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Bilateral peripheral corneal infiltrates after simultaneous myopic laser in situ keratomileusis
Bilateral peripheral corneal infiltrates after simultaneous myopic laser in situ keratomileusis Edward Y.W. Yu, MD, Srinivas K. Rao, DO, Arthur C.K. Cheng, MRCS, Ricky W.K. Law, FRCS, Alfred T.S. Leung, FRCS, FRCOphth, Dennis S.C. Lam, FRCS, FRCOphth We describe a patient with multiple superior corneal infiltrates in both eyes, separated from the limbus by an intervening clear zone, that appeared 1 day after uneventful laser in situ keratomileusis. The overlying epithelium was intact, and the flap and interface were uninvolved. Based on these features, a clinical diagnosis of sterile corneal infiltrates was made and the eyes were treated with topical antibiotics and steroids. The infiltrates resolved during the ensuing weeks without corneal scarring. Good visual acuity was maintained. Recognition of this benign complication is important because aggressive corneal scrapings are not required. The infiltrates appear to be immunogenic in origin, although the exact etiopathogenesis is not clear. J Cataract Refract Surg 2002; 28:891– 894 © 2002 ASCRS and ESCRS
L
aser in situ keratomileusis (LASIK) is currently considered the treatment of choice for the correction of moderate to high myopia. Despite its increasing popularity, new complications continue to be reported.1– 4 The occurrence of infectious corneal infiltrates is of particular concern because these may cause significant loss of vision.4 We report what is to our knowledge the first case of bilateral peripheral presumed sterile corneal infiltrates in both eyes of a patient after uneventful simultaneous LASIK. The clinical features, treatment, and Accepted for publication July 17, 2001. From the Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, University Eye Center, Hong Kong Eye Hospital, Hong Kong, China (Yu, Cheng, Law, Leung, Lam), and Sankara Nethralaya, Chennai, Tamil Nadu, India (Rao). Presented in part as a poster at the Symposium on Cataract, IOL and Refractive Surgery, San Diego, California, USA, April 2001. Supported in part by the Action for Vision Eye Foundation, Hong Kong. None of the authors has a financial interest in any material or method mentioned. Reprint requests to Professor Dennis S.C. Lam, Chairman, Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, University Eye Center, Hong Kong Eye Hospital, 147, Argyle Street, Hong Kong, China. E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
outcomes of this condition are described. Recognition of this distinct entity may help the clinician avoid unnecessary invasive tests such as corneal scraping.
Case Report A 37-year-old Chinese man had bilateral simultaneous LASIK for the treatment of myopia. His preoperative manifest refraction was – 6.50 ⫹1.00 ⫻ 102 in the right eye and – 6.25 ⫹1.25 ⫻ 100 in the left eye. The best corrected visual acuity (BCVA) was 20/25 and 20/20, respectively. He wore soft contact lenses with no complications related to their use. Slitlamp biomicroscopy revealed healthy lid margins and palpebral conjunctiva. There was a small pannus in the superior cornea in both eyes. Corneal topography revealed bilateral regular astigmatism corresponding to the manifest refraction. After informed consent was obtained, proparacaine 0.5% (Alcaine威) and ofloxacin 0.3% (Tarivid威) eyedrops were instilled. Next, LASIK was performed using the Hansatome威 microkeratome (Bausch & Lomb) and the Multiscan Keratom laser (Keratome-F, Schwind). A new blade was used in the first eye, and the same was used to create the flap in the fellow eye. Surgery was uneventful, and there was no limbal bleeding in either eye after the flap was created. The excimer ablation was performed using a 6.5 mm ablation zone, and full correction of the refractive error was attempted. At the conclusion of the surgery, a drop of prednisolone acetate 1% (Pred Forte威) was applied. Postoperatively, no bandage con0886-3350/02/$–see front matter PII S0886-3350(01)01095-1
CASE REPORTS: YU
Figure 1. (Yu) The right eye of the patient 1 day after LASIK. Note the superior conjunctival injection and multiple corneal stromal infiltrates separated from the limbus by a clear zone. The flap is well positioned with a clear interface.
Figure 2.
tact lens was used. The patient was reexamined at the slitlamp 30 minutes after surgery when the flaps were in good position with a clear interface. A rigid shield was applied to both eyes, and the patient was instructed not to use topical medication in either eye for 24 hours. On the first postoperative day, the patient presented with moderate pain and photophobia in both eyes. The uncorrected visual acuity was 20/50 in each eye. Visual acuity did not improve with pinhole in the right eye and was 20/35 in the left eye. Slitlamp biomicroscopy revealed bilateral moderate injection of the superior bulbar conjunctiva with no discharge. Multiple, yellowish, creamy anterior stromal infiltrates were seen in the superior cornea in both eyes (Figures 1 and 2). The infiltrates were located between 12 and 2 o’clock in the right eye and between 10 and 2 o’clock in the left eye and were more extensive in the left eye. The infiltrates were separated from the limbus by a 1.0 to 2.0 mm zone of clear cornea and were oriented in a circumferential manner limited to the anterior stroma with no posterior extension. The epithelium overlying these infiltrates was intact, and there was no anterior chamber reaction. The infiltrates were present above the hinge of the flap, and the flap was in good position. The interface was clear in both eyes. Because the multifocal stromal infiltrates occurred beyond the site of surgical alteration of the cornea and the overlying epithelium was intact, an immunologic etiology was suspected and corneal scrapings were deferred. The patient was treated with ofloxacin 0.3% eyedrops 10 times daily, fluorometholone 0.1% (Flucon威) eyedrops 8 times daily, tropicamide 0.5% and phenylephrine chloride 0.5% (Mydrin-P威) eyedrops 3 times daily, and unpreserved tear substitutes hourly. Twenty-four hours later, the pain and irritation had decreased, and the infiltrates appeared less intense. The infiltrates gradually regressed and on postoperative day 6, BCVA
was 20/30 with ⫹0.75 ⫹0.50 ⫻ 125 in the right eye and 20/25 with ⫹0.25 ⫹0.75 ⫻ 120 in the left eye. Slitlamp biomicroscopy revealed partial resolution of the infiltrates. Seven weeks after surgery, there was complete resolution of the infiltrates. The patient had no complaints, and the BCVA was 20/25 in both eyes with ⫹0.75 ⫹0.50 ⫻ 160 in the right eye and ⫹0.75 ⫹0.50 ⫻ 140 in the left eye.
892
(Yu) The left eye of the patient 1 day after LASIK. Findings were similar to those in the right eye, but the infiltrates are more extensive.
Discussion Sterile corneal stromal infiltrates have been reported after photorefractive keratectomy (PRK).5–7 The etiology of these infiltrates has been related to the use of topical nonsteroidal antiinflammatory drugs (NSAIDs) without concurrent steroids,5 topical anesthetic abuse,6 and immunologic reaction.7 The use of topical NSAIDs after corneal refractive surgery inhibits the cyclooxygenase pathway of arachidonic acid metabolism. The lipooxygenase pathway is still functional, however, and this causes excessive production of leukotrienes and hydroxyeicosatetraenoic acid.8 These are potent neutrophil chemotactants and result in the accumulation of these cells in the corneal stroma, producing infiltrates. The use of steroids blocks the synthesis of the precursor arachidonic acid, and hence the concomitant use of steroids is recommended when NSAIDs are used after excimer surgery.8 Anesthetic abuse after refractive surgery results in epithelial breakdown, and inflammatory cells accumulate in the exposed stroma, producing infiltrates.6 In both condi-
J CATARACT REFRACT SURG—VOL 28, MAY 2002
CASE REPORTS: YU
tions, the infiltrates occur at the site of treatment with the excimer laser, are usually associated with epithelial breakdown, and heal with scarring. A more recent report describes bilateral inferior multiple corneal infiltrates after PRK that responded to treatment with topical steroids and antibiotics. The lesions resolved without scarring within 1 week with good visual acuity and were thought to be of immune etiology.7 Haw and Manche9 describe a patient who developed unilateral, multiple, superior infiltrates after bilateral simultaneous LASIK. There was a history of dry eye, chalazion excision, and blepharitis. Corneal scrapings did not reveal the presence of pathogens, and the condition resolved within 1 week of treatment with topical steroids. The authors highlight the similarity of the condition to marginal keratitis seen in patients with staphylococcal lid margin disease and emphasize that this condition is distinct from diffuse lamellar keratitis (DLK). Wessely-type immune rings in the cornea have also been reported after phototherapeutic keratectomy.10 The authors postulate that this may be caused by the presence of heat shock proteins that are derived by the interaction of the excimer laser energy with the bacteria of the ocular surface. Because the body is already sensitized to the presence of these antigens, the liberation of a large volume of these proteins is followed by an immune response manifested as corneal infiltrates. The occurrence of the infiltrates in the superior cornea at the site of the corneal vascularization in our patient supports this hypothesis. However, it is unclear why this phenomenon is not observed more frequently after excimer laser corneal surgery. In summary, the findings in our patient appear to represent a distinct entity—sterile corneal infiltrates outside the zone of treatment in LASIK—that appeared 1 day postoperatively. The patient did not use topical medications after surgery. In the absence of discharge, epithelial ulceration, and increased anterior chamber reaction, invasive investigations such as corneal scraping may be deferred and reassessed pending results of treatments. The creation of epithelial defects in the vicinity of the margin of the corneal flap may predispose to the occurrence of epithelial ingrowth.11 Epithelial injury from scraping can also induce alterations in the metabolism and oxygenation of the cornea, which may enhance sterile inflammatory processes leading to DLK.12
Treatment with topical antibiotic and steroids leads to prompt resolution of the infiltrates with minimal corneal scarring and good visual acuity. Although the use of steroid eyedrops after LASIK may help prevent this condition, they must be used cautiously because the epithelial defect at the margins of the flap is still present and this may potentiate infectious keratitis. Clinicians must be aware of this distinct complication because the treatment and outcomes are quite different from those of corneal infiltrates of infectious etiology after LASIK. Nevertheless, although this case illustrates the most likely diagnosis as sterile infiltrates based on the appearance, because cultures were not performed, it may have been infectious and responded to the concomitant use of antibiotics postoperatively. The presence of postsurgical infiltrates is an important issue in the postoperative management of LASIK patients as infiltrates can result in potentially disastrous complications. In cases with atypical infiltrates with possible infectious etiology, a low threshold for aggressive workup cannot be overemphasized.
References 1. Chaudhry NA, Smiddy WE. Displacement of corneal cap during vitrectomy in a post-LASIK eye. Retina 1998; 18:554 –555 2. Leung ATS, Rao SK, Lam DSC. Traumatic partial unfolding of laser in situ keratomileusis flap with severe epithelial ingrowth. J Cataract Refract Surg 2000; 26: 135–139 3. Farah ME, Ho¨ fling-Lima AL, Nascimento E. Early rhegmatogenous retinal detachment following laser in situ keratomileusis for high myopia. J Refract Surg 2000; 16: 739 –743 4. Sridhar MS, Garg P, Bansal AK, Gopinathan U. Aspergillus flavus keratitis after laser in situ keratomileusis. Am J Ophthalmol 2000; 129:802– 804 5. Teal P, Breslin C, Arshinoff S, Edmison D. Corneal subepithelial infiltrates following excimer laser photorefractive keratectomy. J Cataract Refract Surg 1995; 21:516 – 518 6. Kim JY, Choi YS, Lee JH. Keratitis from corneal anesthetic abuse after photorefractive keratectomy. J Cataract Refract Surg 1997; 23:447– 449 7. Rao SK, Fogla R, Rajagopal R, et al. Bilateral corneal infiltrates after excimer laser photorefractive keratectomy. J Cataract Refract Surg 2000; 26:456 – 459 8. Sher NA, Krueger RR, Teal P, et al. Role of topical corticosteroids and nonsteroidal antiinflammatory drugs in
J CATARACT REFRACT SURG—VOL 28, MAY 2002
893
CASE REPORTS: YU
the etiology of stromal infiltrates after excimer photorefractive keratectomy. (letter) J Refract Corneal Surg 1994; 10:587–588 9. Haw WW, Manche EE. Sterile peripheral keratitis following laser in situ keratomileusis. J Refract Surg 1999; 15:61– 63 10. Teichmann KD, Cameron J, Huaman A, et al. Wessely-
894
type immune ring following phototherapeutic keratectomy. J Cataract Refract Surg 1996; 22:142–146 11. Wang MY, Maloney RK. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol 2000; 129:746–751 12. Haw WW, Manche EE. Late onset diffuse lamellar keratitis associated with an epithelial defect in six eyes. J Refract Surg 2000; 16:744 –748
J CATARACT REFRACT SURG—VOL 28, MAY 2002
L
aser in situ keratomileusis (LASIK) is currently considered the treatment of choice for the correction of moderate to high myopia. Despite its increasing popularity, new complications continue to be reported.1– 4 The occurrence of infectious corneal infiltrates is of particular concern because these may cause significant loss of vision.4 We report what is to our knowledge the first case of bilateral peripheral presumed sterile corneal infiltrates in both eyes of a patient after uneventful simultaneous LASIK. The clinical features, treatment, and Accepted for publication July 17, 2001. From the Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, University Eye Center, Hong Kong Eye Hospital, Hong Kong, China (Yu, Cheng, Law, Leung, Lam), and Sankara Nethralaya, Chennai, Tamil Nadu, India (Rao). Presented in part as a poster at the Symposium on Cataract, IOL and Refractive Surgery, San Diego, California, USA, April 2001. Supported in part by the Action for Vision Eye Foundation, Hong Kong. None of the authors has a financial interest in any material or method mentioned. Reprint requests to Professor Dennis S.C. Lam, Chairman, Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, University Eye Center, Hong Kong Eye Hospital, 147, Argyle Street, Hong Kong, China. E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
outcomes of this condition are described. Recognition of this distinct entity may help the clinician avoid unnecessary invasive tests such as corneal scraping.
Case Report A 37-year-old Chinese man had bilateral simultaneous LASIK for the treatment of myopia. His preoperative manifest refraction was – 6.50 ⫹1.00 ⫻ 102 in the right eye and – 6.25 ⫹1.25 ⫻ 100 in the left eye. The best corrected visual acuity (BCVA) was 20/25 and 20/20, respectively. He wore soft contact lenses with no complications related to their use. Slitlamp biomicroscopy revealed healthy lid margins and palpebral conjunctiva. There was a small pannus in the superior cornea in both eyes. Corneal topography revealed bilateral regular astigmatism corresponding to the manifest refraction. After informed consent was obtained, proparacaine 0.5% (Alcaine威) and ofloxacin 0.3% (Tarivid威) eyedrops were instilled. Next, LASIK was performed using the Hansatome威 microkeratome (Bausch & Lomb) and the Multiscan Keratom laser (Keratome-F, Schwind). A new blade was used in the first eye, and the same was used to create the flap in the fellow eye. Surgery was uneventful, and there was no limbal bleeding in either eye after the flap was created. The excimer ablation was performed using a 6.5 mm ablation zone, and full correction of the refractive error was attempted. At the conclusion of the surgery, a drop of prednisolone acetate 1% (Pred Forte威) was applied. Postoperatively, no bandage con0886-3350/02/$–see front matter PII S0886-3350(01)01095-1
CASE REPORTS: YU
Figure 1. (Yu) The right eye of the patient 1 day after LASIK. Note the superior conjunctival injection and multiple corneal stromal infiltrates separated from the limbus by a clear zone. The flap is well positioned with a clear interface.
Figure 2.
tact lens was used. The patient was reexamined at the slitlamp 30 minutes after surgery when the flaps were in good position with a clear interface. A rigid shield was applied to both eyes, and the patient was instructed not to use topical medication in either eye for 24 hours. On the first postoperative day, the patient presented with moderate pain and photophobia in both eyes. The uncorrected visual acuity was 20/50 in each eye. Visual acuity did not improve with pinhole in the right eye and was 20/35 in the left eye. Slitlamp biomicroscopy revealed bilateral moderate injection of the superior bulbar conjunctiva with no discharge. Multiple, yellowish, creamy anterior stromal infiltrates were seen in the superior cornea in both eyes (Figures 1 and 2). The infiltrates were located between 12 and 2 o’clock in the right eye and between 10 and 2 o’clock in the left eye and were more extensive in the left eye. The infiltrates were separated from the limbus by a 1.0 to 2.0 mm zone of clear cornea and were oriented in a circumferential manner limited to the anterior stroma with no posterior extension. The epithelium overlying these infiltrates was intact, and there was no anterior chamber reaction. The infiltrates were present above the hinge of the flap, and the flap was in good position. The interface was clear in both eyes. Because the multifocal stromal infiltrates occurred beyond the site of surgical alteration of the cornea and the overlying epithelium was intact, an immunologic etiology was suspected and corneal scrapings were deferred. The patient was treated with ofloxacin 0.3% eyedrops 10 times daily, fluorometholone 0.1% (Flucon威) eyedrops 8 times daily, tropicamide 0.5% and phenylephrine chloride 0.5% (Mydrin-P威) eyedrops 3 times daily, and unpreserved tear substitutes hourly. Twenty-four hours later, the pain and irritation had decreased, and the infiltrates appeared less intense. The infiltrates gradually regressed and on postoperative day 6, BCVA
was 20/30 with ⫹0.75 ⫹0.50 ⫻ 125 in the right eye and 20/25 with ⫹0.25 ⫹0.75 ⫻ 120 in the left eye. Slitlamp biomicroscopy revealed partial resolution of the infiltrates. Seven weeks after surgery, there was complete resolution of the infiltrates. The patient had no complaints, and the BCVA was 20/25 in both eyes with ⫹0.75 ⫹0.50 ⫻ 160 in the right eye and ⫹0.75 ⫹0.50 ⫻ 140 in the left eye.
892
(Yu) The left eye of the patient 1 day after LASIK. Findings were similar to those in the right eye, but the infiltrates are more extensive.
Discussion Sterile corneal stromal infiltrates have been reported after photorefractive keratectomy (PRK).5–7 The etiology of these infiltrates has been related to the use of topical nonsteroidal antiinflammatory drugs (NSAIDs) without concurrent steroids,5 topical anesthetic abuse,6 and immunologic reaction.7 The use of topical NSAIDs after corneal refractive surgery inhibits the cyclooxygenase pathway of arachidonic acid metabolism. The lipooxygenase pathway is still functional, however, and this causes excessive production of leukotrienes and hydroxyeicosatetraenoic acid.8 These are potent neutrophil chemotactants and result in the accumulation of these cells in the corneal stroma, producing infiltrates. The use of steroids blocks the synthesis of the precursor arachidonic acid, and hence the concomitant use of steroids is recommended when NSAIDs are used after excimer surgery.8 Anesthetic abuse after refractive surgery results in epithelial breakdown, and inflammatory cells accumulate in the exposed stroma, producing infiltrates.6 In both condi-
J CATARACT REFRACT SURG—VOL 28, MAY 2002
CASE REPORTS: YU
tions, the infiltrates occur at the site of treatment with the excimer laser, are usually associated with epithelial breakdown, and heal with scarring. A more recent report describes bilateral inferior multiple corneal infiltrates after PRK that responded to treatment with topical steroids and antibiotics. The lesions resolved without scarring within 1 week with good visual acuity and were thought to be of immune etiology.7 Haw and Manche9 describe a patient who developed unilateral, multiple, superior infiltrates after bilateral simultaneous LASIK. There was a history of dry eye, chalazion excision, and blepharitis. Corneal scrapings did not reveal the presence of pathogens, and the condition resolved within 1 week of treatment with topical steroids. The authors highlight the similarity of the condition to marginal keratitis seen in patients with staphylococcal lid margin disease and emphasize that this condition is distinct from diffuse lamellar keratitis (DLK). Wessely-type immune rings in the cornea have also been reported after phototherapeutic keratectomy.10 The authors postulate that this may be caused by the presence of heat shock proteins that are derived by the interaction of the excimer laser energy with the bacteria of the ocular surface. Because the body is already sensitized to the presence of these antigens, the liberation of a large volume of these proteins is followed by an immune response manifested as corneal infiltrates. The occurrence of the infiltrates in the superior cornea at the site of the corneal vascularization in our patient supports this hypothesis. However, it is unclear why this phenomenon is not observed more frequently after excimer laser corneal surgery. In summary, the findings in our patient appear to represent a distinct entity—sterile corneal infiltrates outside the zone of treatment in LASIK—that appeared 1 day postoperatively. The patient did not use topical medications after surgery. In the absence of discharge, epithelial ulceration, and increased anterior chamber reaction, invasive investigations such as corneal scraping may be deferred and reassessed pending results of treatments. The creation of epithelial defects in the vicinity of the margin of the corneal flap may predispose to the occurrence of epithelial ingrowth.11 Epithelial injury from scraping can also induce alterations in the metabolism and oxygenation of the cornea, which may enhance sterile inflammatory processes leading to DLK.12
Treatment with topical antibiotic and steroids leads to prompt resolution of the infiltrates with minimal corneal scarring and good visual acuity. Although the use of steroid eyedrops after LASIK may help prevent this condition, they must be used cautiously because the epithelial defect at the margins of the flap is still present and this may potentiate infectious keratitis. Clinicians must be aware of this distinct complication because the treatment and outcomes are quite different from those of corneal infiltrates of infectious etiology after LASIK. Nevertheless, although this case illustrates the most likely diagnosis as sterile infiltrates based on the appearance, because cultures were not performed, it may have been infectious and responded to the concomitant use of antibiotics postoperatively. The presence of postsurgical infiltrates is an important issue in the postoperative management of LASIK patients as infiltrates can result in potentially disastrous complications. In cases with atypical infiltrates with possible infectious etiology, a low threshold for aggressive workup cannot be overemphasized.
References 1. Chaudhry NA, Smiddy WE. Displacement of corneal cap during vitrectomy in a post-LASIK eye. Retina 1998; 18:554 –555 2. Leung ATS, Rao SK, Lam DSC. Traumatic partial unfolding of laser in situ keratomileusis flap with severe epithelial ingrowth. J Cataract Refract Surg 2000; 26: 135–139 3. Farah ME, Ho¨ fling-Lima AL, Nascimento E. Early rhegmatogenous retinal detachment following laser in situ keratomileusis for high myopia. J Refract Surg 2000; 16: 739 –743 4. Sridhar MS, Garg P, Bansal AK, Gopinathan U. Aspergillus flavus keratitis after laser in situ keratomileusis. Am J Ophthalmol 2000; 129:802– 804 5. Teal P, Breslin C, Arshinoff S, Edmison D. Corneal subepithelial infiltrates following excimer laser photorefractive keratectomy. J Cataract Refract Surg 1995; 21:516 – 518 6. Kim JY, Choi YS, Lee JH. Keratitis from corneal anesthetic abuse after photorefractive keratectomy. J Cataract Refract Surg 1997; 23:447– 449 7. Rao SK, Fogla R, Rajagopal R, et al. Bilateral corneal infiltrates after excimer laser photorefractive keratectomy. J Cataract Refract Surg 2000; 26:456 – 459 8. Sher NA, Krueger RR, Teal P, et al. Role of topical corticosteroids and nonsteroidal antiinflammatory drugs in
J CATARACT REFRACT SURG—VOL 28, MAY 2002
893
CASE REPORTS: YU
the etiology of stromal infiltrates after excimer photorefractive keratectomy. (letter) J Refract Corneal Surg 1994; 10:587–588 9. Haw WW, Manche EE. Sterile peripheral keratitis following laser in situ keratomileusis. J Refract Surg 1999; 15:61– 63 10. Teichmann KD, Cameron J, Huaman A, et al. Wessely-
894
type immune ring following phototherapeutic keratectomy. J Cataract Refract Surg 1996; 22:142–146 11. Wang MY, Maloney RK. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol 2000; 129:746–751 12. Haw WW, Manche EE. Late onset diffuse lamellar keratitis associated with an epithelial defect in six eyes. J Refract Surg 2000; 16:744 –748
J CATARACT REFRACT SURG—VOL 28, MAY 2002