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Setting Sights on Diabetes

Written by Dr. T. Mark Johnson - Retinal Surgeon, Retina Group of Washington.

settingSightsOnDiabetesDiabetes is emerging as a global public health crisis. Recent statistics suggest that the incidence and prevalence of diabetes are rising at alarming rates. It is estimated that the world prevalence of diabetes amongst adults in 2010 was 6.4%, affecting 285 million people.

Models suggest that the prevalence in 2030 will reach 7.7%, affecting 439 million people. This is not equally distributed with the largest increase in diabetic patients being observed in developing countries where the prevalence may rise by almost 70%. More sobering is that these numbers do not account for pre-diabetic patients who, in the absence of intervention, are at high risk of progressing to overt diabetes. In some countries, such as China, this at risk population may be as large as 15%.

Diabetes is characterized by sustained elevations of systemic blood sugar. Prolonged elevation of blood sugar leads to progressive injury to the smallest blood vessels in the body (capillaries). This microvascular injury leads to the major complications of diabetes including damage to the eyes leading to visual impairment, kidneys leading to renal failure, nerves leading to progressive loss of peripheral sensation, large blood vessels leading to myocardial infarction and stroke and impaired wound healing increasing infection rates.

The majority of diabetes worldwide results from progressive insulin resistance that occurs in adult populations. This form of diabetes is typically referred to as Type II or non insulin dependent diabetes. In contradistinction from the acute presentation of childhood Type I diabetes where there is a complete failure to produce insulin Type II diabetes has an insidious onset. Patients typically have no symptoms until advanced complications are manifest. Diagnosis requires routine screening during periodic health examinations. Thus a rising diabetic and pre-diabetic prevalence in underserved areas presents daunting public health challenges.

The cost of diabetes and its complications are enormous. In the United States it has been estimated that the per capita annual medical care costs are $13,243 for diabetic patients and $2,560 for non-diabetic patients. The costs of diabetic complications are not limited to the direct medical costs of patient care. There are significant societal economic costs that result from morbidity of diabetic complications and premature mortality related to diabetes. Studies in the United States have estimated that approximately 880,000 work days are lost per year due to illness secondary to diabetes. The annual indirect costs resulting from resulting from lost workdays, restricted activity days, mortality, and permanent disability due to diabetes totaled $39.8 billion.

settingSightsOnDiabetes 01Diabetic retinopathy represents one of the most common complications of diabetes. The retina is a multi-layered light sensitive tissue that lines the inner eye. The outer retinal photoreceptors, called rods and cones, convert light impulses into neuronal impulses that are relayed to the visual centers of the brain via the optic nerve. The center of the retina is called the macula and is responsible for central vision (reading, perception of color) while the remainder of the retina is responsible for perception of the peripheral visual field. (FIGURE 1) The blood vessels of the retina are frequently damaged in diabetic patients. Retinal microvascular injury can lead to two primary complications. Damage to the capillary walls can result in leaking and subsequently the tissue of the retina becomes swollen (referred to as macular edema). (FIGURE 2) Damage to the capillary walls can also lead to small vessel closure and subsequent ischemia (oxygen deprivation). The resulting tissue injury triggers abnormal blood vessels to grow into the middle of the eye (termed proliferative diabetic retinopathy) leading to the eye becoming filled with blood (vitreous hemorrhage) or resulting in a secondary scarring process that detaches the retina from the back of the eye. (FIGURE 3a and 3b) Any of these processes (edema, hemorrhage or retinal detachment) can lead to profound and permanent visual loss.

Visual impairment has profound impacts on the individual as well as society. The quality of life associated with significant visual impairment is on par with that of a major disabling stroke. The indirect economic costs of visual impairment due to disability are staggering. In Australia it is estimated that the indirect costs of visual disability near $5 billion dollars annually.

Significant progress has been made in recent decades to prevent and treat diabetic retinopathy. Large multi-centered trials have focused on the prevention and treatment of diabetic retinopathy. Studies such as the Diabetes Complications and Control Trial (DCCT), UK Prospective Diabetes Study (UKPDS) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study have all demonstrated that intensive control of blood sugar, as measure by the hemoglobin A1C, reduces the risk of progressive diabetic complications including diabetic retinopathy. Thus access to timely and aggressive diabetic care is paramount to preventing complications.

While prevention of diabetic retinopathy would be ideal it has proven to be an elusive goal. It has been clear from the prevention trials that improved glycemic control reduces complications but does not eliminate them. Even in well controlled diabetics retinopathy can still arise and progress. Furthermore these prevention trials represent a select subset of motivated, carefully monitored diabetic patients. A population study in the United States found that most average patients' diabetes was too poorly controlled to even be considered as a candidate for these prevention studies. Clearly in developed countries diabetic control is proving to be a significant and somewhat overwhelming problem. This speaks to the urgent need to develop systems for screening, monitoring and treating early diabetes in the developing countries that will carry the future burden of diabetes.

Successful treatments have been developed to address the visual complications of diabetic retinopathy. Moderate and severe visual loss secondary to proliferative diabetic retinopathy and macular edema can be significantly reduced with the appropriate application of laser photocoagulation. Laser therapy can be applied using a simple outpatient treatment. Advances in technology have made the lasers readily portable to remote areas. Laser therapy has durable effects on prevention of visual loss. (FIGURE 4 and 5) Laser therapy has been demonstrated to be highly cost effective. Pan retinal photocoagulation therapy has a remarkably low cost of $594 per line of visual acuity saved. Laser photocoagulation has also been found to be cost effective with an approximate cost of $3101 per quality adjusted life year (QALY). Newer pharmacologic therapies are being introduced in the treatment of retinopathy. In the treatment of macular edema they appear to offer a greater chance of visual improvement compared to laser photocoagulation. While they have been demonstrated to be safe and effective they can require long term, multi-session therapy. In addition the drug costs associated with this approach may be significant and may make them less attractive in areas where health care dollars are spread thinly. Future research into pharmacologic therapy is needed to better understand how to best utilize medication to restore sight in advanced cases of retinopathy in a cost effective manner.

settingSightsOnDiabetes 02One important lesson gleaned from the diabetic retinopathy laser trials was that treatment was highly effective at preventing vision loss but had a more modest effect in recovering visual acuity. Thus it is critical to identify patients with clinically significant retinopathy and apply treatment before significant vision loss occurs. Therefore there is a need for improved access to screening. Screening for retinopathy can be achieved through a simple direct examination of the retina or through review of retinal photographs. Graded retinal photos are more sensitive for detection of retinopathy, particularly early stages of disease. Screening for diabetic retinopathy has significant obstacles including patient compliance and inadequate number of available, trained personnel to conduct screenings. In the United States only 60% of diabetic patients are estimated to receive adequate screening for diabetic retinopathy. Recent advances in technology provide opportunity for accessible remote screening of large populations for diabetic retinopathy. Telemedicine programs utilizing non mydriatic digital cameras have allowed for screening in remote areas with the images being reviewed and graded by trained observers in distant centers. Initial studies in developing countries have demonstrated telemedicine screening programs to be effective in detection of retinopathy. In one study in Northwest Cameroon 24 % of eyes screened had detectable diabetic retinopathy and 10 % of all eyes had vision threatening retinopathy in need of laser therapy.

The global diabetic epidemic presents new challenges to global leaders in public health. Undiagnosed, untreated and undertreated diabetes has the potential to result in catastrophic numbers of visually impaired people worldwide. The direct and indirect economic costs in the developed world are staggering and in the developing world potentially crippling. The availability of portable, durable and effective treatments for diabetic retinopathy provides an opportunity to prevent this potential disaster. Recognition of the importance of early and timely detection of retinopathy is critical. Cooperation between public officials, local health providers and vitreo-retinal specialists to utilize technologies such as telescreening for at risk populations and providing access to laser therapy offers hope to millions of people at risk for future blindness.

References

Diabetes Control and Complications Trial. The effect of intensive diabetic treatment on the progression of diabetic retinopathy in insulin dependent diabetes mellituse. Arch Ophthalmol. 1995;113:36-51

UK Prospective Diabetes Study Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of diabetes complications in patients with type 2 diabetes. Lancet. 1998;352:837-853.

GHD Winter 2014 Digital Edition

GHD Contributors - Winter 2013

David B. Agus, MD, Shamsia Anwari, F.E. Baralle, MD, PhD, Dr. Seth Berkley, Vittorio Cammarota, The Honourable Gunilla Carlsson, Francis Collins, MD, PhD, Dr. Suraya Dalil, Ambassador Mark Dybul, Dr. Thomas Evans, The Right Honourable Stephen Harper, Karl Hofmann, His Excellency Jakaya Kikwete, Gregory T. Lucier, Partha P. Majumder, PhD, Dr. Carole Presern, Scott C, Ratzan MD,MPA, Dr. David Reddy, Janet Hatcher Roberts, Professor Jeffrey D. Sachs, Dr. Sima Samar, His Excellency Dr. Jorge Sampaio, Dr. Ataulhaq Sanaie, Dr. Khaled Seddiq, Dr. Richard Sezibera, Dr. Ahmed Shadoul, Jill Sheffield, Michel Sidibé, Prabhjot Singh, Her Excellency Ellen Johnson Sirleaf, Kari Stoever, H.E Jakaya Kikwete, Hervé Verhoosel, Princess Sarah Zeid