Can glaucoma patients benefit from cell therapy approach?

Sustained delivery is needed to ensure that patients do not have to remember to take their medication every day. 

The future of glaucoma will likely not resemble the current state of management of the disease, with numerous advances on the horizon, according to Harry Quigley MD, the A. Edward Maumenee Professor of Ophthalmology at Johns Hopkins School of Medicine, Baltimore, MD.

Delivering the Bryan St. L. Liddy Lecture on the topic of the future of glaucoma therapy during the annual Sally Letson Symposium, Dr. Quigley stressed that patients are looking for treatments other than daily administration of eye drops.

Related: Reshaping medical treatment of glaucoma management 

“If I quit my career without having gotten rid of eye drops, then I will have failed,” Dr. Quigley told symposium attendees. “We need sustained delivery in some form, so patients do not have to remember to take something everyday. Sustained delivery of IOP drugs will get around a lot of problems.”

One of the advantages of sustained delivery tr with patients, according to published research, which showed that glaucoma patients would consider these alternatives to daily eye drops if they avoided the need for surgery or showed superior efficacy over eye drops. (J Glaucoma. 2018 Apr;27(4):328-335.)

Patient adherence glaucoma patients have been largely left on their own to stick to a daily regimen of using eye drops. Some technology innovations have looked at trying to increase adherence. These include cell phone robo-calls or texts, noted Dr. Quigley.

In one study, individuals randomly selected to receive reminders were more adherent to their therapy than those who were not. They increased adherence from 53% to 64% (P < .05). However, there was no statistical change amongst the 32 participants in the control group. JAMA Ophthalmol.2014 Jul;132(7):845-50.

Another innovation is the Kali Drop device, a wireless monitoring device that provides accurate adherence monitoring, uses telephone feedback, and sends data to an ophthalmologist’s office in real time. 

“It will pop up on your screen if they (patients) have not touched their drops,” said Dr. Quigley.

Related: Teleglaucoma lets patients be more engaged in care 

Identifying progression 
Identifying patients who will experience catastrophic worsening, and ruling out those who will not, can be done by modifying the frequency with which visual field tests are conducted, according to Dr. Quigley.

“They represent under 10% of all patients, but we need to identify them as rapidly as we can,” Dr. Quigley explained.

Conducting an annual visual field test is not sufficient to identify patients who will have rapid progression of disease, underlined Dr. Quigley.

“If you will do a (visual) field (test) a year, it will take you four or five years to detect the patient is worsening, and if they are one of these catastrophic worsening people, by then, the horse is already out of the barn,” he said. 

Dr. Quigley routinely performs five field tests in the first 18 months with a new patient, as well as measuring IOP before initiating medical therapy, in order to detect patients with and without fast disease progression, resuming a schedule of annual visual field tests for those without fast disease progression.

Related: Looking beyond IOP when managing glaucoma patients 

“It is well worthwhile and I explain to the patient why we are doing this, that some people get rapidly worse,” he said. “I also explain that at the end of doing this series of tests, we will know that patient is one of the people who will not get worse very fast at all and that patient can be re-assured.”

However, better biomarkers are needed to reveal if patients with glaucoma are getting worse and at risk of losing their vision, Dr. Quigley pointed out.

Biomechanical changes
One of the avenues of research to help uncover which patients will worsen quickly and which will not, is an examination of the biomechanics of the lamina cribosa, according to Dr. Quigley. 

Researchers have observed that the anterior depth of the lamina cribosa varies according to different IOPs, which can be viewed with optical coherence tomography. (Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2566-2577.)

Additionally, glaucomatous eyes have been observed to not display the same degree of change in the lamina in response to IOP reductions as non-glaucomatous eyes. This observation and understanding the biomechanics of the sclera has led to new insights into the pathogenesis of glaucoma and has revealed new therapeutic targets and novel treatments like rho-associated protein kinase (ROCK) inhibitors. (Transl Vis Sci Technol. 2018 Nov 14;7(6):6.)

Related: Rho kinase inhibitors getting to the heart of the matter 

Sustained-release delivery 
Success in animal models is pointing to the sustained release of dorzolamide as a way to lower IOP and protect against the loss of retinal ganglion cells. 

In both rat and rabbit glaucoma models, Dr. Quigley and colleagues have achieved success with the injection of the therapy as microparticles, to halt the progression of glaucoma. (Mol Pharm. 2016 Sep 6;13(9):2987-95. Transl Vis Sci Technol. 2018 Mar 28;7(2):13.)

“We have produced three-month long pressure-lowering (of IOP) with delivery of one treatment,” Dr. Quigley noted. “The hope is that it will get to six months (between treatments).

Going forward, researchers hope to take their work to the next step. The ultimate goal is ensuring that patients have positive results and improved quality of life. 

Translating this animal research to patients is clearly possible, so that the future scenario of glaucoma treatment would mean patients make a visit to the ophthalmologists a couple of times in the span of a year.

“You would inject the patient every six months, and the patient would get in the car and drive home,” he concluded. “That should be quite feasible.”

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