Development Of Proliferative Retinopathy Research Articles

The role of growth hormone and IGF-1 in retinopathy: a prospective study of retinopathy in patients with acromegaly and impaired fasting glucose

AimsTo investigate the effects of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis on the incidence and progression of retinopathy.MethodsWe enrolled 91 patients with acromegaly and 123 subjects with impaired fasting glucose (IFG) between 2008 and 2016 to examine the incidence and prevalence of retinopathy. Patients attended follow-ups in our clinics and underwent examinations according to the national guidelines for diabetes management. Both cohorts attended follow-ups until June 2019.ResultsBoth groups had similar HbA1c, cholesterol, and blood pressure levels. However, patients with acromegaly had higher GH (8.05 ± 16.18 vs. 0.78 ± 1.25 ng/mL) and IGF-1 (547.0 ± 342.1 vs. 146.7 ± 51.4 ng/mL) levels than in subjects with IFG. During the follow-up period, 8 patients (8.8%) with acromegaly and 12 patients (9.8%) with IFG developed some degree of retinopathy. Three patients with acromegaly and two with IFG progressed to proliferative retinopathy. Patients with acromegaly had the same incidence of non-proliferative retinopathy (odds ratio [OR] 0.830; 95% CI 0.318–2.164) and a non-statistically significantly higher incidence of proliferative retinopathy (OR 2.461; 95% CI 0.404–14.988).ConclusionThe data reveals that GH and IGF-1 might play a crucial role in the development of proliferative retinopathy and influence its progression. Therefore, we suggest screening patients with acromegaly should be similar to diabetes patients.

Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials

Intensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more intensive glucose control, compared with less intensive glucose control, on the risk of microvascular events. In this meta-analysis, we obtained de-identified individual participant data from large-scale randomised controlled trials assessing the effects of more intensive glucose control versus less intensive glucose control in adults with type 2 diabetes, with at least 1000 patient-years of follow-up in each treatment group and a minimum of 2 years average follow-up on randomised treatment. The prespecified and standardised primary outcomes were kidney events (a composite of end-stage kidney disease, renal death, development of an estimated glomerular filtration rate <30 mL/min per 1·73m2, or development of overt diabetic nephropathy), eye events (a composite of requirement for retinal photocoagulation therapy or vitrectomy, development of proliferative retinopathy, or progression of diabetic retinopathy), and nerve events (a composite of new loss of vibratory sensation, ankle reflexes, or light touch). We used a random-effects model to calculate overall estimates of effect. We included four trials (ACCORD, ADVANCE, UKPDS, and VADT) with 27 049 participants. 1626 kidney events, 795 eye events, and 7598 nerve events were recorded during the follow-up period (median 5·0 years, IQR 4·5-5·0). Compared with less intensive glucose control, more intensive glucose control resulted in an absolute difference of -0·90% (95% CI -1·22 to -0·58) in mean HbA1c at completion of follow-up. The relative risk was reduced by 20% for kidney events (hazard ratio 0·80, 95% CI 0·72 to 0·88; p<0·0001) and by 13% for eye events (0·87, 0·76 to 1·00; p=0·04), but was not reduced for nerve events (0·98, 0·87 to 1·09; p=0·68). More intensive glucose control over 5 years reduced both kidney and eye events. Glucose lowering remains important for the prevention of long-term microvascular complications in adults with type 2 diabetes. None.

Microalbuminuria and diabetic retinopathy in type 2 diabetic patients: From risk association to risk prediction.

Microalbuminuria and diabetic retinopathy in type 2 diabetic patients: From risk association to risk prediction.

Risk of retinal neovascularization in the second eye in patients with proliferative diabetic retinopathy

This study aimed to evaluate the risk of proliferative diabetic retinopathy (DR) in the fellow eye of an eye with existing proliferative DR. Our DR screening programme database listed 1513 diabetes patients alive at the time of the study. Seventy-six had proliferative DR in one or both eyes. In 28 of the 76 (37%) diabetes patients, proliferative DR was diagnosed in both eyes at the same examination. Another 28 patients developed proliferative DR in the second eye within 5 years of its diagnosis in the first eye, bringing the total number of diabetes patients with proliferative DR in both eyes at 5 years to 56 (74%). Almost all the diabetes patients eventually developed proliferative DR in the second eye. The median duration of diabetes before the development of proliferative retinopathy was 19 years for type 1 and 14 years for type 2 diabetes. Proliferative DR is a bilateral disease. Diabetes patients with proliferative DR in one eye are at high risk of developing neovascularization in the second eye and close follow-up is recommended.

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications.

Mild cognitive dysfunction is not uncommon in adults with Type 1 diabetes, but its pathogenesis remains unclear. Previous cross-sectional studies had suggested that microangiopathy might affect brain integrity and lead to "central neuropathy." To assess the relationship between changes in cognitive performance and the incidence of new micro- and macrovascular complications, 103 young and middle-aged adults (mean age: 40 yrs) with childhood-onset Type 1 diabetes were followed over a 7-year period, and were compared to 57 demographically-similar adults without diabetes. All subjects completed a comprehensive battery of neurocognitive tests on two occasions. Diabetic subjects also received repeated medical assessments to diagnose the onset of clinically significant complications. Relative to control subjects, diabetic adults showed significant declines on measures of psychomotor efficiency; no between-group differences were evident on learning, memory, or problem-solving tasks. The development of proliferative retinopathy and autonomic neuropathy during the follow-up period predicted decline in psychomotor speed (p<0.01), as did incident macrovascular complications (p<0.05), systolic blood pressure at follow-up (p<0.01), and duration of diabetes (p<0.01). This study shows that cognitive efficiency may decline over time in diabetic adults, and that this neurocognitive change may be linked, at least in part, to the occurrence of complications like proliferative retinopathy and elevated blood pressure. Therapeutic interventions that reduce the risk of vascular complications may have a similarly beneficial effect on the brain and reduce the risk of neurocognitive dysfunction in diabetic patients.

Association of macular involvement with proliferative retinopathy in Type 2 diabetes.

To determine whether documented evidence of pre-existing maculopathy is present in Type 2 diabetic patients who require photocoagulation or vitrectomy for proliferative disease. This is a retrospective case notes review. The study was performed at Queen's Medical Centre, UK. All patients listed in the laser register and operating theatre register over 5 years (March 1994 to March 1999) who had undergone pan retinal photocoagulation (PRP) for diabetic retinopathy, in one consultant firm, were studied. The medical records of patients who had undergone vitrectomy as their first treatment for proliferative diabetic retinopathy in a vitreo-retinal firm over the 5 years were examined. The proportion of patients with documented maculopathy before development of proliferative retinopathy was determined. All except 1/134 or 0.7% (95% confidence interval 0.1-4.5%) patients had documentation of macular signs in at least one eye prior to the patient's first session of PRP. Of the remaining 133, 104 (78%) had had focal or grid photocoagulation of the macula. The median time between the documentation of maculopathy before the first PRP treatment session was 16 months (interquartile range 7-36). Fourteen patients had vitrectomy and endolaser performed as the initial treatment for proliferative disease. All patients had documented maculopathy before the onset of proliferative disease. The results of this study suggest that in Type 2 diabetes, proliferative disease occurs relatively late compared with maculopathy. In such patients, maculopathy is almost invariably present when proliferative disease is detected.

ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy

Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.

To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.

Existence of early-onset NIDDM Japanese demonstrating severe diabetic complications.

To identify the clinical characteristics of early-onset NIDDM patients with severe diabetic complications. The clinical cases of a large number of diabetic patients who visited a diabetes center within the period 1970-1990 were reviewed. Of a total of 16,842 diabetic patients, 1,065 (6.3%) had early-onset NIDDM (diabetes diagnosed before 30 years of age). These 1,065 patients were divided into two groups, those who developed proliferative retinopathy before the age of 35 (n = 135) and those who did not (n = 930). Development of proliferative retinopathy, nephropathy, renal failure, blindness, and atherosclerotic vascular disease were compared between the two groups. The subgroup of 135 patients was characterized by poor glycemic control, often requiring insulin therapy and a higher familial prevalence of diabetes, and contained a greater proportion of women than the subgroup of 930 patients. Of the 135 patients, 99 (67%) developed proliferative retinopathy before the first visit. The 135 patients developed severe progressive complications in contrast to the 930 patients. A total of 81 patients (60%) developed diabetic nephropathy at a mean age of 31 years, 31 (23%) developed renal failure requiring dialysis at a mean age of 35 years, 32 (24%) became blind at a mean age of 32 years, and 14 (10%) developed atherosclerotic vascular disease at a mean age of 36 years. Some Japanese early-onset NIDDM patients develop severe diabetic complications in their youth. Most of them had no symptoms nor regular treatment regarding diabetes until they were noticed to have developed severe diabetic complications. Although the relevant prevalence and the pathogenetic mechanism underlying the rapid onset of the complications remain to be determined, prolonged inadequate treatment of and familial predisposition to diabetes may be contributing factors. Careful diabetes care in the twenties, not only for IDDM but also for NIDDM patients, is warranted.

Proliferative diabetic retinopathy is related to cardiovascular autonomie neuropathy in non-insulin-dependent diabetes mellitus

The aim of the study was to define the relationship between the presence of proliferative diabetic retinopathy and nephropathy with objectively defined autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients. The research design used was a cross-sectional, case control study. A cohort of NIDDM patients was classified, according to live cardiovascular autonomic tests described by Ewing, as: (1) no involvement - no abnormal tests (n = 17); (2) cardiovascular autonomic neuropathy - two out of five abnormal tests (n = 18). Age, age at diagnosis, plasma creatinine, fasting plasma glucose, glycated haemoglobin and blood pressure measurements were not statistically different among the two groups. According to indirect ophthalmoscopy and the presence of macroproteinuria and microalbuminuria, respectively, patients were also classified as having proliferative, non-proliferative or no retinopathy and with or without nephropathy. The results showed a striking relationship between cardiovascular autonomic neuropathy and proliferative diabetic retinopathy. Relative odds for nephropathy, non-proliferative diabetic retinopathy and proliferative retinopathy were, respectively, 16.0, 10.1 and 34.7. When odds ratios were adjusted for the presence of nephropathy, hypertension, non-proliferative and proliferative retinopathy, only proliferative retinopathy was significantly associated (odds ratio, 7.1). It was concluded that in NIDDM the presence of cardiovascular autonomic neuropathy is strongly associated with proliferative retinopathy. Long-term prospective studies on large cohorts of patients must be done to evaluate if having autonomic dysfunction would be a risk factor or a risk indicator of an etiologic process underlying the development of proliferative retinopathy.

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5±785.0 mUL −1, mean±SEM) compared to patients with nonproliferative retinopathy (325.5±73.2 mUL −1, P<0.003) and those without retinopathy (318.6±47.3 mUL −1, P<0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (216.3±21.5 μgL −1) was significantly higher than in patients with nonproliferative retinopathy (126.3±14.85 μgL −1, P<0.004) and without retinopathy (135.2±37.26, P<0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations ( r=0.56, P<0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance ( r=0.67, P<0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in prédicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.

Physical Activity and the Risk of Progression of Retinopathy or the Development of Proliferative Retinopathy

To determine if physical activity is associated with the 6-year risk of progression of retinopathy or incidence of proliferative retinopathy. Participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy who were free of proliferative retinopathy at the 1984 to 1986 examination and in whom diabetes had developed when younger than 30 years of age (n = 606) were evaluated after a 6-year follow-up period. Stereoscopic fundus photographs were graded for the presence and severity of retinopathy. Physical activity was assessed by a questionnaire. There were no associations between any of the measures of physical activity and two-step progression of retinopathy or the development of proliferative retinopathy during the follow-up period. No associations were seen even for those with more severe preproliferative retinopathy at the 1984 to 1986 examination or for the subset engaging in strenuous activity such as weight lifting. Physical activity does not appear to be associated with either an increased or decreased risk of progression of retinopathy or the development of proliferative retinopathy in people with insulin-dependent diabetes mellitus.

Development of proliferative retinopathy in a gestational diabetes patient following rapid metabolic control

Rapid glucose control was achieved by insulin therapy in a patient diagnosed to have gestational diabetes at 8 weeks of pregnancy. A decrease of the initially high hemoglobin A 1c level (16.2%) to normal values (5.9%) was achieved within 12 weeks. At 31 weeks severe bilateral proliferative diabetic retinopathy developed. To our knowledge this case is the first report of a patient with gestational diabetes who developed de novo proliferative diabetic retinopathy.

Development of proliferative retinopathy in Japanese patients with IDDM: Tokyo Women's Medical College Epidemiologic Study

We studied the development of proliferative diabetic retinopathy (PDR) in Japanese insulin-dependent diabetes mellitus (IDDM). Subjects were 373 patients who were diagnosed as IDDM between 1951 and 1984, before the age of 30 years, and had no PDR at the first visit to the Diabetes Center. Development of PDR was analyzed by Kaplan-Meier's life-table method in relation to the duration of IDDM. The cumulative incidence of PDR was 20% at 15 years of duration of IDDM, 40% at 19 years, and 70% at 29 years. Female patients ( n = 233) developed PDR significantly faster than males ( n = 140) ( P < 0.002). In both sexes, patients with onset of IDDM at 0–8 years showed significantly slower development than patients with the onset at 9–17 ( P < 0.0001) and 18–29 years ( P < 0.001). Impact of femaleness on the development was the greatest in patients with age at onset of IDDM at 9–17 years ( P < 0.005). Analysis according to the calendar year at onset of IDDM and diabetes duration at the first visit to the Diabetes Center did not show any significant influence on the development of PDR. In conclusion, sex and age at onset of IDDM may be associated with increased risk for the development of PDR in relation to the duration of diabetes in Japanese IDDM.

Genetic variation around the collagen IV 1a gene locus and proliferative retinopathy in type 2 diabetes mellitus.

The development of proliferative retinopathy in type 2 diabetes mellitus may be under genetic control. A well-documented pathological change in the fundal capillaries of patients with diabetic retinopathy is basement membrane thickening, with an increased amount of collagen IV protein. Variation at the collagen 1a IV gene therefore may explain familial susceptibility to this complication. It has been previously reported that genetic variation at the collagen 1a locus, as shown by allelic association with a HindIII restriction site, predisposes to diabetic nephropathy where basement membrane thickening is also prevalent. In order to test the hypothesis that the collagen 1a IV gene locus is important in the development of diabetic retinopathy, a population association study was performed comparing allele frequencies of the HindIII RFLP in diabetic patients with retinopathy and controls. No statistically significant differences were found between allele frequencies or genotypes in the two groups. The future use of similar studies in diabetic retinopathy is discussed.

Epidemiology of proliferative diabetic retinopathy.

This review examines recent epidemiological data about the prevalence and incidence of and risk factors for proliferative diabetic retinopathy. In addition, the relation of proliferative retinopathy to other systemic complications associated with diabetes is reviewed. The data come mostly from the baseline and 4-yr follow-up examinations of a large population-based study, the WESDR, which involved 996 younger-onset insulin-dependent people whose diabetes was diagnosed at < 30 yr of age and 1370 older-onset people whose diabetes was diagnosed at > or = 30 yr of age, and who were taking or not taking insulin. The major finding is that proliferative retinopathy is a prevalent complication (23% in the WESDR younger-onset group, 10% in the WESDR older-onset group that takes insulin, and 3% in the group that does not take insulin). Hyperglycemia, longer duration of diabetes, and more severe retinopathy at baseline were associated with an increased 4-yr risk of developing proliferative retinopathy. However, higher blood pressure at baseline was associated only with the development of proliferative retinopathy in the younger-onset group. The presence of proliferative diabetic retinopathy was associated with an increased 4-yr risk of loss of vision, cardiovascular disease, diabetic nephropathy, and mortality. In the WESDR, a significant number of diabetic people with proliferative retinopathy at risk for vision loss were not under the care of an ophthalmologist or had not undergone panretinal photocoagulation. These data suggest that hyperglycemia and, possibly, high blood pressure are related to proliferative retinopathy. They also suggest that once proliferative diabetic retinopathy is detected, people should have a medical evaluation, because it is a strong indicator for the presence and development of systemic disease. These data also indicate that diabetic patients and their physicians should be aware of the need for routine ophthalmological examinations to detect and treat proliferative retinopathy.

Development of proliferative retinopathy in NIDDM. A follow-up study of American Indians in Oklahoma.

To determine the incidence of and risk factors for the development of proliferative diabetic retinopathy (PDR) in Oklahoma Indians, we performed a cohort follow-up study of 927 Indians who underwent detailed eye examinations between 1972 and 1980. The mean age of participants was 52 yr with a duration of diabetes of 6.9 yr at baseline. At follow-up, 513 (55.3%) were alive, 407 (43.9%) were deceased, and 7 (0.8%) could not be traced. After a mean follow-up time of 12.7 yr, the overall incidence of PDR among those who survived and who underwent follow-up ophthalmic examinations (354 participants) was 18.6%; 45% of those with background retinopathy at baseline developed PDR. Significant independent predictors of PDR, determined by multivariate analysis, were fasting plasma glucose level, duration of diabetes, plasma cholesterol, systolic blood pressure, and therapeutic regimen. A fasting plasma glucose level greater than or equal to 11.1 mM (200 mg/dl) increased the risk of retinopathy to 3.6 times that for a level less than 7.8 mM (140 mg/dl); 74% of those who had background retinopathy and a baseline fasting glucose greater than or equal to 11.1 mM (200 mg/dl) developed PDR. Over half of all participants with plasma cholesterol levels greater than or equal to 7.8 mM (300 mg/dl) developed PDR in the follow-up interval. Elevated systolic blood pressure was a particularly significant risk factor for those with a long duration of diabetes. Proliferative retinopathy poses a serious health threat to Oklahoma Indians and represents a cause of visual impairment that may be preventable by early diagnosis of PDR and intervention with photocoagulation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of proliferative retinopathy in NIDDM. A follow-up study of American Indians in Oklahoma

Development of proliferative retinopathy in NIDDM. A follow-up study of American Indians in Oklahoma

Increased platelet thromboxane receptor sensitivity in diabetic patients with proliferative retinopathy.

Platelet aggregation to collagen in 12 Type 1 (insulin-dependent) diabetic patients with background retinopathy and 12 Type 1 diabetic patients with proliferative retinopathy was compared with an age- and sex-matched control group. An analogue of prostaglandin H2, 11,9 epoxymethano-prostaglandin H2, which directly stimulates thromboxane receptors, and EP 092, which is a competitive thromboxane A2 receptor antagonist, were used to investigate changes at platelet thromboxane receptor level in these groups. The concentration of collagen (EC50) required to give 50% of maximum aggregation did not differ between the two diabetic groups and the control group. However, platelets from the proliferative retinopathy group were significantly more sensitive to the thromboxane mimetic (11,9 epoxymethano-prostaglandin H2) (p less than 0.005) than the background retinopathy and control groups. This change may be a factor in the development of proliferative retinopathy.

Diabetic papillopathy and proliferative retinopathy

Diabetic papillopathy has been characterized as a syndrome in which predominantly young, insulin-dependent diabetics develop transient edema of the optic disc with minimal impairment of the function of the optic nerves. In this study, four patients with long-standing insulin-dependent diabetes mellitus and acute disc swelling in one or both eyes were evaluated. The most unusual finding in these cases was that three had proliferative retinopathy either at the time the disc edema was discovered or very shortly afterwards. The fourth patient also developed this condition subsequently. It is important to be aware of diabetic papillopathy and to recognize the condition early enough so that the patient may be spared unnecessarily extensive neurological evaluations and invasive procedures. Patients with diabetic papillopathy should be closely observed so that the presence or development of proliferative retinopathy may be established.