Volume 8, Number 11
November 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.



FDA Approves JETREA for Treatment of Symptomatic VMA
In a recent press release, ThromboGenics NV announced that the FDA has approved its JETREA (ocriplasmin) in the United States for the treatment of symptomatic vitreomacular adhesion (VMA)...

First Successful Human Dosing in a Safety and Tolerability Study in Patients With Retinal Disease
Clearside Biomedical Inc. recently announced the successful dosing of patients in a safety and tolerability clinical study using its proprietary ocular microinjection platform to deliver therapeutics to treat retinal disease...

And More...

CNV Complicating GA in AMD

French investigators conducted this retrospective, interventional, consecutive case series to assess the morphological and functional outcomes after intravitreal ranibizumab injections for choroidal neovascularization (CNV) complicating geographic atrophy (GA).

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.

They included 21 treatment-naïve eyes of 21 consecutive patients (four men, 17 women, mean age 86.9 ± 1.6 years) and found that in 95.2% of eyes, a type II 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).

According to the investigators, 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.

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 efficacy of ranibizumab in these cases is likely due to GA progression.

Source: Querques G, Massamba N, Coscas F, et al. Choroidal neovascularisation complicating geographi atrophy in age-related macular degeneration. Br J Ophthalmol. 2012;Oct 17. [Epub ahead of print]. DOI: 10.1136/bjophthalmol-2012-302191.


Impact of Lutein and Zeaxanthin on Macular Pigment and Visual Function in Early AMD

In China, the following randomized, double-masked, placebo-controlled trial was performed to determine whether supplementation with lutein and zeaxanthin improves macular pigment and visual function in patients with early age-related macular degeneration (AMD). It was determined that among patients with early AMD, supplementation with lutein and zeaxanthin improved macular pigment, which played a causative role in boosting visual function and might prevent the progression of AMD.

Participants with probable AMD who were 50 to 79 years of age were screened for study eligibility from the local communities and 108 subjects with early AMD were recruited. These patients were randomly assigned to receive 10 mg/day lutein (n=27), 20 mg/day lutein (n=27), 10 mg/day lutein plus 10 mg/day zeaxanthin (n=27); or placebo (n=27) for 48 weeks. Macular pigment optical density (MPOD) and visual function variables were assessed at baseline, 24 weeks and 48 weeks. The primary outcome was MPOD. Secondary outcomes were visual function variables including best-corrected visual acuity (BCVA), contrast sensitivity (CS), photorecovery time and Amsler grid testing results.

It was observed that MPOD increased significantly by a mean ± standard error of 0.076 ± 0.022 density unit in the 20-mg lutein group and 0.058 ± 0.027 density unit in the lutein and zeaxanthin group during 48 weeks. There was a significant dose-response effect for lutein supplementation, and the changes in MPOD from baseline to 48 weeks were correlated negatively with baseline MPOD in all active treatment groups (r=–0.56; p<0.001). At 48 weeks, a trend toward improvement was seen in BCVA, and there was a significant between-group difference in CS at three and six cycles/degree between the 20-mg lutein group and the placebo group. It was also reported that the increase in MPOD related positively to the reduction in the logarithm of the minimum angle of resolution BCVA (r=–0.31; p<0.01) and the increases in CS at four spatial frequencies (r ranging from 0.26 to 0.38; all p<0.05).

Future studies are required to evaluate the effect of these carotenoids on the incidence of late AMD.

Source: Ma L, Yan SF, Huang YM, et al. Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration. Ophthalmology. 2012;119(11):2290–2297.


AMD Risk Three Years Following Cataract Surgery

The authors of this Australian clinic-based cohort sought to clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD).

They followed cataract surgical patients aged 65+ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study and included patients who remained unilaterally phakic for at least 24 months after recruitment. They performed annual examinations with retinal photography and assessed AMD using side-by-side grading of images from all visits. The authors also made paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated <12 months previously) using generalized estimating equation models. Incident early AMD was defined as the new appearance of soft indistinct/reticular drusen or coexisting retinal pigmentary abnormally and soft distinct drusen in eyes at risk of early AMD. Additionally, incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD.

Among 2,029 recruited, eligible participants, 1,851 had cataract surgery performed at Westmead Hospital, Sydney, and 1,244 (70.7%) had 36-month postoperative visits. Of these participants, the study authors reported that 1,178 had gradable photographs at baseline and at least one follow-up visit. They also noted that of 308 unilaterally operated participants at risk of late AMD, this developed in four (1.3%) operated and seven (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23–2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74–1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07–2.52). There was no difference in the three-year incidence of large soft indistinct or reticular drusen between the two eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79–1.60).

In conclusion, prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD or soft/reticular drusen over three years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes.

Source: Wang JJ, Fong CS, Rochtchina E, et al. Risk of age-related macular degeneration 3 years after cataract surgery: paired eye comparisons. Ophthalmology. 2012;119(11):2298–2303.


Assessment of the Cumulative Effect of Risk Alleles in CFH, ARMS2 and VEGFA on the Response to Ranibizumab Treatment in AMD

Intravitreal ranibizumab injections currently are the standard treatment for neovascular age-related macular degeneration (AMD). However, a broad range of response rates has been observed, the reasons for which are poorly understood. Researchers used this pharmacogenetic case series study to evaluate the impact of high-risk alleles in CFH, ARMS2, VEGFA, vascular endothelial growth factor (VEGF) receptor KDR, and genes involved in angiogenesis (LRP5, FZD4) on the response to ranibizumab treatment and on the age of treatment onset. In contrast to previous studies, the data were stratified according to the number of high-risk alleles to enable the study of the combined effects of these genotypes on the treatment response.

The researchers included a cohort of 430 eyes of 397 neovascular AMD patients and calculated the change in visual acuity (VA) between baseline and after three ranibizumab injections. They performed genotyping of single nucleotide polymorphisms in the CFH, ARMS2, VEGFA, KDR, LPR5 and FZD4 genes and assessed associations using linear mixed models. Main outcome measures were the VA change after three ranibizumab injections and the age of neovascular disease onset.

Following ranibizumab treatment, the study researchers reported that AMD patients without risk alleles in the CFH and ARMS2 genes (4.8%) demonstrated a mean VA improvement of 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, whereas no VA improvement was observed in AMD patients with four CFH and ARMS2 risk alleles (6.9%; p=0.014). They also found that patients with four high-risk alleles in CFH and ARMS2 were 5.2 years younger than patients with one or two risk alleles, respectively (63.5%; p<0.0001). According to the researchers, the mean age at which the first ranibizumab treatment was carried out among AMD patients with all six risk alleles in CFH, ARMS2 and VEGFA was 65.9 years (2%) versus 75.3 years in patients with zero or one high-risk allele (8.8%; p=0.001). They noted that after ranibizumab treatment, patients with six high-risk alleles demonstrated a mean VA loss of 10 ETDRS letters (p<0.0001).

This study evaluated the largest pharmacogenetic AMD cohort reported to date. A cumulative effect of high-risk alleles in CFH, ARMS2 and VEGFA seems to be associated with a younger age of onset in combination with poor response rates to ranibizumab treatment.

Source: Smailhodzic D, Muether PS, Chen J, et al. Cumulative effect of risk alleles in CFH, ARMS2, and VEGFA on the response to ranibizumab treatment in age-related macular degeneration. Ophthalmology. 2012;119(11):2304–2311.


Influence of Systemic Beta-Blockers on the Need for Repeated Intravitreal Injections in Patients With Wet AMD Treated by Bevacizumab

To evaluate the effect of concomitant systemic therapy in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated by intravitreal bevacizumab and to propose a mechanism for different inter-individual response, scientists performed this retrospective, nonrandomized, single-center, consecutive interventional case series study.

They treated 46 eyes from 46 patients with CNV secondary to AMD by monthly intravitreal 1.25 mg bevacizumab injections on a pro re nata regimen. They revised patients' files and recorded changes in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), central foveal thickness as determined by spectral domain optical coherence tomography, number of injections performed, occurrence of severe adverse effects, and systemic concomitant medication. The scientists also evaluated the effect of systemic medication on final BCVA, central foveal thickness and number of injections performed.

The most frequent systemic medications recorded were angiotensin-converting-enzyme inhibitors in 19 patients, beta-adrenergic blocking agents (n=18), nonsteroidal anti-inflammatory drugs (n=17), diuretics (n=16), calcium channel blockers (n=14), benzodiazepines (n=11), proton-pump inhibitors (n=9) and statins (n=8). According to the study scientists, 32 patients had arterial hypertension. They noted that average follow-up was 25.1 months (standard deviation [SD]=8.9), average gain in BCVA was 0.9 (SD=13.6) and –2.1 letters (SD=15.9) at 12 months and 24 months, respectively, and that the average reduction in central foveal thickness was 111 µm (SD=54) and 105 µm (SD=71) at 12 months and 24 months, respectively. Furthermore, they observed that the average number of intravitreal injections required was 6.7 (SD=3.2) and that patients on treatment with systemic beta-adrenergic blocking agents required less intravitreal injections (5.2, SD=2.4 vs. 7.9, SD=3.4). This difference was statistically significant (p=0.0068, multiple linear regression).

Concomitant systemic beta-adrenergic blocking agents treatment may reduce the need for repeated intravitreal injections of bevacizumab in patients with CNV associated with AMD.

Source: Montero JA, Ruiz-Moreno JM, Sanchis-Merino E, et al. Systemic beta-blockers may reduce the need for repeated intravitreal injections in patients with wet age-related macular degeneration treated by bevacizumab. Retina. 2012;Oct. 24. [Epub ahead of print]. DOI: 10.1097/IAE.0b013e3182695ba0.


Use of Intravitreal Ranibizumab for DME With Prompt Versus Deferred Laser Treatment

The authors of the following multicenter, randomized clinical trial sought to report the three-year follow-up results within a previously reported randomized trial evaluating prompt versus deferred (for ≥24 weeks) focal/grid laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic macular edema (DME).

They included 361 participants with visual acuity (VA) of 20/32 (approximate Snellen equivalent) and DME involving the fovea. Ranibizumab was administered every four weeks until no longer improving (with resumption if worsening) and random assignment to prompt or deferred (≥24 weeks) focal/grid laser treatment. Best-corrected visual acuity (BCVA) and safety at the 156-week (three-year) visit were the main outcome measures.

According to the authors, the estimated mean change in VA letter score from baseline through the three-year visit was 2.9 letters more (9.7 vs. 6.8 letters; mean difference, 2.9 letters; 95% confidence interval, 0.4–5.4 letters; p=0.02) in the deferral group compared with the prompt laser treatment group. They reported that in the prompt laser treatment group and deferral group, respectively, the percentage of eyes with a ≥10-letter gain/loss was 42% and 56% (p=0.02), whereas the respective percentage of eyes with a ≥10-letter gain/loss was 10% and 5% (p=0.12). The authors also noted that up to the three-year visit, the median numbers of injections were 12 and 15 in the prompt and deferral groups, respectively (p=0.007), including one and two injections, respectively, from the two-year up to the three-year visit. At the three-year visit, the percentages of eyes with central subfield thickness of 250 µm or more on time-domain optical coherence tomography were 36% in both groups (p=0.90). In the deferral group, 54% did not receive laser treatment during the trial. Systemic adverse events seemed to be similar in the two groups.

These three-year results suggest that focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better, and possibly worse, for vision outcomes than deferring laser treatment for 24 weeks or more in eyes with DME involving the fovea and with vision impairment. Some of the observed differences in VA at three years may be related to fewer cumulative ranibizumab injections during follow-up in the prompt laser treatment group. Follow-up through five years continues.

Source: Diabetic Retinopathy Clinical Research Network, Elman MJ, Qin H, Aiello LP, et al. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trail results. Ophthalmology. 2012;119(11):2312–2318.


Concentration of Cytokines in Aqueous Humor of Eyes With DME

To measure cytokine concentrations in aqueous humor of eyes with diffuse diabetic macular edema (DME), investigators conducted an interventional clinical comparative study that included a study group of 23 patients with diffuse DME and a control group of 22 patients undergoing cataract surgery. They measured cytokine concentrations in aqueous humor samples using a Luminex xMAP suspension array technology.

In the study group as compared with the control group, they measured significantly higher concentrations for epidermal growth factor (p<0.001), human growth factor (p<0.001), intercellular adhesion molecule-1 (ICAM-1; p<0.001), interleukin (IL)-1a2 (p=0.04), IL-6 (p=0.001), IL-8 (p<0.001), interferon gamma–induced protein (p=0.004), monocyte chemoattractant protein-1 (p<0.001), monokine induced by interferon gamma (p<0.001), matrix metalloproteinase (MMP) 1 (p=0.02), MMP 9 (p<0.001), plasminogen activator inhibitor 1 (p<0.001), placenta growth factor (p<0.001), tissue growth factor beta (p=0.003), vascular cell adhesion molecule (p<0.001) and vascular endothelial growth factor (VEGF, p<0.001). The study investigators found that retinal macula thickness was significantly associated with the concentrations of the epidermal growth factor (p=0.005; ρ=0.45), ICAM-1 (p<0.001; ρ=0.65), IL-3 (p=0.002; ρ=0.48), IL-6 (p=0.003; ρ=0.47), IL-8 (p<0.001; ρ=0.71), monocyte chemoattractant protein-1 (p=0.001; ρ=0.53), monokine induced by interferon gamma (p<0.001; ρ=0.57), MMP 9 (p<0.001; ρ=0.61), tissue growth factor beta (p=0.01; ρ=0.42), placenta growth factor (p=0.004; ρ=0.46), vascular cell adhesion molecule (p=0.006; ρ=0.44) and VEGF (p=0.01; ρ=0.42). They reported that in multivariate analysis, macular thickness remained to be significantly associated with the concentration of ICAM-1 (p=0.03; r=0.30). VEGF concentrations were correlated with concentration of placenta growth factor (p<0.001; ρ=0.78), plasminogen activator inhibitor 1 (p=0.001; ρ=0.54), ICAM-1 (p<0.001; ρ=0.47), monokine induced by interferon gamma (p=0.004; ρ=0.44), monocyte chemoattractant protein-1 (p=0.003; ρ=0.43), vascular cell adhesion molecule (p=0.01; ρ=0.38), IL-6 (p=0.02; ρ=0.35), IL-8 (p=0.02; ρ=0.37), epidermal growth factor (p=0.01; ρ=0.39) and macrophage migration inhibitory factor (p=0.01; ρ=0.37), they noted.

To conclude, numerous cytokines are associated with the presence and the amount of DME. Among these cytokines, ICAM-1 was the most significantly associated with the disease parameters.

Source: Jonas JB, Jonas RA, Neumaier M, Findeisen P. Cytokine concentration in aqueous humor of eyes with diabetic macular edema. Retina. 2012;32(10):2150–2157.


Aqueous Concentrations of Angiogenic and Inflammatory Cytokines in DME and ME Due to BRVO

The involvement of cytokines in the aqueous humor is important in the development and progression of diabetic macular edema (DME) and macular edema (ME) due to branch retinal vein occlusion (BRVO). In this Korean prospective, observational case series, the concentrations of cytokines in the aqueous humour of eyes with DME and BRVO were measured and compared.

Aqueous samples were obtained from 18 eyes with DME (DME group), 12 eyes with BRVO (BRVO group) and 16 normal eyes (control group). The aqueous levels of cytokines, including interleukin (IL)-2, IL-5, IL-6, IL-8, IL-12p70, IL-13, monocytochemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), platelet-derived growth factor-AA (PDGF)-AA, transforming growth factor-α (TGF-α), interferon-γ (IFN-γ), epidermal growth factor, fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) were measured.

It was noted that the aqueous levels of IL-8, MCP-1, PDGF-AA and VEGF were higher, and IL-13 was lower in the DME group compared with the control group. The aqueous levels of IL-8 and VEGF were higher in the BRVO group than in the control group, and compared with the IL-6 and MCP-1 levels in the BRVO group, those levels were significantly higher in the DME group. Correlation analyses revealed that IL-8 was positively and IFN-γ was negatively correlated with the severity of MO in the DME group. Furthermore, in the BRVO group, IL-8 was positively correlated with severity of ME and retinal ischemia.

In conclusion, DME and BRVO may differ in terms of pathogenesis because the cytokine concentrations in the aqueous humor differ. The results suggest that the inflammatory reaction may be more activated in DME than in BRVO, and ischemic insult may play a central role in the development of BRVO.

Source: Lee WJ, Kang MH, Seong M, Cho HY. Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular edema and macular edema due to branch retinal vein occlusion. Br J Ophthalmol. 2012;96(11):1426–1430.


Treating Recent Onset RVO With Subcutaneous Nadroparin Calcium

Italian scientists investigated whether nadroparin calcium may play some role in the treatment of recent onset (≤3 weeks' duration) retinal vein occlusion (RVO).

They treated 24 RVO patients with subcutaneous nadroparin calcium (200 I.U./kg/day) for six weeks and measured best-corrected visual acuity (BCVA) and macular thickness in the affected eye at baseline and after three and six months. Additionally, they used 24 RVO patients treated with oral pentoxifyline, matched for age, gender, RVO type, eye involvement and BCVA at presentation, randomly selected from the RVO register, as controls. According to the scientists, median BCVAs at baseline, month 3 and month 6 were 20/70 (range: 20/1,000–20/20), 20/40 (range: 20/100–20/20) and 20/30 (range: 20/200–20/20) in cases and 20/70 (range: 20/1,000–20/20), 20/60 (range: 20/320–20/25) and statistically significant at months three (p=0.025) and six (p=0.024). Moreover, they found that in the study group, the mean macular thickness was 510 ± 207 µm at baseline, 384 ± 198 µm after three months, and 313 ± 170 µm after six months. Differences between baseline and months three and six were statistically significant (p=0.004 and p<0.001).

Results suggest that nadroparin calcium might become a potential candidate for the treatment of RVO, but larger trials are necessary to confirm these preliminary findings.

Source: Pinna A, Simula P, Zinellu A. Subcutaneous nadroparin calcium in the treatment of recent onset retinal vein occlusion: a pilot study. J Ocul Pharmacol Ther. 2012;28(5):448–454.


Effect of Vitrectomy and Panretinal Photocoagulation on the Occurrence of Neovascular Glaucoma in CRVO With Vitreous Hemorrhage

In the following study, researchers evaluated the best-corrected visual acuity (BCVA) and occurrence of neovascular glaucoma with vitrectomy (VT) and panretinal photocoagulation or without VT in central retinal vein occlusion (CRVO) associated with vitreous hemorrhage (VH). They found that the visual outcomes of CRVO with VH are unfavorable whether VT was performed; however, VT and panretinal photocoagulation improved VA and reduced the incidence of neovascular glaucoma in CRVO with VH.

They reviewed the charts from patients diagnosed as having CRVO with VH at Chang Gung Memorial Hospital (Taiwan) and grouped them based on whether they also underwent VT. BCVA and incidence of neovascular glaucoma were the main outcome measures.

According to the researchers, 83 eyes had CRVO with VH from 83 patients (VT group, 56 eyes; non-VT group, 27 eyes). They reported no significant difference between the VT and non-VT groups in terms of age, gender, diabetes, hypertension, lens status and follow-up period. The non-VT group had a better BCVA (p=0.018) and less VH (p=0.025) than the VT group at baseline; however, the VT group had a better BCVA at the end of the follow-up than the non-VT group (p<0.001). Most importantly, there was a higher neovascular glaucoma development (37%) in the non-VT group compared with that (14.3%) in the VT group (p=0.025).

Source: Chuang LH, Wang NK, Chen YP, et al. Vitrectomy and panretinal photocoagulation reduces the occurrence of neovascular glaucoma in central retinal vein occlusion with vitreous hemorrhage. Retina. 2012; Oct 30. [Epub ahead of print]. DOI: 10.1097/IAE.0b013e31826af52d.


Efficacy of PDT With or Without Intravitreal Bevacizumab for PCV

In Taiwan, this retrospective, interventional case series compared the long-term results of the efficacy of photodynamic therapy (PDT) with or without intravitreal bevacizumab (IVB) injections for polypoidal choroidal vasculopathy.

A total of 69 eyes of 69 patients with macula-involved polypoidal choroidal vasculopathy were included and all patients were followed up for more than two years. Additionally, the treatment outcomes between groups were compared and the factors influencing visual improvement at 24 months of follow-up were investigated.

It was reported that 36 patients received PDT combined with IVB and that 33 patients received PDT monotherapy. At three months, the mean logarithm of minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 0.73 to 0.53 in the combined therapy group (p<.001) and from 0.79 to 0.72 in the PDT monotherapy group (p=.02), with a significant difference in treatment efficacy between the two groups (p<.001). However, the improvements in BCVA were not statistically significant after 21 months in the combined therapy group and 15 months in the monotherapy group. The difference in treatment efficacy between the two groups was not significant after six months. Furthermore, initial BCVA (p=.005), lesion size (p=.011), patient age (p=.018) and location of polyps (p=.006) significantly predicted the final visual outcome rather than treatment modality (p=.243).

PDT combined with IVB for symptomatic PCV was temporarily superior to PDT monotherapy, and the treatment efficacy decreased with time. Initial BCVA, lesion size and location were more significant than treatment modality as the factors influencing final visual improvement.

Source: Lee YA, Yang CH, Yang CM, et al. Photodynamic therapy with or without intravitreal bevacizumab for polypoidal choroidal vasculopathy: two years of follow-up. Am J Ophthalmol. 2012;154(5):872–880.


Involvement of Mineralocorticoid Receptor in Rat and Human Ocular Chorioretinopathy

Because glucocorticoids induce and aggravate central serous chorioretinopathy (CSCR) and are known to bind to the mineralocorticoid receptor (MR), CSCR may be related to inappropriate MR activation. The authors of this French study sought to assess the effect of MR activation on rat choroidal vasculature and translate the results to CSCR patients.

Intravitreous injection of the glucocorticoid corticosterone in rat eyes induced choroidal enlargement. Aldosterone, a specific MR activator, elicited the same effect, producing choroid vessel dilation and leakage. The authors identified an underlying mechanism of this effect: aldosterone upregulated the endothelial vasodilatory K channel KCa2.3. They noted that its blockage prevented aldosterone-induced thickening. To translate these findings, they treated two patients with chronic nonresolved CSCR with oral eplerenone, a specific MR antagonist, for five weeks, and observed impressive and rapid resolution of retinal detachment and choroidal vasodilation as well as improved visual acuity. The study authors noted that the benefit was maintained five months after eplerenone withdrawal.

Their results identify MR signaling as a pathway controlling choroidal vascular bed relaxation and provide a pathogenic link with human CSCR, which suggests that blockade of MR could be used therapeutically to reverse choroid vasculopathy.

Source: Zhao M, Célérier I, Bousquet E, et al. Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy. J Clin Invest. 2012;122(7):2672–2679.


Treatment of Acute CSCR With Half-Fluence PDT

In evaluating the results of indocyanine green angiography-guided verteporfin (Visudyne, Novartis Pharma AG) photodynamic therapy (PDT) with half-fluence rate in the treatment of acute symptomatic central serous chorioretinopathy (CSCR), investigators performed a retrospective review over 12 months of 19 consecutive patients with subfoveal fluid because of acute symptomatic CSCR proved by spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography, treated with indocyanine green angiography-guided verteporfin (6 mg/m²) PDT with half-fluence rate (25 J/cm²). They defined acute symptomatic CSC as first episode of symptoms and duration of symptoms before treatment of &lge;12 weeks.

The study investigator noted that best-corrected visual acuity (BCVA) at baseline was 47 letters (±10; n=19) according to the Early Treatment Diabetic Retinopathy Study chart. They also found that at 12 months, after PDT, the mean BCVA improved to 56 letters (p=0.003). Pretreatment central foveal thickness was 406 μm and decreased by a mean of 163 µm at Month 12 control (p<0.001). At month 1 following PDT, subretinal fluid in SD-OCT was completely resolved in all 19 patients. None of the patients developed any recurrence of symptoms over 12 months and no ocular or systemic side effects were observed during 12 months follow-up.

Indocyanine green angiography–guided half-fluence PDT with verteporfin is effective in treating acute symptomatic CSCR, resulting in visual improvement and complete resolution of exudative macular detachment, the investigators concluded.

Source: Smretschnig E, Ansari-Shahrezaei S, Moussa S, et al. Half-fluence photodynamic therapy in acute central serous chorioretinopathy. Retina. 2012;32(10):2014–2019.


Enhanced Depth Imaging OCT in the Evaluation of Choroidal Thickness in RP

A prospective, case-control study of 21 patients from the Cole Eye Institute with retinitis pigmentosa (RP) imaged using the Spectralis optical coherence tomography (OCT) and an enhanced depth imaging (EDI) protocol sought to investigate the spectral-domain ocular coherence tomography features of the choroid in patients with RP using EDI.

Submacular choroidal thickness measurements were obtained beneath the fovea and at 500 µm intervals for 2.5 mm nasal and temporal to the center of the fovea. These measurements were compared to choroidal thickness measurements from 25 healthy age-matched controls with similar refractive error range and no clinical evidence of retinal or glaucomatous disease. Additionally, statistical analysis was performed to compare choroidal thickness at each location between the two groups and to correlate choroidal thickness with best-corrected visual acuity (BCVA) and central retinal thickness.

Mean ages were 40.6 years for control patients and 45.1 years for RP patients (p>0.05). It was noted that mean choroidal thickness measurements were 245.6 ± 103 µm in RP patients and 337.8.2 ± 109 µm in controls (p<0.0001). There was no correlation between subfoveal choroidal thickness and visual acuity or retinal thickness in the RP patients when compared to the control group.

In conclusion, submacular choroidal thickness, as measured by SD-OCT EDI, is significantly reduced in patients with RP, but did not correlate with visual acuity or retinal thickness in RP patients. Further research is needed to better understand the pathophysiological significance of the choroidal alterations present in RP.

Source: Dhoot DS, Huo S, Yuan A, et al. Evaluation of choroidal thickness in retinitis pigmentosa using enhanced depth imaging optical coherence tomography. Br J Ophthalmol. 2012; Oct 23. [Epub ahead of print]. DOI: 10.1136/bjophthalmol-2012-301917.






FDA Approves JETREA for Treatment of Symptomatic VMA

In a recent press release, ThromboGenics NV announced that the FDA has approved its JETREA (ocriplasmin) in the United States for the treatment of symptomatic vitreomacular adhesion (VMA). The approval was based on data from ThromboGenics' Phase III program, where JETREA was shown to be superior to placebo for the treatment of symptomatic VMA (26.5% vs. 10.1%; p<0.01). The recommended dose of JETREA is 0.125 mg (0.1 mL) of the diluted solution administered by intravitreal injection to the affected eye once as a single injection. The agent is provided as a single-use glass vial containing 0.5 mg in 0.2 mL solution for intravitreal injection (2.5 mg/mL). View important safety and prescribing information about JETREA at www.jetrea.com.

Source: ThromboGenics NV, October 2012.




First Successful Human Dosing in a Safety and Tolerability Study in Patients With Retinal Disease

Clearside Biomedical Inc. recently announced the successful dosing of patients in a safety and tolerability clinical study using its proprietary ocular microinjection platform to deliver therapeutics to treat retinal disease. The open-label safety and tolerability study involved the administration of bevacizumab into the suprachoroidal space (SCS) of the eye using the company's proprietary microinjection platform. Administration of the SCS was achieved in all patients and was confirmed via ophthalmoscope. The four patients in the trial suffer from advanced wet age-related macular degeneration (AMD). Clearside's in-office injection procedure delivers drugs to the choroid and retina through the suprachoroidal space, allowing medication to be applied directly to the affected area. As demonstrated in previous nonclinical studies and the initial clinical study, dosing into the SCS appears to be safe and well-tolerated in the first month of safety assessments. Get more information at www.businesswire.com.

Source: Clearside Biomedical Inc., November 2012.




FDA Clears SupraScan 577 Laser System

In a recent press release, Quantel Medical announced that it received FDA 510(k) market clearance of its SupraScan 577 Laser for treating a wide range of retinal diseases. The company says that the SupraScan 577 combines three of the most clinically sought-after components in a retina laser: 577 nm yellow wavelength, pattern scanning and MicroPulse tissue-sparing laser emission modes, making it the first yellow laser on the market capable of pattern scanning delivery in both conventional and tissue-sparing MicroPulse modes available in the United States.

Source: Quantel Medical, November 2012.




Data for Brachytherapy Device in Wet AMD Presented

Results from a cohort study evaluating the use of the minimally invasive SalutarisMD retrobulbar episcleral brachytherapy device developed by Salutaris Medical Devices to treat wet age-related macular degeneration (AMD) were presented at the recent American Society of Radiation Oncology (ASTRO) Annual Meeting. The study assessed the feasibility and tolerability of the SalutarisMD investigational treatment for wet AMD using a single dose of episcleral brachytherapy in conjunction with intraocular anti-vascular endothelial growth factor (VEGF) injections in a cohort of six subjects. All six subjects showed improvement in vision and three required no additional anti-VEGF injections within the 90-day trail period. Further information about the data from this study can be accessed here.

Source: SalutarisMD, October 2012.




Positive Results From Phase IIb Study of Fovista Presented

Data from a large, prospective, randomized, controlled Phase IIb clinical trial of Ophthotech Corporation's Fovista anti-platelet-derived growth factor (PDGF) therapy (1.5 mg) in patients with wet age-related macular degeneration (AMD) was presented during Retina Subspecialty Day at the American Academy of Ophthalmology Annual Meeting on November 10, 2012. According to Ophthotech, this is the first clinical trial to show statistically significant superior efficacy over Lucentis (ranibizumab) monotherapy for the treatment of wet AMD. The fully masked Phase IIb trial evaluated the efficacy and safety of Fovista given in combination with Lucentis, compared with Lucentis monotherapy, for the treatment of patients with wet AMD. A total of 449 patients were randomized every four weeks for 24 weeks: Fovista 0.3 mg in combination with Lucentis 0.5 mg; Fovista 1.5 mg in combination with Lucentis 0.5 mg; or sham in combination with Lucentis 0.5 mg. The primary efficacy endpoint in the study was the mean change in visual acuity from baseline at the week 24 visit. For additional details, visit www.ophthotech.com.

Source: Ophthotech Corporation, October 2012.




 

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