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Volume 14, Number 28
Monday, July 14, 2014
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JULY IS EYE INJURY PREVENTION MONTH




In this issue: (click heading to view article)
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######### Rates of RNFL Thinning in Glaucoma Suspect Eyes
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######### Treatment With Aflibercept for Patients With Exudative AMD Who Were Incomplete Responders to Multiple Ranibizumab Injections
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######### Visual Outcome of Ranibizumab in Typical Neovascular AMD and PCV
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######### Corneal Endothelial Changes and the Different Stages of Keratoconus
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Rates of RNFL Thinning in Glaucoma Suspect Eyes

In the following prospective, observational cohort study, investigators compared the rates of retinal nerve fiber layer loss in patients suspected of having glaucoma who developed visual field damage with those who did not develop VFD and aimed to determine whether the rate of RNFL loss can be used to predict the development of VFD.

Participants consisted of glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study.

The investigators measured global and quadrant RNFL thickness using spectral-domain optical coherence tomography (Spectralis HRA+OCT, Heidelberg Engineering). They defined VFD as having three consecutive abnormal visual fields. Additionally, they compared the rate of RNFL loss in eyes developing VFD to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFL thickness slope to predict the risk of developing VFD, while adjusting for potential confounding variables. Main outcome measures were the rate of RNFL thinning and the probability of developing VFD.

The study investigators included 454 eyes of 294 glaucoma suspects in this study. They reported that the average number of SD-OCT examinations was 4.6 (range, two to nine), with median follow-up of 2.2 years (0.4 to 4.1 years). They also noted that 40 eyes (8.8%) developed VFD and that the estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (–2.02 µm/year vs. –0.82 µm/year; p<0.001). Furthermore, the joint longitudinal survival model showed that each 1 µm/year faster rate of global RNFL loss corresponded to a 2.05-times higher risk of developing VFD (hazard ratio, 2.05; 95% confidence interval, 1.14 to 3.71; p=0.017).

To conclude, the rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-µm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.

SOURCE: Miki A, Medeiros FA, Weinreb RN, et al. Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes. Ophthalmology. 2014;121(7):1350–1358.


Treatment With Aflibercept for Patients With Exudative AMD Who Were Incomplete Responders to Multiple Ranibizumab Injections

The authors of this prospective, open-label, single-arm clinical trial sought to determine the efficacy of 2.0 mg aflibercept in the management of patients with recalcitrant exudative age-related macular degeneration.

They saw patients monthly and gave them mandatory 2.0 mg aflibercept at baseline, months one, two and four. They also performed pro re nata retreatment at months three and five upon evidence of disease on spectral domain-optical coherence tomography. End point at month six: mean change in Early Treatment Diabetic Retinopathy Study best corrected visual acuity and central subfield thickness, mean number of aflibercept injections, percentage of p.r.n. injections required, patients with no fluid on SD-OCT and patients losing more than 15 letters.

At baseline, 46 patients with a mean of 42 prior anti-vascular endothelial growth factor-A intravitreal treatments had a mean of 74.2 letters (Snellen equivalent 20/32) and mean CST of 347 µm, the authors found. They noted that ETDRS letters remained stable throughout the trial; at month six, mean BCVA change was +0.2 letters (range –10 to +13; p=0.71). Anatomically, mean CST improved significantly from baseline at each study visit including –23.6 µm at month one and –27.3 µm at month six (p=0.018). Moreover, 71 of 90 (79%) possible p.r.n. injections were required and a mean of 5.6 aflibercept injections out of the maximum six were administered. Finally, 10 of 45 (22%) patients had no retinal fluid on SD-OCT at month six and no patient lost more than 15 letters.

Aflibercept 2.0-mg treatment maintained mean visual acuity improvements previously achieved with high-dose 2.0-mg ranibizumab injections in recalcitrant wet AMD patients. Aflibercept 2.0-mg treatment led to significant anatomic improvement and was required monthly in most patients.

SOURCE: Wykoff CC, Brown DM, Maldonado ME, Croft DE. Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial). Br J Ophthalmol. 2014;98(7):951–955.


Visual Outcome of Ranibizumab in Typical Neovascular AMD and PCV

To investigate the two-year outcomes of intravitreal injections of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy, factors associated with visual outcomes were examined in this retrospective review of the medical records of 128 consecutive eyes with treatment-naïve subfoveal AMD treated with ranibizumab and followed for ≥ 24 months. The association between visual outcomes and single nucleotide polymorphisms in ARMS2 A69S and CFH I62V genes were also examined.

A total of 58 eyes were diagnosed with typical neovascular AMD and 70 eyes with PCV. In typical neovascular AMD eyes, VA improved at three months (p=0.020), but returned to the baseline level at six months. Thereafter, VA was maintained until 24 months. It was also noted that in PCV eyes, VA significantly improved at three months (p=0.015) and persisted at 12 months (p=0.025), but the VA improvement dissipated by 24 months. With regard to genetic associations with VA and VA change, neither VA nor VA change showed significant associations with these SNPs at all time points in typical neovascular AMD. In the PCV eyes, there were significant associations between ARMS2 A69S and VA at baseline and one year (p=0.017 and p=0.025, respectively). However, VA change showed no significant difference among these genotypes in PCV.

In conclusion, intravitreal ranibizumab significantly improved the VA initially, but this improvement did not persist at two years post-treatment. In PCV, ARMS2 A69S polymorphism is associated with the baseline and 12-month VA, but is not associated with the visual prognosis at 24 months.

SOURCE: Hata M, Tsujikawa A, Miyake M, et al. Two-year visual outcome of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophtalmol. 2014; June [Epub ahead of print].


Corneal Endothelial Changes and the Different Stages of Keratoconus

Researchers performed this cross-sectional cohort study to examine the corneal endothelial count and morphology in patients with keratoconus by specular microscopy and to correlate them to the stage of keratoconus.

They enrolled 40 eyes of 29 patients with keratoconus and evaluated corneal endothelium using specular microscopy. The researchers obtained corneal topography and thickness data from Scheimpflug-based corneal tomography. They classified eyes into stages one through four of keratoconus according to Amsler classification, using keratometry and pachymetry readings obtained from corneal tomography.

According to the researchers, 11 eyes (27.5%) had stage one, 17 eyes (42.5%) had stage two and 12 eyes (30%) had stage three. Specular microscopy was not possible in stage four. There was no statistically significant correlation between the stage of keratoconus and the endothelial cell density (r=0.018; p=0.91), coefficient of variation (r=–0.011; p=0.94) or percentage of hexagonality (6A) (r=–0.112; p=0.51). When mild-to-moderate keratoconus (stages one and two) was compared with severe keratoconus (stage three), the difference was not significant regarding ECD (p=0.1), CV (p=0.3) or 6A (p=0.4). However, there was a trend toward lower ECD and percentage of hexagonality, and a higher CV with advancing disease.

The researchers in this study found that up to stage three, keratoconus does not significantly affect the corneal endothelium, as measured by specular microscopy. Eyes with stage four could not be studied by specular microscopy and may require other imaging methods such as confocal microscopy.

SOURCE: El-Agha MS, El Sayed YM, Harhara RM, Essam HM. Correlation of corneal endothelial changes with different stages of keratoconus. Cornea. 2014;33(7):707–711.





  • OPTIMIS FUSION RECEIVES FDA 510(k) CLEARANCE. Quantel Medical recently announced FDA 510(k) clearance for its Optimis Fusion integrated laser platform. The Optimis Fusion system combines advanced selective laser trabeculoplasty photoregeneration therapy and traditional YAG photodisruption treatments to offer ophthalmologists a versatile armamentarium for treating both cataract and glaucoma in an efficient combination platform. According to Quantel, the Fusion's unique SLT mode provides a first-choice treatment for managing glaucoma and lowering intraocular pressure, while the YAG mode delivers high-performance photodisruption for capsulotomy and peripheral iridotomy surgical procedures. Additionally, the Gaussian laser beam profile allows for precise laser delivery at minimum energy levels, avoiding adverse side effects such as lens pitting. Get more information here.

  • INSITE TO SUBMIT NDA FOR BLEPHARITIS TREATMENT. InSite Vision has announced that it intends to submit a New Drug Application for DexaSite (dexamethasone 0.1% in DuraSite) as a treatment for blepharitis in adults during 2015, following completion of remaining chemistry and manufacturing work. InSite will meet with key European regulatory authorities in Q3 2014 to request this same DexaSite Marketing Authorization Application filing path, as well as feedback on the need, if any, for additional AzaSite Plus (dexamethasone 0.1% and azithromycin 1% in DuraSite) data and/or endpoints to support an AzaSite Plus MAA filing in bacterial-related blepharitis.

  • RPS RESTRUCTURES LICENSING AGREEMENT WITH NICOX. Rapid Pathogen Screening Inc. has reported the restructuring of the North American licensing rights to the AdenoPlus test as well as two diagnostic tests in development. Effective August 1, 2014, RPS will resume responsibility for marketing these tests to eye-care professionals in the United States and all medical professionals in Canada. In 2012, RPS and Nicox entered into a licensing agreement giving Nicox access to RPS's diagnostic tests, but now, AdenoPlus and the future development products will be marketed to eye-care professionals through RPS's dedicated eye-care team, which has extensive industry experience and currently markets InflammaDry, a test for dry-eye disease. The team will leverage and support this expanded product portfolio, accelerating access for both existing and new customers. Under the amended agreement, Nicox will no longer contribute to development costs, but may pay additional development milestones, up to a potential maximum of $525,000, related to approval of products outside North America. Read the press release for additional details.

  • PHASE III DRY EYE TRIALS WITH RGN-259 TO COME IN ASIA. RegeneRx Biopharmaceuticals Inc. and G-treeBNT Co. Ltd. jointly announced that G-treeBNT is preparing to file an Investigational New Drug and sponsor a Phase III clinical trial with RGN-259 (a thymosin beta 4-based preservative-free eye drop) in patients with moderate to severe dry eye initially in South Korea, followed by Japan and Australia, with follow-up on registrations in certain additional Asian and Pacific Rim countries, if appropriate. According to RegeneRx, the proposed Phase III trial is based on data generated in a 72-patient, double-masked, placebo-controlled trial sponsored by RegeneRx and conducted by Ora Inc., as well as data generated in a recently completed nine-patient physician-sponsored, double-masked, placebo-controlled clinical trial in patients with severe dry-eye syndrome, both conducted in the United States. Both Phase II trials resulted in statistically significant sign and symptom improvements in central cornea staining and ocular discomfort.

  • THE VISION CARE INSTITUTE UNVEILS NEW EDUCATIONAL APP. To help eye-care professionals educate patients about the causes and effects of UV exposure and steps they can take to help protect their eyes from harmful ultraviolet rays, The Vision Care Institute LLC, part of the Johnson & Johnson Family of Companies, has launched a new educational resource: The Vision Care Institute UV Protection App. Practitioners and office staff can use the app during patient evaluations and follow-up communications to demonstrate the cumulative effects of UV rays on the eyes, the impact of environmental exposure to the eyes throughout the day, steps to take to help protect eyes from harmful UV radiation, and who needs protection. The app is free and designed specifically for use with the iPad. It can be downloaded via the Apple App Store.

  • BRIGHTFOCUS FOUNDATION AWARDS GRANTS FOR VISION DISEASE RESEARCH. BrightFocus Foundation announced the recipients of new research grant awards to fund research projects on glaucoma and macular degeneration. With these latest grants, the organization has now provided more than $8.7 million in research funding in 2014. Find out about the new grantees and their projects here.



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