Studies of the device Perfect Capsule in an animal model to reduce lens epithelial cell proliferation

Abstract: The sealed-capsule irrigation device, the Perfect Capsule, is a surgical device designed to target lens epithelial cells (LECs) during cataract surgery and prevent posterior capsule opacification (PCO). This is especially important in cases in which the posterior capsule must stay intact after cataract surgery, such as when implanting accommodative lenses. It also can be used when PCO is expected to be extensive, such as in pediatric cataract surgery. This thesis was created to evaluate the use of the Perfect Capsule in small young eyes with very proliferative lens epithelial cells in an animal model with young rabbits. In the first study, 30 4-week-old rabbits had bilateral clear lens extraction. The Perfect Capsule was implanted in one eye and sealed-capsule irrigation was performed with either balanced salt solution (BSS), distilled deionized water (DDW), or 5-fluorouracil (5-FU) 50 mg/ml for 5 minutes. The capsule then was flushed with BSS to wash out the residual substance. The contralateral eye did not undergo sealed-capsule irrigation. The after-cataract was evaluated clinically and in images taken at 5.5 weeks after surgery and histologically after the endpoint 6 weeks postoperatively. Only 5-FU effectively prevented the development of after-cataract. The second study evaluated the safety of irrigation with 5-FU in 30 8-week-old rabbits. Clear lens extraction was performed in one eye and the Perfect Capsule was implanted in three of the four groups. In one group, the capsule was irrigated for 5 minutes with BSS, in the second group with 5-FU 50 mg/ml, and in the third group with 5-FU 50 mg/ml and then BSS to wash out the residual substance. In the fourth group, the Perfect Capsule was not used; to mimic leakage in the device 0.2 ml of 5-FU 50 mg/ml was instilled in the capsule, left for 30 seconds, and washed out with I/A. Safety was evaluated by comparing pachymetry, endothelial cell count, and histologic findings after the endpoint of 24 or 48 hours postoperatively (half of each group at each time point). There was no difference in pachymetry or endothelial cell count among the groups. Histology showed no damage in the central or peripheral retina or the trabecular meshwork due to the substance used. We concluded that it is safe to use the Perfect Capsule with 5-FU even if leakage occurs. The third study evaluated the possibility of lowering the 5-FU concentration and maintaining a sufficient preventive effect on LEC proliferation. We also evaluated irrigation with thapsigargin, which was reported to be effective in in vitro human studies. Thirty 4-week-old rabbits had clear lens extraction in one eye. The Perfect Capsule was implanted and the capsule was irrigated for 2 minutes with either BSS, 5-FU 50 mg/ml, 5-FU 25 mg/ml, or thapsigargin and then BSS for 10 seconds. The after-cataract was evaluated clinically and in images taken 5 weeks postoperatively and histologically at 6 weeks postoperatively. The 50 mg/ml concentration of 5-FU successfully prevented after-cataract formation. Thapsigargin was ineffective in this animal model. In the fourth study, we used transmission electron microscopy (TEM) to determine if the posterior capsule is damaged by 5-FU or thapsigargin or just by the use of the Perfect Capsule. Clear lens extraction was performed in 4-week-old rabbits. We studied two eyes that were irrigated for 2 minutes with BSS, two eyes with 5-FU 50 mg/ml, two eyes with 5-FU 25 mg/ml, and two eyes with thapsigargin. The substances were washed out with BSS for 10 seconds. We also included two control eyes that had not had surgery. At 6 weeks postoperatively, the capsules were extracted and fixed for TEM. The analyses showed no ultrastructural damage to the posterior capsules in any group.