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Introduction: This review examines how mechanisms that are not related to tear dysfunctions may contribute to the development of symptoms of dry eye disease and help to explain why dry eye symptoms do not correlate with signs. Consideration is also given to the significance of tear deficiencies which cannot contribute to an examination of symptom-sign correlation. Areas covered: Tear deficiencies which are not routinely assessed include inflammation, mucin quantity and quality, as well as corneal neuropathy and blink inefficiency. Expert opinion: Tear deficiencies detected in an examination of patients reporting symptoms of dry eye disease become the targets for remedial approaches but not always with satisfactory outcomes. Other possible influences on symptoms could include genetic predispositions, sex, ethnicity, race, health literacy, mental health conditions, lower perceived health-related quality of life, and psychological factors. However, these possible influences cannot be assessed in most dry eye disease clinical settings. Consequently, too often symptoms of dry eye cannot correlate with signs of tear dysfunction that are not identified (and so not treated). Consequently, noncompliance with treatment recommendations may not be relevant to the persistence of symptoms or signs when treatment does not address tear dysfunctions which are difficult to assess. [ABSTRACT FROM AUTHOR]

To examine whether corneal epithelial dendritic cells (CEDC) could serve as an indicator to distinguish obstructive meibomian gland dysfunction (MGD) with or without ocular surface inflammation (OSI). We performed a case-control study on patients with diagnosed obstructive MGD between August 2017 and November 2019. 30 MGD cases and 25 healthy controls were recruited. The classification of MGD patients with and without OSI was based on the tear pro-inflammatory cytokine levels. Compared with the MGD without OSI and the control group, a higher CEDC density was detected in the MGD with OSI subgroup. The presence of >15.6 cells/mm2 CEDC had a sensitivity of 73% and specificity of 75% for the diagnosis of MGD with OSI. OSI is not present in all patients with obstructive MGD. Evaluation of CEDC density in the central cornea may help identify whether MGD is concomitant with OSI. [ABSTRACT FROM AUTHOR]

Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining. One hundred participants were recruited based on OSDI, TO, TFBUT, TMH, and LLP to be categorised as healthy (Group 1) or EDE (Group 2). Group 2 was divided into Group 2A (mild symptoms), 2B (moderate), and 2C (severe). MGLA, conjunctival hyperemia, and corneal staining were measured. Positive correlation between MGLA, conjunctival hyperemia, and corneal staining were found (all r ≥ 0.221, p ≤ 0.027). Significant differences were found: MGLA between Group 1 vs. 2C and 2C vs. 2A or 2B; conjunctival hyperemia between Group 1 vs. 2A, 2B or 2C; corneal staining between Group 1 vs. 2B or 2C and 2A vs. 2B or 2C (all p ≤ 0.049). Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) and other inflammatory ocular disorders have been reported to be associated with decreased corneal endothelial cell density (CECD), however the mechanism of underlying endothelial cell loss remains unknown. We conducted a comprehensive literature search of English-written publications on dry eye disease, corneal endothelial cell loss, Sjögren's syndrome, and Graft Vs Host Disease (GVHD), to review the effects of DED and other inflammatory ocular surface conditions on CECD. A total of 78 studies were included in our study. Loss of corneal neurotrophic support, cytotoxic stress, and a heightened immune response, all of which may occur secondarily to a common causative agent such as inflammation, are major contributors to reduced CECD. More studies are needed to determine how the interrelated pathways of altered corneal nerve function and upregulated expression of inflammatory activity influence corneal endothelial cell loss. [ABSTRACT FROM AUTHOR]

To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD). Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1β, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark. Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line. [ABSTRACT FROM AUTHOR]

Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions. Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis. Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile. This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues. [ABSTRACT FROM AUTHOR]

The richly innervated corneal tissue is one of the most powerful pain generators in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache, and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain. [ABSTRACT FROM AUTHOR]