A 64-year-old white female presented with a history of decreased vision in her right eye that had persisted for two weeks. Her medical history was remarkable for hypercholesterolemia. She also admitted to smoking one pack of cigarettes per day for the last 45 years. Her best-corrected visual acuity was 20/80 O.D. and 20/25 O.S. We noted a small afferent pupillary defect in her right eye. Intraocular pressure measured 12mm Hg O.D. and 15mm Hg O.S.

Dilated fundus examination of the right eye revealed intraretinal and superficial hemorrhages throughout the entire posterior pole, with several cotton-wool spots. The veins were tortuous and dilated (figure 1). Optic nerve head edema and macular edema were also evident in her right eye. We diagnosed the patient with macular edema secondary to a central retinal vein occlusion (CRVO).

What is a potential treatment option for this patient?

Laser Photocoagulation
Next to diabetic retinopathy, vein occlusion is the most prevalent retinal vascular complication you will see in clinical pratice.¹ More importantly, resultant macular edema is one of the most common causes for decreased visual acuity in patients with vein occlusions.

The Branch Vein Occlusion Study (BVOS) showed that laser photocoagulation was a viable treatment option for macular edema secondary to branch retinal vein occlusion (BRVO).² This finding was reaffirmed by recent results from the Standard Care vs. Corticosteroid for Retinal Vein Occlusion (SCORE) study.³ Results from the SCORE study showed that laser treatment was comparable to steroid injections for the treatment of macular edema secondary to BRVO. Furthermore, the overall safety profile was greater for the laser treated group. So, based on these data, laser treatment remains the standard of care for macular edema associated with BRVO.

However, not all cases of macular edema are resolved with the use of laser treatment. Although clinical trials, such as the Central Vein Occlusion Study (CVOS), showed moderate effectiveness of laser photocoagulation in patients with macular edema secondary to CRVO, there was no statistically significant effect on visual acuity when compared to untreated patients.⁴

So, treatment options for cases of macular edema secondary to CRVO were still fairly limited.

1. Fundus image of our patient’s right eye revealed the presence of intraretinal and superficial hemorrhages, as well as several cotton-wool spots. What treatment option would you recommend? Image Courtesy: Alan Kabat, O.D.	2. Ozurdex (Allergan), a biodegradable polymer delivery system that contains dexamethasone, is the first FDA approved intravitreal steroid implant for the treatment of macular edema secondary to retinal vein occlusion.

Ozurdex
Today, off-label treatment options for macular edema secondary to BRVO and/or CRVO are being used more frequently. Recent clinical results have shown that anti-vascular endothelial growth factor (VEGF) therapy and intravitreal steroid injections are offering new hope for these patients.³ However, the therapeutic benefits associated with these treatment modalities have a relatively short duration. Nevertheless, a recently approved delivery system may expand our treatment options by providing long-standing release and sustained efficacy.

In June 2009, Ozurdex (dexamethasone, Allergan) became the first FDA-approved intravitreal steroid implant for the treatment of macular edema secondary to retinal vein occlusion.5 Ozurdex is a biodegradable polymer implant that is injected through a 22-gauge applicator (figure 2).⁵ The delivery system contains dexamethasone, a potent, highly soluble corticosteroid with a short half-life. The effects of Ozurdex typically persist for one to three months, but longer periods of action have been shown clinically.6-8 Also, because its therapeutic effects may last more than three months, fewer re-injections are required.

FDA approval of Ozurdex was based on two parallel clinical trials.⁵ Approximately 1,300 subjects participated in these two double-masked, randomized studies.⁵ Two thirds of the subjects had macular edema associated with BRVO and one third had macular edema associated with CRVO. Most subjects had macular edema for more than three months.

Subjects were randomly assigned to receive either a single Ozurdex implant or a placebo injection. The studies showed that subjects in the treatment group achieved a visual improvement of three lines or more compared to patients in the placebo group.^5,7

This improvement was observed in 20% to 30% of treated subjects within one to two months, compared to just 10% of the subjects in the placebo group. Optimal visual improvement was observed at day 60, and a significant difference between the two groups was noted by day 90.⁷

Steroid use is limited by some side effects, however. Based on the Ozurdex clinical trials, the most common documented side effects were an increase in intraocular pressure (25%) and a higher incidence of conjunctival hemorrhages (20%).5 Cataract formation (4%), while less common, was another noteworthy complication. Additionally, the use of any steroid may increase the chance for ocular infection. And, when referring patients for steroid treatment, you must be aware of a history of herpes simplex virus or any other potential contraindications, such as advanced glaucoma.

Standard of care continues to evolve. Current clinical trial results and the approval of new therapies, such as Ozurdex, provide new, viable treatment options for patients who present with macular edema secondary to retinal vein occlusion. As optometrists, we need to be familiar with these treatment options in order to facilitate appropriate patient education and timely referral. Because some therapeutic modalities may offer long-term treatment, you may be involved in the comanagement of these patients. So, knowing the efficacy and safety profiles of these cutting-edge treatments is also necessary.

Drs. Shechtman and Karpecki are members of the Allergan Speakers’ Bureau. They have no direct financial interest in Ozurdex.

1. Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 2000;98:133-41.
2. Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984 Sep 15;98(3):271-82.
3. The Standard Care vs. Corticosteroid for Retinal Vein Occlusion (SCORE) Study. National Eye Institute. Clinical Trial:  NCT00105027. Available at: www.clinicaltrials.gov/ct2/show/NCT00105027?term=SCORE&rank=4 (Accessed December 15, 2009).
4. The Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. Ophthalmology. 1995 Oct;102(10):1425-33.
5. Allergan. Ozurdex: How Ozurdex Works. Available at: www.ozurdex.com/how-ozurdex-works.aspx (Accessed December 15, 2009).
6. Haller JA, Dugel P, Weinberg DV, et al. Evaluation of the safety and performance of an applicator for a novel intravitreal dexamethasone drug delivery system for the treatment of macular edema. Retina. 2009 Jan;29(1):46-51.
7. Haller JA. Six-month randomized controlled clinical trial of an intravitreal dexamethasone implant in macular edema associated with retinal vein occlusion. Paper presented at the American Society of Retina Specialists Retina Congress 2009. New York: October 4, 2009.
8. Fialho SL, Behar-Cohen F, Silva-Cunha A. Dexamethasone-loaded poly (epsilon-caprolactone) intravitreal implants: a pilot study. Eur J Pharm Biopharm. 2008 Mar;68(3):637-46.