Current Advances in Mechanisms and Treatment of Dry Eye Disease: Toward Anti-inflammatory and Immunomodulatory Therapy and Traditional Chinese Medicine

Dry eye is currently one of the most common ocular surface disease. It can lead to ocular discomfort and even cause visual impairment, which greatly affects the work and quality of life of patients. With the increasing incidence of dry eye disease (DED) in recent years, the disease is receiving more and more attention, and has become one of the hot research fields in ophthalmology research. Recently, with the in-depth research on the etiology, pathogenesis and treatment of DED, it has been shown that defects in immune regulation is one of the main pathological mechanisms of DED. Since the non-specific and specific immune response of the ocular surface are jointly regulated, a variety of immune cells and inflammatory factors are involved in the development of DED. The conventional treatment of DED is the application of artificial tears for lubricating the ocular surface. However, for moderate-to-severe DED, treatment with anti-inflammatory drugs is necessary. In this review, the immunomodulatory mechanisms of DED and the latest research progress of its related treatments including Chinese medicine will be discussed.

A clinical study of correlation between pterygium and dry eye

To study the clinical correlation between pterygium and dry eye and to evaluate the status of tear film in patients with pterygium.100 eyes with pterygium were compared with 100 control eyes without pterygium. Patients between 20–70 years were included in the study. Detailed history was taken and Schirmer’s test and TBUT were performed on all to evaluate the status of dry eye. Schirmer’s test ˂10 mm and TBUT ˂10 seconds was considered abnormal. Maximum number (52) of patients affected with dry eye in both the groups were in the age group 31-40 years which statistically showed age as a significant factor of association for both pterygium and dry eye (P<0.01). Schirmer’s test was slightly reduced in patients with pterygium(18.73±5.69 mm). TBUT was significantly reduced in the case group (12.26±2.24sec). TBUT decreased maximally in 51-60 yrs age group (13.00±2.77sec) with pterygium showing a tear film unstability. On comparison of pterygia and controls with normal and abnormal tear film, Odd’s Ratio was 1.14 showing risk of dry eye in pterygia patients to be 1.14 times higher than controls. A close relationship exists between ocular irritation symptoms and functional evidence of tear instability. Schirmer’s test and TBUT should routinely be used in the outpatient department to diagnose dry eye in patients with pterygium and these patients should be promptly treated to prevent any sight threatening complications.

A study to assess the efficacy of topical cyclosporine A 0.05% in the management of dry eye with meibomiam gland dysfunction

: Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Meibomian Gland Dysfunction (MGD) is an abnormality of the meibomian gland that blocks the secretion of lipids. Without sufficient lipid production, tears evaporate quickly causing Dry Eye.MGD is associated with multiple pathological mechanisms including inflammation, microbial factors and lipid deficiencies. Topical Cyclosporine A (CsA) 0.05% is a calcineurin inhibitor that reduces inflammation by specifically inhibiting T‑cell activity, which reduces ocular surface inflammation and improves tear film dynamics. This was a prospective observational study done on 100 patients at the Department of Ophthalmology Basaveshwar teaching and general hospital, on patients of dry eyes due to meibomian gland dysfunction. Patients who were diagnosed with dry eyes due to meibomian gland dysfunction were invited to take part in the study. Patients were divided randomly into two groups of 50 patients each. This study, was explained in detail to them. An informed consent was obtained. Patients fulfilling the inclusion criteria were listed.All OSDI scores (symptom intensity, frequency and aggravation) revealed decreasing patterns throughout the observation period in both the groups. In single analysis, the cyclosporine A 0.05% group showed a significant improvement for each score at 3 months (p < 0.01, p = 0.01, p = 0.02, respectively). The mean TBUT after treatment in the group A (cyclosporine A group) increased to 12.36± 3.58(p<0.001) seconds, and in the group B (Control group) the TBUT score increased to 11.01±3.06 seconds. After 3 Months, there was statistically significant improvement in the mean Schirmer’s scores in both the treatment groups, however improvement was significantly greater in Cyclosporine A group. Prior to the treatment in group A (Cyclosporine A) mean Lissamine staining score was 2.73±0.15 and post treatment it reduced to 1.32±0.15 which was statistically significant (P<0.001). In group B (Control group) score before treatment was 2.46±0.15 and after treatment it reduced to 2.39±0.27 (p=0.11), not much difference was seen. : Findings from our study showed that there were significant improvements in the dry eye conditions due to defect in meibomian gland by treatment of topical Cyclosporine A 0.05% and sodium hyaluronate 0.1%.

Correlations Between Single-Photon Emission Computed Tomography Parameters of Salivary Glands and Dry Eye Tests in Patients With Sjögren's Syndrome

ObjectiveTo evaluate the correlations between Single-Photon Emission Computed Tomography (SPECT) parameters of salivary glands and dry eye parameters in patients with Sjögren's syndrome (SS).MethodsA total of 28 patients with SS participated in this prospective study. Dry eye assessments include tear film break-up time (TBUT), corneal fluorescein staining scoring (CFS), Schirmer's I test (SIT) examination and SPECT of salivary gland. The following quantitative parameters were derived from SPECT imaging for salivary glands: Uptake index (UI), the time needed to achieve the minimum counts after Vit C stimulation (Ts), and excretion fraction (EF). The relation between the aforementioned parameters and TBUT, CFS and SIT were analyzed with SPSS 22.0 software.ResultsAll the 28 eyes of the 28 subjects were examined. The mean SIT was 6.04 ± 4.64 mm/5 min (0–18 mm/5 min); the mean CFS was 3.07 ± 2.65 (0–10) and the mean BUT was 2.11 ± 1.97 s (0–9 s). The mean EF value was 0.52 ± 0.12 (0.26–0.75) in parotid glands and 0.45 ± 0.10 (0.30–0.67) in submandibular glands, respectively. The mean UI value was 9.33 ± 1.68 (6.03–13.20) in parotid glands and 9.92 ± 1.48 (7.08–12.60) in submandibular glands, respectively. The mean Ts (min) was 5.32 ± 3.01 (2.00–12.00) in parotid glands and 11.09 ± 7.40 (2.00- 29.00 min) in submandibular glands, respectively. It was found that EF positively correlates with SIT in patients with SS (r = 0.499 and 0.426 in parotid glands and submandibular glands, with P < 0.05), while no significant correlation was found between the UI, Ts and CFS, TBUT (P > 0.05).ConclusionsThe EF was positively correlated with SIT in patients with SS, it could reflex the dysfunction of salivary glands in SS patients. So, EF may be a valuable parameter for the diagnosis of SS patients with lacrimal gland secretion dysfunction.

miR-204–containing exosomes ameliorate GVHD-associated dry eye disease

MSC-exo eye drops alleviate GVHD-associated dry eye disease by shifting M1 macrophages to M2 via miR-204.

TLR4-Dependent DUOX2 Activation Triggered Oxidative Stress and Promoted HMGB1 Release in Dry Eye

Dry eye disease (DED) is one of the most common ocular surface diseases worldwide. DED has been characterized by excessive accumulation of reactive oxygen species (ROS), following significant corneal epithelial cell death and ocular surface inflammation. However, the key regulatory factor remains unclear. In this study, we tended to explore whether DUOX2 contributed to DED development and the underlying mechanism. Human corneal epithelial (HCE) cells were treated with hyperosmolarity, C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Expression of mRNA was investigated by RNA sequencing (RNA-seq) and quantitative real-time PCR (qPCR). Protein changes and distribution of DUOX2, high mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and 4-hydroxynonenal (4-HNE) were evaluated by western blot assays and immunofluorescence. Cell death was assessed by Cell Counting Kit-8 (CCK8), lactate dehydrogenase (LDH) release, and propidium iodide (PI) staining. Cellular ROS levels and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. RNA-seq and western blot assay indicated a significant increase of DUOX2 dependent of TLR4 activation in DED both in vitro and in vivo. Immunofluorescence revealed significant translocation of HMGB1 within corneal epithelial cells under hyperosmolar stress. Interestingly, after ablated DUOX2 expression by siRNA, we found a remarkable decrease of ROS level and recovered MMP in HCE cells. Moreover, knockdown of DUOX2 greatly inhibited HMGB1 release, protected cell viability and abolished inflammatory activation. Taken together, our data here suggest that upregulation of DUOX2 plays a crucial role in ROS production, thereafter, induce HMGB1 release and cell death, which triggers ocular surface inflammation in DED.

Benefits and Safety of Astaxanthin in the Treatment of Mild-To-Moderate Dry Eye Disease

Objectives: To evaluate the effect of astaxanthin in the treatment of mild-to-moderate dry eye disease (DED) in middle-aged and elderly patients.Methods: 120 eyes of 60 middle-aged and elderly patients with mild-to-moderate DED were enrolled in this prospective, one-group, quasi-experimental study. Six milligram Astaxanthin tablets (Weihong Haematococcus Pluvialis Astaxanthin, Hangzhou Xinwei Low Carbon Technology R&D Co., Ltd., China) were administered orally, twice daily for 30 ± 2 days. History of eye diseases, treatment, systemic disease, and medication before the test were recorded. In addition, the ocular surface disease index (OSDI) questionnaire, non-invasive tear break-up time (NIBUT), fluorescein break-up time (FBUT), corneal fluorescein staining (CFS) score, eyelid margin signs, meibomian gland (MG) expressibility, meibum quality, meibomian gland dropout (MGDR), Schirmer I test (SIt), tear meniscus height (TMH), bulbar conjunctiva congestion degree, blink frequency, incomplete blink rate, and thickness of tear film lipid layer were collected before treatment, 2 weeks after the initiation of treatment, and at the end of treatment. Visual acuity (VA), intraocular pressure (IOP), anterior segment, fundus, discomfort symptoms and other adverse reactions were also monitored throughout the study to assess the safety.Results: OSDI score, NIBUT, BUT, CFS score, eyelid margin signs, MG expressibility, meibum quality, and blink frequency improved significantly to varying degrees after treatment compared with those before the treatment (P < 0.05), while TMH, SIt, conjunctival congestion, the thickness of tear film lipid layer, MGDR, incomplete blink rate, VA and IOP did not differ (P > 0.05).Conclusions: Oral administration of astaxanthin improves the symptoms and signs of middle-aged and elderly patients with mild-to-moderate DED.