Volume 14, Number 24
Monday, June 16, 2014

In this issue: (click heading to view article)
######### Daytime vs. Nighttime Effects of Brimonidine on IOP and Aqueous Humor Dynamics in Participants with Ocular Hypertension
######### Visual Acuity Following Cataract Surgery in Patients with AMD
######### Long-Term Impact of Multiple Intravitreal Anti-VEGF Injections on IOP
######### Tear Mucin 5AC in Office Workers Using Visual Display Terminals
######### Briefly

Daytime vs. Nighttime Effects of Brimonidine on IOP and Aqueous Humor Dynamics in Participants with Ocular Hypertension

In this randomized, double-masked, crossover study, researchers evaluated the effects of brimonidine on daytime and nighttime intraocular pressure and aqueous humor dynamics in volunteers with ocular hypertension.

They enrolled 30 participants with OHT (58.6 ± 1.7 years old, mean ± SEM) and for six weeks, participants self-administered 0.2% brimonidine or placebo t.i.d. During daytime and nighttime visits, measurements included aqueous flow (Fa) by fluorophotometry, outflow facility (C) by tonography, episcleral venous pressure (Pev) by venomanometry and seated and supine IOP by pneumatonometry. Uveoscleral outflow (U) was calculated mathematically.

The researchers determined that when treated with placebo, nighttime supine Pev (11.2 ± 0.25 mmHg) was higher (p<0.05) compared with daytime seated Pev (10.2 ± 0.25 mmHg), and Fa and U were significantly reduced at night. Brimonidine significantly lowered seated IOP at 9:00 a.m. and 11:00 a.m., 9:00 p.m. and 11:00 p.m. and supine IOP at 9:00 a.m. and 11:00 a.m. Furthermore, brimonidine increased U at 9 a.m. and 11 a.m. (p<0.01) and had no effect on daytime and nighttime Fa, C or Pev.

To conclude, in subjects with OHT, brimonidine treatment for six weeks significantly reduces seated IOP during the day by increasing uveoscleral outflow. The lack of IOP effect at night can be explained by failure to overcome a normal nighttime reduction of uveoscleral outflow.

SOURCE: Fan S, Agrawal A, Gulati V, et al. Daytime and nighttime effects of brimonidine on IOP and acqueous humor dynamics in participants with ocular hypertension. J Glaucoma. 2014;23(5):276–281.

Visual Acuity Following Cataract Surgery in Patients with AMD

The authors of the following cohort study sought to evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration.

Their study 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. The authors analyzed the pre- and postoperative characteristics of participants who underwent cataract extraction during the five-year trial. They obtained both clinical data and standardized red-reflex lens and fundus photographs at baseline and annually. These photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Additionally, cataract surgery was documented at annual study visits or by history during telephone calls at six months. Analyses were conducted using multivariate repeated-measures regression. The main outcome measure was change in best-corrected visual acuity after cataract surgery compared with preoperative BCVA.

Adjusting for age at time of surgery, gender, interval between pre- 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 GA, 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).

Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity, the study authors concluded.

SOURCE: Age-Related Eye Disease Study 2 Research Group, Huynh N, Nicholson BP, Agrón E, et al. Visual acuity after cataract surgery in patients with age-related macular degeneration: Age-Related Eye Disease Study 2 Report Number 5. Ophthalmology. 2014;121(6):1229–1236.

Long-Term Impact of Multiple Intravitreal Anti-VEGF Injections on IOP

Investigators in South Korea evaluated the long-term effects of multiple intravitreal anti-vascular endothelial growth factor injections on intraocular pressure in eyes with neovascular age-related macular degeneration or retinal vein occlusion in the following retrospective cohort study.

They enrolled patients who underwent multiple (more than three) intravitreal anti-VEGF injections and who were followed for more than 12 months after their last injection. IOP elevation was defined as an increase of 5 mmHg over the baseline measurement on two consecutive visits. The investigators determined frequency of IOP elevation and calculated the hazard ratio of each putative risk factor for IOP elevation using the Cox proportional hazard model for all participants, incorporating underlying disease as a covariate, as well as for each cohort.

Included in the analysis were 629 eyes with neovascular AMD and 95 eyes with RVO. Twenty eyes with neovascular AMD (3.0%) and seven eyes with RVO (7.4%) experienced IOP elevation after multiple anti-VEGF injections, with an overall incidence of 3.7%, the investigators noted. In the Cox proportional hazard analysis of total participants, they found that a diagnosis of RVO (3.424, p=0.005), a history of glaucoma (8.441, p=0.001) and low baseline IOP (0.865, p=0.040) were all significant risk factors for IOP elevation following multiple anti-VEGF injections.

A history of multiple intravitreal anti-VEGF injections was not a significant risk factor for IOP elevation in our study. IOP elevation was more common in eyes with RVO than with AMD after anti-VEGF injection.

SOURCE: Kim YJ, Sung KR, Lee KS, et al. Long-term effects of multiple intravitreal antivascular endothelial growth factor injections on intraocular pressure. Am J Ophthalmol. 2014;157(6):1266–1271.

Tear Mucin 5AC in Office Workers Using Visual Display Terminals

There are limited reports on the relationship between mucin 5AC (MUC5AC) concentrations in tears, working hours and the frequency of ocular symptoms in visual display terminal users. This institutional, cross-sectional study evaluated these relationships among patients with dry-eye disease and individuals serving as controls to determine the relationship between MUC5AC concentration in the tears of VDT users based on the diagnosis of dry-eye disease and frequency of ocular symptoms.

Participants included 96 young and middle-aged Japanese office workers. Both eyes of 96 volunteers (60 men and 36 women) were studied. Participants working in a company that used VDTs completed questionnaires about their working hours and the frequency of ocular symptoms. Dry-eye disease was diagnosed as definite or probable, or it was not present. Tear fluid was collected from the inferior fornix after instillation of 50 μL of sterilized saline and the MUC5AC concentration was normalized to tear protein content and expressed as MUC5AC (nanograms) per tear protein (milligrams). The differences in MUC5AC concentration between dry-eye disease groups, between VDT working hours (short, intermediate and long), and between symptomatic and asymptomatic groups were evaluated with 95% CIs based on nonparametric Hodges-Lehmann determination. Ocular surface evaluation, prevalence of dry-eye disease and MUC5AC concentration served as main outcome measures.

It was reported that the prevalence of definite and probable dry-eye disease was 9% (n=9) and 57% (n=55), respectively. The mean MUC5AC concentration was lower in the tears of VDT users with definite dry-eye disease than in those with no dry-eye disease (p=0.02; Hodges-Lehmann estimator, –2.17; 95% CI, –4.67 to –0.30). The mean MUC5AC concentration in tears was lower in the group that worked longer hours than in the group that worked shorter hours (p=0.049; estimated difference, –1.65; 95% CI, –3.12 to 0.00). Furthermore, MUC5AC concentration was lower in participants with symptomatic eye strain than in asymptomatic individuals (p=0.001; estimated difference, –1.71; 95% CI, –2.86 to –0.63).

In conclusion, the data obtained in the present study suggest that office workers with prolonged VDT use, as well as those with an increased frequency of eye strain, have a low MUC5AC concentration in their tears. Furthermore, MUC5AC concentration in the tears of patients with dry-eye disease may be lower than that in individuals without dry-eye disease.

SOURCE: Uchino Y, Uchino M, Yokoi N, et al. Alteration of tear mucin 5AC in office workers using visual display terminals: The Osaka Study. JAMA Ophthalmol. 2014;Jun 5. [Epub ahead of print].

  • TEARLAB AND THE SJÖGREN'S FOUNDATION PROMOTE DRY-EYE DISEASE AWARENESS MONTH. TearLab is again partnering with the Sjögren's Foundation to promote Dry-Eye Disease Awareness Month. Throughout July, TearLab will be raising awareness through professional communications and in-clinic materials, including staff buttons. For every “selfie” taken of a staff member wearing a button, TearLab will donate $1 to the Sjögren's Syndrome Foundation. Photos can be submitted via tweet to @TearLab or emailed to marketingresourcegroup@tearlab.com.Want to know more? Click here.

  • ALLERGAN REJECTS VALEANT'S SECOND REVISED, UNSOLICTED PROPOSAL. In recent news regarding Valeant Pharmaceutical's second unsolicited proposal for a merger with Allergan, after consulting with its independent financial and legal advisors, Allergan's board of directors has unanimously determined that the latest revised, unsolicited proposal dated May 30, 2014 by Pershing Square Capital Management, LP, and Valeant Pharmaceuticals International Inc. substantially undervalues Allergan, creates significant risks and uncertainties for its stockholders, and is not in the best interests of the company and its stockholders. Additionally, in a letter from Allergan chairman and CEO David E.I. Pyott, CBE, to Valeant's chairman and CEO Michael Pearson, Mr. Pyott states that the Allergan board doesn't believe Valeant's latest proposal offers sufficient or certain value to warrant discussions between the two companies. Read the latest here.

  • HEIDELBERG ENGINEERING PRESENTS XTREME RESEARCH AWARD TO NASA OCULAR HEALTH STUDY. Heidelberg Engineering's annual 2014 Xtreme Research Award was presented to the NASA Ocular Health Study during the recent award ceremony in Orlando. Dr. Nimesh Patel, assistant professor at the University of Houston, College of Optometry and a consultant to NASA accepted the award and presented the award lecture. In the presentation, entitled “OCT in Zero G,” he provided details about the use of Spectralis Optical Coherence Tomography on board the International Space Station. NASA certified the Spectralis for use on board the ISS after a rigorous test program was successfully completed in 2013. According to NASA, “The purpose of the prospective observational study of ocular health on the International Space Station crew is to collect evidence to characterize the risk and define the visual changes, vascular changes, and central nervous system (CNS) changes, including intracranial pressure, observed during long-duration exposure to microgravity, including post-flight time course for recovery to baseline.” A video recording of the Xtreme Research Lecture by Dr. Patel is available here.

  • INSITE VISION AND SENJU PHARMACEUTICAL TO DEVELOP AND COMMERCIALIZE AZITHROMYCIN OPHTHALMIC SOLUTION USING DURASITE IN JAPAN. InSite Vision Inc. and Senju Pharmaceutical Co. Ltd. have entered into a collaboration and license agreement to develop and market InSite's azithromycin ophthalmic solution using DuraSite including AzaSite 1% and AzaSite Xtra 2% ocular antibiotics in Japan. Senju has agreed to pay InSite an upfront license fee, additional development milestone fees and a percentage royalty on net sales. Read more at www.insitevision.com.

  • EYLEA INJECTION SUBMITTED FOR EU MARKETING AUTHORIZATION FOR TREATMENT OF MACULAR EDEMA SECONDARY TO BRVO. Regeneron Pharmaceuticals Inc. and Bayer HealthCare have announced that Bayer HealthCare has submitted an application to the European Medicines Agency seeking marketing authorization in the European Union for Eylea (aflibercept) Injection for the treatment of macular edema following branch retinal vein occlusion. The EMA submission is based on the positive Phase III, double-masked, randomized, active-controlled VIBRANT trial of patients with macular edema following BRVO. For additional details, visit www.regeneron.com.

Review of Ophthalmology® Online is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 11 Campus Boulevard, Newtown Square, PA 19073.

To subscribe to other JMI newsletters or to manage your subscription, click here.

To change your email address, reply to this email. Write "change of address" in the subject line. Make sure to provide us with your old and new address.

To ensure delivery, please be sure to add reviewophth@jobsonmail.com to your address book or safe senders list.

Click here if you do not want to receive future emails from Review of Ophthalmology Online.

Advertising: For information on advertising in this e-mail newsletter or other creative advertising opportunities with Review of Ophthalmology, please contact sales managers James Henne or Michele Barrett.

News: To submit news or contact the editor, send an e-mail, or FAX your news to 610.492.1049