RESUMEN
BACKGROUND: Electrical stimulation has a long history in ophthalmology. Subthreshold electrical stimulation can have beneficial therapeutic effects on hereditary degenerative retinal diseases. Suprathreshold stimulation is able to elicit visual perceptions and, if multielectrode fields are arranged as an array, usable pictures can be perceived by blind patients. OBJECTIVES: This is a review article on the current situation and studies on therapeutic transcorneal electrical stimulation. Moreover, the challenges, surgical concepts and visual results of active retinal implants are discussed. MATERIAL AND METHODS: This article gives an overview on transcorneal electrical stimulation and active retinal implants based on published results, with special emphasis on the clinical application. RESULTS: The results of initial controlled studies on therapeutic transcorneal electrical stimulation in hereditary retinal diseases were very promising. The largest controlled study so far in patients with retinitis pigmentosa (RP) has yielded many positive trends and some significant improvements in electrophysiological data. Currently, two retinal implants have regulatory approval, the Argus II retinal prosthesis system® (SecondSight®) and the Alpha-IMS© (Retina Implant AG). Both systems can be used to improve visual perception and under test conditions can achieve visual acuities of 0.02 and 0.04, respectively. CONCLUSION: In-depth analyses and follow-up studies in larger patient groups are currently planned to definitively clarify the potential of therapeutic transcorneal electrical stimulation in RP patients. The challenges of currently available active retinal implants are the technical biostability and the limited spatial resolution.
Asunto(s)
Terapia por Estimulación Eléctrica/instrumentación , Degeneración Retiniana/congénito , Degeneración Retiniana/terapia , Trastornos de la Visión/congénito , Trastornos de la Visión/prevención & control , Prótesis Visuales , Terapia por Estimulación Eléctrica/métodos , Análisis de Falla de Equipo , Medicina Basada en la Evidencia , Humanos , Diseño de Prótesis , Degeneración Retiniana/diagnóstico , Resultado del Tratamiento , Trastornos de la Visión/diagnóstico , Agudeza VisualRESUMEN
Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].).
Asunto(s)
Ceguera/terapia , Proteínas Portadoras/genética , Proteínas del Ojo/genética , Terapia Genética , Vectores Genéticos , Degeneración Retiniana/terapia , Adolescente , Adulto , Ceguera/congénito , Ceguera/genética , Ceguera/patología , ADN Complementario , Dependovirus/genética , Técnicas de Transferencia de Gen , Humanos , Inyecciones , Mutación , Retina/patología , Retina/fisiopatología , Degeneración Retiniana/congénito , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Agudeza Visual , cis-trans-IsomerasasRESUMEN
Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.