Volume 14, Number 11
Monday, March 17, 2014


In this issue: (click heading to view article)
######### VA Following Cataract Surgery in Patients with AMD
######### Impact of Doxycyline vs. Placebo on Retinal Function and DR Progression in Patients with Severe Nonproliferative or Non-High-Risk Proliferative DR
######### Correlation of FAF with Foveal Microstructures and Vision in BRVO
######### 2% Rebamipide (OPC-12759) Ophthalmic Suspension in Patients with Dry Eye
######### Briefly

VA Following Cataract Surgery in Patients with AMD

The following cohort study evaluated visual acuity (VA) outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD).

Participants consisted of 1,232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD.

Preoperative and postoperative characteristics of participants who underwent cataract extraction during the five-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the six-month telephone calls. Analyses were conducted using multivariate repeated-measures regression. Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA was the main outcome measure.

Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n=30) gained 11.2 letters (95% confidence interval [CI], 6.9 to 15.5), eyes with moderate AMD (n=346) gained 11.1 letters (95% CI, 9.1 to 13.2), eyes with severe AMD (n=462) gained 8.7 letters (95% CI, 6.7 to 10.7), eyes with noncentral geographic atrophy (n=70) gained 8.9 letters (95% CI, 5.8 to 12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n=324) gained 6.8 letters (95% CI, 4.9 to 8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (p<0.0001).

In conclusion, mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity.

SOURCE: Huynh N, Nicholson BP, Agrón E, et al; Age-Related Eye Disease Study 2 Research Group, Writing Committee. Visual acuity after cataract surgery in patients with age-related macular degeneration: Age-Related Eye Disease Study 2 Report Number 5. Ophthalmology. 2014;Mar 11. [Epub ahead of print].

Impact of Doxycyline vs. Placebo on Retinal Function and DR Progression in Patients with Severe Nonproliferative or Non-High-Risk Proliferative DR

Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR). In a proof-of-concept clinical trial, researchers investigated whether low-dose oral doxycycline monohydrate can: slow the deterioration of, or improve, retinal function; or induce regression or slow the progression of DR in patients with severe nonproliferative DR (NPDR) or non-high-risk proliferative (PDR); and sought to determine the potential usefulness of visual function end points sought to expedite the feasibility of conducting proof-of-concept clinical trials in patients with DR. They conducted a randomized, double-masked, 24-month proof-of-concept clinical trial.

They included 30 patients (from hospital-based retina practices) with one or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study (ETDRS)-defined high-risk PDR. The researchers randomized patients to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months. Main outcome measures were change at 24 months compared with baseline in functional factors (frequency doubling perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2 testing, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomic factors (ETDRS DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters). From baseline to month 24, the researchers noted that mean FDP foveal sensitivity decreased in the placebo group (–1.9 dB) and increased in the doxycycline group (+1.8 dB) (p=0.02). They detected a higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group at six months (p=0.04), and this significant difference persisted at 12 and 24 months. They did not detect a difference between the groups with respect to the other visual function outcomes and all anatomic outcomes assessed.

To the researchers' knowledge, this is the first observation suggesting a link between a low-dose oral anti-inflammatory agent and subclinical improvement in inner retinal function. Oral doxycycline may be a promising therapeutic strategy targeting the inflammatory component of DR. Furthermore, study results suggest that FDP, which primarily measures inner retinal function, is responsive to intervention and may be a useful clinical trial end point for proof-of-concept studies in patients with DR.

SOURCE: Scott IU, Jackson GR, Quillen DA, et al. Effect of doxycycline vs. placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2014;Mar 6. [Epub ahead of print].

Correlation of FAF with Foveal Microstructures and Vision in BRVO

To investigate the correlation of fundus autofluorescence (FAF) with the findings of spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA) in patients with branch retinal vein occlusion (BRVO) and to determine the visual prognostic factors, the authors of this study retrospectively obtained an evaluation of FAF, SD-OCT images and VA before and after intravitreal injection of bevacizumab (pre- and post-IVB) in 42 patients with BRVO who underwent intravitreal bevacizumab injections as their first treatment. They graded the FAF of fovea on a scale of one to four.

According to the authors, the visual acuity post-IVB was associated with the VA pre-IVB. Additionally, preservation of external limiting membrane and photoreceptor inner and outer segment junction pre- and post-IVB were associated with better VA post-IVB. Eyes with less FAF pre-IVB were closely associated with better VA post-IVB.

The shorter length of photoreceptor inner and outer segment junction and external limiting membrane defect and less FAF pre-IVB showed a significant association with better VA post-IVB. These associations could help to predict potential restoration of photoreceptor integrity and visual recovery in patients with BRVO, in whom photoreceptor integrity before treatment could not be adequately evaluated, even with SD-OCT.

SOURCE: Park B, Kim J, Chung H, et al. Correlation of fundus autofluorescence with foveal microstructures and vision in branch retinal vein occlusion. Retina. 2014;34(3):531–538.

2% Rebamipide (OPC-12759) Ophthalmic Suspension in Patients with Dry Eye

Investigators in Japan studied the efficacy and safety of 2% rebamipide ophthalmic suspension administered q.i.d. for 52 weeks in patients with dry eye.

They enrolled 154 patients with dry eye in this multicenter, open-label, single-arm study. After a two-week screening period, patients received 2% rebamipide, instilled as one drop in each eye, q.i.d. for 52 weeks. The researchers assessed the signs and symptoms measures at baseline, at weeks two and four, and at every four weeks thereafter. The objective signs were fluorescein corneal staining score, lissamine green conjunctival staining score, and tear-film breakup time, while subjective symptoms were dry-eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain and blurred vision). The safety variable was the occurrence of adverse events.

For all objective signs and subjective symptoms, the scores significantly improved at week two compared with baseline (p<0.001, paired t test), the investigators reported. Interestingly, they observed further improvements of those scores at every visit up to week 52. No deaths were reported, yet serious adverse events that were not thought to be drug-related were observed in six patients. The incidence of any of the adverse events did not markedly increase throughout the 52-week treatment period.

The results of this study show that 2% rebamipide is effective in improving both the objective signs and subjective symptoms of dry-eye patients for at least 52 weeks. In addition, 2% rebamipide treatment was generally well-tolerated.

SOURCE: Kinoshita S, Awamura S, Nakamichi N, et al.; Rebamipide Ophthalmic Suspension Long-term Study Group. A multicenter, open-label, 52-week study of 2% rebamipide (OPC-12759) ophthalmic suspension in patients with dry eye. Am J Ophthalmol. 2014;157(3):576–583.

  • GRANT SUPPORTS THROMBOGENICS' RESEARCH OF NEW THERAPEUTIC FOR DME. ThromboGenics NV has been awarded a €3 million (roughly $4,185,300 U.S.) grant from the Flemish agency for Innovation by Science and Technology (IWT) to support research into potential new biotherapeutics for the treatment of diabetic macular edema (DME). According to ThromboGenics, the aim of these new therapeutics will be to reduce vascular leakage and inflammation. Specifically, the company plants to use the funding to develop a much better understanding of the role of a novel pathway in DME as the basis for discovering new pre-clinical therapeutic candidates. The new candidates will be generated by ThromboGenics leveraging the AMP-Rx protein design technology, which the company licensed from Eleven Biotherapeutics in May 2013. A key part of the IWT grant-funded work will be the development of new in vitro assays and in vivo models to identify biotherapeutics that activate the pathway. Get additional details at www.thrombogenics.com.
  • FIRST PATIENTS IN MULTICENTER STUDY IMPLANTED WITH FLUIDVISION ACCOMMODATING IOL ANNOUNCED. PowerVision Inc. has announced that the first 10 patients have received lens implants in its multicenter clinical study assessing the performance of the FluidVision accommodating intraocular lens (IOL) in cataract patients. The study will form the basis for PowerVision's CE marking of the FluidVision lens in the European Union, which is expected to occur sometime next year. Patients received their implants at the three eye centers in South Africa that are participating in the study. Four sites in Germany are also participating in the study and will begin enrolling patients later in 2014. The FluidVision lens is a fluid-controlled accommodating IOL that contains fluid inside the lens that moves in response to the natural muscle forces in the eye. It provides true accommodation by mimicking the eye's natural accommodative process, becoming thicker when the patient needs to see up close or thinner when he or she needs to see far away. For more information, visit clinicaltrials.gov, study identifier NCT02049567.
  • STERIMEDIX INTRODUCES NEW HYDRODISSECTION CANNULA. In a recent press release, Sterimedix unveiled a new cannula designed to enhance hydrodissection following a laser capsulotomy. Available in 25g, the instrument is angled and flattened in the horizontal plane for easier insertion under the capsule, and has two side ports to improve the dissecting flow of fluid to overcome any persistent adherence of the capsule and cortex. The cannula is supplied packed and sterile, in boxes of 10 pieces.
  • TRACON AND SANTEN TO DEVELOP AND COMMERCIALIZE TRC105 IN OPHTHALMOLOGY. Tracon Pharmaceuticals and Santen Pharmaceutical Co., Ltd. have entered into an exclusive agreement for the development and global commercialization of Tracon's anti-endoglin antibodies, including TRC105, a novel, first-in-class, clinical stage antibody to endoglin (CD105), an endothelial cell receptor that is essential for the process of angiogenesis, in ophthalmology. Under the terms of the agreement, Santen will make a $10 million up-front payment and certain milestone payments to Tracon in the development phase, and will pay commercialization milestone and tiered royalties on global sales of TRC105 in ophthalmology. Additionally, Santen will fund 100% of all global development, and commercialization activities, including the initiation of IND-enabling studies. Tracon will continue ongoing Phase II development of TRC105 in a number of oncology indications, and will retain global rights on application of its anti-endoglin antibody portfolio outside of ophthalmology. Find out more here.

  • PARAMETER EXPANSION ANNOUNCED FOR ACUVUE OASYS BRAND CONTACT LENSES FOR ASTIGMATISM. Effective April 15, 2014, Acuvue Oasys Brand Contact Lenses for Astigmatism will be available in more parameters, reports Johnson & Johnson Vision Care Inc. Parameters are being expanded to include –6.00 to +6.00 in 0.25D steps (cylinders: –0.75, –1.75, –2.25; axis: full circle in 10° steps) and from –6.50 to –9.00 in 0.50 steps (cylinders: –0.75, –1.25, –1.75, –2.25; axis: full circle in 10° steps). Effective March 31, 2014, diagnostic lenses for Acuvue Advance Brand Contact Lenses for Astigmatism will no longer be available from Johnson & Johnson Vision Care Inc. Access more information here.
  • REGENERX AND DIGITAL ARIA ENTER PRODUCT LICENSE AGREEMENTS. RegeneRx Biopharmaceuticals Inc. has entered into two product license agreements with Digital Aria Co. Ltd. for Digital Aria to develop RegeneRx's RGN-259 preservative-free eye drop product candidate in Asia (excluding China, Hong Kong, Taiwan and Macau) and its RGN-137 topical dermal gel product candidate in the United States. License terms include commercial milestone payments of up to $7 million and a double-digit royalty on commercial sales, if any. Digital Aria will be required to initiate Phase II clinical trials in the United States and Australia within three years. RegeneRx will receive a royalty-free license outside of the licensed territories to any improvements made by Digital Aria to RegeneRx's product candidates. Additionally, Digital Aria will pay for all costs associated with the development of any potential product within the licensed territories and RegeneRx retains the manufacturing and supply rights for the active pharmaceutical ingredient (Tβ4) in the licensed territories. Furthermore, Digital Aria will make an equity investment into RegeneRx of $2.35 million, enabling RegeneRx to move forward with its ophthalmic clinical program, and retains a 10-month option to purchase additional common stock for $825,000. Learn more at www.regenerx.com.

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