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Glaucoma is a group of eye diseases that damage the optic nerve and can cause vision loss and blindness. The most common form of glaucoma in the United States is primary open-angle glaucoma. High eye pressure inside the eye — or high intraocular pressure (IOP) — is the only known risk factor for glaucoma that can be changed with treatment.

Although there’s no cure for glaucoma, clinical studies funded by NEI provide doctors, patients, and caregivers with the information they need to make informed health care decisions. The results of these studies also inform future research to develop improved therapeutic strategies to delay, prevent, and treat glaucoma.

Putting decades of eye health research into context

Scientific research is cumulative, with new breakthroughs advancing the field and changing the landscape. And given NEI’s long history of research, results that were groundbreaking decades ago may be less directly relevant today. The studies showcased here represent landmarks in eye health research that laid the groundwork the treatments, diagnostic tools, and prevention options that exist today.

Glaucoma Laser Trial

In 1984, researchers started the NEI-funded Glaucoma Laser Trial (GLT, NCT00000144). The trial looked at the safety and efficacy of argon laser therapy as a first-line treatment for primary open-angle glaucoma. The GLT recruited 271 people with primary open-angle glaucoma and randomly assigned one eye to receive argon laser therapy — and the other eye to receive the standard medical treatment (timolol eye drops).

The GLT found that after 2 years of follow-up, argon laser therapy was as safe and effective as the standard medical treatment to lower eye pressure. Because glaucoma is a progressive and chronic disease, researchers continued to follow patients in the GLT Follow-up Study (GLTFS) to gather longer-term results.

Glaucoma Laser Trial Follow-up Study

The NEI-funded Glaucoma Laser Trial Follow-up Study (GLTFS, NCT00000144) monitored patients with primary open-angle glaucoma who had participated in the GLT (Glaucoma Laser Trial). The GLTFS continued to follow patients to see if the benefits of argon laser therapy were as long lasting as the benefits of the standard medical treatment (timolol eye drops). The GLTFS followed 203 of the 271 GLT participants for an average of 7 years after their diagnosis.

The GLTFS confirmed GLT findings that argon laser therapy was as safe and effective as the standard treatment to lower eye pressure. Researchers also found that compared to the standard treatment, argon laser therapy’s side effects were temporary and more tolerable — and didn’t change patients’ results.

Fluorouracil Filtering Surgery Study

In 1985, researchers started the NEI-funded Fluorouracil Filtering Surgery Study (FFSS, NCT00000122). The study investigated whether the drug 5-fluorouracil (5-FU) is a safe and effective way to stop the growth of scar tissue after glaucoma surgery. This scar tissue can lower eye fluid outflow and raise eye pressure — and some people need another surgery to remove it. The FFSS recruited 213 people who needed glaucoma surgery and randomly assigned them to receive 1 of 2 treatments after their surgery:

  • 5-FU injections plus standard post-surgical care
  • Standard post-surgical care only

The FFSS showed that 5-FU injections were safe and effective at reducing the need for additional surgery among people who had undergone glaucoma surgery. A 5-year follow-up to this study confirmed the benefit of 5-FU for patients at high risk of needing a second surgery to get rid of scarring — but cautioned against its routine use in patients with good prognoses.

Advanced Glaucoma Intervention Study

In 1988, researchers started the NEI-funded Advanced Glaucoma Intervention Study (AGIS, NCT00000148). AGIS was a multicenter, randomized clinical trial that evaluated 2 sequences of surgery treatments for glaucoma to find out which sequence better preserved vision. The AGIS recruited 581 patients with advanced glaucoma and randomly assigned them to receive 1 of 2 treatment sequences:

  • Argon laser trabeculoplasty (ALT) followed by trabeculectomy, if needed
  • Trabeculectomy followed by ALT, if needed

Both groups got a second trabeculectomy if their initial treatment plan didn’t work.

AGIS was one of the earliest studies to show that lower eye pressure was associated with slower vision loss over time. And after 7 years of follow-up, the AGIS found that Black/African American patients responded better to the treatment sequence that started with ALT, while white patients responded better to the sequence that started with trabeculectomy. This finding was made possible by the fact that over half the patients were Black/African American — 332 Black/African American patients and 249 white patients. Still, researchers noted that not all patients of each racial group responded to the treatment sequences in the same way.

Early Manifest Glaucoma Trial

In 1992, researchers started the NEI-funded Early Manifest Glaucoma Trial (EMGT, NCT00000132). The trial evaluated the effects of immediate treatment to reduce eye pressure versus no treatment or delayed treatment. The EMGT recruited 255 people with newly diagnosed (early) open-angle glaucoma and randomized them to receive:

  • Immediate laser treatment (trabeculoplasty) plus medical treatment (betaxolol hydrochloride) to lower eye pressure
  • No treatment — but if glaucoma progressed, researchers offered treatment

The EMGT was the first large, multicenter trial of early glaucoma that included a “no treatment” group. The trial showed that treatment to reduce eye pressure can slow glaucoma progression in many people with early glaucoma and higher eye pressure. It also showed that in people with early glaucoma, eye pressure remained stable without treatment for an average of 6 years, regardless of their eye pressure at the beginning of the trial. But because glaucoma progression can be variable and difficult to predict, eye care professionals should follow glaucoma progression closely and individualize treatment for each person.

Collaborative Initial Glaucoma Treatment Study

In 1993, researchers started the NEI-funded Collaborative Initial Glaucoma Treatment Study (CIGTS, NCT00000149). The study evaluated if surgery was effective as an immediate treatment to lower eye pressure for open-angle glaucoma. The CIGTS recruited 607 people with newly diagnosed open-angle glaucoma and randomly assigned them to 1 of 2 treatments:

  • Topical medications to lower eye pressure
  • Trabeculectomy (filtration surgery

The CIGTS found that immediate filtration surgery lowered eye pressure more than medication. But patients who received filtration surgery were more likely to need follow-up cataract surgery. After 4 years of follow-up, both treatments groups had similar vision outcomes. So researchers concluded there was no benefit of immediate filtration surgery for people with newly diagnosed open-angle glaucoma.

Ocular Hypertension Treatment Study

In 1994, researchers started the partially NEI-funded Ocular Hypertension Treatment Study (OHTS, NCT00000125). The study measured the effects of using any type of commercially available eye drops to treat high eye pressure and assessed if this medical treatment could prevent primary open-angle glaucoma. The OHTS recruited 1,636 people with high eye pressure and randomized them to either:

  • Use commercially available pressure-lowering eye drops
  • Be observed but receive no treatment

The OHTS confirmed that high eye pressure is a risk factor for developing primary open-angle glaucoma and that using pressure-lowering eye drops can safely and effectively delay or prevent this disease. The study also showed that Black/African American people are at higher risk of developing primary open-angle glaucoma and can benefit from early treatment with pressure-lowering eye drops if they have high eye pressure. But eye care professionals should individualize treatment for each patient.

Ocular Hypertension Treatment Study: 20-Year Follow-Up

The NEI-funded Ocular Hypertension Treatment Study (OHTS): 20-Year Follow-Up (NCT00000125) of OHTS participants found that only about 25% of people in the study had developed vision loss in one or both eyes after 20 years. The follow-up study aimed to identify risk factors to determine which patients need pressure-lowering treatment and which may only need monitoring. The report findings suggest that patients with high eye pressure may not always need treatment to prevent vision loss.

Last updated: July 17, 2023