Advanced glaucoma calls for aggressive, personalized care
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Early detection and appropriate management allow most patients to stave off progression of glaucoma beyond the mild to moderate stages and preserve vision.
However, between 3% and 17% of eyes worsen at rates of vision loss that could lead to perimetric blindness within 20 years, according to studies.
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“Despite careful monitoring, some patients progress right under our nose,” Deborah Ristvedt, DO, said. “They are patients with aggressive, high-risk glaucoma who get worse despite our best efforts.”
In addition, large studies have shown that in developed countries, 10% to 39% of patients with glaucoma present with advanced disease in at least one eye.
“A significant percentage of patients who get to advanced glaucoma often present that way. Since glaucoma can remain asymptomatic for a long time, they go undetected and only come for a visit when they notice they are not seeing well,” OSN Glaucoma Section Editor Thomas W. Samuelson, MD, said.
Managing advanced glaucoma requires an aggressive, personalized and sometimes creative approach, with a higher investment in terms of time and resources, but satisfactory outcomes can result.
“Fortunately, we have access to newer medications and newer techniques and technologies, and we see from more and more studies that these patients can do quite well. It is a different era from even 10 years ago with many exciting options,” Ristvedt said.
Compliance still a central issue
Poor adherence to topical medical therapy is often the cause of progression in cases that could otherwise be successfully controlled. “These cases are particularly frustrating because in many cases vision loss could have been prevented,” Samuelson said.
A retrospective analysis of combined visual field and pharmacy data from the Kaiser Permanente electronic health record database showed an average follow-up adherence of 73%, ranging from 20% to 80%, among patients with glaucoma. Patients with higher adherence had more stable visual fields compared with patients with low adherence.
“Compliance with follow-up visits is even more important. If patients show up for their appointment, we have the opportunity to detect progression and identify why the treatment isn’t working. If compliance is the problem, we can do something to treat the disease differently and maybe change from medical to surgical therapy,” Samuelson said.
Different situations
Patients who progress despite regular monitoring and treatment are usually those with aggressive, high-risk glaucoma.
“Many have normal-tension glaucoma and are more susceptible to IOP fluctuations despite good IOP control. Some secondary glaucomas can be high risk, such as pseudoexfoliation glaucoma. In Minnesota, we have a large Scandinavian population, and they are genetically predisposed to pseudoexfoliation syndrome. These are patients who could be very stable for a long time, but all of a sudden, they have these big IOP spikes and often are not symptomatic,” Ristvedt said.
In patients who are progressing, she looks at many potential risk factors, including lifestyle, activities, nutrition and cardiovascular status. Some may be on medications that significantly lower blood pressure at nighttime, affecting ocular perfusion. Cerebrospinal fluid (CSF) pressure has been found to be an identifier affecting the optic nerve. If the CSF pressure is too high, optic nerve swelling can be identified. If the CSF pressure is too low, glaucomatous changes can occur due to the pressure difference through the lamina cribrosa.
Patients who are newly diagnosed with advanced glaucoma are usually those who do not pursue regular vision care.
“Maybe they have enjoyed relatively good vision all their life. Maybe they have a busy life and don’t take care of themselves. In recent years, the pandemic has kept people from attending routine health checkups,” Samuelson said.
Although the diagnosis of advanced disease is unfortunate, treating this group of people can be gratifying, according to Sarah Van Tassel, MD.
“They can be exquisitely sensitive to selective laser trabeculoplasty, they have a virgin conjunctiva because they never had other procedures before, they haven’t been subjected to years and years of topical therapy, and a lot of them do quite well despite the new diagnosis of advanced disease,” she said.
Detecting early and monitoring regularly
The only way to detect rapid and severe progression is to do structure and function testing often, Van Tassel said.
“How often is a matter of math but also of negotiation with your patients,” she said.
It is also a matter of making good use of your ancillary professionals, according to Samuelson.
“As a surgeon, I spend half of my time in the OR, so I rely on my referring ophthalmology and optometric colleagues to help monitor some of the clinical appointments. I see patients at their initial visit, make a treatment plan and then bring them back at specific intervals for a visual field (VF) or for OCT with specific parameters, like target IOP and steps to take in case of disc or VF changes,” he said.
OCT is useful for high-risk patients when they are still at the mild to moderate stage, according to Ristvedt.
“It allows us to see how stable their retinal nerve fiber layer is and what their ganglion cell complex looks like and to identify any sign of thinning of the optic nerve rim,” she said.
At an advanced stage, monitoring relies on VF testing, which should be performed twice a year instead of once a year.
“In case of paracentral loss, we should switch from a 24-2 or 30-2 to a 10-2 to really look at that central visual field,” Ristvedt said.
“In some severe cases, even VF testing is only of modest clinical value, so we must rely on IOP measurement and ask patients how they feel they are doing. Often, these really advanced patients do have a sense of how their peripheral vision is changing because it is so close to fixation for them,” Van Tassel said.
Good communication and establishing trust with patients are key for early detection and monitoring of glaucoma progression, according to OSN Associate Medical Editor Leon W. Herndon Jr., MD.
“A good relationship early on leads to better compliance. I show my patients the data: If they are compliant and come to the follow-up appointments, they are likely to maintain good vision for the rest of their life, so the best advice I can give them is to stick to the plan,” he said.
Patients with advanced disease should be put in contact with vision rehabilitation services.
“At Duke University, we have a well-equipped vision rehab service that we utilize quite often to help these patients maximize the little vision they have,” he said.
The lower the better
There are no specific guidelines in the U.S. for the treatment of advanced glaucoma, but there are Preferred Practice Patterns for primary open-angle glaucoma issued by the American Academy of Ophthalmology.
“They advise that the initial treatment should aim at lowering the pressure between 20% and 30% of the patient’s untreated baseline. Target IOP should then be adjusted up or down based on the severity of the disease and the velocity of progression. With that in mind, for many people with severe disease, the target is adjusted far down below 15 mm Hg because many of us perceive that ultralow pressures are needed in severe disease almost regardless of what the starting pressure was,” Van Tassel said.
Low teens or even single-digits IOP should be aimed for in these patients, according to Ristvedt.
“The Advanced Glaucoma Intervention Study suggested that the lower the better,” she said. “If you started with a high pressure, IOP routinely below 18 mm Hg is better for the optic nerve, and you tend to see less progression. But if you manage to lower the pressure below 14 mm Hg consistently, these patients with advanced glaucoma tend to do even better.” Some will need IOP in the single digits.
“Try to get it down as low as you can safely get it down, and monitor the patient closely. But be aware that if you get the pressure down too low, you might have to deal with hypotony-related problems,” Herndon said.
Novel options for medical therapy
Novel drugs and surgical techniques have broadened the therapeutic options for patients with advanced glaucoma and offer the opportunity to individualize care more than in the past.
“In my 25-plus years of practice, I had seen no new glaucoma medications until 5 years ago when netarsudil (Rhopressa, Aerie Pharmaceuticals), a Rho kinase (ROCK) inhibitor, entered the market. ROCK inhibitors are a very powerful class of medications, and I use them, but they have side effects such as red eye, which is often a reason for discontinuation,” Herndon said.
More recently, the FDA approved sustained-release Durysta (bimatoprost intracameral implant, Allergan), designed to last for 6 months and possibly longer.
“We have now the ability to take treatment out of the patients’ hands, and this is helpful in cases where patients have trouble delivering drops because of arthritis or other problems. Unfortunately, the FDA approved only the one-time dosing, which is not sufficient for a disease like glaucoma. Other sustained-release delivery systems are coming out in the future, and we need more of these options for patients who are struggling with their compliance,” he said.
Aerie’s Rocklatan, a fixed combination of netarsudil and latanoprost, has also been a good addition to existing medications, according to Samuelson.
“Unlike a lot of medications which do better when the pressure is high, netarsudil often works with physiological starting pressure, and on occasion, we can achieve single-digit pressure with this combination. I often use it for patients with advanced disease when I am trying to go from pressures of 13 mm Hg or 14 mm Hg to 9 mm Hg or 10 mm Hg. Netarsudil helps achieve single digits partly because it improves trabecular outflow and partly because it dilates vessels and reduces episcleral venous pressure,” he said.
“Durysta allows us to take a drug holiday,” Ristvedt said. “Patients who have side effects from prostaglandins or difficulties with multiple medications can get a 6- to 12-month holiday from the drops. In 30% of patients, the effect even lasts for 2 years.”
She is looking forward to the approval of iDose (Glaukos), a travoprost-eluting stent that is placed in the angle and is expected to maintain efficacy for at least 2 years.
When surgery is needed
“I switch from medical treatment to surgery sooner than I did before,” Herndon said. “We have safer options than 10 years ago, so I go to surgery fairly quickly when I see progression and patients don’t tolerate the medications. I do minimally invasive glaucoma surgery for mild to moderate glaucoma, but for severe disease, only trabeculectomy can lower the pressure to the level we need in many cases. I don’t waste much time. I consider the age of the patient and life expectancy, general health status, how rapidly the disease is progressing and family history of glaucoma blindness. I tell my patients that we need to be aggressive, that we cannot give them back what they have lost, but we can and must preserve what they have.”
“Some studies say that tube surgery is more effective than trabeculectomy at 5 years, but if you need pressure in the single digits, the only option is still trabeculectomy,” he said.
In some patients who have moderate to severe disease and show signs of progression, Herndon considers ab externo implantation of a Xen gel stent (Allergan).
“Among the MIGS available, it is the most effective because you go subconjunctival rather than act on the drainage angle. I can always do trabeculectomy or tube surgery later,” he said.
“With Xen, I have gone back and forth,” Samuelson said. “In recent years, I have been using the open conjunctiva ab externo approach, and my impression is that patients seem to do better than when I was using a transconjunctival approach. In the last several months, I have had some very good responses, but for those who are most in trouble, I do trabeculectomy. Another advantage of Xen is for patients who come from far away because Xen is less dependent on postoperative care. Needling is important, but not as important as suture lysis is to trabeculectomy.”
Tubes are Samuelson’s first choice in specific cases, such as lake swimmers in whom bleb infection may be an issue. In patients who come from rural environments, tubes are a good choice because they are less dependent on postoperative care and timely suture lysis.
“Contact lens wearers sometimes do better with a tube, and certainly patients who have failed trabeculectomy or Xen,” he said.
Both Samuelson and Herndon said they are looking forward to having the PreserFlo microshunt (Santen) approved in the U.S. as a less invasive alternative to trabeculectomy.
“PreserFlo is still awaiting FDA approval, and we are hoping to have it soon in our armamentarium,” Herndon said.
More options
In patients with advanced glaucoma at presentation, Van Tassel tries SLT first.
“It is a wonderful method to start in eyes that have not been previously treated. I almost never use SLT for people who are on medications and progressing, but for these new cases, a judicious trial with laser or medications is always important before jumping right into surgery,” she said.
Treatment decisions in advanced disease are particularly complex when the patient is functionally monocular or when the damage is already so severe that peripheral vision defects are affecting fixation and threatening central vision because of the high risk for postoperative surgical complications, she said.
Ristvedt starts off with SLT or MIGS in newly diagnosed advanced glaucoma as a way to stabilize IOP, open the angle and optimize the natural outflow pathway.
“We have to be very careful about IOP spikes, but I still think that is a great starting point. We know that trabeculectomy and tube shunts fail over time in 50% of the cases, so I like to do whatever I can early on to optimize things, knowing that a different kind of surgery will probably be needed eventually to get the pressure down to the low teens or even single digits,” Ristvedt said.
If patients are not candidates for angle-based surgery or SLT, or if they need immediate IOP lowering to the low teens or single digits, she starts with Xen.
“I think of what I can do in a minimally invasive manner to still get a big reduction in pressure,” she said.
In patients who are progressing despite regular monitoring, she takes some time to reassess and discuss compliance.
“Right in the chair, I ask them to put in their eye drops to observe how they do it. It is amazing how often they are missing the eye and don’t really know it,” she said.
She also considers the potential for nighttime IOP spikes, switching to a biodegradable implant to provide around-the-clock IOP control or opening up the outflow pathway for better stability.
A case-by-case personalized approach is mandatory at these advanced stages and is possible nowadays given the many options available, Ristvedt said.
“I think of what I can do as aggressively as possible without going directly to a trabeculectomy or a tube shunt. A lot of times I start with medications that might lower the pressure most aggressively, such as ROCK or nitric oxide inhibitors. Then I look at SLT or Durysta to get stability, and finally I look at opening up the angle. Many of those patients who come with advanced glaucoma can do well if you first optimize their natural outflow pathway and are less likely to go on to incisional surgery right away,” she said. “Individualized care is key.”
Looking at glaucoma from a different perspective
Working on glaucoma from a different perspective might also entail using some of the many options offered nowadays after, rather than before, incisional surgery.
“If after trabeculectomy IOP is in the mid-teens and I want to go in the low teens, I consider adding Durysta, trying to keep the patients off medications, because they have likely been using them for a long time and struggle with ocular surface disease and other problems,” Ristvedt said.
The newer medications, particularly Rhopressa, may also be beneficial in patients who have had prior filtering surgery to optimize the effects by decreasing resistance in the trabecular meshwork and by lowering episcleral venous pressure.
“And we still have use for going back to the angle after someone has had trabeculectomy. I have plenty of patients who had trabeculectomy earlier on, and I have done canaloplasty with goniotomy with great success when the pressure started going up to the 20s. You go back to the angle, optimize and get back the pressure to the mid-teens,” she said.
Surgeons are becoming more creative and proactive about pressure reduction, she said, based on scientific evidence that early intervention prevents visual field progression and need for incisional surgery.
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- For more information:
- Leon W. Herndon Jr., MD, can be reached at Duke Eye Center, 2351 Erwin Road, Durham, NC 27705-4699; email: leon.herndon@duke.edu.
- Deborah Ristvedt, DO, can be reached at Vance Thompson Vision, 2600 Jefferson St., Alexandria, MN 56308; email: deborah.ristvedt@vancethompsonvision.com.
- Thomas W. Samuelson, MD, can be reached at Minnesota Eye Consultants, 10709 Wayzata Blvd., Minnetonka, MN 55305; email: twsamuelson@mneye.com.
- Sarah Van Tassel, MD, can be reached at Weill Cornell Medicine, Ophthalmology, 1305 York Ave., 11th Floor, New York, NY 10021; email: sjh2006@med.cornell.edu.
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