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Anti-inflammatory therapy improves signs and symptoms of dry eye
Dysfunction of the lacrimal gland/ocular surface unit results in ocular surface inflammation.
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HOUSTON — Basic and clinical research during the past decade has provided a bounty of insight into the pathogenesis of dry eye. Three concepts regarding dry eye have become clear in this time, according to Stephen C. Pflugfelder, MD, of the Baylor College of Medicine here.
“Dry eye results from dysfunction of an integrated lacrimal gland/ocular surface functional unit; ocular surface inflammation is a common feature of dry eye disease; and anti-inflammatory therapies improve signs and symptoms of dry eye,” he said.
Lacrimal gland dysfunction
The first concept is that dry eye re sults from dysfunction of an integrated lac rimal gland/ocular surface functional unit.
“Stimulated trigeminal afferent sensory nerves on the ocular surface synapse with efferent parasympathetic secretor motor fibers in the brain stem that innervate the lacrimal gland. Stimulation of this reflex arc results in delivery of tear fluid onto the ocular surface on demand,” Dr. Pflugfelder said.
The most severe keratoconjunctivitis sicca is associated with loss of the ability to reflex tear. Dry eyes are associated with decreased corneal sensation that blunts the afferent arc.
“Patients with Sjögren’s syndrome have been reported to have serum antibodies against lacrimal gland cholinergic receptors blunting the efferent arc. Cholinergic blockade in mice induces severe dry eye,” he said.
Dr. Pflugfelder reported on a comparison of aqueous tear production measured by the Schirmer eye test versus the severity of keratoconjunctivitis sicca measured by rose bengal staining. The comparison indicated that people with Schirmer eye test scores less than 10 mm could be stratified into two groups: those with mild and severe rose bengal staining.
“More than 90% of the group with severe rose bengal staining have lost the ability to reflex tear in response to sensory stimulation,” he said.
In the past 2 years, two groups have reported that up to 80% of patients with Sjögren’s syndrome have circulating antibodies against M3 acetylcholine receptors in their lacrimal gland. “When these antibodies bind to the receptor, it blunts the efferent limb,” Dr. Pflugfelder said.
Ocular surface inflammation
The second concept regarding dry eye pathogenesis is that ocular surface inflammation is a common feature of dry eye disease.
“We now know that both aqueous tear deficiency and meibomian gland disease result in ocular surface inflammation,” Dr. Pflugfelder said.
“Evidence for this inflammation in cludes increased concentration and reactive oxygen species in the tear fluid; in creased concentration in activity of proteolytic enzymes such as the elastase, plasmin and matrix metalloproteinase 9; and increased expression of immune ac t ivation markers in the conjunctiva. Also, there is an inflammatory cell infiltrate in the conjunctival epithelium and stroma.”
In normal eyes, expression of HLA class 2 antigen is limited only to the dendritic Langerhans antigen presenting cells on the conjunctival surface. In dry eyes, there is strong aberrant expression of HLA antigens on all the conjunctival epithelial cells, according to Dr. Pflugfelder.
Many of these immunopathologic findings are induced by inflammatory cytokines. A number of pro-inflammatory cytokines have been detected in either the tear fluid or the conjunctival epithelium of patients with dry eye disease, including IL-1 alpha and beta, IL-6, IL-8 and tumor necrosis factor alpha.
Many of the stresses created on the ocular surface in the dry eye lead to increased production and release of IL-1. These include apoptosis, increase in shear forces, hyperosmolarity, which is a common feature of all dry eye disease, free radicals and other pro-inflammatory factors.
Anti-inflammatory therapy
The final concept regarding dry eye research is that anti-inflammatory therapy has improved both the signs and symptoms of dry eye disease.
“Corticosteroids have been reported to improve signs and symptoms of dry eye, to improve tear clearance and to normalize ocular surface mucous production. Patients often have a sustained benefit from just a 2-week pulse treatment with topical corticosteroids,” Dr. Pflugfelder said.
The immune modulatory agent cyclosporine has also been shown to be effective in treating dry eye.
“In meta-analysis, phase 3 clinical trials of 0.5% and 1% cyclosporine showed statistically significant differences in artificial tear use with a decrease in the treated patients, an increase in goblet cell density, a decrease in corneal fluorescein staining, an increase in Schirmer test scores and an improvement in blurred vision symptoms,” he said.
A note from the editors
Dr. Pflugfelder is a recognized expert in the area of dry eyes. His comments are based on his research and vast clinical experience. My clinical experience mirrors his suggestions. The use of steroidal anti-inflammatory medications in patients with dry eyes helps control the symptoms that often plague our patients. I often use this when lubrication alone is not sufficient to control severe symptoms. Further studies may indicate if anti-inflammatory and immunosuppressive medications play a positive role in the early form of the disease to keep the ocular surface from progressive pathologic changes. If I use steroids I monitor patients carefully for potential side effects such as infections, increased intraocular pressure and melts.
Eduardo Alfonso, MD
OSN Board Member
For Your Information:
- Stephen C. Pflugfelder, MD, can be reached at the Cullen Eye Institute, 6565 Fannin, Houston, TX 77030; (713) 798-4944; fax: (713) 798-8739.