A 53-year-old black male presented with a chief complaint of decreased visual acuity in his right eye. His medical history was remarkable for diabetes, which was controlled with insulin. His ocular history included non-proliferative diabetic retinopathy (DR) with diabetic macular edema (DME). He received grid laser photocoagulation two times in each eye over the last 10 years. His last treatment was four months earlier.
His best-corrected visual acuity measured 20/40 O.D. and 20/20- O.S. Dilated fundus examination revealed areas of cotton-wool spots, exudates and hemorrhages throughout the posterior poles in both eyes. Also, both maculae exhibited significant thickening, which was worse in his right eye. Optical coherence tomography confirmed 500µm of macular thickening in his right eye (figure 1) and 258µm of macular thickening in his left eye.
What is a possible treatment option for this patient?
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1. OCT confirmed 500µm of macular thickening in our patient’s right eye. |
Laser Treatment and DME
Currently, focal/grid laser photocoagulation is the mainstream treatment for patients with DME.1-3 In 1985, the results from the Early Treatment Diabetic Retinopathy Study (ETDRS) indicated that patients who underwent laser photocoagulation were 50% less likely to experience moderate vision loss than patients who received no treatment.1,2
More recently, the Diabetic Retinopathy Clinical Research Network (DRCR.net) study group reaffirmed that laser photocoagulation was indeed the best treatment option for patients with DME (when compared to steroid injections).3
Laser photocoagulation, however, is not without its shortcomings, and it may not be effective for all cases of DME. Focal DME has proven to react better to laser photocoagulation than diffuse DME; a number of patients with diffuse DME who undergo the procedure still experience moderate vision loss.1,2 Additionally, while laser photocoagulation may halt the progression of DME and is associated with decreased retinal thickness, the procedure does not routinely yield visual acuity gain.2
Anti-VEGF Therapy
During the last decade, we have gained a much better understanding of the pathophysiology of DME, which has resulted in the development of novel treatment options.
For example, we now know that hypoxia causes increased levels of vascular endothelial growth factor (VEGF) and has been shown to contribute to the breakdown of the retinal vascular barrier. This breakdown contributes to the development of DME. Also, injections of VEGF in animal models have caused increased vascular permeability and macular edema.4,5 So, because VEGF plays a critical role in the development of macular edema, anti-VEGF therapy could be an effective treatment for DME.6,7
Findings of several clinical trials support the off-label use of anti-VEGF therapy for DME.8,9 These studies have shown that DME patients on anti-VEGF therapy exhibit decreased retinal thickness, improved visual acuity and enhanced safety parameters
(see “Anti-VEGF Combats DME,” July 2009).
READ-2
Most recently, the Ranibizumab for Edema of the Macula in Diabetes 2 (READ-2) study data showed positive outcomes for anti-VEGF therapy, when compared to focal/grid laser photocoagulation.10 READ-2’s sample size included 126 patients from 14 different sites. Subjects were randomly selected to receive one of three treatments: ranibizumab injection (group 1), laser photocoagulation (group 2) or a combination of ranibizumab injection and laser photocoagulation (group 3).
Patients in group 1 received 0.5mg of ranibizumab at baseline, one, three and five months.10,11 Patients in group 2 underwent focal/grid laser photocoagulation at baseline and three months, if necessary. Patients in group 3 received an injection of ranibizumab followed by laser/grid photocoagulation at baseline and three months.
After six months, 22% of patients from group 1 exhibited at least a three-line improvement in visual acuity from baseline. In contrast, no patients from group 2 and just 8% of patients from group 3 showed a three-line improvement. Additionally, overall foveal thickness was reduced in all three groups. These results validate those of the READ-1 trial.10,11
As For Our Patient...
We referred our patient to a retinal specialist who recommended anti-VEGF therapy. Unfortunately, however, we lost him to follow-up.
Preliminary results from the READ-2 study suggest that injections of anti-VEGF agents might be a viable treatment option for patients with DME. Keep in mind, however, that these results must be carefully considered because of the small patient sample sizes and the relatively short study durations of studies to date. Additional research with larger patient pools and extended evaluation periods are necessary. Future data from ongoing clinical trials, such as RIDE, RESOLVE and RISE, will provide more concrete results regarding the role and efficacy of anti-VEGF therapy in the treatment of DME.
1. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology. 1991 May;98(5 Suppl):766-85.
2. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Arch Ophthalmol. 1985 Dec;103(12):1796-806.
3. Beck RW, Edwards AR, Aiello LP, et al. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009 Mar; 127(3):245-51.
4. Derevjanik NL, Vinores SA, Xiao WH, et al. Quantitative assessment of the integrity of the blood-retinal barrier in mice. Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2462-7.
5. Ozaki H, Hayashi H, Vinores SA, et al. Intravitreal sustained release of VEGF causes retinal neovascularization in rabbits and breakdown of the blood-retinal barrier in rabbits and primates. Exp Eye Res. 1997 Apr;64(4):505-17.
6. Funatsu H. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology. 2005 May;112(5):806-16.
7. Aiello LP. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7.
8. Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, et al. Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6-month follow-up. Ophthalmology. 2007 Apr;114(4):743-50.
9. Scott IU, Edwards AR, Beck RW, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology. 2007 Oct;114(10):1860-7.
10. Nguyen QD, Shah SM, Heier JS, et al. Primary end point (6M) results of the ranibizumab for edema of macular in diabetes (READ-2) study. Ophthalmology. 2009; Nov;116(11):2175-81.
11. Do D. The READ-2 Study: Ranibizumab for edema of the macula in diabetes. Clinical trial identifier: NCT00407381. Available at: http://clinicaltrials.gov/ct2/show/NCT00407381 (Accessed July 8, 2010).