title: [Assessment of postoperative pain after corneal collagen cross-linking by iontophoresis vs the rapid epithelium-off technique in progressive keratoconus patients].
abstract: BACKGROUND
  Cross-linking (CXL) increases corneal biomechanical strength in progressive keratoconus. Since riboflavin cannot penetrate intact corneal epithelium, removal of epithelium is necessary for the classic CXL procedure (epi-off), but can cause severe postoperative pain. To avoid this problem, a method preserving the epithelium (epi-on) is used. In this study, we aimed to evaluate and compare postoperative pain after epi-off CXL and epi-on CXL.
  
  
  METHODS
  We present a retrospective study assessing the level of pain postoperatively in 38 patients between the age of 12 and 53 years who underwent CXL procedures at the University Hospital of Clermont-Ferrand from July 2013 to May 2014. Epi-off consisted of manual corneal de-epithelialization and riboflavin instillation for 20minutes, followed by UVA exposure for 9minutes. The epi-on technique used an applicator on the eye, filled with riboflavin, and a generator delivered a continuous low-level current for 5minutes. The duration of light exposure was similar in both groups. Postoperative medications were the same for both techniques. Assessment of pain and analgesic intake were reported by the patient on paper questionnaires. Pain was evaluated from preoperatively up until the end of the month. Statistical analyses were performed in bilateral formulation to an alpha type I and error risk of 5%.
  
  
  RESULTS
  Twenty-three epi-off patients and 15 epi-on patients. Twenty-nine men and 9 women (76.3%/23.7%). Mean age: 28 years. Reference base time was the return from the operating room. In the epi-off group, pain increased significantly until the morning of D2 and did not return to its intraoperative level until noon D2, 1.8±2.0 vs 2.5±2.5 (P=0.12). Pain remained stable until the morning of D4. From noon D4 until D30, it was significantly less than intraoperatively 1.8±2.0 vs 0.7±1.4 (P=0.01). In the epi-on group, pain was significantly higher than intraoperatively until noon of D1 2.5±2.2 vs 3.8±2.5 (P=0.01). From the evening of D1, it returned to its intraoperative level until the evening of D2 2.5±2.2 vs 2±1.7 (P=0.34). From the morning of D3 it was significantly less than intraoperatively 2.5±2.2 vs 0.8±0.9 (P=0.001). Considering all measurement times, there was no significant difference between the two groups (P=0.75), except from evening of D2 until evening of D3 in favor of iontophoresis: 1.9±2.3 vs 1.0±1.3 (P=0.038).
  
  
  CONCLUSIONS
  Epi-on seems less painful in the short term (up to noon of D1 for epi-on vs morning of D2 for epi-off) and with a shorter duration than epi-off. This can be explained by the absence of corneal de-epithelialization. However, the reduction in pain is not significant at all postoperative times, and a risk of epithelial abrasion during placement and removal of the corneal applicator may exist.
  
  
  CONCLUSIONS
  Iontophoresis maintains the corneal epithelium, decreases pain and improves patient comfort. A new study involving more patients and strict monitoring of medication intake would strengthen the validity of these results.
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France. Electronic address: caromaurin@hotmail.fr.
authors.forename: C
authors.initials: C
authors.lastname: Maurin
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: Daniel
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Bonnin
authors.affiliation: Délégation recherche clinique et innovation, CHU de Clermont-Ferrand, Villa annexe IFSI, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: B
authors.initials: B
authors.lastname: Pereira
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Monneyron
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Peltier
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Monier
authors.affiliation: Service d'ophtalmologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Chiambaretta
mesh_terms: D000328:Adult; D000700:Analgesics / Q000627:therapeutic use; D003094:Collagen; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000627:therapeutic use*; D019573:Epithelium, Corneal / Q000601:surgery; D005260:Female; D006801:Humans; D007322:Instillation, Drug; D007478:Iontophoresis; D007640:Keratoconus / Q000188:drug therapy*; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D012189:Retrospective Studies; D012256:Riboflavin / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000700:Analgesics; D003432:Cross-Linking Reagents; D003094:Collagen; D012256:Riboflavin
keywords: Corneal collagen cross-linking; Cross-linking du collagène cornéen; Douleur; Iontophoresis; Iontophorèse; Keratoconus; Kératocône; Pain