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Peer Review | May/Jun '14

Dry Eye Disease and Refractive Surgery

The term dry eye disease (DED) is more of an umbrella diagnosis rather than one specific entity. This diagnosis includes aqueous deficiency, meibomian gland dysfunction (MGD), blepharitis, rosacea, allergies, medication-induced scarring, and chemical or thermal burns. When diagnosing a patient with DED either before or after refractive surgery, it is imperative for the physician to emphasize what specific deficiency the patient is exhibiting in order to more effectively treat it.

A careful history and physical exam are key in helping us point to the specific perpetrator. We should inquire about the presence of tearing, burning, stinging foreign body sensation, redness, mucous or watery discharge, eye fatigue, and use of eye drops. Past medical history of dermatologic diseases, rheumatoid arthritis, lupus, scleroderma, sarcoidosis, hepatitis C, HIV, previous facial trauma, or radiation to the orbit and menopausal status in women are important to know.

Physicians should examine the skin, eyelids, and adnexa and perform a slit-lamp exam focused on tear film integrity, eyelashes, anterior and posterior eyelid margins, puncta, fornix, and bulbar and tarsal conjunctiva. A detailed examination of the cornea should also be conducted to assess for localized areas of dryness, epithelial erosions, punctate staining, filaments, epithelial defects, basement membrane irregularities, mucous plaques, keratinization, pannus formation, thinning, infiltrates, ulceration, scarring, neovascularization, or any evidence of prior refractive surgery.1,2


A tear film and ocular surface evaluation including tear film inspection, tear break-up time (TBUT), and ocular surface staining should be included in every preoperative refractive surgery exam. Li et al3 used TBUT measurements to compare the effects of LASIK and ReLEx smile (Carl Zeiss Meditec) on dry eye symptoms. TBUT was statistically decreased after ReLEx smile at the 1-week, 1-month, and 3-month postoperative visits, while it was decreased at all visits up to 6 months after femtosecond LASIK. Although there have not been any studies published on the specific relationship between refractive surgery and anterior blepharitis or MGD, assessing the lid margin and meibomian gland function is an important part of the preoperative evaluation.

As more options become available to objectively quantify DED severity, such as lactoferrin, matrix metalloproteinase-9 (MMP-9) testing, and tear osmolarity, it will be interesting to see how these may affect laser refractive surgery evaluations.


LASIK, advanced surface ablation (such as PRK, epi-LASIK, and LASEK), and ReLEx smile are the main surgical options for refractive surgery. Each procedure has pros and cons, and individualized discussions between physicians and patients should take place in order to determine the best treatment option.

One advantage of PRK is that it carries a lower risk of tear dysfunction when compared with LASIK because the long posterior ciliary nerves are preserved. Patients who undergo PRK have less change from preoperative TBUT and tear osmolarity. However, subjectively, patients do not report a statistically significant increase of dry eye symptoms after LASIK when compared with PRK.4

Thin-flap LASIK may cause less decrease in corneal sensation, and patients generally return to normal tear function faster than with traditional LASIK. 4 When thin-flap LASIK was compared with PRK, PRK-treated eyes had less absolute decrease in corneal sensitivity, but there was no difference in Schirmer scores between the two treatment modalities.

Compared with LASIK, LASEK has been shown to result in less decrease in corneal sensitivity and in a faster recovery. However, thin-flap LASIK versus LASEK showed no significant postoperative corneal sensitivity difference up to 6 months postoperatively.4

When comparing microkeratome versus femtosecond laser LASIK flaps, femtosecond LASIK appears to lead to a quicker normalization of the ocular surface, as a faster recovery time in central corneal sensitivity and fewer dry eye symptoms occurred in the femtosecond LASIK group.5

Different platforms for performing the same surgical technique can cause variations in postoperative dry eye. When comparing the Intralase (Abbott Medical Optics) and VisuMax (Carl Zeiss Meditec), both femtosecond laser LASIK platforms, higher levels of inflammatory proteins and lower levels of lacrimal gland proteins were reported in the Intralase-operated eyes compared with the VisuMax-treated eyes. 6

ReLEx smile is a fairly new procedure that is rapidly gaining popularity. Because it is still a very new technique, there are conflicting views as to whether it decreases central corneal sensitivity or not. When subjectively comparing dry eye symptoms between femtosecond LASIK and ReLEx smile patients, Ocular Surface Disease Index (OSDI) scores increased significantly in both groups in comparison to preoperative scores, but they returned to preoperative levels by 1 month postoperatively. Patients who underwent ReLEx smile had significantly less corneal fluorescein staining than those who underwent femtosecond LASIK.3 ReLEx smile procedures seem to be associated with fewer postoperative ocular surface issues because there is less transection of corneal nerves in the anterior third of the corneal stroma as compared with femtosecond LASIK.3


Perioperative treatment options for patients with ocular surface disease (OSD) include artificial tears, nutritional supplementation, topical cyclosporine, topical steroids, punctal plugs, and newer treatments such as matrix metalloproteinase (MMP) inhibitors, as it is known that MMPs, especially MMP-9, play a major role in the inflammatory response component of OSD.7

Although less conventional and arguably risky, preoperative moderate to severe DED may not be an absolute contraindication to LASIK if managed appropriately with treatments such as artificial tears, topical autologous serum, and punctal occlusion, for example.8 Topical cyclosporine 0.05% emulsion after LASIK may effectively accelerate the recovery of corneal sensitivity, which suggests the benefit of improved corneal stromal nerve regeneration.9 Topical cyclosporine may also promote an expedited visual recovery and refractive stability after LASIK or PRK.10,11

Amniotic membrane could be another potential treatment for postrefractive surgery OSD. One case report showed the effectiveness of the application of an amniotic membrane after PRK in a patient with marked haze and residual myopia after excimer laser surgery. The patient’s haze was reduced by 50%, but his vision did not significantly improve.12

Recently, 3% diquafasol tetrasodium ophthalmic solution has gained popularity for the treatment of post-LASIK DED. Toda et al8 found that combination therapy with sodium hyaluronate and diquafosol tetrasodium significantly improved near uncorrected vision at 1 week and 1 month after LASIK and distance functional visual acuity at 1 month postoperatively.

Postoperatively, more severe DED can be quite recalcitrant to conventional therapy. Patients can have significant positive symptoms rather than a lack of sensation, such as chronic foreign body sensation, burning, and sometimes hyperesthesia. Such patients may require more specialized, advanced forms of dry eye therapy, including autologous serum tears, thermal pulsation therapy, or intense pulsed light to the lids or scleral lenses, although there is little published on the efficacy of these therapies, specifically on DED induced by corneal refractive surgery.

13 described one patient with DED after hyperopic LASIK whose symptoms improved using daily gas-permeable scleral contact lenses. Noda-Tsuruya et al14 demonstrated that the use of autologous serum drops after LASIK improved the TBUT and led to decreased ocular surface staining compared with the use of artificial tears alone; however, no statistically significant difference was observed in subjective dryness scores between the two treatment modalities.


OSD is a common risk factor and complication of refractive surgery that must be part of the evaluation and surgical discussion. Advanced surface ablation and thin-flap LASIK appear to result in less overall DED and should be preferentially considered for patients with greater risk factors or mild DED. Postoperative DED is generally transient but can be chronic in upward of 20% of patients and will likely require a customized combination of therapies for stabilization. The emerging surgical techniques and pre- and postoperative dry eye management options on the horizon show a promising future for corneal refractive surgery and patients with OSD.

1. Garcia-Zalisnak D, Nash D, Yeu E. Ocular surface disease and corneal refractive surgery. Curr Opin Ophthalmol. 2014; in press.

2. AAO Cornea/External Disease PPP Panel, Hoskins Center for Quality Eye Care. Dry Eye Syndrome Summary Benchmark - 2013.

3. Li M, Zhao J, Shen Y, et al. Comparison of dry eye and corneal sensitivity between small incision lenticule extraction and femtosecond LASIK for myopia. PLoS One. 2013;8(10):e77797.

4. Nettune G, Pflugfelder S. Post-LASIK tear dysfunction and dysesthesia. Ocul Surf. 2010;8(3):135-145.

5. Salamao MQ, Ambrosio R, Wilson SE. Dry eye associated with laser insitu keratomileusis: mechanical microkeratome versus femtosecond laser. J Cataract Refract Surg. 2009;35:1756-1760.

6. Souza S, Petznick A, Tong L, et al. Comparative analysis of two femtosecond LASIK platforms using iTRAQ. Comparative analysis of two femtosecond LASIK platforms using ITRAQ quantitative proteomics. Invest Ophthalmol Vis Sci. 2014;55(6):3396-3402.

7. Sambursky R, O’Brien TP. MMP-9 and the perioperative management of LASIK surgery. Curr Opin Ophthalmol. 2011;22(4): 294-303.

8. Toda I, Takeshi I, Teruki F, Ichihashi Y, Tsubota, K. Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis. Am J Ophthalmol. 2014;157(3):616-622.

9. Peyman GA, Sanders DR, Batlle JF, Féliz R, Cabrera G. Cyclosporine 0.05% ophthalmic preparation to aid recovery from loss of corneal sensitivity after LASIK. J Refract Surg. 2008;24(4):337-343.

10. Salib GM, McDonald MB, Smolek M. Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dry-eye patients having laser in situ keratomileusis. J Cataract Refract Surg. 2006;32(5):772-778.

11. Ursea R, Purcell TL, Tan BU, et al. The effect of cyclosporine A (Restasis) on recovery of visual acuity following LASIK. J Refract Surg. 2008;24(5):473-476.

12. Dua H, Gomes J, King A, Maharajan V. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51-77.

13. Segal O, Barkana Y, Hourovitz D, et al. Scleral contact lenses may help where other modalities fail. Cornea. 2003;22(4):308-310.

14. Noda-Tsuruya T, Asano-Kato N, Toda I, Tsbota K. Autologous serum eye drops for dry eye after LASIK. J Refract Surg. 2006;22(1):61-66.

Debora Garcia-Zalisnak, MD

Debora Garcia-Zalisnak, MD, is a resident at Eastern Virginia Medical School. Dr. Garcia Zalisnak may be reached at debora.e.garcia@gmail.com.