Volume 13, Number 3
Monday, January 21, 2013


In this issue: (click heading to view article)
######### Use of RAPD to Screen for Glaucoma

######### Retinal Sensitivity Following Intravitreal Triamcinolone Acetonide Injection for ME Secondary to BRVO
######### Treatment of Noninfectious Uveitis with Secukinumab
######### Link Between Hyperoxia and Regression of Vitreous Neovascularization
######### Briefly



Use of RAPD to Screen for Glaucoma

A single individual masked with regard to disease presence examined 107 subjects prospectively recruited from a mixed population of glaucomatous and nonglaucomatous patients for an afferent pupillary defect (RAPD). Researchers sought to assess the RAPD by swinging flashlight as a potentially useful screening test for glaucomatous optic neuropathy.

All subjects underwent a swinging flashlight test with, when necessary, the aid of neutral density filters to determine whether or not a RAPD was present. A determination of glaucoma diagnosis, as well as classification of disease stage, was subsequently assessed based upon review of history and ophthalmic examination. The study researchers ascertained this clinical information regarding glaucomatous disease without knowledge of study RAPD status. The acquisition of such clinical information and performance of swinging flashlight testing for RAPD was conducted by different individuals, the latter being a non-ophthalmologist.

The researchers noted that statistical analysis demonstrated an odds ratio of 9.71 (95% CI, 3.72–25.40) for glaucomatous disease if a RAPD was present, with a sensitivity of 66.7% and a specificity of 82.9%. They also found that subanalysis of patients who had not previously undergone cataract surgery revealed an odds ratio of 17.05 (95% CI, 4.73–61.44) for glaucomatous disease if a RAPD was present, with a sensitivity of 68.8% and a specificity of 88.6%.

RAPD screening by a swinging flashlight test with neutral density filters was moderately sensitive and strongly specific for glaucoma. Sensitivity, specificity and predictive value improved when patients who had previously undergone cataract surgery were removed from the analysis.

SOURCE: Charalel RA, Lin HS, Singh K. Glaucoma screening using relative afferent pupillary defect. J Glaucoma. 2013; Jan 3. [Epub ahead of print].


Retinal Sensitivity Following Intravitreal Triamcinolone Acetonide Injection for ME Secondary to BRVO

To evaluate the effect of intravitreal triamcinolone acetonide (IVTA) on retinal sensitivity in cases of macular edema (ME) secondary to branch retinal vein occlusion (BRVO), the authors of this prospective Turkish study examined 14 eyes of 14 cases of BRVO.

They assessed logMAR visual acuity, central 4° retinal sensitivity by MP-1 microperimetry and optical coherence tomography foveal thickness in each eye at baseline and one, three and six months after IVTA injection.

Ages ranged from 60 to 79 years (mean 68 ± 8 years) and at one, three and six months, the logMAR visual acuity had increased from 0.71 ± 0.21 to 0.42 ± 0.21, 0.46 ± 0.30, and 0.46 ± 0.27; the mean foveal thickness had decreased from 540 ± 88 µm to 254 ± 51 µm, 288 ± 84 µm, and 280 ± 91 µm; and the mean retinal sensitivity had increased from 4.7 ± 2.5 dB to 7.9 ± 2.7 dB, 8.2 ± 3.6 dB and 8.3 ± 4.6 dB, respectively.

To conclude, in eyes with ME secondary to BRVO, IVTA injections result in a significant increase in not only the visual acuity, but also the central 4° retinal sensitivity in six months of follow-up.

SOURCE: Senturk F, Ozdemir H, Karacorlu M, et al. Retinal sensitivity improvement after intravitreal triamcinolone acetonide injection for macular edema secondary to branch retinal vein occlusion. Ind J Ophthalmol. 2013;61(1):3–7.


Treatment of Noninfectious Uveitis with Secukinumab

The results of three multicenter, randomized, double-masked, placebo-controlled, dose-ranging Phase III studies (SHIEDL, INSURE and ENDURE) were reviewed to determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis.

A total of 118 patients with Behçet's uveitis (SHIELD study); 31 patients with active, noninfectious, non–Behçet's uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non–Behçet's uveitis (ENDURE study) were enrolled.

After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every two weeks (q2w), secukinumab 300 mg monthly (q4w) or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w or placebo in the ENDURE study. Main outcome measures were a reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other endpoints included best-corrected visual acuity, ISM use (expressed as a standardized ISM score) and safety outcomes.

After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (p=0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. It was reported that overall, there was no loss in visual acuity reported in any treatment group during follow-up in all three studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the three studies.

The primary efficacy endpoints of the three studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM.

SOURCE: Dick AD, Tugal-Tutkun I, Foster S, et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology. 2013; Jan 4. [Epub ahead of press].


Link Between Hyperoxia and Regression of Vitreous NV

Neovascularization (NV) is a sight-threatening complication of retinal ischemia in diabetes, retinal vein occlusion and retinopathy of prematurity. Current treatment modalities, including laser photocoagulation and repeated intraocular injection of VEGF antagonists, are invasive and not always effective, and may carry side effects. Investigators studied the use of hyperoxia as an alternative therapeutic strategy for regressing established vitreous NV in a mouse model of oxygen-induced ischemic retinopathy. They found that hyperoxia treatment (HT, 75% oxygen) may be clinically useful to specifically treat proliferative NV in ischemic retinopathy.

They initiated HT on postnatal day (P)17 after the onset of vitreous NV. They also used immunohistochemistry and quantitative PCR to assess retinal vascular changes in relation to apoptosis, and expression of VEGFR2 and inflammatory molecules. Additionally, they studied the effects of intravitreal injections of VEGF-A, VEGF-E, PlGF-1 and VEGF trap were.

The study investigators observed that HT selectively reduced NV by 70% within 24 hours and that it robustly increased the level of cleaved caspase-3 in the vitreous NV between six and 18 hours and promoted infiltration of macrophage/microglial cells. The HT-induced apoptosis was preceded by a significant reduction in VEGFR2 expression within the NV and an increase in VEGFR2 within the surrounding neural tissue. Intravitreal VEGF-A and VEGF-E (VEGFR2 agonist), but not PlGF-1 (VEGFR1 agonist), prevented HT-induced apoptosis and regression of NV. In contrast, VEGF trap and VEGFR2 blockers mimicked the effect of HT. However, intravitreal VEGF trap induced increases in inflammatory molecules, while HT did not have such unwanted effect.

SOURCE: Liu H, Zhang W, Xu Z, et al. Hyperoxia causes regression of vitreous neovascularization by down-regulating VEGF/ VEGFR2 pathway. Invest Ophthalmol Vis Sci. 2013;Jan 10. [Epub ahead of print].

  • CLEARSIDE BIOMEDICAL PLANS CLINICAL TESTING OF CLS1001 SUPRACHOROIDAL INJECTABLE SUSPECTION FOR TREATMENT OF EYE DISEASES. According to Clearside Biomedical Inc., the standard 30-day review period by the FDA relating to the company's Investigational New Drug (IND) Application for CLS1001 (triamcinolone acetonide) Suprachoroidal Injectable Suspension for the treatment of sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unrespsonsive to topical corticosteroids has concluded and clinical testing can proceed. Clearside Biomedical treats the pathological changes to the blood retinal barrier that lead to retinal blindness by delivering therapeutics through the suprachoroidal space using a proprietary microinjection dosage form that allows compartmentalization within the distinct areas of the eye. It is currently targeting the initiation of a Phase I–II clinical trial in the United States in the first quarter 2013 to evaluate the safety and tolerability of the product candidate in subjects with non-infectious uveitis. Additional details can be found here.
  • HYDROGEL VISION CORP. INTRODUCES NEW LENS AND NEW ONE-WEEK MODALITY. Hydrogel Vision Corp. has expanded its product line with a new lens and a new modality: Icuity H2O – one-week replacement. The lens is made with hioxiflcon A, a non-ionic ultra hydrating material that retains 99% of its water content throughout the wearing time. The company says the lens is a new option for patients who would benefit from a more frequent replacement, but don't want to incur the cost of a daily disposable lens. Icuity H2O comes in a Median and Steep base curve. Available parameters are: Median +6.00 to –10.00 and Steep –0.25 to –10.00. Lens comfort, movement and fit are stable throughout the day. Free diagnostic sets of Icuity H2O are available directly through Hydrogel Vision and through any of their authorized distributors. For more information, visit www.hydrogelvision.com.
  • HAAG-STREIT SURGICAL AND HAAG-STREIT USA SIGN EXCLUSIVE AGREEMENT. At last week's Cataract Surgery 2013 meeting in Sarasota, Florida, Haag-Streit Surgical and Haag-Streit USA signed an exclusive agreement that will bring a line of surgical microscopes widely used throughout Europe to the American marketplace. The line includes Haag-Streit's Hi-R NEO 900 for ophthalmology and other models that will be used in neurosurgery, otolaryngology, dentistry and plastic surgery. Eyecare professional Ray Wright will serve as director of Haag-Streit USA's new operating unit, and Mike Luley joins the team as Director of Sales. Click here to learn more.
  • ILUVIEN RECEIVES MARKETING AUTHORIZATION IN SPAIN FOR TREATMENT OF DME. The Spanish Agency of Drugs and Medical Devices has granted marketing authorization to Alimera Sciences Inc.'s sustained release intravitreal implant, ILUVIEN, for the treatment of vision impairment associated with chronic diabetic macular edema (DME) considered insufficiently responsive to available therapies. The implant delivers sub-microgram levels of fluocinolone acetonide for up to 36 months. The Spanish authorization is the sixth national approval in the European Union.
  • NEW PRESERVATIVE-FREE GLAUCOMA DRUG APPROVED IN JAPAN. Santen Pharmaceutical Co. Ltd. has announced that Japan's Ministry of Health, Labour and Welfare granted manufacturing and marketing approval for the glaucoma and ocular hypertension treatment drug, TAPROS Mini Ophthalmic Solution 0.0015%. The drug is a sterile, preservative-free, disposable-type unit-dose product containing the same active ingredient tafluprost, a prostaglandin F2α analogue, at the same concentration, with equivalent IOP-lowering effect as TAPROS Ophthalmic Solution 0.0015%, a glaucoma and ocular hypertension drug co-developed by Santen Pharmaceutical Co. Ltd. and Asahi Glass Co. Ltd. Read more at www.santen.com.
  • JETREA EARNS POSITIVE OPINION FOR TREATMENT OF VMT IN EU. In a recent news release, Alcon reported the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for Jetrea (ocriplasmin) for the treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter &lge; 400 µm. Currently, the only available treatment in the European Union is “observation” or “watchful waiting” until a patient becomes eligible for surgical intervention at a very late stage of the disease. The EU regulatory submission was based on data from two pivotal Phase III clinical trials that evaluated the safety and efficacy of a single administration of Jetrea. Both studies met their primary endpoint and demonstrated that Jetrea successfully resolved VMT and macular hole compared to placebo. Alcon, a division of Novartis, acquired the rights to commercialize Jetrea outside the United States from ThromboGenics, which retains the rights to commercialize the drug in the United States.

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