Alternative Genetic Diagnoses in Axenfeld-Rieger Syndrome Spectrum.

Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. PITX2 and FOXC1 variants explain the majority of individuals with Axenfeld-Rieger syndrome (ARS) but leave ~30% unsolved. Here, we present pathogenic/likely pathogenic variants in nine families with ARA/ARS or similar phenotypes affecting five different genes/regions. USP9X and JAG1 explained three families each. USP9X was recently linked with syndromic cognitive impairment that includes hearing loss, dental defects, ventriculomegaly, Dandy-Walker malformation, skeletal anomalies (hip dysplasia), and other features showing a significant overlap with FOXC1-ARS. Anterior segment anomalies are not currently associated with USP9X, yet our cases demonstrate ARA, congenital glaucoma, corneal neovascularization, and cataracts. The identification of JAG1 variants, linked with Alagille syndrome, in three separate families with a clinical diagnosis of ARA/ARS highlights the overlapping features and high variability of these two phenotypes. Finally, intragenic variants in CDK13, BCOR, and an X chromosome deletion encompassing HCCS and AMELX (linked with ocular and dental anomalies, correspondingly) were identified in three additional cases with ARS. Accurate diagnosis has important implications for clinical management. We suggest that broad testing such as exome sequencing be applied as a second-tier test for individuals with ARS with normal results for PITX2/FOXC1 sequencing and copy number analysis, with attention to the described genes/regions.

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.

Surgical Timing for Congenital Ptosis Should Not Be Determined Solely by the Presence of Anisometropia.

PURPOSE: Timing of surgery in children with congenital ptosis is a critical component of care, and anisometropia is frequently cited as an indication for early intervention. The purpose of this study is to evaluate the change in refractive error following surgery for congenital ptosis to better inform decisions regarding the timing of surgery. METHODS: A retrospective review of clinical records was performed on patients who underwent surgical correction of congenital ptosis in an academic oculoplastic surgery practice from 2002 to 2017. Patients with complete preoperative and postoperative refractive data were included in the study. Changes in refractive error following surgery were analyzed. RESULTS: Among 184 pediatric patients who underwent ptosis surgery during the study period, 56 patients (71 eyes) met inclusion criteria. The mean age at surgery was 5.1 years. Mean refractive error change in all the operated eyes was a 0.82 D decrease in spherical equivalent (p = 0.1920) and a 0.40 D increase in cylinder (p = 0.0255). There were no statistically significant changes in spherical equivalent or cylinder in the control eyes. CONCLUSIONS: The authors data did not show movement toward normalization of refractive error following ptosis surgery. In fact, it showed a statistically significant worsening of astigmatism following surgery. Because refractive error does not improve following surgery, anisometropia should not be the sole indication for early surgery in congenital ptosis.

Giant Dermatofibrosarcoma Protuberans With Bilateral Orbital Involvement.

Dermatofibroma sarcoma protuberans (DFSP) is a rare, locally aggressive soft tissue sarcoma with a tendency for recurrence after excision. Although reports of unilateral orbital and bilateral eyelid disease exist, there have been no prior reports of DFSP with bilateral orbital involvement and no previously described cases of DFSP associated with transient optic neuropathy. The authors present a case report of a 34-year-old woman with a giant scalp DFSP involving the bilateral orbits. Despite radical resection with 5 cm margins where possible, multiple positive margins remained including deep positive margins at the bilateral superomedial retroseptal soft tissue. The patient completed adjuvant radiation for surgically unresectable disease. This case highlights the challenge of achieving local control given the disease extent and infiltration of the bilateral eyelids and orbits. This is the first reported case of DFSP with bilateral orbital involvement and associated transient optic neuropathy.

Etiology and Management of Allergic Eyelid Dermatitis.

PURPOSE: Allergic dermatitis is a common but often misdiagnosed condition that can present with a variety of findings including inflammation, eyelid malposition, and tearing. This study was performed to identify likely etiologies, along with presenting findings and treatment strategies for allergic dermatitis. METHODS: A retrospective review of clinical records was performed of patients diagnosed with allergic dermatitis in academic oculoplastics practices from 2002 to 2014. Initial consultation included review of medications and cosmeceuticals. Suspected allergens were discontinued and an ophthalmic steroid was applied. Persistent allergic dermatitis led to further medication changes or formal allergy testing in an effort to identify the causative agent. RESULTS: Sixty-one patients were identified; average age was 66 years old (range: 33-94), and 45 of the patients were women (74%). Average follow up was 7 months (range: 1-60 months). Reasons for referral included epiphora (31.2%), ectropion (24.6%), blepharitis/dermatitis (18.0%), and "droopy" eyelid (14.8%). Presenting symptoms included irritation (77.1%) and tearing (50.8%). Average duration of symptoms was 16.5 months (range: 2 days-8 years). The 3 most common etiologies were eye drops (54.2%), creams/lotions (24.6%), and cosmetics (13.1%). Rubbing/manipulation was also thought to be a significant factor in 30% of the patients. Overall, the initial treatment regimen led to at least partial resolution in 88% of patients and 66% experienced complete resolution. Patients resistant to therapy were referred for patch testing. At follow up, 98% of patients had improvement in their symptoms and 90% of patients had complete resolution of their symptoms. CONCLUSIONS: Allergic eyelid dermatitis is commonly related to eye drops and topical cosmetics or skin care products. Identification and elimination of causative agents is the mainstay of management. Topical corticosteroids often facilitate resolution of the associated inflammation. Therapy resistant patients may benefit from formal allergy testing.

Ophthalmologic correlates of disease severity in children and adolescents with Wolfram syndrome.

PURPOSE: To describe an ophthalmic phenotype in children at relatively early stages of Wolfram syndrome. METHODS: Quantitative ophthalmic testing of visual acuity, color vision, automated visual field sensitivity, optic nerve pallor and cupping, and retinal nerve fiber layer (RNFL) thickness assessed by optical coherence tomography (OCT) was performed in 18 subjects 5-25 years of age. Subjects were also examined for presence or absence of afferent pupillary defects, cataracts, nystagmus, and strabismus. RESULTS: Subnormal visual acuity was detected in 89% of subjects, color vision deficits in 94%, visual field defects in 100%, optic disk pallor in 94%, abnormally large optic nerve cup:disk ratio in 33%, thinned RNFL in 100%, afferent pupillary defects in 61%, cataracts in 22%, nystagmus in 39%, and strabismus in 39% of subjects. RNFL thinning (P < 0.001), afferent pupillary defects (P = 0.01), strabismus (P = 0.04), and nystagmus (P = 0.04) were associated with more severe disease using the Wolfram United Rating Scale. CONCLUSIONS: Children and adolescents with Wolfram syndrome have multiple ophthalmic markers that correlate with overall disease severity. RNFL thickness measured by OCT may be the most reliable early marker.