Study explores ranibizumab as treatment for ROP

Intravitreal ranibizumab (Lucentis, Genentech) appears to be effective for treatment of severe retinopathy of prematurity (ROP) and associated with less persistent suppression of systemic VEGF compared with bevacizumab (Avastin, Genentech), according to research reported by Shunji Kusaka, MD.

“Some previous studies also showed very transient systemic suppression in infants treated with intravitreal ranibizumab for ROP, but our study provides the largest dataset,” said Dr. Kusaka, professor of ophthalmology, Kindai University Sakai Hospital, Osaka, Japan.

He acknowledged that the study he presented still has a small sample size along with several other limitations-it was not a randomized controlled trial, it had short-term follow-up, and safety profiles were not investigated.

“At least in the short-term, however, we did not see any efficacy difference between bevacizumab and ranibizumab,” Dr. Kusaka said. “If we are thinking about systemic safety, maybe in the future we should use ranibizumab instead of bevacizumab.”

Study rationale

In a previous study investigating infants treated with bevacizumab for ROP, Dr. Kusaka and colleagues showed that bevacizumab was measureable in serum and that the serum VEGF level was reduced for at least 2 weeks. He also mentioned a study from Taiwanese investigators that found serum VEGF was suppressed for up to 8 weeks in infants treated with intravitreal bevacizumab for ROP.

“It was shown that in adults with age-related macular degeneration, ranibizumab caused less suppression of plasma VEGF than aflibercept (Eylea, Regeneron) or bevacizumab,” Dr. Kusaka said. “So we were interested in whether in infants with ROP, intravitreal ranibizumab would cause less systemic VEGF suppression than bevacizumab.”

Study design and patient characteristics

The study analyzed data from two consecutive cohorts of patients. It included 37 eyes of 21 patients treated with bevacizumab (0.25 mg/eye) from January 2012 to June 2015 and 27 eyes of 14 patients treated with ranibizumab (0.25 mg/eye) between July 2015 and July 2016.

The indications for anti-VEGF therapy varied. In 35 eyes, anti-VEGF was injected as salvage therapy, 17 eyes received anti-VEGF injection as an adjunct to vitrectomy, and only 12 eyes in the study received the anti-VEGF injection as monotherapy.

“In Japan, we still consider laser as first-line treatment,” Dr. Kusaka explained.

All of the infants were outborn. The two groups were similar in their baseline characteristics. Overall follow-up ranged from 3 to 65 months, but the mean follow-up was significantly longer for the bevacizumab group than for the ranibizumab-treated eyes (11 versus 39 months).

Outcomes

The efficacy analyses showed both anti-VEGF agents were effective in reducing the activity of ROP-improvements were noted in vascular tortuosity, dilatation, and tunica vasculosa lentis.

The rate of recurrence (defined as conditions requiring further treatment) was higher in the ranibizumab group than in eyes treated with bevacizumab (26% vs. 10%). The difference in recurrence rates did not achieve statistical significance, although the study may have been underpowered to detect a difference.

The interval between treatment and recurrence was also not significantly different between the ranibizumab and bevacizumab groups.

The retina re-attached in all bevacizumab eyes and in 26 (96%) of the ranibizumab-treated eyes.

VEGF data

Blood samples were obtained in the ranibizumab-treated eyes prior to injection and after 1, 7, 14, and 28 days. Measurement of serum VEGF by enzyme-linked immunoabsorbent assay showed a statistically significant reduction from baseline on the first day after injection, but not at any of the subsequent timepoints.

During the discussion, members of the session panel raised the question of whether laser pretreatment may alter the blood-brain barrier and affect the ability of the anti-VEGF agent to enter the bloodstream. Dr. Kusaka responded that a thorough analysis of differences in serum VEGF concentrations with patients categorized by therapeutic indication had not yet been conducted.

Dr. Kusaka has no relevant financial disclosures.