The aim of the DEWS Definition and Classification Subcommittee was to provide a contemporary definition of dry eye disease, supported within a comprehensive classification framework. A new definition of dry eye was developed to reflect current understanding of the disease, and the committee recommended a three-part classification system. The first part is etiopathogenic and illustrates the multiple causes of dry eye. The second is mechanistic and shows how each cause of dry eye may act through a common pathway. It is stressed that any form of dry eye can interact with and exacerbate other forms of dry eye, as part of a vicious circle. Finally, a scheme is presented, based on the severity of the dry eye disease, which is expected to provide a rational basis for therapy. These guidelines are not intended to override the clinical assessment and judgment of an expert clinician in individual cases, but they should prove helpful in the conduct of clinical practice and research.

The definition and classification of dry eye disease: Report of the definition and classification subcommittee of the international Dry Eye WorkShop (2007)

The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Central to the scheme is a positive diagnosis of DED with signs and symptoms, and this is directed towards management to restore homeostasis. The scheme also allows consideration of various related manifestations, such as non-obvious disease involving ocular surface signs without related symptoms, including neurotrophic conditions where dysfunctional sensation exists, and cases where symptoms exist without demonstrable ocular surface signs, including neuropathic pain. This approach is not intended to override clinical assessment and judgment but should prove helpful in guiding clinical management and research.

TFOS DEWS II Definition and Classification Report

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

Background The Stevens–Johnson syndrome, ocular pemphigoid, and thermal or chemical burns can cause scarring and opacification of the cornea and loss of vision. Transplantation of epithelial cells from the limbus of the contralateral cornea can restore useful vision. However, this procedure requires a large limbal graft from the healthy eye and is not possible in patients who have bilateral lesions. Methods We took specimens of limbal epithelial cells from the healthy contralateral eyes of six patients with severe unilateral corneal disease. The epithelial cells were cultured and expanded on amniotic membrane. The amniotic membrane, together with the sheet of limbal epithelial cells, was transplanted to the denuded corneal surface of the damaged eye after superficial keratectomy to remove fibrovascular ingrowth. The mean (±SD) follow-up period was 15±2 months. Results Complete reepithelialization of the corneal surface occurred within two to four days of transplantation in all six eyes receiving transplan...

https://www.nejm.org/doi/pdf/10.1056/NEJM200007133430202

Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells.

Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

AIM—To evaluate the efficacy of autologous serum application for the treatment of dry eye in Sjogren's syndrome.
METHODS—The stability of essential components (EGF, vitamin A, and TGF-β) in preserved serum were examined following preservation at 4°C and −20°C. In a primary clinical trial, 12 patients with Sjogren's syndrome were treated with autologous serum (diluted to 20% with sterile saline) for 4 weeks, and vital staining of the ocular surface was compared before and after treatment. The effects of serum on mucin (MUC-1) expression were observed in cultured conjunctival epithelial cells in vitro.
RESULTS—EGF, vitamin A, and TGF-β were well preserved for up to 1 month in the refrigerator at 4°C and up to 3 months in the freezer at −20°C. Rose bengal and fluorescein scores improved significantly from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks, respectively. The additive effect of human serum for cultured conjunctival epithelial cells showed significant MUC-1 upregulation on the cell surface.
CONCLUSION—Autologous serum application is a safe and efficient way to provide essential components to the ocular surface in the treatment of dry eye associated with Sjogren's syndrome.

Keywords: autologous serum; Sjogren's syndrome; tears ocular surface

https://bjo.bmj.com/content/bjophthalmol/83/4/390.full.pdf

Treatment of dry eye by autologous serum application in Sjögren's syndrome

Meibomian gland dysfunction in patients with Sjögren syndrome

AIMS To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT). METHODS At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure. RESULTS Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjogren’s syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD. CONCLUSIONS Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary.

https://bjo.bmj.com/content/bjophthalmol/83/10/1125.full.pdf

Dry eye after haematopoietic stem cell transplantation.

BACKGROUND--Several studies in the past have attempted to demonstrate the efficacy of sodium hyaluronate in the treatment of dry eyes. However, results have been conflicting and a definite conclusion has not yet been reached. This study recruited a larger group of patients and has incorporated for the first time both fluorescein and rose bengal staining in the evaluation of the epithelium. METHODS--Eighteen albino rabbit corneas were used in a basic animal study to demonstrate the efficacy of sodium hyaluronate by comparing the effects on the rate of epithelial healing. The optimal concentration to be used in the clinical trial was determined from the results of the basic study. In the clinical study 104 patients with dry eye syndrome were enrolled in a double masked controlled clinical trial. Patients received sodium hyaluronate drops in one eye and control medication in the other eye for 4 weeks. Grading of subjective symptoms and clinical examinations were performed at 2 and 4 weeks. RESULTS--In the animal study sodium hyaluronate at concentrations of 0.1% and 0.5% significantly accelerated the recovery time of iodine vapour induced corneal erosions (p < 0.01). In the clinical study no statistical significance was observed in the improvement of subjective symptoms or rose bengal staining, while fluorescein scores significantly improved in eyes receiving sodium hyaluronate (p = 0.0001) at 4 weeks. CONCLUSION--Sodium hyaluronate drops applied in six daily doses could not be demonstrated to offer advantages over conventional tear supplies in the improvement of subjective symptoms, but may play a role in maintaining a healthy corneal epithelium.

https://bjo.bmj.com/content/bjophthalmol/79/11/1007.full.pdf

Masafumi Ono

Papers

Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

Treatment of dry eye by autologous serum application in Sjögren's syndrome

Meibomian gland dysfunction in patients with Sjögren syndrome

Dry eye after haematopoietic stem cell transplantation.

Sodium hyaluronate eyedrops in the treatment of dry eyes.