Stefanie L. Davidson

The Impact of Pediatric Vision Disorders in Adulthood

In addition to refractive errors such as myopia and astigmatism, ocular disorders that occur in infants, toddlers, and children may present lifelong problems for the child. Conditions such as strabismus, amblyopia, and retinopathy of prematurity may require adaptations in adulthood. In addition, vision disorders that occur in childhood may manifest as problems well into adulthood. When visual impairment is present, there may be further effects on overall health, self-perception, educational attainment, job choices, and a number of other social factors.

Visual acuity outcomes in pediatric glaucomas

PURPOSE To evaluate and compare the visual acuity prognosis in the various pediatric glaucoma subtypes and to determine risk factors for vision loss. METHODS The medical records of pediatric glaucoma patients from 2000 to 2010 at Childrens Hospital of Philadelphia were retrospectively reviewed. Visual acuities, surgeries, glaucoma subtype, and etiology of vision impairment were recorded. Univariate and multivariate analyses were performed to determine the risk factors for visual impairment. RESULTS A total of 133 eyes (36.8% primary congenital glaucoma, 28.6% aphakic glaucoma, 12.0% glaucoma associated with anterior segment dysgenesis, 12.0% Sturge-Weber glaucoma) of 88 patients were included. At last follow-up (median length, 5 years), 46.6% eyes achieved excellent (≥20/70) visual acuity. Of the glaucoma subtypes, primary congenital glaucoma conferred the best visual prognosis, with 69.4% eyes with excellent (≥20/70) visual acuity at final follow-up. Factors most associated with visual impairment (<20/200) were unilateral disease, multiple surgeries, poor vision at diagnosis, and other ocular comorbidities. The most common primary etiology for vision impairment was amblyopia (54.9%). CONCLUSIONS Patients with glaucoma early in life appear to have a better visual acuity prognosis than previously reported, with those with primary congenital glaucoma faring better than other glaucoma subtypes. Recognition of risk factors for visual impairment can better guide clinical management and counseling of patients.

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

PURPOSE To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. METHODS Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. RESULTS Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. CONCLUSIONS Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

A 781-kb deletion of 13q12.3 in a patient with Peters plus syndrome†

Chad R. Haldeman-Englert1, Taiyabah Naeem1, Elizabeth A. Geiger1, Ashley Warnock1, Holly Feret1, Melissa Ciano1, Stefanie L. Davidson2, Matthew A. Deardorff1,3, Elaine H. Zackai1,3, and Tamim H. Shaikh1,3,* 1Division of Human Genetics, The Childrens Hospital of Philadelphia, Philadelphia, PA 2Division of Ophthalmology, The Childrens Hospital of Philadelphia, Philadelphia, PA 3Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications

Abstract Purpose: To describe the retinal structure in a patient with cobalamin C (cblC) disease. Methods: A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). Results: The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5–10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. Conclusions: A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.

Simultaneous bilateral intraocular surgery in children

BACKGROUND Simultaneous bilateral intraocular surgery (SBIS), defined as sequential bilateral intraocular surgery completed in one visit to the operating room, is a controversial topic. The reluctance of ophthalmologists to perform SBIS has been mainly attributable to concerns about bilateral catastrophic complications (endophthalmitis, expulsive hemorrhage, or retinal detachment). Herein we report our experience with SBIS in children and review the literature. METHODS The medical records of 44 patients who underwent 48 cases of SBIS between 1994 and 2009 were reviewed. Of the 48 cases, 27 were bilateral cataract extractions, 1 including intraocular lens placement; 21 were cases of bilateral glaucoma surgeries, including goniotomy, trabeculotomy, and filtering tube placement. Bilateral surgeries were performed in one session under general anesthesia with strict aseptic separation of the 2 surgeries. RESULTS All but one of the cataract cases were performed in patients <1 year of age, and the majority (15/27) were performed in patients < or =1 month of age. Postoperative complications included aphakic glaucoma (5 patients) and reproliferation of lens material (3 patients). The majority of patients who underwent glaucoma procedures were <1 year of age (19/21), with 4 of 21 <1 month of age. One eye developed hyphema that required anterior chamber wash out. There were no catastrophic complications from the surgery or anesthesia (death, asphyxia, cardiac or respiratory arrest, or seizures) in either group. CONCLUSIONS Simultaneous bilateral intraocular surgery was performed safely in 48 cases during a 15-year period. In selected pediatric cases requiring bilateral intraocular surgery for glaucoma or cataract, SBIS may reduce risks related to anesthesia and delayed surgery.

The Effects of Fetal Surgery on Retinopathy of Prematurity Development

Background Fetal surgery is selectively offered for severe or life-threatening fetal malformations. These infants are often born prematurely and are thus at risk for retinopathy of prematurity (ROP). It is not known whether fetal surgery confers an increased risk of developing severe ROP relative to published rates in standard premature populations ≤37 weeks of age grouped by birth weight (<1500 grams or ≥1500 grams). Design This is a retrospective chart review. Methods We reviewed the charts of 137 patients who underwent open fetal/fetoscopic surgery from 1996–2004. Surgical indications included twin-twin transfusion syndrome (TTTS), myelomeningocele (MMC), congenital diaphragmatic hernia (CDH), sacrococcygeal teratoma (SCT), cystic adenomatoid malformation of the lung (CCAM), and twin reversed arterial perfusion sequence (TRAP). Of these, 17 patients had local ROP examination data. Binomial tests were performed to assess whether rates of ROP in our fetal/fetoscopic surgery cohort were significantly different from published rates. Results There were 5 patients each with an underlying diagnosis of TTTS and MMC, 2 patients each with CDH and TRAP, and 1 patient each with SCT, CCAM, and mediastinal teratoma. The mean gestational age at surgery was 23 4 /7 ± 2 3 /7 weeks, mean gestational age at birth was 30 ± 2 5 /7 weeks, and mean birth weight was 1449 ± 510 grams (610–2485). Compared to published rates of ROP and threshold ROP, our fetal surgery patients had significantly higher rates of ROP and threshold ROP in both the <1500 grams and the ≥1500 grams group (all p-values <0.05). Conclusions Fetal/fetoscopic surgery appears to significantly increase the rate of ROP and threshold ROP development. Greater numbers are needed to confirm these observations.

Amblyopia treatment: 1998 versus 2004.

PURPOSE To determine whether there has been a change in treatment practice patterns of patients with amblyopia between the late 1990s and 2004. METHODS A questionnaire survey was mailed to 1,200 AAPOS members listed in the 2004 AAPOS directory. Seven scenarios were presented that described patients with amblyopia and the clinician was asked to choose from six treatment options. Respondents were asked to indicate their preferred initial treatment in 1998 (or during their initial year of practice if later than 1998) and in 2004. The scenarios were not necessarily those of patients who would meet the eligibility criteria for the Amblyopia Treatment Studies because they also included scenarios to assess the impact of amblyopia treatments in general. RESULTS Three hundred eighty-nine surveys (33.1%) were returned. In four of the seven scenarios, comments suggested that a change in practice was attributable to recent publications of Pediatric Eye Disease Investigator Group trials. In all seven scenarios, atropine would have been offered in 2004 as an alternative to patching in 1998, and in five of the seven scenarios the combination of simultaneous atropine and patching would have been prescribed. In six of the seven scenarios, some type of nonspecific near work would now be prescribed as an adjunct treatment. CONCLUSION A change in practice patterns was observed for some, but not all, scenarios. In many scenarios, this change was directly attributed to the recent Pediatric Eye Disease Investigator Group trials.