Discussion
To conclude, we found that ocular symptom severity, captured both with DE and pain questionnaires, was related to all components of sleep quality, except for the use of sleep medication. Of all PSQI sleep components, sleep disturbances (eg, waking up in the middle of the night or early morning, needing to get up to use the bathroom, having trouble breathing comfortably, coughing, snoring loudly, feeling too cold or too hot, having bad dreams and experiencing pain) were most closely related to DE symptoms (DEQ-5 and OSDI), ocular pain (NRS and NPSI-E) and convergence insufficiency (CISS). On the other hand, signs of tear and ocular surface dysfunction were less related to aspects of sleep. Of these, ocular surface inflammation and meibum quality were most closely related to subjective sleep quality, which was an individual’s assessment of their overall sleep quality.
Our findings share both similarities and differences compared with prior studies that have used the PSQI. In the China Hangzhou study (n=3070), the OSDI was used to assess DE symptoms, and a Chinese version of the PSQI was used to assess sleep quality. Patients were classified based on DE severity using OSDI scores: normal (score 0–12), mild (score 13–22), moderate (score 23–32) and severe (score 33–100). Similar to our results, mean PSQI global scores were higher in groups with worse DE symptoms (normal=4.7±2.8, mild=5.4±3.1, moderate=6.1±3.1 and severe=6.5±3.4, p<0.001). In contrast to our model, which identified sleep disturbances as the only sleep component related to OSDI, the Chinese study found broader relationships between DE symptoms and sleep. Specifically, the PSQI total scores and all subscores, with the exception of medication use, remained significantly related to DE symptoms after controlling for confounding variables (β=0.13, 95% CI 0.10 to 0.16, p<0.001).24 Our inclusion of mental health indices in the multivariable analysis may have contributed to the noted differences. A limitation of the Hangzhou study is that DE signs were not assessed, and as such, comparisons with our study are limited to symptoms only. Sleep quality has also been examined in a Japanese population (n=301) where mild DE was defined by symptoms and signs controlled by hyaluronate and severe DE by the need for additional medications. Individuals with severe DE had worse PSQI total scores (mean=6.4±3.3, p<0.05), sleep duration (PSQI 3: mean=1.5±0.8, p<0.05) and sleep efficacy (PSQI 4, mean=0.40±0.77, p<0.05) compared with the mild group. Similar to our study, no significant relationships were noted between DE signs (TBUT, Schirmer) and PSQI scores.25 In the Netherlands, DE symptom presence (defined by the Women’s Health Study Dry Eye Questionnaire)26 and sleep quality (PSQI) were captured in 71 761 individuals (59% women). Similar to our study, DE symptom presence was related to sleep disturbances (PSQI 5: OR=2.24, 95% CI 1.98 to 2.53, p<0.001) and daytime dysfunction (PSQI 7: OR=2.95, 95% CI 2.59 to 3.36, p<0.001), when corrected for age and sex.27 Taken together, these data suggest that sleep disorders are more related to ocular symptoms than signs, with sleep disturbances most closely relating to ocular symptoms across several populations.
Other investigators used different questionnaires to examine sleep quality. For example, the ISI has been used to examine relationships between ocular disease parameters and sleep. The ISI is a seven-item instrument measuring a patient’s perception of his or her insomnia with a focus on aspects such as sleep onset, sleep maintenance, early morning awakenings, dissatisfaction with current sleep patterns, interference of sleep problems with daily functioning, noticeability of sleep problems by others and distress or worry caused by the sleep problem.28 In our prior study, we found that ISI scores were related to DE symptoms (DEQ-5, r=0.43, p<0.01; OSDI, r=0.46, p<0.01) and ocular pain (NRS: r=0.39, p<0.01) but not with DE signs (including meibum quality), to a similar magnitude as found in the current study.8 In another recent study involving 1393 participants in China, those with DE symptoms, defined as a score of >12 out of 100 on the OSDI, also had higher ISI scores (mean=10.48±7.27, p=0.003) compared with those without DE symptoms (mean=3.57±5.10, p=0.003).29
It is interesting to note that similar to prior reports,30 DE signs were similarly distributed across our three DE symptom groups (none, mild-moderate and severe), highlighting the disconnect between symptoms and signs of disease. We hypothesise that this observation is driven by the reality that DE symptoms, specifically ocular pain, can arise from multiple sources, including nociceptive and neuropathic/nociplastic mechanisms. Nociceptive pain occurs as a result of the normal physiological response to mechanical, heat and chemical stimuli and can be driven by tear (eg, instability), ocular surface (eg, inflammation) and environmental (eg, air pollution) causes, to name a few.31 Neuropathic and nociplastic pain, on the other hand, are driven by somatosensory system dysfunction, leading to changes in how sensory signals are processed both at the periphery and in the central nervous system.32 Patients with neuropathic/nociplastic pain may report feeling dryness (or another ocular pain complaint) despite having minimal abnormalities in tear and epithelial health. This may explain why sleep disturbances, which may also be impacted by central nervous system dysfunction, are more closely related to ocular symptoms rather than signs.
Based on our cross-sectional study design, we cannot comment on whether ocular symptoms lead to sleep abnormalities if sleep abnormalities lead to ocular symptoms or if shared contributors underlie both conditions. While the pathophysiological mechanisms that underlie the connection between ocular symptoms and sleep disturbances are unclear, several potential mechanisms have been proposed. One potential mechanism is that ocular pain itself may lead to a disruption in sleep. In fact, the PSQI has a specific question regarding experiencing pain as part of its sleep disturbance components. A second hypothesis is that the presence of distress from ocular symptoms may lead to poor sleep quality.25 Prior studies have noted that ocular symptoms have a negative effect on feelings and daily activities, such as reading, driving, watching television and computer use.33–36 Decreased quality of life may lead to chronic stress and anxiety with a negative impact on sleep.37 A third hypothesis is that central nervous system abnormalities (eg, central sensitisation) that can be seen with a variety of conditions related to ocular symptoms (eg, fibromyalgia and migraine) underly the noted associations. A fourth hypothesis is that individuals with poor sleep quality use electronics or read at night which may impact both ocular symptoms and sleep quality.34 In total, more research is needed to understand potential mechanisms that underlie the noted associations and their directionality.
There are several limitations to our study that must be considered when evaluating our findings. First, as noted above, the cross-sectional nature of our study does not allow an evaluation of directionality. Second, our patient population consisted of US veterans, the majority of whom were men. As such, our results may not be generalisable to the broader public. Third, the subjective nature of self-reported sleep quality and ocular symptoms versus the objective capture of ocular findings may contribute to the noted differential relationships. Assessing sleep quality using objective metrics, such as with a formal sleep study, would have strengthened the study design. Fourth, there may have been unaccounted confounders (lifestyle, diet and physical activity) that impacted our findings. Fifth, while we chose not to apply Bonferroni adjustments given their tendency to address a universal null hypothesis and inflate type II errors, this decision could be viewed as a limitation. Specifically, it may increase the risk of type I errors (false positives), particularly in the context of multiple comparisons, potentially affecting the interpretation of our findings.22 Finally, while minimal, missing data may have reduced our statistical power and induced bias in our results.
Despite these limitations, our study supports prior research that links DE to impaired sleep quality and highlights that the strongest association is with respect to ocular symptoms and sleep disturbances. Addressing sleep disturbances such as nocturia (the need to void more than one time during sleep), breathing issues (such as in the setting of obstructive sleep apnoea) and nighttime waking may beneficially impact ocular symptoms, although this suggestion needs further study. Previous research has found that sleep quality can be improved using a variety of methods. In one Iranian study, 32 individuals with insomnia underwent 3 sessions of exercise therapy weekly for 12 weeks (three movements for the upper limbs and three movements for the lower limbs). Exercise therapy was found to improve sleep quality (mean PSQI preintervention versus postintervention: 13.94 vs 9.94, p=0.01) compared with a control group that did not receive any interventions (14.56 vs 13.88, p=0.55).38 Given the availability of techniques that may improve sleep quality, it is important for eye care providers to consider a holistic approach in their management of DE although it is not yet known if improving sleep quality will impact DE status.
Conversely, treating DE may improve sleep quality. A Japanese study of 71 individuals with DE (defined by the Japanese Dry Eye Society)39 40 found that treating DE with topical therapy improved sleep quality (PSQI). Interestingly, the effect was more pronounced in individuals with newly diagnosed DE (diagnosed at the time of study enrollment) compared with established DE (diagnosed prior to study enrollment) (35% vs 20%, p<0.05). Additionally, improved sleep quality (PSQI) was correlated with reduced depression severity (Hospital Anxiety and Depression Scale score), again more so in individuals with newly diagnosed DE (r=0.5, p<0.05) compared with established DE (r=0.3, p<0.05).41 As such, addressing both DE symptoms and sleep disturbances as early as they are identified may help reduce sleeping problems and improve mental health simultaneously.
