may have developed, and the medication should be discontinued.

While the recommended dosage is one drop twice daily, we have had patients who, for economic or other reasons, reported using one drop daily without any recurrence of symptoms. It is expected that at some point after discontinuation of the medication, or reduction to some subthreshold dosage, surface disruption, inßammation and the full cycle will recur, but reports of such long-term follow-up and experimentation are not yet available.

Similarly, whether the early introduction of Cyclosporine-A therapy in patients easily controlled without this medication will prevent progression represents an interesting question that should be addressed in future studies.

As already mentioned, dry eye syndrome in general, waxes and wanes over the years, clearly progresses in some, but the risk and rate of progression is not now predictable, as no controlled longitudinal studies have been reported. SjšgrenÕs syndrome patients, with their documented autoimmunity, might represent an excellent cohort for such a controlled study.

12.4.2.4 Level 4

In Level 4 disease, the symptoms are severe enough to create major changes and limitations in a patient’s lifestyle and visual functioning.

More severe signs and symptoms represent Level 4, characterized by marked punctate staining of the cornea, often involving the central area. Filamentary keratitis may also be noted in advanced and generally much more symptomatic cases. Filaments of desquamated epithelial cells are noted dangling on the cornea. Patients exhibiting these Þlaments usually have marked pain, chronic irritation, and photophobia.

At this level of disease, careful reconsideration of all possible co-existent and contributory eye disorders must be made.

A co-existent blepharitis, for example, should be treated aggressively with systemic tetracyclines as well as all topical measures including lid hygiene and compresses.

Punctal occlusionÑOne must also consider at this point temporary or permanent punctal plugs.

Generally, punctal occlusion is one of the most dramatic and helpful interventions in the treatment of moderate-to-severe dry eye in appropriate candidates.

By blocking the puncta and canaliculi, drainage of applied lubricantsand whatever natural tears occur can be reduced substantially, if not eliminated, providing signiÞcant and quick relief.

While it has been reported that punctal occlusion should not be performed prior to the initiation of Cyclosporine-A therapy topically for fear of accumulating a reservoir of toxic cytokines and inßammatory by-products that would exacerbate the condition, for generations, punctal occlusion has been carried out without beneÞt of this immunomodulator.

The concern of the rare initial exacerbation is rendered somewhat moot, as most clinicians prescribe topical Cyclosporine-A, plus or minus steroids, prior to punctal occlusion as part of the generally accepted escalation of therapy indicated by signs and symptoms.

When the extent of disease warrants the most aggressive intervention, all therapies, punctal occlusion, and the initiation of topical steroids with cyclosporine, along with ancillary daytime artiÞcial tears and nighttime ointments, can be initiated and continued simultaneously.

Severe corneal staining, often widely conßuent, associated with possible erosions and even some conjunctival scarring may be noted upon examination.

Treatment in such instances consists of adding to the aforementioned aggressive therapy serious consideration of systemic anti-inflammatory and immunomodulatory agents in co-operation with the treating rheumatologist.

More obvious and effective ocular protection such as

¥Snugly fitting moisture goggles,

¥The constant use of humidifiers in the patientÕs immediate environment

¥Partial tarsorrhaphy (surgically closing the temporal and sometimes the medial portions of the eyelids to limit the exposed area) may now be acceptable to the patient, given the severity of symptoms and disability.

Be aware that some eye care professionals recommend bandage contact lenses for dry eye patients.

These soft contact lenses canÑin theoryÑ serve as a reservoir of lubricating ßuid as well as a possible evaporation barrier.

In our experienceÑand we believe it conforms with general experience in ophthalmology practices unless the patients have quite mild dry eyesÑthese lenses easily dry themselves and may present more of an irritant and potential stimulus to infection.

A particular type of bandage lens called the Boston Lens is an expensive moisturizing lens that may be used in selected patients with severe corneal problems and must be carefully followed by an ophthalmologist skilled in their use.

Contact lenses in general must be used with extreme caution in dry eye patients. Even if well tolerated, corneal hypesthesia may be present and the risks of corneal erosions and increased susceptibility to serious corneal infection exist.

AgainÑlast but not leastÑin the most extreme instances of dry eye syndrome, particularly in those with known vasculitis, as in SjšgrenÕs syndrome or advanced rheumatoid disease, a definite but fortunately remote risk of corneal melting and perforation exists.

While a microperforation or an area of dangerous thinning might not be immediately apparent without biomicroscopy, if suspected based on a sudden change in symptoms or vision, or a reported leak or burst of ßuid from the eye, or a shallow or absent anterior chamber, such a patient should be referred immediately to an ophthalmologist.

Sealing of perforations with ophthalmic glue and reinforcement of thin areas with autologous or donor cornea or sclera may be necessary as an emergency operative procedure to save an eye otherwise destined for blindness and a potential nidus of infection for systemic spread.

There are a variety of new compounds and approaches to therapy in the pipeline that we can hopefully anticipate adding to our arsenal in the future (studies currently in progress are listed on http://www.clinicaltrials.gov).

¥Topical picrolimus (a drug similar to tacrilimus)

¥Topical Voclosporin (LX214), a compound similar to cyclosporine)

¥Topical soft steroid eye drops such as Lotemax, which are used for short duration

¥An adenosine A3 receptor agonist (CF101)

¥Rebamipide topical drops, an agent used previously to augment gastric mucin content

¥Diquafosol (INS 365), a purine P2Y2 agonist that reached late-stage clinical trial, which was designed to help transport water directly across the conjunctival membrane

¥Topical androgens have been examined

However, while some preliminary studies and anecdotal reports suggest that these agents may be helpful, and in reasonable recommended doses seem harmless, the deÞnitive evidence has yet to appear.

12.5Practical Suggestions for the Selection of Artificial Tears

12.5.1 Types of Artificial Tears Available

Rheumatologists and ophthalmologists generally initiate therapy by reaching into their pharmaceuticals sample cabinet and seeing what samples of artiÞcial tears that they have available. Alternatively, they initiate therapy by telling the patient to go to the local pharmacy or grocery store and pick up an assortment of artiÞcial tears to try.

However, upon following our own suggestion, we were struck by the bewildering array of choices that confront the patient in the Òeye careÓ aisle of the pharmacy or grocery store (Fig. 12.2). These products differ in terms of content and price.

A partial listing of artiÞcial tears in alphabetical order is provided in Table 12.1. A partial listing of artiÞcial tears based on the ingredient is provided in Table 12.2.

In addition to the wide variety of brands available, many of artiÞcial tears with similar sounding names and descriptions come in mild,

moderate, and severe or intensive formulationsÑ terms that refer to the relative viscosity of each preparation. Also, tears may come in branded form that are more expensive than the generic or store brand. However, it is extremely difÞcult to compare the brand versus the generic. Thus, Table 12.3 lists the basic components of artiÞcial tears.

The polymer component determines the viscosity of the tear, which the patient may describe as how long the tear lasts. The preservative in the tears may also contribute to the tolerability of the tear.

A literature search reveals relatively few crossover studies that compare different artiÞcial tear preparations, and most of these trials are short-term trials.

12.5.2General Guidelines for the Dry Eye Patient

We generally start with a selection of branded artiÞcial tears that patients have told us are tolerated (Table 12.4). As guidelines listed in Table 12.5, we emphasize to patients that:

¥Treatment is a trade-off between preserved tears (that are cheaper) and non-preserved