1 Postrefractive surgery dry eye Guilherme G. Quinto, Walter Camacho and Ashley Behrens The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Correspondence to Ashley Behrens, MD, The Wilmer Eye Institute, 600 North Wolfe St., 255 Woods Building, Baltimore, MD , USA Tel: ; Current Opinion in Ophthalmology 2008, 19: Purpose of review To report the recently published literature on ocular surface changes after refractive surgery, as well as the outcomes of treatment modalities on postrefractive surgery dry eye. Recent findings Cyclosporine, the first US Food and Drug Administration approved agent to treat the underlying pathological mechanism of chronic dry eye, has demonstrated promising results in dry eye patients. Further, there may be an additive effect of topical cyclosporine and punctal occlusion. Femtosecond lasers for corneal flaps in laser in-situ keratomileusis seem to induce fewer signs and symptoms of dry eye and may be attributed to the creation of thinner flaps. Summary Dry eye is one of the most common complications after photorefractive keratectomy and laser in-situ keratomileusis. Keratorefractive surgery is known to cause damage to the corneal sensory nerves. Several studies have demonstrated a decrease in corneal sensation, tear secretion, and tear film stability several months after keratorefractive surgery. For patients with preoperative dry eye, the ocular surface must be treated accordingly prior to surgery. Keywords dry eye syndrome, laser in-situ keratomileusis, management, ocular surface, photorefractive keratectomy Curr Opin Ophthalmol 19: ß 2008 Wolters Kluwer Health Lippincott Williams & Wilkins Introduction One of the most common complications of photorefractive keratectomy (PRK) and laser in-situ keratomileusis (LASIK) is dry eye syndrome [1,2 ]. Although dry eye after refractive surgery is usually transient, some patients complain of severe symptoms, which may negatively influence their satisfaction with the outcome of the procedure [3,4]. Both keratorefractive procedures have been reported to perturb the ocular surface homeostasis by causing a decrease in corneal sensitivity, tear film instability, decreased aqueous tear production, and corneal and conjunctival epitheliopathy . This review summarizes the recently published literature on the ocular surface changes after keratorefractive surgery and its treatment modalities. Dry eye syndrome Dry eye syndrome encompasses diverse etiologies and varies greatly in severity. In addition, correlations between symptoms, clinical signs, and diagnostic test results are variable, making the diagnosis and treatment of this condition challenging [6 ]. Due to this need, an International Task Force consisting of 17 dry eye expert clinicians was gathered to elaborate diagnostic and treatment guidelines for dry eye syndrome using a Delphi consensus technique . One of the recommendations of the panel was that the term dry eye syndrome be replaced with dysfunctional tear syndrome to reflect current understanding of the pathophysiology of the disease . DEWS Definition and Classification Subcommittee [7 ] provided a contemporary definition of dry eye disease supported within a comprehensive classification framework. A new definition of dry eye was developed to reflect current understanding of the disease, and the committee recommended a three-part classification of dry eye, based on etiology, mechanism, and disease stage. These guidelines are not intended to override the clinical assessment and adjustment of an expert clinician in individual cases. Dry eye syndrome is defined as a disorder of the tear film caused by tear deficiency or excessive tear evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort [8 10]. Diagnosis is made after analyzing patients complaints, objective signs, and abnormal results of dry eye ß 2008 Wolters Kluwer Health Lippincott Williams & Wilkins
2 336 Refractive surgery tests . The symptoms are usually described by patients as burning, dryness, or foreign-body sensation, often associated with ocular pain, blurred vision, photophobia, and visual fatigue. The clinical signs of dry eye include positive vital staining of ocular surface, decreased tear film breakup time and Schirmer tests, reduced corneal sensitivity, and decreased functional visual acuity . The quality of life can be significantly affected by dry eye symptoms, as documented by several validated survey instruments . The psychological impact of this chronic condition is suggested by a utility assessment of patients willingness to trade years at the end of life for an opportunity to be free of dry eye, which found that the utility of moderate dry eye was similar to that of moderate angina . Etiology The pathophysiologic definition of dry eye was changed to a dysfunction of the integrated ocular surface-secretory glandular functional unit . Communication between the ocular surface and 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 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 gland and the ocular surface is created . Adequate aqueous tear production and clearance with normal mucous gland function are finely controlled by balancing the innervation of the ocular surface and the tearsecreting glands to prevent surface dryness. The dry eye from keratorefractive surgery results mostly from damage to the corneal sensory nerves. Inflammation plays an important role as well in the pathogenesis of dry eye, and it has been elucidated over the past decade . Decreased tear production and tear clearance lead to chronic inflammation of the ocular surface. This inflammatory response consists of cellular infiltration of the ocular surface by activated T lymphocytes, 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 matrix metalloproteinase MMP-9 in the tear fluid. Significant positive correlation has been observed between the levels of inflammatory cytokines in the conjunctival epithelium and the severity of symptoms of ocular irritation, corneal fluorescein staining, and severity of conjunctival squamous metaplasia in patients with Sjögren s syndrome keratoconjunctivitis . Tear secretion and tear film instability Keratorefractive surgery seems to cause tear-deficient dry eye by a neural-based mechanism. Since the usual standard method to evaluate reduced tear volume and tear flow is the Schirmer test, studies have consistently included these data when reporting dry eye incidence . Several recent studies have demonstrated the decrease on corneal barrier, tear secretion, and tear film stability. Polunin et al.  showed that the corneal barrier function decreased after PRK and LASIK treatments, and the recovery was more delayed after LASIK than after PRK. Yu et al.  investigated the effect of LASIK on tear function in 96 eyes of 58 patients for the correction of myopia. LASIK significantly altered the tear break-up time, Schirmer test values, and basal tear secretion. They also concluded that patients with preexisting tear flow abnormality measured with Schirmer test values less than 10 mm was a significant risk factor for experiencing dry eye symptoms at 1 month after surgery. Lee et al.  compared tear secretion and tear film instability following PRK (36 eyes of 21 patients, ranging from 2.50 to 6.00 D) and LASIK (39 eyes of 25 patients, ranging from 3.25 to 9.75 D). At 3 months following surgery there was significantly decreased tear secretion and tear film stability in LASIK patients compared with PRK patients. Although not statistically significant at 6 months, tear secretion and tear film stability were still decreased in LASIK and these values never reached preoperative levels. Nejima et al.  evaluated corneal barrier function, tear secretion, and tear stability after PRK (28 eyes of 15 patients) and LASIK (115 eyes of 59 patients). Both procedures decreased epithelial barrier function, reduced tear secretion, and deteriorated tear film stability (P < 0.05). Increases in corneal epithelial permeability were, again, more prolonged after LASIK than after PRK. A significant intergroup difference in permeability was observed 1 month after surgery (P < 0.05). In their study, tear break-up time was significantly shorter in the LASIK group than in the PRK group up to 3 months after surgery (P < 0.045). Konomi et al.  have shown recently that preoperative tear volume may affect the recovery of the ocular surface after LASIK, increasing the risk of chronic dry eye. In this study, patients were classified into two main outcome groups: the nondry eye group and the chronic dry eye group, on the basis of dry eye status 9 months after surgery. All parameters, except rose bengal staining, were significantly deteriorated after surgery but returned to preoperative levels within 3 9 months. The chronic dry
3 Postrefractive surgery dry eye Quinto et al. 337 eye group had significantly lower preoperative Schirmer test values, both with and without anesthesia, and showed delayed recovery in goblet cell density, rose bengal staining, Schirmer test values without anesthesia, and tear break-up time after surgery. Results of preoperative Schirmer tests without anesthesia positively correlated with tear break-up time 9 months after surgery. Preoperative Schirmer test values without anesthesia appeared to be predictive of the development of chronic dry eye after LASIK. Corneal sensation Corneal sensitivity is essential for the maintenance of normal corneal structure and function . Inevitably, surgical procedures such as PRK and LASIK induce loss of normal sensitivity which may compromise the protective blink reflex, delay epithelial wound healing, and even induce neurotrophic keratitis or sterile corneal melts [22,23]. In PRK, the damage is to the sensory nerve endings that terminate in the corneal epithelium that is removed by mechanical scraping during the procedure . In both PRK and LASIK, there is additional damage to the nerves in the stroma removed by the laser procedure and the greater the myopic correction, the greater the dry eye symptoms . In LASIK, the superior hinged corneal flap is made through the stroma, transecting the posterior corneal nerve trunks that enter the cornea at the 3 and 9 o clock positions and provide the sensory innervation to the cornea . Several studies have compared PRK and LASIK in terms of their influence on corneal sensation. Campos et al.  reported that in a series of 14 eyes that had undergone PRK, patients with preoperative myopia of less than 6.50 D recovered 95.7% of central corneal sensitivity after 3 months, whereas patients with severe myopia (more than 9.00 D) recovered 86.2% of the original corneal sensitivity at the same time period. Chuck et al.  evaluated 28 eyes of 18 patients (range D) who underwent LASIK. Preoperative and postoperative corneal sensation at the nasal flap hinge, at the central cornea and within the temporal flap edge was measured before and after LASIK for a 3-week period using the Cochet-Bonnet esthesiometer. Corneal sensation initially decreased in all three positions of the flap measured after LASIK and the greatest decrease was in the central cornea. Near preoperative corneal sensation returned by 3 weeks. Furthermore, the degree of sensation loss did not appear to correlate with the ablation depth. Pérez-Santoja et al.  evaluated the recovery of postoperative corneal sensitivity after LASIK (17 eyes of 17 patients, ranging from 3.25 to 6.75 D) and PRK (18 eyes of 18 patients, ranging from 3.12 to 7.00 D) for correction of low myopia. Corneal sensitivity was tested at the center of the cornea, and in four additional central points 2 mm from the corneal center. They showed that corneal sensitivity after LASIK was reduced at the ablation zone during the first months (P < 0.05), and, only after 6 months, it returned to its preoperative values. In the PRK group, corneal sensitivity recovered its preoperative values 1 month after surgery (P > 0.05) except for the central corneal point which took 3 months to recover. Comparing both groups, corneal sensitivity was more compromised after LASIK than PRK during the first 3 months (P < 0.05), except for the nasal central point, although no differences were found between both groups at 6 months (P > 0.05). Matsui et al.  compared the effects of PRK (22 patients, ranging from 2.00 to 7.75 D) and LASIK (13 patients, ranging from 4.38 to D) on corneal sensation. After PRK, corneal sensitivity was decreased slightly at 3 days, began to recover at 1 week, and returned to preoperative values at 3 months, but none of the changes was statistically significant (P > 0.05). After LASIK, corneal sensation was significantly decreased at 3 days, 1 week and 1 month; it recovered slightly at 3 months, although it remained significantly less than preoperatively. Nejima et al.  have demonstrated that LASIK induces greater and more prolonged damage to corneal sensation than PRK. After PRK, corneal sensation was significantly deteriorated compared with the preoperative level up to 6 months postoperatively. After LASIK, corneal sensation did not return to the normal level throughout the 12 months postoperatively. Use of intraoperative mitomycin C Recently, encouraging results have been reported in reducing haze after high myopic PRK corrections by administering a single intraoperative application of diluted mitomycin C (MMC) solution . Bedei et al.  evaluated the prophylactic use of MMC to reduce haze formation and refractive regression after PRK for high myopic defects (over 5.00 D). The application of MMC 0.02% solution immediately after PRK produced lower haze rates and had better predictability and improved efficacy 1 year after treatment. Kymionis et al. , however, reported a patient with dry eye after bilateral PRK ( left eye and right eye) with MMC treatment in the left eye. The patient developed dry eye symptoms and superficial punctate keratopathy (SPK) in the eye treated with MMC for 15 months postoperatively whereas no evidence was noted in the control eye, except for mild haze. Uncorrected visual acuity was 20/20 in both eyes at 15 months.
4 338 Refractive surgery Femtosecond laser The solid-state femtosecond laser creates variable thickness and size corneal flaps for LASIK. The femtosecond laser seems to have advantages over mechanical microkeratomes including improved predictability of the flap thickness and diameter, better flap uniformity, better predictability of hinge position and size, astigmatic neutrality, and reduced incidence of epithelial defects, buttonholes, and cap perforation . Mian et al. [2 ] have reported dry eye after LASIK in 66 eyes (33 patients) with the femtosecond laser (assessed by the Ocular Surface Disease Index), with values of 22.9% after the first week postoperatively, and 21.9% after the first month (P < ). Overall, symptoms were mild and resolved over the first month. The lower incidence of dry eye signs and symptoms with the femtosecond laser may be attributed to the application of lower suction on the eye and creation of thinner flaps, resulting in a greater residual stromal bed and a decreased corneal denervation. They also demonstrated that loss of central corneal sensation persisted significantly longer than dry eye signs and symptoms and was, in fact, still present at the 1-year postoperative examination. Furthermore, they showed that when performing LASIK with femtosecond laser, either with superior hinge or nasal/temporal hinge position, there was no effect on either corneal sensation or dry eye parameters. In fact, decreased corneal sensation and LASIK-induced neurotrophic epitheliopathy  seemed to correlate well with the degree of preoperative myopia, depth of laser treatment, and flap thickness. Rodriguez et al. [31 ] have studied the effect of the LASIK procedure performed with femtosecond laser (34 eyes, preoperative spherical equivalent D) and a manual microkeratome (30 eyes, preoperative spherical equivalent D). All patients in both groups showed a decrease in goblet cells after LASIK that recovered after 6 months. At 1 week, 1 month and 3 months, goblet cell counts were lower with the femtosecond group than with microkeratome group (P < 0.001). This finding is probably explained because of the length of time that the suction ring exerted pressure on the conjunctiva, which is considerably larger in the femtosecond laser compared with the microkeratome. These changes in the goblet cells may contribute to the development of the ocular surface syndrome after LASIK. Preoperative dry eye The efficacy and safety of refractive surgery is not necessarily affected by preexisting dry eye. Preexisting dry eye, however, is a risk factor for symptomatic postkerat orefractive surgery dry eye with measurable lower tear function and supra-vital staining of the ocular surface. Preoperative conjunctival staining represents a risk factor for postoperative dry eye, and corneal staining is considered to be a relative contraindication of surgery until the ocular surface has been stabilized. Patients with symptoms of dry eye but no signs of corneal or conjunctival staining are generally good candidates for refractive surgery. Patients who have dry eye symptoms with mild conjunctival staining should be treated accordingly in order to stabilize the ocular surface prior to surgery . Many patients who want to have excimer laser refractive surgery are not able to wear contact lenses because of preexisting dry eye or secondary dry eye caused by longterm contact lens use. Commonly, these patients continue to report dry eye symptoms after surgery, despite an improvement in visual acuity following successful correction of the refractive error . Patients with dry eye syndrome are typically considered poor surgical candidates because of an increased association with postoperative complications, including severe dry eye, fluctuating vision, abnormal wound healing, and persistent epithelial defects which can predispose to an increased incidence of diffuse lamellar and microbial keratitis [5,22,32,33]. Patients without preoperative dry eye may experience symptoms and decreased tear function for several months after keratorefractive surgery. Moreover, patients with preoperative dry eye exhibited more severe symptoms and ocular surface damage after keratorefractive surgery compared with patients without preexisting dry eye, although efficacy and predictability were comparable between these groups . A retrospective study was carried out by Toda et al.  in which the patients were preoperatively categorized into two groups the dry eye group and the nondry eye group according to selected criteria for characterization of dry eye. Subsequently, the incidence of complications, loss of best corrected visual acuity (BCVA), and dry eye symptoms/tear function were compared in the two groups postoperatively. No difference was identified in the incidence of intraoperative and postoperative complications and loss of BCVA between groups. Dry eye symptoms and tear function were more compromised in the dry eye group preoperatively and also postoperatively, 1 year after the surgery. Despite this, symptoms and tear function returned to preoperative levels in both groups. The authors suggest that these results may indicate that LASIK may be performed safely and effectively in patients with preoperative dry eye. Albietz et al.  examined the relationship between chronic dry eye and refractive regression after LASIK for myopia. The regression after LASIK occurred in 12 (27%) of 45 patients with chronic dry eye and in 34 (7%) of 520 patients without dry eye (P < ). Patients with chronic dry eye had significantly worse outcomes than those without (6 months, P ¼ 0.004; 12 months, P ¼ 0.008). The risk for regression
5 Postrefractive surgery dry eye Quinto et al. 339 was associated with higher attempted refractive correction, greater ablation depth, and dry eye symptoms after LASIK. Management The majority of patients with dry eyes respond to conventional treatment aimed at optimizing the ocular surface microenvironment. The ecosystem of the ocular surface depends on dynamic interactions of healthy adnexae, adequate blink reflex, normal tear production, and ocular surface tissue, consisting mostly of cornea and conjunctiva. Conventional therapeutic options include intensive tear supplements, punctal occlusion, contact lenses, and an appropriate management of the adnexal disease . Artificial tears have been the primary treatment of the postkeratorefractive surgery dry eye [36,37]. Despite attempts to improve composition, artificial tears can never replace those produced by the lacrimal gland. In the last decade, it has been recognized that tears with preservatives may be toxic to the ocular surface epithelium. Therefore, it has been recommended to use preservative-free artificial tears in some cases [9,37]. While artificial tears improve symptoms of dry eye, they do not eliminate the underlying inflammatory process . Meibomian gland dysfunction is another common and critical component of ocular surface inflammation. Patients with meibomian gland dysfunction due to blockage of the glands may also benefit from warm compresses, lid scrubs and massages that would help breaking up the oils and open up the ducts within the glands [11,39]. This particular problem is best controlled with systemic antibiotics, such as doxycycline for a period of 4 6 weeks or more . These antibiotics have shown the capacity of thinning these glands secretions, to maintain the natural flow of their secretions. Anti-inflammatory therapy using topical corticosteroids has also been reported to be an efficacious therapy for patients with dry eye . Marsh and Pflugfelder  reported the efficacy of a topical administration of 1% nonpreserved methylprednisolone for patients with severe dry eye, demonstrating relief from irritation, a decrease in fluorescein staining, and resolution of SPK. While topical steroids may have the most rapid anti-inflammatory action, treatment is not advisable for long-term management because of the side effects of corticosteroids, especially cataract formation and glaucoma . In 2002, the Federal Drug Administration approved cyclosporine for the treatment of dry eye. Cyclosporine 0.05% ophthalmic emulsion was the first treatment to target the underlying pathological mechanism for chronic dry eye: the immune-mediated inflammation. Cyclosporine has minimal side effects compared with steroids and may be used for long periods of time without deleterious effects in the eye [38,41,42]. In addition, cyclosporine offers the advantage of immunomodulation without the risk of corticosteroids side effects, as opposed to immunosuppression. This treatment has been shown to increase tear production and reduce inflammation based on T-cell recruitment as well as increasing goblet cell numbers, and preventing lymphocyte infiltration within the lacrimal and accessory glands and conjunctiva . Salib et al.  carried out a study to evaluate two treatments for dry eye, and refractive outcomes in patients with dry eye having LASIK. Forty-two eyes of 12 myopic patients (ranging from 1.00 to D) with dry eye were treated with unpreserved artificial tears or cyclosporine 0.05% ophthalmic emulsion twice a day beginning 1 month before LASIK. Treatment with the study drug was discontinued for 48 h following refractive surgery and then resumed for three additional months. Statistically significant increases from baseline were found in Schirmer values for artificial tears at 1 month (P ¼ 0.036) and cyclosporine before surgery and 1 week, 1 month, and 6 months after surgery (P < 0.018). Mean refractive spherical equivalent in cyclosporine-treated eyes was significantly closer to the intended target at 3 and 6 months after surgery than in artificial-tear-treated eyes (P ¼ 0.007). Thus, treatment with cyclosporine 0.05% provided greater refractive predictability at 3 and 6 months after surgery than unpreserved artificial tears, according to this study. Punctal plugs is another tool that appears to be a relatively safe, effective, and reversible method of preserving aqueous and artificial tears on the ocular surface to reduce the signs and symptoms of dry eye . Studies have shown that dry eye patients may often decrease and sometimes eliminate the need for artificial tear preparations . Albietz et al.  reported that postoperative ocular surface management, which included the use of punctal plugs when indicated, improved symptoms and goblet cell density in patients who had undergone PRK or LASIK. Since punctal occlusion and topical cyclosporine treat dry eye under different mechanisms, Roberts et al. [48 ] carried out a study to examine their efficacy separately and then in combination. They evaluated three treatment regimens consisting of topical cyclosporine twice daily, punctal plugs, and a combination of cyclosporine and plugs over 6 months. As a result, all three treatment groups were effective and increased tear volume to a similar extent over the course of the study. At 1 and 3 months, however, groups that included punctal plugs were superior to cyclosporine alone in improving Schirmer scores. These results are consistent with the known function of punctal occlusion in physical conservation of existing tears. In summary, although all the treatments in this study effectively treated
6 340 Refractive surgery chronic dry eye, some trends regarding specific modalities are evident. In the near term, punctal occlusion (alone or in combination with cyclosporine) produced the most rapid improvements in wetness, as assessed by Schirmer testing and patient self-medication with artificial tears, consistent with the tearing conserving function of punctal plugs. Over the longer term, the cyclosporine-containing regimen resulted in improvement in the same measures that were statistically indistinguishable from, or were superior to, the plugs-only regimen. Furthermore, only the cyclosporine-containing regimen significantly improved ocular surface staining over time. These observations are consistent with the known roles of topical cyclosporine in addressing the underlying immune pathophysiology of chronic dry eye disease. There may be an additive effect of topical cyclosporine and punctal occlusion, and patients with punctal occlusion may also benefit from adjunctive cyclosporine. Autologous serum has also been used as a potential treatment for dry eye. It contains anti-inflammatory agents and MMP inhibitors that are especially useful in patients with autoimmune-associated inflammatory processes, such as Sjögren s [38,49]. The efficacy of autologous serum application for the treatment of corneal transplantation or other ocular surface disorders , such as superior limbic keratitis , dry eye in graft-versus-host disease , or Stevens-Johnson syndrome , has been reported. These studies suggest that autologous serum may improve almost all types of dry eye. Noda-Tsuruya et al.  evaluated the efficacy of autologous serum eye drops for dry eye after LASIK. The results showed that break-up time test and vital staining were significantly improved after LASIK in the autologous serum eye drops group, whereas no change was reported in the artificial tear group at 6 months postoperatively. These findings suggest that autologous serum eye drops could be effective for postoperative dry eye induced by LASIK. Toda et al.  performed LASIK in three patients who suffered from Sjögren s syndrome and showed decreased reflex tearing. They inserted punctal plugs and prepared the autologous serum at the first visit of each patient. The LASIK procedure was scheduled to be undertaken after the ocular surface damage was healed by the treatment. LASIK was then performed uneventfully, and no complications were observed in any of the patients. These results indicate that LASIK may be safely performed on patients with severe dry eye, if the ocular surface damage is energetically treated before surgery. Conclusion LASIK and PRK may exacerbate preexisting dry eye, or trigger a previously nonexistent dry eye. The symptoms after keratorefractive surgery are usually transient but may cause significant discomfort in patients. Attention must be paid to dry eye in candidates undergoing keratorefractive surgery, and appropriate methods of management must be made available to these patients. The incidence of postkeratorefractive procedure dry eye may be reduced by identifying patients at risk for dry eye, maximizing tear film stability preoperatively, and minimizing dry eye through intra and postoperative interventions, both pharmacological and surgical. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 366). 1 Paiva CS, Chen Z, Koch DD, et al. The incidence and risk factors for developing dry eye after myopic LASIK. Am J Ophthalmol 2006; 141: Mian SI, Shtein RM, Nelson A, Musch DC. Effect of hinge position on corneal sensation and dry eye after laser in situ keratomileusis using a femtosecond laser. J Cataract Refract Surg 2007; 33: There was no difference in corneal sensation between superior-hinged and temporal-hinged flaps at 1 week, 1, 3, 6, and 12 months after surgery. Mild dry eye disease was present early after myopic LASIK with IntraLase laser. 3 Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea 2006; 25: Berry S, Mangione CM, Lindblad AS, McDonnell PJ. Development of the national eye institute refractive error correction quality of life questionnaire: focus groups. Ophthalmology 2003; 110: Wilson SE. Laser in situ keratomileusis-induced (presumed) neurotrophic epitheliopathy. Ophthalmology 2001; 108: Wilson SE, Stulting RD. Agreement of physician treatment practices with the International Task Force guidelines for diagnosis and treatment of dry eye disease. Cornea 2007; 26: Topical cyclosporine treatment appears to be associated with the cure of symptoms and signs in chronic dry eye patients. 7 The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: A new definition of dry eye was developed, and the committee recommended a three-part classification based on etiology, mechanism, and disease stage. 8 Ang RT, Dartt DA, Tsubota K. Dry eye after refractive surgery. Curr Opin Ophthalmol 2001; 12: Lemp MA. Report of the National Eye Institute/Industry Workshop on clinical trials in dry eyes. CLAO J 1995; 21: Tseng SC, Tsubota K. Important concepts for treating ocular surface and tear disorders. Am J Ophthalmol 1997; 124: Toda I. LASIK and dry eye. Compr Ophthalmol Update 2007; 8: Vitale S, Goodman LA, Reed GF, et al. Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjogren s syndrome-related dry eye. Health Qual Life Outcomes 2004; 2: Schiffman RM, Walt JG, Jacobsen F, et al. Utility assessment among patients with dry eye disease. Ophthalmology 2003; 110: Lee HK, Lee KS, Kim HC, et al. Nerve growth factor concentration and implications in photorefractive keratectomy vs laser in situ keratomileusis. Am J Ophthalmol 2005; 139: Solomon R, Donnenfeld ED, Perry HD. The effects of LASIK on the ocular surface. Ocul Surf 2004; 2: Polunin GS, Kourenkov VV, Makarov IA, Polunina EG. The corneal barrier function in myopic eyes after laser in situ keratomileusis and after photorefractive keratectomy in eyes with haze formation. J Refract Surg 1999; 15: Yu EYW, Leung A, Rao S, Lam DSC. Effect of laser in situ keratomileusis in tear stability. Ophthalmology 2000; 107: Lee JB, Ryu CH, Kim J, et al. Comparison of tear secretion and tear film instability after photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:
7 Postrefractive surgery dry eye Quinto et al Nejima R, Miyata K, Tanabe T, et al. Corneal barrier function, tear film stability, and corneal sensation after photorefractive keratectomy and laser in situ keratomileusis. Am J Ophthalmol 2005; 139: Komomi K, Chen LL, Tarko RS, et al. Preoperative characteristics and a potential mechanism of chronic dry eye after LASIK. Invest Ophthalmol Vis Sci 2008; 49: Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED, et al. Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 1997; 23: Pérez-Santoja JJ, Sakla HF, Cardona C, et al. Corneal sensitivity after photorefractive keratectomy and laser in situ keratomileusis for low myopia. Am J Ophthalmol 1999; 127: Matsui H, Kumano Y, Zushi I, et al. Corneal sensation after correction of myopia by photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 2001; 27: Donnenfeld ED, Solomon K, Perry HD, et al. The effect of hinge position on corneal sensation and dry eye after LASIK. Ophthalmology 2003; 110: Campos M, Hertzog L, Garbus JJ, McDonnell PJ. Corneal sensitivity after photorefractive keratectomy. Am J Ophthalmol 1992; 114: Chuck RS, Quiros PA, Perez AC, McDonnell PJ. Corneal sensation after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26: Gambato C, Ghirlando A, Moretto E, et al. Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes. Ophthalmology 2005; 28: Bedei A, Marabotti A, Giannecchini I, et al. Photorefractive keratectomy in high myopic defect with or without intraoperative mitomycin C: 1-year results. Eur J Ophthalmol 2006; 16: Kymionis GD, Tsiklis NS, Ginis H, Diakonis VF. Dry eye after photorefractive keratectomy with adjuvant mitomycin C. J Refract Surg 2006; 22: Munoz G, Albarra n-diego C, Sakla HF, et al. Transient light-sensitivity syndrome after laser in situ keratomileusis with the femtosecond laser: incidence and prevention. J Cataract Refract Surg 2006; 32: Rodriguez AE, Rodriguez-Prats JL, Hamdi IM, et al. Comparison of goblet cell density after femtosecond laser and mechanical microkeratome in LASIK. Invest Ophthalmol Vis Sci 2007; 48: Impression cytology showed a greater reduction in goblet cell populations after IntraLase femtosecond than after microkeratome, probably because of the length of time that the suction ring exerted pressure on the conjunctiva. 32 Albietz JM, Lenton LM, McLennan SG. Chronic dry eye and regression after laser in situ keratomileusis for myopia. J Cataract Refract Surg 2004; 30: Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Ophthalmol 2002; 120: Toda I, Asano-Kato N, Hori-Komai Y, et al. Ocular surface treatment before laser in situ keratomileusis in patients with severe dry eye. J Refract Surg 2004; 20: Noble BA, Loh RSK, MacLennan S, et al. Comparison of autologous serum eye drops with conventional therapy in a randomized controlled crossover trial for ocular surface disease. Br J Ophthalmol 2004; 88: Gipson IK, Hori Y, Argueso P. Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf 2004; 2: Pflugfelder SC, Solomon A, Stern ME. The diagnosis and management of dry eye: a twenty-five-year review. Cornea 2000; 19: Stern ME, Pflugfelder SC. Inflammation in dry eye. Ocul Surf 2004; 2: Lemp MA. Evaluation and differential diagnosis of keratoconjunctivitis sicca. J Rheumatol (Suppl) 2000; 61: Marsh P, Pflugfelder SC. Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology 1999; 106: Perry HD, Donnenfeld ED. Topical 0.05% cyclosporine in the treatment of dry eye. Expert Opin Pharmacother 2004; 5: Sall K, Stevenson OD, Mundorf TK, et al. 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: Avunduk AM, Avunduk MC, Varnell ED, Kaufman HE. The comparison of efficacies of topical corticosteroids and nonsteroidal antiinflammatory drops on dry eye patients: a clinical and immunocytochemical study. Am J Ophthalmol 2003; 136: 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: Baxter SA, Laibson PR. Punctal plugs in the treatment of dry eyes. Ocul Surf 2004; 2: Tai MC, Cosar CB, Cohen EJ, et al. The efficacy of silicone punctal plug therapy. Cornea 2002; 21: Albietz JM, McLennan SG, Lenton LM. Ocular surface management of photorefractive keratectomy and laser in situ keratomileusis. J Refract Surg 2003; 19: Roberts CW, Carniglia PE, Brazzo BG. Comparison of topical cyclosporine, punctal occlusion, and a combination for the treatment of dry eye. Cornea 2007; 26: Plug-containing regimens increased wetness initially; cyclosporine appeared to promote long-term ocular surface health. The effects may be additive. Patients with punctual occlusion may benefit from adjunctive cyclosporine. 49 Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by autologous serum application in Sjögren s syndrome. Br J Ophthalmol 1999; 83: Tsubota K, Higuchi A. Serum application for the treatment of ocular surface disorder. Int Ophthalmol Clin 2000; 40: Goto E, Shimmura S, Shimazaki J, Tsubota K. Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea 2001; 20: Ogawa Y, Okamoto S, Mori T, et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant 2003; 31: Noda-Tsuruya T, Asano-Kato N, Toda I, Tsubota K. Autologous serum eye drops for dry eye after LASIK. J Refract Surg 2006; 22:61 66.