Abstract
Purpose::
The tolerability of repetitive ocular iontophoretic applications was investigated with 5 daily transscleral treatments and a consecutive 14 day regiment in which the device was intentionally misplaced to encompass a portion of the cornea. For both studies, pigmented rabbits received a 2.5 mA/5 min application with 0.9% saline solution. Ocular examinations were conducted at the end of the 5 day study, while the misplacement group was evaluated at 15 and 29 days post treatment.
Methods::
In both the transscleral and misplacement studies, pigmented rabbits (n=10) were administered with one 5 min iontophoretic administration with the Eyegate II device filled with saline. No intensity (0 mA) was applied in left eyes and 2.5 mA applied in right eyes. This administration was performed one time per day for five and 14 consecutive days for the transscleral and transscleral-corneal studies, respectively. All animals were sacrificed at the end of the 5 day study, while 5 animals were sacrificed at day 15 in the 14 day treatment group. The remaining 5 animals were monitored during a recovery period of 14 days and were sacrificed on day 29. Ocular evaluations were made using the Draize scale, McDonald-Shadduck scale, lissamine green test, confocal corneal microscope and ERG.
Results::
Following administration, mild hyperemia was observed in both treatment and control animals. Mild conjunctiva chemosis and low scores corneal haze were observed in both eyes of the 14 day treatment arm with a main score of 1 (scale: 0-4). No other eye structures were modified or affected. All clinical observations were reversible by day 29. In the 14 day treatment arm, fluorescein staining was observed on both the control and treated eyes in 8 animals at day 15 and persisted by day 29 in 3 of the 5 remaining animals. Transitory corneal irritation was observed, by lissamine green staining, 5 min after administration on both eyes of the misplacement arm that fully resolved within 24 hours. Confocal microscopy, as well as histopathological examinations, revealed epithelial abrasions by day 15 in both the control and test eyes. By day 29, the test eyes were fully resolved, while the control eyes revealed slight epithelial abrasions of the conjunctiva.
Conclusions::
Five daily consecutive applications of the Eyegate II Delivery System is extremely well tolerated, producing only transient hypermia, which was independent of applied current. Even in an extreme misuse situation (14 consecutive daily applications) which causes the device to partially cover the cornea, no clinical abnormalities were observed in the test group at the 14 day recovery period.
Keywords: ocular irritancy/toxicity testing • anterior segment • cornea: epithelium