Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant

Background Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. Methods Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. Results Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 μm (1 month; p = 0.003,) to 361 μm (2 months; p = 0,002) and to 415 μm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 μm (1 month; p < 0,001) and to 343 μm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. Conclusions In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity

In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain

[Rationale]: Aripiprazole is an atypical antipsychotic drug with high in vitro affinity for 5-HT1A, 5-HT2A and dopamine (DA) D2 receptors. However, its in vivo actions in the brain are still poorly characterized.[Objective]: The aim was to study the in vivo actions of aripiprazole in the rat and mouse brain.[Methods]: Brain microdialysis and single-unit extracellular recordings were performed.[Results]: The systemic administration of aripiprazole reduced 5-HT output in the medial prefrontal cortex (mPFC) and dorsal raphe nucleus of the rat. Aripiprazole also reduced extracellular 5-HT in the mPFC of wild-type (WT) but not of 5-HT1A (−/−) knockout (KO) mice. Aripiprazole reversed the elevation in extracellular 5-HT output produced by the local application of the 5-HT2A/2C receptor agonist DOI in mPFC. Aripiprazole also increased the DA output in mPFC of WT but not of 5-HT1A KO mice, as observed for atypical antipsychotic drugs, in contrast to haloperidol. Contrary to haloperidol, which increases the firing rate of DA neurons in the ventral tegmental area (VTA), aripiprazole induced a very moderate reduction in dopaminergic activity. Haloperidol fully reversed the inhibition in dopaminergic firing rate induced by apomorphine, whereas aripiprazole evoked a partial reversal that was significantly different from that evoked by haloperidol and from the spontaneous reversal of dopaminergic activity in rats treated with apomorphine.[Conclusions]: These results indicate that aripiprazole modulates the in vivo 5-HT and DA release in mPFC through the activation of 5-HT1A receptors. Moreover, aripiprazole behaves as a partial agonist at DA D2 autoreceptors in vivo, an action which clearly distinguishes it from haloperidol.This work was supported by grants from the Spanish Ministry of Education and Science (SAF 2004-05525) and Bristol Myers Squibb. PC and AB are recipients of a Ramón y Cajal contract from the Ministry of Science and Technology. LDM is recipient of a predoctoral fellowship from IDIBAPS. Support from the Spanish Ministry of Health, Instituto de Salud Carlos III, Red de Enfermedades Mentales (REM-TAP Network) is also acknowledged.Peer reviewe