The effect of pH, dilution, and temperature on the viscosity of ocular lubricants--shift in rheological parameters and potential clinical significance.

OBJECTIVE: To investigate the effect of temperature, dilution, and pH on the viscosity of ocular lubricants. DESIGN: Laboratory based investigation of viscosity. PARTICIPANTS: No human subjects. METHODS: Hypromellose 0.3%, sodium hyaluronate 0.4%, carboxymethylcellulose sodium 0.5%/glycerin 0.9%, and carmellose sodium 0.5% were investigated. Ostwald capillary viscometers were utilised for viscosity measurements. The kinematic viscosity of each lubricant was tested quantitatively from 22 to 40 °C, and over a pH range of 5-8 under isothermal conditions. The kinematic viscosity of each eye drop was also tested under dilution by varying the mass fraction of each eye drop under isothermal conditions. MAIN OUTCOME MEASURE: Changes in kinematic viscosity. RESULTS: Hypromellose 0.3% had an initial pH of 8.34, while the other lubricants had a pH close to neutral. From 22 to 35 °C, the kinematic viscosity of sodium hyaluronate 0.4 fell by 36% from 37.8 to 24.4 mm(2)/s, carboxymethylcellulose sodium 0.5%/glycerin 0.9% fell by 35% from 16.98 to 11.1 mm(2)/s, hypromellose fell by 37% from 6.89 to 3.69 mm(2)/s, and carmellose sodium 0.5% fell by 25% from 2.77 to 1.87 mm(2)/s. At 32 °C only sodium hyaluronate 0.4%, and carboxymethylcellulose sodium 0.5%/glycerin 0.9% retained sufficient kinematic viscosity to maintain precorneal residence. Kinematic viscosities of all the topical lubricants were unaffected by pH but decreased significantly with dilution. CONCLUSIONS: This study suggests that currently used ocular lubricants have limited bioavailability due to reductions in viscosity by temperature and dilutional changes under physiological conditions. Developing lubricants with stable viscosities may maximise therapeutic efficacy.

Free radicals and the pH of topical glaucoma medications: a lifetime of ocular chemical injury?

INTRODUCTION: Preservatives in ophthalmic preparations are known to cause ocular surface damage. Excipients can also contribute to oxidative stress in the compromised ocular surface. We evaluated commonly used topical glaucoma medications to ascertain pH levels and the intrinsic presence of free radicals. METHODS: Samples of 27 topical glaucoma preparations were analysed for total free radical presence using a Randox Kit for total antioxidant status. Analytical grade indicator paper was used to ascertain pH levels. RESULTS: Free radical concentrations for these 27 glaucoma preparations ranged from 0 to 4.54 mmol/l, with a median value of 0.66 mmol/l (mean value of 0.662 mmol/l, SD 0.839). Levels of pH ranged from 4.0 to 7.4, with a median value of 6.5 (mean 6.252, SD 0.826). There was no evidence of a direct correlation between these two variables (r=0.232, P=0.275). CONCLUSION: This study is the first to document the range of pH and concentrations of free radicals intrinsically present in commonly used glaucoma medications. Long-term exposure to preservatives, free radicals, and pH levels could all contribute to ocular surface damage. The effect of excipients could be responsible for patient intolerance when changing products in the compromised ocular surface.

Observation of the in vivo movement of host keratocytes into donor tissue following corneal graft; a novel technique.

BACKGROUND/AIMS: The cornea is a highly cellular structure that exists in a dynamic state of cell loss, renewal and replacement. The limbus contains corneal epithelial stem cells. The progenitor or stem cell of the keratocyte remains poorly defined. The authors sought to investigate the in vivo movement of corneal stromal and epithelial cells using a chromosome in situ hybridisation (CISH) technique on human tissue. METHODS: Four explanted sex-mismatched human corneal buttons were studied using the CISH technique to identify corneal epithelial and keratocyte cells containing the Y chromosome. Keratocyte identity and lack of infiltrating inflammatory cells were confirmed by immunohistochemistry. The sex mismatch of donor (XX) and host (XY) suggested any identified Y chromosomes cells were of host origin having migrated into the donor tissue. RESULTS: Host corneal epithelial cells were identified in all four buttons, and corneal stromal keratocytes were present in three of the four specimens in the central corneal area. CONCLUSION: Defining the corneal cell movements and the location of the progenitor or stem cells has important clinical implications. This study has successfully used the CISH technique to demonstrate the in vivo centripetal movement of corneal stromal keratocytes and epithelial cells. The CISH technique may allow further investigation of the corneal stromal dynamics using archival tissue.

Surveillance of severe chemical corneal injuries in the UK.

AIM: To estimate the incidence of severe chemical corneal injuries in the UK and describe presenting clinical features and initial management. METHODS: All patients with severe chemical corneal injury in the UK from December 2005 to November 2006 inclusive were prospectively identified using the British Ophthalmological Surveillance Unit. Reporting ophthalmologists provided information regarding presentation and follow-up. RESULTS: Twelve cases were identified, giving a minimum estimated incidence in the UK of severe chemical corneal injury of 0.02 per 100,000. 66.7% of injuries were in males of working age, 50% occurred at work, and alkali was causative in 66.7%. Only one patient was wearing eye protection at the time of injury, 75% received immediate irrigation. Six patients required one or more surgical procedures, most commonly amniotic membrane graft. At 6 months' follow-up, the best-corrected visual acuity was 6/12 or better in five patients, and worse than 6/60 in two. CONCLUSION: The incidence of severe chemical corneal injury in the UK is low. The cases that occur can require extended hospital treatment, with substantial ocular morbidity and visual sequelae. Current enforcement of eye protection in the workplace in the UK has probably contributed to a reduced incidence of severe ocular burns.