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Perioperative Use of Rho‑Kinase
Inhibitors has Beneficial Effect
on Corneal Endothelium after
Phacoemulsification
Website:
www.meajo.org Majed Alkharashi1,2, Omar AlAbbasi3,4, Moustafa Magliyah5,6
DOI:
10.4103/meajo.
MEAJO_27_19 Abstract:
PURPOSE: Does perioperative use of Rho‑Kinase (ROCK) inhibitors have beneficial effect on corneal
endothelial cells after phacoemulsification? SETTING: This study was conducted at King Abdulaziz
University Hospital in Riyadh.
DESIGN: This was a prospective study assessing the effect of ROCK inhibitors on corneal endothelium
after phacoemulsification.
METHODOLOGY: Three patients have used ROCK inhibitor 1  day before and 1  week after
phacoemulsification surgery, and specular microscopy and Pentacam were done preoperatively
and 3 months postoperatively.
1
Department of
Ophthalmology, King RESULTS: Endothelial cell density decreased to 11.3%, 9.45%, and 4.09% in eyes with ROCK
Saud University, Riyadh, inhibitors and 23.9% in one eye without ROCK inhibitor.
Saudi Arabia, 2Cornea CONCLUSION: Perioperative ROCK inhibitor use has a possible protective effect on corneal
and Anterior Segment endothelium.
Consultant, King Abdulaziz Keywords:
University Hospital,
Corneal endothelium, phacoemulsification, rho‑kinase inhibitors
Riyadh, Saudi Arabia,
3
Department of Cornea
and Anterior Segment,
King Khaled Eye Specialist Introduction and Descemet membrane endothelial
Hospital, Riyadh, keratoplasty, surgical intervention still has
Saudi Arabia, 4Department
of Ophthalmology, Ohud
Hospital, Madinah,
C orneal endothelium is known as a
single layer of cells which are normally
not regenerated once damaged. Humans
some issues such as technical difficulty, risk
of graft rejection, and intraocular infection.[5]

Saudi Arabia, 5Vitreoretinal are born with 6000 cells/mm2 endothelial Tissue engineering therapy through
Division, King Khaled cells.[1] These cells decrease at an average Rho‑kinase (ROCK) signaling pathway
Eye Specialist Hospital, inhibition has demonstrated diverse
of 0.6% each year.[2] Endothelial density
Riyadh, Saudi Arabia,
of <500 cells/mm2 imposes high risk of therapeutic potential in vascular diseases,
6
Department of
Ophthalmology, Prince corneal decompensation and consecutively cancer, neuronal degenerative disease,
Mohammed Medical City, hazy vision.[3] The only approved solution asthma, and glaucoma through changing
AlJouf, Saudi Arabia for corneal decompensation is corneal cell behavior. [6‑9] Topical preparation of
transplantation. [4] Although corneal ROCK inhibitor Ripasudil hydrochloride
Address for endothelial transplantation has become hydrate (Glanatec® ophthalmic solution
correspondence: 0.4%; referred to as ripasudil) was found
Dr. Moustafa Sameer
less invasive with the evolution of
Magliyah, Descemet stripping endothelial keratoplasty to be useful as glaucoma treatment by
7880 Al Amir stimulating drainage of aqueous humor
Ahmad‑Madinat Al Ummal, through direct action on trabecular
Unit No.: 1, Al Khubar This is an open access journal, and articles are
distributed under the terms of the Creative Commons
meshwork [10] with only minor adverse
34441‑4537, Saudi Arabia.
Email: mussam8@yahoo. Attribution‑NonCommercial‑ShareAlike 4.0 License, which
com allows others to remix, tweak, and build upon the work How to cite this article: Alkharashi M, AlAbbasi O,
non‑commercially, as long as appropriate credit is given and Magliyah M. Perioperative use of rho-kinase inhibitors
Received: 21‑02‑2019 the new creations are licensed under the identical terms. has beneficial effect on corneal endothelium after
Revised: 31‑12‑2019 phacoemulsification. Middle East Afr J Ophthalmol
Accepted: 12‑01‑2020 2019;26:246-9.
Published: 29-01-2020 For reprints contact: reprints@medknow.com

246 © 2020 Middle East African Journal of Ophthalmology | Published by Wolters Kluwer - Medknow
[Downloaded free from http://www.meajo.org on Monday, June 8, 2020, IP: 152.207.218.221]
Alkharashi, et al.: Rho‑kinase inhibitors after phacoemulsification
events reported including conjunctival hyperemia,
photophobia, other eye discomfort, and asthma.[9,11]
Further studies demonstrated another promising
ophthalmic use after showing that ROCK inhibitors
can promote corneal endothelial cell proliferation[12]
and healing.[13] The proposed mechanism for ROCK
inhibitors action on corneal endothelium is mediated
through phosphatidylinositol 3‑kinase signaling that
subsequently regulates two proteins of the G1 phase of
the cell cycle.[14] Currently, no studies demonstrate the
proper dosage of ROCK inhibitors in various corneal
diseases, nor any contraindications for their ophthalmic
usage.[5] Ripasudil has demonstrated its therapeutic
potential targeting corneal endothelium in the treatment
of acute corneal endothelial damage following eye
surgeries. [15] Further studies suggested that ROCK
inhibitors might be used to prevent postoperative acute
corneal edema due to corneal endothelial dysfunction.[16]
This study was done to detect the effects of perioperative
use of ripasudil on healthy corneal endothelium in patients
who undergo uncomplicated phacoemulsification
cataract surgery.
Methodology
After ethical approval was granted from the department
committee, three male patients of 65, 62, and 67 years
of age were planned for phacoemulsification surgery.
Patients 1 and 3 were hypertensive on medications.
Preoperative evaluation included detailed history,
bestcorrected visual acuity, slitlamp examination, fundus
examination, Goldmann applanation tonometry and
specular microscopy. All patients who were chosen had
grade 3 nuclear cataract using Pentacam Nucleus Staging
Software which depends on Pentacam’s Scheimpflug
camera with a grade from 0 to 5. Informed consent was
taken from all the participants with all benefits and risks
being explained to each patient of the procedure as well
as the use of ROCK inhibitor. 1 mM Ripasudil (Glanatec®
ophthalmic solution 0.4%) was instilled to the study
eye three times a day preoperatively and then the same
dosage was used postoperatively for 1 week.
The change in corneal endothelial cell density  (ECD)
was compared with the normal population using
specular microscopy (using Specular Microscope, SP
3000P, Topcon), with the IMAGEnet imaging system
(Topcon Medical Systems, Inc., Oakland, USA) done
preoperatively and 3 months after surgery in all three
patients. Measurements of central corneal ECD (cells/
mm2), coefficient of variation in corneal endothelial cells
(CV), percentage of hexagonal cells, and central corneal
thickness (CCT) were taken.
All patients were operated by a single surgeon using
a standard endocapsular, stop and chop technique
Middle East African Journal of Ophthalmology ‑ Volume 26, Issue 4, October-December 2019 247
using the same machine (Infiniti vision system; Alcon
Laboratories; Inc., Fort Worth, TX, USA).
A 2.2 mm superotemporal self‑sealing clear corneal
incision was made just in front of the vascular arcades of the
corneoscleral limbus using a calibrated 2.2 mm keratome.
Ocular viscoelastic device (Sodium Hyaluronate; Provisc)
was injected into the anterior chamber. A paracentesis
incision of 1 mm was made 60° apart with a 20‑gauge
microvitreoretinal blade. Iris hooks were used for the
second and the right eye of third patients for mechanical
dilation because of age‑related pupil suboptimal dilation.
After the capsulorrhexis, hydrodissection followed
by nucleus rotation, nucleus removal was done by a
single method, that is, stop and chop technique. After
emulsification of nuclear fragments, irrigation aspiration
of residual cortical matter was done. A foldable
intraocular lens was implanted inside the capsular bag.
After this, the removal of the viscoelastic material was
done, and finally, the incision was hydrated using a
30‑gauge cannula. One 10‑0 nylon suture was applied
to the main wound of the second patient only, while the
main wound on other patient was sealed with stromal
hydration. The eye was bandaged which was opened
next morning. Intraoperative Cumulative Dissipated
Energy  (CDE) was calculated as mean tortional
power  ×  0.4  ×  phacoemulsification time as the only
phacoemulsification power used was the tortional.
Results
Four eyes of three patients were included. Right
eyes were operated in patients 1 and 2, whereas both
eyes were operated in patient 3. In the first patient,
preoperative visual acuity of the right eye was 20/60.
Intraoperative CDE used was 45 and there was 11.3% loss
in ECD, 2.9% change in hexagonality, and 0.91% increase
in CCT. Postoperative visual acuity was 20/20 3 months
postoperatively. In the second patient, preoperative
visual acuity of the right eye was 20/80. CDE used was 12
and had 9.45% ECD loss, 4.05% change in hexagonality,
and 0.68% increase in CCT. Visual acuity was improved
to 20/25 3 months postoperatively. In the third patient,
whose preoperative visual acuities were 20/60 and
20/50, only the right eye was instilled with ROCK. CDE
used was 23 in both eyes. The ECD was reduced by 4.09%
in the right eye while reduced only by 23.9% in the left
eye. CCT increased 1.59% in both eyes. Three months
postoperatively, visual acuity was improved to 20/20
in both eyes. Table 1 shows CED, CV, and hexagonality
preoperatively and 3 months postoperatively in the 4
eyes of 3 patients, with the calculation of intraoperative
CDE and percentages of change in CED and CCT.
Discussion
The evolution of ROCK inhibitors ophthalmic uses has
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Alkharashi, et al.: Rho‑kinase inhibitors after phacoemulsification

Table 1: Corneal endothelial cell density, CV, and hexagonality preoperatively and 3 months postoperatively in
the 4 eyes of 3 patients, with the calculation of intraoperative Cumulative Dissipated Energy and percentages of
change in corneal endothelial cell density and central corneal thickness
Preoperative CDE 3 months postoperative Change in endothelium
1st patient CED 2893 45 CD 2566 11.3%
CV 32% CV 37%
HEX 68% HEX 66%
CT 546 CT 551 0.91%
2nd patient CED 2392 12 CD 2166 9.45%
CV 25% CV 28%
HEX 74% HEX 71%
CT 587 CT 591 0.68%
3rd patient OD Using rho (right) CED 2663 23 CD 2554 4.09%
CV 46% CV 49%
HEX 54% HEX 51%
CT 563 CT 574 1.59%
3rd patient Without rho (left) CED 2619 23 CD 1992 23.9%
CV 25% CV 33%
HEX 77% HEX 58%
CT 567 CT 576 1.59%
CED: Corneal endothelial cell density, CDE: Cumulative dissipated energy, CD: Cell density, HEX: Hexagonality, CV: Coefficient of variation in corneal endothelial
cells, CT: Computed tomography

prompted researchers to prove their beneficial effects on
corneal endothelium, especially after damage caused by
phacoemulsification surgery.[5] Some researchers propose
that ROCK inhibitors promote proliferation of corneal
endothelial cells.[17] However, the specific mechanism
by which ROCK inhibitors affect corneal endothelium is
not clear. In this study, loss of CED ranged from 4.09%
to 11.3% when ROCK inhibitor was applied, which is
less than what was found in the normal population by
Xing Du et al.[18] (12.4%) and Walkow et al.[19] (11.9%).
Changes in CCT after the use of ROCK inhibitors were
0.91%, 0.68%, and 1.59% when ROCK inhibitors were
used, which are comparable to changes detected by
0.6% found in the normal population by Salvi et al.[20]
and less than changes detected by Das et al. (1.7%)[21] and
Vasavada et al. (4.3%).[22] For the patient who had bilateral
phacoemulsification surgery with the use of ROCK
inhibitors in the right eye only (patient 3), loss of CED in
the left eye was higher after phacoemulsification (23.9%)
despite the use of the same intraoperative CDE. Changes
in CV and hexagonality were more in the left eye for
which ROCK inhibitor was not applied, although there
was similar changes in CCT in both eyes (1.59%). The
minimal changes in CED and CCT in comparison to
normal population indicate that ROCK inhibitors have
beneficial effect on corneal endothelial cells when
administered topically perioperatively. The authors
can argue that the use of iris hooks along with corneal
suturing in patient 2 and only iris hooks in the right eye of
patient 3 might have compromised corneal endothelium
even further without the use of ROCK inhibitors. The
limited effect of ROCK inhibitors on postoperative visual
acuity in our patients, might limit their clinical usefulness
to cases with expected significant corneal endothelial
compromise after phacoemulsification, such as Fuch’s
Corneal Endothelial Dystrophy, as well as patients
with dense cataracts. The use of ROCK inhibitors might
prevent postoperative significant visual deterioration.
Limitations of the study include small number of patients
and further studies are needed to know the ideal dosage
regimen for best action on corneal endothelium and to
know the exact mechanism by which ROCK inhibitors
act on corneal endothelium to promote its healing after
phacoemulsification.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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