Intraretinal Microvascular Abnormalities Research Articles

Characterization of In Vivo Retinal Lesions of Diabetic Retinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy.

Purpose To characterize hallmark diabetic retinopathy (DR) lesions utilizing adaptive optics scanning laser ophthalmoscopy (AOSLO) and to compare AOSLO findings with those on standard imaging techniques. Methods Cross-sectional study including 35 eyes of 34 study participants. AOSLO confocal and multiply scattered light (MSL) imaging were performed in eyes with DR. Color fundus photographs (CF), infrared images of the macula (Spectralis, Heidelberg), and Spectralis spectral domain optical coherence tomography SDOCT B-scans of each lesion were obtained and registered to corresponding AOSLO images. Main Outcome Measures Individual lesion characterization by AOSLO imaging. AOSLO appearance was compared with CF and SDOCT imaging. Results Characterized lesions encompassed 52 microaneurysms (MA), 20 intraretinal microvascular abnormalities (IRMA), 7 neovascularization (NV), 11 hard exudates (HE), 5 dot/blot hemorrhages (HEM), 4 cotton wool spots (CWS), and 14 intraretinal cysts. AOSLO allowed assessment of perfusion in vascular lesions and enabled the identification of vascular lesions that could not be visualized on CF or SDOCT. Conclusions AOSLO imaging provides detailed, noninvasive in vivo visualization of DR lesions enhancing the assessment of morphological characteristics. These unique AOSLO attributes may enable new insights into the pathological changes of DR in response to disease onset, development, regression, and response to therapy.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group: Report 3: Baseline Retinopathy and Clinical Features Predict Progression of Diabetic Retinopathy

To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH). Multicenter, national cohort study. Anonymized data of 50 254 patient eyes with diabetes mellitus at 19UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014. Time to progression of PDR and VH were calculated with Cox regression after stratifying by baseline diabetic retinopathy (DR) severity and adjusting for age, sex, race, and starting visual acuity. Progression to PDR in 5 years differed by baseline DR: no DR (2.2%), mild (13.0%), moderate (27.2%), severe nonproliferative diabetic retinopathy (NPDR) (45.5%). Similarly, 5-year progression to VH varied by baseline DR: no DR (1.1%), mild (2.9%), moderate (7.3%), severe NPDR (9.8%). Compared with no DR, the patient eyes that presented with mild, moderate, and severe NPDR were 6.71, 14.80, and 28.19 times more likely to develop PDR, respectively. In comparison to no DR, the eyes with mild, moderate, and severe NPDR were 2.56, 5.60, and 7.29 times more likely to develop VH, respectively. In severe NPDR, the eyes with intraretinal microvascular abnormalities (IRMA) had a significantly increased hazard ratio (HR) of developing PDR (HR 1.77, 95% confidence interval [CI] 1.25-2.49, P= .0013) compared with those with venous beading, whereas those with 4-quadrant dot-blot hemorrhages (4Q DBH) had 3.84 higher HR of developing VH (95% CI 1.39-10.62, P= .0095). Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.

Retinopathy with central oedema in an INS C94Y transgenic pig model of long-term diabetes.

Diabetic retinopathy is a severe complication of diabetes mellitus that often leads to blindness. Because the pathophysiology of diabetic retinopathy is not fully understood and novel therapeutic interventions require testing, there is a need for reliable animal models that mimic all the complications of diabetic retinopathy. Pig eyes share important anatomical and physiological similarities with human eyes. Previous studies have demonstrated that INS C94Y transgenic pigs develop a stable diabetic phenotype and ocular alterations such as cataracts. The aim of this study was to conduct an in-depth analysis of pathological changes in retinas from INS C94Y pigs exposed to hyperglycaemia for more than 2years, representing a chronic diabetic condition. Eyes from six INS C94Ypigs and six age-matched control littermates were analysed via histology and immunohistochemistry. For histological analyses of retinal (layer) thickness, sections were stained with H&E or Mallory's trichrome. For comparison of protein expression patterns and vessel courses, sections were stained with different antibodies in immunohistochemistry. Observed lesions were compared with reported pathologies in human diabetic retinopathy. INS C94Ypigs developed several signs of diabetic retinopathy similar to those seen in humans, such as intraretinal microvascular abnormalities, symptoms of proliferative diabetic retinopathy and central retinal oedema in a region that is cone rich, like the human macula. The INS C94Ypig is an interesting model for studying the pathophysiology of diabetic retinopathy and for testing novel therapeutic strategies.

Retinal Microvasculature in Nonproliferative Diabetic Retinopathy: Automated Quantitative Optical Coherence Tomography Angiography Assessment

Purpose: To perform a qualitative and quantitative assessment of the foveal microvasculature in eyes with diabetic maculopathy using optical coherence tomography angiography (OCT-A). Methods: Retrospective case series of 48 eyes with diabetic maculopathy and 47 healthy eyes evaluated by Spectralis OCT-A. Perifoveal arcade disruptions, linear vascular dilations, microaneurysms, intraretinal microvascular abnormalities and flow-void areas were qualitatively analyzed on OCT angiograms both for the superficial (SCP) and deep (DCP) capillary plexuses. A fully automated microstructural analysis of the foveal avascular zone (FAZ) metrics, vascular and avascular surfaces was performed. Quantitative values from diabetic patients were compared with those of healthy subjects. Results: A moderate agreement between SCP and DCP in terms of diabetes-induced vascular lesions in the qualitative assessment was shown. The comparative quantitative analysis between SCP and DCP in diabetic patients revealed a statistically significant difference (p < 0.05) in terms of FAZ perimeter and FAZ surface. No statistically significant difference was shown in total vascular and avascular surfaces. A statistically significant difference between the diabetic and control groups was noticed both for SCP and DCP considering FAZ metrics and vascular surfaces. Conclusions: A qualitative and quantitative OCT-A approach on retinal vascular perfusion may offer an objective and reliable method for monitoring disease progression in diabetic retinopathy.

Optical Coherence Tomography Angiography in Diabetes.

Diabetic retinopathy is a progressive microvascular disease that leads to increased vessel permeability, retinal ischemia, and retinal neovascularization. Optical coherence tomography angiography (OCTA) is a novel angiography technique that has the capability to advance our understanding of diabetic eye disease by providing high-resolution images of retinal and choroidal microvasculature blood flow and structure. Using OCTA, the vascular changes of diabetic retinopathy including microaneurysms, retinal non-perfusion, intraretinal microvascular abnormalities, and neovascularization can be clearly visualized. OCTA offers several advantages over fluorescein angiography (FA) in that it is faster, safer, and non-invasive, allows better visualization of retinal vessels in both the superficial and deep capillary layers, and can provide quantitative measurements of areas of non-perfusion of the macula and nerve. OCTA capillary perfusion density maps and average perfusion density values provide an easy way to grade progressive vascular change. Despite these advantages, imaging with OCTA can only provide a limited view of the peripheral retina and is unable to demonstrate leakage, staining, or pooling. OCTA requires patients to maintain good fixation to obtain high-resolution images which can be a challenge for those with severe macular disease. In patients who cannot safely undergo FA, OCTA may serve as an alternative form of angiography that can be safely and more frequently performed for the management of diabetic retinopathy.

Optical coherence tomography angiography — novel method to access retinal microcirculation in patients with diabetic retinopathy

Introduction. Optical coherence tomography angiography (OCTA) is a novel technique that allows visualization of retinal capillary network without the need for contrast usage. Being easy to perform and non-invasive, it might become significantly competitive to fluoroangiography. Material and methods. The study included 45 patients (90 eyes) with diabetes type 1 and 2 and nonproliferative and proliferative diabetic retinopathy as well as 35 healthy volunteers (70 eyes) as a control group. Beside full ophthalmic examination, all patients underwent OCTA (RTVue XR Avanti; Optovue) examination. Obtained images were used to assess the presence of morphologic changes of the retina characteristic for diabetic retinopathy (capillary density and regularity as well as occurrence of microaneurysms, ischemic areas, intraretinal microvascular abnormalities and neovascularizations). The assessment was carried out on two levels of retinal capillary plexus. Additionally, measurement of foveal avascular zone (FAZ) was performed. The results were compared with those obtained from the control group. Results. All examined eyes in the studied group exhibited one or more anomalies characteristic of diabetic retinopathy as seen on the OCTA scans, both in superficial and deep vascular plexus. In the control group we have detected capillary irregularity (9% in a superficial and 11% in a deep vascular plexus) and capillary rarefication (7% in a superficial and 9% in a deep vascular plexus) and no other anomalies were found. Mean FAZ area measured in superficial vascular plexus was 382 ± 134 square micrometers and was significantly larger (p < 0,001) in comparison to the control group (259 ± 103 square micrometers). Conclusions. Optical coherence tomography angiography is a useful diagnostic tool used to assess vascular changes in the retinal microcirculation in diabetic patients. Its main advantages are noninvasiveness, repeatability and a high quality of images acquired from the chosen level of the retina.

Neue Möglichkeiten in der retinalen Diagnostik mittels OCT-Angiografie

Instruments for using OCT angiography (OCTA) in daily clinical practice have recently become available. The aim of this paper is to report the possibilities, advantages and limitations of OCTA in the clinical diagnosis of diseases of the posterior segment of the eye. Patients with diabetic retinopathy, retinal vascular occlusions, and age-related macular degeneration who had been assigned to fluorescein angiography (FA) additionally underwent an AngioPlex™-OCTA examination, which captures a 6 × 6 mm scanning area centred on the fovea. If deemed necessary, 3 × 3 mm volume scans were created in regions of interest. The findings of FA and OCTA were correlated and compared. The OCTA procedure took only a few seconds, was easily integrated into the standard OCT diagnostic imaging procedure, and delivered highly detailed, three dimensional images of the entire microvasculature of the retina and choroid. Microvascular changes, such as microaneurysms, intraretinal microvascular abnormalities, non-perfused areas, alterations in the foveal avascular zone (FAZ) and neovascularization were reliably detected. Overall, OCTA results were in good agreement with the results of the FA. Additionally, OCTA provided more detailed and three dimensional information and thus permitted a better assessment of the spatial extension of microvascular abnormalities. Due to OCTA's limited scanning area, vascular alterations in the mid-periphery were detected only if their location had already been determined by FA. Although OCTA does not show leakage, macular oedema can be diagnosed from OCTA, together with OCT thickness measurements. OCTA provides important three dimensional information on vascular alterations and is already an indispensable diagnostic method. As the procedure takes just a few seconds and can be performed non-invasively, OCTA is well suited as a monitoring method and may allow early diagnosis. In this sense, prospective studies are required to determine precise OCTA analytical strategies for specific diseases. It is very likely that OCTA will revolutionise the diagnosis of retinal and choroidal diseases; however, it is not yet clear estimated to what extent it will replace FA.

Evaluation of Preretinal Neovascularization in Proliferative Diabetic Retinopathy Using Optical Coherence Tomography Angiography

To describe a method for visualizing preretinal neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA) and report the findings in the surrounding vasculature. Patients with PDR diagnosed on clinical examination who received OCTA scans using the RTVue XR Avanti (Optovue, Fremont, CA) were evaluated. To visualize preretinal neovascularization, OCT angiograms were segmented to project vasculature above the internal limiting membrane (ILM). OCT angiograms were segmented between the ILM and Bruch's membrane to show adjacent retinal vasculature. Thirteen eyes were determined to have preretinal neovascularization in the posterior pole based on OCTA. One OCT angiogram was not of sufficient quality and thus was eliminated from further study. Eleven eyes (92%) had neovascularization adjacent to retinal capillary nonperfusion and six (50%) were adjacent to intraretinal microvascular abnormalities (IRMAs). OCTA provided high-resolution, depth-resolved blood flow information, allowing for visualization of preretinal neovascularization, IRMA, and adjacent capillary nonperfusion.

CAPILLARY PLEXUS ANOMALIES IN DIABETIC RETINOPATHY ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To analyze the foveal microvasculature in eyes with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). In this retrospective study of 20 eyes of 14 patients with DR imaged using OCTA and FA, clinical features of DR such as microaneurysms, capillary nonperfusion areas, and intraretinal microvascular abnormalities were analyzed. In the superficial plexus, a rarefaction of capillaries with capillary nonperfusion areas was present in all eyes. Some of these nonperfused areas were not detected on FA and were better delimited on OCTA. Conversely, in the deep plexus, capillary nonperfusion areas were seen only in 35% (7/20) of eyes, whereas DR led to an alteration of the normal capillary vortex pattern in all eyes. Only 62% of microaneurysms visualized on FA were detected by OCTA (P = 0.02). Intraretinal microvascular abnormalities were well detected by both FA and OCTA. Optical coherence tomography angiography allowed detecting DR anomalies in both superficial and deep capillary plexus in all eyes. The ability of OCTA to detect microaneurysms was lower than that of FA although its accuracy for assessing capillary nonperfusion was better and may enable a proper grading of DR progression.

OCT angiography for the evaluation of macular ischemic micro‐angiopathies

SummaryThe management of maculopathies related to the retinal vascular micro‐angiopathies, has been significantly improved since the initiation of intravitreal therapeutical approaches. A detailed evaluation of the vascular abnormalities by Optical coherence tomography (OCT) angiography offers an accurate evaluation of the therapeutical indications and their beneficial anatomical effects. OCT angiography has several advantages, such as 3D visualization of retinal and choroidal circulations (including the choriocapillaris). Using this non‐invasive alternative method, ischemia, microaneurysms, intraretinal microvascular abnormalities and the detection of neovascularization can be clearly visualized by a closer observation of each layer of the retinal capillaries. As an alternative to dye‐based angiography, in addition to the 3D tomographic macular imaging, OCT angiography may be clinically useful to evaluate the microvascular status and therapeutic effect of treatments for macular ischemic microangiopathies.

Optical Coherence Tomography Angiography of Diabetic Retinopathy in Human Subjects.

Optical coherence tomography angiography (OCTA) is a novel, non-invasive OCT technique capable of imaging the retinal vasculature. This study aims to evaluate the retinal microvasculature in diabetic human subjects with OCTA and assess potential clinical applications. Cross-sectional study of 33 subjects with diabetic retinopathy. OCTA was performed on 3 mm × 3 mm sections using a swept-source OCTA prototype and a phase- and intensity-based contrasting algorithm. OCT angiograms were studied with corresponding clinical examination and fluorescein angiograms, when available, to assess accuracy and clinical utility. OCTA was able to demonstrate most clinically relevant vascular changes in subjects with diabetic retinopathy, including microaneurysms, impaired vascular perfusion, some forms of intraretinal fluid, vascular loops, intraretinal microvascular abnormalities, neovascularization, and cotton-wool spots that were largely consistent with fluorescein angiography. OCTA generates high-resolution angiograms that illustrate many of the clinically relevant findings in diabetic retinopathy and offers a novel complement or alternative to fluorescein angiography. Although currently an investigational technique, OCTA in combination with standard OCT imaging is at least as good as fluorescein angiography in the evaluation of the macular complications of diabetic retinopathy.

Reevaluating the Definition of Intraretinal Microvascular Abnormalities and Neovascularization Elsewhere in Diabetic Retinopathy Using Optical Coherence Tomography and Fluorescein Angiography

To evaluate the agreement between clinical examination, spectral-domain ocular coherence tomography (SD OCT), and fluorescein angiography (FA) in diagnosing intraretinal microvascular abnormality (IRMA) and neovascularization elsewhere (NVE) and define the SD OCT features that differentiate NVEs from IRMAs. Retrospective study. Data were collected from 23 lesions from 8 diabetic patients, seen from July 2012 through October 2013 at Moorfields Eye Hospital, United Kingdom. Main outcomes were SD OCT features and FA leakage of IRMA and neovascular complex. The agreement between 3 evaluations was analyzed by Fleiss' kappa. The following 5 SD OCT features significantly differentiated IRMAs from NVEs: (1) hyperreflective dots in superficial inner retina (P = .002); (2) the outpouching of internal limiting membrane (ILM) (P = .004); (3) the breach of ILM (P = .004); (4) the breach of posterior hyaloid (P = .0005); (5) hyperreflective dots in vitreous (P = .008). The agreement was moderate between 3 evaluations (κ = 0.48, P = 7.11 × 10(-5)) but substantial between clinical and SD OCT evaluation (κ = 0.72, P = .00055). There was no significant agreement between OCT evaluation and FA leakage (κ = 0.249, P = .232). SD OCT will be a valuable adjunct in evaluating IRMA and NVE, since it can verify the histopathologic correlate. SD OCT provides subtle anatomic insights and may be more accurate than clinical examination or leakage on FA, our current method of diagnosing this important endpoint, which has implications in future trial design for proliferative diabetic retinopathy prevention.

P.6.c.002 Blockade of central serotonin 2B receptors reduces cocaine-induced hyperlocomotion independently of subcortical DA outflow

Diabetic retinopathy (DR) is characterized by the development of intraretinal microvascular abnormalities. Endoplasmic reticulum (ER) stress is known to play a pathogenic role in vascular impairment in DR. The present study demonstrated that the treatment of human retinal endothelial cells with ER stress inducers such as thapsigargin (Tg) and tunicamycin (Tm) significantly increased the permeability of exogenously added FITC–dextran, accompanied by a decrease of transendothelial electrical resistance (TEER). The expression of claudin-5 among tight junction proteins was significantly decreased by the treatment with Tg or Tm. A p38 MAPK inhibitor, SB203580, and an NF-κB inhibitor, dexamethasone, significantly suppressed the Tg-induced down-regulation of claudin-5, decrease of TEER and leakage of added FITC–dextran. The translocation of NF-κB p65 subunit to the nucleus was also inhibited by the addition of SB203580 or dexamethasone. The effects of dexamethasone are thought to be due to the transrepression of the above signaling and direct regulation of claudin-5 gene.

Peripheral Lesions Identified by Mydriatic Ultrawide Field Imaging: Distribution and Potential Impact on Diabetic Retinopathy Severity

To assess diabetic retinopathy (DR) as determined by lesions identified using mydriatic ultrawide field imaging (DiSLO200; Optos plc, Scotland, UK) compared with Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field film photography. Prospective comparative study of DiSLO200, ETDRS 7-standard field film photographs, and dilated fundus examination (DFE). A total of 206 eyes of 103 diabetic patients selected to represent all levels of DR. Subjects had DiSLO200, ETDRS 7-standard field film photographs, and DFE. Images were graded for severity and distribution of DR lesions. Discrepancies were adjudicated, and images were compared side by side. Distribution of hemorrhage and/or microaneurysm (H/Ma), venous beading (VB), intraretinal microvascular abnormality (IRMA), and new vessels elsewhere (NVE). Kappa (κ) and weighted κ statistics for agreement. The distribution of DR severity by ETDRS 7-standard field film photographs was no DR 12.5%; nonproliferative DR mild 22.5%, moderate 30%, and severe/very severe 8%; and proliferative DR 27%. Diabetic retinopathy severity between DiSLO200 and ETDRS film photographs matched in 80% of eyes (weighted κ = 0.74,κ = 0.84) and was within 1 level in 94.5% of eyes. DiSLO200 and DFE matched in 58.8% of eyes (weighted κ = 0.69,κ = 0.47) and were within 1 level in 91.2% of eyes. Forty eyes (20%) had DR severity discrepancies between DiSLO200 and ETDRS film photographs. The retinal lesions causing discrepancies were H/Ma 52%, IRMA 26%, NVE 17%, and VB 4%. Approximately one-third of H/Ma, IRMA, and NVE were predominantly outside ETDRS fields. Lesions identified on DiSLO200 but not ETDRS film photographs suggested a more severe DR level in 10% of eyes. Distribution in the temporal, superotemporal, inferotemporal, superonasal, and inferonasal fields was 77%, 72%, 61%, 65%, and 59% for H/Ma, respectively (P<0.0001); 22%, 24%, 21%, 28%, and 22% for VB, respectively (P = 0.009); 52%, 40%, 29%, 47%, and 36% for IRMA, respectively (P<0.0001), and 8%, 4%, 4%, 8%, and 5% for NVE, respectively (P = 0.03). All lesions were more frequent in the temporal fields compared with the nasal fields (P<0.0001). DiSLO200 images had substantial agreement with ETDRS film photographs and DFE in determining DR severity. On the basis of DiSLO200 images, significant nonuniform distribution of DR lesions was evident across the retina. The additional peripheral lesions identified by DiSLO200 in this cohort suggested a more severe assessment of DR in 10% of eyes than was suggested by the lesions within the ETDRS fields. However, the implications of peripheral lesions on DR progression within a specific ETDRS severity level over time are unknown and need to be evaluated prospectively.

Chronic hyperglycemia inhibits vasoregression in a transgenic model of retinal degeneration

Vasoregression characterizes diabetic retinopathy in animal models and in humans. We have recently demonstrated that vasoregression is earlier initiated in a rat model of ciliopathy-induced retinal neurodegeneration (TGR rat). The aim was to assess the balance between vasoregressive effects of chronic hyperglycemia and photoreceptor degeneration on adult vascular remodelling. The retinas were analyzed at 4 and 9 months after streptozotocin-induced diabetes. Neurodegeneration was determined by quantitation of cell numbers and retinal layer thickness. Vasoregression was assessed by quantitative retinal morphometry in retinal digest preparations. Retinal VEGF levels were measured by ELISA. Glial activation, expression and location of HSP27 and phosphorylated HSP27 were evaluated by immunofluorescence staining. Unexpectedly, the numbers of acellular capillaries were reduced at both time points and led to fewer intraretinal microvascular abnormalities in late stage diabetic TGR. Concomitantly, inner nuclear layers (INLs) in diabetic TGR rats were protected from cell loss at both time points. Consequently, glial activation was reduced, but VEGF level was increased in diabetic TGR retinas. Expressions of HSP27 were upregulated in glia cells in the preserved INL of diabetic TGR. Chronic hyperglycemia preserves the microvasculature in the retinal model of neurodegeneration. Cell preservation in the retinal INL was associated with protective gene regulation. Together, these data indicate that diabetes can induce vasoprotection, in which retinal glia can play a particular role.

RETINAL NEOVASCULARIZATION SECONDARY TO PROLIFERATIVE DIABETIC RETINOPATHY CHARACTERIZED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY

The purpose of this study was to characterize diabetic retinal neovascularization (NV) and accompanying retinal and vitreal morphologic changes using high-resolution spectral domain optical coherence tomography. A cross-sectional retrospective analysis was performed on 16 eyes of 14 nonconsecutive subjects with proliferative diabetic retinopathy that were seen between August 2011 and December 2011 at the New England Eye Center, Boston, MA. Patients who had NV of the disk, NV elsewhere, and intraretinal microvascular abnormalities were scanned using optical coherence tomography directly over the region of the abnormal vessels. Characteristic changes of the retinal vasculature, retina, and vitreous were seen in the 16 eyes with NV. This study describes optical coherence tomography characteristics of 1) NV of the disk, 2) NV elsewhere, 3) intraretinal microvascular abnormality, 4) NV causing traction without retinal detachment; and 5) NV causing traction with retinal detachment. The morphologic appearance of vitreous traction was found to be consistent with the previous histologic reports. It is possible to image diabetic NV using spectral domain optical coherence tomography and to visualize the spectrum of retinal, retinal vascular, and vitreal changes seen through these areas of abnormal retinal vasculature.

Diabetic retinopathy.

This paper describes the importance of diabetic retinopathy in the loss of visual function. We exposed the most important risk factors, such as diabetes duration, poor metabolic control, pregnancy, puberty, hypertension, poor control of blood lipids, renal disease, and sleep apnea syndrome. We describe the pathogenesis of the disease, small retinal vessel microangiopathies which produce extravasation, edema and ischemia phenomena. We put special emphasis on the vascular endothelial growth factor (VEGF) and its pathogenic importance. They are also described the main clinical symptoms as microaneurysms, intraretinal hemorrhages, hard and soft exudates, intraretinal microvascular abnormalities (IRMA), venous disorders, formation of new vessels and diabetic macular edema (the latter being the most common cause of vision loss). Finally we describe the latest diagnostic techniques and eye treatment, with special emphasis on obesity surgery importance as more important preventive factor to eliminate the predisposing and precipitating disease symptoms.

Retinal Image Analysis for Abnormality Detection-An Overview

Problem statement: Classification plays a major role in retinal image analysis for detecting the various abnormalities in retinal images. Classification refers to one of the mining concepts using supervised or unsupervised learning techniques. Approach: Diabetic retinopathy is one of the common complications of diabetes. Unfortunately, in many cases, the patient is not aware any symptoms until it is too late for effective treatment. Diabetic retinopathy is the leading cause of blindness. Diabetic retinopathy results in retinal disorders that include microaneursyms, drusens, hard exudates and intra-retinal micro-vascular abnormalities. Results: An automatic method to detect various lesions associated with diabetic retinopathy facilitate the opthalmologists in accurate diagnosis and treatment planning. Abnormal retinal images fall into four different classes namely Non-Proliferative Diabetic Retinopathy (NPDR), Central Retinal Vein Occlusion (CRVO), Choroidal Neo-Vascularization Membrane (CNVM) and Central Serous Retinopathy (CSR). Conclusion: In this study, we have analyzed the various methodologies for detecting the abnormalities in retinal images automatically along with their merits and demerits and proposed the new framework for detection of abnormalities using Cellular Neural Network (CNN).

Subclinical Capillary Changes in Non-Proliferative Diabetic Retinopathy

To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea. Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed. Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits. AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.

Individualized optimization of the screening interval for diabetic retinopathy: a new model

Screening programmes for diabetic retinopathy follow guidelines that ensure that vision-threatening complications are detected even when the disease progression is fast. This implies that patients with slow disease progression will be recommended examinations more often than needed. On the basis of previously defined individual risk factors, multiple logistic regression was used to develop a model for individualized determination of the screening interval in diabetic retinopathy, while adjusting for the fact that in the data set used to construct the model, the screening interval acted as a time-dependent confounder. The model was tested on 1372 patients screened during year 2000. It was possible to construct a model for calculating the optimal screening interval in low-risk patients in whom the recommended screening interval was longer than 12 months. When the probability of reaching a treatment requiring event was set to 0.5%, none of the patients reached a treatment end-point in a validation of the model, and the screening interval was prolonged on average 2.9 times in patients with type 1 diabetes and 1.2 times in those with type 2 diabetes. The predictive strength of the model depended on the number of variables included. It is possible to construct a model for optimizing the examination interval during screening for diabetic retinopathy in low-risk patients. The model can potentially be improved by identifying unknown or unmeasured confounders and by including knowledge of risk factors before and after the examination on the basis of which the prediction is made.