#########
Volume 12, Number 41
Monday, October 8, 2012
#########


OCTOBER IS WORLD BLINDNESS AWARENESS MONTH




In this issue: (click heading to view article)
#########
######### RNFL Atrophy and VF Loss Over Time in Glaucoma Suspect and Glaucomatous Eyes

#########
######### A Look at VEGF in Patients with Exudative AMD Treated with Ranibizumab
#########
######### Sustained Elevation of IOP Following Intravitreal Injections of Bevacizumab in Neovascular AMD
#########
######### VF Progression in Glaucoma
#########
######### Briefly

 

 





RNFL Atrophy and VF Loss Over Time in Glaucoma Suspect and Glaucomatous Eyes

The following prospective, longitudinal clinical trial compared the detection of progressive retinal nerve fiber layer thickness (RNFL) atrophy identified using time-domain optical coherence tomography (TD-OCT) with visual field (VF) progression using standard automated perimetry in glaucoma suspect and preperimetric glaucoma patients or perimetric glaucoma patients.

Eligible eyes with two years or more of follow-up underwent TD-OCT and standard automated perimetry every six months. The occurrence of VF progression was defined as the first follow-up visit reaching a significant (p<.05) negative visual field index slope over time. RNFL progression or improvement was defined as a significant negative or positive slope over time, respectively. Specificity was defined as the number of eyes with neither progression nor improvement, divided by the number of eyes without progression. Additionally, Cox proportional hazard ratios were calculated using univariate and multivariate models with RNFL loss as a time-dependent covariate.

A total of 310 glaucoma suspect and preperimetric glaucoma eyes and 177 perimetric glaucoma eyes were included. It was reported that 89 eyes showed VF progression and 101 eyes showed RNFL progression. The average time to detect VF progression in those 89 eyes was 35 ± 13 months, and the average time to detect RNFL progression in those 101 eyes was 36 ± 13 months. In multivariate Cox models, average and superior RNFL losses were associated with subsequent visual field index loss in the entire cohort (every 10-µm loss; hazard ratio, 1.38; p=.03; hazard ratio, 1.20; p=.01; respectively). Among the entire cohort of 487 eyes, 42 had significant VF index improvement and 55 had significant RNFL improvement (specificity, 91.4% and 88.7%, respectively).

Structural progression is associated with functional progression in glaucoma suspect and glaucomatous eyes. Average and superior RNFL thickness may predict subsequent standard automated perimetry loss.

SOURCE: Sehi M, Zhang X, Greenfield DS, et al. Retinal nerve fiber layer atrophy is associated with visual field loss over time in glaucoma suspect and glaucomatous eyes. Am J Ophthalmol. 2012;Oct 2. [Epub ahead of print].




http://www.revophth.com/ResFellowEdu2012







A Look at VEGF in Patients with Exudative AMD Treated with Ranibizumab

Researchers in Germany performed this nonrandomized, prospective, clinical study to analyze the temporal correlations of vascular endothelial growth factor (VEGF) suppression, morphologic recurrence of choroidal neovascularization (CNV) and visual acuity loss in eyes with exudative age-related macular degeneration (AMD) treated with ranibizumab.

They included 47 eyes of 47 patients with exudative AMD undergoing intravitreal ranibizumab injections and took aqueous humor specimens before each intravitreal ranibizumab injection. They also performed visual acuity testing, spectral domain optical coherence tomography (SD-OCT) and Steadman's fundoscopy before each injection. VEGF A was measured by Luminex multiplex bead analysis (Luminex Inc.). Main outcome measures were intraocular VEGF concentration, recurrence of CNV activity shown by SD-OCT and vision loss.

Ranibizumab resulted in complete VEGF suppression within a mean period of 37.8 days (standard deviation [SD] ± 4.8 days; range, 26–49 days), the researchers noted. They also found that recurrences of CNV activity as determined by SD-OCT occurred 93.7 days (SD ± 69.9 days; range, 57–368 days) after the last ranibizumab treatment. The VEGF levels were never suppressed when a recurrence occurred and functional recurrence (visual acuity) occurred 114.3 days (SD ± 81.4 days; range, 57–398 days) after previous treatment. The researchers also observed that the VEGF levels did not differ significantly between baseline and recurrence (69.3 pg/ml vs. 74.14 pg/ml; 95% confidence interval, –18.87 to 9.12).

In conclusion, a monthly intravitreal injection of 0.5 mg ranibizumab yields a durable VEGF inhibition. The recurrences of CNV as determined by SD-OCT are always preceded by a loss of intraocular VEGF suppression and usually followed by loss of visual acuity in the further course.

SOURCE: Muether PS, Hermann MM, Viebahn U, et al. Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab. Ophthalmology. 2012;119(10):2082–2086.



http://www.revophth.com/ChicOS2012






Sustained Elevation of IOP Following Intravitreal Injections of Bevacizumab in Neovascular AMD

The use of intravitreal anti-vascular endothelial growth factor (VEGF) agents in general, and of bevacizumab (Avastin) in particular, has become the common first-line treatment of neovascular age-related macular degeneration (AMD). Several reports addressed the possible elevation of intraocular pressure (IOP) following intravitreal injection of anti-VEGF. The authors of the following Israeli retrospective cohort study aimed to determine the prevalence of sustained IOP elevation following intravitreal bevacizumab injections for neovascular AMD and to identify possible risk factors for the development of increased IOP.

In this study, they included 174 consecutive patients (201 eyes) receiving intravitreal bevacizumab (1.25 mg/0.05 ml) as treatment for neovascular AMD. The authors reviewed the records of the study patients for age, gender, history of glaucoma, phakic status, IOP levels, length of follow-up, total number of injections, intervals between injections and IOP management in eyes that exhibited IOP elevation. Sustained IOP elevation was defined as IOP ≥22 mmHg and a change from baseline of ≥6 mmHg recorded on at least two consecutive visits and lasting ≥30 days. The study authors identified risk factors for an IOP increase from the association between the studied variables and IOP elevations.

They found sustained IOP elevation in 22 of 201 eyes (11%) and they noted that increased IOP was controlled with topical medications in all eyes. Among the variables studied, only male gender [OR = 3.1, 95% CI (1.1, 8.5) p=0.029] and length of interval between injections less than eight weeks [OR = 3.0, 95% CI (1.1, 7.9), p=0.028] emerged as risk factors for IOP elevation in a multivariable model. The prevalence of IOP elevation was significantly higher when the interval between injections was less than eight weeks than when it was eight or more weeks (17.6 and 6%, respectively, p=0.009). Pre-existing glaucoma was not associated with IOP elevation (p=0.9).

Sustained IOP elevations can occur in normotensive eyes undergoing intravitreal bevacizumab treatment for neovascular AMD. This phenomenon was related to shorter intervals between injections, with eight weeks being taken as the cut-off point. AMD eyes that receive intravitreal bevacizumab injections need to be monitored for IOP changes, especially those in which the intervals between injections are less than eight weeks.

SOURCE: Mathalone N, Arodi-Golan A, Sar S, et al. Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2012;250(10):1435–1440.







VF Progression in Glaucoma

To establish a method for estimating the overall statistical significance of visual field deterioration from an individual patient's data, and to compare its performance to pointwise linear regression, investigators in Canada used the Truncated Product Method to calculate a statistic S that combines evidence of deterioration from individual test locations in the visual field.

The overall statistical significance (p value) of visual field deterioration was inferred by comparing S with its permutation distribution, derived from repeated reordering of the visual field series. The investigators evaluated the permutation of pointwise linear regression (PoPLR) and pointwise linear regression in data from patients with glaucoma (944 eyes, median mean deviation –2.9 dB, interquartile range: –6.3, –1.2 dB) followed for more than four years (median 10 examinations over eight years). They estimated false-positive rates from randomly reordered series of this dataset, and also estimated hit rates (proportion of eyes with significant deterioration) from the original series.

The study investigators found that the false-positive rates of PoPLR were indistinguishable from the corresponding nominal significance levels and were independent of baseline visual field damage and length of follow-up. They reported that at p<0.05, the hit rates of PoPLR were 12%, 29% and 42%, at the fifth, eighth and final examinations, respectively, and at matching specificities they were consistently higher than those of pointwise linear regression.

To conclude, in contrast to population-based progression analyses, PoPLR provides a continuous estimate of statistical significance for visual field deterioration individualized to a particular patient's data. This allows close control over specificity, essential for monitoring patients in clinical practice and in clinical trials.

SOURCE: O'Leary N, Chauhan BC, Artes PH. Visual field progression in glauocoma: estimating the overall significance of deterioration with permutation analyses of pointwise linear regression (PoPLR). Invest Ophthalmol Vis Sci. 2012;53(11):6776–6784.









  • iSONEP DOSING IN NEXUS PHASE II STUDY INITIATED. Lpath Inc. has begun the dosing of iSONEP in its Nexus Phase II study, with several wet AMD patients treated since September 21, 2012. In the double-blind, multi-site trial, the company plans to dose 160 subjects who have not responded completely to a VEGF inhibitor (either Lucentis or Avastin). Subjects will be randomized into four arms: VEGF inhibitor alone; combination of a VEGF inhibitor and iSONEP (lower dose); combination of a VEGF inhibitor (higher dose); and iSONEP alone (higher dose). Endpoints to be studied include changes in best-corrected visual acuity, retinal thickness and lesion size. Furthermore, the trial will also investigate iSONEP's ability to flatten pigmented epithelial detachments. Get more information here.
  • STEMCELLS INC. TAKES FIRST STEP IN AMD CLINICAL TRIAL. The first patient in StemCells Inc.'s Phase I/II clinical trial in dry age-related macular degeneration (AMD) has been enrolled and transplanted. The open-label, dose-escalation trial is designed to evaluate the safety and preliminary efficacy of the company's proprietary HuCNS-SC (purified human neural stem cells) product candidate as a treatment for dry AMD and is expected to enroll a total of 16 patients. The HuCNS-SC cells will be administered by a single injection into the space beneath the retina in the most affected eye and patients' vision will be evaluated using both conventional and advanced state-of-the-art methods of ophthalmological assessment. Evaluations will be performed at predetermined intervals over a one-year period to assess safety and signs of visual benefit and patients will then be followed for an additional four years in a separate observational study. Those interested in participating in the trial should call (214) 364-3911. Visit the company's website to learn more.
  • BAUSCH + LOMB PARTNERS WITH CIRLE, RECEIVES FDA APPROVAL OF LOTEMAX GEL. Bausch + Lomb recently announced a new research partnership with Cirle Inc., in which the two organizations will be better positioned to explore novel, early-stage technologies and develop them into breakthrough innovations that fill previously unmet needs for the eye health community and the patients they serve. The partnership with Bausch + Lomb's Pharmaceutical business will encompass a wide variety of cutting-edge research projects including new compounds and technologies, and may ultimately be extended across Bausch + Lomb's Surgical and Vision Care divisions to include devices as well.

    Additionally, the FDA has approved Bausch + Lomb's New Drug Application (NDA) for Lotemax (loteprednol etabonate ophthalmic gel) 0.5% gel drop formulation, a new topical corticosteroid formulation in its line of loteprednol ophthalmic products. Lotemax Gel is a corticosteroid indicated for the treatment of postoperative inflammation and pain following ocular surgery. For more details on these latest announcements, visit www.bausch.com.
  • FACEBOOK “LIKES” TRANSLATE INTO DONATIONS. During this month, AllAboutVision.com will donate $5 to Optometry Giving Sight when someone “Likes” AllAboutVision.com on Facebook. According to AllAboutVision.com, the promotion helps commemorate World Sight Day on October 11. Optometry Giving Sight funds sustainable programs that provide eye exams and eyeglasses in communities in a developing country with little or no eye care. Through these programs, a $5 donation (or one “Like”) can provide an eye exam and glasses to one person.
  • FDA APPROVES CYSTARAN 0.44% FOR TREATMENT OF CORNEAL CYSTINE CRYSTALS. Sigma-Tau Pharmaceuticals Inc. has received approval from the FDA for Cystaran (cysteamine ophthalmic solution) 0.44%, a topical ophthalmic therapeutic developed in partnership with the National Institutes of Health for the treatment of patients suffering from corneal cystine crystal accumulation as a result of cystinosis. The drug is a cystine-depleting agent that lowers the cystine content of cells in patients with cystinosis. In the United States, Cystaran is designated an Orphan Drug, and has been granted seven years of market exclusivity. It is planned to be available in the future through specialty pharmacy distribution channels. Click here to learn more.
  • COOPERVISION ANNOUNCES NEW OPERATING REGION. CooperVision Inc. has established a new operating region, which will include the economies of India, Pakistan, the Middle East, Turkey, Russia and Africa. The company expects the new operating unit, effective November 1, 2012, to maximize its growing presence and accelerate growth in key emerging markets. In related news, CooperVision's current vice president of Marketing for Europe, the Middle East and Africa, Michael Wilkinson, has been named General Manager for the new region.
  • GLAUKOS CORPORATION MAKES “THE NEXT BIG THING” LIST. The Wall Street Journal has named Glaukos Corporation to its 2012 “The Next Big Thing” list, which identifies and ranks venture-backed companies across all industries that have the capital, executive experience and investor know-how to succeed. The company was selected from a 2012 pool of nearly 6,000 businesses and achieved a final ranking at number seven this year, and a selection as the nation's highest ranking health care startup company. This is the second consecutive selection for Glaukos to the top 50 startup company finalist list. View the complete list and learn more here.




Review of Ophthalmology® Online is published by the Professional Publications 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 publisher Rick Bay, or 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