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P G Griffiths

Publications and source records attributed to P G Griffiths.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of visual function in chronic progressive external ophthalmoplegia.

AIMS: To assess the visual function of patients with chronic progressive external ophthalmoplegia (CPEO) using the Visual Function Index (VF-14). To identify discriminatory questions that reflect visual disability in mitochondrial ocular myopathies. To investigate the relationship between visual impairment and the ocular parameters routinely measured in clinical practice. METHODS: We studied 40 CPEO patients. Each patient underwent ophthalmological assessment, including best-corrected visual acuity, ptosis measures, and fundus examination for pigmentary retinopathy, and orthoptic assessment including cover test in the primary position, assessment of diplopia, and measurement of uniocular fields of fixation using the Goldmann perimeter. Patients were interviewed by telephone by an independent observer and their visual function was assessed using the VF-14. RESULTS: A total of 38 patients (95%) were visually impaired. The mean VF-14 was 72 (95% CI 66-79). Patients reported having the most difficulty with reading small print and driving at night. No significant correlation was found between the VF-14 and ocular motility parameters, ptosis, or pigmentary retinopathy. CONCLUSIONS: CPEO is associated with significant visual impairment. Measures of visual disability should be included in studies of natural history and treatment of mitochondrial ocular myopathies.

Activities of Daily Living↗
PubMed2006

The role of mitochondrial haplogroups in primary open angle glaucoma.

AIM: To investigate a possible association between mitochondrial haplogroups and primary open angle glaucoma (POAG). METHODS: Genomic DNA was extracted from 140 POAG patients and 75 healthy individuals. Restriction enzyme digest analysis of polymerase chain reaction (PCR) amplified fragments was used to determine the mitochondrial haplogroup of each patient and control. RESULTS: The median age was 73 years for the POAG patients (range 51-87, SD 8.01) and 78 years for the controls (range 68-90, SD 4.4). Mean IOP was 20.8 mm Hg for the patients (SD 2.6) and 16.2 mm Hg for the controls (SD 3.4). Median cup/disc ratio was 0.8 and 0.3 for patients and controls respectively. No statistically significant difference was found in the haplogroup distribution between the POAG patients and the healthy individuals (Fisher's exact test). CONCLUSION: In this cohort, mitochondrial haplogroups do not appear to contribute to the pathogenesis of POAG.

Aged↗
PubMed2005

Surgery for traumatic optic neuropathy.

BACKGROUND: Traumatic optic neuropathy (TON) is an important cause of severe visual loss following blunt or penetrating head trauma. Following the initial insult optic nerve swelling within the optic nerve canal or compression by bone fragments are thought to result in secondary retinal ganglion cell loss. Optic nerve decompression with steroids or surgical interventions or both have therefore been advocated to improve visual prognosis in TON. OBJECTIVES: The aim of this review was to examine the effects and safety of surgical interventions in the management of TON. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1980 to 2005 wk 31), NRR 2005 Issue 3, LILACS (September 2004) and the reference lists of other reviews and book chapters on TON. We also contacted researchers in the field. There were no date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We planned to include only randomised controlled trials of TON in which any form of surgical intervention either on its own or in combination with steroids was compared to steroids alone or no treatment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the titles and abstracts identified from the search strategy. No studies were found that met our inclusion criteria and therefore none were included for analysis. MAIN RESULTS: No studies were found that met our inclusion criteria. AUTHORS' CONCLUSIONS: The current body of evidence consists mostly of small, retrospective case series. Given the wide range of surgical interventions used in TON it is very difficult to compare these studies, even qualitatively. However, there is a relatively high rate of spontaneous visual recovery and no evidence that surgical decompression of the optic nerve provides any additional benefit. On the other hand surgery carries a definite risk of complications such as postoperative cerebrospinal fluid leak and meningitis. The decision to proceed with surgery in TON therefore remains controversial and each case needs to be assessed on its own merits. Although there is an urgent need for an adequately powered, randomised controlled trial of surgical intervention in TON, this will prove a difficult endeavour.

Humans↗
PubMed2005

Optic neuropathies--importance of spatial distribution of mitochondria as well as function.

Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic atrophy and toxic amblyopia are an important cause of irreversible visual failure. Although they are associated with a defect of mitochondrial energy production, their pathogenesis is poorly understood. A common feature to all these disorders is relatively selective degeneration of the papillomacular bundle of retinal ganglion cells resulting central or caecocentral visual field defects. The striking similarity in the pattern of clinical involvement seen with these disparate disorders suggests a common pathway in their aetiology. The existing hypothesis that the optic nerve head has higher energy demands than other tissues making it uniquely dependent on oxidative phosporylation is not satisfactory. First, other ocular tissues such as photoreceptors, which are more dependent on oxidative phosporylation are not affected. Second, other mitochondrial disorders, which have a greater impact on mitochondrial energy function, do not affect the optic nerve. The optic nerve head has certain unique ultra structural features. Ganglion cell axons exit the eye through a perforated collagen plate, the lamina cribrosa. There is a sharp discontinuity in the density of mitochondria at the optic nerve head, with a very high concentration in the prelaminar nerve fibre layer and low concentration behind the lamina. This has previously been attributed to a mechanical hold up of axoplasmic flow, which has itself been proposed as a factor in the pathogenesis of a number of optic neuropathies. More recent evidence shows that mitochondrial distribution reflects the different energy requirements of the unmyelinated prelaminar axons in comparison to the myelinated retrolaminar axons. The heterogeous distribution of mitochondria is actively maintained to support conduction through the optic nerve head. We propose that factors that disrupt the heterogeneous distribution of mitochondria can result in ganglion cell death. Evidence for this comes from studies of cultured cells with the dominant optic atrophy mutation in which mitochondrial distribution is altered and from some forms of hereditary spastic paraparesis which are associated with optic atrophy. The responsible mutations do not affect ATP production until late in the disease but do affect mitochondrial arrangement, again showing that mitochondrial distribution as well as energy production by individual mitochondria may be important in the pathogenesis of ganglion cell death. Greater understanding of the factors localising mitochondria within the ganglion cell axon in particular the interaction with cytoskeleton is required to formulate new treatments. Boosting energy production alone may not be an effective treatment.

Animals↗
PubMed2004

Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders.

While skeletal muscles generally perform specific limited roles, extraocular muscles (EOMs) have to be responsive over a wider dynamic range. As a result, EOMs have fundamentally distinct structural, functional, biochemical and immunological properties compared to other skeletal muscles. While these properties enable high fatigue resistance and the rapid and precise control of extraocular motility, they might also explain why EOMs are selectively involved in certain disorders, such as chronic progressive external ophthalmoplegia (CPEO), myasthenia gravis and Graves' ophthalmopathy. This review first gives an overview of the novel myofibre classification in EOMs and then focuses on those properties that might explain why ophthalmoplegia should be so prominent in these disorders.

Adaptation, Physiological↗
PubMed2004

Medically unexplained visual loss in adult patients.

PURPOSE: To evaluate the characteristics of patients with nonorganic or medically unexplained visual loss (MUVL) presenting to a neuro-ophthalmology clinic. METHODS: A retrospective review of the case notes of patients identified from our diagnostic register. All patients had been followed up for at least 18 months and investigations (including, in all cases, neuroimaging) had failed to reveal any underlying pathology. To be included, patients had to have at least one inconsistent feature on visual function testing. RESULTS: : We identified 58 patients with MUVL. A total of 79% of patients were female and 21% were male. In total, 36% of patients had been seen in other medical specialties with unexplained symptoms. In all, 60% of patients complained of glare or pain. Of the patients with bilateral visual loss, the acuities were frequently the same in each eye and the most common pattern of visual field loss was concentric contraction. Those with unilateral visual loss had a more variable pattern of visual failure. In total, 22% of patients showed some visual recovery though this was usually incomplete. In one patient, organic pathology accounting for the visual symptoms became apparent after the end of the 18 month follow-up period. CONCLUSIONS: Medically unexplained symptoms, in general, form an important part of the workload in most medical specialties. Unexplained symptoms in ophthalmology have not been well studied. Terminology should be brought into line with that used in other medical specialties. Further work may help in the identification of positive diagnostic features of MUVL which should not be simply a 'diagnosis of exclusion'.

Adolescent↗
PubMed2003

Nurse prescribing in glaucoma.

AIMS/PURPOSE: To investigate a nurse-led assessment clinic of new referrals of possible glaucoma. To determine the potential for nurse prescribing. To review the background literature about nurse prescribing. METHODS: Audit of the outcomes of patients attending the nurse-led glaucoma assessment clinic during two defined periods (169 patients). An audit of all patients started on timolol or latanoprost treatment by a nurse following a protocol. RESULTS: A total of 46 patients were commenced on treatment at the clinic, 31 on timolol, 14 on latanoprost, and one on brimonidine. Four of these had the treatment stopped at the review clinic in order to reassess the diagnosis. Four patients in the timolol group developed side effects requiring a change in medication, but these could not have been predicted from their past medical history. Nine patients had treatment changed or added to because the intraocular pressure was felt to be inadequately controlled. During the two 3-month audits, a further 11 patients were commenced on treatment for glaucoma at the review clinic. CONCLUSIONS: Initial data from this clinic suggest that nurses possess the diagnostic skills necessary to prescribe for new glaucoma patients. The legal and administrative frame works are developing for more nurses to be able to prescribe. With the newer prostaglandin treatments for glaucoma being available, nurses may usefully and safely be able to prescribe first-line treatments for glaucoma.

Aged↗
PubMed2002

The epidemiology of Leber hereditary optic neuropathy in the North East of England.

We performed the first population-based clinical and molecular genetic study of Leber hereditary optic neuropathy (LHON) in a population of 2,173,800 individuals in the North East of England. We identified 16 genealogically unrelated families who harbor one of the three primary mitochondrial DNA (mtDNA) mutations that cause LHON. Two of these families were found to be linked genetically to a common maternal founder. A de novo mtDNA mutation (G3460A) was identified in one family. The minimum point prevalence of visual failure due to LHON within this population was 3.22 per 100,000 (95% CI 2.47-3.97 per 100,000), and the minimum point prevalence for mtDNA LHON mutations was 11.82 per 100,000 (95% CI 10.38-13.27 per 100,000). These results indicate that LHON is not rare but has a population prevalence similar to autosomally inherited neurological disorders. The majority of individuals harbored only mutant mtDNA (homoplasmy), but heteroplasmy was detected in approximately 12% of individuals. Overall, however, approximately 33% of families with LHON had at least one heteroplasmic individual. The high incidence of heteroplasmy in pedigrees with LHON raises the possibility that a closely related maternal relative of an index case may not harbor the mtDNA mutation, highlighting the importance of molecular genetic testing for each maternal family member seeking advice about their risks of visual failure.

Adult↗
PubMed2001

Effectiveness of testing visual fields by confrontation.

Many tests are used to examine visual fields by confrontation, but such methods have not been thoroughly compared with an accepted reference standard. The choice of test might affect the identification of subtle defects in the visual field. We prospectively compared seven confrontation field tests with full-threshold automated static perimetry among 138 outpatients in an eye clinic. Our primary outcome was detection of a defect in the visual field. With automated perimetry, most field defects were small or shallow. Most confrontation field tests were insensitive in the identification of field loss. The most sensitive method was examination of the central 20 degrees visual field with a small red target (73% [95% CI 63-82]). Assessment of the visual field should thus include such a test.

Adolescent↗
PubMed2001

Mitochondrial abnormalities in ageing macular photoreceptors.

PURPOSE: To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing. METHODS: Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones. RESULTS: Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere. CONCLUSIONS: The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.

Adolescent↗
PubMed1999

Evaluation of bupivacaine-induced muscle regeneration in the treatment of ptosis in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome.

PURPOSE: Ptosis is common in patients with mitochondrial disease. Whilst surgical shortening of the levator muscle can mechanically elevate the lid, this procedure does not restore normal movement and leaves patients at risk of corneal exposure due to concomitant ophthalmoparesis. Recent studies have shown that bupivacaine-induced muscle regeneration is capable of reversing the molecular genetic and biochemical defect in patients with mitochondrial myopathies. This study was undertaken to assess the potential of this approach in restoring levator muscle function in patients with mitochondrial disease and ptosis. METHODS: The levator muscle of one eye in five patients with molecularly genetically confirmed mitochondrial DNA disease and ptosis was directly injected with 3 ml of bupivacaine hydrochloride (0.75%). Levator function was compared before and 3 months after the injection. RESULTS: No objective clinical improvement in levator function was detected following bupivacaine administration. DISCUSSION: The lack of functional recovery seen in our patients is most likely to result from a failure of bupivacaine to induce sufficient regeneration necessary to improve levator muscle function. This result indicates that consideration now needs to be given to the use of alternative and more potent myotoxic agents capable of inducing a more widespread regenerative response from the endogenous muscle satellite cells which contain low or undetectable amounts of mutant mitochondrial DNA.

Adult↗
PubMed1999

Histochemical localisation of mitochondrial enzyme activity in human optic nerve and retina.

AIMS: To demonstrate the quantitative distribution of mitochondrial enzymes within the human optic nerve and retina in relation to the pathogenesis of ophthalmic disease. METHODS: Enucleations were performed at the time of multiple organ donation and the optic nerve and peripapillary retina immediately excised en bloc and frozen. Reactivities of the mitochondrial enzymes cytochrome c oxidase and succinate dehydrogenase were demonstrated in serial cryostat sections using specific histochemical assays. RESULTS: In the optic nerve the unmyelinated prelaminar and laminar regions were rich in both cytochrome c oxidase and succinate dehydrogenase. Myelination of fibres as they exited the lamina cribrosa was associated with an abrupt reduction in enzyme activity. Within the retina, high levels of enzyme activity were found localised within the retinal ganglion cells and nerve fibre layer, the outer plexiform layer, inner segments of photoreceptors, and the retinal pigment epithelium. CONCLUSIONS: Mitochondrial enzyme activity is preserved in human optic nerve and retina retrieved at the time of multiple organ donation. The distribution of enzyme activity within the eye has implications for the understanding of the pattern of ophthalmic involvement seen in mitochondrial diseases and the site of ganglion cell dysfunction in those patients with optic nerve involvement.

DNA, Mitochondrial↗