The three year COPE certification for this course has expired so it can no longer be used to obtain CE credits. No representation is made that the information included in the course is still valid or correct. The course is presented for reader interest only. No examination is available for this course.
It is estimated that 16 million Americans have diabetes mellitus, and as many as half of them are undiagnosed.(1) Because it is estimated that about 60% of diabetics have some manifestation of diabetic eye disease, it is not uncommon for the optometric physician to be the first practitioner to see signs or hear of symptoms that relate to diabetes.
Diabetes mellitus is the leading cause of death and disability in the United States for 20 - 74 year olds, and is the leading cause of new blindness in the U.S. for 20 - 64 year olds. In fact, diabetics have a 25 times greater risk of blindness than non-diabetics. Early diagnosis and appropriate intervention are essential to lessen the risk and severity of vision loss. Unfortunately, even patients who know they are diabetic often have not had their eyes examined. One study from 1984 indicated that between 26% and 32% of patients with diabetes had never had an eye examination.(2)
There are many ocular manifestations of diabetes, and they typically increase with age, duration of disease, and poor blood sugar control. Some of these manifestations do not increase the patientís risk of vision loss, and can be treated with supportive therapy. They include such things as color vision deficiencies, refractive error changes, accommodative dysfunction, sluggish pupillary reflexes, and iris depigmentation. Others, such as reduced corneal sensitivity and dry eye syndrome can increase the patientís risk for serious and sight threatening infection. Additional causes of vision loss in the diabetic include an increased incidence of cataracts, and primary open angle glaucoma. However, the most sight threatening condition is diabetic retinal disease, which can include neovascularization of the iris and retina, macular edema and ischemic optic neuropathy. The remainder of this article will emphasize diabetic retinopathy's diagnosis and treatment because it has been shown that its early treatment can prevent vision loss.(3)
The laboratory test of choice for diagnosing DM is measuring the fasting plasma glucose (FPG). In order to make a diagnosis of DM, the FPG must be ≥126mg/dl and the patient must have the classic signs of DM including increased hunger (polyphagia), increased thirst (polydipsia) and increased urination (polyuria). If the classic signs are not present, the fasting glucose result must be ≥126mg/dl at least two times.
Diabetes is classified as one of two types, a distinction that becomes important in determining the likelihood of vision loss. Type 1 diabetes is believed to be an autoimmune condition with destruction of the insulin producing islet cells in the pancreas. Its typical onset is before the age of 30, and accounts for 5 to 10% of DM cases. Patients with this disease have an absolute dependency on exogenous insulin and typically are acutely symptomatic at onset.
Type 2 diabetes typically has an onset after the age of 40, and is generally found in obese adults. Type 2 diabetes accounts for approximately 90% of DM cases. There tends to be a strong family history of DM and it represents a resistance of body tissues to insulin. These patients are often asymptomatic, so they may go undiagnosed for many years. Because of this, type 2 diabetics are more likely to have retinopathy at the time of diagnosis. The presence of type 2 diabetes is also more likely to be suspected by the optometric physician, when a routine examination shows the common ocular manifestations discussed above.
The examination should include at least all of the elements listed in Table 1.
Table 1: Eye examination for patients with diagnosed DM
An eye examination that includes dilation and stereoscopic evaluation of the fundus is necessary to rule-out ocular complications of diabetes. Dilation is very important because the detection and classification of diabetic retinopathy, which is the most common cause of permanent vision loss in the diabetic, will be correct in only 50% of eyes examined without dilation.(4)
It is important to understand the epidemiology of diabetic retinopathy (DR) to provide appropriate care and education for your diabetic patients. For patients with type 1 diabetes, diabetic retinopathy does not usually occur until at least 5 years after diagnosis. In addition, agents such as human growth hormone, tend to provide a protective effect and decrease the occurrence of vision-threatening diabetic retinopathy before puberty. For this reason, it is suggested that patients with type 1 DM do not need to receive their first ocular examination to rule-out diabetic retinopathy until 5 years after diagnosis. Yearly evaluations are then indicated, as the risk of developing DR increases with the duration of the disease. Type 1 diabetics who have had their disease for greater than 10 years after puberty have a 60% chance of manifesting retinopathy. Once the duration exceeds 15 years, 80-90% will have some form of retinopathy. Of patients who have had type 1 diabetics for more than 20 years, 50% will have proliferative diabetic retinopathy.(5)
As previously stated, type 2 diabetics are more likely to have diabetic retinopathy at initial diagnosis than type 1 diabetics, so they should be examined at the time of diagnosis and then yearly. Approximately 20% of type 2 patients will have some retinopathy at diagnosis. As the duration of diabetes increases, type 2 diabetics also experience an increased risk of developing diabetic retinopathy, but typically have less risk than a patient with type 1 diabetes of equal duration. Between 60 and 80% of type 2 diabetics will manifest retinopathy after 15 years, and only 20% will progress to proliferative retinopathy after 25 years of duration.(6)
Pregnancy increases the risks of developing or worsening diabetic retinopathy. For this reason, female patients of child-bearing age should be asked about pregnancy history as well as any plans for starting a family. Female patients should be examined prior to conception or early in the first trimester of pregnancy, and then at least every 3 months during the pregnancy. If the patient has severe DR at the initial examination, she may need to be examined each month.
The pathophysiology of diabetic retinopathy is not fully understood, but is related to plasma glucose levels. Some tissues in the body do not need insulin to move glucose into their cells. These tissues include the crystalline lens, blood vessel walls, nerves, and the kidneys. The excess glucose in the blood moves into the cells of these tissues and is often metabolized to sorbitol. Because sorbitol is a large molecule, it cannot diffuse out of the cells. This leads to an osmotic imbalance that causes the infusion of fluid into the cells and results in injury. In the eye, the intramural pericytes of retinal capillaries are affected, leading to weakening of the retinal capillary walls. This can lead to microaneurysm formation, the first clinically detectable lesion of DR.
Microaneurysms are saccular outpouchings of the retinal capillaries. Although they can be mistaken for dot hemorrhages, they are typically smaller, rounder and have more discrete edges than dot hemorrhages. Typically, a red spot that is less than 1/12 of a disc diameter in its longest diameter, and has sharp margins should be considered a microaneurysm. 1/12 of a disc diameter is about the width of the average major vein at the disc margin. Microaneurysms can be seen in Figure 1. Because they represent weakening of the capillary walls, they can be associated with retinal edema due to serum leakage from the vessels.
Hemorrhages are also an early sign of diabetic damage to blood vessels. It is common to see dot and blot hemorrhages that occur deeper in the retina, as well as the more shallow flame-shaped hemorrhages that follow the retinal nerve fiber layer. Dot and blot hemorrhages can be seen in Figure 1 and should be compared to the flame-shaped hemorrhages in the same figure.
Lipid is a component of the serum that leaks from vessels with damaged cell walls. This protein is too large to be reabsorbed by the normal walled vessels that reabsorb the fluid. Because of this, lipid is left in the retinal layers as hard exudates in long-standing retinal edema. Hard exudates are yellow and somewhat waxy in appearance and can be seen in Figures 1 and 2. When exudates appear in a circular pattern, it is common to find a microaneurysm in the center of the circle. Hard exudates that occur in the macular area indicate a poor prognosis for maintaining good visual function.
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| Fig. 1 | Fig. 2 |
Cotton-wool spots (CWS) are also known as soft exudates and are due to capillary occlusion in the retinal nerve fiber layer that interferes with axoplasmic flow. CWS indicate areas where the retina is not getting enough oxygen. A CWS appears as a white, soft edged area and are located in the superficial retina. A CWS can be seen and compared with hard exudates in Figure 2. Because the appearance of a CWS can change the classification of the severity of the DR, they are an important finding to note and differentiate from hard exudates.
Intraretinal microvascular abnormalities (IRMA) are enlarged channels of pre-existing blood vessels. They are formed due to poorly functioning or occluded capillaries which prevent normal blood flow. IRMA is often found close to a CWS, and tend to look like they are detouring vessels. IRMA can be mistaken for neovascularization, but IRMAís flat appearance and failure to leak on fluorescein angiography can be helpful in the differentiation. Although IRMA is not neovascularization, it is common for the development of neovascularization to start in an area of IRMA. An area of IRMA can be seen in Figure 3.
Venous changes can also occur in diabetic retinopathy. These changes appear as beading or sausage-like segmentation of the veins. They indicate that there is significant retinal hypoxia and are a very significant risk factor for progression to proliferative diabetic retinopathy (PDR). Venous beading can be seen in Figure 3 and 4.
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| Fig. 3 | Fig. 4 |
Neovascularization or new blood vessel growth can occur anywhere within the retina, but it is typically within the posterior pole. When it is at or within 1 disc diameter (DD) of the disc margin, it is called neovascularization of the disc (NVD). At other locations, it is known as neovascularization elsewhere (NVE). It is common for translucent fibrous tissue to be adjacent to the new blood vessels, and these fibrous tissues can adhere to the vitreous. This causes the more raised appearance of neovascularization compared to IRMA. Neovascularization is made up of weak, poorly formed blood vessels that can bleed easily. NVD typically bleeds more easily than NVE. NVD can be seen at the arrow in Figure 4 and NVE and vitreous hemorrhage can be seen within the circle in Figure 5. The occurrence of neovascularization increases the risk of visual loss in the diabetic patient.
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| Fig. 5 |
Macular edema is another common cause of visual loss in diabetics which is associated with hyperglycemia. Macular edema is a collection of of intraretinal fluid in the macular area of the retina. The macular edema is considered clinically significant if the center of the macula is involved or at risk. Retinal thickening is best seen with a dilated pupil and a contact fundus lens at the biomicroscope.
In order to determine the best treatment for a patient with diabetic retinopathy, it is important to classify the changes seen. The main classifications of diabetic retinopathy include nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and clinically significant macular edema (CSME). The goal of these classifications is to develop a simple method of grouping eyes with similar prognoses for the development of PDR. Guidelines for classification and treatment are based on the results of studies such as the Diabetic Retinopathy Study (DRS), the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetic Retinopathy Vitrectomy Study (RDVS). These studies used standard reference photos from the Arlie House Classification System to determine the level of diabetic retinopathy and developed general management recommendations based on the current classification of DR manifested by a patient. The most significant reference photos can be easily obtained from the American Optometric Association by requesting item SDC1, General Guidelines for the Management of Diabetic Retinopathy Chart. Alternatively, all of the reference photos can be seen on the web page of the Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences at the University of Wisconsin - Madison at: http://eyephoto.ophth.wisc.edu/ResearchAreas/Diabetes/DiabStds.htm
Nonproliferative diabetic retinopathy (NPDR) is divided into mild, moderate, severe and very severe gradings.(7) The extent of the common findings in DR such as intraretinal hemorrhages, microaneurysms, venous beading and IRMA determine the level of severity. These gradings are significant in that they indicate how likely the patient is to develop proliferative diabetic retinopathy. In fact, for each one-level increase, there is approximately double the risk of progression to proliferative diabetic retinopathy in one year. Proliferative diabetic retinopathy is divided into early and high-risk groups. The original gradings suggested by the ETDRS study have many levels and are quite complex. They can be found in the reports generated from that research.(8,9,10) Because the prognosis and treatment is similar for many of the original ETDRS classifications, most eyecare practitioners use a slightly compacted version for determining the level of diabetic retinopathy. A summary of the classifications delineated in the American Optometric Association (AOA) practice guidelines will be presented here.
In order for a patient to be classified as having mild NPDR, the patient must have at least one microaneurysm (MA) and one or more of the following findings: retinal hemorrhage, venous loops, or hard exudate. In order to classify as mild NPDR, the patientís fundus must show fewer diabetic changes than is found in standard photo 2A of the Airlie House Classification System, and must not have any characteristics that would allow classification as moderate or severe NPDR. An example of a fundus that would be classified as mild NPDR can be seen in Figure 6. Patients with mild NPDR and no macular edema typically require no further testing. They can be seen yearly, unless they are pregnant, planning to become pregnant, or controlling their blood sugar very poorly.
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| Fig. 6 |
Moderate NPDR is indicated by hemorrhages or microaneurysms more pronounced than standard photo 2A. In addition, the occurrence of soft exudates, venous beading or IRMAís also lead to a classification of moderate NPDR. An example of a fundus that would be classified as moderate NPDR, primarily due to venous beading, can be seen in Figure 7. Moderate NPDR with no macular edema should have fundus photos taken and are typically re-evaluated in 6 - 8 months. The presence of edema in the macular area, which does not meet the definition of clinically significant macular edema, indicates the need for fundus photography in patients with both mild and moderate NPDR. These patients should be seen again in no longer than 4 ñ 6 months.
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| Fig. 7 |
Severe NPDR represents an increase in the amount of ischemia present in the eye. It is indicated by evaluating the four midperipheral retinal quadrants using the "4-2-1" rule. The presence of any one of the following indicates severe NPDR:
An example of a fundus that would be rated as severe NPDR because it has hemorrhages and microaneurysms greater than standard photo 2A can be seen in Figure 8. If two of the features of severe NPDR are present, the retinopathy should be classified as very severe NPDR. An example of a fundus appearance that would be classified as very severe NPDR can be seen in Figure 9. This patient has IRMA > standard photo 8A as indicated by the arrow and VB > standard photo 6B in two quadrants. Patients with severe NPDR have a substantial risk of developing PDR. There is a 52% risk of developing PDR in 1 year with15% being classified as high-risk PDR. For patients with very severe NPDR, the risk of developing PDR within one year is 75%, with 45% being high-risk.(7) Because patients with severe and very severe NPDR have a similar risk of developing high risk PDR they should be managed in similar fashions, and followed closely, as often as once every 2-3 months. It is important to note that it may be appropriate to perform scatter (pan-retinal) photocoagulation on some of these patients, especially type 2 diabetics for whom close follow-up is impractical. Consideration should be given to focal laser treatment if macular edema is present, even if it is not clinically significant. This is because studies have shown that PRP can cause a worsening of macular edema, and focal laser treatment prior to PRP may prevent visual acuity loss. As in patients with moderate NPDR, focal laser treatment of the macula should be considered prior to PRP as it may help maintain visual acuity.
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| Fig. 8 | Fig. 9 |
As alluded to above, proliferative diabetic retinopathy (PDR) is most often classified into one of two categories: early (non-high risk) or high risk. The extent and location of new blood vessel growth, as well as the occurrence of pre-retinal and vitreous hemorrhages help differentiate these two classifications. Patients with early PDR may have neovascularization in the retina or the disc, as well as vitreous hemorrhages. However, none of the characteristics of high-risk PDR can be present. If any one or more of the following characteristics is present, the PDR must be classified as high-risk:
High-risk PDR needs to be referred with in 24-48 hours to an ophthalmologist with experience in dealing with diabetic retinopathy. Although not included in the category of high-risk PDR, the occurrence of neovascularization of the iris also indicates the need for scatter photocoagulation. Figure 10 shows non-high-risk PDR because of the occurrence of NVE < 1/2 DA as seen within the black circle. Figure 11 shows high-high risk PDR.
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| Fig. 10 | Fig. 11 |
The occurrence of macular edema can influence the appropriate management of the diabetic patient. As discussed previously, retinal thickening that is not in the center of the macula and not a threat to the center of the macula is not considered clinically significant. The edema is considered to be clinically significant macular edema(CSME) if one or more of the following is present:
Figure 12 shows a fundus with CSME due to the hard exudates with retinal thickening inferior temporal to the macula.
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| Fig. 12 |
As can be seen in Table 2, the occurrence of macular edema always suggests the need to document with fundus photography. The occurrence of macular edema also tends to shorten the follow-up time in NPDR. In addition, whenever macular edema is present, a retinal consult should be obtained. This should be done within 2-4 weeks for all classifications of DR except high-risk PDR. In high-risk PDR the retinal consult should be obtained in 24-48 hours for both types of macular edema. The risk of visual loss is reduced by more than 50% for patients who receive appropriate laser treatment, compared to controls.(11)
General management guidelines as suggested by the American Optometric Association Clinical Practice Guidelines and the American Academy of Ophthalmology Preferred Practice Patterns can be found in Table 2. The most conservative recommendation from either source is summarized in the table, however, you should consult these references for more detailed information. The full text of the AOA practice guideline on the Care of the Patient with Diabetes Mellitus can be found at http://aoanet.org. Once at this site navigate to the section on clinical care guidelines. The full text of the Diabetic Retinopathy Preferred Practice Pattern (PPP) Ophthalmology Monograph 14 is available to AAO members at http://www.aao.org/aaoweb1/oec/432.cfm
| Classification | Photography | Fluorescein Angiography |
Retinal Consult |
Follow-up (Months) |
Focal Laser Treatment |
Scatter Laser Treatment |
| No DR or Mild NPDR without ME |
No | No | No | 12 | No | No |
| Mild NPDR with Non-CSME |
Yes | Occ. | 2- 4 weeks | 4-6 | No | No |
| Mild NPDR with CSME |
Yes | Yes | 2- 4 weeks | 2-4 | Yes | No |
| Moderate NPDR without ME |
Yes | No | No | 6-8 | No | No |
| Moderate NPDR with Non-CSME |
Yes | Occ | 2- 4 weeks | 4-6 | No | No |
| Moderate NPDR with CSME |
Yes | Yes | 2- 4 weeks | 2-4 | Yes | No |
| Severe or Very Severe NPDR without ME |
Yes | Occ | 2- 4 weeks | 3-4 | No | Rarely |
| Rarely Severe of Very Severe NPDR with Non-CSME |
Yes | Occ | 2- 4 weeks | 2-3 | Occ | Occ after focal |
| Severe or Very Severe NPDR with CSME |
Yes | Yes | 2- 4 weeks | 2-3 | Yes | Occ after focal |
| Non-high-risk PDR without ME |
Yes | Occ | 2- 4 weeks | 2-3 | No | Occ Non-high-risk |
| PDR with Non-CSME |
Yes | Occ | 2- 4 weeks | 2-3 | Occ | Occ after focal |
| Non-high-risk PDR with CSME |
Yes | Yes | 2- 4 weeks | 2-3 | Yes | Occ after focal |
| High risk PDR without ME |
Yes | Occ | 24 - 48 hours | 2-3 | No | Yes |
| High-risk PDR with Non-CSME |
Yes | Yes | 24 - 48 hours | 1-2 | Usually | Yes |
| High-risk PDR with CSME |
Yes | Yes | 24 - 48 hours | 1-2 | Yes | Yes |
*Please see full text of guidelines as described above for specifics.
When laser treatment is deemed necessary, the patient should be informed of the risks and benefits of the procedures. They should understand that the goal of laser treatment is to reduce the rate of visual loss, and not to improve vision. It is also important to let the patient know that more than one treatment session is typically required to achieve the desired treatment. The patient will typically be followed every 1- 4 weeks until scatter photocoagulation is complete. For focal laser treatment of macular edema, the treatments are typically given 2-4 months apart.
Although this article has emphasized the diagnosis and treatment of diabetic retinopathy, it is important to realize that the comprehensive eye examination can reveal many other ocular effects due to diabetes about which the practitioner should be aware, and able to manage appropriately. Such things as dry eye, reduced corneal healing, accommodative dysfunction, poor pupil responses and cataracts are quite commonly found and should be treated appropriately. Treatment should include supportive measures and education. For instance, the patient who is manifesting muscle paralysis should be evaluated to rule-out other causes and then informed that when the condition is cause by DM it usually resolves by itself in 3- 6 months. These patients should be educated on options to decrease diplopia, including prisms and patching. Conditions such as glaucoma are typically treated aggressively as they can cause permanent vision loss.
It is vitally important to provide your patient with complete education about DM and its visual complications. Patients should be informed that DR often occurs without the patient experiencing any symptoms, and that regular eye examinations can save vision because these examinations allow early diagnosis and appropriate treatment. It is important to let the patient know that appropriate treatment may be 90% effective in preventing severe vision loss (defined as VA < 5/200).(3)
Complete discussions on the importance of controlling blood sugar and systemic conditions such as hypertension and serum lipid levels for maintaining good vision should also be included. Patients should be informed that studies show the development and progression of DR can be delayed with good blood sugar control. In fact, the long term risk of progression is five times lower in type 1 DM patients who maintain good blood sugar control.(12) Studies have also shown that the risk of developing moderate vision loss is higher for patients with elevated levels of serum cholesterol. Additionally, patients should be urged to quit smoking, as studies show that smoking is associated with an increased risk of loss of vision due to DR.
Finally, make sure that you provide the patient's primary care doctor with information about the results of your examination. This step will improve the overall care that is given to the diabetic patient, and increase their chances of maintaining usable vision.
To provide optimal patient care, it is crucial for the optometric physician to understand the manifestations of diabetic retinopathy. Understanding the risks of progression and the treatment indicated by each classification of DR is also vital. To provide the best treatment it is important that the optometric physician provide patient education about the need for regular follow-up, the need for good blood sugar control and the need for treatment of systemic conditions that can influence the occurrence of diabetic retinopathy. It is also necessary to work with the patient's primary care provider to improve the management of this disease. Only by providing this optimal care will the optometric physician be doing his or her best to prevent visual loss from diabetes mellitus.
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