OHTS confirms clinical practices, leaves some questions unanswered

The study identified risk factors for progression to glaucoma, but specialists are still weighing who to treat and when.

In June, the Ocular Hypertension Treatment Study released 5-year findings indicating that topical IOP-lowering medications can delay the onset of primary open-angle glaucoma. In addition, the OHTS report revealed other important findings regarding patient risk factors for progression to glaucoma.

The results of the OHTS confirm some long-held suspicions about the way primary open-angle glaucoma (POAG) progresses, and they validate practices that some glaucoma specialists may already have been following without evidence. But overall, what will these study results mean for the management of the ocular hypertensive patient? How will they affect glaucoma specialists and general ophthalmologists?

To answer this question and more, Ocular Surgery News spoke with glaucoma specialists about how the OHTS has influenced their daily practice patterns and how it may affect them in years to come.

Now that ophthalmologists have had a chance to absorb the findings of the OHTS, this article summarizes the thoughts of some leading ophthalmologists on the subject. Interviewees shared with us the lessons learned from the OHTS and the questions raised but still unanswered by the study.

Study design

The OHTS was a prospective, randomized, multicenter clinical trial that evaluated the safety and efficacy of topical ocular hypotensive medications in preventing or delaying the onset of visual field loss or optic nerve damage in patients at moderate risk of developing POAG.

The study randomly assigned 1,636 patients at 22 centers across the United States to receive either close observation or treatment with topical IOP-lowering eye drops. There were 817 patients enrolled in the treatment group and 819 patients enrolled in the observation group.

The set goal for patients in the treatment group was reduction of their IOP by 20%, and the target IOPs were to be less than 24 mm Hg.

Target IOP was reached in both eyes in 87% of the treatment group, and an additional 7% of patients reached target IOP in at least one eye.

Lowering IOP by about 20% reduced the incidence of glaucoma by more than 50% in the treatment group, compared to the observation group. At 5 years, the researchers found a 4.4% incidence of developing glaucoma in the treatment group and a 9.5% incidence in the observation group.

The OHTS confirmed previously suspected glaucoma risk associations such as family history, black race, elevated IOP, increased cup-to-disc ratio and older age.

Quality-of-life questions

In light of the results, the ophthalmologists we interviewed said the study will influence nuances of their current management of ocular hypertensive patients. But some said the results leave some management questions regarding patients’ quality of life unanswered.

“One thing everyone agrees on is that the study has helped us figure out which subgroups of patients would be better off being treated than others. In other words, it has helped us identify risk factors for progression from ocular hypertension to glaucoma. So, if we do decide to treat some of the patients we can more precisely focus in on the ones at the greatest risk of developing glaucoma,” said Kuldev Singh, MD, director of the glaucoma service at Stanford University.

David J. Palmer, MD, a glaucoma specialist and a clinical assistant professor of ophthalmology at Northwestern University Medical School, emphasized the positive news from the study — that more than 90% of patients left untreated were stable over the course of the study.

“The inference is that not every ocular hypertensive patient needs treatment. ... One needs to consider the long-term treatment benefits with respect to the patient’s age and account for potential systemic medication interactions,” Dr. Palmer said. “The ultimate question is whether the patient will have a better quality of life long-term on treatment.”

Robert Feldman, MD, a glaucoma specialist with the University of Texas-Houston Health Science Center, expressed the same concerns regarding quality of life.

“What the OHTS study really does more than anything else is prove that we can reduce the risk of developing visual field defects. What it doesn’t answer is whether we should be treating patients early on or not,” he said.

“Once you put a patient on a medication you have changed their life. You have made their life worse. You have effectively told them they have glaucoma or, even if you tell them they are a suspect, you have now intervened in their life where they have to do something different every day, and have the side effects of the medications,” Dr. Feldman continued.

“Ultimately, our goal is to keep patients functionally seeing for their entire life. The question is: Does treating patients early and preventing that early, mild visual field defect affect their long term outcomes, because when they get those mild defects they are still asymptomatic. We can treat them earlier and prevent it, but should we? Is that in the best interest of the patient? We have no clue.”

For Dr. Feldman, the decision to medicate or observe is multifaceted. It involves balancing the patient’s risk of developing glaucoma against the possibility that the patient will not develop functionally significant glaucoma during his or her lifetime.

“If you have a 40-year-old patient who has a pressure of 28 mm Hg and has a family history, that is a patient I would treat. On the other hand, if the patient is 70 years old and has a pressure of 28, normal visual fields and normal optic nerves, even with a family history I probably would not treat them because during their lifetime they are not likely to develop a functional visual loss from the glaucoma because it is a slowly progressive disease,” Dr. Feldman said.

“You have to balance the ability to prevent damage against the likelihood that they are going to go on to develop a functional visual loss during their lifetime. And there really isn’t any good data on that. There is a lot of controversy about how many people actually go blind from glaucoma, depending on what study you reference. We really don’t know the risk factors and the rate of progression to blindness. But certainly the younger they are, the more aggressive we should be in treating them,” he said.

Corneal thickness findings

Joel S. Schuman, MD, professor of ophthalmology, chief of the glaucoma and cataract service and vice chairman at the New England Eye Center, said a secondary finding of the OHTS may be just as important as the primary finding, if not more so.

“The second important finding is that you can select out a population that is at extremely high risk of developing optic nerve head and visual field changes. Specifically, the study identifies the role of central corneal thickness in that discrimination,” he said.

The OHTS found that central corneal thickness is “a powerful predictor for the development of POAG.” Patients with a central corneal thickness of 555 µm or less had a threefold greater risk of developing POAG than participants with a corneal thickness of more than 588 µm.

“So if you have a person that has the specified abnormalities, in other words a normal-to-thin cornea, a pressure of 26 [mm Hg] or higher, they are at a very high risk of developing visual field or optic nerve head changes,” Dr. Schuman said.

Most ophthalmologists we interviewed for this article, both general ophthalmologists and glaucoma specialists alike, agreed that the corneal thickness findings of the OHTS had immediately affected their management of hypertensive patients. Dr. Schuman and others said they now take corneal thickness measurements on all patients on their first visit. Prior to OHTS, they were taking these measurements only on selected individuals.

“That gives us information on how to interpret the applanation tonometry as well as an understanding that corneal thickness may be an independent risk factor. In other words, there may be something else about corneal thickness that plays a role as opposed to just its effect on IOP. Corneal thickness may also tell us something about the structure of the sclera or the lamina cribrosa,” Dr. Schuman said.

Dr. Singh said whether to perform pachymetry measurements on every patient with ocular hypertension will be an ongoing debate.

“To me, that may be the one factor that may change in our practices, the necessity to do corneal pachymetry. But it’s too early to tell whether that will be incorporated into the practices of most ophthalmologists,” Dr. Singh said.

Dr. Feldman agreed that the OHTS findings relating to corneal thickness are revelatory.

“It confirms what we have been talking about for the past 5 years. The thicker the cornea, then the pressure will be measured too high,” he said.

Dr. Feldman explained the phenomenon further. He said a patient with a cornea 100 µm or so thicker than a normal cornea, “depending on how you are measuring, which instrument you are measuring with and what the normal is, that increased thickness might account for 5 or 6 mm Hg of IOP on Goldmann tonometry. So a patient who measures 28 mm Hg on Goldmann may really be 22, and so their risk goes along with someone with a normal corneal thickness who measures 22 mm Hg,” he said.

“I think pachymetry should be measured on every glaucoma patient on the initial visit so you can set your target appropriately,” Dr. Feldman said. “Same thing for ocular hypertensive patients. I think of ocular hypertensive patients as glaucoma patients who don’t have damage. Whether they ever develop it or not is another issue.”

Patient awareness

The OHTS established that treating ocular hypertensive patients with topical IOP-lowering medications can delay and possibly prevent the onset of POAG. But although this news was greeted with fanfare by the ophthalmic community, it does not seem to have penetrated the public consciousness to a great extent.

Since the release of the OHTS results, most ophthalmologists interviewed for this article said they have not seen a rise in the number of patients requesting IOP-lowering medications. Despite the attention granted the study in the general media, respondents said there have been relatively few patients even indicating an awareness of the study. But some patients have picked up on it and are asking questions.

Michael S. Berlin, MD, a glaucoma and cataract surgeon in practice in Los Angeles, said it is still too early for public awareness to bring in patients for screening. However, he expects this may change in the near future, given greater national publicity of the findings of the OHTS and the availability of a Medicare-covered glaucoma screening for eligible patients.

Jonathan Myers, MD, a glaucoma specialist in practice in Philadelphia, said the release of the study created some confusion among his patients regarding how glaucoma is diagnosed and treated.

“Many patients misinterpreted the news reports as suggesting that there was a new treatment that cured glaucoma. The study’s release and publicity served as a springboard for a lot of useful discussions with people,” Dr. Myers said.

Dr. Palmer said he has seen an accelerating trend toward patient self-education regarding glaucoma and glaucoma medications. Internet-savvy patients are raising questions about possible treatment options, he said.

“No special requests have been noted on any particular agent, although more questions are asked about prostaglandins in general as a class,” Dr. Palmer said.

Dr. Singh said he believes it is too early to tell how the OHTS results have affected the general population. He said some patients are aware of the study and have come in inquiring about the results.

“I don’t think they have come in demanding treatment or demanding that they be taken off treatment, but rather looking for more information regarding the study,” Dr. Singh said. “It’s too early to tell whether the patients will want more or less treatment based on the study results. My sense is that prior to this study the general ophthalmologist was more likely to treat an ocular hypertensive patient than a glaucoma specialist. Whether that will change based on the study results still remains to be seen.”

Level of IOP reduction

In the study, one goal of treatment was to lower IOP by 20%. This raises the question of the role of topical medications that can lower IOP by more than 20%, such as the new class of prostaglandin analogues and related drugs.

Eve J. Higginbotham, MD, a glaucoma specialist and chair of the department of ophthalmology at the University of Maryland in Baltimore and one of the authors of the OHTS, said the targeted threshold of 20% was an achievable goal based on the drugs that were available at the time the OHTS initiated. Until the past few years, the initial first-line medication for glaucoma patients was most commonly a beta-blocker. In most patients a 20% reduction could be achieved with once or twice daily administration of beta-blocker monotherapy.

“This was not considered burdensome for patients with ocular hypertension,” Dr. Higginbotham said.

However, she noted that the introduction of latanoprost in 1996 raised the possibility of reducing IOP by as much as 30% with a single drop once a day.

“These days, a once-daily prosta-glandin analogue or related drug can reduce IOP more than 20% in the majority of patients. In addition, these drugs can flatten the diurnal curve, which can enhance the protective effect of treatment,” Dr. Higginbotham said.

“One can only speculate to what extent the results of OHTS would have been different if more patients had been started on a prostaglandin analogue,” she continued. “Perhaps instead of an overall 22% reduction, there may have been a reduction of 25% to 30%, and the protective benefit of medication may perhaps have been more pronounced.”

Is laser an option?

Two ophthalmologists speculated on the possibility of using modalities other than topical medications as initial treatment for ocular hypertensive patients. Some forms of laser therapy might be appropriate while others would not, they said.

According to Dr. Feldman, using argon laser trabeculoplasty (ALT) in glaucoma suspects is “probably is not a good idea.”

“It’s only going to last about 5 years on average,” he said. “So 5 years down the road you are right back where you started. If you are talking about someone who has 40 or 50 more years to live, if you do an ALT, then 5 years from now you have blown your shot at using that laser therapy because you have only one shot. I tend to save it until we need it and put patients on medication before considering ALT.”

Another less destructive laser option for initial treatment of ocular hypertension in the glaucoma suspect population may be selective laser trabeculoplasty (SLT).

Dr. Schuman, who has done investigative work on SLT, explained that the procedure is a means of treating the trabecular meshwork with light in order to stimulate the cells in the meshwork to improve function and reduce outflow resistance or improve outflow facility.

“It seems to work in ways similar to standard ALT, except with far less damage to the tissue to achieve the desired effect. The pressure-lowering effect of SLT seems very similar to ALT but with much less tissue damage. The benefit of that might be that SLT could be a repeatable procedure,” he said.

Dr. Feldman agreed that SLT may be an option for primary treatment of ocular hypertension, “if it works out that SLT is repeatable. But, there is no data to support that yet. It’s theoretical,” he said.

For Your Information:

• Michael S. Berlin, MD, can be reached at 8733 Beverly Blvd., Suite 301, Los Angeles, CA 90048; (310) 855-1112; fax: (310) 855-1211; e-mail: berlin@csmc.edu.
• Robert Feldman, MD, can be reached at Dept. of Ophthalmology, 6411 Fannin St., 7th Floor, Houston, TX 77030; (713) 704-0667; fax: (713) 704-4864; e-mail: ppts@swbell.net. Dr. Feldman has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Eve J. Higginbotham, MD, can be reached at the University of Maryland School of Medicine, Department of Ophthalmology, 419 W. Redwood, Suite 580, Baltimore, MD 21201; (410) 328-5929; fax: (410) 328-6346; e-mail: fcwejh6786@aol.com. Dr. Higginbotham has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.
• Jonathan Myers, MD, can be reached at Wills Eye Hospital, 840 Walnut St., Philadelphia, PA 19107; (215) 928-3197; fax: (215) 928-0166.
• David J. Palmer, MD, can be reached at 8901 West Golf Rd., Suite 201, Des Plaines, IL 60016; (847) 390-8660; fax: (847) 390-0616; e-mail: djpiop@aol.com. Dr. Palmer has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Joel S. Schuman, MD, can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington Street, Box 450, Boston, MA 02111; (617) 636-7950; fax: (617) 636-4866; e-mail: jschuman@lifespan.org. Dr. Schuman has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Kuldev Singh, MD, MPH, can be reached at Stanford University Department of Ophthalmology, Blake Wilbur W3002, Stanford, Calif. 94305-5353; (650) 723-5517; fax: (650) 723-7918; e-mail: kuldev.singh@forsythe.stanford.edu. Dr. Singh has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Reference:

• Kass MA, Heuer DK, et. al. The ocular hypertension treatment study. Arch Ophthalmol. 2002;120:701-713.