To evaluate the efficacy of photodynamic therapy with verteporfin with intravitreal bevacizumab for polypoidal choroidal vasculopathy.
Retrospective case study.
This study included 29 treatment-naïve patients with polypoidal choroidal vasculopathy followed up for 12 months after the first combined therapy. Patients received 1.25 mg intravitreal bevacizumab 1 week before photodynamic therapy with verteporfin. The main outcomes measures were visual acuity and the number of required retreatments.
The mean best-corrected visual acuity (BCVA) level was 0.25 at baseline and 0.31, 0.39, 0.44, 0.44, and 0.45 at 1, 3, 6, 9, and 12 months after treatment, respectively. A significant ( P < .01) improvement in the mean BCVA was observed at 3, 6, 9, and 12 months after combined therapy. At 12 months, the mean improvement in BCVA from baseline was 2.69 lines; the BCVA improved in 15 eyes (51.7%) by 3 lines or more, was stable in 13 eyes (44.8%), and decreased in 1 eye (3%) because of a massive subretinal hemorrhage 7 months after the first treatment. Eighteen eyes (62%) required 1 combined treatment during follow-up. Polypoidal lesions recurred in 6 eyes (21%). An abnormal branching vascular network persisted in all eyes. The mean number of treatments with combined therapy averaged 1.59. No complications, including endophthalmitis, uveitis, or ocular hypertension, developed.
Combined treatment consisting of photodynamic therapy with verteporfin and intravitreal bevacizumab for polypoidal choroidal vasculopathy seemed to be effective for improving visual acuity and reducing retreatment rates and complications. Further study is needed to determine the long-term clinical results.
Polypoidal choroidal vasculopathy (PCV) is characterized by recurrent, serosanguineous detachments of the retinal pigment epithelium (RPE) and peculiar choroidal vascular lesions consisting of polypoidal structures and network vessels. Spaide and associates confirmed that PCV has 2 basic choroidal vascular changes: branching networks of vessels in the inner choroid and polypoidal lesions at the border of the network of vessels. Although PCV first was reported to develop in the peripapillary areas, it often occurs in the macular area in Japanese patients. The incidence of PCV is higher in Japanese and other Asian populations than in white patients, with a prevalence of 54.7% in Japanese patients with neovascular age-related macular degeneration (AMD).
Photodynamic therapy (PDT) with verteporfin has shown good results for PCV, but patients with PCV should be followed up for long periods because of the high recurrence rate of the polypoidal lesions. PCV also is associated with a risk of massive submacular hemorrhage after PDT.
Recently, increased vascular endothelial growth factor (VEGF) was reported in histologic samples from eyes with PCV, suggesting that VEGF may have a role in the pathogenesis of PCV. Anti-VEGF therapy prevents formation of choroidal neovascularization (CNV) and decreases leakage from CNV secondary to AMD. VEGF antagonists such as bevacizumab (Avastin; Genentech, Inc., South San Francisco, California, USA) reduce vascular leakage and improve visual outcomes in patients with CNV secondary to AMD. Short-term studies have shown that intravitreal bevacizumab (IVB) may reduce the fluid resulting from PCV, but that it seems to be ineffective for diminishing the choroidal vascular changes. Thus, when administered as monotherapy, frequent injections are required. However, PDT may close neovascular membranes, leading to longer-term stabilization.
Although combined therapy with PDT and antiangiogenic agents has been reported to prolong the intervals between injections for patients with AMD, no long-term results have been reported for combined therapy for PCV. The purpose of the current study was to clarify the efficiency of combined therapy with IVB injections and PDT for PCV at 12 months of follow-up.
We retrospectively reviewed the therapeutic outcomes of 29 eyes of 29 patients with PCV who were treated at Gunma University Hospital between February 2007 and January 2008 with full-fluence PDT combined with 1.25 mg IVB within 1 week before PDT. The institutional review board approved the study protocol.
The inclusion criteria for this study were patient age older than 50 years, symptomatic PCV in the macular area, best-corrected visual acuity (BCVA) of 0.7 or worse, and a greatest linear dimension (GLD) of 6000 μm or less. The exclusion criteria were CNV caused by other diseases, such as pathologic myopia (spherical equivalent, ≤ −6 diopters); any contraindications to fluorescein angiography (FA), indocyanine green angiography (ICGA), verteporfin, or bevacizumab; the presence of an RPE tear; uncontrolled hypertension; a recent myocardial infarction; or cerebral vascular accidents. The enrolled patients were followed up for 12 months after the first treatment.
PCV was diagnosed based on the presence of polyplike choroidal vessel dilatation with or without a branching vascular network on ICGA using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). The polypoidal lesions were either a single polyp or a cluster of polyps.
We evaluated the outcomes of 29 eyes based on the data at 12 months after the first treatment. Three eyes were excluded from the 32 consecutive eyes enrolled at baseline because they dropped out during the 12-month study. None of the 3 patients appeared at the hospital after 6 months. The BCVAs of these 3 eyes at baseline were 0.5, 0.09, and 0.1, and the BCVAs at the final visit at 6 months were 0.9, 0.15, and 0.4. The examinations included measurement of the BCVA (Landolt ring tests), FA, and ICGA using a Topcon fundus camera (TRC50LX/ImageNet2000; Topcon, Tokyo, Japan), Heidelberg Retina Angiography, spectral-domain optical coherence tomography (OCT, Cirrus OCT; Humphrey Instruments, San Leandro, California, USA; or 3D OCT1000;Topcon Corp, Tokyo, Japan). OCT and fundus images were obtained at baseline and at 1, 3, 6, 9, and 12 months later. FA and ICGA were performed every 3 months until the final treatment.
BCVA was measured as decimal visual acuity using a Landolt chart and converted to logarithm of the minimal angle of the resolution for statistical analysis. We defined improvement of VA as a logarithm of the minimal angle of the resolution VA improvement of 0.3 or more; VA loss was defined as a decline of 0.3 or more; VA was considered stable if it remained within 0.3. A paired t test was used to determine the significance of the difference in the logarithm of the minimal angle of the resolution VA before and after combined therapy. After providing informed consent, all patients were treated with an IVB injection (1.25 mg/0.05 mL) 3.5 mm posterior to the corneal limbus using a 30-gauge needle after topical anesthesia. PDT was administered 7 days after the IVB injection. PDT with verteporfin (Visudyne; Novartis Pharma K.K., Tokyo, Japan) was performed in accordance with the standard protocol using a 689-nm laser system (Carl Zeiss Japan, Tokyo, Japan) that delivered 50 J/mm 2 during an 83-second exposure time. We calculated the GLD based on the findings of ICGA. The GLD covered the entire PCV lesion, including the polypoidal lesions and the branching vascular network vessels. Additional treatment with PDT and IVB was considered every 3 months based on ICGA, FA, and OCT findings. The end point of the treatment was resolution of the macular exudative changes, which were confirmed by OCT and the resolution of the active polypoidal lesions on ICGA. The OCT images were used to evaluate the exudative changes of the lesions (subretinal fluid, intraretinal edema, serous or hemorrhagic pigment epithelial detachment [PED], and subretinal hemorrhage).
The Table shows the clinical data from the 29 Japanese patients (29 eyes) at baseline and after treatment. All 29 eyes diagnosed with PCV on ICGA were classified as having occult with no classic CNV (27 eyes; 93%) or predominantly classic CNV (2 eyes; 7%) using FA. The mean BCVA levels at baseline and 1, 3, 6, 9, and 12 months after treatment were 0.25, 0.31, 0.39, 0.44, 0.44, and 0.45, respectively ( Figure 1 ). A significant improvement in the mean BCVA from baseline was observed using the paired t test at 1 month ( P = .014), 3 months ( P < .01), 6 months ( P < .01), 9 months ( P < .01), and 12 months ( P < .01). The mean change in BCVA at 1, 3, 6, 9, and 12 months from baseline was an increase of 1.07, 2.10, 2.59, 2.52, and 2.69 lines, respectively. All eyes (100%) had stabilized VA 3 months after combined therapy. At 3 months, the BCVA in 9 eyes (31%) improved by 3 lines or more, and the BCVA was stable in 20 eyes (69%). The VA did not decrease in any eyes ( Figure 2 ). At 12 months, overall, 28 eyes (97%) had stabilized VA. At 12 months, the BCVA in 15 eyes (52%) improved by 3 lines or more, and 13 eyes (45%) had stable VA ( Figure 3 ). The BCVA decreased in 1 eye (3%) because of massive subretinal hemorrhage 7 months after first combined therapy.
|Patient No.||Age (yrs)||Gender||FA Findings||GLD (μm)||BCVA||Polyp||SRF||PED||Complications||No. of Treatments|
|Baseline||1 Mos||3 Mos||6 Mos||9 Mos||12 Mos|