From DMEK to DWEK
New technique requiring no donor tissue showing promise in the treatment of Fuchs’ dystrophy
Professor Friderich E Kruse MD
A technique combining Descemetorhexis without endothelial keratoplasty (DWEK) and a postoperative topical regimen of the rho-kinase (ROCK) inhibitor ripasudil (Glanatec, KOWA), is showing promise in the treatment of Fuchs’ dystrophy, said Professor Friderich E Kruse MD at the 10th EuCornea Congress in Paris France.
“The primary advantage of this technique is that you do not need a graft. A graft as we know is foreign tissue and has certain immunological disadvantages. There are also significant cost-savings with this technique,” said Prof Kruse, University of Erlangen-Nürnberg, Erlangen, Germany.
He noted that since the 1990s there has been a trend in the treatment of endothelial disease towards less invasive procedures that leave as much of the host cornea intact as possible. Procedures like Descemet’s stripping automated endothelial keratoplasty (DSAEK) ultra-thin DSAEK and Descemet’s membrane endothelial keratoplasty (DMEK) have therefore become standard treatments for bullous keratopathy and Fuchs’ dystrophy.
Continuing in that same evolutionary path, research now suggests, and clinical evidence supports, the feasibility of treating Fuchs’ endothelial dystrophy simply by performing a 4.0mm Descemetorhexis and allowing the corneal endothelium’s own natural healing ability to restore the missing tissue and provide a clear cornea. Moreover, the studies also show that the rho-kinase inhibitor, ripasudil, can enhance and speed up the corneal endothelium’s regeneration.
“We were all taught that corneal endothelial cells would not migrate or proliferate. But this not completely true. For example, if you look at DMEK grafts that are decentred or there is a gap between the graft and host endothelium, endothelial cells often migrate into the gap after a few months,” Prof Kruse said.
He added that several anecdotal reports have described cases of spontaneous corneal endothelium regeneration following accidental Descemetorhexes occurring during cataract surgery. Furthermore, research published by Gerrit Melles MD, has demonstrated that endothelial cells from the host and/or the graft would similarly migrate to fill the gap in eyes that have undergone quarter-DMEK grafts, although some eyes required rescue DMEK procedures.
Reports on several small series of Fuchs’ dystrophy patients undergoing primary DWEK have also shown varied results, with success rates ranging from no success in three eyes to 14 successes in 17 eyes. The early trials showed that the technique appeared to be successful in most eyes in studies where a 4.0mm Descemetorhexes was used.
The studies also suggest that the success of DWEK procedures is limited to the subtype of Fuchs’ dystrophy where the guttae is at the centre and there is good endothelium in the periphery. It is not effective for bullous keratopathy, where most of the endothelium is affected.
Drops for ocular hypertension improve endothelial re-growth
A more recent development in the DWEK technique has been the use of ripasudil eyedrops following surgery. Ripasudil is a rho-kinase inhibitor approved in Japan in 2016 in for the treatment of ocular hypertension and glaucoma. The Rho-associated protein kinase (ROCK) enzyme has two isoforms, ROCK-1 and Rock-2. They are activated in response to wounding or integrin stimuli and they play a critical role in cell adhesion, migration, proliferation, differentiation and apoptosis via modulation of the cytoskeleton.
In the laboratory, ripasudil, a ROCK-1 inhibitor, has been shown to promote corneal endothelial cell proliferation in cultured human cells and wound healing and corneal endothelium regeneration in an in vivo rabbit eye model.
Recent clinical trials are now appearing to bear out the laboratory findings regarding the potential value of the ROCK-inhibitor in eyes undergoing DWEK. For example, in a study involving 12 patients who underwent 4.0mm Descemetorhexes, a regimen of topical ripasudil treatment resulted in clear corneas in eyes where DWEK was not initially successful (Moloney et al, Cornea 2017;36:642-648).
A subsequent double-blind study involving 18 patients undergoing 4.0mm DWEK procedures showed that those receiving a two-week regimen of ripasudil eyedrops four times daily recovered vision significantly more quickly (4.6 weeks vs. 6.5 weeks, p<0.01) and had a statistically significantly higher average endothelial cell density than those who did not receive the eyedrops (Macsai et al, Cornea 2019; 38 :529-534) . Prof Kruse and his associates are now conducting a similar double-blind trial comparing outcomes of DWEK with and without ripasudil. He noted that the agent is not yet approved in Europe although a phase II multi-centre randomised controlled trial involving 60 patients undergoing DWEK is now in the planning stages. He commented that a disadvantage of DWEK is its long recovery period of up to four months, during which time vision is very poor. In contrast, a patient undergoing DMEK will generally recover the vision they had before surgery by one week after surgery. “After Descemet’s stripping, visual acuity goes down tremendously the patient only has hand movements and that is certainly something for both the doctors and the patients to consider when deciding whether to adopt this technique,” Prof Kruse said.