Anti-VEGF Drugs

The BEAT-ROP (Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity) Cooperative Group conducted a prospective, randomized, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3 ROP with plus disease. Compared with conventional laser therapy, a statistically significant treatment benefit for bevacizumab was demonstrated for zone I ROP, whereas zone II disease had similar outcomes with either treatment. Normal peripheral retinal vascularization continued after treatment with intravitreal bevacizumab, whereas laser therapy led to permanent destruction of the peripheral retina. Recurrences occurred significantly later with bevacizumab than with laser therapy. Therefore, prolonged, close follow-up is essential. The study was too small and the follow-up period too short to allow proper evaluation of the safety of intravitreal bevacizumab for the treatment of ROP. Infants treated with anti-VEGF monotherapy have an incidence of recurrence of 8.3% and a mean recurrence time of 51.2 weeks. If available, fluorescein angiography is a great tool for follow-up of treated patients to assess eyes for reactivation or progression of the retinopathy.

Figure 8-8 Wide-angle photograph shows a fundus after it has undergone laser photocoagulation for threshold ROP. A, Plus disease is visible posteriorly, and avascular retina is apparent in the inferior and inferior temporal fundus (bottom right). Arborization of the vasculature leading up to the ridge and associated fibrovascular proliferation is pronounced. B, In a different patient, the image shows the pigment clumping, denoting healed laser photocoagulation, and the normalization of the retinal vasculature posteriorly.

(Part A courtesy of Colin A. McCannel, MD; part B courtesy of Audina Berrocal, MD.)

The results of the BEAT-ROP study, and other published evidence, have dramatically changed how zone I ROP, and probably all ROP, is treated. However, to date little data are available that assess the safety, especially the long-term safety, of using anti-VEGF therapy to treat ROP. Furthermore, there is mounting evidence that the disease can recur or reactivate following anti-VEGF treatment, which is rarely seen following ablative therapy. Continued investigation of long-term safety and efficacy data remains critical for understanding the exact role of anti-VEGF therapy in the management of this unique population.

• Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical management of recurrent retinopathy of prematurity after intravitreal bevacizumab monotherapy. Ophthalmology. 2016; 123(9):1845–1855.

• Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011; 364(7):603–615.

Intravitreal injection technique

Intravitreal injections can be performed at the patient’s bedside in the neonatal intensive care unit (NICU) (Video 8-1). The preparation is very similar to that of an adult intravitreal injection. The neonatal nurse prepares the infant for the injection. The eye is sterilized with a 5% betadine solution. A sterile eyelid speculum for each eye is used to retract the lids. Given an infant’s small eye size, the injection site should be 1.5 mm posterior to the limbus, compared with 3–4 mm in adults. Meticulous attention must be paid to the lens anatomy to avoid puncturing it with the injection needle, because the lens is larger in premature infants relative to the overall eye size compared with adults. Risks associated with the injection include cataracts, endophthalmitis, bleeding, and retinal detachment.

VIDEO 8-1 Intravitreal injection at bedside.

Courtesy of Audina M. Berrocal, MD.

Access all Section 12 videos at www.aao.org/bcscvideo_section12.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.