Conjunctival HLA-DR Expression and Its Association With Symptoms and Signs in the DREAM Study

Roy, Neeta S.; Wei, Yi; Yu, Yinxi; Ying, Gui‐Shuang; Kuklinski, Eric; Barry, Brendan; Maguire, Maureen G.; Dana, Reza; Brightwell-Arnold, Mary; Asbell, Penny A.

doi:10.1167/tvst.8.4.31

Cited by 7 publications

(8 citation statements)

References 52 publications

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“…It has been demonstrated that HLA-DR expression by conjunctival cells is increased in patients with uveitis and DED compared with those with vernal keratoconjunctivitis and normal subjects [ 49 ]. Likewise, it is known that high HLA-DR expression in conjunctival epithelial cells associated with high conjunctival staining may identify a subgroup of DED patients prone to epithelial disease that possibly need a different approach from current treatment standards [ 50 ]. These results suggest an involvement of the Th2 system on the ocular surface in uveitis; thus, exploring the ocular surface in uveitis may represent a new way to understand better the immune pathways involved in this complex disease [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical relationship between dry eye disease and uveitis: a scoping review

Rojas-Carabali

Mejia-Salgado

Cifuentes-González

et al. 2023

J Ophthal Inflamm Infect

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This scoping review examined the relationship between Dry Eye Disease (DED) and Uveitis. We searched Pubmed, Embase, and LILACS databases for articles in which at least one patient had DED and uveitis concomitantly. The search produced 2381 records, and 24 studies were included in the qualitative synthesis. We concluded that DED and uveitis of any etiology could appear concomitantly in patients of any age. However, both diseases seem to coexist more frequently in middle-aged women and cases of anterior uveitis. Therefore, it is crucial that ophthalmologists actively look for the coexistence of ocular surface abnormalities, especially in patients with these characteristics. Future studies should establish and quantify the risk factors and pathophysiological mechanisms of this coexistence to achieve an early diagnosis of both etiologies and comprehensive management of these patients.

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Section: Discussionmentioning

confidence: 99%

Clinical relationship between dry eye disease and uveitis: a scoping review

Rojas-Carabali

Mejia-Salgado

Cifuentes-González

et al. 2023

J Ophthal Inflamm Infect

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“…Use of a questionnaire may result in misclassifying depression, diluting the strength of associations. However, our prespecified screening cutoff (≤42 in MCS score) has been validated in the US general population and used in various clinical trials to screen for depression . In addition, participants may have been taking medications classified as antidepressants for indications other than clinical depression.…”

Section: Discussionmentioning

confidence: 99%

“…Samples were assayed for percentage HLA-DR positive in total cells, epithelial cells, and white blood cells. Detailed methodology for evaluation of HLA-DR expression has been published …”

Section: Methodsmentioning

confidence: 99%

Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study

Zhou

Murrough

et al. 2022

JAMA Ophthalmol

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IMPORTANCE Depression is more prevalent in patients with dry eye disease (DED) than in the general population; however, the association between severity of DED and depression needs further evaluation.OBJECTIVE To investigate the association between depression and severity of DED symptoms and signs, including inflammatory markers. DESIGN, SETTING, AND PARTICIPANTS Secondary cross-sectional and longitudinal analysis performed in April to December 2020 of data from Dry Eye Assessment and Management (DREAM) study, a randomized clinical trial from October 2014 to July 2016 including patients with moderate to severe symptoms and signs of DED. Enrolled from 27 ophthalmology and optometry centers, both academic and private, in 17 US states, 535 patients were followed up for 1 year. EXPOSURE Participants screened positive for depression if they scored 42 or less on the Mental Component Summary (MCS) of the 36-Item Short Form Health Survey.MAIN OUTCOMES AND MEASURES Symptoms of DED were assessed by Ocular Surface Disease Index (OSDI) and Brief Ocular Discomfort Index (BODI) and signs assessed by tear film breakup time, Schirmer test, corneal and conjunctival staining, tear osmolarity, and meibomian gland dysfunction at baseline, 6 months, and 12 months. A composite severity sign score was calculated from all 6 signs. Inflammatory markers (cytokines in tears and HLA-DR expression by conjunctival surface cells) were measured for some trial participants. Features of DED were compared between participants with and without depression and adjusted for age, sex, race, visits, and baseline comorbidities.RESULTS Among the 535 participants, mean (SD) age was 58 (13.2) years, 434 participants (81%) were women, and 398 (74.4%) were White. Participants who screened positive for depression had worse DED symptoms by OSDI (effect size = 0.45, P < .001) and BODI (effect size = 0.46, P < .001) and composite DED sign score (effect size = 0.21, P = .006). Lower MCS score (ie, worse depression) was correlated with higher OSDI score (ie, worse DED symptoms) at baseline (Spearman ρ = −0.09, P = .03), 6 months (ρ = −0.20, P < .001), and 12 months (ρ = −0.21, P < .001). Inflammatory markers did not differ by depression status.CONCLUSIONS AND RELEVANCE Depression was associated with more severe dry eye symptoms and overall signs, suggesting that among patients with moderate to severe DED, those with depression may be likely to have more severe DED. These findings support consideration of depression as a comorbidity when managing patients with DED. Further study is needed to elucidate the relationship.

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“…HLA-DR, a surface receptor that is constitutively expressed on antigen-presenting cells, such as dendritic cells, monocytes, B cells, and activated T cells, is one of the most studied inflammatory markers in DED. 13,20 The two previous trials studying the efficacy of v3 on DED that investigated the effect on the expression of HLA-DR showed a decrease in the percentage of conjunctival cells that express HLA-DR or in the intensity of HLA-DR expression. 6,21 In contrast, the present analysis did not show any significant differences between supplementation with v3 versus refined olive oil in patterns of HLA-DR expression in conjunctival surface total, epithelial, or white blood cells.…”

Section: Discussionmentioning

confidence: 99%

“…Details on sample collection, processing, and flow cytometry assessments have been previously published. 13 In short, conjunctival samples were collected separately from both eyes by filter paper-based impression cytology using an established standard operating protocol. 14 Samples were collected from patients at baseline, 6 months, and 12 months.…”

Section: Measurement Of Hla-dr Expressionmentioning

confidence: 99%

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study

Roy¹,

Yu²,

Ying³

et al. 2022

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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Objectives: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-17A, interferon-g, and tumor necrosis factor-a in dry eye disease patients in the Dry Eye Assessment and Management study. Methods: Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (v3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank-sum test (cytokines). Results: No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between v3 and placebo groups at 6 months (n¼435) or 12 months (n¼436). The median concentration percent change differed between v3 and placebo groups at 6 months for IL-6 (236.6 vs. 24.5%, P¼0.02, n¼75) and for IL-8 (3.7% vs. 72.6%, P¼0.02, n¼68); at 12 months, they did not differ (P$0.18). No other differences between the treatment groups were detected. Conclusions: v3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.

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Conjunctival HLA-DR Expression and Its Association With Symptoms and Signs in the DREAM Study

Cited by 7 publications

References 52 publications

Clinical relationship between dry eye disease and uveitis: a scoping review

Clinical relationship between dry eye disease and uveitis: a scoping review

Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study

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