Pediatric Ophthalmology

Pediatric Ophthalmology Publications

Guzman Aparicio MA, Liebman DL, Chodosh J, Freitag SK, Kazlas M, Mai DD, Marando CM, Mukai S, Wu AM, Chen TC. Two pediatric cases of reticular corneal epithelial edema associated with netarsudil. Am J Ophthalmol Case Rep 2022;27:101638.Abstract
Purpose: To report two pediatric cases of reticular corneal epithelial edema associated with the use of netarsudil ophthalmic solution 0.02%. Observations: In Case 1, a six-year-old male with glaucoma following cataract surgery was treated with netarsudil for thirteen months and developed diffuse reticular corneal epithelial edema on post-operative day one after undergoing transscleral diode cyclophotocoagulation for persistently elevated intraocular pressures. In Case 2, a three-month-old male with bilateral ocular hypertension developed unilateral inferior reticular corneal epithelial edema five weeks after initiation of netarsudil, which had been discontinued in the fellow eye two weeks prior. In both cases, the reticular epithelial edema resolved following cessation of netarsudil. Conclusions and Importance: Netarsudil-associated reticular corneal epithelial edema can occur in infants and young children.
Vemula SK, Kim SA, Muvavarirwa T, Bell JL, Whitman MC. Impaired Extraocular Muscle Innervation Is Present Before Eye Opening in a Mouse Model of Infantile Nystagmus Syndrome. Invest Ophthalmol Vis Sci 2022;63(10):4.Abstract
Purpose: To determine if extraocular muscles (EOMs) from mice with nystagmus show abnormalities in myofiber composition and innervation, as seen in EOMs from human nystagmus patients, and to determine when in development those changes occur. Methods: Balb/c albino mice were crossed to pigmented mice to generate heterozygous mice, which were mated to create experimental litters containing albinos and wild-type controls. Orbits were harvested from adult animals (12 weeks old); on postnatal day (P)0, P10, P14, and P21; and from 6-week-old animals. EOM sections were collected from the intraorbital portion of the muscles. Sections were immunostained for slow and fast myosin and for neuromuscular junctions (NMJs). The proportion of each myofiber subtype and the density and size of NMJs were quantified. Initial innervation patterns were assessed using whole-mount immunostaining of embryonic day (E)13.5 embryos expressing IslMN:GFP. Results: Adult albino EOMs display an increased proportion of slow myofibers, larger slow myofibers, and a decreased density of NMJs-similar to human nystagmus patients. The percentage of NMJs on slow myofibers is also lower in albino animals. The initial innervation pattern of the incoming ocular motor neurons is normal in E13.5 albino embryos. Differences in the proportion of slow and fast myofiber subtypes are present as early as P14, and a lower percentage of NMJs on slow myofibers is present by P21. There is a lower density of NMJs on albino EOMs as early as P10, prior to eye opening. Conclusions: Changes in NMJ development observed before eye opening indicate that nystagmus is not solely secondary to poor vision.
Pineles SL, Henderson RJ, Repka MX, Heidary G, Liu GT, Waldman AT, Borchert MS, Khanna S, Graves JS, Collinge JE, Conley JA, Davis PL, Kraker RT, Cotter SA, Holmes JM, Holmes JM. The Pediatric Optic Neuritis Prospective Outcomes Study: Two-Year Results. Ophthalmology 2022;129(8):856-864.Abstract
PURPOSE: Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. DESIGN: Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. PARTICIPANTS: A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3-<16 years) who completed their 2-year study visit. METHODS: Participants were treated at the investigator's discretion. MAIN OUTCOMES MEASURES: Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. RESULTS: A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5-15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n = 11, 39%), myelin oligodendrocyte glycoprotein-associated demyelination (n = 8, 29%), multiple sclerosis (MS) (n = 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n = 3, 11%), and acute disseminated encephalomyelitis (n = 2, 7%). Two participants (7%; 95% confidence interval [CI], 1-24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI, -0.08 to 0.3 [20/20+1-20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60-90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n = 2 participants, 3 eyes), MS (n = 2 participants, 2 eyes), and isolated ON (n = 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48-0.88 [20/50+1-20/150-1]). CONCLUSIONS: Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes).
Hoyek S, Wang M, Berrocal AM, Wong A, Place EM, Mason-Suares H, Lin AE, Mukai S, Patel NA. Combined X-linked familial exudative vitreoretinopathy and retinopathy of prematurity phenotype in an infant with mosaic turner syndrome with ring X chromosome. Ophthalmic Genet 2022;:1-6.Abstract
BACKGROUND: Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features. METHODS: Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment. RESULTS: We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon's triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye. CONCLUSIONS: In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes.
VanderVeen DK, McClatchey TS, McClatchey SK, Nizam A, Lambert SR, Lambert SR. Effective lens position and pseudophakic refraction prediction error at 10½ years of age in the Infant Aphakia Treatment Study. J AAPOS 2022;Abstract
BACKGROUND: The refraction prediction error (PE) for infants with intraocular lens (IOL) implantation is large, possibly related to an effective lens position (ELP) that is different than in adult eyes. If these eyes still have nonadult ELPs as they age, this could result in persistently large PE. We aimed to determine whether ELP or biometry at age 10½ years correlated with PE in children enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: We compared the measured refraction of eyes randomized to primary IOL implantation to the "predicted refraction" calculated by the Holladay 1 formula, based on biometry at age 10½ years. Eyes with incomplete data or IOL exchange were excluded. The PE (predicted - measured refraction) and absolute PE were calculated. Measured anterior chamber depth (ACD) was used to assess the effect of ELP on PE. Multiple regression analysis was performed on absolute PE versus axial length, corneal power, rate of refractive growth, refractive error, and best-corrected visual acuity. RESULTS: Forty-three eyes were included. The PE was 0.63 ± 1.68 D; median absolute PE, 0.85 D (IQR, 1.83 D). The median absolute PE was greater when the measured ACD was used to calculate predicted refraction instead of the standard A-constant (1.88 D [IQR, 1.72] D vs 0.85 D [IQR, 1.83], resp. [P = 0.03]). Absolute PE was not significantly correlated with any other parameter. CONCLUSIONS: Variations in ELP did not contribute significantly to PE 10 years after infant cataract surgery.
Mercado CL, Froines CP, Gaier ED, Wang Q, Indaram M, Wan MJ, Shah AS, Koo EB. Prevalence and Characteristics of Cytomegalovirus Ocular Disease in Children: A Multi-Center Study. Clin Ophthalmol 2022;16:2209-2217.Abstract
Purpose: The objective of this study was to identify the prevalence of CMV ocular disease in children and to identify associated risk factors for ocular involvement. Design: Retrospective multicenter, cross-sectional study. Methods: Setting: Hospitalized patients screened for CMV viremia by PCR between 2005 and 2018 at four pediatric referral centers. Participants: Seven-hundred and ninety-three children showed CMV viremia (>135 copies/mL by polymerase chain reaction; PCR). Main Outcomes and Measures: (1) Occurrence of ophthalmologic examination. (2) Presence of CMV ocular disease, defined as retinitis, vasculitis, hemorrhage, optic nerve atrophy, or anterior uveitis in the setting of CMV viremia without other identifiable causes. Results: A total of 296/793 (37%) underwent ophthalmologic examination following CMV viremia. A total of23/296 patients (8%) had ocular symptoms prompting evaluation while the rest had eye exams for baseline screening unrelated to CMV viremia. Of these, 13 cases (4% of those with an eye exam) with ocular disease were identified (three congenital CMV, five severe combined immunodeficiency disorder (SCID) status post-stem cell transplantation, three hematologic malignancy status post-stem cell transplantation for two of them, one Evans syndrome status post-stem cell transplantation, and one medulloblastoma status post-bone marrow transplantation). No patients with solid organ transplantation developed CMV ocular disease in our cohort. Conclusion: CMV ocular disease was a rare occurrence in this cohort without an identifiable pattern across sub-groups. Excluding the three congenital CMV cases, nine out of ten patients with CMV ocular disease were status post-stem cell transplantation. We provide integrated screening guidelines based on the best available evidence for this rare condition.
Patel NA, Acaba-Berrocal LA, Hoyek S, Fan KC, Martinez-Castellanos MA, Baumal CR, Harper AC, Berrocal AM, of (ROPIC) RPIC. Practice Patterns and Outcomes of Intravitreal Anti-VEGF Injection for Retinopathy of Prematurity - An International Multicenter Study. Ophthalmology 2022;Abstract
PURPOSE: To report practice patterns of intravitreal injections of anti-Vascular Endothelial Growth Factor (VEGF) for Retinopathy of Prematurity (ROP) and outcomes data with a focus on retreatments and complications. DESIGN: Multicenter, international, retrospective, consecutive series. SUBJECTS: Patients with ROP treated with anti-VEGF injections from 2007 to 2021. METHODS: Twenty-three sites (16 Unites States [US] and 7 non-US sites) participated. Data collected included demographics, birth characteristics, exam findings, and methods of injections. Comparisons between US and non-US sites were made. MAIN OUTCOME MEASURES: Primary outcomes included number and types of retreatments as well as complications. Secondary outcomes included specifics of the injection protocols including types of medication, doses, distance from limbus, use of antibiotics, and quadrants where injections were delivered. RESULTS: A total of 1677 eyes of 918 patients (43% females, 57% males) were included. Mean gestational age was 25.7 weeks (range 21.2-41.5), and mean birth weight was 787 g (range 300-2,700). Overall, a 30 G needle was most commonly utilized (51%) and the quadrant injected was most frequently the inferior-temporal (51.3%). The distance from the limbus ranged from 0.75 to 2 mm, 1 mm being the most common (65%). Bevacizumab was the most common anti-VEGF (71.4%), with a dose of 0.625 mg in 64% of cases. Overall, 604 (36%) of eyes required retreatment. Of those, 79.8% were retreated with laser alone, 10.6% with anti-VEGF injection alone, and 9.6% with combined laser and injection. Complications following anti-VEGF injections occurred in 15 (0.9%) eyes and no cases of endophthalmitis were reported. Patients in the US had lower birth weights and gestational ages (665.6 g and 24.5 weeks, respectively) compared to non-US patients (912.7 g and 26.9 weeks, respectively) (p<0.0001). Retreatment with reinjection and laser was significantly more common in the US compared to the non-US group (8.5% vs 4.7% [p=0.0016] and 55% vs 7.2% [p<0.001], respectively). There was no difference in the incidence of complications between the two geographical subgroups. CONCLUSION: Anti-VEGF injections for ROP were safe and well tolerated despite a variance in practice patterns. Infants with ROP receiving injections in the United States tended to be younger, smaller, and were treated earlier with more re-treatments than non-United States neonates with ROP.
Bothun ED, Shainberg MJ, Christiansen SP, VanderVeen DK, Neely DE, Kruger SJ, Cotsonis G, Lambert SR, Lambert SR. Long-term strabismus outcomes after unilateral infantile cataract surgery in the Infant Aphakia Treatment Study. J AAPOS 2022;Abstract
PURPOSE: To characterize long-term strabismus outcomes in children in the Infant Aphakia Treatment Study (IATS). METHODS: This study was a secondary data analysis of long-term ocular alignment characteristics of children aged 10.5 years who had previously been enrolled in a randomized clinical trial evaluating aphakic management after unilateral cataract surgery between 1 and 6 months of age. RESULTS: In the IATS study, 96 of 109 children (88%) developed strabismus through age 10.5 years. Half of the 20 children who were orthophoric at distance through age 5 years maintained orthophoria at distance fixation at 10.5 years. Esotropia was the most common type of strabismus prior to age 5 years (56/109 [51%]), whereas exotropia (49/109 [45%]) was the most common type of strabismus at 10.5 years (esotropia, 21%; isolated hypertropia, 17%). Strabismus surgery had been performed on 52 children (48%), with 18 of these (35%) achieving microtropia <10Δ. Strabismus was equally prevalent in children randomized to contact lens care compared with those randomized to primary intraocular lens implantation (45/54 [83%] vs 45/55 [82%]; P = 0.8). Median visual acuity in the study eye was 0.56 logMAR (20/72) for children with orthotropia or microtropia <10Δ versus 1.30 logMAR (20/400) for strabismus ≥10Δ (P = 0.0003). CONCLUSIONS: Strabismus-in particular, exotropia-is common irrespective of aphakia management 10 years following infant monocular cataract surgery. The delayed emergence of exotropia with longer follow-up indicates a need for caution in managing early esotropia in these children. Children with better visual acuity at 10 years of age are more likely to have better ocular alignment.
Alnahdi MA, Alkharashi M. Ocular manifestations of COVID-19 in the pediatric age group. Eur J Ophthalmol 2022;:11206721221116210.Abstract
The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.

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