Treatment for Severe Disease

Severe Dry Eye Syndrome

Patients with severe dry eye syndrome (DES), particularly that associated with Sjögren syndrome or other autoimmune disorders, require more advanced treatment. The oral secretagogues pilocarpine and cevimeline are two cholinergic agents that act as muscarinic receptor agonists. They counteract the inhibition of exocrine gland function effected by Sjögren syndrome autoantibodies directed against muscarinic receptors. Both pilocarpine and cevimeline have documented efficacy for DES, and therapeutic failure of one oral secretagogue does not predict failure of the other. Biological tear substitutes (i.e., eye drops containing biological fluids similar in composition to tears) are another option for patients with severe DES. Autologous serum is particularly useful, as it is rich in components found in tears, including nutrients, vitamins and growth factors. For patients who cannot tolerate repeated blood sampling (or who have conditions, such as systemic inflammation, that may preclude it), allogeneic serum is an option, although caution must be exercised in case a foreign antigen immune response is mounted. Platelet preparations, including platelet-rich plasma, may also be used; they have higher growth factor levels but lower fibronectin and vitamin content compared to serum. The efficacy of blood-based products in reducing DES-associated signs and symptoms is evidentially supported in patients with Sjögren syndrome. Another useful and effective approach for patient with severe DES is the use of rigid gas-permeable scleral lenses (i.e., lenses that rest on the sclera and completely enclose the cornea). However, fitting, insertion and removal difficulties may limit compliance. In some cases, soft lenses may be appropriate, but carry a higher risk of infection. Other medications compounded into drops or ointments have been used with varying degrees of reported success, including dapsone, spironolactone, topical hormones, tacrolimus, albumin, n-acetyl cysteine and amniotic membrane placement or amniotic membrane extract in the form of drops.

If all of the above approaches fail to provide sufficient improvement, the remaining options include longer-term topical glucocorticoid use and surgery. Surgical punctal occlusion (punctal cautery) should be attempted only if punctal plugs fail to achieve the desired improvement. It is achieved by thermal or laser cautery of the puncta, and is difficult to reverse. Punctal cautery should generally be performed in a stepwise fashion, one punctum at the time per eye per session. Human amniotic membrane grafts (now commercially available in cryopreserved or dried form) may also be used to reverse epithelial scarring common in severe DES. Finally, other surgical procedures such as a limited tarsorrhaphy (i.e., suture of the upper and lower eyelids) and minor salivary gland transplantation (i.e., transplantation of a portion of the patient’s labial mucosa to their conjunctival fornix), may provide symptomatic relief in selected cases.