Review of Ophthalmology Online Review of Ophthalmology Online

Volume 13, Number 51
Monday, December 23, 2013

In this issue: (click heading to view article)
######### Pharmacogenetic Associations with VEGF Inhibition in Participants with Neovascular AMD

######### Prognostic Factors of Eyes with Naïve Subfoveal Myopic CNV Following Intravitreal Bevacizumab

######### Link Between IOP and Rate of Progression in Treated Glaucoma
######### Early Peripheral Laser Photocoagulation of Nonperfused Retina Improves in Patients with CRVO
######### Briefly


Pharmacogenetic Associations with VEGF Inhibition in Participants with Neovascular AMD

Researchers designed this cohort study, which combines information about patients' genotypes with information from a randomized controlled trial about responsiveness to anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD) to determine if prespecified genetic polymorphisms influence responsiveness to VEGF inhibition in neovascular AMD.

The objectives were to replicate three reported pharmacogenetic associations of response in neovascular AMD and to test for novel associations. Participants consisted of 509 subjects with neovascular AMD, enrolled in the Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) trial. The reseachers classified participants as responders or nonresponders to VEGF inhibition based on the optical coherence tomography (OCT) metric of total retinal thickness (TRT). They computed the change in TRT from baseline to the latest time point for which OCT data were available (three, six, nine or 12 months). The classified eyes with changes in TRT greater than or equal to the 75th percentile or more as responders, and those with changes less than or equal to the 25th percentile or lower as nonresponders. The study researchers tested three previously reported associations of response to VEGF inhibition in neovascular AMD involving single nucleotide polymorphisms (SNPs) at the CFH, FZD4 and HTRA1/ARMS2 loci for replication and tested an additional 482 SNPs using a candidate gene approach. They estimated associations as odds ratios (ORs) with confidence intervals (CIs). The primary outcome was evidence of a genetic association with response to VEGF inhibition as measured by change in TRT.

The researchers classified 126 participants as responders and 128 as nonresponders. They reported that the SNP rs10490924 in HTRA1/ARMS2 showed a borderline association with responsiveness after Bonferroni correction (OR, 1.53; CI, 0.99 to 2.36; p=0.055, Bonferroni correction). None of the other 484 additional SNPs tested for association was significant after Bonferroni correction for multiple testing. The smallest corrected p value was 0.84 (p=0.002, uncorrected) for rs9679290 in the EPAS1 (HIF2A) gene on chromosome 2. Four of the 10 most significant results were in this gene.

The researchers estimated pharmacogenetic associations using high-quality phenotype data from a randomized controlled clinical trial of neovascular AMD. They observed no significant association or replication of previous associations. Further investigation of the EPAS1 (HIF2A) gene, however, may, be merited.

SOURCE: Lotery AJ, Gibson J, Cree AJ, et al; Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) Study Group. Pharmacogenetic associations with vascular endothelial growth factor inhibition in participants with neovascular age-related macular degeneration in the IVAN study. Ophthalmology. 2013;120(12):2637–2643.

Prognostic Factors of Eyes with Naïve Subfoveal Myopic CNV Following Intravitreal Bevacizumab

Investigators in South Korea sought to determine the efficacy of one intravitreal bevacizumab injection followed by pro re nata (one + p.r.n.) injection in cases of subfoveal myopic choroidal neovascularization (CNV) and to identify CNV-recurrence–related prognostic factors in this retrospective observational case series.

They included 103 eyes of 89 consecutive naïve patients who had subfoveal myopic CNV and had been followed for at least two years. Of those eyes, 24 had recurrences. The remaining eyes were stable after the initial treatment.

According to the investigators, the average patient age was 51.1 ± 15.2 years and the average follow-up duration was 44.1 ± 12.7 months. They noted that at baseline and at the one-year, two-year and final visits, the average best-corrected visual acuities (BCVAs) were 0.57 ± 0.45, 0.38 ± 0.51, 0.40 ± 0.52, and 0.41 ± 0.41 logMAR, respectively. The investigators reported that recurrence rate during follow-up was 23.3%. They also found that BCVA improved by 0.2 logMAR after 2.7 injections in the eyes without recurrence but by only 0.08 logMAR after 6.9 injections in the eyes with recurrence. In univariate analysis, they determined that recurrence was associated with older age, more myopic refraction, thinner choroid, larger CNV lesions, and subfoveal hemorrhage at baseline. In multivariate analysis, only baseline CNV lesion size associated significantly with CNV recurrence (p=0.002). Recurrence, baseline BCVA, choroidal thickness and CNV size associated significantly with final BCVA (p=0.026, <0.0001, 0.007 and 0.002, respectively). Baseline choroidal thickness, CNV size, age, and presence of lacquer cracks associated significantly with injection number (p<0.0001, <0.0001, 0.026 and 0.035, respectively).

To conclude, one + p.r.n. intravitreal bevacizumab monotherapy effectively stabilized subfoveal myopic CNV. The CNV size, the baseline BCVA, and the choroidal thickness were the main prognostic factors of subfoveal myopic CNV after one + p.r.n. injection of bevacizumab.

SOURCE: Yang SH, Kim JG, Kim JT, Joe SG. Prognostic factors of eyes with naïve subfoveal myopic choroidal neovascularization after intravitreal bevacizumab. Am J Ophthalmol. 2013;156(6):1202–1210.


Link Between IOP and Rate of Progression in Treated Glaucoma

To evaluate the relationship between intraocular pressure (IOP) and the rate of visual field (VF) progression in treated glaucoma, a clinic-based, retrospective study analyzed data of consecutive primary open-angle (POAG) and angle-closure glaucoma patients with ≥5 VFs between 1989 and 2008.

The Guided Progression Analysis software, which provides the rate of change of Visual Field Index per year, was used to assess the rate of progression (ROP). IOP measurements during the VF examination visits were extracted, and mean, peak and fluctuation (SD) of IOP during the follow-up were calculated. Additionally, relationships between IOP parameters and ROP were analyzed using regression models. Other risk factors evaluated were age, sex, type of glaucoma, presence of hypertension and diabetes, severity of VF loss at presentation, glaucoma surgery during follow-up, number of anti-glaucoma medications, and follow-up duration.

During the study period, 296 eyes of 213 glaucoma patients had undergone ≥5 VFs. IOP fluctuation was the only IOP parameter significantly associated with ROP (β=–0.37, p=0.02). Evaluated in a multivariate model with other risk factors, the severity of VF damage at presentation (β=0.08, p=0.002) and IOP fluctuation (β=–0.35, p=0.02) remained significantly associated with ROP. Furthermore, greater IOP fluctuation was seen in eyes undergoing glaucoma surgery and eyes requiring more anti-glaucoma medications during follow-up.

Long-term IOP fluctuation was the most important IOP parameter associated with increased ROP of glaucomatous VF loss. This association is likely due to the confounding effect of enhanced therapy in eyes suspected to be progressing.

SOURCE: Rao HL, Addepalli UK, Jonnadula GB, et al. Relationship between intraocular pressure and rate of visual field progression in treated glaucoma. J Glaucoma. 2013; 22(9):719–724.

Early Peripheral Laser Photocoagulation of Nonperfused Retina Improves in Patients with CRVO

The authors of this prospective, proof-of-concept study randomized 22 central retinal vein occlusion (CRVO) patients into two arms to evaluate the effect of combination of ranibizumab and laser photocoagulation to peripheral retinal areas of nonperfusion in patients with non-ischemic CRVO without neovascularizations.

They treated the RL group (ranibizumab + laser; n=10) with ranibizumab plus additive laser photocoagulation and the control R group (n=12) with ranibizumab only. All patients received three initial monthly ranibizumab injections followed by p.r.n. regimen. The authors documented the changes in best-corrected visual acuity (BCVA) and in central retinal thickness (CRT) over six months.

They noted that the median of BCVA improved in the RL group from 65 ETDRS letters (interquartile range IQR=10 letters) at baseline to 70 (IQR=23.2) letters at month six. They also found that in the control group, BCVA remained stable [baseline: 61 (IQR=19.5) and month six: 61 (IQR=22) letters]. CRT decreased between baseline and final visit in the RL group from 547 (IQR=513) µm to 246.5 (IQR=346.3) µm, and in the control group from 637.5 (IQR=344) µm to 423 (IQR=737) µm. More pronounced improvements in BCVA were seen in the RL group (medians=14 vs. 6.5 letters) although the observed group differences were not statistically significant due to small samples.

In conclusion, the selective laser photocoagulation of peripheral areas of nonperfusion seems to lead to additional visual improvement in patients with CRVO. A larger replication trial is necessary to confirm the results of this proof of concept study.

SOURCE: Rehak M, Tilgner E, Franke A, et al. Early peripheral laser photocoagulation of nonperfused retina improves vision in patients with central retinal vein occlusion (results of a proof of concept study). Graefes Arch Clin Exp Ophthalmol. 2013; Dec [Epub ahead of print].

  • BIOHEART TO CONDUCT DRY AMD STUDY. Bioheart Inc. announced that it will enroll up to 100 patients in a study to determine the safety and efficacy of adipose-derived stem cells or AdipoCell in patients with dry age-related macular degeneration (AMD). Bioheart says that the study has been reviewed and approved by the Institutional Review Board of the International Cellular Medicine Society.
  • FIRST PATIENT DOSED IN PHASE IIA PROOF-OF-CONCEPT TRIAL FOR QLT091001 IN IMPAIRED DARK ADAPTATION. InSite Vision Inc. has announced top-line results from its recently completed confirmatory Phase III clinical trial of BromSite (ISV-303) for the reduction of inflammation and pain following cataract surgery. The drug combines a low dose (0.075%) of the nonsteroidal anti-inflammatory drug (NSAID) bromfenac with InSite Vision's DuraSite drug delivery technology. The trial enrolled 248 patients undergoing cataract surgery in a two-arm trial designed to evaluate the efficacy and safety of BromSite against the DuraSite vehicle alone. Patients were randomized and then dosed twice-a-day beginning the day before surgery and continuing the day of surgery and for 14 days post-surgery. In this second pivotal trial, BromSite achieved statistically significant superiority compared to vehicle (p=0.01) in alleviating ocular inflammation (measured by the absence of cells in the anterior chamber of the eye) at Day 15 among patients following cataract surgery compared to the vehicle arm. BromSite also achieved statistically significant superiority compared to vehicle (p<0.001) for the secondary endpoint of post-surgical reduction in pain. BromSite also achieved a third endpoint of reduction in inflammatory flare (p<0.01) that was incorporated into the protocol based on feedback from European regulatory authorities. BromSite was well-tolerated, with no safety concerns or drug-related serious adverse events reported. InSite plans to conduct additional clinical studies post-approval, with the goal of adding prevention of cystoid macular edema to the BromSite label. Click here to find out more.
  • ABBOTT'S IDESIGN DX SYSTEM ALL SET FOR USE BY U.S. OPHTHALMOLOGISTS. Abbott's iDesign Dx system is finally available for ophthalmologists in the United States to capture five optical measurements in one three-second scan to determine a patients' visual abnormalities. According to Abbott, the highly advanced diagnostic tool measures the internal optics and surface of the eye more precisely than conventional methods, allowing doctors to fully evaluate imperfections that result in poor vision. Doing so, says Abbott, enables ophthalmologists to screen patients more efficiently to determine whether they are eligible for LASIK or other refractive surgery and to assist in diagnosis of other conditions. The iDesign Dx system uses advanced wavefront-sensing technology to measure and map “aberrated” eyes and measures not only the optical system, but also individual components of the eye. It launched in 2013 in the United States for diagnostic use. In Europe and a number of countries around the world, including Australia, Brazil, Canada, India, Japan and New Zealand, the iDesign Advanced WaveScan Studio (not approved in the United States) is currently approved for LASIK treatment, planning, screening and diagnostics. Read about it at

  • CARL ZEISS VISION AIMS TO SPREAD THE WORD ABOUT DIGITAL EYE STRAIN. Carl Zeiss Vision has released a consumer-oriented infographic designed to heighten awareness of the symptoms of digital eye strain to a broad range of media outlets, including newspapers and health-oriented websites. The infographic explains in simple terms key symptoms and causes of digital eye strain and how eye wear designed for computer and digital device use, like the new Zeiss Officelens, can address the symptoms. Zeiss Officelens is designed to eliminate the difficulties that ECPs have experienced with computer lenses in the past. The infographic is available for eye-care practitioners to download at


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