OBJECTIVE: To evaluate the long-term safety and efficacy of multiple intravitreal ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration. DESIGN: An open-label, multicenter, extension study. PARTICIPANTS: Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with ranibizumab in the initial study (ranibizumab treated-initial; n = 600); (2) patients randomized to control who crossed over to receive ranibizumab (ranibizumab treated-XO; n = 190); and (3) ranibizumab-naïve patients (ranibizumab untreated; n = 63). METHODS:Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months. MAIN OUTCOME MEASURES: Incidence and severity of AEs. RESULTS: There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the ranibizumab treated-initial/ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure≥30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the ranibizumab treated-initial, ranibizumab treated-XO, and ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the ranibizumab treated-initial and ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the ranibizumab treated-initial and ranibizumab treated-XO groups, and 3.2% in the ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the ranibizumab treated-initial group versus -11.8 in the pooled ranibizumab treated-XO and ranibizumab untreated groups. CONCLUSIONS:Multiple ranibizumab injections were well tolerated for ≥4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
RCT Entities:
OBJECTIVE: To evaluate the long-term safety and efficacy of multiple intravitreal ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration. DESIGN: An open-label, multicenter, extension study. PARTICIPANTS: Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with ranibizumab in the initial study (ranibizumab treated-initial; n = 600); (2) patients randomized to control who crossed over to receive ranibizumab (ranibizumab treated-XO; n = 190); and (3) ranibizumab-naïve patients (ranibizumab untreated; n = 63). METHODS:Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months. MAIN OUTCOME MEASURES: Incidence and severity of AEs. RESULTS: There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the ranibizumab treated-initial/ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure ≥30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the ranibizumab treated-initial, ranibizumab treated-XO, and ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the ranibizumab treated-initial and ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the ranibizumab treated-initial and ranibizumab treated-XO groups, and 3.2% in the ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the ranibizumab treated-initial group versus -11.8 in the pooled ranibizumab treated-XO and ranibizumab untreated groups. CONCLUSIONS: Multiple ranibizumab injections were well tolerated for ≥4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.