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.

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.

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.

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.

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.

Tortuosity of arterioles and venules in quantifying plus disease.

BACKGROUND: Plus disease is the major criterion for laser treatment of retinopathy of prematurity. ROPtool is a computer program that traces retinal blood vessels and measures their tortuosity. Our objectives were to determine (1) whether examiners could accurately discriminate between arterioles and venules and (2) whether tortuosity sufficient for plus disease and pre-plus disease was assessed most accurately by considering arterioles, venules, or both. METHODS: One hundred retinal vessels were identified in 25 images randomly selected from 184 total images. Three pediatric ophthalmologists independently designated vessels as arteriole or venule. Seventy-seven images that had at least 1 traceable arteriole and venule in each quadrant were analyzed by ROPtool, and the results were compared with the consensus of 3 expert examiners. Receiver operating characteristics (ROC) curves were generated and areas under the curves calculated to quantify the diagnostic utility of ROPtool's assessment of tortuosity of arterioles, venules, and both. RESULTS: Three pediatric ophthalmologists agreed on the designation of arteriole or venule for 83 of 100 blood vessels. With the use of expert consensus as the reference standard, areas under the ROC curves for identification of tortuosity sufficient for plus disease were 0.91, 0.70, and 0.93 for arterioles, venules, and both, respectively. Areas under the ROC curves for identification of tortuosity sufficient for pre-plus disease were 0.91, 0.63, and 0.90 for arterioles, venules, and both, respectively. CONCLUSIONS: When considering whether tortuosity is sufficient for plus or pre-plus disease, the assessment of either arterioles alone or of arterioles and venules together resulted in high diagnostic accuracy.

Travoprost in children: adverse effects and intraocular pressure response.

Because of the limited ability to perform controlled, randomized studies in children, the safety and effectiveness of topical medications in pediatric glaucoma is sometimes difficult to determine. Although travoprost has been commercially available since 2001, there are no published reports on its use in children. This retrospective study found travoprost to have minimal adverse events in children and to reduce IOP in select cases of pediatric glaucoma.

Aqueous drainage device surgery in refractory pediatric glaucomas: I. Long-term outcomes.

PURPOSE: To determine the long-term outcomes and complications of aqueous drainage device surgery in children with congenital and aphakic glaucoma. METHODS: Chart review of consecutive children treated with aqueous drainage device surgery at Duke University Eye Center from 1995 to 2006, recording demographic, glaucoma-related, and anterior segment examination findings. RESULTS: Included are 30 children (38 eyes) with congenital glaucoma and 32 children (41 eyes) with aphakic glaucoma. Median follow-up was 5.5 years (0.5-10.5) in the congenital glaucoma group and 3.5 years (0.5-13.8) in the aphakic glaucoma group. Pre-aqueous drainage device median intraocular pressure (IOP) was 29 mmHg in the congenital glaucoma group and 36 mmHg in the aphakic glaucoma group. Post-aqueous drainage device median IOP was 14 and 15 mmHg in the congenital and aphakic glaucoma group, respectively (p < 0.0001 vs pre-aqueous drainage device IOP). Post-aqueous drainage device pupil abnormalities were noted in 16% and 7% of eyes in the congenital glaucoma and aphakic glaucoma groups, respectively, and cataract occurred in 20% of phakic eyes in the congenital glaucoma group. Reoperation was necessary in 26% and 22% of eyes in the congenital glaucoma and aphakic glaucoma groups, respectively. One-year Kaplan-Meier success was 92% and 90% in the congenital and aphakic glaucoma groups, respectively, but fell by 10 years to 42% and 55%, respectively. Vision-threatening complications occurred in 10% of eyes overall. DISCUSSION: Aqueous drainage device surgery is moderately successful in children with refractory congenital and aphakic glaucoma. Common complications include corneal touch and cataract; iris abnormalities occur less commonly.

Aqueous drainage device surgery in refractory pediatric glaucoma: II. Ocular motility consequences.

PURPOSE: To determine the prevalence of complications relating to ocular motility and alignment in children with refractory congenital and aphakic glaucoma treated with aqueous drainage device surgery. METHODS: Chart review of consecutive children treated with aqueous drainage devices at Duke University Eye Center from 1995 to 2006 for ocular motility abnormalities and strabismus as well as sensorimotor testing results before and after aqueous drainage device placement. RESULTS: Thirty-eight eyes of 30 children with congenital glaucoma and 41 eyes of 32 children with aphakic glaucoma were included. Optotype visual acuity testing could be performed in a minority of children preoperatively. After aqueous drainage device surgery, 14 and 20 eyes, respectively, were >20/100 in the congenital glaucoma and aphakic glaucoma groups. Only a few children had stereopsis or demonstrated binocular function on Worth 4-Dot testing in both groups before and after aqueous drainage device surgery. Horizontal and vertical strabismus was common, especially after aqueous drainage device surgery and occurred in 57% of congenital glaucoma patients and 47% of aphakic glaucoma patients. Motility limitation (both vertical and horizontal) was also common and occurred in 37% overall. DISCUSSION: Ocular motility abnormalities and strabismus were common in children after aqueous drainage device surgery. These potential problems should be considered when aqueous drainage device surgery is planned, especially in children with binocularity.

Retinopathy of prematurity in infants with birth weight>or=1250 grams-incidence, severity, and screening guideline cost-analysis.

PURPOSE: To determine the incidence and severity of retinopathy of prematurity (ROP) in infants with birth weight (BW) 1250 to 1800 g, to examine the influence of systemic conditions on the development of ROP in this population, and to evaluate the cost-effectiveness of various screening guidelines. METHODS: We reviewed records from 259 consecutive infants with BW 1250 to 1800 g who were screened for ROP over a 3-year period. Extracted data included presence and severity of ROP, and the following potential risk factors (RF) for ROP development: sepsis, meningitis, necrotizing enterocolitis, intraventricular hemorrhage greater than stage I, pneumothorax, direct bilirubin>2 mg/dl, central line placement, antibiotic treatment>14 days, greater than seven red blood cell (RBC) transfusions, and mechanical ventilation>96 hours. RESULTS: The overall incidence of ROP in this population was 4.2%. Two infants had stage 3 ROP, one with plus disease. Infants with stage 3 ROP had significantly lower BW (1299 versus 1484 g, P=0.013) and gestational age (GA) (28 versus 31 weeks, P=0.002) than those with no ROP. No infant with BW>1500 g developed treatable ROP. Conditions that best predicted ROP development in the 1501 to 1800 g BW group were sepsis, ventilation >96 hours, antibiotic use >14 days, RBC transfusions greater than seven units, and central line placement (P=0.001, P=0.001, P=0.012, P=0.014 and P=0.035, respectively). All infants with BW>1500 g who developed ROP had greater than or equal to two of these RF. CONCLUSIONS: All cases of high-risk ROP would have been identified by current screening guidelines. Modified screening criteria of infants with (1) BW