Volume 14, Number 12
Monday, March 24, 2014


In this issue: (click heading to view article)
######### Growth of GA on FAF and Polymorphisms of CFH, CFB, C3, FHR1-3 and ARMS2 in AMD
######### Long-Term Result of Repeat Dexamethasone Implants in Eyes with Noninfectious Uveitis
######### Impact of Axial Length and Post-Injection Reflux on Sustained IOP Elevation as a Result of Intravitreal Anti-VEGF Therapy
######### Risk of Cataract Surgery with Use of Selective Serotonin Reuptake Inhibitor
######### Briefly

Growth of GA on FAF and Polymorphisms of CFH, CFB, C3, FHR1-3 and ARMS2 in AMD

Identification of the genetic risk factors that contribute to geographic atrophy (GA) could lead to advancements in interventional trials and/or therapeutic approaches for combating vision loss. The authors of the following prospective, controlled, multicenter study investigated whether single-nucleotide polymorphisms (SNPs) are associated with the presence and progression of established GA in age-related macular degeneration (AMD).

They included 154 patients with GA/AMD and 141 age-matched control participants at eight Spanish hospitals and collected samples of DNA to analyze SNPs within AMD-related genes (CFH, CFB, C3, FHR1-3 and ARMS2). The authors also used fundus autofluorescence (FAF) imaging to evaluate GA progression during a two-year period in 73 patients with GA/AMD. Finally, they used logistic regression to analyze the associations of SNPs, age, body mass index and cigarette smoking with the rate of progression and relative growth of GA.

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.

These findings confirm that genetic risk factors related to the presence of GA are not identical to those associated with GA progression. In fact, the authors demonstrate that gene variants of CFH and CFB, as well as demographic risk factors, confer significant risk for GA progression (both rate of progression and relative growth) within a Spanish population.

SOURCE: Caire J, Recalde S, Velazquez-Villoria A, Garcia-Garcia L, et al; for the Spanish Multicenter Group on AMD. Growth of geographic atrophy on fundus autofluorescence and polymorphisms of CFH, CFB, C3, FHR1-3, and ARMS2 in age-related macular degeneration. JAMA Ophthalmol. 2014; Feb 20. [Epub ahead of print].

Long-Term Result of Repeat Dexamethasone Implants in Eyes with Noninfectious Uveitis

UK researchers aimed to describe the long-term outcome of eyes with uveitis after repeated treatment with dexamethasone implants (Ozurdex, Allergan) in this retrospective, observational case series of 38 eyes (27 patients) with uveitis that were treated with 61 dexamethasone implants.

All eyes underwent dexamethasone pellet implantation and anatomic and functional outcomes, as well as ocular complications, were noted. The main outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze score, and presence of increased intraocular pressure or cataract.

According to the researchers, average follow-up was 17.3 ± 1.8 months after the first implant (median, 13.3 months; range, three to 54.5 months; 54.65 eye-years), with 14 eyes (36.9%) receiving a single implant and 24 eyes (63.1%) receiving multiple implantations. After the first implantation, average BCVA improved significantly from 0.47 ± 0.05 logarithm of the minimum angle of resolution (logMAR) units (Snellen equivalent, 20/60) to 0.27 ± 0.07 logMAR (Snellen equivalent, 20/37; p<0.001); CRT decreased by 263 ± 44.22 µm (p=0.003), although macular edema persisted in 50% of eyes, and the percentage of eyes achieving a vitreous haze score of zero increased from 58% to 83% (p=0.03). The median duration of therapeutic effect after the first injection was six months (range, two to 42 months), with a similar response achieved after each repeat implantation. The accumulated effect of repeat dexamethasone implants resulted in a continued improvement in BCVA (R²=0.91; p<0.0001), with significant improvement and stabilization of CRT. After repeated implantations, two eyes had progression of posterior subcapsular opacities, although neither required surgery. There were seven instances of increased intraocular pressure of more than 21 mmHg at a rate of 0.13 per eye-year, all of which responded to pharmacologic treatment.

The study researchers concluded that the accumulated effect of repeat dexamethasone pellet implantations improves retinal thickness and resolves ocular inflammation, resulting in restoration of ocular function. Ocular complications were minimal, with no eyes requiring surgery for increased ocular pressure or progression of cataract.

SOURCE: Tomkins-Netzer O, Taylor SR, Bar A, et al. Treatment with repeat dexamethasone implants results in long-term disease control in eyes with noninfectious uveitis. Ophthalmology. 2014; Mar 19. [Epub ahead of print].

Impact of Axial Length and Postinjection Reflux on Sustained IOP Elevation as a Result of Intravitreal Anti-VEGF Therapy

The purpose of this study was to assess an association of axial length (AL) or post-injection reflux with transient or sustained intraocular pressure (IOP) elevation in patients with neovascular age-related macular degeneration (AMD) receiving anti-vascular endothelial growth factor (anti-VEGF) injections.

A total of 147 eyes from 74 consecutive patients with neovascular AMD who presented to a single physician over a two-month period had ALs measured by IOLMaster. Twenty-one patients had pre-injection and immediate post-injection IOP measured and immediate reflux assessed.

Overall, 9.5% of eyes had been identified with sustained IOP elevation in a previous study. AL did not significantly differ between eyes that had (AL, 23.96 ± 0.66 mm; n=14) and had not experienced sustained IOP elevation (AL, 23.44 ± 1.24 mm; n=133; p=0.12, t-test). By linear regression analysis, the relationship between experiencing sustained IOP elevation and AL was not statistically significant (R²=0.0165; p=0.121). The relationship between AL and immediate post-injection IOP elevation was also not statistically significant (R²=0.0001; p=0.97). Immediate post-injection IOP increase did differ between eyes without reflux (30.2 ± 9.3 mmHg; n=12) and those with reflux (1.1 ± 7.2; n=9; p<0.001).

In conclusion, axial length does not seem to be a predictor of transient or sustained IOP elevation. Repeated trabecular meshwork trauma related to the absence or presence of reflux and immediate post-injection IOP elevation may be a contributing factor.

SOURCE: Hoang QV, Jung JJ, Mrejen S, Freund KB. Influence of axial length and postinjection reflux on sustained intraocular pressure elevation as a result of intravitreal anti-vascular endothelial growth factor therapy. Retina. 2014;34(3):519–524.

Risk of Cataract Surgery with Use of Selective Serotonin Reuptake Inhibitor

Investigators conducted this population-based, case-control study to examine whether selective serotonin reuptake inhibitor use is associated with an increased risk of cataract surgery. They discovered that selective serotonin reuptake inhibitor use of one or more years in people aged 50+ years is associated with an increased risk of cataract surgery.

Eligible patients were county residents in the Rochester Epidemiology Project. Cases included 6,024 county residents aged 50+ years who underwent first-eye cataract surgery between January 1, 2004 and December 31, 2011. Controls included 6,024 residents who never had cataract surgery and were matched to cases by age, sex, and date of surgery. The investigators used logistic regression models to compute odds ratios for differences in selective serotonin reuptake inhibitor use between cases and controls, and to adjust for confounding variables. They used Rochester Epidemiology Project databases to assess cataract surgery and selective serotonin reuptake inhibitor treatment. Selective serotonin reuptake inhibitor served as the main outcome measure.

In the cataract surgery cohort of 6,024 residents, 1,024 (17%) were selective serotonin reuptake inhibitor users, compared to 788 (13%) in the matched cohort of 6,024 residents never having cataract surgery (p<0.001). The study investigators noted that selective serotonin reuptake inhibitor use of one or more years was associated with an increased risk of cataract surgery (OR=1.36; 95% CI, 1.23 to 1.51; p<0.001). The associations were similar in women (OR=1.37; 95% CI, 1.22 to 1.55; p<0.001) and men (OR=1.34; 95% CI, 1.12 to 1.61; p=0.002). The risk of cataract surgery was highest with citalopram use (OR=1.53, 95% CI, 1.33 to 1.77; p<0.001).

SOURCE: Erie JC, Brue SM, Chamberlain AM, Hodge DO. Selective serotonin reuptake inhibitor use and increased risk of cataract surgery: a population-based, case-control study. Am J Ophthalmol. 2014; Mar 17. [Epub ahead of print].

  • PHASE III CLINICAL TRIAL UNDER WAY FOR SUSTAINED-RELEASE DEXAMETHASONE. Ocular Therapeutix has announced the initiation of its Phase III clinical program to evaluate the safety and efficacy of its sustained-release dexamethasone, an ophthalmic corticosteroid for the treatment of postoperative inflammation and pain following cataract surgery. The dexamethasone is administered as a one-time, bioabsorbable intracanalicular plug for release of the steroid to the ocular surface for up to 30 days. In the first of two prospective, multicenter, randomized, parallel-arm, double-masked, vehicle-controlled studies, 240 patients undergoing clear corneal cataract surgery will be enrolled at sites throughout the United States. Following surgery, patients will be randomized to either the dexamethasone treatment group or a placebo vehicle plug. Completion of the trial, and the beginning of a second Phase III trial is expected later this year. Read more at www.ocutx.com.
  • FDA RESPONDS TO AVEDRO'S CORNEAL CROSS-LINKING NDA. Avedro Inc. has received a complete response letter from the FDA regarding the New Drug Application (NDA) for its riboflavin ophthalmic solution/KXL System. In the letter, the FDA identified a number of areas of the application that require additional information. Avedro CEO David Muller, PhD, says the company plans to work closely with the FDA to resolve these issues as quickly as possible to make the treatment available to patients in the United States. Click here for additional details.
  • BAUSCH + LOMB LAUNCHES PEROXICLEAR. Bausch + Lomb recently announced the introduction of PeroxiClear 3% hydrogen peroxide cleaning and disinfecting solution. According to the company, PeroxiClear solution contains Triple-Moist Technology, which helps to provide up to 20 hours of moisture, plus neutralizes in only four hours, compared to six hours, as with other peroxides. PeroxiClear solution will be available in major retailers starting in April and May 2014. Want to learn more? Visit www.bausch.com.
  • JETREA APPROVED IN SWITZERLAND FOR TREATMENT OF VMT. According to a press release from ThromboGenics NV, a Swissmedic has approved Jetrea (ocriplasmin) for the treatment of adults with vitreomacular traction, including when associated with macular hole of diameter less than or equal to 400 µm. The company's partner, Alcon, holds the commercialization rights to Jetrea outside the United States and will be responsible for the launch of the drug in Switzerland.

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