Rho-kinase (ROCK) inhibitors—initially explored for their impact on corneal wound healing and endothelial regeneration—now show the potential to also increase aqueous outflow and reduce intraocular pressure (IOP).1,2 But, unlike corneal wounds, glaucoma doesn’t “heal.” Glaucoma patients usually have daily drop regimens to control their IOP, which could cause issues for the cornea.

Reports out of Japan suggest that these drugs change the corneal endothelial cell (CEC) morphology and density (CECD).3-5 A 2015 study reported temporal morphological changes in CECs post-instillation of a ROCK inhibitor.3 That research indicated that CECs had indistinct cell borders, with a few very dark or swollen cells. A second study from the same year found mild protrusions along the cell-to-cell borders, also attributed to ROCK inhibitor use.4 Now, a third Japanese study suggests those changes are temporary at most and that they may have been built on flawed data.5

The second study was based on data collected with non-contact specular microscopy (NCSM) software, according to the authors of the newest research.5 The confusion came based on “transient morphological changes” within one hour of the ROCK inhibitor’s instillation, they said.5 But, they believe their new study shows those changes return to normal within approximately six hours.5

To determine this, they performed an observational study of 163 eyes of 163 patients with glaucoma in whom CEC morphological change was evaluated by CECD calculated via NCSM before and at one or three months after instillation.

The patients were divided into the following three groups based on the elapsed time post-instillation: early (<2 hours), middle (≥2<6 hours) and late (≥6 hours). The median rate of CECD change was 5.68% for the early group, −4.95% for the middle group and −0.07%, for the late group.5

1. Serle J. Novel addition for IOP reduction. Glaucoma Today. glaucomatoday.com/articles/2017-sept-oct/novel-addition-for-iop-reduction. September/October 2017. Accessed May 4, 2020.

2. Liu H, Heiland M, Rosen D, et al. Rho kinase inhibitors. Eye Wiki. eyewiki.aao.org/Rho_kinase_inhibitors. April 7, 2020. Accessed May 4, 2020.

3. Nakagawa H, Koizumi N, Okumura N, et al. Morphological changes of human corneal endothelial cells after Rho-associated kinase inhibitor eye drop (ripasudil) administration: a prospective open-label clinical study. PLoS One 2015;10:e0136802.

4. Okumura N, Okazaki Y, Inoue R, et al. Rho-associated kinase inhibitor eye drop (ripasudil) transiently alters the morphology of corneal endothelial cells. Invest Ophthalmol Vis Sci. 2015;56:7560-7.

5. Maruyama Y, Ikeda Y, Mori K, et al. Morphological change and recovery of corneal endothelial cells after rho-associated protein kinase inhibitor eye-drop (ripasudil 0.4%) instillation. BMJ Ophthalmol. April 8, 2020. [Epub ahead of print].