In a study published in Contact Lens and Anterior Eye, researchers evaluated the association between relative contributions of objective and subjective indicators of dry eye disease (DED) and chronic pain.
Give me some background first.
Chronic pain is defined as pain that reoccurs or lasts for 3+ months and is the leading cause of disability globally.
In 2021, an estimated 20.9% of adults in the United States experienced chronic pain, while 6.9% experienced high-impact chronic pain—a pain that causes significant restriction to daily activities.
Now on to DED: This ocular surface disease (OSD) occurs when the eyes do not produce enough tears or when the tears do not function correctly.
Now, talk about the study.
Investigators conducted a systematic review and meta-analysis of studies that did one or all of the following:
- Reported DED signs and symptoms
- Reported the prevalence of DED signs and symptoms in individuals with chronic pain compared to controls
Then: They applied the International Association for the Study of Pain (IASP) International Classification of Diseases (ICD)-11 codes for chronic pain conditions.
- Outcomes were defined as DED signs and symptoms.
What was included in the analysis?
Fourteen observational studies comprised of 3,281,882 individuals were included
Databases utilized were the following:
And how was the study conducted?
Risk of bias assessment was performed using the Newcastle-Ottawa scale (NOS) while a random effects meta-analysis calculated mean differences (MD) and odds ratios (OR).
Additionally, subgroup analysis of various chronic pain conditions explored their relative association with DES signs and symptoms.
Lastly, the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to evaluate evidence certainty.
Quick refresh: GRADE is a system that provides a transparent grading quality of evidence and strength of recommendations.
Findings?
- Meta-analysis found high-quality evidence that individuals with chronic pain were more likely to experience symptoms of DED than controls
- OR = 3.51 (95%CI: 3.45,3.57)
- DED symptoms were more severe than controls with a clinically meaningful effect size
- MD = 18.53 (95%CI: 11.90, 25.15)
- Tear film osmolarity showed no significant differences between the chronic pain and pain-free groups
- Group differences for DED signs were not considered clinically meaningful
Tell me more.
Individuals with chronic pain had:
- More rapid tear film disruption
- MD = -2.45 (95%CI: −4.20, −0.70)
- Reduced tear production MD = -5.57 (95%CI: −9.56, −1.57)
- Compared with controls (with moderate evidence quality)
- High-quality evidence revealed they had lower basal tear production (anesthetized) than controls
- MD = -2.59 (95%CI: −3.60, −1.58)
Limitations?
One study included in this research by Lee et al. had a large impact on the analysis. The study evaluated ICD-9 medical record codes representing dry eye and non-ocular pain disorders.
Which means: The effect size for DED symptoms in chronic pain may have disproportionately skewed towards it.
Additionally, individuals in the Lee et al. study were mostly male (91.8 %) United States veterans.
Only one of the studies included in the analysis controlled for depression. For a full overview of limitations, see the study.
Expert opinion?
The authors stated that dry eye symptoms may be more prevalent and severe in chronic pain conditions due to “a shared sensory dysfunction related to neuropathic and/or nociplastic pain mechanisms.”
Take home.
More severe and clinically significant symptoms of DED were shown in individuals with chronic pain compared to controls.
The authors stated, "Advancing understanding of this potential pathophysiological mechanism may guide clinical management.”