minocycline and Macular-Degeneration

To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD).. Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 μg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 μm.. Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 μm (±75).. This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD.

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Dexamethasone; Drug Therapy, Combination; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Glucocorticoids; Humans; Intravitreal Injections; Macular Degeneration; Male; Middle Aged; Minocycline; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Porphyrins; Prospective Studies; Ranibizumab; Retinal Neovascularization; Treatment Outcome; Verteporfin; Visual Acuity

Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline.. Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis.. Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions.. This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.

Topics: Anti-Bacterial Agents; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cell Death; Cell Proliferation; Cells, Cultured; Cytoprotection; Humans; Light; Macular Degeneration; Minocycline; Pigment Epithelium of Eye; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Anti-Bacterial Agents; Humans; Inflammation; Macular Degeneration; Minocycline