Associations between Subjective Happiness and Dry Eye Disease: A New Perspective from the Osaka Study

<div><p>Importance</p><p>Dry eye disease has become an important health problem. A lack of concordance between self-reported symptoms and the outcome of dry eye examinations has raised questions about dry eye disease.</p><p>Objective</p><p>To explore the association between subjective happiness and objective and subjective symptoms of dry eye disease.</p><p>Design</p><p>The study adopted a cross-sectional design.</p><p>Setting</p><p>All the employees of a company in Osaka, Japan.</p><p>Participants</p><p>672 Japanese office workers using Visual Display Terminals (age range: 26–64 years).</p><p>Methods</p><p>The dry eye measurement tools included the Schirmer test, conjunctivocorneal staining, the tear film break-up time, as well as the administration of a dry eye symptoms questionnaire. Happiness was measured by the Subjective Happiness Scale.</p><p>Main Outcome Measures</p><p>Dry eye examination parameters, dry eye symptoms questionnaires, and the Subjective Happiness Scale score.</p><p>Results</p><p>Of the 672 workers, 561 (83.5%) completed the questionnaires and examinations. The mean Subjective Happiness Scale score was 4.91 (SD = 1.01). This score was inversely correlated with the dry eye symptom score (r = -0.188, p < 0.001), but was not associated with objective findings which include conjunctivocorneal staining, low Schirmer test score, or low tear film break-up time. The level of subjective happiness was the lowest in the group without objective results, but reported subjective symptoms of dry eyes (p < 0.05).</p><p>Conclusions and Relevance</p><p>There is evidence of the relationship between subjective happiness and self-reported symptoms of dry eyes. Findings of this study revealed a new perspective on dry eye disease, including the potential for innovative treatments of a specific population with dry eye disease.</p></div

Oxidative lipid and DNA changes in the meibomian glands.

<p>A, Late phase lipid peroxidation marker 4-HNE stainings show dense staining in the 50 week old Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i>^−/−) mice. Wild type (WT) mice specimens also had some staining but not to the extent observed in the same age <i>Sod1</i>^−/− mice. Bar = 50 micrometer. B, The extent of cellular staining with 4-HNE was significantly higher in the <i>Sod1</i>^−/− than the WT mice at 50 weeks (<i>p</i> = 0.0022). Note the significant timewise elevation in the anti-4-HNE staining from 10 to 50 weeks in the <i>Sod1</i>^−/− mice. C, Staining with 8-OHdG antibodies in <i>Sod1</i>^−/− and WT mice samples at 10 and 50 weeks. Meibomian gland acinar cell nuclei showed scant staining in 10 week <i>Sod1</i>^−/− and WT mice. Bar = 100 micrometer. There was a marked increase in nuclear staining from 10 to 50 weeks, especially in <i>Sod1</i>^−/− mice. Relatively more acinar nuclei were stained with anti-8-OHdG antibodies in the <i>Sod1</i>^−/− mice at 50 weeks compared to meibomian gland specimens from the same age WT mice. D, Quantitative assessment for the cellular staining of anti-8-OHdG antibodies showed a statistically significant timewise increase from 10 to 50 weeks in <i>Sod1</i>^−/− and WT mice (<i>p</i> = 0.0003, <i>p</i> = 0.0011, respectively). A significant timewise elevation in staining was observed in the <i>Sod1</i>^−/− and WT mice at 50 weeks (<i>p</i> = 0.0133). Five tissue sections of each animal's eye were analyzed to produce the figure. Data represent the mean ± standard deviation for 7 mice from the <i>Sod1</i>^−/− group and 6 mice from the wild type group at 10 and 50 weeks.</p

Correlation of SHS score with objective findings from dry eye examinations and subjective symptom scores.

<p><i>Note</i>. SHS = Subjective Happiness Scale; SD = standard deviation; <i>r</i> = Pearson’s correlation coefficient; BUT = breakup time.</p><p>Correlation of SHS score with objective findings from dry eye examinations and subjective symptom scores.</p

Transmission electron microscopic examination of the mitochondrial alterations.

<p>Marked ultrastructural changes in the mitochondria including swelling, disorientation, shortening, and disorganization of cristae were noted at 50 weeks in the Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i>^−/−) mice. We observed abnormalities in 40 percent of the 50 week wild type (WT) mice and 80 percent in the age matched <i>Sod1</i>^−/− mice. No such phenotypic alterations were observed in the mitochondria of the 10 to 50 week WT mice. Bar = 1 micrometer. Five tissues sections from each eye of the 6 animals in each mice group were analyzed to produce the representative images.</p

Adjusted result of the Subjective Happiness Scale score: dry eye, gender, age, and body mass index.

<p><i>Note</i>: SHS = Subjective Happiness Scale; SE = Standard error.</p><p>Adjusted result of the Subjective Happiness Scale score: dry eye, gender, age, and body mass index.</p

Aqueous tear production, tear stability and ocular surface epithelial cell damage assessment.

<p>A, The weight adjusted tear quantity decreased significantly from 10 to 50 weeks in the Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i>^−/−) mice (<i>p</i> = 0.0012). The tear quantity was also significantly lower in the <i>Sod1</i>^−/− mice compared to the age matched wild type (WT) mice at 10 and 50 weeks (<i>p</i> = 0.0079 and <i>p</i><0.0001, respectively). B, The mean tear break-up time values decreased significantly from 10 to 50 weeks in the <i>Sod1</i>^−/− mice (<i>p</i> = 0.0330). The tear stability was significantly worse in the <i>Sod1</i>^−/− mice compared to WT mice at 50 weeks (<i>p</i> = 0.0004). C, Fluorescein staining scores were significantly higher in the <i>Sod1</i>^−/− mice compared to the WT mice both at 10 (<i>p</i> = 0.0005) and 50 (<i>p</i> = 0.0006) weeks. Fluorescein staining also increased significantly from 10 to 50 weeks in both the <i>Sod1</i>^−/− and WT mice (<i>p</i> = 0.0113 and <i>p</i> = 0.0032, respectively). Data represent the mean ± standard deviation of 9 mice from the <i>Sod1</i>^−/− groups and 10 mice from the WT groups, at 10 and 50 weeks.</p

Meibomian gland histopathological alterations and tissue fibrosis in the <i>Sod1</i>^−/− and wild type mice.

<p>A, Representative images for meibomian glands from the 10 and 50 week Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i>^−/−) and wild type (WT) mice show normal meibomian gland acinar units morphology. Note the extensive periglandular inflammatory infiltration, and meibomian gland changes in the <i>Sod1</i>^−/− mice at 50 weeks. Bar = 50 micrometer. B, Mallory stainings show increased fibrosis (dark blue stained areas) from 10 to 50 weeks in the <i>Sod1</i>^−/− mice. Similar changes were observed in the WT mice but not to the extent observed in the <i>Sod1</i>^−/− mice. Bar = 50 micrometer. C, Meibomian gland acinar unit density significantly decreased from 10 to 50 weeks in both <i>Sod1</i>^−/− mice and the WT mice (<i>p</i> = 0.0007 and <i>p</i> = 0.0175, respectively). Meibomian gland acinar unit density was also significantly lower in the <i>Sod1</i>^−/− mice compared to the WT mice at 50 weeks (<i>p</i> = 0.0003). Five tissue sections of each mouse eye were analyzed to produce the meibomian gland acinar unit density values. Data represent the mean ± standard deviation for at least 7 mice from the <i>Sod1</i>^−/− groups and 10 mice from the WT groups, at 10 and 50 weeks. Five tissues sections from each eye of 7 animals (5 images per animal's eye) for each group were analyzed to produce the representative Mallory staining images.</p

Comparison of Subjective Happiness Scale and dry eye symptom scores.

<p><i>Note</i>. DED = Dry eye disease; SHS = Subjective Happiness Scale</p><p>Comparison of Subjective Happiness Scale and dry eye symptom scores.</p

Comparison of SHS score between objective and subjective classifications.

<p>SD = standard deviation.</p

Comparison of dry eye symptom scores between objective and subjective classifications.

<p>SD = standard deviation.</p