Purpose
To compare visual outcomes after intravitreal anti–vascular endothelial growth factor (VEGF) injection or photodynamic therapy (PDT) for idiopathic choroidal neovascularization (CNV).
Design
Retrospective study.
Methods
Among 29 eyes (28 patients), 15 eyes (15 patients) received anti-VEGF therapy and 14 eyes (13 patients) received PDT. Best-corrected visual acuity (BCVA, logMAR [logarithm of minimal angle of resolution]) at baseline and 1, 3, 6, 12, and 24 months after initial treatment were compared. The eyes were classified by BCVA changes: improved (improvement ≥0.3 logMAR), decreased (deterioration ≥0.3 logMAR), and stable.
Results
Mean BCVA was 0.56 ± 0.38 logMAR (20/72 in Snellen equivalent) in the PDT group and 0.44 ± 0.59 logMAR (20/55 in Snellen equivalent) in the anti-VEGF group at baseline ( P = .104, Mann-Whitney U test). The anti-VEGF group showed significantly better mean BCVA at each follow-up visit when compared with that of PDT ( P = .004 at 1 month, P = .002 at 3 months, P = .037 at 6 months, P = .031 at 12 months, and P = .049 at 24 months; Mann-Whitney U test, respectively). When compared with the baseline, mean BCVA at each follow-up visit was better in the anti-VEGF group ( P = .196 at 1 month, P = .007 at 3 months, P = .046 at 6 months, P = .046 at 12 months, and P = .049 at 24 months; Wilcoxon signed rank test, respectively), whereas BCVA in the PDT group was not. At 24 months, all eyes (100.0%) treated with anti-VEGF showed stable or improved BCVA, whereas 3 eyes (21.3%) showed visual deterioration after PDT.
Conclusions
Anti-VEGF therapy was superior to PDT for idiopathic CNV, and superior efficacy was sustained until 24 months.
Idiopathic choroidal neovascularization (CNV) is defined as CNV in patients younger than 50 years without any apparent primary ocular or systemic diseases. Diagnosis of idiopathic CNV is made by exclusion of any other predisposing diseases for CNV together with an age of onset younger than 50 years.
The natural history and final visual outcomes of idiopathic CNV are generally considered to be more favorable than CNV attributable to age-related macular degeneration (AMD). Although idiopathic CNV has a relatively favorable prognosis, it is also known that significant individual variations exist, and the natural course of this disorder can be unpredictable. Additionally, irreversible visual loss can sometimes occur during the patient’s most productive years. This loss can be severe and permanent, and may not be reversed with further treatment.
Various treatment modalities have been used, including photodynamic therapy (PDT) with verteporfin, which has been shown to be safe and effective for idiopathic CNV. Because idiopathic CNV appears as classic CNV, PDT is thought to be effective and has been recommended as treatment for idiopathic CNV. However, the visual results of PDT are inconsistent and highly variable. Along with inconsistent clinical outcome after PDT, damage to the retinal pigment epithelium (RPE) after PDT for the treatment of idiopathic CNV raised concerns about the safety of PDT for idiopathic CNV.
One of the recent advancements in the treatment of CNV is the use of anti–vascular endothelial growth factor (VEGF) agents, such as ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) and bevacizumab (Avastin; Genentech Inc). After 2 major trials, ANCHOR and MARINA, anti-VEGF therapy has been used worldwide for the treatment of wet AMD and myopic CNV, and intravitreal injection of anti-VEGF agent has become widely accepted.
Several studies also attempted to evaluate the efficacy of anti-VEGF therapy for idiopathic CNV, and they showed favorable visual outcome after anti-VEGF therapy. However, no comparative study has been conducted for the use of intravitreal anti-VEGF therapy or PDT for idiopathic CNV.
Herein we describe our investigation comparing visual outcomes after treatment with intravitreal anti-VEGF injection or PDT in patients with idiopathic CNV.
Methods
Enrollment of Study Subjects
A retrospective review was conducted of the medical records of 29 eyes of 28 patients with naïve idiopathic CNV who received intravitreal bevacizumab or ranibizumab injections or PDT alone between March 1, 2005 and February 28, 2009 at the Department of Ophthalmology, Yonsei University Medical Center, Seoul, Korea. Informed consent was obtained from all participants. This retrospective study was performed with the approval of the Institutional Review Board of Yonsei University College of Medicine and conducted in accordance with the tenets of the Declaration of Helsinki.
Inclusion criteria for idiopathic CNV in this study were: (1) patients younger than 50 years; (2) absence of concurrent ocular diseases in the study eyes that compromised or could have compromised vision and ocular condition; (3) no signs of pathologic myopia, including chorioretinal atrophy, posterior staphyloma, and lacquer cracks at the time of diagnosis; (4) best-corrected visual acuity (BCVA) <1.3 logarithm of the minimal angle of resolution (logMAR) (Snellen equivalent >20/400); (5) minimum follow-up period of 24 months; and (6) subfoveal or juxtafoveal CNV. Exclusion criteria were: (1) history of prior treatment for CNV, including laser, submacular surgery, or radiation; (2) a history of sub-Tenon injection of triamcinolone acetonide, PDT, or anti-VEGF injection within 6 months before the baseline treatment of idiopathic CNV; (3) cataract surgery during follow-up; and (4) significant hepatic disease such as active hepatitis, hypersensitivity, or allergy to fluorescein or indocyanine green (ICG) dye (excluded because of absence of the angiographic studies).
Examination
All patients received a complete ocular examination, including BCVA testing using a Snellen visual acuity chart, slit-lamp biomicroscopy, dilated fundus examination with indirect ophthalmoscope, color fundus photography, digital fluorescein angiography (FA), ICG angiography (ICGA), and optical coherence tomography (OCT) at baseline. FA and ICGA were obtained by using the Heidelberg Retina Angiograph system (Heidelberg Engineering, Heidelberg, Germany) with confocal scanning laser ophthalmoscope.
Follow-up visits were arranged 1 week after each baseline treatment and then 1 month after, with examination including BCVA, dilated fundus examination with indirect ophthalmoscope, fundus photography, and OCT. Examinations were scheduled at 3-month intervals. In addition, patients were asked to come earlier in cases of visual loss and/or recurrence of metamorphopsia. Additional FA, ICGA, OCT, and dilated fundus examination were performed whenever physicians suspected recurrence of idiopathic CNV or in cases of visual loss and/or recurrence of metamorphopsia. Recurrence was defined when CNV leakage was observed in FA or subretinal fluid was visible on OCT.
The patients’ characteristics were retrieved from their medical charts, including age at initial diagnosis, sex, refractive errors, BCVA determined using Snellen charts, and axial length. Snellen BCVA results were converted to a logMAR value for statistical analysis. Refractive errors of all patients were measured by an autorefractometer without cycloplegia. Greatest linear dimension (GLD) of idiopathic CNV was measured by FA images. All the examination data at baseline and at 1-, 3-, 6-, 12-, and 24-month follow-ups were interpreted retrospectively.
When BCVA was converted to logMAR vision for statistical analysis, we classified the patients into 3 groups: improved, stable, and decreased BCVA. An improvement of 0.3 or more in logMAR visual acuity was defined as improved VA, and a deterioration of at least 0.3 logMAR visual acuity was defined as decreased BCVA.
Photodynamic Therapy
PDT with verteporfin was performed according to previous studies. All patients treated with PDT received a 6 mg/m 2 infusion of verteporfin (Visudyne; Novartis AG, Bulach, Switzerland) over a period of 10 minutes followed by delivery of diode laser at 689 nm to the CNV 15 minutes after the commencement of infusion. A total light energy of 50 J/cm 2 and light dose rate of 600 mW/cm 2 for 83 seconds were used to cover the entire lesion. The PDT lesion included an additional 500 μm covering the borders on each side. Retreatment for recurrence was considered based on FA, ICGA, and OCT findings. Retreatment was performed every 3 months with PDT if CNV leakage was observed in FA or subretinal fluid was present on OCT.
Intravitreal Anti–Vascular Endothelial Growth Factor Injection
For intravitreal anti-VEGF injection, topical anesthesia was applied and 10% (w/v) povidone-iodine was used to scrub eyelids and lashes. Povidone-iodine eyedrops (1.25%, w/v) were applied, and a sterile lid speculum was put between the eyelids. Anti-VEGF agents, either bevacizumab 1.25 mg or ranibizumab 0.05 mg, were injected into the vitreous cavity through the superior sclera using a 30-gauge needle, at a position 3.5 mm posterior to the corneal limbus in phakic eyes and 3.0 mm posterior in aphakic/pseudophakic eyes. Pressure was applied to the injection site using a sterile cotton swab for 1 minute, to prevent leakage and to lower the intraocular pressure. After injections, all patients were instructed to apply antibiotic eyedrops for 1 week. Retreatment was performed with anti-VEGF if CNV leakage was observed in FA or subretinal fluid on OCT as monthly pro re nata intravitreal injections of anti-VEGF.
Primary Outcome
The primary outcome measure was the mean BCVA from baseline and each follow-up. To compare the visual outcome after intravitreal anti-VEGF and PDT for idiopathic CNV, we categorized patients into 2 groups according to the baseline treatment of idiopathic CNV: PDT (14 eyes of 13 patients) and anti-VEGF (15 eyes of 15 patients).
Statistical Analysis
Because data from the study group did not follow a normal distribution by Kolmogorov-Smirnov test, nonparametric analysis was used. To compare mean BCVA between 2 groups, Mann-Whitney U test was used. The Wilcoxon signed rank test was used to compare the baseline BCVA to that at each visit of each treatment group. Statistical analysis was performed using SPSS 18.0 for Windows (SPSS Inc, Chicago, Illinois, USA). P values of less than .05 were considered statistically significant.
Results
Baseline Characteristics
A total of 29 eyes of 28 patients with naïve idiopathic CNV were included in the study. Mean age at diagnosis was 35.12 ± 8.87 years (range 20-47 years), and there were 11 male and 17 female patients. All eyes were phakic. Mean spherical equivalent refractive error was −1.75 ± 3.26 diopters, and mean axial length was 25.23 ± 0.50 mm. Mean GLD was 940.5 ± 183.5 μm, and all eyes (100.0%) showed dark rim on ICGA through late phases. The location of idiopathic CNV was subfoveal in 11 eyes (37.9%) and juxtafoveal in 18 eyes (62.1%).
The eyes were divided into 2 groups based on the initial treatment: PDT group (14 eyes) and anti-VEGF group (15 eyes). The mean number of PDT was 1.33 ± 1.01 times in the PDT group, and the mean number of anti-VEGF injections was 3.71 ± 0.38 times in the anti-VEGF group. Two eyes of 2 patients received intravitreal ranibizumab injections, and 13 eyes of 13 patients received intravitreal bevacizumab injections. Baseline characteristics of the 2 groups are shown in the Table ; there were no significant differences between the 2 groups.
| PDT Group(14 Eyes) | Anti-VEGF Group (15 Eyes) | P Value a | |
|---|---|---|---|
| Age of onset (y) | 35.15 ± 7.13 | 35.00 ± 9.21 | .910 |
| Greatest linear dimension (μm) | 985.45 ± 190.30 | 1007.78 ± 175.60 | .540 |
| Refractive error (diopters) | −1.63 ± 2.80 | −1.72 ± 2.10 | .518 |
| Axial lengths (mm) | 25.14 ± 0.10 | 25.28 ± 0.64 | .470 |
| Subfoveal CNV, eyes (%) | 5 (35.7%) | 6 (40.0%) | .217 |
| BCVA at baseline | |||
| logMAR | 0.56 ± 0.38 | 0.44 ± 0.59 | .104 |
| (Snellen equivalent) | (20/72 ± 20/47) | (20/55 ± 20/77) |
a Mann-Whitney U test was used for statistical analysis; P < .05 was set for clinical significance.
Visual Outcomes
At the baseline, mean BCVA was 0.56 ± 0.38 logMAR (20/72 in Snellen equivalent) in the PDT group and 0.44 ± 0.59 logMAR (20/55 in Snellen equivalent) in the anti-VEGF group ( P = .104, Mann-Whitney U test). At 24 months, mean BCVA was 0.42 ± 0.62 logMAR (20/52 in Snellen equivalent) in the PDT group and 0.09 ± 0.15 logMAR (20/24 in Snellen equivalent) in the anti-VEGF group ( P = .049, Mann-Whitney U test). When compared with the PDT group, mean BCVA at each follow-up visit was better in the anti-VEGF group ( P = .004 at 1 month, P = .002 at 3 months, P = .037 at 6 months, P = .031 at 12 months, and P = .049 at 24 months; Mann-Whitney U test, respectively). Changes of mean BCVA during 24 months in the 2 groups are depicted in Figure 1 .
When compared with baseline, mean BCVA at each follow-up visit was significantly better in the anti-VEGF group, except at 1 month ( P = .196 at 1 month, P = .007 at 3 months, P = .046 at 6 months, P = .046 at 12 months, and P = .049 at 24 months; Wilcoxon signed rank test, respectively). However, in the PDT group, mean BCVA at each follow-up visit was not significantly improved when compared with baseline ( P = .576 at 3 months, P = .681 at 6 months, P = .417 at 12 months, and P = .452 at 24 months; Wilcoxon signed rank test, respectively). In addition, mean BCVA was worse than baseline in the PDT group ( P = .870, Wilcoxon signed rank test).
We also categorized the BCVA at each follow-up into 3 groups: improved ( Figure 2 ), stable ( Figure 3 ), and decreased ( Figure 4 ). Mean BCVA improved in 6 eyes (42.9%) at 24 months in the PDT group, whereas 8 eyes (53.3%) at 24 months showed improvement in the anti-VEGF group ( Figure 2 ). Similarly, mean BCVA in the PDT group was stable in 5 eyes (35.8%) at 24 months, whereas 7 eyes (46.7%) were stable at 24 months in the anti-VEGF group ( Figure 3 ). Although none of the eyes treated with anti-VEGF therapy lost vision during 24 months, 3 eyes (21.3%) lost 0.3 logMAR or more at 24 months in the PDT group ( Figure 4 ). The 3 eyes with deteriorating BCVA showed RPE atrophy.
