Conjunctivochalasis (CCh) is defined as a redundant, nonedematous conjunctiva, typically located below the bulbar conjunctiva interposed between the eyeball and the lower eyelid. Clinically, conjunctival folds, which generally affect elderly people, are a frequent cause of chronic ocular discomfort, such as irritation, epiphora, dryness, and blurred vision. Information regarding the pathogenesis of CCh is scanty and conflicting.
1
Hughes
2 considers the formation of conjunctival folds to be a senile change. This involves the loss of subconjunctival connective tissue, leading to a loss of adherence of the bulbar conjunctiva to the sclera and a more superficial inferior fornix. Abnormalities in extracellular conjunctival components, such as degeneration of elastic fibers or increased collagenolytic activity, have also been reported. In contrast, Meller et al.
1,3 and Li et al.
4 have suggested that elastotic degeneration could be exacerbated by the presence of inflammation at the ocular surface. They report that inflammatory cytokines such as IL-1β and TNF-α in tear can in principle be derived from the cornea, and may be responsible for the increased levels of MMPs in cultured fibroblasts, derived from CCh patients. Tumor necrosis factor α and other interleukins, such as IL-1 and IL-6, are liberated immediately after an aggression to the eye and are considered to be “pro-inflammatory.” Pflugfelder et al.
5 have reported an increase in the levels of IL-1α and IL-1β and coexpression with MMP-9 in the tears of patients with Sjögren's syndrome. These molecules are interrelated since IL-1β, a potent inductor of inflammation at the ocular surface, is activated extracellularly by proteases such as trypsin, plasmin, elastase, cathepsin-9, and MMP-9. Of all these proteins, MMP-9 is the enzyme that is the quickest and most effective in transforming IL-1β from its inactive to its active form. These findings suggest that both IL-1 and MMP-9 are implicated in inflammatory processes on the ocular surface, in such a way that a cytokine-mediated inflammation cycle is produced.
6 In an earlier study of our group, we have found that some proteins are overexpressed in tear from CCh patients compared with controls; these include MMP-9, IL-1β, and IL-6, which are all involved in inflammation, degradation, and remodeling processes.
7
Conjunctivochalasis is characterized by a redundant bulbar conjunctiva and delayed tear clearance. This delayed clearance may be a consequence of a tamponade effect of the conjunctival folds on the lacrimal punctum, an obstruction at the level of the tear meniscus, a concomitant lid laxity, or a combination of all these factors.
8 Jordan and Pelletier,
9 using a dye clearance test, have observed fluorescein retention in a patient with CCh, suggesting the presence of a functional blockade of tear clearance. We have studied the effect of removing the redundant conjunctiva and re-establishing tear clearance and its effects in the concentration of pro-inflammatory enzymes in tears. The accumulation of extracellular matrix–degrading enzymes in tears may contribute to the pathogenesis of this disease, since MMPs are a family of enzymes that participate in tissue remodeling
10–12 and, pathologically, they cause disruption or disintegration of extracellular matrices.
13–16 In the cornea, MMP-9 is the primary matrix-degrading enzyme produced by basal corneal epithelial cells
17 and neutrophils
18 and is known to degrade the major components of the epithelial basement membrane, such as collagen type IV
19 and VII,
20 and to impede re-epithelialization of the cornea.
21 This enzyme has been implicated in the early phase pathology of some diseases such as peripheral ulcerative keratitis,
22,23 corneal erosions,
24 rosacea,
25 pterygium,
26 and keratoconus.
27 Since tear film MMP content and clinical evidence of pathology progression have been reported to be correlated, it has been suggested that the zymographic visualization of these enzymes in tears could be reliably used to monitor disease activity.
28 Zymography is a frequently used technique, since most MMPs are secreted as inactive zymogens (pro-MMPs) that require extracellular matrix components for their activation.
29
This study was designed to evaluate the efficacy of surgical treatment for this disease, by monitoring pro–MMP-9 levels in the tears as a marker related with inflammation and degradation of connective tissue before and after surgery and the correlation of these levels with clinical signs and symptoms.