Corneal nerves in health and disease

The cornea is the most sensitive structure in the human body. Corneal nerves adapt to maintain transparency and contribute to corneal health by mediating tear secretion and protective reflexes and provide trophic support to epithelial and stromal cells. The nerves destined for the cornea travel from the trigeminal ganglion in a complex and coordinated manner to terminate between and within corneal epithelial cells with which they are intricately integrated in a relationship of mutual support involving neurotrophins and neuromediators. The nerve terminals/receptors carry sensory impulses generated by mechanical, pain, cold and chemical stimuli. Modern imaging modalities have revealed a range of structural abnormalities such as attrition of nerves in neurotrophic keratopathy and post-penetrating keratoplasty; hyper-regeneration in keratoconus; decrease of sub-basal plexus with increased stromal nerves in bullous keratopathy and changes such as thickening, tortuosity, coiling and looping in a host of conditions including post corneal surgery. Functionally, symptoms of hyperaesthesia, pain, hypoaesthesia and anaesthesia dominate. Morphology and function do not always correlate. Symptoms can dominate in the absence of any visible nerve pathology and vice-versa. Sensory and trophic functions too can be dissociated with pre-ganglionic lesions causing sensory loss despite preservation of the sub-basal nerve plexus and minimal neurotrophic keratopathy. Structural and/or functional nerve anomalies can be induced by corneal pathology and conversely, nerve pathology can drive inflammation and corneal pathology. Improvements in accuracy of assessing sensory function and imaging nerves in vivo will reveal more information on the cause and effect relationship between corneal nerves and corneal diseases

12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study

Background/aims: To examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK.Methods: A retrospective study of all patients who were diagnosed with IK and underwent corneal scraping between July 2007 and October 2019 (a 12-year period) at a UK tertiary referral centre. Relevant data, including demographic factors, microbiological profiles and in vitro antibiotic susceptibility of IK, were analysed.Results: The estimated incidence of IK was 34.7 per 100 000 people/year. Of the 1333 corneal scrapes, 502 (37.7%) were culture-positive and 572 causative microorganisms were identified. Sixty (4.5%) cases were of polymicrobial origin (caused by ≥2 different microorganisms). Gram-positive bacteria (308, 53.8%) were most commonly isolated, followed by Gram-negative bacteria (223, 39.0%), acanthamoeba (24, 4.2%) and fungi (17, 3.0%). Pseudomonas aeruginosa (135, 23.6%) was the single most common organism isolated. There was a significant increase in Moraxella spp (

Corneal Densitometry as an Indicator of Corneal Health

PurposeTo establish prospectively the normal values of corneal density of healthy subjects using the Pentacam Scheimpflug system (Oculus, Inc., Wetzlar, Germany) and to investigate alteration in corneal density during active and healed stages of bacterial keratitis.DesignProspective, comparative case series.Participants and ControlsSixty-four eyes of 40 healthy controls and 36 eyes of 35 patients with bacterial keratitis were studied.MethodsThis study was conducted at the Queen's Medical Centre, Nottingham, United Kingdom. A Pentacam system was used to study corneal density. Corneal densitometry readings in subjects with bacterial keratitis were recorded during the active stage and 4 to 6 weeks after complete healing. Densitometry was recorded at the site of infection and at a point in clear cornea furthest away from the infectious infiltrate. Corneal thickness also was measured.Main Outcome MeasuresDensitometry values of normal cornea, at the site of corneal ulcer or abscess, and at a distant point of clear cornea during active and healed keratitis.ResultsThe mean densitometry value of normal corneas was 12.3±2.4. In infectious keratitis, the densitometry values were greatest at the site of the active infection and significantly more than in controls. The densitometry values at the points of clear cornea furthest away from the site of infection also were significantly higher than in controls during active disease, but failed to return to normal values, despite complete resolution of infection. The density of the infiltrates was much higher than that of residual scars after healing of ulcers. No correlation was found between the pachymetry and the densitometry values.ConclusionsDensitometry of active infectious corneal infiltrates is more than that resulting from the corneal scarring after healing. Persistent increase in density of clear cornea furthest away from the focus of corneal infection suggests that the host response extends beyond the immediate area of infection and indeed may occur through the entire cornea. These changes persist beyond 4 weeks of healing, which was the duration of follow-up of this study. Densitometry can be used as an objective measure of the corneal response to infection and to monitor response to therapy

Management of postkeratoplasty astigmatism by paired arcuate incisions with compression sutures

Purpose: To analyse the efficacy of paired arcuate incisions and compression sutures technique in the management of post penetrating keratoplasty (PK) astigmatism. Methods: A paired arcuate incision with compression sutures procedure was used to treat 26 eyes with post- PK astigmatism ranging from 6.00 to 16.50 dioptres (D). The incisions were placed at the 7.0 mm optical zone inside the graft-host junction at a depth of 80% of corneal thickness. A 45° paired arc length was planned for eyes with preoperative astigmatism between 6D and 9D, and a 60° paired arc length was planned for eyes with preoperative astigmatism of >9D. At 3 months, corneal topography and refraction was performed and suture(s) removed if indicated. Net and vector astigmatism changes were calculated to determine the efficacy of the procedure. The indications for PK included keratoconus, Fuch's endothelial dystrophy, pseudophakic bullous keratopathy and corneal scar. Results: There was a statistically significant reduction in the mean magnitude of astigmatism from 9.66±2.90D preoperatively to 4.37±2.53D postoperatively in the whole group. The mean decrease in the astigmatism was 4.37±2.05D (58.4%) and 6.23±3.63D (52.6%) in patients with 6-9D and >9D, respectively. Vector power calculations also showed a significant astigmatism reduction in all groups. The safety and efficacy indices were 1.40 and 0.28, respectively. Conclusions: Manual astigmatic keratotomy is a viable technique with relatively good safety and efficacy outcomes. Based on the results we propose that increasing the arc length to a minimum of 60° for astigmatism of 6-9D, and to 75° for astigmatism >9D, is likely to have a greater beneficial effect

Variable Expression of Human beta Defensins 3 and 9 at the Human Ocular Surface in Infectious Keratitis

Purpose.: The authors have previously reported the presence of the antimicrobial peptides human beta defensin (hBD) 3 and hBD9 on the ocular surface (OS). These play an important role in infection and inflammation. In the present study, the authors studied the gene expression levels of hBD3 and hBD9 in healthy subjects and during and after healing of infectious keratitis. Methods.: Human OS specimens were obtained by impression cytology from healthy controls and patients with Acanthamoeba and Gram-negative and -positive bacterial keratitis (BK), both during active infection and after healing. The gene expression levels of hBD3 and hBD9 were determined using quantitative real-time polymerase chain reaction (RT-PCR). Results.: hBD3 and hBD9 were constitutively expressed in all healthy controls. During acute Acanthamoeba keratitis (AK), hBD3 levels were markedly increased and then returned close to normal levels after healing. In BK, hBD3 gene expression was moderately increased and then decreased after healing. In contrast to hBD3, hBD9 was significantly downregulated in both AK and Gram-positive BK, whereas it showed an insignificant decrease in Gram-negative BK. After healing, the expression showed upregulation except in Gram-positive BK, where it continued to decline. Conclusions.: This is the first study that demonstrates the gene expression of hBD3 and hBD9 in response to infection. It illustrates that not all antimicrobial peptides (AMPs) behave in a similar manner. Some are upregulated and some are downregulated, suggesting a diverse role of AMP in infection and inflammation. The results point to a role of AMP-mediated host defense in Acanthamoeba keratitis as well