March 2021

ASCRS NEWS

ASCRS/EyeWorld Journal Club
Review of “Diffuse lamellar keratitis after LASIK with low-energy femtosecond laser”


by Nhon Le, MD, Margaret Wang, MD, Rohini Sigireddi, MD, Zaina Al-Mohtaseb, MD, and Mitchell Weikert, MD


Mitchell Weikert, MD
Residency Program Director
Cullen Eye Institute
Baylor College of Medicine
Houston, Texas


Nhon Le, MD
Resident
Cullen Eye Institute
Baylor College of Medicine
Houston, Texas

Cullen Eye Institute residents; top, from left: Rohini Sigireddi, MD, Nhon Le, MD; bottom: Margaret Wang, MD
Source: Cullen Eye Institute

Laser-assisted in situ keratomileusis (LASIK) is a refractive procedure involving the creation of a thin corneal flap with a microkeratome or femtosecond laser followed by excimer laser ablation to reshape the cornea. While LASIK is a low-risk procedure, diffuse lamellar keratitis (DLK)—a potentially devastating complication—can occur. DLK is a non-infectious, inflammatory response characterized by fine, white, inflammatory infiltrates beneath the corneal flap.1 The incidence of DLK after microkeratome and femtosecond LASIK is estimated to be between 0.4–7.7% and 0.4–37.5%, respectively.1–7 The mechanism of DLK is not fully understood but has been ascribed to debris from surgical instruments, bacterial endotoxins, meibomian gland secretions, powder from surgical gloves, marking pens, surgical drapes, iatrogenic epithelial defects, and femtosecond laser energy.8–14 In this large retrospective, noncomparative case series, Leccisotti and Fields evaluated the incidence, clinical course, and prognosis of DLK in patients undergoing low-energy femtosecond LASIK in combination with sterile techniques to limit interface contamination. Our review will summarize the study’s results, highlight its contributions to the literature of DLK in low-energy femtosecond LASIK, and discuss its limitations.

Design and methods

This study reviewed LASIK data of 37,315 eyes from 19,602 patients treated by one surgeon at a practice in Italy from 2012–2019. Inclusion criteria involved patients between the ages of 20–60 years with best preoperative vision >20/32 and cycloplegic spherical equivalents between –10.0 and +6.5 D. Exclusion criteria included any systemic collagen disease, diabetes, previous ocular disease or surgeries affecting central vision, and topical intraocular pressure treatment. Patients underwent preoperative evaluation including comprehensive eye examination with manifest and cycloplegic refraction, pachymetry, Placido topography, Scheimpflug tomography, and anterior segment optical coherence tomography (AS-OCT). The surgeon used the low-energy LDV femtosecond laser (Ziemer) for LASIK flap creation in combination with techniques to control interface
contamination, including single-use instruments, powderless gloves, and the avoidance of corneal marking. The Technolas 217P or Technolas 317 Teneo excimer laser (Bausch + Lomb) was used for the refractive ablation. Postoperatively, patients were followed for at least 6 months. Standard DLK grading, first described by Linebarger, was used.15

Summary of results

Incidence

Of the 37,315 eyes (of 19,602 patients), DLK was observed in 236 eyes (0.63%) in 149 patients (0.76%). Grade 1 DLK occurred in 231 eyes (0.62%). Grade 2 DLK occurred in one eye of a single patient. Grade 3 DLK was observed in both eyes of one patient (patient 1) and one eye of another patient (patient 2). Grade 4 DLK was seen in a total of five eyes of three patients (patient 1, bilateral grade 3 DLK that progressed to bilateral grade 4 disease; patient 2, right eye; patient 3, both eyes). Among the 1,889 patients who underwent unilateral LASIK, DLK was observed in 12 (0.63%) patients. Among the 17,713 patients who underwent bilateral LASIK, DLK was observed in 137 (0.77%) patients. Grade 2–4 DLK was only seen in patients who underwent bilateral LASIK. The mean age of patients diagnosed with grade 2–4 DLK was 47 years, 9.48 years greater than the mean age of eyes without DLK. DLK outbreaks were not observed. 

Clinical course

Grade 1 and 2 DLK: All patients with grade 1 and 2 DLK fully recovered and retained uncorrected distance visual acuity (UDVA) >20/20 after treatment with dexamethasone 0.1% topical solution every 2 hours while awake for 5 days. 
Grade 3 and 4 DLK: Patient 1 had bilateral grade 3 DLK that progressed to bilateral grade 4 DLK despite flap lifting and irrigation. At 2 years postoperatively, the corrected distance visual acuity (CDVA) was 20/20 and 20/25 with a hyperopic shift in both eyes. The patient underwent repeat femtosecond LASIK with creation of a new flap in the left eye without complications and had a CDVA of 20/25 (–0.25 x 95). 
Patient 2 had grade 4 DLK in the right eye and grade 3 in the left eye but did not undergo flap lifting and irrigation due to a delayed presentation. After treatment with the steroid regimen described above, the patient recovered to a CDVA of 20/40 with a hyperopic shift in the right eye and a UDVA of 20/20 in the left eye.
Patient 3 was initially thought to have bilateral bacterial conjunctivitis but was later diagnosed with bilateral grade 4 DLK. Given the concern for possible bacterial conjunctivitis, flap lifting and irrigation were not performed. This patient was treated with netilmicin 0.3% and dexamethasone 0.1% four times daily for 5 days (followed by a taper over 2 weeks). At 12 months postoperatively, the CDVA was 20/25 and 20/32 with a hyperopic shift in both eyes. 
In all cases of grade 4 DLK, stromal thinning and reabsorption was seen at 1 month, followed by partial recovery from 3 months to 2 years. OCT measurements of central corneal epithelial thickness, which were available in three eyes (patient 2 and 3), showed a significant compensatory increase at 12 months. However, no patients made a full-thickness recovery.

Analysis

While previous studies involving femtosecond LASIK showed DLK incidence rates as high as 37.5% with higher energy settings, Leccisotti and Fields demonstrated that low-energy femtosecond settings in combination with techniques to reduce interface contaminants resulted in a low incidence of DLK (0.63% of eyes).7 Their study reported that all patients with grade 1 and 2 DLK recovered without sequelae. Epithelial changes throughout the course of grade 4 DLK were previously not well described in the literature. Leccisotti and Fields illustrated that thinning and opacification of the cornea in patients with grade 4 DLK peaked at 1 month postoperatively and slowly recovered within 2 years, although no patients attained a full-thickness recovery. In the single patient who underwent flap lift and irrigation for bilateral grade 3 DLK, treatment was unable to prevent progression to grade 4 DLK. Further, this manuscript presented the first published case, known to Leccisotti and Fields, of repeat femtosecond LASIK for hyperopic shift in a patient with grade 4 DLK, who ultimately had a satisfactory outcome after the retreatment.
The authors demonstrated that low-energy femtosecond laser, single-use instruments, powderless gloves, and the avoidance of corneal markings can result in a low incidence of DLK. However, given the noncomparative nature of the study, the effect each factor had in reducing the incidence of DLK is unknown. Identifying the contribution of each factor on the rate of DLK is important in enabling providers to identify and adopt practice patterns with the most benefit to patient outcomes. Further, a comparison of the authors’ DLK rates prior to and after their adoption of low-energy femtosecond laser LASIK would better elucidate the effect that their technique had in reducing the risk of DLK. Future prospective, randomized controlled trials may help adjudicate the effects low-energy femtosecond laser settings and sterile techniques to reduce interface contamination each have on the incidence of DLK.

The ASCRS Journal Club is a virtual, complimentary CME offering exclusive to ASCRS members that brings the experience of a lively discussion of two current articles from the Journal of Cataract & Refractive Surgery to the viewer. Co-moderated by Nick
Mamalis, MD, and Leela Raju, MD, the February session featured a presentation by Haripriya Aravind, MS, lead author of “Comparison of surgical repositioning rates and outcomes for hydrophilic vs. hydrophobic single piece acrylic toric IOLs.” The second manuscript, “Diffuse lamellar keratitis after LASIK with low-energy femtosecond laser,” was presented by Nhon Le, MD, resident, Cullen Eye Institute, Baylor College of Medicine. To view the February Journal Club session, visit: https://ascrs.org/clinical-education/journal-club/schedule/february-2021.


References

1. Stulting RD, et al. The epidemiology of diffuse lamellar keratitis. Cornea. 2004;23:680–688.
2. McLeod SD, et al. Bilateral diffuse lamellar keratitis following bilateral simultaneous versus sequential laser in situ keratomileusis. Br J Ophthalmol. 2003;87:1086–1087.
3. Gil-Cazorla R, et al. Incidence of diffuse lamellar keratitis after laser in situ keratomileusis associated with the IntraLase 15 kHz femtosecond laser and Moria M2 microkeratome. J Cataract Refract Surg. 2008;34:28–31.
4. Johnson JD, et al. Diffuse lamellar keratitis: incidence, associations, outcomes, and a new classification system. J Cataract Refract Surg. 2001;27:1560–1566.
5. Haft P, et al. Complications of LASIK flaps made by the IntraLase 15- and 30-kHz femtosecond lasers. J Refract Surg. 2009;25:979–984.
6. Javaloy J, et al. Confocal microscopy comparison of IntraLase femtosecond laser and Moria M2 microkeratome in LASIK. J Refract Surg. 2007;23:178–187.
7. Tomita M, et al. Comparison of DLK incidence after laser in situ keratomileusis associated with two femtosecond lasers: Femto LDV and IntraLase FS60. Clin Ophthalmol. 2013;7:1365–1371.
8. Moyer PD, et al. Interface keratitis after LASIK may be caused by microkeratome lubricant deposits. Invest Ophthalmol Vis Sci. ARVO abstract 3454.
9. Holland SP, et al. Diffuse lamellar keratitis related to endotoxins released from sterilizer reservoir biofilms. Ophthalmology. 2007;107:1227–1233.
10. Fogla R, et al. Diffuse lamellar keratitis: are meibomian secretions responsible? J Cataract Refract Surg. 2001;27:493–495.
11. Kaufman SC, et al. Interface inflammation after laser in situ keratomileusis. Sands of the Sahara syndrome. J Cataract Refract Surg. 1998;24:1589–1593.
12. Cosar CB, et al. The efficacy of hourly prophylactic steroids in diffuse lamellar keratitis epidemic. Ophthalmologica. 2004;218:318–322.
13. Moilanen JA, et al. Keratocyte activation and inflammation in diffuse lamellar keratitis after formation of an epithelial defect. J Cataract Refract Surg. 2004;30:341–349.
14. Choe CH, et al. Incidence of diffuse lamellar keratitis after LASIK with 15 KHz, 30 KHz and 60 KHz femtosecond laser flap creation. J Cataract Refract Surg. 2010;36:1912–1918.
15. Linebarger EJ, et al. Diffuse lamellar keratitis: diagnosis and management. J Cataract Refract Surg. 2000;26:1072–1077.

Contact

Le: nhon.le@bcm.edu
Weikert: mweikert@bcm.edu
 

Diffuse lamellar keratitis after LASIK with low-energy femtosecond laser

Antonio Leccisotti, MD, PhD, Stefania Fields, AO, MSc
J Cataract Refract Surg. 2021;47(2):233–237.

Purpose: To evaluate the incidence, evolution and prognosis of diffuse lamellar keratitis (DLK) in a large series of laser-assisted in situ keratomileusis (LASIK) with low-energy femtosecond laser.
Setting: Private practice, Siena, Italy
Design: Retrospective, consecutive, non-comparative case series study.
Methods: Single-use instruments, powder-free gloves and no corneal marking were used. Flap was created by a low-energy femtosecond laser (Ziemer Z2 and Z4).
Results: A total of 37,315 eyes of 19,602 patients were reviewed. DLK was observed in 236 eyes (0.63%) of 149 patients (0.76%). Grade 1 DLK was observed in 231 eyes of 142 patients, grade 2 in 1 eye: treated with topical steroids, they had no visual consequences. Three patients had bilateral grade 3–4 DLK: one of them, with bilateral grade 3, despite flap lifting and irrigation worsened to stage 4 (central stroma thinning and flattening), partially recovered in 2 years and underwent repeat femtosecond LASIK for hyperopic shift in one eye. In all the 5 eyes developing grade 4 DLK, corneal thickness decreased until the first month, then partially recovered; mean final tissue loss at 1–2 years was 35 µm. Compensatory epithelial thickening was observed.
Conclusion: DLK after low-energy femtosecond LASIK is rare; severe DLK (stages 3 and 4) was only found in 6 eyes (0.016%). Flap lifting and irrigation may not prevent progression. Spontaneous reformation of stromal tissue and epithelial thickening improve visual acuity in the long term; residual hyperopic shift can be corrected by repeat femtosecond LASIK.

Review of “Diffuse lamellar keratitis after LASIK with low-energy femtosecond laser” Review of “Diffuse lamellar keratitis after LASIK with low-energy femtosecond laser”
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