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Glaucoma treatment efforts may benefit from emphasis on disease modification
The focus should shift from trumping generic latanoprost to altering disease course, a specialist suggests.
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 Douglas J. Rhee |
In light of recent studies assessing the safety and efficacy of ROCK inhibitors and adenosine agonists, one clinician recommended that treatment efforts be focused more specifically on disease modification.
“In a generic market, there is the fear that whatever compound comes out next has to be better than generic latanoprost, and that is an incredibly high hurdle,” Douglas J. Rhee, MD, OSN Glaucoma Board Member, said in a telephone interview. “But I do not think that is necessarily the best way to look at the field.”
As evidence mounts regarding new classes of glaucoma therapeutics, there remains little information on their ability to alter disease course. Dr. Rhee said that patients might be better served by therapies that attack the root pathogenesis of glaucoma rather than simply offer palliative care.
“We know a lot about the disease, but we do not know enough yet about the pathophysiology within the trabecular meshwork to directly interrupt it. … We should be looking at disease-modifying therapies which, even if they do not have as much pressure-lowering efficacy right off the bat, interrupt the disease process. Long term, this will be more cost-effective and better for the patient,” he said.
Deciphering pathophysiology
According to Dr. Rhee, ROCK inhibitors have not demonstrated the same pressure-lowering efficacy or tolerability, in terms of hyperemia, as prostaglandin analogues in early trials. Some require twice-daily dosing as opposed to once-daily dosing.
“But if you can prove that there is some dysfunction of cellular mechanics that is part of the disease, then perhaps a ROCK inhibitor would make a lot of sense,” he said, noting that paracellular outflow issues may be involved in glaucoma pathophysiology.
The exact mechanism of action for adenosine agonists has not been fully elucidated at this point, so an understanding of whether these drugs are disease modifying also remains unknown.
“The real bang for your buck is if you find something that affects extracellular matrix turnover in the trabecular meshwork because that has definitely been shown to be a part of the pathophysiology. If you can find something that interrupts that, you have got a real blockbuster,” Dr. Rhee said.
Significance of efforts
Like many of his colleagues, Dr. Rhee is eager to determine whether adenosine agonists are disease modifying because this would affect their place in the treatment paradigm. As it stands, prostaglandin analogues are relatively well tolerated, and the cost of latanoprost makes it difficult for another treatment to supersede it.
“This would be an easier conversation if latanoprost was not generic, but when you have such a low-cost option, all of a sudden things are up in the air,” Dr. Rhee said.
Despite uncertainty regarding the widespread use of newer therapeutics, Dr. Rhee said it is significant that they are even being considered for the glaucoma marketplace. Such developments denote private industry’s interest in formulating new treatment options, which is highly desirable in American ophthalmology. – by Michelle Pagnani
- Douglas J. Rhee, MD, can be reached at Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02144; 617-573-3670; fax: 617-573-3707; email: dougrhee@aol.com.
- Disclosure: Dr. Rhee is a consultant for Alcon, Allergan, Novagali, Merck and Santen and receives research funding from Alcon and Merck.