Complex processes drive ocular surface disease

Take home message: Ocular surface disease and health are affected by numerous interactions and cascades with complex mechanisms in disease states.

By Lynda Charters; Reviewed by James McCulley, MD

Dallas-When it comes to ocular surface health, there are many interactions and cascades. The disease states have complex mechanisms.

“There is no simple approach to pathophysiology or treatment in dry eye disease,” said James McCulley, MD, professor and chairman, Department of Ophthalmology, University of Texas Southwestern Medical School, Dallas.

More in this issue: Point-of-care testing may improve accuracy of dry eye diagnosis

“The irony is that the more we learn about this disease, the more we realize how little we truly know,” he added.

Ocular surface disease and health are driven by integrated complex processes with numerous interactions and cascades with complex mechanisms in disease states.

A recent investigation at the University of Texas Southwestern Medical School, Dallas, showed that in patients with chronic blepharitis with associated aqueous deficient dry eyes no bacterial pathogen could be identified.

However, the study did find evidence of bacterial lipolytic exoenzyme activity with a decrease in critical polar lipids with associated excessive aqueous tear evaporation and meibomian gland drop out.

NEXT: Continued

When Dr. McCulley began to delve into this area of research more than four decades ago, he found that patients with chronic blepharitis often had superficial punctate epithelial erosions. This was especially true of the patients with meibomianitis and seemed to be secondary to a tear lipid abnormality and not staphylococcal exotoxins.

Though this observation resulted in extended research funding by the National Eye Institute/National Institutes of Health, there is still no surgical treatment available for these patients, Dr. McCulley noted.

In their later work, in the early 1980s, Dr. McCulley and colleagues published a classification of chronic blepharitis (Ophthalmology 1982;89:1173-1180)-staphylococcus, seborrhea (alone, with staphylococcal superinfection, with meibomian seborrhea, or with secondary meibomianitis), primary meibomianitis, meibomian gland dysfunction with seborrhea sicca, and others such as atopic, psoriatic, and fungal causes.

Dr. McCulley recently focused his research to identify an association among the different types of chronic blepharitis, changes in meibomian secretions, and underlying causes of aqueous deficiency in dry eyes.

Initially, he and his colleagues classified patients with chronic blepharitis based on his classification system. The investigators then cultured lid and conjunctival cul-de-sac aerobic and anaerobic pathogens and assessed the frequently recovered bacteria for production of lipolytic exoenzymes.

They also performed in-depth lipid biochemical analyses of the meibomian sections of each patient, determined the presence of associated aqueous deficient dry eyes clinically, measured the tear evaporative rate using an evaporometer, and performed meibography to assess the anatomic changes in the meibomian glands.

NEXT: Dr. McCulley reported the following key findings...

·      the only statistically significant bacterium identified was Staphylococcus aureus in the staphylococcal and mixed staphylococcal/seborrheic groups;

·      coagulase-negative staphylococcus and S. aureus frequently produced lipolytic exoenzymes that can break down meibomian gland secretions;

·      chemical analysis of meibum showed a complex of nonpolar and polar lipids with statistically significant decreases in splingomyelin and phosphatidylethanolamine in patients with associated aqueous deficient dry eyes;

·      all patients with associated aqueous deficient dry eyes had excessive aqueous tear evaporation and meibomian gland drop out compared with normal patients.

This analysis resulted in one unexpected observation, according to Dr. McCulley, namely, that 25% to 50% of all types of patients with chronic blepharitis had keratoconjunctivitis sicca with possible contributions from hyposecretion, hyperevaporation, and/or molecular surface toxicity.

He cited a detergent effect of OXFFA, FUFA, PA on the lipid layer leading to loss of integrity and a direct detergent effect on epithelial cell membrane leading to cell death and dry spot formation with inflammation and possible contribution to an aqueous deficient dry eyes component.

James McCulley, MD

E: james.mcculley@utsouthwestern.edu

Dr. McCulley has no financial interest in any aspect of this report.