Pre-Perimetric Glaucoma Risk

With 20 years of follow-up since publication of its initial results, the Ocular Hypertension Treatment Study’s (OHTS) findings provide a strong basis for treating pre-perimetric glaucoma in ocular hypertension patients with the glaucoma risk factors the study identified, said S Fabián Lerner MD.

Dr Lerner noted the original OHTS study was a randomised controlled clinical trial involving 1,636 OHT patients without glaucoma designed to determine whether early treatment with intraocular pressure IOP-lowering medication could reduce the patients’ incidence of POAG. Another aim of the study was to determine whether baseline demographic and clinical factors can predict the level of risk an OHT patient has for developing POAG.

The study showed that at 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group. Risk factors such as older age, higher IOP, thinner central corneal thickness (CCT), larger vertical cupdisc ratio measurements, and higher visual field pattern standard deviation (PSD) values also were significantly associated with an increased risk for glaucoma development.ⁱ

A subsequent study showed a glaucoma risk calculator based on the OHTS’s findings performed well in assessing the five-year glaucoma development in separate OHT patient populations.ⁱⁱ

“The impact of the risk calculator was that in simulated case scenarios, glaucoma specialists changed their recommendations in OHT cases when they included a risk calculator, and specialists were more consistent with OHTS published results,” Dr Lerner said.

The OHTS phase 2 was designed to determine whether delaying treatment with IOP-lowering medications was detrimental to the observation group patients, he said. Participants randomised to observation for 7.5 years received IOP-lowering medications for a mean 5.5 years. Participants in the treatment group continued with treatment. The study showed the medications’ protective effect had a relatively rapid onset, and protection was better for the high-risk group.ⁱⁱⁱ

“Initiating ocular hypotensive medications in OHTS subjects originally randomised to observation significantly reduced the velocity of visual field progression. The greater the amount of absolute IOP reduction, the more important the improvement of visual field change,” Dr Lerner said.

OHTS phase 3, conducted from 2016 to 2019, provided further information on the natural history of OHT and the impact of treatment. It showed that after 20 years follow-up or over a lifetime (within 2 years of death), the cumulative incidence of POAG was 49.3% in the observation group and 41.9% in the medication group. In addition, African Americans had a higher risk at 55.2%, compared with 42.7% among other races.^iv

The study also provided further validation of the OHTS-based glaucoma risk calculator showing the highest risk of glaucoma was among those in the highest risk quartile (59.8%), followed by those in the medium risk profile (47%) and the lowest risk profile (31.7%).

“Consider early treatment for OHT in patients with high and maybe moderate risk. Individualised assessment of risk is useful—therefore, take into consideration a patient’s family history, social situation, life expectancy, health status, preferences, and possible side effects of treatment,” Dr Lerner concluded. “Future risk models may include optical coherence tomography information, genetics, and other factors.”

Dr Lerner presented this report at the Virtual World Ophthalmology Congress.

ⁱ Kass MA et al. Archives of Ophthalmology, 2002; 120: 701–703.

ⁱⁱ FA Medeiros et al. Arch Ophthalmol, 2005; 123(10): 1351–1360.

ⁱⁱⁱ Gordon M, Kass M. American Journal of Ophthalmology, 2018 May; 189:xxiv–xxvii.

^iv Kass MA et al. JAMA Ophthalmology, 2021; 139: 558–566.

S Fabián Lerner MD is Professor and Head of Ophthalmology, University Favaloro School of Medical Sciences and director, Fundación para el Estudio del Glaucoma, Buenos Aires, Argentina. glaucomas@yahoo.com.ar