April 2019


Research highlight
Unique SMILE complication
Sterile multifocal inflammatory keratitis

by Maxine Lipner EyeWorld Senior Contributing Writer

Slit lamp photos of sterile multifocal inflammatory keratitis, grades 1 to 4 (left to right)
Source: Dan Reinstein, MD


Concern over diffuse lamellar keratitis (DLK) isn’t limited to LASIK. Patients who have undergone SMILE may be vulnerable to a similar condition, according Dan Reinstein, MD. Investigators led by Dr. Reinstein conducted a retrospective review of 4,000 SMILE patients.1 They found that 0.45% of cases had DLK, with one-third of those presenting as a unique sterile multifocal inflammatory keratitis.

New syndrome emerges

Interest in this SMILE-related presentation was spurred by a case of a patient who presented with a few small focal infiltrates 1 day after uncomplicated SMILE surgery.2 “Before this case, we had seen a few cases of classic DLK after SMILE,” Dr. Reinstein said. “Because of the unique appearance in this particular case, infection was our leading differential diagnosis.” Frustratingly, every culture, scrape, and test came back negative for any infectious component. “It was a scary case, but fortunately everything resolved and the patient ended up seeing very well,” Dr. Reinstein said. Since all pathology came back clear, investigators were fairly confident that the multifocal infiltrate appearance was a sterile inflammatory reaction that was unique to SMILE.
One year later, investigators encountered a similar case. Again, this occurred on day 1 following SMILE surgery and involved the presentation of a few small focal infiltrates, which differed from the diffuse “sands of Sahara” appearance linked to cases of DLK after LASIK, Dr. Reinstein noted. “With the knowledge of how the first case went, we were more comfortable treating it as a sterile inflammatory response and covering with antibiotics,” he said. Each subsequent case with a similar appearance was treated using the same protocol.
The team, while analyzing data for their recently published SMILE textbook,1 which includes a retrospective review of all of their DLK cases after SMILE, put together a case series.3 The investigators found that DLK occurred in 18 out of 4,000 eyes. Of these 18 cases, six were described as sterile multifocal inflammatory keratitis. All six of the eyes were treated with topical steroids and ultimately resolved.

Comparison to DLK

In such SMILE cases, the major difference is in the appearance, as the name suggests, Dr. Reinstein explained. “Classic DLK in both LASIK and SMILE usually appears as a very fine, localized, or diffuse scattering of inflammatory cells,” he said. “In sterile multifocal inflammatory keratitis there are a number of isolated focal infiltrates that are not typical of interface inflammation seen after LASIK.” The small focal infiltrates may or may not be in conjunction with a background classic DLK.
Treatment protocol revolved primarily around quelling the inflammation with steroids. “The protocol, after learning from our first case, was to treat with aggressive topical steroids while covering with a broad-spectrum antibiotic,” Dr. Reinstein said, adding that this is similar to the standard treatment protocol for DLK after LASIK.
Investigators determined that at the 1-year mark all of the eyes had responded well, with no eyes losing any lines of corrected distance visual acuity, Dr. Reinstein reported. There was also no change in contrast sensitivity.
Investigators think that this does not arise from the same source as traditional DLK. “Our leading theory at the moment lies in how the interface differs between LASIK and SMILE,” Dr. Reinstein said. With SMILE, energy from the femtosecond laser causes microscopic divots in the stromal tissue when creating an interface; in LASIK, performing an excimer laser ablation essentially smooths the stromal bed. “In SMILE, no excimer laser is needed, so no additional smoothing takes place,” Dr. Reinstein said. “One idea may be that the inflammatory cells tend to clump into the divots rather than racing across a smooth ablated interface.”
When performing SMILE, Dr. Reinstein advises practitioners to keep the possibility of sterile multifocal inflammatory keratitis occurring postoperatively in mind. “Our take-home message is that these eyes must be followed very closely,” he said. Localized stromal melting may be more likely due to the focal nature of this condition. With this in mind, practitioners may want to perform an interface washout earlier than with the classic appearance of DLK, Dr. Reinstein recommended. In addition, these cases should be followed closely because it is important to rule out an infectious component if there is any doubt about the origin, he concluded.

About the doctor
Dan Reinstein, MD
London Vision Clinic
London, U.K.


1. Reinstein DZ, et al. The Surgeon’s Guide to SMILE: Small Incision Lenticule Extraction. SLACK Inc. 2018.
2. Stuart A, et al. Atypical presentation of diffuse lamellar keratitis after small-incision lenticule extraction: Sterile multifocal inflammatory keratitis. J Cataract Refract Surg. 2018;44:774–779.
3. Reinstein DZ, et al. Incidence and outcomes of sterile multifocal inflammatory keratitis and diffuse lamellar keratitis after SMILE. J Refract Surg. 2018;34:751–759.

Financial interests
: Carl Zeiss Meditec, ArcScan

Contact information
: dzr@londonvisionclinic.com

Unique SMILE complication Sterile multifocal inflammatory keratitis Unique SMILE complication Sterile multifocal inflammatory keratitis
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