21st Meeting of the
European Association for the Study of Diabetes
Eye Complications Study Group (EASDec)
Gdańsk Poland 13th - 15th May 2011
FREE PAPER SESSIONS
POSSIBLE ROLE OF ANGIOTENSIN II RECEPTOR BLOCKADE IN THE GLUCOTOXICITY ON HUMAN RETINAL PERICYTES
E. Berrone, E. Beltramo, S. Tarallo, M. Porta
Department of Internal Medicine, University of Turin, Italy
DESIGN. Diabetic retinopathy (DR) is characterized by capillary degeneration and pericyte drop-out. Angiotensin II (Ang II) regulates several pathological events, including cellular proliferation/hypertrophy. Elevated Ang II and/or increased sensitivity to Ang II have been etiologically associated with major vascular diseases. Clinical studies have suggested that inhibitors of the angiotensin-converting enzyme (ACE) can slow the progression to advanced stages of DR, while antagonists of the angiotensin AT1 receptor resulted in significant regression of DR in type 2 diabetic patients.
PURPOSE. The objective of this study was to verify if the Ang II receptor blocker (ARB) candesartan can act as an anti-apoptotic and protective factor for human retinal pericytes (HRP) in diabetic-like conditions.
METHODS. Pericytes were kept alternatively in high (HG) or normal (NG) glucose at 48h intervals for 8 days, with or without 10, 2, 1 or 0.2 µmol/ml candesartan. Control cells were cultured in stable NG or HG. Bax and bcl-2 mRNA expression, as markers of glucose-induced apoptosis, was determined by RT-PCR, apoptosis by ELISA and cell proliferation by cell counts and BrdU incorporation-ELISA. Senescence-associated β-galactosidase activity was also evaluated.
RESULTS. Intermittent, but not stable, high glucose decreased proliferation and increased apoptosis in HRP, consistently with our previous findings. Candesartan, 1 and 0.2 µmol/ml, when added to intermittent high glucose, was able to normalize apoptosis (both DNA fragmentation and Bcl-2/Bax expression), while higher concentrations had no significant effects. Even if candesartan does not influence proliferation, it seemed capable of reducing intermittent high glucose-activated senescence.
CONCLUSIONS. Candesartan has a significant anti-apoptotic effect on HRP, but further studies are necessary to better understand the mechanisms through which it works, in particular the signalling pathways involved and/or influenced by AngII.
MITOCHONDRIAL-DERIVED ROS CONTROLS MMP2 ACTIVITY BY RETINAL CAPILLARY PERICYTES EXPOSED TO HIGH GLUCOSE
J.M. Tarr1, L. Gatti3, N. Mustapha2, L. Lapazio3, K. Kaul1, A. Datti3, A. Orlacchio3
1Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
2Forest Research Institute, Malaysia
3Molecular Department of Biochemical Science and Biotechnologies, University of Perugia, Italy
DESIGN. In vitro study using bovine retinal pericytes.
PURPOSE. Diabetic retinopathy (DR) is the leading cause of blindness in the working age population and is characterised by vascular changes to the retinal capillary bed. Recent studies have suggested the role of matrix metalloproteinase (MMPs), particularly MMP-2 in the pathogensis of DR. In this study, we explored the potential roles of NADPH oxidase and mitochondrial-derived reactive oxygen species (ROS) in glucose-induced MMP-2 activity of cultured bovine retinal capillary pericytes (BRP).
METHODS. Passage 2-3 confluent cultures of BRP were exposed to normal (5.6 mM) glucose (NG) and high (25 mM) glucose (HG) for 48hr. In some experiments, NADPH oxidase inhibitors (500 uM apocynin, 1 uM scrambled and unscrambled gp91ds-tat), mitochondrial targeted antioxidant (1 uM MitoQ) and MMP-2 inhibitor (50 uM Oleoyl-N-hydroxylamide) were added to NG and HG medium. Conditioned medium and cell lysates were collected for gelatin zymography, intracellular glucose, caspase-3 activity, cell (nuclear and cytosol) fractionation, intracellular ROS production, and activation of nuclear matrix protein poly (ADP-ribose) polymerase (PARP).
RESULTS. Exposure to HG significantly increased MMP-2 activity (100 ± 0 vs. 103.8 ± 1.9, n = 7, P < 0.05). The addition of 1 μM MitoQ (103.8 ± 1.9 vs. 97.7 ± 2.5, p < 0.05, n =7) and MMP-2 inhibitor (103.8 ± 1.9 vs. 83.5 ± 5.1, p < 0.05, n =7) significantly reversed this glucose-induced MMP-2 activity. In contrast, NADPH oxidase inhibitors failed to reverse glucose-induced MMP-2 activity in BRP. The study also demonstrated 1) increased MMP-2 activity in the nucleus of BRP exposed to HG compared to NG (100 ± 0 vs. 106.8 ± 6.7, P <0.05) 2) the potential of MitoQ to reverse increased nuclear MMP-2 activity and intracellular glucose accumulation when exposed to HG, and 3) cellular MMP-2-caspase-3-PARP crosstalk in BRP exposed to HG.
CONCLUSIONS. This data indicates the potential role of mitochondrial derived ROS in the activation of MMP-2 and the subsequent effects on the extracellular matrix.
FENOFIBRATE EFFECT ON DIABETIC RETINOPATHY
N. Grigoryeva1, E. Shklyarov1, F. Shadrichev1, 2, O. Kryaneva1
1Regional Diabetological Centre, Saint-Petersburg, Russia
2Pavlov State Medical University, Saint-Petersburg, Russia
PURPOSE. To estimate the fenofibrate effect on diabetic retinopathy
METHODS. Type 2 diabetic patients (n=60) with nonproliferative diabetic retinopathy were included into the study. Thirty-five patients (70 eyes) were assigned to receive fenofibrate 200 mg/day, and 25 patients (50 eyes) were assigned to a control group. All patients were followed during 1 year. Complete ophthalmic examination including 7-field stereoscopic retinal photography and optical coherent tomography was performed at baseline, month 6 and month 12 visits. In addition fluorescein angiography was carried out, when needed. At each visit, blood pressure measurement and biochemical blood assay were done.
RESULTS. In the fenofibrate group, retinopathy progressed in 12.8% of cases (9 eyes) over the 12-month period. No neovascularization was registered. Grid photocoagulation for macular edema was necessary in 2.9% of cases (2 eyes). In 7.1% of cases (5 eyes), regression of retinopathy level was detected.
In the control group, retinopathy progressed in 28.0% of cases (14 eyes). In 6.0% of cases (3 eyes), proliferative diabetic retinopathy developed. 5 eyes (10.0%) required grid photocoagulation for macular edema. Retinopathy regression was revealed in 4.0% of cases (2 eyes).
The lipid profile assessment in the fenofibrate group showed significant lowering of total cholesterol, triglycerides, low-density lipoproteins and very low-density lipoproteins (р = 0.001). There was a trend of high-density lipoproteins increase (р = 0.11). In the fenofibrate group, no significant changes in both mean systolic and diastolic blood pressure were observed. In the control group, significant systolic pressure increase was present (р = 0.03), while the diastolic one showed no reliable difference (р = 0.92).
CONCLUSIONS. Fenofibrate treatment can be effectively applied for lipid profile normalization and prevention of clinically significant retinal changes in patients with type 2 diabetes mellitus. Fenofibrate use significantly lowers the risk of progression of diabetic retinopathy from 28.0% to 12.8% (р = 0.04), and the need for laser treatment from 16.0% to 2.9% (р = 0.02).
The increase of systolic blood pressure, high mean levels of triglycerides and very low-density lipoproteins were shown to be significant risk factors for progression of diabetic retinopathy and macular edema.
LONG-TERM ASSOCIATIONS BETWEEN SERUM LIPIDS AND PANRETINAL PHOTOCOAGULATION IN TYPE 1 DIABETES
J. Grauslund1, J S. Jørgensen2, A. Green3, A K. Sjølie1
1Department of Ophthalmology, Odense University Hospital, Odense, Denmark
2Department of Ophthalmology, Vejle Hospital, Vejle, Denmark
3Research Unit of Clinical Epidemiology, Center for National Clinical Databases, South, Odense University Hospital, Odense, Denmark
DESIGN. Cohort study
PURPOSE. To examine the predictive value of serum lipids on the need for panretinal photocoagulation (PRP) treatment in a long term follow-up of a cohort of Danish type 1 diabetic patients.
METHODS. A total of 243 type 1 diabetic patients were identified from a population-based cohort. Of these, 25 patients (10.3%) already had proliferative diabetic retinopathy (PDR) at baseline and were thus excluded from the study. The remaining 218 patients were followed from January 1993 to November 2006. Serum levels of lipids were collected at baseline. PRP treatment was considered as indicative of PDR during follow-up. Date of PRP was documented from the Danish National Patients Registry.
RESULTS. At baseline median age and duration of diabetes was 45.9 years (range 23.9-78.4 years) and 30 years (range 20-72 years), respectively. There was an equal distribution between men (50.5%) and women (49.5%). Serum triglyceride was independently associated with incident PRP. After adjustments for baseline age, duration of diabetes and gender, each 1 mmol/L increase in serum triglyceride was associated with a hazard ratio of 1.54 (95% confidence interval 1.09-2.18, p=0.02) of PRP. On the other hand, total cholesterol, HDL cholesterol and LDL cholesterol were not associated with a higher risk of incident PRP.
CONCLUSIONS. In a 13-year follow-up of a population-based cohort of long-term type 1 diabetic patients, serum triglyceride was associated with a 54 percent increased risk of PRP treatment which was used as a surrogate endpoint of PDR. These findings expand to the knowledge obtained by the FIELD and ACCORD studies that found a beneficial effect of fenofibrate treatment on diabetic retinopathy.
THE PREDICTIVE POWER OF MICROANEURYSM COUNT ON DEVELOPMENT OF SIGHT THREATENING RETINOPATHY AND THE RESPONSE TO TREATMENT WITH AN ANGIOTENSIN RECEPTOR BLOCKER. RESULTS FROM THE DIRECT PROGRAMME
A.K. Sjølie for the DIRECT Programme Study Group
Odense University Hospital, Odense, Denmark
DESIGN. Multicenter randomized clinical trial
PURPOSE. To study the association between baseline retinal microaneurysm (MA) score and development of diabetic maculopathy (CSME) and proliferative retinopathy (PDR) , and response to treatment with candesartan in people with diabetes.
METHODS. MAs were scored from yearly retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. CSME and/or PDR were classified according to the ETDRS definitions. Patients were normoalbuminuric, and normotensive with type 1 and type 2 diabetes or treated hypertensive with Type 2 diabetes at baseline. They were randomised to treatment with candesartan 32 mg daily or placebo and followed for 4.6 years.
RESULTS. A higher MA score at baseline predicted an increased risk of progression to CSME and /or PDR (HR per MA score 1.12, 95% CI 1.03-1.21, p =0.006 in type 1, HR 1.21, 1.07-1.36, p = 0.003 in type 2), although the number of events was low (37 events in type 1, and 22 events in type 2 patients). Although fewer progression events were observed in patients treated with Candesartan compared to placebo, this difference was not statistically significant (HR for Candesartan 0.77, 0.40-1.47, p=0.4 in type 1, and HR 0.72, 0.30-1.70, p=0.4 in type 2).
CONCLUSIONS. MA counts are valuable surrogate markers of retinopathy progression, and of particular importance when considering therapies aimed at very early stages of retinopathy.
DETERIORATION OF THE GLOMERULAR FILTRATION RATE AND HIGH VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL IN THE EYE ARE SEEMED TO BE THE MARKERS OF DIABETIC RETINOPATHY PROGRESSION AFTER CATARACT SURGERY
A.G. Kuzmin, D.V. Lipatov, T.A. Chistyakov, O.M. Smirnova, M.I. Arbuzova, A.V. Ilyin, M.V. Shestakova
Endocrinology Research Centre, Moscow, Russia
DESIGN. Prospective observation study for 12 months in humans.
PURPOSE. To estimate the influence of vascular endothelial growth factor (VEGF) in aqueous humor (AH) and glomerular filtration rate (GFR) on diabetic retinopathy (DR) progression after cataract surgery.
METHODS. There were 120 patients included in the study, they all had Type 1 or 2 diabetes mellitus and underwent cataract surgery with phacoemulsification and intraocular lens implantation. All patients had a full ophthalmological examination and glycemia, glycated hemoglobin, GFR were analysed before surgery. At the start of the surgery, samples of AH were obtained to establish VEGF value (by the enzyme-linked immunosorbent assay). Visual acuity (VA) was tested at 5th day and at 12 month after surgery and neovascular complications such as neovascular glaucoma (NG) and proliferative DR were established in order to calculate relative risk..
RESULTS. DR was found to be more severe in patients with higher VEGF levels in AH. Patients with severe nonproliferative DR (NPDR) and proliferative DR (PDR) had poorer VA after operation than patients with mild NPDR, although before surgery VA-s were not different. Patients with high VEGF level in the AH had 9,62-fold increased risk of DR progression (p=0,0004), had NG in 25% of the cases and had lower VA at 12.months. The incidence of the NG in patients with GFR above 60 ml/min/1,73m2 was 3%, in patients with reduced GFR (below 60 ml/min/1,73m2) was 17%. VA at 12 month was similar in these groups. Reduced GFR was associated with 5,9-fold risk of NG progression after cataract surgery (p=0,009). There was no correlation between GFR and VEGF value in the AH.
CONCLUSIONS. Increased VEGF level in the AH and reduced GFR significantly enhanced the risk of NG development after cataract surgery in patients with diabetes.
RISK FACTORS FOR DIABETIC EYE COMPLICATIONS IN SHORT DURATION (1-10 YEARS) OF TYPE 1 DIABETES IN WARMIA AND MAZURY, POLAND
J. Pieczynski1, E. Bandurska-Stankiewicz2, W. Matuszewski2, J. Rutkowska2, D. Wiatr-Bykowska2
1Ophthalmology Unit, General District Hospital, Olsztyn, Poland
2Chair and Clinic of Endocrinology, Diabetology and Internal Medicine, University of Warmia and Mazury, Olsztyn, Poland
DESIGN. Prospective study
PURPOSE: To estimate the risk factors of diabetic eye disease in short duration (1-10 yrs) of Type 1 diabetes mellitus (DM1) in Warmia and Mazury region of Poland
METHODS: We report on 143 out of the 331 registered patients (69 females and 74 males) with 1-10 yrs DM1 duration registered in Olsztyn Diabetic Centre. After visual acuity and intraocular pressure were measured, complete detailed ophthalmic examination was carried out with fully dilated pupils. in order to establish diabetes related eye complications. Metabolic control was also determined: HBA1c, BMI, blood pressure, renal function, and lipids were measured. Statistical analysis was carried out to find the relation between risk factors and eye complications.
RESULTS. Twenty-three patients (42 eyes) with diabetic eye complications were found (13 females and 10 males). The average age was 24 years and average DM1 duration was 6.9 years. The average age at onset of DM1 was 16.8. The following eye complications were observed: diabetic retinopathy (15 patients, 26 eyes), diabetic maculopathy (1 patient), cataract (7 patients, 13 eyes) and glaucoma (2 patients). We found correlations between diabetic eye complications and DM1 duration as well as between the time of diabetes onset and puberty and eye complications. No relations between diabetic eye complications and metabolic control were observed.
CONCLUSIONS. We found that 15% of all DM1 patients had diabetic eye complications. The most common eye complication was diabetic retinopathy. Risk factors for diabetic eye complications were DM1 duration and DM1 onset after puberty (≥13yrs).
BLINDNESS AND FREQUENCY OF VITRECTOMY IN YOUNG DANISH TYPE 1 DIABETIC PATIENTS. A 15-YEAR FOLLOW-UP.
R. Broe1, B. S. Olsen2, J. Grauslund1, P. Hougaard1,2, A. K. Sjølie1
1Department of Ophthalmology, Odense University Hospital, Denmark
2Pediatric Department, Glostrup Hospital, Denmark
DESIGN. Cohort study
PURPOSE. To investigate the prevalence of blindness and frequency of vitrectomy in a nationwide Danish cohort of young type 1 diabetic patients.
METHODS. In 1986-89 a cohort of 80% of all Danish type 1 diabetic patients below the age of 18 (n=720) was identified. In 1995, 324 patients from the original cohort participated in a clinical examination including retinal photography. In 2010, patients registered as blind by the Danish Society for the Blind were identified. Furthermore, data from the Danish National Patient Registry was used to determine the number of patients who had undergone vitrectomy and the date of their first surgery. Results were correlated to age, gender, diabetes duration and HbA1c.
RESULTS. Of the 324 patients examined in 1995, 6 have been registered as blind (4 males and 2 females), 5 were between 21 and 29 years old at registration. They had all had vitrectomy performed and mean HbA1c in 1995 was 10.8 ± 1.3%.
Thirty seven patients (11%) have undergone vitrectomy. At the time of their first surgery the mean age of patiens was 29.5 ± 4.9 years and the mean duration of DM was 22.7 ± 4.9 years. The rate of male patients were significantly higher among the vitrectomized patients (65%) than among the non-vitrectomized (53%, p<0.05). There was no difference according to age or duration of diabetes between the two groups.
For the vitrectomized patients, mean HbA1c in 1995 was 11.1 ± 1.9% compared to the remaining patients (mean HbA1c 9.9 ± 6.8 %, p<0.05).
CONCLUSIONS. One in ten patients had undergone vitrectomy in a 15-year follow-up of a population-based cohort of Danish type 1 diabetic patients. The mean age at the time of surgery was less than 30 years.
Our results indicate that high levels of HbA1c in childhood and adolescence, as well as male gender, increase the risk of severe diabetic retinopathy, causing need of vitrectomy and blindness at a very young age.
CARDIOVASCULAR DISEASE AND MORTALITY ARE RELATED TO WHICH VISION THREATENING COMPLICATION THAT DEVELOPS IN TYPE 2 DIABETIC PATIENTS.
K. Tilma, T. Bek
Department of Ophthalmology, Århus University Hospital, Denmark
DESIGN. Cross-sectional epidemiological study.
PURPOSE. Diabetic retinopathy may lead to one or both of two vision threatening manifestations, i.e. proliferative diabetic retinopathy and diabetic maculopathy, but the background for developing either one or both of these two complication types is unknown. The purpose of the present study was to identify clinical and epidemiological parameters differentiating patients who develop either of the two vision threatening complications.
METHODS. All 1430 patients with either T1D or T2D who had been treated with laser photocoagulation for diabetic maculopathy or proliferative diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital between 1997 and 2009 were included. The Danish National Patient Register was searched for all diagnoses registered at previous admission to hospitals and deaths in the country, and the Death Certificate Register at the Danish National Board of Health was reviewed to collect registered causes of death in these patients.
RESULTS. Patients with T2D had a significantly higher age at diagnosis of diabetes mellitus, age of first treatment, age of death, systolic blood pressure and BMI than patients with T1D, whereas HbA1c was higher in T1D than in T2D patients. Significantly more patients with T2D than with T1D had died and been hospitalized with cardiovascular diagnoses, the latter being more frequent in patients who had been treated for maculopathy than for proliferative diabetic retinopathy in T2D, whereas no relation to treatment type was found for T1D patients.
CONCLUSIONS. Cardiovascular disease and mortality is higher in T2D patients who develop diabetic maculopathy than in patients who develop proliferative diabetic retinopathy, whereas no relation to treatment type exists for T1D patients. These differences may help understanding the mechanism of development of either of the two vision threatening complications in diabetic retinopathy.
SURVIVAL ANALYSIS OF DIABETIC PATIENTS UNDERGOING VITRECTOMY
G.M. Morphis1, T.A. Sandigha1, I.A. McKay2, D.M. Broadbent1, S.P. Harding3, H. Heimann1
1St. Paul's Eye Unit, Royal Liverpool University Hospital, UK
2Department of Statistics, Glasgow, UK
3Department of Eye and Vision Science, University of Liverpool, UK
DESIGN. Retrospective review
PURPOSE. Proliferative diabetic retinopathy (PDR) is the most severe form of diabetic eye disease. We aimed to describe survival rates of patients with diabetes that had undergone vitrectomy in the past, to determine what clinical factors might be associated with their survival times and to compare these rates with those of diabetics that were being followed conservatively.
METHODS. Retrospective review of 87 diabetic patients that had vitrectomy in the past for either non clearing vitreous hemorrhage or tractional retinal detachment compared to 145 patients with diabetes that did not require any vitrectomy in the past. Clinical factors investigated included hypertension, heart disease, neuropathy and nephropathy.
RESULTS. The 3 year survival rate of patients requiring vitrectomy (yrs) was 0.69±0.06. compared to 0.91±0.02 in patients with conservative treatment. The 5 year death rate was 3 times greater in patients that required surgical management (0.51 vs 0.17). Coexistent cardiovascular disease in the same group was found to be associated with significantly less survival rate (0.51±0.09, p<0.001).
CONCLUSIONS. Vitrectomy in patients with diabetes is an indicator of advanced generalised disease and associated with reduced life expectancy. Coexistent cardiovascular disease further decreases survival rates. Such patients require special attention in terms of their general condition.
RETINAL GLIAL CELLS ACTIVATION IN DIABETICS WITH AND WITHOUT RETINOPATHY: AN IN VIVO STUDY
E. Midena1, F. Martini1, A. Rediu1, M. Casciano1, S. Vujosevic2
1Department of Ophthalmology, University of Padova, Padova, Italy
2Fondazione G.B. Bietti, IRCCS, Roma, Italy
DESIGN. observational case series
PURPOSE. To evaluate if retinal glial cells activation may be detected in vivo in eyes without and with nonproliferative diabetic retinopathy.
METHODS. Eighty-eight subjects were enrolled: 58 subjects were affected by diabetes mellitus and 30 normals served as controls. Proliferative diabetic retinopathy, previous laser photocoagulation, intraocular surgery or intravitreal injection, and refractive error > 6 diopters were the main exclusion criteria. One eye of each subject was used for statistical analysis. Thirty patients had no diabetic retinopathy (no DR group), 28 patients had non proliferative DR without macular edema (DR group). Full ophthalmic examination, stereoscopic fundus photography, and spectral domain-OCT (SD-OCT; RS-3000, Nidek, Japan) were performed in all eyes. After automatic segmentation (layering) of 5 retinal layers by SD-OCT, the thickness of these layers was automatically calculated in the foveal and pericentral area, and values compared among groups. The thickness of selected, more specific layers (inner limiting membrane, inner plexiform and nuclear layers, outer plexiform layer) was also manually quantified. All measurements were performed twice by two independent graders.
RESULTS. No statistically significant differences were found for age among all groups, and for diabetes duration among diabetics. In the no DR and DR groups, using automatic layering, the mean thickness of inner retina was significantly reduced compared to controls (p<.001), no change was detected in the outer retina, both in the fovea and pericentral area. A significant increase of inner limiting membrane, inner plexiform and nuclear layers was found in DR eyes vs controls (p<0.001), versus a significant decrease of retinal ganglion cell and retinal nerve fiber layers. The inter-grader agreement was at least substantial for all measurement.
CONCLUSIONS. Increased thickness of retinal layers mainly corresponding to retinal glial cells, even before the appearance of clinically detectable retinopathy, confirms in vivo early glial cells activation in diabetic retina. Glial activation may be detected by spectral domain OCT using targeted analysis. These data strongly suggests a very early reactive and degenerative processes both in neural and glial cells of diabetic retina.
DIABETIC CHOROIDOPATHY: A SPECTRAL DOMAIN OCT STUDY
S. Vujosevic2, E. Pilotto2, F. Martini2, A. Rediu2, E. Midena1,2
1Fondazione G. B. Bietti, IRCCS, Roma, Italy
2Department of Ophthalmology University of Padova, Padova, Italy
DESIGN. Observational case-series
PURPOSE. To investigate if choroidal involvement (diabetic choroidopathy) may be observed in diabetic patients with and without diabetic retinopathy (DR), by spectral domain OCT.
METHODS. Eighty seven subjects were enrolled:59 diabetic patients (102 eyes) and 28 normals. Exclusion criteria were: previously treated diabetic retinopathy (DR), refractive error higher than +/- 3D, treated or untreated glaucoma. All patients underwent: full ophthalmic examination, stereoscopic color fundus photography and spectral domain OCT(SD-OCT: RS-3000, Nidek, Japan). SD-OCT was performed in the macula and peripapillary region. SD-OCT examination consisted in linear scans, 6 mm in length, centered onto the fovea, and circle scan positioned around the optic disc (3.46mm in diameter). Choroidal thickness (CT) was measured manually at the fovea, and at 1, 2, 3mm distance along all scans in the macula. Peripapillary CT was measured at 8 points along the circle scan. All measurements were performed independently by two masked graders.
RESULTS. Mean age was not significantly different between diabetics and controls. In the macular area, CT was significantly lower in the nasal quadrant vs all other quadrants (p<0.0001), in both groups. In the peripapillary area, CT was significantly lower in the inferior quadrant vs all other quadrants (p<0.05), in both groups. Mean macular and peripapillary CT progressively and significantly decreased with increasing level of DR (non proliferative and proliferative DR vs controls, p<0.05). No significant CT difference was found between controls and diabetic eyes without detectable DR. Diabetic macular edema did not influence CT. Choroidal thickness in the macula and peripapillary area was highly correlated in diabetics (R>0.7, p<0.0001). Intergrader agreement was almost perfect for all measurements, (k>0.9).
CONCLUSIONS. In diabetic patients diabetic retinopathy precedes diabetic choroidopathy. Diabetic choroidopathy starts when DR is already present and parallels it afterwards. SD-OCT clearly confirms in vivo previously reported histopathologic choroidal observations. The role of choroid in the pathophysiology of DR needs to be further investigated.
PREVALENCE OF DIABETIC RETINOPATHY AND VISUAL IMPAIRMENT IN DIABETIC PATIENTS IN SUB-SAHARAN AFRICA
S.P. Harding1, S.J. Glover1,2, P.I. Burgess1, D.B. Cohen2, H.W.C. Hofland2, E.E. Zijlstra2, T.J. Allain2
1Ophthalmology Research Unit, University of Liverpool, UK
2College of Medicine, University of Malawi, Blantyre, Malawi
DESIGN. Cross-sectional study
PURPOSE. There is little published data on the prevalence of diabetic retinopathy in Sub-Saharan Africa. We report the prevalence of all grades of retinopathy and associations with systemic parameters in patients attending a secondary care diabetes clinic in Blantyre, Malawi.
METHODS. Cross-sectional study of all patients attending for diabetes care. Clinical examination and biochemical testing comprised: visual acuity (VA), grade of retinopathy (slit lamp biomicroscopy), microvascular complications, glycaemic control, hypertension, HIV status. Sight threatening diabetic retinopathy (STDR): moderate preproliferative retinopathy or worse, circinate maculopathy or exudates within one disc diameter of the foveal centre or clinically significant macular oedema (CSMO).
RESULTS. Type 2 diabetes (n= 249): prevalence (95% confidence interval (CI)) of any retinopathy, STDR and proliferative diabetic retinopathy (PDR) was 32.5% (26.7-38.3), 19.7% (14.7–24.6) and 4.8% (2.2–7.5) respectively. Presence of STDR was associated with albuminuria (odds ratio (OR) 2.61; p=0.02), presence of neuropathy (OR 3.371; p=0.005) and insulin use (OR 5.296; p=0.0004) but not with HIV status. Type 1 diabetes (n= 32): prevalence of any retinopathy, STDR and PDR was 28.1% (12.5–43.7), 18.8% (5.2–32.2) and 12.5% (1.0–24.0) respectively. 12.1% of the study population had VA worse than 6/18 (20/60).
CONCLUSIONS. This study provides baseline information on prevalence of all grades of retinopathy and STDR in an urban/semi-urban diabetic population in sub-Saharan Africa. Prevalence of STDR was high and in type 2 diabetes was associated with albuminuria, neuropathy and insulin use.
THE IMPACT OF DIABETES ON THE CHARACTERISTICS OF TYPE 2 MACULAR TELANGIECTASIA
T. Peto1, T.E. Clemons2, F.B. Sallo1, I. Leung1
1Moorfields Eye Hospital NSH Foundation Trust, London, UK
2EMMES Corporation, Rockville, Maryland, USA
DESIGN. The Natural History Observation study of Type 2 Macular Telangiectasia (MacTel) has been running for 6 years now. It has been noted that a high proportion of patients with MacTel also have diabetes, but the impact of this on the characteristics of MacTel has not been evaluated before.
PURPOSE. The aim of this study was to analyse the impact of diabetes on the characteristics of MacTel.
METHODS. Of 555 probands enrolled into the study, 188 had diabetes (96% Type 2). All had colour fundus, fluorescein angiographic and OCT images and these were graded on the ETDRS scale for severity of retinopathy and maculopathy. MacTel was graded for disease characteristics. Once grading was finalised, stage of MacTel and corresponding clinical data including visual acuity and diabetes control were analysed.
RESULTS. Patients with MacTel and diabetes had an average HbA1c of 6.9±1.4%. Patients with diabetes who have early stages of MacTel had borderline significantly worse starting visual acuity than those without diabetes (Stage 1: p=0.101; Stage 2: p=0.06, Stage 3: 0.114; no difference in Stage 4-5 MacTel). After adjustment for duration of Mactel and staging, patients with uncontrolled diabetes had significantly lower visual acuity at baseline compared to probands with no history of diabetes, despite having no difference in the severity of diabetic retinopathy or maculopathy, (No diabetes 70.3±0.7 letters, Diabetes controlled: 66.4±1.3 (p=0.008); Diabetes uncontrolled 65.±1.6; p=0.02). During the up to 5-year follow-up, only one patient developed treatable maculopathy and none developed proliferative diabetic retinopathy.
CONCLUSIONS. The relationship between MacTel and diabetes mellitus appears intricate. Diabetes seems to have a clinically meaningful impact on visual acuity and progression of MacTel, especially in early stages of the disease. On the other hand, patients with MacTel and diabetes do not seem to develop treatable diabetic retinopathy or maculopathy with the same rate as general diabetic population. Further investigations are necessary for developing an optimal management strategy to preserve the vision of these patients.
FILTERING NORMAL DIABETIC RETINOPATHY IMAGES THROUGH EVOLUTIONARY COMPUTATION
H. L. Tang1,2, T. Peto2, J. Goh1, Y. Jin1, C. Chuluunkhuu3
1Department of Computing, University of Surrey, UK
2Reading Centre, Department of Research and Development, Moorfields Eye Hospital NHS Foundation Trust, UK
3London School of Hygiene and Tropical Medicine, UK
DESIGN. In the UK diabetic retinopathy (DR) screening programme, about 2/3rd images are normal. On average, graders take about 1.5 times longer to decide an image as normal. An automated system has been developed for filtering normal cases. This system firstly learnt to understand DR images through image samples collected from various sources. The system was then tested on a new set of data, 1680 images from 420 patients, which has a clinical grading, and a grading by Reading Centre at Moorfields Eye Hospital, UK.
PURPOSE. To evaluate an automated diabetic retinopathy image analysis system as a possible aid to a more productive screening service.
METHODS. To address the complicated variability and subtlety in DR images, an integrated approach was developed to combine detection evidence from various processing stages, especially a contextual environment each time a clinical sign may appear was dynamically captured through a context model. The system first detected the basic clinical signs such as exudates, micro aneurysms (MA), haemorrhage, and anatomical structure, e.g. optic disc, macula and blood vessels, using various image processing techniques followed by a reasoning process. For each above content, multiple classifiers were implemented. For example, for MA alone, there were 180 classifiers. This is to address the variability in DR images. The multiple classifiers were then optimised through genetic algorithms to obtain the best set of classifiers. Statistical modelling method, Hidden Markov Models, were then utilised to recognise contextual relationships among the candidate regions. The Hidden Markov Models were also optimised through evolutionary algorithms to obtain the “best” representation of the context.
RESULTS. The system was tested on 1680 previously unseen images taken from 420 patients. The sensitivity was 95% and the specificity was 98%. Among all the images that the system decided as normal, 99% were true normal according to the double manual grading results.
CONCLUSIONS. The current automated system seems to be able to filter out majority of normal images with good accuracy. This result provides a better understanding of the potentials of utilising evolutionary computation to maximise the detection accuracy.
HOW ACCURATE ARE PHOTOGRAPHIC SURROGATE MARKERS USED TO DETECT MACULAR OEDEMA IN THE ENGLISH NATIONAL SCREENING PROGRAMME?
H.M. Wharton1, J.M. Gibson1,2, P.M. Dodson1,2
1Departments of Ophthalmology and Diabetes, Heartlands Hospital, Birmingham, UK
2School of Life and Health Sciences, Aston University, Birmingham, UK
DESIGN. Retrospective analysis
PURPOSE. Macular oedema is not directly visible on two dimensional digital photographs such that surrogate markers need to be used. In the English National Screening Programme these are exudate within one optic disc diameter (DD) of the fovea, group of exudates within two DD of the fovea and haemorrhages or microaneurysms (HMA) within one DD of the fovea with best corrected visual acuity (VA) worse than 6/9. All patients who present with any of these surrogate markers at screening are referred to an ophthalmology clinic for slit lamp examination. The purpose of this audit was to determine how many patients with positive maculopathy diagnosis on photography were truly identified by optical coherence tomography (OCT) with macular oedema.
METHODS. Data was collected from patients attending digital diabetic retinopathy screening. Patients who presented with surrogate markers for macular oedema also had an OCT scan. The fast macula scan on the Stratus OCT was used and an ophthalmologist reviewed the scans to determine whether macular oedema was present.
RESULTS. Maculopathy by exudates: Of 155 patients 45 (29%) showed thickening on the OCT of these 12 required laser. Those who also had pre-proliferative retinopathy (n=20) were more likely to have macular oedema (75%) than those with background diabetic retinopathy.
Maculopathy by HMA and VA worse than 6/9: Of 66 patients 11 (16.7%) showed thickening on the OCT. 5 (7.6%) of these had macular oedema, 5 (7.6%) epi-retinal membrane, and 1 (1.5%) age related macular degeneration. None of these patients required laser.
CONCLUSIONS. The likelihood of the presence of macular oedema and requiring laser treatment is greater with macular exudation than HMA within one DD and reduced VA. Overall the surrogate markers used show low specificity for macular oedema, however combining OCT with photography does identify those with macular oedema who require a true referral for an ophthalmological slit lamp examination.
PROLIFERATIVE DIABETIC RETINOPATHY (R3) REFERRALS FROM THE DIGITAL DIABETIC RETINOPATHY SCREENING PROGRAM: URGENCY OF APPOINTMENT IN THE HOSPITAL EYE SERVICE ACHIEVED AND NEEDED?
T. K. Geletew1, P.M. Amrelia1, H.M. Wharton1, P.M. Dodson1,2, J.M. Gibson1,2, A. Wright1
1Department of Ophthalmology and Diabetes, Birmingham Heartlands Hospital, UK
2Department of Health and Life Sciences, Aston University, Birmingham, UK
DESIGN. Retrospective analysis
PURPOSE. To assess the clinical characteristics and outcomes of patients identified with proliferative diabetic retinopathy (PDR) referred from the screening program to the hospital eye services (HES)
METHODS. a retrospective analysis of urgently referred PDR cases to Birmingham Heartlands HES from august 2008 until July 2010
RESULTS. 130 urgent diabetic retinopathy referrals were made and reviewed. 103 (68% male, 80% type 2 diabetes) were referred for PDR with a mean age of 59 years, mean diabetes duration of 17.8years. 69% were on insulin treatment at the time of the screening, with mean HbA1c of 10.4% (range-5.7 to 16.5%). 65% of the patients were offered appointments at HES within two weeks after referral from the screening. 50.5% of the patients were seen in the HES within 2 weeks, 22 and 16 % were seen 2-4 and 4-8 weeks after referral respectively. 6 patients never attended ophthalmology examination during the two years of review. Of all the attendees, 56% were booked for pan retinal photocoagulation (PRP) & 9(9.3%) for macular laser respectively on their 1st HES visit. 75% of the patients were newly diagnosed PDR and 26 had previous PRP laser but lost to follow up. 63 patients ( 66%) received either PRP or macular laser treatment (85.7% of which is PRP). 63% of the PRP treatment was performed within a month of first HES attendance. Retinopathy grading discrepancy between the screening program and HES was noted in 20% (21 patients).
CONCLUSIONS. This data suggests that the digital screening programme is appropriately identifying high risk patients with PDR with timely PRP laser treatment in the majority of patients but raises concern over patients lost to follow up (hence failsafe tracking of appointment attendance), and review of grading discrepancies between the ophthalmology and screening service.
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