As cataract removal is the most frequently performed surgical procedure worldwide, surgeons have made great strides in keeping complications to a minimum. But despite its excellent safety profile, cataract surgery can still negatively impact the corneal endothelium. Surgeon must therefore exercise great care, as fragile endothelial cells cannot regenerate.

Or can they? Some early research shows regrowth potential from use of rho-associated kinase inhibitors, particularly ripasudil. Consequently, a recent study aimed to assess the protective effect of the drug on corneal endothelial cells after surgery. The prospective designed and non-randomized investigation included 43 total patients divided into two groups: one in which ripasudil was administered (22 patients, 23 eyes) and a control group (21 patients, 21 eyes).

All patients had grade 3 nuclear cataract and underwent phacoemulsification with intraocular lens implantation. For the ripasudil group, one drop was administered three times a day for five days. Outcome measures were recorded preoperatively as well as 12 months post-op and included central corneal thickness (CCT) and endothelial cell density (ECD).

One previous study reported early apoptosis reduction of corneal endothelial cells using a prophylactic ROCK inhibitor by 37.1% and late reduction by 45.3% for late apoptosis.

One previous study reported early apoptosis reduction of corneal endothelial cells using a prophylactic ROCK inhibitor by 37.1% and late reduction by 45.3% for late apoptosis. Photo: Bhawan Minhas, OD. Click image to enlarge.

The median ECD was 2,398 cells/mm2 at baseline in the ripasudil group and 2,503 cells/mm2 at baseline in the control group. After 12 months post-op, the median in the ripasudil group was 2,262 cells/mm2 vs. 2,170 cells/mm2  in the control group. Endothelial cell loss (ECL) was worse in the control group at 12.8% vs. the much lower 4.5% seen in the ripasudil group. However, it was seen that CCT, age, sex and surgery duration were not significant factors. No groups experienced observed adverse effects.

In their discussion, the study authors explain how new drugs, including ROCK inhibitors, have recently entered the market. Rho kinase, the protein kinase used in these drugs, contributes to cell size regulation and shape via cytoskeleton structure. As they elucidate further, “initially released as a glaucoma drug, ROCK inhibitors were later recognized for their potential to protect the corneal endothelium due to their ability to enhance cell adhesion, promote cell migration and growth and exhibit antiapoptotic properties.”

To add to the study’s results, the authors do point out that best-corrected visual acuity was comparable between groups, but it is well-established that substantial ECL may trigger corneal endothelial decompensation and necessitate a corneal transplant.

“Thus,” the authors argue, “ripasudil use may be beneficial in reducing ECL, which could potentially result in a decreased need for corneal transplantation. It is conceivable that its use could be indicated in patients with borderline or low ECD.”

They do caution, however, that “there is a critical need for future research to ascertain the optimal dosing, duration and frequency of ripasudil administration, alongside an evaluation of its long-term safety and efficacy.”

Alkharashi M, Abusayf MM, Otaif W, Alkharashi A. The protective effect of rho-associated kinase inhibitor eye drops (ripasudil) on corneal endothelial cells after cataract surgery: a prospective comparative study. Ophthalmol Ther. April 30, 2024. [Epub ahead of print].