D. Guven

Long-term stimulation by active epiretinal implants in normal and RCD1 dogs

An epiretinal prosthesis, consisting of an extraocular microelectronic stimulator and an intraocular electrode array, was implanted in one eye of three blind and three sighted dogs. Three dogs (2 blind, 1 normal) were stimulated for 120 days, and two dogs (both normal) for 60 and 103 days respectively for 8-10 h/day at levels of 0.1 mC cm(-2) and 0.05 mC cm(-2), with each stimulus level presented to half of the array. One blind dog was kept as an inactive implant control. During the study period, electroretinograms (ERG) and fundus photographs were recorded. At the end of the study period, the dogs were sacrificed and histological and morphometric evaluation was made of the retina. No inflammatory reaction, neovascularization or hemorrhage was observed during the follow-up examinations. ERGs were unchanged. Stimulus levels used were of sufficient amplitude to elicit cortical evoked potentials. Histological evaluation showed no inflammatory infiltrates or changes in retina morphometry related to electrical stimulation when compared to the unstimulated control eye. Morphometric analysis revealed no consistent differences relating to electrical stimulation. In summary, chronic electrical stimulation of the dog retina at up to 0.1 mC cm(-2) with an epiretinal prosthesis does not appear to adversely affect the retina.

Retinal pigment epithelial abnormalities after internal limiting membrane peeling guided by indocyanine green staining.

X-linked retinoschisis (XLRS) is a rare genetic disorder associated with stellate maculopathy in all affected patients and peripheral schisis in one-half of affected patients. 1 Although the pathophysiology of the disease remains largely unknown, histopathologic reports have focused on the breakdown of Müller cells and the schisis at the level of the nerve fiber layer in the periphery. 2 Optical coherence tomography is capable of high-resolution cross-sectional imaging in vivo. We used optical coherence tomography to examine the macular findings of two patients with XLRS.

Effect of oxygenated intraocular irrigation solutions on the electroretinogram after vitrectomy.

Purpose: To investigate the effect of oxygenated intraocular irrigating solutions on electroretinograms (ERGs) for postvitrectomy rabbits. Methods: Eight groups of five rabbits each underwent pars plana vitrectomy on the right eye; the left eye of each rabbit served as control. The intraocular irrigating solutions were balanced salt solution (BSS), BSS-plus, BSS + oxygen (BSS + O2), BSS-plus + O2, and combinations of each with the addition of endoillumination (L). All animals were evaluated by single-flash scotopic electroretinography on the operated and nonoperated eyes before surgery and at 1 hour, 1 day, 1 week, and 1 month after surgery by an unmasked observer. The main outcome measures were dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios. The results for the different groups were compared by analysis of variance. Results: Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios ± SD for BSS-plus and BSS-plus + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.01 ± 0.09, 0.50 ± 0.11, 0.95 ± 0.11, 0.97 ± 0.11, and 0.99 ± 0.08 and 0.98 ± 0.08, 0.59 ± 0.10, 0.92 ± 0.06, 0.97 ± 0.08, and 0.97 ± 0.10, respectively. At both 1 hour and 1 day after surgery, rabbits treated with BSS-plus + O2 had an earlier b-wave return to baseline findings, but the differences were not statistically significant (P > 0.05). Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios ± SD for BSS and BSS + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.02 ± 0.10, 0.47 ± 0.09, 0.77 ± 0.07, 0.89 ± 0.07, and 0.89 ± 0.07 and 1.02 ± 0.06, 0.62 ± 0.16, 0.94 ± 0.09, 0.97 ± 0.08, and 0.96 ± 0.06, respectively. One hour and 1 day after surgery, ERG readings for rabbits treated with BSS + O2 exhibited a statistically significantly earlier return of ERG voltage to baseline values compared with both BSS and BSS + L (P = 0.05 and P = 0.02, respectively). One day after surgery, rabbits treated with BSS alone had the lowest ERG ratios. One week and 1 month after surgery, for all solutions tested other than BSS, ERG values were within normal limits. Conclusion: The use of oxygenated solutions appears to affect ERG readings after pars plana vitrectomy. Further studies to evaluate the role of oxygenated solutions in different vitreoretinal surgical procedures are warranted.

Retinal thickness in normal and RCD1 dogs using optical coherence tomography.

BACKGROUND AND OBJECTIVE To compare retinal thickness and retinal nerve fiber layer (RNFL) thickness values obtained by optical coherence tomography (OCT) in normal dogs and dogs with rod-cone dysplasia type 1 (RCD1). MATERIALS AND METHODS Eight eyes of 6 normal hound-bred dogs and 12 eyes of 6 dogs with RCD1, 2 to 5 years of age, were examined using the Fast RNFL Thickness, Fast Macular Thickness, and line scan protocols of OCT. RESULTS Retinal thickness was significantly higher in the tapetal fundus than in the non-tapetal fundus, in both normal (P = .0036) and RCD1 (P < .0001) dogs. Superotemporal, superonasal, and inferior retinal thickness values were significantly higher in normal dogs (P < .0001). Area centralis thickness was 183.5 +/- 10.66 microm in normal dogs and 136.16 +/- 13.12 microm in RCD1 dogs (P < .0001). There was no difference in RNFL thickness between normal and RCD1 dogs (P > .05). CONCLUSION OCT scanning in dogs is considered to be a useful method of evaluation in future retinal studies in this animal model.

Chronic electrical stimulation of the canine retina

An electronic retinal prosthesis is under development to treat retinitis pigmentosa and age-related macular degeneration, two presently incurable diseases of the outer retina. Previous studies have established the feasibility of the retinal prosthesis. The goal of these experiments was to investigate chronic stimulation of the retina. These effects were measured by direct examination of the implant, electrophysiology of the retina, electrically elicited responses, and examination of histology post-implant. Implants were placed in 6 dogs. The implant featured an implantable stimulator and a 4/spl times/4 array of 460-micron diameter platinum disks positioned on the retina. 6 dogs were chronically stimulated at 0.05 mC/cm/sup 2/ and 0.1 mC/cm/sup 2/ for up to 60 days (10-12 hours/day). No retinal damage was evident from the stimulus. Some mechanical damage of the retina due to array misalignment was apparent in early implants, but this was minimized with improved surgical technique. Bright flash electroretinograms showed no changes in retinal function comparing pre and post implant recordings. Electrically evoked cortical responses were recorded from 1 dog showing that the functional connection between the retina and the remained. Histological analysis revealed normal retina under the array of 1 dog that had been stimulated for 25 days.

Intraocular impedance as a function of the position in the eye, electrode material and electrode size

A critical element of a retinal prosthesis is the electrode assembly, which is placed on the retina. It is via this interface that the nerve cells are stimulated to produce the perception of light. The electrode impedance is an integral part in determining the design of the stimulating electrode and the attached circuit. The impedances involved are not only the tissue impedance but the electrode itself contributes to the impedance. Further on the electrode impedance depends not only the material of the electrode but also the size of the electrode. This paper discusses the results obtained by the intraocular impedance measurements with varying electrode size, electrode material and position of the electrode within the eye.

Helical intravitreal triamcinolone acetonide implant: a 6-month surgical feasibility study in rabbits.

BACKGROUND AND OBJECTIVE To investigate the surgical feasibility and safety of a long-term intravitreal triamcinolone acetonide (TA) sustained delivery system. MATERIALS AND METHODS Pigmented rabbits were implanted with sustained-release formulations containing 925 microg of TA within a non-biodegradable polymer coating: Dose A (n = 15) with a slow delivery rate of 1 to 2 microg/day and Dose B (n = 15) releasing 3 to 5 microg/day. Additionally, a control group (n = 10) using a device coated with polymer only was implanted. The devices were surgically implanted through a 30-gauge sclerotomy into the vitreous cavity. The animals were clinically observed for up to 6 months after the surgery with complete ophthalmologic examinations. Histologic evaluation of a subset of eyes was performed at the conclusion of the study. RESULTS Implants were successfully implanted in all 40 eyes. Ocular examinations revealed excellent implant tolerability. In all eyes, there was no significant postoperative inflammation at 1 week of follow-up. There was no increase in intraocular pressure during the follow-up period and histologic evaluation demonstrated no significant abnormalities. Minimal and localized vitreous hemorrhage was observed in 22.5% of implanted eyes and mostly cleared at 1 month after surgery. During the 6 months of follow up, localized lens opacities associated with physical implant contact developed in 66.6% of eyes. CONCLUSION The surgical procedure using the intravitreal TA sustained delivery device is feasible. Surgical complications were generally mild, with lens opacities attributable to unique anatomical features of the rabbit eye. Long-term follow-up and histology revealed excellent implant tolerability.

Cortical response after chronic electrical stimulation of canine retina

Electrical stimulation of the canine retina (in normal and RCD1) is carried out. An electronic retinal prosthetic chip is implanted which contain an implantable stimulator and 16 platinum electrodes disks of 460/spl mu/ diameter placed on the retina. Three dogs were chronically stimulated at 0.05 mC/cm/sup 2/ and 0.1 mC/cm/sup 2/ for 120 days (8-10 hours per day). Bright flash electroretinograms (ERGs) were recorded on the three dogs and found no recordable ERG from a blind dog. After completion of the stimulation protocol cortical subdural electrodes were implanted to record the cortical response for the electrical stimulation of the retina. The aim of this study is to evaluate the electrical evoked cortical responses in normal and blind dogs implanted with subdural electrodes.