Association for Research in Vision and Ophthalmology meeting highlights new therapeutics

Key Points

This year's annual gathering for the Association for Research in Vision and Ophthalmology (ARVO) meeting in Fort Lauderdale, FL, produced an array of posters and sessions on all the therapeutic areas. In this review, we'll take a look at the presentations that we considered to be highlights of ARVO 2009.

Retina research

Regeneron continues its work on a fusion protein (VEGF Trap-Eye) that binds to all VEGF-A isoforms and PIGF. Results from the 12-month phase II study (n = 157) in neovascular age-related macular degeneration demonstrated that the drug lowers central retinal thickness, total macular volume, and choroidal neovascularization compared with baseline values after 1 year.¹ Older age (best-corrected visual acuity [BCVA] mean increase of 8.26 letters) and worse baseline visual acuity (VA), mean 7.54 letters, were among the predictive factors of greater VA gains with the protein.²

Despite 3 decades of advances in research and diagnosis, diabetic retinopathy (DR) still is a major concern in patients with type 1 or type 2 diabetes.⁴ Research into new therapeutics continues, and a literature search of ongoing or recently conducted clinical trials for DR was conducted to analyze the progress being made, mostly with systemic anti-angiogenic or anti-inflammatory agents being repurposed for ophthalmic use.

Data were subdivided based on indication (non-proliferative diabetic retinopathy [NPDR], panretinal photocoagulation, and diabetic macular edema [DME]). Eighty-five percent of the 57 identified trials were for DME and PDR, presumably a result of NPDR trials. The slow progression of DR may account for the limited success of several of the recent phase III trials.⁵

The slow progression of DR may mean that positive results of drug trials sometimes are not immediately apparent. The initial study of ruboxistaurin (RBX, Eli Lilly) showed minimal efficacy, with 5.5% of patients in the treatment group experiencing 15 letters or greater decline in VA compared with 9.1% of the placebo group.⁶

In contrast, a 6-year open-label extension study found that 32 mg/day of RBX significantly reduced the incidence of sustained moderate vision loss despite cessation of treatment (median interval 466 days).⁷ Only 8% of patients in the treatment group experienced sustained vision loss, compared with 26% of patients taking placebo, suggesting RBX may indeed have a long-term protective effect.

Dry eye

Researchers continue to attempt to unearth the etiologies and pathophysiologies of dry eye. Different environmental conditions, including the Buenos Aires wildfires^8-9 and air pollution,¹⁰ were noted to cause detrimental effects to the ocular surface, thereby contributing to dry eye symptoms.

Other research attempted to define the impact dry eye has on patients' daily lives. The Inter-blink Interval Visual Acuity Decay (IVAD) test, developed by researchers at Ora Inc., provides a quantitative measure of the VA decay that occurs between a patient's blinks.

A poster using this measure shed light on the ability of treatment to extend VA maintenance between blinks, important for quality-of-life maintenance.¹¹ Symptomatic break-up time (SBUT) is the time to patient-reported ocular discomfort following a blink. Findings demonstrated correlation of SBUT with corneal sensitivity, because patients with dry eye and lower corneal sensitivity take longer to report ocular discomfort after a blink than normal subjects, suggesting that these patients may have neural loop problems.¹²

Five tear film break-up patterns (TFBUPs) have been established (linear, wispy, spotting, fractured, and amorphous blob), and in a subset of patients, TFBUPs changed from baseline when exposed to the controlled adverse environment (CAE). Exposure to the CAE demonstrated that the linear TFBUP was the most prominent pattern post-CAE exposure. Of eyes that changed patterns, the greatest decrease in tear film break-up time (TFBUT) occurred in those with the post-CAE linear patterns. The linear pattern has been previously associated with more severe signs and symptoms of dry eye.¹³ The dynamic response of the tear film to the CAE may be observable by TFBUPs and may be indicative of changes in the tear film's functionality. The use of TFBUP assessment as a means of identifying patients with a response and evaluating therapies for dry eye warrants further investigation.¹⁴

Other researchers presented findings of the repeatability of tear ferning in healthy subjects. The tears collected from 69% of subjects displayed identical ferning patterns in all five drops analyzed.¹⁵