Attendance in a national screening program for diabetic retinopathy: a population-based study of 205,970 patients.

AIMS: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. METHODS: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). RESULTS: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). CONCLUSIONS: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments.

Diabetic retinopathy in people with Type 2 diabetes and obesity treated by Roux-en-Y gastric bypass compared with non-operated controls: with focus on the role of diabetes remission in a cross-sectional and a 6-year follow-up study.

AIM: Whether or not Roux-en-Y gastric bypass (RYGB) and the derived metabolic improvements are beneficial to diabetic retinopathy is controversial. We aimed to determine the presence and development of retinopathy in individuals with obesity and Type 2 diabetes treated by RYGB compared with non-operated controls, and to determine the role of diabetes remission. METHODS: We graded fundus photography using the Wisconsin Epidemiologic Study of Diabetic Retinopathy in 96 individuals with obesity and Type 2 diabetes treated by RYGB 6 years after surgery compared with 48 non-operated controls. In a subsample, we investigated the development of retinopathy over time. In the secondary analysis, we divided the RYGB group according to diabetes remission. RESULTS: RYGB surgery was not statistically associated with less retinopathy [relative risk (RR) 0.82, 95% CI 0.59 to 1.14], when adjusted for diabetes duration, sex, age and BMI. During 5.9 years of follow-up, retinopathy grading in the RYGB group was unchanged, whereas the control group displayed worse grading by 0.69 steps (95% CI 0.18 to 1.19). The RYGB group with diabetes remission (52%) showed a trend towards less retinopathy [adjusted RR (aRR) 0.45; 95% CI 0.19 to 1.06] than controls, and less retinopathy (aRR 0.33; 95% CI 0.11 to 0.94) than the RYGB group without remission in the cross-sectional data. CONCLUSIONS: In a cross-sectional setting, individuals with Type 2 diabetes treated by RYGB showed a tendency towards less retinopathy than non-operated controls, in particular diabetes remission following RYGB was associated with less retinopathy. Moreover after 5.9 years, retinopathy in the RYGB group had progressed less than in the control group. (Clinical Trial Registry No: NCT02625649).

Incidence of neuromyelitis optica spectrum disorder in the Central Denmark Region.

OBJECTIVES: Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure AQP4-IgG in patients who fulfilled the clinical and radiological criteria of NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD in the region, according to both the 2006 Wingerchuk criteria and the 2015 International Panel for NMO Diagnosis criteria. MATERIALS AND METHODS: Medical records of all patients diagnosed with a demyelinating disorder in the region from 1 January 2012 to 31 December 2013 were reviewed. Patients were classified as having (i) "NMO" if the 2006 criteria were met, (ii) "NMOSD with AQP4-IgG" or (iii) "NMOSD without/unknown AQP-IgG" if the new 2015 NMOSD criteria were met. Patients with core symptoms were invited to provide a blood sample for AQP4-IgG analysis with an enzyme-linked immunosorbent assay and a cell-based indirect immunofluorescence assay. RESULTS: In 191 patients with core symptoms, one met the 2015 NMOSD with AQP4-IgG criteria. Two patients met the 2006 NMO and 2015 NMOSD without/unknown AQP4-IgG criteria. Among 108 patients providing a blood sample, all were seronegative. The estimated incidence of NMO (2006 criteria) and NMOSD (2015 criteria) was 0.08 and 0.12 per 100 000 person-years, respectively. CONCLUSION: NMO/NMOSD is a rare disease in the Central Denmark Region, with a considerably lower incidence rate than previously estimated in a neighbouring region.

Intraocular currents, Bernoulli's principle and non-drainage scleral buckling for rhegmatogenous retinal detachment.

For many years, it is not fully understood how non-drainage scleral buckling surgery brings about spontaneous reattachment of the detached retina when retinal breaks remain open at the end of surgery. Various explanations have been put forward, but none more interesting than the effect of fluid currents associated with eye movements. One such explanation involved the physics of the Bernoulli's principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he described an equation based on the conservation of energy. The sum of pressure energy, potential energy and kinetic energy remains constant. Bernoulli's equation usually applies to closed system such as the flow of fluid through pipes. When fluid flows through a constriction, the speed of fluid increases, the kinetic energy increases. If there was no change in elevation (potential energy), then the increase in kinetic energy must be accompanied by a decrease in pressure energy. In ophthalmic surgery, the Bernoulli's effect is the basis for venturi pumps that drive vitrectomy and phacoemulsification machines. This essay expounds on how Bernoulli's effect might be relevant to scleral buckling for retinal detachment repair. In the era when vitrectomy is increasing the primary surgical operation for retinal detachment, the pervasive advice is to emphasise the importance of patient adopting head posture and remaining still postoperatively. The exception is non-drainage scleral buckling surgery. Early postoperative mobilisation may be vital to achieve reattachment.

Laws of physics help explain capillary non-perfusion in diabetic retinopathy.

The purpose is to use laws of physics to elucidate the mechanisms behind capillary non-perfusion in diabetic retinopathy. In diabetic retinopathy, loss of pericytes weakens capillary walls and the vessel dilates. A dilated capillary has reduced resistance to flow, therefore increased flow in that vessel and decreased in adjoining capillaries. A preferential shunt vessel is thus formed from the dilated capillary and the adjacent capillaries become non-perfused. We apply the laws of Laplace and Hagen-Poiseuille to better understand the phenomena that lead to capillary non-perfusion. These laws of physics can give a foundation for physical or mathematical models to further elucidate this field of study. The law of Laplace predicts that a weaker vessel wall will dilate, assuming constant transmural pressure. The Hagen-Poiseuille equation for flow and the Ostwald-de Waele relationship for viscosity predict that a dilated vessel will receive a higher portion of the fluid flow than the adjoining capillaries. Viscosity will decrease in the dilated vessel, furthering the imbalance and resulting in a patch of non-perfused capillaries next to the dilated 'preferential' shunt vessel. Physical principles support or inspire novel hypotheses to explain poorly understood phenomena in ophthalmology. This thesis of pericyte death and capillary remodelling, which was first proposed by Cogan and Kuwabara, already agrees with histological and angiographical observations in diabetic retinopathy. We have shown that it is also supported by classical laws of physics.

Dorzolamide-induced relaxation of porcine retinal arterioles in vitro depends on nitric oxide but not on acidosis in vascular smooth muscle cells.

The carbonic anhydrase inhibitor dorzolamide can induce relaxation of retinal arterioles with a consequent increase in blood flow and oxygenation of the retina. It has been shown that the mechanisms underlying this relaxation are independent of extracellular acidosis and CO2. The purpose of the present study was to investigate the possible involvement of nitric oxide (NO) and intracellular acidosis in dorzolamide-induced relaxation of retinal arterioles. Porcine retinal arterioles were mounted in a wire myograph and dorzolamide induced relaxation was studied after 1) the addition of the NO synthase inhibitor l-NAME (3 × 10(-4) M) or the guanylyl cyclase inhibitor ODQ (3 × 10(-6) M), and 2) after loading the smooth muscle cells with the pH sensitive fluorophore SNARF-1-AM and studying changes in vascular tone and intracellular fluorescence after the induction of hypoxia, addition of lactate (10(-2) M), and extracellular acidification (pH = 7.0) alone and in the presence of dorzolamide (10(-3) M). Dorzolamide significantly relaxed retinal arterioles (p < 0.03), and the effect was significantly higher in the presence of perivascular tissue than in isolated vessels at the highest concentration (p < 0.01). In the presence of perivascular tissue dorzolamide-induced relaxation could be reduced by NO inhibition (p < 0.02). Dorzolamide increased intracellular acidification (p < 0.02) during extracellular acidosis, but there was no relation between relaxation and intracellular acidosis. In conclusion, dorzolamide-induced vasorelaxation depends on NO and the perivascular retinal tissue, but is independent of acidification in the extracellular and the intracellular space of retinal vascular smooth muscle cells. Other factors than NO and acidification are involved in dorzolamide-induced relaxation of retinal arterioles.

Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy.

AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world.

Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles.

BACKGROUND AND PURPOSE: Small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance calcium-activated potassium channels are involved in regulation of vascular tone and blood pressure. The present study investigated whether NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) and CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine), which are selective openers of SK(Ca) and IK(Ca) channels and of SK(Ca)2 and SK(Ca)3 channels, respectively, enhance endothelium-dependent vasodilatation in porcine retinal arterioles. EXPERIMENTAL APPROACH: In porcine retinal arterioles, SK(Ca)3 and IK(Ca) protein localization was examined by immunolabelling. Endothelial cell calcium was measured by fluorescence imaging. For functional studies, arterioles with internal diameters of 116 +/- 2 microm (n = 276) were mounted in microvascular myographs for isometric tension recordings. KEY RESULTS: SK(Ca)3 and IK(Ca) protein was localized in the endothelium. Bradykinin, but not NS309 or CyPPA increased endothelial cell calcium. Pre-incubation with NS309 or CyPPA enhanced bradykinin relaxation without changing endothelial cell calcium. This enhanced relaxation was abolished by blocking SK(Ca) channels with apamin. In the presence of NS309 or CyPPA, mainly inhibition of NO synthase with asymmetric dimethylarginine, but also inhibition of cyclooxygenase with indomethacin, reduced bradykinin relaxation. Bradykinin relaxation was completely abolished by NO synthase and cyclooxygenase inhibition together with a NO scavenger, oxyhaemoglobin. CONCLUSIONS AND IMPLICATIONS: In porcine retinal arterioles, bradykinin increases endothelial cell calcium leading to activation of SK(Ca) and IK(Ca) channels. Without altering endothelial cell calcium, NS309 and CyPPA open SK(Ca) channels that enhance NO-mediated bradykinin relaxations. These results imply that opening SK(Ca) channels improves endothelium-dependent relaxation and makes this channel a potential target for treatments aimed at restoring retinal blood flow.

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients.

AIMS/HYPOTHESIS: We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. METHODS: Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. RESULTS: At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001). CONCLUSIONS/INTERPRETATION: Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.

Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects.

AIM: Elevated pulse pressure (PP) is associated with microvascular complications in Type 2 diabetic patients. In non-diabetic subjects, elevated PP has been associated with endothelial dysfunction. The relation between endothelial dysfunction and PP in diabetic subjects has not previously been examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group A; e.g. ICAM-1 [median (interquartile range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r = 0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1, respectively). CONCLUSION: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate these associations.

Plasma concentrations of osteoprotegerin during normo- and hyperglycaemic clamping.

OBJECTIVE: Plasma levels of osteoprotegerin (OPG) are elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. In previous studies a positive correlation was found between plasma levels of OPG and markers of glycaemic control in diabetic subjects. The aim of the present study was to examine the effect of acute hyperglycaemia on plasma levels of OPG in non-diabetic subjects. MATERIAL AND METHODS: Nine healthy, lean, male subjects were examined in a randomized, blinded, cross-over study design during hyperglycaemic (plasma glucose = 15 mmol/L, study H) as well as during euglycaemic (plasma glucose = 5 mmol/L, study E) conditions. Blood samples were collected at baseline and at t=240 min. RESULTS: Plasma OPG decreased slightly during study H (1.26+/-0.39 versus 1.19+/-0.35 ng/mL, p<0.05), whereas the level did not change significantly during study E (1.40+/-0.46 ng/mL versus 1.57+/-0.50 ng/mL, NS). The decrease in plasma OPG during hyperglycaemia did not correlate with the change in plasma glucose but correlated significantly with changes in serum insulin (r=-0.70, p=0.038). CONCLUSIONS: Acute hyperglycaemia does not seem to increase plasma levels of OPG in non-diabetic subjects, whereas hyperinsulinaemia may suppress plasma levels of OPG. This finding indicates that the elevated plasma levels of OPG observed in diabetic subjects with poor metabolic control cannot be ascribed to hyperglycaemia per se.

Impaired retinal autoregulation in small retinal arterioles before and after focal laser treatment for diabetic maculopathy.

AIMS: To study the effect of an acute increase in the arterial blood pressure on the diameter response of retinal arterioles supplying areas with focal diabetic macular oedema before and after laser photocoagulation, and control arterioles supplying areas without oedema. METHODS: In 17 diabetic patients the diameter response of arterioles after an increase in the arterial blood pressure induced by isometric exercise was studied using the retinal vessel analyser (RVA). In each patient a study arteriole supplying a focal area of macular oedema as well as a control arteriole supplying a retinal area without retinopathy lesions was selected, and the diameter response of these vessels was performed immediately before, and 1 hour and 3 months after focal laser photocoagulation of the focal oedema area. RESULTS: The diameter response was impaired in both study arterioles and control arterioles before focal laser photocoagulation. The treatment induced regression of the focal retinal oedema, but did not affect the diameter response in the arteriole supplying this area (p = 0.85). CONCLUSION: Impairment of the diameter response in small arterioles from diabetic patients does not parallel the regional distribution of retinopathy lesions. Other factors than disturbed autoregulation are probably involved in generating flow disturbances and oedema in diabetic maculopathy.

Pathogenicity of Helicobacter pylori infection.

Numerous Helicobacter pylori virulence factors, including various enzymes (urease, catalase, lipase, phospholipase and proteases), vacuolating cytotoxin (a product of expression of the vacA gene), and the immunogenic protein CagA, encoded by the cagA gene localised in the H. pylori pathogenicity island, are involved in the pathomechanism of infection caused by these organisms. This review presents the current state of knowledge concerning the molecular mechanisms and epidemiology of H. pylori infection, based on the published literature and recent unpublished observations.

Diabetic retinopathy: a review of the aarhus approach to studies on epidemiology, computerised grading, and the pathophysiology of the disease.

Diabetic retinopathy is one of the leading causes of blindness in the western world (Munier et al 1998). The challenges for improving the visual prognosis in this disease are comprehensive, and involve a multitude of methodological approaches. Thus, ongoing research programmes are aimed at studying as diverse aspects of diabetic retinopathy as epidemiology, genetics, screening, diagnosis, treatment, and understanding of the pathophysiology of the disease. This review presents the scientific approach followed at Aarhus University Hospital in relation to three of these aspects-epidemiology, computerised grading, and elucidation of the pathophysiology of diabetic retinopathy.

Quantitative analysis of retinopathy in type 2 diabetes: identification of prognostic parameters for developing visual loss secondary to diabetic maculopathy.

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.

Early detection of diabetes retinopathy by new algorithms for automatic recognition of vascular changes.

Diabetes mellitus often results in diabetic retinopathy caused by pathological changes of the retinal vessel tree. Early detection of these changes can delay the disease. Image processing can reduce the workload of screeners and can play a central role in quality assurance tasks. Therefore we aimed at the refinement and development of image processing algorithms to improve the quality and cost effectiveness of screening and diagnosis of diabetic retinopathy. In order to support ophthalmologists in their routine and to enable the quantitative assessment of vascular changes in colour fundus photographs a multi-resolution approach was developed which segments the vessel tree efficiently and precisely into digital images of the retina. The vessel tracker aims at determining as correctly as possible the retinal vascular network captured on a digital image irrespective of its origin. In addition to the tracker, algorithms were developed to detect the optic disk, bright lesions such as cotton wools spots, and dark lesions such as haemorrhages. The following classification of veins and arteries identifies arteries in 78.4 % and veins in 66.5% correctly. This helps selecting conspicuous images from a great number of patients.

Feasibility of using the TOSCA telescreening procedures for diabetic retinopathy.

AIMS: The TOSCA project was set up to establish a tele-ophthalmology service to screen for diabetic retinopathy (DR) in Europe. The aim of this study was to determine the feasibility of establishing telemedicine-based digital screening for detecting DR and to evaluate the satisfaction of both patients and healthcare professionals with the screening procedures used within the TOSCA project. METHODS: The study was a non-randomized, multicentre study carried out in four different countries over a period of 3 months. Patients (n = 390) with diabetes aged > 12 years were included. Two digital retinal images per eye (macular and nasal) were taken and exported to a central server. Patients were asked to complete a questionnaire to assess satisfaction. Accredited graders carried out grading remotely and the results were reported back to the referring centre. Previously graded patient data chosen randomly to represent examples of both DR and no DR were also sent anonymously to the grading centre at a frequency of approximately every 10 patients. RESULTS: Most (99%) of the images were assessable enabling a retinopathy grade to be assigned to the patient. Patients found the retinal photography procedures acceptable; only 6% in one centre would not recommend the procedure. Healthcare professionals (photographers and graders) were also satisfied with the overall procedures. The average time taken to grade each patient was approximately 5 min. CONCLUSIONS: This study demonstrated that it is feasible to electronically transmit and grade retinal images remotely using the TOSCA process. Built-in quality assurance procedures proved acceptable.

The prognostic value of post-treatment retinopathy after panretinal photocoagulation for proliferative diabetic retinopathy in type 1 diabetes.

PURPOSE: To study the prognostic value of post-treatment retinopathy after panretinal laser photocoagulation for proliferative diabetic retinopathy in type 1 diabetes mellitus. Proliferative diabetic retinopathy is treated with panretinal photocoagulation, which significantly reduces the risk of visual loss from this complication. However, no parameters are presently known that can be used to define an optimal control interval after the initial panretinal photocoagulation treatment that ensures enhancement of the treatment in cases where this is needed. METHODS: In this retrospective cohort study, 85 eyes from 56 type 1 diabetic patients were identified who had been subjected to panretinal photocoagulation for proliferative diabetic retinopathy before 1990. The patients were divided into two groups: Group 1 had four or fewer microaneurysms only at the first post-treatment examination whereas Group 2 had more retinopathy. RESULTS: At the first photographic examination after treatment the eyes in Group 1 had a significantly lower visual acuity (VA) (mean =0.23, range: 0.01-1.00) than the patients in Group 2 (mean=0.48, range: 0.01-1.6). During the follow-up period the VA was further reduced in Group 2 but not in Group 1. Three eyes out of six in Group 1 had improvement of VA from below to above 0.1, whereas 6 eyes out of 12 in Group 2 experienced progression of retinopathy with a consequent worsening of VA to below 0.1 after a mean of 10.8 years (range: 6.8-15.9) after treatment. CONCLUSIONS: The severity of post-treatment retinopathy can be used to assess the need for enhancing photocoagulation of proliferative diabetic retinopathy in type 1 diabetes. The interval between post-treatment examinations can be increased to several years when the initial treatment has reduced retinopathy to a minimal level.

An unusual retinal vascular morphology in connection with a novel AIPL1 mutation in Leber's congenital amaurosis.

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.