Review of Ophthalmology® > Review of Ophthalmology Online > October 29, 2012

Volume 12, Number 44

Monday, October 29, 2012

OCTOBER IS WORLD BLINDNESS AWARENESS MONTH

In this issue: (click heading to view article)

		Assessing Glaucoma Risk Using Corneal Hysteresis With CCT and IOP

		Intravitreal siRNA PF-04523655 for DME

		Differential Associations of Myopia with Major Age-Related Eye Diseases

		Impact of Subconjunctival Bevacizumab on CNV

		Briefly

Assessing Glaucoma Risk Using Corneal Hysteresis with CCT and IOP

This prospective, observational, cross-sectional study's objective was to determine whether adjusting corneal hysteresis (CH) values for central corneal thickness (CCT) and intraocular pressure (IOP) improves its capability to differentiate primary open-angle glaucoma (POAG) from ocular hypertension (OH).

Included were 169 eyes of 169 subjects with a diagnosis of POAG (n=81) or OH (n=88). CH, IOP and CCT values were obtained using the Ocular Response Analyzer (ORA), Pascal Dynamic Contour Tonometer (DCT), Goldmann applanation tonometer (GAT) and ORA ultrasound pachymeter. Additionally, correlational, regression and t-test analyses were conducted before and after the sample was divided into low, intermediate and thick CCT subgroups.

It was noted that in the full sample, CH and CCT were moderately correlated (r=0.44, p<0.001) and although both were related to diagnosis in univariate regression analysis, only CH was independently related to glaucoma diagnosis in multivariate analysis. After the sample was divided into CCT tertiles, CH was significantly lower in POAG vs. OH eyes within all three CCT subgroups, and CH was the only multivariate variable that differentiated POAG from OH in each CCT subgroup. Furthermore, the relationship between CH and diagnosis was more robust within the CCT subgroups compared with the full sample, suggesting that integrating CCT into CH interpretation is beneficial. It was also reported that adjusting for CH for IOP did not aid diagnostic precision in this study.

To conclude, these findings suggest that combining CH and CCT for glaucoma risk assessment improves diagnostic capability compared to using either factor alone. Conversely, adjusting CH for IOP provided no clear clinical benefit in this study.

SOURCE: Pensyl D, Sullivan-Mee M, Torres-Monte M, et al. Combining corneal hysteresis with central corneal thickness and intraocular pressure for glaucoma risk assessment. Eye. 2012;26(10):1349–1356.

Intravitreal siRNA PF-04523655 for DME

The purpose of the following multicenter, prospective, masked, randomized, active-controlled, Phase II interventional clinical trial was to evaluate the safety and efficacy of three doses of PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP801 gene, for the treatment of diabetic macular edema (DME) compared to focal/grid laser photocoagulation.

Investigators enrolled 184 DME patients with best-corrected visual acuity (BCVA) of 20/40 to 20/320 inclusive in the study eye. They randomly assigned patients to 0.4 mg, 1 mg, 3 mg PF-04523655 intravitreal injections or laser. Change in BCVA from baseline to month 12 was the main outcome measure.

According to the investigators, all doses of PF-04523655 improved BCVA from baseline through month 12. They noted that at month 12, the PF-04523655 3 mg group showed a trend for greater improvement in BCVA from baseline than laser (respectively 5.77 vs. 2.39 letters; p=0.08; [two-sided α=0.10]). The study was terminated early at month 12 based on pre-determined futility criteria for efficacy and discontinuation rates. PF-04523655 was generally safe and well-tolerated, with few adverse events considered treatment-related. By month 12, the discontinuation rates in the PF-04523655 groups were higher than the laser group and were inversely related to dose levels.

The study investigators concluded that PF-04523655 showed a dose-related tendency for improvement in BCVA in DME patients. Studies of higher doses are planned to determine the optimal efficacious dose of PF-04523655. PF-04523655 may offer a new mode of therapeutic action in the management of DME.

SOURCE: Nguyen QD, Schachar RA, Nduaka CI, et al. Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS Study). Invest Ophthalmol Vis Sci. 2012;Oct 16. [Epub ahead of print].

Differential Associations of Myopia with Major Age-Related Eye Diseases

The authors of this population-based, cross-sectional study aimed to determine the associations of myopia and axial length (AL) with major age-related eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), age-related cataract and primary open-angle glaucoma (POAG).

They included 3,400 Indians in Singapore (75.6% response rate) aged 40 to 84 years and determined refractive error by subjective refraction. The authors also determined AL by noncontact partial coherence laser interferometry and defined AMD and DR from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System and Airlie House classification system, respectively. They clinically diagnosed age-related cataract using the Lens Opacity Classification System (LOCS) III system and defined glaucoma according to International Society for Geographical and Epidemiological Ophthalmology criteria. Main outcome measures were AMD, DR, age-related cataract and POAG.

Myopic eyes (spherical equivalent [SE] <–0.5D were less likely to have AMD (early plus late AMD) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25–0.79) or DR (OR, 0.68; 95% CI, 0.46–0.98) compared with emmetropic eyes; each millimeter increase in AL was associated with a lower prevalence of AMD (OR, 0.76; 95% CI, 0.65–0.89) and DR (OR, 0.73; 95% CI, 0.63–0.86), the authors reported. They found that myopic eyes were more likely to have nuclear (OR, 1.57; 95% CI, 1.13–2.20) and posterior subcapsular (OR, 1.73; 95% CI, 1.10–2.72) cataract, but not cortical cataract (p=0.64) and that each millimeter increase in AL was associated with a higher prevalence of posterior subcapsular cataract (PSC) (OR, 1.29; 95% CI, 1.07–1.55), but not nuclear (p=0.77) or cortical (p=0.39) cataract. They also noted that eyes with high myopia (SE <–6.0D) were more likely to have POAG (OR, 5.90; 95% CI, 2.68–12.97); each millimeter increase in AL was associated with a higher prevalence of POAG (OR, 1.43; 95% CI, 1.13–1.80).

In conclusion, myopic eyes are less likely to have AMD and DR, but are more likely to have nuclear cataract, PSC and POAG. The associations of myopia with AMD, DR and POAG are mostly explained by longer AL. However, the association between myopia and nuclear cataract is explained by lens refraction rather than AL.

SOURCE: Pan CW, Cheung CY, Aung T, et al. Differential associations of myopia with major age-related eye diseases: the Singapore Indian Eye Study. Ophthalmology. 2012;Oct 18. [Epub ahead of print].

Impact of Subconjunctival Bevacizumab on CNV

In London, researchers sought to evaluate the off-label use of subconjunctival bevacizumab for corneal neovascularization (CNV). They found that three subconjunctival injections of 2.5 mg bevacizumab are more effective than placebo at inducing the regression of recent-onset CNV.

They randomly assigned 30 patients with recent-onset CNV from various causes into a double-masked, placebo-controlled trial. Each received three 0.1 mL injections containing either 2.5 mg bevacizumab or 0.9% saline at monthly intervals. The researchers used dexamethasone 0.1% drops q.i.d. for the first month, when they modified the date if clinically indicated. They noted that the primary outcome was change in area of corneal involvement by CNV from baseline to three months measured using specialized imaging technology.

The mean area of CNV reduced by –36% (range –92% to +40%) in the 15 eyes that received bevacizumab compared with an increase of 90% (range –58% to +1,394%) in eyes that received saline placebo (analysis of covariance [ANCOVA]; p=0.007), the researchers reported. They also found that one outlier in the placebo arm developed corneal graft rejection with aggressive neovascularization (+1,384%), but even when this patient was excluded, the mean reduction in CNV in the placebo group (–3%, range –58% to +40%) was still significantly different from the treatment arm (ANCOVA; p=0.016). Changes in best-corrected visual acuity, central corneal thickness, intraocular pressure and endothelial cell counts were similar between groups. Moreover, the intervention was well-tolerated with no major safety concerns.

The study researchers feel that further studies are needed to confirm this effect and their data suggest that a sample size of 40 patients per treatment group is required.

SOURCE: Petsoglou C, Balaggan KS, Dart JK, et al. Subconjunctival bevacizumab induces regression of corneal neovascularization: a pilot randomized placebo-controlled double-masked trial. Br J Ophthalmol. 2012;Oct 20. [Epub ahead of print].

ACCUTOME INTRODUCES THREE NEW FEMTOSECOND LASER SURGICAL TOOLS. Accutome has released three new instruments: the Eippert Femtosecond Spatula, the Solomon Femtosecond Chopper and the LRI Enhancement Forceps, all of which help surgeons who use femtosecond cataract lasers to create precise subservice cuts to the eye. Learn more about these new instruments at www.accutome.com.

POSITIVE TOPLINE RESULTS FROM PHASE III DRY EYE STUDY OF LIFITEGRAST. SARcode Bioscience Inc. recently announced topline results from OPUS-1, a pivotal Phase III study of lifitegrast ophthalmic solution, 5.0%, versus placebo for the treatment of dry eye disease. A total of 588 subjects were included in the study, in which lifitegrast demonstrated superiority over placebo in the improvement of inferior and total corneal staining scores from baseline to week 12 (p=0.0007 and p=0.0148, respectively). According to SARcode Bioscience, lifitegrast also significantly improved the most commonly reported symptoms of dry eye disease in the study, which were ocular discomfort and eye dryness. The company recently commenced a year-long safety study (SONATA) and will soon begin a second pivotal Phase III confirmatory study (OPUS-2), both of which will support a planned New Drug Application filing. Read more about it here.

ADENOPLUS DIAGNOSTIC TEST AVAILABLE IN THE UNITED STATES. French company Nicox S.A. has launched AdenoPlus in the United States. The rapid point-of-care diagnostic test is FDA-cleared and CLIA-waived and aids in the differential diagnosis of acute conjunctivitis. According to Nicox, the AdenoPlus, which as 90% sensitivity and 96% specificity, is fast and easy to use. The four-step process takes less than two minutes to complete and provides a definite result in just 10 minutes. Visit the company's website for additional information.

NEW MULTIFOCAL TORIC SOFT LENS AVAILABLE FROM ALDEN OPTICAL. Alden Optical has launched ASTERA Multifocal Toric and says the lens will offer practitioners a higher level of performance for presbyopes who can benefit from custom lens prescriptions and/or astigmatic correction. Alden Optical partnered with Precilens to incorporate its C2 center-near multifocal optics, which feature large, stabilized, spherical zones at near and distance. The lens is available in custom prescriptions and multiple replacement cycles as well as without cylinder for spherical wearers who require custom lens prescriptions or designs. For more information, including ASTERA Multifocal Toric parameters, click here.

POSITIVE EFFICACY TRENDS FROM DATA IN PLUG COMBINATIONS IN PHASE II STUDIES FOR GLAUCOMA. QLT Inc. announced that results from two Phase II clinical studies, PPL GLAU 12 and PPL GLAU 13, demonstrate positive trends (with statistically and clinically significant findings) on the efficacy and safety of the Latanoprost Punctal Plug Delivery System (L-PPDS) in subjects with ocular hypertension (OH) and open-angle glaucoma (OAG). A total of 57 intent to treat (ITT) subjects were included in PPL GLAU 12 and 77 ITT subjects were included in PPL GLAU 13. Two ITT datasets were analyzed: one including all IOP values regardless of plug loss, and the other with IOP excluded after first plug loss/removal. For both studies, mean IOP changes from baseline were statistically significant at all time points. One arm (the 95 µg lower/blank plug upper configuration) showed a clinically significant IOP lowering of approximately 5.0 mmHg at four, eight and 12 weeks for both ITT datasets. Retention rate by eye of plugs in the lower puncta was >95% through week 12 in PPL GLAU 12 and through week 10 in PPL GLAU 13 (week 12 retention was 92%). Retention of upper plugs by eye was 69%, 53% and 48% at weeks four, eight and 12, respectively, in PPL GLAU 12. In PPL GLAU 13, retention of upper plugs was 76%, 65% and 58% at weeks four, eight and 12, respectively. The L-PPDS was well-tolerated over the testing period with adverse events (AEs) similar to those reported for commercial punctal plugs and the previous PPL GLAU 11 study. The majority of AEs were ocular in nature. Across all treatment arms throughout the duration of the studies, tearing and comfort ratings were in the acceptable range. Additional IOP clinical results of studies PPL GLAU 12 and PPL GLAU 13 can be accessed on QLT's website.

OPHTHOTECH TO PRESENT POSITIVE RESULTS FROM PHASE IIb STUDY AT AAO RETINA SUBSPECIALTY DAY. Data from a large, prospective, randomized, controlled Phase IIb clinical trial of Ophthotech Corporation's Fovista anti-platelet-derived growth factor (PDGF) therapy (1.5 mg) in patients with wet age-related macular degeneration (AMD) will be presented during Retina Subspecialty Day at the American Academy of Ophthalmology Annual Meeting on November 10, 2012. According to Ophthotech, this is the first clinical trial to show statistically significant superior efficacy over Lucentis (ranibizumab) monotherapy for the treatment of wet AMD. The fully masked Phase IIb trial evaluated the efficacy and safety of Fovista given in combination with Lucentis, compared with Lucentis monotherapy, for the treatment of patients with wet AMD. A total of 449 patients were randomized every four weeks for 24 weeks: Fovista 0.3 mg in combination with Lucentis 0.5 mg; Fovista 1.5 mg in combination with Lucentis 0.5 mg; or sham in combination with Lucentis 0.5 mg. The primary efficacy endpoint in the study was the mean change in visual acuity from baseline at the week 24 visit. For additional details, visit www.ophthotech.com.

ABBOTT-SHAPETECH PARTNERSHIP WILL LEAD TO NEW POLYMERS FOR CATARACT IOLS. Abbott and ShapeTech LLC recently announced that they have entered into a collaboration to jointly develop new polymers for intraocular lenses (IOLs) used in cataract surgery. Abbott's vision care division, Abbott Medical Optics (AMO), will work together with ShapeTech to innovate new materials for IOLs that may provide additional benefits for cataract patients and their physicians. While terms of the deal remain confidential, AMO will have the exclusive right to manufacture and commercialize any technologies successfully developed from the partnership. Get more information at www.abbottmedicaloptics.com.

ORBIS MOURNS LOSS OF ALBERT UELTSCHI. ORBIS Emeritus Board Chairman Albert L. Ueltschi, 95, passed away at his Florida home on October 18, 2012. In the mid-1970s, he was instrumental in founding ORBIS International and overseeing the acquisition and conversion of a DC-8 aircraft into the world's only Flying Eye Hospital, which had its first flight in 1982. Most recently, Mr. Ueltschi provided the lead donation for ORBIS's latest Flying Eye Hospital, which is scheduled to launch in 2013. He also served as the Chairman of ORBIS International for many years. Click here to read more.

THE GLAUCOMA FOUNDATION NAMES 2012 WINNER OF ROBERT RITCH AWARD. Dr. George L. Spaeth has been named the 2012 recipient of The Glaucoma Foundation's Dr. Robert Ritch Award for Innovation and Excellence in Glaucoma, which recognizes the contributions of individuals who have played a significant and unique role in promoting the medicine and science of glaucoma. Dr. Spaeth was director of the William and Anna Goldberg Glaucoma Service and Research Laboratories at the Wills Eye Institute/Jefferson Medical College from 1968 to 2007 and has held the Louis J. Esposito Research Professorship there since 2000. Among his academic contributions is the development of the gonioscopic grading system, providing quantitative measures of the anterior chamber angle, and the Disc Damage Likelihood Scale (DDLS), a tool for classifying and monitoring the optic nerve in glaucoma. Additionally, he has authored hundreds of papers in peer-reviewed literature and has written more than 100 book chapters and 22 books. He will be presented with the award at The Glaucoma Foundation's 26th Annual Black & White Ball at The Pierre in New York City on December 5th.

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