Using imaging to manage diabetic retinopathy

November 2, 2017

By Marco Gonzalez, MD
Gary Shienbaum, MD

Article

Creating a partnership between the optometrists and retinal practices will enhance the care of patients and serve as a continuing source of education and reference for the OD community. This constant communication will help diabetic patients who are suffering from this multifactorial disease that affects their bodies. DR must be addressed from the optometrist’s point of view, retinal specialist’s point of view, and the primary-care physician’s point of view.

The incidence of diabetes continues to rise, affecting more than 100 million adults in the United States who are now living with diabetes or pre-diabetes.¹ An estimated 34.6 percent of patients with diabetes have diabetic retinopathy (DR), which is the most common cause of vision loss among working adults.²

The development of DR is directly correlated to the duration of the disease as well as comorbidities such as hypertension, hypercholesterolemia, and metabolic control (HbA1c). In this article, we review the stages of DR and discuss the imaging modalities that can be used to diagnose and manage this vision-threatening disease.

Stages of diabetic retinopathy

Diabetic retinopathy is classified as non-proliferative with the absence of neovascularization and proliferative when it is associated with abnormal new blood vessel growth.

Non-proliferative diabetic retinopathy (NPDR) is further divided into mild, moderate, severe, and very severe. Mild NPDR is classified by the presence of microaneurysms. Any additional signs, such as hemorrhages, cotton-wool spots, hard exudates, venous beading, or intraretinal microvascular abnormalities (IRMA) constitute moderate NPDR. Severe NPDR is determined by the “421 rule,” defined as four quadrants of hemorrhages, two quadrants of venous beading, or one quadrant of IRMA. Two of those indicators in any variance designates very severe NPDR.

Proliferative diabetic retinopathy (PDR) is diagnosed by characteristics of neovascularization and further divided into non-high risk or high risk. High-risk characteristics of PDR include neovascularization of the disc (NVD) covering one quarter to one third of the disc area, NVD of less than one quarter of the disc area accompanied by a fresh pre-retinal or vitreous hemorrhage, or NVD of greater than one half of the disc area accompanied by a pre-retinal or vitreous hemorrhage. This stage often requires prompt referral and proper treatment implementation.

Diabetic macular edema

It is important to note that diabetic macular edema (DME) may be observed at any stage of the disease and is the most common cause of visual impairment. Almost 10 percent of patients with diabetes develop macular edema.³

The Early Treatment Diabetic Retinopathy Study (ETDRS) set forth criteria and management for macular edema related to diabetes and recommended treatment with laser for only those cases identified as clinically significant macular edema (CSME).⁴

CSME is defined as:

• Retinal thickening within 500 µm of the center of the fovea

• Hard exudates within 500 µm of the center of the fovea associated with adjacent retinal thickening

• One disc area of retinal thickening within one disc diameter of the center of the fovea

The advent of new diagnostic modalities, such as optical coherence tomography (OCT), has expanded and redefined DME into center-involving and non-center involving. Center-involving DME is often accompanied by a decrease in visual acuity and subfoveal involvement. Common treatments implicated for the care of DME today include antivascular endothelial growth factor (anti-VEGF) therapies and intravitreal steroids.

Given that both DR and DME may be initially asymptomatic and have the potential to lead to complications as well as visual impairment, it is critical to make the diagnosis early to initiate prompt treatment and proper follow-up. Today’s diagnostic testing aids in both the diagnosis and management of the disease.

Dilated fundus examination

Screening for DR is a critical element for early intervention and reducing the risk of visual impairment. The first step begins with a comprehensive dilated examination.

Because diabetes may affect any tissue in the eye, testing includes but is not limited to:

• Best-corrected visual acuity assessment

• Pupillary testing

• Extra-ocular motility assessment

• Evaluation of confrontation fields

• Refractive manifestations evaluation

• Tonometry

• Slit-lamp assessment

• Dilated fundus examination

Regular comprehensive eye examinations with dilation can also lead to the detection of undiagnosed diabetes. Complications of diabetes include a host of ocular manifestations that go beyond DR, including but not limited to:

• Opthalmoplegia

• Glaucoma

• Early onset of cataracts

• Other vascular retinopathies

• Anterior ischemic optic neuropathy

• Ocular surface disease

• Diabetic papillopathy

Fundus photography

In its early stages, DR is asymptomatic, which is why it is important for all diabetic patients to receive yearly dilated fundus examinations as recommended by the American Diabetes Association.⁵ Fundus photography, particularly widefield capabilities such as Optos, is often used to document the presence of any signs related to DR. These baseline images may be used to further document changes and progression and help determine whether a patient has DR and needs consultation with a retinal specialist.

Ultra-widefield imaging, fluorescein angiography

With the advent of ultra-widefield imaging, we can identify DR in the periphery of diabetic patients, which is a critical aspect of the examination. Hemorrhagic changes in the mid-periphery may be associated with further progression. DR is often under classified, and while fundus photography of the posterior pole may appear to be normal, the periphery can show numerous hemorrhaging. Ultra-widefield imaging may lead to a more accurate classification of the disease.⁶

Ultra-widefield fluorescein angiography (UWFA) (Optos) reveals more retinal vascular pathology in patients with DR, which may alter the classification of DR and influence treatment.⁶ UWFA is commonly implemented in cases categorized as NPDR. Such patients may show only moderate DR in the posterior pole, while the periphery reveals further findings of neovascularization. UWFA may also help reveal areas of non-perfusion, which can guide laser treatment, especially in cases of DME that may not be responding well to therapy. UWFA’s assessment of areas of non-perfusion may lead to identification of early signs of complications, such as neovascularization, which allows closer follow up and prompt treatment.

The presence of neovascularization, with or without vitreous hemorrhage, warrants prompt referral to a retina specialist. Established treatment options include pan-retinal photocoagulation (PRP) and/or anti-VEGF intravitreal injections to help incite regression of neovascular fronds.^4,7

Recently, a large randomized control trial by the Diabetic Retinopathy Clinical Research Network revealed non-inferiority of monthly anti-VEGF injections to PRP.⁸ In today’s practice, the decision to pursue one modality over another is tailored to the individual patient because anti-VEGF injections, although extremely effective, require excellent patient follow-up to ensure adequate long term control of disease.

OCT

Spectral domain optical coherence tomography (SD-OCT) (Cirrus HD-OCT, Carl Zeiss Meditec; iVue, Optovue; Spectralis, Heidelberg Engineering; 3D OCT-1 Maestro, Topcon) has become essential in diagnosing and monitoring DME. In our experience, we have found that its use has led to a decrease in the amount of macular angiography imaging performed in recent years.

Given that DME can be asymptomatic and present at any stage of the disease, OCT becomes a critical element in the assessment of DME. SD-OCT is also important in guiding continuous treatment. SD-OCT may prove to be valuable in the assessment of concomitant maculopathies, such as epiretinal membranes and vitreomacular traction. Additionally, it may help determine causes attributing to poor visual prognosis, such as the loss of photoreceptor integrity line.⁸

Advancements in OCT have included the ability to evaluate the retinal vasculature without the use of dye. This novice tool is known as OCTA (AngioPlex OCT Angiography, Carl Zeiss Meditec; AngioVue, Optovue). The capillary plexus is an area of interest in the evaluation of patients with DR. OCTA’s use in evaluating patients with DR may aid in the proper identification of microaneurysms, which are often indiscernible using ophthalmoscopy alone, and yet they represent the earliest sign of the disease (mild NPDR). Additionally, subtle areas of IRMA or neovascularization are easily denoted using OCTA, which may not always be detected with ophthalmoscopy alone.

Ischemia, which is a critical pathophysiology element of the underlying disease, may further be assessed using OCTA. It provides both structural and blood flow changes simultaneously at different layers of the retina. Alterations in both the retinal vasculature and structure may be invisible fundoscopically, and thus, both SD-OCT and OCTA can aid in the diagnosis of the disease and help to properly classified the stage of the disease.

Looking ahead

References

1. Centers for Disease Control and Prevention. New CDC report: More than 100 million Americans have diabetes or prediabetes. Available at: https://www.cdc.gov/media/releases/2017/p0718-diabetes-report.html. Accessed August 11, 2017.

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2. Romero-Aroca P. Managing diabetic macular edema: The leading cause of diabetes blindness. World J Diabetes. 2011 Jun 15;2(6):98-104.

3. Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1987 Jul;94(7):761-74.

4. Johnson EL, Pfotenhauer K, Bradley S, Kalyani RR, Shubrook JH. Highlights From the American Diabetes Association's 2017 Standards of Medical Care in Diabetes for Osteopathic Physicians. J Am Osteopath Assoc. 2017 Jul 1;117(7):457-472.

5. Wessel MM, Aaker GD, Parlitsis G, Cho M, D'Amico DJ, Kiss S. Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. Retina. 2012 Apr;32(4):785-91.

6. Ghasemi Falavarjani K, Tsui I, Sadda SR. Ultra-wide-field imaging in diabetic retinopathy. Vision Res. 2017 Jul 20. pii: S0042-6989(17)30118-9. doi: 10.1016/j.visres.2017.02.009

7. Diabetic Retinopathy Clinical Research Network. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: A randomized trial. JAMA 2015;314(20):2137-2146.

8. Ruia S, Saxena S, Gemmy Cheung CM, Gilhotra JS, Lai TY. Spectral Domain Optical Coherence Tomography Features and Classification Systems for Diabetic Macular Edema: A Review. Asia Pac J Ophthalmol (Phila). 2016 Sep-Oct;5(5):360-7.