Dry eye in a tropical setting

The Fourth International Tear Film and Ocular Surface (TFOS) conference was held between November 17-20 in Puerto Rico, a tropical island that nestles between the chilly north Atlantic Ocean and the warmer waters of the Caribbean Sea. Over 400 scientists, clinicians, and industry representatives attended from countries ranging, geographically and alphabetically, from Australia to Wales. Delegates were indulged with more than 70 lectures and 300 poster presentations, crammed into a very busy schedule.

basic science of dry eye
Anthony Bron, UK, opened the symposium with a review of the basic science of the tear film and clinical understanding of dry eye. In discussing the latter, he emphasised the distinction between tests that diagnose the condition and those that establish its cause.
Debra Schaumberg, US, summarised current epidemiological knowledge of dry eye, noting the influence of age, sex, and other risk factors. Clinically important dry eye occurs in 8 per cent of US women and 5 per cent of US men over the age of 50 years, with less severe and/or frequent occurrences more widespread. The prevalence of dry eye increases with age, nearly doubling between the ages of 50 and 75 years. Women have an approximately two-fold risk compared to men, even greater in those receiving hormonal therapy following menopause.
Additionally, but to a lesser extent, dry eye seems to be more common in individuals with a low dietary intake of omega-3 fatty acids, and even more so when combined with excessive omega-6 fatty acids. Studies, however, conflict over the optimum ratio of these nutrients.
Kazuo Tsubota, Japan, suggested racial differences in the prevalence of dry eye - the condition affects 70 per cent of the elderly Japanese population, which is far higher than data reported previously for other areas of the world. This may be due to the unique diagnostic criteria for dry eye in Japan that does not consider patient symptoms. He also noted that dry eye is not just a disorder of ocular discomfort, but is associated with reduced visual function.
In a study conducted by his research group, there was no difference in visual acuity on eye opening between subjects with the condition and normals, though resolution ability declined more rapidly in the dry eye group with enforced lid opening. This occurred because of time-dependent increases in high-order aberrations/irregular astigmatism reflecting premature break-up of the tear film, demonstrable with corneal topography.
In an extension of this investigation, it was found that during the first week post-Lasik, despite excellent VA immediately following a blink, a profound reduction in vision occurred soon after due to tear film instability. This, in combination with the knowledge that Lasik reduces blink rate, due to changes in corneal sensitivity, and that in normals, blink rate is inversely proportional to speed when driving, suggests that refractive surgery patients should be advised not to drive (particularly not fast) in the early postoperative period.

tear proteomics
In lectures discussing the basic science of the tear film, Ilene Gipson, US, stressed the importance of transmembrane mucins on the ocular surface, in distinction to secreted mucins present in tear fluid. Their hydrophilic extracellular domains render the epithelium wettable by tears and act as a disadhesive; and, in addition to these glycocalyx functions, by virtue of intracellular cytoplasmic tails, are likely involved in cellular signalling.
Franz Grus, Germany, discussed the current status and potential clinical implications of tear proteomics, the analysis of proteins in tears. This field has prospered from the development of techniques that facilitate the analysis of small-sample volumes and the detection of substances at very low concentrations, such as cytokines and neuropeptides. Tear fluid contains more than 400 proteins, with large intersubject variability.
Disease-specific protein biomarkers may aid the diagnosis of ocular and systemic disease, and enable the quantification of treatment efficacy. Ben Glasgow, US, reviewed the multifunctional role of tear lipocalin, one of the major proteins in tears. By binding with lipid it lowers the surface tension of aqueous tears and aids tear stability; moreover, this potent lipid scavenging ability undermines the traditional model of tear break-up involving lipid diffusion down to the ocular surface. Additionally, lipocalin contributes to the non-Newtonian rheology of tears.
The importance of tear proteins in the physiochemical properties of tear fluid were also highlighted by Thomas Millar, US, who presented evidence that tear proteins were largely responsible for the low surface tension of tears, with mucin and lipid combinations having a minor role; and, John Tiffany, UK, who argued that tear rheology was primarily a consequence of loose reversible aggregations between proteins and lipids, with subsidiary contributions from protein-mucin combinations.

genetics of dry eye
Stephen Richards, US, investigating the genetics of dry eye, showed preliminary data that the expression of genes in lacrimal tissue are influenced by gender and levels of circulating androgens (male sex hormones).
In the lacrimal gland, more than 500 genes are affected by sex, and over 2,000 by androgens; with two-thirds of the variation between males and females attributable to differences in androgen levels. These findings explain, at least in part, the significant sex-associated differences known to exist in physiology and pathophysiology of the lacrimal gland. Frank Schirra, US, demonstrated that in addition to lacrimal tissue, meibomian glands are also androgen target organs.
In this study, testosterone (a type of androgen) was shown to enhance lipid biosynthesis, metabolism, and transport.

closed eye tear film
Robert Sack, US, reviewed the closed eye tear film, which differs markedly from that in the open eye environment.
On eye closure, lacrimal flow is diminished, sIgA concentration is increased, complement C3 is activated to C3c, and leukocytes accumulate. This may represent a fundamental shift in host-defence strategy from a largely passive defence, to one that more actively protects the cornea in order to protect it from entrapped microorganisms and general detritus that are no longer flushed from the ocular surface.
However, this state of sub-clinical inflammation increases the vulnerability of the ocular surface to inflammatory and immune-mediated reactions during eye closure, possibly accounting for the relatively high levels of these reactions with overnight wear of contact lenses.

clinical techniques
Regarding clinical techniques, several presentations suggested that there is more diagnostic information to be inferred from tear break-up than simply the time of its occurrence after eye opening.
Carolyn Begley, US, found that the rate of dry spot expansion was faster in subjects with dry eye versus controls, and was better able to differentiate the two groups than TBUT.
Haixia Liu, US, considering the spatial location of tear break-up, reported that a central location was more common in a dry eye group than in controls, in whom a superior location related to thinning at the 'black line', next to the adjacent tear meniscus, was more prevalent.
Moreover, Katrina Wilcox, US, stressed that TBUT must be considered in relation to the interblink interval. She found that short TBUTs are usually associated with short interblink intervals, but that this relationship is disturbed in postmenopausal women, placing them at greater risk of an exposed, unprotected ocular surface.
With regard to the treatment of dry eye, Pasquale Aragona, Italy, showed that a month of oral essential fatty acid treatment (sachets containing 112mg linoleic acid and 15mg gamma-linolenic acid, twice a day) reduced symptoms and fluorescein staining of the ocular surface, but had no statistically significant effect on TBUT, in a group of 40 subjects with dry eye compared to a placebo sachet. This double-blind, randomised, crossover trial was well designed, and supports the notion that dietary supplements may assist management of the condition, at least in a subset of the population.
In view of this research, it may be prudent to advocate a diet high in fish to patients with dry eye; although, one candid delegate noted that, in his part of the world, any benefits such a diet conferred might be outweighed by the increased risk of mercury poisoning.
Ian Pearce, UK, compared an artificial tear-containing lipid to a similar drop, not containing lipid. When instilled, the former was associated with a lower rate of tear evaporation. However, although both drops improved symptoms and TBUT, differences between the drops for these functions were not statistically significant.
Amy Schauberg, US, presented evidence on a promising treatment, Diquafosal (INS365), a purinergic receptor agonist that stimulates transconjunctival water flow and mucin secretion from conjunctival goblet cells. A multicentre, double-blind, placebo-controlled clinical trial found that dry eye subjects treated with this agent obtained greater improvements in corneal staining than placebo.

conclusion
The meeting was closed by Michael Lemp, US, speaking on behalf of the Dry Eye Workshop (DEWS), a group of internationally-recognised experts invited to discuss topics concerning dry eye research. In this lecture, he gave a preliminary account of an ongoing group of meetings that will eventually produce a new definition and classification of dry eye, and an extensive report reviewing current and new diagnostic methodologies with recommendations for their incorporation into clinical practice and clinical trial design.
With this exciting prospect, and minds teeming with ideas, delegates dispersed to mull over what was said and seen, until the next Tear Film and Ocular Surface conference, to be held in four years time.

 Michael Johnson is an optometrist in private practice and a senior optometrist at Bristol Eye Hospital