David G. Morrison

The Infant Aphakia Treatment Study: Design and Clinical Measures at Enrollment

OBJECTIVE To compare the use of contact lenses and intraocular lenses (IOLs) for the optical correction of unilateral aphakia during infancy. METHODS In a randomized, multicenter (12 sites) clinical trial, 114 infants with unilateral congenital cataracts were assigned to undergo cataract surgery with or without IOL implantation. Children randomized to IOL treatment had their residual refractive error corrected with spectacles. Children randomized to no IOL treatment had their aphakia treated with a contact lens. MAIN OUTCOME MEASURES Grating acuity at 12 months of age and HOTV visual acuity at 4 1/2 years of age. APPLICATION TO CLINICAL PRACTICE This study should determine whether either treatment for an infant with a visually significant unilateral congenital cataract results in a better visual outcome. RESULTS Enrollment began December 23, 2004, and was completed January 16, 2009. The median age at the time of cataract surgery was 1.8 months. Fifty patients were 4 to 6 weeks of age at the time of enrollment; 32, 7 weeks to 3 months of age; and the remaining 32, more than 3 to less than 7 months of age. Fifty-seven children were randomized to each treatment group. Eyes with cataracts had shorter axial lengths and steeper corneas on average than the fellow eyes. CONCLUSIONS The optimal optical treatment of aphakia in infants is unknown. However, the Infant Aphakia Treatment Study was designed to provide empirical evidence of whether optical treatment with an IOL or a contact lens after unilateral cataract surgery during infancy is associated with a better visual outcome.

Patching vs atropine to treat amblyopia in children aged 7 to 12 years: A randomized trial

OBJECTIVE To compare patching with atropine eyedrops in the treatment of moderate amblyopia (visual acuity, 20/40-20/100) in children aged 7 to 12 years. METHODS In a randomized, multicenter clinical trial, 193 children with amblyopia were assigned to receive weekend atropine or patching of the sound eye 2 hours per day. Main Outcome Measure Masked assessment of visual acuity in the amblyopic eye using the electronic Early Treatment Diabetic Retinopathy Study testing protocol at 17 weeks. RESULTS At 17 weeks, visual acuity had improved from baseline by an average of 7.6 letters in the atropine group and 8.6 letters in the patching group. The mean difference between groups (patching - atropine) adjusted for baseline acuity was 1.2 letters (ends of complementary 1-sided 95% confidence intervals for noninferiority, -0.7, 3.1 letters). This difference met the prespecified definition for equivalence (confidence interval <5 letters). Visual acuity in the amblyopic eye was 20/25 or better in 15 participants in the atropine group (17%) and 20 in the patching group (24%; difference, 7%; 95% confidence interval, -3% to 17%). CONCLUSIONS Treatment with atropine or patching led to similar degrees of improvement among 7- to 12-year-olds with moderate amblyopia. About 1 in 5 achieved visual acuity of 20/25 or better in the amblyopic eye. CLINICAL RELEVANCE Atropine and patching achieve similar results among older children with unilateral amblyopia. TRIAL REGISTRATION (clinicaltrials.gov) Identifier: NCT00315328.

Intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity

BACKGROUND While laser photocoagulation remains the standard of care in the treatment of advanced retinopathy of prematurity (ROP), regression is not seen in all cases (especially in aggressive posterior disease) following laser alone. We report the results of the use of the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in eyes with ROP at high risk for progression. METHODS Records of all infants with ROP treated with bevacizumab were reviewed. Bevacizumab was given when conventional laser therapy was not possible in patients with poor pupillary dilation from iris rubeosis, dense vitreous hemorrhage, or increasing vascular activity and vitreoretinal traction despite completed laser therapy. We recorded birth weight, gestational age at birth, severity of ROP, anatomic result, any additional ophthalmic interventions, and early or late adverse systemic effects. RESULTS Thirteen eyes of 7 infants (median gestational age, 25 weeks; median birth weight, 700 g; follow-up, 9 months [range, 2-17]) were treated with an intravitreal injection of 0.75 mg bevacizumab under sterile conditions by 1 surgeon following detailed discussion with family and attending neonatologists. Injection was not used as monotherapy in any case. Definitive treatment (laser or vitrectomy) was completed successfully within 72 hours of injection. No systemic complication attributable to bevacizumab treatment has been recorded within 2 to 17 months of follow-up. CONCLUSIONS Treatment with bevacizumab may be used to improve visualization for more definitive laser or surgical treatment and may facilitate disease regression without obvious systemic toxicity. Optimization of dosing, timing, and indications will require additional study.

Primary treatment of nasolacrimal duct obstruction with nasolacrimal duct intubation in children younger than 4 years of age.

PURPOSE To report the outcome of nasolacrimal duct intubation as the primary treatment of congenital nasolacrimal duct obstruction (NLDO) in children younger than 4 years of age. METHODS A total of 182 eyes of 139 children receiving intubation with planned tube retention for 2 to 5 months were enrolled in a prospective, nonrandomized observational multicenter study (19 sites). Children were ages 6 months to <45 months at the time of surgery, with no previous nasolacrimal surgical procedures and had at least one of the following clinical signs of NLDO: epiphora, mucous discharge, and/or increased tear lake. RESULTS Treatment success was defined as absence of epiphora, mucous discharge, and increased tear lake at the outcome visit, 1 month after tube removal. The surgical outcome was assessed in 150 eyes (82% of cohort). The proportion of eyes treated successfully was 91% (95% CI: 86%-95%). The outcome dye disappearance test was normal in 125 (86%) eyes, indeterminate in 13 (9%), and abnormal in 7 (5%) of the 145 eyes tested. Monocanalicular tubes were used in 74% of cases. The tube was removed before the planned minimum retention time of 2 months in 61 eyes (41%). For 23 eyes, the early removal was attributed to inadvertent displacement by the patient. CONCLUSIONS In children 6 months to <45 months of age, nasolacrimal duct intubation in a nonrandomized and noncomparative trial was a successful primary treatment of NLDO in about 90% of cases not lost to follow-up.

Longitudinal follow-up of hypermetropic children identified during preschool vision screening

PURPOSE Early childhood hypermetropia is an important risk factor for the development of amblyopia and esotropia. Understanding the natural history of these complications aids in management decisions. METHODS A retrospective observational review was undertaken of 149 patients referred from a preschool photoscreening program who were determined to have hypermetropia of >or=+3.75 D spherical equivalent on criterion standard examination and were treated/followed by one group of academic pediatric ophthalmologists. The prevalence and incidence of accommodative esotropia and amblyopia were determined. RESULTS At presentation 19% of hypermetropic children had amblyopia, 32% had esotropia, and 13% had both. Follow-up data of 108 patients during a mean of 40 months showed that 20 (24%) of 83 initially nonamblyopic patients developed amblyopia and that 22 (33%) of 67 initially nonstrabismic patients developed accommodative esotropia. Of patients initially managed with observation, 38% (6 of 16) developed amblyopia, and 31% (5 of 16) developed accommodative esotropia as compared with 21% (14 of 67) and 33% (17 of 51), respectively, for those given full or partial refractive correction. For patients without amblyopia or strabismus at presentation, only 20% developed amblyopia and 35% esotropia. Strabismic patients responded well to treatment, with no cases developing partially accommodative strabismus requiring surgery during follow-up. CONCLUSIONS In this case series we found a high prevalence of amblyopia and strabismus. The results support the importance of early preschool vision screening and spectacle correction of moderate to high hypermetropia (>+3.50 D) to reduce the risk of amblyopia, although more research is needed.

Resolution of congenital nasolacrimal duct obstruction with nonsurgical management

OBJECTIVE To determine how often nasolacrimal duct obstruction (NLDO) resolves with 6 months of nonsurgical management in infants aged 6 to less than 10 months. METHODS As part of a randomized trial evaluating the cost-effectiveness of immediate office probing vs observation with deferred probing for unresolved cases, 107 infants aged 6 to less than 10 months who had NLDO and no history of nasolacrimal duct surgery were prescribed 6 months of nasolacrimal duct massage and topical antibiotics as needed. Resolution of the NLDO was assessed 6 months after study entry and was defined as the absence of all clinical signs of NLDO (epiphora, increased tear lake, or mucous discharge) and not having undergone NLDO surgery. Exploratory analyses assessed whether baseline characteristics, including age, sex, laterality, and prior treatment, were associated with the probability of NLDO resolving without surgery. RESULTS At the 6-month examination, which was completed for 117 of the 133 eyes (88%), the NLDO had resolved without surgery in 77 eyes (66% [95% CI, 56%-74%]). None of the baseline characteristics we evaluated were found to be associated with resolution. CONCLUSIONS In infants 6 to less than 10 months of age, more than half of eyes with NLDO will resolve within 6 months with nonsurgical management. Knowledge of the rate of NLDO resolution in infancy without surgery will help clinicians and parents effectively discuss treatment options.

The Infant Aphakia Treatment Study: Evaluation of cataract morphology in eyes with monocular cataracts

PURPOSE To describe a video-documented assessment of cataract type in the eyes of patients with monocular infantile cataract who were enrolled in the Infant Aphakia Treatment Study. METHODS The Infant Aphakia Treatment Study is a randomized clinical trial in which the investigators compared intraocular lens (IOL) versus contact lens correction in 114 infants, aged 28 days to <7 months. A total of 83 videos were available for morphological analysis of cataract. Three examiners reviewed all surgical recordings and agreed on the cataract characteristics by using a score sheet to record the lens layer or configuration of the opacity. RESULTS Nuclear cataract was present in 45 of 83 eyes (54%). Posterior capsule plaque was observed in 73 eyes (88%). All eyes with fetal nuclear cataract had associated posterior capsule plaque. Cortical cataract without nuclear involvement was seen in 21 eyes (25%). Posterior bowing of the posterior capsule was noted in 4 eyes (5%). Evidence of persistent fetal vasculature (PFV) was present in 18 eyes (22%). PFV was the only finding in 5 eyes but was also seen in combination with nuclear (7 eyes) and cortical cataracts (6 eyes). The entire lens was white in 3 eyes (4%), whereas the lens was partially resorbed in 7 (8%) eyes. Anterior capsule fibrosis was noted in 5 eyes with advanced cataract (1 with total cataract, 4 with partially resorbed lens). CONCLUSIONS Nuclear opacities were common, but many different cataract types presented in infancy. PFV occurred in isolation or in association with cataract. Posterior capsule plaque was frequently noted, especially when a nuclear cataract was present.

Pilot study of levodopa dose as treatment for residual amblyopia in children aged 8 years to younger than 18 years.

P rior studies have evaluated levodopa as an adjunct toocclusiontherapyinthetreatmentofamblyopia. Improvement in visual acuity after completion of a course of levodopa has been reported; however, regression has occurred in several studies after stopping the medication. Reportedadverseeffectsof levodopaweremild.They haveincludednausea,headache,fatigue,moodchanges,emesis,dizziness,drymouth,decreasedappetite,andnightmares. Inpreparationforconductingaphase3randomizedtrial, weconductedaprospective randomizedpilot study toprovide a preliminary assessment of the efficacy and safety of 2 doses of levodopa combined with daily ocular occlusion therapyofthefelloweyeinolderchildrenandteenagerswith residualamblyopiafromstrabismus,anisometropia,orboth.

Stereopsis Results at 4.5 Years of Age in the Infant Aphakia Treatment Study

PURPOSE To determine whether stereopsis of infants treated for monocular cataracts varies with the type of optical correction used. DESIGN Randomized prospective clinical trial. METHODS The Infant Aphakia Treatment Study randomized 114 patients with unilateral cataracts at age 1-7 months to either primary intraocular lens (IOL) or contact lens correction. At 4.5 years of age a masked examiner assessed stereopsis on these patients using 3 different tests: (1) Frisby; (2) Randot Preschool; and (3) Titmus Fly. RESULTS Twenty-eight patients (25%) had a positive response to at least 1 of the stereopsis tests. There was no statistically significant difference in stereopsis between the 2 treatment groups: Frisby (contact lens, 6 [11%]; IOL, 7 [13%]; P = .99), Randot (contact lens, 3 [6%]; IOL, 1 [2%]; P = .62), or Titmus (contact lens, 8 [15%]; IOL, 13 [23%]; P = .34). The median age at surgery for patients with stereopsis was younger than for those without stereopsis (1.2 vs 2.4 months; P = .002). The median visual acuity for patients with stereopsis was better than for those without stereopsis (20/40 vs 20/252; P = .0003). CONCLUSION The type of optical correction did not influence stereopsis outcomes. However, 2 other factors did: age at surgery and visual acuity in the treated eye at age 4.5 years. Early surgery for unilateral congenital cataract and the presence of visual acuity better than or equal to 20/40 appear to be more important than the type of initial optical correction used for the development of stereopsis.

Comparison of sensory outcomes in patients with monofixation versus bifoveal fusion after surgery for intermittent exotropia.

INTRODUCTION The predictive value of preoperative stereopsis on the surgical outcome of patients with intermittent exotropia is unknown. We hypothesize that it may predict motor and sensory outcome. We report our experience with fusional status at near measured using Titmus circles before and after eye muscle surgery for intermittent exotropia. METHODS In this retrospective case series, 95 children underwent bilateral lateral rectus muscle recession. Visual acuity, near stereoacuity, and ocular alignment were measured before surgery and 2 months postoperatively. RESULTS Testing variability by use of Titmus circles was examined. A change of greater than 3 stereo circles was found to be substantial (90% confidence interval). Of the 42 children with poor-to-nondetectable stereopsis preoperatively (400 arcsec or worse), 3 improved substantially (140, 140, 60 arcsec). The remaining 53 had moderate- (200 arcsec) to high-grade (60 arcsec or better) stereopsis preoperatively. The majority of children had no change in stereopsis after surgery. Only 4 children had improved stereopsis after surgery; 6 lost stereopsis, of whom 4 had persistent small-angle esodeviations, whereas 1 child had a large overcorrection requiring additional surgery. All children who maintained or improved their stereopsis postoperatively were orthotropic or had persistent exodeviation after surgery. No child with high-grade stereopsis at 2 consecutive preoperative visits lost stereoacuity after surgery. CONCLUSIONS A persistent small-angle esotropia at the 2-month postoperative visit is associated with a loss of near stereopsis (p=0.0001) and may occur more frequently in children with subnormal stereopsis preoperatively than in patients with bifoveal fixation. Prism or reoperation may be necessary to treat this complication.