The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

TFOS DEWS II Diagnostic Methodology report

The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjogren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.

TFOS DEWS II pathophysiology report

The members of the Management and Therapy Subcommittee assessed current dry eye therapies. Each member wrote a succinct evidence-based review on an assigned aspect of the topic, and the final report was written after review by and with consensus of all subcommittee members and the entire Dry Eye WorkShop membership. In addition to its own review of the literature, the Subcommittee reviewed the Dry Eye Preferred Practice Patterns of the American Academy of Ophthalmology and the International Task Force (ITF) Delphi Panel on Dry Eye. The Subcommittee favored the approach taken by the ITF, whose recommended treatments were based on level of disease severity. The recommendations of the Subcommittee are based on a modification of the ITF severity grading scheme, and suggested treatments were chosen from a menu of therapies for which evidence of therapeutic effect had been presented.

Management and therapy of dry eye disease: Report of the management and therapy subcommittee of the international Dry Eye WorkShop (2007)

Impaired functional visual acuity of dry eye patients

The tear film lipid layer is the major barrier to evaporation from the ocular surface A decrease in its thickness or functional integrity may cause evaporative dry eye (EDE) Obstructive meibomian gland dysfunction (MGD) is the most common cause of EDE and occurs as a primary disorder or secondary to acne rosacea, seborrheic or atopic dermatitis, and with cicatrizing conjunctival disorders, such as trachoma, erythema multiforme, and cicatricial pemphigoid MGD may be an incidental finding in asymptomatic eyes, or it may be responsible for irritative lid symptoms in the absence of dry eye MGD-dependent EDE is diagnosed on the basis of a defined degree of MGD in a symptomatic patient showing typical ocular surface damage in the absence of an aqueous tear deficiency When MGD occurs in a background of aqueous tear deficiency (ATD), then an additional evaporative component may assumed, depending on the extent of meibomian obstruction However, definitive criteria are not yet established The clinical severity of dry eye is greatest when ATD and EDE occur together, particularly in Sjogren syndrome A hypothesis is proposed to explain the steps leading to primary, simple MGD and subsequent EDE

The contribution of meibomian disease to dry eye.

Objective: To study patterns of eye blinking in normal subjects and patients with dry eye. Methods: We developed an automated, noninvasive blink monitor that permits quantitative analysis of 6 parameters of blinking. We used this method under normal conditions and then examined the effects on the patterns of blinking in patients with dry eye; several steps in this method were designed to exacerbate or ameliorate ocular surface desiccation. Results: The mean (±SD), maximum, and coefficient of variation of the interblinking time in normal subjects and patients with dry eye were 4.0±2.0 and 1.5±0.9 seconds, 8.9±4.0 and 4.2±2.4 seconds, and 55%±21% and 65%±24%, respectively. Those values for the blinking time were 0.20±0.04 and 0.27±0.16 seconds, 0.35±0.12 and 0.99±1.30 seconds, and 23%±9% and 46%±34%, respectively. The use of artificial tears or spectacles with moist panels and moist inserts tended to normalize the patterns of blinking in the patients with dry eye, whereas exposure to wind made them more abnormal. Conclusions: Our technique permitted a rigorous analysis of blinking that was previously unavailable. We have shown that local ocular surface conditions alone can significantly affect patterns of blinking. This method should be applicable to studying psychologic and any other factors that may influence blinking.

https://jamanetwork.com/journals/OPHTH/articlepdf/641677/archopht_114_6_012.pdf

Yukio Okusawa

Papers

Quantitative Videographic Analysis of Blinking in Normal Subjects and Patients With Dry Eye

Use of high-speed, high-resolution thermography to evaluate the tear film layer