Advanced Glaucoma Intervention Study (AGIS)
Chat Highlights
October 1, 2008

On Wednesday, October 1, 2008, Dr. Michael Pro, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Advanced Glaucoma Intervention Study (AGIS)".

Moderator: Welcome back to chat Dr. and chatters. Our topic this evening is Advanced Glaucoma Intervention Study (AGIS). First, is this study complete or ongoing?

Dr. Pro: This study is completed, although the data analysis is ongoing, with papers still being generated.

The main outcomes of interest were visual function (visual field and visual acuity). Other important outcomes were information regarding intraocular pressure, complications of surgery, time to treatment failure, and extent of need for additional medical therapy.

P: Who was conducting the research and what types of patients were participating?

Dr. Pro: Between 1988 and 1992, investigators at 12 participating AGIS clinical centers enrolled 789 eyes of 591 patients.

Phakic patients, 35 to 80 years of age, with open-angle glaucoma no longer controlled by maximally tolerated medical treatment were recruited. The eligible eyes had to have a best corrected visual acuity score of at least 56 letters (Early Treatment Diabetic Retinopathy Study charts) and meet specified criteria for combinations of consistently elevated IOP, despite maximum-tolerated and effective medical therapy, glaucomatous VF defect, and/or optic disc rim deterioration.

P: What were some of the AGIS clinical centers?

Dr. Pro: The Advanced Glaucoma Intervention Study and the clinical centers were researchers and physicians in numerous academic and private glaucoma practices. One of the important contributors to this study is the Jules Stein Institute at UCLA.

P: What are "phakic" patients?

Dr. Pro: Good question; sorry for the medical lingo. Phakic means having one's natural lens, or not having had cataract surgery.

P: Did any answers come out of the study?

Dr. Pro: Great question; let me get back to the study design.

Eyes were randomly assigned to one of two surgical-intervention sequences: either argon laser trabeculoplasty–trabeculectomy–trabeculectomy (ATT) or trabeculectomy–argon laser trabeculoplasty–trabeculectomy (TAT). Follow-up study visits were scheduled three and six months after enrollment and every six months thereafter.

The most important predictors for visual field (VF) progression were:

• to be older age at the time of first glaucoma intervention;
• greater intraocular pressure (IOP) fluctuation;
• higher mean IOP; and,
• lower baseline AGIS VF score.

Length of follow-up and the number of glaucoma interventions have also been found to be less important, but significant, risk factors for glaucomatous VF progression.

I am indebted to the work of the numerous AGIS authors for these results; the major papers began to appear in 2004 and are still being published.

P: What is visual acuity of 56 letters?

Dr. Pro: That is a score on a special type of visual acuity chart, but it implies fairly good central acuity.

P: At what stage is glaucoma considered "advanced"? What are the indicators?

Dr. Pro: That was mostly determined by a score that was formulated for the visual fields. The researchers created a unique and somewhat complicated grading system to determine a baseline visual field score. They then compared the visual fields using their model over successive visits. Thus, the major conclusions from this study are based on visual field results, and not on any changes to the optic nerves.

P: When glaucoma is advanced can they stop the progression?

Dr. Pro: Well, that gets to the main conclusion of AGIS.

In the Associative Analysis, eyes with 100 percent of visits with intraocular pressure less than 18 mm Hg over six years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50 percent of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score.

In plain language the target IOP for this study was 18mmHg. If a patient was over that target then a specific intervention was performed. This intervention was randomized at the time of patient enrollment, either getting a trabeculectomy or having a laser (ALT). Eyes that had an IOP less than 18 100 percent of the time over six years did not progress on the visual fields.

P: Shouldn't visual field results and optic nerve damage relate?

Dr. Pro: Yes, we would expect the optic nerve damage to correlate to the visual fields, but that was not part of the study design.

P: Why were they using ALT? I keep hearing that ALT is not as effective as SLT. Is it because the study started 20 years ago?

Dr. Pro: Yes, there was no SLT then, which gets back to the study design. By the time the papers for AGIS were coming out, some of the conclusions already seemed outdated. For instance, AGIS suggested that black patients did better if ALT was performed first, and white patients did better if trabeculectomies were done first. Overall, however black patients were shown to do worse than whites, and most glaucoma specialists are now not routinely considering that conclusion of the study in terms of treatment sequence. We have better surgeries today and better drops.

P: Does advanced glaucoma usually mean that blindness is immanent?

Dr. Pro: No, it does not have a strict definition. In this study it was based on visual field scoring, but in practice I consider glaucoma to be advanced if a patient has moderate to severe scotoma inferiorly and superiorly, or a very dense hemifield defect.

P: We need "scotoma inferiority" and "dense hemifield defect" defined. (At least, I do!)

Dr. Pro: A scotoma is a blind spot in your visual field, a dense hemifield defect means a big blind area in one half of your visual field, top or bottom.

P: Is AGIS going to be of any significant assistance in stemming the damage caused in glaucoma and in its prevention?

Dr. Pro: Yes, AGIS was a turning point for treatment. It and similar studies supported the idea of aggressive IOP control. Prior to these studies, glaucomists would consider the reduction of the baseline IOP by 30 percent to be sufficient for slowing glaucoma progression. AGIS and other studies showed that reductions of 40 or even 50 percent were often needed.

P: Will this aggressive IOP control be with medication or surgery?

Dr. Pro: For aggressive control it seems to be either medication or surgery.

P: There are so many variables here! Who is to say that all of the study participants were compliant in using their drops? How was that monitored?

Dr. Pro: For this study the patients had already failed to control the IOP with drops prior to the study start, so were being treated with the proscribed sequences.

P: If the glaucoma becomes advanced is there any hope that new technology will be able to reverse or stem the deterioration?

Dr. Pro: AGIS and other studies have shown that the visual fields and functioning can improve with better IOP control, but there is a baseline of damage that represents dead neurons. Ultimately some kind of optic nerve regeneration will be needed, but no therapies are available right now.

Moderator: That's all the time we have. Dr. Pro, this has been very interesting. Thank you for your time and information.

Dr. Pro: Thank you. Good night.

On October 15, Dr. Pro discussed "Collaborative Normal-Tension Glaucoma Study (CNTGS)" in the Chat room. Click here for highlights of that meeting.

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