No abstract

Drug-loaded hydrogel devices are emerging as an effective means of localized and sustained drug delivery for the treatment of corneal conditions and injuries. One such device uses a novel, thiolated crosslinked carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) film to deliver drug to the ocular surface upon placement into the inferior fornix of the eye. While proven to be very safe and effective, the CMHA-S film tends to dislodge in the highly-lubricated ocular environment, thereby reducing drug delivery efficiency and drug efficacy. In this study, we used a three-dimensional computational finite element model of the eye to determine the effect of geometry and surface friction on film retention in the inferior fornix, and to evaluate multiple geometrical film designs. Retention of the film was dependent on geometry and on the friction ratio of the film to the eyelid and globe. These effects were interactive. When the ratio of friction on the lid side to the globe side of the film was low, geometry played a large role in the film's displacement. When this ratio was high, differences in displacement due to geometry were negligible. The optimal relationship of friction between the film and its eyelid-side and globe-side surfaces was found to be linear with at least 1.4 times greater friction required on the eyelid-side for immobilization. A geometry similar to a half cylinder was found to be most effective with this friction ratio in retaining the film in the inferior fornix and in contact with the globe. Other geometries will likely require other friction ratios. In summary, CMHA-S film retention can be achieved through simple modifications of geometry and manipulation of surface interaction with the eye.

While several studies have qualitatively investigated age- and region-dependent adhesion between the vitreous and retina, no studies have directly measured the vitreoretinal strength of adhesion. In this study, we developed a rotational peel device and associated methodology to measure the maximum and steady-state peel forces between the vitreous and the retina. Vitreoretinal adhesion in the equator and posterior pole were measured in human eyes from donors ranging 30 to 79 years of age, and in sheep eyes from premature, neonatal, young lamb, and young adult sheep. In human eyes, maximum peel force in the equator (7.24 ± 4.13 mN) was greater than in the posterior pole (4.08 ± 2.03 mN). This trend was especially evident for younger eyes from donors 30 to 39 years of age. After 60 years of age, there was a significant decrease in the maximum equatorial (4.69 ± 2.52 mN, p = 0.016) and posterior pole adhesion (2.95 ± 1.25 mN, p = 0.037). In immature sheep eyes, maximum adhesion was 7.60 ± 3.06 mN, and did not significantly differ between the equator and posterior pole until young adulthood. At this age, the maximum adhesion in the equator nearly doubled (16.67 ± 7.45 mN) that of the posterior pole, similar to the young adult human eyes. Light microscopy images suggest more disruption of the inner limiting membrane (ILM) in immature sheep eyes compared to adult sheep eyes. Interestingly, in human eyes, ILM disruption was significantly greater in the posterior pole (p < 0.05) and in people over 60 years of age (p < 0.02). These findings supplement the current discussion surrounding age-related posterior vitreous detachment, and the risk factors and physiological progressions associated with this condition. In addition, these data further our understanding of the biomechanical mechanisms of vitreoretinal adhesion, and can be used to develop age- appropriate computational models simulating retinal detachment, hemorrhaging, or retinal trauma.

These data suggest that methylcellulose can be used to create a friction differential on the film, but a potentially increased degradation rate with the methylcellulose must be considered in the design.