Dry eye syndrome is an ubiquitous ophthalmic condition effecting as many as 80% of the population over the age of 80.1 The ageing of the general population has highlighted a whole series of problems relating to qualitative and quantitative changes in the three layered ocular surface tear film. The tear film constitutes a clear uniform layer assisting the undistorted transmission of light rays, protecting the underlying structures and the feeling of normality2 achieved by reducing sensations from the richly innervated surface tissues. The syndrome is also expressed as a potentially debilitating condition afflicting in particular certain segments of the population such as contact lens wearers, individuals who have had refractive surgery, peri menopausal women and those subject to a variety of autoimmune conditions. More than 10% of the population demonstrates tear film abnormalities.3 Despite its pervasiveness, adverse life style and job performance associations, and overall direct and indirect financial impact, improvement in diagnostic and therapeutic modalities has not been forthcoming. The morbidity is significant but only a very small number of those afflicted are associated with severe blinding pathology and thus many may perceive the condition as an annoyance rather than a true public health problem which needs to be addressed.

Our appreciation of the larger division of dry eye disease into aqueous deficient and evaporative related effects has not resulted in refinement of the physiopathology of the disease into well-defined subgroups or the development of targeted therapeutic modalities. Tear osmolarity may help to differentiate normal from dry eyes but despite relatively sophisticated measurement techniques remains a gross tool with limited utility to further classify the disease. A combination of subject symptoms and less than objective clinical tests continues to constitute the basis for generic diagnosis. Schirmer strips, invasive tear break-up time testing and surface staining techniques remain unchanged. New questionnaires are developed but patient responses continue to be subject to the vagaries of subject reporting. While we recognise the importance of inflammatory, environmental and numerous other factors, the natural history and evolution of the specifics and their interaction in the dry eye syndrome remain obscure.3 ,4 To what extent are genetic predisposition, gender and comorbid disease entities related to the onset and progression of dry eye disease?

The mainstay of physician directed therapy continues to be over the counter artificial tear substitutes. The more recently advocated mild anti-inflammatory, cyclosporine, has not been associated with any precise therapeutic mode of action. Since we now have a number of tools to study biological effects, we now recognise and have identified cytokines, inflammatory mediators and other proteins which contribute to the inflammatory component of the disease. External factors such as occupation, geography, environment and systemic medications play a role. Yet, therapeutic options have not increased appreciably.

Drug companies now rely heavily upon marketing techniques to promote their over the counter products. The agents being utilised are those long identified as not harmful in a decades old, FDA approved monograph. Thus, the search for new compounds with demonstrated scientific validity has assumed a lower priority. The truly objective association of ocular surface findings with subject symptoms and functional capacity has remained obscure.

Despite the paucity of objectively valid clinical diagnostic and therapeutic modalities, there is widespread agreement that dry eye syndrome represents an increasing problem, particularly in view of the ageing population. A number of scientists work diligently in ocular surface translational research laboratories throughout the world. Is this the long awaited harbinger of future progress?

One area of intense interest relates to the question of environmental influence. The construction of chambers capable of mimicking and maintaining environmental conditions has been an important development. Carrying the concept one step further has seen the ability to independently vary temperature, humidity and air flow to create artificial environments in which patient evaluation can occur. Furthermore, adverse environmental conditions enable the evaluation of the challenged ocular surface. Controlled adverse effects are highly useful in evaluating the efficacy of topical therapy. Yet, the use of these chambers while promising has not been associated with the ability to ascribe the results of traditional testing with modifications in subject symptoms or improved efficacy of treatment evaluations.

The development of ancillary technology applied to the ocular surface has been an area of promise in the objective analysis of ocular surface dynamics. Thus, non-invasive and totally objective techniques have led to the creation of a whole new field of interest which utilises sophisticated optical techniques rather than the century old biomicroscope.5 Ocular surface metrology applies techniques developed in other disciplines for objective analysis of the tear film. Optical coherence tomography, refined for the ocular surface, enables the capture of micron-resolution images. Thus, the possibility of simultaneous measurement of the tear film thickness and volume. Utilising wave front analysis, an off shoot of astronomy, we are now able to recognise the precise moment of tear film break-up as well as its spatial location. The quality of the image presented to the macula can be monitored as it evolves over the ocular surface during the blink cycle. Measuring the polarised images reflected from the ocular surface ellipsometry now enables measuring of the lipid layer and calculation of its refractive index.6 We can associate four groups of lipids of varying thickness with subgroups of meibomian gland dysfunction. Homogeniety and heterogeneity of lipid coverage can be visualised as the lipid layer is reformed during the blink cycle. An enhanced thermal camera coupled with special software enables dynamic thermal imaging of a variety of points or areas on the ocular surface. By observing ocular surface rate of change in a controlled environment situation the impact of evaporation on tear film stability can be evaluated.

Further manipulation of these technologies and deploying them in multimodal fashion will surely enable observation of the interaction of a variety of factors occurring simultaneously over the ocular surface within each blink cycle. The addition of a controlled and variable venue for the performance of these studies will constitute a valuable tool in our effort to unravel the multifactorial relationships which characterise dry eye syndrome.

The ultimate goal however is to develop a series of new products which can be deployed on an individual basis to treat targeted aspects of the overall disease.

In the December issue of British Journal of Ophthalmology, Drs Liew, Zhang, Kim and Akpec have correctly called attention to the association of autoimmune mediated pathology as expressed in Sjögren's Syndrome to ocular surface disease.7 A high index of suspicion enables the eye physician to make an appropriate diagnosis. Their work also demonstrates the potential life threatening association of lymphoma. Ocular surface disease is clearly more than an annoying condition.