Minimizing Post-LASIK Dry Eye
Aggressive preoperative and intraoperative management will reduce the incidence of this complication.
BY ERIC DONNENFELD, M.D., F.A.C.S.

With LASIK, interaction between the ocular surface and the eyelid is affected because the excimer laser alters the anterior curvature of the cornea by removing stromal tissue. After LASIK, the cornea overlying the flap is largely anesthetic for 3 to 6 months, which causes a decrease in tear production.^1-4  

In this article, I discuss how LASIK affects corneal sensation and how careful preoperative, intraoperative, and postoperative management can reduce the incidence and severity of dry eye.

Who Is Affected?

All patients experience dry eye transiently following LASIK.⁵  Yu et al. reported that 60% of patients experienced dry eye at 1 month following LASIK, ⁶ and Hovanesian et al. reported that 50% of patients experienced dry eye symptoms at 6 months.⁷ I and my fellow researchers have reported that 15% of patients experience moderate dry eye that lasts at least 3 months, and 5% experience severe dry eye that lasts at least 6 months. ⁸  

Generally, patients who had dry eye or were marginally compensated with borderline dry eye before surgery will have symptoms. Most patients with post-LASIK dry eye will complain of fluctuating visual acuity between blinks and at different times of the day. In our experience, these symptoms usually resolve 2 to 4 weeks after surgery.

What Causes Post-LASIK Dry Eye?

LASIK-associated dry eye can be caused by:

► high pressure induced by the suction ring during flap creation, which may damage the conjunctival goblet cells and compromise the mucin layer of the tear film⁴  

	Supravital staining of the conjunctiva with lissamine green in the classic staining pattern of dry eye.

► significant alterations to the corneal curvature that occur after LASIK, which alter tear wetting as the lids move over the modified ocular surface

► medicamentosum caused by epithelial-toxic antibiotics, nonsteroidal anti-inflammatory (NSAID) drops, and preservatives such as benzalkonium chloride (BAK), which may induce transient dry eye symptoms.

Because intact corneal sensation drives tear production, corneal denervation associated with LASIK is the most significant cause of post-LASIK dry eye. During LASIK, the corneal nerve trunks are severed by the microkeratome, and the anterior stromal nerves are disrupted by photoablation. Both processes damage corneal innervation. The reduction in corneal neuronal feedback to the brain stem reduces brain stem innervation of the lacrimal glands, diminishing tear production. As the nerves regenerate postoperatively, corneal sensation returns over, approximately, a 6-month period, which may explain the transient dry eye and return of tear function over time.²  

Sensory Denervation: A Self-Perpetuating Cycle

The recognition that the ocular surface and the lacrimal glands function as an integrated unit represents a major advance in our understanding of dry eye syndrome.^9,10  Communication between the ocular surface and the lacrimal glands occurs through a sensory/autonomic neural reflex loop. The sensory nerves innervating the ocular surface connect with efferent autonomic nerves in the brain stem that stimulate secretion of tear fluid and proteins by the lacrimal glands. Ocular surface sensitivity lessens as aqueous tear production and clearance decrease, which exacerbates dry eye because the decreased sensory-stimulated reflex tearing diminishes the ability of the lacrimal glands to respond to ocular surface insults, creating a self-perpetuating cycle between the lacrimal glands and the ocular surface.

The anesthetic cornea created by the LASIK flap and photoablation worsens dry eye by reducing the afferent pathways from the cornea to the brain stem, which reduces the efferent signal from the brain stem to the lacrimal glands to produce tears. It has been reported that even with unaltered tear production post-LASIK there is corneal staining, leading to the notion that neurotrophic keratitis rather than dry eye may be responsible for some of the corneal changes following LASIK.¹¹  

Fluorescein staining of the cornea with the classic staining pattern of dry eye.

Corneal Flaps Play a Role

The cornea is one of the most densely innervated and highly sensitive tissues in the body. Corneal sensation, which is vital for maintaining corneal epithelial integrity and tear film function, is provided by the long ciliary nerves of the ophthalmic division of the 5th (trigeminal) cranial nerve. The long ciliary nerve trunk travels in the suprachoroidal space where it branches several times before entering the cornea at the limbus. The large nerves enter the limbus predominantly at the 9 o'clock and 3 o'clock positions, and then they bifurcate and move toward the 12 o'clock and 6 o'clock positions. After a second bifurcation, they again run toward the 9 o'clock and 3 o'clock positions. The nerves initially enter the cornea in the middle third of the stroma, but course anteriorly as they branch, eventually forming a plexus in the sub-Bowman's layer that densely innervates the central cornea. Next, they penetrate Bowman's membrane and terminate in the epithelium at the wing cell layer. The fact that the long ciliary nerves enter the eye at the 9 and 3 o'clock positions explains why corneal sensation is significantly greater at the temporal and nasal limbus than inferiorly.^12-15  

In vivo confocal microscopy shows that LASIK-induced alterations in the sub-Bowman's nerve plexus are directly related to decreased corneal sensation. Corneal sensation following LASIK is greatest near the hinge and decreases toward the central cornea and the peripheral cornea away from the hinge.³  One advantage of the hinge on the LASIK flap is that it provides a conduit for corneal innervation; the corneal nerves entering through the hinge are preserved, maintaining corneal sensation in this area. Because the corneal nerves predominantly enter the cornea at the 9 and 3 o'clock positions, a vertical flap (superior hinge) will transect both of the major areas of corneal innervation, whereas a horizontal corneal flap (nasal hinge) will transect only one of these areas.^12,13  

We demonstrated in a self-controlled, masked clinical study that eyes with a superior-hinge flap have a significantly greater loss of sensation and increased corneal and conjunctival lissamine staining at all time intervals compared with eyes that have a nasal-hinge flap.⁸  Our study also revealed a trend toward lower Schirmer scores and shorter tear break-up time (TBUT) in eyes with a superior-hinge flap compared with eyes that have a nasal-hinge flap. In another study, we found that loss of corneal sensation and dry eye syndrome were less pronounced in corneas with a wide nasal-hinge flap than in those with a narrow nasal-hinge flap. This finding can be explained anatomically by the smaller percentage of corneal innervation severed by the wider-hinge flap.¹⁶  

Punctate epithelial erosions and rose bengal staining have been noted on post-LASIK corneal flaps a few days to weeks after surgery.¹¹  This surface abnormality has been seen in patients with no evidence of dry eye preceding LASIK and is likely neurotrophic epitheliopathy as there is no difference in mean tear production between patients who have significant punctate epithelial erosions and rose bengal staining and those who don't. Signs and symptoms of LASIK-induced (presumed) neurotrophic epitheliopathy usually resolve about 6 months postoperatively, and this abnormality is more common and severe in patients with pre-existing dry eye disease.

	Meibomian gland disease with inspisated orifices.

Careful Preoperative Screening Can Prevent Postoperative Dry Eye

Screening patients thoroughly before refractive surgery can prevent symptomatic postoperative dry eye. The dry eye history is perhaps the most important part of the patient's work-up. Many dry eye patients are actually pre-selected candidates for refractive surgery because they're uncomfortable wearing contact lenses or are contact-lens intolerant, so any mention of contact-lens intolerance should signal the possibility of underlying dry eye. Note long-term contact-lens wear, especially hard-lens wear, as this decreases corneal sensation and would add to the decrease seen with LASIK surgery and contribute to decreased tear production.⁹  

Any eye irritation, including sandy-gritty irritation, dryness, burning, or foreign body sensation, suggests dry eye. Carefully inspect the lids of patients who report eye irritation when they wake up from sleeping for signs of meibomitis. Pay especially close attention to the status of the meibomian gland orifices, the width of the palpebral fissure, and the volume of the tear film in patients who report their symptoms worsen as the day goes on. Stenosis and closure of the meibomian glands, large palpebral fissure width, and decreased tear production all increase tear film osmolarity and cause dry eye. We perform tear testing, including TBUT; examine for tear debris in the inferior cul-de-sac; and do Schirmer testing with anesthesia. Most importantly, we perform supravital staining of the conjunctiva with lissamine green or rose bengal and fluorescein staining of the cornea to look for the classic staining pattern of dry eye.

It's Easier to Treat Dry Eye Before LASIK Than After

Pre-existing dry eye doesn't necessarily affect the efficacy and safety of LASIK, but it is a risk factor for symptomatic post-LASIK dry eye, with measurably lower tear function and supravital staining of the ocular surface.^6-9,17  Preoperative conjunctival staining is a risk factor for dry eye postoperatively, and corneal staining is a contraindication for surgery until the ocular surface has been stabilized. Female gender and reduced preoperative tear film stability are two other factors for chronic dry eye after LASIK.⁴  If a patient has dry eye symptoms preoperatively, it's important to maximize the health of the ocular surface prior to surgery because it's easier to successfully pre-treat the patient than to react postoperatively.

Patients with symptoms of dry eye but no signs of corneal or conjunctival staining are usually excellent candidates for LASIK. If patients have dry eye symptoms with mild conjunctival staining, they should be treated with artificial nonpreserved tears, such as Refresh Plus, to stabilize the ocular surface before surgery.

Patients with corneal staining should also be treated with transiently preserved tears, such as Refresh Tears; lubricating ointment at night; cyclosporine ophthalmic emulsion (Restasis); and, if necessary, punctal occlusion.

For patients with meibomian gland disease, we add oral doxycycline 100 mg b.i.d. for 2 weeks and then daily for an additional month. Patients with chronic meibomian gland dysfunction may also have an increased risk of sterile corneal infiltrates after LASIK.⁸  In our opinion, these patients benefit from a lipid emulsion tear such as Refresh Endura, which improves TBUT.

A controlled study showed that patients with moderate to severe dry eye who want LASIK achieve a better visual outcome if they are pre-treated with Restasis 0.05% b.i.d. for 1 to 3 months and then reassessed before LASIK is performed.¹⁹  Restasis is the first medication approved by the FDA to treat the pathogenesis of dry eye disease rather than just the symptoms. We advise our patients to use Restasis with transiently preserved tears, but we ask them to not use the tears for 30 minutes after the Restasis to avoid washing it out of the tear film. We don't use Refresh Endura with Restasis because the common vehicle can create an oily tear film and compromise vision.

Inflammation: A Proven Cause of Surgical Dry Eye

The importance of inflammation in the pathogenesis of idiopathic dry eye disease and following refractive surgery is now well known. Decreased tear production and clearance lead to chronic inflammation of the ocular surface. This inflammatory response consists of activated T-lymphocyte cellular infiltration of the ocular surface with increased expression of adhesion molecules and inflammatory cytokines, increased concentrations of inflammatory cytokines in the tear fluid, and increased activity of matrix degrading enzymes such as MMP-9 in the tear fluid.²⁰  Significant positive correlation has been observed between the levels of inflammatory cytokines in the conjunctival epithelium and the severity of ocular irritation symptoms, corneal fluorescein staining, and severity of conjunctival squamous metaplasia in patients with Sjögren's syndrome keratoconjunctivitis.^21,22 Reports of the clinical efficacy of anti-inflammatory therapies provide direct proof that inflammation is key in causing dry eye.^9,23,24  

Structured Intraoperative Management Reduces Dry Eye Risk

Structured intraoperative management of LASIK can decrease the risk of dry eye by preserving the corneal epithelium and preventing corneal abrasions. We minimize the use of topical anesthetics by giving the first dose of the topical anesthetic when the patient enters the laser suite and the second dose immediately before surgery. To reduce the risk of a corneal abrasion, we lubricate the ocular surface with proparacaine, which has a glycerin base, prior to the keratome pass. Once the flap has been replaced, we place a small amount of carboxymethylcellulose 1% (Celluvisc) on the corneal surface to prevent surface desiccation. We apply a nonpreserved NSAID, a fluoroquinolone, and prednisolone acetate 1% intraoperatively before removing the lid speculum. We then instruct the patient to close the eyes for 15 minutes before we examine the flap and then to keep the eyes closed for 4 hours to promote epithelial healing. Postoperatively, the patient uses a fluoroquinolone and prednisolone acetate 1% 4 times a day for 5 days.^25,26  

To promote epithelial healing and reduce the incidence of post-LASIK dry eye, we give each patient a schedule of artificial tear use: on the first postoperative day, a viscous tear every 2 hours and for the remainder of the first postoperative week, either nonpreserved or transiently preserved tears.^27,28  If the patient has symptoms of dry eye following LASIK, we insert inferior punctal plugs to stabilize the ocular surface. If this isn't successful, we add oral doxycycline. We have found that many patients with meibomian gland disease also benefit from a lipid emulsion applied b.i.d. and nutritional supplements containing omega-3 fatty acids and eicosapentaenoic acid (EPA). For patients who have recalcitrant, long-term dry eye problems, adding Restasis b.i.d. for 6 months provides significant benefit.

Consider Alternatives to LASIK

Photorefractive keratectomy (PRK) is a possible alternative for patients who are not candidates for LASIK or prefer not to have a corneal flap. Although PRK has not been as popular as LASIK because of delayed healing and pain related to epithelial removal prior to the procedure, recent improvements, including small, flying Gaussian spots, pupil trackers, and mitomycin C for haze, have increased its effectiveness. However, PRK induces a decrease in corneal sensitivity due to eradication of the subepithelial nerve plexus and a decrease in tear flow and tear film stability.^29-35  

Laser subepithelial keratomileusis (LASEK) is a relatively new technique indicated for patients who are candidates for PRK.^36-40  With LASEK, the corneal nerves are not transected. Although intraepithelial nerves are severed when the epithelium is lifted, and superficial nerves are destroyed in the area of photoablation, the deeper nerves and their trunks are spared. After the epithelium is scored at 8.0 mm, an 8.5-mm well is placed over the central cornea and filled with 20% alcohol for 30 to 40 seconds. The epithelium is then retracted with a microhoe to raise an epithelial flap. Photoablation is performed conventionally (as in PRK or LASIK), and the epithelium is gently repositioned with an irrigation cannula. Indications for LASEK are the same as those for PRK. LASEK is suitable for patients with thin corneas or occupations that predispose them to ocular trauma; or who have anatomic abnormalities such as flat corneas, steep corneas, and deep-set eyes; or who have had filtering blebs, retinal detachment surgery, or glaucoma surgery.

Dry eye with poor epithelial wound healing continues to be an absolute contraindication for refractive surgery. For patients who have moderate epithelial healing problems, LASIK is preferable because it involves less healing as there is no disruption to the corneal epithelium. Patients with dry eye symptoms but minimal corneal signs of dry eye may benefit from LASEK. Kanellopoulos et al. determined there is less loss of corneal sensation with PRK than with LASIK and based on this observation there is likely less loss of sensation with LASEK than with LASIK.¹ So LASEK may better preserve corneal sensation and reduce dry eye symptoms following refractive surgery.

For LASIK, PRK, and LASEK, we have found that supporting the ocular surface with transient or nonpreserved tears, gels, and ointments results in safer and faster visual rehabilitation and improved visual outcomes.

Dr. Donnenfeld is co-director of the External Disease/Cornea Department, Manhattan Eye, Ear and Throat Hospital, New York, surgical director of the Lions Eye Bank for Long Island, North Shore University Hospital, and assistant clinical professor of ophthalmology, New York University Medical College. He is a founding partner at Ophthalmic Consultants of Long Island. He can be reached at eddoph@aol.com.

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