Insights into the genotype-phenotype relationship of ocular manifestations in Kabuki syndrome.

We aim to assess if genotype-phenotype correlations are present within ocular manifestations of Kabuki syndrome (KS) among a large multicenter cohort. We conducted a retrospective, medical record review including clinical history and comprehensive ophthalmological examinations of a total of 47 individuals with molecularly confirmed KS and ocular manifestations at Boston Children's Hospital and Cincinnati Children's Hospital Medical Center. We assessed information regarding ocular structural, functional, and adnexal elements as well as pertinent associated phenotypic features associated with KS. For both type 1 KS (KS1) and type 2 KS (KS2), we observed more severe eye pathology in nonsense variants towards the C-terminus of each gene, KMT2D and KDM6A, respectively. Furthermore, frameshift variants appeared to be not associated with structural ocular elements. Between both types of KS, ocular structural elements were more frequently identified in KS1 compared with KS2, which only involved the optic disc in our cohort. These results reinforce the need for a comprehensive ophthalmologic exam upon diagnosis of KS and regular follow-up exams. The specific genotype may allow risk stratification of the severity of the ophthalmologic manifestation. However, additional studies involving larger cohorts are needed to replicate our observations and conduct powered analyses to more formally risk-stratify based on genotype, highlighting the importance of multicenter collaborations in rare disease research.

A novel variant in the TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy.

PURPOSE: To report a case of 16-month-old boy with a novel variant TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. OBSERVATION: A 16-month-old otherwise healthy boy was referred to Boston Children's Hospital for evaluation of strabismus. Ocular examination revealed intermittent esotropia, left hypotropia, and limited left eye elevation in both adduction and abduction. Full cycloplegic hyperopic correction of +3.50 diopters (D) over both eyes was given to the patient. Over several months, refraction of the right eye showed progressive myopia (-6.00 D) with new onset iris heterochromia. Fundus examination showed there was a large area of chorioretinal atrophy with abrupt ending of the blood vessels; anterior to the ora serrata there were diffuse vitreous bands and veils that reached the lens anteriorly in direct contact with the lenticular opacity. A novel heterozygous nonsense likely pathogenic variant was identified in the TSPAN12 gene (NM_012338.3) c.315T>A (p.Cys105Ter) confirming the diagnosis of FEVR. CONCLUSION AND IMPORTANCE: Asymmetric FEVR rarely present with unilateral axial myopia however association with acquired heterochromia and cataract has never been reported. We report a case of FEVR caused by a novel TSPAN12 likely pathogenic nonsense variant presenting as unilateral progressive myopia, acquired heterochromia, and pediatric cataract.

Torsional incomitance after asymmetrically adjusted Harada-Ito procedures for the simultaneous correction of vertical and torsional deviations in bilateral trochlear nerve palsy.

BACKGROUND: Adjustable bilateral Harada-Ito procedures have been described, sometimes with asymmetric adjustment used to correct vertical misalignment when coexisting with torsional strabismus. We investigated the causes of significant postoperative torsional incomitance noted in some patients undergoing these procedures. METHODS: The medical records of patients who underwent bilateral Harada-Ito procedures for bilateral trochlear nerve palsy between 1980 and 2018 were reviewed retrospectively. Cases with simultaneous operation on any other oblique or vertical rectus muscle were excluded. Surgical results, especially using Lancaster red-green (Lan R-G) plots, were correlated with the procedures performed. RESULTS: A total of 17 patients were included. At their last follow-up visit (mean, 12 months after surgery), 9 were diplopia free. Of the 8 with continuing diplopia, 2 had undercorrection and 1 had Brown syndrome. In 5 patients with continuing diplopia, there was relative intorsion of the eye movement paths in upgaze and relative extorsion of these paths in downgaze, a type of torsional incomitance. Asymmetric adjustment with tightening of one superior oblique tendon, and often loosening of the contralateral superior oblique tendon, had been performed in those 5 cases. Only 1 of the successful cases had the same type of asymmetric adjustment. There was a positive association between the severity of the preoperative Lan R-G pattern and postoperative diplopia. CONCLUSIONS: Asymmetric adjustment of bilateral Harada-Ito procedures when attempting to correct the coexisting vertical misalignment can cause significant torsional incomitance with incomplete correction of extorsion in downgaze and intorsion in upgaze. This pattern may result in postoperative diplopia that is surgically challenging to correct.

Optical Coherence Tomography Angiography in Prematurity.

Purpose: During normal foveal development there is a close interaction between the neurosensory and vascular elements of the fovea making it vulnerable to prematurity and retinopathy of prematurity (ROP). We aim to assess this potential effect on foveal development in preterms evaluated simultaneously with both optical coherence tomography (OCT) and OCT angiography (OCTA).Method: Unrestricted literature search in the PubMed and Cochrane library databases yielded 20 distinct citations. Fifteen were relevant and reviewed.Results: In preterms, OCTA demonstrated a significant decrease in the foveal avascular zone area and an increase in foveal vessel density. OCT showed a decrease in foveal pit depth and an increase in the thickness of the subfoveal retinal layers. Some studies correlated these changes with reduced vision.Conclusion: Changes in the vascular and neurosensory retina were found in premature children. It remains unclear whether this is related to prematurity alone or ROP and its treatment.