Purpose. To produce a two-dimensional reconstruction map of the living human sub-basal corneal nerve plexus using in vivo confocal microscopy.

To investigate and correlate the corneal, refractive, topographic and familial characteristics of a large cohort with keratoconus. Prospective observational study of 200 consecutive patients presenting with keratoconus during the 4 year-period 1997–2000. Subjects were examined at enrolment and at a final review. Data were collected on demographic characteristics, referral route, symptoms, refractive correction, eye rubbing, family history, medical history, slit-lamp biomicroscopic corneal signs, and computerized corneal topography. Mean age at enrolment was 30.9±10.4 (range, 12.2–72) years (N=200, 62.5% male, 93% white Caucasian) with a 5% family history of keratoconus. Atopic diseases included asthma (23%), eczema (14%), and hay fever (30%). Only 9% wore contact lenses before referral. Mean follow-up was 1004 days ±282 (range, 390–1335) and 9.7±8.9 (range, 1.1–60) years from diagnosis. The mean simulated K1 corneal power at enrolment was 51.74±5.36 (range, 42.59–67.32) D and 88.5% exhibited bilateral keratoconus. Fifty-three (15%) topographically confirmed cones exhibited no clinical corneal signs at presentation. At enrollment, 56% had a pachymetry <0.480 mm increasing to 77% at final review. Forty-eight percent of subjects reported significant eye rubbing and there was a highly statistically significant difference (two sample t-test P=0.018) between keratoconus and control groups. TMS-2 axial corneal power was strongly associated with corneal scarring and age at diagnosis. The size of the scarring effect was 2.2 D (95% confidence interval (CI) 1.34, 3.06). This study provides an overview of a large population with keratoconus highlighting presenting features and clinical and topographic progression over a 4 year-period.

Aims: To quantify and establish baseline normative data for age-related differences in cellular and innervation density in the normal, healthy, human cornea using laser scanning in vivo confocal microscopy. Methods: Cross-sectional study of 85 normal subjects assessed via corneal topography and laser scanning in vivo confocal microscopy. Results: Mean age was 38±16 years (range 18–87 years) and 60% of subjects were female. Anterior keratocyte density declined by 0.9% per year (r = −0.423, p<0.001), posterior keratocyte density declined by 0.3% per year (r = −0.250, p = 0.021) and endothelial cell density declined by 0.5% per year (r = −0.615, p<0.001). Sub-basal nerve fibre density declined by 0.9% per year (r = −0.423, p0.05). No association was observed between subject gender and corneal cell or innervation density. Conclusions: Using laser scanning in vivo confocal microscopy this study highlights a significant, and relatively linear, reduction in keratocyte and endothelial cell density with increasing subject age. Interestingly, corneal sub-basal nerve fibre density also significantly decreases with increasing age. In vivo laser scanning confocal microscopy provides a safe, non-invasive method for the establishment of normative data and assessment of alterations in human corneal microstructure following surgery or disease processes.

An extensive electronic search was undertaken in January 2004 to identify all relevant peer-reviewed publications on Orbscan slit-scanning/Placido computerized topography. Ninety-one publications were identified. These address elevation topography and best-fit sphere, accuracy and repeatability of anterior and posterior corneal elevation and keratometric maps, comparison of Orbscan-acquired data and Placido-based computerized videokeratography instruments, pachymetry measurement and correlation with ultrasound, screening eye-bank corneas, detection of keratoconus, identifying corneal ectasia after refractive surgery, and miscellaneous applications. Studies were analyzed and critically compared in relation to attributes, applications, and limitations of Orbscan corneal topography. The review highlights advantages of this technique in assessing the cornea in health and disease and after surgery and identifies specific aspects that require further investigation and clarification.

The exponential evolution of in vivo confocal microscopy (IVCM) has led to a significant enhancement in our knowledge of the living cornea in both its physiological and pathological states. Studies using white light and coherent light-based IVCM have enabled detailed quantitative analysis of sub-basal nerve parameters, and have also resulted in the elucidation of the two-dimensional architecture of the normal corneal sub-basal nerve plexus. However, accurate and repeatable methods for quantitative analysis of stromal nerves imaged by IVCM remain to be developed. The effect of corneal surgery on central corneal nerves has been well documented in many IVCM studies, and these studies provide an indication of the regenerative capacity of corneal nerves. IVCM has also clearly demonstrated the involvement of corneal nerves in diseases such as keratoconus, although it remains unclear whether these alterations are a cause of, or occur secondary to, the disease process. IVCM has also been proposed as non-invasive method of accurately diagnosing and assessing the progression of diabetic neuropathy, highlighting the potential application of this technique as an indicator of systemic disease. This review consolidates our knowledge of how IVCM has contributed significantly to our greater understanding of corneal nerves in the living human cornea in health and disease.