Diffuse lamellar keratitis in a patient undergoing collagen corneal crosslinking 18 years after LASIK surgery.

Abstract

Purpose:

To report a case of diffuse lamellar keratitis (DLK) following corneal collagen crosslinking in an eye with a remote history of LASIK surgery.

Methods:

Case report and literature review.

Results:

This report describes the development of unilateral stage IV DLK in a patient who underwent bilateral corneal crosslinking for corneal ectasia 18 years after laser in situ keratomileusis (LASIK) surgery. The patient was treated with high dose topical steroids that were tapered over one month and multiple flap lifts. The ultimate best-corrected visual outcome was 20/60.

Conclusions:

Diffuse lamellar keratitis (DLK) is a potential sight-threatening complication of refractive surgery that can occur at any time in the postoperative period, even years after the procedure. Undergoing a subsequent corneal procedure that may disrupt or promote inflammation within the surgical flap-stromal interface, such as corneal collagen crosslinking, is a recognized risk factor for the development of DLK. This case suggests that patients with any history of LASIK surgery undergoing corneal crosslinking or other lamellar corneal surgeries may benefit from closer follow up (e.g., daily) than patients with no history of LASIK.

Introduction:

Progressive thinning of the corneal stroma, a process known as corneal ectasia, can lead to astigmatism and decreased vision. Laser in situ keratomileusis (LASIK) is a well-recognized risk factor for the development of ectasia, though the incidence of post-LASIK ectasia has been decreasing over the years perhaps owing to improved risk assessment prior to LASIK and advances in LASIK technology, especially in relation to flap creation^1,2. Interestingly, the development of post-LASIK ectasia can occur at seemingly any time following surgery, from weeks to years after the procedure^3,4. Corneal collagen crosslinking is a procedure commonly used to halt the progression of corneal ectasia, including post-LASIK ectasia^5,6. Recognized complications of corneal crosslinking procedure include the development of corneal haze, infection, and scarring⁷.

Diffuse lamellar keratitis (DLK), a disorder in which inflammatory cells infiltrate the interface of the flap and stromal bed, is another potential complication of LASIK and other lamellar corneal surgeries that involve flap creation^8,9. DLK typically occurs within the first week of LASIK, but can also arise years later idiopathically or after subsequent corneal procedures^9,10. Severity of the disorder ranges from minor inflammation to sight-threatening corneal melting, scarring, and astigmatism⁹. Risk factors for the development of DLK include surgical epithelial defects, epithelial sloughing, retained blood in the flap-stroma interface, and iatrogenic exposure of the cornea to irritative substances⁹. In this report, we present a case of a patient who developed DLK with overlying flap melting after undergoing corneal collagen crosslinking for corneal ectasia 18 years after initial LASIK surgery.

Case report:

A 53-year-old female presented at the request of her primary care optometrist for evaluation of decreasing vision in both eyes over the preceding 6 months. She had a history of LASIK for high myopia 18 years prior and had been in scleral contact lenses for 4 years. Best-corrected visual acuity in scleral contact lenses was 20/40 in the right eye and 20/30+2 in the left eye. Examination revealed healthy tear film and ocular surface. Both corneas were steep inferiorly with clear LASIK flap without evidence of striae or apical scarring. The lenses of both eyes demonstrated 2+ nuclear sclerotic cataracts and both retinal exams were unremarkable to exam. Additional testing included Pentacam tomography, shown in Figure 1, which confirmed the presence of posterior corneal elevation, central thinning, and irregular astigmatism secondary to corneal ectasia in both eyes. Upon discussion, the patient elected to pursue corneal collagen crosslinking in both eyes.

Figure 1:

Pentacam tomography of the right eye at presentation demonstrating irregular astigmatism with inferior steepening and posterior surface elevation consistent with ectasia.

The patient underwent uneventful corneal collagen crosslinking in the left eye using the Dresden protocol as previously described⁵. Briefly, the corneal epithelium was removed using dehydrated alcohol solution and gentle debridement with a 64 blade to a diameter of 9 mm centered on the pupil. Extreme care was taken not to disrupt the flap edge during debridement. One drop of Photrexa Viscous was given every 2 minutes for 30 minutes and pachymetry was confirmed to be above 400 μm. Irradiation was performed at 3 mW/cm² for 30 minutes (dose 5.4 J/cm²), and a bandage contact lens was placed. A drop of prednisolone and moxifloxacin were given and prescribed to be used QID for first postoperative week and BID for the second postoperative week. As per our routine protocol, a collagen plug was placed in the lower punctum to reduce corneal dryness in order to facilitate rapid epithelial healing. The patient was noted to recover uneventfully, with full epithelial closure on postoperative day 4. By month 6, K_max had remained stable and topography demonstrated a reduction in astigmatism by 1.3D.

Following successful crosslinking of the left eye, the patient then underwent the same procedure on the right eye. There were no abnormal events noted during the course of the procedure. The patient reported to routine follow up on day 4 with a complaint of mild light sensitivity. Uncorrected distance vision was 20/200 with pinhole acuity improving to 20/50. The bandage contact lens was in place overlying an epithelial defect with diffuse inflammatory cellular infiltrate noted in the flap interface (Figure 2). The inflammation extended into the stroma of the overlying flap as seen on anterior segment OCT (Figure 3). Differential diagnosis of the interface inflammation included stage IV diffuse lamellar keratitis and infectious keratitis, and the flap was lifted for irrigation and culture that day. Prednisolone was increased to hourly dosing while awake, and moxifloxacin was continued at QID. Cultures returned negative for bacteria and fungi and the patient improved on a 1-month topical steroid taper. An additional flap lift, clean, and suture was performed at the one month post-operative visit due to epithelial ingrowth, but the patient ultimately did well with best-corrected distance vision 20/60 at postoperative month 8 (Figure 4).

Figure 2:

External photograph of the right eye four days after crosslinking showing diffuse cellular infiltrate within the flap interface.

Figure 3:

Anterior segment OCT of the right eye four days after crosslinking demonstrating hyperreflectivity within the interface and overlying stroma with epithelial defect.

Figure 4:

External photographs of the right eye eight months after crosslinking and treatment of DLK.

Discussion:

The case presented here illustrates the infrequently reported diffuse lamellar keratitis (DLK) as a complication of corneal-collagen crosslinking. While our case is similar to previously-reported cases of DLK after corneal crosslinking^11,12, there are a few important differences. First, the crosslinking procedure in the prior reports by Kymionis et al. and Mannschreck et al. was performed for ectasia at four and three years after LASIK, respectively, while ours was performed 18 years after initial flap procedure. Additionally, the case reported by Kymionis et al. does not appear to have followed the Dresden protocol described by Seiler and colleagues⁵, as only 6 mm diameter area of cornea was debrided instead of at least 7 mm, and the patient underwent a shorter treatment duration. The patient described in our report underwent crosslinking consistent with the Dresden protocol⁵. Common to all cases is the event of epithelial debridement, which may in fact be the precipitating event for the development of DLK.

One of the suggested pearls of management in these previous cases of DLK is that flap lift may compromise the effect of the crosslinking procedure¹¹. Both cases reported previously were managed with topical steroid therapy alone^{11, 12}. Interestingly, the patient reported by Mannschreck et al. did in fact experience continued progression of ectasia 4 months following crosslinking despite not being managed with a flap lift. In contrast, our patient presented with a much more advanced picture of stage IV DLK with overlying flap melt at time of diagnosis, and required emergent flap lift alongside medical management. The patient required an additional flap lift, clean, and suture for epithelial ingrowth after the initial flap lift, but yet did not experience any significant progression of ectasia. This report therefore suggests that the efficacy of corneal crosslinking can be maintained after multiple flap lifts at least out to 8 months. However, it should be noted that the patient lost 2 lines of best-corrected visual acuity in a scleral contact lens following the episode of DLK, likely owing to development of residual corneal haze following the associated flap melting that had occurred.

A typical follow-up protocol after corneal crosslinking requires the patient to return on postoperative day four for examination and contact lens removal. DLK in the patient described here may have been caught earlier if she had returned at earlier time points, such as postoperative day one. Daily follow up was utilized by Kymionis et al., who diagnosed DLK and began treatment for their patient on postoperative day two¹¹. In another report of DLK after crosslinking, it is unclear the time point at which it was diagnosed post-operatively¹². For this reason, it is our strong suggestion that all patients undergoing corneal collagen crosslinking for ectasia following LASIK should be seen on postoperative day one in order to ensure clear interface in addition to proper fitting of contact lens and management of patient expectations.

While DLK most commonly occurs within a week following refractive surgery, it can also occur after many years^13–15, and subsequent corneal surgery seems to be a significant risk factor for developing late-onset DLK after LASIK¹⁶. Corneal crosslinking may be an especially important risk factor for developing LASIK-associated DLK, and it may be seen with increasing frequency as crosslinking in this setting becomes more commonplace. The patient described in this case report had a remote history of LASIK 18 years prior to her crosslinking procedure, suggesting that the risk of DLK in post-LASIK eyes persists for decades. Such a presentation is consistent with the understanding that DLK can be triggered at any time following lamellar corneal surgeries, as the potential space at the flap-stroma interface persists indefinitely and remains a potential site of an inflammation if subsequent epithelial trauma occurs⁹. Thus, epithelial removal seems to be the most likely inciting factor for the development of DLK in these cases. However, it is also possible that the crosslinking procedure itself could also promote the development of interface inflammation. This latter possibility is highlighted by the association between DLK and crosslinking seen in eyes undergoing LASIK with concurrent crosslinking¹⁷. Regardless, it may be prudent to have patients with any history of LASIK surgery who are undergoing corneal crosslinking to be monitored daily in the immediate postoperative period, as these patients are at high risk for flap interface inflammation.