RESUMEN
Purpose: Genome editing is an emerging group of technologies with the potential to ameliorate dominant, monogenic human diseases such as late-onset retinal degeneration (L-ORD). The goal of this study was to identify disease stages and retinal locations optimal for evaluating the efficacy of a future genome editing trial. Methods: Twenty five L-ORD patients (age range, 33-77 years; median age, 59 years) harboring the founder variant S163R in C1QTNF5 were enrolled from three centers in the United Kingdom and United States. Patients were examined with widefield optical coherence tomography (OCT) and chromatic perimetry under dark-adapted and light-adapted conditions to derive phenomaps of retinal disease. Results were analyzed with a model of a shared natural history of a single delayed exponential across all subjects and all retinal locations. Results: Critical age for the initiation of photoreceptor loss ranged from 48 years at the temporal paramacular retina to 74 years at the inferior midperipheral retina. Subretinal deposits (sRET-Ds) became more prevalent as critical age was approached. Subretinal pigment epithelial deposits (sRPE-Ds) were detectable in the youngest patients showing no other structural or functional abnormalities at the retina. The sRPE-D thickness continuously increased, reaching 25 µm in the extrafoveal retina and 19 µm in the fovea at critical age. Loss of light sensitivity preceded shortening of outer segments and loss of photoreceptors by more than a decade. Conclusions: Retinal regions providing an ideal treatment window exist across all severity stages of L-ORD.
Asunto(s)
Terapia Genética , Degeneración Retiniana , Humanos , Adulto , Persona de Mediana Edad , Anciano , Enfermedades de Inicio Tardío/genética , Enfermedades de Inicio Tardío/patología , Enfermedades de Inicio Tardío/terapia , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Degeneración Retiniana/terapia , Colágeno/genética , Masculino , Femenino , Fóvea Central/patología , Tomografía de Coherencia Óptica , Terapia Genética/métodos , Edición GénicaRESUMEN
PURPOSE: To report the ocular hypertensive response to high-dose systemic corticosteroid in a pediatric patient. DESIGN: Observational case report. METHODS: A 9-year-old patient with leukemia received oral prednisolone at a dosage of 2.3 mg/kg/d for 5 weeks, followed by a 4-month break and then a 4-week course of oral dexamethasone at 10 mg/d. Detailed ocular examination was performed for both eyes before and regularly throughout the two courses of treatment. RESULTS: The intraocular pressure in both eyes rose to almost 40 mm Hg after only 8 days of oral corticosteroid. On stopping systemic corticosteroid, the intraocular pressure rapidly returned to baseline level within 2 days. A similar intraocular pressure profile was recorded for both eyes during the course of oral dexamethasone. The patient remained largely asymptomatic throughout. CONCLUSIONS: Systemic corticosteroid may give rise to significant but asymptomatic ocular hypertension in pediatric patients.
