**3. Social and economic risk factors**

Social and economic factors have a fundamental impact on the visual prognosis of diabetic eye disease. A number of studies have investigated the negative influence of deprivation on the prevalence of diabetes, access to evaluation and care, level of metabolic control, and rate of complications and were reported in systematic reviews for type 1 [19] and type 2 diabetes [20]. Remoteness [odds ratio (OR) 2.02] and diabetes in combination with never having had an eye examination (OR 14.47) were among the main risk factors for vision loss in indigenous Australians, and blindness prevalence was 2.8 times higher among them than in non-indigenous Australians after age and gender adjustment [21]. The presence of PDR was associated with low income (OR = 3.6 for developing PDR if income was less than \$20000) in the Proyecto VER Study in the USA involving 4774 Hispanics over the age of 40, after controlling for other factors [22]. Deprivation, as a comprehensive measure of income, employment, health and disability, education, crime, barriers to housing, services, and living environment at the level of small geographic areas, was developed in the UK as a numerical index per residential code and used in a large national database study of 79,775 diabetic patients to highlight its effect on visual acuity and need for early treatment at first hospital presentation [23]. The OR of presenting with "sight impairment" at first visit to the hospital eye service was gradually decreasing from 1.29 in the most deprived group to 0.77 in the least deprived one, and OR for "severely sight impaired" was 1.17 in the most deprived decile versus 0.88 in the least deprived one. The risk of sight-threatening maculopathy and vitreous hemorrhages showed little variations across the deprivation range, and tractional retinal detachment was less likely in the two least deprived deciles. The large scale of the study and use of "real-world" multicenter in-hospital dataset provided statistical strength to the conclusion that the impact of deprivation extends to late presentation of retinopathy, significant loss of vision at presentation,

and a pattern of advanced retinal complications that affect the treatment these patients receive. Financial factors are often self-reported by diabetic patients who are missing screening appointments and treatment sessions. However a study in Tanzania revealed that the reasons for poor compliance are more complicated. The clarity of referral process and ease of navigation through the unfamiliar hospital environment are essential, particularly for the elderly and less educated patients from remote areas [24]. Another formidable obstacle is the widespread complacency and fatalistic resignation with the notion that retinopathy will inevitably end up with blindness. Constant assurance and encouragement that diabetic eye disease is a treatable condition with good prognosis is a practical strategy to prevent delays in diagnosis of sight-threatening complications. Lack of education greatly affects the health awareness and adherence with retinopathy management. In Kuwait, 16% of the men and 46% of the women over 65 years are illiterate, and 20% of the men and 24% of the women in the same age group can only read and write [25]. This is a significant barrier to in-depth understanding and compliance with recommended treatment and lifestyle and eventually compromises the visual outcome despite the high economic standard of the Kuwaiti nationals and availability of services in the country. Family support greatly improves the continuum of care and is essential for the regular attendance of the patients, especially females from a more conservative background.

Progression of nonproliferative to proliferative disease was investigated in several large cohort studies [26, 27]. Disease severity was estimated by the EDTRS classification and taken separately for each eye or concatenated as the bilateral grade, and progression was defined as the increase of two or more steps in severity. The rate of progression to PDR varied greatly—it was from 4 to 9.9% in the first 4–5 years and 8–12% in the next 5 years and reached a cumulative level of 31% after 16 years and 42% after 25 years in type 1 and type 2 diabetics. There are differences between the populations and methodology applied in the hospital-based and community-based studies as more patients with severe disease that required active management were probably referred to tertiary care centers [28–32].

The diagnosis of diabetic macular edema has evolved with the introduction of stereoscopic photography of the posterior pole and optical coherence tomography (OCT). The presence of any edema and clinically significant edema (CSME) by the modified EDTRS classification has been investigated in multiple hospital series and population-based studies. Detection of DME in non-stereoscopic fundus photographs is less sensitive to milder forms with recent onset, and probably the reported prevalence covers the more severe chronic stage. The prevalence of CSME in type 1 patients was from 5.73% in Spain to 9.4% in Brazil [33, 34]. Among patients with type 2 diabetes, it was in the range from 1.4% in Portugal to 12.8% in Denmark [35, 36]. There are reports indicating that the prevalence of DME in Central and Eastern Europe [37], North Africa, and Middle East [38] is considerably higher, and further research on the magnitude of CSME and risk factors for its progression will contribute to the estimates of sight-threatening retinopathy globally.

#### **4. Diabetic nephropathy**

Diabetic nephropathy (DN), the primary cause of chronic kidney disease, is significantly associated with incidence and progression of diabetic retinopathy as demonstrated in Brazilian [39], Spanish [40], Korean [41], Taiwanese Chinese [42], and Australian [43] patients. The presence of chronic kidney impairment had adjusted a hazard ratio of 5.01 for nonproliferative and 9.7 for proliferative disease

**231**

baseline [47].

**6. Diabetic foot syndrome**

*Diabetic Retinopathy and Blindness: An Epidemiological Overview*

as compared to patients without nephropathy. At 5-year follow-up, the hazard ratio of progression to PDR was 2.26 in patients with DN, and it was related to the levels of microalbuminuria and estimated glomerular filtration rate with cutoff

kidney disease increased the risk of progression to proliferative disease; however diabetic nephropathy did not significantly affect the development or progression of DME. Among the Taiwanese Chinese patients, diabetic macular edema had high crude hazard ratio association with cerebrovascular accidents and lesser one for hypertension and use of statins; however the significance was lost after controlling

Diabetes affects 17% of pregnancies worldwide and can be pre-existing type 1, gestational, or type 2, in some of the patients—previously undiagnosed. The highest rate of diabetes in pregnancy is recorded in Southeast Asia, 25%, and the prevalence of pre-existing diabetes is highest among women from the Middle East and North Africa—3.1%. Australian mothers who were born in high diabetes risk areas such as Polynesia, Asia, and the Middle East are 1.4 times more likely to have type 2 diabetes during pregnancy [45]. Similarly, in the USA and UK, patients belonging to Black, Asian, Hispanic, and Pacific Island ethnic minorities had higher proportion of pre-existing diabetes and pre-existing type 2 DM. Progression of retinopathy during pregnancy is related to the level of diabetic retinopathy prior to conception and was noted in 58% of the patients with moderate or more severe DR at baseline. Duration of diabetes type 1 greater than 15 years and type 2 more than 6 years was significantly associated with higher rate of progression of retinopathy in patients with pre-existing proliferative disease. Poor glycemic control prior and during pregnancy was an independent risk factor for retinopathy progression; however tight control and rapid optimization of metabolic control in such patients were associated with worsening of retinopathy. As the long-term benefits of proper glycemic management outweigh the short-term risk of deteriorating retinopathy, optimal control is currently recommended prior to and as soon as possible after conception for the health of the mother and fetus. Progression of retinopathy during pregnancy was significantly higher in diabetic patients with preeclampsia, with sight-threatening complications in 50% of the diabetic women with preeclampsia compared to 8% without it [46]. Other risk factors for deteriorated retinopathy during pregnancy include young age of type 1 onset, insulin treatment in type 2 prior to pregnancy, low vision at baseline, and pre-existing macular edema at

Diabetic foot syndrome is one of the important consequences of long-term uncontrolled diabetes, which occurs due to a combination of peripheral neuropathy and microvasculopathy in the lower extremities. It may vary from a minor ulceration to necrosis of tissues, sometimes warranting amputation [48]. Several hospital

series demonstrated the presence of retinopathy in 90–95% and proliferative disease and severe nonproliferative changes in 39–55% in such patients independent of the ulcer severity [49]. Diabetic foot syndrome in type 1 and type 2 diabetic patients with retinopathy was associated with higher levels of HbA1c, serum creatinine, older age, and lower hematocrit, particularly elevated in the subgroup

[44]. Hypertension and DN in patients with chronic

*DOI: http://dx.doi.org/10.5772/intechopen.88756*

for age, sex, comorbidities, and medications.

**5. Pregnancy in diabetic patients**

below 60 mL/min/1.73 m<sup>2</sup>

*Diabetic Retinopathy and Blindness: An Epidemiological Overview DOI: http://dx.doi.org/10.5772/intechopen.88756*

as compared to patients without nephropathy. At 5-year follow-up, the hazard ratio of progression to PDR was 2.26 in patients with DN, and it was related to the levels of microalbuminuria and estimated glomerular filtration rate with cutoff below 60 mL/min/1.73 m<sup>2</sup> [44]. Hypertension and DN in patients with chronic kidney disease increased the risk of progression to proliferative disease; however diabetic nephropathy did not significantly affect the development or progression of DME. Among the Taiwanese Chinese patients, diabetic macular edema had high crude hazard ratio association with cerebrovascular accidents and lesser one for hypertension and use of statins; however the significance was lost after controlling for age, sex, comorbidities, and medications.

#### **5. Pregnancy in diabetic patients**

*Visual Impairment and Blindness - What We Know and What We Have to Know*

and a pattern of advanced retinal complications that affect the treatment these patients receive. Financial factors are often self-reported by diabetic patients who are missing screening appointments and treatment sessions. However a study in Tanzania revealed that the reasons for poor compliance are more complicated. The clarity of referral process and ease of navigation through the unfamiliar hospital environment are essential, particularly for the elderly and less educated patients from remote areas [24]. Another formidable obstacle is the widespread complacency and fatalistic resignation with the notion that retinopathy will inevitably end up with blindness. Constant assurance and encouragement that diabetic eye disease is a treatable condition with good prognosis is a practical strategy to prevent delays in diagnosis of sight-threatening complications. Lack of education greatly affects the health awareness and adherence with retinopathy management. In Kuwait, 16% of the men and 46% of the women over 65 years are illiterate, and 20% of the men and 24% of the women in the same age group can only read and write [25]. This is a significant barrier to in-depth understanding and compliance with recommended treatment and lifestyle and eventually compromises the visual outcome despite the high economic standard of the Kuwaiti nationals and availability of services in the country. Family support greatly improves the continuum of care and is essential for the regular attendance of the patients, especially females from a more conservative

Progression of nonproliferative to proliferative disease was investigated in several large cohort studies [26, 27]. Disease severity was estimated by the EDTRS classification and taken separately for each eye or concatenated as the bilateral grade, and progression was defined as the increase of two or more steps in severity. The rate of progression to PDR varied greatly—it was from 4 to 9.9% in the first 4–5 years and 8–12% in the next 5 years and reached a cumulative level of 31% after 16 years and 42% after 25 years in type 1 and type 2 diabetics. There are differences between the populations and methodology applied in the hospital-based and community-based studies as more patients with severe disease that required active management were probably referred to tertiary care

The diagnosis of diabetic macular edema has evolved with the introduction of stereoscopic photography of the posterior pole and optical coherence tomography (OCT). The presence of any edema and clinically significant edema (CSME) by the modified EDTRS classification has been investigated in multiple hospital series and population-based studies. Detection of DME in non-stereoscopic fundus photographs is less sensitive to milder forms with recent onset, and probably the reported prevalence covers the more severe chronic stage. The prevalence of CSME in type 1 patients was from 5.73% in Spain to 9.4% in Brazil [33, 34]. Among patients with type 2 diabetes, it was in the range from 1.4% in Portugal to 12.8% in Denmark [35, 36]. There are reports indicating that the prevalence of DME in Central and Eastern Europe [37], North Africa, and Middle East [38] is considerably higher, and further research on the magnitude of CSME and risk factors for its progression will contrib-

Diabetic nephropathy (DN), the primary cause of chronic kidney disease, is significantly associated with incidence and progression of diabetic retinopathy as demonstrated in Brazilian [39], Spanish [40], Korean [41], Taiwanese Chinese [42], and Australian [43] patients. The presence of chronic kidney impairment had adjusted a hazard ratio of 5.01 for nonproliferative and 9.7 for proliferative disease

ute to the estimates of sight-threatening retinopathy globally.

**230**

background.

centers [28–32].

**4. Diabetic nephropathy**

Diabetes affects 17% of pregnancies worldwide and can be pre-existing type 1, gestational, or type 2, in some of the patients—previously undiagnosed. The highest rate of diabetes in pregnancy is recorded in Southeast Asia, 25%, and the prevalence of pre-existing diabetes is highest among women from the Middle East and North Africa—3.1%. Australian mothers who were born in high diabetes risk areas such as Polynesia, Asia, and the Middle East are 1.4 times more likely to have type 2 diabetes during pregnancy [45]. Similarly, in the USA and UK, patients belonging to Black, Asian, Hispanic, and Pacific Island ethnic minorities had higher proportion of pre-existing diabetes and pre-existing type 2 DM. Progression of retinopathy during pregnancy is related to the level of diabetic retinopathy prior to conception and was noted in 58% of the patients with moderate or more severe DR at baseline. Duration of diabetes type 1 greater than 15 years and type 2 more than 6 years was significantly associated with higher rate of progression of retinopathy in patients with pre-existing proliferative disease. Poor glycemic control prior and during pregnancy was an independent risk factor for retinopathy progression; however tight control and rapid optimization of metabolic control in such patients were associated with worsening of retinopathy. As the long-term benefits of proper glycemic management outweigh the short-term risk of deteriorating retinopathy, optimal control is currently recommended prior to and as soon as possible after conception for the health of the mother and fetus. Progression of retinopathy during pregnancy was significantly higher in diabetic patients with preeclampsia, with sight-threatening complications in 50% of the diabetic women with preeclampsia compared to 8% without it [46]. Other risk factors for deteriorated retinopathy during pregnancy include young age of type 1 onset, insulin treatment in type 2 prior to pregnancy, low vision at baseline, and pre-existing macular edema at baseline [47].

#### **6. Diabetic foot syndrome**

Diabetic foot syndrome is one of the important consequences of long-term uncontrolled diabetes, which occurs due to a combination of peripheral neuropathy and microvasculopathy in the lower extremities. It may vary from a minor ulceration to necrosis of tissues, sometimes warranting amputation [48]. Several hospital series demonstrated the presence of retinopathy in 90–95% and proliferative disease and severe nonproliferative changes in 39–55% in such patients independent of the ulcer severity [49]. Diabetic foot syndrome in type 1 and type 2 diabetic patients with retinopathy was associated with higher levels of HbA1c, serum creatinine, older age, and lower hematocrit, particularly elevated in the subgroup

with proliferative disease—all characteristics of concomitant chronic kidney disease and neuropathy in poorly controlled, long-lasting diabetes. Despite the lack of data on macular edema, the presence of any stage of diabetic foot ulcer is emerging as a predictor for retinopathy deterioration [50, 51].
