Glaucoma
Spring 2024
by Liz Hillman
Editorial Co-Director
It’s heartbreaking and hard to understand: A patient has glaucoma and despite a normal or low IOP, their disease is progressing. Marlene Moster, MD, and Pradeep Ramulu, MD, PhD, provided their thoughts on diagnosis of normal tension glaucoma (NTG), establishing true progression, and how to manage worsening disease in this patient population.
According to Dr. Ramulu, half or more glaucomas develop at low pressures. “Once you start getting to really low pressures, it can be a bit of a surprise that someone has glaucoma … because most of the people who have glaucoma developing at low pressures are still in the upper half of what’s normal, usually 15 mm Hg and above,” Dr. Ramulu said. “When you start getting below that, it becomes relatively uncommon. The more troubling, and less common, scenario is someone who appears to be getting worse when their eye pressure is well controlled.”
Is it really NTG?
When it comes to establishing an initial diagnosis of NTG, Dr. Moster and Dr. Ramulu said it’s important to ensure that it’s truly NTG.
Dr. Moster said when a patient is sent in for a diagnosis and treatment of NTG, it’s important to look for red flags so that other treatable optic neuropathies are not missed. “For example, we look very carefully for an atypical visual field with temporal loss. If the cupping is similar in both eyes but there is a large afferent pupillary defect, I’m concerned there is a neurologic process going on. We look for color loss, dyschromatopsia, because there is not much color loss in glaucoma, but there is profound loss in neurologic disease,” she said. “I look for pallor of the rim of the optic nerve more than cupping; asymmetric pallor is indicative of neurologic disease.”
She said that other neurologic symptoms to watch out for are headache, motility defects, and diplopia.
“Also, I look for decreased vision out of proportion to what I would expect looking at the optic nerve because with neurologic disease, vision is usually poor, but with glaucoma, even at the end, there is good central vision. I also look for ganglion cell layer loss that is atypical on OCT, looking for an atypical paracentral defect that will show up on the ganglion cell complex or nasal defect that is atypical. Also, very young patients are unlikely to have normal tension glaucoma and may instead have neurologic disease,” she said.
If a patient has a red flag, Dr. Moster said she refers the patient to neuro-ophthalmology for further testing.
Establishing progression
When visual fields and/or OCT suggest that a patient with NTG is progressing despite a low IOP, Dr. Ramulu said he likes to first establish that it’s true progression. He asks the patients about their symptoms. Are they experiencing a drop in vision that is commensurate with what he would expect from the imaging and visual fields?
He has a discussion with patients about whether they’re using their topical IOP-lowering medications as directed.
“I say, ‘We’re going to start talking about operations, and if you’re not using your medicines properly, please tell me because I don’t want to do an operation if you’re just not using your medications as you should be,’” he said of his patient conversation. “Usually at that point when faced with something tangible that has some risks, patients say, ‘I haven’t been using them consistently.’”
He’ll also check ability to administer drops. Patients might in fact be taking their drops, but if they’re not getting onto the eye correctly, they’re not working. You need to make sure they’re taking what you say they should take, when you say, how often, and that the drop is making it into their eye, Dr. Ramulu said.
If it’s clear patients are medication compliant, their testing indicates progression that’s occurring with good control of IOP, and they say they’ve experienced a change in vision, Dr. Ramulu said his next step is home tonometry. His practice uses a service that helps patients rent out a home tomometer, allowing them to check pressures more regularly at their home. There are three categories of patients that you’ll find with data from home tonometry.
- People who always have very low pressures. When you check them at home, their pressure is never going above 12–13 mm Hg, Dr. Ramulu said. Maybe there is the occasional reading of 15 mm Hg, but the average may be 10 mm Hg. He said the standard deviation or variability of the reading is small and the pressure is extremely well controlled.
- People whose average pressure is 12–13 mm Hg but who sometimes get into the upper teens and occasionally up to 20 mm Hg. “You would think they would be controlled, but it’s believable that they could be getting worse,” Dr. Ramulu said.
- People with extreme pressure fluctuations. Dr. Ramulu said these people might wake up with their pressure at 30 mm Hg but then it comes down over the course of the day. “I’ve seen a handful of those. One heartbreaking story is someone who came in, and he was hand motion. He was telling me … that he was seeing worse and worse. His pressure was 10 mm Hg on a bunch of medicines. We did a trial on him, and every morning he was up into the 30s. He had been losing vision for years, but no one found this out. It was very unfortunate that he lost so much vision in both eyes as a result,” Dr. Ramulu said.
Treating progressing NTG
Dr. Moster said her current strategy, when it’s clear that a patient has NTG that’s progressing despite low to normal IOP, is to look at the T-max, the highest pressure, and try to lower that by 30%, using caution to not go below episcleral venous pressure, which won’t happen without surgery.
Because the pressures of these patients often rise at night, Dr. Moster said her topical therapy is tailored toward prostaglandins, which have been shown to lower pressure at night. She also said topical carbonic anhydrase inhibitors have been shown to lower pressure at night. Rhopressa (netarsudil ophthalmic solution, Alcon), Rocklatan (netarsudil/latanoprost ophthalmic solution, Alcon), and Vyzulta (latanoprostene bunod ophthalmic solution, Bausch + Lomb) are valuable for normal to low tension glaucoma because they lower pressure at night with a prostaglandin component, but they also work in symbiotic ways to lower pressure, Dr. Moster said.
Dr. Moster will use alpha agonists in some low tension glaucoma patients and SLT early in patients who are admittedly non-compliant with topical therapies. She also sees a place for Durysta (bimatoprost intracameral implant, Allergan) for patients who are non-compliant. For patients who are not yet ready for surgery, she’ll combine Durysta with SLT before or after to lower the pressure 20–30%.
There is still a role for beta blockers, according to Dr. Moster, because they are once daily and can be taken in the morning. “I have patients put it near their toothbrush,” Dr. Moster said. “For prostaglandins in people who are non-compliant, I ask them to put it on the kitchen table and have them use it earlier in the evening right after dinner.”
When surgery is the best option for the patient, Dr. Moster said she’s a “big fan of combining cataract surgery and MIGS because in NTG every millimeter of mercury counts.” She mentioned the full range of MIGS options that she likes to use.
“They’re all very effective in helping the pressure come down an extra few millimeters of mercury,” Dr. Moster said. “If they’re still progressing, I’m in favor of the XEN Gel Stent [Allergan] in normal tension, even though the success rate is not as high as a trabeculectomy. Trabeculectomies are the gold standard for bringing the pressure into the single digits, but then I’m worried about the increase of complications.”
Dr. Ramulu said the group whose home tonometry shows large spikes in pressure are the “low-hanging fruit” for a pressure-lowering surgery. The type of procedure he’ll select depends on their disease stage, lens status, and other considerations.
For patients whose pressure is averaging below their target pressure but who are having occasional jumps to 18–20 mm Hg, he said it’s harder to know what to do. “I’ll usually offer it to them. The goal isn’t necessarily to get the pressure any lower than it is on average but to have all the readings be at that average.” In these cases, Dr. Ramulu said he will often do the procedure in the worse eye first and monitor it closely over a year. If the visual fields appear stable and their progression trajectory has changed, he’s able to approach the second eye with more information.
Finally, Dr. Ramulu said the patients who are consistently presenting with low pressures based on home tonometry are tough. He noted publications that discuss trabeculectomy for people with pressures of 10 mm Hg, but you need to be careful with this group.
“You’re going to get some hypotony, macular folds, maculopathy, choroidal effusions. When we create low pressures, we’re not precise enough to dial someone in to 7 or 8,” Dr. Ramulu said.
If he does perform a trabeculectomy on patients with low pressures, Dr. Ramulu said he modifies his technique. “The best results I’ve gotten with these patients are when I’ve left the flap tighter than I normally would,” he said.
Dr. Moster also engages primary care doctors for systemic conditions that can affect patients with NTG. She asks whether hypertensive medications they might be taking at night could be switched to during the day. She also asks for sleep apnea tests because if left untreated, obstructive sleep apnea can be associated with progression.
In addition to traditional glaucoma therapies—drops, laser, and surgical procedures—and looking at how systemic conditions could affect progression, Dr. Moster asks her patients to take antioxidants, such as gingko, resveratrol, turmeric, and enzyme CoQ10. She said that there is evidence in the literature that these may help but acknowledged that it isn’t very well established.
There are also behavioral elements that she discusses with patients to reduce the risk of progression. These include avoiding headstands if they do yoga and always keeping their head above their heart in general during exercise. She also said wearing tight neckties, playing wind instruments that require forceful blowing, or lifting heavy weights with Valsalva maneuvers are discouraged.
While she’s treating and monitoring these patients, Dr. Moster said she regularly documents the optic nerves, especially looking for optic disc hemorrhages and treating them more aggressively. “It’s been shown that these patients progress faster when hemorrhages are occurring,” Dr. Moster said.
Dr. Moster said that there is a new mindset for treatment of NTG, which is to test more frequently, treat earlier, treat more aggressively, and change therapy often. Also, you should choose a therapy that works for the patient’s lifestyle. “That’s very important because medicines don’t work in the bottle,” she said.
Article Sidebar
Expanding IOP monitoring technology
Ophthalmologists have been saying for some time that obtaining pressures just a few times a year is not enough for most glaucoma patients. Technology was needed to allow convenient, more frequent measurements of IOP. A few companies have responded to the call with some technology already in use and others in development.
iCare HOME (iCare)
This is a home tonometry system that is already FDA approved and is what Dr. Ramulu has some of his patients use. He said there is a charge for the service he uses to provide the device to patients. From a learning standpoint, he said most of his patients have been able to use the handheld technology without prior training. Some patients download the app and provide readings directly to their physician, while others send the device back to the facilitating company when the trial is complete, and the company provides the physician with the data.
Dr. Moster said she has also used iCare HOME with some of her patients, as well as the Olleyes virtual visual field test. She said she’s changed therapies quite a bit based on the information provided by these sources. “iCare HOME makes great sense because the patient has skin in the game, they’re monitoring their pressure, they’re becoming more compliant based on this, and it’s all for their own benefit,” she said.
Triggerfish (Sensimed)
This FDA-approved contact lens is able to provide 24-hour continuous IOP data.
Eyemate (Implandata Ophthalmic Products)
This is a permanent implantable, biocompatible microsensor that currently has the CE mark. Data from the implant is transmitted via a wireless connection to an app that can provide the patient with information about their disease and a medication schedule and the doctor with data to monitor therapeutic response.
About the physicians
Marlene Moster, MD
Professor of Ophthalmology
Sidney Kimmel Medical College
Thomas Jefferson University
Philadelphia, Pennsylvania
Pradeep Ramulu, MD, PhD
Chief, Division of Glaucoma
Wilmer Eye Institute
Johns Hopkins University
Baltimore, Maryland
Relevant disclosures
Moster: None
Ramulu: Perfuse Therapeutics
Contact
Moster: marlenemoster@gmail.com
Ramulu: pramulu@jhmi.edu
