THE LATEST PUBLISHED RESEARCH

Pilot Study of Steroid and Focal Laser for Mild DME
The Diabetic Retinopathy Clinical Research Network reported that peribulbar administration of triamcinolone acetonide with or without focal photocoagulation is not likely to be of substantial benefit for the treatment of mild diabetic macular edema (DME).

Network researchers conducted a prospective, Phase II, multicenter, randomized clinical trial involving 129 eyes of 109 patients. At baseline, mean visual acuity in the study eyes was 20/25, and mean central subfield thickness as measured by optical coherence tomography was 328 µm. Patients were randomized to receive either focal photocoagulation, a 20-mg anterior sub-Tenon injection of triamcinolone, a 20-mg injection and focal photocoagulation after four weeks, a 40-mg injection, or a 40-mg injection and focal photocoagulation after four weeks. The last follow-up visit was at 34 weeks.

While the results suggested that a higher proportion of eyes had central subfield thickness <250 µm at 17 weeks after the combined treatment, changes in retinal thickening and visual acuity were not significantly different among the five groups at 34 weeks. Based on the outcome of the study, the researchers concluded that a Phase III trial of this treatment approach from mild DME is not needed.

Source: Diabetic Retinopathy Clinical Research Network. Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study. Ophthalmology 2007;114(6):1190-1196.

Literature Review: RPE Tears and Anti-VEGF Therapy
The authors of a literature review recommended that certain age-related macular degeneration patients treated with vascular endothelial growth factor -inhibiting injections be informed of the potential for tears of the retinal pigment epithelium and their potential effect on visual prognosis. The reviewers identified 33 cases of RPE tear after treatment with pegaptanib (Macugen), bevacizumab (Avastin), or ranibizumab (Lucentis) reported in the literature. Information on the clinical features of 25 of those cases was available, and the authors included a retrospective analysis of an additional five cases, for a total of 30 cases.

Features common among the cases included advanced age, the presence of fibrovascular pigment epithelial detachment (PED) or PED associated with choroidal neovascularization, and diagnosis of the tear within four to eight weeks of the first or second injection.

Sources: Chang LK, Sarraf D. Tears of the retinal pigment epithelium: an old problem in a new era. Retina 2007;27(5):523-534.

Rate of CNV Recurrence 18 Months after PDT
Researchers in Vancouver, British Columbia, Canada, conducted a prospective, interventional cohort study to determine the incidence of CNV recurrence 18 months after cessation of photodynamic therapy with verteporfin (Visudyne). The group consisted of 108 patients with CNV secondary to AMD. Recurrences were classified primarily on the basis of hemorrhage and increased lesion size.

Imaging of a study patient’s left eye after successful PDT treatment (A) and recurrence of CNV at a follow-up visit (B).

CNV recurred in 36 (33 percent) of the 108 eyes. In 23 (64 percent) of those eyes, the recurrences were clinically meaningful. Only visual acuity measured at the final PDT treatment visit significantly differed between the cases that recurred and those that did not.

Source: Potter MJ, Szabo SM. Recurrence of choroidal neovascularisation after photodynamic therapy in patients with age-related macular degeneration. Br J Ophthalmol 2007;91:753-756.

Costs for Saving a Line of Vision
A study conducted at Miami’s Bascom Palmer Eye Institute was designed to quantify the relative cost of new AMD therapies vs. vision saved. The study was a review of landmark AMD treatment studies but also included representative treatment studies for other retinal conditions for comparison.

The study defined and tabulated several parameters to estimate Snellen lines of vision saved for each condition. A regimen of office visits, ancillary testing and treatments was outlined. Costs were tabulated using Medicare-allowable costs, and costs of visual benefit (per line of vision) for each condition were calculated. Life expectancy was factored in to calculate the cost of a line of vision for each year (line-year). The proportions of costs allocated to professional, technical and pharmaceutical expenses were tabulated for each therapy.

The cost per line of vision saved for AMD therapies ranged from $997 for laser for extrafoveal choroidal neovascularization, to $5,509 for PDT for occult lesions, to $12,482 for pegaptanib injections. This compared to $651 for retinal detachment repair, $1,658 for macular hole repair, $2,411 for epiretinal membrane peeling, $5,458 for diabetic macular edema laser, $594 for panretinal photocoagulation, and $2,984 to $4,178 for diabetic vitrectomy. The costs per line-years ranged from $77 to $1,248 for AMD and $21 to $194 for the comparison conditions. The proportion of costs for pegaptanib treatment was 17 percent for professional fees and 70 percent for pharmaceutical fees. Assumptions incorporated in estimating costs for pegaptanib could easily have doubled, however, because second-year costs might approximate first-year costs and the maintenance of treatment effect has not been well established.

Source: Smiddy WE. Relative cost of a line of vision in age-related macular degeneration. Ophthalmol 2007;114(5):847-54.

Potential New Target for Uveal Melanoma Treatment
Researchers in Chile found that the receptor MC1R is present in uveal melanoma and may provide a new therapeutic target for treatment. Investigators used two novel monoclonal antibodies, MP1.1C11 and MP1.1B7, to examine the expression of MC1R in uveal melanomas. They analyzed tissue samples obtained from 17 patients for expression of MC1R using immunohistochemistry. Additionally, they treated uveal melanoma cell lines with proinflammatory cytokines and analyzed MC1R cell surface expression by flow cytometry.

MC1R was expressed to a significantly greater extent than other melanoma markers. It was detected in 95 percent of the tested tissue, including one liver metastasis. In contrast, MART-1 was expressed by 66 percent of the analyzed samples, S100-specific protein by 33 percent and gp-100 by 67 percent of the analyzed samples. Results also showed that even though MC1R is mainly located intracellularly, its cell surface expression can be promoted by cytokines such as IFN-gamma, TNF-alpha, IL-4 and IL-10.

The study authors wrote that these results support the inclusion of MC1R in the panel of markers for diagnosing uveal melanoma.

Source: Lopez MN, Pereda C, Ramirez M, et al. Melanocortin 1 receptor is expressed by uveal malignant melanoma and can be considered a new target for diagnosis and immunotherapy. Invest Ophthalmol Vis Sci 2007;48(3):1219-27.

Inflammation Plays a Role in RAP
Immunohistochemical and other analyses performed in an animal model (very low-density lipoprotein receptor [VLDLr] knockout mice) of retinal angiomatous proliferation indicated that an inflammatory process is involved in the development of neovascularization.

Expression of VEGF and basic fibroblast growth factor was significantly greater in the lesion areas, and increased expression of glial fibrillary acidic protein indicated Müller cell activation around the lesion areas. Expression of the proinflammatory cytokine IL-18 (interleukin 18) and the inflammation mediator intercellular adhesion molecule-1 was increased before significant intraretinal neovascularization. Furthermore, the researchers reported, phosphorylation of Akt and mitogen-activated protein kinase and translocalization of nuclear factor kappa B were greater in VLDLr knockout mouse retinas.

Source: Li C, Huang Z, Kingsley R, et al. Biochemical alterations in the retinas of very low-density lipoprotein receptor knockout mice: an animal model of retinal angiomatous proliferation. Arch Ophthalmol 2007;125(6):795-803.