RESUMEN
Purpose: To describe the ophthalmological manifestations in transgender patients on gender-affirming hormone therapy. Methods: A retrospective chart review study was conducted. Female-to-male (FTM) and male-to-female (MTF) transgenders on gender-affirming hormone therapy evaluated at a single center were included. Candidates were collected using a phrase-identifying search tool within the electronic medical record system. Descriptive analyses were conducted to report the demographics, hormonal therapies, clinical findings, and visual outcomes. Results: A total of 17 patients were included, seven were FTM, and ten were MTF transgenders. The median age was 26.0 years (range; 20.0-30.0) in the FTM group and 35.0 years (range; 23.0-67.0) in the MTF group. Testosterone therapy in FTM patients comprised 30-60 mg of intramuscular injections weekly or 50 mg of transdermal gel daily. MTF patients used mainly 2-4 mg of estradiol and 100-300 mg of spironolactone tablets daily. A total of 27 eyes were affected, 12 in FTM and 15 in MTF patients. The median visual acuity was 20/25 in FTM (range; 20/20-20/60) and 20/25 in MTF (range; 20/20-20/400). The most common diagnoses in FTM patients were neurologic (71.4 %), particularly idiopathic intracranial hypertension, while MTF transgenders presented mainly with chorioretinal diseases (40.0 %). Compliance with medical recommendations and follow-up appointments was seen in 71.4 % of FTM and 50.0 % of MTF patients. At the last visit, the median visual acuity was 20/50 (range; 20/20-20/70) in FTM and 20/25 (range; 20/20-20/70) in MTF patients. Conclusions and importance: Transgenders presented a variety of ocular findings. A cause-and-effect association cannot be stated, yet eye specialists must be cognizant of these findings to provide appropriate treatment.
RESUMEN
Hypomorphic variants decrease, but do not eliminate, gene function via a reduction in the amount of mRNA or protein product produced by a gene or by production of a gene product with reduced function. Many hypomorphic variants have been implicated in inherited retinal diseases (IRDs) and other genetic ocular conditions; however, there is heterogeneity in the use of the term "hypomorphic" in the scientific literature. We searched for all hypomorphic variants reported to cause IRDs and ocular disorders. We also discuss the presence of hypomorphic variants in the patient population of our ocular genetics department over the past decade. We propose that standardized criteria should be adopted for use of the term "hypomorphic" to describe gene variants to improve genetic counseling and patient care outcomes.
RESUMEN
Signal peptide (SP) mutations are an infrequent cause of inherited retinal diseases (IRDs). We report the genes currently associated with an IRD that possess an SP sequence and assess the prevalence of these variants in a multi-institutional retrospective review of clinical genetic testing records. The online databases, RetNet and UniProt, were used to determine which IRD genes possess a SP. A multicenter retrospective review was performed to retrieve cases of patients with a confirmed diagnosis of an IRD and a concurrent SP variant. In silico evaluations were performed with MutPred, MutationTaster, and the signal peptide prediction tool, SignalP 6.0. SignalP 6.0 was further used to determine the locations of the three SP regions in each gene: the N-terminal region, hydrophobic core, and C-terminal region. Fifty-six (56) genes currently associated with an IRD possess a SP sequence. Based on the records review, a total of 505 variants were present in the 56 SP-possessing genes. Six (1.18%) of these variants were within the SP sequence and likely associated with the patients' disease based on in silico predictions and clinical correlation. These six SP variants were in the CRB1 (early-onset retinal dystrophy), NDP (familial exudative vitreoretinopathy) (FEVR), FZD4 (FEVR), EYS (retinitis pigmentosa), and RS1 (X-linked juvenile retinoschisis) genes. It is important to be aware of SP mutations as an exceedingly rare cause of IRDs. Future studies will help refine our understanding of their role in each disease process and assess therapeutic approaches.
