Dry Eye Therapy Research Articles

Sleep position and the ocular surface in a high airflow environment

PurposeTo study the relationship between sleep position and ocular surface symptoms and signs in an high air flow environment. MethodsProspective observational study of new patients attending the dry eye clinic was performed. Patients with pre-existing ocular history, relevant systemic history (e.g. Sjogren’s syndrome) or who were using topical or systemic therapy for dry eye were not included. Data were collected from the patient to document their dry eye symptoms; preferred dependent sleeping side and their bedroom airflow. All patients were examined by a clinician blind to the patient’s responses where Schirmer’s test and slit lamp examination were performed looking for the presence of lagophthalmos and corneal epitheliopathy. Results48 patients enrolled into the study of which 23 were males and 25 were females with a normal and comparable age distribution. The study found a strong association between patients’ preferred sleeping side and the incidence of corneal epitheliopathy in the contralateral eye particularly in patients with evidence of lagophthalmos. Dry eye symptoms were found to be worse and tear production lower on the contralateral side to the preferred sleeping side particularly in patients who sleep in a high airflow environment. ConclusionIn patients sleeping in a high airflow environment with nocturnal lagophthalmos, this study observed an association between preferred dependent sleep position and increased dry eye symptoms, lower Schirmer’s scores and increased corneal epitheliopathy in the contralateral eye.

English

Dry eye is a multi-factorial disease; the therapy should improve the symptoms and signs of dry eye as well as address the underlying pathophysiology of the disease. Artificial tear substitutes have been used for treating dry eye syndromes for decades and succeeded in enhancing the comfort of patients. They are currently the main therapy for dry eye and likely to remain the mainstay treatment modality. However, the currently used artificial tears have obvious limitations and its usage has to be personalized based on the patient's need. This article briefs you on silent

Dry eye disease in French elderly subjects: the Alienor Study

To describe dry eye disease in French elderly subjects. The Alienor Study is a population-based study on age-related eye disease in 963 residents of Bordeaux (France), aged 73 years or more. Self-reported dry eye disease and use of artificial tears were documented through face-to-face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break-up time measurements (TBUT). Definite dry eye disease was defined as self-reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22. Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31-0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02-2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02-2.29). This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).

Emphasizing clinical investigation on anti-inflammatory therapy of dry eye

Inflammation is a defensive reaction and the most common pathological manifestation of dry eye.In addition,excessive inflammatory response is considered to be the most common pathogenic factor and main cause of dry eye.Currently,the active mechanism of anti-inflammatory drugs has been well-known,and topical antiinflammatory therapy for dry eye is exerting a role at certain extend.However,some adverse responses of these drugs are emerging during the treating procedure.Therefore,it is emphasized that a large sample size of and multicenter randomized-controlled clinical trial is needed to identify the different effects of various anti-inflammatory drugs for different types of dry eye diseases,which will offer a basis for standardized anti-inflammatory treatment for dry eye. Key words: Dry eye; Anti-inflammatory therapy; Randomized-controlled clinical trial

Effect of Humidity Variations in a Controlled Environment Chamber on Tear Evaporation After Dry Eye Therapy

Many dry eye (DE) patients are sensitive to adverse environments where tear evaporation rate (TER) increases. Pilot study-A controlled environment chamber was used to determine the time of exposure required for TER to reach steady state equilibrium at 40% relative humidity (RH). Study 1-To assess the difference between normal and DE subjects in their tear physiology response. Study 2-To determine, under varying environmental conditions, the efficacy of an emulsion eye drop on tear physiology. Pilot study-TER adaptation time was determined by exposing 3 normal and 3 DE subjects to RH of 40% at 72°F for 0, 5, 10, 15, 20, and 25 minutes. Study 1-The difference in noninvasive tear breakup time (NITBUT) and TER responses between DE and normal subjects were determined at various RH from 5% to 70% (at 72°F) for 20 subjects (10 normal subjects; 10 DE subjects). Study 2-To assess the efficacy of an emulsion eye drop, the same 20 subjects were dosed four times per day for 7 days with a drop containing emulsified castor oil and reassessed. Pilot study-Evaporation at 40% RH showed a peak (around 5 minutes) followed by a decline to steady state level at 10 minutes. Dry eye subjects showed greater evaporation than normal subjects at 40% and 5% RH but not at 70%, where TER declined to zero in both groups. No significant change in NITBUT was found in either group for the various exposure times of the test period (P>0.05). Study 1-TER was higher in DE compared with normal subjects at 5% or 40% RH, however reduced to almost zero in both groups at 70% RH. A significant difference in NITBUT was found between the DE and normal groups at each humidity (P<0.05). Study 2-An emulsion-based drop effectively lowered the TER, especially in DE patients. For NITBUT, a significant improvement in both normal and DE subjects was found at 5% and 40% but not at 70% RH levels. Pilot study-TER measurements required at least 10 minutes in the chamber to obtain a steady-state TER with no significant change to NITBUT. Study 1-TER has a reverse correlation with environmental humidity in the range of 5% to 70%, with TER reduced to zero at 70% RH. Dry eye subjects had a higher TER at all RH levels below 70%, and NITBUT is significantly different between DE and normal subjects at all humidities. Study 2-Emulsion-based drops reduced TER in DE patients by an amount equivalent to that obtained by raising environmental humidity by 30%. Noninvasive tear breakup time was improved in both normal and DE subjects at lower RH levels.

Effectiveness of Dry Eye Therapy Under Conditions of Environmental Stress

Purpose: Dry eye is often characterized by increased tear evaporation due to poor tear film quality, especially of the lipid component of the tear film. Using an environmental chamber to induce environmental stress, this study compared the effect of three lubricant eye drops on various aspects of tear physiology in a crossover design (evaporation was the principal outcome measure).Methods: Three eye drop formulas were tested: 0.5% carmellose sodium (Drop C), 0.5% carmellose sodium with added lipid (Drop C-L) and 1.0% glycerine with added lipid (Drop G-L). Nineteen control and 18 dry eye subjects used each product for 2 weeks, three times per day, in a random order, with a minimum 1-week washout between treatment periods. Tear evaporation, break up time, osmolarity, tear structure (by interferometry) and patient symptoms were assessed with the subjects adapted for 10 min in an environmental chamber controlled at 20% relative humidity and 22 °C. The treatment effects were analyzed using general linear model repeated measures analyses of variance.Results: In dry eye subjects, evaporation, break up time, osmolarity and symptoms improved for all formulas (p < 0.05). Normal subjects showed some improvements: evaporation with C-L, osmolarity with C and symptoms with C-L and G-L. Change in evaporation was greater for both C-L and G-L versus C (p < 0.05), and there was a trend for C-L to reduce evaporation more than G-L (p < 0.11). There were no significant treatment effects on tear film structure.Conclusion: Overall, the eye drop formula containing both carmellose sodium and lipid (C-L) produced a greater treatment effect on tear evaporation than the other formulations containing only one of these ingredients. This study also demonstrates the utility of a controlled environmental chamber in showing the difference in performance between dry eye treatments.

Thymosin β4: a potential novel dry eye therapy

The purpose of this manuscript is to review the clinical entity of dry eye syndrome (DES) and to provide a scientific basis and rationale for the usage of thymosin beta 4 (Tβ4) as a novel therapy for DES. DES is a common disorder affecting an estimated 25-30 million people in the United States alone and is characterized by inflammation of the ocular surface. Consequently, patients can suffer from burning, irritation, severe discomfort, foreign body sensation, and blurry and decreased vision. Recent animal studies of DES demonstrate that Tβ4 eye drops significantly reduce corneal fluorescein staining, indicating improved wound healing. Based on previous studies, there is clear support for further clinical investigation and development of Tβ4 as a novel, safe, and effective agent to treat dry eye. Herein, we discuss the scientific and clinical rationales that make Tβ4 a potential ideal candidate therapeutic for DES.

The Lid Wiper – a specialized structure at the inner eyelid margin for distribution of the tear film

AbstractPurpose The lid wiper is an epithelial structure at the inner eyelid border that distributes the thin precorneal tear film during the up‐phase of the blink. Clinically it is the first area of the ocular surface that shows epithelial alterations in dry eye disease.Methods A literature review on the posterior lid margin and lid wiper is discussed together with own data and considerations of the relevance of the lid wiper region in ocular surface physiology and pathology.Results The posterior side of the inner lid border has an epithelium of conjunctival morphology with goblet cells. It forms an elevation of about 100µm (10‐12 cell layers) thickness immediately at the crest of the inner border with a slope towards the subtarsal fold. The lid wiper hence forms a distinct epithelial lip that is the only region of the upper lid in contact with the globe as verified by functional tests. It extends along the upper and lower eyelid margins, has a width of typically about 1mm, narrower in the middle and wider to the temporal and nasal sides. The lid wiper of the upper lid appears as a suitable device to distribute the thin precorneal tear film during the blink as supported by the finding that in conditions with increased friction, such as dry eye disease and contact lens wear, the lid wiper is the first zone of the ocular surface that shows a pathological vital staining indicating epithelial destruction.Conclusion The lid wiper is of underestimated importance for tear film distribution and ocular surface integrity as well as a sensitive early indicator of dry eye disease. Integration and scoring of lid wiper epitheliopathy in dry eye diagnosis and therapy schemes could be a valuable addition to clinical practice. Support DFG KN317/11

Antientzündliche Therapie beim Trockenen Auge

Dry-eye is a multifactorial disease consisting of different pathomechanisms including instability of the tearfilm, increase of tearfilm osmolarity and most importantly inflammation of the ocular surface. In this context numerous signalling pathways and related immune mechanisms were identified all pointing towards autoimmune reactions as key parameters within this complex system. As autoimmunity tends to act independently from regulatory mechanisms, inhibition of related inflammatory processes is crucial in dry-eye therapy. Currently therapeutic agents such as steroids, cyclosporin, antibiotics, omega-3 and -6 fatty acids, etc. are available and readily used in daily practice. However, these therapies possess functional or legal restrictions that may limit their application. New strategies such as anti-lymphangiogenic therapies may have the potential to substitute or enhance current treatments. Independent of any anti-inflammatory therapy a detailed examination of the individual patient is necessary due to the complexity of the disease to provide individual and successful treatment.

Depression, Post-traumatic Stress Disorder, and Dry Eye Syndrome: A Study Utilizing the National United States Veterans Affairs Administrative Database

To study the scope of dry eye syndrome (DES) in veterans on a national level and to evaluate the relationship between psychiatric diagnoses and DES. Case-control study. Patients were seen in a Veterans Affairs (VA) eye clinic between 2006 and 2011. Patients were divided into cases and controls with regard to their dry eye status (cases = ICD-9 code for DES plus dry eye therapy; controls = patients without ICD-9 code plus no therapy). The prevalence of DES and the influence of psychiatric diagnoses on the risk of DES. A total of 2 454 458 patients were identified as either a dry eye case (n = 462 641) or control (n = 1 991 817). Overall, 19% of male patients and 22% of female patients had a diagnosis of DES, with female sex imparting an increased risk of DES at each decade compared to male sex (odds ratio [OR] 1.22-2.09). Several conditions were found to increase DES risk, including post-traumatic stress disorder (OR 1.92, 95% CI 1.91-1.94) and depression (OR 1.92, 95% CI 1.91-1.94) (analyses adjusted for sex and age). The use of several systemic medications was likewise associated with an increased risk of DES, including antidepressant medications (OR 1.97, 95% CI 1.79-2.17) and antianxiety medication (OR 1.74, 95% CI 1.58-1.91). Multivariate analysis (adjusted for age and sex) revealed that for psychiatric diagnoses, both the use of medication and the diagnosis remained significant risk factors when considered concomitantly, although the magnitude of each association decreased. DES is a disease associated with depression and post-traumatic stress disorder, and is prevalent among male and female veterans receiving eye care services. The association could be driven by underlying disease physiology or medications used to treat psychiatric conditions. Regardless of the causal link, this suggests that individuals with a known psychiatric diagnosis should be questioned about dry eye symptoms and, if applicable, referred to an eye care physician.

Effect of Topically Applied Epithelial Sodium Channel Inhibitors on Tear Production in Normal Mice and in Mice with Induced Aqueous Tear Deficiency

Dry eye syndromes affect a significant proportion of the population worldwide with reported prevalence ranging from 6% to more than 34%. Patients with dry eye can experience intense pain due to eye irritation, gritty/scratchy feeling in the eyes, blurry vision, and light sensitivity. Available treatments for dry eye syndromes remain mainly palliative. The purpose of the present study was to test the hypothesis that inhibiting sodium absorption via the epithelial sodium channel (ENaC) will increase ocular hydration in both normal as well as in animals with experimentally induced dry eye. ENaC inhibitors were dissolved in an aqueous buffer that mimics the composition of tears and were applied topically to the ocular surface of isoflurane-anesthetized mice. The effect of ENaC inhibitors was compared with that of the secretagogue uridine triphosphate (UTP; 1%), a purinergic receptor agonist which was shown to increase tear volume in animals. Tear production was measured for 10 s using phenol red-impregnated cotton threads. Fluorescein staining that assesses ocular surface damage was performed at baseline and then at days 1, 2, and 3 after the induction of dry eye in mice. Our data show that the inhibition of ENaC led to a time- and concentration-dependent increase in tear volume in normal mice. The effect of ENaC inhibition after a single application outperformed UTP, as it was long-lasting with tear volume still above baseline values 8 h postdosing. ENaC inhibition, which led to increased tear production, improved fluorescein scores in our dry eye model, when compared with nontreated or animals treated with buffer or UTP. We conclude that the inhibition of ENaC provides long-lasting increases in ocular surface hydration and that ENaC blockers could provide an effective new therapy for chronic dry eye.

Autologous serum in treatment of dry eye

INTRODUCTION. The treatment of dry eye by autologous serum is a simple and inexpensive treatment option. It is particularly effective in severe forms of dry eye as well as for chemical eye injuries, and it is justified by the presence of essential tear components which are not found in preparations of artificial tears. The aim of this study was to analyze the effects of autologous serum therapy in the patients with dry eye. MATERIAL AND METHODS. We monitored the effect of one-month treatment of dry eye by autologous serum (used with artificial tear preparations) in 50 rheumatology patients (23 men and 27 women) aged 26-65 years at the Department of Ophthalmology, Clinical Center Nis. We analyzed ocular discomfort and the values of objective parameters for the evaluation of tear film at baseline and one month later (Schirmer I, Tears Break Up Time and Rose Bengal). RESULTS. A statistically significant reduction of subjective complaints was found in the patients after the treatment by autologous serum (p<0.05), along with a minimal improvement of objective tests for checking the tear film quality. DISCUSSION AND CONCLUSION. The use ofautologous serum in dry eye therapy should provide benefit to the patients, relieve symptoms and improve objective parameters for the evaluation of dry eye. Both doctors and patients should be adequately informed, and proper screening of potential users of this method should be done. Not only additional tests of therapeutic effect of autologous serum (as well as of umbilical cord serum or autologous plasma) are needed but also parallel clinical and histopathological examination and analysis of the effects of this type of treatment of dry eye.

Transduction, Tropism, and Biodistribution of AAV Vectors in the Lacrimal Gland

The lacrimal gland (LG) delivers defensive and metabolic factors to the ocular surface. These functions may be disrupted in several diseases, and for most of them there is no cure. The aim of this study is to investigate conditions and limitations for using adeno-associated virus (AAV) vectors as gene transfer agents to LG. Eight-week-old Balb/c mice were used to investigate route, gene expression, and time course of AAV gene vector transfer to LG. AAV vectors encoding firefly luciferase were administered to the LG and luciferase expression was evaluated in vivo by immunohistochemistry. Ocular surface and neutralizing antibodies were also evaluated. The present work revealed that AAV vectors are able to delivery DNA to the LGs of mice. Direct injection had the highest level of transduction, and topical ocular drops the lowest. Overall, the AAV strain with highest transduction activity as measured by both luminescence and immunohistochemistry was AAV9, followed by AAV 5w8 and AAV5. Transduction was not different between sexes, could be detected as soon as 24 hours after injection, and lasted for at least 30 days (study termination). No tissue damage was observed when compared with controls. All vectors with detectable LG transduction induced neutralizing antibodies. LG gene delivery by AAV vectors appears to be both safe and well tolerated. The choice of vector influences both the overall transduction activity, as well as the spread of vector to other organs. This work supports the use of AAV-mediated gene therapy for dry eye.

Prevalence and Risk Factors of Dry Eye Syndrome in a United States Veterans Affairs Population

To evaluate the prevalence of dry eye syndrome (DES) and its associated risk factors in a US Veterans Affairs population receiving ocular care services. Retrospective study. settings: Patients were seen in the Miami and Broward Veterans Affairs eye clinics between 2005 and 2010. patients population: Patients were divided into cases and controls with regard to their dry eye status (cases = ICD9 code for DES plus dry eye therapy; controls = patients without ICD9 code plus no therapy). main outcome measures: The prevalence of DES and its associated risk factors. A total of 16 862 patients were identified as either a dry eye case (n = 2056) or control (n = 14 806). Overall, 12% of male and 22% of female patients had a diagnosis of DES, with female gender imparting a 2.40 increased risk (95% confidence interval [CI] 2.04-2.81) over male gender. Several medical conditions were found to increase DES risk including post-traumatic stress disorder (odds ratio [OR] 1.97, 95% CI 1.75-2.23), depression (OR 1.91, 95% CI 1.73-2.10), thyroid disease (OR 1.81, 95% CI 1.46-2.26), and sleep apnea (OR 2.20, 95% CI 1.97-2.46) (all analyses adjusted for gender and age). The use of several systemic medications, including anti-depressant medications (OR 1.97, 95% CI 1.79-2.17), anti-anxiety medication (OR 1.74, 95% CI 1.58-1.91), and anti-benign prostatic hyperplasia medications (OR 1.68, 95% CI 1.51-1.86), was likewise associated with an increased risk of DES. The prevalence of DES was found to be high in both men and women in our eye care population. This is the first study to demonstrate that in a veteran population, several diagnoses were significantly associated with DES, including post-traumatic stress disorder and depression.

Tear osmolarity and dry eye

Dry eye is a common eye disease, and its incidence rate has been escalating. The increased tear osmolarity is one of the main reasons for complaint, damage and inflammation of dry eye patients. With the breakthrough of testing technology for tear osmolarity, more research and application of tear osmolarity was reported, and papers on tear osmolarity of normal eye and dry eye in different regions were also published. In this article, the progress of the tear osmolarity research, the range of tear osmolarity and its application in diagnosis and therapy of dry eye was introduced, and the prospect for the clinical application of hypotonic artificial tears was also discussed.

A review on recent advances in dry eye: Pathogenesis and management

Keratoconjunctivitis sicca, more commonly known as dry eye, is an extremely common and often unrecognized disease. It is the condition in ophthalmology that in its mild grade of severity will affect most of the population at one time or other. Due to a wide variety of presentations and symptoms, it often frustrates the ophthalmologists as well as patients. Due to multifactorial and elusive etiology, it is often challenging to treat dry eye. Ocular surface disorders are also clinically important to treat especially in terms of visual acuity. Xero-dacryology is therefore becoming a very important branch of ophthalmology. Recent studies have given insight into the inflammatory etiology of dry eye. The conventional and main approach to the treatment of dry eye is providing lubricating eye drops or tear substitutes. However, the newer treatment approach is to target the underlying cause of dry eye instead of conventional symptomatic relief. In light of the above knowledge, the present article focuses on newer theories on pathogenesis of dry eye and their impact on dry eye management.Method of Literature Search:A systematic literature review was performed using PubMed databases in two steps. The first step was oriented to articles published for dry eye. The second step was focused on the role of inflammation and anti-inflammatory therapy for dry eye. The search strategy was not limited by year of publication. A manual literature search was also undertaken from authentic reference books on ocular surface disease.

Novel starch based copolymers (DiHydroxyl Starch) as ocular lubricants: Synthesis and characterizations

AbstractDry eye syndrome is an ocular tear deficiency disorder that affects millions of people in the United States. It has been recognized as a significant lifestyle issue and is among the most frequently established diagnoses in ophthalmology. Tear substitutes (or artificial tear formulations) are the mainstay of dry eye therapy. While many commercial products are available, their efficacy is limited because of their short retention time in the eye, and/or low patient acceptance. In this study, our objectives were to obtain water soluble products with opened glucose rings along the starch backbone, and tear substitute formulations based on these products with strengthened mucoadhesion, shear thinning behavior, improved tear film stability, and no irritancy to the eye. To this end we have synthesized a series of starch based copolymers, DiHydroxyl Starches (DHS). This modification of starch is not a new science, but the application of these polymers to tear substitutes is novel. These polymers were characterized as ocular lubricants utilizing both in vitro and in vivo testing. Specifically, mucoadhesion and rheological behavior were examined. Their performance as ocular lubricants was evaluated utilizing the tear‐film break up times of rabbits before and after application of the copolymers. In addition, the effect of autoclaving and ocular toxicity were tested. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Advancements in anti-inflammatory therapy for dry eye syndrome

Purpose The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting. Methods The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome. Results Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects. Conclusions Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

Extending the Duration of Tear Film Protection in Dry Eye Syndrome: Review and Retrospective Case Series Study of the Hydroxypropyl Cellulose Ophthalmic Insert

options for extending the duration of tear film protection in dry eyes include artificial tear formulations with enhanced viscosity/polymeric systems, ocular ointments and gels, and, recently, the hydroxypropyl cellulose ophthalmic insert (Lacrisert®; distributed by Aton Pharma, inc., Lawrenceville, NJ, USA). The goal in using these agents is to achieve a balance between maximizing tear film stability and ocular surface retention, while simultaneously maintaining or improving vision, comfort, and convenience. In this article, various agents are reviewed, and findings are presented from a retrospective study of patients who used hydroxypropyl cellulose ophthalmic inserts within the previous 2 years. The median length of therapy with the insert was 5.3 years, and nearly 65% of patients had used it for more than 2 years. Findings suggest that the hydroxypropyl cellulose ophthalmic insert is a relatively safe, tolerable, and effective therapy for dry eye, either alone or in conjunction with other therapies.

Autoimmunity in Dry Eye Is Due to Resistance of Th17 to Treg Suppression

Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an incomplete understanding of its specific cellular and molecular pathogenic elements. Using a validated mouse model of DED, herein we functionally characterize the different T cell subsets, including regulatory T cells (Tregs) and pathogenic effector T cells, and determine their contribution to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg suppression in DED. In addition, we clearly show that in vivo blockade of IL-17 significantly reduces the severity and progression of disease, which is paralleled by a reduction in the expansion of Th17 cells and restoration of Treg function. Our findings elucidate involvement of a previously unknown pathogenic T cell subset (Th17) in DED that is associated specifically with Treg dysfunction and disease pathogenesis and suggest a new target for dry eye therapy.