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

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.

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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

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

Purpose:To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution of patients with aqueous-deficient or evaporative subtype of DED.Methods:Schirmer tests and meibomian gland dysfunction (MGD) (Foulks–Bron scoring) were evaluated in both eyes of 299 normal s

Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study.

PurposeTo evaluate the safety and effectiveness of the LipiFlow System compared to the iHeat Warm Compress (WC) for adults with meibomian gland dysfunction (MGD).MethodsThis was a non-significant risk, prospective, open-label, randomized, crossover multicenter clinical trial. One hundred thirty-nine

http://journals.lww.com/corneajrnl/Documents/A_New_System,_the_LipiFlow,_for_the_Treatment_of.pdf

A new system, the LipiFlow, for the treatment of meibomian gland dysfunction.

This review presents the rationale and supporting data for a recent paradigm shift in our understanding of meibomian gland dysfunction (MGD). The historical understanding of MGD has been that of an infectious hypersecretory disorder with obvious signs of inflammation, hypersecretion, and purulent excreta. The current understanding of MGD now includes the polar concept of a less obvious or nonobvious type of hyposecretory obstructive MGD, where inflammation and other signs of pathology may be absent unless special examination techniques are employed. A new term, nonobvious obstructive MGD (NOMGD), is used to describe what may be the most common form of obstructive MGD. Obstructive MGD is an area of growing importance because obstructive MGD is now recognized to be the most common cause of evaporative dry eye, and because NOMGD seems to be the precursor to obvious obstructive MGD, it is also an important area to understand. The prevalence of NOMGD seems to be very high but currently significantly underdiagnosed. This review presents the relevant anatomy and physiology, concepts of obstructive MGD, the usual absence of inflammation in obstructive MGD, nomenclature and classification of obstructive and NOMGD, clinical diagnosis of NOMGD emphasizing the necessity for diagnostic expression, the use of a new instrument for diagnostic expression providing a standardized method of assessing meibomian gland functionality, the complementary roles of the aqueous and lipid layers, and the specific treatment of NOMGD, emphasizing that the success of treatment of all forms of obstructive MGD is dependent on the relief of the obstruction.

Nonobvious obstructive meibomian gland dysfunction.

PURPOSE To evaluate the long-term rate of progression of keratoconus in eyes implanted with Intacs (Addition Technology Inc) at 5-year follow-up. METHODS Data of 105 eyes from 85 patients who had undergone consecutive Intacs implantation between January 2001 and December 2005 were studied retrospectively for progression of keratoconus. Progression of keratoconus was defined as an increase in steep keratometry (K) of ≥ 1.00 diopter (D) over 4 years between 1- and 5-year follow-up. All eyes were categorized into three subgroups: eyes with documented preoperative progression (change in steep K ≥ 1.00 D over 12 months preoperatively), eyes with documented absence of preoperative progression, and eyes with no record of preoperative progression. RESULTS Ninety-two eyes were available for analysis. Overall, 91.3% (84/92) of eyes demonstrated no progression between 1- and 5-year follow-up. In the sub-group analysis, 92.9% (52/56) of eyes with documented preoperative progression demonstrated no progression. Additionally, no statistically significant differences were noted in mean steep, flat, and average keratometry; manifest refraction spherical equivalent; and uncorrected and corrected distance visual acuity (P>.05) between 1- and 5-year follow-up. CONCLUSIONS Results of our study demonstrate the long-term stability of refractive and topographic outcomes following Intacs implantation in eyes with keratoconus. The finding that 92.9% of eyes with progressive keratoconus did not progress postoperatively indicates that Intacs implantation may be a potential therapeutic option to halt progressive keratoconus.

Refractive and topographic stability of Intacs in eyes with progressive keratoconus: five-year follow-up.

Purpose The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD). Methods This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining. Results In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53), SPEED score (11.00±3.30 to 5.42±2.15), TBUT (6.26±2.01 to 8.44±1.81), corneal staining (0.38±0.50 to 0.12±0.33) and conjunctival staining (1.69±1.93 to 0.62±0.85). In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91), SPEED score (13.42±4.17 to 9.42±5.47) and conjunctival staining (2.38±1.88 to 1.13±1.51), but the improvement in TBUT (6.90±2.56 to 7.59±2.03) and corneal staining (0.21±0.41 to 0.13±0.34) was not statistically significant (p=0.262 and p=0.414, respectively). At 3 months, SPEED score was significantly better in the VTP group (p<0.05); other parameters were comparable between the two groups. Conclusion A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single VTP presents a favorable alternative to long-term antibiotic use.

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Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

Purpose To measure the effects from a single vectored thermal pulsation treatment of the meibomian glands on dry eye signs and symptoms in patients who tested positively versus negatively for novel Sjogren's syndrome (SS) biomarkers. Methods The retrospective study included the deidentified data of 102 eyes of 59 patients with dry eye and meibomian gland dysfunction (MGD), who were also tested for novel biomarkers for SS and underwent a single 12-minute LipiFlow thermal pulsation procedure. All patients were already being treated with individualized dry eye therapy but remained symptomatic. Meibomian gland secretion (MGS) scores, Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores and tear breakup times (TBUTs) before and 8 weeks after thermal pulsation treatment were analyzed. Results Twenty-three patients tested positive for novel biomarkers of SS and 36 patients tested negative. At baseline, MGS, SPEED and TBUT of both SS-positive and SS-negative patients were equivalent. At 8 weeks' post-treatment, mean MGS score, SPEED and TBUT were 13.0±7.8, 12.5±6.8 and 9.6±4.6, respectively, in SS-positive patients and 15.9±7.9, 10.0±6.3 and 8.3±4.6, respectively, in SS-negative patients (P 0.05). Conclusion LipiFlow treatment in MGD patients who were SS-positive for novel biomarkers of SS demonstrated improvement in signs and symptoms of dry eye. While improvement in MGS scores in SS-negative patients was higher than that observed in SS-positive patients, SPEED and TBUT were equivalent between these two groups.

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Meibomian gland dysfunction patients with novel Sjögren's syndrome biomarkers benefit significantly from a single vectored thermal pulsation procedure: a retrospective analysis.

Raman Bedi

Papers

A new system, the LipiFlow, for the treatment of meibomian gland dysfunction.

Nonobvious obstructive meibomian gland dysfunction.

Refractive and topographic stability of Intacs in eyes with progressive keratoconus: five-year follow-up.

Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

Meibomian gland dysfunction patients with novel Sjögren's syndrome biomarkers benefit significantly from a single vectored thermal pulsation procedure: a retrospective analysis.