Purpose
To evaluate the visual and anatomic outcomes of intravitreal bevacizumab in patients with subfoveal idiopathic choroidal neovascularization (CNV).
Design
Prospective, nonrandomized, interventional case series.
Methods
Forty patients with subfoveal idiopathic CNV were included in this clinical trial. Their eyes were treated with a single intravitreal injection of 1.25 mg bevacizumab followed by as-needed dosing indicated by the presence and recurrence of intraretinal edema, subretinal fluid (SRF), or pigment epithelial detachment (PED), based on optical coherence tomography (OCT) performed monthly. Visual, clinical, angiographic, and anatomic changes were observed over a 12-month follow-up period.
Results
After 12 months of follow-up, the mean logarithm of minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 0.53 (20/68 in Snellen equivalent) at baseline to 0.29 (20/39 in Snellen equivalent; P < .001). Mean central retinal thickness determined by OCT decreased from 321 μm to 237 μm ( P < .001). All eyes (100%) had stable or improved vision, and 28 eyes (70%) showed an improvement of 2 lines or more. All lesions were in the cicatricial stage of CNV at 12 months of follow-up, with no leakage of fluorescein in the late phase of fluorescein angiography and no intraretinal edema, SRF, and/or PED detected by OCT. No drug-related systemic or ocular side effects were observed.
Conclusions
Intravitreal bevacizumab is generally well tolerated and improves BCVA in eyes with subfoveal idiopathic CNV over a period of 12 months. Large, randomized, controlled, long-term clinical trials are required to further evaluate the efficacy and optimal strategy of this treatment modality.
Choroidal neovascularization (CNV) is associated with various disorders, often causing severe loss of vision and eventually resulting in blindness. In the elderly, CNV is most commonly caused by age-related macular degeneration (AMD). Younger patients (aged <50 years) may also develop CNV as a result of underlying conditions such as pathologic myopia, ocular histoplasmosis, angioid streaks, and other inflammatory, traumatic, or hereditary disorders. However, in a distinct subset of young patients with CNV, no apparent primary ocular or systemic diseases can be detected, and such cases are generally categorized as idiopathic CNV.
The natural progression of the disease and the visual prognosis in patients with subfoveal idiopathic CNV are generally more favorable than those in patients with CNV attributable to AMD. However, severe visual loss can occur in some eyes without treatment, thus having a significant impact on a patient’s quality of life. Although there is a lack of evidence based on randomized controlled trials, photodynamic therapy (PDT) with verteporfin has been shown to be effective and is recommended as the first-line treatment for patients with subfoveal idiopathic CNV. However, visual outcomes of PDT for idiopathic CNV are inconsistent and variable. Moreover, severe damage to the retinal pigment epithelium (RPE) has been reported after PDT for the treatment of idiopathic CNV. In addition, the high cost of PDT limits its use, particularly in developing countries.
An alternative treatment for patients with CNV is anti–vascular endothelial growth factor (VEGF) therapy. Bevacizumab (Avastin; Genentech, San Francisco, California, USA/Hoffmann La Roche, Basel, Switzerland), a recombinant humanized monoclonal antibody against all VEGF isoforms, which was originally developed to treat metastatic carcinoma of the colon and rectum, has been shown to be efficacious against CNV resulting from AMD. Several retrospective case series and short-term prospective studies have analyzed its effect against idiopathic CNV, indicating promising functional and anatomic results. However, in most studies, subfoveal CNV is intermixed with juxtafoveal lesions, producing ambiguous outcomes. In this 1-year prospective study, we report the results of 40 subfoveal idiopathic CNV patients treated with intravitreal bevacizumab.
Methods
The present study was designed as a prospective, consecutive, nonrandomized, noncomparative, interventional study aimed at investigating the visual and anatomic outcomes as well as the safety of intravitreal bevacizumab in patients with idiopathic CNV involving the central foveal avascular zone.
Patient Selection
Forty consecutive patients with subfoveal idiopathic CNV were recruited from the Department of Ophthalmology, the First Hospital of China Medical University, from November 1, 2008 to October 31, 2009. Patients less than 50 years of age with clinical, angiographic, and optical coherence tomographic (OCT) evidence of active subfoveal idiopathic CNV were eligible for participation in the study. Active CNV was defined as evidence of leakage within the lesion on fluorescein angiography (FA) and the presence of intraretinal edema, subretinal fluid (SRF), or pigment epithelial detachment (PED) based on OCT. In the study, eligible best-corrected visual acuity (BCVA) of eyes ranged from 20/400 to 20/25. Study exclusion criteria included clinical features suggesting that CNV was secondary to other causes such as AMD, pathologic myopia with a refractive error of −6 diopters or more, choroiditis, angioid streaks, trauma, or hereditary diseases in the study eye or fellow eye; previous diagnosis of ophthalmic disease; presence of systemic disease; pregnancy; and prior treatment of CNV using thermal laser photocoagulation, PDT, or transpupillary thermotherapy (TTT).
All eyes underwent complete ophthalmologic evaluation at baseline that included BCVA testing using a standard Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, indirect ophthalmoscopy, FA, indocyanine green angiography (ICGA), and OCT (Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA). Central retinal thickness (CRT; thickness of the 1-mm central retina) was measured by the fast macular scan protocol of OCT.
Intravitreal Bevacizumab Injection and Follow-up Assessment
Each patient received an intravitreal injection of 1.25 mg bevacizumab (0.05 mL) at baseline. All injections were given under sterile conditions in the operating room. Povidone-iodine solution was used to clean the eyelids, and a lid speculum was inserted. Next, topical anesthesia was applied, and the conjunctiva was irrigated with 5% povidone-iodine. A 30-gauge needle was inserted through the pars plana, and 0.05 mL of bevacizumab was injected into the vitreous cavity. Follow-up examinations were performed 1 day, 1 week, and 1 month after the injection and at monthly intervals thereafter over a period of 12 months. BCVA testing, slit-lamp examination, IOP measurement, indirect ophthalmoscopy, and OCT were performed at each study visit. FA and ICGA were performed at 3-month intervals. After the initial injection, retreatment was suggested whenever persistent or recurrent intraretinal edema, SRF, and/or PED were indicated by OCT.
Outcome Measurements
The primary outcome was the proportion of eyes that had improved (≥2 lines), stable (within 1 line), or deteriorated (≥2 lines) vision at the 12-month follow-up. Other outcome measures included change in the mean BCVA and CRT from baseline to 12 months, angiographic and anatomic changes, number of treatments, and ocular and systemic safety.
Statistical Analysis
Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS; version 15.0.1; SPSS Inc, Chicago, Illinois, USA). Snellen visual acuity was converted to logMAR equivalent for statistical analysis. Data were expressed as mean ± standard deviation (SD) and median (range). Normally distributed continuous variables were compared using the paired t test. The Wilcoxon signed rank test was used for comparing data that were not normally distributed. The association between the change in CRT and BCVA outcomes was assessed using the Pearson correlation analysis. A P value of < .05 was considered statistically significant.
Results
Baseline Characteristics
Forty consecutive patients (40 eyes) with subfoveal idiopathic CNV were included in this study. All patients in our study were Chinese; 24 were female (60%) and 16 male (40%). The mean age at the beginning of the study was 31.6 ± 7.1 years (range, 18−44 years). All fellow eyes had a normal fundus. Snellen BCVA at baseline ranged from 20/200 to 20/25, with a median of 20/63. The mean ± SD logMAR BCVA before treatment was 0.53 ± 0.22 (20/68 in Snellen equivalent). The baseline mean ± SD CRT was 321 ± 82 μm, as measured by OCT.
Visual Outcomes
After one month of follow-up, the mean ± SD logMAR BCVA increased significantly to 0.34 ± 0.20 (Wilcoxon signed rank test; P < .001). The mean logMAR BCVA continued to improve during the study period, and the mean ± SD logMAR BCVA improved to 0.29 ± 0.18 after 12 months of follow-up (Snellen equivalent of 20/39) (Wilcoxon signed rank test; P < .001). At 12 months of follow-up, the Snellen BCVA ranged from 20/20 to 20/100, with a median of 20/32, and the mean improvement in BCVA was 2.4 lines (range, 0−6 lines). The mean change from baseline in BCVA over 12 months is shown in Figure 1 .
At 12 months of follow-up, 28 of the 40 eyes (70%) showed an improvement of 2 lines or more in BCVA, 12 eyes (30%) remained unchanged, and no eye had a deterioration of 2 lines or more. Twenty-four eyes (60%) had a final BCVA of 20/40 or better, and all eyes (100%) had a final BCVA of 20/100 or better.
Changes in Optical Coherence Tomography and Angiography
The measurement of CRT one month after the initial treatment showed a highly significant reduction in the mean ± SD CRT to 265 ± 81 μm (paired t test; P < .001). After 1 year of follow-up, the mean ± SD CRT further decreased to 237 ± 74 μm (paired t test, P < .001). The mean change from baseline in CRT over 12 months is shown in Figure 2 . There was a statistically significant correlation between improvement in mean BCVA (logMAR) and decrease in mean CRT at 12 months of follow-up (Pearson correlation analysis; r = 0.46, P = .003).
At 12 months of follow-up, all 40 eyes were in the cicatricial stage of CNV. FA showed absence of leakage from CNV lesions and no intraretinal edema, SRF, or PED was indicated by OCT. In addition, no recurrence of CNV was observed during the 12-month follow-up. An example of the FA and OCT changes of a patient is shown in Figure 3 .
Repeat Intravitreal Injections
A total of 80 intravitreal injections were given during the 12-month study period, with a mean of 2 injections per eye. Twenty-four of the 40 eyes (60%) needed reinjections (range, 2−4 injections), of which 12, 8, and 4 patients required 2, 3, and 4 injections, respectively. All retreatments were performed within 3 months after the initial treatment.
Complications
After 12 months of follow-up, no patient experienced a severe ocular (endophthalmitis, retinal detachment, or uveitis) or nonocular (thromboembolic event or systemic hypertension) adverse event attributable to intravitreal bevacizumab.
Results
Baseline Characteristics
Forty consecutive patients (40 eyes) with subfoveal idiopathic CNV were included in this study. All patients in our study were Chinese; 24 were female (60%) and 16 male (40%). The mean age at the beginning of the study was 31.6 ± 7.1 years (range, 18−44 years). All fellow eyes had a normal fundus. Snellen BCVA at baseline ranged from 20/200 to 20/25, with a median of 20/63. The mean ± SD logMAR BCVA before treatment was 0.53 ± 0.22 (20/68 in Snellen equivalent). The baseline mean ± SD CRT was 321 ± 82 μm, as measured by OCT.
Visual Outcomes
After one month of follow-up, the mean ± SD logMAR BCVA increased significantly to 0.34 ± 0.20 (Wilcoxon signed rank test; P < .001). The mean logMAR BCVA continued to improve during the study period, and the mean ± SD logMAR BCVA improved to 0.29 ± 0.18 after 12 months of follow-up (Snellen equivalent of 20/39) (Wilcoxon signed rank test; P < .001). At 12 months of follow-up, the Snellen BCVA ranged from 20/20 to 20/100, with a median of 20/32, and the mean improvement in BCVA was 2.4 lines (range, 0−6 lines). The mean change from baseline in BCVA over 12 months is shown in Figure 1 .
