Postrefractive Surgery Dry Eye Guilherme G

Home , Ablation, Dry eye syndrome, Myopia, Refractive error, Refractive surgery

Postrefractive surgery dry eye Guilherme G. Quinto, Walter Camacho and Ashley Behrens

The Wilmer Ophthalmological Institute, The Johns Purpose of review Hopkins University School of Medicine, Baltimore, Maryland, USA 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 Correspondence to Ashley Behrens, MD, The Wilmer Eye Institute, 600 North Wolfe St., 255 Woods eye. Building, Baltimore, MD 21287-0005, USA Recent findings Tel: +1 410 502 0461; e-mail: [email protected] 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 Current Opinion in Ophthalmology 2008, 19:335–341 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 19:335–341 ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins 1040-8738

gathered to elaborate diagnostic and treatment guidelines Introduction for dry eye syndrome using a Delphi consensus technique One of the most common complications of photorefractive [3]. One of the recommendations of the panel was that the keratectomy (PRK) and laser in-situ keratomileusis term ‘dry eye syndrome’ be replaced with ‘dysfunctional (LASIK) is dry eye syndrome [1,2]. Although dry eye tear syndrome’ to reflect current understanding of the after refractive surgery is usually transient, some patients pathophysiology of the disease [3]. complain of severe symptoms, which may negatively influence their satisfaction with the outcome of the procedure [3,4]. Both keratorefractive procedures have been DEWS Definition and Classification Subcommittee [7] reported to perturb the ocular surface homeostasis by provided a contemporary definition of dry eye disease causing a decrease in corneal sensitivity, tear film instabil- supported within a comprehensive classification frame- ity, decreased aqueous tear production, and corneal and work. A new definition of dry eye was developed to conjunctival epitheliopathy [5]. This review summarizes reflect current understanding of the disease, and the the recently published literature on the ocular surface committee recommended a three-part classification of changes after keratorefractive surgery and its treatment dry eye, based on etiology, mechanism, and disease modalities. stage. These guidelines are not intended to override the clinical assessment and adjustment of an expert clinician in individual cases. Dry eye syndrome Dry eye syndrome encompasses diverse etiologies and Dry eye syndrome is defined as a disorder of the tear film varies greatly in severity. In addition, correlations between caused by tear deficiency or excessive tear evaporation, symptoms, clinical signs, and diagnostic test results are which causes damage to the interpalpebral ocular surface variable, making the diagnosis and treatment of this con- and is associated with symptoms of ocular discomfort dition challenging [6]. Due to this need, an International [8–10]. Diagnosis is made after analyzing patients’ com- Task Force consisting of 17 dry eye expert clinicians was plaints, objective signs, and abnormal results of dry eye

1040-8738 ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins

tests [11]. The symptoms are usually described by escein staining, and severity of conjunctival squamous patients as burning, dryness, or foreign-body sensation, metaplasia in patients with Sjo¨gren’s syndrome kerato- often associated with ocular pain, blurred vision, photo- conjunctivitis [15]. phobia, 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 Tear secretion and tear film instability corneal sensitivity, and decreased functional visual acuity Keratorefractive surgery seems to cause tear-deficient dry [11]. eye by a neural-based mechanism. Since the usual stan- dard method to evaluate reduced tear volume and tear flow The quality of life can be significantly affected by dry eye is the Schirmer test, studies have consistently included symptoms, as documented by several validated survey these data when reporting dry eye incidence [8]. Several instruments [12]. The psychological impact of this recent studies have demonstrated the decrease on corneal chronic condition is suggested by a utility assessment barrier, tear secretion, and tear film stability. Polunin et al. of patients’ willingness to trade years at the end of life for [16] showed that the corneal barrier function decreased an opportunity to be free of dry eye, which found that the after PRK and LASIK treatments, and the recovery was utility of moderate dry eye was similar to that of moderate more delayed after LASIK than after PRK. Yu et al. [17] angina [13]. 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 Etiology values, and basal tear secretion. They also concluded that The pathophysiologic definition of dry eye was changed patients with preexisting tear flow abnormality measured to a dysfunction of the integrated ocular surface-secretory with Schirmer test values less than 10 mm was a significant glandular functional unit [14]. Communication between risk factor for experiencing dry eye symptoms at 1 month the ocular surface and lacrimal glands occurs through a after surgery. sensory autonomic neural reflex loop. The sensory nerves innervating the ocular surface connect with efferent Lee et al. [18] compared tear secretion and tear film autonomic nerves in the brain stem that stimulate instability following PRK (36 eyes of 21 patients, ranging secretion of tear fluid and proteins by the lacrimal glands. from 2.50 to 6.00 D) and LASIK (39 eyes of 25 patients, Ocular surface sensitivity has been found to decrease as rangingÀ from À3.25 to 9.75 D). At 3 months following aqueous tear production and clearance of tears from the surgery there wasÀ significantlyÀ decreased tear secretion and ocular surface decrease. This decrease in surface sen- tear film stability in LASIK patients compared with PRK sation exacerbates dry eye because sensory stimulated patients. Although not statistically significant at 6 months, reflex tearing is decreased, resulting in decreased ability tear secretion and tear film stability were still decreased in of the lacrimal glands to respond to ocular surface insults. LASIK and these values never reached preoperative Thus, a self-perpetuating cycle between the lacrimal levels. Nejima et al. [19] evaluated corneal barrier function, gland and the ocular surface is created [14]. Adequate tear secretion, and tear stability after PRK (28 eyes of aqueous tear production and clearance with normal 15 patients) and LASIK (115 eyes of 59 patients). Both mucous gland function are finely controlled by balancing procedures decreased epithelial barrier function, reduced the innervation of the ocular surface and the tear- tear secretion, and deteriorated tear film stability secreting glands to prevent surface dryness. The dry (P < 0.05). Increases in corneal epithelial permeability eye from keratorefractive surgery results mostly from were, again, more prolonged after LASIK than after damage to the corneal sensory nerves. Inflammation plays PRK. A significant intergroup difference in permeability an important role as well in the pathogenesis of dry eye, was observed 1 month after surgery (P < 0.05). In their and it has been elucidated over the past decade [15]. study, tear break-up time was significantly shorter in the Decreased tear production and tear clearance lead to LASIK group than in the PRK group up to 3 months after chronic inflammation of the ocular surface. This inflam- surgery (P < 0.045). matory response consists of cellular infiltration of the ocular surface by activated T lymphocytes, with Konomi et al. [20] have shown recently that preoperative increased expression of adhesion molecules and inflam- tear volume may affect the recovery of the ocular surface matory cytokines, increased concentrations of inflamma- after LASIK, increasing the risk of chronic dry eye. In this tory cytokines in the tear fluid, and increased activity of study, patients were classified into two main outcome matrix degrading enzymes such as matrix metalloprotei- groups: the nondry eye group and the chronic dry eye nase MMP-9 in the tear fluid. Significant positive corre- group, on the basis of dry eye status 9 months after lation has been observed between the levels of inflam- surgery. All parameters, except rose bengal staining, were matory cytokines in the conjunctival epithelium and the significantly deteriorated after surgery but returned to severity of symptoms of ocular irritation, corneal fluor- preoperative levels within 3–9 months. The chronic dry

eye group had significantly lower preoperative Schirmer (18 eyes of 18 patients, ranging from 3.12 to 7.00 D) for test values, both with and without anesthesia, and showed correction of low myopia. Corneal sensitivityÀ wasÀ tested at delayed recovery in goblet cell density, rose bengal the center of the cornea, and in four additional central staining, Schirmer test values without anesthesia, and points 2 mm from the corneal center. They showed that tear break-up time after surgery. Results of preoperative corneal sensitivity after LASIK was reduced at the ablation Schirmer tests without anesthesia positively correlated zone during the first months (P < 0.05), and, only after with tear break-up time 9 months after surgery. Preopera- 6 months, it returned to its preoperative values. In the tive Schirmer test values without anesthesia appeared to PRK group, corneal sensitivity recovered its preopera- be predictive of the development of chronic dry eye after tivevalues1monthaftersurgery(P > 0.05)exceptforthe LASIK. central corneal point which took 3months to recover. Comparing both groups, corneal sensitivity was more compromised after LASIK than PRK during the first Corneal sensation 3 months (P < 0.05), except for the nasal central point, Corneal sensitivity is essential for the maintenance of although no differences were found between both normal corneal structure and function [21]. Inevitably, groups at 6months (P > 0.05). surgical procedures such as PRK and LASIK induce loss of normal sensitivity which may compromise the protec- Matsui et al. [23] compared the effects of PRK (22 patients, tive blink reflex, delay epithelial wound healing, and ranging from 2.00 to 7.75 D) and LASIK (13 patients, even induce neurotrophic keratitis or sterile corneal melts ranging fromÀ 4.38 toÀ 11.00 D) on corneal sensation. [22,23]. In PRK, the damage is to the sensory nerve After PRK, cornealÀ sensitivityÀ was decreased slightly at endings that terminate in the corneal epithelium that 3 days, began to recover at 1 week, and returned to pre- is removed by mechanical scraping during the procedure operative values at 3 months, but none of the changes was [8]. In both PRK and LASIK, there is additional damage statistically significant (P > 0.05). After LASIK, corneal to the nerves in the stroma removed by the laser pro- sensation was significantly decreased at 3 days, 1 week cedure and the greater the myopic correction, the greater and 1 month; it recovered slightly at 3 months, although the dry eye symptoms [8]. In LASIK, the superior hinged it remained significantly less than preoperatively. corneal flap is made through the stroma, transecting the posterior corneal nerve trunks that enter the cornea Nejima et al. [19] have demonstrated that LASIK induces at the 3 and 9 o’clock positions and provide the sensory greater and more prolonged damage to corneal sensation innervation to the cornea [24]. Several studies have than PRK. After PRK, corneal sensation was significantly compared PRK and LASIK in terms of their influence deteriorated compared with the preoperative level up to on corneal sensation. 6 months postoperatively. After LASIK, corneal sensation did not return to the normal level throughout the Campos et al. [25] reported that in a series of 14 eyes that 12 months postoperatively. had undergone PRK, patients with preoperative myopia of less than 6.50 D recovered 95.7% of central corneal sensitivity afterÀ 3 months, whereas patients with severe Use of intraoperative mitomycin C myopia (more than 9.00 D) recovered 86.2% of the Recently, encouraging results have been reported in original corneal sensitivityÀ at the same time period. reducing haze after high myopic PRK corrections by administering a single intraoperative application of diluted Chuck et al. [26] evaluated 28 eyes of 18 patients (range mitomycin C (MMC) solution [27]. Bedei et al. [28] 1.50–11.25 D) who underwent LASIK. Preoperative and evaluated the prophylactic use of MMC to reduce haze postoperative corneal sensation at the nasal flap hinge, at formation and refractive regression after PRK for high the central cornea and within the temporal flap edge myopic defects (over 5.00 D). The application of was measured before and after LASIK for a 3-week MMC 0.02% solution immediatelyÀ after PRK produced period using the Cochet-Bonnet esthesiometer. Corneal lowerhazeratesandhadbetterpredictabilityandimproved sensation initially decreased in all three positions of the efficacy 1 year after treatment. Kymionis et al. [29], how- flap measured after LASIK and the greatest decrease was ever, reported a patient with dry eye after bilateral PRK in the central cornea. Near preoperative corneal sensation (–5.50 0.50 170 left eye and 5.00 1.00 180 right returned by 3 weeks. Furthermore, the degree of sensation eye) withÀ MMCÂ treatment in theÀ leftÀ eye. TheÂ patient loss did not appear to correlate with the ablation depth. developed dry eye symptoms and superficial punctate keratopathy (SPK) in the eye treated with MMC for Pe´rez-Santoja et al. [22] evaluated the recovery of post- 15 months postoperatively whereas no evidence was noted operative corneal sensitivity after LASIK (17 eyes of in the control eye, except for mild haze. Uncorrected visual 17 patients, ranging from 3.25 to 6.75 D) and PRK acuity was 20/20 in both eyes at 15 months. À À

sidered to be a relative contraindication of surgery until Femtosecond laser the ocular surface has been stabilized. Patients with symp- The solid-state femtosecond laser creates variable thick- toms of dry eye but no signs of corneal or conjunctival ness and size corneal flaps for LASIK. The femtosecond staining are generally good candidates for refractive laser seems to have advantages over mechanical micro- surgery. Patients who have dry eye symptoms with mild keratomes including improved predictability of the flap conjunctival staining should be treated accordingly in thickness and diameter, better flap uniformity, better order to stabilize the ocular surface prior to surgery [15]. predictability of hinge position and size, astigmatic neutrality, and reduced incidence of epithelial defects, Many patients who want to have excimer laser refractive buttonholes, and cap perforation [30]. Mian et al. [2] have surgery are not able to wear contact lenses because of reported dry eye after LASIK in 66 eyes (33 patients) with preexisting dry eye or secondary dry eye caused by long- the femtosecond laser (assessed by the Ocular Surface term contact lens use. Commonly, these patients continue Disease Index), with values of 22.9% after the first week to report dry eye symptoms after surgery, despite an postoperatively, and 21.9% after the first month improvement in visual acuity following successful correc- (P < 0.00001). Overall, symptoms were mild and resolved tion of the refractive error [18]. Patients with dry eye over the first month. The lower incidence of dry eye signs syndrome are typically considered poor surgical candidates and symptoms with the femtosecond laser may be attri- because of an increased association with postoperative buted to the application of lower suction on the eye and complications, including severe dry eye, fluctuating vision, creation of thinner flaps, resulting in a greater residual abnormal wound healing, and persistent epithelial defects stromal bed and a decreased corneal denervation. They which can predispose to an increased incidence of diffuse also demonstrated that loss of central corneal sensation lamellar and microbial keratitis [5,22,32,33]. persisted significantly longer than dry eye signs and symptoms and was, in fact, still present at the 1-year postoperative examination. Furthermore, they showed Patients without preoperative dry eye may experience that when performing LASIK with femtosecond laser, symptoms and decreased tear function for several months either with superior hinge or nasal/temporal hinge pos- after keratorefractive surgery. Moreover, patients with ition, there was no effect on either corneal sensation or dry preoperative dry eye exhibited more severe symptoms eye parameters. In fact, decreased corneal sensation and and ocular surface damage after keratorefractive surgery LASIK-induced neurotrophic epitheliopathy [5] seemed compared with patients without preexisting dry eye, to correlate well with the degree of preoperative myopia, although efficacy and predictability were comparable depth of laser treatment, and flap thickness. Rodriguez between these groups [34]. et al. [31] have studied the effect of the LASIK procedure performed with femtosecond laser (34 eyes, preoperative A retrospective study was carried out by Toda et al. [33] in spherical equivalent 3.1 3.1 D) and a manual micro- which the patients were preoperatively categorized into keratome (30 eyes,À preoperativeÆ spherical equivalent two groups – the dry eye group and the nondry eye group – 2.0 3.8 D). All patients in both groups showed a according to selected criteria for characterization of dry decreaseÀ Æ in goblet cells after LASIK that recovered after eye. Subsequently, the incidence of complications, loss of 6 months. At 1 week, 1 month and 3 months, goblet cell best corrected visual acuity (BCVA), and dry eye symp- counts were lower with the femtosecond group than with toms/tear function were compared in the two groups post- microkeratome group (P < 0.001). This finding is probably operatively. No difference was identified in the incidence explained because of the length of time that the suction of intraoperative and postoperative complications and loss ring exerted pressure on the conjunctiva, which is of BCVA between groups. Dry eye symptoms and tear considerably larger in the femtosecond laser compared function were more compromised in the dry eye group with the microkeratome. These changes in the goblet cells preoperatively and also postoperatively, 1 year after the may contribute to the development of the ocular surface surgery. Despite this, symptoms and tear function syndrome after LASIK. 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 preoperative dry eye. Albietz et al. [32] examined the The efficacy and safety of refractive surgery is not necess- relationship between chronic dry eye and refractive arily affected by preexisting dry eye. Preexisting dry eye, regression after LASIK for myopia. The regression after however, is a risk factor for symptomatic postkerat LASIK occurred in 12 (27%) of 45 patients with chronic dry orefractive surgery dry eye with measurable lower tear eye and in 34 (7%) of 520 patients without dry eye function and supra-vital staining of the ocular surface. (P < 0.0001). Patients with chronic dry eye had signifi- Preoperative conjunctival staining represents a risk factor cantly worse outcomes than those without (6 months, for postoperative dry eye, and corneal staining is con- P 0.004; 12 months, P 0.008). The risk for regression ¼ ¼

was associated with higher attempted refractive correction, target the underlying pathological mechanism for chronic greater ablation depth, and dry eye symptoms after dry eye: the immune-mediated inflammation. Cyclospor- LASIK. ine 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 Management offers the advantage of immunomodulation without the The majority of patients with dry eyes respond to risk of corticosteroids’ side effects, as opposed to immu- conventional treatment aimed at optimizing the ocular nosuppression. This treatment has been shown to increase surface microenvironment. The ecosystem of the ocular tear production and reduce inflammation based on T-cell surface depends on dynamic interactions of healthy recruitment as well as increasing goblet cell numbers, and adnexae, adequate blink reflex, normal tear production, preventing lymphocyte infiltration within the lacrimal and and ocular surface tissue, consisting mostly of cornea and accessory glands and conjunctiva [43]. Salib et al. [44] conjunctiva. Conventional therapeutic options include carried out a study to evaluate two treatments for dry intensive tear supplements, punctal occlusion, contact eye, and refractive outcomes in patients with dry eye lenses, and an appropriate management of the adnexal having LASIK. Forty-two eyes of 12 myopic patients disease [35]. (ranging from –1.00 to –10.63 D) with dry eye were treated with unpreserved artificial tears or cyclosporine 0.05% Artificial tears have been the primary treatment of the ophthalmic emulsion twice a day beginning 1 month postkeratorefractive surgery dry eye [36,37]. Despite before LASIK. Treatment with the study drug was attempts to improve composition, artificial tears can discontinued for 48 h following refractive surgery and then never replace those produced by the lacrimal gland. In resumed for three additional months. Statistically signifi- the last decade, it has been recognized that tears cant increases from baseline were found in Schirmer values with preservatives may be toxic to the ocular surface for artificial tears at 1 month (P 0.036) and cyclosporine epithelium. Therefore, it has been recommended to use before surgery and 1 week, 1 month,¼ and 6 months after preservative-free artificial tears in some cases [9,37]. surgery (P < 0.018). Mean refractive spherical equivalent While artificial tears improve symptoms of dry eye, they in cyclosporine-treated eyes was significantly closer to the do not eliminate the underlying inflammatory process intended target at 3 and 6 months after surgery than in [38]. artificial-tear-treated eyes (P 0.007). Thus, treatment with cyclosporine 0.05% provided¼ greater refractive Meibomian gland dysfunction is another common and predictability at 3 and 6 months after surgery than unpre- critical component of ocular surface inflammation. served artificial tears, according to this study. Patients with meibomian gland dysfunction due to block- age of the glands may also benefit from warm compresses, Punctal plugs is another tool that appears to be a relatively lid scrubs and massages that would help breaking up the safe, effective, and reversible method of preserving oils and open up the ducts within the glands [11,39]. This aqueous and artificial tears on the ocular surface to reduce particular problem is best controlled with systemic anti- the signs and symptoms of dry eye [45]. Studies have biotics, such as doxycycline for a period of 4–6 weeks or shown that dry eye patients may often decrease and some- more [39]. These antibiotics have shown the capacity of times eliminate the need for artificial tear preparations thinning these glands secretions, to maintain the natural [46]. Albietz et al. [47] reported that postoperative ocular flow of their secretions. surface management, which included the use of punctal plugs when indicated, improved symptoms and goblet cell Anti-inflammatory therapy using topical corticosteroids density in patients who had undergone PRK or LASIK. has also been reported to be an efficacious therapy for Since punctal occlusion and topical cyclosporine treat dry patients with dry eye [36]. Marsh and Pflugfelder [40] eye under different mechanisms, Roberts et al. [48] reported the efficacy of a topical administration of 1% carried out a study to examine their efficacy separately nonpreserved methylprednisolone for patients with severe and then in combination. They evaluated three treatment dry eye, demonstrating relief from irritation, a decrease in regimens consisting of topical cyclosporine twice daily, fluorescein staining, and resolution of SPK. While topical punctal plugs, and a combination of cyclosporine and plugs steroids may have the most rapid anti-inflammatory action, over 6 months. As a result, all three treatment groups were treatment is not advisable for long-term management effective and increased tear volume to a similar extent over because of the side effects of corticosteroids, especially the course of the study. At 1 and 3 months, however, groups cataract formation and glaucoma [38]. that included punctal plugs were superior to cyclosporine alone in improving Schirmer scores. These results are In 2002, the Federal Drug Administration approved consistent with the known function of punctal occlusion cyclosporine for the treatment of dry eye. Cyclosporine in physical conservation of existing tears. In summary, 0.05% ophthalmic emulsion was the first treatment to although all the treatments in this study effectively treated

chronic dry eye, some trends regarding specific modalities must be paid to dry eye in candidates undergoing are evident. In the near term, punctal occlusion (alone or in keratorefractive surgery, and appropriate methods of combination with cyclosporine) produced the most rapid management must be made available to these patients. improvements in wetness, as assessed by Schirmer testing The incidence of postkeratorefractive procedure dry eye and patient self-medication with artificial tears, consistent may be reduced by identifying patients at risk for dry eye, with the tearing–conserving function of punctal plugs. maximizing tear film stability preoperatively, and Over the longer term, the cyclosporine-containing regi- minimizing dry eye through intra and postoperative men resulted in improvement in the same measures that interventions, both pharmacological and surgical. were statistically indistinguishable from, or were superior to, the plugs-only regimen. Furthermore, only the cyclosporine-containing regimen significantly improved ocular References and recommended reading Papers of particular interest, published within the annual period of review, have surface staining over time. These observations are con- been highlighted as: sistent with the known roles of topical cyclosporine in of special interest of outstanding interest addressing the underlying immune pathophysiology of Additional references related to this topic can also be found in the Current chronic dry eye disease. There may be an additive effect World Literature section in this issue (p. 366). of topical cyclosporine and punctal occlusion, and patients 1 Paiva CS, Chen Z, Koch DD, et al. The incidence and risk factors for with punctal occlusion may also benefit from adjunctive developing dry eye after myopic LASIK. Am J Ophthalmol 2006; 141: cyclosporine. 438–445. 2 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 Autologous serum has also been used as a potential treat- laser. J Cataract Refract Surg 2007; 33:1190–1194. ment for dry eye. It contains anti-inflammatory agents and 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 MMP inhibitors that are especially useful in patients with eye disease was present early after myopic LASIK with IntraLase laser. autoimmune-associated inflammatory processes, such as 3 Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi Sjo¨gren’s [38,49]. The efficacy of autologous serum approach to treatment recommendations. Cornea 2006; 25:900–907. 4 Berry S, Mangione CM, Lindblad AS, McDonnell PJ. Development of the application for the treatment of corneal transplantation national eye institute refractive error correction quality of life questionnaire: or other ocular surface disorders [50], such as superior focus groups. Ophthalmology 2003; 110:2285–2291. limbic keratitis [51], dry eye in graft-versus-host disease 5 Wilson SE. Laser in situ keratomileusis-induced (presumed) neurotrophic [52], or Stevens-Johnson syndrome [50], has been epitheliopathy. Ophthalmology 2001; 108:1082–1087. 6 Wilson SE, Stulting RD. Agreement of physician treatment practices with the reported. These studies suggest that autologous serum International Task Force guidelines for diagnosis and treatment of dry eye may improve almost all types of dry eye. Noda-Tsuruya disease. Cornea 2007; 26:284–289. Topical cyclosporine treatment appears to be associated with the cure of symp- et al. 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