Diabetic Retinopathy: Going Beyond the Exam and OCT

Helping your patients achieve the best results possible.

By Lik Thai Lim, MB BCh, FRCOphth, and Jonathan D. Walker, MD

When managing patients with diabetic retinopathy, it is critical to stress the importance of being compliant with the treatment regimen. Our ability to treat the disease has expanded dramatically with better imaging modalities, intravitreal injections, delicate lasers, and small-gauge surgery. When one observes how patients’ eyes can improve with optimal glucose control and how treatments are much more effective in such patients, however, it becomes clear that it is worth the time to encourage both patients and their physicians to optimize systemic management.


When talking with patients about systemic glycemic control, do not accept the answer, “My sugar is good.” Nowadays, patients should be aware of their long-term glucose control as measured by their hemoglobin A1C (A1C) level. This test measures the percentage of hemoglobin molecules that have been glycosylated, and the number reflects the patient’s glucose control over the preceding 2 to 3 months. A patient who is unaware of this test needs to be educated and encouraged to visit his or her medical doctor for testing. Most diabetologists strive for a goal of 7% or less, although some patients may do better with a slightly higher number.1 For instance, recent studies have suggested that intensive control in some patients with type 2 disease may actually increase the risk of mortality, and those patients may be better served with less aggressive control.2 It is not our role to suggest a specific A1C level for our patients. We do, however, need to remind patients to do the best they can to preserve both their vision and overall health.

It is well known that the risk of microvascular diabetic complications increases with increasing A1C levels.3 Data from the DCCT revealed the skyward acceleration of diabetic retinopathy severity that occurs with poor control (Figure 1). Newer treatments are far more effective at preventing damage, but they do not work as well in patients with poor systemic control. Even if patients do not need treatment, those with poor control should be followed more frequently because their disease is more likely to progress faster compared to patients with good control. Individuals with poor control may need earlier referral if they are risk for developing treatable disease. For example, a patient with severe nonproliferative retinopathy and good control may simply need to be watched, whereas someone with the same level of retinopathy with very poor control may need to be treated with early panretinal photocoagulation to prevent retinal neovascularization.


Other systemic factors can play a role in the progression of retinopathy. These include hypertension, renal failure, lipid abnormalities, and anemia. In fact, these factors can cause acute deterioration of patients’ retinopathy in a far more dramatic fashion than poor glucose control alone. For instance, if a patient presents with progressive renal failure and macular edema, the edema may resolve without treatment when the renal failure is treated.

Hypertension as a risk factor for retinopathy is particularly well studied. The most robust data come from the United Kingdom Prospective Diabetes Study (UKPDS).4 Elevated blood pressure can be as important as glucose control—both in terms of contributing to chronic damage and causing acute problems in the setting of accelerated hypertension. Blood pressure should be checked routinely in patients with diabetes, particularly if it is not clear how diligent they are with their medical follow-up. Current recommendations for blood pressure control in this population suggest that the goal should be less than 130/80 mm Hg—but, as with glucose control, some patients may be safer with a higher level.5

Dyslipidemia also appears to accelerate the progression of retinopathy, and it is believed that lowering serum lipid levels may help decrease the risk of vision loss for patients with diabetes.6-8 There will likely be patients who present with excessive amounts of hard exudates which will noticeably improve once their lipids are treated. Patients should be encouraged to work on their lipid levels in addition to monitoring their glucose and blood pressure.

Diabetic nephropathy can also be associated with retinopathy progression.8,9 This is particularly true if the patient has rapidly progressive renal failure; kidney function should always be assessed in patients with aggressive retinopathy. Anemia also seems to play a role in retinopathy progression. Although there are no large randomized trials on this issue, it is believed that treatment of significant anemia may help slow the progression of retinopathy, particularly if the anemia is secondary to kidney disease.10

Additional factors that may play a role in retinopathy progression include obstructive sleep apnea, smoking, obesity, and physical inactivity.11 Perhaps the strongest, albeit nonmodifiable risk factor, is disease duration. Diabetic retinopathy is also affected by ethnicity; the prevalence is higher in individuals of South Asian, African, Latin American, and indigenous tribal descent compared to white populations.12


The treatment of diabetic retinopathy has been revolutionized by a number of new interventions, including the use of intravitreal anti-vascular endothelial growth factor drugs such as bevacizumab (Avastin, Genentech, Inc.) and ranibizumab (Lucentis, Genentech, Inc.). The efficacy of these medications, however, can still be limited in patients with poor control and who present with advanced disease.

Fortunately, researchers are expanding our understanding of the pathophysiology of diabetic retinopathy and other diabetic complications. Diabetes is well known to increase the toxic effects of metabolic abnormalities such as hyperglycemia, dyslipidemia, and hypertension. This occurs through a number of mechanisms including oxidative stress, activating protein kinase C, increased sorbitol, and the formation of toxic advanced glycosylation end products (A1C is one such end product). It is being recognized, however, that diabetes also interferes with the regenerative ability of protective factors such as insulin, platelet-derived growth factor, nitric oxide, and antioxidant enzymes. Figure 2 demonstrates this “one-two punch” created by diabetes; it damages tissues and then prevents the body from making repairs.13

This line of research is very promising because it may lead to ways of preventing diabetic complications that go beyond controlling the usual risk factors such as glucose level and hypertension. In other words, we may be able to avoid damage, and perhaps even repair injured tissue, without being as dependent as we now are on patients’ ability to comply with their medical care. This is especially important in the developing world, where the number of diabetic patients is increasing, yet the resources available to treat them are limited.


For now, encouraging patients to take better care of their diabetes is vital, even if there are more complicated factors to consider. If patients do improve their control, be aware of a problem that can make them very discouraged: despite better control, they are almost never rewarded with total reversal of their diabetic complications. Typically, around the time that they develop retinopathy, patients begin to manifest other systemic complications. This is often the point when previously noncompliant patients start to understand the importance of good control, and for the first time ever, they begin to take better care of themselves. There is, however, a certain inertia to diabetic complications, such that patients’ conditions worsen regardless of their new tight control. Patients can become frustrated and can easily draw the incorrect conclusion that it does not make any difference whether they maintain good diabetes control. Those in the position to care for these patients have to be sensitive to this issue and be ready to address it.

It may be helpful to point out to patients that they are dealing with damage that began years ago and that they cannot necessarily make this old damage disappear with good control. Individuals with diabetes need to understand that their eye disease is like a moving freight train: it takes a while to bring things to a halt. Fortunately, it always pays off to have better control, but it just takes a while for patients to appreciate it. As you treat these people over time, you will see patients who persevere with excellent control and actually reverse the level of their disease. Such experiences will make you a much better advocate for the importance of good control.


As part of encouraging good control, it is also important to remember that diabetics are also more likely to have problems with depression and anxiety—both of which can interfere with managing their disease. Even something as simple as telling patients they have mild background retinopathy can be emotionally charged. For some patients, being told they have retinopathy may force them to face something they have been denying—and for the first time, they may have to face fears about ending up blind, having an amputation, or dying at an early age. This is a huge issue to drop into someone’s life. Try to listen beyond their questions and comments for signs of anxiety or depression. Do not hesitate to ask about these feelings and take the time to inform the patient’s other doctors if you are worried.

There is another issue that is becoming more problematic as our health care system evolves, and that is the increasing prevalence of high-deductible insurance plans. These plans often become the opposite of insurance for patients with chronic diseases. Patients may be responsible for the first several thousand dollars of their care and then have onerous copays beyond that. These plans are favorable for employers and insurance companies that want to minimize risk and provide cheaper products. They are also ideologically satisfying to people who feel that health care becomes better when patients have to pay more to get care. Unfortunately, the data suggest that this does not happen. Instead, anyone unfortunate enough to become sick will struggle financially to obtain the care they need, and the overall outcomes become worse.14 For diabetic patients, this often means they have to scrimp on their care, resulting in poorer control and worsening retinopathy. Be aware of patients’ financial situations and be willing to be flexible about payments in order to help them obtain proper care. It may be necessary to advocate on behalf of the patient with their treating ophthalmologists so that they can continue to receive the treatment they need.


The information presented in this article may sound like a lot of work; however, it does not take more than a few moments to ask about the various risk factors and encourage patients to do their best. Be prepared to alter management depending on how well patients control their disease. Also, listen for any indications that patients may be getting depressed about their conditions, and be aware of their financial situation as it applies to obtaining proper care. Treating diabetic retinopathy involves acknowledging that the patient exists in a matrix far more complex than what is seen in the retina. The matrix includes things such as a patient’s systemic control, socioeconomic status, and even insurance coverage, as well as whether he or she has hard exudates within 500 μm of the fovea. If we do not address all these issues, it is difficult to help our patients receive the best care we can provide.

The above article is excerpted from Dr. Walker’s book, Diabetic Retinopathy for the Comprehensive Ophthalmologist. The book is available from Amazon.com and as a free download at http://www.drcobook.com/.

Lik Thai Lim, MB BCh, FRCOphth, is on the staff at the Tennent Institute of Ophthalmology in Glasgow, Scotland.

Jonathan Walker, MD, is a retina specialist in private practice and is an assistant clinical professor at Indiana University School of Medicine, Fort Wayne. Dr. Walker may be reached at (260) 436-2181; retinopathytext@gmail.com.

  1. Executive summary: standards of medical care in diabetes--2012. Diabetes Care. 2012;35(suppl 1):S4-S10.
  2. Riddle MC, Karl DM. Individualizing targets and tactics for high-risk patients with type 2 diabetes: practical lessons from ACCORD and other cardiovascular trials. Diabetes Care. 2012;35(10):2100-2107.
  3. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. Sep 30 1993;329(14):977-986.
  4. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703-713.
  5. Arauz-Pacheco C, Parrott MA, Raskin P. The treatment of hypertension in adult patients with diabetes. Diabetes Care. 2002;25(1):134-147.
  6. Leiter LA. The prevention of diabetic microvascular complications of diabetes: is there a role for lipid lowering? Diabetes Res Clin Pr. 2005;68 (suppl 2):S3-S14.
  7. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370(9600):1687-1697.
  8. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383-393.
  9. Cruickshanks KJ, Ritter LL, Klein R, Moss SE. The association of microalbuminuria with diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology. 1993;100(6):862-867.
  10. Sinclair SH, Malamut R, Delvecchio C, Li W. Diabetic retinopathy: treating systemic conditions aggressively can save sight. Cleve Clin J Med. 2005;72(5):447-454.
  11. Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007;298(8):902-916.
  12. Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv Ophthalmol. 2012;57(4):347-370.
  13. Jeong IK, King GL. New perspectives on diabetic vascular complications: the loss of endogenous protective factors induced by hyperglycemia. Diabetes Metab. 2011;35(1):8-11.
  14. Woolhandler S, Himmelstein DU. Consumer directed healthcare: except for the healthy and wealthy it’s unwise. J Intern Med. 2007;22(6):879-881.