Central Focal Interface Opacity After Laser in situ Keratomileusis

Graham E. Fraenkel, MB, BS; Peter R. Cohen, MB, BS, FRACS, FRACO; Gerard L. Sutton, MB, BS, FRACS, FRACO; Michael A. Lawless, MB, BS, FRACS, FRACO; Christopher M. Rogers, MB, BS, FRACS, FRACO

ABSTRACT
BACKGROUND: The acute onset of a focal central interface opacity with visual loss following LASIK has not been described in the peer reviewed literature. Non-peer reviewed reports of various inflammatory lesions have been recorded. METHODS: We describe three cases in which an acute focal stromal interface opacification was identified within 1 week of laser in situ keratomileusis (LASIK). Each case was performed by a different surgeon on a different day, but using the same method, materials, and the Summit Apex Plus excimer laser. Immediately after surgery, all eyes were normal with good unaided vision. The appearance of the central stromal opacity was associated with acute visual deterioration. Preoperative and postoperative cycloplegic refractions, videokeratography, and postoperative slit-lamp biomicroscopy were performed. Each case was treated with intensive topical corticosteroids. RESULTS: Each case demonstrated a central circular opacity in the interface between corneal flap and stromal bed, with associated variable stromal thinning. Resolution of the pathological process followed 2 to 4 weeks of treatment with topical corticosteroids and subsequent improvement in slitlamp biomicroscopy, corneal topography, and vision. Etiology was uncertain. CONCLUSION: Central interface opacification is a rare but visually important inflammatory complication of LASIK. [J Refract Surg 1998;14:571-576]

he acute onset of central interface opacification with visual loss following LASIK has not been described in the peer reviewed literature. Non-peer reviewed reports of various inflammatory lesions have been recorded. We describe three cases in which an acute stromal interface opacification was identified within 1 week of laser in situ keratomileusis (LASIK). The clinical entity described here is different than the diffuse interface inflammation sometimes described as shifting sands of the Sahara following LASIK. CASE 1
A 38-year-old male presented for correction of bilateral myopia. He had no significant past ocular or medical history. Ophthalmic examination was otherwise normal. Cycloplegic refraction was -3.75 diopters (D) both eyes. Spectacle-corrected visual acuity was 6/6 in both eyes. Videokeratography was performed. He received consecutive bilateral LASIK for a correction of -3.80 D. Ansell Medical NuTex hypoallergenic powder free Latex surgical gloves were worn by the surgeon. A total of 5 drops of tetracaine hydrochloride 1.0% (Amethocaine Minims, Smith and Nephew Pty. Ltd, Sydney, Australia) were placed on the cornea at the beginning of the procedure. The cornea was then rinsed with balanced salt solution sterile irrigating solution (Alcon Laboratories Aust. Pty. Ltd, Sydney, Australia) from a single dose bottle. The cornea was dried with Merocel surgical spears prior to marking with single use 1% gentian violet. The suction ring of the Chiron automated microkeratome (Chiron, Sydney, Australia) was then placed on the eye and suction applied. The cornea was rinsed again with balanced salt solution. The microkeratome, with a depth limiting plate of 160 m, was passed across the eye to create the corneal flap. This was raised and folded back with a Rycroft cannula to be placed nasally for the duration of the excimer ablation. The flap was not covered during the ablation.

From the Sydney Refractive Surgery Centre, Chatswo od, New South Wales, Australia. The authors have no proprietary interest in the materials presented. Correspondence: Christopher Rogers, Level 3, 270 Victoria Ave, Chatswo od, NSW 2067, Australia. Tel: 61-2-9424-9999; Fax: 61-29410-3000; Email: srsc@acay.com.au Received: October 14, 1997 Accepted: April 24, 1998

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Figure 1: Slit-lamp microscopy, Case 1 (right eye) 1 week after surgery. (A) Paracentral corneal interface opacification, (B) broad slit shows flattening of cornea overlying disciform lesion due to stromal interface necrosis, and (C) fine slit shows corneal inflammation at the level of the corneal cap and stromal bed interface.

acetate 1% t.i.d. for both eyes was prescribed. Four days later he complained of pain in the left eye of 2 days duration. Uncorrected visual acuity was right eye 6/24 and left eye, count fingers. Slit-lamp microscopy revealed an epithelial defect in the left eye. Both eyes showed a discrete paracentral 3 mm diameter circular area of stromal opacity at the interface of flap and stromal bed paracentrally. Folds in the epithelial basement membrane were seen in this area. These changes were located slightly nasal in the left eye and slightly temporal to the visual axis in the right eye. The anterior chambers were quiet.

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The multizone ablation was performed to an outer zone diameter of 6.5mm with a Summit Apex Plus excimer laser (Summit Pty. Ltd. Waltham, Mass), with a fluence of 180 mJ/cm2 and a repetition rate of 10 Hz. The patient maintained fixation while centration was observed through the operating microscope. Afterwards the ablated stromal bed was rinsed with balanced salt solution and the was cap replaced. A further rinse with balanced salt solution beneath the flap was performed via a Rycroft cannula. The flap was rechecked at 2 and 20 minutes postoperatively. All disposable sterilizable equipment, except for the microkeratome and blade, was new for the patients second eye. The procedure was otherwise the same for each eye. The patient was discharged after both procedures were completed. Neither eye was patched but shields were worn bilaterally. One day after surgery, uncorrected visual acuity was 6/12 both eyes. Tobramycin 0.1% and prednisolone

The differential diagnosis at this stage included topical medication toxicity and microbial keratitis. Therefore, topical medications were ceased and Ciprofloxacin 0.3% (Ciloxin, Alcon Laboratories, Aust Pty. Ltd, Sydney, Australia) was prescribed 4 times per day. Three days later, uncorrected visual acuity was right eye 6/18 and left eye 6/60. At near, he could read N6. The epithelium in the left eye had healed and the stromal interface changes showed improvement. Ciprofloxacin was continued and slit-lamp biomicroscopy was performed (Fig 1). Videokeratography was repeated (Fig 2). Two weeks after surgery uncorrected visual acuity was right eye 6/18, left eye 6/60. A diagnosis of presumed noninfective inflammation was made. Ciprofloxacin was ceased and fluoromethalone alcohol 0.1% prescribed b.i.d. both eyes for 2 weeks. Five weeks after surgery, uncorrected visual acuity was right eye 6/12, and left eye 6/36. Spectacle-corrected visual acuity was right eye 6/9 with a spherical equivalent refraction of +0.75 -1.25 x 98, left eye 6/15 with +3.50 -1.75 x 125. The interface changes were much improved on slit-lamp biomicroscopy.

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Figure 2: Videokeratography and keratography of the right eye (A) before LASIK, (B) 1 week after LASIK, and (C) 4 months after LASIK.

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CASE 2
Fluoromethalone was continued b.i.d. for both eyes. Two months postoperatively, uncorrected visual acuity was right eye 6/12, and left eye 6/30. Spectaclecorrected visual acuity was right eye 6/9 with +1.00 -1.00 x 90, and left eye 6/9 with +3.50 -1.50 x 95. Slit-lamp biomicroscopy showed decreased interface opacity and folds. The fluoromethalone was ceased. Four months postoperatively, uncorrected visual acuity was right eye 6/7.5, left eye 6/12, and spectacle-corrected visual acuity was 6/6 in both eyes with a right eye spherical equivalent refraction of 0.00 -0.75 x 97, and left eye +2.25 -0.75 x 115. Videokeratography was performed (Fig 3). A 36-year old male presented for correction of myopic astigmatism. He had no significant past ocular or medical history. Ophthalmic examination was otherwise normal. Spectacle-corrected visual acuity was 6/6 both eyes with cycloplegic refractions of right eye -6.75 -1.00 x 8, left eye -7.75 -0.75 x 163. He received consecutive bilateral LASIK for a correction of right eye -7. 00 D, and left eye -8.00 D. The same operative technique, laser, and parameters were used as in the first patient, but a different surgeon (CR) performed the procedure, without gloves. Initial postoperative care was the same as for the first patient. The first postoperative day, uncorrected visual acuity was 6/6 in both eyes. Ofloxacin (0cuflox 0.3%,

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Figure 3: Videokeratography and keratography of the left eye (A) before LASIK, (B) 1 week after LASIK, and (C) 4 months after LASIK.

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Allergan, Australia Pty. Ltd, Sydney, Australia) and prednisolone acetate 1.0% were prescribed q.i.d. At day 3 the patient noticed some photophobia and decreased vision but did not present at this time. Six days postoperatively, uncorrected visual acuity had deteriorated to right eye 6/24, and left eye 6/18. Spectacle-corrected visual acuity was right eye 6/9, and left eye 6/9 with a spherical equivalent refraction of right eye -0.25 -0.75 x 69, left eye -0.50 -1.00 x 120. Significant paracentral interface inflammation was present binocularly with an appearance similar to the first patient, though not as severe. Prednisolone acetate 1.0% was prescribed hourly for both eyes. At 4 weeks after surgery, uncorrected visual acuitywas right eye 6/9, and left eye 6/9. Spectacle-corrected visual acuity was right eye 6/7.5 with +1.75 -2.20 x 72, and left eye 6/7.5 with +1.00 -0.50 x 178. Slit-lamp biomicroscopy showed a marked decrease in interface opacity and basement membrane folds.

CASE 3
A 34-year old male presented for correction of bilateral myopic astigmatism. Cycloplegic spherical equivalent refraction was right eye -1.50 -1.50 x 100 , and left eye -1.50 -1.00 x 72. Spectaclecorrected visual acuity was 6/6 in both eyes.

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LASIK was performed in the left eye for a spherical correction (spectacle plane) of -1.50 D, and cylindrical correction of -1.00 x 72 with an ablation zone of 6.5 mm. Postoperatively, the eye was treated with topical chloramphenicol and prednisolone acetate 1.0% q.i.d. Five weeks postoperatively, spectacle-corrected visual acuity was 6/6 with a spherical equivalent refraction of +0.25 -1.00 x 90. LASIK was then performed in the right eye for a correction of -1.50 -1.50 x 100. On the first postoperative day, uncorrected visual acuity was 6/7.5 in the right eye. Postoperative drops were the same as for the left eye. The flap was intact and the eye was quiet. At 1 week, uncorrected visual acuity was 6/60 in the right eye. A central well circumscribed opacity and edema was seen at the flap interface on slit-lamp biomicroscopy. Prednisolone 1.0 % was used hourly in the right eye. One week later, spectacle-corrected visual acuity improved to 6/18 and the edema had decreased. Prednisolone acetate 1.0 % was continued t.i.d. in the right eye. However, a few punctate epithelial erosions were seen, so topical acyclovir ointment was also prescribed b.id. for the right eye. Three weeks after surgery, spectacle-corrected visual acuity was 6/15 with a spherical equivalent refraction of +2.00 -0.50 x 45. Central stromal folds were seen. No punctate epithelial erosions were present. Acyclovir and prednisolone acetate 1.0% was ceased. Prednisolone phosphate 0.5% was started topically q.i.d. Five weeks postoperatively, uncorrected visual acuity in the right eye was 6/60 and spectacle-corrected visual acuity was 6/12 with a spherical equivalent refraction of +2.25 -1.50 x 120. No change was observed in the stromal folds but opacity had decreased significantly. Prednisolone phosphate 0.5% was continued t.i.d.

DISCUSSION LASIK has been performed and reported in the literature since 1990.1 In this article, we describe acute onset central stromal opacification at the LASIK flap-bed interface. This is a rare and previously unreported complication of LASIK. In each case a different surgeon was involved, but each surgeons technique was nearly identical. Each procedure was performed using the same equipment, the same laser, and the same disposables. On each day, up to 14 LASIK procedures were done before, and up to 6 after the procedure involved, but no procedure preceding or following those described here developed this complication. At the beginning of each laser session the excimer laser was calibrated according to the standard protocol recommended by
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the manufacturer. No departures from calibration standards were found on any of the 3 days on which the procedures described were performed. The etiology of this problem remains obscure. Multifocal or diffuse areas of inflammation with white cell recruitment have been identified (GO Waring III, MD, personal communication, 1997) and we have also seen some cases of shifting sands of the Sahara. The clinical entity described in this report is different. It is characterized by a central dense opacity associated with stromal folds and corneal thinning. With time the density lessens and the edges become feathery. In all cases, vision and slit-lamp biomicroscopy were routine on the first postoperative day, but then deteriorated between days 2 and 7. Stromal necrosis has been previously described following infective, chemical, and physical causes such as herpes simplex virus, Acanthamoeba, Serratia mascerans, Pseudomonas keratitis, Aspergillus, chemical injuries, polysulfone intracorneal lenses, and thermal keratoplasty for keratoconus.2-9 The absence of a foreign body or obvious nidus of infection within the affected area, and the putative response to topical corticosteroids suggests that an infective cause is unlikely. Chemical causes might include gentian violet10,11, Amethocaine12, or residues from cleaning of the microkeratome or manufacture of the blade. Lipids or other tear film materials may represent a toxic stimulus and physical causes could include heat due to friction from the microkeratome blade.13 As the lesion occurred almost at the apex of the cornea there may be a contribution to this clinical picture by the pressure of the cornea against the depth plate or blade involved, which would be expected to be maximal at this point. Another possible hypothesis is that central interface inflammation may arise from the pressure infusion of a chemical agent into the central or paracentral stroma as a result of the pass of the microkeratome. This chemical agent may then precipitate a sterile stromal enzymatic digestion.14 Similarly residual epithelial cells may release further enzymes or cytokines leading to an alteration in the glycosaminoglycans and subsequent collagen lamellae compaction. This may explain the apparent corneal thinning. Any inflammation present may be inhibited by the use of topical corticosteroids15, allowing stromal regeneration and resolution of the opacification, with a recovery in spectacle-corrected Snellen visual acuity and improvement in corneal topography. Nevertheless, these patients were on

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corticosteroids at the time of reduced vision and their role in management is unclear. Knowledge of the clinical appearance of this rare but important complication of LASIK and vigilance in the first postoperative week is required to ensure early recognition. Importantly, all patients affected with this inflammation have had improved visual function after resolution. REFERENCES
1. Pallikaris IG, Papatzanaki ME, Stathi EZ, Frenschock O, Georgiadis A. Laser in situ keratomileusis. Lasers Surg Med 1990;10:463-468. 2. Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea 1987;6:286-291. 3. Mietz H, Font RL. Acanthamoeba keratitis with granulomatous reaction involving the stroma and anterior chamber. Arch Ophthalmol 1997;115:259-263. 4. Lyerly D, Gray L, Kreger A. Characterization of rabbit corneal damage produced by Serratia keratitis and by a serratia protease. Infect Immun 1981;33:927-932. 5. Van Horn DL, Davis SD, Hyndiuk RA, Pederson HJ. Experimental Pseudomonas keratitis in the rabbit: bacteriologic, clinical, and microscopic observations. Invest Ophthalmol Vis Sci 1981;20:213-221. 6. Heidemann DG, Dunn SP, Watts JC. Aspergillus keratitis

7. 8. 9. 10. 11. 12. 13. 14. 15.

after radial keratotomy. Am J Ophthalmol 1995;120:254256. Wagoner MD. Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol 1997;41:275-313. Lane SL, Lindstrom RL, Cameron JD, Thomas RH, Mindrup EA, Waring GO 3rd, McCarey BE, Binder PS. Polysulfone corneal lenses. J Cataract Refract Surg 1986;12:50-60. Arentsen JJ, Rodriques MM, Laibson PR. Histopathologic changes after thermokeratoplasty for keratoconus. Invest Ophthalmol Vis Sci 1977;16:32-38. Schoppelrey HP, Mily H, Agathos M, Breit R. Allergic contact dermatitis from pyoctanin. Contact Dermatitis 1997;36:221224. Hosford GN, Smith JG. Treatment of ocular methylrosaniline poisoning with fluorescein solution. JAMA 1952;150:1482-1484. Kalveram K, Gunnewig W, Wehling K, Forck G. Tetracaine allergy: cross-reactions with para-compounds? Contact Dermatitis 1978;4:376. Betney S, Morgan PB, Doyle SJ, Efron N. Corneal temperature changes during photorefractive keratectomy. Cornea 1997;16:158-161. Kenyon KR. Inflammatory mechanisms in corneal ulceration. Trans Am Ophthalmol Soc 1985;83:610-663. Basu R, Avaria M, Jankie R. Effect of hydrocortisone on the mobilisation of leucocytes in corneal wounds. Br J Ophthalmol 1981;65:694-698.

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