Lucentis for uveitis-related cystoid macular edema A new proof-of-concept study finds that Lucentis (ranibizumab) is able to improve vision and decrease uveitis-associated cystoid macular edema (CME) in patients that have failed to respond to standard corticosteroid therapy.

Uveitis is an inflammatory condition that affects the uvea (iris, ciliary body, and choroid), and is an important cause of visual loss. Unlike other causes of blindness such as age-related macular degeneration (AMD) or glaucoma, which predominantly affect the elderly, uveitis affects people of all ages. Most cases of uveitis are thought to be immune-mediated in origin and are effectively treated with medications to suppress the function of the immune system.

Cystoid macular edema (CME) is the most common cause of visual impairment in uveitis patients. CME occurs when multiple cyst-like (cystoid) areas of fluid appear in the macula and cause retinal swelling or edema that may persist long after the inflammation has subsided. While corticosteroid injections may reduce CME and improve vision, the effect is often variable. A recent study on refractory uveitic CME demonstrated that only 50% of patients had improved 2 lines of visual acuity (VA) at 3 months. Furthermore, side effects such as increased intraocular pressure (IOP) and cataract formation have been reported as high as 30% to 43% and 29%, respectively.

The pathophysiology of CME associated with uveitis is not completely understood but is thought to be a consequence of increased vascular permeability. VEGF is suspected to play a role in the loss of vascular integrity in the eye and is known to be induced by inflammatory cytokines. Therefore, inhibition of inappropriate VEGF activity is a potential new approach to treatment of CME in this population.

Methods and Results

In this prospective, noncomparative, interventional case series seven consecutive patients with controlled uveitis and refractory CME who had failed corticosteroid treatment were studied. One eligible patient chose not to participate and another did not complete follow-up for nonmedical reasons. Intravitreal Lucentis injections (0.5 mg) were given monthly for 3 months, followed by reinjection as needed. The primary outcome was the mean change in best spectacle-corrected visual acuity (VA) from baseline to 3 months, and the secondary objective was the mean change in central retinal thickness (CRT) on ocular coherence tomography. Six-month outcomes were also assessed.

At 3 months, the mean increase in acuity for the 6 patients who completed follow-up was 13 letters (2.5 lines), and the mean decrease in CRT was 357 µm. Both VA and CRT improved significantly between baseline and 3 months (P = .03 for each). Although most patients required reinjection, this benefit was maintained at 6 months. There were no significant ocular or systemic adverse effects.

Discussion

In this prospective series of 7 patients with refactory uveitic macular edema, off-label intravitreal Lucentis was successful in reducing CRT and improving VA at 3 and 6 months. This is the first published report of Lucentis used for the treatment of uveitic macular edema. This study is particularly notable given that these patients had long-standing CME and had failed multiple other medical treatment options. Although most patients needed a reinjection between 3 and 6 months, the benefit in VA and reduction of CME seen at 3 months was maintained at 6 months.

This study found that the statistically significant improvement in CRT, as measured by OCT, was accompanied by a significant improvement in VA. Moreover, the improvement in VA was greater than that found with intravitreal steroid injections for uveitic CME and greater than that found in the trials of Lucentis for AMD.

Avastin (bevacizumab) has also been investigated as an off-label treatment for uveitic macular edema. Both Codero Coma et al and Mackensen and et al report in retrospective case series that intravitreal injections of Avastin were associated with a short-term significant improvement in uveitis-related CME as measured by OCT. However, the improvement in CRT found in these studies was less than that found in our study with Lucentis. In addition, neither of those studies found a statistically significant improvement in VA. The potential increased benefit from Lucentis suggested by this study compared to the Avastin studies must be weighed against cost-effectiveness issues. One potential advantage of using Lucentis instead of Avastin is that it has been shown to be 5-fold to 20-fold more potent than full-length Avastin. In addition, the long-term safety of Lucentis has been studied in Phase III and post-surveillance studies.

The researchers conclude that intravitreal Lucentis led to an increase in VA and regression of uveitis-associated CME in patients refractory to or intolerant of standard corticosteroid therapy. They state that further studies of this promising treatment are warranted.

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Am J Ophthalmol 2009;148:303–309