Low-dose Lucentis may help treat high-risk retinopathy of prematurity

Some degree of recurrence occurred in a case series, but subsequent laser led to complete regression.

Issue: June 25, 2015

Primary treatment of high-risk posterior retinopathy of prematurity with 0.2 mg Lucentis initially led to rapid and complete regression of the disease, with continued growth of normal-appearing retina peripherally, according to a case series.

However, some degree of ROP recurrence in mid to anterior zone 2 was noted 8 to 11 weeks after injection in all eight eyes of the four infants.

“These infants were pending hospital discharge to remote locations, with limited access to follow-up retina examinations at the time of ROP recurrence,” lead author Caroline R. Baumal, MD, of Tufts University School of Medicine in Boston, told Ocular Surgery News. “Laser to the peripheral avascular retina was performed, leading to complete regression of ROP without anatomic sequelae.”

Unanswered questions

Baumal said there are many unanswered questions about the use of anti-VEGF agents for ROP, including whether such medications should be used primarily or for rescue after laser, dosage, choice of drug, safety issues, and long-term anatomic and refractive outcomes.

Baumal also noted that Lucentis (ranibizumab, Genentech) has a shorter half-life and has less effect on systemic VEGF levels in adults compared with Avastin (bevacizumab, Genentech).

“Hypothetically, ranibizumab may have less potential for systemic effects in infants,” she said.

In her practice, Baumal has observed that after treatment with 0.625 mg bevacizumab for posterior ROP, it took a prolonged time period of 6 to 9 months for the retina to fully vascularize, necessitating multiple office visits after discharge from a neonatal intensive care unit.

“These factors led me to consider whether the anti-VEGF agent or dose could be altered to maximize results,” she said.

The investigators obtained weekly images with RetCam (Clarity Medical Systems). Fluorescein angiography was also scheduled for cases of ROP that were stage 3 or plus and for after therapy.

“It was surprising that there was recurrent stage 3 in all of the eyes in our preliminary series,” Baumal said. This was in contrast to a series from Castellanos and colleagues that described complete ROP regression and subsequent retinal vascularization after a single 0.25 mg ranibizumab injection.

“However, in that series, the level of infant prematurity (gestational age/birth weight) was less severe, and the zone of ROP requiring treatment was not mentioned,” Baumal said.

In a more recent series, Wong and colleagues observed reactivation of ROP in five of six eyes treated primarily with 0.25 mg ranibizumab.

“Thus, recurrence appears possible with either a 0.2 mg or 0.25 mg dose of ranibizumab,” Baumal said. “However, the premature infant eye is approximately one-third of the size of the adult eye. This needs to be considered when adjusting medications for premature infant eyes. There may be issues related to the accuracy of measuring these small drug doses.”

Delayed laser treatment

Although laser was ultimately performed on all eyes in the current study, it was limited to the periphery.

“If laser had been the initial treatment for ROP, it would have required more extensive posterior placement for initial posterior ROP,” Baumal said. Delaying the laser “appeared to allow further peripheral vascularization of the retina and reduce more posteriorly placed laser.”

Hypothetical advantages of ranibizumab include a reduced half-life and a reduction of risks in that no compounding is required.

“Subsequent to publishing this series, I have treated some infants primarily with a single dose of 0.2 mg ranibizumab, for which laser was not required,” Baumal said. “Still, I recommend cautious monitoring after primary anti-VEGF treatment in view of the potential for ROP recurrences.”

Baumal’s new study entails evaluating long-term outcomes in infants treated with anti-VEGF agents for ROP.

“This includes ocular findings such as refraction, visual acuity, anatomic findings and systemic follow-up,” she said. – by Bob Kronemyer

References:

Baumal CR, et al. Ophthalmic Surg Lasers Imaging Retina. 2015;doi:10.3928/23258160-20150422-05.
Castellanos MA, et al. Br J Ophthalmol. 2013;doi:10.1136/bjophthalmol-2012-302276.
Wong RK, et al. Retina. 2015;doi:10.1097/IAE.0000000000000578.

For more information:

Caroline R. Baumal, MD, can be reached at Tufts University School of Medicine, New England Eye Center, Department of Ophthalmology, 800 Washington St., P.O. Box 450, Boston, MA 20111; email: cbaumal@tuftsmedicalcenter.org.
Disclosure: Baumal reports she is a paid consultant to Allergan and has received a travel grant from Optovue.