Physiologically relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells and application to healthy volunteers: A viable workflow and a cautionary tale.

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p < 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p > 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5-15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.

Verrucous squamous carcinoma of the nasal septum.

We document only the second reported case of verrucous squamous carcinoma of the nasal septum. In both cases previous surgical treatment for assumed squamous papillomata had resulted in multiple recurrences necessitating formal surgical resection. Our patient has remained tumour-free during long-term follow-up.

Immunocytochemical detection of Candida albicans in formalin fixed, paraffin embedded material.

AIM: To assess the ability of the commercially available monoclonal antibody 1B12 (BioGenex, San Ramon, USA) to identify C albicans in formalin fixed, paraffin wax embedded material (FFPE). METHODS: Broth cultures of 20 strains of seven Candida species were resuspended in 4% agarose blocks, fixed in formalin for 24 hours, and embedded in paraffin wax. In addition, 16 blocks of FFPE tissue known to contain periodic acid-Schiff positive fungal hyphae were examined. Antigen retrieval involved microwave treatment of specimens in citrate buffer (0.01 M; pH 6.5) before addition of 1B12 antibody for 24 hours. Bound antibody was subsequently detected using a biotinylated link antibody and a peroxidase conjugated streptavidin. RESULTS: Only C albicans strains were 1B12 positive in the agarose blocks. All FFPE tissue blocks were found to contain 1B12 positive hyphal structures, indicating the presence of C albicans. CONCLUSIONS: The ability to identify candida organisms penetrating the lesional tissue in cases of chronic hyperplastic candidosis will help to clarify the role of individual Candida spp in this important form of oral candidosis.

Are we screening too many babies for retinopathy of prematurity?

A retrospective, hospital-records-based study of neonates screened for retinopathy of prematurity (ROP) was undertaken to determine whether the inclusion criteria for screening could have been safely altered to reduce the numbers of babies screened whilst not missing any stage III disease. Babies from six neonatal intensive care units in Birmingham were screened by a single examiner. Between November 1989 and November 1995, 1611 babies were examined and 1429 of these fell within the inclusion criteria of current guidelines for ROP screening produced by the Royal College of Ophthalmologists and the British Association of Perinatal Medicine--any baby < or = 1500 g birthweight or < or = 31 weeks gestational age. Thirty-nine (39) babies developed stage III ROP of which 31 (2.2%) were from Birmingham. In addition 8 babies with stage III ROP were referred from elsewhere. All 39 babies with stage III ROP had a birthweight < or = 1250 g or a gestational age of < or = 29 weeks, but 2 fell outside one criterion, indicating the need for both to be used. Had these inclusion criteria been utilised during this period, then 30% fewer babies would have been examined (432 of 1429). The importance of using both birthweight and gestational age as inclusion criteria is discussed, and the dangers of altering the indications for national screening on the basis of one study population is emphasised.

Diabetic eye disease: a natural history study.

In previous studies on diabetic retinopathy it has not been possible to relate risk factors to reduced vision because of the influence of vision-preserving treatment. Demographic data, cardiovascular risk factors and ocular features from the diabetic population of the Seychelles are described. Diabetic retinopathy in this population had not been modified by laser treatment. The population described consists of entirely type 2, maturity onset diabetics. Using a multivariate logistic regression model, the risk factors were deduced for three outcome variables: (1) reduced vision, defined as 6/36 or worse in both eyes; (2) the presence of diabetic retinopathy; and (3) the presence of maculopathy, preproliferative and proliferative retinopathy, grouped as severe retinopathy. Insulin treatment was associated with all outcome variables, duration from diagnosis of diabetes with retinopathy of all forms, and increasing age with reduced vision and severe retinopathy. Hypertensive diabetic patients were twice as likely to have reduced vision as compared with non-hypertensive diabetic individuals.

Effectiveness of occlusion therapy in ametropic amblyopia: a pilot study.

AIMS/BACKGROUND: To examine the relative contributions of non-specific (for example, spectacle correction) and specific (that is, occlusion therapy) treatment effects on children with ametropic amblyopia. To assess the importance and practicality of objectively confirming the prescribed occlusion dose. METHODS: Subjects were entered into a two phase trial. In the first ('pretreatment') subjects were provided with spectacle correction and underwent repeat visual acuity (VA) and contrast sensitivity (CS) testing until acuity in their amblyopic eye had stabilised. Subjects then progressed to the second phase ('treatment') in which they underwent direct, unilateral occlusion for 1 hour per day for 4 weeks. Patching was objectively monitored using an occlusion dose monitor. RESULTS: Eight subjects completed the trial, all but one of whom achieved > 80% concordance with the occlusion regimen. Within the pretreatment phase, mean amblyopic eye VA improved by 0.19 log units (p = 0.008) while mean CS gained 0.09 log units (p = 0.01). An identical improvement in mean VA was recorded in the fellow eyes (p = 0.03) while mean CS gained 0.11 log units (p = 0.02). Within the treatment phase, mean VA further improved (0.12 log units, p = 0.009) although this gain had halved by the end of treatment and was no longer statistically significant (p = 0.09). CONCLUSIONS: Visual performance improved significantly during pretreatment whereas further gains seen during occlusion were not sustained. Evaluation of occlusion regimens must take into consideration the potentially confounding influence of 'pretreatment effects' and the necessity to confirm objectively the occlusion dose a child receives.

Reliability of visual acuity in children with reduced vision.

We examined the test-retest reliability of visual acuity in 18 children referred to the Hospital Eye Service with reduced vision. Unaided distance acuities were recorded, using logarithmically scaled letter charts, on two occasions separated by an interval of one week during which no clinical intervention took place. Coefficients of repeatability were found to be +/- 0.25 and +/- 0.21 log units in left and right eyes, respectively. A further analysis of 14 subjects' data each of whom had one eye with consistently poorer acuity in both test sessions yielded coefficients of repeatability of +/- 0.15 and +/- 0.22 log units in, respectively, the better and poorer eyes. The reliability of visual acuity recorded in the better eye closely approximates to that previously found in normal adults, whilst that of the poorer eye appears more comparable to that of adult clinical populations.

Geographical variations in rates of ophthalmic surgery.

AIMS/BACKGROUND: Geographical variations in health care are common. There is, however, no simple explanation for why they arise. Variations in rates of ophthalmic surgery in the population aged 65 and over were investigated, with the aim of determining their cause. METHODS: Routine data sources were used to obtain the 1991-2 age and sex standardised rates for English health districts with an ophthalmic unit. Weighted least squares regression was used to study the relation between these rates and various factors describing the population and the provision of care. RESULTS: Surgery rates varied more than threefold. High rates of surgery were associated with high throughput and bed numbers (both p < 0.001), high proportions of day case surgery (p < 0.001), long waiting lists (p < 0.001), and a high number of theatre sessions (p = 0.002). Conversely, a high percentage of emergency admissions was associated with lower rates of surgery (p = 0.004). These six variables accounted for 58% of the variation. CONCLUSION: Geographical variations were found to exist, less than two thirds being explained by differences in the provision of care. The remaining variation may partly be attributed to private practice and the lack of consensus for many ophthalmic procedures (the 'surgical signature'), including a lowering of the threshold for surgery. These findings have implications for the planning of ophthalmic services.

Compliance in amblyopia therapy: objective monitoring of occlusion.

AIM/BACKGROUND: This study aimed to determine the feasibility of objective compliance monitoring of amblyopia therapy in clinical research. Occlusion has been the mainstay of amblyopia therapy for over 250 years, yet it has never been subjected to rigorous evaluation. Treatment regimens range arbitrarily from a few minutes to most of the waking hours of the day. Compliance is problematic and as, hitherto, accurate objective monitoring has been impossible it is not known how much occlusion is required to effect an improvement in vision. METHODS: An occlusion dose monitor (ODM) has been developed. The ODM consists of a modified occlusion patch and a miniature battery driven datalogger which periodically monitors patch skin contact. The patch is a standard disposable item with two miniature electrocardiogram electrodes attached to its undersurface. The datalogger comprises a high speed static RAM and a clock driven address counter. Data are retrieved using an IBM PC/AT computer. Fifteen child amblyopes were randomly allocated unilateral occlusion of 1, 4, or 8 hours per day for 4 weeks. Owing to data loss, presumed because of accumulation and discharge of static electricity, an additional child was included in the 8 hour group. Outcome measures were objective (ODM) and subjective (diary) compliance with treatment, logMAR visual acuity, and contrast sensitivity. RESULTS: Objective monitoring of occlusion is technically feasible and clinically informative. CONCLUSION: Objective monitoring of occlusion has opened up new research opportunities which, it is hoped, will enable the dose-effect relation of occlusion therapy in the various types of amblyopia to be investigated objectively, and facilitate the design of effective therapeutic regimens.

Factors affecting non-attendance in an ophthalmic outpatient department.

The object of the study was to establish the non-attendance rates in an ophthalmic outpatient department and any non-attendance patterns that may be useful in managing future outpatient resources. A detailed retrospective survey of monthly non-attendance rates was carried out in the outpatient department of a dedicated eye hospital over a 1 year period looking at differences in non-attendance between morning and afternoon clinics and new and review patients. A total of 43,004 scheduled outpatient appointments predominantly from the suburban population of the Merseyside region were made at St Paul's Eye Hospital from the 1 February 1990 to 31 January 1991. Five thousand four hundred and twenty-four appointments were missed giving an overall non-attendance rate of 12.6%. Non-attendance rates for morning and afternoon appointments were 12.0% and 13.0%, respectively: and for new and review patients, 11.9% and 12.8%, respectively. Logistic regression analysis showed that patients with afternoon appointments were on average 1.10 times more likely to non-attend than morning patients (P = 0.002), and that review patients were 1.09 times more likely to non-attend than new patients (P = 0.04). In order to maximize outpatient department efficiency, a reduction in non-attendance is essential. Establishing patterns for non-attendance provides us with a framework around which we can plan measures to compensate for outpatient non-attendance.

Non-attendance at ophthalmology outpatient clinics.

Non-attendance at outpatient clinics is a common problem, resulting in inefficiency and wasted resources. To establish the reasons why patients failed to attend their outpatient clinic appointment and to assess what proportion of these failed attendances were potentially preventable, we conducted a 13-month prospective postal survey of clinic non-attenders to our hospital. Of 5248 appointments made during the study, 521 were not kept (9.9%). Of these, 224 patients replied to the questionnaire, a response rate of 43%, with new patients more likely to not attend than old patients (odds ratio 2.7, P < 0.001). From the replies, 27.3% of non-attendances could be described as 'clerical error' with a further 17.9% due to patients failing to remember their appointment. Based on the replies received, a better organized outpatient booking system and a simple postal reminder could potentially prevent at least 40% of non-attendances.

Unrecognised and unregistered visual impairment.

Recent community based studies have shown that only a minority of visually impaired people who are eligible to be registered as partially sighted or blind are actually registered as such. To determine how many unregistered but eligible people are attending ophthalmic clinics a prospective study was undertaken of all patients (n = 1543) attending ophthalmic outpatient departments, at a single specialty eye hospital and two district general hospitals over a 1 week period. All patients with visual acuity < or = 6/18 or restricted visual field were interviewed. Registration status and factors affecting this were then determined. Although 95/174 patients interviewed were eligible for registration, 68 as partially sighted and 27 as blind, only 46 (48.4%) of these were registered. Asians and Afro-Caribbeans were under-represented in the group eligible for registration. Active treatment impeded registration. Patients having four or more hospital visits were on average 16 times more likely to be registered as those who had fewer attendances. Disabilities, in addition to visual impairment, were present in 40% (n = 38). This study shows that there is unregistered visual impairment in patients attending ophthalmic departments. As registration triggers multidisciplinary support, ophthalmologists need to be more alert to the benefits and criteria for partial sight and blind registration.

Binocular inhibition of visual performance in patients with cataract. The influence of test reliability.

Patients with cataract may show binocular inhibition: their sight improves on closing the eye in which vision is poorer. Of 36 patients questioned, one-third reported this to be the case. To quantify this phenomenon, all patients undertook a battery of tests of spatial visual performance and, in an attempt to define the reliability of their scores, were tested on two separate occasions. Patients generally performed inconsistently: at best, of 8 patients who demonstrated inhibition on a single test, only 5 did so again when re-tested after a short interval. In general, the magnitude of inhibition was less than that which could be reliably detected using the test battery. In addition, self-reported inhibition was not predictive of inhibition measured psychophysically. It is concluded that clinical tests of form vision lack either the necessary reliability or sensitivity to identify patients with cataract who report inhibition of binocular visual function.

Reliability of the Cambridge Low Contrast Gratings.

We examined the reliability of the Cambridge Low Contrast Gratings over four sessions at intervals of 1 hour, 1 day and 1 week. The 95% ranges of difference scores were found to be +/- 10.3 and +/- 10.5 test units for left and right eyes respectively. These reliability estimates span almost one-quarter of the test's dynamic range and one-third of the subjects' performance range. Practice effects were not found to be significant. Though previous reports have emphasized the usefulness of the Cambridge Gratings in screening for eye disease, caution is advised when interpreting changes that occur over time.

Oral tetracycline in the treatment of recurrent corneal erosions.

We report the results of a prospective, randomised controlled, 24 week trial to assess the efficacy of oral tetracycline and oral tetracycline with topical prednisolone in the treatment of recalcitrant recurrent corneal erosions, i.e. those which fail to respond to standard therapy. A total of 30 patients were randomly allocated to either standard treatment (group A), standard treatment and oral tetracycline (group B) or standard treatment, oral tetracycline and topical prednisolone (group C). Treatment groups B and C were instructed to perform daily lid hygiene. There was a significant reduction in the number of recurrent corneal erosions during the 24 week study period in group B (p = 0.04) and in group C (p = 0.0003) but not in group A (p = 0.66). There was a significant difference in the accelerated healing time of recurrent corneal microerosions between groups A and B (p = 0.001) and between groups A and C (p = 0.001). There was a significant improvement in the symptom scores during the study in treatment groups B and C (p = 0.005) but not in group A (p = 0.15). We conclude that lid hygiene and oral oxytetracycline 250 mg twice daily for 12 weeks with or without topical prednisolone for the first 7 days is beneficial in the management of recalcitrant recurrent corneal erosions.

The predictive value of post-operative intraocular pressures following trabeculectomy.

The value of post-operative intraocular pressure (IOP) in predicting the outcome of trabeculectomy was investigated in a retrospective study of single eyes of 203 Caucasian patients with uncomplicated chronic open angle glaucoma from the Birmingham and Midland Eye Hospital. Post-operative IOPs were recorded on day 1, at 2 weeks, and at 3, 6, 12 and 24 months. Surgical failure, defined as an IOP of 21 mmHg or above throughout the study period, occurred in 66 eyes by 24 months (32.5% failure). Discriminant analysis for the first day post-operative IOP showed a reliability of prediction of success (RPS) and failure (RPF) of 76.4% and 74.4% respectively, with an accuracy of prediction of success (APS) and failure (APF) of 92.6% and 42.6%. At 2 weeks, APS remained high (90.3%) and APF increased with time (63.2%). Certainty of success prediction at any stage is high and certainty of failure prediction becomes greater with time. In terms of IOP on the first post-operative day, 92.6% of successes may be correctly predicted if the IOP < 17 mmHg and 42.6% of failures may be predicted if the IOP > or = 17 mmHg. This study suggests that identification of patients at risk of failure on the basis of IOP in the early post-operative period is possible and that closer follow-up and early medical or surgical intervention may be indicated.