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Retinopathy of prematurity: Where are we today?
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Retinopathy of prematurity is one of the major causes of childhood blindness. In developed nations, despite the progress made in neonatal care, rates are still high due to the rising number of surviving premature infants with very low or extremely low birth weight.
As a consequence of technological progress, ROP and ROP-related blindness in developing countries is also on the increase. Providing timely treatment to prevent irreversible blindness in rural areas and implementing fundus screening programs for ROP are major challenges in these parts of the world.
Telemedicine ROP programs such as the KIDROP (Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity) program in India have proved successful. Using the RetCam Shuttle (Clarity Medical Systems), specially trained technicians took wide-field digital fundus images, covering 20,214 imaging session of 7,106 infants in 77 months. ROP was detected in 22.39% of the screened infants, of which only 3.57% were treated. Fifty of the 254 treated infants were outside the American screening guidelines cut-off.
ROP is caused by abnormal growth of retinal blood vessels in immature retinas. VEGF plays a major role in this process. Retinal hypoxia induces VEGF overexpression, creating pathologic and excessive neovascularization.
Laser therapy is the standard treatment for vision-threatening ROP. Anti-VEGF agents, which are widely used to treat numerous ocular neovascular diseases in adults, were tentatively introduced for the treatment of ROP in 2007. In 2011, the BEAT-ROP prospective study on Avastin (bevacizumab, Genentech/Roche) intravitreal injection brought a new perspective to the treatment of ROP. Unlike laser therapy, anti-VEGF injections preserve the peripheral retina and induce less myopia. However, concern remains about the potential ocular and systemic effects of VEGF suppression, and further evaluation through prospective studies is needed.
Several reviews and meta-analyses explore the safety and efficacy of VEGF inhibitors for the treatment of ROP. In their systematic review and meta-analysis, Pertl and co-authors studied 24 original reports. They were essentially observational studies involving 1,457 eyes treated with VEGF inhibitors for ROP. The use of anti-VEGF drugs seemed to be associated with low recurrence rates and few ocular complications. The authors acknowledged that reduced induction of myopia and preservation of visual field may be potential benefits of this treatment modality, but recognized that the risk of systemic side effects cannot be properly assessed due to lack of data.
During the World Congress of Paediatric Ophthalmology and Strabismus in September, Helen Mintz-Hittner, MD, presented some new data from the studies of the BEAT-ROP Cooperative Group. She started from the consideration that growth factors in the peripheral retina are responsible for the development of the anterior segment and that anomalies in the peripheral retina can be at the origin of an abnormal development of the optical components and the macula of premature infants. Recent studies have demonstrated an improvement of macular OCT when infants are treated with bevacizumab as compared with laser. However, she said that the window of 45 to 55 weeks of adjusted age requires more frequent examination. Initial appearance as aggressive posterior ROP was recognized as the most important risk factor for ROP recurrence. Plus disease and intravitreal neovascularization at two sites were also reported as major indicators of recurrence. After the first injection, the follow-up schedule proposed by the BEAT-ROP group is to perform more frequent examinations every 1 to 2 weeks adjusted age, especially if the infant had previous aggressive posterior ROP, when the advancing edge only advanced one to three diameters after the first injection or in case of extended hospital stay and low birth weight. After this critical period, monitoring every 2 to 3 weeks is recommended, especially when the advancing edge has advanced more than three diameters after the first injection. According to Mintz-Hittner, intravitreal bevacizumab monotherapy appears beneficial with an increased visual field, less induced myopia, and improved macular OCT and visual acuity. However, recurrences with more injections can cause adverse outcomes.
In summary, tele-ROP programs provide a useful screening strategy for ROP in low- and middle-income countries. VEGF inhibitor monotherapy has proved beneficial to improve peripheral retina preservation and decrease induced myopia. Further studies are needed to assess the safety of intravitreal VEGF inhibitors, with the hope that topical treatment might one day become available.
- Reference:
- Pertl L, et al. PLoS One. 2015;doi:10.1371/journal.pone.0129383.
- For more information:
- Dominique Brémond-Gignac, MD, PhD, is an OSN Europe Edition Board Member. She is head of the Ophthalmology Department at the University Hospital Necker Enfants-Malades, APHP, Paris, France. She can be reached at dominique.bremond@aphp.fr.
Disclosure: Brémond-Gignac reports no relevant financial disclosures.