Takeshi Morimoto

Testing of semichronically implanted retinal prosthesis by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa.

PURPOSEnTo examine the safety and effectiveness of a retinal prosthesis that is implanted semichronically in two patients with advanced retinitis pigmentosa (RP).nnnMETHODSnTwo eyes of two patients with advanced RP had a retinal prosthesis implanted in a sclera pocket of one eye. The visual acuity of both eyes before the implantation was bare light perception. Phosphenes were elicited by suprachoroidal-transretinal stimulation (STS). The internal devices of the STS were implanted under the skin on the temporal side of the head, and the 49 electrode-array was implanted in the scleral pocket of one eye. Biphasic electrical pulses (duration, 0.5 ms; frequency, 20 Hz) were delivered through nine active electrodes. The threshold current was determined by currents ≤1 mA. Behavioral tasks were used to determine the functioning of the prosthesis.nnnRESULTSnThe surgery was completed without a retinal detachment and retinal/vitreous hemorrhage. The implanted STS system remained functional for the 4-week test period. Phosphenes were elicited by currents delivered through six electrodes in Patient 1 and through four electrodes in Patient 2. The success of discriminating two bars was better than the chance level in both patients. In Patient 2, the success of a grasping task was better than the chance level, and the success rate of identifying a white bar on a touch panel increased with repeated testing.nnnCONCLUSIONSnSemichronic implantation of a microelectrode-STS system showed that it was safe and remained functional for at least 4 weeks in two patients with advanced RP. (www.umin.ac.jp/ctr number, R000002690.).

Transcorneal electrical stimulation promotes survival of photoreceptors and improves retinal function in rhodopsin P347L transgenic rabbits.

PURPOSEnTo determine whether transcorneal electrical stimulation (TES) has neuroprotective effects on the photoreceptors, and whether it slows the rate of decrease of the electroretinogram (ERG) in rhodopsin P347L transgenic (Tg) rabbits.nnnMETHODSnSix-week-old Tg rabbits received TES through a contact lens electrode on the left eye weekly for 6 weeks. The right eyes received sham stimulation on the same days. Electroretinograms (ERGs) were recorded before and at 12 weeks after the TES. After the last ERG recordings, the animals were euthanized for morphologic analysis of the retinas. Immunohistochemical (IHC) analysis was performed to detect the immunostaining by peanut agglutinin (PNA) and rhodopsin antibodies in the retinas.nnnRESULTSnThe a- and b-wave amplitudes of the photopic ERGs and the b-wave amplitudes of the scotopic ERGs at higher stimulus intensities were significantly larger in the TES eyes than in the sham stimulated eyes (P<0.05, respectively). Morphologic analyses showed that the mean thickness of the outer nuclear layer (ONL) in the visual streak at 12 weeks was significantly thicker in TES eyes than in sham-stimulated eyes (P<0.05). IHC showed that the immunostaining by PNA and rhodopsin antibody in the TES-treated retinas was stronger than that in the sham-stimulated retinas.nnnCONCLUSIONSnTES promotes the survival of photoreceptors and preserves the ERGs in Tg rabbits. Although further investigations are necessary before using TES on patients, these findings indicate that TES should be considered for therapeutic treatment for RP patients with a P347L mutation of rhodopsin.

Characteristics of Retinal Reflectance Changes Induced by Transcorneal Electrical Stimulation in Cat Eyes

Transcorneal electrical stimulation (TES) activates retinal neurons leading to visual sensations. How the retinal cells are activated by TES has not been definitively determined. Investigating the reflectance changes of the retina is an established technique and has been used to determine the mechanism of retinal activation. The purpose of this study was to evaluate the reflectance changes elicited by TES in cat eyes. Eight eyes of Eight cats were studied under general anesthesia. Biphasic electrical pulses were delivered transcornealy. The fundus images observed with near-infrared light (800–880 nm) were recorded every 25 ms for 26 s. To improve the signal-to-noise ratio, the images of 10 consecutive recordings were averaged. Two-dimensional topographic maps of the reflective changes were constructed by subtracting images before from those after the TES. The effects of different stimulus parameters, e.g., current intensity, pulse duration, frequency, and stimulus duration, on the reflective changes were studied. Our results showed that after TES, the reflective changes appeared on the retinal vessels and optic disc. The intensity of reflectance changes increased as the current intensity, pulse duration, and stimulation duration increased (P<0.05 for all). The maximum intensity of the reflective change was obtained when the stimulus frequency was 20 Hz. The time course of the reflectance changes was also altered by the stimulation parameters. The response started earlier and returned to the baseline later with higher current intensities, longer pulse durations, but the time of the peak of the response was not changed. These results showed that the reflective changes were due to the activation of retinal neurons by TES and might involve the vascular changes induced by an activation of the retinal neurons.

One-Year Outcome of 49-Channel Suprachoroidal–Transretinal Stimulation Prosthesis in Patients With Advanced Retinitis Pigmentosa

PurposenTo determine the feasibility of a 49-channel suprachoroidal-transretinal stimulation (STS) retinal prosthesis that was implanted for 1 year.nnnMethodsnThree patients with advanced retinitis pigmentosa (RP) and with less than or equal to hand motion (HM) vision were studied. A 49-channel STS system was implanted in a scleral pocket, and the stability of the prosthesis, adverse events, and its efficacy were investigated.nnnResultsnThe electrode array was implanted in a scleral pocket located under the parafoveal area through a scleral incision at 14 mm in patient (Pt) 1, 16 mm in Pt 2, and 18 mm in Pt 3 from the sclerocorneal limbus. No complications occurred during surgery in all cases. During the follow-up period, iridocyclitis developed in Pt 2 and Pt 3, which was successfully treated with topical medications. The implanted devices continued functioning and elicited phosphenes in all cases. The results of localization tests (P < 0.05) and table tests (P < 0.05) were significantly better with the prosthesis turned on than turned off in Pt 3. The deviations of the walking tests were smaller with the prosthesis turned on than off in Pt 2 and Pt 3 at multiple times after the implantation.nnnConclusionsnThe 49-channel STS retinal prosthesis was able to elicit phosphenes in all patients with advanced RP for the entire 1-year experimental period without major complications. Better results on visual tasks were found in the eyes in which the electrode array was implanted closer to the fovea centralis.

Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal–transretinal stimulation prosthesis in middle-sized animals

PurposeTo investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal–transretinal stimulation (STS) prosthesis in middle-sized animals.MethodsThe prosthesis consisted of two arrays with 50 to 74 electrodes. To test the feasibility of implanting the prosthesis and its efficacy, the prosthesis was implanted for 14xa0days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14xa0days after the implantation. Then the rabbits were euthanized, eyes were enucleated, and the posterior segment of the eye was examined histologically. In a second experiment, the arrays were implanted into two cats, and their ability to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina.ResultsAll arrays were successfully implanted, and no major complications occurred during the surgery or during the 2-week postoperative period. Neither OCT nor ophthalmoscopy showed any major complications or instability of the arrays. Histological evaluations showed only mild cellular infiltration and overall good retinal preservation. Stimulation of the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging showed that the electrical pulses from the arrays altered the retinal images indicating an activation of retinal neurons. The thresholds were as low as 100xa0μA for a chiasm response and 300xa0μA for the retinal imaging.ConclusionImplantation of a newly-developed dual-array STS prosthesis for 2xa0weeks in rabbits was feasible surgically, and safe. The results of retinal imaging showed that the dual-array system was able to activate retinal neurons. We conclude that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

Retinal nerve fiber layer and ganglion cell complex thicknesses measured with spectral-domain optical coherence tomography in eyes with no light perception due to nonglaucomatous optic neuropathy

PurposeTo measure retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex thickness (GCCT) in eyes with no light perception due to nonglaucomatous optic neuropathy using spectral-domain optical coherence tomography.MethodsFourteen eyes of 14 patients (9 women, 5 men; mean age 56.0 ± 16.6 (standard deviation)xa0years] with no light perception due to optic neuropathy were recruited to this retrospective study. Only clinically stable eyes were included. Eyes were imaged at least 6xa0months after the onset of the disease. Five patients lost light perception due to traumatic optic neuropathy, four patients had ischemic optic neuropathy, two patients had optic neuritis, two patients had compressive optic neuropathy, and one patient had optic nerve atrophy. Global and quadrant RNFLTs were measured with the Cirrus HD-optical coherence tomography (OCT) system; global and hemisphere GCCTs were measured by spectral-domain OCT (RTVue OCT system). Only reliable OCT images were used for further analysis.ResultsReliable RNFL images were obtained in 12 eyes, and reliable GCC images were obtained in 11 eyes. Global, superior, temporal, inferior, and nasal RNFLT were 57.5xa0±xa06.7, 60.6xa0±xa07.6, 54.1xa0±xa011.2, 59.7xa0±xa09.5, and 55.6xa0±xa07.4xa0µm, respectively. Global, superior, and inferior GCC thicknesses were 68.8xa0±xa09.6, 70.7xa0±xa012.2, and 67.8xa0±xa08.8xa0µm, respectively.ConclusionsA considerable proportion of RNFL and GCC remained in eyes with no light perception vision. Clinicians should take this into account when evaluating the severity of optic neuropathy from OCT-measured RNFLT and GCCT.

False reaching movements in localization test and effect of auditory feedback in simulated ultra-low vision subjects and patients with retinitis pigmentosa.

PurposeTo determine the accuracy of reaching movements with localization tests in subjects with simulated ultra-low vision, and to examine the effectiveness of auditory feedback training in improving the accuracy of the reaching movements.MethodsTwenty-one subjects with simulated ultra-low vision and three patients with advanced retinitis pigmentosa (RP) were studied with the localization tester. The localization tester had white square targets with a visual angle of 10° that were projected randomly on a computer monitor screen. The subjects or RP patients were instructed to touch the center of the target. Each subject was tested 20 trials. The distance from the center of the target to the point where subjects touched, the deviation, was calculated automatically by the computer. We also examined the effect of auditory feedback on improving the accuracy of reaching movements.ResultsThe average angle of deviation in the subjects was not significantly correlated with visual acuity. The points touched by subjects with simulated low vision were located downward and horizontally toward the hand they used. They were condensed around the barycenter of the touched points (paired t tests; *pu2009=u20090.037). The touched points of the patients also deviated downward and condensed around the barycenter. The deviations decreased significantly with auditory feedback when trained over 100 trials.ConclusionsThe subjects with simulated ultra-low vision and the advanced RP patients had false orientations against the position of localized target systematically. An auditory feedback system may help to correct the false orientations for reaching movements in patients with very low vision.

Serial measurements of accommodation by open-field Hartmann-Shack wavefront aberrometer in eyes with accommodative spasm.

PurposeTo investigate the serial changes of accommodation and spherical aberration in eyes with accommodative spasm.MethodsFour patients with accommodative spasm and ten healthy subjects were studied. The ocular refractive power (spherical equivalent) and spherical aberration were measured serially with an open-field, binocular Hartmann–Shack wavefront aberrometer. Patients and subjects wore full-correction lenses and were instructed to fixate a target set at 50xa0cm from the eye. The time-average of the refractive power, spherical aberration, and fluctuations of accommodation analyzed by the fast Fourier transform (FFT) of the two groups were compared.ResultsThe averagexa0±xa0standard deviation refractive power in the patients was significantly more negative than that in the healthy subject (−3.12xa0±xa01.06 vs. −1.49xa0±xa00.17xa0D). The integrated intensity of the FFT from 1 to 4xa0Hz was significantly higher in the patients than in the healthy subjects. The spherical aberration in patients was more negative than that in the healthy subjects (−0.033xa0±xa00.048xa0μm vs. 0.002xa0±xa00.027xa0μm).ConclusionsEyes with accommodative spasm are characterized by a lead of accommodation with greater fluctuations and negative spherical aberrations. Excessive accommodation can be measured objectively in such eyes with a binocular wavefront aberrometer without cycloplegics.

Role of electrical activity of neurons for neuroprotection.

Neurons of the central nervous system (CNS) of adult mammals can be damaged in a variety of ways. Most neurons rapidly die after injury. Even if the injured CNS neurons do not die in a short time, the neurons eventually die because they are not able to regenerate their axons to reconnect with their normal targets. In addition, neurons are normally not replaced. Therefore, much work has been directed toward understanding of the molecular regulation of the CNS degeneration following injury, and different experimental strategies are being used to try to protect the damaged neurons. Following axonal lesion, the neurons not only need to survive but also to reconnect to be functionally relevant, and efforts are directed toward not only survival but also axonal regeneration and proper rewiring of injured neurons. Recent experimental data suggest that electrical activity, endogenous or exogenous, can enhance neuronal survival and regeneration in vitro and in vivo. This chapter reviews the evidence that have been obtained on the role of neuronal electrical activity on neuroprotection. We will develop perspectives toward neuroprotection and regeneration of adult lesioned CNS neurons based on electrical activity-dependent cell survival that may be applicable to various diseases of the CNS.

Evaluation of electrochemically treated bulk electrodes for a retinal prosthesis by examination of retinal intrinsic signals in cats

PurposeOur goal was to determine the feasibility of using electrochemically treated bulk platinum electrodes with large charge injection capacity for a retinal prosthesis.MethodsSeven eyes of seven cats were studied. Small retinal areas were focally stimulated with electrochemically treated bulk electrodes (φxa0=xa0500xa0µm) placed in a scleral pocket. Fundus images with near-infrared (800–880xa0nm) light were recorded, and a 2D map of the reflectance changes elicited by the electrical currents was constructed by subtracting the images taken before stimulation from those taken after stimulation. The impedance of each electrode was measured at 1xa0kHz. The degree of retinal elevation by the electrode was measured by optical coherence tomography. Scleral thickness where the electrode array was inserted was measured in histologic sections.ResultsThe diameter of reflectance changes (full width at half maximum) was 0.42xa0±xa00.22xa0mm [meanxa0±xa0standard deviation (SD)] in minor axes and 1.46xa0±xa00.82xa0mm in major axes. The threshold current decreased with a reduction in the residual scleral thickness (R2xa0=xa00.9215; Pxa0=xa00.0002); it also decreased with an increase in retinal elevation (R2xa0=xa00.6259; Pxa0=xa00.0111).The threshold current also decreased with an increase in electrode impedance (R2xa0=xa00.2554; Pxa0=xa00.0147).ConclusionsElectrochemically treated porous platinum electrodes can stimulate localized retinal areas. The threshold current necessary to stimulate the retina was influenced by residual scleral thickness and the electrode tightness of fit against the sclera.