Innovation takes center stage at Association for Research in Vision and Ophthalmology 2008 meeting

Key Points

All eyes were focused on innovation at this year's annual meeting of the Association for Research in Vision and Ophthalmology (ARVO). Researchers presented posters and held special interest groups on topics across the spectrum-from retinal disease and allergy to dry eye and lid margin disease. The following is merely a summary of the highlights.

Retina research

Posterior segment physiology and pathology held the spotlight throughout the meeting. Studies on gene therapy were prominent among the findings presented; one study demonstrated successful results of recombinant adeno-associated viral (rAAV) vector-mediated RPE65 gene replacement.¹ The small study (n = 3) in patients with Leber's congenital amaurosis suggested that subretinal injections of rAAV RPE65 may help to improve vision, as measured by visual acuity, papillary light reflex, and subjective psychophysical measures. Importantly, no serious adverse events were observed.^2,3

Because nanoparticles provide another means of targeted drug delivery, they may be a preferred therapeutic approach in cases in which gene therapy might not be a viable option, such as for age-related macular degeneration.

One study found that the sustained release of a thalidomide derivative (CLT-003, Charlesson) with nanoparticles extended the drug's effects on retinal vascular leakage and endothelial cell growth in rats with diabetes.⁴ An in-vitro study showed that cationic beta-cyclodextrin nanoparticles containing quaternary ammonium groups (QAβCD nanoparticles) carried doxorubicin through the blood retinal barrier. The QAβCD nanoparticle/doxorubicin complexes were as efficacious as, and produced less cytotoxicity, than free doxorubicin.⁵

Other means of posterior drug delivery also are under development, with the goals of prolonging therapeutic effects and using less-invasive administration routes.

A rabbit model study showed an intravitreal biodegradable polymer-based pouch to deliver antiviral ganciclovir for up to 70 days; it has potential applications in antibiotic or steroid delivery.⁶ Thermo-responsive hydrogels encapsulated bevacizumab at body temperature in vitro and remained in solution at room temperature. The gels also successfully held and released bevacizumab, producing no cytotoxic effects. Further investigation will be performed to extend the release time and to make the hydrogels fully biodegradable.⁷

In-vitro results have suggested placental growth factor (PlGF-1) to be used temporarily to increase retinal pigment epithelial (RPE) monolayer permeability and facilitate delivery of therapies to the retina.⁸

Recent research also reflects the constant search for new quantitative measures of retinal structure and function. Many experiments tested the new spectral-domain optical coherence tomograph (SD-OCT) system: a high-definition spectral-domain imaging system (Cirrus, Carl Zeiss Meditec); a high-speed, high-resolution retinal imaging system (Spectralis, Heidelberg); a high-resolution imaging system (Copernicus, Optopol Technology); an ultra-high speed, high-resolution fourier-domain OCT (RTVue, Optovue); and a non-mydriatic retinal camera (3D OCT-1000, Topcon).

Retinal blood flow velocity,^9,10 segmented retinal layer thickness, and deposits near the RPE layer in eyes with geographic atrophy¹¹ were among the endpoints measured by these instruments. Diagnostics of retinal damage in infants has seen innovation in a new handheld SD-OCT for shaken baby syndrome, which provides enhanced imaging of the associated retinal morphology.¹² Research on ultra-high resolution prototype OCT, or UHR-OCT, instruments revealed that with the use of adaptive optics (AO), change in the outer segment optical path length-a functional application of OCT technology-could be measured.¹³ Furthermore, a prototype using an AO scanning laser ophthalmoscope quantified cones in healthy maculas, an ability that might have a role in tracking retinal degeneration.¹⁴

Allergy

Although the clinical presentation of ocular allergic disease is well established, research on allergic mediators continues to be a burgeoning topic.