Macular Colobomata: Comparison of Clinical and Optical Coherence Tomography Features With Serologic Results.

PURPOSE: To assess the correlation between the morphologic features and serology in eyes with macular colobomata (MC). DESIGN: Retrospective comparative case series. METHODS: Setting: Institutional. STUDY POPULATION: Patients presenting with MC to the retina clinic over a period of 2 years (January 2016 to December 2017). Interventional/Observational Procedure: Color fundus and swept-source optical coherence tomography (SSOCT) features were reviewed and assessed in 3 groups based on the serum IgG results: positive for Toxoplasma, positive for cytomegalovirus (CMV), and serology negative. MAIN OUTCOME MEASURE: Morphologic features on clinical and OCT-based examination. RESULTS: A total of 49 eyes of 27 patients were recruited. The mean age was 24.8 ± 14.9 years (range 7-60 years). While the lesion size, the presence of satellite lesions, choroidal excavation, and choroidal lacunae (large choroidal vessels) on SSOCT differed significantly among the groups, pigmentation, retinal fibrosis, shape, retinal vessel pattern, and choroidal vessel visibility did not vary significantly. The lesions in CMV serology-positive cases were mostly solitary (n = 8/8), large (n = 5/8) and deeply excavated (n = 8/8). The lesions in Toxoplasma serology-positive cases were mostly flat to shallow (n = 18/26), medium-sized (n = 19/26), and either a solitary lesion (n = 17/26) or multiple satellite lesions (n = 9/26). The lesions in serology-negative cases were mostly small to medium (n = 13/15), solitary (n = 15/15), deeply excavated lesions (n = 11/15) with choroidal lacunae (n = 8/15). CONCLUSIONS: The clinical and SSOCT features such as the lesion size, the presence of satellite lesions, choroidal excavation, and choroidal lacunae can provide a clue toward the etiology of macular colobomata.

First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: a new dimension to the STRA6 phenotype.

Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting that additional risk loci exist. We used single nucleotide polymorphism (SNP) homozygosity mapping (HM) and targeted next-generation sequencing to identify the causative mutation for autosomal recessive isolated colobomatous microanophthalmia (MCOPCB) in a consanguineous Irish Traveller family. We identified a double-nucleotide polymorphism (g.1157G>A and g.1156G>A; p.G304K) in STRA6 that was homozygous in all of the MCOPCB patients. The STRA6 p.G304K mutation was subsequently detected in additional MCOPCB patients, including one individual with Matthew-Wood syndrome (MWS; MCOPS9). STRA6 encodes a transmembrane receptor involved in vitamin A uptake, a process essential to eye development and growth. We have shown that the G304K mutant STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity. Furthermore, we reproduced the MCOPCB phenotype in a zebrafish disease model by inhibiting retinoic acid (RA) synthesis, suggesting that diminished RA levels account for the eye malformations in STRA6 p.G304K patients. The current study demonstrates that STRA6 mutations can cause isolated eye malformations in addition to the congenital anomalies observed in MWS.