Understanding Of Dry Eye Disease Research Articles

Longitudinal Analysis of Tear Cytokine Ratios in Association with Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study

Purpose To extend cross-sectional data on cytokine ratios (CRs) in dry eye disease (DED) signs by investigating longitudinal change in pro- to anti-inflammatory CRs and associations with change in DED signs and symptoms. Methods Secondary analysis of fifty-four subjects [mean age 57.3 (SD 13.2) years, 85.2% female; 68.5% white] with ≥ 4 uL pooled tear volumes at months 0, 6, and 12. Pro-inflammatory (IL-1b, IL-6, IL-8, IL-17A, IFN-g, and TNF-a) to anti-inflammatory (IL-6, IL-10) cytokine ratios (CR) were calculated. DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)] were measured. Changes over time in DED signs, symptoms, and CRs were evaluated using longitudinal models. Correlations between changes in CR and changes in DED signs and symptoms were evaluated using Spearman correlation coefficients (rho). Results DED signs which improved over time (p < 0.001) included corneal and conjunctival staining score, tear break-up time, tear osmolarity, and composite sign severity score. Using IL-10 as anti-inflammatory, changes in corneal and conjunctival staining and composite severity score significantly correlated with changes in pro- to anti-inflammatory CRs from month 0 to 6 (|rho|: 0.29-0.45, p: 0.003-0.04) but not between month 0 to 12 (|rho|: 0.01 to 0.24, all p > 0.08). DED symptoms decreased across one year (p < = 0.001) for all OSDI measures; these changes did not correlate with changes in CRs (|rho|: 0.00 to 0.29, all p > 0.04). Conclusions Improvement in some DED signs across one year correlated weakly with decreases in pro- to anti-inflammatory CRs, in alignment with the understanding of DED as inflammatory. CRs may provide greater insight than absolute tear cytokine concentrations as possible DED biomarkers. Additional studies that provide standardized clinical information and tear collection and analysis are needed to validate CRs in DED.

Case Series: Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

A New Immortalized Human Lacrimal Gland Cell Line.

The lacrimal gland is crucial for maintaining ocular health by producing the aqueous component of the tear film, which hydrates and nourishes the ocular surface. Decreased production of this component results in dry eye disease, a condition affecting over 250 million people worldwide. However, the scarcity of primary human material for studying its underlying mechanisms and the absence of a cell model for human lacrimal gland epithelial cells present significant challenges. Here, we describe the generation of immortalized human lacrimal gland cell lines through the introduction of an SV40 antigen. We successfully isolated and characterized three cell clones from a female lacrimal gland donor, confirming their epithelial identity through genomic and protein analyses, including PCR, RNAseq, immunofluorescence and cultivation in a 3D spheroid model. Our findings represent a significant advancement, providing improved accessibility to investigate the molecular pathogenesis mechanisms of dry eye disease and potential therapeutic interventions. We identified the expression of typical epithelial cell marker genes and demonstrated the cells' capability to form 2D cell sheets and 3D spheroids. This establishment of immortalized human lacrimal gland cells with epithelial characteristics holds promise for future comprehensive studies, contributing to a deeper understanding of dry eye disease and its cellular mechanisms.

Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series.

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

Establishment of a Severe Dry Eye Model Using Complete Dacryoadenectomy in Rabbits.

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are limited in part due to the lack of informative animal models. The authors recently reported on a method of DED induced by injecting all orbital lacrimal gland (LG) tissues with the lectin concanavalin A. Here, we report a novel model of aqueous-deficient DED based on the surgical resection of all orbital LG (dacryoadenectomy) tissues. Both methods use rabbits because of their similarity to human eyes in terms of the size and structure of the ocular surface. One week after removal of the nictitating membrane, the orbital superior LG was surgically removed under anesthesia, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Dacryoadenectomy induced severe DED, evidenced by a marked reduction in the tear break up time test and the Schirmer's tear test, and significantly increased tear osmolarity and rose bengal staining. Dacryoadenectomy-induced DED lasted at least eight weeks. There were no complications and animals tolerated the procedure well. The technique can be mastered relatively easily by those with adequate surgical experience and appreciation of the relevant rabbit anatomy. Since this model recapitulates the features of human aqueous-deficient DED, it is suitable for studies of ocular surface homeostasis, DED, and candidate therapeutics.

Evidence-based understanding of dry eye disease in pharmacy: overview of the TFOS DEWS II report

Evidence-based understanding of dry eye disease in pharmacy: overview of the TFOS DEWS II report

Patients' Perspectives on Their Dry Eye Disease

PurposeAlthough it has been known that patients' perspectives on their disease can significantly affect their level of functional disability as well as disease outcome, limited data are available on patients' perceptions of their dry eye disease (DED). The aim of this questionnaire-based study was to evaluate patients' perspectives on their DED. MethodsThis cross-sectional study included 91 patients with DED. In addition to clinical evaluation, all patients completed a questionnaire to evaluate their perspectives on their DED. This included their satisfaction with understanding DED, their opinion on the easiness of following doctors' advice, their opinion on the effectiveness of the treatment, their satisfaction with the eye care, and their general outlook on DED. ResultsThis study included 75 (82%) women and 16 men (18%) with a mean age of 57 ± 14 years who had been treated for DED for 5.2 ± 5.4 years. 93% of the patients were satisfied with their understanding of DED, and 76% found it easy to follow their doctors' advice for DED management. Furthermore, 95% thought that the DED treatment had been helpful and 95% were satisfied with their eye care for DED. Forty-eight percent expressed optimism regarding the long-term prospects of their DED. ConclusionsAlthough the majority of DED patients have positive perspectives on their disease, close to half report a lack of optimism regarding the long-term outlook for their condition.

Report of the Inaugural Meeting of the TFOS i2 = initiating innovation Series: Targeting the Unmet Need for Dry Eye Treatment

On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i2 = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i2 meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i2 meeting.

Dry eye disease (DED): A major public health problem

Dry eye disease (DED) is a multifactorial condition, which is complex to both diagnose and treat. Knowledge of how to define and diagnose different types of DED has increased in the last 5 to 6 years, but still, outdated methods and a obsolete way of looking at the problem obstruct many patients in obtaining the right diagnosis and treatment. By keeping updated with new research and reports, medical staff can provide the right diagnoses, information and treatment to patients suffering from DED. To define and diagnose DED involves taking a thorough anamnesis, using correct examination of the eye in a proper order. This article aims to give their readers a better understanding of DED and how to define, diagnose and treat dry eye.

Diagnosis and treatment of dry eye disease: an overview

Dry eye disease (DED) is a multifactorial condition that is complex to diagnose and treat. Our knowledge of how to define and diagnose different types of DED has increased over the last five to six years, but outdated or obsolete methods of looking at the problem prevent many patients from getting the correct diagnosis and treatment. By keeping up to date with new research and reports, healthcare professionals can provide the right diagnosis, information and treatment to patients suffering from the condition. To define and diagnose DED involves taking a thorough history and performing an examination of the eye. This article aims to provide a better understanding of DED and advice on how to define and diagnose DED correctly.

P2Y2 receptor agonists for the treatment of dry eye disease: a review

Recent advances in the understanding of dry eye disease (DED) have revealed previously unexplored targets for drug therapy. One of these drugs is diquafosol, a uridine nucleotide analog that is an agonist of the P2Y2 receptor. Several randomized controlled trials have demonstrated that the application of topical diquafosol significantly improves objective markers of DED such as corneal and conjunctival fluorescein staining and, in some studies, tear film break-up time and Schirmer test scores. However, this has been accompanied by only partial improvement in patient symptoms. Although evidence from the literature is still relatively limited, early studies have suggested that diquafosol has a role in the management of DED. Additional studies would be helpful to delineate how different subgroups of DED respond to diquafosol. The therapeutic combination of diquafosol with other topical agents also warrants further investigation.

Obvious, non‐obvious MGD and new therapy options &amp; the German perspective on MGD

AbstractPurpose The concept of meibomian gland dysfunction (MGD) has drastically changed during the last century. Obstructive MGD has often few or no symptoms although an atrophic process proceeds inside the gland tissue. This conceivably most frequent form of MGD is called non‐obvious MGD or NOMGD.Methods A literature review on MGD together with own findings is discussed in order to explain the different types of MGD and new options for their diagnosis and treatment.Results Historically, MGD was thought to have purulent hypersecretion with ouvert inflammation. Since a few decades it has occurred that MGD also includes obstructive, hyposecretory forms, that had escaped attention because of less obvious symptoms. In fact this represents the vast majority of disease and results from stasis due to hyperkeratinization of the ducts and hardened secretum. It often leads to a still borderline normal tear film and hence symptoms only occur due to environmental stress like air condition, video terminal work or contact lenses. The term MGD was coined only 30 years ago when apparently normal patients became symptomatic after fitting of a contact lens. The diagnosis of tear film lipid deficiencies and the removal of hardened secretum by physical measures require new diagnostic and therapeutic approaches and instruments but may offer, for the first time, a causative approach to dry eye diseaseConclusion Recognition of MGD with tear film instability due to lipid deficiency and with atropic gland destruction has lead to a paradigm shift in the understanding of dry eye disease and to new developments in diagnostics and therapy. This requires new sophisticated forms of lipid layer diagnostics and physical therapy together with addition of lipids to tear substitutions.

Systane lubricant eye drops in the management of ocular dryness.

The understanding of dry eye disease has advanced recently through increasing recognition that the etiology of the condition involves both tear evaporation and insufficient tear production, and that tear film instability and inflammation play roles in the various stages of the disease. Of significance, it has been recognized that lipid layer thickness correlates with tear film stability. The management of dry eye involves various strategies and therapeutic approaches that address one or more etiopathological components of the disease. The purpose of this review is to outline the characteristics and clinical utility of the Systane® ocular lubricants that contain hydroxypropyl-guar and one or both of the demulcents, ie, polyethylene glycol 400 and propylene glycol. Clinically, these products are safe and are indicated for the temporary relief of burning and irritation due to dryness of the eye. In particular, this review describes the formulations, mechanisms of action, and clinical utility of the newest additions to this topical ocular lubricant family, Systane Ultra® and Systane Balance®. Both of these ocular products are formulated with an intelligent delivery system and both provide symptomatic relief to patients with dry eye. However, Systane Balance is a novel formulation that contains both polymer and lipid components designed to protect the ocular surface and replenish tear film lipids simultaneously, a factor that is of particular relevance to patients who have dry eye associated with meibomian gland dysfunction.

Dry Eye Disease as an Inflammatory Disorder

Purpose: Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression.Methods: A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED.Results: New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs.Conclusions: Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

Definition &amp; classification of dry eye

Abstract Purpose: To provide a contemporary definition and comprehensive classification of dry eye disease. Methods: A literature search and a consensus process involving members of the Definition and Classification subcommittee and the DEWS membership. Results: A new definition of dry eye was developed, reflecting the current understanding of dry eye disease. The committee recommended a three part classification comprising i. Aetiology ‐ accommodating the multiple causes of dry eye, ii. Mechanism, indicating how the several causes of dry eye may act through a common pathway, and, iii. Severity, offering a rational basis for therapy in an individual case. In the course of discussions certain principles were established, such that ocular surface health is maintained by a functional unit whose integrity is essential for surface homeostasis. Interruption of the regulatory feedback loops, for instance by reducing the sensory drive to lacrimal secretion, is a potential risk factor for dry eye. Further, it was stressed, that any form of dry eye may interact with and exacerbate any other forms of dry eye, as part of a vicious circle, and that, in time, a change in tissue reactivity may be established leading to a disease which is self‐perpetuating in the absence of its original trigger. Conclusions: The guidelines presented are not intended to override the clinical assessment and judgment of an expert clinician but should prove helpful in the conduct of in clinical practice and research.

Immune modulated inflammation of the ocular surface — a change of paradigm in the understanding of dry eye disease

Immune based inflammation represents an important new approach to the understanding of dry eye disease and is able to cause a negative feedback on protective mechanisms of the ocular surface.

Dry eye disease as a complex dysregulation of the functional anatomy of the ocular surface. New concepts for understanding dry eye disease

Dry eye disease is a disorder of the tear film that results in epithelial damage and in a disruption of the normal homeostasis at the ocular surface. It is widespread and causes symptoms ranging from discomfort to blindness. A review of the existing literature was used to compare different past and recent concepts for the understanding of dry eye disease with a focus on aspects of the integrating functional anatomy of the ocular surface. The understanding of the pathogenesis of dry eye disease has proceeded from the mere recognition of a lack of tears to a consideration of their quality and to the concept of wetting of the ocular surface. However, several other aspects as epithelial differentiation, innervation, hormonal status or immune protection contribute to the intact functional anatomy of the ocular surface. Recently it has been recognized that immunologically regulated mechanisms of inflammation represent a primary or secondary pathogenetic factor for dry eye disease. This is conceivably regulated by the cells of the physiological mucosal immune defence system, the eye-associated lymphoid tissue (EALT). Androgens represent an important trophic factor for the ocular surface and their deficiency predisposes to inflammation. Dry eye disease represents a complex dysregulation of the functional anatomy of the ocular surface that can start from different alterations (e.g. insufficient secretion, defects in wetting or innervation). Immune-based inflammation is able to interconnect and negatively reinforce these different pathomechanisms, resulting in a vicious circle.