Retinal Complications of Diabetes and Vascular Disease

Abstract

Diabetes mellitus has several significant complications that can affect patients in various forms with some of the most profound changes affecting both the function and structure of the eye. The microvascular complications that affect the eye resulting from complications of diabetes include hypertension, vascular retinopathy, diabetic retinopathy, age-related macular degeneration, and glaucoma.

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The primary microvascular complication that has been observed in the eye is diabetic retinopathy. This microvascular complication can result in blindness among the patients affected by diabetes mellitus and among individuals located in Asia and Australia and is the most common medical aliment that results in blindness among individuals between the ages of 20 to 641.

This research will examine the Blue Mountain Eye Study, the Beaver Dam Study, the U.K. Prospective Diabetes Study (UKPDS), and several other studies that examine the symptoms of diabetes and the vascular complications that can result. Each chapter will examine a different complication of diabetes to provide the reader with an in-depth understanding of the medical condition and ending with the prevalence rates of the condition among the populations of Asia and Australia.

General epidemiology of diabetes, and visual-related complications

The World Health Organization (WHO) defines diabetes as a state of chronic hyperglycemia which could lead to microvascular and macrovascular complications, including the retina, cardiovascular, peripheral vascular and cerebrovascular diseases (EKOE and ZIMMET, 8). The WHO has determined that there are over 161 million individuals in the world that have some level of visual impairment resulting in slightly over 9% of the Australian population that is over the age 55 years old being visually impaired and 1.2% of the Australian population are blind. Diabetic eye disease occurs in 6 out of 1,000 Australians over the age of 18 (Australian Institute of Health and Welfare, 2008).

In comparison, a national survey conducted in Japan during the year 2000 determined that the prevalence rate of diabetes in Japan among males between the ages of 60 and 69 was 12.7% while the prevalence rate among women in the same age group was 13.5% (WHO). The prevalence of diabetes increased in the older members of the population which is characteristic of the condition. A similar survey that was conducted in China determined that the prevalence rate of diabetes was 11.3% of the population 60 to 69 years of age or older (WHO). When examining the population studies of Viet Nam the population of the age of 65 displayed a prevalence rate of 11.3% (WHO).

The research conducted by the Australian government has determined that over the past five years, the number of individuals seeking treatment for vision loss related to diabetes or diabetic complications has steadily increased during the previous five years. When individuals sought treatment at one of the hospital settings the average length of time the patients spent at the hospital for these conditions was 2.4 days. The Australian government has estimated that the treatment costs for public hospitals are 232,759 Australian dollars (Australian Institute of Health and Welfare, 2008). As the prevalence of diabetic complications increases the treatment costs will increase as well. This increase in cost could result in individuals not being able to afford the necessary treatment that will prevent the spread of the retinal complications of diabetes.

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The portion of the population in the Asian countries that have been most affected by the rise in diabetes is the working poor. These individuals typically do not have the monetary means to receive medical care resulting in their medical treatment being paid for by the Japanese government. These findings are typical of the other Asian countries (WHO).

Retinal associations of diabetes- its general epidemiology and significance

The most well-known retinal association of diabetes is diabetic retinopathy, the leading cause of blindness among the working population (EKOE and ZIMMET, 2008). The Visual Impairment Project in Melbourne Australia determined that there was a retinopathy prevalence of 29% among individuals aged 40 years old or older among the studies population. In comparison to the Visual Impairment Project, the Blue Mountains Eye Study researchers determined that their population study had a retinopathy prevalence rate of 32% among individuals that were not younger than 49years of age. The third epidemiology study that was conducted in Australia was the Australian Diabetes Obesity and Lifestyle (AusDiab) study in which the population was comprised of individuals that were 25 years of age or older. In this study, the researchers determined that the prevalence rate of retinopathy was 25%. The variations in the prevalence of retinopathy can be attributed to the difference in the age of the population studied by each of the research teams.

When examining the epidemiology studies on diabetic retinopathy that have been conducted in regions of Asia, it was determined that there is a lack of reliable sources of data concerning diabetic retinopathy. The most reliable source of information was obtained from several serial population studies that were conducted by researchers up until1992 to determine the self-determined prevalence rates among the population of adults between the ages of 15 to 69 years of age. The survey discovered that the prevalence of diabetes has increased through the course of the study from 2.0% to 8.6% at the last recorded measurement. As the prevalence rates of diabetes increase, it can be hypothesized that the prevalence rates of diabetic retinopathy will also increase.

Retinal associations of diabetes are generally divided into four large groups which are isolated retinopathy signs in individuals with diabetes or hypertension, changes in the retinal vascular architecture, the classic signs of retinal vascular disease which is generally found in patients with either diabetes or hypertension and isolated retinopathy signs (NGUYEN, WANG, AND WONG, 2007).

The Multi-Ethic Study of Atherosclerosis (MESA) study examined the differences in the prevalence of diabetic retinopathy among different ethnic populations. The ethnicity studied included African-Americans, Caucasians, Hispanics and Chinese-Americans that were at least 45 years of age or older. The researchers determined that the prevalence rate of diabetic retinopathy was the same 37% among the African-American participants and the Hispanic participants. The prevalence rates were lower among the Caucasian and Chinese-American populations. The Caucasian individuals had a prevalence rate of 25%, while the Chinese-American participants had a prevalence rate of 26%. It has been hypothesized that the differences observed by the researchers among the different ethnicities are due to the complex combination of access to health care, genetic susceptibility, duration of diabetes, glycemia levels and the individual’s blood pressure. In addition the prevalence of diabetic retinopathy in this study was higher than the prevalence of diabetes in the Chinese population. This difference in the prevalence rates could be attributed to the composition of the study groups.

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The ADVANCE Retinal Measurements (AdRem) was a sub-study of a population-based study that examined the prevalence of retinal lesions in patients with type 2 diabetes from twenty different countries in the European and Asian regions. The researchers determined that individuals of Chinese ethnic origin demonstrated a 49.4% prevalence of severe retinopathy; individuals of South Asian ethnic origin demonstrated a 46.0% prevalence of severe retinopathy while individuals of Caucasian ethnic origin demonstrated a 31.3% prevalence of severe retinopathy. These statistics have been adjusted for age, gender, systolic blood pressure, the duration of diabetes, the amount of glucose-lowering drugs and the use of insulin. The statistics collected by this study demonstrated an increased rate of diabetic retinopathy due to the fact that the study’s population included individuals that had a high risk of vascular disease. These high-risk individuals elevated the prevalence rates of diabetic retinopathy (Stolk, et. al. 2008).

Vascular retinopathy results in the narrowing of the focal arteriolar as well as generalized narrowing of the vascular system of the eye. In addition the patient experiences cotton wool spots, retinal hemorrhages and microaneurysms resulting from a prolonged elevated blood pressure (Klein, 1993). There have been several studies that have examined the prevalence of hypertensive retinopathy among diverse populations in the United States; however there is a lack of research among the Asian populations (Klein, 1993).

The association between increased blood pressure and the presence of retinal microvascular signs has been consistently shown in epidemiology studies. The data that was obtained from the Beaver Dam Eye study demonstrated that the retinal microvascular signs were seen more often in the percentage of the population that had been diagnosed with hypertension (Klein, 1993). In addition 30 to 40% of the population was at an increased risk of displaying signs of focal arteriolar narrowing. 70 to 80% of the studies hypertensive population also demonstrated the presence of AV nicking in comparison to the non-hypertensive population (Klein, 1993). This research demonstrates the importance of monitoring diabetic individuals who are at risk of developing hypertension to prevent the additional complications that this combination of medical conditions can cause.

The Atherosclerosis Risk in Communities (ARIC) study determined that there is a strong inverse relationship between the retinal arteriolar diameter and the higher blood pressure level (Klein, 1993). The research performed by these two studies indicates that there is a strong correlation between generalized arteriolar narrowing and hypertension (Klein, 1993).

The ARIC and the Beaver Dam Eye Study have determined that there is a portion of the population that has retinopathy lesions without the overt symptoms of diabetes or the possible risk factors. These studies have determined that between 1.2 to 1.8% of the population that is over the age of 40 is affected by these lesions (Liew and Wang, 2007). Currently the pathogenesis is unclear however it has been hypothesized that hypertension and elevated levels of plasma glucose contribute to this condition. The studies determined that except for a small portion of the population of the study that had a family history of diabetes the lesions were not associated with the three-year incident diabetes (Liew and Wang, 2007).

The form of vascular disease that occurs during diabetes results in the development of the hardening of arteries through the development of blockages. These blockages are created through the elevated presence of glucose in the bloodstream. The vascular diseases that can result from these blockages include retinopathy of the eye and high blood pressure. High blood pressure can result in increased pressure on the retina resulting in additional complications of diabetes including vascular retinopathy and glaucoma (Liew and Wang, 2007).

Researchers have suggested that an additional risk factor for the development of glaucoma is diabetes. In some studies such as the Blue Mountains Eye Study and the Beaver Dam Eye Study the research indicated that there was a positive correlation between either the combination of glaucoma and diabetes, or the increase in intraocular pressure and diabetes. It is important to include the monitoring of the increase in intraocular pressure due to it resulting in the eventual damage to the optic nerve. In both of these studies the research determined that there was an increased prevalence of glaucoma in the participants who had been diagnosed with diabetes when compared to the participants who had not been diagnosed with diabetes.

The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that it is possible to reduce the risk of both diabetic retinopathy and the associated blindness through the control of the patient’s blood glucose and blood pressure. The participants in the study showed a 37% reduction in the risk of additional microvascular complications as well as a 21% reduction in the symptoms of diabetic retinopathy. In addition to diabetic retinopathy, diabetes can result in additional functional and pathological changes such as cataracts and glaucoma. These conditions are not related to vascular changes however, they can cause intense visual impairment among diabetic patients.

Retinal associations of vascular diseases- epidemiology and significance

Recent advances in digital retinal photography and imaging techniques have allowed researchers to characterize the subtle retinal vascular changes throughout large population studies, the Blue Mountain Eye Study, The Australian Diabetes, Obesity and Lifestyle study and the Multi-Ethnic Study of Atherosclerosis (Wong, et. al, 2008). When researchers examined data from the Blue Mountain Eye Study, the Australian Diabetes, Obesity and Lifestyle Study and the Multi-Ethnic Study of Atherosclerosis researchers were examining the relationship between fasting glucose and retinopathy to determine if there is a relationship between these conditions and diabetes (Wong, et. al, 2008). The prevalence of diabetic retinopathy in the BMES was 11.5%, in the AusDiab study the prevalence ranged from 8.4% to 10.9% and the MESA study determined that the prevalence rate was 15.8%. These rates of prevalence in the study were then compared to the FPG cutoff of 7.0 mmol/L or higher demonstrating a lack of sensitivity to diabetic retinopathy of less than 40% (Wong, et. al, 2008).

The BMES demonstrated a prevalence of mild retinopathy of 10% even in the presence of low levels of FPG. The prevalence of moderate retinopathy occurred in about 1% of the population combined with low levels of FPG (Wong, et. al, 2008). When examining the AusDiab study the prevalence of mild retinopathy was around 8% combined with the participants demonstrating low levels of FPG, in comparison the level of moderate retinopathy showed a continuous correlation with the increasing levels of FPG (Wong, et. al, 2008). In the MESA study the prevalence of mild retinopathy was recorded above 10% when combined with low levels of FPG (Wong, et. al, 2008). The prevalence rate increased with a direct correlation with the increasing levels of FPG. This data indicates that there is an increasingly large range of possible glycaemic thresholds that can be determined throughout the three studies (Wong, et. al, 2008).

This research indicates that the classification system of diabetes needs to be expanded to include a wider range of FPG glycemic controls. This increase in the range will allow researchers to determine additional vascular changes in the retina while conducting large population studies. In addition these three studies have incorporated a large amount of ethnic diversity allowing coalitions relating to each of the ethnicities involved to be made by researchers (Wong, et. al, 2008).

Rationale for Current Dissertation

To date, the majority of studies have examined the association of retinal associations of diabetes and vascular disease have been carried out in predominantly white Caucasian populations. Further elucidation of ethnic differences in effects of hyperglycemia on early microvascular disease is relevant, particularly amongst Asians where diabetes is likely to see the largest increase in prevalence over the next decade.

Aims of Study

By examining the ocular manifestations of diabetes, including retinal vascular caliber, vascular retinopathy, we will attempt to discover if the subtle changes in the retina, including retinal vascular caliber may be early markers of widespread microvascular changes in diabetes. The study will focus on population studies that have been conducted in Asia and Australia in order to increase the body of knowledge available to these ethnicities.

Hypothesis

With the changes in dietary and exercise routine of the Asian Pacific culture the chances of increasing instances of hyperglycemia will result in massive increase in diabetes and diabetic complications in this population

Diabetes and Retinal Vascular Caliber

Definitions

A retinal vascular caliber is a tool used by medical and research professionals to determine the extent of the retinal vascular complications of diabetes such as hypertension and retinopathy. This measurement is determined through the examination of digital photographs of the eyes of diabetic patients.

Classifications

Retinal vascular caliber is determined by measuring the central retinal vessels as they progress away from the optic disc. Researchers are able to make determinations based on the narrowing or widening of these vessels.

Pathophysiology

The inner two-thirds of the retinal are covered by retinal vessels. The larger retinal arteries and veins are located in the nerve fiber layer. The density of capillaries is highest in the central part of the retina, where there are three to four layers that formed. The retinal capillaries have a caliber of between 5-7 µm which is small when compared to the caliber of choroidal capillaries. In the retinal capillaries the adjacent endothelial cells are connected by the continuous tight junctions which form the blood-retinal barrier.

Experimental studies have previously demonstrated that ocular inflammation is associated with larger retinal venules, which partly reflects an increase in nitrous oxide levels. “The ocular inflammation is also a clear pathogenic factor in the development and progression of diabetic retinopathy. It has also been shown that a larger retinal venular caliber reflects an increased blood flow that is associated with both hyperglycemia and retinal hypoxia” (Wong, et. al, 2008). The inflammation could be one of the earliest vascular changes that occur in diabetic retinopathy (Wong, et. al, 2008). However current research has found no association between the size of the venular caliber and retinopathy in participants that had not been diagnosed with diabetes. Therefore the retinopathy signs that have been diagnosed with diabetes could be due to other complications such as hypertension4.

Both the larger retinal arteriolar and venular calibers have been associated with diabetes however, only the larger retinal venular caliber has been associated with IFG. This association was seen in individuals both with and without diabetes as well as in patients with an increasing severity of diabetic retinopathy. These associations may vary by race or ethnicity. Researchers could use the variations in retinal vascular caliber could as possible markers for both pre-diabetes as well as other early diabetic microvascular damage. These measurements may provide additional clues to understanding the pathophysiology and consequences of impaired glucose metabolism.

Pathogenesis

The measurement of retinal vascular caliber is a diagnostic tool used by the medical community in order to determine an individual’s risk of developing additional macrovascular disorders such as cardiovascular disease or diabetes. Due to this as the underlying macrovascular disease progresses the patient’s retinal vascular caliber will either become larger or smaller (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006). The medical professional can then use this measurement to determine the progression and effect that the other illness is having on the function and structure of the macrovascular system (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Retinal vascular caliber is affected by individual’s specific risk factors such as age, gender, systolic blood pressure, race and ethnicity. A larger retinal arteriolar caliber is seen more often in older male patients that have either a Chinese or white ethnic background (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006). In comparison smaller retinal venular caliber is specifically related to older individuals with a white ethnic background (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Prognosis

The prognosis of retinal vascular caliber relating to diabetes results in the gradual increase of the retinal vascular caliber. The larger retinal vascular caliber is related to an increased BMI, lower levels of HDL-cholesterol (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006). Through the control of these risk factors and the diabetic symptoms, it is possible for the patient to halt the progression of the disease through reversal is not currently possible.

Epidemiology

The Multi-Ethnic Study of Atherosclerosis (MESA) is one of the main studies adding to the body of research on diabetes and retinal vascular caliber. This study examined a multi-ethnic population to determine if there were risk factors specific to the black, Chinese, Hispanic or white ethnic groups in regards to the relationship between venular and retinal arteriolar caliber with cardiovascular complications (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Epidemiology of Retinal Vascular Caliber- for

In the study Relationship of Retinal Vascular Caliber with Diabetes and Retinopathy the researchers were examining the relationship of retinal vascular caliber with diabetes, glycemia, and diabetic retinopathy (NGUYEN, 2008).

The study included 4,585 individuals who demonstrated a normal fasting glucose (NFG), as well as 499 individuals who demonstrated impaired fasting glucose (IFG), 165 individuals who demonstrated retinopathy signs and 727 individuals who had been previously diagnosed with diabetes who also showed signs of retinopathy. The researchers performed a multivariate analysis and determined that the retinal arteriolar caliber increased from 143.8 µm in subjects with NFG to 144.5 µm in IFG and 146.1 µm in individuals with diabetes. The retinal venular caliber was significantly larger with increasing levels of fasting glucose and AIC. In a subgroup analysis separated by ethnicity, the association between wider arteriolar caliber and diabetes was evident only in the Caucasian members of the study; in comparison the Hispanic and Chinese members of the study demonstrated wider venular caliber and diabetes. This study also determined that the eyes of people with diabetes also demonstrated a larger venular but not arteriolar caliber.

After concluding their research study the researchers were able to determine that retinal arteriolar and venular calibers were larger in individuals who had been diagnosed with diabetes. This pattern of association presented differently among the various ethnicities that participated in the study. In addition, retinal venular caliber was associated with signs of retinopathy. This study has added to the body of evidence indicating that the variations in retinal vascular caliber could reflect early diabetic microvascular damage.

Epidemiology of Retinal Vascular Caliber- against

Research has determined that there is a strong association between diabetes and retinal arteriolar narrowing. The first study that demonstrated the association between narrower arteriolar caliber and higher blood pressure was the ARIC study. “Another demonstrated significant differences in endothelial function in the retinal circulation in 19 subjects with hypertension, compared with that in normotensive control subjects” (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006). The MESA study determined that there were weak associations between markers of endothelial dysfunction and larger venular caliber (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Ethnicity and Retinal Vascular Caliber Prevalence

The differences of the venular and arteriolar caliber in the studies population were significant in the four ethnic populations that were studied “Retinal arteriolar caliber was larger in blacks (145.2 ±14.2 µm) and Hispanics (145.9 ± 13.8 µm) than in whites (142.7 ± 14.3 µm) and Chinese (142.8 ± 15.0, P < 0.001 for overall comparison using ANOVA). Venular caliber was largest in blacks (221.8 ± 21.9 µm), intermediate in Hispanics (217.4 ± 20.9 µm) and Chinese (215.0 ± 20.8 µm), and smallest in whites (206.6 ± 21.2 µm, P < 0.001). The AVR was largest in whites, reflecting smaller venular caliber in this group” (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

There was also a strong and inverse correlation between the systolic blood pressure and retinal arteriolar caliber for the four ethnic groups (r = –0.21 to –0.28) (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006). “Venular caliber also correlated inversely with systolic blood pressure (r = –0.06 to –0.13). These relationships were essentially similar among the four racial-ethnic groups (e.g., P = 0.99 comparing the correlation coefficients of arteriolar caliber and systolic blood pressure for whites versus blacks, P = 0.79 for whites versus Hispanics, and P = 0.44 for whites versus Chinese) (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

This research indicates that the prevalence of retinal vascular caliber relating to diabetic symptoms is similar to the ethnicity and prevalence of diabetes.

Hypertension and Retinal Vascular Caliber

Definitions

Hypertensive retinopathy occurs when an individual experiences organ damage resulting from systemic arterial hypertension. This condition results in changes in both the choroid and the optic nerve depending on the severity and chronicity of the disease. Ocular changes that result from malignant hypertension include optic neuropathy and retinopathy (Klein, 1993). This condition is more prevalent in industrialized countries rather than countries that have a higher agrarian base. This condition presents with a “dry” retina with multiple cotton wool spots, rare, exudate, few hemorrhages and rare edema while diabetic retinopathy presents with a “wet” retina resulting in few incidents of cotton wool spots, extensive edema, multiple hemorrhages and multiple exudates (Klein, 1993).

Classifications

Hypertensive retinopathy occurs in two forms: essential (primary) and malignant. Health care professionals do not know the cause of essential hypertension and it is diagnosed when the individual’s average blood pressure is above 140mmHg systolic or 90mmHg diastolic during two subsequent visits. In comparison malignant hypertension is a rare disease resulting in a consistent rapid elevation of the patient’s blood pressure resulting in systolic blood pressure above 200mmHg or the diastolic blood pressure greater than 140mmHg.

Pathophysiology

The pathophysiology of hypertensive retinopathy is the result of prolonged periods of hypertension resulting in alterations to the retinal microvasculature. Hypertension results in the reduction of the lumen size in the medium and large arteries due to the layer of cholesterol in the tunica intima that develops gradually.

The pathophysiology of essential hypertensive retinopathy occurs in the blood vessel walls resulting in arteriosclerotic thickening. These changes result in focal constriction and the dilatation of the retinal arterioles as well as the loss of transparency of the intra-arterial blood column.

The pathophysiology of malignant hypertensive retinopathy includes the constriction of vascular bed due to circulating catecholamines, the obstruction of arterioles, and the breakdown in the blood-retina barrier. These changes in the pathophysiology result in focal arteriolar narrowing, intraretinal transudates, retinal hemorrhages and cotton wool spots.

Pathogenesis

Research has indicated that a combination of environmental and heredity factors are involved in the pathogenesis of essential hypertension. When examining elderly patient’s researchers have noted an increase in the basal smooth muscle tone resulting from sympathetic overactivity and increases in the renin-angiotensin system. Researchers have yet to determine the pathogenesis of malignant hypertensive retinopathy current research is focusing on possible changes in the alteration in hormone levels.

Prognosis

Hypertensive retinopathy does not often result in the significant loss of vision without the addition of other complications. Essential hypertensive retinopathy can be treated through the reduction of the patient’s high blood pressure. This elevation of blood pressure can delay the progression of the retinal changes however, if the patient had already experienced arteriolar narrowing or arteriovenous nicking damages are generally permanent changes.

The prognosis of malignant hypertensive is also dependent upon the progression of the condition and can be controlled through the gradual reduction of the individual’s blood pressure. This reduction must be done gradually in order to prevent the loss of blood flow to the optic nerve head or brain which could result in additional irreversible damage. If malignant hypertensive retinopathy is untreated the mortality rate is 50% at 2 months climbing to 90% at the one-year mark.

Epidemiology

** The retinal circulation allows one to visualize the microcirculation and investigate its relationship to systemic and ocular diseases. Recent studies have shown that changes in retinal vascular caliber may predict a range of cardiovascular diseases, independent of established risk factors. Generalized narrowing of retinal arterioles, for example, has been associated with incident stroke, coronary heart disease, and hypertension, independent of other risk factors. Larger retinal venular caliber has been reported to predict the progression of retinopathy and nephropathy in persons with type 1 diabetes. Association between retinal vascular caliber and ocular disease, such as glaucoma, have also been reported (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Epidemiology of Hypertension and Retinal Vascular Caliber – for

** Despite these data, the pathophysiological mechanisms underlying variations in retinal vascular caliber are unclear. The retinal arteriolar narrowing is thought to reflect structural damage from chronic hypertension. There is evidence that retinal venular caliber may be influenced by systemic inflammation, although not all studies have found consistent relationships, and most have only examined associations with nonspecific inflammatory markers (e.g., white blood cell count, erythrocyte sedimentation rate). There have been no studies that have examined possible racial and ethnic differences in retinal vascular caliber (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Epidemiology of Hypertension and Retinal Vascular Caliber – against

** Research has determined that there is a strong association between hypertension and retinal arteriolar narrowing. The first study that demonstrated the association between narrower arteriolar caliber and higher blood pressure was the ARIC study. “Another demonstrated significant differences in endothelial function in the retinal circulation in 19 subjects with hypertension, compared with that in normotensive control subjects” (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006). The MESA study determined that there were weak associations between markers of endothelial dysfunction and larger venular caliber (Wong, T.Y., Islam A.., Klein R.., Klein B., Cotch MF., Castro C., Sharrett A.R., and Shahar E., 2006).

Ethnicity and Hypertension and Retinal Vascular Caliber Prevalence

The Beaver Dam Eye Study determined that the prevalence of essential hypertension retinopathy was 15%. In comparison the Singapore Malay Eye Study determined that individuals who demonstrated no signs of age-related macular degeneration had a mean systolic blood pressure of 146mmHg while individuals who had been diagnosed with late age-related macular degeneration had a mean systolic blood pressure of 153.6mmHg. These findings are significant because it indicates that the participants of the study also had hypertensive retinopathy. In addition the Singapore Malay Eye Study determined that Asian females were more likely than Asian males to demonstrate either age-related macular degeneration or hypertensive retinopathy.

It is difficult to directly compare the results from the Beaver Dam Eye Study with the Singapore Malay Eye Study due to the differences in the aims of each study. However it is possible for the researchers to make comparisons concerning the measured blood pressure levels and the clinical definition of hypertensive retinopathy to determine if the patients in the Singapore Malay Eye Study were experiencing additional complications other than age-related macular degeneration.

Diabetic Retinopathy

Diabetic retinopathy is the most well-known ocular complication of diabetes and the leading cause of blindness among people 20 to 64 years of age in America. “Up to 4 million Americans with diabetes, 40 years of age and older, have retinopathy, and nearly 1 million have sight-threatened retinopathy” (JEGANTHAN).

Definitions

Diabetic neuropathy is one of the chronic complications of diabetes mellitus. Most of these complications are the result of metabolic alterations in the individual’s body, in the majority of cases the primary metabolic alteration is due to hyperglycemia (JEGANTHAN).

Classifications

Diabetic retinopathy is due to microangiopathy which affects the retinal precapillary arterioles, capillaries, and venules. Diabetic neuropathy causes damage due to the microvascular leakage that is the result of the breakdown of the inner blood-retinal barrier combined with microvascular occlusion. It is possible for researchers to determine the difference between these two pathological mechanisms through the use of fluorescein angiography (JEGANTHAN).

Pathophysiology

Diabetic retinopathy provides an example of the close association that exists between microvascular and macrovascular disease. In the World Health Organization Multinational Study of Vascular Disease IN Diabetes, retinopathy was related to the incidence of MI and death from cardiovascular disease. The US Atherosclerosis Risk in Communities study; indicated that the retinal arteriolar narrowing was related to the risk of coronary heart disease in women in addition to the additional retinal complications. In the European Diabetes study of type 1 diabetes, retinopathy was again related to the incidences of coronary heart disease in women. Microvascular disease is believed to contribute to the burden of heart disease in diabetes with women being at an increased risk (Krantz).

Retinopathy in patients with type 2 diabetes is associated with greater mortality after percutaneous coronary intervention, perhaps reflecting the presence of co-morbidities. A further manifestation of the diverse interactions between macrovascular disease and the microvasculature comes in the form of a recently described acute retinopathy following pre-cutaneous coronary intervention. Reduced retinal diameter has been implicated in the pathogenesis of hypertension, which could reflect widespread abnormalities. The early stages of hypertension are associated with capillary rarefaction and ultrastructural changes that may be only partially reversible with attainment of blood pressure control. When hypertension becomes established, the adverse consequences for small and large blood vessels are well recognized and promote vascular damage in subjects with either diabetes or states of prediabetes (Krantz).

Researchers are attempting to clarify the lack of understanding that researchers have of both the underlying risk factors and pathophysiology of isolated retinopathy signs that are seen both in nondiabetic and normotensive individuals. Various researchers have shown that there are associations of signs of retinopathy in individuals that demonstrate various medical conditions including older individuals, patients with an elevated blood pressure as well as hyperglycemia (Nguyen).

Animal models and human studies suggest that chronic inflammation and glucose-induced arteriolar endothelial dysfunction are related to the development of classic diabetic retinopathy (Nguyen).

The association of inflammation and signs of isolated retinopathy in people without diabetes supports the hypothesis that inflammatory processes may also be a possible pathway that underlies early subclinical microvascular disease in the pre-diabetes or prehypertension state (Nguyen).

Pathogenesis

The three stages of retinopathy are the nonproliferative stage which is also known as stage I. This stage is characterized by an increase in retinal capillary permeability, vein dilation, microaneurysm formation, and superficial and deep hemorrhages. The second stage is the pre-proliferative stage. In this a progression of retinal ischemia with areas of poor perfusion that culminate in infarcts. The third stage which is also known as the proliferative stage is the result of neovascularization and fibrous tissue formation within the retina or optic disc (NGUYEN).

The traction of the new vessels on the vitreous humor may cause retinal detachment or hemorrhage into the vitreous humor. Macular edema is the leading cause of decreased vision among individuals with diabetes. Hard exudates and microaneurysm can result in loss of vision. The blurring of the vision could also be a consequence of hyperglycemia and sorbitol accumulation in the lens. Cataract formation and dehydration of the lens, aqueous humor, and vitreous humor reduce visual acuity (NGUYEN).

Prognosis

Overall, the duration of diabetes and proper glycaemic control has consistently been shown to be the strongest predictors of both the incidence and prevalence of diabetic retinopathy. These important risk factors combined with the basis for guidelines that were aimed at decreasing the prevalence and incidences of diabetic retinopathy and visual impairment due to diabetic retinopathy in the future. Both the knowledge of the association of retinopathy with risk factors that have been thought to be associated with other diabetes complications combined with other chronic diseases must be important as the public health strategies are improved to assist in the prevention of diabetes through preventative care. Future research will need to account for both the established and hypothesized risk factors in creating the study design and when the data is analyzed.

Epidemiology

Epidemiology of Diabetic Retinopathy- for

Epidemiological studies in the U.S. have provided data on the prevalence and risk factors of diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) reported both the prevalence and incidence of diabetic retinopathy in a community-based cohort of white persons with diabetes in Wisconsin. Using stereoscopic fundus photographs of seven fields to define retinopathy, the WESDR has shown that in persons with type 1 diabetes (younger-onset diabetes who were on insulin treatment), about 71% had retinopathy at diagnosis, with 23% having PDR and 6% having clinically significant macular edema (CSME). In individuals with type 2 diabetes who were diagnosed with older-onset diabetes, who were not on insulin treatment, of those patients 39% had retinopathy at diagnosis, with 3% having PDR and 4% having CSME. In individuals with type 2 diabetes who were on insulin treatment, the prevalence of diabetic retinopathy was higher, with 70% having some retinopathy, 14% PDR and 11% CSME. A more recent meta-analysis of eight population-based studies that included the WESDR that had used standardized photographic methods to grade retinopathy estimated that in the United States, 40% of individuals with type 2 diabetes aged 40 years and older have diabetic retinopathy, with 8% of the studies population were experiencing a disease that severely threatened their sight. (Wong and Klien).

The most consistent risk factor for diabetic retinopathy is hyperglycemia. In the WESDR, participants with mean glycosylated hemoglobin levels above 12% had a three-fold higher risk of retinopathy than those with HbA1c levels under 12%, independent of diabetes duration and other risk factors (Wong and Klien).

Two large clinical trials have confirmed the importance of glycemic control in reducing the risk of retinopathy. The Diabetes Control and Complications Trial (DCCT) was a multi-centered trial that assessed the effect of intensive glycemic control on the development and progression of diabetic retinopathy and other vascular complications in 1,441 patients with type 1 diabetes. After a follow-up of 6.5 years, patients randomized to tight glycemic control (with an average glycosylated hemoglobin of 7%) had a 75% lower incidence of retinopathy and 50% lower rate of progression to more severe retinopathy as compared to patients randomized to conventional treatment (glycosylated hemoglobin of 9%) (Wong and Klien).

There were several clinically important observations from the DCCT regarding the relationship between glycemic control and the risk of diabetic retinopathy. First, the DCCT confirmed observations from other studies that tight glycemic control may lead to an early worsening of retinopathy. The DCCT showed that early worsening occurred in the first year of the trial in the intensive glycemic control group and reversed after 18 months, with the beneficial effect of intensive glycemic control increasing over time. Second, the DCCT demonstrated that there was no threshold glycosylated hemoglobin level above which the risk of retinopathy would be increased markedly. This is supported by data from more recent studies, such as the EURODIAB prospective complications study which showed no glycemic threshold for the development of retinopathy in 764 patients with type 1 diabetes followed for 7 years. Thus, the relationship between glycemia and retinopathy was graded and continuous. Third, the DCCT showed that the beneficial effects of intensive glycemic control were more pronounced when instituted earlier in the development of retinopathy, with progression rates of retinopathy noted to be 7% for patients who had retinopathy for less than 2.5 years and 20% for those who had retinopathy for more than 2.5 years. Finally, on-going observational follow-up of the cohort via the Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that the effects of tight glycemic control persisted over time, with retinopathy progression remaining low in DCCT patients who were originally randomized to tight glycemic control, despite an increase in the levels of glycosylated hemoglobin levels to that found in the conventionally randomized group (Wong and Klien).

It has been estimated that based on the DCCT findings, tight glycemic control may result in a gain of nearly 1 million years of sight for patients with type 1 diabetes in the United States who meet the study criteria (Wong and Klien).

The United Kingdom Prospective Diabetes Study (UKPDS) examined the effect of tight glycemic control on the development and progression of diabetic retinopathy and other complications in 3,867 patients with newly diagnosed type 2 diabetes. After 12-years of follow-up, the UKPDS showed that tight glycemic control (with an overall lowering of mean glycosylated hemoglobin levels of 1%) was associated with a 21% reduction in progression of retinopathy, a 29% reduction in the need for laser treatment, and a 37% reduction in the risk of any microvascular complications (Wong and Klien).

In summary, there is a substantial body of evidence that from epidemiological and clinical trials data that hyperglycemia is an important risk factor for the development and progression of diabetic retinopathy, and that this relationship has no threshold levels. It is important to know that retinopathy risk is not greatly affected by short-term improvements in glycemic control, as there is a lag between metabolic control and changes to the risk of retinopathy (Wong and Klien).

Epidemiology of Diabetic Retinopathy- against

Studies conducted in contemporary populations indicate lower rates of retinopathy in later as compared to earlier studies, although comparisons with older studies are typically hampered by differences in study design, participant characteristics, and changing diabetes definition. Nonetheless, in the meta-analysis of eight population-based studies, estimates of retinopathy prevalence were about 10 to 20% lower in the seven later studies conducted in the 1990s as compared to the WESDR. Furthermore, prospective data from both the UKPDS and the Liverpool Diabetic Eye Study show lower incidence rates for retinopathy, particularly severe or sight-threatening retinopathy, than was reported previously in the WESDR, and other studies in the early 1980s.

Serial data from Sweden have indicated that the prevalence of retinopathy may have decreased in the past decade. One recent study showed that the median diabetes duration before the onset of retinopathy was 17 years in patients with type 1 diabetes, this is a longer time frame than was originally reported in earlier studies. These observations suggest that both the advances in diabetes management as well as improved levels of metabolic and blood pressure control could have created a positive impact in reducing the prevalence and incidence of retinopathy (Wong and Klien).

The advances in both the technology of digital retinal photography as well as increasing imaging techniques have increased the understanding of researchers due to the increase in the availability of documentation that showed precise characterizations of the subtle retinal vascular changes in large populations. These retinal changes can be broadly divided into four groups: 1) the classic retinal vascular changes resulting from diabetes and hypertension, 2) isolated retinopathy signs that are prevalent in individuals with diabetes or hypertension, 3) alterations in retinal vascular caliber, and 4) alterations in retinal vascular architecture.

In the Wisconsin Epidemiologic Study of Diabetic Retinopathy, the 10-year cumulative incidence of cataract surgery was 8% in those with type 1 diabetes and 25% in those with type 2 diabetes. Predictors of cataract surgery included older age, greater severity of diabetic retinopathy, and baseline proteinuria in type 1 diabetes and older age and use of insulin in type 2 diabetes (Jeganthan).

Ethnicity and Diabetic Retinopathy Prevalence

There have also been several epidemiological studies that were done in order to determine the prevalence of diabetic retinopathy in locations other than the United States. In general, whilst direct comparison between reports is limited by differences in participant characteristics and assessment of retinopathy, these studies show that diabetic retinopathy is common. For example, on a study in England in Melton Mowbray showed that retinopathy was present in 41% of participants with type 1 diabetes and 52% in those with type 2 diabetes. In Australia, three population-based studies have assessed diabetic retinopathy from standardized assessments of retinal photographs. The Visual Impairment Project in Melbourne reported a retinopathy prevalence of 29% among persons aged 40 years or older with self-reported diabetes. The Blue Mountains Eye Study in Sydney found a similar overall retinopathy prevalence of 32% among a slightly older population 49 years and older with known or newly diagnosed diabetes. The Australian Diabetes Obesity and Lifestyle (AusDiab) study examined adults 25 years and older from urban and rural communities in Australia found a retinopathy prevalence of 25% among the participants with known diabetes (Wong and Klien).

There are fewer epidemiological data of diabetic retinopathy in Asia, although the prevalence of diabetes seems to have increased substantially in the last few decades. In Singapore, serial population surveys have documented an increase in diabetes prevalence of 2% in 1975, 4.7% in 1985 and 8.6% in 1992 in people between 15 to 69 years. Two population-based studies in India reported diabetic retinopathy prevalence of 27% and 22% in Southern Indian persons with type 2 diabetes. There are little reliable data from other Asian countries (Wong and Klien).

The relationship of diabetic retinopathy with age, gender and race has been extensively analyzed. In type 1 diabetes, the prevalence and incidence of diabetic retinopathy increase with age. In the WESDR, prior to 13 years of age, diabetic retinopathy was infrequent, irrespective of the duration of the disease. In the WESDR, the 4-year incidence of retinopathy increased with age, and was highest in persons 15 to 19 years of age, after which there was a gradual decline. The 4-year progression to PDR was low among younger type 1 WESDR diabetes participants, and there was no participant younger than 13 years of age who developed PDR at the 4-year follow-up examination. These data are supported by similar observations in other cohorts with type 1 diabetes. It has therefore been recommended that retinopathy screening may not be necessary for young children with type 1 diabetes (Wong and Klien).

In contrast to type 1 diabetes, the risk of retinopathy appears to be lower with age in persons with type 2 diabetes. In the older-onset type 2 diabetes participants using insulin in WESDR, the 4-year incidence and progression of retinopathy was lower while the 4-year rate of improvement was higher in older as compared to younger people. Few participants 75 years or older developed PDR after 10 years of follow-up. Other studies indicate similar results. In a study in Rochester, Minnesota, a lower incidence of retinopathy with increasing age was seen in people with type 2 diabetes 60 years and older. The explanation for this age pattern is unknown. While it is possible that older persons have less severe diabetes (less likely to require insulin), these findings may reflect selective mortality (i.e., older persons with severe retinopathy are more likely to die) (Wong and Klien).

Epidemiological studies have not shown a consistent pattern of gender variation in either the prevalence or incidence of retinopathy. In the WESDR, younger-onset men were more likely to have PDR than younger women, but there were no significant differences in the incidence or progression of diabetic retinopathy by gender. In older-onset diabetes participants in the WESDR, there were no significant gender differences in either the prevalence or incidence of retinopathy (Wong and Klien).

There is an abundance of data that show the prevalence of diabetic retinopathy varies between racial/ethnic groups. As compared to Caucasian white populations, native Americans have long been known to have a higher prevalence of type 2 diabetes and a higher prevalence of retinopathy for a given duration of diabetes. Studies comparing rates of retinopathy between racial/ethnic groups in the U.S. have consistently shown a higher prevalence of diabetic retinopathy in African-Americans and Hispanics as compared to whites. In one study, Haffner and colleagues showed that retinopathy prevalence was about two times higher in Hispanics living in San Antonio than non-Hispanic whites in the WESDR. Varma et al. found Mexican Americans living in Los Angeles to have a higher prevalence of proliferative retinopathy and macular edema than whites living in Beaver Dam, Wisconsin (Wong and Klien).

Fewer studies have examined the epidemiology of retinopathy in Asian Americans, but one study reported that the prevalence of retinopathy was significantly lower in second-generation Japanese American males than native Japanese people in Tokyo. One of the few studies to directly compare rates of retinopathy among different racial/ethnic groups was the Multi-Ethnic Study of Atherosclerosis (MESA), which examined the prevalence of diabetic retinopathy in a U.S. population of whites, African-Americans, Hispanics and Chinese-Americans aged 45 years and older. This study showed that the prevalence of retinopathy was similar between African-Americans (37%) and Hispanics (37%) and was lower in whites (25%) and Chinese-Americans (26%) (Wong and Klien).

The underlying reasons for these racial/ethnic differences are complex, and likely to reflect a combination of variations in health care access, genetic susceptibility and other risk factors for retinopathy, such as duration of diabetes, levels of glycemia and blood pressure. Harris and colleagues showed that in the National Health and Nutrition Examination Survey III (NHANES III) that the higher prevalence of retinopathy in African-Americans as compared to whites disappeared once these common risk factors were controlled for.

Likewise, in the Atherosclerosis Risk In Communities (ARIC) study, the higher prevalence of retinopathy in African-Americans (28%) than whites (17%) was largely explained by black-white differences in glycemic control, duration of diabetes, and blood pressure. This data reinforces the need to achieve tighter glycemic and blood pressure controls in African Americans and other groups that display a higher prevalence of retinopathy. It is also worth noting that controlling for these known risk factors had did not have an appreciable effect on the higher retinopathy prevalence rates among Hispanic whites compared to non-Hispanic whites in the NHANES III. This suggests both other unmeasured possible risk factors such as genetics may account for other racial or ethnic variations in the prevalence of retinopathy (Wong and Klien).

Vascular Retinopathy

Definitions

Vascular retinopathy is a medical condition that affects an individual’s retina. This condition is associated with other medical conditions that include arterial hypertension, eclampsia and advanced arteriosclerosis.

Classifications

Vascular retinopathy is a broad category that includes several diseases with similar pathologies. These diseases include hypertensive retinopathy, central retinal vein occlusion, diabetic retinopathy, proliferative diabetic retinopathy, central retinal artery retinopathy, and sickle cell retinopathy.

Pathophysiology

Vascular retinopathy occurs when the blood supply to the eye is interrupted due to prolonged hypertension. This causes retinal vasospasm and additional damage to the arteriolar lumina including narrowing.

Diabetic retinopathy is a common complication of diabetes resulting from microcirculatory changes which occur at a more accelerated rate with diabetes. Hypertensive retinopathy is the result of elevated blood pressure for a prolonged period of time. Sickle cell retinopathy occurs when sickle-shaped cells are unable to navigate through the narrow capillary vessels resulting in the creation of obstructions. The obstructions are responsible for the production of retinal vasospasm damaging the retinal blood vessels. Central retinal artery occlusion could result from a variety of illnesses including infection, temporal arteritis, heart failure, or an embolism. Nonproliferative diabetic retinopathy results in alterations to the lining of the retinal blood vessels. This alteration results in the vessels leaking a fatty substance which can decrease the blood flow to the retina.

Pathogenesis

The pathogenesis of vascular retinopathy begins with a breakdown of the protection offered by the blood-brain barrier resulting in the leakage of vascular fluid and the increased accumulation of extracellular fluid. The second aspect of the process is the occlusion of capillary beds which allow the creation of retinal ischemia. This then results in the development of new blood vessels.

At the microscopic level researchers can view several abnormalities that are characteristic of this condition. At this level, the capillary basement membrane increases in thickness. This increase in thickness impairs the functionality of the basement membrane as it attempts to bind with various molecules.

Prognosis

Vascular retinopathy can develop as either non-proliferative retinopathy or proliferative retinopathy. Therefore the prognosis of vascular retinopathy is dependent upon the type of retinopathy the patient has been diagnosed with.

Epidemiology

Ethnicity and Vascular Retinopathy Prevalence

A study that was designed to determine the prevalence rates of vascular retinopathy is the Veterans Affairs Diabetes Trial (VDAT). When analyzing the results of this study the researchers discovered an increase in the prevalence of retinopathy among the Hispanic individuals of the study population with an incidence rate of 36%. Out of the African American individuals involved in the study demonstrated an increase in retinopathy at 29%2.

Diabetic Retinopathy

Definitions

Diabetic retinopathy is a common complication that affects up to 80% of individuals that have been diagnosed with diabetes for 10 or more years. This illness affects the blood vessels located in the retina (4).

Classifications

Diabetic retinopathy can be broadly divided into an early stage of non-proliferative diabetic retinopathy (NPDR) and a later stage of proliferative diabetic retinopathy (PDR). NPDR includes a spectrum of retinal vascular signs such as microaneurysms, retinal hemorrhages, cotton wool spots and hard exudates4. With increasing severity, retinal venous beading and intra-retinal microvascular abnormalities may develop. These signs usually precede frank new vessel formation, heralding the onset of PDR. Although numerous classifications of diabetic retinopathy have been developed, principally for use in clinical trials, the American Academy of Ophthalmology has adopted a new, simplified classification for use in routine clinical practice.3 In this system, diabetic retinopathy is simply divided into none, mild, moderate, severe, and proliferative (Table 1).

Pathophysiology

Diabetic retinopathy appears to be a response to retinal ischemia resulting from blood vessel changes and RBC aggregation and is influenced by growth hormone and metabolic control. The research has shown that the prevalence and severity of the retinopathy have a strong correlation to the age of the individual and the duration of diabetes. Retinopathy develops more rapidly in individuals with type 2 rather than type 1 diabetes but is present in the majority of all individuals with diabetes mellitus.

The three stages of retinopathy are stage one which is known as the nonproliferative. This stage is characterized by an increase in retinal capillary permeability, vein dilation, and micro-aneurysm formation and superficial or flame-shaped hemorrhages as well as deep or blot-shaped hemorrhages. The second stage is known as the pre-proliferative stage. In this stage, there is a progression of retinal ischemia with areas of poor perfusion that culminate in infarcts. The third stage is known as the proliferative stage. This stage is the result of neovascularization and fibrous tissue formation within the retina or optic disc.

Traction of the new vessels on the vitreous humor may cause retinal detachment or hemorrhage into the vitreous humor. Macular edema is the leading cause of decreased visions among individuals with diabetes. Hard exudates and micro-aneurysms can result in loss of vision. The blurring of vision also can be a consequence of hyperglycemia and sorbitol accumulation in the lens. Cataract formation and dehydration of the lens, aqueous humor, and vitreous humor reduce visual acuity (Smeltzer and Bare, 2004).

Pathogenesis

Researchers are uncertain of the pathogenesis of diabetic retinopathy. Through the analysis of various studies indicate that a possible cause could be related to several possible factors including impaired glucose tolerance, component related to the metabolic syndrome, or hypertension3. While hypertension could be a possible complication additional studies have shown that hypertension is associated with both the prevalence of both retinal hemorrhages and microaneurysms. A contra indicator however is that high blood pressure has not been associated with any of the incidences of these retinopathy signs.

There have been a limited number of studies performed that investigated if impaired glucose tolerance, components related to metabolic syndrome or hypertension are precursors to diabetic retinopathy. In the ARIC study, the signs of retinopathy were not significantly associated with the subsequent incidence of diabetes unless the patient had a previous family history of diabetes. This information indicates that when examining individuals that have an underlying predisposition to diabetes the presence of retinopathy signs could indicate the presence of abnormalities in either their glucose metabolism or microvascular disease.

Epidemiology of Diabetic Retinopathy – For

The ADVANCE Retinal Measurements (AdRem) Study examined a group of individuals from twenty countries including Australasia, Asia, Northern America and Europe, with Chinese, South Asian or Caucasian ethnicities. This study determined that the established risk factors and the presence of retinal lesions were similar across the three ethnic groups (Stolk P, 2008). The patients with South Asian or Chinese ethnicity presented with a longer duration of diabetic retinopathy combined with younger age and lower blood pressure levels than the Caucasian participants of the study. The study also determined that the “mild/moderate retinopathy were 1.24 per percent A1C (95% CI 1.15–1.33), 1.06 per year of diabetes duration (1.04–1.08), and 1.09 per 10 mmHg of systolic blood pressure (1.03–1.14), respectively (all P < 0.001)” (Stolk P, 2008).

While this information indicates that the prevalence of diabetic retinopathy was present in the population study, the sample size of each ethnic population was not sufficient to determine significant associations for the individual ethnicities. The prevalence of diabetic retinopathy was measured at 40.2% which was higher than the prevalence rate of 33.2% determined by the Multi-Ethnic Study of Atherosclerosis (MESA) (Stolk P, 2008).

Ethnicity and Diabetic Retinopathy Prevalence

The epidemiological studies that have been conducted in the United States have provided researchers with both the prevalence and risk factors associated with diabetic retinopathy. “The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) reported both the prevalence and incidence of diabetic retinopathy in a community-based cohort of white persons with diabetes in Wisconsin” (Wong). This study used stereoscopic fundus photographs to define retinopathy. The study showed that 71% of the individuals diagnosed with type 1 diabetes showed symptoms of diabetic retinopathy. The study also showed that 23% showed signs of PDS with 6% showing clinically significant macular edema (CSME). The study discovered that the individuals with type 2 diabetes had a higher incidence of diabetic retinopathy at 70% as well as a 14% incidence of PDR and 11% incidence of CSME. This information is displayed in Figure 1.

In addition to the studies performed in the United States, researchers have performed epidemiology studies in locations around the world. It is difficult for researchers to directly compare the results of these studies. It is possible to determine that the incidences of diabetic retinopathy are prevalent throughout the countries of the world. This can be seen through the examination of a study that was conducted in England in which diabetic retinopathy was discovered in 41% of the participants that had been diagnosed with type 1 diabetes as well as in 52% of the patients diagnosed with type 2 diabetes.

In the three epidemiology studies that have been conducted in Australia, the researchers have been able to asses the prevalence of diabetic retinopathy through the assessment of retinal photographs. “The Visual Impairment Project in Melbourne reported a retinopathy prevalence of 29% among persons aged 40 years or older with self-reported diabetes” ().When the Blue Mountains Eye Study was conducted in Sydney the researchers discovered a similar pattern of diabetic retinopathy among the participants. The study showed a 32% prevalence among the older participants with either known or newly diagnosed diabetes. The third study was the Australian Diabetes Obesity and Lifestyle (AusDiab) study examined adults over the age of 25 that were lived in both rural and urban areas of Australia. In this study the researchers found a prevalence of retinopathy of 25% among the participants who had been previously diagnosed with diabetes ().

Vascular Disease and Age-Related Macular Degeneration

Definitions

Macular degeneration is a medical condition that generally afflicts older adults. This condition is the major source of blindness for individuals that are older than fifty years of age. This medical condition results in a loss of vision from the center of the visual field.

Classifications

The center of the retina that is responsible for central vision is the macula. The proper functioning of an individual’s vision depends on the proper functioning of the macula. These aspects of the vision that are dependent upon the macula include reading, driving and recognition of faces (SMELTZER and BARE, 2004).

The formation of drusen is an early sign of age-related macular degeneration (AMD). Drusen is usually visible to the proper use of an ophthalmoscope. There are two forms of AMD. These forms are neovascular and non-neovascular. Estimates performed by researchers indicate that between 10% and 20% of the patients that have been diagnosed with AMD are afflicted with the neovascular version of AMD. The remaining 80 to 90% of the population that have AMD have been diagnosed with the non-neovascular version of the disease (SMELTZER and BARE, 2004).

Pathophysiology

Age-related macular degeneration is a severe condition that results in the irreversible loss of vision. There are two clinical definitions of AMD, the neovascular or wet version and the atrophic or dry version of the medical condition. The atrophic version could include limited night vision combined with the difficulty in reading. The neovascular version includes leakage of blood or serum, retinal detachment, fibrovascular scarring and the loss of photoreceptors. The neovascular form causes a more severe loss of the patient’s central vision (SMELTZER and BARE, 2004).

Pathogenesis

Macular degeneration is the most common cause of visual loss in individuals age 60 older. It is commonly referred to as age-related macular degeneration. It is characterized by tiny yellowish spots called drusen that are located beneath the retina. This condition is so prevalent among the older population that most individuals older than 60 have at least a few small drusen. There is a wide range of visual loss in patients with macular degeneration, but most patients do not experience total vision loss. Generally the most affected area is the central vision which allows the individual to use their peripheral vision. There are two types of AMD commonly referred to as the wet or dry type (SMELTZER and BARE, 2004).

Between 85% and 90% of individuals have the dry or nonexudative type in which the outer layers of the retina slowly break down. With this breakdown comes the appearance of drusen. When the drusen occur outside of the macular area patients generally have no symptoms. When the drusen occur within the macula there is a gradual blurring of vision that patients may notice when they try to read. There is no known treatment that can slow or cure this type of AMD (SMELTZER and BARE, 2004).

The second type of AMD the wet or exudative type may have an abrupt onset. Patients complain that straight lines appear crooked and distorted or that letters in words appear broken up. This effect results from the proliferation of abnormal blood vessels growing under the retina, within the choroid layer of the eye, a condition known as choroidal neovascularization (CNV). The affected vessels can leak fluid and blood, elevating the retina. Some patients can be treated with a laser treatment that will stop the leakage from these vessels. This treatment is not ideal because vision may be affected by the laser treatment and abnormal vessels often grow back after the treatment (SMELTZER and BARE, 2004).

Prognosis

Atrophic AMD is the prevalent form of the disease and progresses slowly over a period of 5 to 10 years until the patient can be considered legally blind. The exudative AMD is the less common version of the disease; however it can do more damage to the patient’s visual field. 90% of the individuals that have experienced a loss of vision due to AMD have been diagnosed with the exudative type4.

There is currently no treatment option that has provided an effective treatment option for the atrophic version of the disease. Physicians can stabilize the visual acuity of patients diagnosed with the exudative through the destruction of the new vessels with two different forms of therapy5.

Epidemiology

Ethnicity and Vascular Disease and Age-Related Macular Degeneration Prevalence

Individuals who are more likely to be diagnosed with AMD are between 50 and 75 years of age, female and of Caucasian descent. Studies have shown that females are more likely than men to be diagnosed with AMD than men. It is also more prevalent in individuals of Caucasian descent than those of African or Asian descent. Studies have been conducted in France, Germany, Italy and the United Kingdom to determine the prevalence rate of AMD among their population.

There have been no formal epidemiological studies conducted in France to determine the prevalence and incidence of AMD. Despite the lack of research, the medical authorities have estimated that the number of cases is between 800,000 and one million cases of AMD which equals 8% of the population over the age of 65. The estimated number of the French population that are blind due to AMD is around 30,000 with 2,000 more individuals affected each year (5).

The prevalence of blindness has been investigated in several regions of Germany. During this study, the researchers determined that the prevalence rate of blindness due to AMD ranged from 0.01% in individuals aged 60 to 64 while those that were aged 75 to 79 showed a prevalence rate of 0.12%. A more current epidemiology study has indicated to researchers that the estimated rate of blindness due to AMD was 3.92% per 100,000 individuals (5).

A population-based, cross-sectional survey that was conducted in Italy reported that the overall prevalence of advanced AMD in the Italian population that was 60 years old or older was 1.1% of the population. For individuals that were 75 years or older, the prevalence rate was 4.17%. When researchers examined the cause of blindness among the Italian population for AMD-related blindness they determined that 4.1% of the blind population had lost their vision due to AMD (5).

There have been several population-based epidemiological studies have been conducted in order to determine the prevalence rate of AMD among the United Kingdom population. The Melton Mowbray Study in 1980 reported a prevalence rate of 41% in patients that were 76 years old or older. In 1990 a follow-up study was conducted that examined individuals that had participated in the first study that was still living. This study estimated that the prevalence of AMD among individuals of 86 years of age was 50%. In addition the prevalence of blindness was 10.1% percent in the original study, when the population was reexamined the prevalence rate was 20.9% (5).

Vascular Disease and Glaucoma

Definitions

A glaucoma is a group of medical conditions that are responsible for causing damage to the optic nerve. Because the optic nerve is responsible for conveying images from the retina to the brain which allows the individual to see any damage to this pathway would be responsible for the loss of vision. The damage to the optic nerve occurs slowly over time and the individuals that are affected by it generally do not recognize the loss of vision until it has dramatically increased.

Classifications

There are several different types of glaucoma. These types include chronic open-angle glaucoma which is the most common form that is diagnosed. In this version of the medical condition the open drainage angle of the eye becomes blocked which leads to the pressure in the eye gradually increasing. The increase in pressure results in damage to the optic nerve.

The second form of glaucoma is known as angle-closure glaucoma. This medical condition is the result of the drainage angle of the eye becoming narrower until it becomes completely blocked. It is possible that the iris could close off the drainage angle resulting in an increase in pressure. The sudden increase in pressure results in headaches, rainbow haloes as well as nausea and vomiting. This form of glaucoma must be treated as soon as the symptoms develop to prevent blindness. This version of the condition is seen more in individuals of African and Asian descent.

Pathophysiology

A glaucoma is a group of ocular conditions characterized by optic nerve damage. The optic nerve damage is related to the IOP caused by congestion of aqueous humor in the eye. There is a range of pressures that have been considered normal but that may be associated with vision loss in some patients. Glaucoma is one of the leading causes of irreversible blindness in the workplace and is the leading cause of blindness among adults in the United States. It is estimated that at least 2 million Americans have glaucoma and that 5 to 10 million more ate at risk. Glaucoma is more prevalent among people older than 40 years of age, and the incidence increases with age. It is also more prevalent among men than women and in the African-American and Asian populations. Currently, there is no cure for glaucoma but research is ongoing (Smeltzer and Bare, 2004).

Individuals with diabetic symptoms could be more vulnerable to an increase in intraocular pressure than non-diabetic individuals. The researcher believes that the diabetic symptoms increase the severity of the visual loss caused by the increased pressure when compared to non-diabetic individuals experiencing the same level of intraocular pressure resulting in a form of primary glaucoma. There are two primary types of glaucoma that a diabetic patient is at risk for developing. These are primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).

An additional form of glaucoma is neovascular glaucoma. This researcher believes that there is an association between diabetes and neovascular glaucoma with proliferative retinopathy resulting from a continual inability to control their diabetic symptoms.

Pathogenesis

The pathogenesis of glaucoma begins with an increase in intraocular pressure. The increase in intraocular pressure could result in damage to the optic nerve that shows the characteristics of glaucoma. Additional research has indicated that the majority of the damage caused by the increase of pressure is the result of the variations in the pressure rather than the continually increased pressure.

Prognosis

There are available treatment options that can be used to reduce the pressure that is associated with glaucoma. However these treatments have significant side effects which cause the physicians to delay utilizing these treatment options until the patient has suffered the loss of their vision. Due to these complications the medical condition must be detected as early as possible. Since the current treatment options that are used are able to slow the progression of the disease, however, there is no cure and the patient will eventually experience loss of either some or all of their vision5.

Epidemiology

Epidemiology of Vascular Disease and Glaucoma- for

Several epidemiological studies have reported positive associations between diabetes and POAG, which is the most common form of primary glaucoma, or in the absence of glaucoma optic neuropathy an elevated intraocular pressure. Glaucoma is present in 5 percent of the diabetic population which is higher than the 2 percent rate that occurs in the non-diabetic population.

The association between diabetes and POAG is supported by two separate biological mechanisms. The first supportive evidence is that the microvascular damage that results from diabetes could impair the blood flow to the anterior optic nerve resulting in damage to the optic nerve. Diabetes also impairs the auto-regulation of posterior ciliary circulation, which may increase the glaucomatous optic neuropathy. The second supportive evidence is that individuals with diabetes simultaneously have cardiovascular risk factors such as hypertension. It has been postulated that these cardiovascular risk factors could affect the vascular perfusion of the optic nerve head.

PACG has a characteristic display of either narrow or closed anterior chamber angles, resulting in the impediment of the drainage of aqueous humor leading to increased intraocular pressure. Diabetic patients with PACG appear to have abnormal glucose tolerance when compared to diabetic patients with POAG or those that do not have any form of glaucoma.

Neovascular glaucoma is seen in diabetic patients with a history of poorly controlling their diabetic symptoms. Between 32 and 43 percent of neovascular glaucoma cases are caused by proliferative diabetic retinopathy.

Diabetes has been suggested as a major risk factor for the development of glaucoma. Several population-based studies have found a positive association between diabetes and glaucoma or between diabetes and raised intraocular pressure, the major risk factor for glaucomatous optic nerve damage. In the Blue Mountains Study and Beaver Dam Eye Study, people with diabetes were two times more likely to have glaucoma than those without diabetes. However, not all population-based studies have found this association (Wong and Klien).

Ethnicity and Vascular Disease and Glaucoma Prevalence

Epidemiology studies have shown that the leading cause of blindness in the United States after diabetes retinopathy is glaucoma. When examining the leading cause of bilateral blindness in the world population, glaucoma once again is ranked as the second most prevalent cause. A study that was conducted in Salisbury Maryland found that the prevalence rate of glaucoma increased from 4% among the participants that were 65 to 74 years of age to 16% in the population that was between 80 to 84 years of age.

When examining epidemiology studies conducted in Australia, the researchers determined that age-related macular degeneration had a greater prevalence rate than either glaucoma or diabetic retinopathy. This is an alteration in the research that has been conducted in the United States where research has placed diabetic retinopathy has consistently had an increased rate of prevalence among the population when compared to age-related macular degeneration.

Currently the main source of information on the prevalence of open-angle glaucoma in the American population comes from the Beaver Dam Eye Study. One concern held by researchers when examining the data collected from this study is that the population of the study was primarily Caucasian. Therefore it is difficult to extrapolate the data to include other ethnic populations. In this study, the researchers determined that the rate of prevalence among the participants of the study was 2.1% and that the prevalence of open-angle glaucoma increases with the age of the participant. The conclusion drawn by the researchers of the study was that the research was comparable to the prevalence rates among other Caucasian populations.

In comparison to primarily Caucasian population that participated in the Beaver Dam Eye study, the Baltimore Eye study attempted to address the concern raised by conducting a cross-sectional study with a multi-racial study population. When researchers examined the African American population they determined that the prevalence rates of primary open-angle glaucoma were also dependent upon the age of the participant. Among the participants between the ages of 40 to 49 years of age the prevalence rate was 1.2%. This rate increased to 11.3% among the older participants than 80 years of age. When examining the participants of Caucasian descent the prevalence rate among individuals between the ages of 40 to 49 years old was 0.9%. In comparison the prevalence rate among those that were older than 80 years of age demonstrated a prevalence rate of 2.2%.

This research demonstrated that African Americans could be at an increased risk of developing primary open-angle glaucoma as they increase in age when compared to individuals of Caucasian descent. In addition to being at an increased risk for the development of glaucoma, individuals of African American descent are at an increased risk for developing this condition between 6 to 10 years earlier than the reported rate of glaucoma among those of Caucasian descent. The fact that African Americans develop this medical condition earlier than Caucasians increases the length of time that the condition was experienced by the individual.

Strengths and Limitations of Dissertation

One of the strengths of the study was the use of previous primary research studies that have examined the prevalence of diabetes and there complications among Hispanic, Chinese and white ethnic populations. These research studies include the Blue Mountain Eye Study, and the Multi-Ethnic Study of Atherosclerosis (MESA) These studies have been used as source documents in other research studies.

This study was limited due to the lack of previous research conducted in order to determine the prevalence of retinal complications that can occur due to complications of diabetes in various ethnic populations. Specifically the lack of previous research concerning the prevalence rates of diabetes and retinal complications in the Asian ethnic populations.

Future Directions

Researchers are using advances in their understanding of diabetic complications and available technology in order to find improved methods of treating the retinal complications of diabetes. Currently treatment options include medications that control the symptoms of diabetes and hypertension as well as slow the growth of the abnormal blood vessels which result in age-related macular degeneration.

In addition, researchers are working to increase the ability of retinal imaging as both a diagnostic tool and method of evaluating a patient’s risk for developing a macrovascular complication of diabetes.

Diabetic Medications

One of the best ways to prevent the retinal complications associated with diabetes is by properly maintaining the blood glucose levels of the patient. There are several medications that diabetic patients can use to prevent the fluctuations in their blood sugar that begin the progression of diabetic complications. Three of these medications are Lantus SubQ, Actos Oral, and Amaryl Oral. These medications are used in combination with proper diet and exercise programs.

Lantus SubQ is similar to human insulin and provides the benefit of working for a longer duration than other forms of manufactured insulin. Actos Oral works by restoring the patient’s ability to respond to the insulin produced naturally resulting in the lowering of the patient’s blood sugar. Amaryl Oral stimulates the body’s release of insulin. While these medications work in different manners the end result is similar.

Hypertensive Medications

Some of the retinal complications associated with diabetes are the result of prolonged periods of hypertension. To prevent these complications from developing researchers have created several treatment options that result in the lowering of the patient’s blood pressure. This can be accomplished through the use of diuretics, beta-blockers and calcium channel blockers. These medications provide several different treatment options that decrease the patient’s blood pressure.

Diuretics increase the excretion of sodium and water which results in the volume of fluid in the bloodstream being decreased. Beta-blockers are used in order to decrease the strength of the cardiac contractions resulting in the lowering o the patient’s blood pressure. Calcium channel blockers create several reactions in the body; the first is the decreased strength of the cardiac contractions while the second is the dilation of the arteries which increases the resistance to the flow of blood. This combination of actions results in the lowering of the patient’s blood pressure.

Anti-VEGF Agents

Anti-VEGF medications block the vascular endothelial growth factor (VGEF) that results in the progression of the wet version of macular degeneration. This protein results in the growth of new abnormal vessels in the eye which leads to macular degeneration. This medication is injected directly into the eye which allows the medication to decrease the effectiveness of the VGEF resulting in the slower growth of the abnormal blood vessels.

Retinal Vascular Caliber Imaging

Researchers have shown that a subjective evaluation of the retinal vasculature is unreliable resulting in the development of more objective methods of assessing the topography. This has been accomplished through the use of digital image analysis techniques.

One device is the retinal vessel analyzer (RVA) which combines the functionality of a PC to control the inputs received from a retinal fundus camera, CCD video camera, and a monitor for electronic image acquisition. This technology allows the researchers to obtain a real-time assessment of the retinal vascular diameters. In addition the system can automatically correct for variations due to minor eye movement.

References

  1. BERTRAM HAUSSLER, U.B. OLIVER MAST, WOLFGANG THEFELD 92005) Risk and Potential Risk Reduction in Diabetes Type 2 Patients in Germany. The European Journal of health Economics, 6, 152-158.
  2. E.H. HART (2003) Quality of Life Patients with Type 1 Diabetes Mellitus. Quality of Life Research, 12, 1089-1097.
  3. Hart, H. H. (2005) Change in Perceived Health and Functioning over Time in Patients with Type 1 Diabetes Mellitus. Quality of Life Research, 14, 1-10.
  4. KIFLEY, A. Retinal Vascular Caliber, Diabetes and Retinopathy
  5. STOLK P., CRUICKSHANK K., HUGHES A., STANTON J., MCG S., DIEDERICK T., GROBBEE D., VINGERLING J., (2008) Retinal Vascular Lesions in Patients of Caucasian and Asian Origin with Type 2 Diabetes. Diabetes Care, 31, 708-713.
  6. THANKH NGUYEN, WANG JIE JIN, TIEN YEIN (2008) Retinal Vascular Changes in Pre-Diabetic and Prehypertension
  7. TIKELLIS G (2007) The Relationship of Retinal Vascular Calibre to Diabetes and Retinopathy: The Australian Diabetes, Obesity and Lifestyle Study
  8. JEGANTHAN V., WANG E.S., JAN JIE, WONG TIEN YIN (2008) Ocular Associations of Diabetes, Other then Diabetic Retinopathy. American Diabetes Associations
  9. ZIMMET J.M., (2001) The Epidemiology of Diabetes Mellitus: An International Perspective, West Sussex, England
Retinal Complications of Diabetes and Vascular Disease
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