Improving the Identification and Care of Patients with Diabetic Retinopathy – A Clinical Exchange Program for Optometrists
RELEASE DATE: July 31, 2018
EXPIRATION DATE: July 19, 2021
Steven Ferrucci, OD
Chief, Optometry Section
Sepulveda VA Medical Center
Southern California College of Optometry
Coordinator, Primary Eye Care
Department of Veterans Affairs Residency
Victor Gonzalez, MD
Medical Director and Founder
Valley Retina Institute, PA
Clinical Assistant Professor
University of Texas Health Science Center at San Antonio
San Antonio, Texas
Clinical Assistant Professor
University of Texas Health Science Center at Houston
LEARNING METHOD AND MEDIUM
This educational activity consists of a supplement and ten (10) study questions. The participant should, in order, read the learning objectives contained at the beginning of this supplement, read the supplement, answer all questions in the post test, and complete the Activity Evaluation/Credit Request form. To receive credit for this activity, please follow the instructions provided on the post test and Activity Evaluation/Credit Request form. This educational activity should take a maximum of 1.0 hour to complete.
This continuing education (CE) activity captures content from a regional dinner meeting series.
By 2030, approximately half of all Americans will have diabetes (55 million) or prediabetes (108 million), and approximately half of those will have some form of diabetic retinopathy (DR). Early recognition of DR by optometrists often precedes a diagnosis of diabetes and is critical for the preservation of sight in affected patients. Recognition of risk factors for diabetes can enable early identification of patients at high risk for DR. Staging criteria for DR have been developed to inform a decision on when to refer patients to a retina specialist vs when patients can be safely managed in the optometry practice. Recently completed clinical trials have led to a US Food and Drug Administration–approved treatment specifically for DR, and informed discussion of treatment options among optometrists, patients, and retina specialists enhances the quality of care. The purpose of this activity is to provide optometrists with current strategies needed to recognize patients at risk for diabetes and DR, identify patients at early stages of disease, and confidently make referral for possible treatment; and to discuss evidence-based treatment options with both retina specialists and patients.
This educational activity is intended for optometrists.
Upon completion of this activity, participants will be better able to:
- Recognize the risk factors for diabetes in patients presenting for routine eye examinations
- Discuss the importance of early diagnosis of DR in patients with diabetes
- Identify when to refer patients to a retina specialist for further evaluation
- Describe current and emerging treatments for DR to patients with diabetes
- Discuss evidence-based prevention and treatment strategies for DR with retina specialists
COPE approved for 1.0 CE credit for optometrists.
COPE COURSE ID: 58710-PS
COPE COURSE CATEGORY: Treatment & Management of Ocular Disease: Posterior Segment (PS)
Steven Ferrucci, OD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Annidis Corporation; Bausch & Lomb Incorporated; CenterVue SpA; MacuLogix, Inc; and Shire; Honoraria from promotional, advertising or non-CME services received directly from commercial interests or their Agents (eg, Speakers Bureaus): Alcon; and Optovue, Incorporated.
Victor Gonzalez, MD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Alcon; Alimera Sciences; Allergan; Bausch & Lomb Incorporated; Bayer AG; Genentech, Inc; PanOptica; Regeneron Pharmaceuticals, Inc; ThromboGenics NV; and Valeant; Contracted Research: Alcon; Alimera Sciences; Allegro Ophthalmics, LLC; Allergan; Astellas Pharma Europe Ltd; Clearside Biomedical, Inc; EyeGate; Genentech, Inc; Iconic Therapeutics, Inc; Merck & Co., Inc; Ohr Pharmaceutical; Ophthotec Corporation; PanOptica; Regeneron Pharmaceuticals, Inc; Santen Pharmaceutical Co, Ltd; ThromboGenics NV; and Valeant; Ownership Interest (Stock options, or other holdings, excluding diversified mutual funds): Alimera Sciences; and PanOptica.
EDITORIAL SUPPORT DISCLOSURES
The staff of MedEdicus have no relevant commercial relationships to disclose.
The contributing physicians listed above have attested to the following:
1) that the relationships/affiliations noted will not bias or otherwise influence their involvement in this activity;
2) that practice recommendations given relevant to the companies with whom they have relationships/ affiliations will be supported by the best available evidence or, absent evidence, will be consistent with generally accepted medical practice; and
3) that all reasonable clinical alternatives will be discussed when making practice recommendations.
PRODUCT USAGE IN ACCORDANCE WITH LABELING
Please refer to the official prescribing information for each drug discussed in this activity for approved indications, contraindications, and warnings.
This continuing education activity is supported through an unrestricted educational grant from Genentech, Inc.
TO OBTAIN CE CREDIT
We offer instant certificate processing and support Green CE. Please take this post test and evaluation online by clicking the Take Test button at the end of this activity. Upon passing, you will receive your certificate immediately. You must answer 7 out of 10 questions correctly in order to pass, and may take the test up to 2 times. Upon registering and successfully completing the post test, your certificate will be made available online and you can print it or file it. Please make sure you take the online post test and evaluation on a device that has printing capabilities. There are no fees for participating in and receiving CE credit for this activity.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of MedEdicus LLC; Genentech, Inc; or Review of Optometry.
This CE activity is copyrighted to MedEdicus LLC ©2018. All rights reserved. 152
Table 1. Risk Factors for Diabetes Mellitus5-7
Specific Ethnic Backgrounds
Pertinent Medical History
Ocular complications of diabetes mellitus (DM) account for a large proportion of vision loss in the United States, and the prevalence of DM is rising rapidly. In just a few years, there will be more than 40 million people with DM in the United States1; 40% to 45% of them will have some form of diabetic eye disease—either diabetic retinopathy (DR), diabetic macular edema (DME), or both.2 In fact, diabetic eye disease is the leading cause of vision loss and new-onset blindness in working Americans aged 20 to 74 years.2 Recognizing DM and diabetic eye disease will be an increasingly important clinical task for optometrists in the coming years. Vision loss from DM can be prevented, and optometry is at the forefront of prevention. The best strategy for preserving vision is the prevention of DR, which can be accomplished by understanding and managing the many aspects of DM that contribute to vasculopathy and tissue damage. Equally important is the detection of DR because both DR and DME can be treated, thereby saving vision. In this educational activity, the risk factors for DM in patients presenting for routine eye care will be discussed, strategies for the detection of DR will be reviewed, novel therapies for DR will be described, optimal referral practices for DR care will be clarified, and the optometrist's role in preventing vision loss from DR will be delineated.
The Diabetes Epidemic
The prevalence of DM has reached epidemic proportions. More than 30 million people in the United States currently have DM,3 whereas another 84 million have prediabetes and are at risk of developing the disease.3 By 2020, 43 million people in the United States will have DM, and by 2030, approximately half of all Americans will have DM (55 million) or prediabetes (108 million).1
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. There are several types of diabetes.4 Type 1 diabetes arises from the destruction of insulin-producing beta cells in the pancreas, leading to an absolute deficiency of insulin. Type 2 diabetes is characterized as a progressive insulin secretory defect on the background of insulin resistance. Diabetes can also arise during pregnancy (gestational diabetes), and existing diabetes can be more refractory to treatment during pregnancy. Together, these conditions share a final common pathway of chronic hyperglycemia that leads to both microvascular and macrovascular complications, as discussed subsequently.
There are many known risk factors for DM, including a family history of DM, a sedentary lifestyle, and certain ethnicities, such as African American, Native American, Hispanic, Asian American, and Pacific Islander (Table 1).5-7 In addition, several comorbid medical conditions increase the risk of DM, such as obesity, cardiovascular disease, hypertension, hypercholesterolemia, sleep apnea, and smoking.
|Figure 1. Systemic comorbidities associated with diabetes8-12
Click image to enlarge
Diabetes is associated with several other serious systemic conditions that arise as complications of the disease (Figure 1).8-11 These include microvascular diseases, such as DR, diabetic nephropathy, and diabetic neuropathy, as well as macrovascular diseases, such as coronary heart disease and stroke.12 The concurrence of these serious and potentially life-threatening diseases underscores the importance of timely diagnosis and treatment of diabetes in affected individuals. Many patients will have DR before they are diagnosed with diabetes13; thus, the optometrist can play an integral role in the diagnosis of systemic diabetes.
Spectrum and Pathophysiology of Diabetic Retinopathy
The primary pathophysiologic insult in microvascular complications of DM, including DR, is to the small blood vessels of the body.14 High intravascular concentrations of glucose damage the pericytes—the small support cells that line the microvasculature and help maintain its health and function. In the eye and other tissues, glucose-mediated damage to retinal microvascular pericytes can lead to vasoconstriction, thickening of the capillary wall basement membrane, and, ultimately, tissue ischemia.
Diabetic retinopathy is generally classified as nonproliferative or proliferative, according to the absence or presence of new blood vessels growing in response to chronic ocular ischemia. In its early stages, DR is nonproliferative (Figure 2). The primary site of damage in DR is the retinal capillaries. Early loss of retinal capillary pericytes causes weakening of capillary walls. Focal loss of capillary support can give rise to outpouchings in the capillaries, which are called microaneurysms. Weakened capillaries can also rupture, leading to retinal dot/blot hemorrhages and, upon resorption of blood, residual lipid accumulations in the retinal tissue, which are seen as hard exudates. These microvascular insults contribute to tissue nonperfusion and hypoxia in capillary beds that can cause focal retinal ischemia, which is seen as cotton wool spots. In some cases, shunt vessels will develop to supply areas of nonperfused retina; these are called intraretinal microvascular abnormalities (IRMAs).
|Figure 2. Moderate nonproliferative diabetic retinopathy with microaneurysms, dot/blot hemorrhages, hard exudates, cotton wool spots, and intraretinal microvascular abnormalities
Image courtesy of Steven Ferrucci, OD
Click image to enlarge
In 2003, the Global Diabetic Retinopathy Project Group developed a classification scheme to grade the severity of DR (Table 2).15 Under this rubric, nonproliferative DR (NPDR) is classified as mild, moderate, or severe according to the severity of the classic NPDR lesions described previously. Mild NPDR is typically characterized by the presence of microaneurysms only. Severe NPDR follows a 4-2-1 rule: more than 20 intraretinal hemorrhages in each of the 4 quadrants; venous beading in 2 or more quadrants; or prominent IRMAs in 1 or more quadrants; and no signs of proliferative DR. Moderate NPDR falls between mild and severe, with more than just microaneurysms but less than severe NPDR. The presence of cotton wool spots, mild venous beading, or mild IRMAs can also be used to classify NPDR as moderate, so long as these features do not satisfy the 4-2-1 rule for severe NPDR.
At the time of DM diagnosis, approximately 20% to 30% of patients with DM will have some form of NPDR. After living with the disease for 15 or more years, most patients (approximately 80%-97.5%) will have NPDR.16,17 Untreated NPDR can lead to proliferative DR (PDR). Ischemic tissues in eyes with NPDR release vascular endothelial growth factor (VEGF), a potent angiogenic molecule that triggers the growth of new blood vessels in an effort to restore tissue perfusion.18 Neovascularization of the retina in a diabetic eye heralds the onset of PDR. Neovascularization might occur on the surface of the optic disc or elsewhere in the retina (Figure 3). In the classification rubric described previously, PDR is described as neovascularization of the retina, vitreous/preretinal hemorrhage, or both.15 PDR poses a greater threat to vision than does NPDR. As blood vessels grow in response to VEGF release in eyes with PDR, fibrous tissue accompanies vascular tissue growth. These vessels are fragile and prone to leak and rupture, causing significant retinal and vitreal hemorrhages. As the fibrovascular tissues proliferate, they create traction within the retina that can lead to retinal tears and detachments. At the time of DM diagnosis, PDR is uncommon, but after living with DM for 15 or more years, 15.5% to 25% of eyes will develop PDR.16,17
|Table 2. Classification of Diabetic Retinopathy Severity by Findings15|
|Disease Severity Level||Findings Observable on Dilated Ophthalmoscopy
|No apparent retinopathy
|Mild nonproliferative diabetic retinopathy
|Moderate nonproliferative diabetic retinopathy
||More than just microaneurysms; may include cotton wool spots, mild venous beading, or mild intraretinal microvascular abnormalities, but not satisfy the 4-2-1 criteria for severe nonproliferative diabetic retinopathy
|Severe nonproliferative diabetic retinopathy
Any of the following:
And no signs of proliferative retinopathy
|Proliferative diabetic retinopathy
||Neovascularization and/or vitreous/preretinal hemorrhage
In addition to DR, another form of diabetic eye disease is DME. In addition to its angiogenic activity, VEGF is also a potent vascular permeability factor and causes retinal capillaries to become leaky.18 Fluid escaping from these capillaries collects within the retinal tissue of the macula, leading to edema. DME can occur in eyes with or without other forms of DR19 and is a common cause of vision loss in people with DM. At the time of DM diagnosis, only 3% of people will have DME, but after living with DM for 20 or more years, approximately 30% of people will develop DME.20
Treatment Options for Diabetic Retinopathy
The single most important strategy for treating DR is prevention. Systemic microvascular complications of DM can be prevented by adequately controlling blood glucose levels.21 The American Diabetes Association defines treatment goals as blood glucose levels of 70 to 130 mg/dL before meals and up to 180 mg/dL after meals.22 Hemoglobin A1c (HbA1c) is a long-term indicator of blood glucose control and should ideally be maintained below 7% in most patients. More intense glucose control (HbA1c < 6.5%) can be reasonable for young, otherwise healthy patients. Less intense therapy (HbA1c of 7.5%-8.5% or higher) can be appropriate for older or less healthy patients.22
Once DR is present, the approach shifts from prevention to treatment. Historically, DR was treated with laser photocoagulation, but in the anti-VEGF treatment era, pharmacologic interventions became available to treat DR with or without DME while avoiding thermal collateral damage to retinal tissue (Figure 4).23-29
Pharmacologic therapy for DR is directed at inhibiting the vasoproliferative and vascular permeability activities of VEGF, the principal driver of PDR. Anti-VEGF drugs were initially developed for the treatment of systemic solid tumors and were first used in eye care to treat age-related macular degeneration. The first use of an anti-VEGF drug to treat PDR was reported in 2006.24 Since then, 2 drugs—ranibizumab and aflibercept—have been approved by the US Food and Drug Administration to treat various forms of DR. Aflibercept is approved for the treatment of DME and DR in eyes with DME,26,28 whereas ranibizumab is approved for the treatment of all forms of DR.29 A third VEGF inhibitor—bevacizumab—has not been approved by the US Food and Drug Administration to treat DR, but is often used off-label for this indication.30,31
|Figure 3. Proliferative diabetic retinopathy with neovascularization
Image courtesy of Steven Ferrucci, OD
Click image to enlarge
The role of anti-VEGF therapy to treat DR was first suggested by observations made in the RISE and RIDE registry trials, which evaluated ranibizumab for the treatment of DME.32 To more robustly evaluate the role of ranibizumab in treating DR, the Diabetic Retinopathy Clinical Research Network (DRCRnet) implemented Protocol S, which compares ranibizumab with panretinal photocoagulation (PRP) for the treatment of DR.33 In this study, 394 eyes with PDR were randomized to receive ranibizumab 0.5 mg for up to every 4 weeks or PRP to assess the effect of treatment on visual acuity at 2 years using a noninferiority analysis. After 2 years of therapy, ranibizumab-treated eyes gained a mean of 2.8 ETDRS (Early Treatment Diabetic Retinopathy Study) letters and PRP-treated eyes gained a mean of only 0.2 ETDRS letters (P < .001) (Figure 5). Several secondary outcomes were assessed. The ranibizumab group had less peripheral vision loss (-23 dB vs -422 dB; P < .001), a lower vitrectomy rate (4% vs 15%; P < .001), and a lower rate of DME development (9% vs 28%; P < .001) than the PRP group. Ocular inflammation was more common in the PRP group than in the ranibizumab group (4% vs 1%; P = .02). One eye in the ranibizumab group developed endophthalmitis. The rates of major cardiovascular events were comparable between the 2 groups.
Post hoc analysis of the VIVID and VISTA trials evaluating aflibercept for the treatment of DME also suggested improvement of DR.34 This improvement led to the CLARITY study, which was designed specifically to evaluate aflibercept's effect on PDR.35 In this study, eyes with PDR received either aflibercept 2 mg monthly for 3 months and then as needed or PRP as needed, and were followed for 12 months. At 12 months, aflibercept-treated eyes gained an average of 1.1 ETDRS letters, whereas PRP-treated eyes lost an average of 3.0 letters (P < .0001). Visual disturbances (9% in each group) and inflammation (3% with PRP and 8% with aflibercept) were the most common adverse events.
Case reports and small retrospective studies of patients treated with off-label bevacizumab for PDR have also been reported.36 In these studies, best-corrected visual acuity stabilized or improved, central macular thickness improved, and retinal neovascularization regressed.
|Figure 4. The history of therapy for diabetic retinopathy23-29
Abbreviations: DME, diabetic macular edema; DR, diabetic retinopathy; PDR, proliferative diabetic retinopathy; VEGF, vascular endothelial growth factor.
Click image to enlarge
A head-to-head trial of all 3 anti-VEGF agents (ranibizumab, aflibercept, bevacizumab) was conducted by the independent DRCRnet to evaluate the effects on both DME and DR.30,37 In this study (Protocol T), monthly injections with ranibizumab 0.3 mg, aflibercept 2 mg, or bevacizumab 1.25 mg were given for 24 months. Outcomes at 1 year differed significantly between the ranibizumab and aflibercept groups and between the bevacizumab and aflibercept groups, depending on baseline visual acuity,38 but at 2 years, no significant difference between ranibizumab and aflibercept was seen.30 In eyes with better baseline visual acuity (20/32-20/40), mean visual acuity gains from baseline were 8.6, 7.8, and 6.8 letters with ranibizumab, aflibercept, and bevacizumab, respectively (differences not significant). In eyes with worse baseline visual acuity (20/50 or worse), mean gains were 16.1, 18.1, and 13.3 letters, respectively; only the aflibercept-bevacizumab difference was significant (P = .02).30 In the same study, improvement in DR severity was seen in 31%, 24.8%, and 22.1% of eyes receiving ranibizumab, aflibercept, and bevacizumab, respectively, at 24 months.37 Increased intraocular pressure (16%, 17%, and 12%), vitreous hemorrhage (5%, 7%, and 8%), and inflammation (2%, 3%, and 1%) were the most common ocular adverse events observed in the ranibizumab, aflibercept, and bevacizumab, treatment groups, respectively.30
Several clinical trials have demonstrated that individuals with untreated or laser-treated NPDR are at a high risk of progression to PDR.32,39,40 Because there is no current treatment mandate for NPDR, the DRCRnet is currently conducting a study (Protocol W) to investigate the safety and efficacy of prompt anti-VEGF treatment vs observation (sham injection) in eyes with severe NPDR and no center-involved DME.41 The primary outcome measure will be the proportion of patients developing PDR, PDR-related outcomes, or center-involved DME at 2 years. Similarly, the ongoing PANORAMA study is evaluating treatment of moderate and severe NPDR with aflibercept vs sham injection.42 The primary outcome measure is improvement by ≥ 2 steps from baseline on the Diabetic Retinopathy Severity Scale score at weeks 24 and 52.
|Figure 5. Visual acuity changes over time in the ranibizumab and panretinal photocoagulation arms of Protocol S33
Reproduced with permission from JAMA. 2015. 314(20): 2137-2146. Copyright©2015 American Medical Association. All rights reserved.
Click image to enlarge
Diagnosing Diabetic Retinopathy
Because DR can be treated, its recognition and diagnosis is important. A careful, comprehensive clinical eye examination is often all that is needed to detect the various forms of DR. For this reason, the American Diabetes Association recommends routine eye examinations—including a dilated fundus examination—annually in all patients with diabetes.22 The use of a handheld condensing lens at the slit lamp provides adequate magnification to see microaneurysms, dot/blot hemorrhages, and other DR lesions within the posterior pole through a dilated pupil. Fundus photography can also be a useful adjunct to the clinical examination. Both mydriatic and nonmydriatic cameras can obtain excellent images of the posterior pole and, in some cases, the peripheral retina. In cases of suspected DME (eg, in eyes with decreased central visual acuity and/or blunting of the foveal reflex on clinical examination), optical coherence tomography imaging of the macula can often reveal subtle intraretinal fluid pockets. Ultrawide field retinal imaging can also play a role in DR detection.43 Retinal images as wide as 200° can be obtained through an undilated pupil, capturing approximately 82% of the retina. A high-resolution wide-field image can often reveal peripheral DR even in eyes with little or no posterior pole DR (Figure 6).
Eyes with predominantly peripheral DR lesions may be at increased risk of future DR progression.44 One drawback to this technology is that up to 10% of eyes cannot be adequately imaged.45 Imaging is an excellent way to document clinical findings and can serve as a powerful educational tool for patients to better understand their disease and the need for active management, but photography alone should not replace a thorough dilated clinical examination.
When to Watch and When to Refer
Diabetic retinopathy is treatable, but not every case requires treatment. Many cases of DR are mild, pose no threat to visual acuity, and can be safely observed over time. Other cases might pose an imminent threat to, or already affect, visual acuity. What is the appropriate referral point? The American Optometric Association has developed guidelines to assist in this decision-making process (Figure 7).46 In general, if clinical signs of DR are identified in a patient not currently diagnosed with diabetes, the patient should be referred to a primary care provider or an endocrinologist. Likewise, if a patient with known diabetes is failing to meet metabolic targets (eg, blood glucose levels, weight loss, and dietary adherence), referral to the primary care provider or endocrinologist can be of value.
|Figure 6. Wide-field image showing peripheral hemorrhages, with no detectable diabetic retinopathy at the macula
Image courtesy of Steven Ferrucci, OD
Click image to enlarge
Most cases of NPDR can be safely observed. The natural history of DR has been comprehensively characterized in a well-designed longitudinal study (Wisconsin Epidemiologic Study of Diabetic Retinopathy).47 Patients with DM who have no DR at the time of initial examination have an approximately 35% to 50% chance of developing NPDR within 4 years. Approximately 25% to 35% of patients with NPDR will progress to worse NPDR over 4 years. Of patients who do not have PDR at the initial visit, 2% to 7% will develop PDR over a 4-year period.
Cases of severe NPDR should be referred to a retina specialist for evaluation and possible treatment. All cases of definite and suspected PDR and DME should also be referred for evaluation and treatment. Any case in which the diagnosis is unclear or in which the optometrist is not completely comfortable with the examination, diagnosis, or prognosis should be referred.
When referring a patient to a retina specialist, communication is critically important. A letter should precede or accompany the patient that clearly describes the following: the level of retinopathy seen on examination; a comparison of current examination findings to past examination findings, if applicable (including copies of imaging studies, if obtained); the duration of diabetes; the current level of systemic disease control (eg, blood glucose level and HbA1c); current diabetes therapy; and the specific concerns that prompted the referral. In return, the retina specialist should communicate to the optometrist the relevant findings on clinical examination, the definitive diagnosis, the treatment and follow-up plan, and copies of any imaging studies obtained.
The Optometrist's Role in the Management of Diabetic Retinopathy
Given that optometry is at the forefront of comprehensive eye care in the United States, optometrists can have a significant effect on the burden of DR and DR-related vision loss. There are several key roles for these clinicians in addressing DR.
|Figure 7. Guidelines for the referral of patients with known or suspected diabetes mellitus and/or diabetic retinopathy46
Abbreviations: DM, diabetes mellitus; DME, diabetic macular edema; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.
Click image to enlarge
1. Make the Diabetes Mellitus Diagnosis
At least 40% of people with DM in the United States will have clinical signs of DR before their systemic condition is diagnosed.2 If signs of DR are seen in a patient who does not report a diagnosis of DM, careful consideration should be given to the differential diagnosis. Conditions that resemble DR include retinal vein occlusions, hypertensive retinopathy, radiation retinopathy, ocular ischemic syndrome, HIV (human immunodeficiency virus) retinopathy, and retinopathies associated with hemoglobinopathies, including sickle cell disease. A careful history and examination can effectively rule out many of these entities. Consultation with the patient's primary care physician is warranted for systemic evaluation, definitive diagnosis, and management of systemic disease.
2. Encourage Achievement of Metabolic Goals
Every encounter with a patient with diabetes is an opportunity to reinforce the importance of a healthy diet, physical activity, and adherence to systemic diabetes therapy. Achievement and maintenance of metabolic goals—control of blood sugar, blood pressure, lipids, and other key parameters—is the surest way to prevent microvascular complications of DM, including DR.
3. Make the Diabetic Retinopathy Diagnosis
To make the diagnosis of DR, the optometrist must possess the clinical skills to recognize DR on examination. Familiarity with the clinical findings of DR and expertise in the examination techniques necessary to identify DR are essential. There are additional barriers to the diagnosis of DR as well. Despite the recommendations from virtually all diabetes and eye care societies that all patients with diabetes should undergo a yearly dilated eye examination,5,22,46,48 approximately 30% to 50% of US adults with DM do not obtain these examinations.36 Improving adherence to the annual examination guidelines will require performance improvement on the parts of primary care providers, endocrinologists, optometrists, ophthalmologists, and patients. Optometrists can improve the rate of annual eye examinations by encouraging and motivating patients with diabetes to keep their annual eye examination appointments. Of those who do seek annual evaluations by their optometrists, approximately 15% do not undergo a dilated eye examination.37 Optometrists can thus improve adherence to guidelines by ensuring that all patients with diabetes are dilated for their annual eye examinations.
4. Refer Appropriately
The optometrist should be able to identify and stage DR. Mild and moderate NPDR can be typically observed without treatment and reevaluated every 6 to 12 months,5 whereas severe NPDR, PDR, and DME require prompt referral to a retina specialist for treatment.
|Figure 8. Fundus photographs of the patient presented in the case
Images courtesy of Steven Ferrucci, OD
Click image to enlarge.
A 60-year-old male with a 12-year history of type 2 DM was last seen 5 years ago with mild NPDR in both eyes before being lost to follow-up. He now presents with 20/20 visual acuity in both eyes. Upon examination, however, several intraretinal hemorrhages, some venous beading, and white cotton wool spots are discovered (Figure 8).
This patient presents for follow-up after an intervening untreated period of 5 years. Despite having 20/20 vision, he seems to have progressed rapidly during this time, so his disease would now be classified as severe NPDR. This patient is a good example of someone who should be referred to a retina specialist for treatment. With his retinal changes, his vision is not likely to remain 20/20 for very long. His risk of progressing to PDR and/or DME is quite high, as evidenced by the outcomes of untreated cohorts in clinical trials.32,34
Over the next decade, approximately 50% of American adults will have or be at risk for DM and its attendant complications. At least 40% of people diagnosed with DM will already have some form of DR, and as many as 80% will have DR after living with the disease for 15 or more years. Diabetic retinopathy and other microvascular complications of DM arise from vascular toxicity of hyperglycemia, leading to capillary nonperfusion, local tissue ischemia, and activation of the VEGF-mediated angiogenesis pathway. Diabetic retinopathy is classified as nonproliferative or proliferative. Mild and moderate NPDR can usually be safely observed without treatment; severe NPDR and PDR warrant treatment. Likewise, DME can occur in eyes with or without DR. Diabetic macular edema is a leading cause of vision loss in patients with DM and warrants treatment. Intravitreal anti-VEGF therapy can improve visual acuity in eyes with DME and the severity of NPDR and PDR. Patients with severe NPDR, PDR, and DME should be promptly referred to a retina specialist for treatment. The optometrist's role in preserving vision in patients with DM is multitudinous—from making the preliminary diagnosis of DM and encouraging adherence to treatment, to recognizing and referring sight-threatening forms of DR.
1. Rowley WR, Bezold C, Arikan Y, Byrne E, Krohe S. Diabetes 2030: insights from yesterday, today, and future trends. Popul Health Manag. 2017;20(1):6-12.
2. National Eye Institute. Facts about diabetic eye disease. https://nei.nih.gov/health/diabetic/retinopathy. Accessed May 29, 2018.
3. National Center for Chronic Disease Prevention and Health Promotion Division of Diabetes Translation. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control; 2017.
4. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2004;27(suppl 1):S5-S10.
5. American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2016.
6. Centers for Disease Control and Prevention. Who's at risk. https://www.cdc.gov/diabetes/basics/risk-factors.html. Updated July 25, 2017. Accessed May 29, 2018.
7. Office of the Surgeon General. The Health Consequences of Smoking—50 Years of Progress. Rockville, MD: US Dept of Health and Human Services; 2014.
8. Cappuccio FP, Miller MA. Sleep and cardio-metabolic disease. Curr Cardiol Rep. 2017;19(11):110.
9. Lo MC, Abushamat L, Mramba LK. Effect of treating vitamin D deficiency in uncontrolled type 2 diabetes: a randomized, placebo-controlled study [published online ahead of print February 5, 2018]. Am J Ther. doi:10.1097/MJT.0000000000000738.
10. Diabetes Canada. Waist circumference. https://www.diabetes.ca/diabetes-and-you/healthy-living-resources/weight-management/waist-circumference. Accessed May 29, 2018.
11. Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev. 2008;29(4):494-511.
12. Fowler GC. Microvascular and macrovascular complications of diabetes. Clin Diabet. 2011;29(3):116-122.
13. Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes Care. 1992;15(7):815-819.
14. Bandello F, Lattanzio R, Zucchiatti I, Del Turco C. Pathophysiology and treatment of diabetic retinopathy. Acta Diabetol. 2013;50(1):1-20.
15. Wilkinson CP, Ferris FL 3rd, Klein RE, et al; Global Diabetic Retinopathy Project Group. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677-1682.
16. Klein R, Klein BE, Moss SE, David MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol. 1984;102(4):527-532.
17. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984;102(4):520-526.
18. Cai J, Boulton M. The pathogenesis of diabetic retinopathy: old concepts and new questions. Eye (Lond). 2002;16(3):242-260.
19. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017;237(4):185-222.
20. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984;91(12):1464-1474.
21. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854-865.
22. American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37(suppl 1):S14-S80.
23. Beetham WP, Aiello LM, Balodimos MC, Koncz L. Ruby-laser photocoagulation of early diabetic neovascular retinopathy: preliminary report of a long-term controlled study. Trans Am Ophthalmol Soc. 1969;67:39-67.
24. Spaide RF, Fisher YL. Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina. 2006;26(3):275-278.
25. Genentech, Inc. Lucentis approved for treatment of diabetic macular edema (DME) [press release]. https://www.gene.com/media/news-features/news-lucentis-dme. Published August 10, 2012. Accessed May 29, 2018.
26. Regeneron Pharmaceuticals, Inc. Eylea® (aflibercept) injection receives FDA approval for the treatment of diabetic macular edema (DME) [press release]. http://investor.regeneron.com/releasedetail.cfm?ReleaseID=862822. Published July 29, 2014. Accessed May 29, 2018.
27. F. Hoffmann-La Roche Ltd. FDA approves Roche's Lucentis (ranibizumab injection) for treatment of diabetic retinopathy in people with diabetic macular edema [press release]. https://www.roche.com/media/releases/med-cor-2015-02-09.htm. Published February 9, 2015. Accessed May 30, 2018.
28. PR Newswire Association LLC. Eylea® (aflibercept) injection receives FDA approval for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME). https://www.prnewswire.com/news-releases/eylea-aflibercept-injection-receives-fda-approval-for-the-treatment-of-diabetic-retinopathy-in-patients-with-diabetic-macular-edema-dme-300055839.html. Published March 25, 2015. Accessed May 30, 2018.
29. Genentech, Inc. FDA approves Genentech's Lucentis (ranibizumab injection) for diabetic retinopathy, the leading cause of blindness among working age adults in the United States. https://www.gene.com/media/press-releases/14661/2017-04-17/fda-approves-genentechs-lucentis-ranibiz. Published March 25, 2015. Accessed May 30, 2018.
30. Wells JA, Glassman AR, Ayala AR, et al; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123(6):1351-1359.
31. Kiss S, Liu Y, Brown J, et al. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema. Clin Ophthalmol. 2014;8:1611-1621.
32. Ip MS, Domalpally A, Hopkins JJ, Wong P, Ehrlich JS. Long-term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol. 2012;130(9):1145-1152.
33. Gross JG, Glassman AR, Jampol LM, et al; Writing Committee for the Diabetic Retinopathy Clinical Research Network. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314(20):2137-2146.
34. Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122(10):2044-2052.
35. Sivaprasad S, Prevost AT, Vasconcelos JC, et al; CLARITY Study Group. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. Lancet. 2017;389(10085):2193-2203.
36. Arevalo JF, Sanchez JG, Lasave AF, et al. Intravitreal bevacizumab (Avastin) for diabetic retinopathy: the 2010 GLADAOF lecture. J Ophthalmol. 2011;2011:584238.
37. Bressler SB, Liu D, Glassman AR, et al; Diabetic Retinopathy Clinical Research Network. Change in diabetic retinopathy through 2 years: secondary analysis of a randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab. JAMA Ophthalmol. 2017;135(6):558-568.
38. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193-1203.
39. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology. 1991;98(5)(suppl):766-785.
40. Mitchell P, McAllister I, Larsen M, et al. Evaluating the impact of intravitreal aflibercept on diabetic retinopathy progression in the VIVID-DME and VISTA-DME studies [published online ahead of print March 31, 2018]. Ophthalmol Retina. doi:10.1016/j.oret.2018.02.011.
41. Diabetic Retinopathy Clinical Research Network. Policies, protocols, and protocol idea forms. http://drcrnet.jaeb.org/ViewPage.aspx?PageName=Investig_Info. Accessed May 29, 2018.
42. Regeneron Pharmaceuticals. Study of the efficacy and safety of intravitreal (IVT) aflibercept for the improvement of moderately severe to severe nonproliferative diabetic retinopathy (NPDR) (PANORAMA). ClinicalTrials.gov Web site. https://clinicaltrials.gov/ct2/show/NCT02718326. Updated May 22, 2018. Accessed May 30, 2018.
43. Soliman AZ, Silva PS, Aiello LP, Sun JK. Ultra-wide field retinal imaging in detection, classification, and management of diabetic retinopathy. Semin Ophthalmol. 2012;27(5-6):221-227.
44. Silva PS, Cavallerano JD, Haddad NM, et al. Peripheral lesions identified on ultrawide field imaging predict increased risk of diabetic retinopathy progression over 4 years. Ophthalmology. 2015;122(5):949-956.
45. Wilson PJ, Ellis JD, MacEwen CJ, Ellingford A, Talbot J, Leese GP. Screening for diabetic retinopathy: a comparative trial of photography and scanning laser ophthalmoscopy. Ophthalmologica. 2010;224(4):251-257.
46. American Optometric Association. Eye Care in the Patient With Diabetes Mellitus. St Louis, MO: American Optometric Association; 2014.
47. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more. Arch Ophthalmol. 1989;107(2):244-249.
48. Fong DS, Aiello L, Gardner TW, et al; American Diabetes Association. Diabetic retinopathy. Diabetes Care. 2003;26(1):226-229.