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Biomedical subjects

Graham E Holder

Publications and source records attributed to Graham E Holder.

34 records · Page 2Linked to original sources
PubMed2004

Sudden visual loss after removal of silicone oil.

PURPOSE: Removal of silicone oil after vitreoretinal surgery reduces potential complications of glaucoma and cataract and improves visual function in 30% of patients. We report the clinical findings of a series of patients who experienced unexpected and permanent visual loss after removal of silicone oil. METHODS: Seven patients with visual loss after removal of silicon oil were investigated with best-corrected Snellen visual acuity (BCVA) assessment, fundus biomicroscopy, fluorescein angiography, optical coherence tomography, and electrophysiologic examination. RESULTS: Six men and one woman (average age, 42.8 years.) presented with profound BCVA loss, averaging 4.7 Snellen lines (SD 1.4), after silicon oil removal. No other complications associated with oil removal were noted. The retina remained attached in all cases, no patient developed cystoid macular edema or epiretinal membrane, and optical coherence tomographic and fluorescein angiographic findings remained normal. Electrodiagnostic testing showed a range of abnormalities, with the majority of patients showing severe macular dysfunction. CONCLUSIONS: We describe a new phenomenon of unexpected visual loss after oil removal in patients with good visual potential. The pathogenesis remains obscure.

Adult↗
PubMed2004

Localized retinal electrophysiological and fundus autofluorescence imaging abnormalities in maternal inherited diabetes and deafness.

PURPOSE: To investigate retinal function in patients with maternally inherited diabetes and deafness (MIDD) and to correlate the findings with fundus autofluorescence (FAF) imaging. METHODS: FAF was imaged in five patients (age range, 49-60 years) confirmed to have the mitochondrial DNA nucleotide A3243G point mutation. Retinal function was measured by full-field (Ganzfeld) electroretinography (ERG) and pattern ERG, incorporating the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Multifocal ERG (mfERG) was also performed. For analysis of the mfERG data, five regional ring groups of equal eccentricity were formed. For each ring, the peak amplitude (defined as the difference between P1 and N1) and the implicit time of P1 were determined and compared with normative values. RESULTS: Visual acuity in the patients was between 20/20 and 20/40 (Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Irregular increased FAF signals were observed adjacent to and between areas of atrophy of the retinal pigment epithelium (RPE). Ganzfeld ERGs were within normal limits in three patients. Pattern ERG was abnormal in five eyes of three patients. mfERG peak amplitude abnormalities were particularly present in rings 2 and 3 and were consistent with the distribution of FAF abnormalities. In all but one eye, no implicit times changes were present. CONCLUSIONS: Significant mfERG abnormalities with normal Ganzfeld ERG are consistent with nonuniform damage to the central retina in MIDD, in keeping with the FAF findings. Reduced peak amplitudes with normal implicit times in the mfERG suggest localized loss of function and may indicate damage to the cone photoreceptor outer segments or cone photoreceptor loss in MIDD.

DNA, Mitochondrial↗
PubMed2004

Fundus autofluorescence in patients with leber congenital amaurosis.

PURPOSE: Fundus autofluorescence (FAF), as an index of lipofuscin accumulation in the retinal pigment epithelium (RPE), provides indirect information on the level of metabolic activity of the RPE and thus the integrity of the RPE/photoreceptor complex. To investigate whether the photoreceptor/RPE complex is still viable in patients with Leber congenital amaurosis (LCA), FAF imaging was performed. METHODS: Three patients with LCA (patients A, B, and C; ages, 24, 15, and 37 years, respectively) were enrolled and one patient with RP with preserved visual acuity (age, 28 years) was included as a control. The diagnosis was based on history, visual function, and Ganzfeld electroretinography (International Society for Clinical Electrophysiology of Vision [ISCEV] standard). FAF was recorded with a confocal scanning laser ophthalmoscope (cSLO; Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). RESULTS: All patients with LCA had vision reduced to perception of light and had undetectable ERGs. FAF was normal in patient A. In patient B, there was a parafoveal ring of mildly increased FAF. The midperiphery showed mildly decreased FAF. Patient C showed a parafoveal ring of moderately increased FAF. FAF was moderately decreased along the arcades and the midperiphery. The patient with RP showed a parafoveal ring of moderately increased FAF and severely decreased FAF eccentric to the macula including the periphery. CONCLUSIONS: The FAF findings in these patients with LCA suggest that there is continuous metabolic demand from the photoreceptors and that the RPE/photoreceptor complex is, at least in part, anatomically intact, but the photoreceptors have lost function. These findings may have implications for future treatment. It is notable that more than 20 years of severe visual impairment associated with LCA can be associated with normal FAF, indicating that photoreceptor function may be rescuable.

Adolescent↗
PubMed2004

Comparison of fundus autofluorescence with photopic and scotopic fine-matrix mapping in patients with retinitis pigmentosa and normal visual acuity.

PURPOSE: To compare psychophysically determined spatial variations in photopic and scotopic sensitivity across the macula in patients with retinitis pigmentosa (RP) and normal visual acuity who manifest an abnormal high-density ring of fundus autofluorescence (AF). METHODS: Eleven patients with a clinical diagnosis of RP were examined. All had rod-cone dystrophy (International Society for Clinical Electrophysiology of Vision [ISCEV]-standard ERGs), visual acuity of 6/9 or better, and an abnormal parafoveal annulus of high density AF. Fine-matrix mapping (FMM) was performed over macular areas of abnormal high-density AF under photopic and dark-adapted conditions. Pattern ERGs (PERGs) were performed in 9 of 11 patients, by using different sizes of circular checkerboards. RESULTS: Rings of high-density AF varied between patients (approximately 3 degrees -18 degrees in diameter). Photopic sensitivity was preserved over central macular areas, but there was a gradient of sensitivity loss over high-density segments of the ring and severe threshold elevation outside the arc of the ring. Scotopic sensitivity losses were more severe, and they encroached on areas within the ring. The radius of the high-density ring correlated with the lateral extent of preserved photopic sensitivity (r=0.86) and PERG data. CONCLUSIONS: High-density rings of AF, which are present in some patients with RP with normal visual acuity, demarcate areas of preserved central photopic sensitivity. Scotopic sensitivity losses encroach on areas within the ring of high density and may reflect dysfunction before accumulation of lipofuscin.

Adult↗
PubMed2003

Phenotype of retinitis pigmentosa associated with the Ser50Thr mutation in the NRL gene.

BACKGROUND: We previously reported an Ser50Thr mutation in the NRL gene as a cause of autosomal dominant retinitis pigmentosa. OBJECTIVE: To determine the characteristic features of the autosomal dominant retinitis pigmentosa phenotype associated with the NRL Ser50Thr mutation in affected individuals from 4 related families. METHODS: Clinical records were available for 21 affected individuals; 7 underwent more extensive electrophysiologic and psychophysical testing. RESULTS: Night blindness was the first symptom to manifest, with onset between birth and age 16 years. Difficulty with peripheral vision was experienced between 20 and 37 years of age. Visual acuity was well preserved in younger individuals, but those older than 30 years frequently had substantial visual loss (6/36 or worse) associated with macular atrophy. Electrophysiologic testing revealed a nondetectable scotopic electroretinogram with relative preservation of the photopic electroretinogram and pattern electroretinography in the 3 youngest patients tested (aged 15-18 years). In older individuals, all components of the electroretinogram were nondetectable. Dark-adapted visual fields in younger individuals were greatly impaired, but their photopic fields remained relatively well preserved. Older patients had photopic fields limited to just a few degrees. Distinctive peripapillary chorioretinal atrophy seems to develop as the disorder progresses. CONCLUSIONS: The NRL Ser50Thr mutation is associated with selective loss of scotopic function before age 20 years. With time, however, the photopic system becomes affected, leading to loss of the photopic visual field and of visual acuity.

Adolescent↗
PubMed2003

Macular pigment density and distribution: comparison of fundus autofluorescence with minimum motion photometry.

Macular pigment (MP) distribution profiles were measured for 18 subjects using a Moreland anomaloscope modified for motion photometry. The total amount of MP within the central 7 degrees was estimated from the distribution profile by numerical integration. Fundus autofluorescence images were obtained for eight of these subjects using a scanning laser ophthalmoscope. Peak optical density of MP increased with the total amount present, but the correlation was weakened by inter-subject differences in MP distribution. The mean MP distribution derived from mean grey-scale profiles of fundus autofluorescence images correlated closely with that obtained psychophysically (r=0.96). Autofluorescence imaging provides a fast non-invasive method for assessing MP in vivo.

Aging↗
PubMed2003

Age-related changes in the dynamics of human albino visual pathways.

A deficiency of melanin in the retinal pigment epithelium, which regulates the development of neural retina, leads to chiasmal misrouting such that the uncrossed pathway (to the ipsilateral hemisphere) is reduced relative to the crossed pathway (to the contralateral hemisphere). This study examines age-related changes in the flash and pattern appearance visual evoked potentials (VEP) of human albinos. Scalp recorded cortical VEPs to flash (FVEP) and pattern appearance stimulation were recorded in 58 albino (8 months to 60 years) and 34 normal subjects (4-55 years). VEPs were analysed by amplitude and latency. The contralateral hemisphere FVEP amplitude decreased with age in albino subjects, as in both hemispheres in normals. However, the ipsilateral hemisphere FVEP amplitude was significantly lower in young albino subjects, initially giving a marked interhemispheric asymmetry, but this normalized with age. Significant interhemispheric FVEP latency asymmetries were not observed. The contralateral pattern appearance VEP latency in albino subjects decreased with age, as in both hemispheres in normals; the ipsilateral latency increased significantly with age. Significant interhemispheric pattern appearance VEP amplitude asymmetries were not observed. These novel and unexpected observations indicate significant age-related changes in the retinocortical pathways of the human albino. These changes have implications for our understanding of development and plasticity of the central visual pathways.

Adolescent↗
PubMed2003

Electrophysiological and psychophysical differences between early- and late-onset strabismic amblyopia.

PURPOSE: To compare visual evoked potentials (VEPs) and contrast sensitivity in adults with early- or late-onset strabismic amblyopia. METHODS: Twelve adults with early- and 12 with late-onset strabismic amblyopia with similar ranges of visual acuity were studied. Pattern-onset VEPs to 30-minute checks were recorded at a range of contrast levels. Contrast sensitivity (CS) was measured at 3.2 cyc/deg using a two-alternative, forced-choice staircase method. RESULTS: There was no significant difference in VEP CII latency or amplitude between amblyopic and fellow eyes across all contrast levels for the early-onset group, but in the late-onset group, CII latencies were significantly longer and amplitudes smaller in the amblyopic eye. CII responses in both amblyopic and fellow eyes of the early-onset amblyopes were of significantly shorter latency and smaller amplitude than normal. In the late-onset group the CII responses from the amblyopic eye were of significantly increased latency and reduced amplitude compared with normal, whereas latency and amplitude of fellow eye responses did not differ significantly from normal. Late-onset amblyopes showed reduced CS across the central field for the amblyopic eye, but increased CS for the fellow eye compared with normal. In the early-onset group, central CS did not differ between amblyopic and fellow eyes or from normal. CONCLUSIONS: There are significant differences in the electrophysiological and psychophysical characteristics of adults with early- and late-onset strabismic amblyopia.

Adolescent↗
PubMed2003

An early-onset autosomal dominant macular dystrophy (MCDR3) resembling North Carolina macular dystrophy maps to chromosome 5.

PURPOSE: To characterize the phenotype of an autosomal dominant macular dystrophy and identify the chromosomal locus. METHODS: Thirteen members of a four-generation, nonconsanguineous British family were examined clinically and also underwent automated perimetry, fundus fluorescein angiography, and fundus autofluorescence imaging. After informed consent was obtained, blood samples were taken for DNA extraction, and genetic linkage analysis was performed. RESULTS: The retinal changes have an early age of onset and are confined to the macular region. The macular abnormalities vary from mild retinal pigment epithelium (RPE) pigmentary change to atrophy. Drusen-like deposits are present to various degrees and are characteristic of the phenotype. Subretinal neovascular membrane (SRNVM) is an established complication. Genetic linkage analysis established linkage to chromosome 5, region p13.1-p15.33 with a maximum LOD score of 3.61 at a recombination fraction of 0.00 for marker D5S630. The locus for this autosomal dominant macular dystrophy lies between flanking markers D5S1981 and D5S2031. CONCLUSIONS: A novel locus has been identified for early-onset autosomal dominant macular dystrophy on chromosome 5.

Adolescent↗
PubMed2003

Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity.

PURPOSE: To examine the functional significance of central abnormalities present in fundus autofluorescence (AF) images in patients with rod-cone dystrophy and good visual acuity. METHODS: Thirty patients were selected according to three criteria: a clinical diagnosis of retinitis pigmentosa (RP) confirmed with International Society for Clinical Electrophysiology of Vision (ISCEV) standard ERGs, a parafoveal ring of increased high density on fundus AF imaging, and a visual acuity of 20/30 or better. Macular function was assessed with pattern electroretinography (PERG) to checkerboard stimuli of different field sizes. Fundus AF imaging was performed with a confocal scanning laser ophthalmoscope. RESULTS: The radius of the parafoveal ring of high density varied between 1.5 degrees and 9 degrees. The PERG P50 amplitude correlated highly with the radius of the ring of increased autofluorescence (r = 0.80, P < 0.0005, n = 30). PERGs to smaller circular field sizes were present, but increasing field size to beyond that of the high-density autofluorescence ring did not produce further increases in P50 amplitude. There was a high correlation between the minimum stimulus size required to elicit a maximum-amplitude PERG and the radius of the ring (r = 0.87). CONCLUSIONS: The high correlation between AF imaging and PERG, an established technique in the assessment of central retinal function, demonstrates the likelihood that autofluorescence abnormalities have functional significance and may therefore be a valuable additional parameter in the monitoring of these patients.

Adolescent↗
PubMed2002

Clinical variations in assessment of bull's-eye maculopathy.

OBJECTIVES: To evaluate the phenotypic variation in bull's-eye maculopathy and seek possible correlations between functional loss and clinical appearance. METHODS: From January 1, 1999, to September 30, 2000, we prospectively examined patients with bull's-eye lesions. Age of onset, duration of symptoms, visual acuity, clinical appearance, and autofluorescence images were recorded, the area of atrophy measured, and electrophysiologic investigations performed. RESULTS: Forty-seven patients, including 6 sibling pairs, met the study entry criteria. On the basis of autofluorescence imaging, 3 distinct groups were identified. Group 1 showed a distinct ring of increased autofluorescence surrounding an area of decreased autofluorescence. In group 2, the ring of increased autofluorescence was not present. Group 3 displayed a speckled appearance within the affected area. All patients had evidence of central sparing in an area of centrally increased autofluorescence. There was significant correlation with the age of onset, visual acuity, and duration of disease. Electrophysiologic tests revealed that 28 patients had macular dysfunction only, 14 had cone-rod dystrophy, 3 had rod-cone dystrophy, and only 2 (monozygotic twins) had cone dystrophy. The correlation between electrophysiologic and autofluorescence data was poor. The sibling pairs had concordant autofluorescence appearance, but electrophysiologic grouping differed in 2 pairs. CONCLUSIONS: Bull's-eye maculopathy represents a heterogeneous group of disorders. The clinical appearance was not helpful in assessing the degree of retinal dysfunction. The difference in qualitative characteristics of functional loss between siblings implies that these attributes do not necessarily reflect the influence of the primary mutation.

Adolescent↗
PubMed2002

Visual evoked potentials in successfully treated strabismic amblyopes and normal subjects.

PURPOSE: To assess electrophysiological recovery in successfully treated strabismic amblyopes. METHODS: Pattern reversal visual evoked potentials were recorded from 11 successfully treated strabismic amblyopes 7 to 11 years of age and 10 age-matched normal children using 12.5' and 50' checks. RESULTS: Nine amblyopic eyes had recovered to a Snellen acuity of 6/6 or better, and the remaining 2 were 6/9 after patching. Comparison between the amblyopic and the fellow eyes showed significantly lower P100 amplitude for the amblyopic eyes with small checks (difference -16.7%; P <.02) and significantly longer latency with larger checks difference (+5.0%; P <.02). The P100 latencies to stimulation of both the amblyopic and fellow eyes by 12.5' checks were markedly longer than in normal subjects (amblyopic eye, +11.7%, P <.0001; fellow eye, +7.7% P <.002). CONCLUSIONS: Successfully treated amblyopic eyes showed significantly longer latency than did normal eyes with small check stimulation. However, the nonamblyopic fellow eyes also showed significantly longer latency than did normal eyes, suggesting altered central processing.

Amblyopia↗
PubMed2002

Relationship between electrophysiological, psychophysical, and anatomical measurements in glaucoma.

PURPOSE: To evaluate the relationship between electrophysiological, psychophysical, and structural measurements in normal and glaucomatous eyes and to test the hypothesis that there is a continuous structure-function relationship between ganglion cell numbers and visual field sensitivity. METHODS: Thirty-four normal subjects and 40 patients with glaucoma were examined with the pattern electroretinogram (PERG), perimetry and retinal tomography. Transient and steady state (SS) PERGs were recorded, and peak (P)-to-trough (N) amplitude was measured. The unit of differential light sensitivity (DLS) in perimetry is the decibel. The decibel is 10. log(1/Lambert), where the Lambert is the unit of test spot intensity. PERG amplitudes were correlated with decibel and 1/Lambert DLS for the central 18 degrees of the visual field and with neuroretinal rim area in the temporal part of the optic disc. Age-related changes in the structural and functional measurements were sought. The correlation between variables was investigated by linear and quadratic regression analysis. A quadratic (y = ax + bx(2) + c) fit was taken to be significantly better than a linear fit, if the coefficient (b) for the x(2) term was significant at P < 0.05. RESULTS: A quadratic fit between decibel DLS and PERG amplitude (transient PERG: R(2) = 0.40, P = 0.0000; SS PERG: R(2) = 0.32, P = 0.0000) was significantly better than a linear fit. There was a linear correlation between 1/Lambert DLS and PERG amplitude (transient PERG: R(2) = 0.44, P = 0.0000; SS PERG: R(2) = 0.35, P = 0.0000). There was a linear correlation between temporal neuroretinal rim area and PERG amplitude (transient PERG: R(2) = 0.17, P = 0.0003; SS PERG: R(2) = 0.20, P = 0.0001). A quadratic fit between decibel DLS and temporal neuroretinal rim area (R(2) = 0.38, P = 0.0000) was significantly better than a linear fit. There was a linear correlation between 1/Lambert DLS and temporal neuroretinal rim area (R(2) = 0.30, P = 0.0000). Both DLS and PERG amplitude declined with age in the normal subjects. The rate of decline was -0.17%, -0.74%, -0.75%, and -0.78% per year for decibel DLS, 1/Lambert DLS, transient PERG, and SS PERG, respectively. CONCLUSIONS: There is a curvilinear relationship between decibel DLS and both PERG amplitude and neuroretinal rim area, and a linear relationship between 1/Lambert DLS and PERG amplitude and neuroretinal rim area. These findings support the hypothesis that there is no ganglion cell functional reserve but a continuous structure-function relationship, and that the impression of a functional reserve results from the logarithmic (decibel) scaling of the visual field.

Aged↗