The significance of microaneurysms and haemorrhages within one optic disc diameter of the fovea

Free paper session INTRODUCTION. Microaneurysms and haemorrhages within the macula area are a poor predictor of macular oedema as shown by optical coherence tomography (OCT). Our research suggests that it is safe and cost effective to screen patients who present with these surrogate markers annually. PURPOSE. To determine whether microaneurysms (ma) and haemorrhages (hm) within one optic disc diameter of the fovea (ma/hm<1DD) are significant predictors of macular oedema. METHODS. Data were collected over a one-year period from patients attending digital diabetic retinopathy screening. Patients who presented with ma/hm<1DD also had an OCT scan. The fast macula scan on the Stratus OCT was used and an ophthalmologist reviewed the scans to determine whether macular oedema was present. Macular oedema was identified by thickening on the OCT cross-sections. Patients were split into two groups. Group one (325 eyes) included those with best VA?6/9 and group two (30 eyes) with best VA =6/12. Only patients who had no other referable features of diabetic retinopathy were selected. RESULTS. In group one, 6 (1.8%) out of 325 eyes showed thickening on the OCT and were referred to hospital eye service (HES) for further investigation. In group two, 6 (20%) out of 30 eyes showed thickening and were referred to HES. CONCLUSIONS. Ma/hm<1DD become more significant predictors of macular oedema when VA is reduced. Results confirm the grading criteria concerning microaneurysms predicting macular oedema for referable maculopathy in the English national screening programme. OCT is a useful method to accurately identify patients requiring referral to HES.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

The SECURE study:long-term safety of Ranibizumab 0.5 mg in neovascular age-related macular degeneration

Objective - To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Design - Twenty-four–month, open-label, multicenter, phase IV extension study. Participants - Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Methods - Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Main Outcome Measures - Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Results - Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. Conclusions - The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

Value of glycaemic control in diabetes

Full text: Several Lancet publications have questioned the value of glycaemic control in diabetic patients. For example, in their Comment (Sept 29, p 1103),1 John Cleland and Stephen Atkin state that “Improved glycaemic control is not a surrogate for effective care of patients who have diabetes”, and Victor Montori and colleagues (p 1104)2 claim that “HbA1c loses its validity as a surrogate marker when patients have a constellation of metabolic abnormalities”. We are concerned that the reaction against “glucocentricity” in the field of diabetes has gone too far. Even the UK's National Prescribing Centre website, carrying the National Health Service logo, includes comments that undermine the value of glycaemic control. For example, referring to the United Kingdom Prospective Diabetes Study (UKPDS), this site states that “Compared with ‘conventional control’ there was no benefit from tight control of blood glucose with sulphonylureas or insulin with regard to total mortality, diabetes-related death, macrovascular outcomes or microvascular outcomes, including all the most serious ones such as blindness or kidney failure”.3 It is well established that better glycaemic control reduces long-term microvascular complications in type 1 and type 2 diabetes.4 In type 2 diabetes, the UKPDS reported that a composite microvascular endpoint (retinopathy requiring photocoagulation, vitreous haemorrhage, and fatal or non-fatal renal failure) was reduced by 25% in patients randomised to intensive glucose control (p=0·0099).4 To imply that these are not patient-relevant outcomes is to distort the evidence. Many studies have also found that improved glycaemic control reduces macrovascular complications.5 Do not be misled: glycaemic control remains a crucial component in the care of people with diabetes. The authors have received research support and undertaken ad hoc consultancies and speaker engagements for several pharmaceutical companies.

Resveratrol and the eye:activity and molecular mechanisms

Purpose: Alcohol consumption is inversely correlated with the incidence of cardiovascular disease. It is thought that red wine is specifically responsible for these cardiovascular benefits, due to its ability to reduce vascular inflammation, facilitate vasorelaxation, and inhibit angiogenesis. This is because of its high polyphenolic content. Resveratrol is the main biologically active polyphenol within red wine. Owing to its vascular-enhancing properties, resveratrol may be effective in the microcirculation of the eye, thereby helping prevent ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Such conditions are accountable for worldwide prevalence of visual loss. Method: A review of the relevant literature was conducted on the ScienceDirect, Web of Science, and PubMed databases. Key words used to carry out the searches included 'red wine', 'polyphenols', 'resveratrol', 'eye' and 'ocular'. Articles relating to the effects of resveratrol on the eye were reviewed. Results: The protective effects of resveratrol within the eye are extensive. It has been demonstrated to have anti-oxidant, anti-apoptotic, anti-tumourogenic, anti-inflammatory, anti-angiogenic and vasorelaxant properties. There are potential benefits of resveratrol supplementation across a wide range of ocular diseases. The molecular mechanisms underlying these protective actions are diverse. Conclusion: Evidence suggests that resveratrol may have potential in the treatment of several ocular diseases. However, while there are many studies indicating plausible biological mechanisms using animal models and in-vitro retinal cells there is a paucity of human research. The evidence base for the use of resveratrol in the management of ocular diseases needs to be increased before recommendations can be made for the use of resveratrol as an ocular supplement. © 2014 Springer-Verlag.

Is measurement of blood pressure worthwhile in the diabetic eye clinic?

Purpose - The UK Prospective Diabetic Study has confirmed the importance of blood pressure (BP) as a major risk factor for diabetic retinopathy (DR). We wanted to investigate whether measuring the BP in the diabetic eye clinic could identify new hypertensive patients and monitor control in existing ones. Patients and methods - We compared BP in patients attending the diabetic eye clinic with home blood pressure measurement (HBPM) and ambulatory BP measurement (ABPM). In all, 106 patients attending a diabetic eye clinic were selected at random from clinic attendees. BP measurement (on an Omron 705 CP) was performed in the eye clinic and also compared to HBPM three times per day with an Omron 705 CP machine, and was compared to diabetic clinic measurements. In addition, 11 randomly chosen patients had 24 h ABPM to validate the above techniques. Results - In all, 106 patients (70 male and 36 female) were recruited for the study, of which 71 were known to be hypertensive on antihypertensive medication. Of the total, 75 patients (70.8%) had BP>140/85 in the eye clinic, of which 51 (68%) were known to be hypertensive on treatment and this was confirmed in 46 (90%) on HBPM. A total of, 24 patients (22.6%) were newly diagnosed as hypertensive in the eye clinic, which was confirmed by HBPM in 22 patients (92%). The mean BP of the measurements performed in the eye clinic was significantly higher than that carried out in the diabetic clinic (P<0.01). Tropicamide 1% and phenylephrine 2.5% eye drop instillation had no effect on BP. In 11 randomly chosen patients, 24 h ABPM validated both diabetic eye clinic and home BP measurements. Conclusion - Attendance at the diabetic eye clinic is an important chance to detect both new patients with systemic hypertension and those with inadequate BP control. Ophthalmologists should be encouraged to measure BP in their diabetic patients attending diabetic eye clinics, as it is an important risk factor for DR. On the basis of our findings, good BP control is a goal yet to be achieved in diabetic patients with retinopathy.

Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells

Vascular insufficiency and retinal ischemia precede many proliferative retinopathies and stimulate secretion of various vasoactive growth factors, including vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). It is unclear, however, how PlGF, which is elevated in proliferative diabetic retinopathy and is a VEGF homolog that binds only to VEGF receptor (VEGFR)-1, promotes pathological angiogenesis. When primary microvascular endothelial cells were grown on collagen gels, PlGF-containing ligands upregulated Bcl-2 expression and stimulated the formation of capillary-like tube networks that were retained for up to 14 days in culture. The inhibition of VEGFR-1 results in a dramatic decrease in the number of capillary connections, indicating that VEGFR-1 ligands promote branching angiogenesis. In contrast, VEGF-induced tube formations and Bcl-2 expression were significantly decreased at the end of this period. Flow cytometry analysis of annexin-V/propidium iodide-stained cells revealed that PlGF and PlGF/VEGF heterodimer inhibited apoptosis in serum-deprived endothelial cells. These two growth factors stimulated a survival signaling pathway phosphatidylinositol 3-kinase (PI3K), as identified by increased Akt phosphorylation and because blocking PI3K signalling by adenovirus-mediated overexpression of wild-type phosphatase and tensin homolog on chromosome 10 (PTEN) disrupted angiogenesis and decreased Bcl-2 expression by PlGF and PlGF/VEGF heterodimer, whereas a dominant-negative PTEN mutant enhanced endothelial sprout formation and Bcl-2 expression. Together, these findings indicate that PlGF-containing ligands contribute to pathological angiogenesis by prolonging cell survival signals and maintaining vascular networks.

Severe visual impairment due to diabetes mellitus:can this be influenced by community & hospital retinal screening and formal hospital diabetic annual review?

Purpose: Diabetes is a leading cause of visual impairment in working age population in the UK. This study looked at the causes of Severe Visual Impairment(SVI) in the patients attending diabetic eye clinic and influence on the rate of SVI, over a 12 year period, after introducing retinal screening programmes in the hospital and the community in 1993 (review in 1992, 1998 & 2004). Methods: Medical records of all the patients attending the diabetic eye clinic over a period of 5months(April to August) in 1992, 1998 and 2004 were reviewed. The data collected for each patient included age, sex, ethnic origin, diabetes (type,duration &treatment), the best corrected visual acuity (present and at time of presentation), type and duration of retinopathy and attendance record to both diabetic clinic and diabetic eye clinic. In this study, SVI is defined as a visual acuity of 6/36 or worse in at least one eye. Results: In 1992, of a total 245 patients, 58patients(23.6%) had SVI {38 (15.5% of total) due to diabetic retinopathy [31(12.6%) maculopathy, 2(0.8%) vitreous haemorrhage and 5(2%) retinal detachment] and 20(8.1%) due to non–diabetic retinopathy causes}. In 1998, of a total 297, 77patients(25.9%) had SVI {33(11.1% of total) due to diabetic retinopathy [19(6.4%) maculopathy, 9(3%) proliferative retinopathy, 8(2.7%) vitreous haemorrhage and 3(1%) retinal detachment]and 44(14.8%)due to non–diabetic retinopathy}. In 2004, of a total 471, 72patients(15.2%) had SVI{46(9.7%of total) due to diabetic retinopathy [37(7.8%) maculopathy, 1(0.2%) proliferative retinopathy, 6(1.8%) vitreous haemorrhage and 2(0.4%) retinal detachment]and 26(5.5%) due to non– diabetic retinopathy causes}. Conclusions: Introduction of formalised annual diabetic review including retinal screening and a community retinal screening programme has reduced the rate of severe visual impairment due to diabetic retinopathy, in patients attending diabetic eye clinic, from 15.5% in1992 to 9.7% in2004. Keywords: diabetic retinopathy

Pain response in patients undergoing panretinal photocoagulation by continuos wave Nd-YAG laser

Purpose: Current panretinal laser photocoagulative parameters are based on the Diabetic Retinopathy Study, which used exposures of 0.1 - 0.5 second to achieve moderate intensity retinal burns. Unfortunately, many patients find these settings painful. We wanted to investigate whether reducing exposure time and increasing power to give the same endpoint, is more comfortable and effective. Methods: 20 patients having panretinal photocoagulation for the first time underwent random allocation to two forms of laser treatment: half of the retinal area scheduled for treatment was treated with Green Yag laser with conventional parameters {exposure time 0.1 second (treatment A), power density sufficient to produce a visible grey - white burns}. The other half treated with shorter exposure 0.02 second (treatment B). All patient were asked to evaluate severity of pain on a visual analogue scale ranging from 0 - 10 (0 = no pain, 10 = most severe pain). All patients were masked as to the type of treatment. The order of carrying out the treatment on each patient was randomised. Fundus photographs were taken of each hemifundus to confirm treatment. Results: Of the 20 patients, 17 had proliferative diabetic retinopathy, 2 had ischaemic central retinal vein occlusion and one had ocular ischaemic syndrome. The average pain response to treatment A was 5.11 on a visual analogue scale with a mean power of 0.178 Watt; the average pain response to treatment B was 1.40 with a mean power of 0.489 Watt. Short exposure laser burns were significantly less painful (P < 0.001). Conclusion: Shortening exposure time with increased power is more comfortable for patients undergoing panretinal photocoagulation than conventional parameters.

25th RCOphth Congress, President's Session paper:25 years of progress in medical retina

The quarter century since the foundation of the Royal College of Ophthalmologists has coincided with immense change in the subspecialty of medical retina, which has moved from being the province of a few dedicated enthusiasts to being an integral, core part of ophthalmology in every eye department. In age-related macular degeneration, there has been a move away from targeted, destructive laser therapy, dependent on fluorescein angiography to intravitreal injection therapy of anti-growth factor agents, largely guided by optical coherence tomography. As a result of these changes, ophthalmologists have witnessed a marked improvement in visual outcomes for their patients with wet age-related macular degeneration (AMD), while at the same time developing and enacting entirely novel ways of delivering care. In the field of diabetic retinopathy, this period also saw advances in laser technology and a move away from highly destructive laser photocoagulation treatment to gentler retinal laser treatments. The introduction of intravitreal therapies, both steroids and anti-growth factor agents, has further advanced the treatment of diabetic macular oedema. This era has also seen in the United Kingdom the introduction of a coordinated national diabetic retinopathy screening programme, which offers an increasing hope that the burden of blindness from diabetic eye disease can be lessened. Exciting future advances in retinal imaging, genetics, and pharmacology will allow us to further improve outcomes for our patients and for ophthalmologists specialising in medical retina, the future looks very exciting but increasingly busy.

Improving the cost-effectiveness of photographic screening for diabetic macular oedema:a prospective, multi-centre, UK study

Background/aims: Retinal screening programmes in England and Scotland have similar photographic grading schemes for background (non-proliferative) and proliferative diabetic retinopathy, but diverge over maculopathy. We looked for the most cost-effective method of identifying diabetic macular oedema from retinal photographs including the role of automated grading and optical coherence tomography, a technology that directly visualises oedema. Methods: Patients from seven UK centres were recruited. The following features in at least one eye were required for enrolment: microaneurysms/dot haemorrhages or blot haemorrhages within one disc diameter, or exudates within one or two disc diameters of the centre of the macula. Subjects had optical coherence tomography and digital photography. Manual and automated grading schemes were evaluated. Costs and QALYs were modelled using microsimulation techniques. Results: 3540 patients were recruited, 3170 were analysed. For diabetic macular oedema, England's scheme had a sensitivity of 72.6% and specificity of 66.8%; Scotland 's had a sensitivity of 59.5% and specificity of 79.0%. When applying a ceiling ratio of £30 000 per quality adjusted life years (QALY) gained, Scotland's scheme was preferred. Assuming automated grading could be implemented without increasing grading costs, automation produced a greater number of QALYS for a lower cost than England's scheme, but was not cost effective, at the study's operating point, compared with Scotland's. The addition of optical coherence tomography, to each scheme, resulted in cost savings without reducing health benefits. Conclusions: Retinal screening programmes in the UK should reconsider the screening pathway to make best use of existing and new technologies.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema:a prospective, multicentre, UK study

Objectives: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. Design: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. Setting: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Participants: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Interventions: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. Main outcome measures: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Results: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Conclusions: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. © Queen's Printer and Controller of HMSO 2013.

The association between glycated haemoglobin levels and P100 visual evoked potentials in diabetes mellitus

Diabetes mellitus (DM) is a metabolic disorder which is characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. The long-term specific effects of DM include the development of retinopathy, nephropathy and neuropathy. Cardiac disease, peripheral arterial and cerebrovascular disease are also known to be linked with DM. Type 1 diabetes mellitus (T1DM) accounts for approximately 10% of all individuals with DM, and insulin therapy is the only available treatment. Type 2 diabetes mellitus (T2DM) accounts for 90% of all individuals with DM. Diet, exercise, oral hypoglycaemic agents and occasionally exogenous insulin are used to manage T2DM. The diagnosis of DM is made where the glycated haemoglobin (HbA1c) percentage is greater than 6.5%. Pattern-reversal visual evoked potential (PVEP) testing is an objective means of evaluating impulse conduction along the central nervous pathways. Increased peak time of the visual P100 waveform is an expression of structural damage at the level of myelinated optic nerve fibres. This was an observational cross sectional study. The participants were grouped into two phases. Phase 1, the control group, consisted of 30 healthy non-diabetic participants. Phase 2 comprised of 104 diabetic participants of whom 52 had an HbA1c greater than 10% (poorly controlled DM) and 52 whose HbA1c was 10% and less (moderately controlled DM). The aim of this study was to firstly observe the possible association between glycated haemoglobin levels and P100 peak time of pattern-reversal visual evoked potentials (PVEPs) in DM. Secondly, to assess whether the central nervous system (CNS) and in particular visual function is affected by type and/or duration of DM. The cut-off values to define P100 peak time delay was calculated as the mean P100 peak time plus 2.5 X standard deviations as measured for the non-diabetic control group, and were 110.64 ms for the right eye. The proportion of delayed P100 peak time amounted to 38.5% for both diabetic groups, thus the poorly controlled group (HbA1c > 10%) did not pose an increased risk for delayed P100 peak time, relative to the moderately controlled group (HbA1c ≤ 10%). The P100 PVEP results for this study, do however, reflect significant delay (p < 0.001) of the DM group as compared to the non-diabetic group; thus, subclincal neuropathy of the CNS occurs in 38.5% of cases. The duration of DM and type of DM had no influence on the P100 peak time measurements.

Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Epidemiology of diabetes and complications among adults in the Republic of Ireland 1998-2015: a systematic review and meta-analysis

Background: Accurate estimates of the burden of diabetes are essential for future planning and evaluation of services. In Ireland, there is no diabetes register and prevalence estimates vary. The aim of this review was to systematically identify and review studies reporting the prevalence of diabetes and complications among adults in Ireland between 1998 and 2015 and to examine trends in prevalence over time. Methods: A systematic literature search was carried out using PubMed and Embase. Diabetes prevalence estimates were pooled by random-effects meta-analysis. Poisson regression was carried out using data from four nationally representative studies to calculate prevalence rates of doctor diagnosed diabetes between 1998 and 2015 and was also used to assess whether the rate of doctor diagnosed diabetes changed over time. Results: Fifteen studies (eight diabetes prevalence and seven complication prevalence) were eligible for inclusion. In adults aged 18 years and over, the national prevalence of doctor diagnosed diabetes significantly increased from 2.2 % in 1998 to 5.2 % in 2015 (p trend ≤ 0.001). The prevalence of diabetes complications ranged widely depending on study population and methodology used (6.5–25.2 % retinopathy; 3.2–32.0 % neuropathy; 2.5-5.2 % nephropathy). Conclusions: Between 1998 and 2015, there was a significant increase in the prevalence of doctor diagnosed diabetes among adults in Ireland. Trends in microvascular and macrovascular complications prevalence could not be examined due to heterogeneity between studies and the limited availability of data. Reliable baseline data are needed to monitor improvements in care over time at a national level. A comprehensive national diabetes register is urgently needed in Ireland.