Dry Eye Pathology Research Articles

Effect of Lutein on Ocular Goblet Cell, IFN-γ, and IL-17 Concentration in Dry Eye-Induced Mice Model.

Introduction Dry eye disease affects a substantial number of individuals globally and significantly impacts their quality of life and productivity. Understanding the underlying mechanisms and managing dry eye disease poses substantial challenges. Recent research has highlighted the involvement of various inflammatory mediators in the pathogenesis of dry eye disease, including the cytokines interferon (IFN)-γ and interleukin (IL)-17.Activation of stress signaling pathways and residential immune cells on the ocular epithelial surface ignites epithelial changes, destabilizes tear film, amplifies inflammation and creates an endless loop. Lutein is a β-carotenoid antioxidant which has been proven to be beneficial in many ocular diseasesdue to its protective and anti-inflammatory effect induced by various stimulators. Lutein also acts as a direct and indirectantioxidant agent,suppressing oxidative stress and mitigating oxidative damage. The purpose of this research is to investigate the potential therapeutic effects of lutein in a mouse model of dry eye, aiming to elucidate its impact on ocular manifestation, goblet cells count, IFN-γ and IL-17 level. Methods Desiccating stress was induced in C57BL/6 mice. In a separate group, lutein was administered subcutaneously on a daily basis throughout the experimental period. Clinical manifestations of dry eye, including ocular surface changes, were documented photographically. Goblet cell concentration was assessed through Periodic Acid-Schiff (PAS) staining, and the levels of IFN-γ and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). Data obtained from these assessments were compared between the experimental groups to determine the potential effects of lutein on dry eye pathology and cytokine levels. Results Significant differences were observed in clinical observations and goblet cell concentrations among the groups; however, no statistically significant differences were found in the levels of IFN-γ and IL-17 between the groups. The untreated group exhibited significantly higher opacities and irregularities compared to the lutein-treated group, whereas the mean goblet cell count was highest in the lutein-treated group. Conclusion Lutein administration improves clinical observations and goblet cell concentrations in a mouse model of dry eye. The treated group exhibited improved ocular surface integrity, but no significant differences in the tested cytokine levels were observed. These findings suggest that lutein supplementation could be a promising therapeutic option for managing dry eye disease. Further research is needed to understand the underlying mechanisms and long-term effects of lutein in dry eye management.

Extracellular protein homeostasis: The dawning of a new age for human disease therapies?

Extracellular protein homeostasis: The dawning of a new age for human disease therapies?

Cornea Classic: Stern, Beuerman, Fox, Gao, Mircheff, and Pflugfelder, "The Pathology of Dry Eye: The Interaction Between the Ocular Surface and Lacrimal Glands" (1998).

In one of the most frequently cited articles from Cornea , Stern et al's "The pathology of dry eye: the interaction between the ocular surface and lacrimal glands" (1998) revolutionized our current understanding of the pathophysiology of dry eye disease.

The Potential Role of Regulated Cell Death in Dry Eye Diseases and Ocular Surface Dysfunction.

The research on new treatments for dry eye diseases (DED) has exponentially grown over the past decades. The increased prevalence of dry eye conditions, particularly in the younger population, has received much attention. Therefore, it is of utmost importance to identify novel therapeutical targets. Regulated cell death (RCD) is an essential process to control the biological homeostasis of tissues and organisms. The identification of different mechanisms of RCD stimulated the research on their involvement in different human pathologies. Whereas apoptosis has been widely studied in DED and included in the DED vicious cycle, the role of RCD still needs to be completely elucidated. In this review, we will explore the potential roles of different types of RCD in DED and ocular surface dysfunction. Starting from the evidence of oxidative stress and inflammation in dry eye pathology, we will analyse the potential therapeutic applications of the following principal RCD mechanisms: ferroptosis, necroptosis, and pyroptosis.

Effects of hyperosmolarity on annexin A1 on ocular surface epithelium in vitro

Osmotic stress is an important challenge to cell function. Dry eye pathology is characterized by elevated tear film osmolarity as consequence of decreased tear secretion and/or increased evaporation. Dry eye pathogenesis is not completely clarified. However, it is known that tear hyperosmolarity induces NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-cointaining 3) inflammasome activation and inflammatory mediators release that leads to ocular surface damage.Annexin A1 is a protein involved in anti-inflammatory or pro-resolution actions in different tissues while its presence and biological role on ocular surface has been scarcely examined. In this study, potential changes in annexin A1 protein expression and secretion on the ocular surface after exposure to hyperosmolar conditions were evaluated. In addition, considering the significant role of inflammation in dry eye pathology, the potential anti-inflammatory activity of Ac2-26, an annexin A1 peptide mimicking its N-terminus, was assessed.Cytosolic and membrane staining was detected for annexin A1 in corneal and conjunctival epithelial cells. A native form of annexin A1 together with a truncated form were detected by western blot analysis. Under hyperosmotic conditions increased protein levels of intracellular and secreted annexin A1 as well as higher expression of its receptor Fpr2 (formyl peptide receptor type 2) were found. Treatment with mimetic peptide Ac2-26 ameliorated NLRP3 activation and interleukin 1β (IL-1β) release triggered by elevated osmolarity in corneal and conjunctival epithelial cells. These findings suggest a potential role of annexin A1 and its mimetic peptide modulating key inflammatory events associated to dry eye.

A novel serine protease inhibitor as potential treatment for dry eye syndrome and ocular inflammation

Dry eye syndrome (DES), a multifactorial disorder which leads to ocular discomfort, visual disturbance and tear film instability, has a rising prevalence and limited treatment options. In this study, a newly developed trypsin-like serine protease inhibitor (UAMC-00050) in a tear drop formulation was evaluated to treat ocular inflammation. A surgical animal model of dry eye was employed to investigate the potential of UAMC-00050 on dry eye pathology. Animals treated with UAMC-00050 displayed a significant reduction in ocular surface damage after evaluation with sodium fluorescein, compared to untreated, vehicle treated and cyclosporine-treated animals. The concentrations of IL-1α and TNF-α were also significantly reduced in tear fluid from UAMC-00050-treated rats. Additionally, inflammatory cell infiltration in the palpebral conjunctiva (CD3 and CD45), was substantially reduced. An accumulation of pro-MMP-9 and a decrease in active MMP-9 were found in tear fluid from animals treated with UAMC-00050, suggesting that trypsin-like serine proteases play a role in activating MMP-9 in ocular inflammation in this animal model. Comparative qRT-PCR analyses on ocular tissue indicated the upregulation of tryptase, urokinase plasminogen activator receptor (uPAR) and protease-activated receptor 2 (PAR2). The developed UAMC-00050 formulation was stable up to 6 months at room temperature in the absence of light, non-irritating and sterile with compatible pH and osmolarity. These results provide a proof-of-concept for the in vivo modifying potential of UAMC-00050 on dry eye pathology and suggest a central role of trypsin-like serine proteases and PAR2 in dry eye derived ocular inflammation.

Advances in the diagnosis and treatment of dry eye.

The core mechanism of dry eye is the tear film instability. Tear film-oriented diagnosis (TFOD) is a concept to clarify the cause of tear film instability by tear film, and tear film-oriented treatment (TFOT) is a concept to treat dry eye disease by replacing the lacking components of the tear film layer based on the TFOD. In TFOD, the fluorescein breakup pattern of the tear film is important, and the subtype of dry eye can be judged to some extent from the breakup patterns. Current noninvasive devices related to the dynamic analysis of the tear film and visual acuity enabled the diagnosis of dry eye, subtype analysis, and the extent of severity. In Asian countries, secretagogues represent the main treatment in TFOT. Since meibomian gland dysfunction is a factor that greatly affects the tear breakup time, its treatment is also essential in the dry eye treatment strategy. A newly discovered dry eye subtype is the short breakup time-type (BUT) of dry eye. The only abnormal finding in this disease is the short BUT, suggesting a relationship with ocular neuropathic pain and eye strain. Recently, data from many studies have accumulated which show that dry eye is a life-style disease. In addition to the treatment of dry eyes, it is becoming possible to prevent the onset by intervening with the daily habits, diet, exercise and sleep, etc. It has been pointed out that oxidative stress is also involved in the pathology of dry eye, and intervention is being carried out by improving diet and taking supplements. Future research will be needed to link clinical findings to the molecular biological findings in the tear film.

Preliminary Data Regarding Decreased Catalase Specific Activity in the Tears as a Result of Environmental Stress

Oxidative stress represents the imbalance between the production of reactive oxygen species and the organism�s capacity to produce antioxidants. This phenomenon has captured lately a lot of attention, with an additional increased interest being manifested towards the relationship between psychological stress and oxidative stress. In the present study we decided to observe the changes which occur in stress environmental conditions applied to rats subjected to swimming and treadmill exercises, by focusing on a preliminary determination of (CAT) specific activity, an enzyme known to catalyse the decomposition of hydrogen peroxide into water and oxygen, and a valuable antioxidant protector, with possible implications into the dry eye pathology. Our results could suggest a possible dry eye animal model induced through stress and a possible implication of the oxidative stress markers in the occurrence of this ocular pathology, as suggested by the significant decrease in the CAT activity registered in rat tears collected after the application of environmental stressors (e.g. swimming and running) versus the control group.

Desiccating stress-induced chemokine expression in the epithelium is dependent on upregulation of NKG2D/RAE-1 and release of IFN-γ in experimental dry eye.

The Th1-associated chemokines CXCL9, CXCL10, and CXCL11 coordinate migration of CXCR3(+) Th1 cells. The objective of this study was to evaluate the role of the innate immune system in stimulating chemokine expression in an experimental model of dry eye and bridge the gap between innate and adaptive immunity. Desiccating stress (DS) induced very early (6 h) expression and production of Th1-associated chemokines in cornea and conjunctiva of C57BL/6 and RAG1 knockout (KO) mice, demonstrating that chemokine expression does not require innate T cells. We then demonstrated that activating the innate immune system prior to adoptive transfer of T cells to RAG1KO mice increased disease severity. Interestingly, lack of induction of chemokines CXCL9, CXCL10, and CXCL11 in IFN-γKO mice provided evidence that their expression requires IFN-γ for induction. Treatment of RAG1KO mice with anti-NK1.1 prevented the increase of CXCL9, CXCL10, and CXCL11 in response to DS, compared with isotype controls. Additionally, DS increased the expression of NKG2D in the conjunctiva. The expression of the NKG2D ligand, retinoic acid early inducible gene 1, also increased at the ocular surface at both the protein and gene levels. Neutralization of NKG2D at the ocular surface decreased the expression of CXCL9, CXCL10, CXCL11, and IFN-γ. In summary, upregulation of CXCL9, CXCL10, and CXCL11 expression in experimental dry eye is T cell-independent, requiring IFN-γ-producing NKG2D(+) NK cells that are activated in response to DS-induced stress signals. This study provides insight into the events that trigger the initial immune response in dry eye pathology.

Practical issues concerning tear protein assays in dry eye.

Dry eye is a common clinical condition diagnosed by cumulative evidence of symptoms and signs. Many new treatments in dry eye are either expensive, invasive, have potential for side effects, or are not easily accessible. In severe dry eye, the ideal modality of treatment to begin with is often not clear as specific molecular disturbances are not evident from just examination of clinical manifestations. Assessing the effects of ongoing treatment is not straight forward since there is lack of agreement between clinical signs and symptoms. There is a need to have more objective methods of selecting treatment for dry eye and monitoring the effect of treatment.Recently, there are many new technologies applied to the discovery of tear biomarkers, for e.g., mass spectrometry based proteomics techniques and multiplex assays such as the bead-based sandwich indirect immunofluorescent assays. Tear proteins assays have even been made available as point-of-care devices. This review focuses on the evidence for the involvements of tear proteins in dry eye, possible changes in tear concentrations with therapy and the strength of evidence regarding dry eye pathology. Much remains to be done in terms of developing office-based assays and ascertaining their reliability, but current evidence suggests that tear proteins have a role in the clinical practice of dry eye.

Spdef Null Mice Lack Conjunctival Goblet Cells and Provide a Model of Dry Eye

Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease.

Comparison of mucin levels at the ocular surface of postmenopausal women with and without a history of dry eye.

To determine if levels of the glycocalyx membrane mucins, MUC1 and MUC16, and the secreted goblet cell mucin MUC5AC are altered in conjunctival cells and tears of postmenopausal women presenting with a history of non-Sjögren dry eye and if mucin levels correlate with dry eye clinical diagnostic data. Eighty-four postmenopausal women with a history of non-Sjögren dry eye and 30 normal subjects were recruited for this study. Impression cytology samples were collected for mucin messenger RNA (mRNA) and protein analysis. Tears were collected for mucin protein assay. Quantitative polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were used to quantitate MUC1, MUC16, and MUC5AC levels. Postmenopausal women with a history of dry eye displayed significantly increased MUC1 mRNA expression and cellular protein compared with normal subjects (P < 0.001 and P < 0.01, respectively). Similarly, cellular MUC16 protein levels were significantly higher (P < 0.001). Mucin levels were found to be correlated with the clinical characterization of the subjects, including staining and symptoms. Although cellular MUC5AC protein levels were increased in symptomatic subjects, the increase did not reach statistical significance. Elevation in MUC1 and MUC16 mRNA and/or protein levels in postmenopausal women with non-Sjögren dry eye with a history of dry eye may be a compensatory response to irritation and inflammation associated with the disease. Understanding the pattern of mucin expression associated with the dry eye pathology may clarify factors involved in the progression of the disease and enhance the development of targeted therapies.

Effect of lacritin, a novel glycoprotein, on ocular surface and tear film integrity

AbstractPurpose Dry eye is extremely common and debilitating. Treatment options are palliative at best and do not address the underlying pathology. Lacritin, a newly discovered glycoprotein, is secreted naturally in human tears by the lacrimal gland. Human recombinant lacritin stimulated tear secretion in normal rabbits and is well tolerated, leading us to hypothesize that topical application of lacritin will not adversely affect ocular surface and tear film integrity.Methods We compared full length lacritin construct with cyclosporin (Restasis®), in terms of tear break up time (TBUT) and goblet cell density using impression cytology. Lacritin (10, 50 μg/ml), or cyclosporin (0.05%), were administered bilaterally to New Zealand white rabbits three times daily for 14d (n=4/group).Results TBUT after lacritin (10 or 50 μg/ml) treatment was 12±2sec, which was similar to vehicle alone, but significantly decreased after cyclosporine treatment for 14d (6±3sec, p&lt;0.001). Preliminary results indicate that goblet cell density decreased by 7±8% after cyclosporine but was not decreased after lacritin. No local irritant effects were noted by slit lamp examination after lacritin treatment, but redness and mild congestion were present in the cyclosporin group.Conclusion Thus, treatment with lacritin was better tolerated than cyclosporin. This data suggests that lacritin does not adversely ocular surface and tear film integrity when compared to cyclosporine. Evaluation with inflammatory markers, such as CD‐11c, is currently ongoing. Glycoproteins, such as, lacritin, represent a new, unique therapeutic approach that may more closely address the pathology of dry eye. Commercial interest

Lacritin, a Novel Tear Glycoprotein, Stimulates Tear Production in Rabbits without Ocular Toxicity

Dry eye is extremely common and debilitating disease. Current treatment options like artificial tears and cyclosporin are palliative and do not effectively address the underlying pathology of dry eye. Lacritin is a newly discovered glycoprotein that occurs naturally in human tears, produced solely by meibomian, lacrimal and salivary glands. Human recombinant lacritin stimulates tear secretion in cultured rat lacrimal acinar cells, leading us to hypothesize that topical application of lacritin will increase production of tears of normal composition. Bilateral tear production in New Zealand white rabbits was measured at 60, 120 and 240 min after a single topical administration of 50μl lacritin (1, 10, or 50 μg/ml). Tears were collected and slit lamp examination and ocular surface staining measured before and 240 min after treatment. Tear pH, protein and electrolyte concentrations were then measured. A 50 μg/ml lacritin dose increased tear production by 40% within 60 min and maintained for 240 min (p&lt;0.05). With other doses, a significant increase (55% from baseline, p&lt;0.05) was observed only at 240 min. No local irritant effects were noted by slit‐lamp examination. The composition (pH, Na2+ and K+) of tears was also not different from normal tears. In conclusion, lacritin is a novel, safe and effective candidate for dry eye therapy. Lacritin, being mitogenic, may also help restore the natural tear film.

APLICACIONES DEL SUERO AUTÓLOGO EN LA CONSULTA DEL SERVICIO DE OFTALMOLOGÍA EN EL HOSPITAL DONOSTIA

Introduction: The etiology of a dry eye is related to the lack of growth factors, responsible of keeping an adequate spread of the ocular epithelium surface. These components are found in blood. That is the reason why, the use of autologous serum is a therapeutic option for a dry eye. The autologous serum is a preparation of centrifuged own blood-based 3,000 revs per minute. Objetive: Registering the prescription procedure, preparation, and dispensing of autologous serum collyrium. Material and Method: In 2004 it was agreed with the Ophthalmology Service to define a protocol for the autologous serum collyrium. Results: From May 2004 to April 2006, 42 patients have been treated. In 2004 collyrium was elaborated for 11 patients, in 2005 for 32 patients and until April 2006 for 22 patients. A half of the patients needed to be described at least once, being the cases with GVHD the most described: an average of 8 exemptions for every patient. Conclusions: The increase of the demand justifies the registration of this preparation. The collyrium preparation and dispensing by the Pharmacy Service assure its sterility and stability and it makes possible more efficient pharmaceutics assistance and a correct collyrium use. All treated patients with autologous serum got better from their pathology of dry eye. Likewise, their life quality has been improved, having less vision upsets and a better vision.

Regulation of MUC16 by inflammatory mediators in ocular surface epithelial cell lines

The aim of the present study was to evaluate the regulation of membrane-anchored mucin MUC16 by proinflammatory cytokines and bacterial components at the ocular surface. Expression and distribution of MUC16 in conjunctival (HCjE) and corneal (HCE) epithelial cell lines was monitored by RT-PCR and immunohistochemistry. To determine the regulation of MUC16, cultured HCjEs and HCEs were stimulated with different cytokines, bacterial components and bacterial supernatants, and analyzed by real-time PCR, immunodot blot and immunohistochemistry. The results indicate that MUC16 is differentially regulated between HCjEs and HCEs after challenge with inflammatory mediators and suggest shedding of MUC16 from the ocular surface epithelia into the tear film. This seems to be precisely regulated. MUC16 shedding can be differentially increased and decreased, suggesting a protective function of membrane-anchored MUC16 and supporting the hypothesis that dysregulation of membrane-anchored MUC16 at the ocular surface may be involved in dry eye pathology.

Effect of Suction Ring Application During LASIK on Goblet Cell Density

To study the effect of LASIK surgery on conjunctival goblet cells as one of the proposed mechanisms for dry eye occurring after LASIK. This prospective study included 22 eyes (11 patients) that underwent LASIK for the correction of myopia. Three pairs of samples were taken from the bulbar conjunctiva of each eye. The first pair was taken preoperatively before application of the suction ring. The second and third pairs were taken from the same sites at 1 week and 1 month consecutively. The first site was at 12 o'clock and the second at the inferotemporal quadrant between 7 and 8 o'clock. Time of suction was recorded. Preoperatively, mean goblet cell density was 424 +/- 105 cells/mm2 (range: 284 to 630 cells/mm2). All postoperative samples showed a statistically significant decrease in goblet cell count: 216 +/- 81 cells/mm2 (range: 40 to 325 cells/mm2) at 1 week and 218 +/- 99 cells/mm2 (range: 50 to 396 cells/mm2) at 1 month. Other parameters of conjunctival impression cytology were normal. The difference between the samples in the inferior conjunctiva preoperatively and 1 week postoperatively was greater than that of the superior conjunctiva. Recovery rate in both sites was similar and the damage did not correlate with the duration of suction. The application of the microkeratome suction ring induced changes in the perilimbic conjunctiva. These changes contribute to the pathology of dry eye. Goblet cell count remains affected at 1 month postoperatively.

Drainage of Tears: Impact on the Ocular Surface and Lacrimal System

The human efferent tear ducts are part of the lacrimal system. Because little knowledge exists concerning the physiology of the nasolacrimal system, and hence its pathophysiology, the nasolacrimal system has received almost no consideration as a possible factor in dry eye. The human nasolacrimal ducts consist of the upper and the lower lacrimal canaliculus, the lacrimal sac, and the nasolacrimal duct. As a draining and secretory system, the efferent tear ducts play a role in tear transport and nonspecific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a surrounding vascular system. This system is similar to a cavernous body that is subject to autonomic control and regulates tear outflow. Tear duct-associated lymphoid tissue (TALT) is present in the efferent tear ducts, displaying the cytomorphological and immunophenotypic features of mucosa-associated lymphoid tissue (MALT). Under normal conditions, tear fluid components are constantly absorbed into the blood vessels of the surrounding cavernous body. These vessels are connected to the blood vessels of the outer eye and could act as a feedback signal for tear fluid production, which ceases if these tear components are not absorbed. In this way, dry eye could be initiated. Defective stimulation of TALT could result in abnormal immune deviation at the ocular surface, leading to an autoimmunological response that causes dry eye pathology.

Nasolacrimal ducts and the dry eye

The knowledge regarding the pathogenesis, diagnosis, and treatment of dry eye has made large advances in recent years. However, many questions are still unanswered. Although the nasolacrimal ducts are part of the tear system they have been paid nearly no attention regarding dry eye. The present knowledge about the nasolacrimal ducts is presented and discussed in a context with dry eye. A PubMED search was conducted for articles published from 1966 to the present; in addition, review articles as well as book chapters were considered and discussions with investigators in the field were performed. As a draining and secretory system, the nasolacrimal ducts play a role in tear transport and non-specific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a vascular system that surrounds the nasolacrimal sac and nasolacrimal duct. This system is comparable to a cavernous body and it is connected to the blood vessels of the outer eye. Also it is subject to vegetative control. Organized mucosa-associated lymphoid tissue (MALT) is present in the nasolacrimal ducts displaying the cytomorphological and immunophenotypic features of MALT. The normally constant absorption of tear fluid components into the blood vessels of the surrounding cavernous body that are connected to the blood vessels of the outer eye, could be a feedback signal for tear fluid production, which comes to a halt if these tear components are not absorbed. Thus, dry eye could be initiated. Defective stimulation of tear duct-associated lymphoid tissue (TALT) could result in abnormal immune deviation at the ocular surface leading to an autoimmunological response that causes dry eye pathology.

The Pathology of Dry Eye

Homeostasis of the tear film involves delicate hormonal and neuronal regulatory mechanisms. The eye appears to be a target organ for sex hormones, particularly the androgens, as they modulate the immune system and trophic functions of the lacrimal glands and the functioning of the meibomian glands. The cornea, lacrimal glands, mucous cells, and meibomian glands are all richly innervated, indicating the importance of nervous regulation in their function. Parasympathetic, sympathetic, and sensory innervation play complex stimulatory or inhibitory roles, and neuronal pathways interact via complex surface results cascades. Abnormalities at any point in these pathways can cause overall dysregulation of lacrimal function. Whatever the initial causes of dry eye, chronic dryness of the ocular surface results in inflammatory reactions and gradual destruction of the lacrimal glands and conjunctival epithelium. Once dry eye disease has developed, inflammation is the key mechanism of ocular surface injury, as both the cause and consequence of cell damage. In practice, dry eye can be associated with Sjögren's syndrome, allergies, infection, blepharitis, and preservative-containing eye drops.