Bilateral same-day intravitreal injections? Yes!

8 01 2010

One of the growing issues in treating age-related macular degeneration (AMD) is to reduce the burden of treatment for the patients, many of whom are elderly, and may require injections of VEGF inhibitors every 4-8 weeks. A long-standing tradition in ophthalmology has been to avoid bilateral same-day surgical intervention. The rationale has been that if you operate on two eyes on the same day, any infection that develops in one eye may spread to the other eye, and that if there is any contamination of instruments or compounds used during the surgery, operating on both eyes on the same day increases the likelihood that both eyes will be adversely affected.

Intravitreal injections, which have become standard of care for treatment of AMD are fairly innocuous in terms of surgical insult. The “wound” is a 31 gauge needle entry site. Nevertheless, endophthalmitis may develop. For example, in the VISION study of intravitreal pegaptanib, the incidence of endophthalmitis was 0.16%. In the MARINA study of intravitreal ranibizumab, it was 0.05%. And in the ANCHOR study of ranibizumab, it was 0.05% (3 cases our of 5,921 injections). A study by Pilli et all reported an incidence of 0.029% (3 cases in 10,254 injections). These incidences were for unilateral injections.

So, is there an increased risk for bilateral same-day injections? Lima et al (Yannuzzi’s group) out of New York published their retrospective analysis of bilateral same-day intravitreal injections of VEGF inhibitors in the October 2009 issue of Retina. They report that of 1,534 bilateral injections (3,068 injections total), the incidence of culture-proven endophthalmitis was 0.065%, and the incidence of acute intraocular inflmaation was 0.033%. None of those cases were bilateral. There were no cases of retinal breaks. They conclude that it appears that there is no increased risk for same-day bilateral injections of VEGF inhibitors, as the complication rates are similar.

It’s noteworthy that all patients in their study were done in the office, and received surface disinfection with 5% providone-iodine solution, followed by 2 days of either polytrim or ofloxacin qid.

The study is very useful and gives comfort to those of us considering bilateral same-day injections. In any disease process where the incidence of an occurence is very low, large numbers of patients are needed to determine whether or not there is a difference in incidence between groups, and so, it is fair to say that there is no obvious increase in the risk of complications from bilateral VEGF inhibitor injections, while recognizing the limitation of the comparison.

ANCHOR Study: Lucentis is better than Photodynamic Therapy for Classic ARMD

29 10 2009

Here’s the abstract for the two-year study results.  There are a few key points:  Ranibizumab patients maintained vision better (90%) vs. PDT patients (65%).  More ranibizumab patients gained vision (about 35-40%) than PDT patients (6%).  Injections were monthly.

Ophthalmology. 2009 Jan;116(1):57-65.e5.
Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study.
Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group.

Collaborators (87)
Vitreoretinal Consultants, Methodist Hospital, Houston, Texas 77030, USA.
Comment in:

Ophthalmology. 2009 Aug;116(8):1593.
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.