THE LATEST PUBLISHED RESEARCH

PDT Plus Steroid for AMD: 2-Year Follow-Up
After two years of treatment with photodynamic therapy (PDT) and intravitreal triamcinolone for choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), vision in 30 eyes of 30 study subjects remained stable on average.

In the prospective, nonrandomized, interventional case series, the 30 eyes received PDT followed by 19.4 +/- 2.1 mg of intravitreal triamcinolone. Fifteen of the eyes had not received any previous treatment, and 15 of the eyes previously had received PDT. Fifteen eyes that had been treated with PDT served as the control group.

In the eyes naïve to treatment, best-corrected visual acuity (BCVA) did not change significantly. On average, eyes previously treated with PDT lost 0.6 lines of BCVA. Eyes in the control group lost an average of 2.2 lines. The combination treatment reduced the need for retreatment with PDT compared with historical controls. During the follow-up period, naÏve eyes required a mean 1.9 PDT treatments, previous-PDT eyes required 1.2, and control-group eyes required 3.9.

Source: Ruiz-Moreno JM, Montero JA, Zarbin MA. Photodynamic therapy and high-dose intravitreal triamcinolone to treat exudative age-related macular degeneration: 2-year outcome. Retina 2007:27(4):458-461.

One-Year PrONTO Study Results
One-year results from the two-year PrONTO study have been published. PrONTO is evaluating an OCT-guided, variable-dosing regimen with ranibizumab (Lucentis) for patients with neovascular AMD. At one year, visual acuity results were similar to those achieved in the Phase III clinical trials of ranibizumab, but patients required fewer injections.

Mean visual acuity improved by 9.3 letters (p<.001), and mean central retinal thickness decreased by 178 µm (p<.001). In 35 percent of patients, acuity improved by 15 or more letters. The mean number of injections administered was 5.6, and once the macula was fluid-free the mean injection-free interval was 4.5 months.

In the open-label, prospective, single-center, nonrandomized, investigator-sponsored study, 40 patients with subfoveal CNV, central retinal thickness of at least 300 µm and visual acuity between 20/40 and 20/400 initially received three monthly intravitreal injections of ranibizumab (0.5 mg). At baseline, 15 percent of lesions were predominantly classic, 60 percent were minimally classic and 25 percent were occult. Twenty-five percent of all the lesions were classified as retinal angiomatous proliferations (RAP). After the first three injections, patients were treated again if they met any of the following criteria (since last visit): visual acuity loss of five letters or more with any fluid on OCT; increase in central retinal thickness of at least 100 µm; new hemorrhage; new classic CNV; persistent fluid detected by OCT one month after an injection.

Source: Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007;143(4):566-583.

Elevated Inflammation Biomarkers Precede AMD in Women
An analysis involving 27,687 subjects (mean age 54.6 years) in the Women’s Health Study supported the theory that inflammation plays a role in AMD. Elevated circulating levels of high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and fibrinogen preceded development of the disease.

Researchers measured the levels of the three inflammation biomarkers in baseline plasma samples and prospectively identified 150 cases of AMD among the subjects. None of the subjects had AMD at baseline. The researchers used proportional hazards models to examine the relationship between the biomarkers and AMD.

After adjustment for multiple risk factors, the models showed a 3.09 hazard ratio (HR) for AMD among women in the highest quintile of hsCRP compared with those in the lowest quintile (p=.02) and a 1.87 HR for sICAM-1 (p=.07). The relationship between fibrinogen and AMD was J-shaped, with a HR of 2.01 for women in the highest fifth compared with the second fifth.

Source: Schaumberg DA, Christen WD, Buring JE, et al. High-sensitivity C-reactive protein, other markers of inflammation, and the incidence of macular degeneration in women. Arch Ophthalmol 2007;125(3):300-05.

Long-Term Beta Carotene Supplementation and ARM
Results of a 12-year, randomized, double-masked, placebo-controlled trial involving 22,071 healthy U.S. male physicians showed that long-term supplemental use of beta carotene does not increase or decrease the risk of developing age-related maculopathy (ARM).

The study participants, ages 40 to 84, were randomly assigned to receive either 50 mg of beta carotene every other day or placebo. After 12 years, 162 cases of ARM (responsible for a reduction in BCVA to 20/30 or worse) developed in the beta carotene group, and 170 cases developed in the placebo group. Results were similar for the secondary end points of ARM with or without vision loss and advanced ARM.

Source: Christen WG, Manson JE, Glynn RJ, et al. Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians. Arch Ophthalmol 2007;125:333-339.

Short-Term Response to Bevacizumab for RAP
Via a retrospective review of consecutive cases of newly diagnosed or recurrent RAP, researchers evaluated treatment response following intravitreal injection of 1.25 mg of bevacizumab (Avastin) during a three-month period. They reported that the treatment significantly decreased macular thickness and improved or stabilized visual acuity.

The mean baseline visual acuity of the 23 treated eyes was 20/80, and mean central macular thickness was 335 µm. Optical coherence tomography imaging was available for 22 eyes, and pigment epithelial detachments (PEDs) were present in nine eyes at baseline.

At one month, median acuity improved to 20/60, mean central macular thickness decreased to 202 µm, and PED was present in two eyes. Among the 17 eyes available for three-month follow-up, five (29.4 percent) had better visual acuity (halving of the visual angle), one (5.9 percent) had worse acuity, and 11 (64.7 percent) had the same acuity. Median visual acuity at month three was 20/60 (20/25-20/400). No adverse events occurred.

Source: Meyerle CB, Freund KB, Iturralde D, et al. Intravitreal bevacizumab (Avastin) for retinal angiomatous proliferation. Retina 2007;27(4):451-457.

Six-Month Results Following Bevacizumab for DME
The Pan-American Collaborative Retina Study Group reported six-month results from its interventional, retrospective, multicenter study of bevacizumab for diabetic macular edema (DME). They reviewed the cases of 88 consecutive patients (110 eyes) with DME. The analysis included 78 eyes of 64 patients that received at least one intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab.

Mean logMAR visual acuity changed from 0.87 to 0.6 (p<0.0001). Acuity remained stable in 32 eyes (41.1 percent), improved by two or more lines in 43 eyes (55.1 percent), and decreased by two or more lines in 3 eyes (3.8 percent). Mean central macular thickness decreased from 387.0 +/-182.8 µm to 275.7 +/-S108.3 µm (p<0.0001). Sixteen eyes (20.5 percent) required a second injection at a mean of 13.8 weeks, and six eyes (7.7 percent) required a third injection at a mean of 11.5 weeks. No ocular or systemic adverse events occurred.

Source: Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, et al. Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6-month follow-up. Ophthalmology 2007;114(4):743-750.

Comparison of Two Laser Techniques for DME
In a randomized study conducted by the Diabetic Retinopathy Clinical Research Network, modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation reduced central subfield retinal thickness more effectively than mild macular grid (MMG) photocoagulation. The two techniques produced similar visual acuity results. In the MMG technique, microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present.

In the study, patients with previously untreated DME were randomized to receive either modified ETDRS photocoagulation (162 eyes) or MMG photocoagulation (161 eyes). They were treated again if DME persisted. At 12 months, in eyes with baseline central subfield thickness of 250 µm or greater, thickness decreased by an average of 88 µm in the modified ETDRS group and by 49 µm in the MMG group. In addition, mean visual acuity changed by zero letters in the modified ETDRS group and decreased by two letters in the MMG group.

The researchers concluded that modified ETDRS focal photocoagulation should continue to be a standard approach for treating DME, and a larger long-term trial of the MMG technique is not justified.

Source: Fong DS, Strauber SF, and the Writing Committee for the Diabetic Retinopathy Clinical Research Network. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol 2007;125:469-480.

Surgical Adjuvants Not Useful in Primary RRD Surgeries
Results of a double-masked, prospective, randomized, placebo-controlled study indicated that a combination of 5-fluorouracil (5FU) and low-molecular-weight heparin (LMWH) should not be used routinely during surgery for unselected primary rhegmatogenous retinal detachment (RRD). Use of the adjuvants did not improve the anatomic or visual success rate of vitrectomy. Furthermore, at six months, visual acuity in patients who presented with a macula-sparing detachment was significantly worse in the treatment group (p=0.0091).

The 641 patients were recruited from two specialized vitreoretinal units in England. All of them underwent primary vitrectomy and gas endotamponade. The treatment group also received 5 IU/ml LMWH and 200 µg/ml 5FU in the perioperative infusion fluid.

At 6 months, the final complete anatomical reattachment rate was 97.9 percent in both the treatment and placebo groups. There was no significant difference between the two groups in patients who presented with a macula-involving retinal detachment.

Source: Wickham L, Bunce C, Wong D, et al. Randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy. Ophthalmology 2007;114(4):698-704.