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Many patients have diabetes for between 10 and 20 years or more before DR develops, so the key to managing ocular complications in patients with diabetes is regular evaluations.
As long as they remain asymptomatic, patients with type 2 diabetes can easily forget about the devastating systemic consequences of the disease. And this comfort level may be their downfall, because diabetic retinopathy (DR) is a sneaky, sight-stealing thief that can burst onto the scene with little or no advance warning.
DR does not develop in every patient with diabetes. However, the estimated prevalence of DR in the United States from 2005 to 2008 was a substantial 28.5% in diabetic adults, and the prevalence of vision-threatening DR was 4.4%, said Mary Elizabeth Hartnett, MD, professor, Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City.
One way pharmacists can promote patient education is by reminding patients of the inherent visual risks associated with diabetes and emphasizing the importance of regular ocular evaluations to rule out the presence of DR or to facilitate early intervention to prevent progression.
Diabetes affects the retinal vasculature and the existing normal retinal blood vessels in several ways.
Sometimes diabetes causes retinal capillary damage and leakiness in the macula and leads to retinal swelling, known as macular edema, which can reduce central vision.
Other times the retinal capillaries are damaged outside the macula, and the retina is starved for oxygen and nutrients. This can lead to release of substances that promote blood vessel growth into the vitreous.
In both cases, certain growth factors, such as vascular endothelial growth factor (VEGF), can be involved, Hartnett said.
The disease is characterized by a number of symptoms and signs. Patients should be alert for the appearance of floaters or strands in their vision, central blurred/distorted vision, and transient visual blurring resulting from lens swelling in uncontrolled diabetics.
These symptoms are frequently present only in advanced retinopathy, thus highlighting the need for screening examinations in all diabetic patients.
Clinical findings include the presence of microaneurysms, flame-shaped hemorrhages, cotton-wool spots, intraretinal microvascular abnormalities (IRMA), retinal edema/exudates, and venous beading, said Michael Allingham, MD, PhD, assistant professor of ophthalmology, Duke University Eye Center, Durham, N.C.
Types of DR are characterized as nonproliferative and proliferative.
In mild disease nonproliferative DR (NPDR) presents as a few microaneurysms. In moderate disease, it appears as hemorrhages, microaneurysms, and exudates. And in severe instances, those same characteristics can appear in all four ocular quadrants; as venous beading in two quadrants minimally; or as IRMA in one quadrant.
Proliferative DR (PDR) is characterized by neovascularization, preretinal hemorrhage, vitreous hemorrhage, and traction retinal detachment, Allingham said.
Diabetic macular edema (DME), one of the most important vision-threatening forms of DR, results from a combination of chronic microvascular damage to the retinal endothelium and probably a variety of other cellular types, including neurons, glial cells, and pericytes that culminates in fluid accumulation in the macula and affects the ability to read fine print and the central vision, said Allingham.
He also noted that it is not uncommon for some patients with diabetes to have both near-normal central vision and very advanced peripheral retinopathy that requires treatment.
Because DR develops over an extended period, with many affected patients having diabetes for between 10 and 20 years or more before DR develops, the key to managing ocular complications in patients with diabetes is regular ocular evaluations.
“The real challenge with these patients is that they can have advanced asymptomatic DR. We recommend that patients with diabetes have eye examinations at least yearly to screen for the presence of DR,” Hartnett said.
Another wrinkle when dealing with this patient group, according to Allingham, is that millions of individuals have diabetes but don’t know it.
“Diabetes can be so insidious that people can write off the symptoms for extended periods before diagnosis. For these reasons, most retina specialists recommend at least a complete dilated fundus examination for all newly diagnosed diabetic patients. Most general ophthalmologists can perform this examination in asymptomatic individuals,” he said.
The stated guidelines of the American Academy of Ophthalmology recommend yearly monitoring for patients without retinopathy.
Because signs of DR do not develop for an extended period of time, some screening guidelines have been changing, he added, in response to the shortage of ophthalmologists and patient reluctance to undergo dilated eye examinations without a clear vision-related problem.
For example, he said, the Department of Veterans’ Affairs (VA) has instituted a photographic screening service in which patients can show up at a participating VA facility and have a color fundus photograph taken; if an abnormality is identified, the patient can be referred for a full examination by an ophthalmologist. This evaluation simplifies the process by allowing the fundus photograph to be substituted for a dilated fundus examination.
Hartnett and Allingham adhere to much the same course of management. Upon diagnosis of DR, the frequency of subsequent ocular evaluations depends on the severity of the disease. When NPDR is mild, no specific treatment is indicated and patients should be reevaluated every nine months. In the case of moderate disease, they should be monitored every four to six months.
With severe-to-very-severe NPDR or PDR with new abnormal blood vessels growing on the optic nerve or iris, early treatment can be considered, or evaluations every two to three months at most.
“The clinical monitoring is based on estimating the patient’s risk of progressing to a treatable or vision-threatening form of diabetes,” Allingham said.
There is no evidence-based ophthalmic treatment for NPDR. Patients are observed. The standard recommendations emphasize serum glucose and blood pressure control to reduce the risk of ocular and systemic complications, said Allingham.
For PDR, there is no FDA-approved pharmacologic agent. Panretinal photocoagulation (PRP) is used to perform thermal laser ablation of the peripheral and nonperfused retina.
“Patients with high-risk PDR are considered to have crossed a threshold in which patients are at high risk for vision loss,” he said.
Patients with PDR also can benefit from the use of anti-VEGF drugs.
“VEGF is a driving force in PDR. Clinical studies have shown that the incidence of progression to PDR or requiring treatment for PDR is reduced in patients receiving intravitreal anti-VEGF therapy for other indications. This is an active research area. We cannot state definitively that anti-VEGF drugs are part of the treatment for PDR, but there is mounting evidence that they can play a role,” he said.
Ranibizumab (Lucentis, Genentech Inc.) and aflibercept (Eylea, Regeneron Pharmaceuticals) have received FDA approval for treatment of macular edema, in 2012 and 2014 respectively. Bevacizumab (Avastin, Genentech Inc.) is used off-label to treat DME.
While anti-VEGF treatment seems to work for PDR, PRP applied to the peripheral retina remains the mainstay of treatment, said Hartnett. An anti-VEGF drug can be used initially or in combination with laser; following full PRP, patients can be monitored often without anti-VEGF treatment.
DME can be treated with a number of pharmacologic agents, with anti-VEGF drugs now the first-line treatment. Historically, the gold standard treatment for more than 30 years was thermal laser (focal or grid laser macular photocoagulation); this approach stabilizes vision but does not improve vision in most patients. Intravitreal steroid injections (triamcinolone acetonide, Kenalog, Bristol-Myers Squibb) are also efficacious for treating DME, but are associated with glaucoma and cataract development, Allingham said.
The latest studies have indicated that intravitreally injected anti-VEGF drugs are beneficial for DME in conjunction with possible laser treatment, Hartnett noted.
Another option for DME is the steroid implant dexamethasone (Ozurdex, Allergan), which recently received FDA approval and is also used for treating retinal vein occlusion, he added.
Because diabetes affects every organ system, numerous clinicians may be involved in controlling the disease.
Pharmacists who are aware of patients who have had diabetes for an extended period of time should recommend that they undergo yearly ocular examinations with an ophthalmologist or optometrist.
“The best approach that a clinician can have for patients with diabetes is to strongly encourage good serum glucose control with an A1c under 7, blood pressure, and cholesterol - the ABCs of monitoring diabetes. A good management plan happens with a good team. Clinical care now requires teamwork among various specialties,” Hartnett said.
Such team management comprises close working relationships with an endocrinologist, a primary care physician or nurse practitioner, an ophthalmologist, acardiologist, anephrologist, a nutritionist, and perhaps an exercise trainer, she said.
She noted that patients with diabetes may have a silent infection or injury that disrupts glycemic control, so it is important for their feet or legs to be checked for sores and dental evaluations made for tooth abscesses.
In order to stop progression, it is of great importance to identify those patients who are asymptomatic, as well as to emphasize the need for at least yearly eye examinations in newly diagnosed patients with diabetes.
Lynda Chartersis a medical writer in Framingham, Mass.