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Pediatric Ophthalmology

Pediatric Ophthalmology | 275 Publications
Tischfield M, Robson C, Gilette N, Chim SM, Sofela F, DeLisle M, Gelber A, Barry B, MacKinnon S, Dagi L, Nathans J, Engle E. Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev Cell. 2017;42(5):445–461.e5.
Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs). Inactivation of Bmp2 and Bmp4 in preosteoblasts and periosteal dura causes skull and CV malformations, similar to humans harboring TWIST1 mutations. Notably, arterial development appears normal, suggesting that morphogens from the skull and dura establish optimal venous networks independent from arterial influences. Collectively, our work establishes a paradigm whereby CV malformations result from primary or secondary loss of paracrine BMP signaling from preosteoblasts and dura, highlighting unique cellular interactions that influence tissue-specific angiogenesis in mammals.
Heidary G. Neuro-Ophthalmic Manifestations of Pediatric Neurodegenerative Disease. J Neuroophthalmol. 2017;37 Suppl 1:S4-S13.
The topic of pediatric neurodegenerative disease is broad and ever expanding. Children who suffer from neurodegenerative disease often have concomitant visual dysfunction. Neuro-ophthalmologists may become involved in clinical care to identify corroborating eye findings when a specific condition is suspected, to monitor for disease progression, and in some cases, to assess treatment efficacy. Ophthalmic findings also may be the harbinger of a neurodegenerative process so a keen awareness of the possible manifestations of these conditions is important. The purpose of this review is to highlight common examples of the neuro-ophthalmic manifestations of pediatric neurodegenerative disease using a case-based approach in an effort to provide a framework for approaching these complex patients.
Agyemang AA, Sveinsdóttir K, Vallius S, Sveinsdóttir S, Bruschettini M, Romantsik O, Hellström A, Smith L, Ohlsson L, Holmqvist B, Gram M, Ley D. Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?. Transl Stroke Res. 2017;
Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.
Yonekawa Y, Wu WC, Nitulescu C, Chan P, Thanos A, Thomas B, Todorich B, Drenser K, Trese M, Capone A. PROGRESSIVE RETINAL DETACHMENT IN INFANTS WITH RETINOPATHY OF PREMATURITY TREATED WITH INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB. Retina. 2018;38(6):1079–1083.
PURPOSE: Fibrovascular contraction and tractional retinal detachment (TRD) are recognized complications associated with the use of anti-vascular endothelial growth factor agents in vasoproliferative vitreoretinopathies. The authors characterize TRDs that developed after intravitreal bevacizumab or ranibizumab therapy for vascularly active retinopathy of prematurity. METHODS: This is an international, multicenter, interventional, retrospective, case series. Thirty-five eyes from 23 infants were included. Inclusion required anti-vascular endothelial growth factor treatment of Type 1 retinopathy of prematurity with progression to TRD. RESULTS: Mean gestational age was 26 ± 2 weeks, and mean birth weight was 873 ± 341 g. Mean postmenstrual age on the day of injection was 35 ± 2 weeks. Retinal detachment was noted a mean of 70 days (median, 34; range, 4-335) after injection. Eleven percent detached within 1 week, 23% within 2 weeks, and 49% within 4 weeks. The highest stage of retinopathy of prematurity noted was 4A in 29%, 4B in 37%, and 5 in 34% of eyes. Time to RD negatively correlated with postmenstrual age at the time of injection (Rho = -0.54; P 0.01). Three TRD configurations were observed: 1) conventional peripheral elevated ridge or volcano-shaped Stage 5 detachment, 2) midperipheral detachment with tight circumferential vectors, and 3) very posterior detachment with prepapillary contraction. Full or partial reattachment was achieved with surgical intervention in 86% of eyes. CONCLUSION: Progressive atypical TRD may occur after anti-vascular endothelial growth factor injections for retinopathy of prematurity. The configuration of the detachment varies with the extent of primary retinal vascularization present at the time of treatment.
Phanphruk W, Alkharashi M, Bilge A, Hunter D. Sedated suture adjustment in children undergoing adjustable-suture strabismus surgery. J AAPOS. 2017;
PURPOSE: To study methods and adverse events of postoperative, sedated suture adjustment after strabismus surgery in the post-anesthesia care unit (PACU). METHODS: We reviewed the postoperative experience of all children ≤18 years of age undergoing adjustable suture strabismus surgery at Boston Children's Hospital over a 3-year period. Time in the hospital, adverse events, and surgical outcomes were reviewed to evaluate safety and healthcare resource utilization. RESULTS: Of 356 patients, 113 required suture adjustment in the PACU, including 24 adjusted while awake and 89 adjusted under sedation. For sedation, sequential boluses of propofol were administered until adjustment was complete. Complete data from the sedated adjustment was available in 76 patients. The median initial bolus was 30 mg; the median total propofol rate was 273 mcg/kg/min. Twelve patients (16%) required only a single bolus of propofol. Of remaining 64 patients, median time from initial to final propofol dose was 7 minutes. Median anesthesiologist time in the PACU was 13 minutes. In the sedated adjustment group, there were no clinically significant adverse events, and the pain score never exceeded 6 (of a possible 10). Median duration of PACU stay was shortest in the group not requiring adjustment. CONCLUSIONS: Sedated suture adjustment allows for fine-tuning of postoperative binocular alignment in children and uncooperative adults. No adverse events were observed in our study group, but the procedure does increase the time patients spend in the hospital. This work will inform disclosure of risks and benefits of sedated adjustment while allowing for more accurate assessment of the cost and quality of adjustable sutures in children.
Gong Y, Fu Z, Liegl R, Chen J, Hellström A, Smith L. ω-3 and ω-6 long-chain PUFAs and their enzymatic metabolites in neovascular eye diseases. Am J Clin Nutr. 2017;106(1):16–26.
Neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, threaten the visual health of children and adults. Current treatment options, including anti-vascular endothelial growth factor therapy and laser retinal photocoagulation, have limitations and are associated with adverse effects; therefore, the identification of additional therapies is highly desirable. Both clinical and experimental studies show that dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis. The ω-3 LC-PUFA metabolites from 2 groups of enzymes, cyclooxygenases and lipoxygenases, inhibit [and the ω-6 (n-6) LC-PUFA metabolites promote] inflammation and angiogenesis. However, both of the ω-3 and the ω-6 lipid products of cytochrome P450 oxidase 2C promote neovascularization in both the retina and choroid, which suggests that inhibition of this pathway might be beneficial. This review summarizes our current understanding of the roles of ω-3 and ω-6 LC-PUFAs and their enzymatic metabolites in neovascular eye diseases.
Alkharashi M, Hunter D. Reduced surgical success rate of rectus muscle plication compared to resection. J AAPOS. 2017;
PURPOSE: To evaluate the surgical success of rectus muscle plication compared to resection and to compare the short- and long-term changes in ocular alignment after both procedures. METHODS: The medical records of all patients who underwent a rectus muscle tightening procedure (resection or plication) at a single institution over a 5-year period by a single surgeon were reviewed retrospectively. Binocular alignment was recorded before and immediately after surgery and again at 6-12 weeks and final follow-up visit. Primary outcome was surgical success rate, defined as distance alignment of ≤10(Δ) for horizontal and ≤6(Δ) for vertical strabismus. Secondary outcomes were reoperation rate and postoperative alignment drift. RESULTS: A total of 72 surgeries were identified for inclusion: 48 resections and 24 plications. Surgical success was significantly higher in the resection group than in the plication group (89% vs 58%; P = 0.005) at both 6-12 weeks' follow-up (P = 0.005) and at mean final follow-up of 19 ± 13 months (range, 3-56 months [n = 48]; P = 0.03). Reoperations were performed in 3 patients in the plication group (12.5%), all for undercorrection; there were no reoperations in the resection group (P = 0.03). CONCLUSIONS: Rectus muscle plication has many potential advantages over resection, including sparing of the ciliary circulation. In our experience, however, patients treated with plication had lower surgical success rates and a higher reoperation rate. Surgeons should monitor their long-term results before considering plication as their procedure of choice over resection.
Altschwager P, Moskowitz A, Fulton A, Hansen R. Multifocal ERG Responses in Subjects With a History of Preterm Birth. Invest Ophthalmol Vis Sci. 2017;58(5):2603–2608.
Purpose: The purpose of this study is to assess cone-mediated central retinal function in children with a history of preterm birth, including subjects with and without retinopathy of prematurity (ROP). The multifocal electroretinogram (mfERG) records activity of the postreceptor retinal circuitry. Methods: mfERG responses were recorded to an array of 103 hexagonal elements that subtended 43° around a central fixation target. The amplitude and latency of the first negative (N1) and first positive (P1) response were evaluated in six concentric rings centered on the fovea. Responses were recorded from 40 subjects with a history of preterm birth (severe ROP, mild ROP, no ROP) and 19 term-born control subjects. Results: The amplitude of N1 and P1 varied significantly with eccentricity and ROP severity. For all four groups, these amplitudes were largest in the center and decreased with eccentricity. At all eccentricities, N1 amplitude was significantly smaller in severe ROP and did not differ significantly among the other three groups (mild ROP, no ROP, term-born controls). P1 amplitude in all preterm groups was significantly smaller than in controls; P1 amplitude was similar in no ROP and mild ROP and significantly smaller in severe ROP. Conclusions: These results provide evidence that premature birth alone affects cone-mediated central retinal function and that the magnitude of the effect varies with severity of the antecedent ROP. The lack of difference in mfERG amplitude between the mild and no ROP groups is evidence that the effect of ROP on the neurosensory retina may not depend solely on appearance of abnormal retinal vasculature.
Wallace D, Kraker R, Freedman S, Crouch E, Hutchinson A, Bhatt A, Rogers D, Yang M, Haider K, VanderVeen D, Siatkowski M, Dean T, Beck R, Repka M, Smith L, Good W, Hartnett ME, Kong L, Holmes J, Pediatric Eye Disease Investigator Group (PEDIG). Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study. JAMA Ophthalmol. 2017;135(6):654–656.
Importance: Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk. Objective: To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies. Design, Setting, and Participants: Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 µL syringes with 5/16-inch, 30-gauge fixed needles. Interventions: Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Main Outcomes and Measures: Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg. Conclusions and Relevance: A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.
VanderVeen D, Melia M, Yang M, Hutchinson A, Wilson L, Lambert S. Anti-Vascular Endothelial Growth Factor Therapy for Primary Treatment of Type 1 Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology. Ophthalmology. 2017;124(5):619–633.

PURPOSE: To review the available evidence on the ocular safety and efficacy of anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) compared with laser photocoagulation therapy. METHODS: A literature search of the PubMed and Cochrane Library databases was conducted last on September 6, 2016, with no date restrictions and limited to articles published in English. This search yielded 311 citations, of which 37 were deemed clinically relevant for full-text review. Thirteen of these were selected for inclusion in this assessment. The panel methodologist assigned ratings to the selected articles according to the level of evidence. RESULTS: Of the 13 citations, 6 articles on 5 randomized clinical trials provided level II evidence supporting the use of anti-VEGF agents, either as monotherapy or in combination with laser therapy. The primary outcome for these articles included recurrence of ROP and the need for retreatment (3 articles), retinal structure (2 articles), and refractive outcome (1 article). Seven articles were comparative case series that provided level III evidence. The primary outcomes included the effects of anti-VEGF treatment on development of peripheral retinal vessels (1 article), refractive outcomes (1 article), or both structural and refractive or visual outcomes (5 articles). CONCLUSIONS: Current level II and III evidence indicates that intravitreal anti-VEGF therapy is as effective as laser photocoagulation for achieving regression of acute ROP. Although there are distinct ocular advantages to anti-VEGF pharmacotherapy for some cases (such as eyes with zone I disease or aggressive posterior ROP), the disadvantages are that the ROP recurrence rate is higher, and vigilant and extended follow-up is needed because retinal vascularization is usually incomplete. After intravitreal injection, bevacizumab can be detected in serum within 1 day, and serum VEGF levels are suppressed for at least 8 to 12 weeks. The effects of lowering systemic VEGF levels on the developing organ systems of premature infants are unknown, and there are limited long-term data on potential systemic and neurodevelopmental effects after anti-VEGF use for ROP treatment. Anti-VEGF agents should be used judiciously and with awareness of the known and unknown or potential side effects.

Wu S, Fan, Wu, Hong J, Xu. The association of maternal factors with epibulbar dermoid of newborn: a retrospective, matched case-control study. Eye (Lond). 2017;31(7):1099–1105.
PurposeTo determine the association of maternal factors and exposure during pregnancy with the incidence in newborns of epibulbar dermoid (ED), a congenital ocular surface benign tumor.Patients and methodsThis is a retrospective, paired case-control study in which 121 children with ED (case group) and 121 children without ED (control group) were recruited. Questionnaire-based interviews with mothers of participants were performed and maternal medical records during pregnancy were reviewed. The questionnaire investigated basic information, personal history, environmental exposure, exposure to maternal diseases, symptoms and corresponding medical treatments during pregnancy, and parental socioeconomic status. The case and control participants were matched for sex, birth weight, gestational age, and parental socioeconomic status level. Univariate and multivariate logistic regression analyses were conducted with ED as the main outcome variable.ResultsFactors significantly associated with ED were: history of maternal inevitable miscarriage (odds ratio (OR), 2.59; 95% confidence intervals (CI), 1.13-5.90), common cold in the first trimester (OR, 3.94; CI, 1.74-8.93), and paternal smoke exposure >half a pack per day during pregnancy (OR, 4.81; CI, 1.74-13.28).ConclusionHistory of maternal miscarriage, common cold exposure in the first trimester, and paternal smoking (>half a pack per day) during pregnancy could result in significant risk factors for ED of newborns. These data also imply that paternal smoking delivers nicotine to maternal respiratory system and uterine microenvironment that may both affect microvascular development and predispose the fetus to future ED.
Oke I, Alkharashi M, Petersen R, Ashenberg A, Shah A. Treatment of Ocular Pyogenic Granuloma With Topical Timolol. JAMA Ophthalmol. 2017;135(4):383–385.

Importance: Pyogenic granulomas, acquired vascular lesions, form on the ocular or palpebral surface related to inflammation from chalazia, trauma, or surgery. They can be unsightly, spontaneously bleed, and cause irritation to patients. Observations: A case series is presented of 4 consecutive children with acquired ocular surface pyogenic granulomas treated at Boston Children's Hospital from 2014 to 2016 with only topical timolol, 0.5%, twice daily for a minimum of 21 days. In all cases, complete resolution occurred within the treatment period with no recurrence for at least 3 months. There were no adverse effects from the timolol during follow-up. Conclusions and Relevance: This case series of 4 children, while limited to no greater than 12 weeks of follow-up and without control children, suggests that ocular surface pyogenic granulomas respond to topical timolol treatment, which has a lower adverse-effect profile than conventional topical steroid treatments or other medical or surgical therapies. If confirmed in larger studies with longer follow-up and controls, this may be the desired treatment modality.

Wan M, Mantagos I, Shah A, Kazlas M, Hunter D. Comparison of Botulinum Toxin With Surgery for the Treatment of Acute-Onset Comitant Esotropia in Children. Am J Ophthalmol. 2017;176:33–39.

PURPOSE: To determine whether botulinum toxin is as effective as strabismus surgery in the treatment of acute-onset comitant esotropia in children. DESIGN: Retrospective, nonrandomized, comparative clinical study. METHODS: Setting: Tertiary care pediatric hospital. STUDY POPULATION: Forty-nine children with acute-onset comitant esotropia. INTERVENTION: Treatment with either botulinum toxin ("chemodenervation group") or standard incisional strabismus surgery ("surgery group"). MAIN OUTCOME MEASURE: Success rate at 6 months (total horizontal deviation of 10 prism diopters or less and evidence of binocular single vision). RESULTS: There were 16 patients in the chemodenervation group and 33 patients in the surgery group. The success rate was not significantly different at 6 months (81% vs 61%, P = .20) or at 18 months (67% vs 58%, P = .74). The median angle of deviation and median stereoacuity were not significantly different at 6 or 18 months. The chemodenervation procedure was not inferior to incisional strabismus surgery at 6 months. The duration of general anesthesia (5 vs 71 min, P < .001) and time in the post-anesthesia care unit (37 vs 93 min, P < .001) were significantly shorter in the chemodenervation group. Botulinum toxin injection payment averaged $874 per procedure compared with $2783 for strabismus surgery. CONCLUSIONS: Botulinum toxin is at least as effective as surgery in the treatment of acute-onset comitant esotropia at 6 months while reducing the duration of general anesthesia and healthcare costs.

Gradstein L, Hansen R, Cox G, Altschwager P, Fulton A. Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism. Doc Ophthalmol. 2017;134(2):135–140.

PURPOSE: We report for the first time electroretinographic (ERG) evidence of progressive retinal abnormalities in a girl who presented in infancy with ocular features of albinism and gradually developed choroidal sclerosis and patchy retinal atrophy leading to a diagnosis of Knobloch syndrome (KS, OMIM 267750, COL18A1). METHODS: At age 2 months, nystagmus and esotropia prompted ophthalmic evaluation. The appearance of choroidal sclerosis and atrophic retinal patches led to further evaluation at age 8 years. Genetics consultation was obtained in infancy and again at age 8 years as retinal findings evolved. Full field ERG responses in both scotopic and photopic conditions were recorded at both ages and compared to those in healthy control subjects. RESULTS: At age 2 months ERG response parameters were within normal limits for age and tyrosinase (TYR) gene sequencing revealed one novel mutation, p.S466F, and the temperature-sensitive polymorphism, p.R402Q, suggesting the diagnosis of oculocutaneous albinism type 1 (OCA1). At age 8 years, there was significant attenuation of both scotopic and photopic ERG responses. Genetic re-analysis led to the identification of a homozygous mutation, c.3213dupC, in the COL18A1 gene, thus confirming the diagnosis of Knobloch syndrome. CONCLUSIONS: Our patient with Knobloch syndrome developed abnormal ERG responses similar to those found in col18a1 knockout mice. Thus, we have documented progressive attenuation of the scotopic and photopic responses in KS.

Alkharashi M, Fulton A. Available Evidence on Leber Congenital Amaurosis and Gene Therapy.. Semin Ophthalmol. 2017;32(1):14–21.

Leber congenital amaurosis (LCA) is a group of severe inherited retinal dystrophies that lead to early childhood blindness. In the last decade, interest in LCA has increased as advances in genetics have been applied to better identify, classify, and treat LCA. To date, 23 LCA genes have been identified. Gene replacement in the RPE65 form of LCA represents a major advance in treatment, although limitations have been recognized. In this article, we review the clinical and genetic features of LCA and evaluate the evidence available for gene therapy in RPE65 disease.

Fu Z, Meng S, Burnim S, Smith L, Lo AC. Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity. Clin Exp Ophthalmol. 2017;45(5):529–538.
BACKGROUND: Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. METHODS: Mouse pups were exposed to 75% oxygen for 5 days and returned to room air for another 5 days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. RESULTS: Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. CONCLUSIONS: Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature.
Gilbert A, Hunter D. Duane syndrome with prominent oculo-auricular phenomenon. J AAPOS. 2017;21(2):165–167.

Duane syndrome is a congenital cranial dysinnervation disorder involving absent or anomalous innervation of the lateral and medial rectus muscles that is sometimes associated with other manifestations of dysinnervation. We describe a patient with right esotropic Duane syndrome with a long-standing retroauricular tugging sensation in right gaze who was noted to have prominent ipsilateral oculo-auricular phenomenon, representing either abnormal enhancement of existing innervation or an uncommon dysinnervation. After successful strabismus surgery the tugging sensation improved but the phenomenon could still be elicited.

Avery R, Katowitz J, Fisher M, Heidary G, Dombi E, Packer R, Widemann B, OPPN Working Group. Orbital/Periorbital Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Multidisciplinary Recommendations for Care.. Ophthalmology. 2017;124(1):123–132.

TOPIC: Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. CLINICAL RELEVANCE: Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome. METHODS: Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials. RESULTS: In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. CONCLUSIONS: This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.

Bothun E, Lynn M, Christiansen S, Kruger S, VanderVeen D, Neely D, Lambert S, Infant Aphakic Treatment Study. Strabismus surgery outcomes in the Infant Aphakia Treatment Study (IATS) at age 5 years.. J AAPOS. 2016;20(6):501–505.

PURPOSE: To report strabismus surgery frequency and outcomes after monocular infantile cataract surgery with or without IOL implantation. METHODS: The Infant Aphakia Treatment Study (IATS) is a randomized, multicenter clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with a unilateral congenital cataract. This report is a secondary outcome analysis of ocular motor data from IATS patients who underwent strabismus surgery prior to age 5 years. RESULTS: Strabismus surgery was performed in 45 (39%) patients (contact lens group [CL], 37%; IOL group, 42% [P = 0.70]). The indications for strabismus surgery were esotropia (62%), exotropia (33%), and hypertropia (4%). Infants who underwent cataract surgery at a younger age were less likely to undergo strabismus surgery (28-48 days, 12/50 [24%]; 49-210 days, 33/64 [52%]; P = 0.0037). Of the 42 patients who underwent strabismus surgery, 14 (33%) had a postoperative distance alignment within 8(Δ) of orthotropia at age 5 years. The 5-year visual acuity of children with strabismus was the same whether or not strabismus surgery had been performed (1.10 logMAR with surgery vs 1.00 without [P = 0.71]). CONCLUSIONS: In this study cohort, cataract surgery performed in the first 6 weeks of life was associated with a reduced frequency of strabismus surgery. Strabismus surgery outcomes in this population are guarded. Surgical improvement of strabismus does not appear to influence long-term visual acuity.

Klevebro, Lundgren, Hammar, Smith, Bottai, Domellöf, Löfqvist, Hallberg B, Hellström. Cohort study of growth patterns by gestational age in preterm infants developing morbidity.. BMJ Open. 2016;6(11):e012872.

OBJECTIVES: To examine differences in growth patterns in preterm infants developing major morbidities including retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC) and intraventricular haemorrhage (IVH). STUDY DESIGN: Cohort study of 2521 infants born at a gestational age (GA) of 23-30 weeks from 11 level III neonatal intensive care units in USA and Canada, and 3 Swedish population-based cohorts. OUTCOMES: Birth weight and postnatal weight gain were examined relative to birth GA and ROP, BPD, NEC and IVH development. RESULTS: Among infants with a birth GA of 25-30 weeks, birth weight SD score and postnatal weight were lower in those developing ROP and BPD. Infants developing ROP showed lower growth rates during postnatal weeks 7-9 in the 23-24 weeks GA group, during weeks 4-6 in the 25-26 weeks GA group and during weeks 1-5 in the 27-30 weeks GA group. Infants with BPD born at 27-30 weeks GA showed lower growth rates during postnatal weeks 3-5. Infants with NEC had lower growth rates after postnatal week 6 in all GA groups, with no significant differences in birth weight SD score. IVH was not associated with prenatal or postnatal growth. CONCLUSIONS: In this cohort study of extremely preterm infants, we found that the postnatal growth pattern was associated with morbidities such as ROP, BPD and NEC as well as with gestational age at birth.

Nihalani, VanderVeen. Benchmarks for outcome indicators in pediatric cataract surgery. Eye (Lond). 2017;31(3):417–421.

PurposeThe purpose of this study was to establish benchmarks for outcome indicators that may help ascertain the quality of pediatric cataract surgery with primary intraocular lens (IOL) implantation.Patients and methodsA retrospective chart review of patients older than 2 years undergoing cataract surgery with primary IOL implantation, by multiple surgeons in a tertiary-care center, from November 2005 to February 2016 was conducted. Patients with ocular comorbidities that would affect the outcomes were excluded. The outcome measures chosen were as follows: (1) final best corrected Snellen visual acuity (BCVA) in patients who had bilateral cataract surgery analyzed at the last clinic visit; (2) prediction error (PE)=expected refraction-actual refraction. Mean PE and mean absolute PE were assessed 1 month postoperatively, irrespective of age or laterality.ResultsMean age at surgery was 8.3±4.6 years and mean follow-up duration was 3.7±2.7 years. The results of outcome measures were as follows: (1) BCVA was 20/40 or better in 96% (n=124 eyes, mean patient age: 8.3±4.6 years). Remaining five eyes had amblyopia with two eyes having BCVA worse than 20/100 that did not respond to amblyopia treatment. (2) Mean PE was 0.3±1.1 D and mean absolute PE was 0.9±0.7 D. PE was within ±0.5 D in 43.0%, ±1.0 D in 66%, and ±2.0 D in 95% (n=235 eyes).ConclusionGood visual acuity after cataract surgery should be expected for children with bilateral cataracts, setting a high benchmark similar to that recommended in adult cataract surgery. Prediction error is greater in pediatric eyes than in adult eyes, setting a lower benchmark. This study establishes benchmark for outcome indicators in pediatric patients older than 2 years undergoing cataract surgery with primary IOL implantation.

Sheldon C, Paley G, Xiao R, Kesler A, Eyal O, Ko M, Boisvert C, Avery R, Salpietro V, Phillips P, Heidary G, McCormack S, Liu G. Pediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric Features at Diagnosis in a Large, Retrospective, Multisite Cohort.. Ophthalmology. 2016;123(11):2424–2431.

PURPOSE: To examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, international, multisite study. PARTICIPANTS: Pediatric patients (2-18 years of age at diagnosis) with IIH. MAIN OUTCOME MEASURES: Body mass index (BMI), height, and weight Z-scores; sexual maturation. METHODS: Cases of IIH were identified retrospectively based on diagnostic code, pediatric neuro-ophthalmologist databases, or both and updated diagnostic criteria (2013) were applied to confirm definite IIH. Anthropometric measurements were converted into age- and gender-specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available, sexual maturation was noted. RESULTS: Two hundred thirty-three cases of definite IIH were identified across 8 sites. In boys, a moderate association between age and BMI Z-scores was noted (Pearson's correlation coefficient, 0.50; 95% confidence interval [CI], 0.30-0.66; P < 0.001; n = 72), and in girls, a weak association was noted (Pearson's correlation coefficient, 0.34; 95% CI, 0.20-0.47; P < 0.001; n = 161). The average patient was more likely to be overweight at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age- and gender-matched reference values, early adolescent patients were taller for age (P = 0.002 in girls and P = 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25% of cases (n = 57/233). Prepubertal participants (n = 12) had lower average BMI Z-scores (0.95±1.98) compared with pubertal participants (n = 45; 1.92±0.60), but this result did not reach statistical significance (P = 0.09). CONCLUSIONS: With updated diagnostic criteria and pediatric-specific assessments, the present study identifies 3 subgroups of pediatric IIH: a young group that is not overweight, an early adolescent group that is either overweight or obese, and a late adolescent group that is mostly obese. Data also suggest that the early adolescent group with IIH may be taller than age- and gender-matched reference values. Understanding these features of pediatric IIH may help to illuminate the complex pathogenesis of this condition.

Gilbert A, Koo E, Heidary G. Evaluation and Management of Acute Acquired Comitant Esotropia in Children.. Semin Ophthalmol. 2017;32(1):8–13.

Acute acquired comitant esotropia (AACE) is characterized by a sudden-onset eye misalignment with an equal angle of deviation in all fields of gaze. This form of esotropia is distinct from common forms of childhood esotropia, such as infantile esotropia and accommodative esotropia, in the rapid tempo and typically later timing of onset; further, AACE is distinct from restrictive or paretic strabismus, which usually results in an incomitant angle of deviation that varies with the direction of gaze. The underlying etiologies for AACE are broad but, in some cases, it may be associated with significant neurologic disease. Therefore, the purpose of this article is to examine and summarize the current literature on AACE to provide a framework for the evaluation and management of this form of acquired strabismus.

Hansen R, Moskowitz A, Akula J, Fulton A. The neural retina in retinopathy of prematurity.. Prog Retin Eye Res. 2017;56:32–57.

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP.