To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular agerelated macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.Design: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.Participants: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV). Methods: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 mm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.Main Outcome Measures: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.Results: Of the 349 participants randomized (intensive arm, n ¼ 174; relaxed arm, n ¼ 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P ¼ 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P ¼ 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P ¼ 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P ¼ 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P ¼ 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P ¼ 0.005).Conclusions: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

Epiretinal membrane peeling improves vision in the majority of patients with significant symptoms, even if preoperative visual acuity is not substantially reduced. Surgery improves functional vision including metamorphopsia not measurable by visual acuity, and thus assessment of functional vision should be included in surgical case planning.

The major classes of contrast agents currently used for magnetic resonance (MR) imaging of the liver include extracellular agents (eg, low-molecular-weight gadolinium chelates), reticuloendothelial agents (eg, ferumoxides), hepatobiliary agents (eg, mangafodipir), blood pool agents, and combined agents. Mechanisms of action, dosage, elimination, toxic effects, indications for use, and MR imaging technical considerations vary according to class. Gadolinium chelates are the most widely used. Ferumoxides are a useful adjunct for detection of hepatocellular carcinoma, particularly when used in combination with gadolinium to achieve improved lesion-to-liver contrast over that achievable with gadolinium alone. Mangafodipir is a prototype hepatobiliary agent that is taken up by lesions with functioning hepatocytes. It may be used for MR cholangiography as well as liver imaging. Although mangafodipir is no longer commercially available in the United States, it is currently marketed and used in Europe. Blood pool agents have not yet been approved for human use in the United States. However, a new combined MR contrast agent, gadobenate dimeglumine, recently was approved, and other agents are in various stages of development.

Animal models, in vitro assays and pilot clinical studies suggest that intravitreal triamcinolone acetonide may be useful in the treatment of age-related macular degeneration. The present case study reports the effect of intravitreal triamcinolone acetonide injection on a subretinal neovascular lesion, microglial morphology and quantitative expression of MHC-II antigens. Triamcinolone acetonide significantly decreased MHC-II expression consistent with immunocytochemical observations which revealed condensed microglial morphology. The modulation of subretinal oedema and microglial morphology correlates with in vitro observations suggesting that downregulation of inflammatory markers and endothelial cell permeability are significant features of the mode of action of triamcinolone acetonide.

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