DIABETIC RETINOPATHY (DR)Defn: Damage to retina from microaneurysms, hemorrhage, macular edema/ischema, or retinal exudates in patients with diabetes mellitus (Taber’s Cyclopedic Medical Dictionary, 2009)

What is it? (Boyd & Altomare, 2008)

Most common diabetic eye disease

Caused by changes in blood vessels of the retina (i.e. thickening of basement membrane, vessels swell & leak and/or abnormal new blood vessels grow on the surface of the retina)

First Nations population at higher risk

Approximately 2 million Canadians have some form of DR

Risk of developing DR increases over time i.e. after 15 years, 80% of Type I pts may have DR & after 19 years up to 84% Type II pts may have DR (American Academy of Ophthamology, 2012)

Approximately 400 become blind each year from DR (Statistics Canada, 2005)

3 Main Types of DR: (Boyd & Altomare, 2008)

1. Macular edema – i.e. diffuse or focal fluid leakage at the macula (can occur at NPDR or PDR stage). The macular can thicken/swell d/t fluid & lipids/protein deposits and results in distortion of central vision (affects detail/form/color)

2. Progressive accumulation of blood vessel change (early stage or non-proliferative diabetic retinopathy – NPDR or “background” stage) – i.e. microaneurysms, intra-retinal hemorrhage & vascular malformation. Vision may be normal S&S may not exist.

3. Retinal capillary closure (proliferative diabetic retinopathy – PDR)– i.e. blood vessels are blocked or closed & parts of the

retina die; new blood vessels may form (neovascularization) but are weak & may not supply the retina with proper blood flow and may also bleed into the eye, blocking vision. Scar tissues may form – shrinking/tearing the retina or detaching it from the back of the eye & may lead to both central and peripheral vision loss or blindness. S&S exist.

PDR: Type I diabetes 23%

PDR: Type II diabetes 14% on insulin therapy and 3% on oral anti-hyperglycemic therapies

SIGNS & SYMPTOMS (American Academy of Ophthamology, 2012)

Vision often is normal (in early stage), and as DR progresses S&S include: blurred vision, difficulty reading or seeing up close, fluctuating vision, double vision, poor night vision, impaired color vision – washed out colors, eye pain, headaches, blotches or spots in vision (dark strings or floaters), vision loss, & blindness. DR usually affects both eyes.

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“Normal” Vision Diabetic Retinopathy

SCREENING (Boyd & Altomare, 2008)

INITIAL SCREENING

If Retinopathy is PRESENT If Retinopathy is ABSENT

TYPE I: at age 15 Dx severity, monitor & treat.

Case by case scenario. Rescreen within months or within a year.

*Review glycemic, BP, lipid control & screen for other complications

Rescreen annually *

TYPE II: at Dx Rescreen in 1-2 years *

TREATMENT & PREVENTION (Boyd & Altomare, 2008)

The KEY: Controlling blood sugar, hypertension, lipid levels with anti-hypertensives, anti-hyperglycemics, insulin, diet & moderate exercise program

Quit smoking reduces risk of DR

Scatter Laser: treats proliferative retinopathy

Focal Laser: treats macular edema

Vitrectomy: treats blood in the vitreous - This procedure involves removing a part of the vitreous humour along with the scar tissue. If retinal detachment has occurred, surgery may be required to reattach the retina.

Pharmacologic intervention: medication injected into eye (i.e. Avastin, an anti-vascular endothelial growth factor - Anti-VEGF)

Nursing Interventions: prevention (health promotion, patient/family education – managing diabetes) & monitoring of condition

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References3

American Academy of Ophthamology. (2012). Diabetic Retinopathy Symptoms. Retrieved from http://www.geteyesmart.org/eyesmart/diseases/diabetic-retinopathy-symptoms.cfm

Boyd, S.R. & Altomare, F. (2008). Retinopathy. Canadian Journal of Diabetes: Canadian Diabetes Association 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. 32, S134- S136. Retrieved from http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf

Statistics Canada. (2005). Sequelae of diabetes. Retrieved from http://www.statcan.gc.ca/pub/82-619- m/2005002/4144152-eng.htm

Taber’s Cyclopedic Medical Dictionary. (2009). Philadelphia, USA: F.A.Davis Company.

DIABETIC NEPHROPATHY (DN)

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Defn: Progressive kidney damage/disease that results as a complication of diabetes – mainly affects the microvasculature in the glomerulus. AKA Kimmelstiel-Wilson disease or intercapillary glomerulonephritis/glomerulosclerosis(MedicineNet.com, 2012).

(Saravana, 2011)

What is it? (McFarlane & Culleton, 2008)

Most common cause of renal failure

Several pathological changes. Most common is glomerulosclerosis – thickening/hardening of the basement membranes, proteins accumulate in the glomeruli which result in decrease function of the kidney. See video

First Nations population at much higher risk - about 12 times higher in Manitoba (Public Health Agency of Canada, 1999)

30-40% of all diabetics (Type I & II) will develop DN (Yee, 2008). Approximately 25-50% Type I may develop End-Stage Renal Failue (ESRF) within 10-20 years of insulin therapy (Black & Hawks, 2005).

VIDEO: http://www.youtube.com/watch?v=ikGl7DPXUK0&feature=related

SIGNS & SYMPTOMS (American Diabetes, 2010; Black & Hawks, 2005)

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Early stage – usually asymptomatic & sometimes with few S&S such as microalbuminaria (small amount of protein albumin in urine), enlarged kidney (via ultrasonography),increased glomerular filtration rate (20-50% increase), increased glomerular basement membrane thickness, mesangial expansion, HTN

Mid to late stages: increased levels of triglyceride & cholesterol, nocturnal polyuria, increased thirst & urination, frothy/foamy urine, edema, less requirement of insulin or anti-diabetic medication, reduced appetite (anorexia) and weakness, anemia, nausea & vomiting, pruritis, breathlessness, palpitation, pica, , increased levels of blood urea nitrogen, creatinine & potassium, proteinuria (KEY manifestation) – renal failure usually develops in approximately 5-10 years after appearance of significant proteinuria.

SCREENING (Canadian Diabetes Association, 2003; McFarlane & Culleton, 2008) Earliest clinically detectable stage: microalbuminuria (urine albumin 30-300mg/day) Overt nephroathy stage: microalbuminuria (urine albumin > 300 mg/day) Random urine test for albumin to creatinine ration (ACR) is the main test used to check for protein in urine.

Usualy 2-3 tests are taken at 1-8 week intervals to determine diagnosis of nephropathy. To screen for other renal diseases (other than nephropathy), a urine dipstick test would also be performed

(Canadian Diabetes Association, 2003)Other additional tests may include: blood urea nitrogen - BUN (product of protein breakdown), serum creatinine (measures creatinine in blood), 24-hour urine protein (measures amount of protein in urine), serum & urine protein electrophoresis test (determines how much and which proteins are excreted), blood levels for phosphorus, calcium,

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bicarbonate & potassium, hemoglobin, hematocrit, red blood cell count, ultrasound, & Kidney biopsy - usually biopsy performed for those with consistent protein in urine and has retinopathy or other complications of diabetes or when dx is unclear (Canadian Diabetes Association, 2003; McFarlane & Culleton, 2008).

TREATMENT & PREVENTION (Canadian Diabetes Association, 2003)

Glucose and blood pressure control will help slow down progression of disease

Lifestyle modification (exercise, diet low in fat, smoking cessation, etc)

Angiotensin converting enzyme (ACE) inhibitors or angiotension receptor II antagonists (ARBs)

Referral to nephrologist recommented if ACR is >75 mg/mmol, persistent hyperkalemia, >30% increase in serum creatinine within 3 montyhs of commencing ACE inhibitor or ARB therapy or creatinine clearance is <60 mL/min

Dialysis/Transplant (for end stage renal failure)

Nursing Interventions: prevention (health promotion, patient/family education – managing diabetes) & monitoring

Tony’s Scenario

1. Information from Tony’s data sheet which may indicate nephropathy:

2. Are those results good indications of nephropathy? (what factors/conditions can affect those results)

3. What other test(s) can be ordered for Tony for nephropathy?

References

3FXAnimation. (2008, November 26). Diabetic Nephropathy. [Video file]. Retrieved from http://www.youtube.com/watch?v=ikGl7DPXUK0&feature=related

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American Diabetes. (2010). Signs and Symptoms of Diabetic Nephropathy. Retrieved from http://www.americandiabetes.com/expert-advice/diabetes-health/signs-and-symptoms-diabetic-nephropathy

Black, J.M. & Hawks, J.H. (2005). Medical-Surgical Nursing: Clinical Management for Positive Outcomes. (8th ed.). St. Louis, Missouri: Saunders Elsevier.

Canadian Diabetes Association (2003). 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Nephropathy. Retrieved from http://www.diabetes.ca/search/results/?

cx=003094135815696782263%3Azxn5luxyt0g&cof=FORID%3A1 1%3BNB%3A1&ie=UTF-8&q=nephropathy&sa=Search

Focosi, D. (2012). Physiology of Homo Sapiens - Urinary Apparatus. Retrieved from http://www6.ufrgs.br/favet/imunovet/molecular_immunology/kidney.html

McFarlane, P., & Culleton, B. (2008). Chronic Kidney Disease in Diabetes. Canadian Journal of Diabetes: Canadian Diabetes Association 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. 32, S126- S131. Retrieved from http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf

MediceNet.com. (2012). Definition of diabetic nephropathy. Retrieved from http://www.medterms.com/script/main/art.asp?articlekey=7225

Public Health Agency of Canada. (1999). Diabetes in Canada: Diabetes and the Aboriginal People. Retrieved from http://www.phac-aspc.gc.ca/publicat/dic-dac99/d12-eng.php

Saravana, M.A. (2011). Diabetic Nephropathy. Retrieved from http://blog.saravanakidneystonecare.com/category/diabetic-nephropathy/

Science, Natural Phenomena & Medicine (2009). Glomerulus. Retrieved from http://science- naturalphenomena.blogspot.com/2009/11/glomerulus.html

Yee, J. (2008). Diabetic Kidney Disease: Chronic Kidney Disease and Diabetes. Diabetes Spectrum, 21. Retrieved from http://spectrum.diabetesjournals.org/content/21/1/8.full.pdf+html

AppendixA: NEPHROPATHY Early glomerular hemodynamic changes

(VIDEO) ↓

Hyperfiltration & Hyperperfusion Systemic HTN

↓

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Microalbuminuria Dysfunction of auto-regulatory response

↓

Increased arterial dilation

Increased mesangial Increased intraglomerular cell matrix production pressure

Increased extracellular matrix deposition & mesangial hypertrophy

↓

Expansion of mesangial area

Decreased glomerular filtration rate Reduction of surface area for filtration

Marks beginning of Renal Failure

↓

Basement Membrane thickens (eventually glomeruloscloerosis - hardening of glomerulus or scarring of the capillary loops) – further ↑ HTN

Increased BUN Decreased glomerular filtration Increased sodium creatinine

↓

Hypertrophy of remaining nephrons Inability to concentrate urine

↓

Further loss of nephron function

Loss of non-excretory function Loss of excretory renal function

Failure to produce Immune disturbancesErythropoietin Decreased sodium re-absorption

in tubuleAnemia, pallor, Infectionweakness & fatigue Water retention

Edema

(3FXAnimation, 2008)Appendix: B

MAIN FUNCTIONS OF KIDNEY FILTRATION BARRIER IN KIDNEY

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(Science, Natural Phenomena & Medicine, 2009)

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(Focosi, 2012)

Diabetic retinopathy and macular edema are detected during a comprehensive eye exam 

1. Visual acuity test. This eye chart test measures how well you see at various distances2. Dilated eye exam. Drops are placed in your eyes to widen, or dilate, the pupils. This allows the eye care

professional to see more of the inside of your eyes to check for signs of the disease. Your eye care professional uses a special magnifying lens to examine your retina and optic nerve for signs of damage and other eye problems. After the exam, your close-up vision may remain blurred for several hours.

3. Tonometry. An instrument measures the pressure inside the eye. Numbing drops may be applied to your eye for this test.

Your eye care professional checks your retina for early signs of the disease, including: Leaking blood vessels. Retinal swelling (macular edema). Pale, fatty deposits on the retina--signs of leaking blood vessels. Damaged nerve tissue. Any changes to the blood vessels.

If your eye care professional believes you need treatment for macular edema, he or she may suggest a fluorescein angiogram. In this test, a special dye is injected into your arm. Pictures are taken as the dye passes through the blood vessels in your retina. The test allows your eye care professional to identify any leaking blood vessels and recommend treatment.

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Fluorescein angiography

Your doctor may order fluorescein angiography to further evaluate your retina or to guide laser treatment if it is

necessary. This is a diagnostic procedure that uses a special camera to take a series of photographs of the retina

after a small amount of yellow dye (fluorescein) is injected into a vein in your arm. The photographs of fluorescein

dye traveling throughout the retinal vessels show:

•   Which blood vessels are leaking fluid;

•   How much fluid is leaking;

•   How many blood vessels are closed;

•   Whether neovascularization is beginning.  

Optical coherence tomography (OCT)

OCT is a non-invasive scanning laser that provides high-resolution images of the retina, helping your Eye M.D.

evaluate its thickness. OCT can provide information about the presence and severity of macular edema (swelling).

U ltrasound

If your ophthalmologist cannot see the retina because of vitreous hemorrhage, an ultrasound test may be done in the

office. The ultrasound can "see" through the blood to determine if your retina has detached. If there is detachment

near the macula, this often calls for prompt surgery.  When your diabetic retinopathy screening is complete, your ophthalmologist will decide when you need to be treated or re-examined.  

Scatter Laser or Also Known As: Pan-retinal photocoagulation

During the procedure, up to 2,000 laser burns are carefully placed away from the central retina, causing abnormal blood vessels to shrink.

Scatter laser treatment does not usually restore previous vision loss, but helps to prevent further vision loss or blindness from occurring. Although scatter laser treatment works fairly well at halting severe diabetic retinopathy, it may cause side effects including reduced peripheral, night and color vision.

Focal Laser Treatment: Leakage of fluid from blood vessels can sometimes lead to macular edema , or swelling of the retina. Focal laser treatment is performed to treat macular edema. Several hundred small burns are placed around the macula in order to reduce the amount of fluid build-up in the macula. This procedure has been shown to reduce further vision loss by 50%. Focal laser treatment can be repeated if necessar

Vitrectomy: Sometimes leaking blood vessels will cause a lot of bleeding (hemorrhage) in the vitreal cavity of the eye. If the bleeding is significant, a vitrectomy may be performed. A vitrectomy is performed under either local or general anesthesia. An ophthalmologist makes a tiny incision in your eye and carefully removes the vitreous gel that is clouded with blood. After the vitreous gel is removed from the eye, a clear salt solution is injected to replace the contents. 

The macula or macula lutea (from Latin macula, "spot" + lutea, "yellow") is an oval-shaped highly pigmented yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is

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often histologically defined as having two or more layers of ganglion cells. Near its center is the fovea, a small pit that contains the largest concentration of cone cells in the eye and is responsible for central, high resolution vision. The macula also contains the parafovea and perifovea.Because the macula is yellow in colour it absorbs excess blue and ultraviolet light that enter the eye, and acts as a natural sunblock (analogous to sunglasses) for this area of the retina. The yellow colour comes from its content of lutein and zeaxanthin, which are yellow xanthophyll carotenoids, derived from the diet. Zeaxanthin predominates at the macula, while lutein predominates elsewhere in the retina. There is some evidence that these carotenoids protect the pigmented region from some types of macular degeneration.Structures in the macula are specialized for high acuity vision. Within the macula are the fovea and foveola which contain a high density of cones (photoreceptors with high acuity).Whereas loss of peripheral vision may go unnoticed for some time, damage to the macula will result in loss of central vision, which is usually immediately obvious. The progressive destruction of the macula is adisease known as macular degeneration and can sometimes lead to the creation of a macular hole. Macular holes are rarely caused by trauma, but if a severe blow is delivered it can burst the blood vessels going to the macula, destroying it.

Black & Hawks – MedSurg Text book p 779

Several pathological changes lead to renal failure in clients with DM. Most common is intercapillary glomerulosclerosis (hardening of glomerulus), or scarring of capillary loops. Progressive

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microangiopathy, called nephrosclerosis, affects the afferent & efferent arterioles & eventually scares the glomerulus, Tubules and interstitium. Pylonephrhitis (kidney infection) can scar the renal parenchyma an dlead to ischemia. It may also lead to renal papillary necrosis and slowing of the papillae. Neurogenic bladder dysfunction may contribute tor enal failure. High incidence of urinary tract infection or increased pressure in the kidney caused by the backup of urine may also contribute to renal dysfunction.

GLOMERULUS: In the kidney, a tubular structure called the nephron filters blood to form urine. At the beginning of the nephron, the glomerulus / ɡ l ɒ ̍ m ɛ rələs/  is a network (tuft) of capillaries that performs the first step of filtering blood.The glomerulus is surrounded by Bowman's capsule. The blood is filtered through the capillaries of the glomerulus into the Bowman's capsule. The Bowman's capsule empties the filtrate into a tubule that is also part of the nephron.A glomerulus receives its blood supply from an afferent arteriole of the renal circulation. Unlike most other capillary beds, the glomerulus drains into an efferent arteriole rather than a venule. The resistance of these arterioles results in high pressure within the glomerulus, aiding the process of ultrafiltration, where fluids and soluble materials in the blood are forced out of the capillaries and into Bowman's capsule.A glomerulus and its surrounding Bowman's capsule constitute a renal corpuscle, the basic filtration unit of the kidney. The rate at which blood is filtered through all of the glomeruli, and thus the measure of the overall renal function, is the glomerular filtration rate (GFR).

The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.Whereas loss of peripheral vision may go unnoticed for some time, damage to the macula will result in loss of central vision, which is usually immediately obvious. The progressive destruction of the macula is adisease known as macular degeneration and can sometimes lead to the creation of a macular hole. Macular holes are rarely caused by trauma, but if a severe blow is delivered it can burst the blood vessels going to the macula, destroying it.

Mesangial cells are specialized cells around blood vessels in the kidneys, at the mesangium. They are specialized smooth muscle cells that function to regulate blood flow through the capillaries, usually divided into two types, each having a very distinct function and location: Extraglomerular mesangial cells Intraglomerular mesangial cells

Intraglomerular mesangial cells are specialized pericytes located among the glomerular capillaries within a renal corpuscle of a kidney.There are three primary functions of intraglomerular mesangial cells: filtration, structural support, and phagocytosis. Intraglomerular mesangial cells provide structural support for and regulate blood flow of the glomerular capillaries by their contractile activity. The initiation of contraction of mesangial cells is similar to that of smooth muscle. Contraction of mesangial cells is coupled with contraction of the basement membrane of the endothelium of glomerular capillaries. This causes a decrease in surface area of the basement membrane and thus a decreased glomerular filtration rate.Intraglomerular mesangial cells are also major contributors to the extracellular matrix which contains fibronectin, type IV collagen, perlecan, and laminin.

Extraglomerular mesangial cells (also known as Lacis cells, Goormaghtigh cells) are light-staining cells in the kidney found outside the glomerulus, near the vascular pole and macula densa.Lacis cells form the juxtaglomerular apparatus in combination with two other types of cells: the macula densa of the distal convoluted tubule and juxtaglomerular cells of the afferent arteriole. This apparatus controls blood pressure through the Renin-Angiotensin-Aldosterone system. The specific function of Lacis cells is not well understood, although it has been associated with the secretion of erythropoietin. [1

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Microalbuminuria occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus. The level of albumin protein produced by microalbuminuria can be detected by special albumin-specific urine dipsticks. A microalbumin urine test determines the presence of the albumin in urine. In a properly functioning body, albumin is not normally present in urine because it is retained in the bloodstream by the kidneys.Microalbuminuria can be diagnosed from a 24-hour urine collection (between 30–300 mg/24 hours) or, more commonly, from elevated concentrations in a spot sample (30 to 300 mg/L). Both must be measured on at least two of three measurements over a two- to three-month period.[1]

An albumin level above the upper limit values is called "macroalbuminuria", or sometimes just albuminuria. Sometimes, the upper limit value is given as one less (such as 300 being given as 299) to mark that the higher value (here 300) is defined as macroalbuminuria.[2]

To compensate for variations in urine concentration in spot-check samples, it is helpful to compare the amount of albumin in the sample against its concentration of creatinine. This is termed the albumin/creatinine ratio (ACR)[3] and microalbuminuria is defined as ACR ≥3.5 mg/mmol (female) or ≥2.5 mg/mmol(male),[4] or, with both substances measured by mass, as an ACR between 30 and 300 µg albumin/mg creatinine.[5] For the diagnosis of microalbuminuria, care must be taken when collecting sample for the urine ACR. An early morning sample is preferred. The patient should refrain from heavy exercises 24 hours before the test. A repeat test should be done 3 to 6 months after the first positive test for microalbuminuria. Lastly, the test is inaccurate in a person with too much or too little muscle mass. This is due to the variation in creatinine level which is produced by the muscle.[6]

Pre-proliferative (or Background) diabetic retinopathy is primarily a disease of retinal blood vessels. It is the result of two major processes affecting the retinal blood vessels: vessel closure and abnormal vessel permeability.

RETINAL BLOOD VESSEL CLOSUREThe earliest vessel closures in diabetic retinopathy are usually the capillaries. These small vessels are critical to the health of the retina, since they are needed to deliver oxygen and nutrients to the area and to carry away carbon dioxide and other waste products. The source of this capillary closure is not completely understood. Theories as to why these vessels close off include:

  Clumping of blood cells or other blood elements.   Abnormality or damage to the endothelium (the cells lining the inner wall of the capillary).

  Swelling of an abnormally permeable vessel wall.

  Compression of the capillary by surrounding retinal swelling.

Regardless of the exact mechanism, diabetics tend to have capillary closure causing areas of decreased oxygen supply to the small patches of retina corresponding to these capillaries. There is an associated dilation of the adjacent capillaries, probably in response to the decreased oxygen level in that part of the retina. In addition, small focal dilations of the retinal capillaries called microaneurysms can develop. These microaneurysms are small sacs budding off from the vessel, often visible as tiny red dots on ophthalmologic examination. It is thought that microaneurysms are the result of weakened capillary walls that allow a bulging outward of the endothelial lining of the capillary.

This is a photograph of retinal vessels which shows the larger artery (A) and vein (V) as well as a tangle of smaller retinal capillaries. Multiple round microaneurysms (arrowhead) can be seen attached to the retinal capillaries.

Localized closure of retinal capillaries (nonperfusion) is not usually noticed by the patient, since the nonperfused area is so small. However, if the nonperfusion is in the central portion of the retina (the fovea), the vision can be significantly reduced. There is no known treatment for this visual loss due to foveal nonperfusion.

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Retinal capillary closure can produce Proliferative diabetic retinopathy in more severe cases. When multiple areas of the retina have lost their blood supply, they start to send out chemical signals called neurogenic factors. These neurogenic factors stimulate the development of new blood vessels that are fragile and can cause bleeding and scar the retina.  This is one way blindness associated with diabetes occurs.

In addition to the closure of capillaries, the very small arteries within the retina may close off. When this happens, larger patches of the retina are deprived of their blood supply. This is manifest clinically by "cotton-wool spots", small fluffy white patches in the retina. Blockage of arterioles may also result in hemorrhages within the retina if the pressure causes a vessel to burst.

 

http://www.zuniv.net/physiology/book/chapter25.html

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