{'fraction_non_alphanumeric': 0.03201438848920863, 'fraction_numerical': 0.016906474820143885, 'mean_word_length': 4.904458598726115, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Letter to the Editor: Fellow Eye Anti-VEGF 'Crunch' Effect in Retinopathy of Prematurity.

Dear Editor, Wood et al.1 describe a neonatal female born at 28 weeks with a weight of 990 grams who, at 37 weeks postmenstrual age, developed Zone 1, Stage 3 retinopathy of prematurity (ROP) with plus disease in the right eye and Zone 1, Stage 2 ROP with plus disease in the left eye. The right eye underwent intravitreal injection with low-dose bevacizumab (0.0625 mg; IVB) (Avastin; Genentech, South San Francisco, CA), whereas the left eye underwent laser ablative therapy. At 42 weeks, the right eye was vascularly quiet despite nasal retinal folds, whereas the left eye had a tractional retinal detachment (TRD). The authors concluded the “atypical” TRD in the left eye was due to a to crossover “crunch” effect from the right IVB. This conclusion is highly unlikely. In macaques weighing between 3 kg to 6 kg (a reasonable surrogate for a 42-week neonate), bevacizumab concentrations in the uninjected contralateral eye were more than 2,500-fold lower than in the injected eye2 (ie, well below the in vitro or in vivo minimum therapeutic threshold). The authors also proposed that the reduction in vascular endothelial growth factor from IVB increased the pro-fibrotic effect of transforming growth factor-beta (TGF-β) based on cytokine analysis from adults with proliferative diabetic retinopathy. Such cytokine changes after IVB have not been consistently reported in adults,3 have not been examined in neonates with ROP, and have not been reported in the uninjected contralateral eye. In contradiction to the authors’ TGFβ hypothesis, the right eye, which received bevacizumab, did not develop a TRD. A more likely explanation is that the laser ablative therapy itself caused the TRD. In a comprehensive study by Coats’ et al.,4 36 eyes of 138 infants who received laser ablative therapy for ROP from a single institution during a period of 4 years developed a TRD, 47% of which occurred within the first 28 days. In comparison, a large 7-year retrospective study across six high-volume ROP centers found 35 neonatal eyes developed a TRD after IVB.5 Though the total number of intravitreal injections was not reported, given the number sites and duration of the study, the incidence rate of TRDs is likely much less than the 13.7% reported following laser ablative therapy. Anecdotally, at our institution, no TRDs have developed after IVB, whereas progressive TRDs have been observed following laser ablative therapy. In summary, consistent with the authors’ observations, but contrary to their conclusions, laser ablative therapy appears to have a greater risk of inducing TRDs in ROP than IVB. Ira Schachar, MD, MSc Department of Ophthalmology Stanford University Stanford, CA