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The aim of the study was to assess the potential use of a model of the colour content in retinal fundus images to screen for sight threatening retinopathy in diabetes. Diabetic retinopathy is the most frequent cause of blindness in the population of working age in industrialised countries, but efficient therapies do exist, and accurate and early diagnosis, and correct treatment can prevent blindness in more than 50% of all cases. However, up to 50% of cases of type 2 diabetes, which comprises 85-90% of all patients, are undiagnosed, with an average delay of 10 years between the onset of the condition and diagnosis. In an other study we have described how there is a linear relation between age and the colour composition of retinal images from non-diabetic subjects. In the present study this relation was compared to the colour composition of retinal images from diabetes patients. We found that for the patients in the present study there is a significant difference in the colour composition between normal subjects and diabetic subjects with retinopathy. Although the number of patients in our study is too small to allow any conclusion, we suggest that this difference potentially may be used as the basis for a simple screening method for sight threatening retinopathy in unrecognised diabetes, or potentially may help estimating the risk of developing diabetic late complications in newly diagnosed type 2 diabetes.

To report the occurrence of registered blindness among diabetes patients in Arhus County, Denmark during 1993-2002.Data were obtained from a database of 7527 diabetes patients, which included all patients in the county who had been treated for or had experienced visual loss due to diabetic retinopathy since 1992. Of these, 1949 had type 1 diabetes and represented 90% of the type 1 diabetes patient population in the county, and 5459 had type 2 diabetes and represented 40% of the type 2 diabetes patient population in the county.The point prevalence of legal blindness was 0.6% for type 1 and 1.5% for type 2 diabetes patients at January 1st, 2003. In type 1 diabetes patients, the major cause of blindness was proliferative diabetic retinopathy (PDR) (66.2% of all blind eyes); in type 2 diabetes patients the major causes were age-related macular degeneration (21.9%), PDR (18.0%) and diabetic maculopathy (DMac) (18.5%). During 1993-2002 there was a significant decrease in the number of blind eyes secondary to PDR (p = 0.008) in type 1 diabetes patients, and a significant increase in the number of blind eyes secondary to DMac (p = 0.005) in type 2 diabetes patients.The major challenge in reducing diabetes-related blindness is related to the detection and treatment of an increased incidence of diabetic maculopathy in type 2 diabetes patients.

The primary aim of TOSCA-Imaging, which was a part of the TOSCA Project financed by EU's Fifth Framework IST Programme, was to develop Internet based software and image data bases for screening and diagnosis of diabetic retinopathy and implementing it into a real life situation. The work consisted of: 1) Construction of an Internet based communication platform for transmitting and analyzing retinal images. 2) Implementation of routines for detecting the first microaneurysm (transition from normal to pathologic), detecting patients needing referral for treatment (presence of venous beading or hard exudates near the fovea), and for serial analysis (image alignment). 3) Construction of a reference image data base. A preliminary validation showed that decisions that depended on a precise detection of individual lesions, e.g. the detection of normality, had a sensitivity and specificity of around 80%, whereas decisions that depended on the detection of lesion patterns, e.g. clinically significant macular oedema, had a sensitivity and specificity of more than 95%. Validation of the reference image data base by double grading by two expert graders suggested a sensitivity and a specificity of just below 90% for any lesion and of more than 95% for predicting the overall retinopathy grade. TOSCA-Imaging has succeeded in its primary aim of developing Internet based software and implementing it into a real life situation, integrating work within image processing done in four different European countries (England, Germany, Ireland, and Denmark) to be accessed from one Internet web site.

Purpose: To determine the prevalence of diabetic retinopathy and the causes of visual impairment in an unselected population of type 2 diabetes patients, and to describe the risk factors for developing diabetic retinopathy in this population. Methods: A total of 10 851 type 2 diabetes patients were identified in the county of Arhus. A representative sample of 378 patients underwent a routine ocular examination, including fundus photography. Blood pressure and serum haemoglobin A1c, total cholesterol, high density lipoprotein cholesterol, triglyceride and apolipoprotein a were measured. Results: The prevalence of diabetic retinopathy in the type 2 diabetes population was 31.5%. In all, 2.9% had proliferative diabetic retinopathy and 5.3% had clinically significant macular oedema. Of the latter, 8/20 (40%) were newly identified and had not yet been laser-treated. There was a positive correlation between severity of retinopathy and duration of diabetes, HbA1c, systolic blood pressure and treatment with insulin. None of the patients had social blindness (visual acuity

Purpose: To describe whether quantitative assessment of early changes in the morphology of retinopathy lesions can predict development of vision-threatening diabetic maculopathy.Methods: We used a nested case-control study, and we studied 11 type 2 diabetes patients who had developed visual loss secondary to diabetic maculopathy. For each diabetes patient, we also studied three matched control patients who had been followed for a comparable period of time without developing visual loss. Fundus photographs describing the early development of retinopathy were digitized and subjected to a full manual quantitative grading on a computer monitor. Differences in the early development of retinal morphology were compared between the two groups. The outcome parameters were changes in the number and area of haemorrhages and exudates in different regions of the fundus, and the weighted distance of these lesions from the fovea and the optic disc.Results: In patients who developed visual loss secondary to diabetic maculopathy there was significant early progression in the total area and number of haemorrhages and exudates. The haemorrhages had progressed in all retinal areas except the area around the optic disc and the temporal vascular arcades. The exudates had progressed temporally from the fovea and in the retinal periphery.Conclusions: The results suggest that a quantitative description of the regional development of early diabetic retinopathy may help in identifying patients who will later develop vision-threatening maculopathy.

Aims: To report a case of an unusual retinal vascular morphology in connection with a novel AIPL1 mutation in a patient with Leber’s congenital amaurosis (LCA). Methods: A patient with LCA and no light perception from birth had both eyes enucleated at the age of 22 years because of excruciating pain. Mutation analysis was performed on known LCA genes. The eyes were processed for casts of the vascular tree, routine histopathology, and electron microscopy. Results: A novel H82Y (244C→T) mutation and a H90D (286G→C) polymorphism were detected in exon 2 of the AIPL1 gene. Both the cast and the histopathological examination showed dilated retinal vessels, mainly venules, primarily localised in the posterior pole. In the mid-peripheral retina the density of capillaries on the arteriolar side of the microcirculatory units was significantly decreased. The vascular system was seen to gradually attenuate towards the retinal periphery, and to stop at a zone located approximately 4 mm from the ora serrata along the whole circumference. In this zone pigmented aggregates characteristic of retinitis pigmentosa were seen to ensheath the retinal vessels. The photoreceptors were almost totally absent and retinal gliosis was present. A decreased number of ganglion cells and an increased vacuolisation of the nerve fibre layer were observed. The retinal pigment cells and Bruch’s membrane appeared normal in all regions. Conclusion: An unusual retinal vascular morphology in an LCA patient is presented and possible pathogenic mechanisms of the findings are discussed.

The optical properties of the human lens change with age and are affected by both ocular and systemic diseases. A usual change is a gradual diffuse browning or sclerosis of the lens nucleus. This nuclear sclerosis leads to selective absorption of short wave (blue) light when broad band (white) light is sent into the eye. During fundus photography a light is flashed in front of the eye which enters the pupil and is reflected from the retina to be recorded on film. The light from the flash will pass twice through the optics of the eye where the short wave lengths will be absorbed. A new method has succeeded in describing the correlation between age and the selective absorption of blue light in the ocular lens. Preliminary studies using this method have shown that the ocular lens displays increased "ageing" in diabetic patients which is probably related to the cumulative exposition to hyperglycemia. The advantages of the method are that it uses clinical data already available in patients with retinal diseases and that it is fast, inexpensive, and non-invasive to carry out. The method is another example of the eye as a significant viewer to the study of generalized diseases and their systemic complications.

To characterize vasomotion in porcine retinal arterioles in vitro using isobaric (pressure myograph) and isometric (wire myograph) methods.Pressure myograph: 208 small porcine retinal arterioles (outer diameter 68 +/- 4 microm) were studied under isobaric conditions in a double-barrelled pipette system. Diameter changes of the arterioles were registered by video recordings. Wire myograph: 60 large porcine retinal arterioles (inner diameter 147 +/- 1.6 microm) were studied under isometric conditions in a small vessel myograph for force measurements.The rates of success in initiating vasomotion were 7.2% using the pressure myograph and 43% using the wire myograph (p0.001). The small vessels studied under isobaric conditions oscillated with a frequency of 0.014 Hz and the episodes lasted 6.0 +/- 1.0 min, whereas the large vessels under isometric conditions oscillated with a significantly faster frequency of 0.043 Hz and lasted 32.1 +/- 4.9 min (p = 0.026).Retinal vasomotion can be studied in vitro using both pressure myograph and wire myograph techniques. The wire myograph is superior to the pressure myograph in initiating and maintaining vasomotion in vitro.

To study the relation between changes in visual acuity, fixation stability and the retinal area covered by hard exudates 3, 6 and 12 months after laser photocoagulation for diabetic maculopathy.Twenty-four eyes of 24 patients with diabetes mellitus were examined 3, 6 and 12 months after retinal photocoagulation for clinically significant macular oedema. Each examination included visual acuity testing (ETDRS charts), quantification of fixation stability using a scanning laser ophthalmoscope (Rodenstock 101) and fundus photography. The fundus photographs were digitised and the retinal area covered by hard exudates determined by image processing.The retinal area covered by hard exudates decreased significantly during the first 6 months after treatment ( P=0.05, paired t-test), but increased again between 6 and 12 months after treatment. The visual acuity showed an increase, albeit non-significant, during the first 6 months after treatment followed by a decrease between 6 and 12 months after treatment. Quantification of fixation stability showed that four patients with central exudates fixated at the border of these lesions, and in two of these patients the disappearance of the exudates resulted in increased visual acuity and a change in fixation to the former exudate area.The retinal area covered by hard exudates decreases during the first 6 months after central photocoagulation, but increases again between 6 and 12 months after the treatment. Hard exudates covering the foveal region contribute to disturbance of central vision.

Background Patients with proliferative diabetic retinopathy (PDR) have increased vitreous levels of insulin-like growth factor (IGF)-I, IGF-II and IGF binding proteins (IGFBPs). This accumulation is probably caused by increased leakiness of the blood–retina barrier and influx of circulating IGFs and IGFBPs. To date, interest has focused on the role of circulating total IGF-I in the development of PDR, and there are only sparse data on circulating levels of free IGF-I and IGFBPs. Methods We compared fasting serum samples from matched groups of Type 1 diabetic patients with no retinopathy (n = 29), non-PDR (n = 13) and PDR (n = 16). We also included matched controls (n = 26). Serum was analysed for free and total IGF-I and -II, free plus dissociable IGF-I, IGFBP-1, -2 and -3, IGFBP-1-bound IGF-I as well as IGFBP-3 proteolysis. Results When compared with controls, diabetic patients (n = 58) showed reduced (P

OBJECTIVE—Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. The disease is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema, the degree of which can be estimated by measurement of retinal thickness. We examined associations between retinal thickness as evaluated by optical coherence tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin excretion rate (UAE), and general vascular leakage as evaluated by the transcapillary escape rate of albumin (TERalb) in type 2 diabetic patients with and without DMa. RESEARCH DESIGN AND METHODS—In 20 type 2 diabetic patients with DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and duration of diabetes, we performed OCT, fundus photography, fluorescein angiography, and 24-h ambulatory blood pressure measurement. UAE was determined by radioimmunoassay. TERalb was determined as the initial disappearance of intravenously injected 125I-labeled human serum albumin. RESULTS—Patients with diabetic maculopathy had higher HbA1c (8.5 ± 1.5 vs. 7.4 ± 1.2%, P < 0.05) and higher total cholesterol (5.8 ± 0.7 vs. 5.2 ± 0.9 mmol/l, P < 0.05) than patients without retinopathy. UAE was higher in the DMa group than in the group with no retinopathy (9.3 ×/÷ 3.1 vs. 3.9 ×/÷ 1.9 μg/min, P < 0.01). There was no difference in TERalb between the two groups (6.0 ± 1.6 vs. 6.6 ± 1.5%, NS). In the group with DMa, OCT, TERalb, and UAE correlated significantly (OCT versus TERalb: r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE versus TERalb: r = 0.81, P < 0.01). Conversely, there were no correlations between these three parameters in the group without retinopathy. CONCLUSIONS—Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic patients.

The morphological appearance of the ocular fundus is one of the key parameters used in the diagnosis and management of retinal disease. However, optical imperfections in the refractive media result in blurring, low luminance and contrast, and changes in the colour composition of the image which can be seen as an increasing yellowish appearance with age. The introduction of a method for quantifying this age-related change in colour content may help in diagnosing and grading pathological changes in the eye lens which are secondary to ocular and systemic diseases.A total of 102 digitized fundus images from 102 healthy subjects (mean age = 50.4 years, range 7.0-94.3 years) were used to build a model for estimating the age of the subject from the colour content of the images.Estimation of age from the fundus images could be done within approximately 16 years. This variation could be reduced considerably by analysis of repeated photographs from the same examination.The colour content of fundus images can be used to estimate the ages of healthy subjects. Furthermore, when the colour content of fundus images deviates from that expected according to subject age, this may indicate causes other than age of increased light absorption in the lens, such as cumulative exposure to hyperglycaemia in diabetic patients. This could potentially be used to identify patients with undiagnosed type 2 diabetes in the general population and help to establish their risk of developing late diabetic complications as the cumulative exposure to hyperglycaemia is unknown at the time of diagnosis of the disease.

Diabetic maculopathy (DMa) is a leading cause of visual loss in the western world. We examined whether plasma from type 2 diabetic patients with DMa contains factor(s) capable of inducing expression of the adhesion molecules E-selectin and VCAM-1 or cellular proliferation in cultured endothelial cells. Four gender-, age-, and duration (diabetes groups)-matched groups of 20 subjects each participated: 1) subjects with normal glucose tolerance (NGT), 2) subjects with impaired glucose tolerance (IGT), 3) type 2 diabetic patients without retinopathy, and 4) type 2 diabetic patients with DMa. Fasting plasma was added to in vitro-grown human umbilical vein endothelial cells for 6 h, after which E-selectin and VCAM-1 expression was measured. Proliferation was evaluated by thymidine incorporation. The individuals were characterized by measurement of 24-h ambulatory blood pressure, urinary albumin excretion rate, Hb A1c, and blood lipids. Plasma from type 2 diabetic patients with DMa induced a significantly higher expression of E-selectin in endothelial cells than did plasma from subjects with NGT (259 ± 23 × 103 vs. 198 ± 19 × 103; arbitrary absorbance units; P < 0.05). There were no significant differences in plasma stimulatory effects on VCAM-1 expression or on thymidine incorporation between groups. These findings suggest that plasma from type 2 diabetic patients with DMa contains factor(s) capable of inducing the expression of E-selectin in endothelial cells. Enhanced expression of E-selectin may contribute to the development of DMa in type 2 diabetes.

To study changes in the spontaneous diameter of small retinal arterioles and bradykinin (BK)-induced vasodilation during inhibition of the synthesis of nitric oxide (NO), prostaglandins (PGs), and cytochrome P450 2C8/9-dependent endothelial-derived hyperpolarizing factor (EDHF).Forty-eight isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barreled pipette system placed in an organ bath, and diameter changes were studied under isobaric conditions. After an equilibration period, the arterioles were incubated with inhibitors of the synthesis of NO, PGs, or cytochrome P450 2C8/9-dependent EDHF, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted, and the diameter was assessed after addition of BK in cumulative concentrations.Inhibition of NOS elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.028), whereas no change in the spontaneous diameter was induced by inhibition of PG or cytochrome P450 2C8/9 dependent EDHF synthesis (P = 0.35 and P = 0.75, respectively). The vasodilating effect of BK was decreased by inhibition of NO (P = 0.002) but not by inhibition of prostaglandin or cytochrome P450 2C8/9-dependent EDHF synthesis (P = 0.82 and P = 0.94, respectively).The results suggest the presence of a spontaneous release of NO, which keeps the retinal microcirculation dilated under normal conditions. The finding of BK-induced relaxation being dependent on the NO synthase (NOS), but not on PGs or cytochrome P450 2C8/9-dependent EDHF may be of importance for understanding the microcirculatory effects of pharmacologic compounds affecting the BK metabolism, such as angiotensin-converting enzyme (ACE) inhibitors.

In nondiabetic subjects pulse pressure (PP) is an independent predictor of cardiovascular disease and microalbuminuria. Reduced circadian blood pressure (BP) variation is a potential risk factor for the development of diabetic complications. We investigated the association between retinopathy, nephropathy, macrovascular disease, PP, and diurnal BP variation in a group of type 2 diabetic patients.In 80 type 2 diabetic patients we performed 24-h ambulatory BP (AMBP) and fundus photographs. Urinary albumin excretion was evaluated by urinary albumin/creatinine ratio. Presence or absence of macrovascular disease was assessed by an independent physician.Forty-nine patients had no detectable retinal changes (grade 1), 13 had grade 2 retinopathy, and 18 had more advanced retinopathy (grades 3-6). Compared to patients without retinopathy (grade 1), patients with grades 2 and 3-6 had higher PP and blunted diurnal BP variation: night PP 55 +/- 10 mm Hg, 64 +/- 10 mm Hg, 61 +/- 15 mm Hg, P.05 and systolic night/day ratio 89.3% +/- 7%, 94.6% +/- 8%, and 92.0% +/- 6%, P.05 (grade 1, 2, and 3-6, respectively). Comparing nephropathy groups (45 normo-, 19 micro-, and 15 macroalbuminuric patients) results were similar: night PP 54 +/- 9 mm Hg, 57 +/- 10 mm Hg, and 70 +/- 15 mm Hg, P.001 and systolic night/day ratio 88.9% +/- 7%, 92.0% +/- 7%, and 94.9% +/- 7%, P.02. Likewise, compared to patients without macrovascular disease (n = 55), patients with this complication (n = 25) had higher AMBP values: night PP 57 +/- 12 mm Hg v 63 +/- 11 mm Hg, P.05 and systolic night/day ratio 89.2% +/- 6% v 94.1% +/- 9%, P.01.Increased PP and blunted diurnal BP variation are hemodynamic abnormalities associated with micro- and macrovascular complications in type 2 diabetes.

PURPOSE: Previous studies have shown that adenosine induces relaxation of isolated retinal arterioles mediated by the A2A receptor, but the contributions to tone regulation of adenosine receptors located both in and around the vascular wall have not been studied in detail.METHODS: Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was recorded after addition of antagonists to the adenosine A1, A2A, A2B, and A3 receptors, followed by removal of the perivascular retinal tissue and repetition of the experiments. Additionally, these responses were studied in concentration-response experiments using specific agonists.RESULTS: Adenosine induced a significant concentration-dependent relaxation at high concentrations that was independent of the perivascular retinal tissue and could be antagonized by the nonspecific adenosine receptor antagonist 8-PSPT. The selective A2A receptor antagonist SCH 58261 and the A2B receptor antagonist MRS 1754 significantly antagonized the relaxing effect of adenosine. Conversely, the selective A1 receptor antagonist KW-3902 and the A3 receptor antagonist MRS 1523 significantly increased the relaxing effect of adenosine, and the corresponding agonists contracted retinal arterioles at intermediate concentrations. The contracting effect of the A1 receptor agonist but not the A3 receptor antagonist depended on the presence of perivascular retinal tissue.CONCLUSIONS: Adenosine has complex effects on retinal vascular tone elicited both from the vascular wall and from the perivascular retina and with receptors mediating contraction at intermediate concentrations and relaxation at high concentration.

Background: Dyschromatopsia is a prominent sign in a variety of central retinal diseases, such as central serous chorioretinopathy (CSC). The changes in colour vision may be due to either optical or neuronal factors in the diseased retina. The relative contribution from the two causes is unknown, but may be elucidated by obtaining knowledge of the anatomical derangement in the diseased retina in CSC. Methods: Twenty-six normal persons had their colour vision tested using the Tomey anomaloscope. The calculation of setting range (SR) and central mean point (CMP) for Rayleigh match and Moreland match was optimized, and normal ranges for these values were defined. Subsequently 24 patients with CSC were examined by anomaloscopy and optical coherence tomography scanning, and the measures of colour vision were related to the anatomical changes observed on the scans. Results: The algorithm for calculating SR and CMP which is integrated into the Tomey anomaloscope could be considerably improved to increase sensitivity and reproducibility of these measures. Fifteen patients had abnormal colour vision. Nine patients had pseudo-protanomaly, seven patients had pseudo-tritanomaly, and three patients had abnormalities in both matches. There was no relation between these colour vision abnormalities and the anatomical derangement as seen by OCT in the diseased central retina. Conclusion: The findings argue against the notion that the density of retinal cell nuclei, the orientation of photoreceptors, or the size of the central serous detachment are related to the colour vision abnormalities in CSC. The question of whether these abnormalities are due to optical or neuronal factors remains open.

Two hereditary conditions, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with amyloid deposition in the central nervous system and neurodegeneration. The two amyloid proteins, ABri and ADan, are degradation products of the same precursor molecule BriPP bearing different genetic defects, namely a Stop-to-Arg mutation in FBD and a ten-nucleotide duplication-insertion immediately before the stop codon in FDD. Both de novo created amyloid peptides have the same length (34 amino acids) and the same post-translational modification (pyroglutamate) at their N-terminus. Neurofibrillary tangles containing the classical paired helical filaments as well as neuritic components in many instances co-localize with the amyloid deposits. In both disorders, the pattern of hyperphosphorylated tau immunoreactivity is almost indistinguishable from that seen in Alzheimer's disease. These issues argue for the primary importance of the amyloid deposits in the mechanism(s) of neuronal cell loss. We propose FBD and FDD, the chromosome 13 dementia syndromes, as models to study the molecular basis of neurofibrillary degeneration, cell death and amyloid formation in the brain.

Purpose: To study the prevalence of risk factors for systemic thromboembolism in patients with retinal vein thrombosis (RVT). Methods: Fifty-four patients younger than 70 years, diagnosed with a retinal vein thrombosis at the Department of Ophthalmology, Arhus University Hospital, were examined for the presence of venous thrombosis risk factors. Results: 23 patients had a central RVT, 26 had a branch RVT, and 4 had a macular RVT. Nineteen (35.2%) of the patients displayed increased levels of plasma homocysteine, one patient (1.9%) the Factor V Leiden mutation, and one patient (1.9%) displayed an antiphospholipid antibody. All other tests for thrombophilia rendered normal. In 15 of the patients with hyperhomocysteinemia, folic acid substitution returned plasma homocysteine to a normal value in 12 cases. Conclusion: A surprisingly high prevalence of hyperhomocysteinemia was detected in this cohort of RVT patients, clearly superseding the prevalence of around 17% found in patients suffering venous thromboembolism in other vascular compartments. Our finding points to the likelihood that hyperhomocysteinemia may be a significant risk factor for retinal vein thrombosis.

Purpose: To study the correlation between changes in visual acuity and changes in fixation stability after retinal photocoagulation for diabetic maculopathy. Material: Twenty-four patients with diabetic maculopathy and visual acuity (VA) ranging between 0.05–0.77 were studied at baseline and 1, 3, 6 and 12 months after retinal photocoagulation. Fixational eye movements were quantified from video recordings of the ocular fundus obtained with the Rodenstock scanning laser ophthalmoscope. Results: No correlation was found between the changes in the quantitative measures of the fixational eye movements (amplitude and retinal area of fixation) and the changes in VA 12 months after retinal photocoagulation. Three patients all with VA

Diabetic eye disease remains a major cause of blindness in the world. Laser treatment for proliferative diabetic retinopathy and diabetic macular edema became available more than two decades ago. The outcome of treatment depends on the timing of laser treatment. The laser treatment is optimally delivered when high-risk characteristics have developed in proliferative retinopathy or diabetic macular edema and before this has significantly affected vision. Laser treatment is usually successful if applied during this optimal period whereas the treatment benefit falls sharply if the treatment is applied too late. In order to optimize the timing of laser treatment in diabetic eye disease screening programs have been established. The oldest screening program is 20 years old and several programs have been established during the last decade. In this paper the organisation and methods of screening programs are described including direct and photographic screening. The incidence and prevalence of blindness is much lower in populations where screening for diabetic eye disease has been established compared to diabetic populations without screening. Technical advantages may allow increased efficiency and telescreening. From a public health standpoint screening for diabetic eye disease is one of the most cost effective health procedures available. Diabetic eye disease can be prevented using existing technology and the cost involved is many times less than the cost of diabetic blindness.

OBJECTIVE: The importance of screening for diabetic retinopathy has been established, but the best method for screening has not yet been determined. We report on a trial of assessment of digital photographs by telemedicine compared with standard retinal photographs of the same fields and clinical examination by ophthalmologists. RESEARCH DESIGN AND METHODS: A total of 129 diabetic inpatients were screened for diabetic retinopathy by slit-lamp biomicroscopy performed by an ophthalmologist and by two-field 50 degrees non-stereo digital fundus photographs assessed by six screening centers that received the images by electronic mail. Conventional 35-mm transparencies of the same fields as the digital photographs were assessed by a retinal specialist and served as the reference method for detection of diabetic retinopathy. Slit-lamp biomicroscopy was the reference method for the detection of macular edema. RESULTS: The prevalence of any form of diabetic retinopathy was 30% (n = 35); of sight-threatening retinopathy including macular edema, the prevalence was 6% (n = 7). The assessment of digital images by the six screening centers resulted in a median sensitivity of 85% and a median specificity of 90% for the detection of moderate nonproliferative or sight-threatening diabetic retinopathy. Clinically significant macular edema (n = 4) was correctly identified in 15 of the 24 grading reports. An additional seven reports referred the patients for further investigation because of concurrent diabetic retinopathy. CONCLUSIONS: Telescreening for diabetic retinopathy by an assessment of two-field 50 degrees non-stereo digital images is a valid screening method. Although detection of clinically significant macular edema using biomicroscopy is superior to digital or standard non-stereo photographs, only few patients with sight-threatening diabetic retinopathy are missed.

Bildverarbeitungsmethoden zur automatischen Analyse von Fundusphotographien hinsichtlich der Entdeckung und Quantifizierung von diabetischer Retinopathie werden entwickelt. Die zentrale Aufgabe dieser Methoden ist die Segmentation der Papille und des Gefasbaumes. Dadurch sollen einerseits pathologische Veranderungen am Verlauf und der Kontur von Gefasasten erkannt und andererseits Lasionen auf dem restlichen Augenhintergrund durch einfache Bildverarbeitungsverfahren lokalisiert werden. Die Segmentation der Papille erfolgt durch ein hierarchisches Filterschema unter Berucksichtigung ihrer Lage und Form. Die Gefase werden durch ein dreistufiges Verfahren extrahiert: 1) Tracken des Gefas Verlaufes, 2) Ermittlung der Gefaskontur und 3) Identifikation von Gefas Verzweigungen. Alle Verfahren basieren auf steuerbaren Filtern.

Twenty areas of retinal vascular occlusion from ten eyes of 6 diabetic patients were studied by immunohistochemistry to type IV collagen (basement membranes), von Willebrand factor (endothelial cells), and to glial fibrillary acid protein (glial cells) on serial sections. In all studied lesions immunoreactivity to type IV collagen and von Willebrand factor was confined to the retinal vascular walls whereas the material accumulated to occlude the vascular lumens centrally displayed immunoreactivity to glial fibrillary acid protein. All arterioles observed in the lesions were occluded. These arterioles had retained their circular shape, and the intravascular glial protein immunoreactivity communicated with the extravascular glial tissue through localised breaks in the vascular wall. The intravascular immunoreactivity was found to continue inside the arteriole along its successive diminishing to reach the capillary level. The venules were only occluded in less than half of the studied lesions. These venules were collapsed to assume a bean-like shape, and sequences with total obliteration of the vascular lumen alternated with sequences where a residual space corresponding to the former lumen displayed immunoreactivity to glial protein. The paper suggests that glial cell invasion, but not endothelial cells or basement membrane thickening, occludes the vascular lumen in areas of retinal non-perfusion secondary to diabetic retinopathy.

Purpose Diabetic retinopathy is characterized by morphological changes in the retina secondary to disturbances in retinal blood flow. Vasomotion is a mechanism for regulating blood flow by spontaneous oscillations in the diameter of retinal resistance arterioles, and has been shown to be disturbed outside the eye in diabetic patients. Therefore, the purpose of the present study was to characterize spontaneous oscillations in the diameter of retinal arterioles in normal persons and in persons with different severity of diabetic retinopathy. Methods Video recordings of the retina were performed in 19 normal persons and three matched groups of type 2 diabetic patients with no retinopathy, mild retinopathy, and diabetic maculopathy. Continuous recordings of a larger retinal arteriole during rest and during an increase in the arterial blood pressure induced by isometric exercise were subjected to power spectrum analysis of spontaneous oscillations in vessel diameter. Results During rest the oscillations in the diameter of retinal arterioles with high frequencies were significantly reduced in patients with diabetic retinopathy. Increased arterial blood pressure did not change the oscillations in normal persons, but further reduced the oscillations in diabetic patients. Conclusions Spontaneous high frequency oscillations in the diameter of larger retinal arterioles are reduced in type 2 diabetic patients, and are further reduced during an increase in the arterial blood pressure. The finding may reflect changes in the vascular walls of importance for diagnosing and predicting the visual prognosis in patients with diabetic retinopathy.

The association between periodic acid Schiff staining and immunoreactivity to laminin, fibronectin, vitronectin, and type VI collagen was studied qualitatively and quantitatively in the retinal vascular bed from 7 eyes of 5 diabetic patients and from 5 eyes of 5 normal persons. In the retina from diabetic patients the number of arterioles showing immunoreactivity to vitronectin, the number of venules showing immunoreactivity to type VI collagen, and the number of both arterioles and venules showing immunoreactivity to laminin and fibronectin, was higher than in normals. There was no difference between the number of capillaries showing periodic acid Schiff staining and immunoreactivity to laminin, fibronectin, and vitronectin when comparing areas of vascular occlusion with adjacent control areas. However, the number of capillaries displaying immunoreactivity to type VI collagen was higher in control areas than in areas of vascular occlusion in diabetic patients and in normal controls. Staining with periodic acid Schiff correlated topographically with immunoreactivity to laminin and fibronectin, but not with immunoreactivity to vitronectin and type VI collagen. In areas of vascular occlusion there was seen no immunoreactivity or histological staining corresponding to the material accumulated to occlude the ghost vessels.

Purpose: To evaluate surgically induced astigmatism using Fourier harmonic series analysis of corneal topography data. Setting: Aarhus Kommunehospital, Aarhus University, Denmark. Methods: We evaluated the results of 46 phacoemulsifications with a 4 or 6 mm scleral tunnel sutureless incision based on the axis of the steepest meridian. We performed conventional keratometry and corneal topography before and up to 1 month after surgery. Using Fourier analysis, the corneal topographic images were broken into spherical power, regular astigmatism, and nonregular astigmatism for individual or aggregate analysis of surgically induced astigmatism. The induced refractive change (average of the difference between preoperative and postoperative corneal topographies) was analyzed and normalized according to the surgical meridian and to right/left eye. Results: Regular astigmatism calculated by Fourier analysis of mires from the keratometer zone correlated well with conventional keratometry readings. Surgery induced a localized flattening in the superior region and a with-the-rule regular astigmatism component in the central area. Conclusion: Surgically induced corneal topography changes can be analyzed by Fourier series harmonic analysis, allowing aggregate data to be broken into optically meaningful quantities.

Quantitative layer-by-layer perimetry is a psychophysical technique believed to assess the functional characteristics of individual retinal layers. In the initial design of the technique, the test procedure was too time consuming for the testing of large field point patterns, and statistical treatment of the measured threshold values was difficult. Therefore, to minimize these limitations, a new design of quantitative layer-by-layer perimetry was developed by incorporating the technique into the existing hardware environment of the computerized perimeter Humphrey Field Analyzer. The present paper describes the theoretical considerations and experimental findings underlying a selection of optimal stimulus parameters to provide a basis for statistical treatment of measured threshold values, and to minimize test duration, while obtaining an acceptable estimate of the threshold level with minimum variance.

Purpose It has been shown that inhibition of prostaglandin synthesis in the perivascular retinal tissue can prevent the relaxation of retinal arterioles induced by N-methyl-d-aspartic acid (NMDA) and adenosine triphosphate (ATP). The purpose of the present study was to identify the prostaglandins involved in this retina-dependent relaxation. Methods Porcine retinal arterioles were mounted in a myograph for isometric tone measurements. The effect of the prostaglandins (PGs) PGE(2), PGF(2α), PGD(2), and PGI(2) and of thromboxane A(2) (TXA(2)) on vascular tone was recorded before and after removal of the perivascular retina, and the specificity of the responses were confirmed by blocking with specific antagonists. Finally, the coupling between prostaglandins found to have a specific vasoactive effect, dependent on the perivascular retina, and the individual vasorelaxing effects of NMDA, ATP, and adenosine were studied. Results All prostaglandins tested showed a significant relaxation of precontracted arterioles at the highest concentrations, whereas PGF(2α) induced a significant constriction of isolated noncontracted arterioles. In the presence of perivascular retinal tissue, the dilating effect of PGE(2) increased significantly, an effect that was blocked by a prostaglandin E prostanoid (EP(1)) receptor blocker, whereas PGD(2) induced a dual response, with a significant contraction at low concentrations and a significant dilation at high concentrations. Inhibition of the cyclo-oxygenase (COX) enzyme with ibuprofen, as well as the EP(1) receptor, blocked the vasodilating effect of ATP, but not that of NMDA and adenosine, in the presence of perivascular retinal tissue. Conclusions ATP-induced vasodilation depends on the production of PGE in the perivascular retina. However, the regulation of retinal arteriolar tone involves COX products other than PGE.

Editor, A netoderma is a rare disease of the elastic connective tissue which is characterized clinically by multiple 5–25 mm-diameter round atrophic papules that bulge outwards from the skin of the trunk, the upper part of extremities and neck. At palpation, the lesions are flaccid and herniate inwards. Histopathologically, there is fragmentation of elastic fibres and loss of elastic tissue in the dermis. The aetiology of anetoderma is unknown, but the disease has been related to antiphospholipid syndrome, systemic lupus erythematosus (Venencie et al. 1984) and infections such as borreliosis (Bauer et al. 2003). In rare cases, the disease has been shown to be inherited or idiopathic. In the eye, anetoderma has been shown to be related to keratoconus, blue sclerae, pseudotumor orbitae and cataract (Brenner et al. 1977, Nunez et al. 1995), whereas no studies have reported a relation between anetoderma and diseases in the posterior segment of the eye. A 27-year-old otherwise healthy woman with previous normal vision was referred with a 2 weeks history of metamorphopsia and blurred vision on the left eye. There was no history of trauma, choroiditis, or other known risk factors for the development of subretinal neovascularization, but anetoderma (Schweninger–Buzzy type) confirmed by skin biopsy had been diagnosed at the age of 12 years. Laboratory examinations for antinuclear antibodies (ANA), cardiolipin antibody and serological tests for Borrelia, syphilis and HIV were negative. The patient was subjected to a routine clinical examination including measurement of visual acuity, slit lamp examination, optical coherence tomography scanning and fluorescein angiography. The clinical examination showed VAD = 1.2 and VAS = 0.1 and both eyes had emmetropia. All other examinations on the right eye were normal. On the left eye, ophthalmoscopy showed central retinal oedema with haemorrhages and exudates. Optical coherence tomography (OCT) scanning of the left eye showed intra-retinal oedema with a central retinal thickness of 452 microns. Fluorescein angiography revealed a classical subfoveal neovascularization (Fig. 1). After three Intra-vitreal injections of ranibizumab on the left eye with 1 month intervals, the central retinal thickness was reduced to 214 microns and visual acuity had increased to 0.8. Subretinal neovascularization is a well documented complication to connective tissue diseases such as pseudoxanthoma elasticum and Ehlers Danlos’ syndrome and may be related to discontinuities or breaks in Bruch’s membrane that forms a barrier for growth of choroidal vessels under normal conditions (Georgalas et al. 2009). The present case report suggests anetoderma as a possible new risk factor for the development of subretinal neovascularization. A more detailed elucidation of the changes in elastic tissue in anetoderma and other connective tissue diseases may help understanding the pathophysiology of subretinal neovascularization in general.

Quantitative layer-by-layer perimetry is a psychophysical technique believed to assess response characteristics of individual retinal layers. This paper presents a new design of this technique, implemented into the existing hardware environment of the computerized perimeter Humphrey Field Analyzer. The technique was optimized for a more simple, fast and reproducible testing of larger visual field point patterns. The paper deals with the design of instrumentation and with methodological aspects of this adaptation of the technique.

In this paper some qualitative aspects of centre-surround interaction produced by transient surround stimulation are investigated, employing a new design of quantitative layer-by-layer perimetry. Using a rotating windmill pattern, a transient response, believed to be organized in the inner plexiform layer of the retina, is assessed in four normal individuals. The paper considers area characteristics of the stimulus pattern used to produce the transient response, and optimal dimensions for this pattern are proposed.