Sofia De Arrigunaga

Kabuki Syndrome (KS) is a rare multiple congenital anomaly syndrome originally described in 1981 by Japanese clinicians. KS belongs to the family of chromatinopathies, a group of disorders characterized by abnormalities in chromatin regulation due to germline mutations in the KMT2D or KDM6A genes. KS is characterized by five cardinal manifestations: (1) postnatal growth deficiency, (2) skeletal anomalies, (3) dermatoglyphic anomalies - including persistent fetal pads, (4) mild-to-moderate intellectual disability, and (5) typical facial features. Ocular abnormalities have been reported in more than one-third of patients with KS, but abnormalities involving the retina are rare. Currently, five accounts describing patients with KS and documented macular lesions exist within the literature. However, only two of these reports provide concurrent genetic confirmation. We describe the unique case of a female infant with molecularly confirmed KS due to a novel pathogenic variant in KMT2D who presented with retinopathy of prematurity (ROP) and bilateral macular lesions. Although our patient accounts for the sixth known case of foveal lesions associated with KS, she represents the third molecularly confirmed case of a de novo, nonsense KMT2D variant with macular abnormalities. In silico analysis with the prediction program MutationTaster found the mutation to be deleterious. Genetic testing, along with ophthalmologic examination and multimodal imaging, are indispensable tools for physicians, especially when confronted with patients suspected of having KS. When effectively used together, these tools can facilitate vision-preserving strategies.

Purpose: The aim of this study was to evaluate the effect of corneal cross-linking on central endothelial cell density (ECD) by comparing masked measurements before and immediately after preparation of cross-linked (CXL) and non–cross-linked (non-CXL) donor corneas. Methods: Thirty donor corneas were randomized 1:1 to either CXL or non-CXL using a modified Dresden protocol. Specular microscopic images of the central corneal endothelium were obtained within 36 hours of recovery and within 3 hours of preparation completion. Images were sent to a central cornea image analysis reading center for ECD determination in a masked, dual-graded manner. Results: Before and after preparation, the mean ECD was 2567 ± 305 cells/mm² and 2525± 339 cells/mm² for the CXL group (n =15) and 2652 ± 365 cells/mm² and 2572 ± 513 cells/mm² for the non-CXL group (n =15), respectively. The mean difference in ECD before and after preparation was not statistically significant for the CXL and non-CXL groups (P = 0.36; P = 0.31, respectively). In addition, an independent sample t test showed no statistically significant difference in the ECD change between the CXL and non-CXL groups (P = 0.67). Conclusions: Our specular microscopic findings show that ex vivo cross-linking of donor corneas does not seem to produce acute decrease of central endothelial cell density. These findings are encouraging and assist in warranting a clinical trial examining its value in reducing refractive errors and improving postoperative visual outcomes in eyes with keratoconus that undergo keratoplasty.