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Ojas Eye Hospital in Bandra, Kandivali, Mumbai

New In Ophthalmology : Endothelial dysfunction could soon be treated without the need of surgery !

June 10, 2020

Specular Microscopy

Slit lamp image of Stage 1 Fuchs dystrophy

Endothelial dysfunction could be due to an inherited condition- Fuchs Endothelial Dystrophy or due to surgical trauma or even external injury to the cornea. This endothelium is the innermost corneal layer which acts as the major pump to maintain the corneal hydration, thickness and ensure clarity. It is important to know thatin case of damage,this endothelium does not have self regenerating capacity.

Damaged endothelium leads to corneal edema( swelling ) and hence foggy vision, glare and haloes. Till now treatment with hypertonic saline drops and ointment provided symptomatic relief in the early stages. The more advanced stages with corneal epithelial swelling ( bullae ) and sub epithelial scarring needed a partial corneal transplant of the posterior layers. ( DSEK/ DSAEK/ DMEK ) which had good anatomical and visual outcomes.

It has been established that these endothelial cells ( inner corneal cells) constitutively have a protein on their surface called RHO KINASE. This is involved in regulation of cell shape and size. They are linked with cell dynamics, cell contraction, cell adhesion and organization of matrix surrounding cells.A new ray of hope for conservative( non surgical ) management of endothelial dysfunctions are ROCK ( Rho kinase ) inhibitors. These can be used either as topical medications or as anterior chamber injections ( along with cultured endothelial cells).

Rho kinase inhibitors help with endothelial cellregeneration and healing. By inhibiting the factors which stop cell growth, these Rho kinase inhibitors allow increase in endothelial cell number. This in turn compensates for the damaged non-functional endothelial cells.

In the early stages of endothelial dystrophy, an eyedrop formulation can be used effectively to slow down cell death and increase cell number. Infact, in Japan ( in 2013 ) a patient with advanced Fuchs also showed improvement in corneal transparency and vision after topical Rho kinase inhibitor drops. These drops have also been used to successfully treat acute post surgery endothelial cell injury that can potentially be blinding. ( Pseudophakic corneal edema )

The RHO kinase inhibitors can be injected into the anterior chamber along with cultured ( externally grown ) endothelial cells. Herein, greater healing is facilitated due to increased cellular adhesion by the Rho kinase inhibitors.

Other benefits of ROCK inhibitors

Open Angle Glaucoma

The Rho kinase inhibitors were initially approved for glaucoma due to its IOP lowering effect. They have a direct action to alter cell shape in the filtering passage, allowing for enhanced egress of fluid out of the eye, so decreasing the pressure inside the eye ( IOP ). They also decrease free radicals which further helps reduce oxidative damage to outflow pathway and Optic Nerve.

In Diabetic retinopathy

Diabetic retinopathy is a microangiopathy, wherein the small vessels of the eye are primarily leaky. RHO kinase pathways promote WBC adhesion to small vessels of the retina, through increased levels of activated adhesion molecules (ICAM-1). Treatment with Rho kinase inhibitor as intravitreal injections would be able to reduce adhesion of leukocytes( White blood cells) to microvascular structures, allowing for a decrease in effects of diabetic retinopathy and macular edema.

Some patients do have conjunctivalhyperemia as a side effect. Few may even develop conjunctival haemorrhages.

Ripasudil, a Rho kinase inhibitor, was the first drug amongst these to gain approval in 2014 ( Japan ) to be specifically used for treatment of ocular hypertension and glaucoma. Ripasudil drop solution was approved at a 0.4% concentration, as a twice daily treatment. Then ,Rhopressa, a Rho kinase inhibitor consisting of Netarsudil, gained United States Food and Drug Administration (FDA) approval in 2017; the first of its kind to do so. Netarsudil drop was approved in a 0.02% concentration, as a one drop four times daily to lower IOP for treatment of glaucoma.


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