OHTS AT 20 YEARS

Michael A Kass MD

The landmark Ocular Hypertension Treatment Study (OHTS) has been funded for a third phase that extends the follow-up period to 20 years, Michael A Kass MD told a Glaucoma Day session of the American Academy of Ophthalmology annual meeting in Las Vegas, USA.

The information gained will help patients and clinicians make better informed, evidence-based decisions about managing ocular hypertension (OHT) and early primary open-angle glaucoma (POAG), said Dr Kass in the American Glaucoma Society Lecture.

EVIDENCE NEEDED

OHT affects somewhere between 4.8 million to 8.5 million people over the age of 40 in the US – a number that will grow as the population ages, Dr Kass said. “Managing these people is associated with substantial cost and effort for patients, clinicians and society,” he added.

But while elevated intraocular pressure (IOP) has long been thought a leading risk factor for POAG, basic questions about managing it remained unanswered as late as the 1990s, Dr Kass noted. These include how often patients should be tested, what tests should be performed, whether early treatment of OHT can prevent or delay POAG; and if treatment works, which patients should be treated and when?

“Many of us thought we knew some of the answers, but there was no level 1 evidence and no clear consensus,” said Dr Kass, who is Professor of Ophthalmology and Visual Sciences at Washington University in St Louis, USA.

So in 1994, with support from the US National Eye Institute, Dr Kass and colleagues launched the OHTS. The prospective, randomised controlled trial evaluated the safety and efficacy of topical ocular hypertensive medications in delaying or preventing POAG. Baseline demographics and clinical factors were identified that predict which patients are more likely to develop POAG, Dr Kass said.

More than 1,600 participants of ages 40 through to 80 years with IOP of 24-32mmHg in one eye and 21-32mmHg in the fellow eye, with normal visual fields and optic discs, were enrolled. Half received medication and half were observed without treatment. Both groups received Humphrey visual field tests every six months and stereoscopic disc photos annually. At five years, visual field and optic disc changes were attributed to POAG by a masked endpoint committee.

Overall, medication produced about a 20 per cent reduction in IOP, Dr Kass reported in 2002. The five-year incidence of POAG was also less than half in the medicated group, at 4.4 per cent compared with 9.5 per cent in the observation group. “OHTS Phase 1 provided proof of concept: medication reduces the incidence of POAG,” he said.

WHO TO TREAT?

However, Phase 1 did not test when medication should begin, if all OHT patients should receive early medication, of if there is a penalty for delaying medication in OHT, Dr Kass said. OHTS Phase 2 was designed to answer these questions.

Beginning in 2002, 672 patients left in the observation group began topical IOP treatment, while 694 patients in the medication group continued treatment. This created a group in which medication was delayed a median of 7.5 years followed by 5.5 years of treatment and a group treated continuously for 13 years.

During OHTS Phase 2 there was no difference in incidence in POAG between the delayed medication and early medication groups, Dr Kass reported in 2010. However, over OHTS Phase 1 and 2, the early medication group had a lower incidence of POAG.

The absolute effect was greatest in patients with the highest risk as determined by a prediction model developed and validated using OHTS data. It incorporates age, IOP, central corneal thickness, cup-to-disc ratio and field pattern standard deviation as significant risk factors. The risk calculator is available at: http://ohts.wustl.edu/risk

Conversely, Phase 2 found little benefit to early treatment for low-risk patients. Phase 1 and 2 demonstrate that the risk of developing POAG continues over at least 15 years, and there are safe and effective treatment options for most OHT patients, Dr Kass added.

REFINING THE PREDICTIVE MODEL

The third phase will re-examine all living participants in the original OHTS cohort. The overall goal is to better understand how treating OHT and early POAG affect later loss of vision and quality of life – and what can be done to reduce the long-term risks, Dr Kass said.

Specific aims include determining the 20-year incidence of POAG, and developing 20-year models for stratifying POAG risk and predicting vision loss rates. Frequency and severity of self-reported limitations from POAG will be correlated with clinical findings to clarify the causal relationship of POAG to disability.

“The true goal of managing patients with OHT is to prevent the development of functional limitations from POAG,” Dr Kass said.

A 20-year model will be particularly helpful because it approaches the life expectancy of patients diagnosed in their 60s and 70s, and half the life expectancy of those diagnosed in their 40s and 50s, he added.

Michael A Kass: kass@vision.wustl.edu