Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication.

The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications.

Apparent Diffusion Coefficient (ADC) Differentiates Retinoblastoma from Coats Disease on MRI.

PURPOSE: Coats' disease can be difficult to differentiate from retinoblastoma. While MR imaging of retinoblastoma and Coats' disease have been examined for differentiating features such as eye size, vitreous seeding, and shape of retinal detachment, there is a lack of data on apparent diffusion coefficient (ADC). ADC is a measure of the diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI DESIGN: Retrospective cross-sectional study METHODS: Patient or study population: Children <18 diagnosed with Coats disease or Retinoblastoma between 1/1/2018-8/1/2022 who had MRI imaging that was reviewable. MAIN OUTCOME MEASURE: Apparent diffusion coefficient (ADC) of the intraocular lesion. Retrospective brain MRIs were obtained from records of 5 eyes of 5 Coats' patients and 29 eyes of 23 patients with retinoblastoma. All MRIs were obtained prior to treatment. The eyedropper tool in Epic's default viewer (Ambra DICOM) was used to measure the ADC of five to eight randomly sampled points within the eye lesions seen on MRI. Average ADC was calculated for each affected eye. Internal reliability was confirmed by re-measuring mean ADC for a random sample of patients masked to their diagnosis and prior measurements. T-test was used to determine if ADC values differ between groups. RESULTS: The mean ADC for retinoblastoma patients (442 +/- 210 mm2/s) differed significantly from the mean for Coats' patients (1364 +/- 309 mm2/s), (p <.001). T-test between baseline and repeat measurements was not significantly different. Since ADC values can differ between different scanners and DW MRI pulse sequences, an ADC threshold may be difficult to generalize across institutes, in our data set a threshold of 900 mm2/s was useful in separating the two diagnoses with a high degree of accuracy. CONCLUSIONS: Clinical features of retinoblastoma and Coats' disease often resemble each other and can lead to misdiagnosis. Since ADCs are derived from diffusion-weighted MRI as an objective parameter, it has the potential to aid in establishing or confirming the diagnosis when retinoblastoma and/or Coats' disease are suspected.

Delayed visual maturation in otherwise normal infants.

BACKGROUND: Children may present in early infancy for evaluation of decreased visual responsiveness. Most such infants have systemic or ocular abnormalities that explain their poor fixation and tracking. Some infants, however, have no other medical or ocular problems. This study evaluated prognostic factors in this latter group of otherwise normal infants with decreased visual responsiveness. METHODS: This was a retrospective cohort study in which medical records of infants evaluated for decreased visual responsiveness were reviewed to identify children who had no history of premature birth or systemic problems associated with developmental delay. Examination findings that were predicted to indicate a good prognosis included: the presence of some reaction to light, normal pupil responses, no nystagmus, and no structural ocular abnormalities. Follow-up information was obtained from office visits and telephone interviews. Main outcome measures were visual acuity and developmental status. RESULTS: Thirty-two children met the criteria noted above. Six were excluded due to lack of follow-up. Four were normal by the time of their initial examination. Follow-up for the remaining patients ranged from 3 months to 11 years (mean 2.94 years). One patient developed strabismus and required surgery. The remaining patients all had normal vision and development. CONCLUSIONS: Otherwise normal infants who present for evaluation of decreased visual responsiveness have a good prognosis if they have some reaction to light, normal pupil responses, absence of nystagmus, and no structural ocular abnormalities. The developmental prognosis for these infants appears to be good. Additional testing at the time of initial evaluation is not indicated.

Congenital inner eyelid folds.

BACKGROUND: We describe the ocular findings in two infants who were found to have unusual internal eyelid folds during routine probing for nasolacrimal duct (NLD) obstruction. MATERIALS AND METHODS: Medical records review of two patients with similar eyelid folds. RESULTS: Both children had unusual eyelid folds that began on the inner eyelid adjacent to the lacrimal canaliculi and extended to a position near the caruncle. Both children had resolution of NLDO following routine surgery, suggesting that the eyelid anomalies were an incidental finding at the time of NLDO surgery. CONCLUSION: The etiology of these unusual inner eyelid folds is not certain but may represent schisis or incomplete separation of the inner eyelid margin.

SUBHYALOID HEMORRHAGE IN EVANS SYNDROME.

PURPOSE: Evans syndrome is a rare disorder characterized by autoimmune hemolytic anemia and immune thrombocytopenia. We report the first case of ophthalmic involvement in a pediatric patient with Evans syndrome, in which painless vision loss was the presenting symptom. METHOD: A 15-year-old girl presented with acute painless loss of vision in her right eye and was found to have bilateral subhyaloid hemorrhages. RESULTS: She was treated with intravenous steroids and transitioned to hydroxychloroquine. Her retinal hemorrhages resolved and her vision improved. CONCLUSION: Nontraumatic subhyaloid hemorrhage is a rare cause of vision loss in children. Evans syndrome should be considered in the differential diagnosis of such patients when hematologic abnormalities are present.

Visual Outcomes in Presumed Congenital Foveal Toxoplasmosis.

PURPOSE: Congenital macular lesions attributed to toxoplasmosis may limit potential visual acuity. The appearance and location of these scars may cause physicians to overlook associated amblyopia. This study reviews the visual outcomes and benefits of amblyopia therapy in children with foveal toxoplasmosis scars. DESIGN: Retrospective observational case series. METHODS: Setting: Single center. PATIENT POPULATION: Children with presumed foveal toxoplasmosis scars who underwent amblyopia treatment. MAIN OUTCOME MEASURE: Charts were reviewed for amblyopia treatment, fundus photographs, optical coherence tomography (OCT), and visual acuity. RESULTS: Median age at presentation was 2.8 years and median follow-up was 6.2 years. Occlusion therapy was undertaken in 9 patients. Median duration of occlusion therapy was 1.7 years. Six patients improved with occlusion therapy (average 4.6 lines gained on optotype acuity). Final visual acuity ranged from 20/25 to 20/250, with 6 of 8 patients better than 20/80. OCT confirmed macular scars in 5 patients, with varying degrees of foveal architecture disruption. CONCLUSION: Despite the striking appearance of the lesions in patients with presumed foveal toxoplasmosis, visual potential may be better than expected. The appearance of the lesions is not always predictive of visual outcome. A trial of occlusion therapy to treat amblyopia should be initiated in these patients to ensure that they reach their maximal visual potential.

Long-term outcomes of strabismus surgery in Mobius sequence.

Purpose: Mobius sequence is a rare disorder that results from underdevelopment of the sixth and seventh cranial nerves, with subsequent facial weakness and impairment of ocular abduction. Approximately half of the affected patients have esotropia with limitation of extraocular movements. This study retrospectively reviews the long-term outcome of strabismus surgery for such patients. Methods: The long-term follow-up results in five children with Mobius sequence, who were observed after strabismus surgery for congenital esotropia, were analyzed. Results: All patients had a limitation of abduction in both eyes. Preoperative esotropia ranged from 20 to 30 prism diopters (PD) (mean 27 PD). Patient age at surgery ranged from 4.5 to 14 months. Bilateral medial rectus muscle recession was performed in all cases, ranging from 4.0 to 6.5 mm. Inferior transposition of the medial rectus muscles was performed in two patients for treatment of V-pattern, and two patients also had surgery for vertical strabismus. Follow-up ranged from 4 to 19.5 years (mean 11.7 years). The final horizontal alignment was <8 PD in all patients, and all demonstrated some binocularity. Conclusion: Bilateral medial rectus muscle recession is an effective treatment for esotropia associated with Mobius sequence, with good long-term stability.

Successful treatment of an exudative choroidal hemangioma with oral propranolol in a 10-year-old boy.

A 10-year-old boy was referred for a circumscribed choroidal hemangioma with underlying exudative detachment of the left eye. To avoid general anesthetics required for laser-based therapy in a child, we began a trial of oral propranolol. The patient's exudative detachment resolved, with resulting improvement in visual acuity, and remained quiescent for 3 years.

Infantile Exotropia and Developmental Delay.

PURPOSE: To evaluate a group of infants with this disorder to determine the long-term outcome of surgery and to assess the need for neurologic evaluations. METHODS: This interventional case series reviewed the records of infants who underwent surgery for the treatment of exotropia with onset during the first year of life. The preoperative ophthalmic and systemic findings, treatment, and developmental and ophthalmic outcomes were reviewed. Surgery was considered successful if the horizontal deviation was less than 10 prism diopters (PD). Developmental assessments were obtained at each visit. RESULTS: Twenty-six patients presented between age 2 and 10 months with exotropia ranging from 20 to 95 PD. Ten (38%) patients had a developmental delay that was recognized at the first visit, 9 of whom had a systemic diagnosis at that time; the other patients remained developmentally normal during a mean follow-up of 7 years. Age at surgery ranged from 4 to 18 months. Surgery was successful in 10 (38%) of 26 patients after 1 surgery and in an additional 13 (50%) of 26 patients after a second surgery. CONCLUSIONS: In this study, the need for more than 1 surgery was higher in infantile exotropia when compared to other forms of childhood strabismus, but most children achieved good alignment with one or two surgeries. Developmental delay is common in patients with infantile exotropia, but this was usually recognized at the time of the initial evaluation. In the current patients, routine neurologic screening or imaging of these otherwise developmentally normal infants was not required. [J Pediatr Ophthalmol Strabismus. 2018;55(4):225-228.].

Outcomes in children with nasolacrimal duct obstruction: Significance of persistent symptoms while stents are in place.

To evaluate the correlation between persistent symptoms while stents are in place and final outcome in children with nasolacrimal duct obstruction (NLDO). A retrospective observational case series, with medical record review that included indications for surgery, surgical procedure, presence of symptoms while stents were in place, and final outcome after stent removal. Twenty-eight children with NLDO had nasolacrimal duct stents placed in 42 eyes. Twenty-one of the 42 eyes (50%) had minimal or no signs or symptoms of NLDO while stents were in place, and 18 of 21 (86%) were symptom-free after stent removal. Twenty-one of the 42 eyes (50%) remained symptomatic while stents were in place. Eleven of these 21 eyes (52%) had good outcomes after stent removal. Ten (48%) of these patients had persistent symptoms after stent removal requiring further treatment. The prognosis for a good outcome is excellent if symptoms of NLDO resolve while stents are in place. The prognosis is poorer if symptoms of NLDO persist, but more than half of such patients still have good outcomes. Careful counseling of parents regarding these outcomes should be performed before considering additional interventions.

Clinical ocular abnormalities in infants with trisomy 13.

PURPOSE: Previous reports of ocular abnormalities associated with trisomy 13 have described pathologic abnormalities, with minimal descriptions of clinical findings. This report describes the clinical findings in four infants with trisomy 13. DESIGN: Retrospective noncomparative case series. METHODS: Review of medical records of four infants with trisomy 13. One patient underwent cataract surgery and treatment of Coats disease. RESULTS: All four infants had inferonasal iris colobomas with unilateral inferonasal cataracts, primarily involving the posterior lens surface. Two patients had pigmented tissue associated with the cataracts. Cataract surgery was performed in one of the patients with good results. This patient also developed a unilateral exudative retinal detachment with peripheral telangiectatic vessels. This resolved after treatment with cryotherapy. CONCLUSIONS: The cataracts in these infants with trisomy 13 had similar clinical features, which were different than those seen in other types of cataracts in infants. In addition, one patient had Coats disease, which has not been previously described in association with trisomy 13. The presence of inferonasal iris colobomas and adjacent sectoral cataracts in patients with other dysmorphic findings should prompt chromosomal analysis for trisomy 13.

Strabismus surgery for elimination of bifocals in accommodative esotropia.

PURPOSE: This study reports the outcomes of strabismus surgery to eliminate bifocals in patients with accommodative esotropia with a high accommodative convergence to accommodation (AC:A) ratio. DESIGN: Retrospective interventional case series. METHODS: Sixteen patients who wore bifocals for treatment of accommodative esotropia with a high AC:A ratio underwent strabismus surgery following prism adaptation testing (PAT) for the near angle of esotropia without bifocals. Outcomes were considered successful if patients had microtropias and maintained fusion without bifocals. RESULTS: All patients had successful outcomes after one or two surgeries. Three of 13 (23%) patients with positive PATs required two surgeries. Two of three (67%) patients with negative PATs required two surgeries. Binocularity remained the same in 13 patients and improved in three patients. Glasses were eliminated entirely in eight of 16 (50%) patients. CONCLUSIONS: Strabismus surgery may eliminate the need for bifocal glasses in patients with accommodative esotropia with a high AC:A ratio, with many patients able to discontinue glasses entirely. Preoperative PAT may help predict the risk of requiring more than one surgery.

Conjunctival pyogenic granulomas after strabismus surgery.

PURPOSE: To measure the incidence and evaluate treatment of pyogenic granulomas after strabismus surgery. DESIGN: Retrospective observational case series. PARTICIPANTS: Four hundred seventy-nine strabismus surgical patients. METHODS: Incidence was determined by review of 472 consecutive patients who underwent strabismus surgery from January 6, 1999 to December 29, 2000. Outcomes were evaluated in 7 additional patients who underwent surgical excision of pyogenic granulomas over a 6-year period from July 5, 1995 to September 19, 2001 (exclusive of the years 1999-2000). MAIN OUTCOME MEASURE: Development and resolution of pyogenic granulomas. RESULTS: Pyogenic granulomas developed in 10 of 472 patients (2.1%). None of these patients had more than 1 pyogenic granuloma, despite having had surgery before or after the event. Treatment of pyogenic granulomas with topical corticosteroids was successful in 90% of patients. Surgical excision was successful in the group of 7 additional patients who did not respond to corticosteroids. CONCLUSIONS: Conjunctival pyogenic granulomas are a potential complication of strabismus surgery. Treatment with topical steroids is an effective initial treatment for most patients with pyogenic granulomas. Surgical excision is effective in patients who do not improve with topical medication. Patients with multiple surgeries do not seem to be at increased risk for pyogenic granulomas, and the occurrence of a pyogenic granuloma does not seem to increase the risk of developing pyogenic granulomas in future surgeries.

Risk of retinopathy in children with type 1 diabetes mellitus before 2 years of age.

PURPOSE: To assess the risk of diabetic retinopathy (DR) in children with type 1 diabetes mellitus (T1DM) diagnosed at a very early age. DESIGN: Observational case series. METHODS: The records of 51 patients were identified through the diabetes database of the Division of Pediatric Endocrinology and Metabolism at Washington University School of Medicine. The patients were diagnosed with T1DM before 2 years of age and were monitored for at least 5 years after diagnosis. The results of ophthalmic screening examinations were reviewed. RESULTS: Fifty-one patients were identified, 33 of whom were monitored for >8 years. None of the patients developed DR. CONCLUSIONS: Children have a negligible risk of developing DR during the first 10 years of life, even if they are diagnosed before age 2. These results indicate that screening for DR is not necessary before age 10.

The effect of initial recognition of abnormalities by physicians on outcome of retinoblastoma.

PURPOSE: The purpose of this study was to assess the effect of early diagnosis by physicians on outcome of retinoblastoma. METHODS: This was an observational case series in which the records of 36 patients with retinoblastoma were reviewed. The age at onset of first symptoms and diagnosis, identity of the individual who first recognized an abnormality, treatment, and outcome were analyzed. RESULTS: Twenty-two patients had unilateral retinoblastoma. Both eyes were preserved in only 2 of these patients, both of whom had abnormalities first noted by their pediatricians. Fourteen patients had bilateral retinoblastoma. Both eyes were preserved in the 5 bilateral patients who were monitored from birth with serial examinations under anesthesia because of family histories of retinoblastoma. Enucleation of at least 1 eye was required in 8 of the 9 bilateral patients whose families first noted abnormalities. Enucleation of at least 1 eye was required in 27 of 28 patients (96%) in whom abnormalities were first noted by parents. CONCLUSION: In this series, the only patients with unilateral retinoblastoma who did not require enucleation were those in whom pediatricians, rather than family members, first noted ocular abnormalities. Both eyes were preserved in all patients with bilateral retinoblastoma who underwent serial examinations under anesthesia because of family histories of retinoblastoma. The prognosis for retinoblastoma appears to be greatly improved when physicians initially detect abnormalities. Educational efforts directed at early detection of retinoblastoma by pediatricians and other primary care providers should be encouraged.

Orbital Causes of Incomitant Strabismus.

Strabismus may result from abnormal innervation, structure, or function of the extraocular muscles. Abnormalities of the orbital bones or masses within the orbit may also cause strabismus due to indirect effects on the extraocular muscles. This paper reviews some disorders of the orbit that are associated with strabismus, including craniofacial malformations, orbital masses, trauma, and anomalous orbital structures.

Initial management of congenital canalicular atresia.

PURPOSE: To evaluate the initial management of pediatric patients with lacrimal canalicular atresia (CA) involving the upper or lower eyelid. METHODS: The medical records of 15 children with symptoms of nasolacrimal duct (NLD) obstruction and CA of either the upper or lower eyelid treated from 1994 to 2014 were retrospectively reviewed. Surgical treatment consisted of nasolacrimal probing through the patent canaliculus. Preoperative findings, treatment, and outcomes were reviewed. Outcomes were considered good if the patients had resolution of signs and symptoms of lacrimal obstruction, fair if the symptoms improved and additional surgery was not required, and poor if additional lacrimal surgery was performed. RESULTS: CA was found in 19 eyes of 15 patients: 11 eyes had upper CA; 8 eyes, lower. All 11 eyes with upper CA improved after NLD probing through the patent lower canaliculus. Of the 8 eyes with lower CA, 4 (50%) had good outcomes and 4 eyes had poor outcomes after NLD probing through the patent upper canaliculus. All of the latter patients improved after subsequent treatment with balloon catheter dilation (BCD), monocanalicular stent placement, or both. CONCLUSIONS: If a patient is found to have upper CA during initial surgery for NLD obstruction, NLD probing through the patent lower canaliculus has a good rate of surgical success. For patients with lower CA, the success rate of NLD probing through the upper canaliculus appears to be lower. Additional treatment during the initial surgery with either BCD or monocanalicular stent placement should be considered in these patients.

Comparison of lateral rectus muscle re-recession and medial rectus muscle resection for treatment of postoperative exotropia.

PURPOSE: To compare the outcomes of unilateral lateral rectus muscle re-recession and medial rectus muscle resection for treatment of recurrent or persistent exotropia. DESIGN: Retrospective nonrandomized clinical trial. METHODS: setting: Hospital-based clinical practice. PATIENT POPULATION: Forty patients with recurrent or persistent exotropia following bilateral lateral rectus muscle recessions. INTERVENTION: Fourteen patients were treated with unilateral medial rectus muscle resection and 26 with unilateral lateral rectus muscle re-recession. MAIN OUTCOME MEASURES: Outcomes were considered successful if the patients had deviations less than 10 prism diopters (PD) at last follow-up. All patients were followed for at least 1 year postoperatively. RESULTS: The mean preoperative deviations were 17.4 PD in the medial rectus muscle resection group and 18.1 PD in the lateral rectus muscle re-recession group. Successful outcomes were achieved in 9 of 14 patients (64%) treated with medial rectus muscle resection and 19 of 26 patients (73%) treated with lateral rectus muscle re-recession. There was no statistically significant difference between these outcomes. Mean follow-up was 4.5 years in the medial rectus muscle resection group and 2.9 years in the lateral rectus muscle re-recession group. CONCLUSIONS: Surgery on a single muscle can be used to treat moderate-angle recurrent or persistent exotropia. Unilateral re-recession of the lateral rectus muscle and medial rectus muscle resection have equivalent success rates.

Retinal degeneration in autoimmune polyglandular syndrome type 1: a case series.

BACKGROUND: Autoimmune polyglandular syndrome type 1 (APS1) is a rare autosomal recessive disorder due to mutations in the AIRE gene. AIM: To report the ocular features and characterise the retinal phenotype in molecularly confirmed APS1. METHOD: This retrospective case series reviewed five molecularly confirmed cases with APS1 known to have ocular involvement (age range: 19 months-44 years; mean follow-up of 8 years). The medical history, ocular history and evaluation, visual field testing, full-field electroretinogram (ERG) and antiretinal antibody results were reviewed. RESULTS: All but one case had decreased vision at first presentation. All cases had peripheral pigmentary retinal changes; macular atrophy was noted in 80% of cases. The most common feature on spectral-domain optical coherence tomography was a disruption of the external limiting membrane and inner segment ellipsoid band (n=3). Fundus autofluorescence imaging demonstrated a parafoveal ring of hyper-autofluorescence (n=1) or a stippled and patchy autofluorescence pattern in the macula (n=1). The visual fields were constricted in all tested patients (n=3). The rod ERG was abnormal in all cases; the relative involvement of rods and cones differed. Four patients who were tested for antiretinal antibodies were found positive by immunohistochemistry (n=3) and/or western blot (n=2). CONCLUSIONS: Photoreceptor degeneration is part of APS1 phenotype and the presence of antiretinal antibodies strongly supports an aetiology similar to that of non-paraneoplastic autoimmune retinopathy. Periodic retinal evaluation and imaging, visual field testing and ERG would assist in monitoring the retinopathy in APS1-related disease.