Evolution of Vitreomacular Traction Following the Use of the Dexamethasone Intravitreal Implant (Ozurdex) in the Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion

Introduction

Dexamethasone is a potent, water-soluble corticosteroid that can be delivered to the vitreous cavity by the dexamethasone intravitreal implant (Ozurdex; Allergan, Inc., Irvine, CA). ¹ The GENEVA study, a large multicenter clinical trial, concluded that in patients with macular edema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), treatment with 1 or 2 doses of the Ozurdex implant (0.7 mg) at a 6-month interval demonstrated a favorable safety and tolerability profile over 12 months of follow-up. ²

Adverse events that were reported at a significantly higher rate in patients receiving the Ozurdex implant included eye pain, ocular hypertension, and anterior chamber cells. ¹ The development or worsening of vitreomacular traction (VMT) after the use of Ozurdex has not been described. We report this case of evolution of VMT after the use of the Ozurdex implant in the treatment of macular edema secondary to CRVO.

Case Report

A 71-year-old male patient presented 2 years previously with a complaint of blurred vision of the left eye. The patient was diabetic and hypertensive and was also being treated for anemia and rheumatoid arthritis. Examination revealed a best corrected visual acuity (BCVA) of 20/20 and 20/25 in the right and left eye, respectively, bilateral cataract, and intraocular pressure (IOP) of 16 and 14 mmHg in the right and left eye, respectively, by applanation tonometry. Anterior segment examination was otherwise unremarkable. Fundus examination revealed no abnormality in the right eye and a CRVO in the left eye.

Fluorescein angiography confirmed the diagnosis of CRVO, and blood samples for complete blood count, erythrocyte sedimentation rate, glycosylated hemoglobin (HgA1c), and a lipid profile revealed no abnormalities. The patient was scheduled for a follow-up with a cardiologist. Two weeks later, the patient presented with progressive diminution of vision in his left eye and reported that his blood pressure had been elevated for the last 2 weeks. BCVA in the left eye was 5/200, and fundus examination revealed macular edema. Fluorescein angiography confirmed the presence of macular edema and showed marked progression of disc edema, macular edema, and hemorrhages. Optical coherence tomography done at this visit confirmed the diagnosis (Fig. 1A) and showed the presence of an incomplete posterior vitreous detachment; however, there was no evidence of VMT. A decision was taken to proceed with an intravitreal injection of 1.25 mg/0.05 cc bevacizumab to the left eye.

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FIG. 1.

(A) Optical coherence tomography (OCT) of the macular area at the time of presentation showing macular edema, an area of sensory macular detachment and incomplete posterior vitreous detachment. (B) OCT of the macular area after receiving intravitreal injections of bevacizumab showing persistence of macular edema along with a small area of vitreomacular traction. (C) OCT of the macular area 1 month after the first Ozurdex implant showing resolution of macular edema and appearance of vitreomacular traction. (D) OCT of the macular area 3 months after the first Ozurdex implant showing recurrence of macular edema and persistence of vitreomacular traction. (E) OCT of the macular area 1 month after the second Ozurdex implant showing resolution of macular edema and separation of vitreomacular traction. (F) OCT of the macular area after the fourth Ozurdex implant showing resolution of macular edema and complete release of vitreomacular traction.

After 5 monthly bevacizumab injections, examination revealed a BCVA of 20/60 and IOP of 16 mmHg in the left eye with minimal persistent macular edema along with a small area of VMT as evidenced by optical coherence tomography (Fig. 1B). A decision was taken to proceed with an intravitreal injection of the Ozurdex implant, as it is an FDA-approved treatment for macular edema due to CRVO that has duration of several months.

One month later, examination of the patient revealed a BCVA of 20/60, IOP of 18 mmHg, and resolution of the macular edema. However, optical coherence tomography (OCT) of the macular area revealed that the VMT was more severe (Fig. 1C).

Three months later, BCVA was 20/100 in the left eye and OCT of the macular area revealed recurrence of edema and subretinal fluid in the macula along with persistence of the VMT (Fig. 1D). A decision was taken to proceed with a second Ozurdex implant.

Examination of the patient 1 month later revealed that the BCVA was 20/80 in the left eye; IOP was 24 mmHg by Goldmann tonometry. OCT examination revealed complete resolution of macular edema and complete release of VMT (Fig. 1E). The patient was prescribed brimonidine eye drops (Alphagan; Allergan, Irvine, CA) to control the high IOP in the left eye.

The patient underwent cataract extraction in the left eye 1 month later, and he had 2 further injections of the Ozurdex implant every 4 months. Examination of the patient 3 months after the last Ozurdex implant revealed a BCVA of 20/80 in the left eye and IOP of 11 mmHg by Goldmann tonometry. The patient was still being treated with brimonidine eye drops. OCT examination revealed no evidence of macular edema (Fig. 1F).

Discussion

Macular edema is a common cause of visual loss in both BRVO and CRVO, ³ and there are several therapies that are used for its treatment. These include laser photocoagulation, ⁴ the antivascular endothelial growth factor therapies, ranibizumab (Lucentis; Genentech, San Francisco, CA),^5–7 and off-label bevacizuma and the corticosteroids triamcinolone acetonide^4,8,9 and dexamethasone. ² The Ozurdex implant is composed of a biodegradable copolymer of lactic acid and glycolic acid containing micronized dexamethasone, which is gradually released over months after insertion into the eye through a small pars plana puncture using a customized applicator system. ¹

VMT syndrome is characterized by incomplete separation of the posterior vitreous with persistent macular attachment. ¹⁰ A variety of macular abnormalities can be seen as a result of the vitreous-exerting traction on the retina, such as increased retinal thickness, cystoid macular edema, macular-hole formation, and limited macular detachment.^11–13 VMT has been described as a rare complication of CRVO ¹⁴ as well as intravitreal injection of bevacizumab. ¹⁵

The natural course of VMT depends on the extent of vitreous surface adhesions as well the presence or absence of epiretinal membranes (ERM). Odrobina et al. found a higher rate of spontaneous resolution of VMT in eyes with less-extensive vitreous surface adhesions and no ERM. ¹⁶ In 1 study of 53 eyes, Hikichi et al. found that the rate of complete posterior vitreous detachment was 11%. ¹⁷

When the patient was initially seen with macular edema, it is likely that he had an incomplete posterior vitreous detachment (PVD) and some VMT. The traction was not evident in OCT Fig. 1A, because it was likely buckled by the edema. After treatment with 5 monthly bevacizumab injections and resolution of the macular edema, the traction became evident. It was decided to treat with intravitreal Ozurdex, as it is the FDA-approved treatment for macular edema due to CRVO, and has a longer duration of action than bevacizumab. After the Ozurdex implant, there was a worsening of VMT. A possible explanation of this worsening is a result of traction of the Ozurdex implant on the vitreous base. The VMT then resolved spontaneously as the implant dissolved. It is unclear whether this would have remained if the implant had been permanent.

This case report is the first to describe the evolution of VMT in a patient with CRVO who has been treated with Ozurdex. Ophthalmologists should have a closer look at OCTs of patients with extensive macular edema for the presence of VMT, which may worsen after injection of the intravitreal implant.