Ординатура / Офтальмология / Английские материалы / Dry Eye and Ocular Surface Disorders_Pflugfelder, Beuerman, Elliot Stern_2004

actually had a detectable bacterial infection. Also in 1991, Bron introduced an extensive clinical classification system for meibomian gland disease based on the clinical appearance of the lid margin [27].

While no universally accepted system for classifying and grading meibomian gland dysfunction currently exists, the relationship between meibomian gland dysfunction and blepharitis has become the central issue. Supplementing this are other aspects such as allergic phenomena and inflammation secondary to bacterial infection, and dermatological conditions such as rosacea, seborrheic dermatitis, and atopy.

X.TREATMENT OF MGD

Meibomian gland dysfunction and related blepharitis is a disease complex with many potential causes. In any individual, the disease may originate with one or more of these causes. Multiple genetic factors for dermatological diseases, lipase activity, and lipid composition can combine with allergies, hormonal influences, and other pathological processes to influence an individual’s disease. Notwithstanding these complexities, most individuals fall into some recognizable pattern or group displaying identifiable problems with common characteristics. This allows development of treatment regimens based on identification of these pathological mechanisms.

Inflammation clearly plays a central role. We may approach the relief of symptoms and treatment of meibomian gland dysfunction first by suppressing inflammation on the ocular surface and then by treating rosacea (if present), reducing the pathological effects of bacterial overgrowth on the lid margin, improving lipid function by reducing lipase activity, and treating any concomitant dry eye. We will consider these general approaches by analyzing each of the treatment modalities currently available. Many treatments have multiple mechanisms of action, while others may still be poorly understood.

Although inflammation is often present with meibomian gland dysfunction, it may be difficult to assess the degree of inflammation involved. Many clinical signs of eyelid inflammation, such as injection and edema, are reasonably easy to identify. Less severe inflammation, though perhaps not easily recognized, may still be clinically significant and should be treated. Topical steroids were generally avoided in the past, since the long-term use of such agents carried a relatively high risk of side effects. Newer compounds, such as loteprednol, have been found to be relatively free of such effects and are still reasonably effective at suppressing surface inflammation [87]. Short-term use of more potent agents may also be considered. Other approaches that treat inflammation should also be considered. Specially compounded topical cyclosporine has been used to treat ocular surface inflammation for years despite being unavailable commercially. An FDA-ap- proved cyclosporine emulsion (Restasis, Allergan, Inc.) is now available [88–90].

Systemic tetracyclines, especially doxycycline and minocycline, have a number of effects that are useful in treating meibomian gland dysfunction. These compounds decrease lipase production, and consequently, fatty acid production [91]. They also suppress inflammation through their ability to retard leukocyte migration [92]. Oral tetracycline decreased nitrous oxide synthesis and reactive oxygen species (ROS) by phagocytic leukocytes [93]. Minocycline inhibits phospholipase 2 activity by interacting with its substrate [94]. There is also evidence that tetracyclines inhibit keratinization [95]. Doxycycline is a potent inhibitor of many matrix metalloproteinases, which may explain some of its antiinflammatory properties [96]. Very low doses appear to be effective, especially if given over a sufficiently long period of time, usually many months, and the effects linger for a long time after cessation of the drug. Systemic tetracyclines are very useful in the treatment of rosacea, although somewhat higher doses may be necessary to treat rosacea than are needed for obstructive meibomian gland disease [43,97]. Topical metronidazole may also be helpful [98].

The role of essential fatty acids, particularly the alpha-3-omega fatty acids found in fish oil and flax seed oil, has received attention following reports of decreased dry eye with high-fish diets [99]. Anecdotal reports suggest that the anti-inflammatory action of these compounds may improve both meibomian gland disease and dry eye symptoms [100]. Following oral ingestion, these essential fatty acids are not secreted in breast milk and may not alter meibomian secretions except through their anti-inflammatory action [101,102].

Physical cleansing of the lid margin, frequently referred to as lid scrubs, is generally acknowledged to be helpful, but the mechanism is not fully understood. Part of the effectiveness probably derives from the removal of bacteria and associated toxins and from the partial expression of lipid which opens clogged meibomian gland ducts [103,104]. Overzealous cleansing should be avoided because it induces inflammation [105]. Short-term topical antibiotics may provide some benefit by decreasing bacterial populations [106].

Dry eye and meibomian gland dysfunction are closely associated [45,48,72]. Meibomian gland dysfunction may cause or exacerbate dry eye through neuronal feedback to the lacrimal gland [52]. Thus, it is important to treat both meibomian gland dysfunction and dry eye, since treating one condition will often help the other. Punctal occlusion, nonpreserved artificial tears and mist, and the use of pilocarpine derivatives as tear stimulants are often helpful [107–110].

XI. SUMMARY

1.Meibomian glands, located in the upper and lower lids, secrete over 100 different lipids, including cholesterols, fatty acids, wax esters, and polar lipids that comprise the lipid layer of the tear film.

2.The innervation and diverse neuropeptides found around meibomian glands suggest that they are under complex neural control.

3.The lipid layer serves primarily to decrease tear film evaporation to a rate about 5% of that expected in the absence of a lipid layer. It also stabilizes the tear film, helping to maintain a smooth optical surface.

4.Any loss of meibomian gland function, whether from gland dropout or meibomian gland dysfunction (MGD), may increase tear evaporation.

5.A complex relationship exists between dry eye and MGD. Low tear production and accumulation of inflammatory products resulting from dry eye can lead to hyperkeratinization of the lid margin and MGD. Conversely, surface inflammation caused by MGD-induced excessive evaporation may be communicated by the neural feedback loop to the lacrimal glands, decreasing their function and exacerbating dry eye.

6.Therapies for MGD are mostly directed toward controlling inflammation, including topical cyclosporine emulsion, short-term topical steroids, and systemic tetracyclines. Lid scrubs are usually helpful, if performed gently to avoid inducing inflammation. Concommitant treatment of dry eye is important because of its close association with MGD.

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