Intravitreal anti-VEGF therapy as an adjunct to laser photocoagulation for severe aggressive posterior retinopathy of prematurity

AbstractPurposeThe aim of the study was to evaluate the role of anti-VEGF therapy as an adjunct to laser ablation therapy in severe aggressive posterior retinopaty of prematurity (AP-ROP).MethodsMedical records of premature infants with a primary diagnosis of AP-ROP treated with 0.625mg/0.025ml intravitreal bevacizumab (IVB) in addition to standard laser photocoagulation as a salvage therapy or primarily combined with laser in a university clinic were reviewed, retrospectively. The anatomical results and complications were evaluated after treatment.Results15 eyes of 9 patients with a mean gestational age of 28.3 weeks (range, 26–31w) and mean birth weight of 1090g (range, 860–1330g) were included in the study. They all had Zone 1 or posterior Zone 2 plus disease staging between severe 3 and 4a. Twelve eyes were treatment naive at the beginning. The mean follow-up was 19.5±11.8 months (range, 11–40 months). The disease regressed totally in 6 eyes (40%), stayed stable as stage 4a in 1 eye (6.7%), progressed to and stabilized at stage 4a in 3 eyes (20%) and progressed to stage 5 in 3 eyes (20%) within 7–10 days. Two eyes (13.3%) developed hypotony and cataract.ConclusionThe association of IVB and laser ablation might decrease the progression rate in severe AP-ROP. Prompt regression of iris neovascularization encourages its use in cases with pupillary rigidity to allow for laser treatment. When used as a salvage therapy it may not change the overall result dramatically

Intravitreally injected anti-VEGF antibody reduces brown fat in neonatal mice

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondriarelated genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. Copyright

Review of effects of anti-VEGF treatment on refractive error

Helen A Mintz-Hittner,1,2 Megan M Geloneck1,2 1Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at UTHealth, 2WT and Louise J Moran Pediatric Eye Clinic (affiliate of Robert Cizik Eye Clinic), Houston, TX, USA Abstract: To examine the effect of anti-vascular endothelial growth factor (anti-VEGF) agents on refractive error in the setting of retinopathy of prematurity (ROP) through a review of the literature, a PubMed search was performed of appropriate search terms, and the results of all relevant studies were extracted and compiled. Eleven relevant articles were identified in the literature, totaling 466 eyes, treated with varied anti-VEGF agents (bevacizumab, ranibizumab, and aflibercept) with mean spherical equivalent refractions ranging from +0.75 D to 3.57 D, with prevalence of high myopia ranging from 0 to 35%. Anti-VEGF monotherapy for ROP leads to low levels of myopia, and there may be a differential effect of specific anti-VEGF agents utilized on refractive outcomes. Keywords: retinopathy of prematurity, ROP, refraction, myopia, bevacizumab, ranibizumab, aflibercep