Preservative-free triamcinolone acetonide suspension developed for intravitreal injection

OBJECTIVES: All commercially available triamcinolone acetonide (TACA) suspensions, used for intravitreal treatment, contain retinal toxic vehicles (e.g., benzyl alcohol, solubilizer). Our aim was to find a convenient and reproducible method to compound a completely preservative-free TACA suspension, adapted to the intraocular physiology, with consistent quality (i.e., proven sterility and stability, constant content and dose uniformity, defined particle size, and 1 year shelf life). METHODS: We evaluated two published (Membrane-filter, Centrifugation) and a newly developed method (Direct Suspending) to compound TACA suspensions for intravitreal injection. Parameters as TACA content (HPLC), particle size (microscopy and laser spectrometry), sterility, and bacterial endotoxins were assessed. Stability testing (at room temperature and 40 degrees C) was performed: color and homogeneity (visually), particle size (microscopically), TACA content and dose uniformity (HPLC) were analyzed according to International Conference on Harmonisation guidelines. RESULTS: Contrary to the known methods, the direct suspending method is convenient, provides a TACA suspension, which fulfills all compendial requirements, and has a 2-year shelf life. CONCLUSIONS: We developed a simple, reproducible method to compound stable, completely preservative-free TACA suspensions with a reasonable shelf-life, which enables to study the effect of intravitreal TACA--not biased by varying doses and toxic compounds or their residues

Time course of morphologic effects on different retinal compartments after ranibizumab therapy in age-related macular degeneration

PURPOSE: To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration. METHODS: Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS). MAIN OUTCOME MEASURES: Morphology and time course of different retinal and subretinal compartments. RESULTS: High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation. CONCLUSION: Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology

Randomised clinical trial of intravitreal Avastin vs photodynamic therapy and intravitreal triamcinolone: long-term results

PURPOSE: To compare 1-year functional and anatomic outcomes of intravitreal bevacizumab (IVB) and photodynamic therapy plus intravitreal triamcinolone (PDT+IVTA) combination in patients with neovascular age-related macular degeneration (AMD). METHODS: In this prospective, randomised, controlled clinical trial, 28 patients were included. All patients were randomised 1 : 1 to 0.04 ml/1 mg of IVB or PDT plus same day 0.1 ml/4 mg IVTA (PDT+IVTA). Follow-up examinations were performed in monthly intervals in IVB group and every 3 months in PDT+IVTA group. Main outcomes were change in mean visual acuity (VA), mean central retinal thickness (CRT) and the mean number of treatments. RESULTS: At month 12, mean VA improved to a 1.5-line gain in IVB group, and lost three letters in PDT+IVTA group (P=0.02). Mean CRT was reduced from 357 microm at baseline to 244 microm at month 12 in IVB group and from 326 microm to 254 microm, respectively, in PDT+IVTA group (P=0.8). The mean number of treatments was 6.8 in the IVB group vs 1.9 in the PDT+IVTA group. No significant local or systemic safety concerns were detected during follow-up time. CONCLUSIONS: Patients treated with IVB showed a significant better VA outcome compared with the PDT+IVTA group despite the fact that both modalities showed equal potency in reducing CRT during a 12-month period

Reticular drusen associated with geographic atrophy in age-related macular degeneration

PURPOSE: To characterize reticular drusen (RDR) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in a prospective, multicenter, natural history study. METHODS: Confocal scanning laser ophthalmoscopy (cSLO) three-field fundus autofluorescence (FAF; exc., 488; em., 500-700 nm), near-infrared reflectance (IR; 820 nm), and blue reflectance (BR; 488 nm) images as well as red-free (RF) and color fundus (CF) camera photographs were recorded in 458 GA patients. The digital images were evaluated by two independent readers with subsequent senior reader arbitration for prevalence and topographic distribution of RDR using a modified Early Treatment Diabetic Retinopathy Study grid. RESULTS: RDR were detected with at least one cSLO modality in 286 of 458 (62%) patients in either eye (bilateral 207 [45%]) and were visible in fundus camera photographs in 66 of 371 (18%) patients (bilateral 48 [13%]). Prevalence of RDR by cSLO imaging was associated with increasing age (P = 0.007) and female sex (P = 0.007), but not with GA total lesion area (P = 0.38). Cohen kappa statistics showed good interobserver agreement for FAF (0.81) and IR (0.82) imaging modes, and moderate agreement was found for BR (0.48), RF (0.48), and CF (0.40). On three-field FAF images RDR were present most frequently superior to the fovea (99%). CONCLUSIONS: RDR represent a common phenotypic hallmark in GA eyes. RDR are readily identified using cSLO imaging technology. These observations may explain the high prevalence determined herein, in contrast to previous reports based on fundus photographs. Incorporation of these novel imaging modalities in future natural history studies may facilitate efforts aimed at defining the role and predictive value of RDR in the progression of AMD. (ClinicalTrials.gov number, NCT00599846.