FP686 : Role of Vitamin D and Dendritic Cells in Symptomatic Evaporative Dry Eye Disease

AIOS – K . C Singhal Award

Dr. Rashmi DeshmukhD17345, Dr.Rohit Shetty, Dr. Rushad Shroff, Dr. SwaminathanSethu

Introduction

Dry eye disease (DED) is one of the common disorders of the eye with an estimated prevalence of 5.5% – 33.7% worldwide(1). There has been widespread interest in understanding the disease and developing new treatment modalities for combating the ocular morbidity caused by it, especially the pain and discomfort associated with DED. Furthermore, in a subset of patients with DED the standard therapeutic strategies failed to alleviate the symptoms (2). There have been multiple studies that have demonstrated increased dendritic cell density (DCD) in dry eye disease(3). Multiple etiologies have also been implicated in the pathophysiology of dry eye. Vitamin D, which is a fat-soluble prohormone, has also been recently associated with dry eye disease(4)(5). In the current study the association between the severity of dry eye symptoms (pain and/or discomfort), corneal dendritic cell density and serum vitamin Dlevel was determined

Methods

The study was approved by the Ethics Committee of ourhospital and was performed in accordance with the guidelines of the Declaration of Helsinki. Informed consent of study subjects was obtained at the time of enrolment. It was a cross sectional study that included 52 patients with EDE (??? The authors have not mentioned what EDE is)and 43 healthy volunteers.Parameters such as Ocular surface disease index (OSDI),Schirmer’s values and TBUT wereevaluated for all subjects. Corneal DCDwas obtained for all subjects by in-vivo confocal microscopy (IVCM) using Rostock Corneal Module/Heidelberg Retina Tomography (RCM/HRT ll; Heidelberg Engineering GmBH, Dossenheim, Germany).Tear/serum vitamin D and cytokines were measured by flow-cytometry-based cytometric-bead-array (CBA) and Enzyme-linked ImmunosorbentAssay(ELISA) respectively.

Results

Increased DCD observed in EDE patients compared to controls exhibited positivecorrelation with OSDI (p<0.05). An inverse correlation was noted between vitamin D and OSDI scores and DCD.Significantly higher levels of tear inflammatory cytokines such as IL-17,IFNγ,MCP1 (Authors have not mentioned fullforms)were observed in EDE patients.

Discussion

The persistence of ocular pain and discomfort in a subset of patients with DED following standard therapeutic strategies and the lack of tear film metrics to predict such population poses a major challenge in the management of Dry eye disease. It is therefore imperative to identify diagnostic modalities that can accurately predict patients whose symptoms may not resolve with conventional therapy or may require additional dietary or environmental interventions along with topical therapy to ensure a favourable prognosis. The role of dendritic cells in modulation of nociception and pain has been previously studied (6)(7). Studies have described a possible role for corneal dendritic cells in the etiopathogenesis of dry eye, keratoconjunctivitissicca and corneal allograft rejection (8)(9). Inflammatory pathologies show an increase in the number of dendritic cells in the cornea (10). In our study the significant increase in the corneal dendritic cells observed in EDE patients was found to have positive association with the OSDI discomfort- related subscale scores and not vision-related OSDI scores.

Studies have demonstrated the association of vitamin D deficiency with DED (11)(4). Earlier reports have suggested Vitamin D deficiency to be associated with neuralgia and chronic pain (12)(11). In the current study we observed a strong inverse correlation between the OSDI scores and vitamin D levels in the EDE cohort. The exact mechanism linking Vitamin D to pain remains elusive however several theories have been put forward. Serotonin which can perpetuate chronic pain response was found to be high in patients with DED (13).Vitamin D is known to affect serotonin synthesis indicating a role of vitamin D in nociception (14). Vitamin D and its agonists have been found to inhibit maturation and induce tolerance in dendritic cells resulting in the arrest of inflammatory processes (15). Lower vitamin D levels were associated with anincrease in DCD with dendritic processes (mature phenotype) in our cohort, which supports the current understanding regarding the immunomodulatory role of vitamin D on dendritic cells.

IL-17, well known for its pathologic role in inflammatory disorders is also involved in nociception by mediating mechanical allodynia by altering the expression of neuronal TRPV4 (authors have not mentioned fullforms)channels essential for transduction of pain stimulus(16)was found to be higher in the tears of patients. An increased IFNγ, MCP1 and ICAM1 was observed in the patients as well. This could exacerbate the ocular symptoms, as they are reported to mediate pain(17)(18)(19).

Conclusions

Vitamin D status is linked to EDE symptoms and associated inflammatory factors.Vitamin D supplement could be beneficial in management of EDE.This is one of the studies that report the association between serum vitamin D status and dry eye. It is essential to obtain mechanistic insights into the aetiopathologic role of vitamin D deficiency and aberrant inflammatory cytokines in the ocular surface health and corneal pain for targeted management of dry eye.

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