Antivascular Endothelial Growth Factor Therapy Improves Visual Acuity, Reduces Clinical Burden

Patients with neovascular age-related macular degeneration (nAMD) experienced improvement in visual acuity on an observe-and-plan regimen with the antivascular endothelial growth factor agent, ranibizumab, which also reduced clinical burden by requiring fewer clinic visits, according to results of a recent study [Br J Ophthalmol. 2014; DOI:10.1136/bjophthalmol-2013-304556].

Although ranibizumab has previously been shown to improve visual acuity in patients with nAMD, the monthly injections that are typically required create a large burden on the care of these patients. Clinicians have already individualized dosing regimens to reduce injection frequency for these patients with success; however, monthly monitoring is still often needed to identify disease recurrence.

Building upon their prior study that determined it was possible to identify a predictable, individual pattern in the need for retreatment, Irmela Mantel, MD, department of ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Switzerland, and colleagues conducted a single-center, prospective study to convert previous results into a clinically-relevant treatment protocol, using an observe-and-plan treatment regimen based on the measurement of an individual’s first disease recurrence interval.

A total of 115 eyes from previously untreated, newly diagnosed patients (n=104) with nAMD and active subfoveal choroidal neovascularization were included in the analysis. The researchers measured best-corrected visual acuity (BCVA) and intraocular pressure, and performed dilated fundus examination and spectral domain optical coherence tomography at baseline and all follow-up visits.

The primary outcome measures included mean BCVA change over time up to 12 months as measured on the ETDRS (Early Treatment of Diabetic Retinopathy Study) trial, mean central retinal thickness (CRT) change, and the number of visits and injections over 12 months.

The observe-and-plan regimen was designed to evaluate a patient’s need for retreatment in an observation phase after 3 loading doses, after which treatment is individualized and given as a series of injections at fixed intervals.

All patients received an initial loading dose of 3 monthly intravitreal injections of 0.5 mg ranibizumab. This was followed by monthly observation visits, which enabled researchers to determine the interval from the third injection until the first signs of disease recurrence. This allowed the treatment plan to be individualized and fixed without intermittent ophthalmic examination for the next 3 injections.

Recurrences at ≥4 months after the last injection indicated a need for retreatment every 3 months; recurrence after 2 and 3 months indicated a need for retreatment every 1.5 months and 2.5 months, respectively. Signs of recurrence at shorter intervals continued on a monthly retreatment regimen for the next 3 injections.

Results showed mean BCVA improved significantly, from 58.3 ETDRS to 67 ETDRS (P<.0001) at 3 months, and improvement was maintained up to month 12. By 12 months, 98% of eyes had lost <15 letters (or 3 lines) and 30% had gained ≥15 letters. The researchers also found mean CRT improved from 342 µm at baseline by a mean of -97 and -99 µm at months 3 and 12, respectively.

The total mean number of injections performed over the 12-month period was 7.8, including the first 3 loading doses. The mean number of clinic visits between months 3 and 12 with ophthalmic examinations was 3.97 and mean treatment interval was 1.97 months.

After loading doses were administered, signs of recurrence were observed in 35% of eyes 1 month after the third injection. After the observation phase, retreatment plans were scheduled for 1.5, 2 to 2.5, and 3-month intervals for 19%, 16%, and 18% of eyes, respectively; 12% remained without signs of recurrence at month 12. Treatment intervals remained stable throughout the follow-up period for 80% of eyes; 15% had intervals progressively lengthened; and 5% required a shortening of their interval by more than 2 weeks. There were no severe ocular or systemic adverse events during the study.

The researchers concluded that the reduction of clinic visits to a mean of <4 visits in the first treatment year should lead to the delivery of more efficient clinical care. Results of the second year of observation are currently in submission for publication. “The overall visual result was maintained, and the number of visits was even smaller than in the first year,” said Dr. Mantel in an interview with First Report Managed Care.