eMedicine Specialties > Ophthalmology > Retina

Macular Edema, Diabetic: Treatment & Medication

Author: Emmanouil Mavrikakis, MD, PhD, Consultant Vitreoretinal Surgeon, Ophthalmology Department, Athens Medical Centre, Greece
Coauthor(s): Wai-Ching Lam, MD, FRCS(C), Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto; Baseer U Khan, MD, Staff Physician, Department of Ophthalmology, University of Toronto, Canada
Contributor Information and Disclosures

Updated: Sep 29, 2009

Treatment

Medical Care

• Systemic
  • Medical treatment should focus on optimizing diabetic and hypertensive control and lowering lipid levels. Optimizing diabetic, hypertensive, and lipid control has been shown to positively impact diabetic retinopathy.⁵
  • These issues are best managed by primary care physicians and internists.
• Ocular
  • Intravitreal triamcinolone acetonide 
    • Intravitreal triamcinolone acetonide (IVTA) has been shown to significantly reduce macular edema and to improve visual acuity, particularly when the macular edema is pronounced.^6,7,8
    • Some studies advocate IVTA as primary therapy, whereas others label it as adjunctive therapy to macular photocoagulation.⁹
    • Action is maximal at 1 week, lasting 3-6 months.
    • Patients should be counseled about the risk (30-40%) of increased intraocular pressure, of which virtually all can be medically controlled.
    • Other adverse effects include a less than 1% chance of retinal detachment, cataract, and endophthalmitis.
  • Intravitreal anti-VEGF agents
    • VEGF increases retinal vascular permeability, causes breakdown of the blood-retina barrier, and results in retina edema. VEGF is up-regulated in diabetic retinopathy.
    • Three currently available anti-VEGF agents are pegaptanib sodium, ranibizumab, and bevacizumab.
    • Pegaptanib sodium is a pegylated aptamer directed against the VEGF-A₁₆₅ isoform. It was the first FDA approved ophthalmologic anti-VEGF agent for the treatment of choroidal neovascularization (CNV) from age-related macular degeneration (ARMD). In a phase 2 prospective clinical trial, it appeared to improve anatomic and visual outcome in patients with diabetic macular edema (DME).¹⁰ Phase 3 trials of pegaptanib sodium for diabetic macular edema are being conducted.
    • Ranibizumab is a recombinant humanized antibody fragment that is active against all isoforms of VEGF-A. Intravitreal ranibizumab is FDA approved for the treatment of exudative ARMD. The RESOLVE study (phase 2, placebo-controlled, randomized, multicenter study) evaluated the effect of ranibizumab in patients with diabetic macular edema. The RESOLVE study is now concluded, and final data should be available soon. The RESTORE study (phase 3, laser-controlled, randomized, multicenter study) is designed to confirm the efficacy and safety of ranibizumab 0.5 mg as adjunctive therapy added to laser photocoagulation and/or as monotherapy in patients with diabetic macular edema. The Diabetic Retinopathy Clinical Research Network is planning two phase 3, prospective, randomized multicenter trials of ranibizumab for diabetic macular edema.
    • Bevacizumab is a full-length recombinant humanized antibody that is active against all isoforms of VEGF-A. It is FDA approved as an adjunctive systemic treatment for metastatic colorectal cancer. Small, nonrandomized pilot studies have documented some efficacy against diffuse diabetic macular edema. The Diabetic Retinopathy Clinical Research Network conducted a phase 2, prospective, randomized, multicenter clinical trial to determine the safety and possible benefits of this agent. They concluded that intravitreal bevacizumab can reduce diabetic macular edema in some eyes, but the study was not designed to determine whether the treatment was beneficial.¹¹ A phase 3 trial would be needed for that purpose.
  • Future therapies
    • The RIDE study is an ongoing placebo controlled trial evaluating the efficacy and safety of intravitreal ranibizumab 0.5 mg injection every 4 weeks for 24 months in patients with diabetic macular edema.
    • VEGF Trap-Eye is a soluble VEGF receptor fusion protein that binds all forms of VEGF-A and related placental growth factor (PGF). When administered as a single 4 mg intravitreal injection in a phase 1 study, a marked decrease in central retinal thickness and mean macular volume was noted.
    • The phase 3 FAME (fluocinolone acetonide in diabetic macular edema) trial is evaluating the Medidur fluocinolone-based injectable implant.
    • The phase 3 trial of Posurdex biodegradable implant (sustained delivery formulation of dexamethasone) for the treatment of diabetic macular edema is underway.
    • Retisert,¹² another steroid implant (fluocinolone acetonide), was evaluated in patients with diabetic macular edema with good results but a concerning adverse effect profile; 90% of patients developed cataracts, and 40% required glaucoma surgery within 3 years.

Surgical Care

Laser photocoagulation continues to be a well-proven therapy to reduce the risk of vision loss from diabetic macular edema.

The Diabetic Retinopathy Clinical Research Network reported results from a multicenter, randomized clinical trial, comparing focal/grid laser photocoagulation and intravitreal triamcinolone for the treatment of diabetic macular edema. They concluded that over a 2-year period focal/grid laser photocoagulation is more effective and has fewer adverse effects than 1-mg or 4-mg doses of preservative free intravitreal triamcinolone for most patients with diabetic macular edema.¹³

Studies on all other surgical modalities have been limited in the number of patients and the scope of disease being treated; therefore, these procedures have limited use and questionable efficacy.

• Focal/grid laser photocoagulation
  • Goals
    • Significant visual improvement is uncommon; the goal of macular laser treatment is to reduce progression.
    • Photocoagulation reduced the risk of moderate visual loss from diabetic macular edema by 50%, from 24% to 12%, 3 years after initiation of treatment.¹
  • Timing
    • Laser treatment is most effective when initiated before visual acuity is lost from diabetic macular edema; this emphasizes the need for diligent monitoring and follow-up care.
    • Laser treatment of diabetic macular edema should precede panretinal photocoagulation (PRP) by at least 6 weeks because PRP before this has been known to worsen diabetic macular edema. PRP should not be delayed in patients with very severe nonproliferative diabetic retinopathy or high-risk proliferative diabetic retinopathy.
  • Treatment
    • Area(s) of leakage can be identified by examination (areas of retinal thickening) or by fluorescein angiography.
    • Burns - 50-100 µm in diameter
    • Focal leakage - Treatment of leaking microaneurysms
    • Diffuse leakage - Grid pattern photocoagulation
    • Important to avoid foveal avascular zone
    • Argon green, krypton yellow, and 532 frequency up-converted diode - Laser to treat focal lesions
    • Scatter laser photocoagulation involves placement of multiple argon blue-green or green or krypton red laser burns.
  • Treatable lesions - Identified clinically or angiographically
    • Focal leaks greater than 500 µm from the foveal center are believed to cause retinal thickening or hard exudates.
    • Focal leaks 300-500 µm from the foveal center causing retinal thickening and hard exudates that persisted after a first treatment and a visual acuity of less than 20/40 provided that the perifoveal capillary network will not be destroyed
    • Areas of diffuse leakage; microaneurysms, intraretinal microvascular abnormality (IRMA), or diffusely leaking macular capillary bed
    • Thickened avascular zones, other than the normal foveal avascular zone
• Pars plana vitrectomy
  • It is widely recognized that there have been recent advancements in small-gauge vitreoretinal surgery.
  • Many studies^14,15 suggest that vitreomacular traction or the vitreous itself may play a role in increased retina vascular permeability. Removal of the vitreous or relief of vitreous traction with vitrectomy may, in some patients, be followed by resolution of macular edema and corresponding visual rehabilitation. However, this treatment may be applicable only to a specific subset of eyes with diabetic macular edema.
  • Patients with refractory CSME and a taut posterior hyaloid face who have not responded to macular laser treatment may benefit from a vitrectomy with possible significant improvement in visual acuity.¹⁴
  • In eyes with diffuse diabetic macular edema without posterior vitreous detachment, vitrectomy with posterior vitreous detachment may be effective in resolving the diabetic macular edema and may lead to an increase in visual acuity.¹⁵

Diet

Lifestyle modification as per primary care physician

Activity

Lifestyle modification as per primary care physician

Medication

Medical management should focus on optimizing diabetic and hypertensive control and lowering lipid levels. These issues are best managed by primary care physicians and internists.

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