E2 ModerateModerate confidencePEM not requiredLongitudinalPeer-reviewedReviewed
Dry eye syndrome and the subsequent risk of chronic fatigue syndrome-a prospective population-based study in Taiwan.
Chen, Chih-Sheng, Cheng, Hui-Man, Chen, Hsuan-Ju et al. · Oncotarget · 2018 · DOI
Quick Summary
This study found that people with dry eye syndrome (DES) are more likely to develop ME/CFS than those without dry eye problems. Researchers followed patients in Taiwan over many years and discovered that those with dry eye had about twice the risk of developing ME/CFS. Even after accounting for age, sex, and other health conditions, the increased risk remained significant.
Why It Matters
This is one of the few studies investigating a potential link between dry eye syndrome and ME/CFS, two conditions that may co-occur in patients. If the association reflects shared biological mechanisms (such as autoimmune, inflammatory, or autonomic dysfunction), understanding this connection could improve diagnosis and help physicians recognize both conditions in affected patients.
Observed Findings
- Dry eye syndrome patients had a 2.08-fold increased unadjusted risk of developing ME/CFS compared to matched controls.
- After adjusting for age, sex, and comorbidities, the risk remained elevated at 1.61-fold.
- Among DES patients with CFS-related comorbidities, the adjusted risk was 1.98-fold.
- DES patients with ≥3 annual medical visits had a 4.88-fold adjusted risk of subsequent CFS diagnosis.
Inferred Conclusions
- Dry eye syndrome is associated with a substantially increased risk of ME/CFS development, even after controlling for demographic and clinical factors.
- The strength of association increases when comorbid conditions and healthcare utilization are considered, suggesting disease burden or severity may modify risk.
- Physicians should screen DES patients for ME/CFS and recognize these conditions as potentially linked.
Remaining Questions
- Does dry eye syndrome play a causal role in ME/CFS development, or do both conditions share a common underlying mechanism (e.g., autoimmune, inflammatory, autonomic)?
- What is the temporal relationship between symptom onset in DES and CFS, and does timing suggest direct causation or concurrent disease?
- How does dry eye severity or type relate to CFS risk, and are specific dry eye subtypes more strongly associated with CFS?
What This Study Does Not Prove
This study demonstrates association, not causation—it does not prove that dry eye syndrome causes ME/CFS. The findings may reflect shared underlying causes (confounding), reverse causation (early ME/CFS symptoms causing dry eye), or simply greater healthcare-seeking behavior in patients with multiple symptoms. Without mechanistic data or symptom-level analysis, the biological basis of the relationship remains unclear.
Tags
Symptom:Fatigue
Method Flag:PEM Not DefinedWeak Case DefinitionExploratory Only
Metadata
- DOI
- 10.18632/oncotarget.25544
- PMID
- 30093979
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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