Serum glial fibrillary acidic protein and neurofilament light chain as biomarkers of retinal neurodysfunction in early diabetic retinopathy: results of the EUROCONDOR study.

AIMS: Neurodegeneration and glial activation are primary events in the pathogenesis of diabetic retinopathy. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of underlying neuroinflammatory and neurodegenerative disease processes. The aim of the present study was to assess the usefulness of these serum biomarkers for the identification and monitoring of retinal neurodysfunction in subjects with type 2 diabetes. METHODS: A case-control study was designed including 38 patients from the placebo arm of the EUROCONDOR clinical trial: 19 with and 19 without retinal neurodysfunction assessed by multifocal electroretinography. GFAP and NfL were measured by Simoa. RESULTS: Serum levels of GFAP and NfL directly correlated with age (r = 0.37, p = 0.023 and r = 0.54, p < 0.001, respectively). In addition, a direct correlation between GFAP and NfL was observed (r = 0.495, p = 0.002). Serum levels of GFAP were significantly higher at baseline in those subjects in whom neurodysfunction progressed after the 2 years of follow-up (139.1 ± 52.5 pg/mL vs. 100.2 ± 54.6 pg/mL; p = 0.04). CONCLUSIONS: GFAP could be a useful serum biomarker for retinal neurodysfunction. Monitoring retinal neurodysfunction using blood samples would be of benefit in clinical decision-making. However, further research is needed to validate this result as well as to establish the best cutoff values.

Periocular basal cell carcinoma results and surgical outcome during a 5-year period in a larger Danish population.

BACKGROUND: To report tumour pathology, surgical procedure, complication rates and overall outcome of periocular basal cell carcinoma (BCC) in the Department of Ophthalmology at Sygehus Lillebaelt, Southern Denmark Region over a 5-year period. METHODS: Medical records for all patients who underwent surgery for periocular BCC between January 2016 and December 2020 were reviewed. All tumours were excised with a 3 mm margin beyond the clinically apparent delimitation of the tumour and analysed by frozen section histological examination. Paraffin sections were subsequently examined for a final histopathological diagnosis. Patient age, gender, date of resection, former cancer history, referring unit and follow-up time were recorded. Furthermore, histological subtypes identified from biopsy and resection, lesion location, lesion diameter, free margin after the first operation, lacrimal punctum involvement, reconstructive techniques and complications were also recorded. RESULTS: A total of 242 surgical excisions from 237 patients were recorded. The mean age was 69.7 ± 12.6 with women significantly predominant compared to men (1.8:1, p < 0.0001, binomial test). The mean tumour diameter was 4.29 mm (range 0.5-20 mm). The most common location and histological subtype was the lower eyelid and nodular BCC respectively (64.9% and 74.0% of cases). In 17.4% of the patients, the initial resection margin on the frozen section histology was not free of tumour cells and the risk was significantly greater for BCC subtypes considered aggressive in terms of growth pattern (morphea form, infiltrative and micronodular features) as compared to non-aggressive BCC subtypes (nodular and superficial) (p = 0.002, X2). In 239 (98.8%) of the patients, the BCC was found to be radically removed after final histopathological examination. The sensitivity of identification of aggressive subtypes of periocular BCC in biopsies was 47.7%. No recurrences were found during the 5-year period. CONCLUSION: This study demonstrated a tendency towards more women than men being diagnosed with periocular BCC. The initial biopsy performed for all patients underestimated the aggressiveness of BCC in almost half of the cases while aggressive BCC subtypes were more likely to need further resection after frozen section compared to non-aggressive subtypes.

Diabetic Retinopathy Predicts Risk of Alzheimer's Disease: A Danish Registry-Based Nationwide Cohort Study.

BACKGROUND: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD). OBJECTIVE: To investigate diabetes and DR as a risk marker of present and incident AD. METHODS: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes. RESULTS: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59-0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81-0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08-1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18-1.53). CONCLUSION: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR.

The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial.

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain-optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR).

Topical Treatment With Brimonidine and Somatostatin Causes Retinal Vascular Dilation in Patients With Early Diabetic Retinopathy From the EUROCONDOR.

Purpose: Structural retinal microvascular changes have been identified as risk markers of diabetic retinopathy (DR). In order to estimate the retinal response of neuroprotective eye drops, we aimed to evaluate the effect of topical retinal neuroprotection on retinal microvascular changes in early DR. Methods: Patients with type 2 diabetes with no or early DR were randomized 1:1:1 to topical treatment with placebo, brimonidine, or somatostatin in a 96-week prospective, phase II to III, European multicenter trial. Retinal vascular calibers were measured semiautomatically in digital fundus images by certified graders at baseline and follow-up and summarized as central retinal arteriolar and venular equivalent (CRAE and CRVE). Results: Of 449 patients originally included, 297 completed the study with gradable retinal images. Median age and duration of diabetes was 64.5 and 9.9 years, and 65.7% were male. At baseline, Early Treatment Diabetic Retinopathy Study levels were 10 (no DR, 42.8%), 20 (minimal DR, 28.3%), and 35 (mild DR, 29.0%), and CRAE and CRVE did not differ between groups. As opposed to patients with no or minimal DR at baseline, patients with mild DR in the active groups developed a larger retinal arteriolar (brimonidine: +6.2 µm, P = 0.006; somatostatin: +7.2 µm, P = 0.006) and venular (brimonidine: +13.9 µm, P = 0.01; somatostatin: +14.3 µm, P = 0.0001) caliber in contrast to those in the placebo group. Conclusions: Topical treatment with brimonidine and somatostatin causes retinal arteriolar and venular dilation in patients with type 2 diabetes and preexisting early DR. Upcoming studies should elaborate on the potential of these findings in arresting early DR.

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial.

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit.

Structural neurodegeneration correlates with early diabetic retinopathy.

PURPOSE: To examine differences in structural and functional neurodegenerative measurements between patients with no and early diabetic retinopathy (DR). METHODS: In this cross-sectional study, we examined 103 patients with type 2 diabetes mellitus. In 7-field fundus photographs acquired with Topcon TRC-NW6S, a single, certified grader determined the presence of DR according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral domain optical coherence tomography (OCT) and by a RETI-scan multifocal electroretinography (mf-ERG) system in rings 1-6. RESULTS: Median age and duration of diabetes were 63.6 and 10 years, respectively, and 46% were men. Median HbA1c was 50 mmol/mol (6.7%), and ETDRS levels were 10 (41.7%, n = 43), 20 (35.0%, n = 36), and 35 (23.3%, n = 24). The duration of diabetes increased with higher levels of DR (p = 0.04), but patients with different level of DR did not differ according to age, sex, blood pressure, HbA1c, and mf-ERG or OCT parameters. In a multiple logistic regression model, macular ganglion cell layer thickness was associated with the presence of DR (OR 1.73 per 5 µm increase, 95% CI 1.06-2.85, p = 0.03). Conversely, retinal nerve fibre layer thickness at optic disc was inversely related to DR (OR 0.69 per 5 µm increase, 95% CI 0.51-0.95, p = 0.02). There were no associations between DR and mf-ERG outcomes. CONCLUSION: In patients with type 2 diabetes, structural neurogenic characteristics were associated with DR. If confirmed by larger prospective studies, these results may indicate that a complex neurovascular interaction is an early event in the pathogenesis of DR.

Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project.

This cross-sectional study evaluated the relationship between 1) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 (P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes.

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside.

The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes.

Correlation between Retinal Vessel Calibre and Neurodegeneration in Patients with Type 2 Diabetes Mellitus in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR).

PURPOSE: To investigate the correlation between retinal vessel calibre and measurements of neurodegeneration in patients with type 2 diabetes (T2D) and no or early diabetic retinopathy (DR). METHODS: Baseline data on 440 patients with T2D from the EUROCONDOR clinical trial were used. DR was graded according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale, and patients with ETDRS levels 10-35 were included. Retinal vessel diameters were measured by semi-automatic software. Calibres were summarized into central retinal artery and vein equivalents (CRAE and CRVE). RESULTS: Median age and diabetes duration were 64.0 and 10.3 years, respectively. ETDRS levels were 10 (42.3%), 20 (27.5%) and 35 (30.2%). The median CRAE and CRVE were 146.7 and 215.3 µm, respectively. CRAE did not differ according to ETRDS level (p = 0.12), but wider CRVE were found in patients with higher ETDRS levels (p = 0.04). In a multivariable linear regression model, CRAE was associated with macular ganglion cell layer thickness (coefficient 0.27 per micrometre, p < 0.01), and CRVE was correlated with macular retinal thickness (coefficient -0.07 per micrometre, p = 0.04) and retinal nerve fibre layer thickness at the optic disc (coefficient 0.32 per micrometre, p < 0.01). CONCLUSION: Retinal vessel calibre was independently associated with structural changes of the neuroretina in patients with no or early DR.

Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy: Which Comes First?

INTRODUCTION: Neurodegeneration is an early component of diabetic retinopathy (DR). It is unclear whether neurodegeneration is an independent factor or a consequence of damaged retinal vasculature. The aims of this study were to review the literature concerning neurodegeneration in diabetic patients without or with early DR, and to examine whether neurodegeneration precedes visible vasculopathy in the pathogenesis of DR. METHODS: A systematic literature search was performed to identify studies which used optical coherence tomography (OCT) or multifocal electroretinography (mfERG) to detect neurodegeneration in patients with no or mild DR as compared to healthy controls. Outcome measures were mean retinal thickness (RT), mean retinal nerve fiber layer (RNFL) thickness and ganglion cell layer (GCL) thickness. Also, mfERG amplitude and implicit time were analyzed. RESULTS: Eleven studies which used mfERG and/or OCT to detect neurodegeneration were included. Two OCT studies found significant thinning of RT, 2 found thinning of RNFL, whereas 1 found thickening of RT, RNFL and GCL in patients without DR. Two mfERG studies found a significant delay of implicit time in the same patient group. Retinal thinning and delay of implicit time were also detected in patients with mild DR. CONCLUSION: Retinal neurodegeneration is an early component of DR, which can precede visible vasculopathy.

High diagnostic value of general practitioners' presumptive diagnosis for pyelonephritis, meningitis and pancreatitis.

INTRODUCTION: In Denmark, patients referred from the general practitioner (GP) to the emergency department (ED) can be referred with either specific symptoms or with a presumptive diagnosis. The aim of the present study was to evaluate the diagnostic accuracy for various presumptive diagnoses made by the GP in a population acutely referred to an ED. METHODS: This was a retrospective cohort study of all registered acute referrals for admission to Kolding ED in 2010. Eight presumptive diagnoses were selected for further studies: meningitis, acute coronary syndrome (ACS), pulmonary embolism, pneumonia, pancreatitis, deep venous thrombosis (DVT), pyelonephritis and intestinal obstruction. The presumptive diagnoses were compared with the final diagnosis on discharge. Sensitivity, specificity, predictive values and likelihood ratios were calculated. RESULTS: A total of 8,841 patients were enrolled. The highest and lowest sensitivities were seen for DVT (90%) and meningitis (36%), respectively; and the highest and lowest values for specificity were observed for meningitis (99%) and ACS (30%), respectively. The positive predictive value had a wide range with the lowest value for ACS (9%) and the highest for pneumonia (59%). For pyelonephritis, meningitis and pancreatitis, the likelihood ratio of a positive test was above 10. The likelihood ratio of a negative test was above 0.1 for all diagnoses. CONCLUSIONS: Patients referred with the presumptive diagnoses pyelonephritis, meningitis and pancreatitis had a high likelihood of having the disease in question. It is important not to discard any of the included presumptive diagnoses even if the GPs fail to suggest them on admission. FUNDING: none. TRIAL REGISTRATION: none.

Retinal Vascular Fractals Correlate With Early Neurodegeneration in Patients With Type 2 Diabetes Mellitus.

PURPOSE: To investigate the correlation between the retinal vascular fractal dimension (Fd) and neurodegenerative changes in patients with no or mild diabetic retinopathy (DR). METHODS: In this cross-sectional study we examined 103 patients with type 2 diabetes mellitus (T2DM) with no or mild DR. In a randomly selected eye of each patient, Fd was calculated using SIVA-Fractal, a specialized semiautomatic software. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral-domain optical coherence tomography (OCT) and by a RETI-scan multifocal ERG (mf-ERG) system in rings one to six. Level of DR was determined by a single trained grader in seven-field fundus photos according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. RESULTS: Mean age and duration of T2DM were 62.3 and 11.6 years, respectively; 46.6% were men. Mean Fd was 1.413 (range, 1.278-1.509) and ETDRS levels were 10 (42.7%), 20 (35.0%), and 35 (22.3%), respectively. Fd correlated inversely with mf-ERG implicit time of ring one (r = -0.25, P = 0.01) and present diabetic neuropathy (P = 0.02), and positively with OCT ganglion cell layer (GCL) thickness (r = 0.20, P = 0.04). In a multivariable linear regression model, Fd was associated with mf-ERG implicit time of ring one (coefficient -0.0021/ms, P = 0.040) and the presence of diabetic neuropathy (coefficient -0.0209 for neuropathy present versus absent, P = 0.041). CONCLUSIONS: In patients with T2DM and no or minimal DR, independent correlations were found between early vascular and neurogenic changes. Thus, retinal vascular fractal analysis might be considered as a tool to identify patients with early neurodegenerative retinal changes.

Comparison between Early Treatment Diabetic Retinopathy Study 7-field retinal photos and non-mydriatic, mydriatic and mydriatic steered widefield scanning laser ophthalmoscopy for assessment of diabetic retinopathy.

AIMS: To compare non-mydriatic, mydriatic and steered mydriatic widefield retinal images with mydriatic 7-field Early Treatment Diabetic Retinopathy Study (ETDRS)-standards in grading diabetic retinopathy (DR). METHODS: We examined 95 patients (190 eyes) with type 1 diabetes. A non-mydriatic, a mydriatic and four steered mydriatic 200° widefield retinal images were captured (Optos 200Tx, Optos plc, Dunfermline, Scotland) and compared to mydriatic 7-field 45° ETDRS images (Topcon 3D OCT-2000, Topcon, Tokyo, Japan). Images were graded for DR according to ETDRS-protocol by a trained and certified grader masked to the results of the corresponding grading. For agreement kappa-statistics were used. RESULTS: Exact level agreement with 7-field images was found in 76.3%, 76.1% and 70.7% for non-mydriatic, mydriatic and steered mydriatic widefield images, respectively. Corresponding values for one-level agreement were 99.0%, 98.9% and 99.5%, respectively. Non-mydriatic matched mydriatic widefield images almost fully with exact and one-level agreement of 96.8% and 100.0%, respectively. Mydriatic steered images resulted in higher grading in 24 eyes. CONCLUSIONS: Widefield images matched 7-field images favorably. Widefield images can be captured without pupil-dilation and only one image is needed. However, because of overlapping eyelashes and distortion some lesion might be missed. Mydriatic steered images in selected cases may solve some of these problems.

Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

AIMS/HYPOTHESIS: Fractal analysis of the retinal vasculature provides a global measure of the complexity and density of retinal vessels summarised as a single variable: the fractal dimension. We investigated fractal dimensions as long-term predictors of microvasculopathy in type 1 diabetes. METHODS: We included 180 patients with type 1 diabetes in a 16 year follow-up study. In baseline retinal photographs (from 1995), all vessels in a zone 0.5-2.0 disc diameters from the disc margin were traced using Singapore Institute Vessel Assessment-Fractal image analysis software. Artefacts were removed by a certified grader, and fractal dimensions were calculated using the box-counting method. At follow-up (in 2011), diabetic neuropathy, nephropathy and proliferative retinopathy were assessed and related to baseline fractal dimensions in multiple regressions adjusted for sex and baseline age, diabetes duration, HbA1c, BP, BMI, vibration perception threshold, albuminuria, retinopathy and vessel diameters. RESULTS: Mean baseline age and diabetes duration were 21.0 and 13.4 years, respectively, and of patients 50.0% were males. The mean fractal dimension was 1.3817. The 16 year incidences of neuropathy, nephropathy and proliferative retinopathy were 10.8%, 8.0% and 27.9%, respectively. Multiple regression analyses showed a lower fractal dimension to significantly predict incident neuropathy (OR 1.17 per 0.01 fractal dimension decrease [95% CI 1.01, 1.36]), nephropathy (OR 1.40 per 0.01 fractal dimension decrease [95% CI 1.10, 1.79]) and proliferative retinopathy (OR 1.22 per 0.01 fractal dimension decrease [95% CI 1.09, 1.37]). CONCLUSIONS/INTERPRETATION: The retinal vascular fractal dimension is a shared biomarker of diabetic microvasculopathy, thus indicating a possible common pathogenic pathway. Retinal fractal analysis therefore is a potential tool for risk stratification in type 1 diabetes.

Retinal vessel calibers predict long-term microvascular complications in type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5-1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.

The 16-year incidence, progression and regression of diabetic retinopathy in a young population-based Danish cohort with type 1 diabetes mellitus: The Danish cohort of pediatric diabetes 1987 (DCPD1987).

The aim was to investigate the long-term incidence of proliferative diabetic retinopathy (PDR), and progression and regression of diabetic retinopathy (DR) and associated risk factors in young Danish patients with Type 1 diabetes mellitus. In 1987-89, a pediatric cohort involving approximately 75 % of all children with Type 1 diabetes in Denmark <19 years of age was identified (n = 720). In 1995, 339 (47.1 %) were re-studied with retinopathy graded and all relevant diabetic parameters assessed. Of those, 185 (54.6 %) were evaluated again in 2011 for the same clinical parameters. All retinal images were graded using modified early treatment of DR study for 1995 and 2011. In 1995, mean age was 21.0 years and mean diabetes duration 13.5 years. The 16-year incidence of proliferative retinopathy, 2-step progression and 2-step regression of DR was 31.0, 64.4 and 0.0 %, respectively, while the incidence of DR was 95.1 %. In a multivariate logistic regression model, progression to PDR was significantly associated with 1995 HbA1c (OR 2.61 per 1 % increase, 95 % CI 1.85-3.68) and 1995 diastolic blood pressure (OR 1.79 per 10 mmHg increase, 95 % CI 1.04-3.07). Two-step progression of DR was associated with male gender (OR 2.37 vs. female, 95 % CI 1.07-5.27), 1995 HbA1c (OR 3.02 per 1 % increase, 95 % CI 2.04-4.48) and 1995 vibration perception threshold (OR 1.19 per 1 Volt increase, 95 % CI 1.02-1.40). In conclusion, one in three progressed to PDR and two in three had 2-step progression despite young age and increased awareness of the importance of metabolic control. After 30 years duration of diabetes, the presence of DR is almost universal.

[Endophthalmitis as the first clinical manifestation of infectious endocarditis]. / Endogen endoftalmitis som første kliniske manifestation af aortaklapendokarditis.

Infectious endocarditis is considered one of the most severe infections in the Western world. Complications include septic embolism, for example to the brain or the eye. Endogeneous endophthalmitis is a rare but severe eye disease. It is important to remember that clinical signs from the eye can be the first manifestation of systemic disease. We present a case report of an 81-year-old woman with endogenous endophthalmitis as the first clinical manifestation of infectious endocarditis.

[Endophthalmitis is an acute disease which threatens the vision]. / Endoftalmitis er en akut synstruende øjensygdom.

Endophthalmitis is one of the most serious and most dreaded complications in ophthalmology. It is most often seen as a complication to intraocular surgery and especially after cataract surgery. Approximately 90% of the cases of endophthalmitis are caused by bacteria. Symptoms and signs may include pain, blurred vision, and hypopyon. Intravitreal injection of antibiotics in combination with vitrectomy or vitreous tap is the mainstay in the treatment of endophthalmitis. Prompt recognition and intervention are essential in preserving the vision of the affected eye in the case of endophthalmitis.