Diabetic Retinopathy and Diabetic Macular Edema Therapeutics

Diabetic Retinopathy and Diabetic Macular Edema Therapeutics

There are three major treatments of Diabetic Retinopathy and Diabetic Macular Edema which are effective to reduce vision impairment: laser surgery, pharmacotherapy, and vitreoretinal surgery.

Laser Surgery

Laser photocoagulation is a well-proven therapy to reduce the risk of vision loss from diabetic macular edema. Treatments include the following:

  • Scatter or panretinal photocoagulation (PRP laser) generally requires 1,200-1,800 individual laser spots, usually spread over two or three sessions. In this technique, the ophthalmologist avoids the macula, the central area of the retina that is responsible for our reading vision, colour vision, and other tasks requiring sharp vision. Scatter laser photocoagulation is used to treat proliferative diabetic retinopathy.
  • Focal laser surgery uses fewer spots and less intense laser power to treat diabetic macular edema. Using a technique called fluorescein angiography and other examination and photographic techniques, the ophthalmologist identifies areas that are leaking fluid into the macula area. These areas are then treated directly with a laser to prevent further leakage of fluid into the macula and to allow fluid that has already leaked to be reabsorbed.

Pharmacological treatment

Intravitreal injections of pharmacological agents, usually corticosteroids or anti-VEGF (Vascular Endothelial Growth Factor) agents, are injections into the vitreous gel inside the eye.  More detail on anti-VEGF therapy can be found below. They are used alone or in combination with laser treatment to treat Proliferative Diabetic Retinopathy and Diabetic Macular Edema. Most patients will require at least 3-4 injections, initially at intervals of 4-6 weeks and may require further injections depending on the response to treatment.

  • Corticosteroids: triamcinolone acetonide, fluocinolone acetonide implants, and dexamethasone drug delivery systems are used to block inflammation associated with Diabetic Retinopathy and Diabetic Macular Edema.
  • Anti-VEGF therapy: Pegaptanib, Bevacizumab, Ranibizumab, Aflibercept are used to block VEGF-mediated inflammation, vascular permeability (vascular leakage) and angiogenesis (growth new fragile leaky blood vessels).

Further detail on Anti VEGF therapy

The 3 most commonly utilized anti-VEGF agents — aflibercept, bevacizumab, and ranibizumab — are effective at improving vision over 1 and 2 years of treatment for Diabetic Macular Edema. However, on average, treatment with aflibercept provided superior visual gains at 1 year as compared with bevacizumab and ranibizumab. Aflibercept remained superior to bevacizumab, but not ranibizumab, based on mean visual acuity outcomes after 2 years of therapy. Although first-line therapy for most eyes with central-involved Diabetic Macular Edema consists of anti-VEGF, intravitreous injections of steroid can also be effective for Diabetic Macular Edema treatment. However, intravitreous steroid use is limited by more frequent ocular side effects, such as cataract and glaucoma.

Anti-VEGF is a viable treatment alternative to PRP in eyes with Proliferative Diabetic Retinopathy, especially for individuals with coexisting Diabetic Macular Edema that already necessitates anti-VEGF therapy. Eyes treated with anti-VEGF for Proliferative Diabetic Retinopathy have equivalent visual acuity outcomes at the 2-year endpoint of the study, compared with those treated with PRP laser. In addition, eyes treated with anti-VEGF exhibited better average visual acuity over the entire course of the 2-year study period. Additional benefits of anti-VEGF as compared with PRP laser include significantly less peripheral visual field loss, decreased rates of Diabetic Macular Edema onset, and fewer vitrectomies over 2 years.

  • Other anti-inflammatory compounds which may prove beneficial include:

– Non-Steroidal Anti Inflammatory Drugs (NSAIDS); Oral dose 

– Vitamins C and E which are antioxidants; Oral dose

– RAS system blockers Losartan, Candesartan, and Enalapril inhibit RAS-mediated inflammation; Oral dose

– Etanercept and Infliximab which target TNFα mediated inflammatory actions; Intravitreal Injection

Vitreoretinal surgery

Vitreoretinal surgery is used in for the treatment of Proliferative Diabetic Retinopathy where bleeding from the leaky vessels into the vitreous does not clear. Vitreoretinal surgery may also be required in cases of Proliferative Diabetic Retinopathy with retinal detachment to remove scar tissue attachments that may be distorting the retina and causing vision loss or wavy vision. Vitrectomy is a type of vitreoretinal surgery which can also be performed to treat Diabetic Macular Edema, particularly when there is an element of vitreoretinal traction leading to retinal thickening. Although retinal thickening is often improved after vitrectomy for Diabetic Macular Edema, visual outcomes are less certain, with approximately a third of patients experiencing substantial visual improvement, but between 20%–30% experiencing substantial visual loss after surgery.