Purpose
To evaluate the effects of intravitreal bevacizumab injections in the treatment of nonsubfoveal choroidal neovascularization (CNV) associated with angioid streaks.
Design
Nonrandomized, interventional, prospective case series.
Methods
Fifteen patients (15 eyes) affected by juxtafoveal or extrafoveal CNV secondary to angioid streaks were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) chart, optical coherence tomography (OCT), and fluorescein angiography (FA). The protocol treatment included a first injection, followed by repeated injections over a 12-month follow-up period on the basis of the detection of new hemorrhage on biomicroscopic examination, any type of fluid on OCT, or presence of leakage on FA. Primary outcome measures: Mean changes in BCVA and proportion of eyes gaining at least 10 letters (2 ETDRS lines) at the end of the follow-up. Secondary outcomes: Mean changes of central macular thickness (CMT) and extension to the fovea.
Results
Mean BCVA did not change throughout the follow-up period, being 0.2 ± 0.2 logMAR at baseline and 0.2 ± 0.3 logMAR at the 12-month examination. A functional improvement of at least 2 ETDRS lines was achieved by 5 eyes (33%), with 3 eyes (20%) gaining 3 lines. Mean CMT at baseline was 215 ± 13 μm and 225 ± 85 μm at the 12-month examination. Two eyes (13.3%) showed CNV extension to the fovea.
Conclusions
Intravitreal bevacizumab injection can be a beneficial approach for the management of nonsubfoveal CNV secondary to angioid streaks over a 1-year follow-up.
Angioid streaks are irregular linear breaks or dehiscence in thickened and calcified Bruch membrane, radiating from the peripapillary area. Angioid streaks may present isolated or associated with various systemic diseases, including pseudoxanthoma elasticum, Paget disease, Ehlers-Danlos syndrome, and sickle cell disease.
Choroidal neovascularization (CNV) is the most important vision-threatening complication of angioid streaks, occurring in at least 1 eye in 72%-86% of cases and involving the second eye in up to 71% of cases. Moreover, the disease generally affects a young population, so that by the age of 50 most patients have a visual acuity of 20/200 or worse in the better eye.
The treatment of angioid streak–related CNV is still debated. Both laser photocoagulation and photodynamic therapy with verteporfin have provided unsatisfactory results owing to the high rate of recurrence, the development of atrophic changes, and the progressive CNV growth. The recent introduction of the anti–vascular endothelial growth factor (anti-VEGF) approach has raised new hopes for a more beneficial management. The results published up to now have been encouraging, generally reporting a visual acuity stability over the follow-up. However, no study has specifically focused on the outcomes of nonsubfoveal CNV secondary to angioid streaks.
The aim of this investigation is to evaluate the effects of the treatment with intravitreal bevacizumab (IVB) for nonsubfoveal CNV associated with angioid streaks over a 1-year follow-up.
Methods
All patients affected by juxtafoveal or extrafoveal CNV secondary to angioid streaks referred to the Department of Ophthalmology of San Raffaele Scientific Institute in Milan from October 2010 to October 2011 were prospectively enrolled in the study. The research was approved by the local institutional review board and adhered to the tenets of the Declaration of Helsinki. Each patient was carefully informed about the purpose of the research and provided signed consent to all procedures.
Inclusion criteria were: diagnosis of angioid streaks; evidence of naïve CNV with juxtafoveal location (1-199 μm from the fovea center) or extrafoveal location (>199 μm from the fovea); best-corrected visual acuity (BCVA) of at least 1.2 logMAR (approximately corresponding to 20/320 Snellen equivalent).
Exclusion criteria were: any other ocular disease that could compromise vision in the study eye; pregnancy; previous corticosteroid therapy (either local or oral administration); uncontrolled systemic hypertension; peripheral vascular disease; or history of thromboembolism or stroke.
Each patient underwent an ophthalmologic examination, including measurement of BCVA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, slit-lamp biomicroscopy, fundus color photography, fluorescein angiography (FA), and optical coherence tomography (OCT). After a first IVB treatment (Avastin, 1.25 mg; Genentech Inc., San Francisco, California, USA; 1.25 mg), all patients were reevaluated monthly over the 12 months of follow-up. Further re-treatments were performed on the basis of the detection of new hemorrhage on biomicroscopic examination, any type of fluid on OCT, or presence of leakage on FA.
Primary outcome measures were the mean change in BCVA and the proportion of eyes gaining at least 10 letters (2 ETDRS lines) at the end of the follow-up.
Secondary outcomes included the central macular thickness (CMT) variations, the changes in CNV size, and the extension to the fovea over the follow-up.
Wilcoxon signed rank nonparametric test for the significance of the difference between the distributions of 2 nonindependent samples involving repeated measures was used for statistical analyses. A 2-tailed P value < .05 was taken as statistically significant. All calculations were performed with SPSS 18 (IBM, Armonk, New York, USA).
Results
Overall, 15 patients (15 eyes) fulfilling the inclusion and exclusion criteria were recruited for the study ( Table ). Mean age of the patients was 51.7 ± 10 years. Five patients were female. One patient (6.6%) had a bioptic diagnosis of pseudoxanthoma elasticum.
| Patient No. | Age | Sex | Baseline BCVA | Final BCVA | Baseline CMT | Final CMT | Number of Injections | Foveal Distance |
|---|---|---|---|---|---|---|---|---|
| 1 | 79 | F | 0 | 0.1 | 200 | 225 | 4 | 186 |
| 2 | 57 | M | 0 | 0.1 | 214 | 102 | 3 | 256 |
| 3 | 55 | M | 0 | 0 | 217 | 210 | 1 | 232 |
| 4 | 47 | M | 0 | 0.1 | 214 | 237 | 2 | 57 |
| 5 | 46 | F | 0 | 0 | 207 | 220 | 2 | 244 |
| 6 | 46 | F | 0 | 0 | 215 | 220 | 1 | 205 |
| 7 | 44 | M | 0.1 | 0.1 | 230 | 228 | 6 | 177 |
| 8 | 41 | M | 0 | 0 | 199 | 197 | 4 | 289 |
| 9 | 40 | M | 0 | 0 | 230 | 199 | 1 | 315 |
| 10 | 41 | M | 0.3 | 0.1 | 220 | 225 | 1 | 297 |
| 11 | 48 | F | 0.6 | 0.4 | 238 | 230 | 3 | 121 |
| 12 | 58 | F | 0.1 | 0.1 | 234 | 199 | 3 | 115 |
| 13 | 59 | M | 0.2 | 0.1 | 235 | 225 | 2 | 144 |
| 14 | 55 | M | 1 | 0.4 | 240 | 299 | 2 | 62 |
| 15 | 60 | M | 0.5 | 0.2 | 225 | 233 | 3 | 85 |
Eight patients (53.3%) showed juxtafoveal CNV, whereas 7 (46.7%) presented with extrafoveal CNV. Mean CNV duration on the basis of the symptoms was 2.1 ± 1.1 months.
Overall, the mean BCVA was 0.2 ± 0.2 logMAR (approximately corresponding to 20/32 Snellen equivalent) at baseline and 0.2 ± 0.3 logMAR at the 12-month examination ( P = .15). Neither the subgroup with extrafoveal CNV nor the one with juxtafoveal CNV presented statistically significant mean BCVA changes throughout the follow-up period. In detail, a functional improvement of at least 2 lines was achieved by 5 eyes (33.3%), with 3 eyes (20.0%) gaining 3 ETDRS lines (all of them presenting with juxtafoveal lesions at baseline) and 2 eyes (13.3%) gaining 2 lines (1 eye with extrafoveal CNV and 1 eye with juxtafoveal CNV at baseline). Seven eyes (46.6%) (all with extrafoveal CNV) turned out to be stable, whereas 3 eyes (20.0%) (2 with juxtafoveal CNV, 1 with extrafoveal CNV) lost 1 ETDRS line.
The mean CMT at baseline was 215 ± 13 μm, changing to 225 ± 85 μm at the 12-month examination ( P = .89). No statistically significant difference, either in the subgroup with extrafoveal CNV or in the subgroup with juxtafoveal CNV, was found. Two eyes (13.3%) originally presenting with juxtafoveal CNV at baseline showed extension toward the fovea.
The mean number of IVB injections was 2.5 ± 1 (range: 1-6) at the end of 12 months (2.3 ± 2 injections in the subgroup with extrafoveal CNV and 2.5 ± 1 injections in the subgroup with juxtafoveal CNV). No systemic or ocular side effects were registered over the whole 12-month follow-up.
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