Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus: A 5-Year Longitudinal Study.

IMPORTANCE: It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross-linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. OBJECTIVE: To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. EXPOSURE: The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3 mW/cm2 irradiance. MAIN OUTCOMES AND MEASURES: Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. RESULTS: Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) µm (range, 372-497 µm). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm2 in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm2 in the corneas of patients with stage 1 or 2 keratoconus was reduced 51% (mean difference, 10.7 mm/mm2 [95% CI, 6.8-14.6 mm/mm2]; P < .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm2 [95% CI, 4.7-12.4 mm/mm2]; P < .001) despite recovery of touch sensitivity to normal levels by 6 months. Preoperatively, more frequent nerve loops, crossings, and greater crossing angles were observed in the corneas of patients with keratoconus compared with healthy corneas. Postoperatively, the frequency of nerve looping increased, crossings were more frequent, and nerve tortuosity increased. Wide-field mosaics indicated persistent disrupted orientation of the regenerating subbasal nerves 5 years after CXL. CONCLUSIONS AND RELEVANCE: Keratoconus is characterized by a neurotrophic deficit and altered nerve morphology that CXL treatment does not address, despite providing a positive biomechanical effect in the stroma. Given the widespread use of CXL in the management of patients with keratoconus, the progression of abnormal innervation after CXL should be recognized.

Injury situations in Freestyle Ski Cross (SX): a video analysis of 33 cases.

BACKGROUND: Although injury risk in Freestyle Ski Cross (SX) is high, little is known about the situations leading up to time-loss injuries. OBJECTIVE: To describe the situations leading up to time-loss injuries in elite Freestyle SX. STUDY DESIGN: Descriptive video analysis. METHODS: Thirty-three video recordings of SX injuries reported through the International Ski Federation Injury Surveillance System for four World Cup seasons (2006/2007 through 2010) were obtained. Five experts in the fields of sport medicine and SX analysed each case to describe in detail the situation leading up to the injury (skiing situation and skier behaviour). RESULTS: Injuries occurred in four different skiing situations: jumping (n=16), turning (n=8), jumping and turning (n=7) and rollers (n=2). All injured skiers lost control before time of injury (n=33), due to skier-opponent contact (n=13), technical errors (n=8) or inappropriate strategy (n=8), which led to a fall (n=29). Contact occurred in 21 of 33 cases, usually unintentional at landing or take-off, caused by the opponent (n=11) or injured skier (n=8). The technical error cases (n=8) were dominated by bad jumping technique (n=6) and too much inside lean in turning situations (n=2), while inappropriate course line and bad timing at take off (n=7) dominated the inappropriate strategy cases (n=8). CONCLUSIONS: We identified four main injury situations in elite SX, dominated by jumping situations. The primary cause of injury was unintentional skier-opponent contact in jumping, bank turning and roller situations. Another common cause of injury was personal errors (inappropriate technique and strategy) at take-off and in turning situations.

Standardized baseline human corneal subbasal nerve density for clinical investigations with laser-scanning in vivo confocal microscopy.

PURPOSE: We established a baseline value for central corneal subbasal nerve density in a large, healthy cohort. METHODS: A total of 106 healthy volunteers (207 eyes) underwent full ophthalmic examination, including laser-scanning in vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve tracing was performed by two human observers and by a fully automated method. Subbasal nerve density was stratified by eye, observer, tracing method, calculation method, and age group. Association of nerve density with age was examined by linear regression and population distribution was examined by nonlinear regression. RESULTS: We analyzed 892 distinct, high quality images of the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean central subbasal nerve density of 19 mm/mm(2) was found in 106 subjects aged 15 to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a consistent 4 to 5 mm/mm(2). Subbasal nerve density followed a normal Gaussian distribution, and correlated negatively with age, with a mean decline of 0.25% to 0.30% per year, independent of eye, observer, or nerve tracing method. Moreover, the use of automated tracing techniques and randomized sampling may improve the speed and reproducibility of subbasal nerve density assessment for clinical applications. CONCLUSIONS: A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations.