Volume 8, Number 12
December 2012


WELCOME to Review of Ophthalmology's Retina Online e-newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

Oraya and Optegra Eye Hospital Group Launch New Wet AMD Therapy
In a press release, Oraya Therapeutics Inc. announced that an agreement has been reached with UK specialist eye hospital group Optegra, to establish Optegra as the world's first clinical centers to offer Oraya Therapy Stereotactic Radiotherapy...

EYLEA Injection Approved by European Commission for Treatment of Patients with Wet AMD; Submitted for EU Marketing Authorization for ME Following CRVO
According to Regeneron Pharmaceuticals Inc., the European Commission has approved EYLEA (aflibercept) Injection for the treatment of patients with wet age-related macular degeneration (AMD)...

And More...

Macular Epiretinal Brachytherapy and Treated AMD

This prospective, multicenter, interventional, noncontrolled clinical trial reported the optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) results of the Macular Epiretinal Brachytherapy in Treated Age-Related Macular Degeneration study.

It included 53 eyes of 53 participants with chronic, active neovascular age-related macular degeneration (AMD) requiring frequent anti-vascular endothelial growth factor (VEGF) retreatment.

Participants underwent pars plana vitrectomy with a single 24-gray dose of epimacular brachytherapy (EMB) delivered with an intraocular, handheld cannula containing a strontium 90/yttrium 90 source positioned over the active lesion. Participants were retreated with ranibizumab administered monthly as needed, using predefined retreatment criteria. They also underwent FFA at baseline, month one and month 12. Patients underwent OCT at baseline and then monthly for 12 months. The FFA and OCT images were evaluated by independent, central reading facilities. Main outcome measures were changes in OCT centerpoint thickness and angiographic lesion size 12 months following EMB.

It was reported that mean centerpoint thickness increased by 50 µm, from 186 to 236 µm (p=0.292), but that 70% of participants had an increase of less than the mean, with a median increase of only 1.8 µm. The FFA total lesion size increased slightly by 0.79 mm², from 14.69 to 15.48 mm² (p=0.710). It was also noted that total choroidal neovascularization (CNV) area increased by 1.17 mm², from 12.94 to 14.12 mm² (p=0.556). The classic CNV area decreased substantially by 3.70 mm², from 3.90 to 0.20 mm² (p<0.01). Predominantly classic lesions showed the greatest response, with mean Early Treatment Diabetic Retinopathy Study visual acuity improving by 1.5 letters (versus –4.0 for all participants combined); mean centerpoint thickness decreased by 43 µm (p=0.875). Furthermore, the angiographic and OCT response did not correlate with lesion size at baseline.

In chronic, active, neovascular AMD, EMB is associated with nonsignificant changes in centerpoint thickness and FFA total lesion size over 12 months.

Source: Petrarca R, Dugel PU, Nau J, et al. Macular epiretinal brachytherapy in treated age-related macular degeneration (MERITAGE Study). Ophthalmology. 2012;Nov 23. [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.07.091.

Benefit of Four Years of Intravitreal Ranibizumab Treatment for Neovascular AMD

Investigators in the United Kingdom sought to analyze the benefit of intravitreal ranibizumab over four years for patients with neovascular age-related macular degeneration (AMD).

They performed a retrospective case note review of all patients who started treatment between August 2007 and September 2009 in their unit, minimum follow-up two years, maximum four years. The main outcome measures were: numbers of patients with different levels of vision; changes in visual acuity; number of treatments; and numbers remaining under follow-up.

According to the investigators, 1,086 eyes of 1,017 patients received treatment. They noted that numbers of patients remaining under follow-up were 892/1,017 (87.71%) at 12 months, 730/1,017 (71.78%) at 24 months, 468/730 (64.11%) at 36 months and 110/217 (50.69%) at 48 months. The main reasons for patients no longer being under follow-up were the consequences of old age or transfer of care. Additionally, 50% of patients had 6/18 or better over four years. The study investigators also reported that patients received on average 5.79 ± 2.53, 9.15 ± 3.79, 11.22 ± 4.92 and 13.7 ± 7.84 injections by 12, 24, 36 and 48 months, respectively.

They suggest that the numbers of patients with a particular level of vision may best reflect the actual benefit of AMD treatment provided by a service. Long-term follow-up is required as only 72/730 (10%) had been discharged at 36 months, half of whom had good vision of greater than 60 letters. Moreover, 83% and 65% of patients needed treatment in the third and fourth year. Follow-up may be for the rest of the patient’s life or at some point they may no longer be well enough to attend.

Source: Pushpoth S, Sykakis E, Merchant K, et al. Measuring the benefit of four years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration. Br J Ophthalmol. 2012;96(12):1469–1473.

Performance of Intravitreal Aflibercept (VEGF Trap-Eye) in Wet AMD

The authors of the following two similarly designed, Phase III studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW 1, VIEW 2]) of neovascular age-related macular degeneration (AMD) compared monthly and every-two-month dosing of intravitreal aflibercept injection (VEGF Trap-Eye) with monthly ranibizumab.

Both studies included 2,419 patients with active, subfoveal, choroidal neovascularization (CNV) lesions (or juxtafoveal lesions with leakage affecting the fovea) secondary to AMD. They were randomized to intravitreal aflibercept 0.5 mg monthly (0.5q4), 2 mg monthly (2q4), 2 mg every two months after three initial monthly doses (2q8), or ranibizumab 0.5 mg monthly (Rq4). The primary endpoint was noninferiority (margin of 10%) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 (losing <15 letters on Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Other key end points included change in best-corrected visual acuity (BCVA) and anatomic measures.

All aflibercept groups were noninferior and clinically equivalent to monthly ranibizumab for the primary endpoint (the 2q4, 0.5q4 and 2q8 regimens were 95.1%, 95.9% and 95.1%, respectively, for VIEW 1, and 95.6%, 96.3% and 95.6%, respectively, for VIEW 2, whereas monthly ranibizumab was 94.4% in both studies). In a prespecified integrated analysis of the two studies, all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in BCVA; all aflibercept regimens also produced similar improvements in anatomic measures. Ocular and systemic adverse events were similar across treatment groups.

The authors found that intravitreal aflibercept dosed monthly or every two months after three initial monthly doses produced efficacy and safety outcomes similar to monthly ranibizumab. These studies demonstrate that aflibercept is an effective treatment for AMD, with the every-two-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring.

Source: Heier JS, Brown DM, Chong V, et al; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537–2548.

CNV Complicating GA in AMD

French researchers investigators examined the morphological and functional outcomes following intravitreal ranibizumab injections for choroidal neovascularization (CNV) complicating geographic atrophy (GA).

In a retrospective, interventional, consecutive case series, they reviewed the charts of all consecutive patients with GA due to age-related macular degeneration (AMD) who received intravitreal ranibizumab injections for the development of CNV at least 24 months earlier.

The researchers included 21 treatment-naive eyes of 21 consecutive patients (four men, 17 women, mean age 86.9 ± 1.6 years). They noted that in 95.2% of eyes, a type 2 CNV was present, extrafoveal in 42.8% of cases. After a mean of 5.0 ± 0.87 (range 1–20) intravitreal ranibizumab injections, best-corrected visual acuity (BCVA) significantly worsened at the 24-month follow-up visit (0.73 ± 0.05 vs. 0.88 ± 0.08 logMAR, respectively; p=0.01). A significant reduction of intraretinal cystic lesions, subretinal fluid and pigment epithelium detachment (p<0.001) and a significant increase of GA area (p=0.003) were present at last visit, the study researchers reported.

They concluded that ranibizumab treatment of GA-associated CNVs provides no BCVA improvement at 24 months follow-up despite an anatomic response of CNV. Low effectiveness of ranibizumab in these cases is likely due to GA progression.

Source: Querques G, Massamba N, Coscas F, et al. Choroidal neovascularization complicating geographic atrophy in age-related macular degeneration. Br J Ophthalmol. 2012;96(12):1479–1483.

Results of PDT Therapy for PCV After Five Years

The following Korean retrospective study evaluated the five-year efficacy of photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV).

Forty-two eyes of 36 patients with PCV followed up for at least 60 months after PDT were reviewed. All eyes were primarily treated with PDT. The main outcome measure was best-corrected visual acuity (BCVA; logMAR [logarithm of minimal angle of resolution]) at baseline and at each follow-up visit. The eyes were also classified into three groups: improved (improvement ≥0.3 logMAR), decreased (deterioration ≥0.3 logMAR) and stable.

During the mean follow-up duration, 73.64 ± 13.47 months, the mean number of PDT was 2.21 ± 1.62 treatments. Recurrence was noted in 33 eyes (78.6%) during follow-up. The mean baseline BCVA was 0.78 ± 0.48 logMAR (20/120 Snellen equivalent), and the final BCVA at 60 months was 0.67 ± 0.52 logMAR (20/93 Snellen equivalent) (p=.050, paired t test). On the final evaluation at 60 months, the mean BCVA was improved in 14 eyes (33.3%), stable in 23 eyes (54.7%) and decreased in five eyes (11.9%).

In conclusion, at 60 months following initial PDT, 88.1% of PCV patients showed stable or improved BCVA after PDT. Despite a high recurrence rate, PDT remained effective for five years, and represents a good therapeutic approach to PCV.

Source: Kang HM, Kim YM, Koh HJ. Five-year follow-up results of photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2012;Dec 4 [Epub ahead of print].

Link Between CSCR and Risk of Ischemic Stroke

Central serous chorioretinopathy (CSCR) is a common maculopathy that features choroidal circulatory disturbance. Scientists in Taiwan aimed to explore the relationship between CSCR and the future development of ischemic stroke in this population-based cohort study.

Data were obtained from Taiwan's national health insurance research database. From 2000 to 2007, 1,814 patients with newly diagnosed CSCR were eligible for inclusion in the study cohort. Using stratified random sampling, the scientists selected 9,648 enrollees matched with the study subjects in terms of sex, age, monthly income, geographical location and time of enrollment as the control group. They also assessed stroke-free survival analysis using a Kaplan–Meier method. Additionally, they performed Cox proportional hazard regressions to calculate the HR of ischemic stroke for the two groups after adjusting for possible confounding variables.

Of the sampled patients, 45 (2.5%) from the CSCR cohort and 157 (1.6%) from the control group developed ischemic stroke during a mean follow-up period of 3.9 ± 2.2 years. According to the study scientists, CSCR patients had a significantly higher incidence of ischemic stroke than those without a diagnosis of CSCR (p=0.003). After adjusting for age, sex and chronic comorbidities at baseline, they found CSCR patients to have a 1.56-fold (95% CI 1.11 to 2.18, p=0.010) greater risk of a subsequent ischemic stroke than the matched controls.

CSCR is an independent indicator for the increased risk of subsequent ischemic stroke development.

Source: Tsai DC, Huang CC, Chen SJ, et al. Central serous chorioretinopathy and risk of ischemic stroke: a population-based cohort study. Br J Ophthalmol. 2012;96(12):1484–1488.

Risk Factors Associated with CRVO

To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients throughout the United States, investigators performed the following longitudinal cohort study.

Participants included all beneficiaries aged ≥55 years who were continuously enrolled in a managed-care network for at least two years and who had two or more visits to an eye-care provider from 2001 to 2009.

They used insurance billing codes to identify individuals with a newly diagnosed CRVO and performed multivariable Cox regression to determine the factors associated with CRVO development. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of being diagnosed with CRVO were the main outcome measures.

The investigators reported that of the 494,165 enrollees who met the study inclusion criteria, 1,302 (0.26%) were diagnosed with CRVO over 5.4 (±1.8) years. They noted that after adjustment for known confounders, blacks had a 58% increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25–1.99), and women had a 25% decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66–0.85). Moreover, they found that a diagnosis of stroke increased the hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23–1.68), and hypercoagulable state was associated with a 145% increased CRVO risk (HR, 2.45; 95% CI, 1.40–4.28). Individuals with end-organ damage from hypertension (HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52–2.42) and 53% (HR, 1.53; 95% CI, 1.28–1.84) increased risk of CRVO, respectively, relative to those without these conditions.

This study confirms that HTN and vascular diseases are important risk factors for CRVO. The study investigators also identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, they show that compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO, whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO.

Source: Stem MX, Talwar N, Comer GM, Stein JD. A longitudinal analysis of risk factors associated with central retinal vein occlusion. Ophthalmology. 2012; Nov 21. [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.07.080.

Electroretinographic Parameters and Inflammatory Factors in BRVO with ME

Branch retinal vein occlusion (BRVO) leads to retinal ischemia, which then induces upregulation of various inflammatory factors, including vascular endothelial growth factor (VEGF). The aim of this Japanese study was to determine whether there was a correlation between inflammatory factors and components of the electroretinogram (ERG) in patients with BRVO.

In 19 BRVO patients with macular edema (ME), vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of four inflammatory factors (VEGF, soluble intercellular adhesion molecule-1 [sICAM-1], interleukin [IL]-6 and monocyte chemotactic protein [MCP]-1). The amplitude and implicit time of the a-wave cone, b-wave cone, and 30 Hz flicker were calculated automatically from the ERG. Correlations between the different components of the ERG and the four inflammatory factors were investigated.

Vitreous fluid levels of two factors (IL-6 and MCP-1) were significantly correlated with the implicit time of the cone b-wave (p=0.035 and p=0.016, respectively). It was also noted that vitreous fluid levels of all four factors (VEGF, sICAM-1, IL-6 and MCP-1) were significantly correlated with the implicit time of 30 Hz flicker (p=0.047, p=0.031, p=0.002 and p=0.009, respectively). Vitreous fluid levels of VEGF, sICAM-1, IL-6, and MCP-1 were significantly higher in patients with an implicit time ≥36 ms than with an implicit time <36 ms (p=0.042, p=0.048, p=0.003 and p=0.024, respectively).

These findings suggest that the implicit times of the cone b-wave and 30 Hz flicker can be used to detect BRVO patients with ME who have a high risk of ischemia.

Source: Noma H, Funatsu H, Mimura T. Association of electroretinographic parameters and inflammatory factors in branch retinal vein occlusion with macular edema. Br J Ophthalmol. 2012; 96(12):1489–1493.

Relationship Between the p53 Codon 72 Polymorphism (rs1042522) and Proliferative Vitreoretinopathy

The following case-controlled gene association study was conducted as a component of the Retina 4 Project (a European multicenter study). In it, the authors compared the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR).

They included 550 DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR. The authors analyzed the p53 codon 72 polymorphism (rs1042522) using allele-specific primer polymerase chain reaction. They analyzed proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries in two phases. In the first, they analyzed subsamples from Spain and Portugal. After significant results were found, samples from the United Kingdom and the Netherlands were analyzed (second phase). The study authors compared genotypic and allelic frequencies between cases and controls in the global sample. They noted that main outcome measures were single significant associations with PVR.

They observed significant difference (p<0.05, Fisher exact test) regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the United Kingdom or the Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01–42.18 and 2.29–10.20, respectively), Portugal (10.49–29.50 and 1.35–8.89, respectively) and the Netherlands (16.49–31.70 and 4.51–15.09, respectively), but no differences in the United Kingdom (7.68–18.1 and 4.85–13.94, respectively). According to the authors, the odds ratio of Pro carriers from Spain and Portugal together was 8.12 (95% confidence interval [CI], 3.72–17.69; p<0.05), whereas the odds ratio of Pro carriers from the United Kingdom and the Netherlands was 2.12 (95% CI, 0.96–4.68; p=0.07). All control samples were in Hardy-Weinberg equilibrium. Considering the entire sample, significant differences were found in genotype frequencies between cases (RR, 30.59%; RP, 43.28%; PP, 26.11% [R=Arg; P=Pro]) and controls (RR, 39.66%; RP, 52.64%; PP, 7.69%) and in Pro homozygote carriers between controls (Pro homozygote 95% CI, 18.67–33.52) and cases (Pro homozygote 95% CI, 5.1–10.2).

Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR.

Source: Pastor-Idoate S, Rodriguez-Hernández I, Rojas J, et al; Genetics on PVR Study Group. The p53 codon 72 polymorphism (rs1042522) is associated with proliferative vitreoretinopathy: the Retina 4 Project. Ophthalmology. 2012;Dec 3. [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.08.019.

Pascal TargETEd Retinal Versus Variable Fluence PANretinal 20 ms laser in DR

To investigate the short-term effects of high-density 20-ms laser on macular thickness using Pascal-targeted retinal photocoagulation (TRP) and reduced fluence/minimally traumatic panretinal photocoagulation (MT-PRP) compared to standard-intensity PRP (SI-PRP) in proliferative diabetic retinopathy (PDR), researchers conducted this prospective, randomized clinical trial.

They treated treatment-naïve PDR with single-session 20-ms Pascal 2,500 burns photocoagulation randomized to one of three treatment arms (TRP:MT-PRP:SI-PRP). Primary outcome measure was change in central retinal thickness (CRT) on OCT and secondary outcomes at four and 12 weeks post-laser included: OCT peripapillary nerve fiber layer (NFL) thickness, PDR disease regression on Optos angiography, SITA-Std visual fields (VF) and visual acuity (VA).

The researchers studied 30 eyes of 24 patients, 10 eyes/arm. At 12 weeks, they noted significant reductions in CRT after TRP (9.6 µm; 95% CI, 1.84 to 17.36; p=0.021) and MT-PRP (17.1 µm; 95% CI, 11 to 23.2; p=0.001), versus SI-PRP (+5.9 µm; 95% CI, –6.75 to 18.55; p=0.32). PDR regression was similar between groups (TRP 70%; MT-PRP 70%; SI-PRP 90%; Κ=0.76) and no significant changes in VA and NFL thickness developed between groups. Additionally, the VF mean deviation scores increased significantly in all groups at 12 weeks ([TRP, +0.70dB; 95% CI, 0.07 to 1.48; p=0.07], [MT-PRP, +0.63dB; 95% CI, 0.12 to 1.15; p=0.02], [SI-PRP, +1.0dB; 95% CI, 0.19 to 1.74; p=0.02]). There were no laser-related ocular complications.

This pilot study reports that high-density 20-ms Pascal TRP and MT-PRP using 2,500 burns did not produce increased macular thickness or any ocular adverse events during the short-term.

Source: Muqit MM, Young LB, McKenzie R, et al. Pilot randomized clinical trial of Pascal TargETEd Retinal versus variable fluence PANretinal 20 ms laser in diabetic retinopathy: PETER PAN study. Br J Ophthalmol. 2012;Nov 24. [Epub ahead of print]. DOI: 10.1136/bjophthalmol-2012-302189.

Topographical Distribution of Retinal and Optic Disc Neovascularization in Early Stages of PDR

In Norway, investigators analyzed the topography of proliferative diabetic retinopathy (PDR) and visualized the distribution of neovascularization of the optic disc (NVD) and elsewhere in the retina (NVE).

They included 174 eyes of 106 patients with early PDR and converted data on the size and location of 391 NVE and 73 NVD into a database of two-dimensional retinal and optic disc charts. They also plotted geometric centers of the neovascular lesions into corresponding areas of the charts, and they visualized topographical distributions of the NVE and NVD by merging the charts and displaying the number of overlapping lesions on color-coded contour maps.

According to the investigators, a total of 141 (36%) NVE were located in the temporal and 250 (64%) in the nasal hemisphere (p<0.0001). They noted that the distribution of the NVD in the temporal and nasal half of the optic disc was 46 (63%) and 27 (37%), respectively (p=0.03). They also found that NVE in type 1 diabetes were located significantly farther from the fovea and optic disc and were more numerous and larger than in type 2 diabetes. Furthermore, the number and diameter of the NVE were also significantly higher when the time from the last examination prior to the appearance of PDR exceeded 12 months.

The majority of NVE are located inferonasal to the optic disc and along the superior vascular arcades, while NVD have a predilection for the upper temporal disc rim. More extensive PDR is found in patients with type 1 diabetes, and those with examination intervals longer than one year.

Source: Jansson RW, Froystein T, Krohn J. Topographical distribution of retinal and optic disc neovascularization in early stages of proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2012; Nov 20. [Epub ahead of print]. DOI: 10.1167/iovs.12-10918.

ELM Status and VA in DME

To evaluate the association between the foveal external limiting membrane (ELM) status and visual acuity (VA) in diabetic macular edema (DME), the spectral domain optical coherence tomography (SD-OCT) images of 127 eyes from 127 patients with DME were retrospectively reviewed. Additionally, the correlation between the logarithm of the minimal angle of resolution (logMAR) VA and the statuses of the foveal ELM, inner segment/outer segment (IS/OS) and cone outer segment tips (COST); foveal macular thickness (FMT); and presence or absence of hard exudates (HE), serous retinal detachment (SRD) and vitreous adhesion were evaluated. The integrity of the ELM, IS/OS and COST was classified into three categories: absent; disrupted; and complete.

There was a strong correlation between VA and the statuses of the ELM (r=0.699, p<0.001), IS/OS (r=0.716, p<0.001) and COST (r=0.471, p<0.001). There was no correlation between FMT and logMAR VA (r=–0.036, p=0.687); however, when the correlation between FMT and VA was analyzed by dividing patients into those with FMT ≤250 µm and those with FMT >250 µm, there was a positive correlation between FMT and VA in eyes with FMT ≤250 µm (r=–0.601, p<0.0001) and a negative correlation in eyes with FMT>250 µm (r=0.290, p<0.01). Other factors HE, SRD and vitreous adhesion did not correlate with VA.

In conclusion, in DME, the ELM status may be as closely related to VA as the IS/OS status.

Source: Ito S, Miyamoto N, Ishida K, Kurimoto Y. Association between external limiting membrane status and visual acuity in diabetic macular edema. Br J Ophthalmol. Nov 21. [Epub ahead of print]. DOI: 10.1136/bjophthalmol-2011-301418.

Treatment of Stable Corneal Neovascularization with Short-term Topical Bevacizumab

In this prospective, nonrandomized, interventional case series, the authors evaluated the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization.

They involved 20 eyes from 20 patients with stable corneal neovascularization and treated them with topical 1.0% bevacizumab for three weeks. They monitored these patients for a total of 24 weeks. Primary outcome measures included neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The study authors closely monitored the occurrence of ocular and systemic adverse events.

They observed that, compared with the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week six (p=.007) and in vessel caliber by week 12 (p=.006). At the final visit, the authors found that neovascular area, vessel caliber and invasion area were reduced by 47.5%, 36.2% and 20%, respectively. The decreases in neovascular area and vessel caliber were statistically significant (p<.001 and p=.003, respectively); however, the reduction in invasion area did not reach statistical significance (p=.06). There were no significant changes in the secondary outcomes, and there were no adverse events.

Short-term topical bevacizumab treatment reduced the extent of stable corneal neovascularization as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area.

Source: Cheng SF, Dastjerdi MH, Ferrari G, et al. Short-term topical bevacizumab in the treatment of stable corneal neovascularization. Am J Ophthalmol. 2012;154(6):940–948.

Oraya and Optegra Eye Hospital Group Launch New Wet AMD Therapy

In a press release, Oraya Therapeutics Inc. announced that an agreement has been reached with UK specialist eye hospital group Optegra, to establish Optegra as the world's first clinical centers to offer Oraya Therapy Stereotactic Radiotherapy for the treatment of wet age-related macular degeneration (AMD). Oraya Therapy is a noninvasive, low-energy X-ray treatment intended as a one-time procedure to reduce or eliminate the need for chronic injections while preserving or enhancing a patient's vision outcomes. It is delivered by the IRay Radiotherapy System in a simple outpatient procedure lasting approximately 20 minutes, with no limitations on patient activities following treatment. The IRay is a CE-marked medical device. In the United States, it is an investigational device and is not available for sale. The new therapy will initially be offered at Optegra Surrey Eye Hospital in Guildford.

Source: Oraya Therapeutics Inc., December 2012.

EYLEA Injection Approved by European Commission for Treatment of Patients with Wet AMD; Submitted for EU Marketing Authorization for ME Following CRVO

According to Regeneron Pharmaceuticals Inc., the European Commission has approved EYLEA (aflibercept) Injection for the treatment of patients with wet age-related macular degeneration (AMD). Per the European Medicines Agency (EMA) approved Summary of Product Characteristics, EYLEA treatment is initiated with one 2-mg injection per month for three consecutive months, followed by one injection every two months. There is no requirement for monitoring by the physician between injections and after the first 12 months of treatment with EYLEA, the treatment interval may be extended based on visual and anatomic outcomes. In such cases, the frequency of monitoring visits is determined by the treating physician and may be more often than the schedule of injections. For more information, go to the company's website.

In related news, Regeneron Pharmaceuticals Inc. and Bayer HealthCare have reported that Bayer HealthCare has submitted an application for marketing authorization in Europe for EYLEA (aflibercept) Injection for the treatment of macular edema following central retinal vein occlusion (CRVO). The submission is based on data from the Phase III COPERNICUS and GALILEO studies. Phase III trials are currently under way with EYLEA in the treatment of diabetic macular edema, branch retinal vein occlusion and myopic choroidal neovascularization. Click here for additional information.

Source: Regeneron Pharmaceuticals Inc., November and December 2012.

KalVista Wins Grant to Further Develop DME Treatment

KalVista Pharmaceuticals has won a (£2.4 million ($3,841,680) grant from the Technology Strategy Board under the UK Government's £180 million Biomedical Catalyst funding initiative for research and development in the life sciences. The company plans to use the new funding to accelerate the development of an oral plasma kallikrein inhibitor for the treatment of diabetic macular edema (DME). Plasma kallikrein is an enzyme recently shown to be elevated in the vitreous of DME patients and to cause excessive vascular permeability in models of diabetes, suggesting its potential as a novel vascular endothelial growth factor (VEGF)-independent target for the treatment of DME. The Biomedical Catalyst grant will allow KalVista to complement preclinical development of oral plasma kallikrein inhibitors identified by the company and prepare a drug candidate ready for Phase I clinical development. Click here for additional details.

Source: KalVista Pharmaceuticals, November 2012.

Meeting Chairs Gear up for Ophthalmology Update 2013

The Ophthalmology Update 2013 meeting is scheduled to take place February 16–17, 2013 at the Hilton La Jolla Torrey Pines. The two-day meeting is chaired by Don O. Kikkawa, MD, and Robert N. Weinreb, MD, and the agenda includes such topics as patient-reported outcomes and disabilities, neuroprotection, the future of retinal prostheses, risk profiling for AMD, collagen cross-linking and more. Register at www.revophth.com/Update2013.

Source: Review of Ophthalmology.

U.K.'s NICE Issues Final Draft Guidance on ILUVIEN

The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has issued final draft guidance indicating that Alimera Sciences Inc.'s ILUVIEN (fluocinolone acetonide intravitreal implant) is not recommended for the treatment of chronic diabetic macular edema (DME) considered insufficiently responsive to available therapies. The Appraisal Committee did, however, acknowledge the clinical effectiveness of ILUVIEN in the treatment of vision impairment associated with chronic DME considered insufficiently responsive to available therapies, but noted that cost-effectiveness thresholds for the product have not yet been met. In response to the final draft guidance, Alimera is developing a Patient Access Scheme (PAS) to address the Appraisal Committee's cost concerns. The goal of the PAS is to determine the appropriate pricing for ILUVIEN to ensure that treatment decisions are based on patient need, rather than cost.

Source: Alimera Sciences Inc., November 2012.

36-Month Results of RISE and RIDE Studies Show Reduced DR Severity with Ranibizumab

Recently presented data from the RISE and RIDE trials show that intravitreal ranibizumab (Lucentis) reduced the rate of diabetic retinopathy (DR) worsening and increased rates of DR improvement in eyes with diabetic macular edema (DME) through 36 months. Both phase III studies evaluated monthly ranibizumab (0.3 mg or 0.5 mg) versus sham for the treatment of DME. In the third year of the study, patients in the sham group were eligible to switch to the 0.5-mg ranibizumab group and a secondary analysis of two or more or three or more step changes from baseline on the ETDRS severity scale in the study eye (n=707) was conducted. At month 36, greater proportions of ranibizumab-treated eyes had ≥ 2-step or ≥ 3-step improvement, and fewer ranibizumab-treated eyes had ≥ 2-step or ≥ 3-step worsening of DR from baseline. The mean change in best-corrected visual acuity was maintained for both groups and began to improve in the placebo group once patients were switched to ranibizumab.

Source: Abstracts PA053 and PA054; American Academy of Ophthalmology 2012 Annual Meeting, November 12, 2012.


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