Middle-aged Man With Blurred and Distorted Vision

A 52-year-old man presents for evaluation of diminished visual acuity. He has had frequent episodes of blurred and distorted vision that first occurred while he was reading but have progressed to interfere with television watching and, most worrisome, with driving. There have also been episodes of small floating spots that usually last for a week or two before resolving. By covering one eye at a time, he can confirm that both eyes are affected.

HISTORY

He received a diagnosis of type 1 diabetes mellitus at age 24. He is reasonably compliant with therapy; he uses insulin four times daily, and almost all his hemoglobin A_1c (HbA_1c) measurements have been lower than 7%. He is not overweight and has diabetic-appropriate lipid levels without the use of statins or other lipid-lowering agents. He has been taking a renin-angiotensin inhibitor (in the absence of hypertension) for 10 years.

PHYSICAL EXAMINATION

Vital signs are normal, including a blood pressure of 110/74 mm Hg. Examination of the retina reveals the presence of hard exudates, blot hemorrhages, and macular edema bilaterally. His visual acuity is 20/200 compared with 20/80 18 months earlier.

Which of the following statements about this patient’s condition and therapy is false?

A. The use of renin-angiotensin inhibitors improves the prognosis of retinopathy independent of blood pressure in persons with type 1 diabetes.

B. Lipid lowering reduces the incidence and progression of retinopathy.

C. Intraocular vascular endothelial growth factor (VEGF) inhibitors are a significantly effective therapy when metabolic control is insufficient.

D. Laser photocoagulation alone is the optimal ocular maneuver at this time.

Answer on next page

Correct Answer: D

This patient, who has had type 1 diabetes for a long time, is experiencing the complication of diabetic retinopathy, still the most common cause of blindness in the United States. Diabetic retinopathy represents a complex pathophysiology involving the “neurovascular unit.” A complete and detailed review was recently published.¹

The pathophysiology initially involves leakage of lipoproteins and blood into the subretinal layers followed by macular edema, ischemia of the nerve fiber layer, and finally proliferation of fibroblasts and new highly permeable vessels with vitreous hemorrhages, retinal detachment, and marked dysfunction of the central macula with concordant, extensive deterioration of vision.¹ Examination of the retina has been a tool of evaluation for more than a century, and we now realize that the findings correlate roughly as follows with the pathophysiology¹:

•“Hard exudates” result from leakage of lipoproteins.

•“Cotton wool spots” are caused by nerve layer infarctions.

•“Neovascularization” represents proliferative changes on the optic disc and retina.

TREATMENT AND PREVENTION

Choice D, laser photocoagulation, has been the very effective mainstay of therapy in cases that have progressed to the point of macular edema and neovascularization. However, recent data and study involving metabolic strategies and eye-specific therapy using VEGF inhibitors have demonstrated a strong and efficacious effect in prevention, slowing of progression, and even regression of advanced lesions such that choice D (photocoagulation alone) is not correct.

Metabolic strategies. A variety of metabolic strategies have proved to have the capacity to prevent diabetic retinopathy or at least slow its progression. These include the following:

•Intensive metabolic control, using glycated hemoglobin (HbA_1c) levels with a target of less than 7%.

•Control of lipid levels with strict targeted end points.

•Use of renin-angiotensin inhibitors, such as lisinopril² and enalapril,³ even in the absence of systemic
hypertension.

These strategies have individually and collectively been shown to reduce the risk and progression of proliferative diabetic retinopathy and the need for laser treatment by 40% to 75% across a wide and diverse group of diabetic populations.^1,4,5 Viewed from another perspective, the incidence and risk of diabetic retinopathy currently compared to 1980, prior to the advent
of these maneuvers, has declined from 77% to 90% to about 50% overall.^1,4,5 Thus, choices A and B are correct as stated and represent part of the proven efficacy of medical, metabolic maneuvers included in the discussion here.

Eye-specific therapies. In addition to metabolic strategies, eye-specific therapies have also grown past the sole use of laser photocoagulation. The most efficacious at this time is the use of VEGF inhibitors, which are antibodies that neutralize VEGF activity responsible for the proliferation of fibroblasts and blood vessels.

The most commonly used VEGF inhibitors are bevacizumab and ranibizumab. When given by a series of intraocular injections, these agents improve visual acuity by 1 to 2 lines using the Snellen chart,¹ results that are significantly better than those achieved with laser photocoagulation alone. Thus, choice C is certainly true.

OUTCOME OF THIS CASE

A more vigorous program of metabolic control—including a strict HbA_1c target of less than 7%, use of a renin-angiotensin inhibitor, and use of a statin to further lower lipid levels—was initiated. A combination of an intraocular VEGF inhibitor and laser therapy was also used, and at 1 year visual acuity had improved by 1 line.