Diabetic Retinopathy & Glaucoma Management

Ocular diseases present numerous challenges to pharmacists. The management of diabetic retinopathy (DR), a major consequence of uncontrolled hyperglycemia, is an area where pharmacists can make an impact on early diagnosis and medication adherence. Glaucoma, while not directly associated with diabetes, presents similar opportunities for pharmacists to make a difference in the areas of screening, prevention, and treatment. Glaucoma occurs earlier and more frequently in persons with diabetes.¹

Diabetic Retinopathy

DR, the most common diabetes-related eye disorder, is caused by changes in retinal blood vessels probably resulting from poor long-term glucose control. Untreated DR—or even delayed treatment—and its complications increase the risk of blindness in the diabetic population 25-fold compared with the non-diabetic population.² Retinopathy within the retina’s macular region signifies the onset of diabetic macular edema (DME), the leading cause of moderate vision loss. According to the International Diabetes Foundation, approximately 14%—or 93 million—of the 285 million people worldwide living with diabetes have DME.³ Within this segment, 28 million people have a vision-threatening form.^41,5

Early diagnosis and treatment can prevent vision loss. Studies have demonstrated that early detection significantly lowers health care costs because such early treatment prevents disease progression and related complications.^1,5

Staging Diabetic Retinopathy

DR is classified in 4 stages. The first 3 stages—collectively called nonprolierative DR—are differentiated as mild, moderate, and severe. The final, more advanced stage—proliferative DR—results in severe vision loss or blindness unless it is treated. Factors influencing the development of DR include diabetes duration, glycemic control, and blood pressure. DR’s prevalence is directly proportional to the duration of diabetes. Among patients who have had diabetes for more than 20 years, DR affects 80% to 100% of patients with type 1 diabetes mellitus and more than 60% of patients with type 2 diabetes mellitus.^2,6

Poor glycemic control, especially when it results in hyperglycemia, is the most critical risk factor associated with DR development. Various clinical trials and epidemiologic studies confirm this association.⁷ Once retinopathy is present, duration of diabetes appears to be a less important factor, and hyperglycemia becomes a more important contributor to retinopathy progression. Studies have demonstrated that intensive hypertension management also slows retinopathy’s progression. Elevated serum lipid levels are also associated with retinopathy development, but there is no evidence that lowering lipid levels improves any eye disease.^8,9

Treatment Paradigms for Diabetic Retinopathy

DR is not curable, but it can be managed. Controlling diabetes so that glycated hemoglobin levels remain between 6% and 7% reduces DR’s progression substantially.7 In the Diabetes Control and Complications Trial (DCCT; a major clinical study conducted from 1983 to 1993 and funded by the National Institute of Diabetes and Digestive and Kidney Diseases), all participants diagnosed with type 1 diabetes were treated with intensive insulin therapy. The study monitored patients for progression to DR. Participants who had no eye damage at enrollment were 76% less likely to develop retinopathy than those in the control group. Participants who enrolled with preexisting eye damage also benefited from tight management of diabetes: their progression to DR was 54% lower than controls.^5,7

Ocular corticosteroids (ie, drops, ointments, subconjunctival injections, orbital and periocular depot or intraocular applications) have been used for their pro-inflammatory and stabilization properties. Researchers also believe they reduce vascular endothelial growth factor (VEGF) levels. Together, these effects prevent some macular edema progression.^8,10

Since 1998, ophthalmologists have used laser photocoagulation for proliferative DR, and it has been the standard treatment. This intervention reduces the incidence of moderate visual loss from 30% to 15% over a 3-year period.^11,12 The effects of laser treatment last for years, and laser surgery can be used concurrently with other treatments.¹⁰

Promising Agents

Most recently, ophthalmologists have reported promising outcomes from anti-VEGF therapy. This intervention differs from laser surgery in that retreatment is necessary periodically. These agents help reduce DME and disc or retinal neovascularization, and are often used with laser treatment. Large phase II and phase III clinical trials for ranibizumab demonstrated visual improvement for up to 3 years with a favorable safety profile; it is currently the only biologic that is FDA-approved for DME.^2,10,13-16 Ophthalmologists use other agents off-label for DR and DME (ie, bevacizumab and the VEGF-trap aflibercept), and the cost can range from less than $100 to more than $1000 per injection. These agents have improved patient quality of life.¹⁶

Glaucoma

Glaucoma is the leading cause of irreversible blindness worldwide and it affects an estimated 2.2 million Americans older than 40 years. Given the aging population, an estimated 3.4 million Americans are projected to have open-angle glaucoma by 2020, and within 15 years, the number of Americans with glaucoma is expected to increase by 50%.¹⁷ Like DR, glaucoma is a silent disease.

Glaucoma is usually associated with increased IOP (usually greater than 20 mm Hg) leading to optic nerve fiber loss, but IOP is not necessarily a component of the disease. A small subset of patients have normal-tension or low-tension glaucoma. Some patients who have elevated IOP never develop glaucoma.¹⁸ The medical community focuses on IOP, however, because to date, it’s the only identified modifiable risk factor. Other risk factors include family history, race, age older than 40 years, and myopia.¹⁹

Types and Etiology

Glaucoma occurs in 2 main forms:

• Primary open-angle glaucoma (POAG) is an acquired, chronic, progressive optic neuropathy accounting for about 90% of all glaucoma. It is called “open” because the eye’s anterior chamber angles—the area between the iris and cornea, through which fluid flows to escape via the trabecular meshwork—remain open. IOP is usually elevated, and the elevation causes optic disc cupping and atrophy. With age, retinal ganglion cell (RGC) damage accumulates slowly and subtly. Patients may not seek help until irreversible visual field defects or significant vision loss is present.^18,19
• Closed-angle (or angle closure) glaucoma—a painful and rapidly developing ocular emergency requiring hospitalization—presents with rapid vision change, nausea, and vomiting.^18,19

Left untreated, glaucoma can damage the retina and optic nerve, leading to gradual vision loss. POAG is a leading cause of preventable blindness. Appropriate screening includes an annual dilated eye exam and treatment with drugs or surgery to stop glaucoma’s progress before vision loss occurs.^18,19

Glaucoma’s exact cause is unknown. Again, IOP is often present, but its causes are not clear. Some researchers hypothesize that glaucoma could be classified as a central neurologic disorder, such as Parkinson’s disease and Alzheimer’s disease, rather than an eye disease. These researchers postulate that changes in the brain lead to RGC degeneration and death, and subsequently the inability to transmit visual information. Interventions directed toward RGCs and the central nervous system may be our best hope for prevention and a cure.^20,21 As researchers pursue this hypothesis, we must rely on available tools to help patients.

Treatment of Glaucoma

Glaucoma patients visit pharmacies frequently, since elevated IOP in POAG requires medication. When IOP surpasses 21 mm Hg, visual field loss increases rapidly in most patients. Patients with IOPs of 28 mm Hg are approximately 15 times more likely to develop field loss than those with pressures of 22 mm Hg. This difference highlights an important treatment consideration: depending on the patient’s type of glaucoma and IOP, he or she may need more aggressive treatment.^22-24

IOP-lowering therapy, which is the only approved form of glaucoma treatment, can slow disease progression but is often insufficient to stop further vision loss.^20,25 Clinicians select agents with an eye toward minimizing the number of medications a patient must take and avoiding significant adverse effects. Several drug classes are used (see Table 1). For approximately 25% to 40% of glaucoma patients, 1 medication will not lower IOP sufficiently; they need a second medication with a different mechanism of action as add-on therapy. Some products are available as fixed combinations for patient convenience.^26,27

In severe cases of POAG, patients who do not respond to or cannot tolerate medication are candidates for surgery. Surgical options include laser trabeculoplasty, trabeculectomy, drainage implants, or ciliary body ablation.²⁹

In closed-angle glaucoma, emergency surgery is needed as soon as the condition is identified. The surgeon will work quickly to decrease the IOP and reduce risk of further optic nerve damage; surgery also reduces risk of open-angle glaucoma developing. The surgeon will choose from among many surgical options including laser surgery, filtering surgery, lens extraction, angle-widening procedures such as goniosynechialysis, or a combination of procedures.²⁹

The Pharmacist’s Role

Patients often struggle with adherence to prescribed topical and systemic medications. A 2010 study of 204 glaucoma patients found that 29% could not successfully instill a drop in their eyes, and a full 61% touched the bottle tip to the ocular surface.³⁰ Strict medication adherence is crucial for patients with DR or glaucoma.

Pharmacy data show that most glaucoma patients do not adhere strictly to their topical therapy regimens, often because they forget. Additionally, many patients fill their prescriptions too early or too late due to multiple factors including medication costs and poor administration technique; some patients use 7 drops before 1 lands in the eye.²⁵ Counseling about, and when possible, demonstration of proper administration of ophthalmic products ensures compliance and prevents unnecessary waste and its associated cost.

Pharmacists can help prevent severe vision loss. Two simple interventions are (1) promoting and conducting community education programs and (2) facilitating eye examinations for local populations at risk of developing DR and glaucoma. Pharmacists must be persistent when educating at-risk patients about routine eye screenings; patients sometimes think they are immune to these silent eye problems, or that ignoring the signs will make them go away. Community pharmacists are the most visible and accessible health care professionals for most patients.³¹ Pharmacists should take advantage of frequent close contact to reinforce the importance of screenings and treatment adherence.

Pharmacists can also become familiar with screening recommendations and promote compliance. Online Table 2 describes the 2014 American Diabetes Association’s Standards of Medical Care in Diabetes recommended retinopathy screening for diabetic patients.¹ For glaucoma, the National Institutes of Health’s National Eye Institute recommends that all people at elevated risk (ie, African Americans 40 years and older, everyone older than 60 years [especially Mexican Americans], and those with a family history of glaucoma) undergo screening every 1 to 2 years.³²

Table 2: 2014 ADA Standards of Medical Care in Diabetes Recommended Retinopathy Screening

Patient Type

Recommendation

Adults with type 1 diabetes

â—ªInitial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 5 years of diabetes onset

Patients with type 2 diabetes

â—ªInitial dilated and comprehensive eye examination by an ophthalmologist or optometrist shortly after diabetes diagnosis

All patients after initial screening

â—ªNo evidence of retinopathy for 1 or more eye exams: consider exams every 2 years

â—ªDR is present: repeat subsequent examinations annually

â—ªRetinopathy is progressing or sight threatening: schedule more frequent examinations

Women with preexisting diabetes who are planning pregnancy or who have become pregnant

â—ªSchedule a comprehensive eye examination and counsel on the risk of development and/or progression of DR

â—ª Schedule examination during the first trimester with periodic examinations throughout pregnancy

â—ª Continue to monitor for 1 year postpartum

DR = diabetic retinopathy

Adapted from reference 1.

While patients with DR or glaucoma frequently have no warning signs of vision loss, some symptoms occur late. Symptoms include blurred or cloudy vision; difficulty seeing in dim light; double vision; floaters, black spots, cobwebs, or flashing lights; pain or pressure in the eye; persistent eye redness; straight lines appearing distorted; and tunnel vision.^1,19,21,32 These symptoms are red flags; pharmacists should refer patients to an ophthalmologist (or as appropriate, an emergency care provider) for assessment. In addition, pharmacists can take a more active role in counseling at-risk patients on the importance of adhering to medications to control hyperglycemia and hypertension.

Ms. Wick is a visiting professor at the University of Connecticut’s School of Pharmacy. She has extensive experience with the geriatric population.

References:

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• Massin P, Lange C, Tichet J, et al. Hemoglobin A1c and fasting plasma glucose levels as predictors of retinopathy at 10 years: the French DESIR study. Arch Ophthalmol. 2011;129(2):188-195.
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