Pediatric Ophthalmology

Wu C, VanderVeen DK. Impact of higher oxygen saturation levels on postnatal weight gain to predict retinopathy of prematurity. Acta Paediatr 2021;
Wu C, Löfqvist C, Smith LEH, VanderVeen DK, Hellström A, Hellström A. Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity. Arch Ophthalmol 2012;130(8):992-9.Abstract
OBJECTIVE: To assess WINROP (, an algorithm using postnatal weight measurements, as a tool for the prediction of retinopathy of prematurity (ROP) in a large geographically and racially diverse study population. METHODS: WINROP analysis was performed retrospectively on conventionally at-risk infants from 10 neonatal intensive careunits.Weight measurements were entered into WINROP, which signals an alarm for an abnormal weight gain rate. Infants were classified into categories of no alarm (unlikely to develop type 1ROP)and alarm (at risk for developing type 1ROP).Use of WINROP requires that an infant has (1) gestational age less than 32 weeks at birth, (2) weekly weight measurements,(3) physiologic weight gain,and(4)absence of other pathologic retinal vascular disease. RESULTS: A total of 1706 infants with a median gestational age of 28 weeks (range, 22-31 weeks) and median birth weight of 1016 g (range, 378-2240 g) were included in the study analysis. An alarm occurred in 1101 infants (64.5%), with a median time from birth to alarm of 3 weeks (range, 0-12 weeks) and from alarm to treatment of 8 weeks (range, 1 day to 22 weeks). The sensitivity of WINROP was 98.6% and the negative predictive value was 99.7%. Two infants with type 1 ROP requiring treatment after 40 weeks' postmenstrual age did not receive an alarm. CONCLUSION: The WINROP system is a useful adjunct for ROP screening that identifies high-risk infants early to optimize care and potentially reduce the overall number of diagnostic ROP examinations.
Yang S, MacKinnon S, Dagi LR, Hunter DG. Superior rectus transposition vs medial rectus recession for treatment of esotropic Duane syndrome. JAMA Ophthalmol 2014;132(6):669-75.Abstract
IMPORTANCE: Superior rectus transposition (SRT) with or without medial rectus recession (MRc) has been introduced as an alternative to MRc alone for treatment of esotropic Duane syndrome; however, the effectiveness of these procedures has not been compared previously. OBJECTIVE: To compare the safety and efficacy of MRc and SRT in treatment of Duane syndrome. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of all patients with esotropic Duane syndrome who underwent surgical treatment from January 1, 2006, through December 31, 2012, in a multispecialty, hospital-based pediatric ophthalmology/adult strabismus practice at Boston Children's Hospital. Patients in the SRT group underwent SRT with or without MRc; those in the non-SRT group underwent unilateral or bilateral MRc. EXPOSURES: Surgical treatment of esotropic Duane syndrome. MAIN OUTCOMES AND MEASURES: Binocular alignment, ocular ductions, head position, stereopsis, and fundus torsion were recorded before surgery and at the 2-month and final postoperative visits. We also evaluated postoperative drift. RESULTS: The medical record review identified 36 patients who underwent 37 procedures, including 19 in the SRT group (13 SRT + MRc and 6 SRT alone) and 18 in the non-SRT group (11 unilateral MRc and 7 bilateral medial rectus resession). Mean MRc was smaller when performed with SRT (3.3 vs 5.3 mm; P = .004). Although the initial deviation was larger in the SRT group, both groups had a similar improvement in esotropia and head turn. Abduction improved by at least 1 unit in 15 of 19 patients in the SRT group (79%) vs 5 of 18 in the non-SRT group (28%). In 24 patients followed up for more than 6 months, mean esotropia decreased from 8.2 to 6.1 prism diopters (Δ) in the SRT group (n = 12) but increased from 7.2 to 10.9Δ in the non-SRT group (n = 12). CONCLUSIONS AND RELEVANCE: The combination of SRT and MRc was more effective than MRc or bilateral medial rectus resession at improving abduction while allowing for a smaller recession to align the eyes and eliminate a compensatory head posture. Although any surgery on the vertical rectus muscles should in theory increase the risk for vertical or torsional complications, to date this theory has not been borne out in our patients. Patients treated with SRT appear to have a reduced likelihood of long-term undercorrection. We therefore recommend SRT with adjustable MRc for treatment of Duane syndrome in patients with larger amounts of esotropia.
Yang Y, Kazlas M, Sharma M, Friedmann A. AML presenting with a preleukemic episode and acquired heterochromia in a child with macrosomia. Pediatr Blood Cancer 2018;65(4)
Ying G-S, Vanderveen D, Daniel E, Quinn GE, Baumritter A, to of Group TAEA-PRPC. Risk Score for Predicting Treatment-Requiring Retinopathy of Prematurity (ROP) in the Telemedicine Approaches to Evaluating Acute-Phase ROP Study. Ophthalmology 2016;123(10):2176-82.Abstract

PURPOSE: To develop a risk score for predicting treatment-requiring retinopathy of prematurity (TR-ROP) in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study. DESIGN: Second analyses of an observational cohort study. PARTICIPANTS: Infants with birth weight (BW) <1251 g who had ≥1 imaging session by 34 weeks of postmenstrual age (PMA) and ≥1 subsequent retinopathy of prematurity (ROP) examination for determining TR-ROP by study-certified ophthalmologists. METHODS: Nonphysician trained readers evaluated wide-field retinal image sets for characteristics of ROP, pre-plus/plus disease, and retinal hemorrhage. Risk score points for predicting TR-ROP were derived from the regression coefficients of significant predictors in a multivariate logistic regression model. MAIN OUTCOME MEASURES: TR-ROP. RESULTS: Eighty-five of 771 infants (11.0%) developed TR-ROP. In a multivariate model, significant predictors for TR-ROP were gestational age (GA) (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.7-18.9 for ≤25 vs. ≥28 weeks), need for respiratory support (OR, 7.0; 95% CI, 1.3-37.1 for high-frequency oscillatory ventilation vs. no respiratory support), slow weight gain (OR, 2.4; 95% CI, 1.2-4.6 for weight gain ≤12 g/day vs. >15 g/day), and image findings at the first image session including number of quadrants with pre-plus (OR, 3.8; 95% CI, 1.5-9.7 for 4 pre-plus quadrants vs. no pre-plus), stage and zone of ROP (OR, 4.7; 95% CI, 2.1-11.8 for stage 1-2 zone I, OR, 5.9; 95% CI, 2.1-16.6 for stage 3 zone I vs. no ROP), and presence of blot hemorrhage (OR, 3.1; 95% CI, 1.4-6.7). Image findings predicted TR-ROP better than GA (area under receiver operating characteristic curve [AUC] = 0.82 vs. 0.75, P = 0.03). The risk of TR-ROP steadily increased with higher risk score and predicted TR-ROP well (AUC = 0.88; 95% CI, 0.85-0.92). Risk score ≥3 points for predicting TR-ROP had a sensitivity of 98.8%, specificity of 40.1%, and positive and negative predictive values of 17.0% and 99.6%, respectively. CONCLUSIONS: Image characteristics at 34 PMA weeks or earlier independently predict TR-ROP. If externally validated in other infants, risk score, calculated from image findings, GA, weight gain, and respiratory support, enables early identification of infants in need of increased surveillance for TR-ROP.

Yonekawa Y, Shah AS, France RM, Ciarlini P, VanderVeen DK. Leukocoria in a 2-year-old boy. J Paediatr Child Health 2014;50(9):744.
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.
Yonekawa Y, Wu W-C, Kusaka S, Robinson J, Tsujioka D, Kang KB, Shapiro MJ, Padhi TR, Jain L, Sears JE, Kuriyan AE, Berrocal AM, Quiram PA, Gerber AE, Paul Chan RV, Jonas KE, Wong SC, Patel CK, Abbey AM, Spencer R, Blair MP, Chang EY, Papakostas TD, Vavvas DG, Sisk RA, Ferrone PJ, Henderson RH, Olsen KR, Hartnett EM, Chau FY, Mukai S, Murray TG, Thomas BJ, Meza AP, Drenser KA, Trese MT, Capone A. Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study. Ophthalmology 2016;123(8):1802-8.Abstract

PURPOSE: To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. DESIGN: International, multicenter, interventional, retrospective case series. PARTICIPANTS: Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. METHODS: Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. MAIN OUTCOME MEASURES: Ocular and systemic adverse events. RESULTS: A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P = 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. CONCLUSIONS: This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.

Zhang YJ, Jimenez L, Azova S, Kremen J, Chan Y-M, Elhusseiny AM, Saeed H, Goldsmith J, Al-Ibraheemi A, O'Connell AE, Kovbasnjuk O, Rodan L, Agrawal PB, Thiagarajah JR. Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis. Eur J Hum Genet 2021;Abstract
WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein's putative involvement in multiple developmental and stem cell maintenance pathways.
Zhang M, Gilbert AL, Hunter DG. Superior oblique myokymia treated with levobunolol. J AAPOS 2018;22(1):67-69.e2.Abstract
Superior oblique myokymia (SOM) is an uncommon condition of unclear etiology that results in episodes of oscillopsia and diplopia. There is no established treatment protocol for SOM. We present 2 cases of SOM successfully managed with topical levobunolol 0.5%; both patients responded to a short course of medication administration and required minimal ongoing therapy. Case 1 was a 69-year-old woman with left SOM who had previously undergone a left Harada-Ito procedure. Her SOM improved immediately on administration of levobunolol and was maintained at follow-up 1 year later. Case 2 was a 49-year-old man with right SOM that affected his ability to work. After 2 days of topical levobunolol 0.5% nightly in the right eye, SOM episodes ceased; he continues to use drops intermittently for occasional recurrences.
Zhongjie F, Kern TS, Ann H, Smith Lois EH. Fatty acid oxidation and photoreceptor metabolic needs. J Lipid Res 2021;:100035.