Relapsing Diffuse Lamellar Keratitis After Laser In Situ KeratomileusisAssociated With Recurrent Erosion Syndrome

Diffuse lamellar keratitis (DLK) is a well-described complication oflaser in situ keratomileusis (LASIK) that generally occurs within the firstweek after surgery. Late-onset cases of DLK have been reported to occur manymonths after surgery and are sometimes associated with recurrent erosions.^1-3 We describe3 patients who had intraoperative epithelial defects and who subsequentlydeveloped DLK multiple times in the same location of the same eye, alwaysfollowing an episode of recurrent erosion.

A 33-year-old woman underwent bilateral LASIK in May 2001 for high myopia.Preoperative evaluation revealed clear corneas with no evidence of anteriorbasement membrane dystrophy. The procedure was uneventful in the right eye.In the left eye, however, a 2.0 × 2.0-mm corneal epithelial defect wasnoted in the superior paracentral location after creation of the flap, andthe epithelium surrounding the defect was noted to be generally poorly adherentto the Bowman layer. A bandage soft contact lens was placed on the left eye,and the patient was instructed to use a combination of 0.1% fluorometholoneand 0.3% ofloxacin eyedrops, 4 times daily, in both eyes. On the first postoperativeday, the patient's uncorrected visual acuity (UCVA) was 20/70 OS. On ophthalmicexamination, the contact lens was in place, and there was mild flap edema,but no epithelial defect or lamellar keratitis was noted. The soft contactlens was removed, and on the next day, the patient manifested acutely withreports of decreased vision, foreign body sensation, photophobia, tearing,and pain in the left eye. Visual acuity was still 20/70 OS, but a recurrent2.0 × 1.9-mm epithelial defect was found in the same location as whenthe defect had first been noted. No lamellar keratitis was found, and a bandagesoft contact lens was placed on the eye. On the third postoperative day, thepatient's visual acuity was decreased to 20/400 OS, and moderately severeDLK was found. Treatment with 1% prednisolone acetate was instituted everyhour around the clock in place of the 0.1% fluorometholone. By 2 days later,the DLK began to recede, and the epithelial defect was healed. Eight monthspostoperatively, the patient's best-spectacle-corrected visual acuity (BSCVA)was 20/20 OS.

At this time, the patient underwent an uneventful LASIK re-treatment(with relifting of the original flaps). Five months after the re-treatment,while the patient was away on vacation, she went to an emergency departmentwith reports of decreased vision, foreign body sensation, photophobia, tearing,and pain in the left eye. She was diagnosed as having a corneal abrasion andprescribed 0.3% ofloxacin, 4 times daily. On seeing an ophthalmologist 2 dayslater, her visual acuity was 20/60 OS, and she had a healing epithelial defectin a location corresponding to that of her previous 2 epithelial defects,as well as interface inflammation consistent with DLK. The patient was instructedto use both 1% prednisolone, every 2 hours, and 0.3% ofloxacin, 4 times daily.Two days later, the patient returned to our care and was found to have respondedwell to topical corticosteroid therapy in the left eye with only trace DLKnoted and with a UCVA of 20/30 OS.

Ten and a half months after re-treatment, the patient was seen withreports of discomfort in her left eye for 2 days and had a BSCVA of 20/15OD and 20/25 OS. Once again, an area of epithelial irregularity was foundin the same area of the superior cornea in which epithelial defects had beenpreviously. An underlying moderate DLK was present in the superior flap interface.Treatment with 1% prednisolone acetate was used every 2 hours initially, witha rapid tapering course. The patient responded well to therapy, and the BSCVAis 20/25 OS.

A 54-year-old woman underwent bilateral sequential LASIK in September2001 for moderate myopia. Because the left eye sustained an intraoperativeepithelial defect in the inferotemporal paracentral location, a bandage softcontact lens was placed on the eye, and the patient was instructed to useboth 0.1% fluorometholone and 0.3% ofloxacin eyedrops, 4 times daily. Thenext day, UCVA was 20/80 OS. Although there was still a 2.0 × 2.0-mmepithelial defect present, no interface inflammation was noted. The defectwas healed by the third postoperative day with a UCVA of 20/20 OS.

Two and a half months later, the patient was seen with a 2-day historyof redness, photophobia, and foreign body sensation in the left eye. The UCVAwas still 20/20 OS, but a 2.0 × 2.5-mm epithelial defect was found inthe same location as previously noted intraoperatively, and moderately severeDLK was found in the interface (Figure 1).A bandage soft contact lens was placed on the eye, and the patient was instructedto use both 1% prednisolone acetate and 0.3% ofloxacin eyedrops, 4 times daily.Clinical improvement was then noted after 2 days, and the frequency of instillationof the corticosteroid eyedrops was tapered. The UCVA remained at 20/20 OS.

Sixteen months post-LASIK, the patient returned with a second episodeof redness, foreign body sensation, and irritation in the left eye. The UCVAwas 20/25 OS. Slitlamp examination revealed a 2.0 × 2.0-mm patch ofloose epithelium in the same location of the previous epithelial defects,but no interface inflammation was noted. A bandage soft contact lens was placed,and 0.3% ciprofloxacin eyedrops, 4 times daily, were prescribed. Three dayslater, although the epithelial defect was almost healed, moderately severeDLK was noted (Figure 2). Treatmentwith 1% prednisolone eye drops was used hourly with rapid resolution of theinflammation. The patient ultimately elected to proceed with anterior stromalmicropuncture in an attempt to treat the recurrent erosions that led to herepisodes of DLK. Five months after the micropuncture procedure was performed,the patient's UCVA remained at 20/20 OS, and she has not had any further episodesof DLK.

A 34-year-old man was referred for recurrent corneal erosions in theright eye following bilateral LASIK performed in February 2003. Accordingto the patient, the right eye developed an epithelial defect intraoperatively,for which a bandage soft contact lens was placed for 1 day. No DLK was reportedin the immediate postoperative period. Although UCVA recovered to 20/20 −1 OU, the 6-month period following the LASIK procedure was punctuated with3 episodes of recurrent erosion, all documented to have occurred in the sameinferior paracentral area of the right cornea. Each episode was treated withlubrication and topical antibiotic eyedrops, but not with topical corticosteroids.The patient was referred to our institution during the third episode of recurrenterosion, 4 days after onset of symptoms of blurred vision and irritation ofthe right eye.

On ophthalmic examination, the UCVA was 20/40 OD and BSCVA was 20/30OD. In the right eye, a 1.5-mm patch of irregular epithelium was noted inthe inferior paracentral cornea, surrounded by a 3-mm area of flap edema,flap haze, and mild interface inflammation with leukocyte clumping. The patientwas diagnosed as having recurrent corneal erosion associated with DLK, thelatter of which was probably in the early-resolution phase. The right eyewas treated with nonpreserved artificial tears and 1% prednisolone every 4hours. One week later, UCVA and BSCVA had improved to 20/20 − 1 OD.The area of previously noted epithelial irregularity was smooth, but in itsplace were a few intraepithelial cysts, which had an appearance consistentwith anterior basement membrane dystrophy. Despite complete resolution ofthe flap edema and DLK, a mild haze persisted within the flap and the LASIKinterface.

While most cases of DLK occur within the first postoperative week, anincreasing number of cases have been reported to occur months after surgery.Most of these late cases of DLK follow an event that resulted in disruptionof the corneal epithelium.^1-3 Thisassociation of late DLK with epithelial defects implies the release of inflammatorystimulants from a site other than the interface itself. In these late-onsetcases of DLK, cytokines and inflammatory mediators released by the injuredepithelium may contribute to the development of DLK through keratocyte injuryand chemotaxis of polymorphonuclear cells.⁴ Thesecytokines can also be released during flap formation, causing early-onsetDLK.⁵ Thus, irritants intrinsic to the patientas opposed to exogenous substances introduced by surgery may be the causeof some cases of early-onset DLK.⁶

Intraoperative epithelial defects have been associated with 38.9% ofthe early-onset DLK cases in 1 series.⁷ Chang-Godinichet al³ described a woman who had recurrenterosions who suffered DLK associated with an intraoperative epithelial defect,and who then had a second episode of DLK in the same eye 2 months postoperatively.Our first patient also had recurrent erosions and DLK associated with an intraoperativeepithelial defect, but our case was unique because she developed 2 separateepisodes of late-onset erosion-associated DLK. Our second and third patientsalso developed separate episodes of late-onset erosion-associated DLK, butwithout the initial episode of early-onset DLK despite the initial intraoperativeepithelial defect. The fellow eye of the woman described by Chang-Godinichet al³ also had an intraoperative epithelialdefect without DLK followed by late-onset DLK associated with an epithelialerosion. To our knowledge, no other such cases have been reported. This findingsuggests that intraoperative epithelial defects may be associated with late-onseterosion-associated DLK even in the absence of perioperative DLK.

Based on our article, it appears that recurrent DLK can occur not onlyin patients with overt preoperative evidence of anterior basement membranedystrophy or in patients with a known history of recurrent erosion, as describedpreviously, but also in asymptomatic patients who develop an intraoperativeepithelial defect attributable to a suspected underlying subclinical anteriorbasement membrane dystrophy. Furthermore, these recurrent episodes of DLKcan occur many months following the primary LASIK or re-treatment procedure,even when no DLK was documented during the initial perioperative period. Giventhat intraoperative epithelial defects occur in approximately 3% to 9.7% ofLASIK cases,^7,8 the numberof patients at risk for late-onset erosion-associated DLK could be high. Thus,consideration should be given to advising potentially at-risk patients whohave undergone LASIK (eg, patients with intraoperative epithelial defects)of the need to seek consultation from an ophthalmologist should symptoms ofrecurrent erosion occur. Treatment in such circumstances should not only addressthe recurrent erosion, but also should include the use of topical corticosteroidsto prevent or treat associated DLK. Furthermore, primary eye care providersand emergency physicians should also become familiar with this potential complication.This subgroup of post-LASIK patients may initially have signs and symptomsof acute erosion and DLK-related inflammation that can readily be mistakenfor a case of corneal abrasion or infectious keratitis. The clinical presentationof diffuse interface inflammation in the setting of mild epithelial disruptionmay be particularly confusing if a prior history of LASIK is not elicited.In patients 1 and 2, prompt and appropriate treatment of each episode of recurrentDLK with frequent administration of topical corticosteroids resulted in goodoutcomes, with no adverse effects on final visual acuity. However, DLK thatis severe or that is not treated aggressively, as in patient 3, may resultin a poorer outcome due to complications such as stromal haze, scarring, epithelialingrowth, and irregular astigmatism.

The authors have no relevant financial interest in this article.

This study was supported in part by the Heed Ophthalmic Foundation Fellowship,Cleveland (Dr Jeng) and unrestricted grants from Research to Prevent Blindness,New York, NY, and That Man May See, Inc, San Francisco (Drs McLeod and Hwang).

Corresponding author: David G. Hwang, MD, Cornea and Refractive SurgeryService, Department of Ophthalmology, 10 Kirkham St, Room K-301, Universityof California, San Francisco, San Francisco, CA 94143-0730 (e-mail: dghwang@itsa.ucsf.edu)