New Zealand White (NZW) rabbits of either sex weighing 2 to 3 kg (Covance Laboratories, Inc., Vienna, VA) were anesthetized with ketamine hydrochloride (35 mg/kg; Fort Dodge, Inc., Fort Dodge, IA) intramuscularly (IM) and xylazine (5 mg/kg; Phoenix Scientific, Inc., St. Joseph, MO) IM. Proparacaine 1% ophthalmic drops (Allergan America, Hormigueros, PR) were used topically on the eye. The pupils were dilated with 1 drop each of phenylephrine hydrochloride 2.5% (Akorn, Inc., Decatur, IL) and tropicamide 1% (Alcon, Inc., Humacao, PR). A baseline eye examination, including fundoscopy with an indirect ophthalmoscope and intraocular pressure measurement, was performed. A toothed forceps was used to lift the conjunctiva and Tenon’s fascia in the superotemporal quadrant, and a 3-mm incision was made with Wescott tenotomy scissors. A pocket was formed in the sub-Tenon’s space, and two adjacent implant A devices were placed on the episclera, 5 mm posterior and parallel to the limbus in one eye. No sutures were used to secure the implants. To avoid bleeding, care was taken not to enter the venous sinus that surrounds the lacrimal gland. The conjunctiva and Tenon’s fascia were reapproximated with a single 9-0 Vicryl suture. Bacitracin ophthalmic ointment was placed in the operative eye twice daily for 3 days. Clinical eye examinations were performed weekly for 1 month and monthly thereafter. Blood was obtained from the rabbits monthly, and serum chemistries, renal and liver function tests, complete blood count, and cyclosporine blood levels were determined. ERGs were recorded from each eye separately after 30 minutes of dark adaptation. A monopolar contact lens electrode (ERG-jet; Universo, La Chaux des Fonds, Switzerland) was placed on the cornea and served as the active electrode. A Barraquer eyelid speculum connected to an electrode wire served as the indifferent electrode, and a subdermal needle electrode inserted in the forehead area as the ground electrode. ERGs were elicited by brief flashes at 0.33 Hz delivered with a photostimulator (model PS22; Grass-Telefactor Instruments, W. Warwick, RI) at maximum intensity, coupled to an 18-inch long optic guide of 0.5-inch diameter. Responses were amplified, filtered, and averaged with a signal-averaging device (Spirit; Nicolet Instruments Corp., Madison, WI). Averages of 20 responses were measured to obtain peak amplitudes of a- and b-waves. Recordings were performed at baseline and every 4 to 8 weeks for 6 months. Differences in the mean amplitudes at each recording were compared with the baseline (preimplant) values for each eye and tested by analysis of variance (ANOVA) on computer (PSI-Plot, ver. 7.0; Poly Software International, Inc., Pearl River, NY). Differences were considered clinically significant if P ≤ 0.05. A subgroup of animals were anesthetized and then euthanatized with an intracardiac pentobarbital overdose (Beuthanasia-D Special; Schering Plough Animal Health Corp., Kenilworth, NJ) at 6 months. The lacrimal glands were removed, and both eyes were enucleated, leaving the implants and overlying conjunctiva intact. All tissues were placed in 10% formalin for a minimum of 7 days. The globes were sectioned vertically across the long axis of the implants and through the optic discs. All tissue specimens were placed in increasing concentrations of ethanol, cleared with xylene using a tissue processor (Jung Histokinette; Leica, Inc., Deerfield, IL), and embedded in paraffin (Shandon Embedding Center; Shandon, Inc, Pittsburgh, PA). Sections of 7-μm thickness were obtained with a microkeratome and stained with hematoxylin and eosin, and representative slide-mounted sections were examined by light microscopy.