J. Clin. Transl. Ophthalmol., Volume 2, Issue 2 (June 2024) – 2 articles

Aim: The study aims to identify if mutations in the SLC4A11 gene are present in Filipino families affected with congenital hereditary endothelial dystrophy (CHED). Methods: This is a family cohort study that investigated the genetic profile of a selected family in northern Luzon, Philippines, whose members were diagnosed with congenital hereditary endothelial dystrophy (CHED). A patient who was diagnosed with CHED prior to this study served as the proband for this family. A detailed family history was obtained and a complete ophthalmologic examination was performed on each of the family members. A total of six affected members and three unaffected members were included in this study. DNA was isolated from peripheral blood samples of the family members, polymerase chain reaction (PCR) was used to amplify the gene’s entire coding region (19 exons and 2 putative promoter regions), and finally, the amplified regions were analyzed using DNA sequencing. Results: Consanguinity was not present in the family. Corneal haze was reported to have been present since birth or shortly thereafter in all the affected patients. Slit-lamp examination showed edematous corneas. Molecular studies of the SLC4A11 gene revealed four novel homozygous point mutations variably presenting in the six affected members, as well as the three unaffected members. One unaffected family member (I-1) had a novel sense mutation absent in the other family members. All affected siblings showed little phenotypic variability. Conclusions: This is the first report that gives us a genetic profile of a northern Luzon family with members affected by CHED. This study supports earlier findings that mutations in the SLC4A11 gene are not consistently the same among different ethnic groups worldwide, probably due to the disease’s genetic heterogeneity. Our study documented five novel mutations, adding to the growing list of mutations probably responsible for acquiring the CHED phenotype. It is possible that there are more novel mutations waiting to be discovered in this hereditary disease. Screening for these specific mutations in other families may prove useful for genetic counseling, prenatal diagnosis, and the future development of gene therapy. Full article

Purpose: to investigate secondary glaucoma resulting from uveitis in a patient infected with Human T-cell Leukemia Virus Type 1 (HTLV-1) pathologically and discuss the management of glaucoma with recurrent uveitis. Clinical course: An octogenarian woman diagnosed as a carrier of HTLV-1 experienced recurrent uveitis and a sudden rise in intraocular pressure (IOP) in both eyes. Due to the uncontrolled IOP and severely damaged visual field in her left eye, a combined procedure of trabeculectomy and DGIS (glaucoma drainage implant surgery, Baerveldt 350) was performed. The presence of HTLV-1 provirus was detected in the aqueous humor. Her trabeculectomy sample was processed for light microscopic observation. Following an irregular follow-up, she presented with a sudden decrease in vision and pain in her fellow eye, four years after the glaucoma surgeries. Her right eye exhibited a significant accumulation of mutton-fat-like keratic precipitates. Results: Clinical manifestations revealed the presence of granulomatous uveitis. The combined glaucoma surgery, along with continuous topical corticosteroid medication post-surgery in her left eye, effectively suppressed the high IOP spikes and the recurrence of uveitis for 4 years. The pathological examination of the outflow pathways showed a range of damages in Schlemm’s canal (SC), including SC endothelial loss, narrowing, and occlusion, as well as loss of trabecular meshwork (TM) cells and fused TM beams. Conclusion: Combined GDIS and trabeculectomy represents a promising approach for managing such refractory cases of secondary glaucoma. Continuous topical corticosteroid medication is strongly recommended to prevent irreversible changes in SC and TM associated with granulomatous uveitis. Full article