Findings from a recent study published in International Ophthalmology evaluated the relationship between tobacco smoking and the development of primary open-angle glaucoma (POAG).
Give me some background.
The impact of smoking on the incidence and susceptibility of POAG has been a recent topic of interest in glaucoma due to its association with various ocular diseases, such as age-related macular degeneration (AMD), cataract, and thyroid eye disease (TED).
Proposed mechanisms linking cigarette smoking to POAG include:
- Vasoconstriction of episcleral veins with increased outflow resistance and intraocular pressure (IOP)
- Alteration of vasoactive mediators (e.g., nitric oxide, endothelin-1) with downstream effects on blood pressure and ocular perfusion
- Oxidative injury to the trabecular meshwork and retinal ganglion cells
Now talk about the study.
In this systematic review, investigators searched Embase, Medline, and Web of Science for articles published from Jan. 1, 1946, up until April 2025.
However, the research team used studies from 2015 onwards in the final publication.
What determined a study’s inclusion in this research?
The inclusion criteria included observational and randomized controlled studies that provided a statistical analysis exploring the association between tobacco smoking and POAG in adult populations.
- The ROBINS-E tool was utilized to assess the risk of bias of studies and meta-analyses were completed using RevMan software.
And what was measured?
Main study outcomes were the effect estimates that measured the association between tobacco smoking and POAG.
Findings?
Across 26 eligible studies encompassing 289,930 participants, there was a prevalence of 6,454 cases of POAG.
The meta-analyses revealed that compared to individuals who had never smoked, the following smoking statuses exhibited no statistically significant association with POAG:
- Current smokers (odds ratio [OR]: 1.00, 95% confidence interval [CI]: 0.76-1.33, p=0.97, n=11)
- Past smokers (OR: 0.92, 95% CI: 0.75-1.11, p=0.38, n=6)
- Current and past tobacco smoking combined (OR: 1.00, 95% CI: 0.84-1.19, p=1.00, n=17)
Note: Heterogeneity ranged from low to substantial across comparisons, and risk of bias was rated as high in 14 of the 26 included studies.
- Plus: The lack of an associative effect was sustained, on exclusion of studies with a high risk of bias.
Expert opinion?
“One possible explanation is that nicotine primarily affects IOP transiently. However, the current literature lacks conclusive evidence regarding the permanence of IOP changes induced by nicotine,” the study authors explained.
- Additionally: Most studies primarily focused on short-term effects and did not explore whether these changes persisted over time or resulted in chronic conditions like POAG.
The study authors noted that the auto-regulatory mechanism of the optic nerve head maintains stable blood flow despite fluctuations in IOP and diurnal variation.
- Consequently: If nicotine were to induce temporary changes in IOP, this buffering process might account for why it does not result in vascular compromise of the optic nerve head.
Any limitations?
A few to note, including:
- Clinical heterogeneity from differences in participant characteristics, methodological heterogeneity from variations in study design, tools or instruments, and between-study heterogeneity from varying definitions for smoking exposure resulted in variability in the findings
- Inconsistent and frequently self-reported exposure definitions were a major source of potential misclassification
- Given the time span covered by the included studies, smoking behaviors and cigarette composition have also changed over time, which may contribute to temporal and contextual heterogeneity
- Statistical heterogeneity was evident in the variation of effect sizes reported across studies and the different statistical methods utilized for data analysis
- Contextual heterogeneity occurred due to differences in study settings, such as primary vs. secondary care, geographical locations, and time periods during which the studies were conducted
Take home.
While this study found no statistically significant association between tobacco smoking and POAG, given the notable morbidity and mortality associated with tobacco smoking and its detrimental impact on systemic and ocular health, tobacco smoking cessation should remain at the forefront of health counseling.