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Introduction
Etiology of Post-LASIK Dry Eye
Preoperative Screening for Dry Eye
Treatment of Dry Eye
Sensory Denervation
Effect of LASIK on Corneal Sensation
Intraoperative and Postoperative Management of LASIK
Conclusions and Future Directions
References

Slides

Post Test

 Refractive Surgery

Etiology, Prevention, and Management of Dry Eye Following LASIK

Renée Solomon, MD · Eric D. Donnenfeld · MD, Henry D. Perry, MD

Introduction

It is important for refractive surgeons to be aware that all LASIK procedures affect the ocular surface and tear film dynamics. The LASIK procedure may have an impact on corneal sensation, aqueous tear production, and wound healing. The LASIK procedure also affects the interaction of the ocular surface and the lids because the excimer laser alters the anterior curvature of the cornea by removing stromal tissue. After LASIK, the cornea overlying the flap is significantly anesthetic for 3 to 6 months,1-3 causing a decrease in tear production.

Dry eye following LASIK is perhaps the most common complication that refractive surgeons face today.1-4 Virtually all patients experience dry eye following LASIK at least transiently.5 Yu and colleagues reported that 60% of patients experienced dry eye 1 month following LASIK,6 and Hovanesian and colleagues reported that 50% of patients experienced symptoms related to dry eye 6 months following LASIK.7 Fifteen percent of patients experience moderate dry eye that lasts at least 3 months, and 5% of patients experience severe dry eye that lasts at least 6 months.8 However, in general, only patients who had dry eye before surgery or who were marginally compensated with borderline dry eye before surgery will have dry eye symptoms. Most patients with post-LASIK dry eye have disruption of the tear film and ocular surface and will experience fluctuating visual acuity between blinks at different times of the day. It is fortunate that, in our experience, the majority of patients' symptoms are resolved in a 2- to 4-week period following surgery.

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Etiology of Post-LASIK Dry Eye

A number of possible causes of LASIK-associated dry eye exist. The high level of pressure induced by the suction ring during LASIK may damage the conjunctival goblet cells, compromising the mucin layer of the tear film.4 Significant alterations to the corneal curvature that occur after LASIK alter tear wetting as the lids move over the modified ocular surface. Medicamentosum, which is caused by epithelial toxic antibiotics, nonsteroidal anti-inflammatory drops (NSAIDs), and preservatives may also induce transient dry eye symptoms. Because intact corneal sensation drives tear production, corneal denervation associated with the LASIK procedure 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 during approximately a 3- to 6-month period.2,9 The return of corneal sensation may help explain the transient dry eye and return of tear function over time.

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Preoperative Screening for Dry Eye

One of the most important ways to prevent symptomatic postoperative dry eye is to screen patients carefully before refractive surgery. Many patients with dry eye are actually pre-selected candidates for refractive surgery because their pre-existing dry eye causes them to be uncomfortable wearing contact lenses or renders them contact lens-intolerant. Any mention of contact lens intolerance during the course of the patient history suggests the possibility of underlying dry eye. Conversely, long-term contact lens wear, especially hard lens wear, should also be noted during the history-taking because long-term contact lens wear decreases corneal sensation. This decrease would be additive to the decrease resulting from LASIK surgery and could contribute to decreased tear production.10

Slide 1

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Slide 2
 The dry eye history is perhaps the most important part of the dry eye work-up. Any eye irritation, including sandy-gritty irritation, dryness, burning, or foreign body sensation, is suggestive of dry eye. The examiner should carefully inspect the lids of patients who report eye irritation upon awakening for signs of meibomianitis. They should pay 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 that their symptoms worsen as the day goes on. Stenosis and closure of the meibomian glands, large palpebral fissure width, and decreased tear production increase tear film osmolarity and cause dry eye. We perform tear testing, including tear break-up time (TBUT), examination for tear debris in the inferior cul-de-sac, and 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 the dry eye (Slide 1, Slide 2).

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Treatment of Dry Eye

The efficacy and safety of LASIK are not necessarily affected by pre-existing dry eye.6,11 However, pre-existing dry eye is a risk factor for symptomatic post-LASIK dry eye with measurably lower tear function and supravital staining of the ocular surface.6,11 Preoperative conjunctival staining represents a risk factor for dry eye postoperatively, and corneal staining is considered to be a relative contraindication for surgery until the ocular surface has been stabilized.4 Women and patients with reduced preoperative tear film stability are at risk for chronic dry eye after LASIK.4 In patients who have dry eye symptoms preoperatively, it is important to maximize the health of the ocular surface prior to surgery because it is easier to successfully pretreat these patients than to treat them postoperatively. Patients with symptoms of dry eye but no signs of corneal or conjunctival staining are generally excellent candidates for LASIK. Patients who have dry eye symptoms with mild conjunctival staining should be treated with artificial nonpreserved tears to stabilize the ocular surface before surgery.12,13

Slide 3

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Patients with corneal staining are also treated with artificial nonpreserved tears, lubricating ointment at night, topical cyclosporin A (Restasis, Allergan, Irvine, Calif.) and, if necessary, punctal occlusion. For patients who have meibomian gland disease (Slide 3), we add 100 mg of oral doxycycline twice a day for 2 weeks and then once a day for an additional month. Patients with chronic meibomian gland dysfunction may also have an increased risk of sterile corneal infiltrates after LASIK.14 In our opinion, patients with meibomian gland dysfunction also benefit from the lipid emulsion tear Refresh Endura (Allergan), which improves TBUT.

In a multicenter, randomized controlled trial, topically applied cyclosporin A (tCSA) 0.05% in a lipid emulsion, Restasis, was found to produce significant improvement in patients in both the signs and symptoms of dry eye disease, as well as to produce a decrease in the levels of inflammatory cells in the conjunctival epithelium.15 No systemic effects from the tCSA with detectable serum levels less than 0.01% of therapeutic levels were present.12 Cyclosporin A offers the advantage of immunomodulation without the risk of corticosteroid immunosuppressive side effects. It has been reported that in a controlled study patients with moderate to severe dry eye who are seeking LASIK achieve a better visual outcome if they are pretreated with tCSA 0.05% twice a day for 1 to 3 months and then reassessed before LASIK is performed.16 tCSA was the first medication approved by the FDA to treat patients for the pathogenesis of dry eye disease rather than the symptoms.

We have found that supplementation with the omega-3 fatty acids provided by eicosapentaenoic acid- (EPA) and docosahexaenoic acid- (DHA) enriched flaxseed oil is beneficial to patients with abnormal meibomian gland secretions. Although peer-reviewed published studies do not exist to document the value of ingesting omega-3 essential fatty acids in the treatment of patients with dry eye, it is known that the meibomian glands use essential fatty acids to manufacture the oil layer of the tear film. It has been observed that omega-3 essential fatty acid treatment produces clear, thin oils that allow the oil to flow better, providing a better cover for the tear film.17 High-performance liquid chromatography mass spectrometry studies have shown that the polar lipid profiles of meibomian gland secretions in women with Sjögren's syndrome are controlled by the dietary intake of omega-3 essential fatty acids. Patients with high intakes of omega-3 fatty acids show single prominent-peak polar lipid patterns, whereas patients with low dietary intakes of omega-3 essential fatty acids show multiple smaller peaks.18 It seems reasonable to infer that dietary omega-3 essential fatty acids are utilized in the production of meibomian secretions and augment the tear film oil layer.

In this discussion, we have noted products that we find useful in the treatment of patients after LASIK. Other refractive surgeons use alternative products with successful results.

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Sensory Denervation

The recognition that the ocular surface and lacrimal glands function as an integrated unit represents a major advance in the understanding of dry eye syndrome. Communication between the ocular surface and lacrimal glands occurs through a sensory/autonomic neural reflex loop.10,19 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 has been found to decrease as aqueous tear production and clearance of tears from the ocular surface decrease. This decrease in surface sensation exacerbates dry eye because sensory-stimulated reflex tearing is decreased, resulting in decreased ability of the lacrimal glands to respond to ocular surface insults. Thus, a self-perpetuating cycle between the lacrimal glands and the ocular surface is created.10,17 The anesthetic cornea created by the LASIK flap and photoablation worsens the dry eye syndrome by reducing the afferent pathways from the cornea to the brainstem, thereby reducing the efferent signal from the brainstem to the lacrimal glands to produce tears. Wilson has reported that, even with unaltered tear production post-LASIK, corneal staining occurs, leading him to postulate that neurotrophic keratitis rather than dry eye may be responsible for some of the corneal changes following LASIK.20

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Effect of LASIK on Corneal Sensation

Slide 4

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The cornea is one of the most densely innervated and highly sensitive tissues in the body. Corneal sensation is vital for maintaining corneal epithelial integrity and tear film function. Corneal sensation is provided by the long ciliary nerves of the ophthalmic division of the fifth (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 (Slide 4). The large nerves then 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.21-23 The nerves next 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 o' clock and 3 o'clock positions explains why corneal sensation is significantly greater at the temporal and nasal limbus than inferiorly.24

Slide 5

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In vivo confocal microscopy has shown that LASIK-induced alterations in the sub-Bowman's nerve plexus are directly related to decreased corneal sensation.3 It has also been shown that corneal sensation following LASIK is greatest near the hinge and decreases toward the central cornea and the peripheral cornea away from the hinge.3 An advantage of the hinge on the LASIK flap is that it provides a conduit for corneal innervation. Slide 6
 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 o'clock and 3 o'clock position,21,22 a vertical flap (superior hinge) will transect both of the major areas of corneal innervation (Slide 5), whereas a horizontal corneal flap (nasal hinge) will transect only one of these areas (Slide 6). Hypothetically, the greater the loss of corneal sensation, the greater the risk for post-LASIK dry eye syndrome.

We demonstrated in a self-controlled, masked clinical study that patients with eyes with superior hinge flaps had a significantly greater loss of sensation and significantly increased corneal and conjunctival lissamine staining at all time intervals compared to patients with eyes with nasal hinge flaps. The study also revealed a trend toward lower Schirmer scores and shorter TBUT in patients with eyes with a superior hinge flap compared to patients with eyes with nasal flaps.8 Furthermore, in a recent study, we found that loss of corneal sensation and dry eye syndrome were both less pronounced in corneas with wide nasal hinge flaps than in those with narrow nasal hinge flaps.25 This finding can be explained anatomically by the smaller percentage of corneal innervation severed by the wider hinge flap than by the narrow hinge flap.

A few days to weeks after surgery, punctate epithelial erosions and rose bengal staining have been noted on post-LASIK corneal flaps.18 This surface abnormality has been seen in patients with no evidence of dry eye preceding LASIK, and is likely neurotrophic epitheliopathy because no difference in mean tear production exists between patients who have significant punctate epithelial erosions and rose bengal staining and patients who do not. The signs and symptoms of LASIK-induced (presumed) neurotrophic epitheliopathy usually resolve approximately 6 months postoperatively. This abnormality is more common and more severe in patients with pre-existing dry eye disease.20

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Intraoperative and Postoperative Management of LASIK

Slide 7

SLIDE 7View full size slide
Careful 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 a 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 (Allergan) on the corneal surface to prevent surface dessication (Slide 7).24,25 We apply the nonpreserved NSAID, ketorolac,26-27 a fluoroquinolone antibiotic, and prednisolone acetate 1% intraoperatively before removing the lid speculum. We instruct patients to close their eyes for 15 minutes before we examine the flap. We then ask them to keep their eyes closed for 4 hours to promote epithelial healing.

Postoperatively, patients use a fluoroquinolone antibiotic and prednisolone acetate 1% four times a day for 5 days. To promote epithelial healing and reduce the incidence of post-LASIK dry eye, patients are given a structured schedule of artificial tear use. On the first postoperative day, patients use a more viscous tear, carboxymethylcellulose 1%, such as Celluvisc or TheraTears Liquid Gel (Advanced Vision Research, Woburn, Mass.)28 every 2 hours. For the remainder of the first postoperative week, they use transiently preserved tears, such as Refresh Plus (Allergan),29 Theratears (Advanced Vision Research), or Genteal (Novartis Ophthalmics, Inc., Duluth, Ga.) drops. If a patient has symptoms of dry eye following the LASIK procedure, then we insert inferior punctal plugs in an attempt to stabilize the ocular surface. If this treatment is not successful, then we add oral doxycycline to the postoperative regimen. We have found that many patients with meibomian gland disease also benefit from Refresh Endura lipid emulsion (Allergan) twice a day and supplementation with nutritional supplements containing omega-3 essential fatty acids and EPA. Finally, for patients who have recalcitrant, long-term dry eye complications, we have found significant benefit from adding tCSA 0.05% twice daily for 6 months.

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Conclusions and Future Directions

LASIK induces significant alterations to the ocular surface. These changes may be transient or permanent. The most common and potentially one of the most devastating non-keratome-related complications of LASIK surgery is dry eye. The incidence of post-LASIK dry eye can be reduced by identifying patients at risk for dry eye, maximizing tear film stability preoperatively, and minimizing dry eye through intraoperative and postoperative therapeutic interventions, both pharmacological and surgical. LASIK surgeons should take the appropriate steps at every stage of the surgical process to optimize the refractive outcome, minimize postoperative complications, and maximize the stability of the ocular surface.

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References

  1. Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED, Deforakis S, Koufalak K, Perry HD. Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg. 1997;23:34-38.
  2. Linna TU, Vesaluoma MH, Perez-Santonja JJ, Petroll WM, Alio JL, Tervo TM. Effect of myopic LASIK on corneal sensitivity and morphology of subbasal nerves. Invest Ophthalmol Vis Sci. 2000;41:393-397.
  3. Chuck RS, Quiros PA, Perez AC, McDonnell PJ. Corneal sensation after laser in situ keratomileusis. J Cataract Refract Surg. 2000;26:337-339.
  4. Albietz JM, Lenton LM, McLennan SG. Effect of laser in situ keratomileusis for hyperopia on tear film and ocular surface. J Refract Surg. 2002;18:113-123.
  5. Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Dry eye after laser in situ keratomileusis. Am J Ophthalmol. 2001;132:1-7.
  6. Yu EY, Leung A, Rao S, Lam DS. Effect of laser in situ keratomileusis on tear stability. Ophthalmology. 2000;107:2131-2135.
  7. Hovanesian JA, Shah SS, Maloney RK. Symptoms of dry eye and recurrent erosion syndrome after refractive surgery. J Cataract Refract Surg. 2001;27:577-584.
  8. Donnenfeld ED, Solomon K, Perry HD, et al. The effect of hinge position on corneal sensation and dry eye after LASIK. Ophthalmology. 2003;110:1023-1029; discussion, 1029-1030.
  9. Michaeli A, Slomovic AR, Sakhichand K, Rootman DS. Effect of laser in situ keratomileusis on tear secretion and corneal sensitivity. J Refract Surg. 2004;20:379-383.
  10. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: The interaction between the ocular surface and lacrimal glands. Cornea. 1998;17:584-589.
  11. Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Ophthalmol. 2002;120:1024-1028.
  12. Albietz JM, McLennan SG, Lenton LM. Ocular surface management of photorefractive keratectomy and laser in situ keratomileusis. J Refract Surg. 2003;19:636-644.
  13. Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Ocular surface treatment before laser in situ keratomileusis in patients with severe dry eye. J Refract Surg. 2004;20:270-755.
  14. Ambrosio R Jr, Periman LM Netto, MV, Wilson SE. Bilateral marginal sterile infiltrates and diffuse lamellar keratitis after laser in situ keratomileusis. J Refract Surg. 2003;19:154-158.
  15. Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000;107:631-639. Erratum in Ophthalmology. 2000;107:1220.
  16. Salib G, McDonald M. Use of cyclosporine 0.05% drops versus unpreserved artificial tears in dry eye patients having LASIK. American Society of Cataract and Refractive Surgery Symposium on Cataract, IOL, Refractive Surgery. Abstracts 2003; Abstract # 669.
  17. Boerner CF: Dry eye successfully treated with oral flaxseed oil. Ocular Surgery News. October 152000:147-148.
  18. Sullivan BD, Cermak JM, Sullivan RM, et al. Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjögren's syndrome. Adv Exp Med Biol. 2002;506:441-447.
  19. Afonso AA, Monroy D, Stern M, Feuer WJ, Tseng SC, Pflugfelder SC. Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms. Ophthalmology. 1999;106:803-810.
  20. Wilson SE. Laser in situ keratomileusis - induced (presumed) neurotrophic epitheliopathy. Ophthalmology. 2001;108:1082-1087.
  21. Muller LJ, Pels L, Vrensen GF. Ultrastructural organization of human corneal nerves. Invest Ophthalmol Vis Sci. 1996;37:476-488.
  22. Muller LJ, Vrensen GF, Pels L, Cardozo BN, Willekens B. Architecture of human corneal nerves. Invest Ophthalmol Vis Sci. 1997;38:985-994.
  23. Auran JD, Koester CJ, Kleiman NJ, et al. Scanning slit confocal microscopic observation of cell morphology and movement within the normal human anterior cornea. Ophthalmology. 1995;102:33-41.
  24. Solomon R, Donnenfeld E, Bolder N, et al. Flap hydration with carboxymethylcellulose versus dehydration following laser in situ keratomileusis surgery (abstract). Invest Ophthalmol Vis Sci. 2000; 41(suppl):S688.
  25. Lawrenson JG, Ruskell GL. Investigation of limbal touch sensitivity using a Cochet-Bonnet aesthesiometer. Br J Ophthalmol. 1993;77:339-343.
  26. Donnenfeld ED, Ehrenhaus M, Solomon R, Mazurek J, Rozell JC, Perry HD. The effect of hinge width on corneal sensation and dry eye after laser in situ keratomileusis. J Cataract Refract Surg. 2004;30:790-797.
  27. Stroobants A, Fabre K, Maudgal PC. Effect of non-steroidal anti-inflammatory drugs (NSAID) on the rabbit corneal epithelium studied by scanning electron microscopy. Bull Soc Belge Ophthalmol. 2000;276:73-81.
  28. Lenton LM, Albietz JM. Effect of carmellose-based artificial tears on the ocular surface in eyes after laser in situ keratomileusis. J Refract Surg. 1999;2 (suppl):S227-S231.
  29. Albietz JM, Lenton LM, McLennan SG, Earl ML. A comparison of the effect of Refresh plus andBion tears on dry eye symptoms and ocular surface health in myopic LASIK patients. CLAO J. 2002;28:96-100.

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