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Purpose: To study corneal innervation in eyes with history of herpetic keratitis and its correlation with corneal sensitivity and biomechanical properties., Methods: A total of 56 eyes were included, of which 16 had a history of unilateral immune stromal herpetic keratitis, 16 were their contralateral eyes, and 20 were healthy controls. Structural analysis of corneal nerve plexus was performed by confocal microscopy. Biomechanical properties were measured with the Ocular Response Analyzer. Corneal sensitivity was assessed by contact (Cochet-Bonnet) and non-contact (Belmonte) esthesiometry., Results: The eyes with a history of herpetic keratitis had reduced sensitivity for mechanical stimuli when compared to healthy eyes (1441.88 ± 83 ml/min vs. 67.9 ± 7.86 ml/min). Nerve fiber density in the corneas with a history of herpetic disease was lower (4.13 ± 2.19 U/image) than in the contralateral eyes (7.44 ± 2.9 U/image, p value = 0.01) and than in healthy controls (10.35 ± 2.01, p value < 0.0001). The best structural and functional correlation was established between the total length of nerves per section and mechanic threshold assessed by Belmonte esthesiometer (Coef. -0.58 p value < 0.0001) and between total length of nerves and corneal resistance factor (CRF) (Coef. -0.64, p value < 0.0001)., Conclusions: The corneal sensitivity impairment in eyes with immune stromal herpetic keratitis can be explained by the loss of nerve fibers. Biomechanical corneal properties are affected as well. Corneal hysteresis (CH) and CRF are lower for the eyes with a history of herpetic keratitis, and also for the contralateral eye when compared to healthy controls.

Angiogenesis and inflammatory mediators are critical pathogenic factors in herpetic stromal keratitis (HSK). Since disease progresses without infectious virus, HSV-DNA and HSV-IgG complexes (HSV-IC) may contribute to HSK by triggering these factors. Production of VEGF and MMP-9 was studied in vitro using corneal epithelial cells (HCE), fibroblasts (HCRF) and macrophages (THP-1). VEGF was elevated in HCRF and THP-1 following treatment with HSV-DNA and HSV-IC. MMP-9 was elevated in THP-1 but not in corneal cells. When anti-HSV-IgG(Fab')2 complexes stimulated THP-1, MMP-9 was reduced to control levels. Pretreatment of THP-1 with anti-TLR-2 and -3 inhibited MMP-9 production. Thus, HSV-IC may stimulate THP-1 through the Fc receptor and TLRs. Proinflammatory cytokines (IL-1b, IL-6, and TNF-alpha) increased VEGF and MMP-9 in corneal cells and macrophages. These studies indicate that the continued presence of HSV-DNA and HSV-IC contribute to angiogenesis and inflammation in HSK. Thus, cytokines and TLRs may be potential targets for intervention.

Neurotrophic keratitis is a degenerative disease of the cornea caused by reduced corneal innervation. Trauma, tumors, inflammatory lesions and surgical procedures can damage the first branch of the trigeminal nerve on its entire course from brainstem to and within the cornea. Loss or reduction of corneal innervation leads to a reduced aqueous phase of the tear film and due to reduced supply with neurotransmitters/trophic factors also to reduced epithelial healing capacity (impaired mitosis and migration). Combined existence of tear film deficiency and impaired epithelial healing capacity predispose to persistent epithelial defects, corneal ulcers and perforation. Early diagnosis and adequate treatment may prevent this catastrophic chain of events.

Purpose: To investigate the functional and morphological long-term outcome of phototherapeutic keratectomy (PTK) for superficial corneal scars of varying origin., Patients and Methods: Between 1989 and 11/2002, 317 PTKs were performed in Erlangen, of which 31 consecutive procedures were assessed in this prospective study. The intended laser ablation depth after epithelial debridement and pannectomy varied from 12 to 150 microm. We used the slit-scanning-mode (Carl Zeiss Meditec AG) with a repetition rate of 20/s or 25/s, a pulse energy of 14.5 mJ (median) and a pulse rate of 2565+/-2036 (222-6962). In most cases a 6.0 mm metal mask was used to protect peripheral Bowman's layer., Results: After a mean follow-up of 2.0+/-1.9 (maximum 6.9) years, best-corrected visual acuity increased from preoperatively 0.3+/-0.2 to 0.5+/-0.3 (increase 87%, no change 10%, decrease 3%). Corneal surface topography regularized significantly (p=0.02). The spherical equivalent increased only slightly from -0.4+/-2.5 D preoperatively to 0.2+/-2.9 D postoperatively. Likewise, mean keratometric central power did not change significantly. In 10 eyes the maximum postoperative haze was mild, in 4 eyes moderate, and there was only one recurrent scar after delayed epithelial healing following epidemic keratoconjunctivitis., Conclusions: In superficial corneal scars of varying origin an o-PTK using the 193 nm excimer laser can moderately increase visual acuity in most cases. Therefore, a lamellar or penetrating keratoplasty might be avoided.