THE LATEST PUBLISHED RESEARCH

Photocoagulation Outperforms Triamcinolone for DME at 2 Years
The Diabetic Retinopathy Clinical Research Network reported two-year results from its multicenter, randomized clinical trial comparing 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with focal/grid photocoagulation for the treatment of diabetic macular edema (DME). In the cohort studied, photocoagulation was more effective and resulted in fewer side effects than either dose of triamcinolone. The report stated that based on these results focal/grid photocoagulation should be the benchmark by which other treatments are evaluated in clinical trials involving DME.

In the study, 840 eyes of 693 patients were randomized to receive focal/grid photocoagulation (n=330), 1 mg of intravitreal triamcinolone (n=256) or 4 mg of intravitreal triamcinolone (n=254). Patients were re-treated for persistent or new edema at 4-month intervals.

At 4 months, mean visual acuity was better in the 4-mg triamcinolone group than in the laser group (p < 0.001) or the 1-mg triamcinolone group (p = 0.001). However, at the 16-month visit and through the primary outcome visit at 2 years, mean visual acuity was better in the laser group than in the other two groups (laser vs. 1 mg triamcinolone, p=0.02; laser vs. 4 mg triamcinolone, p=0.002). In general, optical coherence tomography (OCT) results paralleled the visual acuity results. IOP increased from baseline by 10 mmHg or more at any visit in 4 percent of the laser group, 16 percent of the 1-mg triamcinolone group, and 33 percent of the 4-mg triamcinolone group. Cataract surgery was performed in 13 percent of the laser group, 23 percent of the 1-mg triamcinolone group and 51 percent of the 4-mg triamcinolone group.

Source: Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 2008;published online ahead of print:DOI:10.1016/j.ophtha.2008.06.015.

Fluocinolone Implant for CRVO-Related Macular Edema
At 12 months after implantation of a sustained delivery device containing fluocinolone acetonide, visual acuity improved and macular edema decreased in a significant proportion of eyes with chronic refractory edema due to central retinal vein occlusion. This prospective, noncomparative, interventional case series involved 14 eyes of 14 patients. Median vein occlusion and macular edema duration were 12.5 months (seven to 49 months).

Median visual acuity improved from 20/126 at baseline to 20/80 by 12 months. A significant proportion of eyes gained lines of visual acuity at 12 months compared with baseline (p=.002). Mean central retinal thickness improved from 622 µm at baseline to 307 µm at 12 months (p=.008).

No eye experienced intraoperative complications at the time of implantation. By month 12, all five phakic eyes developed cataract, and 13 of 14 eyes required medical or surgical treatment to lower IOP.

Source: Ramchandran RS, Fekrat S, Stinnett SS, Jaffe GJ. Fluocinolone acetonide sustained drug delivery device for chronic central retinal vein occlusion:12-month results. Am J Ophthalmol 2008;146(2):285-291.

Five-Year Changes in Eyes with Geographic Atrophy
For the first time, population-based data describing five-year changes in eyes with pure geographic atrophy (GA) have been published. Researchers identified 95 people in the Beaver Dam Eye Study who had GA either at baseline, one of the three five-year follow-up examinations or both. They used software to calculate lesion area and greatest linear dimension (GLD). Thirty-two people (53 multiple eye-visit pairs) were seen at multiple visits five years apart with GA in the same eye for evaluation of changes.

When pure GA was first identified, it was a single lesion in 45 percent of cases, multifocal lesions in 18 percent of cases and a merged lesion in 37 percent of cases. Among the 53 eyes with multiple visits, the overall increase in area of atrophy was 6.4 mm² over a five-year period. Eyes with multifocal GA were most likely to have the area of atrophy increase (mean 12 mm²) or progress to the foveal center (83%) or to experience a decrease in vision (mean 22 letters).

The authors of the study paper noted that this information should be useful for clinical trials of potential new treatments for GA.

Source: Klein R, Meuer SM, Knudtson MD, Klein BE. The epidemiology of progression of pure geographic atrophy: the Beaver Dam Eye Study. Am J Ophthalmol 2008;published online ahead of print:DOI:10.1016/j.ajo.2008.05.050.

SD-OCT Imaging of Geographic Atrophy
A recently published report provided proof of concept that GA can be imaged with SD-OCT. Five eyes of patients (mean age 80.4) with confirmed dry AMD were imaged with SD-OCT and fundus autofluorescence. None of the eyes had a history of neovascular AMD or previous treatment with laser photocoagulation, photodynamic therapy or intravitreal injections.

On SD-OCT, because of increased reflectivity from the underlying choroid, GA appeared bright compared with surrounding areas with an intact retinal pigment epithelium. Measurement of the area of GA was comparable between the two methods with a mean difference of 2.7 percent of the total area. Both imaging technologies reproducibly identified GA. However, the researchers noted, SD-OCT collects a three-dimensional dataset that can be analyzed beyond its en face image.

Geographic atrophy imaged and measured using spectral domain OCT. (Image courtesy of Philip J. Rosenfeld, MD, PhD)

The authors of the report also noted that growth of GA has become a primary endpoint in clinical trials evaluating treatments for dry AMD; therefore, the need for reliable GA quantification is increasingly important. They wrote that the manual method they used to identify GA on SD-OCT was reproducible in this small number of patients and could be used to quantify the presence and progression of GA in a large clinical trial.

Source: Lujan BJ, Rosenfeld PJ, Gregori G, et al. Spectral domain optical coherence tomographic imaging of geographic atrophy. Ophthalmic Surg Lasers Imaging 2008;39(4):S8-S14.

Bevacizumab Effective for CNV of Various Etiologies
A group of researchers at a referral-based retinal practice retrospectively analyzed outcomes for 39 eyes of 36 patients treated with 1.25 mg of intravitreal bevacizumab (Avastin) for subfoveal choroidal neovascularization (CNV) secondary to causes other than AMD. They found that all of the eyes responded favorably and similarly despite the varying underlying etiologies.

CNV was secondary to multifocal choroiditis in 12 eyes, to angioid streaks in 11 eyes, to myopic degeneration in 10 eyes, to idiopathic disease in four eyes and to other disease in two eyes. Patients were treated again for persistent or recurrent exudation. Mean follow up was 58.8 weeks.

Median baseline visual acuity was 20/60, which improved to 20/30 at three months (p=.004). At last follow up, median acuity was 20/40, which was an improvement compared with baseline (p<.02) but worse compared with three-month follow up (p<.03). On average, 3.4 injections per eye were administered during the study.

Source: Chang LK, Spaide RF, Brue C, et al. Bevacizumab treatment for subfoveal choroidal neovascularization from causes other than age-related macular degeneration. Arch Ophthalmol 2008;126(7):941-945.

Evaluation of Bevacizumab Safety
According to the results of a retrospective study, intravitreal bevacizumab was well tolerated in 203 consecutive eyes treated for a variety of retinal and choroidal vascular diseases at the Stanford University Department of Ophthalmology between November 15, 2005 and July 14, 2006. Conditions treated with bevacizumab included neovascular AMD, retinal vascular occlusion, diabetic macular edema, neovascular glaucoma and five others. The eyes received a total of 578 injections (1.25 mg). Mean follow-up time was six months.

Five eyes with neovascular AMD developed retinal pigment epithelial (RPE) tears. All five eyes had pre-existing RPE detachments. The five eyes represented 2.9 percent of all AMD eyes treated and 7 percent of the AMD eyes with pre-existing RPE detachments. Other adverse events were rare and included retinal ischemia, subretinal hemorrhage, vitreous hemorrhage, ocular irritation or pain, worsened hypertension and headache. No death or thromboembolic event occurred.

Source: Wong LJ, Desai RU, Jain A, et al. Surveillance for potential adverse events associated with the use of intravitreal bevacizumab for retinal and choroidal vascular disease. Retina 2008;published online ahead of print:DOI 10.1097/IAE.0b013e31817e100f.

The Role of Abnormal Vitreomacular Adhesion in AMD
Based on the results of their study, a group of researchers concluded that hyaloid adhesion to the macula is associated with AMD and frequently causes vitreomacular traction (VMT) in eyes with CNV. They also reported that tractional forces may cause resistance to treatment with anti-vascular endothelial growth factor (VEGF) agents in a subset of patients. Spectral domain OCT (SD-OCT)/scanning laser ophthalmoscopy was used to check for hyaloid adhesion to the posterior pole and VMT in 170 eyes of 94 elderly patients. In the group of patients, 61 had neovascular AMD and 59 had nonexudative AMD. Fifty eyes served as a control group.

Hyaloid adhesion was present in 17 eyes with exudative AMD (27.8 percent), 15 eyes with nonexudative AMD (25.4 percent) and eight control eyes (16 percent). The difference between the groups was statistically significant (p=.002). Among the eyes with hyaloid adhesion, VMT was shown in 10 eyes with exudative AMD (59 percent), two eyes with nonexudative AMD (13 percent) and one control eye (12 percent). VMT was associated with the severity of AMD (p=.0082). In eyes with exudative AMD, the area of hyaloid adhesion was significantly smaller than and concentric to the area of CNV complex.

The study also evaluated surgical treatment in a subset of patients with CNV that did not respond to treatment with an anti-VEGF agent. Five patients with VMT underwent surgical hyaloid removal, which resulted in modest improvement of best-corrected visual acuity and retinal thickness.

Source: Mojana F, Cheng L, Bartsch DU, et al. The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol 2008;146(2):218-227.

Effect of PPV Cannula Insertion Technique on Early Postoperative Hypotony
When a prospective consecutive series of eyes that underwent 25-ga. pars plana vitrectomy (PPV) without tamponade and oblique cannula insertion was compared with a historical consecutive series of eyes that underwent PPV without tamponade and direct cannula insertion, the oblique technique resulted in a lower rate of postoperative day one hypotony. Of the 95 PPVs without tamponade, 55 included oblique cannula insertion and 40 included direct insertion.

With oblique insertions, no statistically significant difference between mean IOP measured before surgery, on postoperative day 1 and on postoperative week 1 was found. Only 1 of the 55 eyes (1.8 percent) had hypotony, defined as IOP less than or equal to 5 mmHg, on postoperative day 1. With direct cannula insertion, four of the 40 eyes (10 percent) had hypotony on postoperative day 1. Mean postoperative day 1 IOP was significantly lower than mean preoperative IOP (p=0.009). Mean preoperative and postoperative week 1 IOPs were similar.

Source: Hsu J, Chen E, Gupta O, et al. Hypotony after 25-gauge vitrectomy using oblique versus direct cannula insertions in fluid-filled eyes. Retina 2008;28(7):937-940.