Bilateral corneal infiltrates after excimer laser photorefractive keratectomy

Bilateral corneal infiltrates after excimer laser photorefractive keratectomy

Bilateral corneal infiltrates after excimer laser photorefractive keratectomy Srinivas K. Rao, DO, Rajesh Fogla, DNB, FRCS, Rama Rajagopal, DO, DNB, G...

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Bilateral corneal infiltrates after excimer laser photorefractive keratectomy Srinivas K. Rao, DO, Rajesh Fogla, DNB, FRCS, Rama Rajagopal, DO, DNB, G. Sitalakshmi, DO, Prema Padmanabhan, MS ABSTRACT A 26-year-old man developed painless inferior subepithelial infiltrates away from the site of ablation in both eyes after excimer laser photorefractive keratectomy (PRK) for myopia. Clinical characteristics of the corneal infiltrates resembled staphylococcal-immune infiltrates. The condition responded to treatment with topical diluted steroids and antibiotics. There was no residual corneal scarring. The infiltrates did not affect the refractive outcome of the surgery. Recognition of this rare entity will help clinicians avoid aggressive investigative and treatment modalities that can affect the results of PRK. J Cataract Refract Surg 2000; 26:456 – 459 © 2000 ASCRS and ESCRS


lthough excimer laser photorefractive keratectomy (PRK) is a relatively new surgical procedure, it is used extensively in the treatment of refractive errors of the eye.1 As with any surgical procedure, complications have been reported. The 2 most common, refractive regression and corneal haze, are related to the amount of attempted myopic correction.2 This has led to the development of modified surgical algorithms for PRK and newer surgical procedures such as laser in situ keratomileusis (LASIK) to treat higher degrees of myopia.3 Rarer, but potentially more serious, complications that can result in visual loss include recurrent epithelial breakdown, sterile corneal infiltrates, reactivation of herpes simplex keratitis, corneal ulceration secondary to infections,1 endophthalmitis,4 and acute corneal necrosis.5 Corneal infiltrates after PRK caused by bacterial,6

viral,7 and fungal infection4 are often associated with use of a soft contact lens. Sterile infiltrates at and adjacent to the site of the laser ablation caused by the use of soft contact lenses and topical nonsteroidal anti-inflammatory drugs (NSAIDs) have been described.8 –12 We describe a patient who developed bilateral, inferior, subepithelial infiltrates of presumed noninfectious etiology after myopic PRK. Topical NSAIDs and a soft contact lens were not used postoperatively. The lesions were painless, did not involve the ablated stroma, and resolved with topical diluted steroids and antibiotics. These infiltrates represent a hitherto unreported complication of excimer PRK. Clinical features, response to treatment, and possible etiopathogenesis are discussed.

Case Report Accepted for publication September 2, 1999. From Sankara Nethralaya, Chennai, India. Supported by Vision Research Foundation, Chennai, India. None of the authors has a proprietary interest in any material used. Reprint requests to Dr. Srinivas K. Rao, Cornea Service, Medical Research Foundation, 18, College Road, Chennai 600 006, India. © 2000 ASCRS and ESCRS Published by Elsevier Science Inc.

A 26-year-old man presented for excimer laser PRK for myopia in both eyes. He was not a contact lens wearer. Systemic history was unremarkable except for an allergy to penicillin. On examination, Snellen best corrected visual acuity (BCVA) was 20/20 in both eyes with a refraction of –1.50 ⫹0.25 ⫻ 180 in the right eye and –1.75 in the left eye. Slitlamp biomicroscopy revealed a normal anterior segment. Intraocular pressure was 16 mm Hg in both eyes. Fundus 0886-3350/00/$–see front matter PII S0886-3350(99)00348-X


examination by indirect ophthalmoscopy revealed lattice degeneration in the superotemporal and inferior retina of the right eye and was normal in the left eye. Keratometry was 41.75 ⫻ 5/42.25 ⫻ 95 and 41.75 ⫻ 170/41.75 ⫻ 80, respectively. Corneal topography did not reveal any abnormality, and central corneal pachymetry was 520 ␮m in both eyes. Informed consent for the procedure was obtained. One drop of pilocarpine 2.0% was instilled in the right eye 45 minutes before the procedure. Proparacaine 2.0% eyedrops were used to anesthetize the ocular surface. A 7.0 mm trephine, centered on the pupil, was used to mark the corneal surface, with the patient fixating on the target in the microscope. The epithelium within the mark was removed mechanically using a blunt scraper. Excimer PRK was performed in the right eye using the Summit Technology Apex Plus laser. A 1.70 diopter (D) correction was performed with an ablation zone diameter of 6.5 mm. Central island treatment software was used. After the procedure, ciprofloxacin 0.3% ointment was instilled in the right eye and the eye was patched. Topical NSAIDs were not used preoperatively or postoperatively. The next day, the patient did not have pain in the operated eye. Minimal conjunctival injection was noted at the inferior limbus. A central 4.0 ⫻ 5.0 mm epithelial defect was present, and the corneal stroma at the site of the ablation was clear. Inferior stromal haze, extending clockwise from 4 to 8 o’clock, was noted. A 1.0 mm clear zone was present between the inferior edge of the stromal haze and the inferior limbus. The overlying epithelium was intact and the anterior chamber quiet. The eye was patched with ciprofloxacin 0.3% eye ointment. The following day, the central epithelial defect had decreased to 4.0 ⫻ 2.0 mm, and the inferior stromal haze appeared more intense. Patching with ciprofloxacin 0.3% ointment was repeated. On the fourth postoperative day, the central corneal epithelial defect had healed and a yellowishwhite infiltrate was seen inferiorly, extending clockwise from 4 to 8 o’clock (Figure 1). The infiltrate was 1.5 mm wide at the thickest central portion and tapered toward the edges. A clear 1.0 mm of cornea was present between the infiltrate and the inferior limbus. There was no surrounding corneal edema or stromal ulceration, and the anterior chamber was quiet. Fluorescein staining revealed epithelial stippling over the site of the corneal infiltrate. A detailed examination of the lids revealed evidence of meibomian seborrhea, with oily lid margins and excessive discharge of clear meibom on pressure over the lid. There was no evidence of blepharitis. On questioning, the patient denied a history of seborrheic dermatitis of the scalp. Rose bengal staining of the ocular surface was negative. Schirmer testing revealed a wetting of 20 mm at the end of 5 minutes in both eyes. Because the clinical features suggested a diagnosis of staphylococcal-immune infiltrates, the patient was treated with oral tetracycline (250 mg) 4 times daily, ciprofloxacin 0.3% eyedrops hourly, ciprofloxacin 0.3% ointment at bed-

Figure 1. (Rao) Slitlamp photograph of the right eye 4 days after uneventful PRK for myopia. Note the linear peripheral subepithelial corneal infiltrate away from the site of treatment. The overlying epithelium is intact.

time, and 1:8 dilution of betamethasone 1.0% eyedrops 4 times daily. Three days later, the infiltrates had regressed considerably, but 2 areas of epithelial breakdown were noted over the center of the infiltrate (Figure 2). With continuation of treatment, the infiltrates cleared over the next week. There was no residual scarring of the inferior cornea. Because the presumed etiology was staphylococcal-immune infiltrates related to lid-margin disease, the patient was advised to postpone surgery in the left eye by 1 month. Oral tetracycline was continued with the addition of lid scrubs and lid massage of both eyes for 1 month. The patient was reviewed 40 days after having PRK in the right eye. Uncorrected visual acuity (UCVA) in the right eye was 20/30. The cornea in the right eye was clear, and the lid margins in both eyes were healthy. He had PRK in the left eye using a surgical approach similar to that used in the right eye.

Figure 2. (Rao) Appearance of the right eye 7 days after PRK. The infiltrate has decreased in extent and intensity. There are 2 areas of epithelial breakdown over the infiltrate (arrows).




Figure 3. (Rao) A slitlamp photograph of the left eye 2 days after myopic PRK reveals peripheral corneal infiltrates (arrow) similar to those in the right eye (Figure 1).

Corneal findings similar to those in the right eye were noted on the first postoperative day (Figure 3). Based on experience with the first eye, diluted topical steroids and antibiotics were instituted in the left eye on the same day. A similar evolution of corneal changes was noted, but the intensity of the stromal infiltrate in the left eye was less and the condition resolved in 7 days without residual scarring. One month after treatment in the left eye, UCVA was 20/20. Slitlamp biomicroscopy revealed a clear cornea in both eyes.

Discussion Serious complications after excimer laser PRK continue to be reported4,5 and include corneal infiltrates of infectious etiology.4,6,7 Corneal infiltrates have also been reported with the use of soft contact lenses and NSAIDs,12 in cases of topical anesthetic agent abuse,13 and for idiopathic reasons.5 An infectious cause is likely if the post-PRK infiltrates are located at the site of epithelial debridement. In our patient, the stromal haze and infiltration occurred outside the area of epithelial debridement. The lack of patient symptoms, gradual evolution of the infiltrate, intact epithelium, and quiet anterior chamber helped rule out a diagnosis of infectious keratitis. Rather than disturb the intact epithelium to obtain corneal scrapings, we opted for a therapeutic trial directed at the most likely etiology: staphylococcal-immune infiltrates. The linear circumferential orientation of the infiltrates with a crescent shape, clear interval, late epithelial breakdown, meibomian seborrhea, and rapid response to diluted steroids and antibiotics appear to confirm the clinical diag458

nosis.14 However, we are unable to explain the occurrence of a similar phenomenon in the left eye after 1 month of treatment directed toward improving lid hygiene. The role of PRK in initiating the corneal reaction is also not clear. A Wessely-type peripheral immune ring has been described after uneventful phototherapeutic keratectomy (PTK) for corneal scarring.15 The patient was treated with diclofenac eyedrops and a bandage contact lens after PTK. We were unable to find a report of a similar occurrence after PRK in the literature. The reports of sterile infiltrates after PRK appear to describe a different entity.8 –12 The typical presentation in these reports is severe pain, decreased visual acuity, ciliary injection of the globe, and subepithelial white infiltrates in the treated area that has already epithelialized or just outside the treatment zone.10 The infiltrates occur on the first to third postoperative day and are sometimes associated with the appearance of immune rings. The reported incidence is about 1 in 250 cases.10 Corneal scrapings are culture negative, and the condition responds to therapy with topical steroids with or without antibiotics. Resolution is accompanied by corneal stromal scarring and reduced BCVA by 1 or 2 lines. It is believed that these infiltrates are related to the use of topical NSAIDs without concomitant use of topical steroids. As NSAIDs block only the cyclo-oxygenase pathway of arachidonic acid metabolism, this can result in a shift of arachidonic acid through the alternative lipo-oxygenase catalyzed pathway. The resulting leukotriene accumulation results in neutrophil chemotaxis and sterile corneal infiltrates.16 Contact-lens-induced hypoxia is also thought to contribute to the formation of these infiltrates.10 Recognition of the causative mechanism and the use of topical steroids, along with NSAIDs, have reduced the occurrence of this entity.12 We did not use a contact lens or NSAIDs in our patient. It is possible that lid manipulation during surgery resulted in increased expression of the meibomian secretions and bacterial toxins into the conjunctival culde-sac. Patching could have trapped this material in the eye, producing an allergic response in the cornea. We have observed acute exacerbation of ocular surface inflammation with sudden occurrence of peripheral corneal infiltration in patients with meibomian gland disease (unpublished data).



Teichmann et al.15 propose that mammalian tissues and micro-organisms release heat shock proteins (HSPs) when subjected to physical, chemical, or biological stress. They hypothesize that the interaction between circulating antibodies against bacterial HSPs (formed from previous exposure) and corneal HSPs produced after laser treatment can result in corneal infiltration. However, we have performed more than 2000 excimer laser procedures since early 1993 using a similar technique, and this is the first instance of such a phenomenon. If related solely to the lid-margin inflammation, we should have seen a higher incidence. A similar phenomenon was recently reported after LASIK in a 53-year-old man with a history of dry eye and chalazion excision.17 After bilateral surgery, the patient developed multiple, creamy-white, subepithelial infiltrates adjacent to the superior border of the keratectomy flap in the left eye only. There was no pain or photophobia, and the eye was quiet. The epithelium overlying the infiltrates was intact. Cultures from the lesion were negative. The infiltrates resolved without residual scarring after 7 days of treatment with hourly topical ofloxacin 0.3% eyedrops and prednisolone acetate 1% eyedrops. The authors comment on the similarity of ocular findings in the left eye to blepharitisinduced marginal keratitis but could not explain the unilateral occurrence. In conclusion, we report a distinct clinical entity— inferior, subepithelial, corneal infiltrates (presumably of noninfectious, immune-mediated etiology)—after excimer laser PRK. The clinical features, course of disease, and response to therapy are typical of staphylococcalimmune infiltrates. However, we have no explanation for the temporal relationship with PRK and the failure of therapy to prevent a similar occurrence in the second eye. We believe that recognition of this entity will allow surgeons to adopt a more conservative treatment approach. Aggressive investigative and treatment modalities could adversely affect the outcome of PRK and are probably not necessary for this relatively benign entity.

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2. Kremer I, Kaplan A, Novikov I, Blumenthal M. Patterns of late corneal scarring after photorefractive keratectomy in high and severe myopia. Ophthalmology 1999; 106: 467– 473 3. Pallikaris IG, Siganos DS. Excimer laser in situ keratomileusis and photorefractive keratectomy for correction of high myopia. J Refract Corneal Surg 1994; 10:498 –510 4. Faschinger C, Faulborn J, Ganser K. Infectio¨se Hornhautgeschu¨re— einmal mit Endophthalmitis—nach PRK mit Einmalkontaktlinse. Klin Monatsbl Augenheilkd 1995; 206:96 –102 5. Mietz H, Severin M, Seifert P, et al. Acute corneal necrosis after excimer laser keratectomy for hyperopia. Ophthalmology 1999; 106:490 – 496 6. Hill VE, Brownstein S, Jackson WB, Mintsioulis G. Infectious keratopathy complicating photorefractive keratectomy (letter). Arch Ophthalmol 1998; 116:1382– 1384 7. Wulff K, Fechner PU. Herpes simplex keratitis after photorefractive keratectomy (letter). J Refract Surg 1997; 13: 613 8. Sher NA, Frantz JM, Talley A, et al. Topical diclofenac in the treatment of ocular pain after excimer photorefractive keratectomy. Refract Corneal Surg 1993; 9:425– 436 9. Sher NA, Krueger RR, Teal P, et al. Role of topical corticosteroids and nonsteroidal antiinflammatory drugs in the etiology of stromal infiltrates after excimer photorefractive keratectomy (letter). J Refract Corneal Surg 1994; 10:587–588 10. Teal P, Breslin C, Arshinoff S, Edmison D. Corneal subepithelial infiltrates following excimer laser photorefractive keratectomy. J Cataract Refract Surg 1995; 21:516 – 518 11. Probst LE, Machat JJ. Corneal subepithelial infiltrates following photorefractive keratectomy (letter). J Cataract Refract Surg 1996; 22:281 12. Arshinoff SA, Mills MD, Haber S. Pharmacotherapy of photorefractive keratectomy. J Cataract Refract Surg 1996; 22:1037–1044 13. Kim JY, Choi YS, Lee JH. Keratitis from corneal anesthetic abuse after photorefractive keratectomy. J Cataract Refract Surg 1997; 23:447– 449 14. Chignell AH, Easty DL, Chesterton JR, Thomsitt J. Marginal ulceration of the cornea. Br J Ophthalmol 1970; 54:433– 440 15. Teichmann KD, Cameron J, Huaman A, et al. Wesselytype immune ring following phototherapeutic keratectomy. J Cataract Refract Surg 1996; 22:142–146 16. Ku EC, Lee W, Kothari HV, Scholer DW. Effect of diclofenac sodium on the arachidonic acid cascade. Am J Med 1986; 80:18 –23 17. Haw WW, Manche EE. Sterile peripheral keratitis following laser in situ keratomileusis. J Refract Surg 1999; 15:61– 63