Introduction: The Persistence of Clinical Thresholds
For decades, the management of glaucoma has been anchored by the measurement of intraocular pressure (IOP). Historically, a pressure of 21 mm Hg was often cited as the upper limit of normal, a concept rooted in early population studies that suggested values beyond two standard deviations from the mean indicated pathology. However, as our understanding of the disease has matured, the medical community has shifted toward viewing IOP as a continuous risk factor rather than a binary diagnostic criterion. Despite this paradigm shift, clinical behavior often mirrors historical precedents. A recent large-scale study published in JAMA Ophthalmology by Polski et al. investigates whether the specific threshold of 22 mm Hg continues to exert a disproportionate influence on the decision to initiate or escalate glaucoma therapy.
The Evolution of IOP Understanding
Glaucoma is characterized by progressive optic neuropathy, where IOP is the only modifiable risk factor. The landmark Ocular Hypertension Treatment Study (OHTS) and the Early Manifest Glaucoma Trial (EMGT) provided robust evidence that lowering IOP reduces the risk of visual field progression. These studies emphasized that there is no universal safe pressure; some patients experience damage at 15 mm Hg (normal-tension glaucoma), while others remain stable at 25 mm Hg (ocular hypertension). Nevertheless, the 22 mm Hg mark remains etched in the clinical consciousness. This study aims to quantify that influence using real-world data from the Sight Outcomes Research Collaborative (SOURCE) repository.
Study Design and Methodology
Data Source and Participant Population
The researchers utilized the SOURCE ophthalmology data repository, a multicenter database containing electronic health record (EHR) data from various academic medical centers across the United States. The retrospective cohort analysis included clinic encounters between October 2009 and January 2022. The study focused on patients diagnosed with glaucoma or suspected glaucoma who had recorded IOP measurements between 12 mm Hg and 25 mm Hg. In total, the analysis spanned 1,866,801 clinic encounters from 184,504 eyes belonging to 94,232 unique patients. The mean age of the participants was 69.5 years, and 58.1% were female.
Primary Outcomes and Statistical Modeling
The primary objective was to determine if treatment was initiated or escalated following a clinical encounter. Escalation was defined as a new prescription for IOP-lowering medication within one week, laser trabeculoplasty within four weeks, or glaucoma surgery within eight weeks. To account for the hierarchical nature of the data (multiple encounters per eye and two eyes per patient), the team employed mixed-effects logistic regression. This model allowed the researchers to calculate the odds ratio (OR) of treatment initiation at specific indicator IOP levels, specifically testing for a ‘step-function’ effect at the 22 mm Hg mark.
Key Findings: The Weight of the 22 mm Hg Mark
The Continuous Relationship vs. The Threshold Effect
The results confirmed that clinicians do, in general, treat IOP as a continuous risk factor. As IOP increased from 12 mm Hg toward 25 mm Hg, the rate of treatment initiation rose steadily. However, a distinct acceleration in the treatment rate was observed once the pressure reached 22 mm Hg. The mixed-effects logistic regression model revealed that an IOP of 22 mm Hg had a significantly greater effect on treatment initiation compared to lower indicator levels. Specifically, the odds ratio for treatment escalation at 22 mm Hg was 1.11 (95% CI, 1.08-1.14), suggesting that hitting this specific number serves as a powerful clinical trigger regardless of other risk factors.
Demographic and Clinical Variations
The study also noted that while the 22 mm Hg threshold was a universal influencer, the baseline rate of treatment varied across different clinical sites and patient demographics. However, the psychological impact of the ‘normal’ vs. ‘abnormal’ boundary remained consistent across the multicenter data, indicating a deeply ingrained clinical heuristic that transcends individual institutional cultures.
Expert Commentary: Heuristics in Clinical Practice
The findings by Polski et al. highlight a common phenomenon in clinical medicine: the use of heuristics, or mental shortcuts, to manage complex decision-making. In glaucoma management, calculating the individualized risk of progression involves integrating age, central corneal thickness, optic nerve head morphology, and visual field indices. The simplicity of a numerical cutoff like 22 mm Hg offers a sense of certainty in an otherwise nuanced field.
The Risk of Over-Reliance on Thresholds
While using 22 mm Hg as a trigger ensures that many patients with elevated pressure receive care, it potentially leads to two clinical pitfalls. First, it may result in over-treatment of ocular hypertensives who have thick corneas and low overall risk. Second, and perhaps more critically, it may lead to under-treatment or delayed escalation in patients with normal-tension glaucoma who are progressing at pressures significantly below 22 mm Hg. If a clinician’s internal alarm only sounds at 22 mm Hg, the patient progressing at 17 mm Hg may miss the window for early intervention.
The Role of Clinical Decision Support (CDS)
The authors suggest that improved clinical decision support systems within EHRs could help mitigate this threshold bias. By providing real-time risk calculations (such as those derived from the Glaucoma Risk Calculator), CDS tools can refocus the clinician’s attention on the patient’s holistic risk profile rather than a single manometric value.
Conclusion: Moving Toward Precision Glaucoma Care
This large-scale cohort study provides compelling evidence that the historical IOP cutoff of 22 mm Hg still exerts a significant influence on glaucoma management decisions. While the medical community has theoretically moved toward a personalized, continuous-risk model, the ‘magic number’ of 22 mm Hg persists as a clinical anchor.
To optimize outcomes, clinicians must remain vigilant against the subconscious bias introduced by historical thresholds. Future efforts should focus on integrating multi-modal data—including structural imaging and functional testing—into automated decision-support tools that encourage treating the patient’s risk rather than just the number on the tonometer. As we move further into the era of precision medicine, the 22 mm Hg mark should be viewed as a historical footnote rather than a clinical boundary.
References
1. Polski A, Brintz BJ, Hess R, et al. Influence of Intraocular Pressure on Clinical Decision-Making in Glaucoma Management. JAMA Ophthalmol. 2026;144(1):e255593. doi:10.1001/jamaophthalmol.2025.5593.
2. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that therapeutic reduction of intraocular pressure admits or delays the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.
3. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.
4. Stein JD, Talwar N, Launer LJ, et al. Longitudinal associations between intraocular pressure and incident Alzheimer disease and related dementias. JAMA Ophthalmol. 2023;141(3):234-242.