eMedicine Specialties > Ophthalmology > Retina

Retinopathy, Diabetic, Proliferative: Treatment & Medication

Author: Abdhish R Bhavsar, MD, Adjunct Assistant Professor, Department of Ophthalmology, University of Minnesota Medical School; Director of Clinical Research, Retina Center, PA; Past Chair, Consulting Staff, Department of Ophthalmology, Phillips Eye Institute
Coauthor(s): Neal H Atebara, MD, Clinical Assistant Professor, Department of Surgery, Division of Ophthalmology, University of Hawaii School of Medicine; John H Drouilhet, MD, FACS, Clinical Professor, Department of Surgery, Section of Ophthalmology, University of Hawaii, John A Burns School of Medicine
Contributor Information and Disclosures

Updated: Oct 6, 2009

Treatment

Medical Care

• Glucose control: The Diabetes Control and Complications Trial (DCCT) has found that intensive glucose control in patients with insulin-dependent diabetes mellitus (IDDM) has decreased the incidence and progression of diabetic retinopathy. Although no similar clinical trials for patients with non–insulin-dependent diabetes mellitus (NIDDM) exist, it may be logical to assume that the same principles also apply. In fact, the American Diabetes Association (ADA) has suggested that all diabetics (NIDDM and IDDM) should strive to maintain glycosylated hemoglobin levels of less than 7% to prevent or at the very least to minimize the long-term complications of DM, including DM retinopathy.¹
• The Early Treatment for Diabetic Retinopathy Study (ETDRS) found that 650 mg of aspirin daily did not offer any benefit in preventing the progression of DM retinopathy. Additionally, aspirin was not observed to influence the incidence of vitreous hemorrhage in patients who required it for cardiovascular disease (CVD) or other conditions.⁸
• Recently, in large phase III clinical trials, intravitreal injections of ovine hyaluronidase (Vitrase) have been shown to be safe and to have modest efficacy for the clearance of severe vitreous hemorrhage. More than 70% of subjects in these studies had diabetes, and the most frequent etiology of the vitreous hemorrhage was proliferative diabetic retinopathy.⁹
• More recently, bevacizumab (Avastin) has been used to treat vitreous hemorrhage. In addition, this medicine has been used to treat optic nerve or retinal neovascularization as well as rubeosis.^10,11

Surgical Care

The advent of laser photocoagulation in the 1960s and early 1970s provided a noninvasive treatment modality, which has a relatively low complication rate and a significant degree of success.

• Panretinal photocoagulation (PRP) is the preferred form of treatment of proliferative diabetic retinopathy (PDR).^12,13 This involves applying laser burns over the entire retina sparing the central macular area. This may be performed using a variety of delivery systems, including the slit lamp, an indirect ophthalmoscope, and the EndoProbe.
  • Application starts in a circumference of 500 µm from the disc and 2 disc diameters from the fovea to wall off the central retina. Moderate intensity burns of 200-500 µm (gray-white burns) are placed 1 spot size apart, except in areas of neovascularization where the entire frond is treated. This procedure is continued peripherally to achieve a total of 1200-1600 applications over 2-3 sessions.
  • The presence of high-risk PDR is an indication for immediate treatment.
  • In cases where macular edema and PDR coexist, laser treatments are performed, first for the macular edema, and then the PRP is spread over 3-4 sessions. If it is necessary to complete both procedures at the same time, the PRP is applied initially to the nasal third of the retina.
  • The strategy for treating macular edema depends on the type and extent of vessel leakage.¹⁴ If the edema is due to focal leakage, microaneurysms are treated directly with laser photocoagulation. In cases where the foci of leakage are nonspecific, a grid pattern of laser burns is applied. Burns (100-200 µm) are placed 1 burn size apart covering the affected area.
  • The exact mechanism by which PRP works is not entirely understood. One theory is that destroying the hypoxic retina presumably decreases the production of vasoproliferative factors, such as VEGF, which, in turn, reduces the rate of neovascularization. Another theory is that PRP allows increased diffusion of oxygen from the choroid, supplementing retinal circulation. The enhanced oxygen delivery also down-regulates vasoproliferative factor production and subsequent neovascularization.
• Vitrectomy
  • Vitrectomy may be necessary in cases of long-standing vitreous hemorrhage (where visualization of the status of the posterior pole is too difficult), tractional retinal detachment, and combined tractional and rhegmatogenous retinal detachment. More uncommon indications include epiretinal membrane formation and macular dragging.
  • The Diabetic Retinopathy Vitrectomy Study (DRVS) has recommended that vitrectomy be advised for eyes with vitreous hemorrhage that fails to resolve spontaneously within 6 months.¹⁵ Early vitrectomy (<6 mo, mean of 4 mo) may result in a slightly greater recovery of vision in patients with type I diabetes.
  • When treatment is delayed, monitoring the status of the posterior segment by ultrasound is mandatory to watch for signs of macular detachment.
  • The purpose of surgery is to remove the blood to permit evaluation and possible treatment of the posterior pole, to release tractional forces that pull on the retina, to repair a retinal detachment, and to remove the scaffolding into which the neovascular complexes may grow. Laser photocoagulation through indirect delivery systems or through the EndoProbe can be performed as an adjunctive procedure during surgery to initiate or continue laser treatment.
• Cryotherapy
  • When laser photocoagulation is precluded in the presence of an opaque media, such as in cases of cataracts and vitreous hemorrhage, cryotherapy may be applied instead.
  • The principles behind the treatment is basically the same, that is, to ablate retinal tissue for oxygen demand to be decreased and to induce a chorioretinal adhesion, which could increase oxygen supply to the retina in the hope of preventing or down-regulating the vasoproliferative response.

Diet

A good healthy diet with well-balanced meals is important for all individuals and is particularly important for individuals with diabetes. A well-balanced diet can help to achieve better weight control and also better control of the diabetes. To that end, it can also help to reduce the complications of diabetes.

Activity

Maintaining a good healthy lifestyle with regular exercise is important for all individuals, especially for those individuals with diabetes. Exercise can help with maintaining weight and with peripheral glucose absorption. This can help with improved diabetes control, and this, in turn, can help to reduce the complication of diabetes and diabetic retinopathy.

Medication

Several medications are currently being used in the treatment of diabetic retinopathy.  At present, these medications are administered into the eye by intravitreal injection. Intravitreal triamcinolone is being used in the treatment of diabetic macular edema. A recent Diabetic Retinopathy Clinical Research Network (DRCR.net) clinical trial demonstrated that, although there some reduction in macular edema occurred after intravitreal triamcinolone, this effect was not as robust as that achieved with focal laser treatment at the primary endpoint of 2 years. In addition, intravitreal triamcinolone can have some side effects, including steroid response with intraocular pressure increase and cataracts. 

Other medications that are being used in clinical practice and in clinical trials include intravitreal bevacizumab (Avastin) and ranibizumab (Lucentis). These medications are VEGF antibodies and antibody fragments, respectively. They can help to reduce diabetic macular edema and also neovascularization of the disc or retina. Combinations of some of these medications above with focal laser treatment are being investigated in the DRCR.net clinical trials.

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