Jakob Grauslund

Global prevalence and major risk factors of diabetic retinopathy

OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

Retinal Vascular Fractals and Microvascular and Macrovascular Complications in Type 1 Diabetes

PURPOSE Fractal analysis is a method to quantify the geometric pattern and complexity of the retinal vessels. This study examined the association of retinal fractal dimension (D(f)) and microvascular and macrovascular complications in a population-based cohort of Danish patients with type 1 diabetes. DESIGN Cross-sectional study. PARTICIPANTS This was a cross-sectional study of 208 long-term surviving type 1 diabetes patients from a population-based Danish cohort identified in 1973. METHODS Retinal photographs were obtained at a clinical examination in 2007 or 2008. D(f) was measured with a semiautomatic computer-based program (International Retinal Imaging Software; National University of Singapore, Republic of Singapore; University of Sydney, Sydney, and University of Melbourne, Melbourne, Australia). D(f) of the retinal vasculature was measured within a predefined circular region of 3.5 optic disc radii centered on the optic disc. Line tracing of the vasculature was provided by the program. Any artifacts were removed by the grader, and the box-counting method then was used by the program to calculate D(f). MAIN OUTCOME MEASURES The association of D(f) with proliferative retinopathy, nephropathy, neuropathy, and macrovascular disease (coronary heart disease, stroke, peripheral artery disease) was examined. RESULTS Retinal fractals were gradable in at least 1 eye in 178 (86.6%) of 208 patients. Median age and duration of diabetes for these patients were 57.8 years and 42 years, respectively. Median D(f) was 1.4610 (range, 1.3774-1.5188). After adjustments for age, gender, duration of diabetes, systolic blood pressure, and smoking, persons with lower D(f) were more likely to have proliferative retinopathy (odds ratio [OR], 1.45 per standard deviation [SD] decrease in D(f); 95% confidence interval [CI], 1.04-2.03) and neuropathy (OR, 1.42 per SD decrease in D(f); 95% CI, 1.01-2.01). There was also a trend of an association between lower D(f) and nephropathy (OR, 1.39 per SD decrease in D(f); 95% CI, 0.97-2.01) but not macrovascular disease. Furthermore, persons with lower D(f) were older. CONCLUSIONS This study adds to the evidence that D(f) may have some role as a global measure of retinal vasculature and its association with systemic disease. Prospective studies clarifying this role are needed. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy, safety, predictability, contrast sensitivity, and aberrations after femtosecond laser lenticule extraction.

Purpose To compare femtosecond lenticule extraction and small‐incision lenticule extraction to treat moderate to high myopia. Setting Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark. Design Prospective clinical single‐masked paired‐eye study. Methods An intrastromal lenticule was cut by a femtosecond laser and manually extracted. In femtosecond lenticule extraction, a laser in situ keratomileusis–like flap allowed removal of the lenticule, whereas in small‐incision lenticule extraction, it was removed through a small incision. Follow‐up was 6 months. Results Thirty‐five patients were treated with femtosecond lenticule extraction in 1 eye and small‐incision lenticule extraction in the other. The mean preoperative spherical equivalent was −7.6 diopters (D) ± 1.0 (SD) (range −6.0 to −9.9 D). After both procedures, 90% of eyes had an uncorrected distance visual acuity of 20/40 or better 1 day postoperatively, increasing to 100% after 6 months. At 6 months, the mean corrected distance visual acuity (CDVA) improved significantly by approximately 1.5 letters on the logMAR chart. No eyes lost or gained 2 lines or more of CDVA after either procedure. The achieved refraction was a mean of −0.04 ± 0.38 D from the attempted refraction after femtosecond lenticule extraction and −0.09 ± 0.39 D after small‐incision lenticule extraction. After both procedures, 88% of eyes were within ±0.50 D. Contrast sensitivity was unchanged. The changes in higher‐order aberrations were similar. Conclusion The all‐femtosecond laser flap‐based and cap‐based techniques produced almost identical results up to 6 months postoperatively in eyes with moderate to high myopia. Financial Disclosure Dr. Hjortdal received travel reimbursement from Carl Zeiss Meditec AG. No other author has a financial or proprietary interest in any material or method mentioned.

Central Corneal Sublayer Pachymetry and Biomechanical Properties After Refractive Femtosecond Lenticule Extraction

PURPOSE To compare central corneal sublayer pachymetry and biomechanical properties after femtosecond lenticule extraction (FLEX) and small-incision lenticule extraction (SMILE). METHODS A prospective, randomized, single-masked clinical trial of 35 patients treated for moderate to high myopia with FLEX in one eye and SMILE in the other. Anterior segment optical coherence tomography imaging (Heidelberg Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany) was used to measure central corneal thickness (CCT) and epithelial, flap/cap, and residual stromal bed thickness centrally. The Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY) was used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Patients were examined before and 6 months after surgery. RESULTS Mean decrease in CCT was 105 μm in FLEX-treated eyes and 106 μm in SMILE-treated eyes (P = .70), which is equivalent to approximately 14 μm/diopters corrected. Mean central epithelial thickness increased 7 ± 6 μm in FLEX-treated eyes and 6 ± 5 μm in SMILE-treated eyes (P = .64). Achieved mean flap/cap thickness was 4 ± 6 μm from the expected thickness in FLEX-treated eyes and 4 ± 9 μm in SMILE-treated eyes (P = .37). CH was reduced 2.7 ± 1.3 mm Hg in FLEX-treated eyes and 3.3 ± 1.2 mm Hg in SMILE-treated eyes (P = .08). CRF was reduced 4.5 ± 1.2 mm Hg in FLEX-treated eyes and 4.6 ± 1.2 mm Hg in SMILE-treated eyes (P = .71). CH and CRF were highly correlated with CCT, but not patient age. CONCLUSIONS In this paired-eye study, the flap-based FLEX and cap-based SMILE resulted in almost identical changes in central corneal sublayer pachymetry and biomechanical properties for moderate to high myopia 6 months after treatment.

Blindness in a 25-Year Follow-up of a Population-Based Cohort of Danish Type 1 Diabetic Patients

PURPOSE To assess the long-term incidence of blindness and to evaluate risk factors for blindness in a population-based cohort of type 1 diabetic patients. DESIGN Retrospective cohort study. PARTICIPANTS A population-based cohort of 573 type 1 diabetic patients, all of whom participated in a clinical ophthalmologic examination in 1981 and 1982 and were followed up for 25 years. METHODS At the baseline examination in 1981 and 1982, visual acuity, level of retinopathy, maculopathy, hemoglobin A(1) (HbA(1)), proteinuria, smoking habits, and blood pressure were evaluated and related to the subsequent development of blindness. Blindness was defined as present in patients who were registered as members of the Danish Association of the Blind between baseline and January 2007. The Danish Association of the Blind is a voluntary organization open for all patients with a best-corrected visual acuity in the best eye of <or=6/60 (20/200) or with complications (i.e., visual fields <10 degrees ) subjectively leading to a best-corrected visual acuity in the best eye of <or=6/60 (20/200). MAIN OUTCOME MEASURES Evaluation of 25-year incidence of blindness, predictors for blindness, and gender-specific incidence rates for blindness. RESULTS The 25-year cumulative crude incidence of blindness was 7.5% (men, 8.0%; women, 6.8%; P = 0.61), corresponding to a mortality-adjusted cumulative incidence of blindness of 9.5% (95% confidence interval [CI], 7.1%-12.0%) and an overall incidence rate of blindness of 4.11 per 1000 person-years (95% CI, 3.03-5.59 per 1000 person-years). Blindness was predicted by HbA(1) and maculopathy at baseline. The odds ratio of blindness during follow-up was 1.69 (95% CI, 1.01-2.84) for a 1% increase in baseline HbA(1) and was 6.18 (95% CI, 1.18-32.47) and 8.61 (95% CI, 2.54-29.23) for patients with maculopathy in combination with nonproliferative retinopathy and proliferative retinopathy, respectively. Age and duration at baseline, gender, proteinuria, smoking, systolic and diastolic blood pressure, and visual acuity at baseline were not associated with the development of blindness. Mortality was higher in patients who had become blind (61.0% vs. 42.1%; P = 0.02). CONCLUSIONS Blindness is still a common complication in type 1 diabetes. Glycemic regulation and the presence of maculopathy are important risk factors for the development of blindness.

Risk factors for mortality and ischemic heart disease in patients with long-term type 1 diabetes.

AIMS The purpose of this study is to evaluate the effect of glycemic regulation, dyslipidemia, and renal dysfunction on mortality (all-cause and cardiovascular) and ischemic heart disease (IHD) in a long-term follow-up of a population-based cohort of Danish type 1 diabetic patients with at least 20 years of diabetes. METHODS A population-based cohort of type 1 diabetic patients was identified as of July 1, 1973 (n=727). In 1993 to 1996, the cohort was reassessed and baseline data were collected from blood and urine samples in 389 patients. Mean (glycemic regulation and lipids) and highest values (creatinine and albuminuria) of the baseline period were used to predict mortality and IHD between baseline and 2006. Data of mortality and morbidity were provided by the Danish Civil Registration System, the Danish Causes of Death Registry, and the Danish National Patient Registry. RESULTS At the follow-up in 2006, 256 patients (65.8%) were still alive. In a statistical model adjusted for age, sex and duration of diabetes, the following parameters were related to all-cause mortality and cardiovascular mortality: glycemic regulation, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (inversely), total cholesterol, creatinine, and macroalbuminuria. Furthermore, all markers except macroalbuminuria were associated with IHD. Microalbuminuria at baseline was not related to any of the endpoints. CONCLUSIONS Glycemic regulation, dyslipidemia, and renal dysfunction were all related to mortality and IHD in a 13-year follow-up of long-term Danish type 1 diabetic patients. These results underscore the better outcome for tightly regulated type 1 diabetic patients, even in long-term survivors.

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.

Eye Complications and Markers of Morbidity and Mortality in Long-term Type 1 Diabetes

The incidence of type 1 diabetes is rising all over the world. Furthermore, the increased life‐expectancy of type 1 diabetic patients is likely to cause a higher number of diabetes‐related micro‐ and macrovascular complications in the years to come.

Long-term Outcomes of Photorefractive Keratectomy for Low to High Myopia: 13 to 19 Years of Follow-Up

PURPOSE To evaluate long-term outcomes after photorefractive keratectomy (PRK). METHODS A retrospective follow-up study of patients who received PRK at 5.0- to 6.5-mm optical zones, using the Summit broad beam excimer laser (Summit Technology, Inc., Waltham, MA) at Odense University Hospital, Odense, Denmark, between 1992 and 1998. One randomly selected eye of each patient was used in the statistical analyses. Re-treated eyes were excluded. RESULTS One hundred sixty eyes were included. Mean follow-up time was 16 years (range: 13 to 19 years). Mean preoperative spherical equivalent was -4.84 ± 2.95 diopters (D) (range: -20.25 to -1.25 D). At last follow-up examination, achieved refraction was -1.00 ± 1.56 D (range: -10.75 to +1.00 D) from attempted refraction, and the change in mean refractive error from 6 months postoperatively was less than 1.00 D. Results from a subgroup of unilateral treated patients indicated that myopic progression was the main reason for the residual refractive error. For eyes with low myopia (n = 124), the proportion of eyes within ± 1.0 D of attempted refraction was 72%, and for eyes with high myopia (-6.00 D or more, n = 36) it was 47%. Forty-five percent had uncorrected distance visual acuity of 20/20 or better at last follow-up examination. Three eyes (2%) lost two or more lines and 13 eyes (8%) gained two or more lines of corrected distance visual acuity. Fourteen percent had haze (grade 0.5 to 2). Eighty-one percent were satisfied with the surgery. CONCLUSION PRK for low degrees of myopia seemed safe and effective up to 19 years after surgery with conventional broad beam laser ablation. Refractive predictability was significantly lower and the occurrence of haze was higher in eyes with high myopia.

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.