Faruk H. Orge

A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity.

OBJECTIVE Retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina in preterm infants, is associated with multiple factors, including oxygenation level. We explored whether the common intermittent hypoxemic events in preterm infants are associated with the development of ROP. STUDY DESIGN Oxygen desaturation events were quantified in 79 preterm infants (gestational age, 24 to 27-6/7 weeks) during the first 8 weeks of life. Infants were classified as requiring laser treatment for ROP versus having less severe or no ROP. A linear mixed model was used to study the association between the incidence of intermittent hypoxia and laser treatment of ROP, controlling for gestational age, sex, race, multiple births, and initial severity of illness. RESULTS For all infants, hypoxemic events increased with postnatal age (P<.001). Controlling for all covariates, a higher incidence of oxygen desaturation events was found in the infants undergoing laser therapy for ROP (P<.001), males (P<.02), and infants of younger gestational age (P<.003). CONCLUSIONS The incidence of hypoxemic events was higher in infants with ROP requiring laser therapy. Therapeutic strategies to optimize oxygenation in preterm infants should include minimization of desaturation episodes, which may in turn decrease serious morbidity in this high-risk population.

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.

Resolution of congenital nasolacrimal duct obstruction with nonsurgical management

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

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.

Hypoxia-hyperoxia paradigms in the development of oxygen-induced retinopathy in a rat pup model.

BACKGROUND Retinopathy of prematurity [ROP] continues to be a significant clinical problem in preterm infants. There is a need for animal models to better understand the roles of hypoxia/hyperoxia in the pathogenesis and management of ROP. OBJECTIVES To test the hypothesis that multiple daily cycles of intermittent hypoxia, followed by brief hyperoxia, would provide a clinically relevant protocol for generation of ROP in a rat pup. METHODS Rat pups were exposed for the first 14 days to one of three protocols: room air [RA], sustained cycles of hyperoxia/hypoxia [SHH] as previously employed to produce ROP in rat pups, and intermittent hypoxia/hyperoxia [IHH] in order to more closely simulate clinical conditions in preterm infants. Retinae were obtained at 18 days and imaged for both avascularization and neovascularization. RESULTS As expected, the SHH group demonstrated significantly increased avascularity [40.9 ± 7.9% of retina] which was minimal in both RA and IHH groups. All SHH exposed pups exhibited neovascularization which occurred in 5/7 IHH exposed retinae versus 0 in the RA group [p = 0.02]. However, mean number of clock hours of neovascularization after IHH was 1.9 ± 2.1 which did not differ from the RA group, and was less than in the SHH group [8.3 ± 1.9, p < 0.001]. CONCLUSION A more clinically relevant intermittent hypoxia/hyperoxia [IHH] protocol does not produce the same degree of ROP as the traditional sustained hypoxia/hyperoxia [SHH] paradigm. Nonetheless, further refinement of our model may provide a suitable model for understanding the lesser degrees of ROP which predominate in preterm infants.

Comparison of fentanyl and morphine in laser surgery for retinopathy of prematurity

PURPOSE To compare complication rates of the analgesics fentanyl and morphine in preterm infants undergoing laser therapy for retinopathy of prematurity (ROP). METHODS In this observational study, the medical records of consecutive preterm neonates undergoing laser treatment of ROP from June 2007 through September 2010 were retrospectively reviewed. Because a fentanyl-based infusion protocol was initiated in November 2009, there was approximately the same number of treatment sessions with morphine and with fentanyl. In both groups, midazolam was used additionally on a case-by-case basis. Analgesia type, complications, and vital signs were documented at 5-minute intervals for all surgeries. The primary outcome was change in ventilation status. Secondary complications included change in temperature and incidence of apneic, bradycardic, and desaturation events. RESULTS A total of 35 patients were included, with 17 in the morphine group (mean gestational age, 24.8 weeks; mean birth weight, 661 g) and 18 in the fentanyl group (mean gestational age, 24.4 weeks; mean birth weight, 681 g). Overall worsening of ventilation status was noted in 29% of patients in the morphine group and 6% of patients in the fentanyl group (P = 0.08; 95% confidence interval, -2% to 48%). Temperature instability (outside of 36.5° to 37.4°C range) was noted in 6% of patients in the morphine group and no patients in the fentanyl group. Apneic events were 3.2 times more common and bradycardic events 1.5 times more common in the morphine group. CONCLUSIONS We found no difference in safety parameters for fentanyl infusion or morphine for analgesia in preterm infants undergoing ROP laser therapy in the neonatal intensive care unit setting. Although estimates of complication rates suggest that fentanyl may be safer, further study is needed to confirm this premise.

Ocular manifestations of X-linked dominant FAM58A mutation in toe syndactyly, telecanthus, anogenital, and renal malformations ('STAR') syndrome.

ABSTRACT Purpose: To report the newest ophthalmic manifestations of a mother-daughter pair diagnosed with toe syndactyly, telecanthus, anogenital and renal malformations (STAR) syndrome, a rare X-linked developmental disorder. Methods: The medical and ophthalmic records were reviewed for a mother-daughter pair diagnosed with FAM58A confirmed STAR syndrome on chromosome Xq28. Results: The mother at birth had left foot syndactyly, telecanthus, anal stenosis, and clitoromegaly and was told at 19 she had a hypoplastic left kidney. The daughter, born at 38 weeks after a complication of oligohydramnios, had a more severe presentation, demonstrating toe syndactyly, telecanthus, anal stenosis, clitoromegaly, bilateral renal hypoplasia, ureteral reflux, urogenital sinus, and congenital heart disease amongst others. The pair shared similar ophthalmic findings, though those of the daughter were more pronounced. They included bilateral, medial upper eyelid prominences with madarosis, mild peripapillary atrophy, and soft macular drusen with the daughter also displaying optic nerve hypoplasia and peripheral anterior synechia in the iridocorneal angle. Conclusion: These ophthalmic findings are the first reported to our knowledge in association with STAR syndrome. The literature frequently demonstrates that patients with developmental anomalies often have ocular manifestations, warranting a full ophthalmic examination when the diagnosis of STAR syndrome has been made or is being considered.

Corneal Changes in Children after Unilateral Cataract Surgery in the Infant Aphakia Treatment Study

PURPOSE We report endothelial cell (EC) characteristics and central corneal thickness (CCT) from the Infant Aphakia Treatment Study (IATS) patients at the 5-year examination. DESIGN Randomized, controlled trial of the treatment of unilateral cataract with aphakic contact lens (CL) versus primary intraocular lens (IOL) implant. PARTICIPANTS A total of 114 infants with unilateral cataract. METHODS The EC density, coefficient of variation (CV), and percent hexagonal cells were measured by noncontact specular microscopy. The CCT was measured using contact pachymetry. Fellow eyes served as controls. MAIN OUTCOME MEASURES Mean differences between treated and fellow eyes of CL and IOL groups were compared with a paired t test. A 1-way analysis of variance model and the Tukey-Kramer multiple comparison procedure were used to assess the effect of a diagnosis of glaucoma or glaucoma suspect. RESULTS A total of 105 subjects (52 with CLs, 53 with IOLs) had specular microscopy or corneal thickness data recorded. Mean EC densities were higher in aphakic eyes compared with fellow eyes (3921 vs. 3495 cells/mm2, P<0.0001). Mean CV was higher (27 vs. 24, P=0.0002) and mean percent hexagonal cells was lower (72% vs. 76%, P=0.002) in aphakic eyes compared with fellow eyes. Mean CCT of aphakic eyes was higher than in controls (637 vs. 563 μm, P<0.0001). There was no difference in EC density in eyes treated with IOLs compared with fellow eyes (3445 and 3487 cells/mm2, P=0.68). Means for CV (25 vs. 24, P=0.07) and percent hexagonal cells (74 vs. 76%, P=0.27) were also not significantly different. Mean CCT was higher in eyes with IOLs (605 vs. 571 μm, P<0.0001) compared with fellow eyes. Compared with treated eyes without glaucoma or glaucoma suspect, treated eyes with glaucoma had lower EC density (3289 vs. 3783 cells/mm2, P=0.03) and treated eyes with glaucoma suspect had greater mean corneal thickness (660 vs. 612 μm, P=0.0036). CONCLUSIONS Cataract extraction during infancy with IOL implantation was not associated with a reduced EC count in treated compared with fellow eyes, although CCT was increased. Extended-wear aphakic CLs may cause corneal polymegathism with increased EC density and CCT. Glaucoma diagnosis was associated with reduced EC counts and increased CCT.

Canalicular laceration repair using a viscoelastic injection to locate and dilate the proximal torn edge.

BACKGROUND Canalicular lacerations are common complications of eyelid trauma in the pediatric population. Irrigating air, water, and colored or viscous agents through the intact canaliculus have been suggested to identify the torn proximal edge. We report our experience in repairing canalicular lacerations using a novel viscoelastic injection technique with a Monoka monocanalicular stent. METHODS The medical records of patients <18 years of age who underwent repair of a canalicular laceration with a monocanalicular stent using superficial viscoelastic deployment to locate the torn canaliculus were retrospectively reviewed. Demographics, cause of eyelid injury, surgical management using our novel viscoelastic injection technique, and outcome were analyzed. RESULTS A total of 38 children with lid lacerations were identified, of whom the 17 with canalicular involvement were included (mean age, 6.27 years). Canalicular injury in these 17 was due to dog bite (9 patients) and shearing trauma (8 patients). In 11 patients, the injury was located in the lower lid; in 4, the upper lid; and in 2, combined upper and lower lids. All patients had good anatomic repair and on follow-up had negative dye disappearance tests and were free of tearing. CONCLUSIONS Deploying viscoelastic superficially near, and injecting into the injured canaliculus can improve visualization of the operative field by retracting the surrounding tissue and tamponading any bleeding, which aids in location and dilation of the torn canaliculus initially and in subsequent steps, eases intubation into the lubricated torn canaliculus and nasolacrimal duct, and avoids iatrogenic injury to an uninjured canaliculus.

The Lacrimal System

The lacrimal system comprises of a series of anatomical structures with specific physiologic properties. Tearing from a nasolacrimal duct obstruction (NLDO) is the most common lacrimal system abnormality encountered by pediatric ophthalmologists. Most NLDOs spontaneously improve with conservative management by 12 months of age, but persistent or atypical cases may be treated with a procedure consisting of probing and irrigation of the lacrimal system. Other less common but significant lacrimal system abnormalities are also discussed.