Joel N. Leffler

Foveal avascular zone and foveal pit formation after preterm birth

Background Vascularisation of the macula takes place between 24 and 27 weeks post-conception. Preterm birth may affect the formation of the foveal avascular zone (FAZ) and foveal depression, and displacement of inner retinal layers away from the incipient fovea. Objective To examine whether vascular abnormalities accompany an inner retinal abnormality, and whether they are coincident. Methods High-density spectral domain optical coherence tomography volume scans were obtained from 24 preterm children and 34 full-term controls (5–16 years). Matlab programs were used to quantify total retinal thickness, thickness of individual retinal layers and metrics of foveal morphology. Summed voxel projections for the ganglion cell layer–inner nuclear layer were used to identify the FAZ. Results Preterm children had significantly smaller FAZ diameters than controls (p<0.0001). The foveal pits of preterm children were significantly shallower and less steep (p<0.0001) and total retinal thickness at the fovea was significantly increased (p<0.0001) compared to controls. The ganglion cell layer–inner plexiform layer and outer nuclear layer were significantly (p≤0.0001) thicker in preterm children than in controls. Conclusions Preterm birth results in abnormal foveal vascularisation, a failure of the inner retinal neurons to migrate away from the fovea, and an elevated outer nuclear layer ratio. The spatial coincidence of inner retinal and vascular abnormalities in preterm children supports the hypothesis that aspects of foveal development are interdependent.

Critical Period For Foveal Fine Structure In Children With Regressed Retinopathy Of Prematurity

Purpose Midgestation is a critical period in the formation of the foveal avascular zone. The authors evaluated the effects of preterm birth on foveal structure in children with regressed retinopathy of prematurity. Methods Children with regressed retinopathy of prematurity with normal-appearing posterior poles (n = 26) and full-term control children (n = 56) were investigated. Frequency-domain optical coherence tomography 9-mm line scans across the fovea were obtained from right eyes. Using a customized segmentation program in MATLAB, total retinal thickness and the thickness of individual retinal layer regions were measured at the fovea (0°) and throughout ±8°. Results Total thickness of the fovea in the retinopathy of prematurity group (287.7 ± 47.6 &mgr;m) was greater than that in the control group (230.1 ± 18.2 &mgr;m). Bilinear fitting was performed to examine the relationship between total thickness and gestational age. Before 28 weeks, foveal thickness decreased with gestational age (14.3 &mgr;m/week); after 28 weeks, foveal thickness decreased only slightly (2.73 &mgr;m/week). Inner retinal layers contributed to the difference in thickness between groups more than outer layers. Foveal thickness was correlated with gestational age at birth but not with visual acuity or refractive error. Conclusion Preterm birth before 28 weeks of gestational age was associated with a failure of the inner retinal layers to migrate away from the fovea, resulting in increased foveal thickness.

Development of Refractive Error in Individual Children With Regressed Retinopathy of Prematurity

PURPOSE We investigated longitudinally the refraction development in children with regressed retinopathy of prematurity (ROP), including those with and those without a history of peripheral retinal laser photocoagulation. METHODS Longitudinal (0-7 years) cycloplegic refraction data were collected prospectively for two groups of preterm children: severe ROP group included those with regressed ROP following bilateral panretinal laser photocoagulation (n = 37; median gestational age [GA] = 25.2; range, 22.7-27.9 weeks) and mild/no ROP group included those with spontaneously regressed ROP or no ROP (n = 27; median GA = 27.1; range, 23.1-32.0 weeks). Analyses were based on spherical equivalent (SEQ), anisometropia, astigmatism, and age (corrected for gestation). RESULTS The prevalence, magnitude, and rate of myopic progression all were significantly higher in the severe ROP group than in the mild/no ROP group. Longitudinal SEQ in the severe ROP group were best fit with a bilinear model. Before 1.3 years old, the rate of myopic shift was -4.7 diopters (D)/y; after 1.3 years, the rate slowed to -0.15 D/y. Longitudinal SEQ in the mild/no ROP group was best fit with a linear model, with a rate of -0.004 D/y. Anisometropia in the severe ROP group increased approximately three times faster than in the mild/no ROP group. In the severe ROP group, with-the-rule astigmatism increased significantly with age. CONCLUSIONS The severe ROP group progressed rapidly toward myopia, particularly during the first 1.3 years; anisometropia and astigmatism also increased with age. The mild/no ROP group showed little change in refraction. Infants treated with laser photocoagulation for severe ROP should be monitored with periodic cycloplegic refractions and provided with early optical correction.

Binocular iPad Game vs Patching for Treatment of Amblyopia in Children: A Randomized Clinical Trial

Importance Fellow eye patching has long been the standard treatment for amblyopia, but it does not always restore 20/20 vision or teach the eyes to work together. Amblyopia can be treated with binocular games that rebalance contrast between the eyes so that a child may overcome suppression. However, it is unclear whether binocular treatment is comparable to patching in treating amblyopia. Objectives To assess the effectiveness of a binocular iPad (Apple Inc) adventure game as amblyopia treatment and compare this binocular treatment with patching, the current standard of care. Design, Setting, and Participants This investigation was a randomized clinical trial with a crossover design at a nonprofit eye research institute. Between February 20, 2015, and January 4, 2016, a total of 28 patients were enrolled in the study, with 14 randomized to binocular game treatment and 14 to patching treatment. Interventions Binocular game and patching as amblyopia treatments. Main Outcomes and Measures The primary outcome was change in amblyopic eye best-corrected visual acuity (BCVA) at the 2-week visit. Secondary outcomes were change in stereoacuity and suppression at the 2-week visit and change in BCVA at the 4-week visit. Results Among 28 children, the mean (SD) age at baseline was 6.7 (1.4) years (age range, 4.6-9.5 years), and 7 (25%) were female. At baseline, the mean (SD) amblyopic eye BCVA was 0.48 (0.14) logMAR (approximately 20/63; range, 0.3-0.8 logMAR [20/40 to 20/125]), with 14 children randomized to the binocular game and 14 to patching for 2 weeks. At the 2-week visit, improvement in amblyopic eye BCVA was greater with the binocular game compared with patching, with a mean (SD) improvement of 0.15 (0.08) logMAR (mean [SD], 1.5 [0.8] lines) vs 0.07 (0.08) logMAR (mean [SD], 0.7 [0.8] line; P = .02) after 2 weeks of treatment. These improvements from baseline were significant for the binocular game (mean [SD] improvement, 1.5 [0.8] lines; P < .001) and for patching (mean [SD] improvement, 0.7 [0.8] line; P = .006). Depth of suppression improved from baseline at the 2-week visit for the binocular game (mean [SD], 4.82 [2.82] vs 3.24 [2.87]; P = .03) and for patching (mean [SD], 4.77 [3.10] vs 2.57 [1.67]; P = .004). Patching children crossed over to binocular game treatment, and all 28 children played the game for another 2 weeks. At the 4-week visit, no group difference was found in BCVA change, with children who crossed over to the binocular games catching up with children treated with binocular games, for a mean (SD) improvement of 0.17 (0.10) logMAR (mean [SD], 1.7 [1.0] lines) for the binocular game vs a mean (SD) improvement of 0.16 (0.12) logMAR (mean [SD], 1.6 [1.2] lines) for the patching crossover (P = .73). Conclusions and Relevance A binocular iPad game was effective in treating childhood amblyopia and was more efficacious than patching at the 2-week visit. Binocular games that rebalance contrast to overcome suppression are a promising additional option for treating amblyopia. Trial Registration clinicaltrials.gov Identifier: NCT02365090.

Improved Binocular Outcomes Following Binocular Treatment for Childhood Amblyopia

Purpose Childhood amblyopia can be treated with binocular games or movies that rebalance contrast between the eyes, which is thought to reduce depth of interocular suppression so the child can experience binocular vision. While visual acuity gains have been reported following binocular treatment, studies rarely report gains in binocular outcomes (i.e., stereoacuity, suppression) in amblyopic children. Here, we evaluated binocular outcomes in children who had received binocular treatment for childhood amblyopia. Methods Data for amblyopic children enrolled in two ongoing studies were pooled. The sample included 41 amblyopic children (6 strabismic, 21 anisometropic, 14 combined; age 4–10 years; ≤4 prism diopters [PD]) who received binocular treatment (20 game, 21 movies; prescribed 9–10 hours treatment). Amblyopic eye visual acuity and binocular outcomes (Randot Preschool Stereoacuity, extent of suppression, and depth of suppression) were assessed at baseline and at 2 weeks. Results Mean amblyopic eye visual acuity (P < 0.001) and mean stereoacuity improved (P = 0.045), and mean extent (P = 0.005) and depth of suppression (P = 0.003) were reduced from baseline at the 2-week visit (87% game adherence, 100% movie adherence). Depth of suppression was reduced more in children aged <8 years than in those aged ≥8 years (P = 0.004). Worse baseline depth of suppression was correlated with a larger depth of suppression reduction at 2 weeks (P = 0.001). Conclusions After 2 weeks, binocular treatment in amblyopic children improved visual acuity and binocular outcomes, reducing the extent and depth of suppression and improving stereoacuity. Binocular treatments that rebalance contrast to overcome suppression are a promising additional option for treating amblyopia.