Mutational Analysis of the Rhodopsin Gene in Sector Retinitis Pigmentosa.

BACKGROUND: To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland. DESIGN: A case series of sector RP in a tertiary ocular genetics clinic. PARTICIPANTS: Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent. METHODS: The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced. MAIN OUTCOME MEASURE: Rhodopsin mutational status. RESULTS: A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO. CONCLUSIONS: The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.

Multidisciplinary assessment of vision in children with neurological disability.

INTRODUCTION: There is no consensus as to the best method of assessing vision in children with neurological disability. There are a variety of tests and approaches that can be used. It is important to look at models of assessment that identify the visual diagnosis and provide appropriate feedback and explanation to parents, carers and educational professionals. METHODS: This study reports on the results of comprehensive visual assessments of fifty children with neurological disability over a three year period. It focuses on the feedback from families and professionals after the assessment report was disseminated. RESULTS: The majority of families and professionals strongly agreed that a specialist assessment was needed in this population. Parents and professionals particularly valued the written report which provided guidance on appropriate visual material including advice relevant to education. CONCLUSION: This study highlights the importance of specialist teams engaging with local child development services and indicates how partnership working can potentially be emotionally supportive as well as developmentally beneficial.

Comparing mfERGs with estimates of cone density from in vivo imaging of the photoreceptor mosaic using a modified Heidelberg retina tomograph.

The spatial variation in central retinal function determined from mfERG was compared to co-localised measurements of cone density in two normal subjects. Individual cone cells in the parafoveal region of the retina were identified from 1 degrees x1 degrees images of the photoreceptor mosaic using a modified Heidelberg retina tomograph (HRT). The variation in cone density compared well with previous histology and retinal imaging studies and was strongly linearly correlated (r=0.98, p<0.001) with mfERG amplitude within the central retina. Retinal function determined from mfERG amplitude appears to directly reflect the density of the cone cells in this region.

Rigid gas permeable contact lenses: out in the cold.

INTRODUCTION: Rigid gas permeable (RGP) contact lens wearers may experience episodes of lens fracture during handling. In this paper, we report the case of a keratoconic contact lens wearer whose lens fractured whilst being handled at sub-zero temperatures. Subsequent studies illustrate how PMMA and RGP contact lenses behave when exposed to sub-zero temperatures. METHODS: Using a previously validated custom-built strain gauge we have measured the force required to invert RGP contact lenses (Fluroperm, DK30-DK151, PMMA and Aquasil; dioptric power -2.00DS) under different temperature conditions. RESULTS: It was found that RGP lenses, frozen to -7 degrees C, required on average 15% less force to cause inversion than when stored at room temperature, regardless of material. It was also found that without due care, lenses of all materials fractured more easily after having been frozen, than lenses kept at room temperature. Fracture rates rose from 8% to 83% if lenses were stored wet (at -7 degrees C) as opposed to dry. CONCLUSION: The authors conclude that practitioners should consider inappropriate contact lens storage and handling as a possible reason for otherwise unexplained acute RGP contact lens fracture.

Investigation of changes in the myopic retina using multifocal electroretinograms, optical coherence tomography and peripheral resolution acuity.

We investigated relationships between retinal structure using optical coherence tomography (OCT) and retinal function using peripheral resolution acuity and multifocal electroretinograms (mfERG) in 56 subjects with a range of refractive errors (+0.50 to -15.00 D). Retinal thinning occurred in moderate and high myopia which appeared to be primarily due to reduced thickness of the middle to inner retina (MIR) (outer plexiform layer to the nerve fiber layer). MIR thickness was correlated with reduced spatial resolution and delayed mfERG timing in the peripheral retina. The findings suggest the structure and function of the post-receptor retina is susceptible to disruption in moderately and highly myopic eyes.

Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers.

Quantitative analysis of the arterial pressure pulse waveform recorded by applanation tonometry of the radial artery can track NO (nitric oxide)-mediated modulation of arterial smooth muscle tone. The changes in pressure pulse waveform morphology result from pulse wave reflection arising predominantly from smaller arteries and arterioles. Employing Doppler ultrasound to record the spectral flow velocity waveform in the ophthalmic artery, we studied the effects of NO modulation on waveforms recorded in the proximity of the terminal ocular microcirculatory bed. In healthy young men (n=10; age 18-26 years), recordings were made at baseline, following 300 mug of sublingual GTN (glyceryl trinitrate) and during the intravenous infusion of 0.25 and 0.5 mg/kg of L-NAME (N(G)-nitro-L-arginine methyl ester). Peaks (P1, P2 and P3) and nodes (N1, N2 and N3) on the arterial flow velocity waveform were identified during the cardiac cycle and employed to quantify wave shape change in response to the haemodynamic actions of the pharmacological interventions. The administration of GTN resulted in a significant (P<0.05) increase in heart rate without significant alteration in blood pressure. At the doses employed, L-NAME did not significantly alter systemic haemodynamics. With the exception of peak Doppler systolic velocity, all other peaks and nodes decreased significantly in response to GTN (P<0.05 for all points compared with baseline). In response to the administration of L-NAME, all peaks and nodes decreased significantly (P<0.05 for all points compared with baseline). The resistive index, a ratio calculated from the peak and trough flow velocities employed to assess change in flow resistance, increased significantly in response to GTN (0.77 at baseline compared with 0.85; P<0.05). Quantification of changes in the flow velocity spectral waveform during the cardiac cycle sensitively identified NO modulation of smooth muscle tone prior to alteration in systemic haemodynamics. Focusing on the resistive index, which identifies isolated points on the waveform describing the excursions of flow, may provide misleading information in relation to the haemodynamic effects of drug interventions.