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Diffuse lamellar keratitis after corneal crosslinking in a patient with post-laser in situ keratomileusis corneal ectasia
CASE REPORT
Diffuse lamellar keratitis after corneal crosslinking in a patient with post-laser in situ keratomileusis corneal ectasia George D. Kymionis, MD, PhD, Dimitrios I. Bouzoukis, MD, Vasilios F. Diakonis, MD, Dimitra M. Portaliou, MD, Aristofanis I. Pallikaris, PhD, Sonia H. Yoo, MD
A 27-year-old man presented with corneal ectasia in his left eye 4 years after myopic laser in situ keratomileusis (LASIK) and was treated with riboflavin–ultraviolet-A (crosslinking). During the first post-treatment days, diffuse lamellar keratitis (DLK) (stage III) developed. The microbiology culture was negative. After intensive treatment with topical corticosteroids, the DLK resolved during the following 2 weeks. Crosslinking for post-LASIK corneal ectasia may induce DLK. Early diagnosis and appropriate treatment with intensive topical corticosteroids is essential to successfully manage this post-crosslinking complication. J Cataract Refract Surg 2007; 33:2135–2137 Q 2007 ASCRS and ESCRS
Corneal collagen crosslinking is a new technique that uses photosensitizer riboflavin and ultraviolet-A (UVA) light to increase corneal resistance and rigidity (stiffening effect).1,2 It is a minimally invasive procedure for stabilizing progressive keratoconus or iatrogenic keratectasia after laser in situ keratomileusis (LASIK).3 Post-LASIK patients are always at risk for diffuse lamellar keratitis (DLK) as any cause of inflammation may provoke the accumulation of white blood cells in the interface.4 In this case report, we present a patient with post-LASIK corneal ectasia who developed DLK after corneal crosslinking. CASE REPORT A 27-year-old man presented at our institute with iatrogenic ectasia in the left eye 4 years after LASIK. The uncorrected
Accepted for publication June 19, 2007. From the Institute of Vision and Optics (Kymionis, Bouzoukis, Diakonis, Portaliou, Pallikaris), University of Crete, Greece; and the Bascom Palmer Eye Institute (Kymionis, Yoo), University of Miami Miller School of Medicine, Miami, Florida, USA. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: George D. Kymionis, MD, PhD, Institute of Vision and Optics, University of Crete, Medical School, Department of Ophthalmology, 71110 Heraklion, Crete, Greece. E-mail: kymionis@ med.uoc.gr. Q 2007 ASCRS and ESCRS Published by Elsevier Inc.
visual acuity (UCVA) was counting fingers and the best spectacle-corrected visual acuity, 20/40 ( 2.75 4.00 140). Corneal topography revealed progressive abnormal astigmatic patterns correlated to corneal ectasia. The preoperative central corneal thickness was 436 mm. Crosslinking therapy using riboflavin and UVA light was proposed to stabilize the ectasia. The patient was appropriately informed and gave written informed consent in accordance with institutional guidelines and the Declaration of Helsinki. The surgical procedure was conducted under sterile conditions. The patient’s eye was anesthetized with proparacaine 0.5% (Alcaine). A 6.0 mm diameter of corneal epithelium was mechanically removed using a rotating brush, and riboflavin 0.1% solution was instilled repeatedly for approximately 10 minutes. Penetration of the cornea and presence of riboflavin in the anterior chamber (riboflavin shielding) was monitored by slitlamp examination. The UVA irradiation was performed using an optical system (UV-X illumination system version 1000) with a light source consisting of an array of UV diodes (365 nm) in conjunction with a potentiometer to allow regulation of voltage. Before treatment, an intended 3.0 mW/cm2 of surface irradiance (5.4 J/cm2 surface dose) was calibrated using a UV light meter at a working distance of 1.0 cm. Irradiance was performed for 30 minutes, corresponding to a dose of 5.4 J/cm2. During treatment, the riboflavin solution was applied every 5 minutes to saturate the cornea with riboflavin and drops of physiological salt solution were applied every 2 minutes to moisten the cornea. After the treatment, a bandage contact lens and topical antibiotic–corticosteroid drops (tobramycin 0.3%– dexamethasone 0.1%, TobraDex) were applied 3 times daily. The patient was examined daily until the epithelium had completely healed. On the first postoperative day, he complained of light sensitivity. Slitlamp examination showed peripheral infiltrates in the interface (stage I DLK). The epithelial defect was 60%. The remainder of the anterior (reaction in the anterior chamber or discharge) and posterior 0886-3350/07/$dsee front matter doi:10.1016/j.jcrs.2007.06.070
2135
2136
CASE REPORT: POST-LASIK CROSSLINKING DLK
Figure 1. Left: Slitlamp photograph of the left eye demonstrates DLK (stage III) with diffuse faint haze and clumped opacities in the flap interface. Right: The inflammation responded rapidly to treatment and by the ninth day, the infiltrates had resolved.
segment examination was within normal limits. Conjunctival microbiology culture was negative. The UCVA was 20/50. An intensive course (every second hour) of a corticosteroid (dexamethasone 1%, Maxidex) was prescribed. On the second postoperative day, the UCVA was 20/200; there was an increase in the interface inflammation, with infiltrates covering the interface, including the central cornea (stage III) (Figure 1, left). No epithelial defect was present, and the therapeutic contact lens was removed. Despite the advanced stage of the disease (stage III), the flap was not lifted because the manipulation could decrease the possible stiffening effect of crosslinking. Instead, the corticosteroid dose was increased hourly in combination with a tapered course of an oral steroid (methylprednisolone, Medrol) starting at 32 mg once a day. The inflammation responded rapidly to the treatment and by the ninth day, the infiltrates had resolved (Figure 1, right). The corticosteroid was tapered over the next 5 weeks without evidence of a DLK recurrence.
DISCUSSION Post-LASIK DLK is an infrequent complication. The reported incidence of this complication varies in etiology and severity from 0.2% in mild cases to 30% in so-called epidemic DLK. Although the number of DLK studies has increased, the cause of this post-LASIK complication has not been established. Contamination of the interface during LASIK from disinfectants; microkeratome blade deposits; povidone–iodine solution; and debris from sponges, drapes, and gauzes has been suggested.5 Late, recurrent, or traumatic epithelial defect and erosion; thermal effect of the laser; and Meibomian gland secretion are also suggested as causes of late postLASIK DLK.6,7 In this case report, we described a post-LASIK patient who developed DLK after corneal crosslinking treatment. Several crosslinking factors, such as epithelium removal and UVA light, could trigger DLK.
Epithelium removal has been related to epithelium-derived cytokines, such as interleukin-1, that stimulate keratocytes to produce chemokines, which attract inflammatory cells.8 Several studies8,9 correlate the presence of epithelial defects during LASIK and postLASIK DLK. Despite the advanced stage of DLK (stage III) and without any additional surgical intervention (flap lift) that could affect the corneal crosslinking, our patient responded rapidly to topical and systemic steroids. In conclusion, crosslinking for post-LASIK corneal ectasia may induce DLK. Early diagnosis and appropriate treatment with intensive topical corticosteroids is essential to successfully manage this post-crosslinking complication. In addition, an intensive postoperative prophylactic steroid treatment for DLK prevention should be considered in these patients. REFERENCES 1. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135:620–627 2. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin–ultraviolet-A-induced cross-linking. J Cataract Refract Surg 2003; 29:1780–1785 3. Kohlhaas M, Spoerl E, Speck A, et al. Eine neue Behandlung der Keratectasie nach LASIK durch Kollagenvernetzung mit Riboflavin/UVA-Licht. [A new treatment of keratectasia after LASIK by using collagen with riboflavin/UVA light cross-linking]. Klin Monatsbl Augenheilkd 2005; 222:430–436 4. Alio´ JL, Pe´rez-Santonja JJ, Tervo T, et al. Postoperative inflammation, microbial complications, and wound healing following laser in situ keratomileusis. J Refract Surg 2000; 16:523–538 5. Stulting RD, Randleman JB, Couser JM, Thompson KP. The epidemiology of diffuse lamellar keratitis. Cornea 2004; 23:680–688 6. Moilanen JAO, Holopainen JM, Helinto¨ M, et al. Keratocyte activation and inflammation in diffuse lamellar keratitis after formation of an epithelial defect. J Cataract Refract Surg 2004; 30:341–349
J CATARACT REFRACT SURG - VOL 33, DECEMBER 2007
CASE REPORT: POST-LASIK CROSSLINKING DLK
7. Asano-Kata N, Toda I, Tsubota K. Severe late-onset recurrent epithelial erosion with diffuse lamellar keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2003; 29:2019–2021 8. Shah MN, Misra M, Wilhelmus KR, Koch DD. Diffuse lamellar keratitis associated with epithelial defects after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:1312–1318 9. Mirshahi A, Bu¨hren J, Kohnen T. Clinical course of severe central epithelial defects in laser in situ keratomileusis. J Cataract Refract Surg 2004; 30:1636–1641
2137
First author: George D. Kymionis, MD, PhD Institute of Vision and Optics, University of Crete, Greece; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
J CATARACT REFRACT SURG - VOL 33, DECEMBER 2007
Diffuse lamellar keratitis after corneal crosslinking in a patient with post-laser in situ keratomileusis corneal ectasia George D. Kymionis, MD, PhD, Dimitrios I. Bouzoukis, MD, Vasilios F. Diakonis, MD, Dimitra M. Portaliou, MD, Aristofanis I. Pallikaris, PhD, Sonia H. Yoo, MD
A 27-year-old man presented with corneal ectasia in his left eye 4 years after myopic laser in situ keratomileusis (LASIK) and was treated with riboflavin–ultraviolet-A (crosslinking). During the first post-treatment days, diffuse lamellar keratitis (DLK) (stage III) developed. The microbiology culture was negative. After intensive treatment with topical corticosteroids, the DLK resolved during the following 2 weeks. Crosslinking for post-LASIK corneal ectasia may induce DLK. Early diagnosis and appropriate treatment with intensive topical corticosteroids is essential to successfully manage this post-crosslinking complication. J Cataract Refract Surg 2007; 33:2135–2137 Q 2007 ASCRS and ESCRS
Corneal collagen crosslinking is a new technique that uses photosensitizer riboflavin and ultraviolet-A (UVA) light to increase corneal resistance and rigidity (stiffening effect).1,2 It is a minimally invasive procedure for stabilizing progressive keratoconus or iatrogenic keratectasia after laser in situ keratomileusis (LASIK).3 Post-LASIK patients are always at risk for diffuse lamellar keratitis (DLK) as any cause of inflammation may provoke the accumulation of white blood cells in the interface.4 In this case report, we present a patient with post-LASIK corneal ectasia who developed DLK after corneal crosslinking. CASE REPORT A 27-year-old man presented at our institute with iatrogenic ectasia in the left eye 4 years after LASIK. The uncorrected
Accepted for publication June 19, 2007. From the Institute of Vision and Optics (Kymionis, Bouzoukis, Diakonis, Portaliou, Pallikaris), University of Crete, Greece; and the Bascom Palmer Eye Institute (Kymionis, Yoo), University of Miami Miller School of Medicine, Miami, Florida, USA. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: George D. Kymionis, MD, PhD, Institute of Vision and Optics, University of Crete, Medical School, Department of Ophthalmology, 71110 Heraklion, Crete, Greece. E-mail: kymionis@ med.uoc.gr. Q 2007 ASCRS and ESCRS Published by Elsevier Inc.
visual acuity (UCVA) was counting fingers and the best spectacle-corrected visual acuity, 20/40 ( 2.75 4.00 140). Corneal topography revealed progressive abnormal astigmatic patterns correlated to corneal ectasia. The preoperative central corneal thickness was 436 mm. Crosslinking therapy using riboflavin and UVA light was proposed to stabilize the ectasia. The patient was appropriately informed and gave written informed consent in accordance with institutional guidelines and the Declaration of Helsinki. The surgical procedure was conducted under sterile conditions. The patient’s eye was anesthetized with proparacaine 0.5% (Alcaine). A 6.0 mm diameter of corneal epithelium was mechanically removed using a rotating brush, and riboflavin 0.1% solution was instilled repeatedly for approximately 10 minutes. Penetration of the cornea and presence of riboflavin in the anterior chamber (riboflavin shielding) was monitored by slitlamp examination. The UVA irradiation was performed using an optical system (UV-X illumination system version 1000) with a light source consisting of an array of UV diodes (365 nm) in conjunction with a potentiometer to allow regulation of voltage. Before treatment, an intended 3.0 mW/cm2 of surface irradiance (5.4 J/cm2 surface dose) was calibrated using a UV light meter at a working distance of 1.0 cm. Irradiance was performed for 30 minutes, corresponding to a dose of 5.4 J/cm2. During treatment, the riboflavin solution was applied every 5 minutes to saturate the cornea with riboflavin and drops of physiological salt solution were applied every 2 minutes to moisten the cornea. After the treatment, a bandage contact lens and topical antibiotic–corticosteroid drops (tobramycin 0.3%– dexamethasone 0.1%, TobraDex) were applied 3 times daily. The patient was examined daily until the epithelium had completely healed. On the first postoperative day, he complained of light sensitivity. Slitlamp examination showed peripheral infiltrates in the interface (stage I DLK). The epithelial defect was 60%. The remainder of the anterior (reaction in the anterior chamber or discharge) and posterior 0886-3350/07/$dsee front matter doi:10.1016/j.jcrs.2007.06.070
2135
2136
CASE REPORT: POST-LASIK CROSSLINKING DLK
Figure 1. Left: Slitlamp photograph of the left eye demonstrates DLK (stage III) with diffuse faint haze and clumped opacities in the flap interface. Right: The inflammation responded rapidly to treatment and by the ninth day, the infiltrates had resolved.
segment examination was within normal limits. Conjunctival microbiology culture was negative. The UCVA was 20/50. An intensive course (every second hour) of a corticosteroid (dexamethasone 1%, Maxidex) was prescribed. On the second postoperative day, the UCVA was 20/200; there was an increase in the interface inflammation, with infiltrates covering the interface, including the central cornea (stage III) (Figure 1, left). No epithelial defect was present, and the therapeutic contact lens was removed. Despite the advanced stage of the disease (stage III), the flap was not lifted because the manipulation could decrease the possible stiffening effect of crosslinking. Instead, the corticosteroid dose was increased hourly in combination with a tapered course of an oral steroid (methylprednisolone, Medrol) starting at 32 mg once a day. The inflammation responded rapidly to the treatment and by the ninth day, the infiltrates had resolved (Figure 1, right). The corticosteroid was tapered over the next 5 weeks without evidence of a DLK recurrence.
DISCUSSION Post-LASIK DLK is an infrequent complication. The reported incidence of this complication varies in etiology and severity from 0.2% in mild cases to 30% in so-called epidemic DLK. Although the number of DLK studies has increased, the cause of this post-LASIK complication has not been established. Contamination of the interface during LASIK from disinfectants; microkeratome blade deposits; povidone–iodine solution; and debris from sponges, drapes, and gauzes has been suggested.5 Late, recurrent, or traumatic epithelial defect and erosion; thermal effect of the laser; and Meibomian gland secretion are also suggested as causes of late postLASIK DLK.6,7 In this case report, we described a post-LASIK patient who developed DLK after corneal crosslinking treatment. Several crosslinking factors, such as epithelium removal and UVA light, could trigger DLK.
Epithelium removal has been related to epithelium-derived cytokines, such as interleukin-1, that stimulate keratocytes to produce chemokines, which attract inflammatory cells.8 Several studies8,9 correlate the presence of epithelial defects during LASIK and postLASIK DLK. Despite the advanced stage of DLK (stage III) and without any additional surgical intervention (flap lift) that could affect the corneal crosslinking, our patient responded rapidly to topical and systemic steroids. In conclusion, crosslinking for post-LASIK corneal ectasia may induce DLK. Early diagnosis and appropriate treatment with intensive topical corticosteroids is essential to successfully manage this post-crosslinking complication. In addition, an intensive postoperative prophylactic steroid treatment for DLK prevention should be considered in these patients. REFERENCES 1. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135:620–627 2. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin–ultraviolet-A-induced cross-linking. J Cataract Refract Surg 2003; 29:1780–1785 3. Kohlhaas M, Spoerl E, Speck A, et al. Eine neue Behandlung der Keratectasie nach LASIK durch Kollagenvernetzung mit Riboflavin/UVA-Licht. [A new treatment of keratectasia after LASIK by using collagen with riboflavin/UVA light cross-linking]. Klin Monatsbl Augenheilkd 2005; 222:430–436 4. Alio´ JL, Pe´rez-Santonja JJ, Tervo T, et al. Postoperative inflammation, microbial complications, and wound healing following laser in situ keratomileusis. J Refract Surg 2000; 16:523–538 5. Stulting RD, Randleman JB, Couser JM, Thompson KP. The epidemiology of diffuse lamellar keratitis. Cornea 2004; 23:680–688 6. Moilanen JAO, Holopainen JM, Helinto¨ M, et al. Keratocyte activation and inflammation in diffuse lamellar keratitis after formation of an epithelial defect. J Cataract Refract Surg 2004; 30:341–349
J CATARACT REFRACT SURG - VOL 33, DECEMBER 2007
CASE REPORT: POST-LASIK CROSSLINKING DLK
7. Asano-Kata N, Toda I, Tsubota K. Severe late-onset recurrent epithelial erosion with diffuse lamellar keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2003; 29:2019–2021 8. Shah MN, Misra M, Wilhelmus KR, Koch DD. Diffuse lamellar keratitis associated with epithelial defects after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:1312–1318 9. Mirshahi A, Bu¨hren J, Kohnen T. Clinical course of severe central epithelial defects in laser in situ keratomileusis. J Cataract Refract Surg 2004; 30:1636–1641
2137
First author: George D. Kymionis, MD, PhD Institute of Vision and Optics, University of Crete, Greece; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
J CATARACT REFRACT SURG - VOL 33, DECEMBER 2007