Diabetic Retinopathy

Topic Highlights

●    Diabetic retinopathy is a vascular disorder of the retina that results from diabetes.

●    Damage caused to the microvasculature and the vasoproliferative response may lead to bleeding in the retina and edema and abnormal growth of blood vessels.

●    Diabetic retinopathy remains a leading cause for blindness, although the condition can be treated effectively.

●    This presentation describes the epidemiology and progression of diabetic retinopathy from nonproliferative to proliferative stage, their symptoms, diagnosis and treatment procedures ' available and upcoming.

Transcript

Diabetes mellitus is a disorder characterized by hyperglycemia, caused by defects in the secretion and/or in the action of insulin. Though diabetes can be controlled, long-term complications of the disease - nephropathy, retinopathy, neuropathy and atherosclerosis are common.

Eye disorders are common in diabetics and can range from mild to severe in nature. Diabetic retinopathy, cataract and glaucoma may be caused by diabetes, with diabetic retinopathy potentially the most severe. Diabetic retinopathy constitutes a set of retinal abnormalities caused by damage to the microvasculature of the retina and to compensatory vasoproliferative responses to this damage in diabetes, and is a leading cause of blindness. The retinal changes in diabetic retinopathy include bleeding from fragile retinal blood vessels, edema, and abnormal growth of blood vessels over the retina.

●   In most developed countries, diabetic retinopathy is the primary cause for blindness among adults.

●    Diabetic retinopathy may be relatively asymptomatic until advanced stages of the disease.

●    Diabetic retinopathy can be effectively treated. Retinal laser photocoagulation is the principle approach used to curb disease advancement.

●    Regular comprehensive eye care allows early diagnosis and preventative management.

A frequent cause of new cases of blindness among adults in the age group of 20-64 years, diabetic retinopathy is chiefly pre-disposed by the duration of diabetes. Both type 1 and type 2 diabetic persons with a long history of diabetes are at risk of developing this vision threatening disease. The majority of persons with type 1 and approximately two thirds of those with type 2 diabetes may show evidence of retinopathy after the second decade of the disease. Apart from the duration of diabetes, poor diabetes and hypertension control can contribute to the onset and progression of the diabetic retinopathy.

Diabetic retinopathy progresses from Nonproliferative (NPDR) in varying degrees from mild, moderate and severe to Proliferative (PDR). The asymptomatic nature of disease onset causes many diabetic patients to unwittingly progress rapidly towards severe vision loss. Early diagnosis, regular eye examinations, and appropriate intervention are key factors in the avoidance of visual impairment and blindness.

Diabetic retinopathy occurs as a result of changes in the microvasculature of the retina. Some of the changes include pericyte death and thickening of the basement membranes of the blood vessels that result in changes in the blood-retinal barrier and make the blood vessels more permeable.

Nonproliferative (NPDR) is the initial stage of the disease. Early NPDR commences with the formation of small balloon-like swellings called micro-aneurysms that appear in the retina's small blood vessels. At this time, direct ophthalmoscopy reveals small red dots or blot hemorrhages, which typically do not produce symptoms unless there is bleeding into the macula. Visual loss in this condition is more typically caused by macular edema, due to the leakage of fluids from the damaged blood vessels that causes the macula to become swollen. This may lead to vision changes such as blurring.

Advanced NPDR occurs with the progression of disease. The significant finding at this stage is the appearance of cotton-wool spots. Cotton wool spots are discrete white spots with feathery edges that appear on the fundus. They arise due to capillary blockage that results in ischemia or infarction of the nerve fibers covering the retina. NPDR presenting with irregular dilatations on the blood vessels or venous beadings, dilated tortuous intra-retinal vessels and extensive hemorrhages on the retina, may progress rapidly to Proliferative Retinopathy.

Proliferative (PDR) is most likely to result in complete loss of vision. This condition is caused by formation of new blood vessels in response to capillary blockage that prevents insufficient supply of blood to the retina. Neovasculazisation does not independently cause symptoms or vision loss. But the fragile nature of the blood vessels causes vitreous hemorrhage, bleeding into the vitreous cavity. New blood vessels may also grow into the angle of the eye's anterior chamber causing Neovascular Glaucoma. The fibrous proliferation accompanying neovascularization is associated with production of contractile proteins by fibrocytes that can cause shrinkage, tearing or detachment of the retina. Retinal detachment or distortion are additional reasons for vision loss in PDR. The ophthalmoscopic changes seen in PDR are neovascularization with or without vitreous hemorrhage and fibrous proliferation, cotton-wool spots, extensive hemorrhages, venous abnormalities such as venous beading, loops and dilation. Macula edema may also be present.

●    Duration of diabetes: is the strongest predictor of diabetic retinopathy. All diabetic persons are at some risk of developing retinopathy. Those who have had diabetes for a longer period of time are at a greater risk.

●    Diabetic women in pregnancy: Women with pre-existing diabetes are at a risk of development or exacerbation of retinopathy during pregnancy.

●    Poor Glycemic control: Optimal glycemic control may considerably reduce the risk of developing diabetic retinopathy.

●    Poor hypertension control: Optimal blood pressure control substantially reduces the risk of retinopathy development.

Early stages of the disease are largely asymptomatic. However ocular symptoms that commonly present are:

●    Transient refraction disturbances, usually myopic in nature.

●    Gradual vision loss, due to maculopathy.

●    Initial symptoms in PDR may include floating specs or spots.

●    Infrequently, ocular pain and erythema may be seen with secondary glaucoma that may occur as sequelae to diabetic  retinopathy.

Early detection of diabetic retinopathy is indispensable to the prevention of visual impairment. The various methods that are employed for diagnosis are

●    Visual acuity test: The most simple and widely used method. An illuminated Snellen chart is used to test each eye separately. A pinhole can correct refractive errors. Maculopathy is indicated when impaired visual acuity does not improve with the use of a pinhole. However, the simplicity of the test can be the reason for decreased sensitivity when performed by inexperienced or non-eye care providers.

●    Retinal examination: Direct opthalmoscopy with mydriasis (pupil dilatation).

●    Non-mydriatic retinal photography: Photographs of the optic disc and the retina generally improve the detection rate of  maculopathy. The recent changes on the retina can be captured and the digital data can be preserved.

●    Fluorescein angiography: Fluorescein, a dye that is injected into the bloodstream, is used to detect the bleeding pattern in the retinal arteries. Bleeding blood vessels can be identified for initiating appropriate treatment.

●    Ocular Coherence Tomography (OCT): This method of scanning is used to measure the thickness of the retina.

●    Tonometry: This is a test to determine intraocular pressure to detect glaucoma.

The high frequency of early onset retinopathy after diagnosis of diabetes and its tendency to rapidly progress to maculopathy underlines the necessity for regular and frequent comprehensive eye check-ups.

Frequent eye examinations are critical both for detection and for monitoring disease progression. Glycemic control and blood pressure control reduce the risk of developing diabetic retinopathy. In its initial stages, treatment may not be required, but in more advanced cases; treatment to curb further damage to the retina is of great importance.

●    Laser photocoagulation: In a widely used technique in treating diabetic retinopathy, laser light is employed to seal  bleeding retinal vessels, as well as providing an approach to reduction of the extent of the ischemic retina.  Neovascularization may be restrained by focal retinal laser treatment. The resulting laser scars help to reduce  neovascularization and may be employed in binding a dislodged retina to the posterior portion of the eye. This  technique is utilized to diminish progress in visual impairment.

●    Scatter laser treatment: Multiple laser burns are made away from the centre of the retina. This technique, which is  referred to as panretinal photocoagulation, causes vessel shrinkage. It may result in loss of peripheral vision and of  color and night vision.

●    Intraocular steroid injection: A treatment for macular edema, this therapy reduces the amount of fluid leaking into the  retina and improves vision. However the steroid injections may need to be administered repeatedly as diabetic  retinopathy is chronic in nature, and this approach is associated with elevation of increased intraocular pressure.  Intraocular steroid injection therapy in conjunction with laser surgery has maximal lasting effects.

●    Cryotherapy: Cryotherapy or freezing is used when laser surgery fails due to the clouding of the usually clear vitreous  fluid with blood. Cryotherapy causes shrinking of abnormal blood vessels and binds the retina to the posterior portion  of the eye.

●    Vitrectomy: Advanced stages of PDR are treated by vitrectomy. This microsurgery replaces the blood-filled vitreous  with a clear solution.

●    Retinal repair: Scar tissue may detach retina from the back of the eye. Severe loss of vision or even blindness can  result if surgery for retinal repair is not performed.

●    PKC (Protein kinase-C) inhibitors: PKC inhibitors such as Ruboxistaurin have shown results in animal models in reducing microvascular complications such as neovascularization and vessel bleeding.

●    Vascular Endothelial Growth Factor (VEGF) antagonists: Preliminary analysis suggests two agents acting to reduce  VEGF activity; Pegaptanib and Ranibizumab have effects in reducing macular edema. Ongoing clinical trials are  evaluating the use of these agents.

Comprehensive, regular ophthalmic examination should be performed for every person with diabetes on an annual basis beginning at the time of diagnosis of type 2 diabetes, and after 3-5 years of type 1 diabetes. Optimal glycemic control can delay disease progression. Optimal blood pressure control can also delay disease progression.

The frequency of eye examinations should be increased when retinopathy is suspected. Diabetic women in pregnancy are vulnerable to developing diabetic retinopathy. An initial eye examination is recommended during the first trimester, with regular follow-up throughout the pregnancy. Counseling on the risk of developing diabetic retinopathy coupled with the eye examination, enhances patient preparedness and the follow-up rate throughout the pregnancy. This guideline is relevant to women with pre-existing diabetes and not to those who develop gestational diabetes.

Patients who have macular edema and NPDR should not delay management and treatment. Early management and treatment may greatly reduce the likelihood of developing vision loss or resorting to vitrectomy. Visual rehabilitation should be encouraged in patients who have partial or complete vision loss.