LASIK-induced neurotrophic epitheliopathy (LINK)

(The most severe cases of post-Lasik dry eye.)
from: http://www.revoptom.com/index.asp?ArticleType=SiteSpec&Page=osc/105700/lesson.htm

Etiologies:

• The “neural feedback loop theory.” Corneal nerve fibers are disrupted during creation of the LASIK flap and stromal ablation --> interferes with the cornea-central nervous system-lacrimal gland regulatory loop -->reduced corneal sensitivity causes a decreased blink rate and diminishes reflex tear production. The combination of these two factors increases the time the cornea is unprotected by the tear film.
  


• Goblet cell damage. A normal lipid layer is necessary to prevent evaporation of the tear film. Likewise, a normal mucin layer is critical to a healthy ocular surface. However, prolonged microkeratome pressure can damage conjunctival goblet cells, disrupting the normal tear film composition. The resultant unstable mucin layer will decrease the tear film break-up time and increase dry eye symptoms.


• Change in corneal curvature. While the change in curvature provides better vision, it also affects how the tear film overlays the cornea. The change in tear function is evident months after surgery. It presents as iron-stained epithelium.


• Osmolarity changes and exposure keratopathy. Studies have also shown an incomplete blink in patients following LASIK, which results in osmolarity changes and potential exposure keratopathy.


• Type of ablation. Hyperopic ablations affect the tear film more than myopic ablations. Specifically, the tear film has more trouble overlaying the steeper cornea following hyperopic surgery, thus causing an increase in dry eye symptoms.

• Higher myopic prescriptions tend to cause greater dryness than lower myopic modifications (due to greater change in corneal curvature, possibly affecting more corneal nerve fibers.)

• Patients who undergo photorefractive keratectomy (PRK) tend to have less dryness problems than LASIK patients.

• Pre-existing dry eye is rarely an absolute contraindication for corneal refractive surgery; however, there are some cases when patients should not have surgery. Patients who have Sjögren’s or Stevens-Johnson syndrome should not undergo surgery because the extent of their pre-existing dryness is too great. Patients who have dryness secondary to other autoimmune diseases, such as rheumatoid arthritis or lupus, are also poor candidates. Patients who are in good health, but have chronic superficial punctate keratopathy (SPK) and moderate to severe dry eye disease should not have corneal refractive surgery.

Screening

To determine if a patient is at risk for developing significant dryness following LASIK, perform a thorough case history and carefully evaluate the tear film. The patient’s history should include age, gender, systemic health, medications and occupational environment.

Women past age 50 are affected by dryness almost twice as often as men over the age of 50. Post-menopausal women who take hormone replacement therapy are at higher risk for developing dryness after surgery. The pre-existing dryness they experience can be exacerbated by the creation of the LASIK flap and laser ablation. Men who take antihormonal or antiandrogen therapy for prostate cancer may also experience significant dry eye symptoms following surgery.

Other systemic diseases that are associated with dry eye include rheumatoid arthritis, acne rosacea, systemic lupus erythematosis, thyroid dysfunction and Sjögren’s syndrome. Numerous medications, such as antihistamines, certain antidepressants, beta-blockers and diuretics, can affect the ocular surface.

A history of either dryness or contact lens intolerance is a risk factor for post-LASIK dryness. These patients often pursue refractive surgery because they have problems with contact lens wear. Long-term contact lens wearers, particularly gas-permeable lens wearers, are prone to dryness. Their existing uncomfortable corneal sensation is exacerbated by the LASIK procedure, which can lead to postoperative dryness.

Evaluate a patient’s tear film before surgery:

• Tear film testing to determine if there is a problem with tear quantity or quality. For instance, the tear film break-up time (TFBUT) is one of the simplest ways to measure tear film stability.


• A Schirmer tear test with anesthetic to measure basal tear secretion. Realize that Schirmer testing may demonstrate variable results because of reflexive tearing and the presence of a residual tear lake in the fornix. Still, the Schirmer test remains the standard measurement of basal tear secretion.


• Lissamine green staining to identify conjunctival or corneal staining, a risk factor for postoperative dryness that should be treated before LASIK.


• Measurement of tear meniscus height, which can be done quickly and easily at the slit lamp. You can observe both tear meniscus and tear quality by looking for heavy debris in the tear film.


• Phenol red thread tear test testing, which also measures tear secretion. You can perform this test in 15 seconds.
  
  There are similar limitations to Schirmer’s testing; specifically, the test may measure the residual tear lake instead of tear secretion.


• Fluorescein dye to stain areas of the cornea and conjunctiva where cell damage has occurred. Any number of conditions may cause cell damage, but dry eye is often the culprit.

Performing each test on every patient being screened for refractive surgery is unnecessary. However, performing the exact same test on all patients may also be inappropriate. To determine if a patient has a pre-existing dry eye problem, it is necessary to document any problems with tear quality and/or quantity. Schirmer tear testing, phenol red thread tear testing, and measuring the tear meniscus height are good ways to determine the tear quantity. TFBUT is a good measurement of tear quality. A breakdown of one or both of these components may necessitate lissamine green or fluorescein staining.

Also, carefully evaluate the eyelids and meibomian gland orifices during the preoperative examination, and aggressively treat any pre-existing blepharitis and meibomianitis. Treating blepharitis will improve tear quality and lessen the risk of infection and inflammation after surgery.

Patients are more likely to comply with a treatment regimen that is simple to follow and comes with written instructions. An informational sheet that describes blepharitis and provides instructions for using of hot compresses and lid hygiene reminds patients to treat their eyelids before surgery.

Cleansing pads are a better choice than baby shampoo for lid hygiene. Treat more advanced cases of blepharitis with topical or oral antibiotics, or combination antibiotic/steroid drops or ointments. Low-dose oral doxycycline b.i.d. for one to two months followed by q.d. dosing for an additional month or longer may be warranted.

Pre-op Treatment

Once you determine that a patient has a dryness problem, you must begin dry eye therapy prior to surgery. The treatment regimen depends on the severity of the condition. Options include:

• Artificial tears. Patients who have mild corneal or conjunctival staining should be pretreated with artificial tears. This optimizes the ocular surface prior to surgery and lessens the chance for intraoperative complications.


• Cyclosporine. Patients who have mild to moderate dryness may benefit from Restasis (cyclosporine 0.05%, Allergan). The typical preoperative regimen is twice a day for one month before surgery. Some doctors wait to see if patients have problems after surgery to begin cyclosporine eye drops. However, it is best to be proactive and start the drops before surgery to give the medication a chance to take effect.
  
  A recent study found that using cyclosporine 0.05% prior to LASIK improved refractive predictability.¹¹ In this study, researchers randomized 21 myopic patients with dry eye to receive unpreserved artificial tears or cyclosporine b.i.d. for one month before undergoing LASIK.
  
  The study drops were discontinued for 48 hours after surgery, and then resumed for three months following surgery.
  
  The patients who received cyclosporine had better uncorrected visual acuity following LASIK compared with patients who received artificial tears.¹⁵
  
  As far as refractive stability, 69% of the cyclosporine group had a manifest refraction spherical equivalent (MRSE) within ±0.50D of emmetropia at six months vs. 26% of those patients using unpreserved artificial tears.¹⁶


• Corticosteroids. Patients with moderate dry eye, particularly patients who manifest superficial punctate keratopathy (SPK), may benefit from topical corticosteroids. In one study, dry eye patients with staining scores higher than 10 or conjunctival chemosis greater than grade 2 were prescribed loteprednol 0.5% q.i.d. for four weeks. At examination, the results showed statistical improvements in corneal staining, hyperemia and chemosis, compared to the control group.¹⁷


• Punctal occlusion. This is another treatment option for patients who have moderate preoperative dryness. Punctal plugs occlude the lacrimal drainage system and may reduce dependency on artificial tears after surgery.² Punctul occlusion is recommended for patients who have lower Schirmer scores or phenol red thread tear testing from decreased tear production.
  
  There are several types of plugs to choose from, namely silicone plugs, intracanalicular plugs, collagen plugs and extended-duration dissolvable plugs. Extended-duration dissolvable collagen plugs that last one to four weeks work well for LASIK patients. The first four weeks after surgery is typically when patients experience the most problems with dryness.

Post-op Treatment

Even with the proper precautions, some patients may experience significant dryness following LASIK. These patients may or may not report symptoms. Frequently, patients present for post-op visits with a white conjunctiva and no signs of dryness, but they complain of blurry vision or halos and glare. The patients are unaware of the irritation to the corneal surface because of the temporary neurotrophic effect of LASIK. Remind patients to use artificial tears following LASIK even if their eyes do not feel dry.

• Artificial tears. Preservative-free artificial tears should be used on all patients for the first month following surgery, regardless of their signs and symptoms. To increase the probability that patients will buy the type of artificial tear you recommend, give them samples and provide coupons for the eye drop in their postoperative kit.
  
  Following the first month post-op, patients can decrease the volume of artificial tears they are using based upon their signs and symptoms. For example, if a patient presents for a one-month post-op visit with no signs or symptoms of dryness, you can lower their dose to b.i.d. and switch them to a bottled tear, such as Optive (Allergan), Systane (Alcon) or Genteal (Novartis Ophthalmics).


• Questionnaires. Dry eye questionnaires are not needed for every patient who seeks refractive surgery. However, if a patient has significant postoperative dryness, the questionnaires may help identify an environmental factor that is exacerbating the dryness. For example, a questionnaire may reveal that the patient uses a table fan while working on the computer to keep cool. The questionnaire may also reveal problems with the patient’s diet or fluid intake. Treating the dry eye problem may be as simple as modifying the patient’s normal habits.


• Cyclosporine. If a post-op patient presents with significant SPK and dryness symptoms, topical cyclosporine eye drops may be beneficial. Studies show topical cyclosporine 0.05% is helpful to patients after LASIK surgery.
  
  Another study found that cyclosporine 0.05% increases goblet cell density.²³ The researchers treated patients diagnosed with dry eye disease with artificial tears or cyclosporine 0.05% for 12 weeks, and found that mean goblet cell density increased by 17% in the cyclosporine group.²³
  
  The artificial tear group exhibited no change in goblet cell density. This indicates that cyclosporine inhibits the pathologic mechanisms that lead to reduced conjunctival goblet cell density in chronic dry eye disease. These results are pertinent to post-LASIK patients, as the microkeratome pressure may damage goblet cells.

• Punctal occlusion. A possible drawback of using topical cyclosporine 0.05% is that it can take from three weeks to three months before the medication takes effect. If a patient desires an immediate effect, punctal plugs are a viable option for treating postoperative dryness; 60-day, three-month and six-month duration punctal plugs are often ideal. Each punctal plug has a varying duration time, but every option works well in refractive surgery patients. If a patient continues to have problems after the initial plugs dissolve, permanent silicone plugs, form-fitting plugs or hydrophobic acrylic plugs may be warranted.

• Topical corticosteroids. Another treatment option is concurrent use of corticosteroids. One hundred twenty patients with dry eye were enrolled in a prospective, multicenter, randomized, controlled, masked study, to evaluate the efficacy and safety of using Lotemax (loteprednol etabonate 0.5%, Bausch & Lomb) in conjunction with Restasis therapy.²⁴ Patients received either Lotemax (test) or an artificial tear (control) in masked bottles q.i.d. for two weeks, and then received the masked test or control drop b.i.d. plus Restasis from days 15 to 60. At day 60, patients achieved an improvement in corneal and conjunctival staining and Schirmer test results. Additionally, patients randomized into the Lotemax group experienced decreased stinging with the start of Restasis.²⁴
  
  At baseline, tear production in both treatment groups increased. When normalized to baseline, however, the Lotemax/Restasis treatment significantly increased tear production by 27%).²⁴ The long-term treatment (60 days) with Lotemax reduced patients' use of artificial tears.

It is important to identify and treat keratitis sicca before the patient undergoes LASIK. The surgeon may recommend modifications to the surgical treatment plan to decrease the risk of significant dryness following surgery. After surgery, encourage patients to maintain their postoperative dry eye therapies to improve their odds of obtaining a favorable and comfortable outcome.