Multi-centre variability of ISCEV standard ERGs in two normal adults.

BACKGROUND: The reproducibility of an individual's full-field ERG between centres has not previously been investigated. METHODS: ERGs were recorded using both silver thread and skin electrodes from the same two normal adult subjects at 15 UK centres using routine, local protocols and a highly standardised, 'ISCEV-specified' protocol matching the values specified in the ISCEV standard; where the ISCEV standard allows options, a single value was chosen. RESULTS: Inter-ocular differences were small, and amplitudes were smaller for skin than silver thread electrodes. No centre produced outlying data points, and ERGs across all 15 centres were remarkably similar. Amplitude variability was less for local protocols (using LED flashes) than for the ISCEV-specified protocol using xenon flashes (22 vs. 24 %, p = 0.01), but peak time variability was less for the ISCEV-specified protocol (6.1 vs. 7.4 %, p = 0.001). Only the DA 0.01 ERG correlated with photometric variability. The bifidity of the DA 3 a-wave doubled its peak time variability compared with the DA 10 a-wave. CONCLUSIONS: Inter-centre amplitude variability was typically within clinically significant thresholds, suggesting that inter-centre variability with suitable standardisation may not add more to total variability than inter-subject variability. Variability improvements gained by the tighter specifications of the ISCEV-specified protocol were possibly more than lost due to imprecisions of xenon flashtubes. Peak time variability was far lower than amplitude variability, corresponding with acceptable variability of biochemical assays. These results represent a vindication of the existence of an ERG standard and suggest that further standardisation would lend itself to greater reproducibility of ERGs worldwide.

Fundus autofluorescence in the diagnosis of cystoid macular oedema.

AIM: To determine the sensitivity and specificity of the non-invasive imaging technique, fundus autofluorescence (AF), in the diagnosis of cystoid macular oedema (CMO), using fluorescein angiography as the reference standard. DESIGN: Retrospective, consecutive, observational case series. METHODS: Ninety-six consecutive patients with CMO suspected clinically were selected from the AF database of the Retina Unit, Ophthalmology Department, Grampian University Hospitals-NHS Trust, between August 2004 and June 2006. Only patients in whom CMO was secondary to (1) cataract extraction, (2) inherited retinopathies, (3) inflammatory eye disease or (4) idiopathic cases were included in this study. Only patients in whom AF images had been performed within 2 weeks of FFA and, when obtained following FFA, there was a minimum gap of 4 days ("washing out" period), were considered eligible for this study. A total of 34 eyes from 34 patients were eligible and were included in this study. FFA was used as the reference test to confirm the presence of CMO, and, based on fluorescein angiography (FFA), CMO was graded as either mild or florid. AF images were examined in a masked fashion for the presence or absence of CMO. The sensitivity and specificity of AF in detecting CMO were then calculated. RESULTS: CMO was seen on AF imaging as round or oval areas at the fovea with an AF signal similar to that of background levels. At this site (fovea), the AF signal is usually reduced compared with background, due to the blockage caused by luteal pigment. The diagnosis of CMO based on AF imaging had 81% sensitivity and 69% specificity when compared with the reference standard FFA. Based on the FFA, there were 12 cases of florid CMO and eight of mild CMO. Of the former, CMO was detected with AF imaging in 100% (12/12 eyes), and of the latter, in 50% (4/8 eyes). CONCLUSIONS: AF imaging can be used as a rapid, non-invasive technique in the diagnosis of CMO.

Functional observations in vitamin A deficiency: diagnosis and time course of recovery.

AIMS: To describe the effects of vitamin A deficiency (VAD) on retinal function and the subsequent recovery following treatment in three patients with systemic conditions (two with Crohn disease; one secondary to IgE syndrome). METHODS: Electrophysiological testing (including pattern electroretinogram, PERG; electroretinogram, ERG; visual-evoked potential) established the diagnosis of VAD. Repeat testing was carried out in two patients to monitor the time course of recovery following intramuscular vitamin A injection. The third patient had repeat recordings following 13 months of oral supplementation. RESULTS: All three patients initially displayed a characteristic absence of rod function associated with VAD. In addition, delayed and reduced amplitude cone ERGs, loss of short wavelength cone (S-cone) function and subnormal macular function were observed in two patients. Restoration of rod and generalised cone function was rapid in the two patients who received intramuscular injection, with normalisation of some electrophysiological responses after only 3 days. Normal S-cone amplitudes and cone latencies were reached within 12 days of vitamin A injection. Macular function returned to within normal limits by 12 days postinjection in one patient, but remained mildly subnormal in the second patient. Full recovery was present after 13 months oral supplementation in the third patient. CONCLUSIONS: Novel observations regarding dark-adapted cone function, S-cone function, and PERG are presented. The differences between the effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptor classes. The importance of rapidly and accurately diagnosing VAD, a treatable condition, is noted.

High glucose concentration decreases insulin-like growth factor type 1-mediated mitogen-activated protein kinase activation in bovine retinal endothelial cells.

Clinical trials have incontrovertibly demonstrated that the onset and progression of diabetic retinopathy (DR) is influenced by the control of glucose levels in patients. In the present study, we examined the effect of glucose concentration on the responsiveness of bovine retinal endothelial cells (BREC) to insulin-like growth factor type 1 (IGF-1). Retinal endothelial cells were isolated from bovine retina and cultured in 5 or 20 mmol/L glucose with or without 100 ng/mL IGF-1. The level of cell growth and p42/44 and p38 mitogen-activated protein kinase (MAPK) activation was determined using the alamarBlue (Serotech) assay and Western blotting, respectively. IGF-1 significantly enhanced cell growth in BREC exposed to 5 mmol/L glucose but not in cells exposed to high glucose concentrations (20 mmol/L). IGF-1 induced a transient activation of p42/44 MAPK, with peak activation at 15 minutes in cells exposed to 5 mmol/L glucose; however, no increase in p42/44 MAPK was evident at the higher glucose concentration of 20 mmol/L. There was no significant change in the level of p38 MAPK during the time period examined when IGF-1 was also present. However, high glucose concentrations alone increased the level of p38 MAPK after 60 minutes and the level of p42/44 MAPK after only 15 minutes exposure in 20 mmol/L glucose. Thus, BREC exposed to high glucose concentrations are not sensitive to IGF-1 and this is due, at least in part, to a reduced activation of the p42/44 MAPK pathway. Furthermore, the presence of IGF-1 appears to exert a protective effect on the cells in high glucose concentration by preventing progression through the cell cycle.