Preventing Glaucoma Blindness

We can do it, so why don’t we? Howard Larkin reports from ASCRS in Las Vegas, USA

Early detection and going beyond IOP lowering will be the keys to reducing progression rates to blindness in glaucoma, which have been stubbornly steady for 20 years, Richard A Lewis MD said during his Binkhorst Medal Lecture.

Hippocrates was the first to describe glaucoma in 375 BC—and for more than 2,000 years, if someone received that diagnosis, they went blind, Dr Lewis said. It wasn’t until the mid to late 19th century that the first effective treatments, such as iridectomy and pilocarpine, were invented.

It was another century before several types of glaucoma and causes were defined and more effective treatments, including medications to lower IOP and surgical trabeculectomies and tubes, finally reduced the probability of going blind—from 25.8% in the 15 years before 1980 to 13.1% in the 15 years after, he observed.

But the rate of progression to blindness remains about 13% to this day. “Which is a lot higher than other ocular diseases. It’s a bit frustrating that we’re having a tough time breaking that barrier,” Dr Lewis noted.

MEDICINES, LASERS, AND MIGS So, what’s happened over the last 20 years? There’s been a lot of seeming progress.

More than $130 million in funding from the US National Eye Institute has helped identify risk factors for early diagnosis, including corneal thickness, cupping, and elevated intraocular pressure (IOP), Dr Lewis said. And the introduction of prostaglandins and ROCK inhibitors have made it possible to meaningfully control IOP, though eye drop side effects remain challenging.

Selective laser trabeculoplasty (SLT) has proven a cost-effective, medium-term IOP control technique. Even more exciting has been the advent of MIGS, including the iStent inject® (Glaukos), Hydrus® (Ivantis), and XEN® (Alcon) devices, Dr Lewis said.

“But here we are in 2021, and we still have this high degree of blindness,” he observed.

WHY PATIENTS STILL GO BLIND Noting that the more advanced glaucoma is at diagnosis, the lower IOP must be to prevent further vision loss, Dr Lewis identified several factors that may be contributing to progression.

First is underdiagnosis. “We don’t determine [when] their pressures are elevated; we don’t determine they have cupping until it is far advanced. They are coming in for presbyopia or cataracts and by then they have lost a fair amount of vision,” Dr Lewis said.

Second is adherence with topical treatment. “They are either unable to take their medications or won’t get those medications renewed,” Dr Lewis said.

Third is inadequate treatment. MIGs devices don’t lower IOP enough, and trabs and tubes have about a 50% failure rate at five years.

“Invariably, they are back on medications and having multiple procedures,” Dr Lewis lamented.

WHAT CAN BE DONE Dr Lewis offered three ways to meet the currently unmet need to prevent visual loss in glaucoma.

First is earlier detection of at-risk patients. Instead of relying on occasional pressure checks and visual field measurements, genetic tests may help identify high-risk patients. While this is challenging since glaucoma is multifactorial, a test is close to approval, Dr Lewis said. Technologies that enable home or even continuous IOP monitoring also are in development, which should improve diagnosis.

Second is more effective IOP-lowering therapies, especially at night when eye drops can be ineffective, and much of the damage may occur. One option in development by John Berdahl MD and Equinox is a pair of goggles that lower pressure on the eyes during sleep, which have been shown to reduce IOP significantly. “You can literally dial in the IOP you want,” Dr Lewis said. New medications that target episcleral as well as conventional outflow might do a better job than current drugs of lowering IOP, he added.

Interventional glaucoma is another approach in which sustained release and injectable delivery might help solve the compliance issue. Directly applying drugs to the trabecular meshwork, as does the DURYSTA® (Allergan) bimatoprost implant, the optic nerve, or other affected area also could improve efficacy, Dr Lewis added. “The current challenge is to find the appropriate medications.”

Third is broadening treatment options beyond lowering IOP. Since glaucoma results from damage to the retinal ganglion cells, therapies that bypass IOP and directly affect this mechanism are promising, Dr Lewis said.

Neuroprotective medications delivered earlier in the disease before major damage has occurred have potential. One delivered as an intravitreal injection is in clinical trials. High-dose vitamin B3 also has been shown to improve visual fields in about 24% of glaucoma patients, he stated.

Genetic technology may also help restore vision eventually, Dr Lewis said. A mouse model has already shown results. “It’s on the horizon.”

Richard Lewis MD pioneered minimally invasive glaucoma surgery (MIGS). He maintains a glaucoma practice in Sacramento, California, USA. Dr Lewis is a past president of both ASCRS and the American Glaucoma Society. rlewiseyemd@yahoo.com