Retrospective Analysis of Sterile Corneal Infiltrates in Patients with Keratoconus after Cross-Linking Procedure

Abstract

Background: This paper's objective is to analyze patients with keratoconus who developed sterile infiltrate after corneal collagen cross-linking (CXL), and to evaluate possible risk factors for their occurrence.

Methods: 543 medical histories of patients after cross-linking (Epi-off, Epi-on) procedure performed according to the Dresden protocol were analyzed retrospectively.

Results: Sterile corneal infiltrates occurred in four men (0.7%) in the age range (16-28) years, the average age being 20.3. The average time from procedure to onset of symptoms was 3.5 days (2-5 days). Inflammatory infiltration resolved in all patients, leaving scars on corneal stroma in two patients. Corneal healing time ranged from 4-12 weeks. In vivo confocal microscopy (IVCM), round inflammatory cells, and Langerhans cells in the epithelium and Bowman's layer were observed at the site of infiltration. The Optical coherence tomography (OCT) shows hyperreflective lesions of various sizes which decreased over time. The corneal topographic parameters and Best-corrected visual acuity (BCVA) improved after the CXL procedure in all of the described cases.

Conclusions: Most likely, damage to the epithelium and the phototoxic effect of the procedure is of significant importance in the formation of sterile corneal infiltrates. Appropriate classification and selection of CXL procedures in combination with protective measures in people at risk may have an overwhelming impact on the incidence of this complication.

Keywords: cross-linking; keratoconus; sterile corneal infiltrate.

Figure 1

Slit-lamp postoperative images showing sterile keratitis seven days after the CXL procedure due to progressive keratoconus. (a) a 16-year-old male patient with paracentral corneal infiltrate and conjunctival hyperemia. (b) a 17-year-old male patient with paracentral corneal infiltrate.

Figure 2

Slit-lamp postoperative images showing sterile keratitis seven days after CXL procedure due to progressive keratoconus. (a) a 28-year-old male patient with paracentral corneal infiltrate and significant conjunctival injection. (b) a 20-year-old male patient with paracentral corneal infiltrate.

Figure 3

Slit-lamp postoperative images showing corneal fluorescein staining seven days after the CXL procedure due to progressive keratoconus. (a) a 20-year-old male patient with paracentral sterile corneal infiltrate not staining with fluorescein (b) a 16-year-old male patient with paracentral corneal infiltrate not staining with fluorescein, who additionally experienced corneal epithelialization in the form of erosion of fluorescein-staining cornea.

Figure 4

Images of confocal microscopy of patients with sterile corneal infiltrate after cross-linking procedure. (A) In deep layers of the epithelium, numerous LG cells of varied maturity (circle) are visible. (B) Single inflammatory cells (circle) visible in the layer of Bowman’s membrane with reduced SNP plexus. (C) Site of ulceration with stimulated keratocytes forming a characteristic honeycomblike network. (D) Hyperreflective tissue surrounding keratocytes corresponding to fibrosis.

Figure 5

Images of confocal microscopy of patients with sterile corneal infiltrate after cross-linking procedure. (A) Stimulated epithelial cells with visible cell nuclei. (B) In the layer of epithelial cells, there are round inflammatory cells (circle), single Langerhans cells and hyperreflective apoptotic epithelial cells (larger than the inflammatory cells-arrow). (C) In deep layers of the epithelium and Bowman’s layer, there are numerous Langerhans cells with protrusions (arrow). (D) Oblique scan-from bottom, a layer of stimulated epithelium through the Bowman’s layer with LG cells, hyperreflective fibrous tissue visible in anterior stroma (from top).

Figure 6

Images of confocal microscopy of patients with sterile corneal infiltrate after cross-linking procedure. Residual form of keratitis (A,B) with hyperreflective tissue corresponding to scar tissue, irregularly structured epithelial cells with impacted apoptotic hyperreflective cells (circle). (C) Corneal stroma layer with hyperreflective structures corresponding to fibrosis and normal keratocyte nuclei.

Figure 7

Images created by the use of optical computed tomography of the anterior segment of the eye of a 20-year-old male patient with peripheral corneal infiltrate after the CXL procedure. (a) Hyperreflective corneal infiltrate seven days after the procedure, 1.83 mm deep and 1.392 mm wide. (b) Hyperreflective residual scar in the corneal stroma six months after the procedure, 0.092 mm deep and 1.323 mm wide.

Figure 8

Image from a slit lamp of the right eye of a 20-year-old male patient, seven days after CXL procedure, for whom preoperative preventive measures were applied due to previous sterile corneal inflammation in left eye. Epithelial cornea, no signs of inflammation.