A Guideline for Managing Patients With DR

Diabetes mellitus is the fastest growing chronic, noncommunicable disease worldwide.¹ One study predicted that the total number of people with diabetes would rise from 171 million in 2000 to 366 million by 2030.¹ According to the World Health Organization, roughly 422 million people worldwide have diabetes.² Knowing that we will encounter a continually increasing number of patients with this disease, it behooves us as optometrists to prepare ourselves as best as possible to be able to competently and successfully manage and comanage these patients when they inevitably end up in our chairs. As part of that preparation, let’s quickly review how diabetes affects the eyes before we cover what to do about it once it does.

A QUICK REFRESHER

Patients with poorly controlled blood sugar are at risk of developing diabetic retinopathy (DR), a complication of diabetes that damages the blood vessels of the retina. There are two main stages of DR: nonproliferative (NPDR), which is the early stage, and proliferative (PDR), which is the advanced stage. Retinal findings further classify both stages by degree of severity (Tables 1 and 2).

Diabetic macular edema (DME) is the swelling and thickening of the macula and is the most common cause of vision loss in people with DR.³ It is estimated that 7.7 million Americans have DR and of those, 750,000 have DME.³

The classification of DME that was historically defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) on the basis of fundoscopic presentation has now evolved to include OCT classification, thanks to the advancement of diagnostic testing. Clinically significant macular edema (CSME) as defined by the ETDRS requires meeting one of the following criteria: thickening at or within 500 µm (1/2 DD) of the center of the fovea, hard exudates at or within 500 µm (1/2 DD) of the center of the fovea with associated thickening, and/or 1 DD of thickening that is within 1 DD of the center of the fovea.^4,5

Using OCT to classify DME, a vast majority of clinical literature divides DME by involvement of the fovea. Retinal thickening located within the central subfield zone (1 mm in diameter) of the fovea is considered center-involving DME, and retinal thickening outside the central subfield zone of the fovea (Table 3) is considered non–center-involving DME.^5,6

REFER OR OBSERVE?

The International Council of Ophthalmology suggests that an existing diagnosis of mild to moderate NPDR with BCVA of ≤ 20/40 warrants a nonurgent referral to a retina specialist, while an existing diagnosis of severe NPDR, PDR, and DME warrants urgent referral.⁶ Clinically speaking, in the presence of non–center-involving DME with good glycemic control and low possibility of progression to PDR, observation of subclinical DME is not unheard of.

The Diabetic Retinopathy Clinical Research Retina Network’s Protocol V study concluded that patients who had good visual acuity (baseline 20/25) and center-involving DME and were only observed maintained good vision when compared with their counterparts who underwent intravitreal injections or laser photocoagulation.⁷ The study found no significant difference in visual acuity over a period of 2 years when comparing patients who underwent treatment with intravitreal drugs (16% VA loss), laser photocoagulation (17% VA loss), or observation only (19% VA loss).⁷

Laser photocoagulation can exacerbate DME in some individuals; however, according to the American Optometric Association’s Evidence-Based Clinical Practice Guideline: Eye Care of the Patient With Diabetes Mellitus, Second Edition, because the relative risk of vision loss in patients without high risk characteristics is low, treatment of center-involving DME should be considered before laser photocoagulation is used.⁸

When deciding whether to refer a patient to a retina specialist or to observe, knowing the etiology of the DME is critical. OCT imaging classifies DME into one of three types: diffuse thickening, cystoid macular edema, or serous retinal detachment.⁴

From a pathophysiology standpoint, diffuse thickening DME results from inflammation and oxidative stress due to hyperglycemia, which causes a breakdown of the inner blood-retina barrier that increases vascular permeability and propagates production of VEGF. With cystoid macular edema, prostaglandins and inflammatory cytokines cause intraretinal cysts. Serous retinal detachment may be a result of increased permeability of the choriocapillaris, possibly caused by a breakdown of the outer blood-retina barrier through the permeable external limiting membrane; this type of DME has the worst visual prognosis.^4,6

Although anti-VEGF therapy remains the gold standard of DME treatment, it is oftentimes used in tandem with focal/grid laser photocoagulation and/or corticosteroid implants and injections. Current literature has begun to highlight the variable presentation of DME on OCT as it relates to a more vascular versus inflammatory etiology; this in turn assists retina specialists in tailoring more targeted treatments for optimal visual outcomes (Table 4).^3,4,6

Ultimately, deciding whether to refer or observe depends on clinician comfort level and experience. For patients with good glycemic control and minimal subjective reduction in vision, some retina specialists who receive referrals of subclinical DME may elect to observe and follow-up in 6 weeks to determine the best course of action.

The common consensus among retina specialists I frequently refer to is that treatment versus observation is based more closely upon overall glycemic control: HgbA1C (7% or less), systemic comorbidities, and result of fluorescein angiography. Retina specialists use fluorescein angiography to help determine the extent of damage to the retina and of subclinical or clinical DME, and to evaluate the risk of progression to PDR. Once the patient is at a point where DME is resolved and good glycemic control is maintained, retina specialists will relinquish the patient back to the referring OD. However, even with resolution of DME, it is not uncommon for referring ODs to alternate dilations with the retina specialist, especially in cases of recalcitrant DME. Retina specialists tend to follow DME patients every 6 to 8 weeks for dilation and possible treatment with the aim to treat and extend the follow-up window.

Bearing this in mind, most ODs will aim to follow severe NPDR or very severe NPDR every 2 to 4 months, thereby alternating dilations with the retina specialist and making sure patients do not get lost to follow-up, as can occur on rare occasions.

Many current advances in imaging allow clinicians to screen patients with diabetes before they develop DME or experience a reduction in vision. For example, OCT angiography allows us to visualize blood vessels to the level of the choriocapillaris, which gives us the ability to determine the possibility of progression from NPDR to PDR.⁹

PREPARE TO CONQUER

By gaining and maintaining a deep understanding of DR, its stages, and treatment options, ODs can play a critical role in the diagnosis and management of the 366 million individuals who may develop diabetes in the next 10 years. Furthermore, staying up to date on new medications and drug delivery methods will broaden the scope of DME prognosis, responsiveness to treatment, and long-term management. By promoting communication between referring ODs and retina specialists and working with patients to help them understand the ramifications of DME, we may be able to minimize the long-term detrimental effects DR has on the population.