What is the prevalence of diabetic macular oedema involving the centre of the macula in patients undergoing digital diabetic retinopathy screening

Free Paper Sessions Design. Retrospective analysis. Purpose. To assess the prevalence of center-involving diabetic macular oedema (CIDMO) and risk factors. Methods. Retrospective review of patients who were screen positive for maculopathy (M1) during 2010 in East and North Birmingham. The CIDMO was diagnosed by qualitative identification of definite foveal oedema on optical coherence tomography (OCT). Results. Out of a total of 15,234 patients screened, 1194 (7.8%) were screen positive for M1 (64% bilateral). A total of 137 (11.5% of M1s) were diagnosed with macular oedema after clinical assessment. The OCT results were available for 123/137; 69 (56.1%) of these had CI-DMO (30 bilateral) which is 0.5% of total screens and 5.8% of those screen positive for M1. In those with CIDMO 60.9% were male and 63.8% Caucasian; 90% had type 2 diabetes and mean diabetes duration was 20 years (SD 9.7, range 2-48). Mean HbA1c was 8.34%±1.69, with 25% having an HbA1c =9%. Furthermore, 62% were on insulin, 67% were on antihypertensive therapy, and 64% were on a cholesterol-lowering drug. A total of 37.7% had an eGFR between 30% and 60% and 5.8% had eGFR <30. The only significant difference between the CIDMO and non-CIDMO group was mean age (67.83±12.26 vs 59.69±15.82; p=0.002). A total of 65.2% of those with CIDMO also had proliferative or preproliferative retinopathy in the worst eye and 68.1% had subsequently been treated with macular laser at the time of data review. Conclusions. The results show that the prevalence of CIDMO in our diabetic population was 0.5%. A significant proportion of macula oedema patients were found to have type 2 diabetes with long disease duration, suboptimal glycemic and hypertensive control, and low eGFR. The data support that medical and diabetic review of CIDMO patients is warranted particularly in the substantial number with poor glycemic control and if intravitreal therapies are indicated.

How accurate are photographic surrogate markers used to detect macular edema in the English national screening programme?

DESIGN. Retrospective analysis PURPOSE. Macular oedema is not directly visible on two dimensional digital photographs such that surrogate markers need to be used. In the English National Screening Programme these are exudate within one optic disc diameter (DD) of the fovea, group of exudates within two DD of the fovea and haemorrhages or microaneurysms (HMA) within one DD of the fovea with best corrected visual acuity (VA) worse than 6/9. All patients who present with any of these surrogate markers at screening are referred to an ophthalmology clinic for slit lamp examination. The purpose of this audit was to determine how many patients with positive maculopathy diagnosis on photography were truly identified by optical coherence tomography (OCT) with macular oedema. METHODS. Data was collected from patients attending digital diabetic retinopathy screening. Patients who presented with surrogate markers for macular oedema 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. RESULTS. Maculopathy by exudates: Of 155 patients 45 (29%) showed thickening on the OCT of these 12 required laser. Those who also had pre-proliferative retinopathy (n=20) were more likely to have macular oedema (75%) than those with background diabetic retinopathy. Maculopathy by HMA and VA worse than 6/9: Of 66 patients 11 (16.7%) showed thickening on the OCT. 5 (7.6%) of these had macular oedema, 5 (7.6%) epi-retinal membrane, and 1 (1.5%) age related macular degeneration. None of these patients required laser. CONCLUSIONS. The likelihood of the presence of macular oedema and requiring laser treatment is greater with macular exudation than HMA within one DD and reduced VA. Overall the surrogate markers used show low specificity for macular oedema, however combining OCT with photography does identify those with macular oedema who require a true referral for an ophthalmological slit lamp examination.

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.

Functional and perceived benefits of wearing coloured filters by patients with age-related macular degeneration

Background: The aim was to investigate the visual effect of coloured filters compared to transmission-matched neutral density filters, in patients with dry age-related macular degeneration. Methods: Visual acuity (VA, logMAR), contrast sensitivity (Pelli-Robson) and colour vision (D15) were recorded for 39 patients (average age 79.1 ± 7.2 years) with age-related macular degeneration, both in the presence and absence of glare from a fluorescent source. Patients then chose their preferred coloured and matched neutral density transmission filters (NoIR). Visual function tests were repeated with the chosen filters, both in the presence and absence of glare from the fluorescent source. Patients trialled the two filters for two weeks each, in random order. Following the trial of each filter, a telephone questionnaire was completed. Results: VA and contrast sensitivity were unaffected by the coloured filters but reduced through the neutral density filters (p < 0.01). VA and contrast sensitivity were reduced by similar amounts, following the introduction of the glare source, both in the presence and absence of filters (p < 0.001). Colour vision error scores were increased following the introduction of a neutral density filter (from 177.6 ± 60.2 to 251.9 ± 115.2) and still further through coloured filters (275.1 ± 50.8; p < 0.001). In the absence of any filter, colour vision error scores increased by 29.1 ± 55.60 units in the presence of glare (F2,107 = 3.9, p = 0.02); however, there was little change in colour vision error scores, in the presence of glare, with either the neutral density or coloured filters. Questionnaires indicated that patients tended to gain more benefit from the coloured filters. Conclusions: Coloured filters had minimal impact on VA and contrast sensitivity in patients with age-related macular degeneration; however, they caused a small reduction in objective colour vision, although this was not registered subjectively by patients. Patients indicated that they received more benefit from the coloured filters compared with neutral density filters. © 2013 The Authors © 2013 Optometrists Association Australia.

Patients with early age-related macular degeneration exhibit signs of macro- and micro-vascular disease and abnormal blood glutathione levels

Background: This pilot study aimed to investigate systemic and retinal vascular function and their relationship to circulatory markers of cardiovascular risk in early age-related macular degeneration (AMD) patients without any already diagnosed systemic vascular pathologies. Methods: Fourteen patients diagnosed with early AMD and 14 age- and gender-matched healthy controls underwent blood pressure, carotid intima-media thickness (C-IMT) and peripheral arterial stiffness measurements. Retinal vascular reactivity was assessed by means of dynamic retinal vessel analysis (DVA) using a modified protocol. Blood analyses were conducted for glutathione levels and plasma levels of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Results: The AMD patients showed significantly greater C-IMT (p = 0.029) and augmentation index (AIx) (p = 0.042) than the age-matched controls. In addition, they demonstrated a shallower retinal arterial dilation slope (Slope AD) (p = 0.005) and a longer retinal venous reaction time (RT) to flickering light (p = 0.026). Blood analyses also revealed that AMD patients exhibited higher oxidized glutathione (GSSG) (p = 0.024), lower redox index (p = 0.043) and higher LDL-C (p = 0.033) levels than the controls. Venous RT parameter correlated positively with blood GSSG levels (r = 0.58, p = 0.038) in AMD subjects, but not in the controls (p > 0.05). Conclusions: Patients diagnosed with early AMD exhibit signs of systemic and retinal vascular alterations that correlated with known risk markers for future cardiovascular morbidity. © 2013 Springer-Verlag Berlin Heidelberg.

Expressions for the nonlinear transmission performance of multi-mode optical fiber

We develop an analytical theory which allows us to identify the information spectral density limits of multimode optical fiber transmission systems. Our approach takes into account the Kerr-effect induced interactions of the propagating spatial modes and derives closed-form expressions for the spectral density of the corresponding nonlinear distortion. Experimental characterization results have confirmed the accuracy of the proposed models. Application of our theory in different FMF transmission scenarios has predicted a ~10% variation in total system throughput due to changes associated with inter-mode nonlinear interactions, in agreement with an observed 3dB increase in nonlinear noise power spectral density for a graded index four LP mode fiber. © 2013 Optical Society of America.

Fokker-Planck equation approach to the description of soliton statistics in optical fiber transmission systems

We derive rigorously the Fokker-Planck equation that governs the statistics of soliton parameters in optical transmission lines in the presence of additive amplifier spontaneous emission. We demonstrate that these statistics are generally non-Gaussian. We present exact marginal probability-density functions for soliton parameters for some cases. A WKB approach is applied to describe the tails of the probability-density functions. © 2005 Optical Society of America.

Spectral density enhancement using coherent WDM

It is shown by numerical simulations that a significant increase in the spectral density of a 40-Gb/s wavelength-division-multiplexing (WDM) system can be obtained by controlling the phase of adjacent WDM channels. These simulations are confirmed experimentally at 40 Gb/s using a coherent,comb source. This technique allows the spectral density of a nonreturn-to-zero WDM system to be increased from 0.4 to 1 b/s/Hz in a single polarization. Optical filter optimization is required to minimize power crosstalk, and appropriate strategies are discussed in this letter. Index Terms-Filtering, optical communication terminals, phase control, wavelength-division multiplexing (WDM).

Information capacity of optical fiber channels with zero average dispersion

We study the statistics of optical data transmission in a noisy nonlinear fiber channel with a weak dispersion management and zero average dispersion. Applying analytical expressions for the output probability density functions both for a nonlinear channel and for a linear channel with additive and multiplicative noise we calculate in a closed form a lower bound estimate on the Shannon capacity for an arbitrary signal-to-noise ratio.

Effect of initial retinal thickness on outcome of intravitreal bevacizumab therapy for diabetic macular edema

Purpose: To investigate whether eyes with diabetic macular edema (DME) and central retinal thickness (CRT) >400 μm had better visual and anatomical outcomes compared to eyes with a CRT <400 μm when treated with intravitreal bevacizumab in a real-world setting. Patients and methods: Patients undergoing intravitreal bevacizumab therapy for DME were identified from the departmental database of a tertiary referral unit. Following the initial injection, a retreatment was performed for any persistent macular edema, unless there had been no previous response to repeated doses. Recorded parameters included visual acuity, CRT on optical coherence tomography (spectral domain optical coherence tomography [SD-OCT]), and SD-OCT characteristics. Comparisons were made between data at baseline and 12 months after the first injection, and differences were tested for statistical significance using the Student's t-test. Results: In all, 175 eyes of 142 patients were analyzed. Patients in group 2 (CRT >400 μm) had significantly more injections than group 1 (CRT <400 μm) (4.0 versus 3.3; P=0.003). Both groups had similar numbers of eyes with preexisting epiretinal membrane and/or vitreomacular traction at baseline. The reduction in CRT was significantly greater in group 2 when compared to group 1 (P<0.0001). In terms of visual gain between baseline and month 12, each gained significantly by a mean of 0.12 logarithm of the minimum angle of resolution units (P=0.0001), but there was no difference between groups 1 and 2 (P=0.99). Conclusion: These results do not support a 400 μm baseline CRT cut-off for treating DME with bevacizumab, in contrast to published data on ranibizumab. Our results also indicate that patients with a thicker CRT require more bevacizumab injections, making treatment less cost-effective for these patients. Our results could be used by practitioners to support the use of bevacizumab in DME without applying a CRT cut-off. © 2014 Mushtaq et al.

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.

Ranibizumab 0.5 mg for diabetic macular edema with bimonthly monitoring after a phase of initial treatment:18-month, multicenter, phase IIIB RELIGHT study

Abstract PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 μm, with 32% of patients having a baseline CRT <300 μm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9-8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9-6.7; P < 0.001) and +6.5 letters (95% CI, 4.2-8.8) at month 18. The proportion of participants gaining ≥10 and ≥15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study. CONCLUSIONS: The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment.

A lower bound on the per soliton capacity of the nonlinear optical fibre channel

A closed-form expression for a lower bound on the per soliton capacity of the nonlinear optical fibre channel in the presence of (optical) amplifier spontaneous emission (ASE) noise is derived. This bound is based on a non-Gaussian conditional probability density function for the soliton amplitude jitter induced by the ASE noise and is proven to grow logarithmically as the signal-to-noise ratio increases.

Perspective work on optical fibre sensors

Optical fibre based sensors are transforming industry by permitting monitoring in hitherto inaccessible environments or measurement approaches that cannot be reproduced using conventional electronic sensors. A multitude of techniques have been developed to render the fibres sensitive to a wide range of parameters including: temperature, strain, pressure (static and dynamic), acceleration, rotation, gas type, and specific biochemical species. Constructed entirely of glass or polymer material, optical fibre devices like fibre gratings offer the properties: low loss, dielectric construction, small size, multiplexing, and so on [1-3]. In this paper, the authors will show the latest developing industrial applications, using polymer optical fibre (POF) devices, and comparing their performance with silica optical fibre devices. The authors address two pressing commercial requirements. The first concerns the monitoring of fuel level in civil aircraft. There is a strong motivation in the aerospace industry to move away from electrical sensors, especially in the fuel system. This is driven by the need to eliminate potential ignition hazards, the desire to reduce cabling weight and the need to mitigate the effects of lightning strikes in aircraft where the conventional metallic skin is increasingly being replaced by composite materials. In this case, the authors have developed pressure sensors based on a diaphragm in which a polymer fibre Bragg grating (POFBG) has been embedded [3]. These devices provide high pressure sensitivity enabling level measurement in the mm range. Also, it has developed an approach incorporating several such sensors which can compensate for temperature drifts and is insensitive to fluid density. Compared with silica fibre-based sensors, their performance is highly enhanced. Initial results have attracted the interest of Airbus from UK, who is keen to explore the potential of optical technology in commercial aircraft. The second concerns the monitoring of acoustic signals and vibration in the subsea environment, for applications in geophysical surveying and security (detection of unwanted craft or personnel). There is strong motivation to move away from electrical sensors due to the bulk of the sensor and associated cabling and the impossibility of monitoring over large distances without electrical amplification. Optical approaches like optical hydrophones [5] offer a means of overcoming these difficulties. In collaboration with Kongsberg from Norway, the authors will exploit the sensitivity improvements possible by using POF instead of silica fibre. These improvements will arise as a result of the much more compliant nature of POF compared to silica fibre (3 GPa vs 72 GPa, respectively). Essentially, and despite the strain sensitivity of silica and POFBGs being very similar, this renders the POF much more sensitive to the applied stress resulting from acoustic signals or vibration. An alternative way of viewing this is that the POF is better impedance-matched to the surrounding environment (water for the intended applications), because although its impedance is higher than that of water, it is nearly an order of magnitude smaller than that of silica. Finally, other future industrial applications will be presented and discussed, showing the vast range of the optical fiber devices in sensing applications.

Nonlinear refraction in optical lattices induced by the wave-soliton interference

In the framework of 1D Nonlinear Shrödinger Equation (NSE) we demonstrate how one can control the refractive angle of a fundamental soliton beam passing through an optical lattice, by adjusting either the shape of an individual waveguide or the relative positions of waveguides. Even for a single scatterer its shape has a nontrivial effect on the refraction direction. In the case of shallow modulation we provide an analytical description based of the effect on the soliton perturbation theory. When one considers a lattice of scatterers, there emanates an additional form factor in the radiation density (RD) of emitted waves referring to the wave-soliton beating and interference inside the lattice. We concentrate on the results for two cases: periodic lattice and disordered lattice of scattering shapes. © 2011 IEEE.