Preclinical Safety and Efficacy Assessments for Novel Femtosecond Lasers in Corneal Refractive Surgery.

Preclinical safety requirements and test methods have been standardized over time to guide medical device developers in the path needed to manufacture safe devices and achieve regulatory approval. Today, femtosecond lasers are commonly used in cataract and refractive surgeries. Currently, an industry standard to guide developers in preclinical testing of ophthalmic lasers does not exist. Consequently, the data presented in regulatory submissions may vary between manufacturers, making the regulatory review process more ambiguous. Here, the authors present a comprehensive discussion of preclinical test methods applied to the evaluation of an ophthalmic laser. We include in vitro and ex vivo models, as well as an in vivo rabbit model subject to corneal refractive treatments, for consideration in a preclinical safety evaluation plan. Scientific rationale to support the ocular endpoints of evaluation in the rabbit model to demonstrate safety is also presented and discussed.

Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model.

INTRODUCTION: To establish the preclinical safety and equivalency of ophthalmic viscosurgical devices (OVDs) comprised of bacterially sourced sodium hyaluronate (HA) to animal sourced HA using pyrogenicity and aqueous exchange models in rabbits and a novel mini-pig model to evaluate corneal endothelial cell protection in vivo. METHODS: HEALON OVD and HEALON5 OVD containing animal-derived HA and HEALON PRO OVD and HEALON5 PRO OVD containing bacterial-derived HA were used. Two rabbit aqueous exchange studies were conducted where aqueous humor was exchanged with OVDs in six animals each to observe potential ocular inflammation, intraocular pressure (IOP) response, corneal health and pachymetry until 7 days post procedure, as well as overall assessment of the OVDs. Endothelial cell protection was evaluated in a Yucatan mini-pig cataract surgery model where HEALON PRO and HEALON5 PRO OVDs were compared to HEALON and HEALON5 OVDs, respectively. Following cataract surgery with use of OVDs in six animals per study, animals were evaluated for ocular and general health, IOP, corneal thickness, ocular inflammation, and endothelial cell protection on days 1, 3, 7 and 14 post-surgery. RESULTS: All rabbit studies demonstrated equivalence between bacterial-derived and animal-derived OVDs. Mild, post-surgical irritation, IOP increase, and corneal thickness measurements were not significantly different in HEALON PRO OVD and HEALON5 PRO OVD compared to HEALON and HEALON5 OVDs, respectively. The mini-pig model developed to investigate endothelial cell protection was successful in demonstrating equivalence between the OVDs studied. Changes in IOP mirrored actual surgical procedures, while corneal pachymetry and endothelial cell density remained constant for all OVDs used. Slit lamp observations showed expected inflammation following surgical procedures, likely due to challenges encountered during surgical procedures. CONCLUSION: Rabbit pyrogenicity and aqueous exchanged paired with a novel simulated cataract surgery mini-pig model demonstrate equivalence of OVDs regardless of HA source. Albeit with challenges, the mini-pig model was shown to be a promising tool for endothelial cell evaluation during the development of new OVDs for ophthalmic use. FUNDING: Johnson & Johnson Surgical Vision, Inc.