RESUMO
This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.
RESUMO
South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic tools for phenotyping, and expensive genetic testing not covered by the public healthcare systems, are seen in all of them. Here, we provide a detailed report of the current status of ophthalmic genetics, described by the personal views of local ophthalmologists from Brazil, Colombia, Argentina, and Chile. By reporting our strengths and weaknesses as a region, we intend to highlight the need for guidelines on how to manage these patients aligned with public health policies. Our region contributes to research worldwide, with thousands of well diagnosed patients from a number of unique and genetically diverse populations. The constant expansion of ophthalmic genetics and molecular diagnostics requires us to join forces to collaborate across South America and with other countries to improve access to next-generation diagnostics and ultimately improve patient care.
Assuntos
Oftalmopatias Hereditárias/diagnóstico , Oftalmopatias Hereditárias/genética , Oftalmologia/tendências , Medicina de Precisão , Oftalmopatias Hereditárias/epidemiologia , Oftalmopatias Hereditárias/terapia , Humanos , América do Sul/epidemiologiaRESUMO
Age-related macular degeneration (AMD) is considered one of the main causes of severe vision loss in older adults. The neovascular form (nAMD) is an advanced stage, which is responsible for the most severe vision loss. Vascular endothelial growth factor (VEGF) is at present the main factor that leads to the development of a neovascular membrane and the increased leakage from the membrane to the retina. At present, anti-VEGF therapy is the only treatment that achieves vision gains in many patients and halts progression in most of them. VEGF blockade can be achieved with several molecules and various treatment regimens, which have been studied with excellent results. Unfortunately, real-world data has shown to be far less efficacious than clinical trials. This gap between clinical trials and real-world results is an unmet medical need that supports the necessity of new treatment modalities for nAMD. Of the various treatments being studied, anti-VEGFs of higher efficacy and longer durability are those more advanced in their development. Brolucizumab and abicipar pegol are 2 new anti-VEGF drugs that had positive results in phase 2 studies and are being tested in phase 3 trials at present. Other promising therapies are antiangiopoietin 2 molecules, which are in phase 2 development. At earlier stages of development but with promising results are squalamine, anti-VEGF-C and -D, and gene therapy. The future will give retina specialists a broad armamentarium with which patients may achieve high visual gains for the long term with a low treatment burden.