Farewell, Fort Lauderdale

The official title to this year’s Association for Research in Vision and Ophthalmology (ARVO) meeting was “Translational Research: Seeing the Possibilities.” But for many of us who have become accustomed to making the springtime trek to the Broward County Convention Center, the theme of the meeting was “Farewell, Fort Lauderdale.” In the midst of this nostalgia, clinicians, scientists, and other ophthalmic professionals experienced another meeting filled with innovative and interesting presentations and the latest in clinical and pre-clinical research.

Retina update

Last year saw the release of interim findings on the Comparison of Age-Related Macular Degeneration Treatments Trial (CATT), the headto- head comparison of bev a ciz u mab (Avastin, Genentech) and ran i biz u mab (Lucentis, Genentech) for treatment of wet age-related macular degeneration (AMD).

This year’s meeting opened with a twin bill that included both results from the completed CATT study and an interim analysis of results from the alternative treatments in the Inhibition of VEGF in Age-Related Choroidal Neovascularisation (IVAN) study.Martin DF et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: Two-year results. Ophthalmology. May 1, 2012. [Epub ahead of print],Chakravarthy U et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: One-year findings from the IVAN Randomized Trial. Ophthalmology. May 10, 2012. [Epub ahead of print]

Take-Home Message The 2012 meeting of the Association for Research in Vision and Ophthalmology provided clinicians, scientists, and other ophthalmic professionals with innovative and interesting presentations and the latest in clinical and pre-clinical research.

Results of the IVAN study mirrored those from the CATT—acuity changes were comparable for bev a ciz u mab and ran i biz u mab, and while monthly injections were numerically superior to p.r.n. therapy, the difference was not significant.

The IVAN study group also conducted a metaanalysis by combining the results with 1-year data from CATT, again with similar results. While primary efficacy results were similar, analysis of secondary endpoints reinforced the idea that there are differences between the two drugs. For example, the group that received monthly ran i biz u mab treatment showed the highest percentage of patients without retinal fluid as measured by optical coherence tomography; however, the ran i biz u mab group also exhibited the highest rates of geographic atrophy.

Editor’s note: For further information about these studies, see Ophthalmology Times June 1, 2012, page 1 (“CATT: Anti-VEGFs equally effective”) and July 15, 2012, page 1 (“CATT safety debate continues”).

Anti-infectives

Longitudinal studies continue to provide key clues in the fight against antibiotic resistance.

A poster presentation by employees of and consultants to Bausch + Lomb examined the antibiotic resistance profile of ocular pathogens, with an update from the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) 2011 surveillance study.

The ARMOR study results displayed resistance trends among ocular bacterial pathogens, such as Streptococcus pneumoniae, at 32 sites using antibiotic susceptibility testing. The 2011 results showed that while almost 46% of S pneumoniae isolates were resistant to azithromycin, all isolates were susceptible to fluoroquinolones. Among the fluoroquinolones, besifloxacin had the lowest MIC90. (Haas W. IOVS. 2012;53: ARVO E-Abstract 6195)

Fluoroquinolones were also the focus of a survey designed to assess ocular pathogen prevalence and emerging antibiotic therapy. The novel isothiazoquinolone (ITQ) ACH-0139586 was tested for activity against common ocular pathogens (Staphylococcus aureus, Staphylococcus epidermidis, S pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa) and compared with moxifloxacin and gatifloxacin.

ITQs, a new class in the quinolone family, exhibit good in vitro and in vivo activities against pathogens such as S aureus, including MRSA isolates.

Fluoroquinolones typically inhibit both DNA gyrase and topoisomerase IV, which are required for the DNA replication process, whereas ITQs add a third mechanism of action as potent DNA primase inhibitors. Inhibition of DNA primase increases efficacy and decreases the chances for developing resistance compared with fluoroquinolones.

The study demonstrated that ACH-0139586 was consistently more potent relative to gatifloxacin and moxifloxacin, regardless of methicillin and fluoroquinolone resistance, and that this was most apparent against evaluated gram-positive pathogens. (Shapiro A. IOVS. 2012;53 ARVO E-Abstract 6259)

Ocular imaging

As in years past, imaging technologies and their applications were ubiquitous at this year’s ARVO meeting, with applications that cover the eye from front to back all on display.

A major theme this year was in vivo confocal microscopy, and there was a particular focus on ocular surface imaging. One study correlated the density of Langerhans’ cells, an indicator of inflammation, with a course of cyclosporine A in patients with severe keratoconjunctivitis sicca. Imaging (Heidelberg Retina Tomograph II, Heidelberg Engineering) of the central cornea showed a significant decrease in Langerhans’ cell density following treatment, and this was correlated with tear-film break-up time increases. (Jacobi C, et al. IOVS. 2012; 53:ARVO E-Abstract 2355)

Another group described the use of confocal imaging to assess age-related changes in normal meibomian glands, where they observed progressive decreases in gland density homogeneity of acinar structures and secretions as a function of subject age. (Canton V, et al. IOVS. 2012; 53: ARVO E-Abstract 86) Studies such as these should be useful in distinguishing the natural aging process from pathological conditions associated with meibomian gland dysfunction.

A number of presentations described advances in imaging technologies for the posterior segment based upon use of adaptive optics in combination with other methods. This technology improves the resolution of images by reducing the effects of wavefront distortions. For example, adaptive optics scanning laser ophthalmoscopy (AOSLO) can provide high-resolution images of individual photoreceptor cells.

The abundance of retinal imaging abstracts at the 2012 ARVO meeting evidenced the burgeoning interest in this technology. One proof-of-concept study examined structural parameters derived from the AOSLO in patients with AMD, with the goal of correlating these parameters with disease severity. In patients with early to intermediate AMD, the cone photoreceptors showed reduced reflectivity and moderately increased cell spacing, while in patients with an advanced stage of the disease the cone mosaic was severely disrupted, and cone density and ref lectivity were significantly decreased compared with those of normal subjects. (Zhang Y, et al. IOVS. 2012;53:ARVO E-Abstract 3174)

AOSLO was also used to characterize hallmark diabetic retinopathy lesions and then compare the findings with those from fundus photography and spectral-domain optical coherence tomography (SD-OCT). Microaneurysms were not clearly distinguished from small dot hemorrhages on ETDRS photos and SD-OCT, but some were identified using AOSLO by observing red blood cell flow within feeding vessels, as well as by observing red blood cells within the microaneurysms themselves.

AOSLO allows for highly detailed in vivo imaging of diabetic retinopathy lesions at the cellular level and is useful in gaining new morphologic characteristics of various hallmark pathologies. (Prager G, et al. IOVS. 2012;53:ARVO E-Abstract 5654).

Contact lenses and drug delivery

A topic that continues to generate interest is that of drug delivery and contact lens wear. With continued growth in technologies of polymer chemistry and manufacture, expanded therapeutic use of lenses is closer to reality. Studies employing lenses for therapeutic use in allergy and dry eye are ongoing, but cutting-edge polymers and other innovations have paved the way for their use in additional treatment areas such as glaucoma and anti-infectives.

A common thread among many presentations this year was exemplified by the investigation of molecularly imprinted hydrogel lenses with hyaluronic acid and timolol maleate. (Guidi G, et al. IOVS. 2012; 53:ARVO E-Abstract 458)

Another presentation described a new hydrogel lens material that was capable of providing a continuous, sustained releasing of antibiotics. Study results suggested that lens drug delivery was superior to that of gatifloxacin 0.3% or moxifloxacin 0.5% delivered by drops. (Kobayakawa S, et al. IOVS. 2012;53:ARVO EAbstract 6102)

While we say so long to Fort Lauderdale, new venues will undoubtedly infuse future meetings with new blood and a new crosssection of ophthalmology, while still maintaining a sharp view of the forefront of basic and clinical research. We look forward to greeting old colleagues and meeting new ones at the 2013 ARVO meeting in Seattle, May 5 to 9.