The effect of coloured overlays and lenses on reading: a systematic review of the literature.

PURPOSE: There are many anecdotal claims and research reports that coloured lenses and overlays improve reading performance. Here we present the results of a systematic review of this literature and examine the quality of the evidence. METHODS: We systematically reviewed the literature concerning the effect of coloured lenses or overlays on reading performance by searching the PsychInfo, Medline and Embase databases. This revealed 51 published items (containing 54 data sets). Given that different systems are in use for issuing coloured overlays or lenses, we reviewed the evidence under four separate system headings (Intuitive, Irlen, Harris/Chromagen and Other), classifying each published item using the Cochrane Risk of Bias tool. RESULTS: Although the different colour systems have been subjected to different amounts of scientific scrutiny, the results do not differ according to the system type, or whether the sample under investigation was classified as having visual stress (or a similarly defined condition), reading difficulty, or both. The majority of studies are subject to 'high' or 'uncertain' risk of bias in one or more key aspects of study design or outcome, with studies at lower risk from bias providing less support for the benefit of coloured lenses/overlays on reading ability. While many studies report improvements with coloured lenses, the effect size is generally small and/or similar to the improvement found with a placebo condition. We discuss the strengths and shortcomings of the published literature and, whilst acknowledging the difficulties associated with conducting trials of this type, offer some suggestions about how future trials might be conducted. CONCLUSIONS: Consistent with previous reviews and advice from several professional bodies, we conclude that the use of coloured lenses or overlays to ameliorate reading difficulties cannot be endorsed and that any benefits reported by individuals in clinical settings are likely to be the result of placebo, practice or Hawthorne effects.

Steroids 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 injury, optic nerve swelling within the optic nerve canal can result in secondary retinal ganglion cell loss. Optic nerve decompression with steroids or surgical interventions or both has therefore been advocated as a means of improving visual prognosis in TON. OBJECTIVES: The aim of this review was to examine the effectiveness and safety of using steroids in TON. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to May 2013), EMBASE (January 1980 to May 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to May 2013), Web of Science Conference Proceedings Citation Index- Science (CPCI-S) (January 1990 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 May 2013. We also searched the reference lists of included studies, other reviews and book chapters on TON to find references to additional trials. The Science Citation Index was used to look for papers that cited the studies included in this review. We did not manually search any journals or conference proceedings. We contacted trial investigators and experts in the field to identify additional published and unpublished studies. SELECTION CRITERIA: We planned to include only randomised controlled trials (RCTs) of TON in which any steroid regime, either on its own or in combination with surgical optic nerve decompression, was compared to surgery alone or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the titles and abstracts identified from the electronic searches. MAIN RESULTS: We included one study that met our selection criteria; a double-masked, placebo-controlled, randomised trial of high dose intravenous steroids in patients with indirect TON diagnosed within seven days of the initial injury. A total of 31 eligible participants were randomised to receive either high dose intravenous steroids (n = 16) or placebo (n = 15), and they were all followed-up for three months. Mean final best corrected visual acuity (BCVA) was 1.78±1.23 Logarithm of the Minimum Angle of Resolution (LogMAR) in the placebo group, and 1.11±1.14 LogMAR in the steroid group. The mean difference in BCVA between the placebo and steroid groups was 0.67 LogMAR (95% confidence interval -1.54 to 0.20), and this difference was not statistically significant (P = 0.13). At three months follow-up, an improvement in BCVA of 0.40 LogMAR occurred in eight eyes (8/15, 53.3%) in the placebo group, and in 11 eyes (11/16, 68.8%) in the treatment group. This difference was not statistically significant (P = 0.38). AUTHORS' CONCLUSIONS: There is a relatively high rate of spontaneous visual recovery in TON and there is no convincing data that steroids provide any additional visual benefit over observation alone. Recent evidence also suggests a possible detrimental effect of steroids in TON and further studies are urgently needed to clarify this important issue. Each case therefore needs to be assessed on an individual basis and proper informed consent is paramount.

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: To examine the effects and safety of surgical interventions in the management of TON. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to May 2013), EMBASE (January 1980 to May 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 May 2013. We also searched the reference lists of other reviews and book chapters on TON. We also contacted researchers in the field. SELECTION CRITERIA: We planned to include only randomised controlled trials (RCTs) 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, RCT of surgical intervention in TON, this will prove a difficult endeavour.

Eyelid surgery in ocular myopathies.

OBJECTIVE: To retrospectively analyse surgical outcome and complications in patients with ocular myopathy undergoing ptosis correction and to introduce preoperative prophylactic lower lid elevation in this group. METHODS: The medical records of all ocular myopathy patients who had undergone oculoplastic surgery between June 1995 and May 2006 were obtained. Patients' demographics, surgical details and measurements, and complications were recorded. RESULTS: 29 patients were identified; 21 with chronic progressive external ophthalmoplegia (CPEO), 7 with myotonic dystrophy (MD) and 1 with oculopharyngeal muscular dystrophy (OPMD). Then, 61 procedures to adjust eyelid height were performed, comprising levator resection, brow suspension, anterior lamellar repositioning, lower lid elevation and upper lid lowering. Palpebral aperture was significantly increased in all patient groups, by procedure and diagnosis, more significantly following brow suspension compared with levator resection. The patients' feedback was very positive. Post-operative complications were few, included corneal exposure and ulceration, ptosis recurrence, arched brow, and sling infection, all of which were successfully treated. CONCLUSION: Our results demonstrate subjective and objective benefit following surgery in these patients, with a low complication rate. The use of pre-operative prophylactic lower lid elevation procedures is a promising modality.

OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.

Pathogenic OPA1 mutations cause autosomal dominant optic atrophy (DOA), a condition characterized by the preferential loss of retinal ganglion cells and progressive optic nerve degeneration. Approximately 20% of affected patients will also develop more severe neuromuscular complications, an important disease subgroup known as DOA(+). Cytochrome c oxidase (COX)-negative fibres and multiple mitochondrial DNA (mtDNA) deletions have been identified in skeletal muscle biopsies from patients manifesting both the pure and syndromal variants, raising the possibility that the accumulation of somatic mtDNA defects contribute to the disease process. In this study, we investigated the mtDNA changes induced by OPA1 mutations in skeletal muscle biopsies from 15 patients with both pure DOA and DOA(+) phenotypes. We observed a 2- to 4-fold increase in mtDNA copy number at the single-fibre level, and patients with DOA(+) features had significantly greater mtDNA proliferation in their COX-negative skeletal muscle fibres compared with patients with isolated optic neuropathy. Low levels of wild-type mtDNA molecules were present in COX-deficient muscle fibres from both pure DOA and DOA(+) patients, implicating haplo-insufficiency as the mechanism responsible for the biochemical defect. Our findings are consistent with the 'maintenance of wild-type' hypothesis, the secondary mtDNA deletions induced by OPA1 mutations triggering a compensatory mitochondrial proliferative response in order to maintain an optimal level of wild-type mtDNA genomes. However, when deletion levels reach a critical level, further mitochondrial proliferation leads to replication of the mutant species at the expense of wild-type mtDNA, resulting in the loss of respiratory chain COX activity.

A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy.

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

Steroids 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 injury, optic nerve swelling within the optic nerve canal can result in secondary retinal ganglion cell loss. Optic nerve decompression with steroids or surgical interventions or both has therefore been advocated as a means of improving visual prognosis in TON. OBJECTIVES: The aim of this review was to examine the effectiveness and safety of using steroids in TON. SEARCH STRATEGY: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 11), MEDLINE (January 1950 to November 2010), EMBASE (January 1980 to November 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (http://clinicaltrials.gov) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 23 November 2010. We also searched the reference lists of included studies, other reviews and book chapters on TON to find references to additional trials. The Science Citation Index was used to look for papers that cited the studies included in this review. We did not manually search any journals or conference proceedings. We contacted trial investigators and experts in the field to identify additional published and unpublished studies. SELECTION CRITERIA: We planned to include only randomised controlled trials (RCTs) of TON in which any steroid regime, either on its own or in combination with surgical optic nerve decompression, was compared to surgery alone or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the titles and abstracts identified from the electronic searches. MAIN RESULTS: We included one study that met our selection criteria; a double-masked, placebo-controlled, randomised trial of high dose intravenous steroids in patients with indirect TON diagnosed within seven days of the initial injury. A total of 31 eligible participants were randomised to receive either high dose intravenous steroids (n = 16) or placebo (n = 15), and they were all followed-up for three months. Mean final best corrected visual acuity (BCVA) was 1.78±1.23 Logarithm of the Minimum Angle of Resolution (LogMAR) in the placebo group, and 1.11±1.14 LogMAR in the steroid group. The mean difference in BCVA between the placebo and steroid groups was 0.67 LogMAR (95% confidence interval -1.54 to 0.20), and this difference was not statistically significant (P = 0.13). At three months follow-up, an improvement in BCVA of 0.40 LogMAR occurred in eight eyes (8/15, 53.3%) in the placebo group, and in 11 eyes (11/16, 68.8%) in the treatment group. This difference was not statistically significant (P = 0.38). AUTHORS' CONCLUSIONS: There is a relatively high rate of spontaneous visual recovery in TON and there is no convincing data that steroids provide any additional visual benefit over observation alone. Recent evidence also suggests a possible detrimental effect of steroids in TON and further studies are urgently needed to clarify this important issue. Each case therefore needs to be assessed on an individual basis and proper informed consent is paramount.

The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.

PURPOSE: Autosomal dominant optic atrophy (DOA) is a major cause of visual impairment in young adults that is characterized by selective retinal ganglion cell loss. To define the prevalence and natural history of this optic nerve disorder, we performed a population-based epidemiologic and molecular study of presumed DOA cases in the north of England. DESIGN: Case series. PARTICIPANTS: Seventy-six affected probands with a clinical diagnosis of DOA were identified from our neuro-ophthalmology and neurogenetics database. METHODS: OPA1 genetic testing was performed using a polymerase chain reaction-based sequencing strategy. OPA1-negative cases were then screened for large-scale OPA1 rearrangements and OPA3 mutations. Additional affected family members identified through contact tracing were examined, and longitudinal visual data were analyzed. MAIN OUTCOME MEASURES: The prevalence and molecular characteristics of DOA in the north of England. Visual function and disease progression among patients with OPA1-positive mutations. RESULTS: The detection rate of OPA1 mutations was 57.6% among probands with a positive family history of optic atrophy (19/33) and 14.0% among singleton cases (6/43). Approximately two thirds of our families with DOA harbored OPA1 mutations (14/22, 63.6%), and 5 novel OPA1 mutations were identified. Only 1 family carried a large-scale OPA1 rearrangement, and no OPA3 mutations were found in our optic atrophy cohort. The minimum point prevalence of DOA in the north of England was 2.87 per 100,000 (95% confidence interval [CI], 2.54-3.20), or 2.09 per 100,000 (95% CI, 1.95-2.23) when only OPA1-positive cases were considered. Snellen visual acuity varied markedly between OPA1-positive cases with a mean of 20/173 (range 20/20 to hand movements), and visual function worsened in 67.4% of patients during follow-up. The mean rate of visual loss was 0.032 logarithm of the minimum angle of resolution per year, but some patients experienced faster visual decline (range = 0-0.171 logarithm of the minimum angle of resolution/year). OPA1 missense mutations were associated with a significantly worse visual outcome compared with other mutational subtypes (P=0.0001). CONCLUSIONS: Dominant optic atrophy causes significant visual morbidity and affects at least 1 in 35,000 of the general population.

Medically unexplained visual loss in adult patients.

PURPOSE OF REVIEW: In this review, we discuss the investigation and management of patients with visual loss that cannot be accounted for by organic pathology. RECENT FINDINGS: Because visual loss in these patients often has a psychosocial basis, we do not like the term 'medically unexplained visual loss' as a diagnostic label. 'Unexplained visual loss' is a useful working diagnosis until occult pathology is excluded and a positive diagnosis of functional visual loss (FVL) can be established. Recent literature highlights the utility and limitations of visually evoked potentials in estimating objective visual acuity. Multifocal electroretinography and ocular coherence tomography are invaluable in revealing occult macular pathology that may not be apparent to clinical examination and full-field electroretinography testing. Cortical visual loss can be mistaken for FVL. There is still no evidence base to guide our management of patients with FVL. However, useful insights can be gained from the literature on functional symptoms in other specialties. SUMMARY: Making the diagnosis of FVL demands vigilance but is important to do. It should mark not just the end of investigation, but the start of treatment. More research is needed to see if treatments used in other functional disorders work in FVL.

Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance.

Mutations in nuclear genes involved in mitochondrial DNA (mtDNA) maintenance cause a wide range of clinical phenotypes associated with the secondary accumulation of multiple mtDNA deletions in affected tissues. The majority of families with autosomal dominant progressive external ophthalmoplegia (PEO) harbour mutations in genes encoding one of three well-characterized proteins--pol gamma, Twinkle or Ant 1. Here we show that a heterozygous mis-sense mutation in OPA1 leads to multiple mtDNA deletions in skeletal muscle and a mosaic defect of cytochrome c oxidase (COX). The disorder presented with visual failure and optic atrophy in childhood, followed by PEO, ataxia, deafness and a sensory-motor neuropathy in adult life. COX-deficient skeletal muscle fibres contained supra-threshold levels of multiple mtDNA deletions, and genetic linkage, sequencing and expression analysis excluded POLG1, PEO1 and SLC25A4, the gene encoding Ant 1, as the cause. This demonstrates the importance of OPA1 in mtDNA maintenance, and implicates OPA1 in diseases associated with secondary defects of mtDNA.

Acute red eye and back pain as a presentation for systemic illness: case report.

BACKGROUND: Acute red eye is a common presentation in both primary and secondary care. Presentation in combination with other systemic symptoms can indicate serious underlying pathology. CASE PRESENTATION: 73-year-old lady presenting with endogenous endophthalmitis and thoracic discitis secondary to sub-acute bacterial endocarditis. CONCLUSION: Acute red eye in combination with systemic symptoms requires immediate investigation. If endogenous endophthalmitis is diagnosed, a source of sepsis should be comprehensively investigated and referral made to individual specialties if necessary.

A polymorphism at codon 31 of gene p21 is not associated with primary open angle glaucoma in Caucasians.

BACKGROUND: Primary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage. An unstable or altered p21 protein could modify the cellular response to genomic injury and abolish the effect of p21. A previous study on a Chinese cohort suggested that the p21 codon 31 polymorphism may alter the state of apoptosis in glaucomatous optic neuropathy, failing to protect the ganglion cells. The aim of this study was to test the hypothesis that a p21 codon 31 polymorphism is associated with POAG on a Caucasian cohort. METHODS: 140 POAG patients and a control group of 73 healthy individuals were included in the study. All the subjects were of Caucasian origin. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for a single nucleotide polymorphism (C/A transversion) in the third base of codon 31 of p21, which leads to a serine (Ser)/arginine (Arg) substitution. RESULTS: The distribution of the genotypes in the POAG patients showed 128 (91.4%) Ser homozygotes, 10 (7.1%) Ser/Arg heterozygotes and 2 (1.5%) Arg homozygotes. In the control cohort, there were 61 (83.6%) Ser homozygotes and 12 (16.4%) Ser/Arg heterozygotes. No Arg homozygotes were present amongst the control group. Both the allelic and genotypic frequencies of the Ser or Arg residues at codon 31 were not significantly different between POAG patients and controls (Fisher's exact test, P = 0.20 for alleles and P = 0.0561 for genotypes). CONCLUSION: This study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG in the Caucasian population.

Using coloured filters to reduce the symptoms of visual stress in children with reading delay.

The way citation distortion can create unfounded authority in a subject area is exemplified in the paper "Coloured filters to reduce the symptoms of visual stress in children with reading delay", published early online in the Scandinavian Journal of Occupational Therapy. The diagnostic criteria for visual stress remain unclear, for which reason the prevalence figures should be viewed with scepticism. Randomized controlled trials with placebo control groups consistently show improvements in experimental and control lenses. This letter is a critical review of the evidence cited in the introduction to the paper. In the light of this the most likely explanation for their results is the placebo effect.

Apolipoprotein E promoter polymorphisms do not have a major influence on the risk of developing primary open angle glaucoma.

PURPOSE: Primary open angle glaucoma (POAG) is a major cause of late onset visual failure of unknown etiology. Recent genetic association studies have implicated the apolipoprotein E (APOE) gene in the pathophysiology of primary open angle glaucoma, but there have been conflicting findings. METHODS: To resolve this issue we studied 140 cases and 73 controls that were carefully phenotyped, and used a logistic regression model to simultaneously analyze the effect of apolipoprotein E genotype and functional polymorphisms in the apolipoprotein E gene promoter while controlling for potentially confounding variables. RESULTS: We found no evidence of an association between the apolipoprotein E promoter region polymorphisms and primary open angle glaucoma. CONCLUSIONS: Apolipoprotein E promoter polymorphisms are unlikely to have a major impact on the pathophysiology of primary open angle glaucoma.

The distribution of mitochondrial activity in relation to optic nerve structure.

BACKGROUND: The observation of a buildup of mitochondria at the level of the lamina cribrosa in the optic nerve head has traditionally been attributed to axoplasmic stasis. However, this region is also the transition zone for myelination, resulting in differing energy requirements. OBJECTIVE: To investigate the relationship between myelination and mitochondrial activity in optic nerve tissue. METHODS: Histological, histochemical, and immunocytochemical techniques were used to demonstrate the distribution of myelin, cytochrome-c oxidase activity, and laminar structure in human optic nerve tissue. A study of rabbit optic nerve and retina and unmyelinated human pituitary stalk was also performed. Cytochrome-c oxidase activity in the human optic nerve tissue was measured using microphotometry. RESULTS: There was a striking inverse relationship between myelination and mitochondrial distribution in all tissue studied. Statistical analysis of microphotometric data showed this distribution to be highly significant. CONCLUSION: We caution against the previous inference of a process of axoplasmic stasis and suggest that, instead, the distribution of mitochondria reflects the functional requirement of different regions of the ganglion cell axon. CLINICAL RELEVANCE: Optic neuropathy is associated with several inherited disorders of mitochondria. We suggest that a fine balance exists between energy demand and tissue function in the optic nerve, which may explain why optic nerve pathological features are seen in those with mitochondrial disease.

The role of apolipoprotein E gene polymorphisms in primary open-angle glaucoma.

OBJECTIVE: To test the hypothesis that genetic polymorphisms of the apolipoprotein E (APOE) gene are associated with primary open-angle glaucoma (POAG), based on the association between neurodegenerative diseases and the APOE genotype. METHODS: Genomic DNA was examined from an unrelated cohort of 137 POAG patients and 75 control subjects from the ophthalmology department of the Royal Victoria Infirmary. The APOE allele frequency (epsilon2, epsilon3, and epsilon4 alleles) was studied by polymerase chain reaction amplification of the related locus (19q13.2), enzymatic digestion of the products, gel electrophoresis, and imaging under UV illumination. For statistical analysis, we used a logistic regression model that included intraocular pressure as a continuous variable to study the possible correlation between POAG and APOE allele frequency. RESULTS: Logistic regression analysis showed no statistically significant association between the frequency of the APOE allele and POAG for the population studied, irrespective of the IOP (epsilon2 odds ratio, 0.82; 95% confidence interval, 0.12-5.79 [P =.84]; epsilon3 odds ratio, 0.39; 95% confidence interval, 0.10-1.49 [P =.17]; and epsilon4 odds ratio, 3.84; 95% confidence interval, 0.80-18.49 [P =.09]). CONCLUSION: In our cohort, the APOE genotype does not constitute a risk factor for developing POAG, even in patients with normal-tension glaucoma.Clinical Relevance Apolipoprotein E polymorphisms do not appear to be contributory to POAG.

Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.

Leber Hereditary Optic Neuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers.