at month 6. (No intergroup analysis report) Decreased FA leakage in both ranibizumab groups compared with CG |
|
| Escariao, 2014 [21] | Case report, – | 1 (1) | 12 |
1.25 mg IVB a single dose injection (OD) |
1 | BCVA improvement from 20/60 to 20/30 at last follow-up | Fully regression of the subfoveal fluid, decreased CMT and decreased FA leakage at last follow-up | ++ |
| Kupitz, 2015 [29] | Non-randomized clinical trial, IIb | 18 (9) | 72 ± 5 |
0.5 mg IVR vs. untreated fellow eyes 12 monthly unilateral injections |
12 |
Reduced BCVA ≥ 2 lines at last follow-up: occurred more in the TG (4 vs. 1) Paracentral scotoma at last follow-up: occurred more in the TG (7 vs. 2) |
Neovascularization occurred more in the TG at last follow-up (4 vs. none) | |
| Aydogan, 2016 [20] | Case series, IV | 6 (5) | 26 ± 11 |
1.25 mg IVB Baseline injection, then re-injection with persistent intraretinal fluid/cysts or decreased BCVA |
2.3 |
BCVA change at 1 month: 0.48 ± 0.29 at baseline improved to 0.68 ± 0.36, but not significant BCVA change at final visit: improved to 0.77 ± 0.35 from baseline (p < 0.05) |
CMT at 1 month: reduction of – 85 ± 153 from baseline of 328 ± 139, but not significant. CMT at 6 months: reduction of – 65 ± 142 from baseline, but not significant |
+ |
| Bénichou, 2017 [30] |
Case report, – |
2 (1) | # |
IAI 3 monthly unilateral injections |
3 | No significant improvement in BCVA at last follow-up | No significant improvement in CMT at last follow-up |
CG control group, CMT central macular thickness, FA fluorescein angiography, F/U follow-up, IAI intravitreal aflibercept injection, IVB intravitreal bevacizumab, IVR intravitreal ranibizumab, No. mean number of injections, OCT optical coherent tomography, TG treatment group, TPT temporal parafoveal thickness, BCVA best corrected visual acuity, # not mentioned