Proliferative Diabetic Retinopathy (PDR)
Overview
Diabetes Mellitus is a group of diseases characterized by high blood glucose levels. Diabetes results from defects in the body's ability to produce and/or use insulin.• Type 1 Diabetes Mellitus is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. In type 1 diabetes, the body does not produce insulin. 5% of people with diabetes have this form of the disease.
• In Type 2 Diabetes Mellitus, either the body does not produce enough insulin or the cells ignore the insulin. This is the most common form of diabetes.
• Gestational Diabetes is seen in pregnant females who develop high blood sugars during the second or third trimester of pregnancy (no previous history)
Pathogenesis (Origin or Development of a Disease)
Diabetic Retinopathy (NPDR/PDR) is caused by damage to blood vessels in the eye from elevated blood sugar. Prolonged hyperglycemia is the major etiologic agent in all of the microvascular complications of diabetes, including diabetic retinopathy. The cellular mechanisms through which hyperglycemia acts currently remain unclear.
Proposed mechanisms for the development of NPDR/PDR include:
• Hyperglycemia may alter the expression of one or more genes, leading to increased (or decreased) amounts of certain gene products that can alter cellular functions.
• Glycosylated proteins can undergo a series of reactions, leading to considerable alteration of proteins.
• Chronic hyperglycemia may produce oxidative stress in cells, leading to the formation of an excess of "toxic end products of oxidation" including peroxides, superoxides, nitric oxide, and oxygen free radicals.
• Chronic hypoxia causes cells in the eye to produce elevated levels of Vascular Endothelial Growth Factor (VEGF)
• VEGF is released into the vitreous cavity and promotes new blood vessel growth (NVD & NVE) and increases vascular permeability (DME/CME)
• New blood vessels (NVD & NVE) can bleed causing Vitreous Hemorrhage (VH)
• Other blood vessels & microaneursyms can leak causing Macular Edema (DME/CME)
Many of the complications of diabetic retinopathy can be prevented or delayed by blood glucose, blood pressure control, consistent medical monitoring by internists, endocrinologists and subspecialists.
Epidemiology
Diabetic retinopathy is a leading cause of new cases of blindness in people aged 20 to 74 years in the USA.
The total number of people with diabetes is projected to rise from 285 million in 2010 to 439 million in 2030.
Diabetic retinopathy is responsible for 1.8 million of the 37 million cases of blindness throughout the world.
Diabetic Retinopathy is the 5th leading cause of blindness worldwide behind only cataracts, glaucoma, macular degeneration & corneal opacities.
Diabetic retinopathy (DR) is the leading cause of blindness in people of working age in industrialized countries.
The best predictor of diabetic retinopathy is the duration of the disease.
• After 10 years of diabetes, nearly 70% of patients with type 1 diabetes and 50% of patients with type 2 diabetes have diabetic retinopathy.
• After 20 years of diabetes, nearly 99% of patients with type 1 diabetes and 80% with type 2 have some degree of diabetic retinopathy.
• 33% of all patients with diabetes have signs of diabetic retinopathy.
Symptoms
Diabetic retinopathy is asymptomatic in early stages but as the disease progresses symptoms may include:
• Sudden or gradual onset of blurred vision
• Sudden onset of red or black floaters
• Decreased central vision
• Fluctuating vision
• Distorted vision
• Dark areas in the vision
• Poor night vision
• Impaired color vision
• Partial or total loss of vision
Diagnostic Testing
Optical Coherence Tomography (OCT) is a type of high-resolution ultrasound used to evaluate the macular anatomy and to rule out cystoid macular edema (DME) or macular atrophy (Macular Ischemia) in PDR patients (rpip-OCT).
Fundus Photography (FP) is a color photos (or a montage of color photos) used to document the level of retinopathy and for comparison to evaluate disease progression at future exams.
Fluorescein Angiography (FA) is used to evaluate the macular and peripheral circulation. Many patients with PDR have loss of normal capillary circulation in the macula (macular ischemia) & peripheral retina (peripheral ischemia), growth of new blood vessels on the optic nerve (NVD), retina (NVE), iris (NVI) or angle (NVE) on the FA.
B-Scan Ultrasound (B-Scan) is used to evaluate the retina in patients with a poor view into the eye secondary to corneal opacities, cataracts, retinal hemorrhage or any other condition that makes visualization of the retina difficult with indirect ophthalmoscopy. B-scan can detect tractional retinal detachment (TRD) in a patient that has a vitreous hemorrhage (VH) that obscures the view of the retina.
Non-Proliferative Diabetic Retinopathy (NPDR) Findings
• Microaneurysms (MA) which are tiny circular aneurysms that form from capillaries that have damaged cells that surround the capillary wall (pericytes) from elevated blood sugars
• Retinal hemorrhages are tiny hemorrhages that form inside the inner retinal layers
• Hard Exudates (HE) are cholesterol and triglyceride (fatty deposits) that leak out of damaged capillaries and form deposits within the retina
• Cystoid Macular Edema (DME or CME) is leakage of serum (clear fluid from the bloodstream) out of damaged capillaries and into the macula and fovea (causing swelling of the macula)
• Cotton-Wool Spots (CWS) are small areas of ischemia within the retina (similar to a tiny stroke in a small area of retina) that causes swelling and a white discoloration in the affected area of retina
• Macular Ischemia (caused by loss of capillaries around the center of the macula)
• Peripheral Ischemia (caused by loss of capillaries in the peripheral retina)
• Venous beading is an irregular dilation and constriction of retinal vein (looks similar to sausage links)
• Diabetic Papillopathy is a sudden ischemic event that occurs in the optic nerve (typically from poorly controlled blood sugars) and causes swelling of the optic nerve and sudden visual loss (similar to a stroke in the optic nerve)
Proliferative Diabetic Retinopathy (PDR) Findings
Proliferative Diabetic Retinopathy (PDR) can be associated with all of the above findings in NPDR and the following additional findings:
• Clinically Significant Macular Edema (CSME) is an area of swelling near the center of the macula (fovea) caused by leakage of fluid and exudates from damaged capillaries in the center of the macula. It is defined by the following parameters:
o the presence of 500um of edema within 500um of the fovea
o the presence of hard exudates associated with edema within 500um of the fovea
o the presence of 1500um of edema within 1500um of the fovea
• Vitreous Hemorrhage (VH) (caused by rupture of NVD or NVE from a partial vitreous separation or traction)
• Fibrovascular Epiretinal Membrane (ERM) formation (caused by NVD/NVE contracting and distorting the macula)
• Tractional Retinal detachment (TRD) (caused by NVD/NVE contracting and/or a partial vitreous separation that detachs the retina around the NVD/NVE)
• Rubeosis Iridis or Neovascularization of the Iris (NVI) caused by the growth of abnormal blood vessels on the iris because of poor circulation inside the eye.
• Neovascular Glaucoma (NVG) (caused by NVI & NVA when abnormal blood vessels grow over the drainage angle of the eye and causing elevated pressure and can lead to optic nerve damage)
Medical Work-Up
A baseline eye exam with dilated fundoscopic exam (DFE) is recommended in Type 1 diabetics 5 years after onset, then annually thereafter. In Type 2 diabetics the first eye exam and DFE is recommended upon diagnosis and then annually.
The treatment of PDR includes a complete medical work-up to evaluate the adequacy of blood sugar control. This includes fasting blood glucose and a Hemoglobin A1C that should be repeated every three months by your primary care physician.
Your primary care physician and/or endocrinologist will prescribe a combination of diet, exercise, lifestyle changes and medication for the control of your blood sugar.
Ideally we would like to see your Hemoglobin A1C at a level of 6.0 or less to prevent worsening and progression of diabetic retinopathy.
Medical Treatment
Anti-Vascular Endothelial Growth Factor Medications (Anti-VEGF) include Avastin, Lucentis & Eylea are all medications approved for the treatment of Cystic Diabetic Macular Edema (DME/CME). This class of medication is typically the first line treatment for DME. Anti-VEGF agents can also induce regression of NVD and NVE with can be helpful to reduce the risk of bleeding during vitrectomy surgery.
Intravitreal Steroids include Ozurdex which is a intermediate acting (effect lasts about 3 months) steroid implant that is injected into the vitreous cavity to treat DME. Ozurdex therapy typically has a treatment effect for 3-4 months and may need to be repeated if DME returns. Ozurdex is typically used as a second line treatment for DME because of associated risks of cataract progression (65%), glaucoma (40%), and the need for glaucoma surgery (0.3%) to control intraocular pressure.
Iluven is an intravitreal long acting (effect lasts up to 3 years) steroid implant that is injected into the vitreous cavity to treat DME. Iluven therapy typically has a treatment effect for up to 3 years or more. Iluven is typically used as a second line treatment for DME because of associated risks of cataract progression (65%), glaucoma (40%), and the need for glaucoma surgery (5%) to control intraocular pressure.
Triessence (Triamcinolone) is a long acting steroid that is injected into the vitreous cavity to treat DME. Triessence therapy typically has a treatment effect for up to 3-6 months. Triessence is typically used as a second line treatment for DME because of associated risks of cataract progression (65%), glaucoma (40%), and the need for glaucoma surgery (5%) to control intraocular pressure. The generic version of Triamcinolone (with preservative) is associated with an additional risk of sterile endothalmitis.
Surgical Treatment
Focal Laser Photocoagulation (focal laser) is a laser therapy used to cauterize and seal (treat) the microaneurysms that leak and cause CSME. It may be used in combination with Anti-VEGF agents when DME & CSME are present together.
Panretinal Photocoagulation (PRP) is the laser therapy used to cauterize areas of peripheral retina where there is poor circulation (peripheral ischemia) and reduce the levels of vascular endothelial growth factor (VEGF) produced by the areas of ischemic retina that are not receiving enough oxygen because of poor circulation. This is the treatment for PDR in patients who present with neovascularization of the disc (NVD), neovascularization elsewhere in the retina (NVE), neovascularization on the iris (NVI), neovascular glaucoma (NVG) and tractional retinal detachment (TRD).
Vitrectomy surgery (PPV) with physical removal of the vitreous hemorrhage is the treatment for a PDR with a dense vitreous hemorrhage (VH) when there is a suspicion that the patient may have a Tractional Retinal Detachment (TRD) hidden by overlying hemorrhage.
The procedure is performed under local anesthesia, in either at one of our outpatient surgical centers or local hospitals (rpil-surgery centers and hospitals).
The surgery is performed through three 25-gauge ports (about the width of a wire paper clip). The surgery begins by placing an infusion canula, a light pipe & a vitrectomy cutter through each of the 3 ports. The infusion cannula keeps a constant pressure in the eye while the vitrectomy cutter removes the vitreous gel and vitreous hemorrhage. As the gel is removed, balance salt solution replaces the gel in the vitreous cavity. The gel that is adherent to the retina is gently lifted off the optic nerve and macula to separate the neovascular adhesions.
The light pipe is used by the surgeon to see the vitreous being removed inside the eye. After the hemorrhage and gel are removed, your physician will place panretinal photocoagulation (PRP) in the mid and far peripheral retina.
After PRP has been placed the surgeon removes the surgical instruments and trocars (3 ports) and the operation is complete. No sutures are typically needed in up to 95% of cases. Antibiotic ointment and a patch are placed over the eye for one night and removed the following day by the technician in our office.
Risks & Benefits of Surgery
The benefits of vitrectomy surgery, in general, are the potential for improved vision, reduced distortion of straight lines (when present pre-operatively), and reduction or elimination of floaters.
Some of the risks of vitrectomy surgery include:
• More rapid cataract progression (in most patients the lens may harden or become cloudy more rapidly after the vitreous gel is removed) that may require cataract surgery 1-2 years after the vitrectomy procedure.
• Vitreous (less than 5%) or choroidal (less than 1%) hemorrhage
• Retinal break or tear (less than 5%) or Retinal Detachment (less than 1%)
• Infection/Endophthalmitis (less than 1 in 500 patients)
• Permanent loss of vision/Blindness (approx. 1 in 10,000)
• These are some of the more common and serious side effects of surgery, but there are additional risks of surgery not listed above.
Post-Operative Care
Patients are typically started on antibiotic and steroid eyedrops the day after surgery. The frequency of these drops will be determined by your surgeon on the first post-operative day. Some patients have a temporary increase in intraocular pressure after even uncomplicated surgery and may require additional pressure lowering drops or oral medication.
Post-Operative Expectations
Vision is usually blurry the first day after surgery. Continued visual improvement often occurs over the first 6-8 weeks but some patients experience improvement even up to 6 months after surgery.
Patients typically experience little to no pain following surgery.
Surface or external irritation (feeling of having something in your eye) is common. A deeper or more intense eye pain in not typical and may signal a more serious issue such as high intraocular pressure, serous or hemorrhagic choroidals or infection. A deeper or more intense eye pain needs to be reported to you physician immediately.
Post-Operative Restrictions
Post-operative restrictions are for 4 weeks after surgery and include:
• Anything that creates a Valsalva Maneuvers such as coughing, sneezing, blowing your nose, straining with bowel movements or exertion, and some of the following:
• Bending at the waist putting your head below your belt line (such as bending to tie your shoes). Bending at the knees with your head up is allowed.
• Heavy lifting greater than 15-20 lbs.
• Strenuous activity (including lifting weights, running, yoga, pilates, aerobics, yard work, snow shoveling, laundry, housecleaning, sexual intercourse) is not recommended as it will increase your risk of developing a retina tear or detachment. Walking, for exercise, after surgery is allowed (in patients who do not require post-operative head down position).
• Showering is allowed immediately after surgery but be sure to keep your eyes closed to prevent shower water from entering your eye.
• Swimming after surgery should be avoided for 4 weeks. You may go into a pool (not under water for the first 4 weeks).
• Working restrictions are job dependent. Patients with desk jobs or who perform light stationary office work may sometimes resume work 2-3 days after surgery. Patients with jobs that require heavy lifting or strenuous activity may be required to be out of work for 2-4 weeks. Ask your physician about your individual work restrictions. We will be happy to provide you with a doctor's note for your work and/or complete your temporary disability paperwork.
• Driving restrictions will be dependent on your post-operative vision and should be discussed with your physician after surgery.
*Please note that this information is for illustrative purposes only, providing a general overview on the topics listed. For any specific questions or concerns regarding your condition, please contact our office so that you can consult with the appropriate person or department to address your needs.