Summer 2006

A Part of the publication series

R E P O R T E RAn Expert Dialogue on Diabetic Retinopathy

Right Toolat theChoosingRight Timethe

ALSO IN THIS ISSUE:

ALL EYE EXAMS ARE NOT CREATED EQUAL What to expect when patients are referred to you.

CLiNiCAL CLOSEUP Sudden vision loss in patients with longstanding diabetes can have various etiologies.

RESEARCh ROUNDUP Reports from the ARVO and ADA meetings on the latest research in screening and diagnostic techniques for diabetic retinopathy.

FEEDBACK FORUM Our expert faculty reply to the most frequently asked questions received in hundreds of replies to the Spring issue.

An Expert Dialogue on Diabetic Retinopathy� R E P O R T E R

Michael J Cooney, MD, MBAVitreous Retina Macula Consultants of New YorkNew York City, New York

Michael J Cooney, MD, MBA, is a practicing vitreoretinal surgeon at the Vitreous Retina Macula Consultants of New York in Manhattan. Dr Cooney completed his medical and surgical retina fellowship and was an assistant professor of ophthalmology at Johns Hopkins until �001. He then joined the faculty at Duke University Eye Center, where he was director of the medical retina service, the Duke Center for Macular Degeneration, and the medical retina fellowship program from �001 to �005. Dr Cooney received his MBA degree from the University of North Carolina, Chapel Hill.

Dr Cooney’s clinical practice focuses on the medical and surgical treatment of vitreoretinal diseases, particularly age-related macular degeneration and diabetic retinopathy. He is actively involved in the clinical development of new diagnostic and therapeutic modalities for vitreoretinal disease and the training of residents and fellows at Manhattan Eye, Ear & Throat Hospital. Dr Cooney has authored over 40 publications and book chapters.PHOTO CREDIT: This photo is the property of Duke University Medical Center.

Byron S Ladd, MDVirginia Eye InstituteRichmond, Virginia

Byron S Ladd, MD, completed his specialty fellowship and residency at the Johns Hopkins University School of Medicine. An Alpha Omega Alpha honor graduate of the Indiana University School of Medicine, Dr Ladd is an Indiana native and completed his undergraduate studies at Indiana University, receiving the Phi Beta Kappa honor. He is a member of the American Academy of Retinal Specialists, the Richmond Academy of Medicine, the Virginia Society of Ophthalmology, the Wilmer Residents Association/Johns Hopkins, the Alpha Omega Alpha Honor Medical Society, and is a Fellow of the American Academy of Ophthalmology.

Dr Ladd is board certified by the American Board of Ophthalmology and specializes in complex vitreoretinal surgery and medical therapy of macular and retinal disease.

ABOUT EDITORRelease Date: Sept �006 | Expiration Date: Sept 30, �007

Program Overview: Diabetic retinopathy is a frequent and costly complication of diabetes. While physicians commonly understand that avoidance of vision loss as a complication of diabetes is a high priority, management of the patient with diabetic retinopathy can be complicated by a lack of symptoms even in sight-threatening states of disease and by the need to coordinate patient care across multiple medical and surgical specialties. Retinopathy Reporter: An Expert Dialogue on Diabetic Retinopathy is a quarterly certified continuing medical education (CME) activity designed to increase awareness and understanding of diabetic retinopathy diagnosis and management among ophthalmologists treating patients with type 1 or type � diabetes. Upon completion of the �006 publication series, the participant should be able to describe the clinical signs of nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME); explain the benefits and limitations of various diagnostic devices and procedures for NPDR, PDR, and DME; summarize appropriate follow-up procedures based on results of these tests; explain the advantages and shortcomings of current pharmaceutical treatments and surgical procedures for NPDR, PDR, and DME; and describe the potential advantages and shortcomings of emerging treatments for NPDR, PDR, and DME in relation to underlying disease pathophysiology.

Intended Audience: This activity was developed for ophthalmologists.

Learning Objectives for This Issue: At the conclusion of this activity, the participant should be able to:

• Recognize that patients with diabetic retinopathy are at increased risk for other eye disorders• Describe the benefits and limitations of fluorescein angiography (FA), ultrasound,

and optical coherence tomography (OCT) to diagnose diabetic retinopathy• Discuss the utility of FA, ultrasound, and OCT in treatment planning for diabetic retinopathy• Explain the benefits and limitations of direct ophthalmoscopy to patients, primary

care physicians, and other non-ophthalmologists

Accreditation Statements: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Center for Accredited Healthcare Education (CAHE) and International Medical Press (IMP). CAHE is accredited by the ACCME to provide continuing medical education for physicians.

CAHE designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Faculty Disclosure: Michael J Cooney, MD, MBAFormal Advisor: Bausch & Lomb, AlconSpeaker’s Bureau: Bausch & Lomb, Alcon, Eyetech, NovartisConsultant: Bausch & LombOwnership Interest: InnoRx

Byron S Ladd, MDFormal Advisor: NovartisResearch Activities: GenentechSpeaker’s Bureau: Novartis

Staff Disclosure: All staff of CAHE and IMP in a position to influence content have filed statements of disclosure with the CME provider. Any conflicts of interest were identified and resolved prior to their involvement in planning this activity. These disclosures are available for review by contacting Steve Weinman at 1 609 936 7015 or e-mail at steve.weinman@cahe.com.

CAHE and IMP staffs have disclosed no conflicts of interest.

Disclaimer: This activity is designed for healthcare professionals for educational purposes. Information and opinions offered by the faculty/presenters represent their own viewpoints. Conclusions drawn by the participants should be derived from careful consideration of all scientific information.

While CAHE makes every effort to have accurate information presented, no warranty, expressed or implied, is offered. The participant should use his/her clinical judgment, knowledge, experience, and diagnostic decision-making before applying any information, whether provided here or by others, for any professional use.

This activity contains references to off-label or investigational use of agents. These agents are highlighted and footnoted in the text.

Commercial Support Acknowledgement: This activity is supported by an educational grant from Eli Lilly and Company.

Method of Participation: CME certificates will be issued to participants after receipt of the CME Demographic & Evaluation Form.

CME INFORMATION

PHOTO CREDIT: This photo is courtesy of Byron S Ladd.

3Summer 2006

WELCOMERetinopathy Reporter: An Expert Dialogue on Diabetic Retinopathy is a certified continuing medical education (CME) activity published quarterly and designed to increase awareness and understanding of diabetic retinopathy diagnosis and management among ophthalmologists treating patients with diabetes. In this issue, we will describe the benefits and limitations of various ophthalmic instruments used by physicians to diagnose diabetic retinopathy and make related treatment decisions. Our lead article explores the barriers to detecting early stages of the disease, including diabetic macular edema (DME).

What Patients Don’t Know About Eye Exams Can Hurt Them: improving Annual Eye Exam Rates and UnderstandingAnnual dilated eye examinations are recommended for nearly all patients with diabetes by both the American Academy of Ophthalmology (AAO) and the American Diabetes Association (ADA), but numerous recent surveys have shown that significant numbers of patients do not have them. Chart reviews of patients enrolled in a large US prepaid healthcare group revealed that only 59.�% to 67% of patients had received an annual eye exam of any type from 1994 to 1995.1 In the US, exam costs and scheduling difficulties are often cited to explain low eye exam rates, and in some subpopulations, these barriers may in fact be quite serious. For example, a pre-Katrina study of Medicaid patients in New Orleans found that the average waiting time for a non-emergency ophthalmology visit exceeded 1 year.� However, among patients on Medicare, a large population with a high incidence of diabetes, the most influential factors in receiving an annual eye exam were its perceived benefits and the ease of the visit.3 Both of these factors can be directly influenced by the ophthalmologist.

Appropriate patient education is the cornerstone of establishing a high level of perceived benefit in an annual eye exam. While patient self-management—the principle that patients take an active role in their own medical treatment—is the standard of care in diabetes,4 self-management instruction may limit discussion of diabetic retinopathy to the need to “get a yearly eye exam.” 5 In fact, patients enrolled in formal self-management courses are significantly more likely to receive an annual dilated eye examination than those who have not had them,6 but the courses do not specify who should perform the exam or how it should be performed, nor do they explain what the findings from such an exam might mean. Worse still, some otherwise-authoritative sources of patient information are misleading, implying that diabetic retinopathy will be symptomatic or that updating a lens prescription is the primary reason for the annual exam recommendation.5,7 Furthermore, only about half of patients with type � diabetes (the more common form of the disease) receive any formal self-management education.6

Ideally, all patients with diabetes would receive their annual dilated eye examination from an ophthalmologist with expertise in diabetic eye disease. However, the reality falls short of the ideal, even among patients with good access to ophthalmologic care, as noted previously. Primary care referral practices and even clinical guidelines may contribute to this problem.

Some primary care physicians may refer patients with type 1 diabetes to ophthalmologists, but refer patients with type � diabetes to optometrists.8 This discrepancy in referral practices may be based upon the mistaken belief that patients with type � diabetes are less likely to have vision-threatening eye disease than patients with type 1 diabetes. Contrary to expectation, patients with type � diabetes frequently have signs of diabetic retinopathy at the time diabetes is first diagnosed. In contrast, it is unusual for patients with type 1 diabetes to present with retinopathy at the time of diagnosis. Among patients with

Perceived benefit and ease of the visit are the 2 most influential factors in Medicare patients receiving an annual eye exam

R E P O R T E RAn Expert Dialogue on Diabetic Retinopathy

An Expert Dialogue on Diabetic Retinopathy4 R E P O R T E R

longstanding diabetes (≥�0 years), patients with type 1 diabetes are more likely to have proliferative diabetic retinopathy (PDR) than patients with type � diabetes. However, diabetic macular edema (DME) is common among patients with type � diabetes, and this condition can cause irreversible vision loss if not treated early. Most studies comparing ophthalmologists and optometrists show nearly comparable performance in diagnosing diabetic retinopathy, but only ophthalmologists can perform laser photocoagulation, the most common treatment for DME and PDR.

Current guidelines for diabetes management offer conflicting advice regarding who should perform the annual eye exam. The ADA recommends that ophthalmologists or optometrists “knowledgeable and experienced in diagnosing the presence of diabetic retinopathy and…aware of its management” conduct the eye exam,4 but the American Association of Clinical Endocrinologists recommends that endocrinologists perform an ophthalmoscopic annual eye exam, with funduscopic examination and photographs “if indicated,” optionally referring to an ophthalmologist “on the basis of age, duration of disease, and findings on current examination.”7 In some cases, patients may have eye exams performed by their primary care physician.

Stereo viewing of the retina is essential to the detection of DME, yet stereo diagnostic instrumentation, such as a standard Slit-Lamp biomicroscope, is rarely found in primary care or endocrinology offices. Typically, the only diagnostic instrument available for eye examinations in these offices is a direct ophthalmoscope. A number of studies and reviews have found wide variation in the sensitivity and specificity of this device to detect sight-threatening diabetic eye disease,9 but at best, the results are poorer than for biomicroscopy with a handheld lens, which is still considered the gold standard. For example, remarkably high degrees of sensitivity and specificity were attained in one study of well-trained diabetologists (eg, endocrinology subspecialists) and

community screeners, and results were comparable for each group (diabetologists: 8�.5% sensitivity, 98% specificity; screeners: 83.3% sensitivity, 96.8% specificity).10 In contrast, other studies have shown that non-ophthalmologists may fail to diagnose diabetic retinopathy in about half of cases.11,1� Even skilled ophthalmologists using direct ophthalmoscopes may miss many cases of diabetic retinopathy.1�

Getting an exam is one thing: understanding what the results mean is another. There are few US studies regarding patient knowledge of eye exams and terminology relative to diabetic retinopathy, but these studies indicate a profound lack of understanding of the purpose, terminology, and risk factors for retinopathy among patients with diabetes. Anecdotally, fewer than �5% of patients with diabetes understand the purpose of a dilated eye exam.13 One study of patients with diabetes found that although 91% of survey respondents agreed that they should get a dilated eye exam if their physician told them it was important, only 36% had heard the term “retinopathy,” 79% were unaware that there are effective treatments for retinopathy, and just 8% could define it.14 Another study found that over half of the patients did not realize that diabetes-related eye complications could be asymptomatic or that there are ways to reduce the risk of eye problems.15 Only 51% of patients receiving care at the Wilmer Eye Institute were aware of A1C and its relationship to diabetic retinopathy.16

Clearly, patients need specific education on diabetic retinopathy to fully appreciate the benefit of having an annual eye exam, and not only do they need this education, they want it. A recent, validated survey of patient expectations for eye care showed that 9�.5% of patients consider a clear, simple explanation of their eye disease by their ophthalmologist to be very or extremely important.17 Many patients also want information about diagnosis (4�.6% to 67.3%) and prognosis (57.9%) but are content to let their ophthalmologist make treatment decisions. For example, only �9.1%

Current guidelines for diabetes management offer conflicting advice regarding who should perform the annual eye exam

Non-ophthalmologists using direct ophthalmoscopy may fail to diagnose diabetic retinopathy in about half of cases.

5Summer 2006

considered it very or extremely important to learn more about their eye medications. About half (46.9%) want their ophthalmologist to inform them of recent treatment advances related to their eye disease. Because patients’ learning preferences and literacy levels vary, it is recommended that educational materials be made available in a variety of media suited to differing degrees of language comprehension.18,19 Multimedia instructional materials and plain-language brochures on diabetic retinopathy are available free or at low cost from a number of sources; ordering details are provided below. In addition to meeting patients’ information needs, face-to-face instruction and the provision of educational materials may increase patient satisfaction with office visits.17

ResourcesThe National Eye Institute (NEI) multimedia instructional kit, Diabetic Eye Disease: An Educator’s Guide is available for $�.00. The NEI also publishes a booklet, Diabetic Retinopathy: What you should know. It is written at a college reading level and can be downloaded at no cost from http://www.nei.nih.gov/health/diabetic/diabeticretino.pdf. Both publications are also available in Spanish. NEI products may be ordered from: http://catalog.nei.nih.gov/productcart/pc/ viewCat_L.asp?idCategory=3�.

The AAO publishes patient education brochures, booklets, and DVDs on diabetic retinopathy in English, with selected items available in Spanish. The color brochure Diabetic Retinopathy: A Closer Look is written at a college reading level and is available at a nonmember cost of $38.00/100 directly from the AAO.

The National Institute of Diabetes and Digestive and Kidney Diseases booklet Prevent Diabetes Problems: Keep Your Eyes Healthy is written at a 6th grade reading level and can be downloaded at no cost from http://diabetes.niddk.nih.gov/dm/pubs/complications_eyes/eyes.pdf.

To estimate the reading level of patient education materials and nonfiction publications, the Fry Readability Scale (FRS) is recommended. Instructions for the FRS can be obtained at no cost from http://school.discovery.com/schrockguide/fry/fry.pdf.

References1. O’Connor PJ, Desai JR, Solberg LI, Rush WA, Bishop DB. Variation

in diabetes care by age: opportunities for customization of care. BMC Fam Pract. �003;4:16.

�. Hartnett ME, Key IJ, Loyacano NM, Horswell RL, Desalvo KB. Perceived barriers to diabetic eye care: qualitative study of patients and physicians. Arch Ophthalmol. �005;1�3:387-391.

3. Sloan FA, Brown DS, Carlisle ES, Picone GA, Lee PP. Monitoring visual status: why patients do or do not comply with practice guidelines. Health Serv Res. �004;39:14�9-1448.

4. American Diabetes Association. Standards of medical care in diabetes—�006. Diabetes Care. �006;�9(suppl 1):S4-S4�. Available at: http://care.diabetesjournals.org/cgi/reprint/�9/suppl_1/s4. Accessed June �9, �006.

5. National Diabetes Education Program. 7 Principles for Controlling Your Diabetes for Life. Bethesda, Maryland: National Institutes of Health, June �00�. NIH Publication No. 99-4343L.

6. Strine TW, Okoro CA, Chapman DP, Beckles GL, Balluz L, Mokdad AH. The impact of formal diabetes education on the preventive health practices and behaviors of persons with type � diabetes. Prev Med. �005;41:79-84.

7. American Association of Clinical Endocrinologists and the American College of Endocrinology. The American Association of Clinical Endocrinologists Medical Guidelines for the Management of Diabetes Mellitus: The AACE System of Intensive Diabetes Self-Management—�00� Update. Endocr Pract. �00�;8(suppl 1):S41-S8�.

8. Lazaridis EN, Qiu C, Kraft SK, Marrero DG. Same eyes, different doctors: differences in primary care physician referrals for diabetic retinopathy screening. Diabetes Care. 1997;�0:1073-1077.

9. Hutchinson A, McIntosh A, Peters J, et al. Effectiveness of screening and monitoring tests for diabetic retinopathy—a systematic review. Diabet Med. �000;17:495-506.

10. Pandit RJ, Taylor R. Quality assurance in screening for sight-threatening diabetic retinopathy. Diabet Med. �00�;19:�85-�91.

11. Sussman EJ, Tsiaras WG, Soper KA. Diagnosis of diabetic eye disease. JAMA. 198�;�47:3�31-3�34.

1�. Emanuele N, Klein R, Moritz T, et al. Comparison of dilated fundus examination by ophthalmologists with 7-field stereo fundus photographs in the Veterans Affairs Diabetes Trial (VADT). American Diabetes Association 66th Annual Scientific Sessions. Washington, DC, June 9-13, �006. Abstract ��15-PO.

13. Foster DT, Wylie-Rosett J, Walker EA. Local survey of optometrists about dilated funduscopic examinations for patients with diabetes: making use of phone book Yellow-page listings. Diabetes Educ. 1996;��:605-608.

14. Walker EA, Basch CE, Howard CJ, Zybert PA, Kromholz WN, Shamoon H. Incentives and barriers to retinopathy screening among African-Americans with diabetes. J Diabetes Complications. 1997;11:�98-306.

15. Pasagian-Macaulay A, Basch CE, Zybert P, Wylie-Rosett J. Ophthalmic knowledge and beliefs among women with diabetes. Diabetes Educ. 1997;�3:433-437.

16. Do DV, Nguyen QD, Bressler NM, et al. Hemoglobin A1C awareness among patients receiving eye care at a tertiary ophthalmic center. Am J Ophthalmol. �006;141:951-953.

17. Dawn AG, McGwin G Jr, Lee PP. Patient expectations regarding eye care: development and results of the Eye Care Expectations Survey (ECES). Arch Ophthalmol. �005;1�3:534-541.

18. Lee PP. Why literacy matters: links between reading ability and health. Arch Ophthalmol. 1999;117:100-103.

19. Marcus EN. The silent epidemic—the health effects of illiteracy. N Engl J Med. �006;355:339-341.

Overwhelmingly, patients want a clear, simple explanation of their eye disease by their ophthalmologist

An Expert Dialogue on Diabetic Retinopathy6 R E P O R T E R

CLINICAL CLOSEUP

Introduction The complexity of managing diabetic retinopathy arises from the numerous possible causes of vision loss. As the following cases illustrate, an ophthalmologist must combine clinical acumen with ancillary tests to determine the appropriate diagnosis and treatment.

CASE 1: ACUTE vISION LOSS IN A NONCOMPLIANT PATIENT WITh DIABETES

Presentation A 53-year-old man with history of diabetes for 17 yearspresented with gradual decline in vision OU for 6 months and sudden visual decline OS for 1 week associated with severe floaters and cobwebs. His last dilated eye exam was 5 years ago. He discontinued taking his oral antihyperglycemic agent and blood glucose monitoring over a year ago.

Physical ExamHeight: 5’10”Weight: �40 lbsBP: 134/86 mm HgBlood glucose: �40 mg/dL

Medical HistoryType � diabetes x 17 years.

MedicationsNone. Patient discontinued glyburide 1 year ago. He denies any hypertension, hypercholesterolemia, or cardiovascular disease.

Ocular HistoryUnremarkable

Family Ocular HistoryPatient has a family history of glaucoma.

ExaminationBest-corrected visual acuity: �0/�5 OD and �/�00 (count fingers at � feet) OS Pupils and External Examination: Normal Intraocular Pressure: 14 OD, 16 OS

Slit Lamp Examination: Normal except for nuclear and posterior subcapsular cataract changes OU; no rubeosis was present OU Dilated Fundus Examination: OD – High-risk proliferative diabetic retinopathy (PDR) (See Figure 1); OS – Dense vitreous hemorrhage (VH) with no view of fundus B-scan Ultrasound OS: Dense vitreous hemorrhage with partial posterior vitreous detachment. Macula attached. Superotemporal vitreoretinal adhesion with localized tractional retinal detachment (TRD) consistent with peripheral neovascularization (See Figure 2)

Assessment1. High-risk PDR, OD�. Vitreous hemorrhage, OS3. Presumed high-risk PDR, OS4. Small extramacular TRD, OS5. Type � diabetes with poor medical compliance

Management ProtocolAfter a lengthy discussion with the patient stressing the importance of medical follow-up and control of blood sugar, panretinal photocoagulation (PRP) OD was initiated that day. The patient explained that he discontinued taking glyburide because he did not think it was necessary and he did not understand the complications associated with diabetes. He was sent directly to his primary care physician for a complete physical and reinitiation of antihyperglycemic medications.

The left eye was monitored weekly with ultrasound for 1 month. During that time, the vitreous hemorrhage did not improve and the small TRD remained stable. However, in order to adequately manage the presumed high-risk proliferative diabetic retinopathy (HRPDR) and restore vision, he underwent a pars plana vitrectomy with PRP.

Figure 1. Case 1: High-risk PDR

Figure 2. Case 1: Vitreous hemorrhage with partial posterior vitreous detachment

7Summer 2006

DiscussionA patient presenting with HRPDR has the highest risk of severe vision loss and the greatest benefit from PRP according to the Diabetic Retinopathy Study (DRS).1 PDR indicates the presence of neovascularization on the optic nerve (NVD) or retina (NVE). High-risk characteristics include severe NVD or neovascularization with preretinal or vitreous hemorrhage. Prompt treatment of HRPDR results in a 50% decrease in severe vision loss compared to untreated eyes.� The Early Treatment of Diabetic Retinopathy Study (ETDRS) revealed that there is no need to wait for HRPDR to develop before treating patients diagnosed with earlier PRP: patients with severe nonproliferative diabetic retinopathy (SNPDR) or non-HRPDR benefit as much as patients with HRPDR, especially those who have difficulty with close follow-up or are noncompliant with medical treatment.3 The benefits of the ETDRS recommendations were even greater in patients with type � diabetes.4

Numerous side effects exist with PRP and need to be discussed with the patient along with the benefits before treatment is initiated. The most significant problems are decreases in night, color, and peripheral vision. In addition, a 1- to �-line permanent decrease in visual acuity has been reported in 14% of patients.� Other minor problems include discomfort, glare, photopsias, and worsening of macular edema.

When the fundus cannot be visualized through severe media opacities like corneal clouding, cataract, or vitreous hemorrhage, the ophthalmologist must resort to contact B-scan ultrasonography for further evaluation. The cross-sectional images provided by B-scan ultrasound provide a fast, noninvasive evaluation of the posterior segment anatomy, but do not provide any information on retinal function. Ultrasonic evaluation allows the detection of posterior vitreous detachments, retinal detachments, vitreous hemorrhage, ocular tumors, and many other posterior segment pathologies without being able to visualize the fundus.5 The role of ultrasound can be particularly important in the management of diabetic retinopathy. In some instances, a patient with undiagnosed diabetes can present with acute vision loss secondary to sudden formation of a white cataract from severe hyperglycemia.6 In this setting, ultrasonic evaluation is necessary to rule out concurrent posterior segment pathology prior to cataract surgery.

Vitreous hemorrhage (VH) from PDR in patients with diabetes is one of the most common conditions to require an ultrasonic study.7 Ultrasound is necessary with a VH to determine if a retinal tear or a tractional or rhegmatogenous retinal detachment is present that would require urgent vitrectomy and treatment of the inciting condition. B-scan is very sensitive for detecting these pathologies, but confusion can occur when vitreoschisis is also present.8

In the absence of a macula-threatening detachment, VH can be monitored for spontaneous resolution if PRP has already been performed. However, the Diabetic Retinopathy Vitrectomy Study (DRVS) concluded that earlier vitrectomy was more beneficial in patients with type 1 diabetes than in patients with type � diabetes.9 Instead of waiting for a year for a VH to clear, early intervention resulted in better visual improvement and less macular distortion from fibrous proliferation.

In recent years, nonsurgical, pharmacologic interventions have shown some promise in facilitating clearance of VH, but none have yet received FDA approval for management of VH. An intravitreal injection of hyaluronidase* provides an enzymatic vitreolysis, which causes liquifaction of the vitreous and facilitates clearance of the red blood cells.10,11 Off-label use of intravitreal bevacizumab* may also help resolution of VH.1� By inhibiting vascular endothelial growth factor (VEGF), bevacizumab causes regression of neovascularization. This presumably reduces additional bleeding and hastens clearance of the existing VH.

CASE 2: ACUTE vISION LOSS DUE TO MACULAR EDEMA ASSOCIATED WITh MACULAR ISChEMIA IN A PATIENT WITh PROLIFERATIvE DIABETIC RETINOPAThy

PresentationA 55-year-old man with history of PDR status post-PRPOU � years earlier presented with abrupt decline in vision OD over the past � weeks. Shortly before the decline in vision he had been treated for pneumonia and malignant hypertension, with a blood pressure of ��0/110 mm Hg.

vitreous hemorrhage is one of the most common conditions to require an ultrasonic study

*Not FDA approved for this indication.

An Expert Dialogue on Diabetic Retinopathy8 R E P O R T E R

Medical HistoryType � diabetes x 5 yearsSevere uncontrolled hypertension (HTN)

MedicationsGlycemic control

• Glipizide• Insulin

Cardiovascular • Benazepril (HTN)• Amlodipine (HTN)• Doxazosin (HTN)• Metoprolol (HTN)• Clonidine (HTN)• Simvastatin (lipid control)

Ocular HistoryStable PDR status post-PRP, OD x 1 year; OS x � years; resolved clinically significant macular edema (CSME) after focal laser photocoagulation, OD x 8 months, OS x �0 months; mild vitreous hemorrhage, OU.

ExaminationBest-corrected visual Acuity: �0/80 OD and �0/50 OS (Decline OD from �0/�0 � months ago)Pupils and External Examination: NormalIntraocular Pressure: 1� mm Hg OUSlit Lamp Examination: Mild nuclear sclerosis OS>OD and no rubeosis, OUDilated Fundus Examination: OD – Regressed PDR with PRP. Severe temporal CSME involving the fovea. Old focal laser scars. Mild old inferior vitreous hemorrhage (See Figure 3); OS – Regressed PDR with PRP. Focal laser scars. No macular edema. Mild old inferior vitreous hemorrhage

Fluorescein Angiogram: OD – Normal arm-retina time and venous filling. Severe arteriole attenuation. Foveal avascular zone is intact without enlargement (See Figure 4).

Large area of capillary nonperfusion in extrafoveal temporal macula. Moderate parafoveal microaneurysms with severe diffuse leakage in late frames throughout posterior pole. Regressed NVD and NVE with PRP laser scars.

Optical Coherence Tomography: OD – Temporal cystic macular edema involving fovea with central retinal thickness (CRT) 417 microns (See Figure 5)

Assessment1. PDR status post-PRP, OU�. Severe CSME, OD3. Macular ischemia, OD4. Resolved macular edema OS5. Mild cataracts, OU6. Type � diabetes7. Severe hypertension

Management ProtocolThe sudden change in vision OD and dramatic clinical changes are secondary to the new macular ischemia that was precipitated by the recent malignant hypertension. The fluorescein angiogram revealed diffuse macular leakage greater in area than the capillary nonperfusion and out of proportion to the number of microaneurysms. Therefore, combined treatment with focal and grid laser photocoagulation with intravitreal steroids was initiated.

DiscussionFor decades, fluorescein angiography (FA) has been thefundamental test for evaluation of retinal pathology.13 FA provides information on retinal perfusion, vascular abnormalities, macular edema, optic neuropathies, ocular tumors, and numerous other ocular conditions. Due to the scope of this publication, the discussion of FA will be limited to its use in the management of diabetic retinopathy and the differentiation of other conditions with microvascular abnormalities. Please refer to the Spring issue of Retinopathy Reporter to review the use of FA for typical diabetic macular edema.

Figure 3. Case �: Severe temporal CSME involving fovea, old focal laser scars, and inferior vitreous hemorrhage

Figure 4. Case �: Fluorescein angiogram

Figure 5. Case �: Cystic macular edema involving fovea (OD)

9Summer 2006

Diabetes mellitus is a risk factor for numerous systemic medical conditions including atherosclerosis, cardiovascular and kidney disease, hypertension, myocardial infarction, thromboembolic events, and stroke.14 Diabetes also increases the risk of ocular disorders such as cataracts, glaucoma, retinal vascular occlusion, ischemic optic neuropathy, and ocular ischemic syndrome. Because these conditions can present with similar retinal findings, the FA is very helpful in differentiating the underlying disorder. Retina specialists are often confronted with determining the etiology of vitreous hemorrhage in patients with diabetes. Although a presumptive diagnosis of PDR is often correct, other causes must be excluded to ensure proper treatment. After a thorough exam with scleral depression excludes a retinal tear, the FA provides additional, invaluable data even when neovascularization is noted. For instance, a marked delay in arm-retina time and delayed venous filling would suggest ocular ischemic syndrome and necessitate carotid artery evaluation along with PRP.15

The FA will also help exclude other causes of VH, including retinal arteriole macroaneurysms, choroidal neovascularization, and retinal vascular occlusions.In diabetic retinopathy, an FA supplies information that complements the clinical exam. The angiogram can help assess the severity of microvascular changes used to stage the degree of retinopathy. Venous beading, intraretinal microvascular abnormalities (IRMA), and neovascularization are often more readily appreciated on FA than biomicroscopy, and the presence of these changes is crucial for the correct observation and management of diabetic retinopathy.16 Furthermore, areas of capillary nonperfusion and the integrity of the foveal avascular zone can only be appreciated with FA. When CSME is associated with areas of severe ischemia or enlargement of the foveal avascular zone, focal laser photocoagulation may be less effective at preventing visual loss, and the risk of progression to proliferative retinopathy is greater.17-19 Therefore, FA provides critical information not only for treating the patient, but also for educating the patient on their overall prognosis.

As this case illustrates, it is very important to consider concurrent medical conditions that can impact the retinal vascular changes. Hypertensive retinopathy has a constellation of ophthalmic findings that includes arteriolar constriction and sclerosis, cotton-wool spots, retinal and disc edema, and retinal hemorrhages. Of these changes, arteriolar narrowing and nicking are the most specific for hypertension.�0 In malignant hypertension, closure of parafoveal capillaries can occur resulting in profound macular edema.�1 In this case, the compounding vascular effects of severe hypertension on a patient with controlled PDR and CSME resulted in acute macular ischemia and edema with a severe decline in vision. Therefore, the ophthalmologist needs to educate the patient with diabetes about the importance of controlling

both blood glucose and hypertension to reduce the risk of progressive retinopathy. Further, when a patient presents with acute vision loss and retinal vascular changes, it is important for the ophthalmologist to check the patient’s blood pressure and refer them to the primary care physician for immediate attention if necessary.

CASE 3: ACUTE vISION DECREASE IN A PATIENT WITh kNOWN PROLIFERATIvE DIABETIC RETINOPAThy AND MACULAR EDEMA

PresentationA 63-year-old man with previously treated proliferative diabetic retinopathy (PDR) and CSME complains of a marked visual decline in his right eye for the past month. He denies any increase in floaters.

For decades, fluorescein angiography has been the fundamental test for evaluation of retinal pathology

Although PDR is often the etiology of vitreous hemorrhage in patients with diabetes, other causes must be excluded to ensure proper treatment

An Expert Dialogue on Diabetic Retinopathy10 R E P O R T E R

potential VMT. The OCT of the right eye reveals a marked 511-micron increase in CRT in comparison to the study 4 months earlier. (See Figures 6a,b). Cross-sectional views of the macula show severe cystoid changes, partial separation of the hyaloid with areas of focal adherence, and “tenting” of the fovea (See Figure 7).

The findings of VMT with CME were reviewed with the patient. Because the condition represents an abnormality of the vitreomacular interface, the need for surgical intervention with pars plana vitrectomy (PPV) was reviewed with the patient. Surgical intervention with PPV and membrane peeling was recommended.

Discussion OCT has become an indispensable diagnostic tool for retina specialists based on its ease of use, speed, sensitivity, objectivity, and reproducibility.�� Before OCT was available, the determination of macular edema (ME) was based on subjective findings from biomicroscopy supported by FA. Clinical determination of ME requires the ability to discern retinal thickening on biomicroscopy, which is often a tedious and lengthy endeavor for the clinician and patient. In addition, the bright slit lamp and use of contact lenses can make the experience uncomfortable for the patient. Before OCT, the ability to adequately judge changes in ME required cumbersome comparisons to previous stereo fundus photographs, which is still fraught with subjectivity. Now with OCT, successive studies can be analyzed by the machine to produce an accurate, quantitative measure of change. This

Medical HistoryType � diabetes x 19 yearsHypertension x �3 yearsHypercholesterolemia

MedicationsGlycemic control

• Glipizide • Metformin

Cardiovascular• Lisinopril (HTN)• Fluvastatin (lipid control)• Gemfibrozil (lipid control)

Ocular HistoryThe patient has previously undergone � focal lasersin each eye for CSME with the last sessions 10 months ago. PRP for PDR completed in each eye 3 years ago. Cataract extraction with intraocular lens implants OU 4 years earlier.

ExaminationBest-corrected visual Acuity: �0/�00 OD and �0/�0 OS(was �0/30 OD 3 months earlier)Pupils and External Examination: Normal OUIntraocular Pressure: 14 mm Hg OUSlit Lamp Examination: Normal except for pseudophakia, OUDilated Fundus Examination: OD – Regressed peripheral neovascularization with PRP. Worsening cystoid macular edema with posterior hyaloidal traction on macula. Old focal laser scars in macula. Normal optic nerve and no vitreous hemorrhage. OS – Regressed neovascularization with PRP. Focal laser with no CSME

Assessment1. Vitreomacular traction (VMT) with worsening

cystoid macular edema, OD�. PDR status post-PRP, OU3. Resolved CSME after focal laser photocoagulation, OU4. Pseudophakia, OU5. Type � diabetes6. Hypertension7. Hypercholesterolemia

Management ProtocolBased on a dramatic recent decline in vision OD withclinical evidence of worsening cystoid macular edema (CME) and hyaloidal traction, repeat optical coherence tomography (OCT) was performed to evaluate

Figure 7. Case 3: Cystoid macular edema with vitreomacular traction, current visit (OD)

Figure 6a. Case 3: Retinal thickness map at prior visit (OD)

Figure 6b. Case 3: Retinal thickness map at current visit (OD)

11Summer 2006

technology can easily detect subclinical macular edema, which may lead to earlier treatment and better outcomes than previously seen in the ETDRS trials.

OCT also provides a graphic representation of vitreomacular interface abnormalities including macular holes and VMT syndrome.�3,�4 In these conditions, an incomplete posterior vitreous detachment exerts abnormal traction on the macular surface.�5 Vitreous traction can also cause DME and tractional detachments of the macula.�6 Posterior hyaloidal traction should be suspected in patients with diffuse, recalcitrant DME, or with sudden worsening of DME. An OCT should be obtained in these situations, which will usually reveal the characteristic changes associated with VMT. If VMT is causing significant visual changes, a vitrectomy is recommended to release the tractional forces.�7

References1. Diabetic Retinopathy Study Research Group. Four risk factors for severe vision loss in diabetic retinopathy. DRS report 3.

Arch Ophthalmol. 1979;97:654-655.�. Diabetic Retinopathy Study Research Group.

Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of DRS findings. DRS report 8. Ophthalmology. 1981;88:583-600.

3. Early Treatment of Diabetic Retinopathy Study Group. Early photocoagulation for diabetic retinopathy. Early Treatment of Diabetic Retinopathy Study report 9. Ophthalmology. 1991;98:766-785.

4. Ferris, F. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc. 1996;94:505-537.

5. Coleman DJ, Daly SW, Atencio A, Lloyd HO, Silverman RH. Ultrasonic evaluation of the vitreous and retina. Semin Ophthalmol. 1998;13:�10-�18.

6. Vinding T, Nielsen NV. Two cases of acutely developed cataract in diabetes mellitus. Acta Ophthalmol. 1984;6�:373-377.

7. Rabinowitz R, Yagev R, Shoham A, Lifshitz T. Comparison between clinical and ultrasound findings in patients with vitreous hemorrhage. Eye. �004;18:�53-�56.

8. Genovesi-Ebert F, Rizzo S, Chiellini S, Di Bartolo E, Marabotti A, Nardi M. Reliability of standardized echography before vitreoretinal surgery for proliferative diabetic retinopathy. Ophthalmologica. 1998;�1�(suppl 1):91-9�.

9. Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe proliferative diabetic retinopathy: two-year results of a randomized clinical trial. Diabetic Retinopathy Vitrectomy Study report �. Arch Ophthalmol. 1985;103:1644-165�.

10. Vitrase for Vitreous Hemorrhage Study Groups. Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage. Am J Ophthalmol. �005;140:585-597.

11. Vitrase for Vitreous Hemorrhage Study Groups. Pooled efficacy results from two multinational randomized controlled clinical trials of a single intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage. Am J Ophthalmol. �005;140:573-584.

1�. Spaide RF, Fisher YL. Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina. �006;�6:�75-�78.

13. Patz A. Principles of fluorescein angiography. Int Ophthalmol Clin. 1977;17:1-19.

14. National Diabetes Data Group. Diabetes in America. �nd ed. National Institutes of Health Publication No. 95-1468. 1995.

15. Mizener JB, Podhajsky P, Hayreh SS. Ocular ischemic syndrome. Ophthalmology. 1997;104:859-864.

16. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern: Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; �003.

17. Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Arch Ophthalmol. 1995;113:1144-1155.

18. Sakata K, Funatsu H, Harino S, Noma H, Hori S. Relationship between macular microcirculation and progression of diabetic macular edema. Ophthalmology. �006;113:1385-1391.

19. Early Treatment Diabetic Retinopathy Study Research Group. Fluorescein angiographic risk factors for progression of diabetic retinopathy. ETDRS report number 13. Ophthalmology. 1991;98(5 suppl):834-840.

�0. Walsh JB. Hypertensive retinopathy. Description, classification, and prognosis. Ophthalmology. 198�;89:11�7-1131.

�1. Hayreh SS, Servais GE, Virdi PS. Macular lesions in malignant arterial hypertension. Ophthalmologica. 1989;198:�30-�46.

��. Massin P, Girach A. Erginay A. Gaudric A. Optical coherence tomography: a key to the future management of patients with diabetic macular oedema. Acta Ophthalmol Scand. �006;84:466-474.

�3. Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of macular holes. Ophthalmology. 1995;10�:748-756.

�4. Gallemore RP, Jumper JM, McCuen BW �nd, Jaffe GJ, Postel EA, Toth CA. Diagnosis of vitreoretinal adhesions in macular disease with optical coherence tomography. Retina. �000;�0:115-1�0.

�5. Smiddy WE, Michels RG, Glaser BM, deBustros S. Vitrectomy for macular traction caused by incomplete vitreous separation. Arch Ophthalmol. 1988;106:6�4-6�8.

�6. Kaiser PK, Riemann CD, Sears JE, Lewis H. Macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction. Am J Ophthalmol. �001;131:44-49.

�7. Capone A Jr, Panozzo G. Vitrectomy for refractory diabetic macular edema. Semin Ophthalmol. �000;15:78-80.

OCT is indispensable for its ease of use, speed, sensitivity, objectivity, and reproducibility

*Image Credits: All retinal images courtesy of Byron S Ladd.

An Expert Dialogue on Diabetic Retinopathy1� R E P O R T E R

Clinical Color Vision Tests Have Limited Value as Screening Tests for Diabetic RetinopathyTritan color deficits are common among patients withmacular disease, including diabetic retinopathy, leading a number of investigators to propose color vision testing as a tool to detect the disease before the loss of visual acuity.5,6 A research team from New York University School of Medicine and Columbia University performed a controlled comparison of 3 color vision tests—the Farnsworth-Munsell 100-hue test (FM100), Roth �8-hue test (R�8), and Lanthony desaturated D15 test (D15)—and reported results at ARVO. Ten patients with severe diabetic retinopathy were examined prior to photocoagulation. Their results were compared against those from an age-similar control group. As expected, the control subjects had color vision within the normal range on the FM100, but on both the R�8 and D15, some control subjects showed a tritan deficit. In patients with diabetic retinopathy, all of whom would be expected to exhibit tritan deficits, there were discrepancies among the 3 tests. No test consistently detected tritan deficits in these patients; nor were the results consistent between tests, which agreed in only 3 of the 10 cases. This study demonstrates the lack of interchangeability among tests of color vision, and a lower rate of false positives for the FM100 versus the R�8 or D15.

Retinal Thinning May Precede Signs of Diabetic RetinopathyStudies of retinal structure in animal models of diabeticretinopathy have suggested that retinal neuronal and glial cell death may precede other clinical signs of the disease. An OCT study performed by researchers from Johns Hopkins University School of Medicine presented at ARVO suggested that retinal thinning consistent with loss of neuronal and glial mass is present in patients with diabetes without clinical signs of diabetic retinopathy.7 The difference in retinal thickness between patients and volunteer controls was most pronounced in the fovea (184 ± �3 microns vs 193 ± �3 microns, P<.000�). The authors suggest that if these results are confirmed, OCT may become a screening tool for early diabetic retinopathy.

Still More Evidence in Favor of Fundus Photography as a Screening Test for RetinopathyThe lack of sensitivity of direct ophthalmoscopy performedby non-ophthalmologists to detect diabetic retinopathy is well known,8 but an abstract presented at the ADA provided evidence that even ophthalmologists cannot accurately detect diabetic retinopathy using direct ophthalmoscopy. In this study, evaluation of 7-field stereo

RESEARCh ROUNDUP Numerous abstracts related to diabetic retinopathy pathophysiology, epidemiology, diagnosis, and treatment were prominently featured at � major scientific and clinical meetings this spring: the Association for Research in Vision and Ophthalmology (ARVO) �006 Annual Meeting, April 30-May 4, �006, in Ft Lauderdale, Florida and the American Diabetes Association (ADA) 66th Annual Scientific Sessions, June 9-13, �006, in Washington, DC. The abstracts summarized below reflect the latest research in screening and diagnostic techniques for diabetic retinopathy, including DME.

The Value of Periodic ScreeningTwo ARVO presentations by the Vanderbilt UniversitySchool of Medicine in conjunction with the Tennessee Valley Veterans Administration Healthcare System underscore the importance of routine periodic eye exams for patients with diabetes.1,� Between June �003 and March �005, 4,94� patients received photographic fundus screening. A stunning 3,454 patients (69.9%) were referred for follow-up care of either diabetic or nondiabetic ocular conditions. A total of 536 (10.8%) were considered urgent referrals; indications included CSME (n = �41 [44.9%]), PDR (n = 96 [17.9%]), optic nerve swelling (n = �4 [4.5%]), exudative age-related macular degeneration (n = 1� [�.�%]), retinal vein occlusion (n = 11 [�.1%]), and thromboembolic disease (n = 11 [�.1%]). These results suggest a high rate of ocular morbidity exists among patients with diabetes in the Veterans Administration Healthcare System.

Equation to Predict Risk of Developing Diabetic RetinopathyThe United Kingdom Prospective Diabetes Study (UKPDS)is one of the landmark studies in diabetes care. This study was organized by Dr Rury Holman, who established the Diabetes Trials Unit at Oxford University. Previously, this group has developed a risk calculation equation and related software for cardiovascular events in patients with type � diabetes without known heart disease.3 At the ADA, this group presented a similar equation for predicting the risk of developing clinical signs of diabetic retinopathy.4 Significant univariate risk factors were gender, A1C, systolic blood pressure, and the presence of macroalbuminuria (urinary albumin ≥300 mg/L). Significant multivariate risk factors were A1C, systolic blood pressure, the presence of macroalbuminuria, and diabetes duration. Contrary to other large prospective studies of diabetes complications, smoking and increased age were associated with lower risk of developing diabetic retinopathy.

13Summer 2006

*Not FDA approved for this indication.

fundus photographs at the University of Wisconsin’s Fundus Photograph Reading Center were twice as likely to detect diabetic retinopathy as skilled ophthalmologists using direct ophthalmoscopes (71% vs 35%, P<.001).9 Although the sensitivity of direct ophthalmoscopy was low (46%), the specificity for detecting any retinopathy was 93%, and the specificity for detecting PDR was 98%. These findings suggest that if a patient is referred to an ophthalmologist due to positive findings on direct ophthalmoscopy, there is a high probability that the patient has retinal disease. The findings further suggest that the use of stereo fundus photographs is highly preferable to direct ophthalmoscopy, even if the exam is performed by a skilled ophthalmologist, a situation that arises more commonly in resource-limited medical settings.

Image Resolution May Limit Sensitivity of Digital Fundus PhotographyDigital imaging is becoming more widely availablein clinical ophthalmology, but concerns about the equivalence of digital images to images on film remain. The current director of the Fundus Photograph Reading Center, Dr Ronald P Danis, Jr, and colleagues presented an abstract at ARVO in which ETDRS Severity Scale grades for digitally scanned fundus images were compared against the original images on film.10 Compressed TIFF images (~1.65 megapixels displayed at 7� ppi on a �0.1-inch LCD monitor) were graded by 8 expert graders. Digital imaging was found to be less sensitive than film imaging (83% vs 91%), and the digital grade was generally a little more than 1 step lower than for film. Microaneurysms, IRMA, and subtle neovascular complexes were the most commonly overlooked lesions on digital images. The authors conclude that further investigation of resolution, compression, and display parameters is needed to optimize digital image grading sensitivity. The authors caution that their results cannot be extrapolated to other digital images, even those of comparable resolution, due to variations in color spacing, brightness, and contrast between camera systems. (NB: fundus images appearing in Retinopathy Reporter have a resolution of at least 300 dpi.)

Panretinal Photocoagulation Causes Optic Nerve Changes Resembling GlaucomaTwo abstracts by independent groups of researchers affiliated with the University of California Davis/Federal University of São Paulo (UCD/FUSP) and The George Washington University (GWU), respectively, provided detailed descriptions of the retinal nerve fiber layer and optic disc following panretinal photocoagulation (PRP) that could be confused with glaucomatous changes.11,1�

The UCD/FUSP group determined that the retinal nerve fiber layer (RNFL) is thinner in patients with diabetes than in age-matched controls, and that patients treated with PRP have thinner RNFL than patients with diabetic retinopathy without PRP.11 The authors suggest that thinning of the RNFL may result from progression of diabetic retinopathy and from axonal degeneration from PRP. The GWU group also found a significant decrease in RNFL after PRP, as well as a significant increase in the cup-to-disc ratio after PRP,1� another finding associated with glaucoma. Together, these studies quantify the effects of PRP on the RNFL, and emphasize the importance of accounting for prior PRP before diagnosing glaucoma in patients with severe diabetic retinopathy.

References1. Rao US, Barahimi B, Recchia C, et al. Incidence and nature

of referrals among diabetic patients enrolled in a fundus photographic screening program. Abstract 980/B913. ARVO �006.

�. Barahimi B, Rao US, Recchia C, et al. Analysis of ophthalmic pathology other than diabetic retinopathy diagnosed by photographic screening of diabetic patients. Abstract 3868/B908. ARVO �006.

3. UKPDS risk engine. [Web site.] Available at: http://www.dtu.ox.ac.uk/index.html?maindoc=/outcomesmodel. Accessed June 13, �006.

4. Coleman RL, Stevens RJ, Aldington SJ, Holman RR. Estimating risk of clinically evident retinopathy in type � diabetes. Abstract ��9-OR. ADA �006.

5. Ong GL, Ripley LG, Newsom RS, et al. Screening for sight-threatening diabetic retinopathy: comparison of fundus photography with automated color contrast threshold test. Am J Ophthalmol. �004;137:445-45�.

6. Maar N, Tittl M, Stur M, Zajic B, Reitner A. A new colour vision arrangement test to detect functional changes in diabetic macular oedema. Br J Ophthalmol. �001;85:47-51.

7. Kashani AH, Shah SM, Haller J, et al. Evaluation of the retina of subjects without diabetes mellitus and subjects with diabetes mellitus without diabetic retinopathy using optical coherence tomography. Abstract 101�/B945. ARVO �006.

8. Sussman EJ, Tsiaras WG, Soper KA. Diagnosis of diabetic eye disease. JAMA. 198�;�47:3�31-3�34.

9. Emanuele N, Klein R, Moritz T, et al. Comparison of dilated fundus examination by ophthalmologists with 7-field stereo fundus photographs in the Veterans Affairs Diabetes Trial (VADT). Abstract ��15-PO. �006 ADA.

10. Hafford DG, Reimers JL Danis RP Jr, et al. Diabetic retinopathy severity assessment from digital images compared to film. Abstract 986/B919. ARVO �006.

11. Lum B, Tanimoto SA, Melo LAS Jr, et al. Comparison of retinal nerve fiber layer thickness among patients with diabetic retinopathy with and without panretinal laser photocoagulation. Abstract 3407/B940. ARVO �006.

1�. Muir GJ, Belyea DA, Nasrallah FP, Olszowy R, Dan JA, Jones BE. Optic disc changes after panretinal photocoagulation imaged by OCT and HRT. Abstract 5705/B799. ARVO �006.

An Expert Dialogue on Diabetic Retinopathy14 R E P O R T E R

*Not FDA approved for this indication

Thank you for your overwhelming response to the Spring issue of Retinopathy Reporter! We received over 100 evaluation forms and questions in less than 1 week! Some of the most frequently asked questions are answered below.

What are the long-term outcomes from triamcinolone* injections for DME? How often can triamcinolone injections be repeated?

Given the lack of long-term, randomized, controlled clinical trials of triamcinolone injections for diabetic retinopathy, the treatments are still considered experimental. According to a recent review of triamcinolone treatment for retinal disorders, single intravitreal injections of triamcinolone have a duration of effect of about 6 to 9 months for a dosage of about �0 mg, and about � to 4 months for a 4 mg dose.1 In a case series of 46 patients with diffuse DME or other eye disorders, patients were given up to 6 intravitreal injections of about �0 mg triamcinolone each, with repeat injections administered at progressively longer intervals between injections, ranging from 6.7 ± �.4 months for the second injection to 10.8 months for the third injection. The most common complications of intravitreal injection are elevated IOP and progression of cataract. Repeat intravitreal injection of triamcinolone does not appear to increase the risk of elevated IOP beyond that incurred by the first injection; however, the risk of cataract development appears to be dose-dependent and more common in patients who also experience elevated IOP. Sub-Tenon’s injection of triamcinolone appears to circumvent some of the side effects of intravitreal injection, but requires a higher dose. Additional information from this review article is available in a summary posted in the Literature Library section of www.CaringForDiabetes.com.

1. Jonas JB. Intravitreal triamcinolone acetonide: a change in a paradigm. Ophthalmic Res. �006;38:�18-�45.

Q: How is bevacizumab* being used to treat diabetic retinopathy?

A: Bevacizumab is a VEGF inhibitor currently approved as a cancer treatment. According to Philip J Rosenfeld, MD, PhD, of the Bascom-Palmer Eye Institute in a session entitled “Avastin in Ophthalmology,” presented at the World Ophthalmology Congress in São Paulo, Brazil, on February ��, �006, the drug is currently being used off-label as a salvage therapy in select cases of sight-threatening retinal disorders.1 No long-term studies of bevacizumab’s safety and efficacy as a treatment for diabetic retinopathy are currently available, but a survey of short-term

Michael J Cooney, MD, MBA

safety results from over 7,000 injections in more than 5,000 patients in 1� countries has been conducted, with encouraging results.�

1. Rosenfeld PJ. Avastin in ophthalmology: a global phenomenon. Undated. Available at: http://aaophp.aao.org/current_insight/avastin_in_Ophthalmology_a_global_phenomenon. Accessed June �8, �006.

�. Fung AE, Rosenfeld PJ, Reichel EZ. Intravitreal Avastin safety survey: results from the World Wide Web. 2006 Annual Meeting of the Association for Research in Vision and Ophthalmology. Ft Lauderdale, Florida, May 4, �006. Poster 5�51/B666.

Q: How can patient adherence to treatment recommendations be improved?

A: There is no question that lack of patient adherence to treatment recommendations is an obstacle to improved diabetes outcomes, but research into motivational factors associated with improved adherence has been limited.1 A comparison study of patients who did and did not respond positively to an educational intervention found that positive responders usually considered diabetes to be a serious disease, incorporated lifestyle modifications required by the disease as a normal part of their daily routine, and had been confronted with a dramatic example—often related to personal experience or events in the lives of those close to them—of the need to take better care of themselves.� This study found that patients with visual or mobility impairments related to their diabetes were often highly motivated to comply with treatment recommendations. Newly diagnosed patients were more likely to follow recommendations than patients with longstanding diabetes. Patients were also more likely to follow recommendations if they felt that their doctors were knowledgeable about diabetes and considered it a serious disease. It may be of interest for patients to know that even mild NPDR can cause difficulty reading and with driving, especially at night; more severe degrees of retinopathy may profoundly impact work, recreational, and social activities.3

1. Peyrot M, Rubin RR, Lauritzen T, Snoek FJ, Matthews DR, Skovlund SE. Psychosocial problems and barriers to improved diabetes management: results of the Cross-National Diabetes Attitudes, Wishes and Needs (DAWN) Study. Diabet Med. �005;��:1379-1385.

�. O’Connor PJ, Crabtree BF, Yanoshik K. Differences between diabetic patients who do and do not respond to a diabetes care intervention: a qualitative analysis. Fam Med. 1997;�9:4�4-4�8.

3. Coyne KS, Margolis MK, Kennedy-Martin T, et al. The impact of diabetic retinopathy: perspectives from patient focus groups. Fam Pract. �004;�1:447-453.

How do I submit a question to the Feedback Forum?

E-mail your question to: RetinopathyReporter@intmedpress.com The editor will select �-4 questions from among those received by the quarterly press deadline.

*Not FDA approved for this indication.

15Summer 2006

CME Demographic & Evaluation Form • Release Date: Sept 2006 | Expiration Date: Sept 30, 2007Please keep a copy for your records. Forms must be postmarked no later than Sept 30, �007 to receive credit.

PARTICIPANT INFORMATION (Please print clearly. Illegible forms may delay receipt of your certificate.)

First Name M Last Name

Address 1

Address � Daytime Telephone

City State ZIP Fax

E-mail Address

Profession MD DO RN PA Other _______________________________________________________________________________ Specialty _______________________________________________________________________________________________________________

CME CREDIT ATTESTATIONThe Center for Accredited Healthcare Education designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

I certify that I completed this CME activity. The actual amount of time I spent in this activity was: _______ Minutes (Not to exceed 60 minutes).

_______________________________________________________________________________________________________________________Signature of Participant (without a signature, credit cannot be issued) Date Completed

CME CREDIT ATTESTATION

On a scale from 1 to 5 (with 1 being low and 5 being high) please rate the following statements pertaining to this CME educational activity.

Low 1

�

Med 3

4

High 5

Coverage of subject matter

Clinical relevance of subject matter

Achievement of educational objectives

Objectively presented and free of bias? Yes No

What one question remains unanswered after having participated in this activity?________________________________________________________________________________________________________________________

Cite one new piece of information learned from this activity.________________________________________________________________________________________________________________________

Please identify 1 or more concrete, measurable change(s) you would like to implement in your practice as a result of participating in this activity.________________________________________________________________________________________________________________________

OUTCOMES ASSESSMENTTo assess impact on clinical behavior, outcomes surveys are conducted at 3 months following and 1 year following educational activities. Surveys are issued to a convenience sampling of activity participants. We appreciate your feedback to these surveys, as it assists us in identifying and meeting additional educational needs.

Additional comments:

________________________________________________________________________________________________________________________

Please send your completed forms to: or fax back to 1 609 275 5029.

Det

ach

alon

g pe

rfor

atio

n, c

ompl

ete,

and

follo

w in

stru

ctio

ns a

t bot

tom

of p

age

Center for Accredited Healthcare EducationDept. 45100�6 Summer�0� Carnegie CenterSuite 10�Princeton, NJ 08540

45100�6 Summer �006

An Expert Dialogue on Diabetic RetinopathyR E P O R T E R

c/o Center for Accredited Healthcare EducationSix Concourse ParkwaySuite 3000 Atlanta, GA 303�8

For additional free CME opportunities such as those listed below visit www.CaringForDiabetes.com

©�006 Designed and produced by International Medical Press 45100�6-06

R E P O R T E RAn Expert Dialogue on Diabetic Retinopathy

Insights Into Diabetic Retinopathy: Diagnostic Advances and Pathophysiologic Discoveries Lead to Innovative Treatment Options

CME Webcast developed from a CME symposium held in Fort Lauderdale, Florida, on Friday, April 28, 2006.

Foresight: Advances in Diagnosis and Management of Diabetic Retinopathy

CME Webcast and CME E-newsletter developed from a live symposium held in conjunction with the World Ophthalmology Congress 2006, in São Paulo, Brazil, on Wednesday, February 22, 2006.