Erick D. Bothun

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.

Glaucoma-Related Adverse Events in the Infant Aphakia Treatment Study: 1-Year Results

OBJECTIVES To report the incidence of glaucoma and glaucoma suspects in the IATS, and to evaluate risk factors for the development of a glaucoma-related adverse event in patients in the IATS in the first year of follow-up. METHODS A total of 114 infants between 1 and 6 months of age with a unilateral congenital cataract were assigned to undergo cataract surgery either with or without an intraocular lens implant. Standardized definitions of glaucoma and glaucoma suspect were created and used in the IATS. RESULTS Of these 114 patients, 10 (9%) developed glaucoma and 4 (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma-related adverse event in the treated eye through the first year of follow-up. Of the 57 patients who underwent lensectomy and anterior vitrectomy, 5 (9%) developed a glaucoma-related adverse event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma-related adverse event. The odds of developing a glaucoma-related adverse event were 3.1 times higher for a child with persistent fetal vasculature and 1.6 times higher for each month of age younger at cataract surgery. CONCLUSIONS Modern surgical techniques do not eliminate the early development of glaucoma following congenital cataract surgery with or without an intraocular lens implant. Younger patients with or without persistent fetal vasculature seem more likely to develop a glaucoma-related adverse event in the first year of follow-up. Vigilance for the early development of glaucoma is needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a child with persistent fetal vasculature. Five-year follow-up data for the IATS will likely reveal more glaucoma-related adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00212134.

Glaucoma-related adverse events in the first 5 years after unilateral cataract removal in the infant aphakia treatment study

IMPORTANCE Glaucoma-related adverse events constitute major sight-threatening complications of cataract removal in infancy, yet their relationship to aphakia vs primary intraocular lens (IOL) implantation remains unsettled. OBJECTIVE To identify and characterize cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study by the age of 5 years. DESIGN, SETTING, AND PARTICIPANTS A multicenter randomized clinical trial of 114 infants with unilateral congenital cataract in referral centers who were between ages 1 and 6 months at surgery. Mean follow-up was 4.8 years. This secondary analysis was conducted from December 23, 2004, to November 13, 2013. INTERVENTIONS Participants were randomized at cataract surgery to either primary IOL or no IOL implantation (contact lens). Standardized definitions of glaucoma and glaucoma suspect were created for the Infant Aphakia Treatment Study and applied for surveillance and diagnosis. MAIN OUTCOMES AND MEASURES Development of glaucoma and glaucoma + glaucoma suspect in operated on eyes for children up to age 5 years, plus intraocular pressure, visual acuity, and axial length at age 5 years. RESULTS Product limit estimates of the risk for glaucoma and glaucoma + glaucoma suspect at 4.8 years after surgery were 17% (95% CI, 11%-25%) and 31% (95% CI, 24%-41%), respectively. The contact lens and IOL groups were not significantly different for either outcome: glaucoma (hazard ratio [HR], 0.8; 95% CI, 0.3-2.0; P = .62) and glaucoma + glaucoma suspect (HR, 1.3; 95% CI, 0.6-2.5; P = .58). Younger (vs older) age at surgery conferred an increased risk for glaucoma (26% vs 9%, respectively) at 4.8 years after surgery (HR, 3.2; 95% CI, 1.2-8.3), and smaller (vs larger) corneal diameter showed an increased risk for glaucoma + glaucoma suspect (HR, 2.5; 95% CI, 1.3-5.0). Age and corneal diameter were significantly positively correlated. Glaucoma was predominantly open angle (19 of 20 cases, 95%), most eyes received medication (19 of 20, 95%), and 8 of 20 eyes (40%) underwent surgery. CONCLUSIONS AND RELEVANCE These results suggest that glaucoma-related adverse events are common and increase between ages 1 and 5 years in infants after unilateral cataract removal at 1 to 6 months of age; primary IOL placement does not mitigate their risk but surgery at a younger age increases the risk. Longer follow-up of these children may further characterize risk factors, long-term outcomes, potential differences between eyes having primary IOL vs aphakia, and optimal timing of unilateral congenital cataract removal. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00212134.

Predictability of Intraocular Lens Calculation and Early Refractive Status: The Infant Aphakia Treatment Study

OBJECTIVE To report the accuracy of intraocular lens (IOL) power calculations and the early refractive status in pseudophakic eyes of infants in the Infant Aphakia Treatment Study. METHODS Eyes randomized to receive primary IOL implantation were targeted for a postoperative refraction of +8.0 diopters (D) for infants 28 to 48 days old at surgery and +6.0 D for those 49 days or older to younger than 7 months at surgery using the Holladay 1 formula. Refraction 1 month after surgery was converted to spherical equivalent, and prediction error (PE; defined as the calculated refraction minus the actual refraction) and absolute PE were calculated. Baseline eye and surgery characteristics and A-scan quality were analyzed to compare their effect on PE. MAIN OUTCOME MEASURES Prediction error. RESULTS Fifty-six eyes underwent primary IOL implantation; 7 were excluded for lack of postoperative refraction (n = 5) or incorrect technique in refraction (n = 1) or biometry (n = 1). Overall mean (SD) absolute PE was 1.8 (1.3) D and mean (SD) PE was +1.0 (2.0) D. Absolute PE was less than 1 D in 41% of eyes but greater than 2 D in 41% of eyes. Mean IOL power implanted was 29.9 D (range, 11.5-40.0 D); most eyes (88%) implanted with an IOL of 30.0 D or greater had less postoperative hyperopia than planned. Multivariate analysis revealed that only short axial length (<18 mm) was significant for higher PE. CONCLUSIONS Short axial length correlates with higher PE after IOL placement in infants. Less hyperopia than anticipated occurs with axial lengths of less than 18 mm or high-power IOLs. Application to Clinical Practice Quality A-scans are essential and higher PE is common, with a tendency for less hyperopia than expected. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00212134.

Interobserver reliability of the prism and alternate cover test in children with esotropia

OBJECTIVE To determine 95% limits of agreement on a measurement and on a difference between 2 measurements for the prism and alternate cover test (PACT) at distance and at near fixation. METHODS In a test-retest reliability study, 143 children aged 60 months or younger with esotropia were examined by 2 masked examiners on 1 or 2 occasions yielding 199 test-retest pairs for PACT at distance fixation and 239 test-retest pairs for PACT at near fixation. RESULTS For angles greater than 20 prism diopters (PD), the 95% limits of agreement on a measurement and on a difference between 2 measurements were +/-7.3 PD and +/-10.4 PD, respectively, for PACT at distance and +/-8.3 PD and +/-11.7 PD, respectively, for PACT at near. For angles of 10 to 20 PD, the 95% limits of agreement on a measurement and on a difference between 2 measurements were +/-4.1 PD and +/-5.8 PD, respectively, for PACT at distance and +/-3.3 PD and +/-4.7 PD, respectively, for PACT at near. CONCLUSION In childhood esotropia, differences of 12 PD or more for angles greater than 20 PD and differences of 6 PD or more for angles between 10 PD and 20 PD are likely to indicate real change. Smaller differences could be real change but could also be due to measurement error.

Outcome of angle surgery in children with aphakic glaucoma

PURPOSE To investigate the outcome of trabeculotomy and/or goniotomy for pediatric aphakic glaucoma. METHODS Retrospective chart review of consecutive children who had congenital cataract surgery between 1990 and 2006 and required goniotomy and/or trabeculotomy for aphakic glaucoma. Treatment success was defined as postoperative intraocular pressure of <or=24 mm Hg despite topical medication use, avoidance of trabeculectomy or shunt placement, and no visually significant complications in the follow-up period. Exclusion criteria included a diagnosis of anterior segment dysgenesis, microcornea, and glaucoma at the time of cataract surgery, and follow-up less than 1 year. RESULTS A total of 14 eyes of 11 patients met inclusion criteria, with a mean follow-up of 4.7 years. Of theses, 2 eyes had goniotomy alone, 3 eyes had goniotomy followed by trabeculotomy, and 9 eyes had trabeculotomy alone. Mean IOP before angle surgery was 35 +/- 10 mm Hg. Mean IOP at the last recorded visit was 22 +/- 4 mm Hg (p = 0.0005). Treatment success was observed in 8 of the 14 eyes (57.1%), with a mean number of angle procedures of 1.4 per eye: 6 eyes (42.8%) were successful after a single angle surgery, each involving an initial trabeculotomy; 3 eyes (21.4%) underwent subsequent shunt placement after initial goniotomy at 6 months, 1.3 years, and 5.5 years after the last angle surgery. CONCLUSIONS When intraocular surgery is indicated to control IOP in pediatric aphakic glaucoma, trabeculotomy and/or goniotomy can be successful in the majority of eyes and may decrease the need for filtering and shunting procedures.

Update on thyroid eye disease and management

Thyroid eye disease is a heterogeneous autoimmune orbital reaction typically manifesting in middle age. The inflammation may parallel or remain isolated from a related inflammatory cascade in the thyroid called Graves’ disease. The orbital manifestations can lead to severe proptosis, dry eyes, strabismus, and optic neuropathy. In this article, we will discuss this unique condition including the ophthalmic findings and management.

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.

Influence of patient height and weight and type of stress on myocardial count density during SPECT imaging with thallium-201 and technetium 99m-sestamibi.

BackgroundThe aim of this study was to determine the variability in myocardial activity with 99mTc-labeled sestamibi and 201Tl tomographic imaging, and to correlate this variability with patient anthropometric data and type of stress.Methods and ResultsConventional tomographic acquisition (all-purpose collimator, 30 views, 40 sec/view) was performed in 249 patients (155 with 99mTc-sestamibi, 84 with 201TI). Normal myocardium was identified in three short-axis tomographic slices between the base and mid-ventricle. To exclude abnormal myocardium, all myocardial activity below and 85% threshold of peak counts was excluded. The average counts per pixel in the remaining myocardium was determined. All data were normalized to a collimator sensitivity of 8.1 counts/min/kBq and corrected for decay. Myocardial count densities in both 201TI and 99mTc-sestamibi studies exhibited a high degree of variability and varied by factors of 3 to 4 and 2.5 to 3 respectively, between the 10th and 90th percentile of count densities. All 99mTc-sestamibi studies showed an inverse correlation (R≈0.7) between myocardial count density and patient weight. For stress 201TI studies in male patients, a similar inverse correlation (R=0.63) was found between patient weight and myocardial count density. No correlation was found for female patients. For rest 99mTc-sestamibi studies, the average myocardial count density was 1245±297 counts/pixel for a 1.11 GBq (30 mCi) injection. This was similar with pharmacologic stress (1224±297 counts/pixel per 1.11 GBq (30 mCi), but significantly higher with exercise (1569±363 counts/pixel per 1.11 GBq (30 mCi) (p<0.005). 201TI studies averaged 327±97 counts/pixel (111 MBq [3 mCi] injection) with exercise and 374±145 counts/pixel/111 MBq (3 mCi) with pharmacologic stress (p=NS). Redistribution studies after exercise/pharmacologic stress (with a 37 MBq [1 mCi] reinjection) averaged 267±83 counts/pixel (148 MBq [3+1 mCi]).ConclusionMeasured count densities in the myocardium demonstrate a high degree of variability that is only weakly correlated with patient anthropometric data. Nevertheless, knowledge of the mean values of myocardial activity as a function of administered dose may be useful in the optimization of rapid imaging procedures for 99mTc-based perfusion agents.

Normal exophthalmometry measurements in a United States pediatric population.

Purpose: The normal distribution of exophthalmometry measurements in a U.S. pediatric population was determined as a reference for clinical practice. Methods: This was a cross-sectional study, in which 673 normal subjects, between 1 and 17 years of age, randomly selected from patients presenting to our institution, were measured with an exophthalmometer. Normal volunteers also participated at a booth at the annual state fair. Subjects were excluded for a prior history of orbital tumor, craniofacial anomaly, thyroid disease, orbital trauma, or inability to tolerate the measurement. Results: A total of 673 subjects (52% female) with a mean age of 9.6 years were studied. There was no difference in exophthalmometric measurements between male and female subjects. Mean exophthalmometric measurements increased with age: less than 4 years old (13.2 mm), 5–8 years old (14.4 mm), 9–12 years old (15.2 mm), and 13–17 years old (16.2 mm). Asymmetric measurements occurred in 100 (14.9%) subjects, with a 2-mm maximal difference in 2 subjects. Conclusion: Exophthalmometric measurements vary with age among the pediatric population. Reference data are presented for each age group in a U.S. cohort.