Correlation Between Retinopathy and Anemia

FACULTY OF MEDICINE TRISAKTY UNIVERSITY JAKARTA, JANUARY 2011 Name: Rizky Perdana Student Number: 030.07.225

Preface

Assalamualaikum Wr Wb, I would like to thank God for his blessing all though my works so I could finish this paper in time. This paper would not been possible without the continued interest and enthusiasm of my family, my incredible friends and so many lecturer whom most grateful. Thanks to lecturer Dr. Karliana for her guidance and help on this paper. This paper titled Correlation Between Retinopathy and Anemia that I arranged in order to complete my English assigment for subject Medical English 3rd in the Faculty of Medicine Trisakti University. And thanks to my friends for their helps, withour their helps and support I would not be able to finish this paper. I apologize for all mistakes that I made in this paper. I hope this paper could be useful for its reader.

Jakarta, January 2011

Rizky Perdana 030.07.225

CONTENT
Preface Content Abstract Chapter I : Introduction Chapter II : Discusion Chapter III : Conclution Reference 2 3 4 5 6 30 31

ABSTRACT
Retinal abnormalities have been described for many years in patients with anemia. Extravascular retinal abnormalities described include flame-shaped hemorrhages, hard Hemorrhages, which may have white centers (roth spot) and cotton-wool spots.

Retinopathy is not caused by inflammatory. A relationship between the severity of the anemia and the severity of the retinopathy has been proposed (1) .However, others have contended that the cause of the anemia may be a more important factor than the actual level of hemoglobin in causing retinal abnormalities (2,3) . Keywords: Anemia, Retinopathy, Roth spot, cotton wool spot

CHAPTER I

INTRODUCTION
This paper is dedicated to discuss about correlation between retinopathy and anemia. Anemia that may caused by so many problems (e.g. iron deficiency, poor of nutrition, bleeding, related to medication etc) can happen in anyone. Base on this study anemia is one of risk factor of retinopathy. the symptoms of retinopathy include blurred vision, fluctuating vision, seeing floating spots, blind spots, changes in colour perception, sudden loss of vision, double vision. These symptoms can affect the performance of patients on daily routine. In fact, ocular manifestation can be the presenting signs or symptoms in up to 90% of patients depending on the underlying hematological disorder (4) . This study defines the frequency of retinal changes in anemic patients who have no coexisting systemic diseases known to be associated with retinal abnormalities, and who have no abnormalities in hemostasis. Further, a method for the objective evaluation of venous tortuosity is described, enabling physicians to evaluate this disorder in anemic patients.

CHAPTER II 5

DISCUSION
2.1 ANEMIA Anemia describes the condition in which the number of red blood cells in the blood is low. For this reason, sometimes describe someone with anemia as having a low blood count. A person who has anemia is called anemic. Blood is comprised of two parts; a liquid part called the plasma and a cellular part. The cellular part contains several different cell types. One of the most important and most numerous types and the most numerous cell type are red blood cells. The other cell types are the white blood cells and platelets. Only red blood cells are discussed in this paper. The purpose of the red blood cell is to deliver oxygen from the lungs to other parts of the body. Red blood cells are produced through a series of complex and specific steps. They are made in the bone marrow (inner part of some bones that make most of the cells in the blood), and when all the proper steps in their maturation are complete, they are released into the blood stream. The hemoglobin molecule is the functional unit of the red blood cells and is a complex protein structure that is inside the red blood cells. Contrary to most cells in the human body, red blood cells do not have a nucleus. Even though the red blood cells (or RBCs) are made within the bone marrow, many other factors are involved in their production. For example, iron is a very important component of the hemoglobin molecule; erythropoietin, a molecule secreted by the kidneys, promotes the formation of red blood cell in the bone marrow.

2.1.1 Anemia Causes Many medical conditions cause anemia. Common causes of anemia include the following:

Anemia from active bleeding: Loss of blood through heavy menstrual bleeding or, wounds can cause anemia. Gastrointestinal ulcers or cancers such as cancer of the colon may slowly ooze blood and can also cause anemia.

Iron deficiency anemia: The bone marrow needs iron to make red blood cells. Iron plays an important role in the proper structure of the hemoglobin molecule. If iron intake is limited or inadequate due to poor dietary intake, anemia may occur as a result. This is called iron deficiency anemia. Iron deficiency anemia can also occur when there are stomach ulcers or other sources of slow, chronic bleeding (colon cancer, uterine cancer, intestinal polyps, hemorrhoids, etc). In these kinds of scenarios, because of ongoing, chronic slow blood loss, iron is also lost from the body (as a part of blood) at a higher rate than normal and can result 7

in iron deficiency anemia.

Anemia of chronic disease: Any long-term medical condition can lead to anemia. The exact mechanism of this process in unknown, but any long-standing and ongoing medical condition such as a chronic infection or a cancer may cause this type of anemia.

Anemia related to kidney disease: The kidneys release a hormone called the erythropoietin that helps the bone marrow make red blood cells. In people with chronic (long-standing) kidney disease, the production of this hormone is diminished, and this in turn diminishes the production of red blood cells, causing anemia. This is called anemia related to chronic kidney disease.

Anemia related to pregnancy: Water weight gain during pregnancy dilutes the blood, which may be reflected as anemia.

Anemia related to poor nutrition: Vitamins and minerals are required to make red blood cells. In addition to iron, vitamin B12 and folate are required for the proper production of hemoglobin. Deficiency in any of these may cause anemia because of inadequate production of red blood cells. Poor dietary intake is an important cause of low folate and low vitamin B12 levels. Strict vegetarians who do not take sufficient vitamins are at risk to develop vitamin B12 deficiency.

Pernicious Anemia: There also may be a problem in the stomach or the intestines leading to poor absorption of vitamin B12. This may lead to anemia because of vitamin B12 deficiency known as pernicious anemia.

Sickle cell anemia: In some individuals, the problem may be related to production of abnormal hemoglobin molecules. In this condition the hemoglobin problem is qualitative, or functional. Abnormal hemoglobin molecules may cause problems in the integrity of the red blood cell structure and they may become crescent-shaped (sickle cells). There are different 8

types of sickle call anemia with different severity levels. This is typically hereditary and is more common in those of African, Middle Eastern, and Mediterranean ancestry.

Thalassemia: This is another group of hemoglobin-related causes of anemia. There are many types of thalassemia, which vary in severity from mild (thalassemia minor) to severe (thalassemia major). These are also hereditary, but they cause quantitative hemoglobin abnormalities, meaning an insufficient amount of the correct hemoglobin type molecules is made. Thalassemia is more common in people from African, Mediterranean, and Southeast Asian ancestries.

Alcoholism: Poor nutrition and deficiencies of vitamins and minerals are associated with alcoholism. Alcohol itself may also be toxic to the bone marrow and may slow down the red blood cell production. The combination of these factors may lead to anemia in alcoholics.

Bone marrow-related anemia: Anemia may be related to diseases involving the bone marrow. Some blood cancers such as leukemia or lymphomas can alter the production of red blood cells and result in anemia. Other processes may be related to a cancer from another organ spreading to the bone marrow.

Aplastic anemia: Occasionally some viral infections may severely affect the bone marrow and significantly diminish production of all blood cells. Chemotherapy (cancer medications) and some other medications may pose the same problems.

Hemolytic anemia: The normal red blood cell shape is important for its function. Hemolytic anemia is a type of anemia in which the red blood cells rupture (known as hemolysis) and become dysfunctional. This could happen due to a variety of reasons. Some forms of hemolytic anemia can be hereditary with constant destruction and rapid reproduction of red blood cells (for example, as in hereditary spherocytosis, hereditary elliptocytosis, and glucose-6-phosphate dehydrogenase or G6GD deficiency) . This type of destruction may also 9

happen to normal red blood cells in certain conditions, for example, with abnormal heart valves damaging the blood cells or certain medications that disrupt the red blood cell structure.

Anemia related to medications: Many common medications can occasionally cause anemia as a side effect in some individuals. The mechanisms by which medications can cause anemia are numerous (hemolysis, bone marrow toxicity) and are specific to the medication. Medications that most frequently cause anemia are chemotherapy drugs used to treat cancers. Other common medications that can cause anemia include some seizure medications, transplant medications, HIV medications, some malaria medications, some antibiotics (penicillin, chloramphenicol), antifungal medications, and antihistamines.

Other less common causes of anemia include thyroid problems, cancers, liver disease, autoimmune diseases (lupus), paroxysmal nocturnal hemoglobinuria (PNH), lead poisoning, AIDS, malaria, viral hepatitis, mononucleosis, parasitic infections (hookworm), bleeding disorders, and insecticide exposure. It is noteworthy that there are many other potential causes of anemia that are not included in this list as these are only some of the more common and important ones.

2.1.2 Anemia Symptoms Because a low red blood cell count decreases oxygen delivery to every tissue in the body, anemia may cause a variety of signs and symptoms. It can also make almost any other underlying medical condition worse. If anemia is mild, it may not cause any symptoms. If anemia is slowly ongoing (chronic), the body may adapt and compensate for the change; in this case there may not be any symptoms until the anemia becomes more severe. fatigue, decreased energy, weakness, shortness of breath, lightheadedness, palpitations (feeling of the heart racing or beating irregularly), looking pale Symptoms of anemia may include 10

Symptoms of severe anemia may include: chest pain, angina, or heart attack, dizziness, fainting or passing out, rapid heart rate Some of the signs that may indicate anemia in an individual may include change in stool color (including black and tarry stools (sticky and foul smelling), maroon-colored, or visibly bloody stools if the anemia is due to blood loss through the gastrointestinal tract), rapid heart rate, low blood pressure, rapid breathing, pale or cold skin, yellow skin called jaundice if anemia is due to red blood cell breakdown, heart murmur, enlargement of the spleen with certain causes of anemia 2.1.3 Anemia Diagnosis

Diagnosis of anemia is by drawing a blood sample for a complete blood count. Based on the results of the test and thorough evaluation of the patient, the doctor may order more tests to determine the exact cause of anemia. The complete blood count may be done as part of a routine general checkup or based upon the presence of signs and symptoms that can be related to anemia. Physical examination and medical history also play a crucial role in diagnosing causes of anemia. Some of the important features in medical history cover questions about family history, previous personal history of anemia or other chronic conditions, medications, color of stool and urine, bleeding problems, and occupation and social habits (such as alcohol intake). While performing a complete physical examination, the physician may particularly focus on general appearance (signs of fatigue, paleness), jaundice (yellow skin and eyes), paleness of the nail beds, enlarged spleen (splenomegaly) or liver (hepatomegaly), heart sounds, and lymph nodes. Because anemia is only a symptom of another disease, doctors will want to determine what condition is causing the anemia. Some people may need many additional tests, and others may need very few. For example, an anemic person with known stomach ulcers may not need multiple blood tests but, may need to have his or her stomach visually evaluated and have the ulcers treated. On the other hand, a person with a family history of anemia and without an obvious source of blood loss may 11

need multiple laboratory tests and other types of testing. Doctors also take into consideration the severity of the anemia when deciding the tests to order. When a person has severe anemia, the cause must be determined rapidly so that it can be treated appropriately. Laboratory Studies The first step in the diagnosis of anemia is detection with reliable accurate tests so that important clues to underlying disease are not overlooked and patients are not subjected to unnecessary tests for and treatment of nonexistent anemia. Detection of anemia involves the adoption of arbitrary criteria. The World Health Organization's criterion for anemia in adults is Hb values less than 12.5 g/dL. Children aged 6 months to 6 years are considered anemic at Hb levels less than 11 g/dL, and children aged 6-14 years are considered anemic when Hb levels are less than 12 g/dL. The disadvantage of such arbitrary criteria is that a few healthy individuals fall below the reference range, and some people with an underlying disorder fall within the reference range for Hb concentration. Usually, US values are slightly higher. Anemia is suggested in males with Hb levels less than 13.5 g/dL and in females with Hb levels less than 12.5 g/dL. Higher values are anticipated in individuals living in altitudes significantly above sea level. Conditions with an increase in plasma volume, such as during the last trimester of pregnancy, are associated with lower values without an existent anemia because the red cell mass is normal. Once the existence of anemia is established, investigate the pathogenesis. If an adequate history has been taken and a physical examination has been performed, the etiology may be obvious, and confirmatory studies and appropriate therapy can be undertaken with a minimum of investigation. If this is not the case, initiate a definite plan of investigation considering the cost to the patient along with a determination of the etiology of the abnormality. A rational approach is to begin by examining the peripheral smear and laboratory values obtained on the blood count. If the anemia is either microcytic (mean corpuscular volume [MCV], <84) or macrocytic (MCV, >96) or if certain abnormal RBCs or WBCs are observed in the blood smear, the 12

investigative approach can be limited (see Table 1, Table 2, and Table 3). Presently, RBC cellular indices are computer calculated and automatically placed on laboratory reports. The formulae for calculating these values follow (reference ranges are in parentheses). RBC is per million cells. MCV = Hct X 10/RBC (84-96 fL) Mean corpuscular Hb (MCH) = Hb X 10/RBC (26-36 pg) Mean corpuscular Hb concentration (MCHC) = Hb X 10/Hct (32-36%)

A rapid method of determining whether cellular indices are normocytic and normochromic is to multiply the RBC and Hb by 3. The RBC multiplied by 3 should equal the Hb, and the Hb multiplied by 3 should equal the Hct. Deviation from the calculated values suggests microcytosis, macrocytosis, or hypochromia versus the presence of spherocytes (MCHC, >36). Table 1. Microcytic Hypochromic Anemia (MCV, <83; MCHC, <31)

Condition

Seru m Iron

Total IronBinding Capacity (TIBC)

Bone Marrow Iron 0

Comment

Iron deficiency Chronic

Responsive to iron therapy

++

Unresponsive to iron therapy

inflammation Thalassemia major Thalassemia N minor

++++

Reticulocytosis and indirect bilirubinemia Elevation of A of fetal hemoglobin, target cells, and poikilocytosis Basophilic stippling of RBCs

++

Lead

++

poisoning Sideroblastic Hemoglobin N

N N

++++ ++

Ring sideroblasts in marrow Hemoglobin electrophoresis 13

 = decreased; = increased; 0 = absent; +'s indicate the amount of stainable iron in bone marrow specimens, on a scale of 0-4; N = normal. Table 2. Macrocytic Anemia (MCV, >95)

Megaloblastic bone marrow

Nonmegaloblastic bone marrow

Deficiency of vitamin B-12 Deficiency of folic acid Drugs affecting DNA synthesis Inherited disorders of DNA synthesis Liver disease Hypothyroidism and hypopituitarism Accelerated erythropoiesis (reticulocytes) Hypoplastic and aplastic anemia Infiltrated bone marrow

Table 3. Various Forms of RBCs

Macrocyte Microcyte Hypochromic Spherocyte

Larger than normal (>8.5 m diameter). See Table 2. Smaller than normal (<7 m diameter). See Table 1. Less hemoglobin in cell. Enlarged area of central pallor. See Table 1. Loss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and certain acquired hemolytic anemias. Hypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, postsplenectomy. Hypochromic cell with a normal diameter and decreased MCV. Thalassemia. Oval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B-12 and folate deficiency). Fragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, malignant hypertension. Slitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact. Drop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia. 14

Target cell

Leptocyte

Elliptocyte

Schistocyte

Stomatocyte

Tear-shaped RBCs

Acanthocyte

Five to 10 spicules of various lengths and at irregular interval on surface of RBCs. Evenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency, preparative artifact. Elongated cell with pointed ends. Hemoglobin S and certain types of

Echinocyte

Sickle cell

hemoglobin C and l. In microcytic hypochromic anemia, seek a source of bleeding. The appropriate laboratory tests are serum iron level and TIBC and either serum ferritin level or stain of bone marrow specimen for iron. If the serum iron level is decreased and TIBC is increased, a diagnosis of iron deficiency can be made, therapy can be initiated, and a search for the cause of the iron deficiency can be started. If this cannot be demonstrated, suspect each of the other causes of a microcytic anemia listed in Table 1, and the order of investigation can be influenced by findings in the history, physical examination, or peripheral smear. Similarly, a reasonable approach with macrocytic anemia is to determine if the bone marrow aspirate is megaloblastic. If so, attempt to incriminate either vitamin B-12 or folic acid deficiency with appropriate laboratory studies. Similar to the establishment of a diagnosis of iron deficiency anemia, a diagnosis of vitamin B-12 or folic acid deficiency does not stop with an abnormal laboratory value for one of these vitamins. Prompt treatment can be instituted, but a continued search for an underlying cause of the vitamin deficiency is indicated. When a normocytic normochromic anemia is encountered, classify the anemia into 3 possible etiologies (ie, blood loss, hemolysis, decreased production). In most anemias, one of these causes is the dominant factor. However, in certain anemias, more than a single cause may play an important role. For example, pernicious anemia is predominantly due to decreased production of erythrocytes, but hemolysis adds significantly to the severity of anemia(5) . 2.1.4 Anemia Treatment Self-Care at Home 15

Very little can be done to self-treat anemia and medical treatment is generally needed. It is important to continue to take any medication that is prescribed for other chronic (long-lasting) medical problems. If the reason for anemia is known, then measures to keep it under control are very important. For example, if anemia is caused by a stomach ulcer, then medications such as aspirin or ibuprofen should be avoided, unless otherwise directed by a doctor. Medical Treatment Medication Medical treatment of anemia varies widely and depends on the cause and the severity of anemia. Medications and treatments that correct the common underlying causes of anemia include the following:

Iron may be taken during pregnancy and when iron levels are low. It is important to determine the cause of iron deficiency and treat it properly.

Vitamin supplements may replace folate and vitamin B12 in people with poor eating habits. In people with pernicious anemia who are unable to absorb sufficient amounts of vitamin B12, monthly injections of vitamin B12 are commonly used to replete the vitamin B 12 levels and correct the anemia.

epoetin alfa (Procrit or Epogen) injection can be used to increase red blood cell production in people with kidney problems. The production of erythropoietin is reduced in people with advanced kidney disease, as described earlier.

Stopping a medication that may be the cause of anemia may also reverse anemia after consultation with a physician.

If alcohol is the cause of anemia, then in addition to taking vitamins and maintaining adequate nutrition, alcohol consumption needs to be stopped. 16

Surgery There are no specific surgical interventions for the treatment of anemia. However, depending on the causes of the anemia, surgery may be a treatment option. Follow-up Follow-up care for anemia will depend on its type. Most will require repeat blood counts. Patients with chronic anemia can usually be cared for on an outpatient basis. Follow-up care is necessary to ensure that therapy is being continued and to assess the efficacy of treatment. 2.1.5 Anemia Prevention Some common forms of anemia are most easily prevented by eating a healthy diet and limiting alcohol use. All types of anemia are best avoided by seeing a doctor regularly and when problems arise. In the elderly, routine blood work ordered by the doctor, even if there are no symptoms, may detect anemia and prompt the doctor to look for the underlying causes. 2.1.6 Anemia Prognosis How well someone with anemia will recover depends on the cause of the anemia and how severe it is. For example, if a stomach ulcer is causing anemia because of bleeding then the anemia can be cured if the ulcer is treated and the bleeding stops. If anemia is caused by kidney failure, however, then it most likely will require long-term treatment. In general, young people recover from anemia more quickly than older people do. Younger people also tolerate anemia better than elderly people because elderly people tend to have more chronic medical problems. Anemia makes almost any medical problem worse.

17

2.2 RETINOPATHY Retinopathy refers to damage to the blood vessels of the retina. The retina, at the back of the eye, provides a window to the circulatory system.

By examining retina, a doctor can inspect a sample of the body's blood vessels and detect early signs of complications of diabetes or high blood pressure, as well as many other diseases (e.g., sickle cell disease, anemia, lupus). Retinopathy can also be seen in premature infants. Retinopathy of prematurity (ROP) is a serious vasoproliferative disorder that affects extremely premature infants. Retinopathy of prematurity often regresses or heals but can lead to severe visual impairment or blindness. Significant retinopathy of prematurity can lead to lifelong disabilities for the smallest 18

survivors of neonatal ICUs (NICUs). It remains a serious problem despite striking advances in neonatology(6). Some of the kinds of damage that your doctor may see in your retina are hypertensive retinopathy, a complication of high blood pressure (hypertension), and diabetic retinopathy, a complication of long-term diabetes. It's unusual for hypertension to impair vision, but hypertensive retinopathy can lead to blockage of retinal arteries or veins, which in turn may eventually result in the loss of vision. Smoking and diabetes increase the risk of developing hypertensive retinopathy. Diabetic retinopathy is a deterioration of the blood vessels in the retina that usually affects both eyes. It is the leading cause of blindness in North America. Almost all people with diabetes show signs of retinal damage after about 20 years of living with the condition. 2.2.2 Causes of Retinopathy Retinopathy is usually a sign of another medical condition. Although several medical conditions (e.g., prematurity, anemia, sickle cell disease, lupus) can cause retinopathy, the most common causes are diabetes and hypertension (high blood pressure). Diabetic retinopathy is a complication of diabetes. Diabetes causes high blood sugar levels, which can damage blood vessels. The damaged vessels around the retina can leak protein and fats, forming deposits that can interfere with vision. The damaged blood vessels are also not as effective at carrying oxygen to the retina, which can also cause damage. In the advanced stage, called proliferative retinopathy, new blood vessels grow in the eye. However, they are weak and often burst, causing bleeding in the eye. The bleeding can cause scarring of the eye and damage vision. Hypertensive retinopathy is a complication of high blood pressure that usually takes many years to develop. High blood pressure damages the blood vessel walls, causing them to thicken and narrow. This reduces the blood supply available to the retina, leading to retinal damage. Eventually, blood can leak into the retina, causing further damage.

19

Retinopathy of prematurity, is a proliferative retinopathy affecting pre-term infant of low birth weight who have often been expose to high ambient of oxygen concentration. The retina is unique among tissue in that it has no blood vessels until the fourth mouth of gestation, at which time vascular complexes emanating from the hyaloid vessels at the optic disc grow toward the periphery. These vessels reach the nasal periphery after 8 month of gestation, but do not reach the temporal periphery until about 1 month after delivery. The incompletely vascularize temporal retina is particulary susceptible to oxygen damage, especially in pre-term infant (6) .

2.2.3 Risk factor There are risk factors of retinopathy: 1. Duration of diabetes is the most important. In patient diagnose with diabetes before age 30 years, the incidence of diabetic retinopathy after 10 years is 50% and after 30 years 90%. 2. Poor metabolic control is less important than duration but is neverless relevant to the development and progression of diabetic retinopathy 3. Hypertension, if poorly controlled is associated with hypertension retinopathy and worsening of diabetic retinopathy. 4. Other (risk factor including smoking, obesity and hyperlipidemia). 5. Pre-term infant of low birth weight who have often been expose to high ambient oxygen concentration. 6. Other medical conditions (e.g., anemia, sickle cell disease, lupus) (6) .

2.2.4 Signs and Symptoms of Retinopathy The primary response of retinal chance arterioles to systemic hypertension is narrowing (vasoconstriction). However, the degree of narrowing is dependent on the amount of preexisting replacement fibrosis (involutional sclerosis). For this reason, hypertensive narrowing is seen in its pure from only in young individual in older patients, rigidity of retinal arterioles due to involutional

20

sclerosis prevent the same degree of narrowing seen in young individuals. In sustained hypertension the inner blood-retinal berrier is disrupted in small areas, with increase vascular permeability. The fundus picture of hypertensive retinopathy is therefore characterize by the following: Arterial narrowing may be focal or generalized. Ophthalmoscopic diagnosis of generalized narrowing is difficult, although the presence of focal narrowing makes it highly probable that blood pressure is raised. Severe hypertension may lead to obstruction of the precapillary arterioles and the development of cotton wool spot. Vascular leakage lead to flame-shape retinal hemorrhages and retinal edema. Chronic retinal oedema may result in the deposition of hard exudates around the fovea in Henle layer with a macular star configuration. Swelling of the optic nerve head is the hallmark of malignant hypertension. Arteriolosclerosis involves thickening of the vessel wall characterized histologically by intimal hyalinization, medial hypertrophy and endothelial hyperplasia. The most important clinical sign is the presence of change at arterivenous crossing (av nipping), which although not necessarily indicative of the severity of hypertension, makes it probable that is has been present for many years. Mild change at arterivenous crossing are seen in patient with involutional sclerosis in the absence of hypertension.

In diabetic retinopathy caracterize by: Microanurysms are located in the inner nuclear layer and are the earlisest clinically detectable lesion. Hard exudates lie within the outer plexiform layer Retinal oedema is initially located between the outer plexiform and inner nuclear layers. Later it may also involve the inner plexiform and nerve fiber layer, until eventually the entire thickness of the retina becomes edematous. With further accumulation of fluid the fovea assumes a cystoid appearance (cystoid nuclear oedema) 21

Hemorrhages.

Active retinopathy of premature severity is determined in term of (a) location, (b) extend, (c) stages, and plus disease as follow: 1) Location is deter minded according to three zones centered on the optic disc Zone I is bounded by an imaginary circle the radius of which is twice the distance

from the disc to the macula Zone II extend concentrically from the edge of zone 1 of the nasal ora serrata and to

an area near the temporal equator 2) 3) Zone III consist of residual temporal temporal crescent anterior Extend of involvement is determined by number of clock hours of retina involved Staging Satge 1 (decermation line). The first pathognomonic sign of ROP is the development

of a thin, tortuous, grey white line running roughly parallel with ora serata which separates avascular immature peripheral retina from vascularized posterior retina. The line is more prominent in the temporal periphery and may have abnormal branching blood vessels leading up to it Stage 2 (ridge). If ROP progresses the demarcation line develops into a elevated ridge

which represent a mesenchymal shunt joining arterioles with veins. Blood vessels enter the ridge and the small isolated neovascular tufts may be seen posterior to it Stage 3, (ridge with extra retinal fibrovascular proliferation). As the disease

progresses, the ridge develops a pink color due to fibrovascular proliferation which grows along the surface of the retina and into the vitreous. This is often associated with dilatation an d tortuosity of the retinal blood vessels posterior to the equator. Retinal hemorrhage is common, and vitreous hemorrhage may develop. The highest incidence of this stage is round the post-conceptual age of 35 weeks 22

Stage 4 (sub-total retinal detachment) is due to progressive fibrovascular proliferation.

The detachment, which starts in the extreme periphery and then spreads centrally, typical develops when the infant is about 10 weeks old Stage 5, is a total retinal detacment

Other concideration Plus disease signifies a tendency to progression and is characterized by the following: 1. iris 2. 3. 4. Development of vitreous haze Dilatation of veins and tortuosity of arteries in the posterior fundus Increasing pre-retinal and vitreous hemorrhage Failure of the pupil to dilated, associated with gross vascular engorgement of the

When these change are present, a plus sign is added to the stage number. Threshold disease is defined as five contiguous clock hours or eight non-contiguous clock

hours of extra retinal neovascullarization (stage 3 disease) in zone 1 or 2, associated with plus disease, and is an indication for treatment (7) .

In anemic retinopathy is characterized by: Hemorrhages, which may have white centers (roth spot) Cotton wool spot Venous tortuosity Flame shaped hemorrhages Retinal edema (7) .

Early in diabetic retinopathy, there may be no symptoms at all. As the disease progresses, symptoms include: blurred vision 23

fluctuating vision seeing floating spots blind spots changes in colour perception sudden loss of vision double vision eye pain in advanced cases The earliest sign of diabetic retinopathy that your doctor may detect is the formation of

microaneurysms. These are balloon outpouchings of small blood vessels in the retina that appear as tiny red dots at the back of the eye; they sometimes break, causing bleeding in the retina and cloudy vision. A more advanced form of diabetic retinopathy, called proliferative diabetic retinopathy, may lead to scars that decrease vision. In proliferative retinopathy, new blood vessels grow over the retina and into the vitreous humour (the gel-like substance between the lens and retina). These blood vessels may swell and burst, causing bleeding and damage to the eye. In some cases, the blood can be reabsorbed, but in many cases the retina can become detached causing total blindness. As with diabetic retinopathy, there may be no symptoms early in hypertensive retinopathy. However, as the condition progresses, symptoms include: headaches vision changes sudden loss of vision in one or both eyes double vision There are no outward physical signs of Retinopathy of prematurity. Only an experienced ophthalmologist examining the eye through a dilated pupil can find signs of this illness. 2.2.5 Diagnosing Retinopathy

24

Diabetic retinopathy is a long-term complication of diabetes. If someone has diabetes, it's extremely important that they have their eyes monitored and examined, as recommended by an ophthalmologist (eye specialist). Examinations involved measurement of visual acuity for distance and near, and fundus examination following papillary dilataion with tropicamide 1% (6) . Diabetic and hypertensive retinopathy are diagnosed in much the same way. An ophthalmologist will examine the retina with an ophthalmoscope, which shines bright light into the back of the eye and allows for a close look at the blood vessels of the retina. The ophthalmologist will look for signs of dilated blood vessels and microaneurysms (see the section of this article entitled Symptoms and Complications). They may also use fluorescein angiography, which involves injecting a dye into a vein of the arm and taking a series of retinal photos to detect signs of leaky blood vessels. This process can pinpoint areas that may be threatening to bleed. In the case of hypertensive retinopathy, an ophthalmologist will look for tiny cholesterol-containing plaques in the retinal blood vessels as well as other blood vessel changes such as narrowing and thickening. 2.2.6 Treating and Preventing Retinopathy The key to treating retinopathy is managing the underlying causes of this condition. Controlling blood sugar levels in diabetes is critical in delaying the onset of diabetic retinopathy. Proper management of diabetes involves taking the prescribed treatments, such as insulin or other diabetes medications, as well as following a healthy diet and exercise program. Keeping blood pressure under control will help prevent hypertensive retinopathy. Reducing high blood pressure with appropriate medications will help prevent complications. Regular exercise, proper diet, and other lifestyle changes such as quitting smoking will go a long way toward reducing the risk of retinopathy. Today, many retinal problems are treated with lasers. If a vein has leaked into the vitreous humour and scarring has occurred, your doctor may advise you to have a vitrectomy. This procedure involves removing a part of the vitreous humour along with the scar tissue. If retinal detachment has occurred,

25

surgery may be required to reattach the retina. Treatment for hypertensive retinopathy includes medications to control blood pressure, laser treatment, and sometime medications injected into the eye (e.g., corticosteroids). But prevention is key for this condition. 2.3 Retinopathy associated with anemia Retinopathy in patients with anemia is well documented. Common findings include hemorrhages that can present at all levels of the retina and choroid, Roths spots, exudates, cotton wool spots, retinal edema and venous tortuosity (Figure 1). Roths spots or white centered hemorrhages are typically associated with bacterial endocarditis, however the association is not exclusive, since they occur in diverse conditions including anemia. The white center could represent focal ischemia, inflammatory infiltrates, infectious organisms, fibrin and platelets, or an accumulation of neoplastic cells
(8)

. The exact pathophysiology of anemic retinopathy is not completely under-

stood. However, it seems to be related to retinal hypoxia, venous stasis, angiospasm and increased capillary permeability (9). Anemic retinopathy is most likely to occur in patients with severe anemia or when thrombocytopenia, a disorder of low platelets, is coexistant
(10)

. The ocular changes found in

anemic retinopathy are nonspecific and may closely resemble diabetic or hypertensive retinopathy (11).

QuickTime and a decompressor are needed to see this picture.

In research of Aisen et al, show that Seven (20%) of the 35 patients with anemia had extravascular retinal lesions. There were no retinal abnormalities noted in the control population. Four anemic patients had both hemorrhages (flame-shaped and striated) and cotton-wool spots, and three had only cotton-wool spots. There were no hard exudates observed (Table 1). Of the anemias, 28 (80%) of 35 were chronic. Within this group of 28 patients, six (21%) had extravascular retinal 26

lesions. Within the group of seven patients with acute anemias, only one (with acute hemolytic anemia) had extravascular retinal lesions, whereas none of the six patients with acute gastrointestinal tract hemorrhage had such lesions. There was no relationship noted between type of anemia and presence of extravascular retinal lesions. Because of the small patient group, no conclusions can be made regarding the presence of extravascular retinal lesions in acute that in chronic anemias. And extravascular retinal lesions were observed more often in male (6/20) than in female (1/15) patients
(12)

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* ACD

indicates anemia of chronic disease; IDA, iron-deficiency anemia; AGIH, acute gastrointestinal tract hemorrhage; AHA, acute hemolytic anemia; and MA, megaloblastic anemia. +Patient had hemorrhages and cotton-wool spots. Patient had cotton-wool spots.
(12)

Many factors have been implicated as causative in the production of the retinopathy of anemia. Duke-Elder and Dobree(2,
13)

theorized that anemia results in diminished oxygenation of

capillaries, producing increased permeability and, ultimately, extravasation of the blood. Ballantyne and Michaelson(1.14) ascribed retinal lesions in anemic patients to altered vascular integrity. In a study of severely anemic patients, Merin and Freund
(14.15)

speculated that aging of the retinal vessels

predisposes a person to the deleterious effects of the anemia on the retina. And 19 (36%) of 53 27

severely anemic adult patients (children excluded) exhibited extravascular retinal lesion. Male-tofemale predominance was observed in Merin and Freund's study, where 14 of 31 adult male and only five of 22 adult female subjects had extravascular retinal abnormalities associated with anemia(14,15) . In regards to the management, anemic retinopathy is reversible with correction of the anemia.

CHAPTER 3

CONCLUSION
28

In conclusion, anemia alone, in the absence of other hematologic abnormalities or diseases associated systemic with retinopathy, may be accompanied by extravascular retinal lesions. Retinopathy is characterized by hemorrhages, which may have white centre (roth spots) and cotton wool spot that shown in Aisen et al research. Age, the duration and type of anemia do not influence the occurance of these changes. Extravascular retinal lesions were observed more often in male than in female patients. The exact pathophysiology of anemic retinopathy is not completely under- stood. However, it seems to be related to retinal hypoxia, venous stasis, angiospasm and increased capillary permeability(3). Most studies have concentrated only on extravascular retinal lesions, tabulating retinal hemorrhages, cotton-wool spots, and hard exudates
(3,16)

. Because these lesions can be objectively

recorded from clinical examination alone. Other changes (eg, vascular abnormalities) have been considered too subtle or subjective for reproducible evaluation. Anemic retinopathy is reversible with correction of the anemia.

Reference

29

1. Ballantyne AJ, Michaelson IC: Disorders of the blood and blood-forming organs, in Textbook of the Fundus of the Eye, ed 2. Baltimore, Williams & Wilkins Co, 1970, pp 287-299 2. Duke-Elder S, Dobree JH: The blood diseases, in Duke-Elder S (ed): System of Ophthalmology. St Louis, CV Mosby Co, 1967, vol 10, p 373-407 3. Macan-Markar MA, Peiris JB, DeSilva GU, et al: Retinopathy in megaloblastic anaemias. Trans R Soc Trop Med Hyg 1969;63:398-406 4. Lanf GE, Spraul CW, Lang GK. Ocular manifestation of hematological diseases. Klin Monatsbl Augenheik 1998;212: 419-27 5. Conrad ME. Anemia. South Alabama: Emedicine; [updated 2009 Dec 02; cited 2010 Sept 23]. Available at: www.emedicine.medscape.com 6. Subramaman KNS, Bahri M. Retinopathy of Prematurity. Georgetown: Emedicine; [updated 2009 jun 29; cited 2010 dec 31]. Available at: www.emedicine.medscape.com 7. Kanski JJ, Menon J. clinical ophthalmology. 5th ed. China: Elsevier Science; 2003; 439-86 8. Kaur B, Taylor D. Fundus hemorrhages in infancy. Surv Ophthalmol 1992;37:1-17 9. Carraro MC, Rossetti L, Gerli GC. Prevalence of retinopathy in patients with anemia or thrombocytopenia. Eur J Haematol 2001;67:238-44 10. Weiss LM. Anemic Retinopathy. Pa Med 1966 Jun;69(6):35-6 11. Motulsky AG. Frequency of sickling disorders in U.S. blacks. N Engl J Med 1973;288:31-3 12. Aisen et al. Retinal Abnormalities Assosiated With Anemia. Arch Ophthalmol. 1983 july;101:1049-52. Available at: www.archophthalmol.com 13. Kagan A, Aurell E, Tibblin G: Signs in the undus oculi and arterial hypertension: Unconventional assessment and significance. Bull WHO 1967;36:231-241 14. Merin S, Freund M: Retinopathy in severeanemia. Am J Ophthalmol 1968;66:1102-1106 15. Marshall RA: A review of lesions in the optic fundus in various diseases of the blood. Blood 1959;14:882-891 16. Foster RM: The incidence of retinal haemorrhages in severe anaemia. Trans R Soc Trop Med

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Hyg 1970;64:99-101

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