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 undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

TFOS DEWS II Management and Therapy Report

Recommended definition of MGD: Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease.

Previous definitions and criteria of MGD: There is no firmly established definition of MGD published in the literature. Most researchers have used a criterion-based approach to describe the condition, with combinations of objective findings and measurements. Anatomic changes of the lid margin, expressibility of meibomian lipids, gland dropout by meibography, evaporimetry, and meibometry are most commonly used (Table 1).



Table 1.

Criteria of Meibomian Gland Dysfunction Used in Previous Works

The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee

Diagnostic tests of meibomian gland dysfunction (MGD) and of MGD-related disorders are based on the demonstration of abnormal anatomy and physiology of the glands and the detection of specific pathologic events. For this reason, this subcommittee report is divided into two sections. In part I, those aspects of meibomian anatomy and physiology that are relevant to currently available tests are described; a fuller account of the anatomy and physiology is provided in the report of the Anatomy Subcommittee of this workshop. In part II, each test and its performance is described in detail. In part III, the practical application of selected tests is summarized and recommendations for future approaches are made. Additional recommendations and a summary of pertinent literature and concepts are presented in Appendices 1 to 17.

/pdf/the-international-workshop-on-meibomian-gland-dysfunction-34ddby5km8.pdf

The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcommittee

The goals of the subcommittee were to review the current practice and published evidence of medical and surgical treatment options for meibomian gland dysfunction (MGD) and to identify areas with conflicting, or lack of, evidence, observations, concepts, or even mechanisms where further research is required. To achieve these goals, a comprehensive review of clinical textbooks and the scientific literature was performed and the quality of published evidence graded according to an agreed on standard, using objective criteria for clinical and basic research studies adapted from the American Academy of Ophthalmology Practice Guidelines1 (Table 1). It should be noted that, in many of the clinical textbooks and previous reports, terminology is often interchanged and the management of anterior and posterior blepharitis and/or meibomitis is often considered concurrently. Thus, a broad scope of documents was reviewed in this process. Consistency in terminology and global adoption of the term “meibomian gland dysfunction” would significantly aid clinical research and clinical care in MGD going forward.



Table 1.

Grading Level of Evidence of Clinical and Basic Research Studies1

/pdf/the-international-workshop-on-meibomian-gland-dysfunction-27326ftgov.pdf

The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction.

Aim: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD).

Methods: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy.

Results: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported.

Conclusion: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment.

https://bjo.bmj.com/content/bjophthalmol/86/12/1403.full.pdf

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device.

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

Disposable eyelid-warming device for the treatment of meibomian gland dysfunction.

PURPOSE To evaluate our newly developed infrared heater (IRH) and compare it to a broad-spectrum heater (BSH) for warming the eyelids. MATERIALS AND METHODS Ten normal subjects were enrolled in this study. All measurements were recorded in a room with temperature 23 degrees C, 40% humidity, and no wind. The IRH is composed of two hard eye patches that have light-emitting diodes (LEDs) emitting near-infrared radiation. We first compared the temperature rises in the cornea, lacrimal gland, and eyelids after warming through closed eyelids with the IRH for 5 and 10 min. Next, we compared warming with the IRH or BSH for 30 min. We then used the IRH for 5 min with the eyes open to confirm its safety. Finally, we determined subjective feeling after warming the eyes. RESULTS Direct comparison of 5 versus 10 min of warming with the IRH showed no significant differences in temperature rises in the upper eyelid (p = 0.09). The IRH caused significantly more heating (p < 0.05) than did the BSH everywhere except the cornea. The temperatures never rose above 37.7 degrees C for either heater during 30 min or with the IRH with the eyes open for 5 min. The subjects' comfort level rose significantly (p < 0.05) after treatment with the IRH. CONCLUSIONS Our study showed the efficacy and safety of warming the eyelids with a newly developed IRH. Only 5 min is necessary to increase ocular temperature and enhance comfort.

Efficacy and safety of infrared warming of the eyelids

AIMS—To determine the relation between dry eye and Meige's syndrome.
METHODS—325 patients with dry eye were divided into those responsive to topical and other forms of treatment (n=276) and those who were not (n=49). A neuropsychiatric examination was performed to check for Meige's syndrome in the latter group.
RESULTS—Twenty eight (57%) of the treatment unresponsive patients were diagnosed with Meige's syndrome.
CONCLUSIONS—There is a subgroup of patients with dry eye who do not respond to simple therapy. More than half of these patients have Meige's syndrome and need psychiatric, as well as ophthalmic, care.

https://bjo.bmj.com/content/bjophthalmol/81/6/439.full.pdf

Asako Mori

Papers

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device.

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

Disposable eyelid-warming device for the treatment of meibomian gland dysfunction.

Efficacy and safety of infrared warming of the eyelids

Dry eye and Meige’s syndrome