Approach ConsiderationsEarly detection and aggressive treatment of dry eye syndrome (DES), or keratoconjunctivitis sicca (KCS), may help prevent corneal ulcers and scarring. The frequency of follow-up care depends on the severity of the signs and symptoms.

Although supplemental lubrication is the mainstay of treatment for mild and moderate aqueous-deficient DES, any concomitant lid disease must also be treated. The use of topical cyclosporine has been shown to enhance the production of the aqueous component of the tear layer, as well as increase goblet cell density. The use of oral omega-3 fatty acids has beneficial anti-inflammatory properties that aid in the production of tears.

Other forms of treatment include the use of plugs that block the puncta (the hole that drains the tears on the lid). Temporary punctal occlusion may be accomplished with collagen (dissolvable) or silicone (permanent) plugs; if these are ineffective, electrocauterization of the puncta may be performed. In some cases, other surgical options may be considered.

Environment-related issues that may exacerbate the DES should be discussed; alternatives may be needed.

Treatment of very severe DES or DES associated with a connective tissue disorder (CTD), including Sjögren syndrome (SS), should be coordinated with an internist or a rheumatologist.

DEWS treatment recommendations

The Management and Therapy Subcommittee of the International Dry Eye WorkShop (DEWS) reviewed the Delphi Panel (the Dry Eye Preferred Practice Patterns of the American Academy of Ophthalmology and the International Task Force Delphi Panel on Dry Eye) approach to the treatment of dry eye and suggested some modifications.[18] The DEWS treatment recommendations are stratified according to the severity of the disease.

level 1 treatment consists of the following:

Education and environmental or dietary modifications Elimination of offending systemic medications Preserved artificial tear substitutes, gels, and ointments Eyelid therapy

If level 1 treatment is inadequate, level 2 measures are added, including the following:

Nonpreserved artificial tear substitutes Anti-inflammatory agents Tetracyclines (for meibomitis or rosacea) Punctal plugs (after inflammation has been controlled) Secretagogues Moisture chamber spectacles

If level 2 treatment is inadequate, level 3 measures are added, including the following:

Autologous serum or umbilical cord serum Contact lenses Permanent punctal occlusion

If level 3 treatment is inadequate, level 4 treatment, consisting of the administration of systemic anti-inflammatory agents, is added.

Agents that have been used to treat DES include the following:

Artificial tear substitutes Gels and ointments Anti-inflammatory agents -Topical cyclosporine, [3, 4] topical corticosteroids, or topical or

systemic omega-3 fatty acids (omega-3 fatty acids inhibit the synthesis of lipid mediators and block the production of interleukin [IL]-1 and tumor necrosis factor alpha [TNF-α])

Topical or systemic tetracyclines Secretagogues - Diquafosol (approved in Japan [5, 6] but not in the United States) Autologous or umbilical cord serum Systemic immunosuppressants

Lubricating supplements are the medications most commonly used to treat DES. If these agents are to be used more frequently than every 3 hours, preservative-free formulations are the treatment of choice. If a patient has SS, the use of systemic immunosuppressants should be considered.

Prescribe artificial tears, preferably preservative-free artificial tears, and a lubricating ointment. Mild DES cases can be treated with drops 4 times a day; more severe cases call for more aggressive treatment, such as drops 10-12 times a day. Thick artificial tear drops or gels can also be used in more severe cases, although these agents tend to blur the vision. Tear ointments can be used during the day, but they are generally reserved for bedtime use because of the poor vision after placement.

Patch with lubrication at night. Place an artificial tear insert into the inferior cul-de-sac every morning.

A randomized, double-masked, vehicle-controlled clinical study evaluated the efficacy and safety of 2 different concentrations of cyclosporine (1% and 0.05%) in aqueous solution compared with vehicle. At day 21 (noted as early in the trial), statistically significant improvement in 4 symptoms and 3 ocular signs were observed when cyclosporine 1% was administered, and equivalent improvement in 3 symptoms and 3 ocular signs was observed when cyclosporine 0.5% was used.[19]

In a 2012 study, diquafosol and sodium hyaluronate showed similar efficacy in improving fluorescein staining scores of dry eye patients and diquafosol was superior in improving rose bengal staining scores. There was no significant difference between groups in adverse event rates.[20]

Specially made glasses known as moisture chamber spectacles, which wrap around the eyes to retain moisture and protect against irritants, may be helpful in some cases of DES.

Contact lenses may be helpful; these are available in the following types:

Silicone rubber lenses Gas permeable scleral-bearing hard contact lenses with or without fenestration Highly oxygen-permeable lenses (overnight wear)

Punctal plugs are often employed in the treatment of DES. Available types include the following:

Absorbable plugs – These plugs are made of collagen or polymers and either dissolve by themselves or may be removed by saline irrigation; occlusion duration ranges from 7 to 180 days

Nonabsorbable plugs – These plugs are made of silicone; 2 main categories of silicone plugs are available for dry eye, punctal plugs and intracanalicular plugs

Thermoplastic plugs (eg, SmartPLUG; Medennium, Irvine, CA) – These plugs is made of a thermosensitive, hydrophobic acrylic polymer that changes from a rigid solid to a soft, cohesive gel when its temperature changes from room temperature to body temperature

Hydrogel plugs (eg Oasis Form Fit; Sigma Pharmaceuticals, Monticello, IA)A study by Mataftsi et al found that punctal plugs offer an effective and safe treatment for children with persistent symptoms and should be considered.[21]

If mucous strands or filaments are present, they should be removed with forceps, and 10% acetylcysteine should be administered 4 times a day. In general, surgical treatment of DES is reserved for very severe cases in which ulceration or impending perforation of the sterile corneal ulcer occurs.

Surgical options include the following:

Sealing of the perforation or descemetocele with corneal cyanoacrylate tissue adhesive Corneal or corneoscleral patching for an impending or frank perforation Lateral tarsorrhaphy - Temporary tarsorrhaphy (50%) is indicated in patients with DES

secondary to exposure keratitis after facial nerve paralysis and after trigeminal nerve lesions that give rise to DES secondary to loss of corneal sensation

Conjunctival flap Surgical occlusion of the lacrimal drainage system [22]

Mucous membrane grafting Salivary gland duct transposition Amniotic membrane transplantation

In a study of punctal occlusion surgery using a high heat-energy–releasing cautery device to treat severe DES and recurrent punctal plug extrusion, Ohba et al concluded that the device was associated with a low recanalization rate and demonstrated improvements in ocular surface wetness and visual acuity.[23]

In patients with dry eyes, close the puncta. If plugs are not available or are repeatedly lost, cautery or hyfrecation is indicated for permanent closure, beginning with the lower puncta and then proceeding to the upper if necessary.

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. For treatment of dry eye syndrome (DES), or keratoconjunctivitis sicca (KCS), artificial tears are administered with and without preservatives, depending on severity. Doxycycline 100 mg daily or twice daily may be given for meibomian gland dysfunction (MGD) if indicated. Topical cyclosporine 0.05% ophthalmic emulsion has proved to be an effective treatment for DES.

In addition to the list below, serum eye drops are unpreserved, are nonantigenic by nature, and contain growth factors, fibronectin, immunoglobulins, and vitamins at concentrations similar to (or higher than) those in tears. Serum eye drops are used for severe DES with punctate epithelial defects and corneal damage to promote reepithelialization. They can be used successfully in patients refractory to other forms of treatment.