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 tarsal glands of Meibom (glandulae tarsales) are large sebaceous glands located in the eyelids and, unlike those of the skin, are unassociated with hairs. According to Duke-Elder and Wyler,1 they were first mentioned by Galenus in 200 AD and later, in 1666, they were described in more detail by the German physician and anatomist Heinrich Meibom, after whom they are named.

Lipids produced by the meibomian glands are the main component of the superficial lipid layer of the tear film that protects it against evaporation of the aqueous phase and is believed also to stabilize the tear film by lowering surface tension.2 Hence, meibomian lipids are essential for the maintenance of ocular surface health and integrity.

Although they share certain principal characteristics with ordinary sebaceous glands, they have several distinct differences in anatomy, location, secretory regulation, composition of their secretory product, and function.

Functional disorders of the meibomian glands, referred to today as meibomian gland dysfunction (MGD),3 are increasingly recognized as a discrete disease entity.4–8 In patients with dry eye disease, alterations in the lipid phase that point to MGD are reportedly more frequent than isolated alterations in the aqueous phase. In a study by Heiligenhaus et al.,9 a lipid deficiency occurred in 76.7% of dry eye patients compared with only 11.1% of those with isolated alterations of the aqueous phase. This result is in line with the observations by Shimazaki et al.10 of a prevalence of MGD in the absolute majority of eyes with ocular discomfort defined as dry eye symptoms. These observations noted that 64.6% of all such eyes and 74.5% of those excluding a deficiency of aqueous tear secretion were found to have obstructive MGD, or a loss of glandular tissue, or both.10 Horwath-Winter et al.11 reported MGD in 78% of dry eye patients or, if only non-Sjogren patients are considered, in 87% compared with 13% with isolated aqueous tear deficiency. It may thus be accepted that MGD is important, conceivably underestimated, and possibly the most frequent cause of dry eye disease due to increased evaporation of the aqueous tears.5,9–12

After some excellent reviews of MGD4,7,8,13,14 in the past, many new findings have been reported in recent years, and other questions remain to be identified and resolved. A sound understanding of meibomian gland structure and function and its role in the functional anatomy of the ocular surface15 is needed, to understand the contribution of the meibomian glands to dysfunction and disease. Herein, we seek to provide a comprehensive review of physiological and pathophysiological aspects of the meibomian glands.

/pdf/the-international-workshop-on-meibomian-gland-dysfunction-1rohh1kg6i.pdf

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland

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

Purpose: To develop current treatment recommendations for dry eye disease from consensus of expert advice. Methods: Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. Results: A new term for dry eye diseasewas proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. Conclusion: Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.

Dysfunctional tear syndrome: a Delphi approach to treatment recommendations.

Scientists have been interested in studying the secretions of the meibomian glands for many years, 1– 8 and diseases associated with the meibomian glands (e.g., cancers, posterior blepharitis) have been noted in the medical literature since at least the early part of the 20th Century. 9 –13 However, the term “meibomian gland dysfunction” (MGD) was only introduced by Korb and Henriquez in 1980. 14 The terminology “meibomian gland disease” was later introduced by Bron et al. 15 as an umbrella term to indicate any disease affecting the meibomian glands (see Definition and Classification). Although the etiology of MGD may differ from that of aqueous-deficient dry eye disease (which is due to insufficient lacrimal gland production), the two conditions share many clinical features, including symptoms of ocular surface irritation and visual fluctuation, altered tear film stability, and potential ocular surface compromise. When MGD is of sufficient degree, it may give rise to the second major subtype of dry eye disease, evaporative dry eye. 16 These subtypes are not mutually exclusive, as has been acknowledged. 16

/pdf/the-international-workshop-on-meibomian-gland-dysfunction-4juj8iwm2r.pdf

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on the Epidemiology of, and Associated Risk Factors for, MGD

Objective: To assess subjective symptoms, tear func- tion factors, and ocular surface morphology in the clinical course of patients with dry eye syndrome under treatment within an observation period of up to 8 years. Methods: In 97 patients (78 women and 19 men) with ocular discomfort, a clinical diagnosis of dry eye syn- drome was made based on typical symptoms and a re- ducedtearfilmbreakuptimeoflessthan10seconds.Sub- sequent evaluations revealed a diagnosis of aqueous tear deficiency in 9 patients, meibomian gland dysfunction in32patients,andaqueousteardeficiencycombinedwith meibomianglanddysfunctionin30patients,aqueoustear deficiency associated with Sjogren syndrome in 12 pa- tients,andaqueousteardeficiencyandmeibomiangland dysfunction associated with Sjogren syndrome in 14 pa- tients. Follow-up assessments were performed 12 to 94 months (mean follow-up, 40 months) after the initial di- agnosis. Main Outcome Measures: In different subgroups of dry eye tear film breakup time, Schirmer test with- out local anesthesia (Schirmer I), fluorescein and rose bengal staining, impression cytology, as well as subjec- tive dry eye symptoms and frequency of tear substitute application were compared at baseline and after a fol- low-up of 1 to 8 years (mean, 3.3 years). Results: At baseline, tear film function and ocular sur- facetestresultsfoundmorepathologicabnormalitiesand more severe subjective symptoms in patients with aque- ousteardeficiencyassociatedwithSjogrensyndromeand aqueous tear deficiency and meibomian gland dysfunc- tion associated with Sjogren syndrome compared with the other groups who had dry eye syndrome. No differ- encesinfrequencyoftearsubstituteapplicationwereob- served. At follow-up, tear breakup time, Schirmer I test results, and corneal fluorescein staining improved com- pared with baseline values, whereas rose bengal stain- ing and impression cytology of the conjunctival surface remained almost unchanged. Subjective symptoms and frequency of artificial tear application were reduced.

https://jamanetwork.com/journals/jamaophthalmology/articlepdf/415735/ecs20250.pdf

Evaluation of the Clinical Course of Dry Eye Syndrome

Background: Many patients with essential blepharospasm also show dry eye signs and symptoms. Botulinum toxin A is an effective treatment for reducing spasms in these patients. In this investigation, the effect of botulinum toxin A injections on tear function and on the morphology of the ocular surface in patients suffering from blepharospasm in combination with a dry eye syndrome was investigated.

Methods: Botulinum toxin A injections were applied to 16 patients with blepharospasm. All patients complained of dry eye symptoms and had reduced tear break up time values. A subjective questionnaire and ocular examinations including tear break up time, Schirmer test without local anaesthesia, and rose bengal staining were evaluated before, 1 week, 1 month, and 3 months after injection. Impression cytology was performed before, 1 month, and 3 months after botulinum toxin A treatment.

Results: Although all patients were relieved of blepharospasm after botulinum toxin injections, only three noticed an improvement in dry eye symptoms. Eight patients noticed no difference and five complained of worsening. Tear break up time was found to be increased 1 week and 1 month after injections. Schirmer test measurements were reduced up to 3 months. Rose bengal staining slightly increased 1 week after injections. Impression cytology showed no definite change in conjunctival cell morphology 1 month and 3 months after botulinum toxin A injections.

Conclusion: In the patients presented here suffering from blepharospasm and dry eye, botulinum toxin A injections were effective in relieving blepharospasm but were not successful in treating dry eye syndrome.

https://bjo.bmj.com/content/bjophthalmol/87/1/54.full.pdf

Botulinum toxin A treatment in patients suffering from blepharospasm and dry eye

.


Purpose: Patients with dermatochalasis often complain of dry eye symptoms. In a prospective study, the influence of upper eyelid blepharoplasty on dry eye symptoms, tear film parameters and ocular surface morphology was evaluated.



Methods:  Patients with upper eyelid dermatochalasis were studied before and 3 months after upper eyelid blepharoplasty. Changes in ocular symptoms and physical examinations such as tear film break-up time, Schirmer test without local anaesthesia, impression cytology of the bulbar conjunctiva and inflammatory reaction were recorded.



Results:  Subjective dry eye symptoms were found in 11 patients (46%) preoperatively and in five patients (21%) postoperatively. Objective dry eye signs were present in eight patients (33%) before blepharoplasty and in nine patients (38%) 3 months postoperatively. Morphological findings did not change within the observation period. The inflammatory reaction shown by impression cytology decreased postoperatively.



Conclusion:  Blepharochalasis may be associated with dry eye. Blepharoplasty might be a means of alleviating dry eye symptoms. The reason for this subjective alleviation might be due to reduced inflammatory reaction, changes in blink mechanism or the fact that patients are more confident about their appearance.

https://onlinelibrary.wiley.com/doi/pdf/10.1034/j.1600-0420.2003.00064.x

Ingrid Floegel

Papers

Evaluation of the Clinical Course of Dry Eye Syndrome

Botulinum toxin A treatment in patients suffering from blepharospasm and dry eye

A conservative blepharoplasty may be a means of alleviating dry eye symptoms.

Acute multifocal placoid pigment epitheliopathy-like lesion as an early presentation of subacute sclerosing panencephalitis

Einseitige Chorioretinitis unklarer Genese