LaboratoryTestingforOptometry 000

Laboratory Testing for Optometry
Author: Tracy Doll, OD COPE #21399-PD 3 credits Introduction A working knowledge of basic medical laboratory testing can be crucial in the event that a systemic condition or infection is a suspect etiology of an ocular finding. The correct diagnosis and appropriate referral to another health care provider can depend entirely on the results of a laboratory test. This paper discusses indications for laboratory tests that are most useful for optometry, including hematology, blood chemistry, urinalysis, serology, the PPD, and cytology and how to interpret their results. Optometrists should always communicate with the patients primary health care provider when considering requesting a medical laboratory test. Primary health care providers may often provide useful information regarding the patients health history and can often recommend other useful tests to order. When in doubt of which medical laboratory test to request, always consult with a primary care physician. Blood Work Blood work consists of three categories: hematology, blood chemistry, and serology. The differences between these is described below: Hematology Hematology, the study of blood and its components, can be broken down into three specific test groupings which will be discussed in detail:

The Complete Blood Count Erythrocyte Sedimentation Rate C-Reactive Protein The Eight Components of the Complete Blood Count: Red Blood Cell Count (RBC) The RBC count tells the clinician the number of erythrocytes per cubic millimeter (mm3 or L). Normal ranges for a CBC can be seen in Table 1 below (1).
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Author: Tracy Doll, OD COPE #21399-PD 3 credits When the RBC count is below the normal range, the patient is diagnosed with anemia. Anemia can be caused by blood loss, iron or vitamin B12 deficiency, or bone marrow dysfunction. Conversely, when the RBC count is above the normal, called polycythemia, it may be due to ominous causes like leukemia (2). Both anemia and polycythemia can lead to cotton-wool spots and/or hemorrhages on the retina: including white centered retinal hemorrhages (Roth Spots), mid-peripheral or peripheral retinal hemorrhages (3). Hemoglobin (Hb) Recall that hemoglobin (Hb) is the iron-containing protein that carries oxygen in the bloodstream, as part of the RBC. Therefore, anemic conditions that reduce RBC count also reduce Hb levels. Polycythemic conditions, like leukemia, can likewise elevate Hb levels, as can lung disease. Elevated Hb levels are expected for patients who live at high altitudes, and might also be seen in smokers (2). The normal range for Hb can be seen in Table 1. Hematocrit (HCT) HCT is also called the packed cell volume, and tells the clinician the percentage of the blood volume occupied by red blood cells. The normal percentage of HCT is 42-52% of blood volume for men and 37-47 % for women (1). Low HCT levels could mean the patient has anemia. Higher HCT is associated with a disease called polycythemia vera (2). Polycythemia vera is a myeloproliferative disorder that causes all of the red blood cell elements in the blood to be over-produced. A stem cell defect is the theorized cause of this disorder. This rare condition usually occurs in the sixth decade of life and most commonly affects Caucasian females of Jewish descent (2). Systemic symptoms of polycythemia vera are a result of the increased red blood cell mass in the blood: headache, pruritis (itching), fatigue, and weight loss. The pruritis is exacerbated by heat (showering or exercising) due to the increased amount of histamine from the red blood cells. Ocular signs of polycythemia vera can include retinal vein thrombosis and occlusions, in addition to cotton wool spots (3). Eventually 5-10% of patients with polycythemia vera will develop acute leukemia (2).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Mean Corpuscular Volume (MCV) The average size of red blood cells is measured by the MCV. A low MCV can indicate that the patient has iron deficiency anemia, while high MCV suggests vitamin B12 deficiency (pernicious anemia). Overall, MCV is used to help diagnose anemia, but it call also occur with recent blood loss, or poor bone marrow function, or folic acid deficiencies (2). Normal levels for the MCV is 80-90 fL (femtoliters) (1). Folic acid plays a crucial role in DNA synthesis, including the DNA of rapidly dividing cells. Erythrocytes, leukocytes, and platelet formation will be affected in folic acid deficiency, resulting in abnormal cells. Vitamin B12 aids folic acid in DNA synthesis. Thus, a B12 deficiency can also interfere with normal blood cell formation. It can result in an elevated MCV, called macrocytic anemia (2). Mean Corpuscular Hemoglobin (MCH) The MCH is a test of the mass of the hemoglobin present in an average red blood cell. The normal range for MCH is 27-31 picograms (see Table 1). Both low (hypochromic) and high (hyperchromic) MCH values can be consistent with anemia. Hyperchromic anemias include folic acid or vitamin B12 deficiency. Hypochromic anemias include iron deficiency and a disease known as thalassemia (3). Thalassemia is a family of congenital disorders that cause decreased production of normal hemoglobin in red blood cells. Abnormal hemoglobin can lead to anemia, spleen disease, infections, gallstones and bone deformities (most common in the face) (2). Platelet Count (PLT) Platelets, once called thrombocytes, are necessary for blood clotting and repairing damaged blood vessels. A normal platelet count is between 150,000- 400,000 platelets/mm3 (see Table 1). Expect PLT values to be elevated with chronic bleeding such as gastric ulcers, in patients who smoke, or those with leukemia. Expect reduced PLT values from autoimmune

Author: Tracy Doll, OD COPE #21399-PD 3 credits thrombocytopenia (resulting in the destruction of RBCs), blood loss, due to anticoagulant medication side effects, like Warfarin (Coumadin). A low PLT can also indicate disease such as an enlarged spleen, septicemia, bone marrow failure due to leukemia, or a condition called myelofibrosis (2,3). In myelofibrosis red blood cells have unregulated proliferation. The platelets that are formed are giant, irregular or fragmented and cannot function normally (2,3). Mean Platelet Volume (MPV) The MPV can tell the clinician the average size of the platelets in a patients bloodstream. Normal platelet volume is 7-11 fL (Table 1). Decreased MPV is consistent with diseases like aplastic anemia. Recent research has shown that a low MPV can also be associated with inflammatory bowel diseases, and high MPV may be an independent risk factor for transient ischemic attack (stroke) and myocardial infarction (3). An elevated MPV can also indicate idiopathic thrombocytopenic purpura. Thrombocytopenia purpura is a blood disorder found in young children, two to four years old. The destruction of platelets in this disorder is often followed by upper-respiratory infections. The cause of this disorder is unknown, but causes children to easily bleed. This condition often will spontaneously go into remission. A more chronic form of this condition can also occur (2). White Blood Cell Count (WBC) WBC count is the number of leukocytes per cubic millimeter (mm3 or L). A normal WBC count is 4,000-10,000/ mm3 (Table 1). A low WBC count is called leukopenia. Infection will classically show the clinician an elevated WBC count. Leukemia (bone cancer) will grossly raise WBC count as well (3) Ocular signs of leukemia include white-centered retinal hemorrhages (Roth Spots) flame hemorrhages and mid-peripheral retinal hemorrhages (75).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Table 1: Blood Components Complete Blood Count Component Red Blood Cell (RBC) Count
Normal Adult Value Nice
Men: 4.7-6.1 million cells/uL Women: 4.2-5.4 million cells/uL Hemoglobin (Hb) Men: 14-18g/dL or 8.7-11.2 mmol/L Women: 12-16 g/dL or 7.4-9.9 mmol/L Hematocrit (HCT) Men: 42-52% Women: 37-47 % Mean Corpuscular Volume (MCV) 80-90 fL (femtoliters/3) Mean Corpuscular Hemoglobin (MCH) 2731 picograms (pg) Platelet Count (PLT) 150,000- 400,000 platelets/mm3 Mean Platelet Volume (MPV) 7-11 fL (femtoliters) White Blood Cell (WBC) Count Men: 5,000-10,000 wbc/mcL3 Women:4,500-11,000 wbc/ mcL3 Source: http://www.webmd.com/a-to-z-guides/complete-blood-count-cbc?page=3 Note that all medical laboratory equipment and hospitals may use different criterion for the norms of the laboratory testing values (though they are always similar). These norms are known as reference values. If a test value is outside of the reference numbers, the laboratory test will be flagged with an L for lower than normal values and an H for higher than normal values. Table 2 below shows an example of a printout for a complete blood count with differential test.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Table 2: Example of CBC with Differntial Medical Laboratory Print Out Southwest Washington Medical Center Test Patient
Complete Blood Count With Differential Components A complete blood count should always be ordered with a differential component because it implies which type of immune response is occurring and give clues to underlying pathology including infection, autoimmune disease, blood disorders, and allergies. Differential blood count (Diff) divides white blood cells into five different types. They are (in order of incidence): 1. Neutrophils: These white blood cells work like a vacuum cleaner, by phagocytizing microorganisms or particles. A higher than normal number of neutrophils are most often due to bacterial infection, but can also arise from arthritis, surgery, trauma, or myocardial infarction. Myeloproliferative disorders are a less likely cause (2,3). 2. Lymphocytes: these white blood cells make antibodies bind to pathogens to coordinate the immune response. They come in three varieties: Cytotoxic (Killer), T-cells and B-cells. Expect them to be elevated in patients with viral infections, active allergies and toxic reactions like food poisoning. The lymphocyte count will be depressed in HIV positive patients, as the disease

Author: Tracy Doll, OD COPE #21399-PD 3 credits selectively attacks and destroys the Helper T-cells (2,3).. Isolated retinal cotton wools spots can be seen in HIV infection (75). 3. Monocytes fight infection by phagocytizing dead or damaged cells and pathogens not fought off by neutrophils or leukocytes. A high count can indicate systemic bacteria, as in septicemia (3).. 4. Eosinophils: seen in response to allergies, parasitic infections, collagen vascular disease and other extensive skin diseases, as well as Addisons Disease. In the latter case, this is called eosinophilia (2,3). 5. Basophils: this fifth type of white blood cell brings about allergic response to antigens, mainly by releasing histamine to cause inflammation. Low numbers of basophils may precede the onset of leukemia (2,3) Table 3: White Blood Cells White Blood Cell Type Neutrophil Normal Values 48 -80k/ mm3 % of total WBC count 40% to 60% Appearance
Lymphocyte
21-47k / mm3
20% to 40%
Monocyte
4 -8k / mm3
2% to 8%
Eosinophils
0-0.70k/ mm3
1% to 4%

Author: Tracy Doll, OD COPE #21399-PD 3 credits
Basophils
0-0.20k / mm3
0.5-1%
Source: 4,5 Please note again, that normal values or reference values will vary slightly from test instrument to test instrument. Table 4 shows the laboratory print out with reference ranges. Note that the printout includes the norm for the percentage of total WBC count.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Table 4: Examples of CBC Differential of White Blood Cells Medical Laboratory Print Out: Southwest Washington Medical Center Test Patient

Author: Tracy Doll, OD COPE #21399-PD 3 credits Erythrocyte Sedimentation Rate (ESR or sed rate) Abnormal blood plasma proteins from inflammatory disease stick to red blood cells and cause them to settle to the bottom of a blood sample more quickly. The height of the RBCs, in mm, settled out of plasma per hour is called the erythrocyte sedimentation rate (ESR) (2). The ESR test has excellent sensitivity but low specificity. In other words, it can detect even subtle inflammation, but cannot tell the clinician which disease state is responsible (3). ESR is elevated in inflammatory conditions including systemic lupus erythematosus, rheumatoid arthritis, tuberculosis, myocardial infarction, polymyalgia rheumatica and hepatitis C, in addition to temporal giant cell arteritis (GCA) (3). If the patient is a suspect for GCA, the first blood test the clinician should order is an ESR (75). Signs and symptoms of GCA include: optic neuritis, positive afferent pupillary defect, vision loss, temporal headache, jaw claudication (muscular pain when chewing) and scalp tenderness. A temporal artery biopsy should also be immediately ordered if temporal arteritis is strongly suspected. The biopsy may be ordered while lab results are being processed. Sometimes, both tests are needed because one test may have equivocal results. The maximum normal ESR for men is equal to the patients age divided by two. The normal maximum ESR for women is equal to (age + 10) divided by two (3,6). A sedimentation rate greater than 50 mm/hr is suggestive of inflammation. Always order a CBC with an ESR, as anemia can falsely increase the ESR. The Westergren ESR type is more commonly used (2).

Author: Tracy Doll, OD COPE #21399-PD 3 credits The Erythrocyte Sedimentation Test
Source: 6 C- Reactive Protein (CRP) Another marker of inflammation is C-Reactive Protein. This plasma protein rises dramatically in systemic inflammation. In addition to CRP being an indicator of acute inflammation, it can also be elevated in stress, trauma, surgery, neoplastic infection or myocardial infarction (7). Clinicians use the CRP to check for inflammatory flare-ups, or to monitor the effectivity a specific treatment regimen. Note that the CRP level is not always elevated by inflammation, thus this test has some false negatives. When it is elevated, CRP levels have been associated with increased risk for diabetes, hypertension and cardiovascular disease (7). Patients with CRP levels of less than 1mg/L are considered low risk, while levels of greater than 3mg/L are considered high risk for cardiovascular disease (76). The role of CRP in coronary artery disease is still being investigated. It is possible that the CRP is not merely a marker of inflammation, but instead plays an active role in inflammatory disease (3). Blood Chemistry Blood chemistry testing includes: glucose tests, lipid profiles, thyroid and kidney function testing.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Glucose Testing Blood glucose testing should be run if diabetes is suspected. Diabetes is a disease that leads to an inability of the body to correctly produce and/or use insulin. As a result, high levels of glucose are present in the bloodstream. These high levels of glucose can eventually lead to blood vessel damage and tissue hypoxia. Systemically, diabetes can lead to peripheral neuropathy and kidney damage (3,8,9). The well-known signs of diabetic eye disease include: fluctuations in visual acuity, cotton wool spots, retinal/ or vitreal hemorrhages, and early onset nuclear sclerotic cataracts. Advanced cases can show neovascularization of the iris, angle, retina, and/or optic nerve (75).
Neovascularization of the retina in diabetes. Photo Source: Dr. Nada Lingel Fasting Plasma Glucose (FPG) or Blood Sugar (FBS) Most clinicians use the fasting blood sugar to test for diabetes. As implied by the name, make sure patients fast for at least 8 hours prior to the FPG. Two reading of elevated levels are needed to diagnose diabetes. Physicians also use fasting glucose testing to determine the

Author: Tracy Doll, OD COPE #21399-PD 3 credits presence of impaired glucose tolerance, a recently established pre-diabetes condition. Note that in healthy patients, blood glucose levels should return to levels below 100 mg/dL relatively quickly, even after meals. See Table 5 (9). Random plasma glucose (RPG) RPG is the glucose level measured without fasting. Normal levels can be seen in Table 5. Diabetic patients will often have glucose testing kits that can help monitor the RPG at home. These kits are widely available and can easily be used in office by eye health care practioners should diabetic eye disease or out of control blood sugar be suspected. No special licensing is necessary for home blood glucose monitoring kit usage. Measurements of RPG in office will require some extra equipment in addition to just the blood monitoring kit, to insure safety for both the practioner and the patient. A home blood monitoring kit uses a lancet to puncture the skin and draw blood. As blood and sharp instrumentation are involved in this testing process, universal precautions need to be taken. The doctor (or technician) administering the test, should always be wearing a new set of latex (or equivalent hypoallergenic) gloves to prevent disease transmission and should wash hands immediately before and after the gloves are worn(10). Used lancets will need to properly disposed of in a sharps container to prevent accidental punctures. Sharps containers can be obtained through local buying groups or local medical laboratories. A good resource for finding sharps container services can be found at: http://www.safeneedledisposal.org/dispcenters (11). Some sharps container services will replace full containers when needed or often times local pharmacies will charge a small fee to dispose of the sharps.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Source:http://web.princeton.edu/sites/ehs/biosafety/livevirusworker/decontamination.htm In RPG testing a droplet of blood taken usually from a patients sterilized finger is squeezed onto the end of a glucose blood test strip. The opposite end of the strip is then inserted into the blood glucose monitor (each monitor will vary). Once the test results are read off of the monitor, the test strip, gloves and any sterile cotton or paper products in contact with blood will have to be properly disposed of to stop possible pathologic transmission. Again proper hand washing following the procedure is a must (10). Similar to a sharps container, a medical waste container can be obtained through waste disposal services. Each practioner should check with his state occupational safety and health division for specific regulations. Links to proper medical disposal procedures and services can be found at the Environmental Protection Agencies Website, http://www.epa.gov/epaoswer/other/medical/index.htm (12). Oral glucose tolerance test (OGTT) Expectant mothers who develop gestational diabetes are often pre-diabetic before pregnancy. The oral glucose tolerance test screens for gestational diabetes. Blood sugar is loaded with 75100 g of glucose solution, and serial blood glucose levels are measured. Thus, a glucose metabolism curve is generated. Impaired ability to metabolize glucose could indicate gestational diabetes (9). The Glycosylated Hemoglobin Test (HbA1c or A1c) Free glucose binds to hemoglobin on red blood cells. The HbA1c measures the amount/percentage of this binding. As red blood cells live on average for 90 days, the HbA1c is a measurement of blood sugar over an approximate three-month time period. It is often used to check compliance with diabetic medications as well as the effectiveness of medical management. In diabetic patients with poor compliance to diet and medications, including insulin, the HbA1c is above 7% (8,9).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Table 5: Laboratory Glucose Testing Glucose Tests Intrepretations Normal range: 65 to 99mg/dL Fasting plasma glucose (Fasting is defined as no caloric intake for atPre-Diabetes: 100 to 125mg/dL Diabetes: >126 mg/dL least 8 hours.) Random plasma glucose Normal range: 65 to 200mg/dL Diabetes: >200 mg/dL Oral glucose tolerance test Normal if: Fasting: <95mg/dL (100g load) 1 hour: <180 mg/dL 2 hours: <155mg/dL 3 hours: <140 mg/dL Two or more of the plasma glucose values must be met or exceeded for a positive diagnosis. Glycosylated hemoglobin Normal Glycemic control: 4% to 6% (HbA1c or A1c) Poor control: >9%
Sources: American Diabetic Association Standards of Care in Diabetes 2007(9) Table 6: Example of an Hemoglobin A1c Medical Laboratory Print Out - Southwest Washington Medical Center Test Patient

Author: Tracy Doll, OD COPE #21399-PD 3 credits Kidney Function Tests Kidney Function Tests should be ordered in the event that kidney problems are suspected. Again, diabetics often have kidney failure. Urea is the primary nitrogenous waste product of human metabolism. High values (>60mg/dL) can indicate renal failure. If blood urea nitrogen (BUN) and creatinine values are high, this likely indicates decreased kidney function. Pregnancy is also known to lower the BUN value (3). The kidneys are also responsible for eliminating creatinine, a byproduct of muscle metabolism. Patients with greater muscle mass will produce more creatinine. When creatinine levels are high, the kidneys are likely to be responsible. A declining creatinine value indicates improving kidney function. Normal levels for creatinine in women are 0.6-1.2mg/dL and for men are 0.51.1mg/dL (77). Lipid Profile Testing : Serum lipids: cholesterol and triglycerides A Lipid profile should be ordered in the event that vascular disease is suspected. Hollenhorst arterial plaques, central/partial retinal vein, or arteriole occlusion, sudden/ transient vision loss, amaurosis fugax and mid/peripheral retinal hemorrhages could point toward vascular disease (14,15). The three parts of total serum cholesterol are as follows: 1. High density lipoproteins: (HDL). The good cholesterol, protects against heart disease by helping remove excess cholesterol deposited in arteries. Higher levels of this cholesterol type are considered to be beneficial and cardio-protective (3,13). 2. Low density lipoproteins: (LDL). The bad cholesterol, LDL cholesterol deposits into arterial walls when its levels are elevated (3,13). 3. Very-low density lipoproteins: (VLDL). The most dangerous form of cholesterol. VLDLs are associated with arterial plaque formation (3,13). Triglycerides are soluble fats that are found in the blood plasma and adipose tissue. Elevated levels are associated with heart disease, hypertension and pancreatitis. High amount are due to excess intake of fatty foods and carbohydrates (3,13).

Author: Tracy Doll, OD COPE #21399-PD 3 credits If ocular ischemic syndrome is suspected in conjunction with amarosis fugax, carotid duplex imaging should be ordered as well (14,15) (see imaging section below). Table 7: Laboratory Glucose Testing Lipid Type Low Values Normal values High Values Triglycerides <150mg/dL (same as the<150mg/dL >200 mg/dL >500 mg is very high normal range) 150-199 mg/dL is borderline 40 - 59mg/dL High-density Men: <40/dL >60 mg/dL is considered to lipoproteins Women: <50mg/dL be cardio-protective
Low-density lipoproteins
<100mg/dL reduces risk130-159mg/dL for heart disease borderline 100 - 129mg/dL- near optimal <40mg/dL >40mg/dL
is>160-189 mg/dL >190mg/dL increases risk of heart disease N/A
Very-low density lipoproteins
Table Source: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf (13). An example of a lipid panel medical laboratory printout can be seen below in Table 8. Note that in addition to a reference range, the printout also contains information that could be useful to any primary care practioner (including optometrists): it includes optimal values for lipid levels.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Table 8: Example of a Lipid Panel Medical Laboratory Print OutSouthwest Washington Medical Center Test Patient
Thyroid Function Tests The pituitary gland secretes Thyroid Stimulating Hormone (TSH), which stimulates the thyroid to produce Triiodothyronine (T3) and Thyroxine (T4), the two main thyroid hormones in the bloodstream (8,16) The pituitary gland regulates the amount of TSH made by measuring the amounts of T3 and T4 already circulating in the blood stream. If high amounts of circulating T3 and T4 are detected, the pituitary will decrease the amount of TSH secreted as there are already enough thyroid hormones in the blood stream. Conversely, when T3 and T4 levels are low, TSH secretion increases. See Table 5 for normal reference levels of thyroid hormones (8,16). Elevated TSH can indicate congenital or primary hypothyroidism, while depressed TSH levels indicate hyperthyroidism (8,16). Elevated levels of T4 and T3 can be found in hyperthyroidism, acute thyroiditis and hepatitis. Depressed levels of T4 and T3 are seen in hypothyroidism and with chronic thyroiditis (8).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Levels of TSH are easier to measure and so are typically obtained first. It is also easier and less expensive to measure T4, so T3 is usually not measured on screening tests Many medications that can affect TSH measurements include: antithyroid medications, lithium, potassium iodide, amiodarone, dopamine, and prednisone (17). Thyroid Functioning Tests should be ordered if Graves Disease or another thyroid condition is suspected. Lid retraction, proptosis (exopthalmometry values greater than 22mm or 3mm or more asymmetry between the eyes), extraocular muscle restrictions, and dry eye could all indicate Graves Disease (17). Patients who have Graves Disease may be euthyroid at the time of diagnosis. Negative laboratory tests do not exclude Graves disease (17). Orbital imaging studies may still be necessary (see imaging section below). Table 9: Thyroid Panel Thyroid Hormone Triiodothyronine (T3)/
Normal Levels 80 to 180ng/dL 2.1-6.3pmol/L Thyroxine (T4) 4.6 to 12g/dL Thyroid stimulating hormone 0.4 to 4.0 mIU/L Source: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm (5,16)

Graves Exophthamos. Source: Dr. Richard London

Author: Tracy Doll, OD COPE #21399-PD 3 credits Table 8: Example of a Lipid Panel Medical Laboratory Print OutSouthwest Washington Medical Center Test Patient
Urinalysis Urinalysis can also be ordered in conjunction with blood testing to help confirm systemic etiology to ocular conditions. This paper focuses on urinalysis correlating to kidney and liver disease. Keep in mind when ordering urinalysis that the urine used for urinalysis should be collected no more than two hours prior testing (18). As previously noted, diabetes is a systemic disease that can affect the health of the kidneys (see ocular signs of diabetes above under glucose testing). The following components of urinalysis can aid in the detection of diabetic kidney disease: Urine Glucose The kidneys will normally filter all of the glucose out of urine, thus any glucose in urine is considered to be an abnormal finding. When excess glucose is present in the blood stream, as in diabetes, the kidney will max out its capacity for re-absorption 180 to 200 mg per dL (18). The excess glucose is then spilled into the urine where it can be detected by using a chemical

Author: Tracy Doll, OD COPE #21399-PD 3 credits dipstick, a color sensitive pad, containing chemical that react with glucose. The color change will reflect the amount of glucose in the urine (19). Glucose can also be present in urine secondary to other systemic conditions including Cushing's syndrome, liver and pancreatic disease, and Fanconi's syndrome (18). Urine Protein In a healthy kidney, only very small particles (weight of less than 20,000 Daltons) can pass through the kidneys filtration system (18,20). In diabetic kidney disease, proteins such as albumin, serum globulins, and proteins secreted by the nephron are allowed to pass into the urine, as the kidney is damaged. Urine proteins in amounts larger than 50 mg per day (10 to 20 mg per dL) are indicative of renal disease (18). Excess amounts or the protein albumin, or microalbuminuria (30 to 150 mg of protein per day), is a sign of early renal disease, particularly in diabetic patients (18). As with urine glucose, urine protein is detected by dip-stick testing. Other systemic conditions that can lead to proteinuria (high levels of urine protein) include: congestive heart failure, dehydration, emotional stress, exercise, fever, seizures, focal segmental glomerulonephritis, IgA nephropathy (i.e., Berger's disease), IgM nephropathy.membranoproliferative glomerulonephritis, Membranous nephropathy, minimal change disease, secondary glomerular causes, Alport's syndrome, amyloidosis, systemic lupus erythematosus), Fabry's disease, infections, malignancies, sarcoidosis, ickle cell disease, Tubular causes, aminoaciduria, Fanconi syndrome, heavy metal ingestion, hypertensive nephrosclerosis, interstitial nephritis, multiple myeloma (18). Urine Ketones Ketones, like urine gluocose and protein are not normally found in urine. Ketones are byproducts of body fat metabolism. As with the previous test the dipstick method is used for ketone detection. Ketonuria also occurs most commonly is associated with uncontrolled diabetes. Pregnancy, hyperthyroidism, carbohydrate-free diets, and starvation can also cause Ketonuria (18,21). In addition to urinalysis being able to detect kidney disease, it can also be an indicator of liver disease.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Bilirubin Bilirubin is a yellowish pigment created by the death of red blood cells. The liver is responsible for filtering and disposing of the deceased red blood cells into the gut. If the liver is not functioning, too much bilirubin could be allowed into the blood stream and lead to a condition known as jaundice, where the yellow pigment deposits in connective tissue. The main eye sign of jaundice is yellowed conjunctiva. Bilirubin does not normally appear in urine, so urinalysis detection of bilirubin can indicate liver disease (18,22,23). Serological Testing Serological testing identifies antibodies in the blood serum. If any autoimmune disease or immune response is suspected to be the culprit for ocular findings, serological tests should be ordered. Recall that ocular inflammation or infection can be caused by an antibody-mediated immune response. Serological Testing includes the following tests: Venereal Disease Research Laboratory/ Rapid Plasma Reagin (VDRL/RPR) Fluorescent Treponemal Antibody Absorption Test (FTA-ABS) The VDRL and RPR are the screening tests for Treponema pallidum, the bacterium that causes syphilis while the FTA-ABS is a blood test used to confirm the presence of antibodies directed against syphilis. Recall that syphilis is most commonly contracted as a sexually transmitted disease (it can also be congential, passed on in utero from mother to child) (24). Because of the expense of the FTA-ABS, many practioners first order a VDRL. If those results are positive, then the FTA-ABS is ordered. Note that VDRL can be negative in latent syphilis or after successful syphilis treatment. All 3 tests can get be falsely positive in pregnancy or systemic lupus erythematosus (24). Eye signs of syphilis infection include: acute and chronic anterior and posterior uveitis (granulomatous in 50% of cases), interstitial keratitis, conjunctivitis, scleritis, chorioretinitis, classic salt and pepper fundus, retinal periphlebitis, optic nerve head inflammation or pallor and secondary cataract. Note that syphilis in known as the great imitator, as it mimics many

Author: Tracy Doll, OD COPE #21399-PD 3 credits ocular conditions. A good medical and social case history is essential in the differential diagnosis of syphilis (24). Angiotensin Converting Enzyme (ACE) ACE is the main test used to screen for sarcoidosis. ACE is 75% sensitive for sarcoid and; it is 95% specific if combined with a gallium scan and chest x-ray (see imaging section below). Sarcoidosis is a granulomatous disease that can affect any of the organs, but most commonly affects the lungs. This condition is most common amongst races of color. It is also seen more often in women, peaking in two different age groupings: 25-35 year olds and 45-65 year olds (25). Eye signs for sarcoidosis include: conjunctivitis, iris nodules, granulomatous uveitis, vitritis, periphlebitis (candle wax drippings), and vasculitis. Tuberculosis, lymphoma, leprosy, diabetes, hyperthyroidism, and alcoholic cirrhosis can all cause false negative results (26). Periphlebitis in Sarcoidosis
http://www.uveitis.org/images/sarc8apost.png

Author: Tracy Doll, OD COPE #21399-PD 3 credits Rheumatoid factor (RF) test Antibodies normally attach to pathogens or foreign material in the body, thus flagging them for destruction by the bodys immune response. In autoimmune disease, the body will create antibodies to the bodys own cells (27). The RF test looks for an autoantibody that specifically binds to immunoglobulin G (IgG) in blood stream. RF test is the main serological test for rheumatoid arthritis. Seventy percent of patients with RA are RF positive. Other autoimmune diseases such as systemic lupus erythematosus and Sjgrens syndrome are also RF positive (27). RF is measured by using a blood titer, a measurement of the amount or concentration of a substance in a solution. A titer is usually expressed as a ratio, the second number indication the number of times a blood sample can be diluted and still detect the antibody (28, 29). RF is considered positive, when the titer value is greater than 1:80 (see Table 10 below). Table 10: Example of a Rheumatoid Factor Medical Laboratory Print Out Southwest Washington Medical Center Test Patient
Please note that only 5% of Juvenile Rheumatoid Arthritis (JRA) patients are RF positive, so the RF serology is not an effective test for JRA. The Erythrocyte Sedimentation Rate is also elevated in RA patients and can be run in conjunction with the RF serology (78). Rheumatoid arthritis is an autoimmune disease that affects the joints. Systemic indications of rheumatoid arthritis are: polyarticular (multiple) joint stiffness and pain (specifically hand, wrist, knee) even in the absence of activity. The proximal joints are the involved, while the distal joints tend to be spared. Ulnar deviation (fingers pointing outward) is common in later stages. Fever and malaise can also be seen (27). Common ocular signs of rheumatoid arthritis include: dry eye, keratoconjunctivitis, episcleritis and scleritis (27).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Ulnar Deviation of the fingers in Rheumatoid Arthritis
http://www.gutenberg.org/files/17921/17921-h/images/fig160.png The Antinuclear Antibody test (ANA) The ANA looks for the presence of autoantibodies aimed toward the cells own DNA. ANA is also measured using a blood titer. Values greater than 1:20 to 1:40 are typically considered significant (3,31). Table 11: Example of a Rheumatoid Factor Medical Laboratory Print Out Southwest Washington Medical Center Test Patient
ANA can have positive test results in 25% of patients with juvenile rheumatoid arthritis, 30% of rheumatoid arthritis, 40-70% with Sjogrens Syndrome, in 60-90% of patients with scleroderma, and in 95% with systemic lupus erythematosus. Patients with syphilis, chronic infections, sarcoidosis, and liver disease can also test ANA positive (30). ANA is positive in 95% of lupus patients (31). Systemic lupus erythematosus usually occurs in young to middle age adult women in races of color. The condition causes the body to make

Author: Tracy Doll, OD COPE #21399-PD 3 credits autoanibodies often against the bodys major organs. Renal failure is often the leading cause of death. These antibodies can also attack the structures of the eye. The major ocular signs include eyelid erythema, plaques and ulceration. Keratitis sicca, stromal/marginal infiltrates, pannus formation, and ultimately, ulceration, or neovascularization can occur due to exposure. Deep interstitial keratitis and kerato-endothelitis can also occur. Migraine headache, diffuse or nodular scleritis, vitreoretinal / choroidal inflammation, subretinal neovascular membrane formation, retinal vascular occlusion and multiple cotton-wool spots are a common retinopathy can also be seen in ocular lupus (30). Systemically, a butterfly-shaped rash overlying the cheeks and nose is often seen. Infiltration of the lungs by sarcoid granulomas can be observed with chest x-ray imaging (see imaging section below) (30). Systemic Lupus Butterfly Rash
Source: http://www.allaboutarthritis.com/AllAboutArthritis/layoutTemplates/html/en/ contentdisplay/printerfriendly_document.jsp?docID=condition/arthritis/clinicalArticle/Lupus.x ml Recall that Rheumatoid Factor is rarely positive in juvenile rheumatoid arthritis (only 5%), while ANA is positive in 25% of children with JRA. Eye signs of juvenile rheumatoid arthritis are: bilateral anterior uveitis (chronic or acute), usually non-granulomatous, band keratopathy, small keratic precipitates, posterior senechiae, posterior subcapsular cataracts, vitritis (anterior not uncommon), cystoid macular edema, hypotony, and maculopathy (82).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Human leukocyte antigen test: (HLA) HLA blood testing detects proteins that are present in high concentrations on the surface of white blood cells, indicating autoimmunity (33). The subtypes of HLA are categorized by letters numbers and can be indicative of pathology. The HLA-B27 marker is found in 95% of patients who have ankylosing spondilitis and 70% of those who have Reiters syndrome (Reactive Arthritis) (3). The main eye signs of ankylosing spondylitis are uveitis with keratic precipitates, posterior/anterior synechiae, posterior subcapsular cataracts, vitritis, retinal vasculitis, epiretinal membrane (34). Chronic lower back stiffness and pain are the most common systemic symptoms (35).
Source: http://hcd2.bupa.co.uk/images/factsheets/ankylosing_edit.gif Reiters syndrome is an autoimmune disease that most commonly affects young (20-40 yearold) males. Eye signs for Reiters Syndrome include: conjunctivitis and uveitis. Systemically common symptoms are urethritis and arthritis. A frequently mentioned way to remember the systemic manifestation triad for Reiters is: Cant See. Cant Pee. Cant Dance with Me (36,37).

Author: Tracy Doll, OD COPE #21399-PD 3 credits HLA- B5 indicates Behets Disease. The major signs of Behets disease, a multisystemic disorder of unknown etiology, are oral and genital ulcers, skin lesions, and synovitis (inflammation of the joints). Oral ulcers are the hallmark for this condition (38). These systemic signs are very often accompanied by anterior/posterior uveitis. Other eye signs include: retinal vasculitis, chorioretinitis, scleritis, keratitis, vitreous hemorrhage, optic neuritis, conjunctivitis, retinal vein occlusion, and retinal neovascularization (38). Other HLA types:
o o o
HLA-DR5 suggests Hashimotos Thyroiditis (79) HLA -DR2 suggestes Lyme Disease (80). HLA -DR2/3 suggests Systemic Lupus Erythematosus, though ANA testing is more routine testing for SLE (81). Enzyme Linked Immunosorbent Assay: (ELISA) and the Western Blot The ELISA is a blood serum testing method, not a specific test for one kind of disease. Blood is exposed to antibodies for specific diseases in the ELISA. If a disease is present, antibodies laced with florescent markers will stick to the disease antigen in the serum, indicating an immune response (8,39,40). ELISA can be used to confirm Toxocarosis. This is useful in children with posterior granulomatous uveitis, where toxocarosis can be a main cause. ELISA is also diagnostic in West Nile and Epstein-Barr viruses, and anthrax (39,40). The main use for ELISA, however, is as a screener for the Human Immunodeficiency Virus (39,40). The Western Blot (WB), like the ELISA is a laboratory testing method, not a specific disease test. The WB testing separates the blood sample proteins out and then exposes these proteins to specific disease antigens, leading to the detection of a disease agent (41). The WB can be used to confirm Mad Cow Disease, Lyme disease and toxoplasmosis (42) along with many other conditions. The WBs main use is to confirm HIV after the ELISA screener. It is the confirmatory test.

Author: Tracy Doll, OD COPE #21399-PD 3 credits The most common early sign of HIV in the eye can be secondary infections such as herpes zoster ophthalmicus, Kaposi sarcoma of the conjunctiva, molluscum contagiosum, conjunctival microvasculopathy, Herpes simplex keratitis or viral keratitis. HIV retinopathy is most commonly seen as cotton wool spots. In later stages of the disease or progression to AIDS, retinochorioditis, in addition to secondary infections such as cytomegalovirus, syphilis and histoplasmosis can also be seen (43). Cotton Wool Spots in HIV retinopathy
http://www.kellogg.umich.edu/theeyeshaveit/acquired/images/cottonwool.jpg
Kaposis Sarcoma
Source: http://medinfo.ufl.edu/year2/mmid/bms5300/images/b21.jpg

Author: Tracy Doll, OD COPE #21399-PD 3 credits PPD Sking Testing Purified Protein Derivative (Mantoux test) The PPD test indicates infection or exposure to Mycobacterium tuberculosis, which can lead to granulomatous disease. It is also postive in the case the patient has received a TB vaccine (as is sometimes given in the military or in European countries), or has successfully resisted the disease and has a natural immune response (44). 0.1mL of tuberculin, a glycerine extract of the tubercule bacilli, is injected into the skin. An immune response is expected in a person who has been previously exposed to the bacteria. The reaction is read 48 to 72 hours later, by measuring the diameter of induration in millimeters. Indurantion is a raised, hardened, palpable area, often reddened. If the PPD is positive, a chest x-ray is indicated (see imaging section below) to confirm active infection.
Source: http://en.wikipedia.org/wiki/Image:Mantoux_tuberculin_skin_test.jpg The amount of the induration considered to be positive can vary depending on the individual (44). 5 mm or more is considered positive in patients with HIV or immunosupression, in those who have had recent contact with persons with TB, patients with nodular or fibrotic changes on chest x-ray consistent with old healed TB.

Author: Tracy Doll, OD COPE #21399-PD 3 credits 10mm or more is considered positive in intravenous drug users, mycobacterology lab personal, health care workers, residents, and employees of high risk highly populated close setting settings such as prisons, homeless shelters and nursing homes. Recent arrivals (<5years) to this country from high-prevalence countries, children less than four years old, or children and adolencents exposed to adults are also in this high risk category. 15mm or more is considered positive in patients who have no known risk factors for TB. Remember, risk factors can include vaccination or a vigorous natural immunity to the bacterium. Should the size of the induration increase 10mm or more within a two year peroid, this is considered a conversion from inactive to active TB (44). Note that false positives are common and can indicate exposure versus active infections. Eye signs of tuberculosis are granulomatous conjunctivitis, scleritis, uveitis, vitritis with snowball cellular aggregates, pars plana snow banking accumulation of cellular aggregates, choroidal granulomas that could be isolated or mutlifocal and lead to scarring, cystoid macular edema and optic nerve head inflammation (83). 75% of patients with active TB have pulmonary involvement, which can lead to symptoms of chest pain, coughing, or coughing up of blood. Transmission of the disease is through airborne droplets released when an infected individual coughs, sneezes, spits or speaks. Other symptoms include general malaise, fever, chills, night sweats, and weight loss (83). Imaging Studies Imaging studies can often be used to aid in the diagnosis of systemic health conditions, in addition to blood and serological testing. The Carotid Duplex, X-Ray, CAT Scan, and MRI are all imaging studies with which the optometrist should become familiar. The Carotid Duplex The Carotid Duplex is an ultrasound that is used to look for plaques, blood clots, stenosis of the blood vessels or other blood flow obstructions in the carotid arteries. Recall that the carotid arteries are the major sources of the blood supply to both the brain and eyes. A duplex ultrasound combines Doppler imaging with traditional ultrasound to form color images of the carotid arteries by measuring how sound waves bounce of the body tissues. Red blood cells will

Author: Tracy Doll, OD COPE #21399-PD 3 credits bounce back the sound waves at a different frequency than the blood vessels and deposits such as cholesterol. The velocity at which the blood is moving through the vessel is also picked up by the duplex. By measuring this velocity at different locations and times, the amount of stenosis can be calculated (46-48). A radiologist will record these velocities and interpret them. A chart, such as the one seen below will be used to calculate the amount of internal carotid artery stenosis (46-48). Table 12: Carotid Artery Stenosis Criterion Stenosis % Peak Systolic Peak End Dyastolic Peak Systolic Velocity in cm/sec Velocity in cm/sec Velocity Ratio <50 <125 -<2 50-69 >70 125-230 >230 40-100 >110 2-4 >4 Appearance No plaque or thickening seen Plaque or thickening seen Visible plaque and/or lumen narrowing Lumen narrowing No detectable lumen
Near May not be --occlusion detectable Total May not be --occlusion detectable Source: http://razi.ams.ac.ir/AIM/0473/005.htm
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Recall that ocular ischemic syndrome (OIS) is a result of low blood supply to the eye. It usually only occurs if there is 90% or greater stenosis of the carotid artery. This will lead to a 50% drop in profusion to the central retinal artery. Common anterior segment findings include advanced cataract, anterior segment inflammation, and iris neovascularization. Posterior segment signs include narrowed retinal arteries, dilated but nontortuous retinal veins, mid-peripheral dotand-blot retinal hemorrhages, cotton-wool spots, optic nerve or retinal neovascularization and spontaneous arterial pulsation. The main symptoms include ocular pain and abrupt (lasting 10 minutes or less) or gradual visual loss (14-15).

Source: http://www.nlm.nih.gov/medlineplus/ency/imagepages/18051.htm

Author: Tracy Doll, OD COPE #21399-PD 3 credits Carotid Duplex Screen Image
Source: http://www.gehealthcare.com/usen/ultrasound/products/msucmecd.html Mid peripheral Hemorrhages as seen in OIS
Source: http://www.revoptom.com/handbook/SECT44a.HTM

Author: Tracy Doll, OD COPE #21399-PD 3 credits X-Ray X-Rays, also called Rntgen rays, are a type of electromagnetic radiation that can be used to image bodily structures. The patient is placed between the X-ray emitting source and a photographic receptor, called a plate. This plate produces shadows of the bodys internal structures being X-rayed. X-rays can pass through soft tissues such as organs and muscles. The X-Rays that pass will turn the receptor plate black when it is developed. Bone and other dense tissues block X-rays and thus do not turn the plate black, appearing white on the plate. If a soft tissue, such as a blood vessel needs to be imaged, radiopaque dyes can be injected to block Xrays, and thus will be seen as white on the scan, similar to the more dense body tissues (49). The Chest X-Ray is often used to confirm granulomatous disease. The chest, lungs, heart, major arteries, ribs, and diaphragm are all included in the final imaging photos. Below is a photo of a healthy pair of lungs. Be sure to notice the black, empty space occupying the lungs: these are areas where the X-rays passed, unblocked. The white spot to the lower left in the photo is the heart (50). Normal Chest X-Ray
Source: http://www.rctradiology.com/generalradiology.html The lungs are common sites for granulomatous infiltration. Recall that sarcoidosis, tuberculosis, and histoplasmosis (see below) are all granulomatous systemic diseases. In Sarcoidosis, the infiltration will cause scarring, which can be seen as a diffuse granular appearance or white spots in areas that should be normally black (50).

Late sarcoidosis: white scars
Early sarcoidosis: granular
Source: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm In tuberculosis, the infiltration of the lungs by tubercules can cause scarring and death of the lung tissue. The areas of infiltration are easily seen in the photo below as white areas and are marked by arrows. A similar appearance can be seen in histoplasmosis (50).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Advanced Tuberculosis Side view front view
Source:http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm Tuberculosis, in addition to causing lung disease, can have eye complications. Tuberculosis can manifest in the eye as anterior or intermediate uveitis, chorioretinitis, panophthalmitis and choroidal tumors (89). Histoplasmosis capsulatum is a fungus endemic to the Ohio Mississippi River Valley. Bird and bat droppings accumulate and create an environment perfect for Hisoplasmosis capsulatum. When the fungus becomes airborne, it can be inhaled and deposits in the lungs, where it causes infection. This infection can spread through the blood stream and take up residence in the eye at the level of the choroid. The triad of ocular signs in histoplasmosis infection includes: 1. Disseminated midperipheral choroiditis, which appears as yellow-white, punchedout lesions from infiltration and subsequent scarring. 2. Macular /paramacular subretinal neovascular membrane, which is seen as a gray-green area surrounding the macula with or without exudates, sub-retinal blood or scarring. 3. Peripapillary atrophy or scarring adjacent to the optic nerve head(51,52).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Histoplasmosis Triad: Choroiditis, Paramacular/papillary scarring
Source: http://www.revoptom.com/HANDBOOK/sect5o.htm Computed Axial Tomography Scans The Computed Axial Tomography (CT or CAT) uses combined x-ray scans from a circular x-ray machine and computer to create cross-sectional and three-dimensional images of body structures called tomograms. The tomogram images show slices through the body. Occasionally contrast dyes, usually iodine-based dye or barium solution, can be injected into the blood stream or taken orally to enhance the difference between bodily tissues (53,54). Graves Ophthalmopathy is supported by positive CT Scan imaging. Recall that Graves eye disease can cause infiltration of the orbital tissues. These are easily imaged with a CT scan. The extraocular muscles will show enlargement at the center (often called the belly), while the tendon insertions are spared (17). Prominent intraconal fat, as well as fat at the apex of the orbit is often seen. A CT scan can show compression of the optic nerve and proptosis.

Author: Tracy Doll, OD COPE #21399-PD 3 credits Graves Ophthalmopathy- Infiltration of Extraocular Muscles
Source: http://www.learningradiology.com/caseofweek/caseoftheweekpix2/cow154lg.jpg CT scans can also be useful in the identification of an orbital blowout fracture. When pressure is applied to the orbital contents, as in blunt force trauma, the weakest point of the orbit can fracture. This fracture of the orbital floor or walls saves the globe from rupture. In this process, orbital fat and muscles can become entrapped. Signs and symptoms of entrapment include: extraocular muscles restrictions, pain on movement and diplopia (especially in up or lateral gaze). Other signs of orbital blowout fracture include enophthalmos, crepitus, rhinorrhea, and periorbital lacerations or ecchymosis. A CT scan shows the best display of inferior orbital rims, naso-ethmoid bones, and the maxillary sinuses. If air and fluid levels can be seen in the maxillary sinus on CT scan, this could be indicative of fracture of the maxillary sinus, which lies beneath the orbital floor (see photo below). In the event that a blowout fracture is suspected, careful examination of the anterior segment for laceration or perforation should be preformed. Blunt force trauma can also put the patient at higher risk for retinal detachment (55).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Blow Out Fracture of Orbital Floor
Source: http://www.hawaii.edu/medicine/pediatrics/pemxray/v6c09.html Orbital cellulitis is another ocular condition that can be confirmed through computed axial tomography. An orbital infection (bacterial, viral, or fungal) posterior to the orbital septum needs to be carefully differentially diagnosed. Orbital cellulitis is an emergent condition as patients are at a high risk of infection spreading to the orbital contents, cavernous sinus, and meninges (56). Meningitis can cause permanent neurological defects or death. Most commonly orbital cellulitis is a result of an extension of an infection of the paranasal sinuses, but can also occur as a result of bacterial infection from trauma or the bloodstream. Signs of orbital cellulitis include decreased visual acuity, pain on eye movements, positive afferent pupillary defect, fever, malaise, rhinorrhea, severe lid edema, fever, tenderness, proptosis, conjunctival chemosis and increased intraocular pressure. A high resolution CT scan (with contrast agent) of the orbit and sinuses can confirm the presence of paranasal sinus opacification. Coronal and axial views are recommended. Suspected orbital cellulitis needs to be immediately referred to emergency medicine, as it is potentially life threatening and will need to be treated with intravenous antibiotics immediately (56). CT scans can also be useful in helping to diagnose orbital masses when proptosis is evident (53,54).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Magnetic Resonance Imaging Magnetic Resonance Imaging (MRI) uses radio waves and magnetic fields to image non-calcific body tissues. The magnetic field forces hydrogen atoms in the body to line up in a specific manner. Radio waves are then sent toward the hydrogen atoms in the body tissues. Different tissues bounce the radio waves back at different speeds. A computer records these bounced signals in two dimensional cross-sections that are later compiled to create a three-dimensional image. The different signals are recorded in different colors on the scan. For instance in the brain, white matter will appear white, gray matter will appear gray, and cerebral spinal fluid will appear black. Contrast agents, usually gadolinium based, are sometimes intravenously injected to enhance the contrast of the tissues (57-59). Contraindications to MRI are pacemakers, ferromagnetic foreign bodies (such as bullet shell fragments) and metallic implants due to the magnetic field the MRI generates. MRI is useful especially in the case diagnosing Multiple Sclerosis. Recall that Multiple Sclerosis (MS) is a demyelinating autoimmune disease that attacks the central nervous system. White matter tracks are those that are affected in the spinal cord and brain. The etiology of MS is unknown, but it does tend to occur more often in Caucasian young adult females who live in temperate climates. Common signs and symptoms of MS are weakness and fatigue and in the eye, most commonly optic neuritis. Worsening of vision following exposure to heat and exercise is called Uthoffs sign. In addition to optic neuritis, other eye signs of multiple sclerosis can include intraocular opthalmoplegia and diplopia. Sharp shooting pain up the back of the neck, when the head is flexed toward the chest, is called Lhermittes sign. These signs and symptoms tend to relapse and recur over time (60). Abnormal MRI scans can be found in up to 90% of MS patients. The inflammation and breakdown of the blood-brain barrier due to the damage from an MS lesions will cause a leak of extravascular fluid. The MRI for suspected MS uses a special sequence called the FLAIR (Fluid Light Attenuation Inversion Recovery) sequence. With the FLAIR sequence, free water appears dark on the MRI, but edematous tissues remain bright. The MS lesions will glow brightly, while cerebral spinal fluid will appear dark black (57-60). MRI can also be used in the diagnosis of Graves Ophthalmopathy. Enlarged extraocular muscles with sparing of the tendons, is a diagnostic sign of Graves disease. Contrast agents are

Author: Tracy Doll, OD COPE #21399-PD 3 credits especially helpful for separating normal orbital fat from infiltration. A fat contrast suppression agent is used, allowing the normal orbital fat to appear black (57-59). Ocular Infection Testing/Cytology Ocular surface infections, especially those involving corneal ulcers, are most often treated empirically using fourth generation fluroquinolones. Fourth generation fluroquinolones include: gatifloxacin (Zymar) and moxifloxacin (Vigamox). Empirical treatment will cure the bacterial infection in ninety percent of cases (61,62). However, ten percent of bacterial infections will not respond to traditional therapies. In these cases, cytological testing becomes necessary. Finding the correct infectious agent could involve any of the following techniques:

Smears: sample of discharge Scrapes: sample of discharge, with some cells Cultures: Samples are plated on nutrient media to encourage growth of micro-organisms Sensitivity: antibiotic- soaked disks are placed onto culture plates and zones of growth are analyzed to determine sensitivity and resistance Stains: stains applied in organism identification Culturing Cultures are most effective taken before initiating treatment of the infection. Cultures can be also be taken after treatment has begun since treating an infection before taking a culture only slightly decreases the rate of positive cultures overall (61). It does, however, take much longer to receive the results of the laboratory testing post treatment, because the infectious agent needs to incubate longer to yield a positive result. In either case, pre- or post-treatment culturing will yield good information to aid in the proper treatment of the patient. To perform a culture, a topical anesthetic is first instilled into the eye. Proparacaine is recommended, as it is a less bactericidal anesthetic (62). Next a sharp instrument such as a sterile platinum spatula, scalpel blade, foreign body spud or sterile cotton swab is used to obtain a scraping from the corneal ulcer (62). Epithelium, necrotic stroma, and infiltrate material are the most useful, so rubbing the leading edge of the lesion is necessary (61,62,63). Discharge alone does contain as much of the infectious agent. In the case that a fungal infection is suspected, as in fusarium keratitis, culturing the contact lens case can also be useful

Author: Tracy Doll, OD COPE #21399-PD 3 credits (63). Contaminating the culture can be avoided by making sure the sample does not touch the eyelids, lashes or other structures. Culturing should be done with care to avoid corneal perforation (62). Culturing is not recommended if extensive corneal thinning has occurred and there is risk of perforation (62). The Media The obtained scraping or smear is then swiped either directly onto a media plate or placed into a culturette tube for transport to a laboratory (where it will be plated) (63). is important to have the culture delivered to the lab within twenty-four hours to maximize the potential for accurate sensitivity testing and identification of the infectious agent (62). If keeping culturing media in the office seems too cumbersome, local laboratories will often courier media. The following media are commonly used in infectious testing for the eye: Stuarts medium is used as a transport in culturettes. Stuarts medium is composed of sodium glycerophosphate 1.0%; sodium thioglycolate 0.1%; calcium chloride dihydrate 0.01% and water. A common system uses a rayon-tipped swab attached to a flexible aluminum wire, which is then used in the scraping/smear (64). The swab is then placed into a 0.5mL ampule of Stuarts medium and sent to the laboratory (64). Sabourauds Agar is the media used when a fungal etiology is suspected. A good case history will lead to the suspicion of a fungal etiology in instances such as contact with vegetation like as a tree branch, or history of therapeutic contact lens wear (66). Fusarium is a fungal infection that has gained popularity in the press lately due to suspected isolated, infected batches of contact lens solution. The patient may be also immune-compromised or be on a ventilator (65). A feathery corneal infiltrate is also suspicious for fungal etiology(65). Fungal infections should not be treated empirically as these infections can often be impossible to differentiate on appearance from bacterial infections (63). The only topical antifungal treatment, Natamycin, is completely ineffective against bacteria and viruses. Natamycin is also very toxic and can cause additional irritation, swelling and redness to the eye (63) Sabourds agar can be easily obtained by a lab and should be refrigerated until it is needed. A positive yield normally takes seventytwo hours to grow (63). After the culture, treatment should be started with a fourth generation fluroquinolone antibiotic in the event that the infection is actually bacterial in nature (63). Once the results of the culture are obtained and deemed positive, treatment with natamycin can be

Author: Tracy Doll, OD COPE #21399-PD 3 credits initiated. Note that it is always a good idea to consult with a corneal specialist in the event that any vision threatening corneal condition exists. A non-nutrient agar with an Escherichia coli heat-killed overlay should be used if Acanthameoba, a parasitic infection, is suspected. The acanthamoeba will eat through the overlay. For the reason this test is known as the Pac-Man test (63). Confocal microscopy is a different method that can also be used to detect the presence of Acanthameoba. This method is noninvasive and may be more sensitive than any staining method in detecting Acanthamoeba in early infections. It detects the parasite in-vivo, including the double-walled cysts and trophozite forms (84). Confocal microscopy is a miroscopic imaging technique used to increase contrast and/or to reconstruct 3-D images by using a spatial pinhole to eliminate out-of-focus light in specimens. The image quality is much better than that of wide-field images in traditional microscopy (85). Ocular signs and symptoms that acanthamoeba has infected the eye are: intense pain that does not match the presentation of the cornea, a bulls-eye lesion on the cornea with radial infiltrates. Poor disinfection of contact lenses with tap or well water, swimming in lenses in lakes or hot tubs can also point to a possible acanthamoeba source (65,67). A red eye that does not respond to antibacterial or antiviral treatment should include acanthamoeba and fungal infection as differential diagnoses. It should be noted that if either cultures are inconclusive for acanthameoba or fungal infection, the patient should be immediately should be referred to a corneal specialist for a corneal biopsy, which is the only truly definitive method (although much more invasive than a culture) (65,67).

Acantheomeoba keratitis. Source: Kertes and Johnson (2007) Other media that can be helpful are:

Chocolate Agar Media will grow most bacteria, including Neisseria and Haemophilus influenzae (86). Thioglycollate broth is used if an anaerobic bacteria is suspected (87). Thayer Martin media will show Neisseria (86). Specific Stains In addition to culturing, staining is often used in the identification of an infectious agent. First, a sample is smeared onto a slide and then chemically or heat fixed to that slide. Different chemicals and dyes are then applied to sample slides. The reaction of the organisms to the various chemicals and dyes can lead to identification of the organism. Giemsa Staining is a mixture of methylene blue and eosin. It has various uses. One main use is its ability to identify white and red blood cell types. Erythrocytes will stain pink, while platelets turn pale pink. Lymphocyte cytoplasm stains sky blue and monocytes have cytoplasm that turns light blue. And lastly, leukocyte nuclear material will stain magenta (69) (see photos under blood testing section above.) Giemsa Staining can also help identify bacteria, fungi (Histoplasma capsulatum) and acanthamoeba (63,66,67,68).

Author: Tracy Doll, OD COPE #21399-PD 3 credits Gram Staining helps to differentiate Gram-positive and Gram-negative bacteria. A crystal violet stain is first applied. Then iodine and decolorizer are added to clean the slide. Finally, a counter stain, safranin is typically applied. Gram-negative bacteria take up safrinin dye and appear red. Gram-positive take up crystal violet dye and appear purple. This type of stain can also identify fungi (68). Potassium hydroxide (KOH) preparation stain is used to identify fungi. When the solution is applied to the slide, all cells other than fungi cells will dissolve. This leaves the fungi exposed for identification (63,68) Papanicolaou (PAP) stains cytoplasmic inclusion bodies found in Chlamydia trachomatis. The PAP staining process includes five dyes (haematoxylin, Orange G, Eosin Y, Light Green SF and Bismark Brown) (88). Acid-fast staining (Ziehl-Neelsen Stain) identifies mycobacterium and Nocardia (a bacteria) species. The reagents used in this staining process are carbol fuchsin, acid alchohol and methylene blue. Acid fast bacteria retain the carbol fuschin and stain a red color. Non-acid-fast bacteria with retain the methylene blue and appear blue (68,70). Mycobacterium will stain red. A long filamentous organism with a dark red center is a typical appearance for Nocarida. Reports of Nocardia infection have been reported following LASIK surgery. The clinical presentation is usually: superficial patchy infiltrates, which may be arranged in a wreath pattern. Most commonly sulfacetamide eyedrops can be tried as the initial drug. Once therapy is initiated, the infiltrate should responds promptly and resolves, with some scarring. Good visual recovery can be usually be expected if treated (71). How to Choose a Lab This article detailed the importance of medical laboratory testing for optometrists. As many eye health and systemic conditions can be diagnosed off of laboratory tests, it is very important that the medical laboratory tests be accurate and reliable. Some consideration should be taken then in ordering tests from a reliable medical laboratory. It is important to check that the medical laboratory of choice is accredited. Both the Federal government and independent organizations accredit medical laboratories. The Clinical Laboratory Improvements amendment passed by the Federal Government in 1988, set

Author: Tracy Doll, OD COPE #21399-PD 3 credits standards by which all laboratories in the United States must adhere (note that if individual state requirements are more stringent, they will apply over the federal requirements). The requirements a laboratory must meet include those involving education and training, proficiency, quality control, and patient safety (72). The Joint Commission is a private organization that evaluates and accredits more than 15,000 health care organizations and programs in the United States. And independent not-for profit organization, the Joint Commission is the nations predominant standards-setting and accrediting body in health care (74). Any medical laboratory an optometrist is considering should meet the Joint Commission Standards for safety (72). The Joint Commission has a search engine on a website that allows the public to check on any medical laboratory to see if it has met standards: http://www.qualitycheck.org/consumer/searchQCR.aspx. Many times the laboratory to which the patient is sent to can depend entirely on the patients insurance. The cost to the patient will vary depending on whether the patient has insurance and what testing the insurance will cover. This being said, it is still important to know whether or not the lab is meeting standards. A health care provider should look for a lab that gives consistent, accurate and timely results. As evidenced by this article, a vision or life-saving diagnosis can be entirely dependent upon the findings. Conclusions The underlying cause/ systemic disease leading to an eye condition can be determined very quickly with proper working knowledge of medical lab testing and results. If you are unsure of which tests to run, consult a medical laboratory technologist or a Primary Care Physician (PCP). It is always a good idea to communicate with the patients PCP when referring for medical laboratory testing. Referring a patient to the proper health care provider with properly completed laboratory testing can increase efficiency of care of the patient and builds relationships with medicine and osteopathic medicine and can help to emphasize the high level of training of optometry as a profession.

Special thank to: Medical Laboratory Technologist Shelley Hubka of the SouthWest Washington Medical Center References
1. Complete Blood Count (CBC). WebMd Medical Reference From Healwise.http://www.webmd.com/a-to-z-guides/complete-blood-count-cbc?page=3 12/04/2006. 2. McKenzie, Shirlyn B. Clinical Laboratory Hematology. Prentice Hall. 2004. p 134-135, 166-168, 240-241, 269-277, 386, 513-519, 713-714. 3. ESR, Erythrocyte-hematocrit-hemoglobin, thalssemia, neutrophilia, myeloid disorders, polycythemia vera, thrombocytopenia purpura, folic acid Falco,Laura A., and Kabat, Alan G. Understanding Medical Lab Tests And Their Results. Optometric Study Center 2005. Review of Optometry. November 2005. 4. Blood Differential. Medline Plus Medcial Encyclopedia. http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm. 03/09/2007. 5. White Blood Cell. Wikipedia The Free Encyclopedia. http://en.wikipedia.org/wiki/White_blood_cell. 12/20/2007. 6. Erythrocyte Sedemendation Rate. Wikipedia The Free Encyclopedia http://en.wikipedia.org/wiki/Erythrocyte_sedimentation_rate. 12/16/2007. 7. Burtis, Carl A. and Ashwood, Edward R. Fundamentals of Clinical Chemistry. 5th Ed. WB Saunders Co. 2001. p 333. 8. Derresteyn Stevens, Christine. Clinical Immunolgy and Serology: A Laboratory Perspective. 2nd Ed. F.A Davis Company. 2003. P161, 214-220, 224, 355-358 ELISA, SLE, ANA, RA, Thyroid, DM2, MS, HIV 9. Standards of Care in Diabetes 2007. Diabetes Care. The American Diabetic Association. http://care.diabetesjournals.org/cgi/content/full/30/suppl_1/S4. 10/2006. 10. Bloodborne Pathogens. .Questions and Answers About Accidental Exposure. Department of Consumer and Business Services. Oregon Occupational Safety and Health Division. http://www.orosha.org/pdf/pubs/2261.pdf. 08/2006 11. Safe Needle Distruction.org. Coalition for Safe Community Needle Disposal. http://www.safeneedledisposal.org/dispcenters

Author: Tracy Doll, OD COPE #21399-PD 3 credits 12. Medical Waste. The U.S Environmental Protection Agency Website. http://www.epa.gov/epaoswer/other/medical/index.htm. 10/12/07. 13. Detection, Evaluation and Treatment of High Cholesterol in Adults (Adult Treatment Panel III) Executive Summary. National Institutes of Health. National Heart, Lung and Blood Institute. NIH Publicaiton No. 01-3670. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf. 05/2001. 14. Ocular Ischemic Syndrome. Handbook of Ocular Disease Management Online. http://www.revoptom.com/handbook/SECT44a.HTM. 2000-2001 15. Leibovitch, Igal, et all. Ocular Ischemic Syndrome. Emedicine Website from WebMD. http://www.emedicine.com/oph/topic487.htm. 06/26/06. 16. TSH. Medline Plus Medical Encyclopedia. National Institute of Health http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm. 10/24/07 17. Yen, Michael T. Ophthalmopathy, Thyroid. Emedicine website from WebMD http://www.emedicine.com/RADIO/topic485.htm. 10/26/06. 18. Simmerville, Jeff A, et all. Urinalysis: A Comprehensive Review. American Family Physician. http://www.aafp.org/afp/20050315/1153.html 03/15/2005. 19. Glucose-Urine. Medline Plus Medical Encyclopedia. National Institute of Health. http://www.nlm.nih.gov/medlineplus/ency/article/003581.htm. 02/03/06. 20. Protein-Urine. Medline Plus Medical Encyclopedia. National Institute of Health. http://www.nlm.nih.gov/medlineplus/ency/article/003580.htm. 10/22/07. 21. Ketones-Urine. Medline Plus Medical Encyclopedia. National Institute of Health. http://www.nlm.nih.gov/medlineplus/ency/article/003585.htm. 12/09/05. 22. Bilirubin-Urine. Medline Plus Medical Encyclopedia. National Institute of Health. http://www.nlm.nih.gov/medlineplus/ency/article/003595.htm. 05/17/07. 23. Jaundice-yellow skin. Medline Plus Medical Encyclopedia. National Institute of Health. http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm. 08/18/06. 24. Rogue, Manolette R. Ocular Manifestations of Syphilis. Emedicine website from WebMD. http://www.emedicine.com/oph/topic453.htm. 09/25/06. 25. Podlipski Gould, Karen. Sarcoidosis. Emedicine website from WebMD. http://www.emedicine.com/DERM/topic381.htm. 02/14/06. 26. Sarcoidosis. Handbook of Ocular Disease Management Online. http://www.revoptom.com/HANDBOOK/oct02_sec7_1.htm\ 2000-2001 27. Matsumoto, Alan K. Rheumatoid arthritis: Clinical Presentation John Hopkins Arthritis Website. 1998-2007http://www.hopkinsarthritis.som.jhmi.edu/rheumatoid/pdf/rheum_clinpres.pdf

Author: Tracy Doll, OD COPE #21399-PD 3 credits 28. Titer. Medline Plus Medical Encyclopedia. National Institute of Health. http://www.nlm.nih.gov/medlineplus/ency/article/002328.htm. 08/28/07. 29. Titer. Wikipedia The Free Encyclopedia. http://en.wikipedia.org/wiki/Titer. 12/17/07. 30. Systemic Lupus Erythematosus. Handbook of Ocular Disease Handbook Online. http://www.revoptom.com/HANDBOOK/oct02_sec7_1.htm. 2001-2000. 31. Joan Frizzell. Diagnostic Tests: Antinuclear Antibody Testing. The American Journal of Nursing, Vol. 97, No. 12. (Dec., 1997), pp. 14-15. 32. HLA. Lab Tests Online. Http://www.labtestsonline.org/understanding/analytes/hla_b27/sample.html. 12/16/07 33. www.labtestsonline.org. ACE. 2001-2006 American Association for Clinical Chemistry. 34. Walton, R Christopher et all. Ankylosing Spondylitis. Emedincine.com http://www.emedicine.com/oph/topic676.htm. 06/06/05 35. Ankylosing Spondylitis. Medline Plus Medical Encyclopedia. http://www.nlm.nih.gov/medlineplus/ency/article/000420.htm. 04/27/07 36. Reactive Arthritis. Wikipedia Online Encyclopedia. Http://en.wikipedia.org/wiki/Reactive_arthritis. 03/11/ 07 37. Scoggins ,Thomas and Boyarsky, Igor. Reactive Arthritis. Emedicine Website from WebMD. http://www.emedicine.com/emerg/topic498.htm. 02/15/07 38. Yousefi, Marjan. Bechets Disease. Emedicine website from WebMD.http://www.emedicine.com/DERM/topic49.htm. 02/26/2007. 39. http://en.wikipedia.org/wiki/ELISA. Wikipedia The Free Encyclopedia. ELISA. 02:36, 15 November 2006. 40. Spector, Anna. ELISA Test-ELISA assay. Your Guide to Infectious Disease. http://infectiousdiseases.about.com/od/patientscorner/qt/ELISA_test.htm. 09/20/07 41. Western Blot. http://en.wikipedia.org/wiki/Western_blot. Wikipedia The Free Encyclopedia.. 08:08, 16 November 2006. 42. Remington JS, Thylliez, Montoya JG. Recent developments for diagnosis of toxoplasmosis. J Clin Microbiol. 2004 Mar;42(3):941-5. 43. Copeland, Robert. Ocular Manifestations of HIV. Emedicine website from WebMD http://www.emedicine.com/oph/topic261.htm. 06/22/06. 44. Mantoux Test. http://en.wikipedia.org/wiki/Mantoux_test. Wikipedia Online Encyclopedia. 12/7/2007. 45. D. G. Neschis, F. J. Lexa, J. T. Davis and J. P. Carpenter. Duplex criteria for determination of 50% or greater carotid stenosis. Journal of Ultrasound in Medicine, Vol 20, Issue 3 207215.http://www.jultrasoundmed.org/cgi/content/abstract/20/3/207

Author: Tracy Doll, OD COPE #21399-PD 3 credits 46. Grant, Edward G. et al. Carotid Artery Stenosis: Gray-Scale and Doppler US DiagnosisSociety of Radiologists in Ultrasound Consensus Conference. Radiology 2003;229:340-346. http://radiology.rsnajnls.org/cgi/content/full/229/2/340 47. Validation of Cartoid Duplex and Power M-Mode Transcranial Doppler for Detection of Internal Carotid Artery Stenosis. http://razi.ams.ac.ir/AIM/0473/005.htm 48. Carotid duplex. Medline Plus Medical Encyclopedia. http://www.nlm.nih.gov/medlineplus/ency/article/003774.htm 08/22/06. 49. X-Ray. http://en.wikipedia.org/wiki/X-ray. Wikipedia Online Encyclopedia. March 12, 2007. 50. Chest X-Ray. Emedicine website from WebMD. http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm. 08/03/2005. 51. Lihteh, Wu, et.al. Presumed Ocular Histoplasmosis Syndrome. http://www.emedicine.com/oph/topic406.htm. 07/24/2007. 52. Presumed Ocular Histoplasmosis Syndrome. Handbook of Ocular Disease Handbook Online. http://www.revoptom.com/HANDBOOK/sect5o.htm 2000-2001. 53. CT Scan. Oncology Channel, by HealthCommunities.com http://www.oncologychannel.com/diagnostictests/CTscan.shtml 03/05/2007. 54. Computerized Axial Tomography (CAT Scan/ CT Scan). Medicine Net.Com. http://www.medicinenet.com/cat_scan/article.htm. 08/28/2005. 55. Widell, Thomas. Fractures, Orbital. Emedicine website from WebMD http://www.emedicine.com/emerg/topic202.htm. 04/25/2005. 56. Harrington, John,M. Cellulitis, Orbital. Emedicine website from WebMD. http://www.emedicine.com/oph/topic205.htm. 11/03/06. 57. Magnetic Resonance Imaging. Wikipedia Online Encyclopedia. http://en.wikipedia.org/wiki/MRI .03 10/2007. 58. MRI. Medline Plus Medical Encyclopedia. http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm. 03/06/2007. 59. Hornak, Joseph P., The Basics of MRI. www.cis.rit.edu/htbooks/mri/ 1996-2007. 60. Brain, Multiple Sclerosis. Emedicine website from WebMD. http://www.emedicine.com/radio/topic461.htm 01/24/2007. 61. Shovlin, Joseph P. A Corneal Ulcer Conundrum. Review of Optometery. Vol. No: 142:9Issue: 9/15/2005 62. Christopher J. Quinn, O.D. Therapeutic Forum What Should You Do About Corneal Ulcers? Review of Optometry Online. 02/15/ 2000. 63. Shovlin, Joseph P. The Fuss Over Fusarium. Review of Optometery. Vol. No: 143:06Issue: 6/15/2006.

Author: Tracy Doll, OD COPE #21399-PD 3 credits 64. Shovlin, Joseph P. An Addition to the Culture Club: Swabs can be cheaper and definitive when culturing corneal ulcers. Review of Optometry. Vol. No: 141:11 Issue: 11/15/04. 65. Shovlin, Joseph P. Culturing the Rare Infection. Review of Optometr Online. 8/2/00. 66. Michael C. Kim, MD, and Carol L. Karp, MD. Managing Fungal Keratitis. http://www.aao.org/aao/news/eyenet/archive/03_01/perls.html 67. Henry, Larry R. Combating Keratitis II: An examination of the parasitic etiology of this condition. Optometric Management. November 2001. 68. Microscopy. The Merck Manuals: Online Medical Library. http://www.merck.com/mmpe/sec14/ch168/ch168b.html.11/2005. 69. Giemsa Stain. Wikipedia Online Encyclopedia. http://en.wikipedia.org/wiki/Giemsa_stain. 11/08/07 70. Ziehl-Neelsen stain. Wikipedia Online Encyclopedia. http://en.wikipedia.org/wiki/ZiehlNeelsen_stain. 12/26/07 71. Sridhar MS, Gopinathan U, Garg P, Sharma S, Rao GN. Ocular nocardia infections with special emphasis on the cornea . Survey ot Ophthalmology. 2001 March-Apr. 45(5): 361-78 72. Eric Seaborg. Lab Oversight: A Building Block of Trust. Lab Tests Online Website http://www.labtestsonline.org/lab/labquality-5.html . 08/10/07. 73. The Joint Commission Website: Quality Check Find a Health Care Organization. http://www.qualitycheck.org/consumer/searchQCR.aspx. 10/2007. 74. The Joint Commission Website. Facts About the Joint Commission. http://www.jointcommission.org/AboutUs/joint_commission_facts.htm. 03/2007. 75. Kanski, Jack. Clinical Ophthalmology. A Systemic Approach. 5th Ed. Butterworth- Heinmann. 2003. p 439-454 (diabetes), 485-486 (leukemia), 684(HIV), 694 (GCA) 76. Inflammation, Heart Disease and Stroke: The Role of C-Reactive Protein. American Heart Association Website. 01/09/08. http://www.americanheart.org/presenter.jhtml?identifier=4648 77. Hect, Frederick Hecht, MD, FAAP, FACMG. Creatinine Blood Test. MedicineNet.com Website.http://www.medicinenet.com/creatinine_blood_test/article.htm. 09/05/05 78. MALCOLM L. BRIGDEN, M.D., B.C. Clinical Utility of the Erythrocyte Sedimentation Rate. American Family Physician. Vol. 60/No. 5 (October 1, 1999). The American Academy of Family Physicians News and Publications Website. http://www.aafp.org/afp/991001ap/1443.html. Accessed 01/09/08 79. Farid NR, Sampson L, Moens H, Barnard JM.The association of goitrous autoimmune thyroiditis with HLA-DR5.Tissue Antigens. 1981 Mar;17(3):265-8.

Author: Tracy Doll, OD COPE #21399-PD 3 credits 80. AC Steere, E Dwyer, and R Winchester Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles. New England Journal of Medicine. Volume 323:219-223 Number 4. July 26, 1990. 81. Tawatchai Paisansinsup, Abbe N. Vallejo, Harvinder Luthra and Chella S. David. HLA-DR Modulates Autoantibody Repertoire, But Not Mortality, in a Humanized Mouse Model of Systemic Lupus Erythematosus. The Journal of Immunology, 2001, 167: 4083-4090. 82. Rogue, Manolette, R. Uveitis, Juvenile Idiopathic Arthritis. Emedicine.com from WebMD. http://www.emedicine.com/OPH/topic675.htm. 02/24/06. 83. Mistr, Susannah K. Tuberculosis. Emedicien.com from WebMD. http://www.emedicine.com/OPH/topic675.htm. 09/26/06. 84. Pfister DR, Cameron JD, Krachmer JH, Holland EJ. Confocal microscopy findings of Acanthamoeba keratitis.Am J Ophthalmol. 1996 Feb;121(2):119-28. 85. V Prasad, D Semwogerere, ER Weeks, Confocal microscopy of colloids"J. Phys.: Cond. Mat. 19, 113102 (2007) 86. Agar plate. Wikipedia Online Encyclopedia. http://en.wikipedia.org/wiki/Agar_plate 01/08/08. 87. Claros, Marina C.Citron, Diane M. and Goldstein, Ellie J.C. Survival of Anaerobic Bacteria in Vsarious Thioglycolate and Chopped Meat Broth Formulations. Journal Of Clinical Microbiology. Vol 33. No9:p2505-2507. 09/1995. 88. Nongynecological Cytology Practice Guidelines prepared by the American Society of Cytopathology, Cytopathology Practice Committee. Adopted by the ASC Executive Board, March 2, 2004. http://www.cytopathology.org/website/article.asp?id=81 Adopted by the ASC Executive Board, March 2, 2004 89. Tuberculosis. Handbook of Ocular Disease Management Online. http://www.revoptom.com/handbook/oct02_sec7_7.htm. Accessed 01/16/2008.

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