Pediatric Ophthalmology

Wallace DK, Kraker RT, Freedman SF, Crouch ER, Bhatt AR, Hartnett EM, Yang MB, Rogers DL, Hutchinson AK, VanderVeen DK, Haider KM, Siatkowski MR, Dean TW, Beck RW, Repka MX, Smith LE, Good WV, Kong L, Cotter SA, Holmes JM, Holmes JM. Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity. JAMA Ophthalmol 2020;Abstract
Importance: Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants. Objective: To find the lowest dose of intravitreous bevacizumab effective for severe ROP. Design, Setting, and Participants: Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019. Interventions: Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. Main Outcomes and Measures: Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg. Conclusions and Relevance: These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.
Gise RA, Heidary G. Update on Pediatric Optic Neuritis. Curr Neurol Neurosci Rep 2020;20(3):4.Abstract
PURPOSE OF REVIEW: The purpose of this review is to provide an update on advances in the understanding of pediatric demyelinating optic neuritis. RECENT FINDINGS: In the past decade, the disease phenotypes for demyelinating syndromes in children have been more clearly defined. Pediatric optic neuritis may present as a clinically isolated syndrome or in the setting of underlying neurologic disease. In addition to optic neuritis associated with multiple sclerosis or neuromyelitis optica, recent work has identified antibodies to the myelin oligodendrocyte glycoprotein (MOG IgG) as a unique demyelinating cause with distinct features regarding treatment and prognosis. The disease phenotypes for demyelinating pediatric optic neuritis have expanded. Treatment strategies vary and are not universally effective for each cause of demyelinating disease. Accurately distinguishing among these unique clinical syndromes is therefore critical for initiation of appropriate treatment to prevent disability, to maximize visual outcomes, and to provide insight into long-term prognosis.
Vongsachang H, Friedman DS, Inns A, Kretz AM, Mukherjee MR, Callan J, Wahl M, Repka MX, Collins ME. Parent and Teacher Perspectives on Factors Decreasing Participation in School-Based Vision Programs. Ophthalmic Epidemiol 2020;27(3):226-236.Abstract
: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median = 5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting 'subsidized' services.: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.
Shoshany TN, Michalak S, Staffa SJ, Chinn RN, Bishop K, Hunter DG. Effect of Primary Occlusion Therapy in Asymmetric, Bilateral Amblyopia. Am J Ophthalmol 2020;211:87-93.Abstract
PURPOSE: Many bilateral amblyopia patients have asymmetric visual acuity (VA). There is no standard treatment for these patients, and outcomes have not been well described. Our goal is to compare VA outcomes in this group based on timing of occlusion therapy. DESIGN: Retrospective interventional comparative case series. METHODS: Setting: Institutional practice. PatientPopulation: Patients diagnosed with amblyopia at Boston Children's Hospital between 2010 and 2014. InclusionCriteria: VA ≥ 0.3 logMAR bilaterally by objective optotype-based measures, interocular difference (IOD) ≥ 0.18 logMAR, age 2-12 years. ExclusionCriteria: Loss to follow-up, managed surgically, deprivation amblyopia. Patients had either primary or secondary occlusion (primary = initiated when VA ≥ 0.3 logMAR bilaterally; secondary = initiated to correct residual IOD once VA improved to ≤0.18 logMAR in the stronger eye). ObservationProcedure: Patient demographics, VA, IOD, and stereopsis were compared between groups. OutcomeMeasures: VA improvement at 12-18 months and at last visits. RESULTS: Of 2,200 patients reviewed, 167 (7.6%) had asymmetric, bilateral amblyopia; 98 met inclusion and exclusion criteria. Patients were equally divided between primary (n = 50) and secondary (n = 48) occlusion groups. There were no differences in demographics, baseline VA, or IOD between groups (P ≥ .22), although the primary occlusion group had a higher proportion of strabismic amblyopia (P = .007). VA in both eyes, IOD, and stereopsis improved similarly between groups, even after stratifying by amblyopia subtype (P ≥ .48). The secondary occlusion group was more likely to achieve 20/30 bilaterally and IOD ≤ 1 line at 12-18 months (P ≤ .4), although this equalized by the last visit. CONCLUSION: In patients with asymmetric, bilateral amblyopia, VA improved by 4 lines in the weaker eye and 2 lines in the stronger eye, while IOD improved by 2 lines, irrespective of occlusion status. Primary occlusion thus provided no further benefit over spectacle correction alone.
Pineles SL, Aakalu VK, Hutchinson AK, Galvin JA, Heidary G, Binenbaum G, VanderVeen DK, Lambert SR. Binocular Treatment of Amblyopia: A Report by the American Academy of Ophthalmology. Ophthalmology 2020;127(2):261-272.Abstract
PURPOSE: To review the published literature assessing the efficacy of binocular therapy for the treatment of amblyopia compared with standard treatments. METHODS: Literature searches with no date restrictions and limited to the English language were conducted in January 2018 and updated in April 2019 in the PubMed database and the Cochrane Library database with no restrictions. The search yielded 286 citations, and the full text of 50 articles was reviewed. Twenty articles met the inclusion criteria for this assessment and were assigned a level of evidence rating by the panel methodologist. Six studies were rated level I, 1 study was rated level II, and 13 studies were rated level III because of the impact on the development and popularization of this technology. RESULTS: Two of the level I and II studies reviewed described a significant improvement in visual acuity in the binocular group versus standard patching standard treatment (the total number of patients in these 2 studies was 147). However, the 5 studies that failed to show a visual improvement from binocular therapy compared with standard treatments were larger and more rigorously designed (the total number of patients in these 5 studies was 813). Level I and II studies also failed to show a significant improvement over baseline in sensory status, including depth of suppression and stereopsis of those treated with binocular therapy. Several smaller level III case series (total number of patients in these 13 studies was 163) revealed more promising results than the binocular treatments studied in the level I and II studies, especially using treatments that are more engaging and are associated with better compliance. CONCLUSIONS: There is no level I evidence to support the use of binocular treatment as a substitute for current therapies for amblyopia (including patching and optical treatment). Furthermore, 2 large randomized controlled trials showed inferior performance compared with standard patching treatment. On the basis of this review of the published literature, binocular therapy cannot be recommended as a replacement for standard amblyopia therapy. However, more research is needed to determine the potential benefits of proposed binocular treatments in the future.
Cheung CSY, Mireskandari K, Ali A, Silverman E, Tehrani N. Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis. Br J Ophthalmol 2020;104(7):938-942.Abstract
BACKGROUND/AIMS: There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. METHODS: A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids >3 times daily and active uveitis (≥1+ cells) during 3.5 years were documented. The main outcome measure was the need for ≥1 ophthalmic surgery at 3.5 years. RESULTS: In group 1, 69.5% of patients required ≥1 ophthalmic surgery at 3.5 years versus 26.9% in group 2 (p=0.005). U-MTX was 28.9±11.8 weeks and 14.2±10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6±46.0 weeks and 82.3±43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use >3 times daily was 85.9±52.7 weeks and 14.6±11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95% CI 1.28 to 123.48; p=0.030). CONCLUSION: Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.
Nolan JG, Vestal M, Stone S, Dagi LR. "Plugged In". Orbit 2020;39(1):73-74.
Gaier ED, Heidary G. Pediatric Idiopathic Intracranial Hypertension. Semin Neurol 2019;39(6):704-710.Abstract
The presentation of idiopathic intracranial hypertension (IIH) in pediatric populations has several important distinctions from that in adults, especially among prepubertal patients, in which there is no apparent association with gender or obesity. Pediatric patients are more likely to be asymptomatic or present with atypical symptoms than their adult counterparts, posing a diagnostic challenge in some cases. It is important to be aware of the ways in which diagnostic criteria for IIH are modified from that of adults. Ideal treatment practices and the natural history of pediatric IIH remain unclear. Acetazolamide is the mainstay of medical treatment, but some patients with significant visual loss may require surgical intervention. Multicenter studies to accrue a large number of cases and future prospective studies will help to better define pediatric IIH and to formulate consensus guidelines for treatment and management of these patients.
Klevebro S, Hellgren G, Hansen-Pupp I, Wackernagel D, Hallberg B, Borg J, Pivodic A, Smith L, Ley D, Hellström A. Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants. Growth Horm IGF Res 2019;50:1-8.Abstract
OBJECTIVE: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. METHODS: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. RESULTS: Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03-1.63), p = .026, and 1.57 (95% CI 1.26-1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19-2.53), p = .004. CONCLUSION: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at (NCT01096784).
Pivodic A, Hård A-L, Löfqvist C, Smith LEH, Wu C, Bründer M-C, Lagrèze WA, Stahl A, Holmström G, Albertsson-Wikland K, Johansson H, Nilsson S, Hellström A. Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics. JAMA Ophthalmol 2019;:1-9.Abstract
Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
Ambrosio L, Hansen RM, Kimia R, Fulton AB. Retinal Function in X-Linked Juvenile Retinoschisis. Invest Ophthalmol Vis Sci 2019;60(14):4872-4881.Abstract
Purpose: To assess retinal function in young patients with X-linked juvenile retinoschisis (XLRS), a disorder that is known to alter ERG postreceptor retinal components and also possibly photoreceptor components. Methods: ERG responses to full-field stimuli were recorded under scotopic and photopic conditions in 12 XLRS patients aged 1 to 15 (median 8) years. A- and b-wave amplitudes and implicit times were examined over a range of stimulus intensities. Rod and cone photoreceptor (SROD, RROD, SCONE, RCONE) and rod-driven postreceptor (log σ, VMAX) response parameters were calculated from the a- and b-waves. Data from XLRS patients were evaluated for significant change with age. Results: A- and b-wave amplitudes were smaller in XLRS patients compared with controls under both scotopic and photopic conditions. Saturated photoresponse amplitude (RROD), postreceptor b-wave (log σ), and saturated b-wave amplitude (VMAX) were significantly lower in XLRS patients than in controls; SROD did not differ between the two groups. SCONE and RCONE values were normal. In XLRS patients, neither a- and b-wave amplitudes nor calculated parameters (SROD, RROD, log σ, VMAX,SCONE, and RCONE) changed with age. Conclusions: In these young XLRS patients, RROD and a-wave amplitudes were significantly smaller than in controls. Thus, in addition to XLRS causing postreceptor dysfunction, an effect of XLRS on rod photoreceptors cannot be ignored.
Shoshany TN, Robson CD, Hunter DG. Anomalous superior oblique muscles and tendons in congenital fibrosis of the extraocular muscles. J AAPOS 2019;23(6):325.e1-325.e6.Abstract
PURPOSE: To evaluate the finding of anomalous superior oblique muscles in congenital fibrosis of the extraocular muscles (CFEOM), a feature not previously emphasized in this condition. METHODS: The medical records of all patients clinically or genetically diagnosed with CFEOM at Boston Children's Hospital between 2010 and 2018 were reviewed retrospectively. Those who underwent strabismus surgery during the study period were included in the analysis. Baseline patient characteristics, type of CFEOM, results of genetic testing, and intraoperative features of the superior oblique muscle or tendon were recorded. RESULTS: Of 24 patients identified (age range, 1 month to 62 years), 10 (42%) had genetically confirmed CFEOM, and 22 underwent strabismus surgery, 14 (64%) involving the superior oblique muscle. Of these, 7 (50%) had anomalously inserted tendons (most commonly attached nasal to the superior rectus muscle), whereas 7 (50%) had increased superior oblique muscle tension. CONCLUSIONS: Half of CFEOM patients who underwent superior oblique surgery had abnormally inserted superior oblique tendons, and 50% had tight muscles or abnormally thin tendons, findings that have not been well-characterized in this condition. The findings suggest that abnormal insertion of the superior oblique muscles and tendons are additional features of the disease process in CFEOM that have not been described previously. These features may contribute to the severe upgaze limitation in CFEOM and highlight the importance of superior oblique tenotomy in surgical management.