Macular Degeneration: Ianchulev T

Shams N, Ianchulev T. · Ophthalmic Medicine, Genentech, One DNA Way, South San Francisco, CA 94080-4990, USA. · Ophthalmol Clin North Am. · Pubmed #16935208 No free full text.

Abstract: VEGF-A is a critical regulator of ocular angiogenesis and vascular permeability and is involved in the pathogenesis of several ocular diseases involving neovascularization or increased vascular permeability, such as neovascular AMD, diabetic ME, and diabetic retinopathy. Currently available therapies for neovascular AMD, such as laser photocoagulation, PDT with verteporfin, and pegaptanib sodium, slow visual loss but do not improve vision for most patients. In contrast, an emerging anti-VEGF agent, ranibizumab, improved vision in 25% to 34% of treated patients in one clinical trial, rather than slowing visual loss and is the first treatment for neovascular AMD to demonstrate visual improvement in a substantial number of patients. This represents a major advance in the treatment of ocular diseases involving neovascularization or increased vascular permeability and provides hope to patients with these debilitating diseases. Since the submission of this article, ranibizumab was approved by the FDA for the treatment of neovascular AMD.

Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T, Anonymous00115. · Vitreoretinal Consultants, Methodist Hospital, Houston, Texas 77030, USA. · Ophthalmology. · Pubmed #19118696 No free full text.

Abstract: OBJECTIVE: The 2-year, phase III trial designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. DESIGN: Multicenter, international, randomized, double-masked, active-treatment-controlled clinical trial. PARTICIPANTS: Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs. INTERVENTION: Patients were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT (active or sham) retreatment was evaluated every 3 months using fluorescein angiography (FA). MAIN OUTCOME MEASURES: The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing <15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure), percentage gaining >or=15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. Adverse events were monitored. RESULTS: Of 423 patients (143 PDT, 140 each in the 2 ranibizumab groups), the majority (>or=77% in each group) completed the 2-year study. Consistent with results at month 12, at month 24 the VA benefit from ranibizumab was statistically significant (P<0.0001 vs. PDT) and clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost <15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained >or=15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). Changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in rates of serious ocular and nonocular adverse events. In the pooled ranibizumab groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study eye (rate per injection = 3/5921 [0.05%]). CONCLUSIONS: In this 2-year study, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV. Rates of serious adverse events were low. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N. · Retina Service, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107, USA. · Am J Ophthalmol. · Pubmed #18222192 No free full text.

Abstract: PURPOSE: To evaluate the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Phase IIIb, multicenter, randomized, double-masked, sham injection-controlled trial in patients with predominantly or minimally classic or occult with no classic CNV lesions. METHODS: Patients were randomized 1:1:1 to 0.3 mg ranibizumab (n = 60), 0.5 mg ranibizumab (n = 61), or sham (n = 63) treatment groups. The primary efficacy endpoint was mean change from baseline visual acuity (VA) at month 12. RESULTS: Mean changes from baseline VA at 12 months were -16.3, -1.6, and -0.2 letters for the sham, 0.3 mg, and 0.5 mg groups, respectively (P < or = .0001, each ranibizumab dose vs sham). Ranibizumab arrested CNV growth and reduced leakage from CNV. However, the treatment effect declined in the ranibizumab groups during quarterly dosing (e.g., at three months the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses, respectively). Results of subgroups analyses of mean change from baseline VA at 12 months by baseline age, VA, and lesion characteristics were consistent with the overall results. Few serious ocular or nonocular adverse events occurred in any group. CONCLUSIONS: Ranibizumab administered monthly for three months and then quarterly provided significant VA benefit to patients with AMD-related subfoveal CNV and was well tolerated. The incidence of serious ocular or nonocular adverse events was low.

Alexander SL, Linde-Zwirble WT, Werther W, Depperschmidt EE, Wilson LJ, Palanki R, Saroj N, Butterworth SL, Ianchulev T. · Genentech, Inc., South San Francisco, California, USA. · Ophthalmology. · Pubmed #18054636 No free full text.

Abstract: PURPOSE: Smoking, age, and nutrition have been associated with the development of neovascular age-related macular degeneration (AMD) and can increase the risk of arterial thromboembolic events (ATEs). This study assesses annual rates of ATEs in new-onset neovascular AMD patients compared with matched controls. DESIGN: Retrospective study. PARTICIPANTS: New-onset neovascular AMD patients and age-, race-, gender-, and database length-matched controls from the 5% Medicare database. METHODS: We conducted a retrospective analysis of the 5% Medicare database from 2001 to 2003. New-onset neovascular AMD patients were included if they were > or =65 years old, had 2 diagnoses of neovascular AMD, and had at least 1 year of data before the first diagnosis of AMD within the dataset. A control group was constructed in a 3:1 ratio from those without a diagnosis of a major eye disorder and matched by age, race, gender, and length of data. Annual prevalence rates were determined for myocardial infarctions (MIs) and ischemic cerebral vascular accidents (CVAs). MAIN OUTCOME MEASURES: Rates of MIs and ischemic CVAs in new-onset neovascular AMD patients and matched controls from 2001 to 2003. RESULTS: There were 15771 new-onset neovascular AMD patients identified and matched with 46 408 controls. Average age was 80.5 years, with 64% > or =80; 65% were female; and 95.9% were white. Inpatient MI rates for neovascular AMD patients and controls were 2.2% and 2.2%, respectively (P = 0.74). Inpatient ischemic CVA rates for neovascular AMD patients and controls were 3.5% and 3.6%, respectively (P = 0.59). Myocardial infarction rates and ischemic CVA rates for both groups increased with age. Subgroups of patients with comorbidities known to be risk factors for ATEs (i.e., hypertension, hyperlipidemia, diabetes, and arrhythmias) had a higher rate of events. Patients with previous ATEs were also at a higher risk of subsequent events, at 7.4% for inpatient MI and 35.1% for inpatient ischemic stroke. CONCLUSION: Despite the shared risk factors associated with neovascular AMD and ATEs, Medicare beneficiaries with neovascular AMD had a rate of ATEs similar to that of matched controls. Rates of ATEs increased in patients with comorbidities and for patients with previous events.