Effect of tongue stimulation on nystagmus eye movements in blind patients.

We have observed dramatic effects of tactile tongue stimulation on nystagmus eye movements in patients with acquired blindness, and we report these results. Six adult subjects (3 subjects with light perception or worse vision and 3 normal subjects) were included in this study. Causes of blindness included traumatic explosion, anterior ischemic optic neuropathy, and central retinal artery occlusion. Duration of blindness was 15, 3 and 1.5 years, respectively. A video eye tracking system (Eyelink 1000) was used to record eye movements. The eye movement recording (EMR) was repeated four times in a span of 20 min. Two of the EMRs were performed without tongue stimulation and two with tongue stimulation in randomized order. A tongue stimulus was applied to the surface of the tongue using a Brainport device that produces an electrical tactile stimulus. The nystagmus waveform characteristics and frequency were analyzed. We found that all blind subjects showed continuous jerk nystagmus with slow and quick phases, mainly in horizontal plane in their primary eye positions. The recorded nystagmus waveforms were jerk with linear velocity slow phases. When the tongue stimulus was applied, the frequency of nystagmus was significantly reduced by 47, 40, and 11%, and relative amplitude was reduced by 43, 45, and 6% for three blind subjects, respectively. In conclusion, we think our results that tongue stimulation influences nystagmus eye movements support a link between non-visual sensory input and ocular motor activity.

Safety and efficacy of gene transfer for Leber's congenital amaurosis.

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.