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Peripheral sterile corneal infiltrates after refractive surgery
Peripheral sterile corneal infiltrates after refractive surgery Tova Lifshitz, MD, Jaime Levy, MD, Ori Mahler, MD, Shmuel Levinger, MD Purpose: To report 5 eyes of peripheral sterile corneal infiltrates after refractive surgery. Setting: Department of Ophthalmology, Soroka University Medical Center, Beer-Sheva, Israel, and Enaim Ophthalmological Center, Jerusalem, Israel. Methods: Three patients had bilateral refractive procedures for correcting myopia. The procedures included laser epithelial keratectomy in 2 eyes, laser in situ keratomileusis (LASIK) in 2 eyes using a keratome, and LASIK in 1 eye using femtosecond laser. Results: All the patients complained of ocular pain between 1 and 3 days after the procedure. A ring stromal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrates and the limbus was observed in 5 eyes without anterior chamber reaction. All cases improved after several days of topical steroid and antibiotic treatment and systemic steroid. Final visual acuity was 20/25 or better in all cases. Conclusions: The exact mechanism of this complication is still unknown, which can be confused with infectious keratitis. It is important to maintain a high degree of suspicion for infectious keratitis because the management is very different. The potential outcome can be much worse if the keratitis is due to an infectious etiology which can appear after all types of refractive laser procedures. J Cataract Refract Surg 2005; 31:1392–1395 ª 2005 ASCRS and ESCRS
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eripheral sterile corneal infiltrates can be associated with several etiologies, including blepharitis-related staphylococcal hypersensitivity infiltrates, Terrien’s marginal degeneration, Mooren’s ulcer, and peripheral ulcerative keratitis associated with autoimmune or
Accepted for publication December 8, 2003. From the Department of Ophthalmology (Lifshitz, Levy), Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, and ‘‘Enaim’’ Ophthalmological Center (Lifshitz, Mahler, Levinger), Jerusalem, Israel. No author has a financial or proprietary interest in any method or material mentioned. Reprint requests to Jaime Levy, MD, Department of Ophthalmology, Soroka University Medical Center, P.O. Box 151, Beer-Sheva 84101, Israel. E-mail: [email protected]. 2005 ASCRS and ESCRS Published by Elsevier Inc.
collagen vascular disease. Laser procedures for correcting refractive errors are increasingly popular. One of the potential complications of these procedures is keratitis, which can be infectious or sterile and might permanently affect the visual acuity. There are reports of presumed sterile peripheral corneal infiltrates after various refractive procedures such as photorefractive keratectomy (PRK),1,2 phototherapeutic keratectomy (PTK),3 and laser in situ keratomileusis (LASIK).4–8 To our knowledge, there are no reported cases following laser-assisted subepithelial keratectomy (LASEK) or LASIK in which the flap was performed with the IntraLase femtosecond laser. Three patients (5 eyes) presented with peripheral sterile corneal infiltrates after LASIK, LASEK, and LASIK performed with IntraLase, respectively. We also review the reported cases of peripheral corneal infiltrates after refractive surgery. 0886-3350/05/$-see front matter doi:10.1016/j.jcrs.2004.12.057
PERIPHERAL STERILE CORNEAL INFILTRATES
Patients and Methods Case 1 A 47-year-old woman sought refractive surgery to correct myopia. Ocular history was unremarkable and negative for contact lens use and episodes of red eyes or discharge. Medical history was unremarkable. Uncorrected visual acuity (UCVA) was 20/400 in both eyes. Best spectacle-corrected visual acuity (BSCVA) was 20/20 in both eyes with a refraction of ÿ2.50 ÿ2.25 175 in the right eye and ÿ2.50 ÿ1.25 175 in the left eye. External and slitlamp microscopy examinations were normal; no meibomian gland dysfunction or blepharitis was obvious. The cornea was normal without epithelial defects or infiltrates. Preoperative corneal topography was within normal limits. The patient had uneventful bilateral LASIK. Fifteen minutes before surgery, chloramphenicol drops were administered 3 times at 5-minute intervals. The patient’s face was prepared with povidone–iodine 10% solution before surgery, and the face and body were covered with sterile sheets. The lashes were retracted with a SteriDrape. Surgery was performed with the Nidek EC-5000 laser after a nasally hinged 160 mm flap was made by the Nidek 2000-MK microkeratome with an 8.5 mm suction ring. Topical lomefloxacin 0.3% was instilled at the end of the procedure. Dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops were prescribed 4 times daily after the procedure. One day after LASIK, UCVA was 20/30 in both eyes. Three days after the procedure, the patient complained of mild pain and red eye bilaterally. A circumferential stromal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrate and the limbus were observed in both eyes (Figure 1). There was no anterior chamber reaction. An immunologic reaction etiology was suspected, and corneal scrapings were therefore deferred. The patient was treated with dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops 8 times a day and oral prednisone 60 mg a day. After 1 day, the pain had decreased, and the infiltrates were less intense. The infiltrates had almost completely disappeared after 1 week, leaving slight stromal haziness. The topical treatment was tapered for 1 month, and the oral prednisone was gradually tapered and stopped after 2 weeks. Six months after the procedure, UCVA was 20/25 in both eyes and the corneas were clear with no scarring. At the last follow-up the patient had no complaint, and no new episodes had occurred.
Case 2 A 25-year-old man had bilateral LASEK for myopia. In both eyes, the preoperative refraction was ÿ2.25, UCVA was 20/120, and BCVA was 6/6. Preoperative pachymetry was 485 mm in both eyes. Medical history was unremarkable. The patient had a history of meibomian gland dysfunction.
Figure 1. Case 1: Left eye 3 days after LASIK procedure, showing a circumferential stromal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrate and the limbus.
Slitlamp examination revealed mild meibomian gland dysfunction without blepharitis. Fifteen minutes preoperatively, chloramphenicol drops were given 3 times at 5-minute intervals. The patient’s face was prepared with povidone– iodine 10% solution before surgery, and the face and body were covered with sterile sheets. The lashes were retracted with a SteriDrape. An epithelial flap was lifted using 20% alcohol for 30 seconds, a routine procedure of LASEK. The stromal ablation was performed using the 217 C Bausch & Lomb excimer laser. The ablated stroma was immediately irrigated with a chilled balanced salt solution. The epithelial flap was then rolled to its original position. A plano soft contact lens was placed on the corneas at the end of the bilateral procedure. Topical gentamycin drops were instilled at the end of the procedure. The patient was instructed to apply dexamethasone sodium phosphate 0.1% and ofloxacin drops 4 times daily. One day postoperatively, the patient complained of pain in both eyes. The UCVA was 20/30 in the right eye and 20/25 in the left eye. Slitlamp examination revealed an almost 360-degree corneal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrate and the limbus (Figure 2, A). In addition, meibomian plugging was observed in upper lid margin in both eyes (Figure 2, B). An immune etiology was suspected, and corneal scrapings were not performed. The contact lenses were removed. Topical steroids and ofloxacin were given 8 times daily, and systemic doxycycline 100 mg a day and prednisone 80 mg a day was started. One day later, the ocular pain had almost disappeared and the corneal infiltrates were significantly less intense. On the fifth postoperative day, the epithelium had completely
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healed and the corneas were completely clear. The UCVA was 20/20 in both eyes. Treatment with dexamethasone sodium phosphate 0.1% 4 times a day was continued for 3 weeks, systemic doxycylcine 100 mg a day for 1 month, and prednisone was gradually tapered and stopped after 2 weeks. Three months following the procedure, UCVA was 20/20 in both eyes, and the corneas were clear without scarring.
Case 3 A 26-year-old man sought refractive surgery to correct myopia. Ocular and medical history was unremarkable. The UCVA was 20/200 in both eyes. The BSCVA was 20/30 in the right eye and 20/25 in the left eye with a refraction of ÿ2.75 ÿ0.75 105 in the right eye and ÿ2.75 ÿ0.75 80 in the left eye. Preoperative corneal topography and Orbscan (Bausch & Lomb) were within normal limits. The patient had bilateral LASIK. Fifteen minutes before surgery, chloramphenicol drops were administered 3 times at 5-minute intervals. The patient’s face was prepared with povidone–iodine 10% solution before the operation, and the face and body were covered with sterile sheets. The lashes were retracted with a SteriDrape. Flaps of 100 mm were fashioned with the IntraLase. The stromal ablation was performed using the wavefront-guided Zyoptix laser (Keracor 217z, v 3.1). Topical lomefloxacin 0.3% was instilled at the end of the procedure. One day later, UCVA was 20/20 in both eyes. A 3 mm corneal yellow–white infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the limbus and the infiltrate were observed in the right eye. The anterior chamber was quiet. Examination of the left eye was completely normal. Because of the peripheral location of the infiltrate, an immune etiology was suspected and corneal scrapings were not performed. Topical treatment of dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops 8 times daily was prescribed. After 1 day, the corneal infiltrate was significantly less intense, disappearing on the fourth postoperative day. The UCVA was 20/20 in both eyes. Treatment with dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops 4 times a day was continued for 3 weeks. Four months after the procedure, the cornea was completely clear with no scar, and UCVA was 20/20 in both eyes. No new episodes of ocular inflammation have occurred.
Discussion Several reports have described presumed sterile peripheral corneal infiltrates after refractive procedures. In 1995, Teal and coauthors1 were the first to describe corneal subepithelial infiltrates following PRK. They surveyed 50 Canadian PRK surgeons and received responses on 30 cases. The reported frequency of this complication was 1 in 300 cases. It was suggested that this complication appeared when surgeons began switch1394
Figure 2. A: Case 2. Right eye 1 day after LASEK procedure with a plano soft contact lens. An almost 360-degree corneal infiltrate peripheral to the flap edge with intact epithelium can be observed, with an intervening clear zone between the peripheral corneal infiltrate and the limbus. B: Same eye showing meibomian plugging in upper lid margin.
ing from patching the eye with bandages following PRK to the use of topical nonsteroidal antiinflammatory drugs (NSAIDs) with or without a contact lens for reducing postoperative pain. The majority of cases (77%) presented during the first 48 hours after the procedure. The most common clinical pattern was a large opacity, often in the shape of an immune ring, with 1 or 2 peripheral opacities. Permanent scarring accompanied by reduced vision was the usual result, with 80% of cases losing best spectacle-corrected visual acuity. Corneal biopsy performed in 1 eye with these immune infiltrates demonstrated infiltration by neutrophils and the presence of an active fibroblastic reaction, without lymphocytes or plasma cells.3
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PERIPHERAL STERILE CORNEAL INFILTRATES
In addition, there are reports of peripheral infiltrates appearing 1 day after the refractive procedure outside the zone of laser treatment resolving after a few days of topical treatment with steroids and antibiotics, and not affecting the final visual outcome.2,6,8,9 The authors suggested a distinct clinical entity for this second group of peripheral presumed sterile corneal infiltrates, based on the course of the disease and final outcome. In these cases, there was no use of NSAIDs or contact lens wear. Others assumed that the excimer laser may liberate a trapped antigen from the corneal stroma or create an antigen,3 resulting in an immune reaction. In the authors’ opinion, there is a strong clinical similarity between the marginal or catarrhal infiltrates appearing in patients with staphylococcal blepharitis and the peripheral infiltrates in patients after laser refractive procedures. In the case of classic marginal keratitis, the pathogenesis has been attributed to a localized corneal hypersensitivity reaction to toxins produced by bacteria colonizing the eyelid margins, usually Staphylococcus aureus, resulting in local deposition of immune complexes in the peripheral corneal stroma.7 There is also a similarity between these 2 processes in the response to treatment with steroids, antibiotic drops, and doxycylcine. There appear to be no reports in the literature of peripheral corneal infiltrates after LASEK or LASIK performed with IntraLase. Only 1 of the patients (Case 2) had obvious preoperative meibomian gland dysfunction and contact lens wear after the procedure. This patient also administered oral doxycylcine because of the preexisting meibomian gland dysfunction. The rationale for doxycylcine use is that it decreases production of bacterial lipases and thus decreases fatty acid levels.10 None of the patients received NSAIDs. In all cases, final visual acuity was 20/25 or better with no permanent corneal scarring. In the first 2 cases, and because of the significant circumferential infiltrate, oral steroids were administered in addition to topical steroids, with an initial dose of 1 mg/kg for 2 weeks. Immune reaction alone seems to be an insufficient explanation because there are only a few reports of this complication and the number of refractive procedures worldwide is enormous. The authors can hypothesize that the mixture of the effects of the laser on the corneal stroma and other ocular or systemic factors unknown to date can trigger this complication. Although the exact
mechanism of this complication remains unclear, recognition of this entity and its differentiation from infectious keratitis is essential to the management of these patients. Appropriate and early management usually results in a rapid disappearance of the infiltrates without affecting the final outcome. Nevertheless, it is important to maintain a high degree of suspicion for infectious keratitis because the management is very different and the potential outcome much worse if the keratitis is due to an infectious etiology. One could perform a culture and treat these cases empirically as infectious for the first 24 to 36 hours. If the cultures come back negative, one could start topical and systemic steroids.
References 1. Teal P, Breslin C, Arshinoff S, Edmison D. Corneal subepithelial infiltrates following excimer laser photorefractive keratectomy. J Cataract Refract Surg 1995; 21:516–518 2. Rao SK, Fogla R, Rajagopal R, et al. Bilateral corneal infiltrates after excimer laser photorefractive keratectomy. J Cataract Refract Surg 2000; 26:456–459 3. Teichmann KD, Cameron J, Huaman A, et al. Wesselytype immune ring following phototherapeutic keratectomy. J Cataract Refract Surg 1996; 22:142–146 4. MacRae S, Macaluso DC, Rich LF. Sterile interface keratitis associated with micropannus hemorrhage after laser in situ keratomileusis. J Cataract Refract Surg 1999; 25:1679–1681 5. Macaluso DC, Rich LF, MacRae S. Sterile interface keratitis after laser in situ keratomileusis: three episodes in one patient with concomitant contact dermatitis of the eyelids. J Refract Surg 1999; 15:679–682 6. Yu EYW, Rao SK, Cheng ACK, et al. Bilateral peripheral corneal infiltrates after simultaneous myopic laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:891– 894 7. Ambro´sio R Jr, Periman LM, Netto MV, Wilson SE. Bilateral marginal sterile infiltrates and diffuse lamellar keratitis after laser in situ keratomileusis. J Refract Surg 2003; 19:154–158 8. Lahners WJ, Hardten DR, Lindstrom RL. Peripheral keratitis following laser in situ keratomileusis. J Refract Surg 2003; 19:671–675 9. Haw WW, Manche EE. Sterile peripheral keratitis following laser in situ keratomileusis. J Refract Surg 1999; 15:61–63 10. Hussein N, Schwab IR, Ostler B. Blepharitis. In: Tasman W, Jaeger EA, eds, Duane’s Clinical Ophthalmology on CD-ROM. Philadelphia, PA, Lippincott Williams & Wilkins, 2004
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P
eripheral sterile corneal infiltrates can be associated with several etiologies, including blepharitis-related staphylococcal hypersensitivity infiltrates, Terrien’s marginal degeneration, Mooren’s ulcer, and peripheral ulcerative keratitis associated with autoimmune or
Accepted for publication December 8, 2003. From the Department of Ophthalmology (Lifshitz, Levy), Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, and ‘‘Enaim’’ Ophthalmological Center (Lifshitz, Mahler, Levinger), Jerusalem, Israel. No author has a financial or proprietary interest in any method or material mentioned. Reprint requests to Jaime Levy, MD, Department of Ophthalmology, Soroka University Medical Center, P.O. Box 151, Beer-Sheva 84101, Israel. E-mail: [email protected]. 2005 ASCRS and ESCRS Published by Elsevier Inc.
collagen vascular disease. Laser procedures for correcting refractive errors are increasingly popular. One of the potential complications of these procedures is keratitis, which can be infectious or sterile and might permanently affect the visual acuity. There are reports of presumed sterile peripheral corneal infiltrates after various refractive procedures such as photorefractive keratectomy (PRK),1,2 phototherapeutic keratectomy (PTK),3 and laser in situ keratomileusis (LASIK).4–8 To our knowledge, there are no reported cases following laser-assisted subepithelial keratectomy (LASEK) or LASIK in which the flap was performed with the IntraLase femtosecond laser. Three patients (5 eyes) presented with peripheral sterile corneal infiltrates after LASIK, LASEK, and LASIK performed with IntraLase, respectively. We also review the reported cases of peripheral corneal infiltrates after refractive surgery. 0886-3350/05/$-see front matter doi:10.1016/j.jcrs.2004.12.057
PERIPHERAL STERILE CORNEAL INFILTRATES
Patients and Methods Case 1 A 47-year-old woman sought refractive surgery to correct myopia. Ocular history was unremarkable and negative for contact lens use and episodes of red eyes or discharge. Medical history was unremarkable. Uncorrected visual acuity (UCVA) was 20/400 in both eyes. Best spectacle-corrected visual acuity (BSCVA) was 20/20 in both eyes with a refraction of ÿ2.50 ÿ2.25 175 in the right eye and ÿ2.50 ÿ1.25 175 in the left eye. External and slitlamp microscopy examinations were normal; no meibomian gland dysfunction or blepharitis was obvious. The cornea was normal without epithelial defects or infiltrates. Preoperative corneal topography was within normal limits. The patient had uneventful bilateral LASIK. Fifteen minutes before surgery, chloramphenicol drops were administered 3 times at 5-minute intervals. The patient’s face was prepared with povidone–iodine 10% solution before surgery, and the face and body were covered with sterile sheets. The lashes were retracted with a SteriDrape. Surgery was performed with the Nidek EC-5000 laser after a nasally hinged 160 mm flap was made by the Nidek 2000-MK microkeratome with an 8.5 mm suction ring. Topical lomefloxacin 0.3% was instilled at the end of the procedure. Dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops were prescribed 4 times daily after the procedure. One day after LASIK, UCVA was 20/30 in both eyes. Three days after the procedure, the patient complained of mild pain and red eye bilaterally. A circumferential stromal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrate and the limbus were observed in both eyes (Figure 1). There was no anterior chamber reaction. An immunologic reaction etiology was suspected, and corneal scrapings were therefore deferred. The patient was treated with dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops 8 times a day and oral prednisone 60 mg a day. After 1 day, the pain had decreased, and the infiltrates were less intense. The infiltrates had almost completely disappeared after 1 week, leaving slight stromal haziness. The topical treatment was tapered for 1 month, and the oral prednisone was gradually tapered and stopped after 2 weeks. Six months after the procedure, UCVA was 20/25 in both eyes and the corneas were clear with no scarring. At the last follow-up the patient had no complaint, and no new episodes had occurred.
Case 2 A 25-year-old man had bilateral LASEK for myopia. In both eyes, the preoperative refraction was ÿ2.25, UCVA was 20/120, and BCVA was 6/6. Preoperative pachymetry was 485 mm in both eyes. Medical history was unremarkable. The patient had a history of meibomian gland dysfunction.
Figure 1. Case 1: Left eye 3 days after LASIK procedure, showing a circumferential stromal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrate and the limbus.
Slitlamp examination revealed mild meibomian gland dysfunction without blepharitis. Fifteen minutes preoperatively, chloramphenicol drops were given 3 times at 5-minute intervals. The patient’s face was prepared with povidone– iodine 10% solution before surgery, and the face and body were covered with sterile sheets. The lashes were retracted with a SteriDrape. An epithelial flap was lifted using 20% alcohol for 30 seconds, a routine procedure of LASEK. The stromal ablation was performed using the 217 C Bausch & Lomb excimer laser. The ablated stroma was immediately irrigated with a chilled balanced salt solution. The epithelial flap was then rolled to its original position. A plano soft contact lens was placed on the corneas at the end of the bilateral procedure. Topical gentamycin drops were instilled at the end of the procedure. The patient was instructed to apply dexamethasone sodium phosphate 0.1% and ofloxacin drops 4 times daily. One day postoperatively, the patient complained of pain in both eyes. The UCVA was 20/30 in the right eye and 20/25 in the left eye. Slitlamp examination revealed an almost 360-degree corneal infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the peripheral corneal infiltrate and the limbus (Figure 2, A). In addition, meibomian plugging was observed in upper lid margin in both eyes (Figure 2, B). An immune etiology was suspected, and corneal scrapings were not performed. The contact lenses were removed. Topical steroids and ofloxacin were given 8 times daily, and systemic doxycycline 100 mg a day and prednisone 80 mg a day was started. One day later, the ocular pain had almost disappeared and the corneal infiltrates were significantly less intense. On the fifth postoperative day, the epithelium had completely
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healed and the corneas were completely clear. The UCVA was 20/20 in both eyes. Treatment with dexamethasone sodium phosphate 0.1% 4 times a day was continued for 3 weeks, systemic doxycylcine 100 mg a day for 1 month, and prednisone was gradually tapered and stopped after 2 weeks. Three months following the procedure, UCVA was 20/20 in both eyes, and the corneas were clear without scarring.
Case 3 A 26-year-old man sought refractive surgery to correct myopia. Ocular and medical history was unremarkable. The UCVA was 20/200 in both eyes. The BSCVA was 20/30 in the right eye and 20/25 in the left eye with a refraction of ÿ2.75 ÿ0.75 105 in the right eye and ÿ2.75 ÿ0.75 80 in the left eye. Preoperative corneal topography and Orbscan (Bausch & Lomb) were within normal limits. The patient had bilateral LASIK. Fifteen minutes before surgery, chloramphenicol drops were administered 3 times at 5-minute intervals. The patient’s face was prepared with povidone–iodine 10% solution before the operation, and the face and body were covered with sterile sheets. The lashes were retracted with a SteriDrape. Flaps of 100 mm were fashioned with the IntraLase. The stromal ablation was performed using the wavefront-guided Zyoptix laser (Keracor 217z, v 3.1). Topical lomefloxacin 0.3% was instilled at the end of the procedure. One day later, UCVA was 20/20 in both eyes. A 3 mm corneal yellow–white infiltrate peripheral to the flap edge with intact epithelium and an intervening clear zone between the limbus and the infiltrate were observed in the right eye. The anterior chamber was quiet. Examination of the left eye was completely normal. Because of the peripheral location of the infiltrate, an immune etiology was suspected and corneal scrapings were not performed. Topical treatment of dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops 8 times daily was prescribed. After 1 day, the corneal infiltrate was significantly less intense, disappearing on the fourth postoperative day. The UCVA was 20/20 in both eyes. Treatment with dexamethasone sodium phosphate 0.1% and lomefloxacin 0.3% drops 4 times a day was continued for 3 weeks. Four months after the procedure, the cornea was completely clear with no scar, and UCVA was 20/20 in both eyes. No new episodes of ocular inflammation have occurred.
Discussion Several reports have described presumed sterile peripheral corneal infiltrates after refractive procedures. In 1995, Teal and coauthors1 were the first to describe corneal subepithelial infiltrates following PRK. They surveyed 50 Canadian PRK surgeons and received responses on 30 cases. The reported frequency of this complication was 1 in 300 cases. It was suggested that this complication appeared when surgeons began switch1394
Figure 2. A: Case 2. Right eye 1 day after LASEK procedure with a plano soft contact lens. An almost 360-degree corneal infiltrate peripheral to the flap edge with intact epithelium can be observed, with an intervening clear zone between the peripheral corneal infiltrate and the limbus. B: Same eye showing meibomian plugging in upper lid margin.
ing from patching the eye with bandages following PRK to the use of topical nonsteroidal antiinflammatory drugs (NSAIDs) with or without a contact lens for reducing postoperative pain. The majority of cases (77%) presented during the first 48 hours after the procedure. The most common clinical pattern was a large opacity, often in the shape of an immune ring, with 1 or 2 peripheral opacities. Permanent scarring accompanied by reduced vision was the usual result, with 80% of cases losing best spectacle-corrected visual acuity. Corneal biopsy performed in 1 eye with these immune infiltrates demonstrated infiltration by neutrophils and the presence of an active fibroblastic reaction, without lymphocytes or plasma cells.3
J CATARACT REFRACT SURG—VOL 31, JULY 2005
PERIPHERAL STERILE CORNEAL INFILTRATES
In addition, there are reports of peripheral infiltrates appearing 1 day after the refractive procedure outside the zone of laser treatment resolving after a few days of topical treatment with steroids and antibiotics, and not affecting the final visual outcome.2,6,8,9 The authors suggested a distinct clinical entity for this second group of peripheral presumed sterile corneal infiltrates, based on the course of the disease and final outcome. In these cases, there was no use of NSAIDs or contact lens wear. Others assumed that the excimer laser may liberate a trapped antigen from the corneal stroma or create an antigen,3 resulting in an immune reaction. In the authors’ opinion, there is a strong clinical similarity between the marginal or catarrhal infiltrates appearing in patients with staphylococcal blepharitis and the peripheral infiltrates in patients after laser refractive procedures. In the case of classic marginal keratitis, the pathogenesis has been attributed to a localized corneal hypersensitivity reaction to toxins produced by bacteria colonizing the eyelid margins, usually Staphylococcus aureus, resulting in local deposition of immune complexes in the peripheral corneal stroma.7 There is also a similarity between these 2 processes in the response to treatment with steroids, antibiotic drops, and doxycylcine. There appear to be no reports in the literature of peripheral corneal infiltrates after LASEK or LASIK performed with IntraLase. Only 1 of the patients (Case 2) had obvious preoperative meibomian gland dysfunction and contact lens wear after the procedure. This patient also administered oral doxycylcine because of the preexisting meibomian gland dysfunction. The rationale for doxycylcine use is that it decreases production of bacterial lipases and thus decreases fatty acid levels.10 None of the patients received NSAIDs. In all cases, final visual acuity was 20/25 or better with no permanent corneal scarring. In the first 2 cases, and because of the significant circumferential infiltrate, oral steroids were administered in addition to topical steroids, with an initial dose of 1 mg/kg for 2 weeks. Immune reaction alone seems to be an insufficient explanation because there are only a few reports of this complication and the number of refractive procedures worldwide is enormous. The authors can hypothesize that the mixture of the effects of the laser on the corneal stroma and other ocular or systemic factors unknown to date can trigger this complication. Although the exact
mechanism of this complication remains unclear, recognition of this entity and its differentiation from infectious keratitis is essential to the management of these patients. Appropriate and early management usually results in a rapid disappearance of the infiltrates without affecting the final outcome. Nevertheless, it is important to maintain a high degree of suspicion for infectious keratitis because the management is very different and the potential outcome much worse if the keratitis is due to an infectious etiology. One could perform a culture and treat these cases empirically as infectious for the first 24 to 36 hours. If the cultures come back negative, one could start topical and systemic steroids.
References 1. Teal P, Breslin C, Arshinoff S, Edmison D. Corneal subepithelial infiltrates following excimer laser photorefractive keratectomy. J Cataract Refract Surg 1995; 21:516–518 2. Rao SK, Fogla R, Rajagopal R, et al. Bilateral corneal infiltrates after excimer laser photorefractive keratectomy. J Cataract Refract Surg 2000; 26:456–459 3. Teichmann KD, Cameron J, Huaman A, et al. Wesselytype immune ring following phototherapeutic keratectomy. J Cataract Refract Surg 1996; 22:142–146 4. MacRae S, Macaluso DC, Rich LF. Sterile interface keratitis associated with micropannus hemorrhage after laser in situ keratomileusis. J Cataract Refract Surg 1999; 25:1679–1681 5. Macaluso DC, Rich LF, MacRae S. Sterile interface keratitis after laser in situ keratomileusis: three episodes in one patient with concomitant contact dermatitis of the eyelids. J Refract Surg 1999; 15:679–682 6. Yu EYW, Rao SK, Cheng ACK, et al. Bilateral peripheral corneal infiltrates after simultaneous myopic laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:891– 894 7. Ambro´sio R Jr, Periman LM, Netto MV, Wilson SE. Bilateral marginal sterile infiltrates and diffuse lamellar keratitis after laser in situ keratomileusis. J Refract Surg 2003; 19:154–158 8. Lahners WJ, Hardten DR, Lindstrom RL. Peripheral keratitis following laser in situ keratomileusis. J Refract Surg 2003; 19:671–675 9. Haw WW, Manche EE. Sterile peripheral keratitis following laser in situ keratomileusis. J Refract Surg 1999; 15:61–63 10. Hussein N, Schwab IR, Ostler B. Blepharitis. In: Tasman W, Jaeger EA, eds, Duane’s Clinical Ophthalmology on CD-ROM. Philadelphia, PA, Lippincott Williams & Wilkins, 2004
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