Childhood glaucoma surgery in the 21st century.

Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma.

Patterns of adherence to NICE glaucoma guidance in two different service delivery models.

PURPOSE: To assess adherence patterns to the UK National Institute of Health and Clinical Excellence (NICE) guidelines on glaucoma management (2009) in a tertiary referral centre shared care setting and in a district general hospital (DGH) setting. METHOD: We performed a retrospective case note analysis of 200 patients from two centres between January and June 2010. The two centres involved were a consultant-guided teaching hospital optometry-led shared care setting (setting 1) and a consultant-led DGH clinic setting (setting 2). The main outcome measures were compliance with eight of the main NICE guidelines on glaucoma diagnosis and management (2009). RESULTS: Both centres showed good adherence to the guidelines regarding the choice of initial treatment (96% vs 100%, settings 1 and 2, respectively) and arranging appropriate monitoring intervals (92% vs 86%). However, significant differences were seen when assessing whether an optic disc image was obtained at the initial visit (74% vs 10%), whether an appropriate initial assessment was performed (96% vs 58%), whether patients' review interval complied with the NICE guidance regardless of hospital cancellations (92% vs 66%), and whether concordance with medication was checked (88% vs 24%) (settings 1 and 2, respectively, P<0.01-Fisher's exact test). CONCLUSION: Our study provides evidence to suggest that a hospital-based shared care service with trained optometrists using assessment sheets compares favourably to non-specialist glaucoma care delivered by ophthalmologists.

Agreement between specially trained and accredited optometrists and glaucoma specialist consultant ophthalmologists in their management of glaucoma patients.

AIMS: Optometrists are becoming increasingly involved in the co-management of glaucoma patients as the burden on the Hospital Eye Service continues to escalate. The aim of this study was to assess the agreement between specially trained optometrists and glaucoma-specialist consultant ophthalmologists in their management of glaucoma patients. METHODS: Four optometrists examined 23-25 patients each and the clinical findings, up to the point of dilation, were documented in the hospital records. The optometrist, and one of two consultant ophthalmologists, then independently examined and documented the optic-disc appearance before recording their decisions regarding the stability and management of the patient on a specially designed proforma. Percentage agreement was calculated together with kappa or weighted kappa statistics, where appropriate. RESULTS: Agreement between consultants and optometrists in evaluating glaucoma stability was 68.5% (kappa (κ)=0.42-0.50) for visual fields, 64.5% (weighted κ=0.17-0.31) for optic discs, and 84.5% (weighted κ=0.55-0.60) for intraocular pressures. Agreement regarding medical management was 96.5% (κ=0.73-0.81) and for other glaucoma management decisions, including timing of follow-up, referral to a consultant ophthalmologist, and discharge, was 72% (weighted κ=0.65). This agreement increased to 90% following a retrospective independent then consensus review between the two consultants and when qualified agreements were included. Of the 47 glaucoma and non-glaucoma queries generated during the study, 42 resulted in a change of management. CONCLUSION: Confirming the ability of optometrists to make appropriate decisions regarding the stability and management of glaucoma patients is essential if their involvement is to continue to develop to meet the demand of an aging population.

Individualised patient care as an adjunct to standard care for promoting adherence to ocular hypotensive therapy: an exploratory randomised controlled trial.

PURPOSE: To evaluate the impact of individualised patient care, as an adjunct to standard care, on adherence to ocular hypotensive therapy. METHODS: A two-arm, single-masked exploratory randomised controlled trial recruited patients newly prescribed ocular hypotensive therapy. The intervention involved an individual assessment of health-care needs and beliefs and a 1-year follow-up period according to need. The primary outcome was refill adherence, measured by collating prescription and dispensing data for 12 months. Secondary outcomes included self-reported adherence, glaucoma knowledge, beliefs about illness and medicines, quality of care, intraocular pressure (IOP) fluctuation, and changes in clinical management assessed at 12 months. The strength of the intervention was measured following withdrawal by reviewing clinical outcomes for a further 12 months. RESULTS: In all, 127 patients were recruited (91% response rate). Intervention-arm patients collected significantly more prescriptions than control-arm patients. Self-report adherence was significantly better in the intervention-arm for patients who forgot drops and those who intentionally missed drops. The intervention group demonstrated significantly more glaucoma knowledge, expressed a significantly stronger belief in the necessity of eye drops and believed that they had more personal control over managing their condition. Control-arm patients had more IOP fluctuation and changes in clinical management. However, this finding only reached significance at 24 months. CONCLUSION: Modelling patient care according to health-care needs and beliefs about illness and medicines can have a significant impact on improving adherence to therapy for this patient group, with the potential benefit of improving clinical outcomes.

High-resolution hyperspectral imaging of the retina with a modified fundus camera.

PURPOSE: to examine the practical feasibility of developing a hyperspectral camera from a Zeiss fundus camera and to illustrate its use in imaging diabetic retinopathy and glaucoma patients. METHODS: the original light source of the camera was replaced with an external lamp filtered by a fast tunable liquid-crystal filter. The filtered light was then brought into the camera through an optical fiber. The original film camera was replaced by a digital camera. Images were obtained in normals and patients (primary open angle glaucoma, diabetic retinopathy) recruited at the Manchester Royal Eye Hospital. RESULTS: a series of eight images were captured across 495- to 720-nm wavelengths, and recording time was less than 1.6s. The light level at the cornea was below the ANSI limits, and patients judged the measurement to be very comfortable. Images were of high quality and were used to generate a pixel-to-pixel oxygenation map of the optic nerve head. Frame alignment is necessary for frame-to-frame comparison but can be achieved through simple methods. CONCLUSIONS: we have developed a hyperspectral camera with high spatial and spectral resolution across the whole visible spectrum that can be adapted from a standard fundus camera. The hyperspectral technique allows wavelength-specific visualization of retinal lesions that may be subvisible using a white light source camera. This hyperspectral technique may facilitate localization of retinal and disc pathology and consequently facilitate the diagnosis and management of retinal disease.

Preliminary survey of educational support for patients prescribed ocular hypotensive therapy.

PURPOSE: to establish the impact of educational support on patients' knowledge of glaucoma and adherence, in preparation for an intervention study. METHODS: structured observation encapsulated the educational support provided during clinical consultations and patient interviews captured the depth of glaucoma knowledge, problems associated with glaucoma therapy, and adherence issues. RESULTS: one hundred and thirty-eight patients completed the study. Education was didactic in nature, limited for many patients and inconsistent across clinics. Patients showed generally poor knowledge of glaucoma with a median score of 6 (range 0-16). A significant association was found between educational support and knowledge for newly prescribed patients (Kendall's tau=0.30, P=0.003), but no association was found for follow-up patients (Kendall's tau=0.11, P=0.174). Only five (6%) patients admitted to a doctor that they did not adhere to their drop regimen, yet 75 (94%) reported at interview that they missed drops. CONCLUSIONS: although important, knowledge alone may not sufficiently improve adherence: a patient-centred approach based on ongoing support according to need may provide a more effective solution for this patient group.

Patterns and rate of adherence to glaucoma therapy using an electronic dosing aid.

AIMS AND PURPOSE: To identify patterns and rates of adherence with travoprost eye drops using the Travatan dosing aid (TDA) and to present a method for graphically presenting adherence data. METHODS: A prospective observational cohort study of patients on travoprost (prostaglandin) monotherapy. Patients were dispensed a TDA and followed up after approximately 3 months of usage. Data were downloaded from the TDA into a computer for analysis. Analysis used inter-dose intervals (the time between each dosing) to look at adherence between days 4 and 75. RESULTS: In all, 100 patients were invited to participate, 53 agreed and complete TDA data sets were obtained from 37. In total 23 of the complete data sets showed good adherence (dosing within +/-4 h of the agreed dosing time on >80% of occasions), 3 patients discontinued usage before 75 days, 4 showed frequent drug holidays (no dosing for > or =8 days) and 7 frequently missed doses with adherence rates of <60%. Of the 16 patients for whom no TDA data was obtained, 5 were lost to follow-up, 4 had faulty/damaged TDAs, 3 changed medication, 3 preferred not to use the TDA, and 1 was hospitalized. CONCLUSIONS: There were four easily defined patterns of adherence; (1) good adherence; (2) discontinued usage; (3) frequent drug holidays; and (4) frequent missed doses with low adherence rates. A new method for graphically presenting adherence data helps clinicians identify the pattern of usage and is a valuable aid to the overall management of patients on travoprost therapy.

The influence of socioeconomic and clinical factors upon the presenting visual field status of patients with glaucoma.

PURPOSE: To investigate the relationship between socioeconomic status and the extent of visual field loss in POAG and treated OHT patients at their first presentation to Manchester Royal Eye Hospital. METHODS: A cohort of 113 glaucoma patients seen between 1995 and 2005 was reviewed. The clinical parameters intraocular pressure, C : D ratio, family history of glaucoma, visual acuity, extent of visual field loss, and demographic parameters: age, gender, ethnicity, and residential postcode were extracted from hospital records. The socioeconomic status of each patient was estimated from the patient's residential postcode with the ACORN index (group 1: affluent and group 2: socioeconomically deprived). RESULTS: In comparison to group 1 (n=49), patients in group 2 (n=64) presented with more advanced field loss, lower educational attainment (18 vs 98% with no or unknown qualification), and were less aware of glaucoma in the family (27 vs 17%). Patients with a number of systemic health problems had worse vision, more severe visual field loss, and worse clinical attendance (P<0.05). CONCLUSIONS: The extent of visual field loss in glaucoma patients at first presentation is related to a combination of clinical and socioeconomic factors including the patient's postcode. This finding could be used to target future case-finding resources.

Agreement between ophthalmologists and optometrists in optic disc assessment: training implications for glaucoma co-management.

BACKGROUND: Many studies have estimated observer variability for optic disc assessment among experts, but there are few data on agreement between optometrists and ophthalmologists. The aim of this study is to report inter- and intraobserver agreement among optometrists and ophthalmologists in optic disc assessment and discuss the implications for glaucoma co-management. METHODS: Twelve observers (six optometrists and six ophthalmologists) graded 48 stereo-pairs of optic disc photographs from 48 patients on two separate occasions. Observers graded the vertical C/D ratio, the narrowest rim width and the presence/absence of disc haemorrhage. Agreement was assessed by calculating the standard deviation (SD) of differences and the kappa statistic, within and between observers. Systematic differences in grading between and within individuals were described by calculating mean differences. RESULTS: Intra-observer agreement is "substantial" and significantly better than inter-observer agreement for all disc features (P<0.0001). Intra-observer agreement is comparable for optometrists and ophthalmologists with regard to C/D ratio estimates. Although some optometrists show close agreement with ophthalmologists, overall agreement between optometrists and ophthalmologists is significantly worse than agreement among ophthalmologists alone for vertical C/D ratio (P=0.002) and disc haemorrhage (P=0.02). There are fewer inter-observer mean differences that differ significantly from zero among ophthalmologists (7%) than among optometrists (67%; chi2=11.63, P<0.001) or between optometrists and ophthalmologists (69%; chi2=16.7, P<0.001). There is evidence of systematic under-reading of C/D ratios by less experienced optometrists. CONCLUSION: Although individual optometrists can show good agreement with ophthalmologists on disc grading, the variation in individual performance indicates that training and accreditation in disc assessment is an essential prerequisite for participation by optometrists in glaucoma co-management.

Pulsatile ocular blood flow in eyes with untreated choroidal melanoma.

PURPOSE: To investigate the effect of choroidal melanoma on pulsatile ocular blood flow (POBF). METHODS: Seventeen patients (10 men and 7 women) with unilateral untreated choroidal melanoma and 22 controls matched for age and sex were studied. Intraocular pressure (IOP), pulse amplitude (PA) and POBF were measured using the OBF Tonograph. In each patient, mean inter-ocular differences were analysed using the paired t-test. The correlation coefficient between tumour thickness and POBF was calculated. To assess the variation of this parameter, the coefficient of variation for three repeated readings was determined for healthy and affected eyes. RESULTS: In the control group, there was no significant difference between eyes in any parameter. In patients with melanoma, there was no significant difference in IOP and PA between affected and unaffected eyes. Mean POBF was significantly higher in affected eyes (1040 microliters min-1) than unaffected eyes (876 microliters min-1) (p = 0.003). There was no correlation between tumour thickness and absolute POBF (r = -0.24) or between tumour thickness and inter-ocular difference in POBF between affected and unaffected eyes (r = -0.17). Mean coefficient of variation of three repeated readings of POBF was 7.76% in healthy eyes and 8.97% in affected eyes. CONCLUSIONS: These findings suggest a high tumour blood flow or a global increase in choroidal blood flow in the presence of melanoma. POBF measurement may be useful in the clinical assessment of eyes with choroidal melanoma.

Effect of beta-carboline derivatives on the binding of L-tryptophan and diazepam to bovine and human albumin.

The effects of 12 beta-carboline derivatives on the binding of L-tryptophan and diazepam to bovine and human albumin have been investigated to seek similarities between the indole binding site on albumin and the benzodiazepine receptor in the brain. The binding of L-tryptophan and diazepam was measured at 37 degrees and pH 7.4 by equilibrium dialysis. Norharmane was the most potent inhibitor of the binding of L-tryptophan and diazepam to both bovine and human albumin. The kinetics of the inhibitory effects of several of the beta-carbolines were studied. Norharmane decreased the value (n) for the number of binding sites for the binding of L-tryptophan to both bovine and human albumin. Norharmane and harmane decreased the apparent association (Ka) but increased n for the interaction of diazepam with bovine albumin. Norharmane also had a similar effect on the binding of diazepam to human albumin. The similarities between the inhibitory effects of the beta-carbolines on the binding of L-tryptophan and diazepam to albumin and the affinity of the beta-carbolines for the central benzodiazepine receptor point to some common structural requirements for binding to the receptor and to albumin.

Brain uptake of L-tryptophan and diazepam: the role of plasma protein binding.

The brain uptake index (BUI) of L-tryptophan and diazepam into the right and left hemispheres and the cerebellum has been measured after a bolus injection into the carotid artery of the anaesthetised rat. The effect of a range of albumin concentrations (38 microM to 1.4 mM; 0.25-9 g/100 ml) on the viscosity and osmotic pressure of the bolus was studied as a preliminary to the brain uptake experiments. Dextran (Mr 60,000-90,000) was included in the injection to ensure constant viscosity and osmotic pressure. An increase in albumin concentration up to 2 g/100 ml substantially reduced the BUI of L-tryptophan, but a further increase in albumin concentration up to 9 g/100 ml resulted in only a slow fall in the BUI of L-tryptophan which was not proportional to the larger fall in the concentration of unbound L-tryptophan. Furthermore, the use of norharmane as an inhibitor of L-tryptophan binding did not reveal a simple relationship between its unbound concentration and BUI. A decrease in the unbound concentration of diazepam also reduced its BUI, but again there was no straightforward relationship between this and unbound diazepam concentration. The differences observed in the BUI of inulin from solutions of either dextran or albumin indicate not only that each macromolecule may exert particular effects on the BUI, perhaps by an influence on cerebral blood flow, but also show how difficult it is to devise solutions for injection which differ in respect of only one variable, that of the unbound ligand concentration.

Milk transfer of rhein in the rhesus monkey.

A HPLC method was developed to measure rhein, a laxatively active metabolite of sennosides A + B, in milk and plasma. Samples from 2 lactating rhesus monkeys were taken over 48 h after oral administration of sennosides (1 mg kg-1). Detectable rhein levels were found in plasma between 2 and 12 h and in milk between 4 and 12 h after administration, but rhein excretion in milk seems to be far below the dose necessary to elicit a laxative effect in the suckling offspring.