Evaluation of Quality of Systematic Reviews and Meta-Analyses Abstracts for Pediatric Strabismus Therapies.

PURPOSE: This study investigates the quality of systematic review abstracts through evaluation of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) abstract guideline adherence, Assessment for Multiple Systematic Reviews Tool (AMSTAR) quality rating, spin, abstract word count, and abstract structure. DESIGN: Cross-sectional study. METHODS: We searched MEDLINE, Embase, and the CEV@US database for articles related to pediatric strabismus. Inclusion criteria regarding pediatric strabismus studies were required to be in English, systematic reviews and/or meta-analyses, and patients less than eighteen years of age. From the search records, two investigators independently screened titles and abstracts to locate eligible reviews and extract study characteristics using AMSTAR-2 and pilot-tested Google forms. RESULTS: Searches retrieved 545 studies, of which 14 were eligible for data extraction. We found one form of spin in 1 abstract (of 14, 7.14%) of our included studies. 11/13 (84.62%) of studies failed to mention risk of bias assessment. There was no significant association between abstract characteristics and quality of the study. We found a significant correlation between AMSTAR-2 rating and PRISMA completion. CONCLUSIONS: Overall, a positive finding was that no spin was found within the abstracts of articles for pediatric strabismus therapies. PRISMA-A adherence was strongly associated with higher quality studies and should be considered for all systematic reviews in ophthalmology. Clinical research of pediatric strabismus is significantly limited in the number of studies present, as evidenced by our data. To improve the quality of abstract reporting, efforts from authors and journals are needed.

Flipped classroom approach to global outreach: cross-cultural teaching of horizontal strabismus to Chinese ophthalmology residents.

AIM: To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States. METHODS: Residents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018. Residents were instructed to watch a pre-class video lecture prior to the in-class-case-based activity. Content tests (5 Ophthalmic Knowledge Assessment Program style questions) and surveys were administered before and after the classroom sessions (100% response rate). These results were compared to that of an American cohort who were taught the same content. RESULTS: The Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents (92% vs 55%, P=0.04) and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style (P-values between 0.008 and <0.001). In both Chinese and American cohorts, we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session (P=0.025 for Chinese residents; P=0.001 for US residents), whereas scores in both groups for the esotropia course did not significantly improve. CONCLUSION: This is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting. The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge. Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings. Finally, the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19, although such a format requires further study.

Comparing the Diagnostic Utility of Conventional Direct Ophthalmoscopy with Smartphone Ophthalmoscopy among Medical Students.

Purpose To compare the diagnostic ability of medical students using smartphone ophthalmoscopy (SO) with conventional direct ophthalmoscopy (DO). Methods Twenty-eight first- and second-year medical students were trained to use the SO and DO. They also attended educational seminars regarding optic nerve and retinal pathology and were given hands-on practice with each ophthalmoscopy method. Students were randomized 2:1 into one of the groups (DO or SO). Students then examined six patients and recorded their findings, ease of use, and confidence level on a questionnaire. Two attending ophthalmologists, masked to the randomization, graded the student questionnaires. A priori power calculation determined the sample size. The primary outcome measure was the percentage of correct diagnoses the students made. Two-sample t -test, Wilcoxon's rank-sum test, and Fisher's exact test were used to compare the outcomes. Results Students using the SO outperformed students using DO in terms of mean percent correct (% correct) diagnosis (smartphone: 42% vs. direct: 23%; p -value = 0.0057), mean % correct photo match (smartphone: mean = 60% vs. direct: 32%; p -value = 0.0052), and mean % correct nerve/retinal descriptors (smartphone: 72% vs. direct: 59%; p -value = 0.0048). There was not a significant difference in terms of perceived ease of use (smartphone: mean = 3.3 vs. direct: mean = 2.6; p -value = 0.0945), or subjective confidence (smartphone: mean = 2.6 vs. direct: mean = 2.1; p -value = 0.0808) between the two groups. Conclusion SO provides an alternate way for medical students to learn, diagnose, and describe ocular pathology.

The flipped-classroom approach to teaching horizontal strabismus in ophthalmology residency: a multicentered randomized controlled study.

BACKGROUND: The flipped-classroom involves watching prerecorded lectures at home followed by group learning exercises within the classroom. This study compares the flipped classroom approach with the traditional classroom for teaching horizontal strabismus didactics in ophthalmology residency. METHODS: In this multicenter, randomized controlled survey study from October 2017 to July 2018, 110 ophthalmology residents were taught esotropia and exotropia sequentially, randomized by order and classroom style. Flipped classroom participants were assigned a preclass video lecture prior to the in-class case-based activity. The traditional classroom included a preparatory reading assignment and an in-person lecture. Residents completed three identical 5-question assessments (pretest, post-test, and 3-month retention) and surveys for each classroom. The primary outcome measured residents' preferences for classroom styles; the secondary outcome compared knowledge acquisition. RESULTS: In our study cohort, the flipped classroom resulted in greater at-home preparation than the traditional classroom (P = 0.001) and was preferred by 33 of 53 residents (62%); 45 of 53 (85%) wished to see the flipped classroom used at least 25% of the time. The exotropia flipped classroom scored higher than traditional classroom on the pretest (3.71/5 [74%] vs 2.87/5 [57%]; P < 0.001) and post-test (4.53/5 [91%] vs 4.13/5 [83%]; P = 0.01) but not the 3-month retention test (3.53/5 [71%] vs 3.37/5 [67%]; P = 0.48). The esotropia classroom styles did not differ on pre- or post-test but demonstrated higher scores for the traditional classroom at 3-month retention (3.43/5 [69%] vs 2.92/5 [58%]; P = 0.03). Advantages cited for flipped classroom include being interactive and engaging while incentivizing better classroom preparation. CONCLUSIONS: The flipped classroom method was received favorably by trainees and may complement traditional methods of teaching.

Incidence and Management of Glaucoma or Glaucoma Suspect in the First Year After Pediatric Lensectomy.

Importance: Glaucoma can occur following cataract removal in children, and determining the risk for and factors associated with glaucoma and glaucoma suspect in a large cohort of children after lensectomy can guide clinical practice. Objective: To estimate the incidence of glaucoma and glaucoma suspect and describe its management in the first year following lensectomy in children before 13 years of age. Design, Setting, and Participants: A multicenter clinical research registry containing data for 1361 eyes of 994 children who underwent unilateral or bilateral lensectomy between June 2012 and July 2015 at 1 of 61 sites in the United States (n = 57), Canada (n = 3), and the United Kingdom (n = 1). Patients were eligible for inclusion in the study if they were enrolled in the registry within 45 days after lensectomy and had at least 1 office visit between 6 and 18 months after lensectomy. Patient data were reviewed, and glaucoma and glaucoma suspect were diagnosed by investigators using standardized criteria. Statistical analysis was performed between June 2017 and August 2019. Exposures: Clinical care 6 to 18 months after lensectomy. Main Outcomes and Measures: Incidence risk using standardized definitions of glaucoma and glaucoma suspect after lensectomy. Results: Among 702 patients included in this cohort study, 353 (50.3%) were male and 427 (60.8%) were white; mean age at lensectomy was 3.4 years (range, 0.04-12.9 years). After lensectomy, glaucoma or glaucoma suspect was diagnosed in 66 of 970 eyes (adjusted overall incidence risk, 6.3%; 95% CI, 4.8%-8.3%). Glaucoma was diagnosed in 52 of the 66 eyes, and glaucoma suspect was diagnosed in the other 14 eyes. Mean age at lensectomy in these 66 eyes was 1.9 years (range, 0.07-11.2 years), and 40 of the 66 (60.6%) were eyes of female patients. Glaucoma surgery was performed in 23 of the 66 eyes (34.8%) at a median of 3.3 months (range, 0.9-14.8 months) after lensectomy. The incidence risk of glaucoma or glaucoma suspect was 15.7% (99% CI, 10.1%-24.5%) for 256 eyes of infants 3 months or younger at lensectomy vs 3.4% (99% CI, 1.9%-6.2%) for 714 eyes of infants older than 3 months (relative risk, 4.57; 99% CI, 2.19-9.57; P < .001) and 11.2% (99% CI, 7.6%-16.7%) for 438 aphakic eyes vs 2.6% (99% CI, 1.2%-5.6%) for 532 pseudophakic eyes (relative risk, 4.29; 99% CI, 1.84-10.01; P < .001). No association was observed between risk of developing glaucoma or glaucoma suspect and any of the following variables: sex, race/ethnicity, laterality of lensectomy, performance of anterior vitrectomy, prelensectomy presence of anterior segment abnormality, or intraoperative complications. Conclusions and Relevance: This study found that glaucoma or glaucoma suspect developed in a small number of eyes in the first year after lensectomy and may be associated with aphakia and younger age at lensectomy. Frequent monitoring for signs of glaucoma following lensectomy is warranted, especially in infants 3 months or younger at lensectomy and in children with aphakia after lensectomy.

The flipped-classroom approach to teaching horizontal strabismus in ophthalmology residency: a pilot study.

PURPOSE: To compare the flipped classroom (home pre-taped lectures followed by in-class group exercise) to the traditional classroom (home reading assignment followed by in-class lecture) for horizontal strabismus didactics in ophthalmology residency. METHODS: All PGY2-4 residents from four U.S. ophthalmology residencies without prior residency flipped-classroom experience were invited to esotropia and exotropia sessions sequentially, with random order and assignment to flipped and traditional classrooms. Content test scores before and after the two classrooms were compared. Surveys were administered to assess participant experience. RESULTS: A total of 40 residents attended each session. Likert scale evaluation of preparatory material and classroom activity did not differ between sessions; however, divided by year of training, 70% of senior residents (PGY3-4) and 39% of first-year (PGY2) residents preferred the flipped classroom over the traditional classroom. Pre- and post-test scores for the flipped classroom exceeded those of the traditional classroom for the exotropia course (P = 0.01 and P = 0.001, resp.) but not for the esotropia course. There was significant improvement between pre- and post-tests for both styles of learning. CONCLUSIONS: The flipped classroom had a favorable effect on test scores for only one of the two strabismus subjects but was preferred over the traditional classroom among PGY3-4 residents.

Angiopoietin-1 is required for Schlemm's canal development in mice and humans.

Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemm's canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed by functional analysis of ANGPT1 variants in a combined in silico, in vitro, and in vivo approach, supporting a causative role for ANGPT1 in disease. By linking ANGPT1 with PCG, these results highlight the importance of ANGPT/TEK signaling in glaucoma pathogenesis and identify a candidate target for therapeutic development.

Reduced penetrance in a large Caucasian pedigree with Stickler syndrome.

BACKGROUND: In a four-generation Caucasian family variably diagnosed with autosomal dominant (AD) Stickler or Wagner disease, commercial gene screening failed to identify a mutation in COL2A1 or VCAN. We utilized linkage mapping and exome sequencing to identify the causal variant. MATERIALS AND METHODS: Genomic DNA samples collected from 40 family members were analyzed. A whole-genome linkage scan was performed using Illumina HumanLinkage-24 BeadChip followed by two-point and multipoint linkage analyses using FASTLINK and MERLIN. Exome sequencing was performed on two affected individuals, followed by co-segregation analysis. RESULTS: Parametric multipoint linkage analysis using an AD inheritance model demonstrated HLOD scores > 2.00 at chromosomes 1p36.13-1p36.11 and 12q12-12q14.1. SIMWALK multipoint analysis replicated the peak in chromosome 12q (peak LOD = 1.975). FASTLINK two-point analysis highlighted several clustered chromosome 12q SNPs with HLOD > 1.0. Exome sequencing revealed a novel nonsense mutation (c.115C>T, p.Gln39*) in exon 2 of COL2A1 that is expected to result in nonsense-mediated decay of the RNA transcript. This mutation co-segregated with all clinically affected individuals and seven individuals who were clinically unaffected. CONCLUSIONS: The utility of combining traditional linkage mapping and exome sequencing is highlighted to identify gene mutations in large families displaying a Mendelian inheritance of disease. Historically, nonsense mutations in exon 2 of COL2A1 have been reported to cause a fully penetrant ocular-only Stickler phenotype with few or no systemic manifestations. We report a novel nonsense mutation in exon 2 of COL2A1 that displays incomplete penetrance and/or variable age of onset with extraocular manifestations.

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity.

Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin-TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm's canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity.

Pediatric Ophthalmologists' Experiences With Abusive Head Trauma.

PURPOSE: To estimate the number of cases of abusive head trauma seen by pediatric ophthalmologists and analyze factors associated with physician subpoenas and court testimonies. METHODS: Pediatric ophthalmologists were surveyed about their experiences with abusive head trauma. The survey was sent to 875 active members of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS). RESULTS: The response rate was 15% (132 surveys). The median pediatric ophthalmologist is consulted 10.0 (interquartile range [IQR] = 4.0 to 19.0) times per year to evaluate patients for abusive head trauma and sees 2.5 (IQR = 1.0 to 6.0) patients with probable abusive head trauma each year. Pediatric ophthalmologists were equally likely to be subpoenaed (4.6% vs 4.8%, P = .84) or to testify (1.9% vs 1.7%, P = .79) whether they did or did not perform retinal photography. Physicians were equally likely to be subpoenaed (4.8% vs 7.1%, P = .92) or to testify (2.2% vs 0.0%, P = .17) whether a child abuse team was involved in patient care or not. Geographic location had no statistical significance on how frequently pediatric ophthalmologists were subpoenaed (P = .17) or testified in court (P = .12). When a pediatric ophthalmologist was subpoenaed to court, the median number of missed clinic days was 1.0 (IQR = 1.0 to 2.0), with an estimated cost of $3,000 (IQR = $1,750 to $4,750) in lost revenue. CONCLUSIONS: Obtaining retinal imaging, having a child abuse team, and geographic location had no significant relationship with how often pediatric ophthalmologists were subpoenaed or testified in court.

Ocular and histologic findings in a series of children with infantile pompe disease treated with enzyme replacement therapy.

PURPOSE: To report the ophthalmologic and histologic findings in a series of children with infantile Pompe disease treated with enzyme replacement therapy (ERT). METHODS: Records of children with infantile Pompe disease treated with ERT who had at least one complete ophthalmic examination and the ocular histopathology of children with infantile Pompe disease who were treated with ERT were reviewed. The patients' clinical history, including external ocular examination, ocular alignment and motility, dilated fundus examination, and cycloplegic refraction, was evaluated. A literature review was performed for ophthalmologic findings in infantile Pompe disease using PubMed. RESULTS: The clinical findings of 13 children were included and the ocular histopathology of 3 children with infantile Pompe disease who were treated with ERT were reviewed. Forty-six percent (6 of 13) had bilateral ptosis, 23% (3 of 13) had strabismus, 62% (8 of 13) had myopia, and 69% (9 of 13) had astigmatism. On histologic examination, there was vacuolar myopathy affecting the extraocular muscles, ciliary body, and iris smooth muscle and glycogen accumulation in corneal endothelial, lens epithelium, and retinal ganglion cells, and within lysosomes of scleral fibroblasts. CONCLUSIONS: It is important that ophthalmic providers are aware of the high prevalence of myopia, astigmatism, and ptosis in children with infantile Pompe disease treated with ERT because they are potentially amblyogenic but treatable factors.

Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants.

PURPOSE: To determine genetic variants associated with severe retinopathy of prematurity (ROP) in a candidate gene cohort study of US preterm infants. METHODS: Preterm infants in the discovery cohort were enrolled through the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, and those in the replication cohort were from the University of Iowa. All infants were phenotyped for ROP severity. Because of differences in the durations of enrollment between cohorts, severe ROP was defined as threshold disease in the discovery cohort and as threshold disease or type 1 ROP in the replication cohort. Whole genome amplified DNA from stored blood spot samples from the Neonatal Research Network biorepository was genotyped using an Illumina GoldenGate platform for candidate gene single nucleotide polymorphisms (SNPs) involving angiogenic, developmental, inflammatory, and oxidative pathways. Three analyses were performed to determine significant epidemiologic variables and SNPs associated with levels of ROP severity. Analyses controlled for multiple comparisons, ancestral eigenvalues, family relatedness, and significant epidemiologic variables. Single nucleotide polymorphisms significantly associated with ROP severity from the discovery cohort were analyzed in the replication cohort and in meta-analysis. RESULTS: Eight hundred seventeen infants in the discovery cohort and 543 in the replication cohort were analyzed. Severe ROP occurred in 126 infants in the discovery and in 14 in the replication cohort. In both cohorts, ventilation days and seizure occurrence were associated with severe ROP. After controlling for significant factors and multiple comparisons, two intronic SNPs in the gene BDNF (rs7934165 and rs2049046, P < 3.1 × 10(-5)) were associated with severe ROP in the discovery cohort and were not associated with severe ROP in the replication cohort. However, when the cohorts were analyzed together in an exploratory meta-analysis, rs7934165 increased in associated significance with severe ROP (P = 2.9 × 10(-7)). CONCLUSIONS: Variants in BDNF encoding brain-derived neurotrophic factor were associated with severe ROP in a large candidate gene study of infants with threshold ROP.

Mutations in SCO2 are associated with autosomal-dominant high-grade myopia.

Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development.

Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes.

PURPOSE: Stickler syndrome is an arthro-ophthalmopathy with phenotypic overlap with Wagner syndrome. The common Stickler syndrome type I is inherited as an autosomal dominant trait, with causal mutations in collagen type II alpha 1 (COL2A1). Wagner syndrome is associated with mutations in versican (VCAN), which encodes for a chondroitin sulfate proteoglycan. A three-generation Caucasian family variably diagnosed with either syndrome was screened for sequence variants in the COL2A1 and VCAN genes. METHODS: Genomic DNA samples derived from saliva were collected from all family members (six affected and four unaffected individuals). Complete sequencing of COL2A1 and VCAN was performed on two affected individuals. Direct sequencing of remaining family members was conducted if the discovered variants followed segregation. RESULTS: A base-pair substitution (c.258C>A) in exon 2 of COL2A1 cosegregated with familial disease status. This known mutation occurs in a highly conserved site that causes a premature stop codon (p.C86X). The mutation was not seen in 1,142 ethnically matched control DNA samples. CONCLUSIONS: Premature stop codons in COL2A1 exon 2 lead to a Stickler syndrome type I ocular-only phenotype with few or no systemic manifestations. Mutation screening of COL2A1 exon 2 in families with autosomal dominant vitreoretinopathy is important for accurate clinical diagnosis.

CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States.

PURPOSE: To screen primary congenital glaucoma patients in the United States for sequence variants within the CYP1B1, LTBP2, and MYOC genes using Sanger and whole exome sequencing. DESIGN: Retrospective case-control study. METHODS: Fifty-seven primary congenital glaucoma patients (47 families), 71 unaffected family members of the primary congenital glaucoma probands, and 101 healthy unrelated individuals were recruited from a single institution. Sanger sequencing of the primary congenital glaucoma gene, CYP1B1, was performed on 47 proband deoxyribonucleic acid samples. Simultaneously, whole exome sequencing was conducted on 3 families, each including more than 1 affected individual. Concurrently, 33 of 47 primary congenital glaucoma probands with extended family deoxyribonucleic acid samples were screened for LTBP2 and MYOC gene mutations. Exome-sequenced variations were validated by additional Sanger sequencing to confirm segregation of filtered disease-causing single nucleotide variations. RESULTS: Seven primary congenital glaucoma families (14.9%) manifested disease phenotypes attributable to CYP1B1 mutations. One primary congenital glaucoma family possessed homozygous mutant alleles, whereas 6 families carried compound heterozygous mutations. Five novel combinations of compound heterozygous mutations were identified, of which 2 combinations were found with whole exome sequencing. No disease-causing mutations within the LTBP2 and MYOC genes were discovered. CONCLUSIONS: This study analyzed CYP1B1, LTBP2, and MYOC mutations in a cohort of primary congenital glaucoma patients from the United States, applying whole exome sequencing as a complementary tool to Sanger sequencing. Whole exome sequencing, coupled with Sanger sequencing, may identify novel genes in primary congenital glaucoma patients who have no mutations in known primary congenital glaucoma genes.

The effects of D-penicillamine on a murine model of oxygen-induced retinopathy.

PURPOSE: To determine the effect of intraperitoneal and intravitreal D-penicillamine (DPA) on retinal neovascularization in a murine model of oxygen-induced retinopathy. METHODS: On postnatal day 7, 16 mice were injected intraperitoneally with 300 mg/kg/day DPA for 3 days followed by 50 mg/kg/day for 7 days. A different group of 7 mice were injected intraperitoneally with 600 mg/kg/day DPA for 3 days followed by 100 mg/kg/day for 7 days. A third group of 14 mice were injected with 1,500 mg/kg/day DPA for 2 days; a control cohort of 17 mice received intraperitoneal phosphate-buffered saline (PBS). An additional 15 mice underwent intravitreal injection of 1 µL of 100 mg/mL DPA in the right eye and 1 µL PBS intravitreally in the left eye as a control. All groups were placed in a 75% oxygen chamber for 7 days then room air for 3 days before being sacrificed and enucleated. The retinas were stained and flat-mounted to determine the severity of retinal neovascularization by quantifying neovascular buds. RESULTS: After intraperitoneal injection, the mean number of glomeruli and tubules was similar in the DPA and PBS groups (P = 1.0), regardless of DPA dosage. The dosage of 1,500 mg/kg/day proved to be uniformly lethal. After intravitreal injections, the mean number of glomeruli (P = 0.16) and tubules (P = 0.7) were similar in the DPA and PBS groups. CONCLUSIONS: Neither intraperitoneal nor intravitreal injection of DPA inhibits retinal neovascularization in a murine model of oxygen-induced retinopathy.

The accuracy of photoscreening at detecting treatable ocular conditions in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) have an increased prevalence of ocular disorders, including amblyopia, strabismus, and refractive error. Health maintenance guidelines from the Down Syndrome Medical Interest Group recommend ophthalmologic examinations every 1 to 2 years for these children. Photoscreening may be a cost-effective option for subsequent screening evaluations after an initial complete examination, but no study has evaluated the accuracy of photoscreening in children with DS. The purpose of this study is to determine the sensitivity, specificity, and positive and negative predictive values of photoscreening in detecting treatable ocular conditions in children with DS. METHODS: Photoscreening and complete ophthalmologic evaluations were performed in 50 consecutive 3- to 10-year-old children with DS. Sensitivity, specificity, and positive and negative predictive values were calculated with the use of ophthalmologic examination findings as the reference standard. RESULTS: Most children were able to complete photoscreening (94% with Medical Technology and Innovations [MTI] and 90% with Visiscreen OSS-C [VR]). Many children had an identified diagnosis on ophthalmologic examination (n = 46, 92%). Of these, approximately one-half (n = 27, 54%) had one or more condition(s) requiring treatment. Both the MTI and VR photoscreening devices had a sensitivity of 93% (95% confidence interval 0.76-0.99) for detecting treatable ocular conditions. The specificities for the MTI and VR photoscreening were 0.35 (0.18-0.57) and 0.55 (0.34-0.74), respectively. CONCLUSIONS: Photoscreening is sensitive but less specific at detecting treatable ocular conditions in children with DS. In specific instances, the use of photoscreening in the DS population has the potential to save time and expense related to routine eye examinations, particularly in children with a normal baseline comprehensive examination.

Clinical and histologic ocular findings in pompe disease.

PURPOSE: Limited information is available on the ocular findings in patients with Pompe disease. METHOD: This study summarizes this information with a systematic literature review; reports the ocular histologic findings seen in a deceased infant with Pompe disease who was receiving enzyme replacement therapy and in a deceased adult with late-onset Pompe disease; and notes the new observation of ptosis in children with infantile-onset Pompe disease who are receiving enzyme replacement therapy. RESULTS: Six articles were found on the ultrastructural-histopathologic eye findings in Pompe disease. Previously reported clinical ocular findings included strabismus and ptosis. Glycogen accumulation and vacuolar myopathy have been seen histologically. CONCLUSION: Based on these clinical and histologic reports, patients with Pompe disease may have an increased incidence of ocular abnormalities, such as ptosis and strabismus, and therefore should undergo ophthalmologic examination.

Latanoprost in pediatric glaucoma--pediatric exposure over a decade.

BACKGROUND: Although numerous studies of latanoprost in adult glaucoma have shown it to be an effective hypotensive agent with a low incidence of side effects, these issues have not been well studied in pediatric glaucomas. The purpose of the current study is to evaluate the safety and intraocular pressure (IOP) lowering effect of latanoprost in various pediatric glaucomas over a long period. SUBJECTS AND METHODS: This retrospective study included all children treated with latanoprost at our institution from 1996 to 2007. Demographic, glaucoma-related, and side-effect information was recorded for each subject. Duration of latanoprost exposure was calculated in child-months (1 child exposed for 1 month). If interpretable IOP data were available, the presence or absence of a treatment response (IOP reduction > or =15% from baseline) was determined for each subject. RESULTS: A total of 115 subjects with latanoprost exposure were identified, with a collective exposure of 2,325 child-months. Exposure for > or =1 year occurred in 52 subjects. Side effects were mild and infrequently reported. Of the 115 subjects, 63 had interpretable IOP data, and 22 (35%) were treatment responders. Predictors of a response included a diagnosis of juvenile open-angle glaucoma, monotherapy, and older age. CONCLUSIONS: This large study of latanoprost-treated children confirms the excellent safety profile of the drug in the treatment of pediatric glaucoma. The study also confirms latanoprost's IOP-lowering ability in older children with juvenile open-angle glaucoma and in some children with aphakic glaucoma. Prospective studies are needed to better define the optimal role of latanoprost in the treatment of pediatric glaucoma, especially congenital glaucoma.