Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy.

PURPOSE: To determine incidence, risk factors, risk period, and characteristics of recurrent retinopathy of prematurity (ROP) treated by intravitreal bevacizumab (IVB) monotherapy. DESIGN: Retrospective case series. PARTICIPANTS: Premature infants with type 1 ROP (subdivided into stage 3+ ROP and aggressive posterior ROP [APROP]) in zone I or zone II posterior who received IVB monotherapy and were followed up for at least 65 weeks adjusted age (AA). METHODS: Retrospective review of infants who demonstrated recurrence of type 1 ROP after IVB monotherapy, including examination of RetCam fundus photographs and fluorescein angiograms. MAIN OUTCOMES MEASURES: Incidence, risk factors, risk period, and characteristics of recurrent ROP. RESULTS: Intravitreal bevacizumab monotherapy in 241 infants (471 eyes) was reviewed. Recurrence incidence was 8.3% (20/241) for infants and 7.2% (34/471) for eyes. Recurrence risk factors of greatest significance were appearance of neovascularization as APROP (P = 0.006), extended duration of hospitalization (P = 0.01), and lower birth weight (P = 0.024). Recurrence risk period was between approximately 45 and 55 weeks AA (90.0% [18/20] for infants and 94.1% [32/34] for eyes), with mean recurrence of 51.2 weeks AA (±4.6 weeks; range, 45.7-64.9 weeks) and mean interval of 16.2 weeks (±4.4 weeks) between treatments. Recurrence characteristics included plus disease (20/20 infants [100%]) and neovascularization, which appeared at the following sites: stage 3+ ROP with confluent neovascularization recurred both at the advancing edge and at the initial ridge and extraretinal fibrovascular proliferative complex (12/14 infants [85.7%]). However, APROP (6/6 infants [100%]) and stage 3+ ROP with nonconfluent neovascularization (2/14 infants [14.3%]) recurred only at the advancing edge. Also, the anterior extent of retinal vascularization was decreased (mean, 1.76 disc diameters [DD] vs. 4.48 DD), and the rate of retinal vascularization was delayed (mean, 0.11 DD/week vs. 0.23 DD/week) in those with versus without recurrence, respectively. After retreatment with IVB, retinal vascularization proceeded minimally and slowly. CONCLUSIONS: Premature children with severe ROP are being treated successfully with IVB monotherapy. However, recurrence is not uncommon, so vigilant follow-up is necessary to ensure timely re-treatment. Knowledge of recurrence incidence, risk factors, risk period, and characteristics allows for tailored clinical management.

Review of effects of anti-VEGF treatment on refractive error.

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.

Ocular Complications in Children with Diabetes Mellitus.

PURPOSE: The effectiveness of annual eye examinations in diabetic children is unclear. We sought to determine the prevalence and onset of ocular pathology in children with diabetes mellitus (DM), identify risk factors for ocular disease, and recommend a screening regimen for asymptomatic children. DESIGN: Retrospective, consecutive cohort study. PARTICIPANTS: Children aged less than 18 years with type 1 or 2 DM examined over a 4-year period. METHODS: All children underwent a complete eye examination, including dilated fundoscopy and cycloplegic refraction. A literature review was performed, identifying the youngest reported age and shortest reported duration of DM before the diagnosis of diabetic retinopathy (DR). MAIN OUTCOME MEASURES: Prevalence of DR, cataract, high refractive error, and strabismus. RESULTS: A total of 370 children (mean age, 11.2 years; range, 1-17.5 years) had 693 examinations, with a mean DM duration of 5.2 years (range, 0.1-16.2 years) and a mean hemoglobin A1c (HbA1c) of 8.6 (range, 5-≥14). No children had DR. A total of 12 children had cataract; 5 required extraction but were identified by decreased vision, not diabetic screening. A total of 19 children had strabismus; only 1 was microvascular paralytic strabismus. A total of 41 children had high refractive error. There were no associations between these conditions and duration or control of DM. In the literature, the youngest age at diagnosis of severe DR was 15 years, and the shortest duration of disease was 5 years. CONCLUSIONS: Diabetic retinopathy is rare in children regardless of duration and control of DM. On the basis of our study and literature review, screening examinations for type 1 diabetes could begin at age 15 years or at 5 years after the diagnosis of DM, whichever occurs later, unless the child is judged by the endocrinologist as being at unusually high risk. Other ocular complications are identifiable through existing amblyopia screening methods.

Correlation between intraocular pressure and body mass index in the seated and supine positions.

PURPOSE: Examine the relationship between intraocular pressure (IOP) and body mass index (BMI) in the seated and supine positions. PATIENTS AND METHODS: A prospective observational study was conducted in which the IOP was measured with a Tono-Pen (Reichert Inc., Depew, NY) in seated and supine positions in eligible participants with a wide range of BMI (18 to 70 kg/m). The paired t test was used to compare seated to supine IOP. Stepwise regression analyses were used to investigate the correlation between IOP and BMI at these positions after adjusting for confounding variables of increased IOP, including age, race, mean arterial blood pressure, and central corneal thickness (µm). RESULTS: The mean sitting IOP (16.3±2.9 mm Hg) was statistically lower than the mean supine IOP (17.7±3.1 mm Hg; P<0.0001). For each 10 unit increase in BMI, there was an increase of 0.55±0.23 mm Hg (P=0.0184) in IOP in the seated position and an increase of 0.49±0.24 mm Hg in IOP in the supine position (P=0.0409). BMI did not have a significant effect on the amount of increase in IOP observed in changing from the seated to supine position. CONCLUSIONS: Higher BMI is correlated with higher IOP in both the seated and supine positions. However, BMI has no significant effect on the amount of increase in IOP observed in changing from the seated to supine position.

Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial.

IMPORTANCE: Children born prematurely who develop retinopathy of prematurity (ROP) often develop myopia, and those who require laser treatment may develop very high myopia, which has considerable clinical consequences. OBJECTIVE: To report refractive outcomes in preterm infants who developed ROP in zone I or zone II posterior as stage 3+ ROP or aggressive posterior ROP (APROP). DESIGN, SETTING, AND PARTICIPANTS: All infants received intravitreal bevacizumab or laser therapy in a prospective, stratified, randomized, controlled, masked, multicenter clinical trial, Bevacizumab Eliminates the Angiogenic Threat for ROP (BEAT-ROP). Children who received intravitreal bevacizumab or laser in the BEAT-ROP clinical trial, with treatment randomized by infant, underwent cycloplegic retinoscopic refraction at a mean age of 2½ years. Fifteen centers with both pediatric and vitreoretinal ophthalmologists participating in level 3 neonatal intensive care units in academic centers with institutional review board approval were included in the trial. Of the originally enrolled 150 infants (300 eyes) in the BEAT-ROP clinical trial, 13 infants (26 eyes) died (6 received intravitreal bevacizumab; 7 received laser) and 19 eyes had intraocular surgery (6 infants bilaterally). Thus, 45 eyes (19 infants bilaterally) were excluded, leaving 131 infants (255 eyes, including 21 eyes that received a successful second treatment for recurrence). INTERVENTIONS: Follow-up of the BEAT-ROP cohort. MAIN OUTCOMES AND MEASURES: Spherical equivalent refractive outcomes and their distribution by ROP zone and treatment. RESULTS: Refractions were available for 109 of 131 eligible infants (83.2%) and 211 of 255 eyes (82.7%). Mean (SD) spherical equivalent refractions were as follows: zone I, -1.51 (3.42) diopters (D) in 52 eyes that received intravitreal bevacizumab and -8.44 (7.57) D in 35 eyes that received laser treatment (P < .001); and zone II posterior, -0.58 (2.53) D in 58 eyes that received intravitreal bevacizumab and -5.83 (5.87) D in 66 eyes that received laser treatment (P < .001). Very high myopia (≥-8.00 D) occurred in zone I in 2 of 52 (3.8%) eyes that received intravitreal bevacizumab and in 18 of 35 (51.4%) eyes that received laser treatment (P < .001). Very high myopia occurred in zone II posterior in 1 of 58 (1.7%) eyes that received intravitreal bevacizumab and in 24 of 66 (36.4%) eyes that received laser treatment (P < .001). CONCLUSIONS AND RELEVANCE: More very high myopia was found in eyes that received laser treatment than in eyes that received intravitreal bevacizumab. This difference is possibly related to anterior segment development that is present with intravitreal bevacizumab but minimal or absent following laser treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00622726.