EW Weekly, December 2, 2016

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December 2, 2016
Volume 21 , Number 45

Opsiria meets endpoint in Phase 3 study

Topline results from the SAKURA (Sirolimus study Assessing double-masKed Uveitis tReAtment) Phase 3 study indicate Opsiria (440 μg sirolimus injection) can effectively and safely reduce intraocular inflammation (as measured by vitreous haze) in non-infectious uveitis of the posterior segment, developer Santen (Osaka, Japan) said in a press release. Opsiria regulates the immune system through the inhibition of mTOR, which acts by interrupting the inflammatory cascade that leads to T-cell activation, differentiation and proliferation, and production of interleukin-2 (IL-2), as well as other pro-inflammatory cytokines, and promoting immune tolerance by inducing T regulatory cells. The two SAKURA studies were multinational, randomized and double-masked, assessing the efficacy and safety of Opsiria as monotherapy in patients with non-infectious uveitis of the posterior segment. The primary endpoint of the studies was to achieve a vitreous haze score of 0 at month 5. Eligible patients were randomized into one of three active treatment arms (44 μg, 440 μg, 880 μg). The first study established the efficacy and safety of Opsiria, and the second found no statistically significant effect between the low and high dose. Based on the totality of the data from the SAKURA studies, Santen plans to file a New Drug Application (NDA) to the U.S. Food and Drug Administration in early 2017. Opsiria was granted orphan status by the FDA and European Commission in 2011.

Eyenovia Phase 2 results demonstrate benefits of micro-formulations

A Phase 2 randomized controlled clinical study has found a micro-formulation of 6 µL of a dilatory agent achieved either equivalent or greater biologic effect compared to standard eyedropper dosing of 40-50 µL, developer Eyenovia (New York) said in a press release. Separately, the 100 participants preferred Eyenovia's high-precision micro-dose to eyedroppers, reporting better head positioning comfort, reduced tearing/overflow, and increased likelihood of adhering to ocular medication regimens.

Study examines use of deep machine learning for detection of diabetic retinopathy

In an evaluation of retinal photographs from adults with diabetes, an algorithm based on deep machine learning had high sensitivity and specificity for detecting referable diabetic retinopathy (DR), according to Lily Peng, MD, Google, Mountain View, California. According to a press release on the study results, automated grading of DR has potential benefits such as increasing efficiency and coverage of screening programs; reducing barriers to access; and improving patient outcomes by providing early detection and treatment. To maximize the clinical utility of automated grading, an algorithm to detect referable DR is needed. Machine learning (a discipline within computer science that focuses on teaching machines to detect patterns in data) has been leveraged for a variety of classification tasks including automated classification of diabetic retinopathy. Deep learning is a machine learning technique that allows an algorithm to program itself by learning the most predictive features directly from the images given a large data set of labeled examples, removing the need to specify rules explicitly. Application of these methods to medical imaging requires further assessment and validation. Dr. Peng and colleagues used their algorithm to evaluate a data set of 128,175 retinal images, which were graded three to seven times for DR, diabetic macular edema, and image gradability by a panel of 54 U.S. licensed ophthalmologists and ophthalmology senior residents between May and December 2015. The resultant algorithm was validated using two separate data sets (EyePACS-1, Messidor-2), both graded by at least seven U.S. board-certified ophthalmologists. The EyePACS-1 data set consisted of 9,963 images from 4,997 patients (prevalence of referable DR [RDR; defined as moderate and worse diabetic retinopathy, referable diabetic macular edema, or both], 8% of fully gradable images); the Messidor-2 data set had 1,748 images from 874 patients (prevalence of RDR, 15% of fully gradable images). Use of the algorithm achieved high sensitivities (97.5% [EyePACS-1] and 96% [Messidor-2]) and specificities (93% and 94%, respectively) for detecting referable diabetic retinopathy.

RESEARCH BRIEFS

  • Surgical circumstances such as blurred vision, accommodation, and target light had little influence on eye movements during LASIK, according to a study. Anna Christina Sasse, MD, and colleagues prospectively randomized 11 eyes of 11 participants to simulated LASIK. Participants were instructed to focus on the fixation light; the treatment laser was blocked, and all other settings were applied according to standard LASIK treatments. To simulate blurred vision a 0.0 D soft contact lens received a 5.0 D myopia laser treatment and was then applied to the participant's eye. To diminish accommodation, a second lens that had a refraction of the patient's spherical equivalent, plus 3.0 D to compensate for accommodation, was used. There were four treatment modalities as follows: (1) blurred lens with target laser on, (2) blurred lens with target laser turned off, (3) +3.0 D lens with target laser on, and (4) +3.0 D lens with target laser turned off. Lateral and torsional eye movements were recorded. Fourier analysis was used to obtain temporal power spectra from dynamic eye movements. The Fn criterion was set as the frequency below which n% of eye movements in the cohort occurred (n=95%, 80%, and 50%). There was one significant difference between the eye movements based on measurement modalities. In one variable in the y-axis, there was movement that showed a significant difference in the F80 criterion. The study is published in the Journal of Cataract & Refractive Surgery.
  • In patients with early open-angle glaucoma (OAG) or ocular hypertension, short-term results found selective laser trabeculoplasty (SLT) was a safe and effective alternative for IOP reduction. M. Chun and colleagues enrolled 45 eyes (45 patients) in their case series; all patients underwent one single SLT session. Follow-up was scheduled at week 1 and months 1, 2, and 3. In order to account for possible influence of IOP fluctuation on laser outcomes, post-laser IOP values of the treated eye of each patient were also analyzed adjusting for IOP changes (between visit variation) of the untreated fellow eye (adjusted analysis). Mean IOP was reduced from 20.8±5.1 to 14.9±2.9 mm Hg at month 3 (p<0.001). Adjusted success rate (defined as IOP reduction≥20%) was 64%, and mean percentage of IOP reduction was 23.1±14.3% at last follow-up visit. Considering unadjusted post-laser IOP values, there was a 20% greater absolute IOP reduction, with a success rate of 76%. Although baseline IOP was significantly associated with both adjusted and unadjusted post-laser IOP reduction, a stronger association was found when unadjusted IOP values were considered. Age, mean deviation index, central corneal thickness and type of glaucoma were not significant predictors. The study is published in BMC Ophthalmology
  • Even after adjustment for age, accommodative lag is greater across several accommodative stimulus levels in patients using topiramate, which may be related to visual symptoms in topiramate users, according to Eren Cerman, MD, and colleagues. They included 16 controls and 22 patients using 100 mg/kg topiramate who were diagnosed with migraine. In most of the accommodation stimuli ranges (0 D, 2.5 D, 3 D, and 5 D), topiramate users had a significantly higher accommodative lag compared to controls (p=0.028, p=0.014, p=0.011, and p=0.011, respectively). The most important causes of accommodative lag were found to be accommodation stimulus and inclusion in the topiramate group. Multivariate linear regression analysis revealed that the two most important predictors of accommodative lag were accommodation stimulus and age. The study is published in the Canadian Journal of Ophthalmology. 

NEW PRODUCT BRIEFS

  • Sun Pharma (Mumbai, India) launched BromSite (bromfenac ophthalmic solution) 0.075% in the U.S. The nonsteroidal anti-inflammatory drug is indicated for the treatment of postoperative inflammation and prevention of ocular pain in patients undergoing cataract surgery.

EYEWORLD WEEK Online is edited by Stacy Majewicz and Michelle Dalton.

EyeWorld Week Online (ISSN 1089-0319), a digital publication of the American Society of Cataract and Refractive Surgery and the American Society of Ophthalmic Administrators, is published every Friday, distributed by email, and posted live on Friday.

Medical Editors: Eric Donnenfeld, MD, chief medical editor; Rosa Braga-Mele, MD, cataract editor; Clara Chan, MD, cornea editor; Nathan Radcliffe, MD, glaucoma editor; and Vance Thompson, MD, refractive editor.

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