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Treatment of DME with Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser

The following multi-center, randomized clinical trial evaluated intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME).

A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea were evaluated. Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (≥24 weeks) laser (n=188) or 4 mg triamcinolone + prompt laser (n=186) and retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. Best-corrected visual acuity and safety at 1 year were the main outcome measures.

It was reported that the 1-year mean change (± standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9±12, p<0.001) but not in the triamcinolone + prompt laser group (4±13, p=0.31) compared with the sham + prompt laser group (+3±13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. Additionally, in the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. It was noted that no systemic events attributable to study treatment were apparent. Furthermore, three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes.

In conclusion, intravitreal ranbizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. It was observed that ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone, but frequently increases the risk of intraocular pressure elevation.

Source: Elman MJ, Aiello LP, Beck RW, et al.; for The Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010; Apr 28 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2010.02.031.

Management of DME with Intravitreal Bevacizumab or Laser Therapy

UK researchers reported the findings at 1 year of a prospective, randomized, masked, single-center, 2-year, two-arm clinical trial comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME).

Participants consisted of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT. The researchers randomized subjects to either ivB (every 6 weeks; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months). The primary endpoint was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms.

According to the researchers, the baseline mean ETDRS BCVA was 55.7 ± 9.7 (range 34–69) in the bevacizumab group and 54.6 ± 8.6 (range 36 – 68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3 ± 10.4 (range 34–79) in the bevacizumab group and 50.0 ± 16.6 (range 8–76) in the laser arm (p=0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (p=0.0002). The odds of gaining ≥10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3–19.7; p=0.019). At 12 months, the researchers reported that central macular thickness decreased from 507 ± 145 µm (range 281–900 µm) at baseline to 378 ± 134 µm (range 167–699 µm) (p<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481 ± 121 µm (range 279–844 µm) to 413 ± 135 µm (range 170–708 µm) (p=0.02). They noted that the median number of injections was 9 (interquartile range [IQR] 8–9) in the ivB group, and the median number of laser treatments was 3 ([IQR] 8–9) in the ivB group, and the median number of laser treatments was 3 (IQR 2–4) in the MLT group.

The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia, the researchers concluded.

Source: Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT Study): 12-month data report 2. Ophthalmol 2010;Apr 22 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2010.03.045.

Efficacy of SRT for the Treatment of DME

To test selective retina therapy (SRT) as a treatment of clinically significant diabetic macular edema (DME), investigators performed a prospective, two-center interventional uncontrolled phase II pilot study. The study included 39 eyes of 39 patients with previously untreated non-ischemic DME that were treated with focal laser treatment using a Q-switched frequency doubled Nd:YLF laser that selectively affects the retinal pigment epithelium while sparing the photoreceptor layer.

The investigators used optoacoustic measurements, fundus fluorescein angiography (FFA) and funduscopy to determine the individual threshold of RPE damage of each patient. They adjusted the pulse energy to apply angiographically visible but funduscopically invisible effects and correlated optoacoustic measurements with funduscopy and FFA. Follow-up examinations at 3 and 6 months post-treatment included best-corrected ETDRS visual acuity (BCVA), FFA, fundus photography and retinal thickness measured by optical coherence tomography. The study investigators noted that the primary outcome measure was change of BCVA. Other outcome measures were change of retinal thickness, presence of hard exudates, leakage in FFA, accuracy of optoacoustic measurements and correlation of BCVA with change of anatomical and systemic parameters.

Mean BCVA improved from 43.7 letters (standard deviation, SD = 9.1) at baseline to 46.1 letters (SD = 10.5) at the 6-month follow up (p=0.02), the investigators observed. They reported that BCVA improved (>5 letters) or remained stable (±5 letters) in 84% of eyes. A total of 13% of eyes improved by ≥10 letters, while 16% of eyes lost more than 5 letters. The investigators noted no severe loss of vision (≥15 letters). Overall, retinal thickness, hard exudates and leakage in FFA did not change significantly (p>0.05), while improvement of BCVA correlated with a reduction of hard exudates (p=0.01) and central retinal thickness (p=0.01). Furthermore, specificity and sensitivity of detecting the angiographic visible threshold of RPE damage by optoacoustic measurements were 86% and 70% respectively. The study investigators noted no adverse effects or pain during or after treatment.

They observed functional and anatomical improvement or stabilization in most patients and concluded that SRT appears to be safe. Optoacoustic measurements accurately detect the individual threshold of RPE damage. The investigators believe that a randomized trial is required to further test efficacy and safety of SRT as a treatment of clinically significant diabetic macular edema.

Source: Roider J, Liew SH, Klatt C, et al. Selective retina therapy (SRT) for clinically significant diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2010; Apr 15 [Epub ahead of print]. DOI: 10.1007/s00417-010-1356-3.

Incidence and Progression of AMD in a Latino Population Over 4 Years

The authors of this population-based cohort study sought to estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). They performed a comprehensive ophthalmologic examination including stereoscopic fundus photography on adult Latinos at baseline and at follow up. They found that age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites.

They authors graded photographs using a modified Wisconsin Age-Related Maculopathy Grading System and for estimations of incidence and progression of AMD, used the Age Related Eye Disease Study (AREDS) Scale. Incidence and progression of early AMD (drusen type, drusen size and retinal pigmentary abnormalities) as well as advanced AMD (exudative AMD and geographic atrophy) were the main outcome measures.

A total of 4,658 of 6,100 subjects (76%) completed the follow-up examination. According to the authors, the 4-year incidence of early AMD was 7.5% (95% CI: 6.7, 8.4) and advanced AMD was 0.2% (95% CI: 0.1, 0.4). The authors reported that progression of any AMD occurred in 9.2% (95% CI: 8.3, 10.1) of at-risk participants and that incidence and progression increased with age. They also noted that incidence of early AMD in the second eye (11.2%) was higher than incidence in the first eye (6.9%). Also, baseline presence of soft indistinct large drusen ≥ 250 µm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy and exudative AMD than smaller or hard or soft, distinct drusen.

The study authors determined that while incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Also, that older people and those with soft, indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft, indistinct large drusen.

Source: Varma R, Foong AW, Lai MY, et al, for the Los Angeles Latino Eye Study Group. Four-year incidence and progression of age-related macular degeneration: The Los Angeles Latino Eye Study. Am J Ophthalmol 2010;149(5):741-751.

AMD in the Asian Population

The authors of this study believe that a clear understanding of AMD prevalence in Asians is essential to meet future demands for eye health care; therefore, they conducted this study to determine the prevalence of age-related macular degeneration (AMD) in Asian populations and to compare this with prevalence in white populations.

They searched published literature reporting AMD prevalence in Asian populations and limited studies examined to those using standardized grading systems (either the Wisconsin Age-Related Maculopathy Grading System or the international classification proposed by the International ARM Epidemiological Study Group). Additionally, they used metaanalytical methods to calculate age-specific pooled prevalence of AMD using inverse-variance weighting in a random effect model. The authors also calculated pooled estimates of age-standardized prevalence and used a metaregression model to examine gender differences and differences between Asian and white populations.

They identified 9 studies reporting AMD prevalence form 4 Asian populations and found that pooled prevalence estimates of early and late AMD in Asian populations aged 40 to 79 were 6.8% (95% confidence interval [CI], 4.6%–8.9%) and 0.56% (95% CI, 0.30%–0.81%), respectively; corresponding prevalence estimates in white populations were 8.8% (95% CI, 3.8%–13.8%) and 0.59% (95% CI, 0.35%–0.84%), respectively. The study authors noted that reliable prevalence estimates of AMD in Asian persons aged ≥80 years were not available owing to small subject numbers in this age category.

They found that among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians. Further studies in Asian populations are warranted to investigate whether certain specific AMD phenotypes or subtypes, such as polypoidal choroidal vasculopathy, are more common.

Source: Kawasaki R, Yasuda M, Song SJ, et al. The prevalence of age-related macular degeneration in asians: a systematic review and meta-analysis. Ophthalmol 2010;117(5):921-927.

Affect of Selective Retina Therapy on GA Due to AMD

Geographic atrophy (GA) due to age-related macular degeneration (AMD) has no currently approved treatment option and typically, increased autofluorescence (AF) levels of different patterns adjacent to the atrophic area indicate lipofuscin-laden RPE cells at a high risk for apoptosis. With that in mind, the authors of this study used selective retina therapy (SRT) to selectively treat retinal pigment epithelium (RPE) cells in an attempt to stimulate RPE proliferation to reduce, or ideally, stop further growth of the atrophic area.

They treated six eyes of six patients with bilateral equally pronounced GA by SRT. The fellow eye of each patient served as control and the authors performed irradiation using a prototype SRT laser. The study authors applied test lesions with increasing energies at the lower vessel arcade to determine the individual angiographic and ophthalmoscopic threshold radiant exposures. They then performed treatment in the area of increased AF adjacent to the GA using energies between both thresholds and evaluated the GA progression rates of treated and fellow eyes.

Following a 1-year follow up, the authors observed a progression of the atrophic area in the treated eyes (0.7–8.0 mm²/yr, mean 3.0 mm²/yr; 46%/yr) whereas the progression rates of the fellow eyes were insignificantly lower (0.46–4.04 mm²/yr, mean 1.9 mm²/yr; 30%/yr; p=0.134). They noted that the progression rate in the treated eyes of two patients increased significantly, while in the other four patients, the progression rates were nearly the same between both eyes. Additionally, one of these two eyes showed an unexpected RPE reaction after treatment, since all laser lesions led to RPE atrophy and thus an accelerated enlargement of the GA occurred.

The authors of this study concluded that SRT in the hyperautofluorescent areas of GA was not able to stop or slow down the progression of GA. However, modified treatment strategies might be more promising (e.g., placing the spots outside the hyperautofluorescent areas where RPE apoptosis is postulated). Moreover, SRT studies on GA might be more successfully performed on specific subgroups of GA, based on autofluorescence and other findings.

Source: Prahs P, Walter A, Regler R, et al. Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2010;248(5):651-658.

Treatment of Macular Edema with Ranibizumab Following BRVO

To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO), researchers conducted this prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial. They included 397 patients with macular edema following BRVO in the study and randomized eligible patients 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).

The researchers noted that mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7–18.5) and 18.3 (16.0–20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1–9.5) in the sham group (p<0.0001 for each ranibizumab group vs sham). The percentage of patients who gained ≥ 15 letters in BCVA at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups 28.8% in the sham group (p<0.0001 for each ranibizumab group vs sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA of ≥20/40 compared with sham patients (41.7%; p<0.0001 for each ranibizumab group vs sham); and CFT had decreased by a mean of 337 µm (0.3 mg) and 345 µm (0.5 mg) in the ranibizumab groups and 158µm in the sham group (p<0.0001 for each ranibizumab group vs sham), the study researchers reported. They reported that the median percent reduction in excess foveal thickness at month 6 was 97.0% and 97.6% in 0.3 and 0.5 mg groups and 27.9% in the sham group. More patients in the sham group (54.5%) received rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with BRVO.

The study researchers found that intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events.

Source: Campochiaro PA, Heier JS, Feiner L, et al, BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmol 2010;Apr 15 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2010.02.021.

Dexamethasone Intravitreal Implant in Patients with Macular Edema Due to RVO

Two identical, multicenter, masked, randomized, 6-month, sham-controlled clinical trials (each of which included patients with branch retinal vein occlusion [BRVO] and patients with central retinal vein occlusion [CRVO]) were conducted to evaluate the safety and efficacy of dexamethosone intravitreal implant (DEX implant; Ozurdex, Allergan, Inc.) compared with sham in eyes with vision loss due to macular edema (ME) associated with BRVO or CRVO. The authors gave a single treatment with DEX implant 0.7 mg (n=427), DEX implant 0.35 mg (n=414), or sham (n=426) to the 1,267 patients with vision loss due to ME associated with BRVO or CRVO. The primary outcome measures for the pooled data from the two studies was time to achieve a ≥15-letter improvement in best-corrected visual acuity (BCVA). Secondary endpoints included BCVA, central retinal thickness and safety.

It was noted that after a single administration, the time to achieve a ≥15-letter improvement in BCVA was significantly less in both DEX implant groups compared with sham (p<0.001). The percentage of eyes with a ≥ 15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (p<0.001). It was also reported that the percentage of eyes with a ≥15-letter loss in BCVA was significantly lower in the DEX implant 0.7-mg group compared with sham at all follow-up visits (p≤0.036). Additionally, improvement in mean BCVA was greater in both DEX implant groups compared with sham at all follow-up visits (p≤0.006). The authors saw improvements in BCVA with DEX implant in patients with BRVO and in patients with CRVO, although the patterns of response differed. They noted that the percentage of DEX implant-treated eyes with intraocular pressure of ≥25 mmHg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. Moreover, the authors observed no significant between-group difference in the occurrence of cataract or cataract surgery.

They concluded that dexamethasone intravitreal implant can both reduce the risk of vision loss and improve the speed and incidence of visual improvement in eyes with ME secondary to BRVO or CRVO and may be a useful therapeutic option for eyes with these conditions.

Source: Haller JA, Bandello F, Belfort R, et al., for the Ozurdex Geneva Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmol 2010;Apr 23 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2010.03.032.

Prevalence of Giant Retinal Tear in the UK

The authors of this study sought to determine the incidence of giant retinal tear (GRT) in the United Kingdom (UK) and to provide epidemiological data, clinical characteristics, treatment methods and short-term outcomes in affected and fellow eyes.

They prospectively identified patients with a newly developed GRT (90° or greater in circumferential extent associated with posterior vitreous detachment) over a 13-month period (January 2007 to January 2008 inclusive) by active surveillance through the British Ophthalmic Surveillance Unit. They obtained questionnaire-based data from reporting ophthalmologists at baseline and at 12 months.

According to the authors, 60 patients (60 eyes) developed a new GRT, giving a UK annual incidence of 0.094 (95% CI 0.072–0.120) cases or 0.091 (95% CI 0.069–0.117) patients per 100,000. They found that the GRT was mostly idiopathic (54.8%), affected middle-aged (mean 42.2 years), white British (93.3%) males (71.7%); with presenting vision worse than 20/40 in 59.7%, foveal detachment in 45.2% and proliferative vitreoretinopathy (PVR) grade C or worse in 11.3%. They managed most by pars plana vitrectomy (93.5%) with laser retinopexy (52.5%) and silicone oil endotamponade (75.8%). The study authors applied prophylactic 360° laser or cryotherapy to 39.0% of fellow eyes and at mean follow up of 11.3 months, they noted that eventual retinal reattachment was attained in 94.7% although only 42.1% achieved vision of 20/40. None of the 19 non-traumatic non-iatrogenic prophylactically treated fellow eyes developed a GRT or RD.

In conclusion, this is the first population-based prospective study evaluating the epidemiology of GRT. Although only a minority presented with PVR-C and high retinal reattachment rates were achieved, less than half maintained driving vision in the GRT eye.

Source: Ang GS, Townend J, Lois N. Epidemiology of giant retinal tears in the United Kingdom: The British Giant retinal tear Epidemiology Eye Study (BGEES). Invest Ophthalmol Vis Sci 2010;Apr 14 [Epub ahead of print]. DOI: 10.1167/iovs.09-5036.

25-Gauge Vitrectomy as a Treatment Option for Rhegmatogenous Retinal Detachment

The aim of this Japanese retrospective, consecutive, interventional case series was to assess the visual outcome and complications of 25-G transconjunctival sutureless vitrecomty (25G-TSV) for rhegmatogenous retinal detachments. The findings indicate that 25G-TSV is a feasible treatment for RRD and leads to retinal reattachment rates comparable with those following conventional vitrectomy.

Included were 84 eyes of 84 consecutive patients with RRD who underwent 25G-TSV. All surgeries were performed by a single surgeon at a single center.

It was reported that the initial and final reattachment rates were 95.2 and 100%, respectively. The mean visual acuity improved from 0.78 logarithm of the minimum angle of resolution (logMAR) units to 0.17 logMAR units at the final examination (p<0.001). A macula-off RRd was present preoperatively in 45 of the 84 eyes, and 11 of these (24.4%) developed postoperative retinal complications. Of these complications, one eye had an intraoperative choroidal detachment, five developed a postoperative macular pucker, one eye had a postoperative macular hole and four eyes developed a retinal detachment. It was noted that the percentages of eyes developing retinal complications in the macula-on group (2.6%) was significantly lower than that in the macula-off group (p=0.004). Additionally, an intraocular pressure (IOP) 35 mmHg was detected in five eyes (6.0%) within the first postoperative week. All of these eyes had a macula-off RRD and none with a macula-on RRD had an elevation of the IOP (p=0.04).

It is important to note that intra- and postoperative retinal complications and postoperative elevation of the IOP can occur especially in eyes with a preoperative macula-off RRD.

Source: Kunikata H, Nishida K. Visual outcome and complications of 25-G vitrectomy for rhegmatogenous retinal detachment; 84 consecutive cases. Eye 2010; Apr 16 [Epub ahead of print]. DOI: 10.1038/eye.2010.41.