Ocular Hypertension Treatment Study (OHTS)
Chat Highlights
August 28, 2002

Norma Devine, Editor

On Wednesday, August 28, 2002, Dr. Elliot Werner, a glaucoma specialist at Wills, and the glaucoma chat group discussed the "Ocular Hypertension Treatment Study (OHTS)."

Moderator:  Welcome back, Dr. Werner.  I understand that you participated in the Ocular Hypertension Treatment Study (OHTS) we are discussing tonight.  

Dr. Elliot Werner:  Yes, I was one of about 20 or so primary investigators around the country.   We recruited patients, enrolled them in the study, and followed them according to the protocol.

P:  Who paid for the study?  

Dr. Elliot Werner:  The study was funded by the Federal government through the National Eye Institute.  

Moderator:  What was the purpose of the study?

Dr. Elliot Werner:  The purpose was to try to answer one of the unanswered questions about glaucoma:   Whether or not treatment of glaucoma patients who have elevated IOP (intraocular pressure), but no evidence of optic nerve damage, will prevent the onset of glaucoma damage.

Moderator:  When did the study start, when did it end, and how was it conducted?  

Dr. Elliot Werner:  The OHTS started about seven or eight years ago, and is still underway.  Patients with elevated eye pressures between 22 mm Hg and 32 mm Hg were identified.  All subjects had normal optic nerves and visual fields, and were randomly assigned to a treatment or no-treatment group.  The treated subjects were treated with medicines to try to achieve at least a 20% decrease in IOP, and/or to bring the IOP below 21 mm Hg.  The control group (untreated subjects) was only observed.  Twice a year, visual field and optic disc evaluations were carried out on both groups to identify subjects who developed signs of glaucoma damage.

P:  In the control group, the onset of glaucoma was discovered BEFORE there was visual field loss 56% of the time.  In the treatment group, that was true only 50% of the time.  Was that difference statistically significant?  If so, does it mean that a patient who is not on medication, but is being monitored, has a better chance of early detection before visual field damage occurs?  

Dr. Elliot Werner:  That difference was not significant, but about half the conversions (the term used to describe changing from OHT to glaucoma) were on the basis of disc changes alone, and no visual field loss had yet been detected.

Moderator:  What was the outcome of the study?

Dr. Elliot Werner:  Of the untreated subjects, approximately nine percent developed glaucoma during the first five years.  Of the treated subjects, about four percent developed glaucoma, so treatment decreased the risk of developing glaucoma by more than fifty percent.

P:  This was a great study, but one thing that concerns me is that all the eye-specific variables (risk factors) such as IOP, central corneal thickness (CCT), cup-to-disc (c/d) ratio, and visual field pattern standard deviation (PSD) are stated as the average values for both eyes of each patient.  We can't tell from reading this study, for example, how many eyes actually developed glaucoma, what the average IOP of those particular eyes was, etc.  We can only determine the number of patients who developed glaucoma, and the average IOPs of all of their eyes (whether their glaucoma was bilateral or not).  Why didn't the researches report these values for individual eyes, instead of averages of both eyes?  After all, each eye can be treated individually.

Dr. Elliot Werner:  Not all of these data have been fully analyzed and statistically tested.  More data will eventually come out.  

P:  Don't such studies point out that the cause of glaucoma is still unknown, and attention is paid to IOP because that is all that can be treated now? 

Dr. Elliot Werner:  You are absolutely correct.  The study did not address the cause of glaucoma, only the effect of treating IOP.  

P:  At age 31, I was diagnosed as ocular hypertensive.  I'm now almost 56 years old.  My visual fields are excellent, my optic nerve shows no sign of damage.  Why, then, am I labeled a "glaucoma" patient?  I thought "glaucoma" was a term only used when damage has actually occurred.

Dr. Elliot Werner:  On the basis of your ocular hypertension, "glaucoma suspect" would be a better term.  

P:  Were the medications used by the participants varied?  If so, was one type of medication more effective than another?

Dr. Elliot Werner:  Any and all currently available glaucoma meds were available for use.  Treatment was individualized according to the patients' medical situation and tolerance.

P:  The study indicates there are sub-groups at higher risk than others.  Are you changing your treatment for any glaucoma suspects, based on the results of the study?

Dr. Elliot Werner:  To a degree, yes, but some of that data are still preliminary.

Moderator:  When will the study be completed?

Dr. Elliot Werner:  An effort is underway to obtain funding and support to follow the subjects for 20 years.

P:  Which glaucoma suspects turned out to be at higher risk?

Dr. Elliot Werner:  Older subjects and patients with thin corneas.

P:  How long does it usually take to go from "glaucoma suspect" to "glaucoma patient?" 

Dr. Elliot Werner:  That varies.  There is a cumulative effect, so that a certain number -- about two percent of the untreated group -- convert to glaucoma each year.

P:  Can IOP vary according to the technique used in measuring it and does anxiety affect IOP? 

Dr. Elliot Werner:  The technique for measuring IOP in the study was standardized.  Each subject had two readings, and the person reading the number from the tonometer was not the doctor who actually took the measurement.  There is no evidence that anxiety affects IOP. 

P:  After the central corneal thickness has been determined and it is normal or thin, at what IOP do you recommend treating OHTN when the optic nerves and visual fields are normal? 

Dr. Elliot Werner:  That is difficult to answer, based on the study, because any IOP over 24 mm Hg has a risk associated with it.

P:  According to Fig. 1 (page 718) in the study, central corneal thickness is a more reliable predictor of primary open-angle glaucoma than intraocular pressure.  Would you please comment?

Dr. Elliot Werner:  That's a complicated subject.  The central corneal thickness apparently introduces an artifact in the IOP measurement, so that in patients with thick corneas, the real IOP is actually lower than the measured IOP.  In thin corneas, the opposite is true.  The result is that people with thin corneas actually have a higher real IOP than what is measured, which puts them at a greater risk.  This effect turned out to be much larger than we would have predicted.

P:  My IOP is good but my doctors says I am a glaucoma suspect.  What are they basing that on?  My daughter just had glaucoma surgery.

Dr. Elliot Werner:  I would need more information, such as what your optic discs look like, to answer the question.

P:  Can holding your breath elevate eye pressure?

Dr. Elliot Werner:  Yes, especially if you strain against the closed windpipe (Valsalva maneuver).

P:  Would you start treatment if the IOP were 24 to 26 mm Hg or wait for glaucomatous changes to occur?

Dr. Elliot Werner:  That's a difficult question to answer.  I would first assess other risk factors, including corneal thickness, and then present the risks of treatment versus non-treatment to the patient to see how he or she felt about it.  

P:  Are suspects with thinner corneas at greater risk because IOP is really being underestimated, or is there a factor inherent in having thin corneas?

Dr. Elliot Werner:  That's not known for sure.  The real IOP is underestimated in patients with thin corneas. But thin corneas may also be associated with other structural abnormalities of the eye that make it more susceptible to glaucoma.

P:  The study clearly should give hope to ocular hypertension patients that they will never get glaucoma. According to the study, 90 percent of the untreated subjects did not progress to glaucoma, compared to 94.5 percent who did progress.  I would love those odds.

Dr. Elliot Werner:  That is a very important observation.  Most OHT patients in the study, treated or untreated, did not convert to glaucoma within five years.  One of the future directions of the study will be to determine whether delaying treatment until early damage occurs makes any difference in the ultimate outcome.

P:  The researchers have recommended NOT trying to adjust intraocular pressure measurements to compensate for central corneal thickness, but rather to view both as independent risk factors (along with other risk factors), because there's no perfect formula for making the adjustment.  Do you agree, and if so, how long will it take most docs to look at it this way?

Dr. Elliot Werner:  Yes, I agree.  But I have no idea how long it takes doctors to adjust their practice.

P:  Were the results of study what you expected?  Were there any surprises?  

Dr. Elliot Werner:  The biggest surprises were the effects of corneal thickness, the fairly significant difference between the treated and untreated groups, and the increasing acceleration of the conversion rate to glaucoma after four years of follow-up in the untreated group.

P:  Since researchers are recommending measurement of central corneal thickness as standard procedure, have insurance companies begun to cover the cost? 

Dr. Elliot Werner:  Not generally.  That is not a billable procedure.

P:  Does the study clarify whether the risks of treatment justify early treatment for prevention when there is only ocular hypertension, but no glaucomatous changes?  

Dr. Elliot Werner:  To a degree, yes.  The risks of treatment in most patients appear to be less than the risks of elevated IOP, but that depends on which meds are used and which other treatments -- that is, surgical -- might be recommended.

P:  How is corneal thickness measured?  Can this be done simply by looking at the cornea, or is it measured by using an instrument?

Dr. Elliot Werner:  An instrument called an ultrasound pachymeter measures corneal thickness.  Its main use is in LASIK patients.  Unfortunately, the machine is fairly expensive.

P:  How involved is the test for corneal thickness?  

Dr. Elliot Werner:  It's very simple.  It's about as involved as measuring the IOP.  

P:  Would most ophthalmologists have an ultrasound pachymeter and be skilled in using it?

Dr. Elliot Werner:  I don't know.  Probably most larger, higher-volume practices do.  

P:  Studies, such as one by Rene-Pierre Copt (U. of Lusanne, Switzerland) in 1999, concluded that patients with POAG who have thin corneas may lead to a misdiagnosis of NTG, while overestimation of the IOP in normal subjects who have thick corneas may lead to a misdiagnosis of ocular hypertension.  Why all the attention to central corneal thickness now?  Is it because of the popularity of LASIK?

Dr. Elliot Werner:  Yes.  And the observation that measured IOP was lower after LASIK. 

P:  Could you explain why diabetics in this study apparently developed glaucoma much less frequently than non-diabetics?

Dr. Elliot Werner:  I'm glad you mentioned that.  The finding was a big surprise, for which there is no apparent explanation.

P:  I thought it was because patients with other eye diseases associated with diabetes were excluded from the study, so you end up with the "cream of the crop," so to speak.  Doesn't that account for it?

Dr. Elliot Werner:  That was one hypothesis, but the question is impossible to answer without doing another experiment.  It may be a statistical coincidence.

P:  Didn't a study find a high incidence of glaucoma patients who were also diabetics?  

Dr. Elliot Werner:  There are a number of such studies with very conflicting results, so the question remains unanswered.

P:  What are the odds that ocular hypertensives will develop glaucoma?  

Dr. Elliot Werner:  Nine percent in five years, depending on other risk factors.  

P:  On the basis of the results of the study, would you assign a different risk value to a number of independent variables such as cup-disc ratio, CCT, IOP, age, etc., and then add them all up to get a specific risk prediction?  Or would you adjust assessment in a more combined, holistic way?

Dr. Elliot Werner:  That analysis is underway at present to see which approach, if any, has the best predictive value.

P:  Did the study consider that some normal-tension glaucoma is actually secondary glaucoma?

Dr. Elliot Werner:  Normal-tension glaucoma patients were not included in the study, only ocular hypertensive patients.

P:  Was the angle of the eye a risk factor?

Dr. Elliot Werner:  All patients had open angles as an inclusion criteria.

Moderator:  Why were people with narrow-angle glaucoma excluded from the study?  

Dr. Elliot Werner:  Because that might be angle-closure glaucoma, not ocular hypertension.

P:  Are the results of the OHTS of significance to normal-tension glaucoma patients? 

Dr. Elliot Werner:  Normal-tension glaucoma patients were not included in the study, which had nothing directly to do with NTG.  

P:  Were patients with aniridia included in the study? 

Dr. Elliot Werner:  No, all patients had no other ocular abnormality other than elevated intraocular pressure. 

P:  Has a correlation between OHT and Sjogren's Syndrome ever been found?

Dr. Elliot Werner:  Not to my knowledge.

P:  Did the OHTS give any consideration to central retinal vein occlusion due to the elevated IOPs associated with ocular hypertension?  

Dr. Elliot Werner:  I don't know of any patients in the OHTS who developed central retinal vein occlusion during the study, but it is possible one or two may have.

P:  Since the risk of central retinal vein occlusion is higher at pressures 30 mm Hg, isn't the debate about whether or not to treat kind of limited to IOPs from 21 to 30 mm Hg?

Dr. Elliot Werner:  To some extent, the OHTS, I think, enrolled patients with IOPs up to 32 mm Hg. 

P:  Dr. Paul Palmberg presented some interesting statistics showing a significantly higher probability of ocular hypertensive patients converting to glaucoma when the IOPs were 25.75 mm Hg and higher, and the cup-to-disc ratio was only 0.3. The conversion rate for five years was 24 to 36%, rather than the 0.5 to 1.0% rate previously estimated.  Do you think this assessment is accurate?  If so, the preventive aspect may be more important than ever.  Is that fair to assume?  

Dr. Elliot Werner:  That is probably true.  The problem is, when you break the study into too many small groups, the validity of the statistics decreases.  

P:  What were some of the risk factors that will affect the odds negatively for a patient with ocular hypertension?  

Dr. Elliot Werner:  I'm sorry.  I don't remember all of them off the top of my head, but they include age, corneal thickness, and the level of intraocular pressure. 

P:  Doctor Werner, how have the results of the study changed your thinking about treating ocular hypertensives (glaucoma suspects), besides getting central-corneal thickness measurements? 

Dr. Elliot Werner:  I am a little more willing to recommend treatment, and I inform patients of the results of the study to find out how they feel about treatment versus being followed.  

P:  It's gratifying to know that all of the data are still being analyzed.  Any idea when more results will be published?

Dr. Elliot Werner:  More information should be coming out over the next year or two.

End of highlights for August 28, 2002.

On September 4, Dr. Myers discussed "When Things Don't Go As Planned" in the Chat room. Click here for highlights of that meeting.

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