Mean Length of Preclinical Detectable Phase for Open-Angle Glaucoma Estimated at 10 Years

The mean preclinical detectable phase (PCDP) for open-angle glaucoma was estimated to be approximately 10 years according to two distinct methods of analysis, with the findings ultimately suggesting a reasonable screening interval of 5 years.

An important component in understanding the natural history of a disease, estimating the PCDP length is needed to define optimum screening intervals, the amount of overdiagnosis, and the effectiveness of screening, according to study investigators.

“A shorter PCDP means that the disease develops to the clinical stages more rapidly and that screening would be needed more often to achieve the same beneficial effect,” wrote study author Johan Aspberg, MD, Department of Clinical Sciences in Malmo, Ophthalmology, Lund University. “Our estimate of the length of the mean PCDP suggests that screening, if repeated, could be done with relatively long intervals.”

The most important risk factor for blindness in open-angle glaucoma is late presentation, most often due to the absence of symptoms until the later stages of the disease. Efforts have been made to make screening more cost-effective and target high-risk populations, but the latest major reviews of glaucoma screening have not recommended population screening for open-angle glaucoma.

In order for screening to be considered justified, investigators noted the PCDP must be long enough to offer a benefit to the participants in terms of survival, improved quality of life, or prevention of disease. A large population screening for open-angle glaucoma was conducted in Sweden from October 1992 to January 1997 and aimed to identify individuals with previously undetected glaucoma for possible inclusion in the Early Manifest Glaucoma Trial (EMGT).

A total of 2029 patients were included in the current study and data were analyzed from March 2020 to October 2021. In order to estimate the PCDP by the 2 methods, investigators calculated the prevalence of glaucoma detected at the screening, the expected clinical incidence, and the clinical incidence of glaucoma yearly after the screening

Assuming that the detection rate was 100%, the first method calculated the prevalence by dividing the prevalence of previously undetected disease at a screening with the incidence rate of preclinical disease. The second used a Markov chain Monte Carlo (MCMC) model simulation that simultaneously derived both the length of the mean PCDP and the sensitivity of the screening.

The screening was attended by 32,918 participants aged 57 to 77 years, including 11,699 men (35.5%) and 21,219 women (64.5%). The clinical incidence for glaucoma increased up to age 85 years and then declined, with clinical incidence among nonresponders to the screening was similar to the total incidence.

Data show the mean length of the PCDP for all patients was 10.7 years (95% CI, 8.71 - 13.0) by the prevalence/incidence method and 10.1 years (95% credible interval [CrI], 8.9 - 11.2) by the MCMC method.

A subgroup analysis of 5-year age cohorts showed a slightly longer PCDP with the prevalence/incidence method in patients aged 55 to 59 years and 60 to 64 years at the screening. The sensitivity of the screening estimated by the MCMC method was 94% (95% CrI, 93 - 96).

Investigators noted the optimum interval between repeated screening examinations depends on the age at screening, screening sensitivity, mean PCDP, and the disease severity of interval cases.

“To investigate the ideal interval between screenings was not within the scope of this investigation, but we anticipate that half of our estimate of the mean PCDP, ie, 5 years, might be a useful interval,” Aspberg concluded.

The study, “Estimating the Length of the Preclinical Detectable Phase for Open-Angle Glaucoma,” was published in JAMA Ophthalmology.