FINASTERIDE (PROSCAR) Dubbi Un solo studio Per quanto tempo deve durare il trattamento? Può essere prescritto anche alle donne? RIFAMPICINA (RIFADIN) Farmaco antitubercolare che blocca la trascrizione dell’RNA Induce il citocromo P450,3A4, che aumenta il metabolismo degli steroidi Razionale Riduce i livelli endogeni di steroidi RIFAMPICINA (RIFADIN) Prima osservazione: Miglioramento di CRSC con terapia antitubercolare (che comprendeva rifampicina) > peggioramento dopo sospensione rifampicina > miglioramento con ripresa farmaco (Ravege. ARVO 2011) RIFAMPICINA (RIFADIN) Oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy RIFAMPICINA (RIFADIN) Nathan C Steinle, Naina Gupta, Alex Yuan, Rishi P Singh Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA Correspondence to Dr Rishi P Singh, Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, i-32, Cleveland OH 44195, USA; [email protected] Accepted 27 June 2011 Published Online First 3 November 2011 ABSTRACT Chronic central serous retinopathy (CSR) is characterised by frequent exacerbations and a poor visual prognosis. Very few therapies exist for chronic CSR, and the existing therapies are often ineffective. Thus, novel therapies to combat this frustrating disorder are needed. Presented here is a case detailing a patient with chronic CSR with persistent subfoveal fluid of 2 years’ duration that completely resolved with 1 month of oral rifampin therapy. As a cytochrome P450, 3A4 inducer, rifampin is thought to favourably alter the metabolism of endogenous steroids, thereby leading to an improvement in CSR manifestations. on 12 May 2008. Because of the lack of the anticipated visual acuity improvement following cataract surgery, the patient was referred to a retina specialist for further evaluation. On exam, the patient was noted to have diffuse macular retinal pigmented epithelial changes in both eyes. A fluorescein angiogram revealed numerous patchy areas of hyperfluorescence in both maculas consistent with the retinal pigment epithelial changes noted on exam (figure 1). Spectral-domain optical coherence tomography (SDOCT) images revealed diffuse subretinal fluid in the right eye, without intraretinal cystic spaces, with preservation of the foveal contour and a thickened underlying choroid (figure 2A). Both the clinical exam and ophthalmic imaging exams pointed towards a diagnosis of multifocal chronic central serous retinopathy (CSR). The patient had a history of non-insulin-dependent diabetes but had no visible diabetic retinopathy in either fundus, and his haemoglobin A1c was 6.1% at the time of the 1 case report con miglioramento di CRSC dopo 2 anni di osservazione riassorbimento completo liquido dopo 1 mese di terapia CASE REPORT A 68-year-old AfricaneAmerican male underwent uncomplicated cataract extraction with posteriorchamber intraocular-lens placement in the right eye (Steinle et al BJO 2012) Downloaded from bjo.bmj.com on November 21, 2012 - Published by group.bmj.com Innovations Oral rifampin utilisation for the treatment of chronic Figure 1 Fundus photographs and fluorescein angiogram (both serous eyes). The photographs reveal diffuse bilateral retinal multifocal central retinopathy pigment epithelium irregularities with patchy hyperpigmentation, while the fluorescein angiogram reveals corresponding diffuse retinal pigment epithelium decompensation with granular hyperfluorescence secondary to chronic central serous Nathan C Steinle, Naina Gupta, Alex Yuan, Rishi P Singh retinopathy. 10 Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA Br J Ophthalmol 2012;96:10e13. doi:10.1136/bjophthalmol-2011-300183 on 12 May 2008. Because of the lack of the anticiABSTRACT pated visual acuity improvement following cataract Chronic central serous retinopathy (CSR) is characterised surgery, the patient was referred to a retina by frequent exacerbations and a poor visual prognosis. specialist for further evaluation. Very few therapies exist for chronic CSR, and the RIFAMPICINA (RIFADIN) Dosaggio 300 mg 2 volte al giorno Effetti collaterali Rash cutaneo Anoressia Sintomi influenzali Colorazione rossastra urine, saliva e lacrime (lac) Aumento enzimi epatici Esami da richiedere prima Enzimi epatici (SGPT e SGOT) Bilirubina Creatinina serica Emocromo RIFAMPICINA (RIFADIN) Dubbi Solo 2 case reports Per quanto tempo deve durare il trattamento? Effetti collaterali gravi (epatite, shock anafilattico, insufficienza renale, s. Steven-Johnson, etc) KETOCONAZOLO (NIZORAL 200 mg) Farmaco antimicotico usato per terapia micosi orali e come shampoo anticalvizie Razionale Inibisce sintesi steroidi Utilizzato per ridurre i livelli di cortisolo endogeno nel Cushing al dosaggio di 600 mg/die (Loli et al. J Clin Endocrinol Metab 1986) KETOCONAZOLO (NIZORAL 200 mg) Acta Ophthalmologica 2010 Fig. 1. Ketoconazole blocks P450scc and 11b-hydroxylase, thus leading to reduced synthesis of pregnenolone and cortisol. KETOCONAZOLO (NIZORAL 200 mg) 2 studi Acta Ophthalmologica 2010 KETOCONAZOLE IN THE TREATMENT OF CHRONIC IDIOPATHIC CENTRAL SEROUS CHORIORETINOPATHY CATHERINE B. MEYERLE, MD, K. BAILEY FREUND, MD, PAWAN BHATNAGAR, MD, VIRAL SHAH, MD, LAWRENCE A. YANNUZZI, MD Purpose: To determine the effect of an adrenocorticoid antagonist (ketoconazole) in the treatment of patients with central serous chorioretinopathy (CSC). Methods: Ketoconazole was given at an oral dose of 600 mg per day for 4 weeks. Laboratory monitoring included 24-hour urinary cortisol and liver function tests at baseline, 4 weeks, and 8 weeks. Changes in greatest linear dimension were followed with fluorescein angiography at baseline, 4 weeks, and 8 weeks. Posterior pole anatomy was assessed with optical coherence tomography at baseline, 4 weeks, and 8 weeks. Ophthalmic examination and best-corrected visual acuity were assessed at each interval visit. Results: Median visual acuity in the study eye remained stable at 20/40 throughout the 8-week follow-up. Median lesion height and greatest linear dimension were stable at 4 weeks and decreased at 8 weeks. Conclusion: Ketoconazole lowered endogenous cortisol after 4 weeks of 600 mg daily. While median visual acuity, lesion height, and greatest linear dimension remained unchanged during the month of drug treatment, there may have been a delayed therapeutic response seen at 8 weeks. RETINA 27:943–946, 2007 B 600 mg/die x un mese Stabilità ad un mese, miglioramento a 2 mesi No gruppo di controllo oth endogenous and exogenous corticosteroids have been implicated in central serous chorioretinopathy (CSC). Many studies have confirmed that exogenous steroid administration is a risk factor for the development of CSC.1–3 Multiple routes of corticosteroid administration have been implicated in CSC pathogenesis including oral, intravenous, inhaled, intranasal, intramuscular, and topical dermatologic.4 –10 There have even been isolated case reports of CSC following vitrectomy with intravitreal triamcinolone From the LuEsther T. Mertz Retinal Research Center/Manhattan Eye, Ear & Throat Hospital, New York, and Vitreous-RetinaMacula Consultants of New York, New York. This work was supported by The Macula Foundation, Inc. The authors have no financial interest in any aspect of the article. acetonide for diabetic macular edema11 and CSC after a periocular steroid injection for iritis.12 Endogenous corticosteroids secreted by the cortex of the adrenal glands are also thought to contribute to the pathogenesis of disease. Bouzas and colleagues reported the development of CSC in endogenous Cushing disease.13 Other risk factors, such as pregnancy and stress, are associated with hypercortisolism.13,14 Many CSC patients have elevated 24-hour urine corticosteroids or plasma cortisol.15,16 Based on the documented association of hypercortisolism with CSC, Jampol and colleagues proposed treatment for chronic cases aimed at lowering endogenous cortisol levels.16 The suggested therapeutic strategy involved corticosteroid antagonists such as Ketoconazole in the treatment of central serous chorioretinopathy: a pilot study Azadeh Golshahi,1 Dietrich Klingmüller,2 Frank G. Holz1 and Nicole Eter1 1 Department of Ophthalmology, University of Bonn, Bonn, Germany Institute of Clinical Biochemistry, University of Bonn, Bonn, Germany 2 ABSTRACT. Purpose: The aim of this study was to evaluate a possible effect of systemic ketoconazole on visual acuity (VA) and retinal thickness in patients with acute central serous chorioretinopathy (CSCR). Methods: Fifteen consecutive patients were treated with ketoconazole 200 mg ⁄ day for a period of 4 weeks. Another 15 patients served as a control group. Baseline examination and review after 4 weeks included VA testing and measurement of neuroretinal or pigment epithelial detachment by optical coherence tomography (OCT). Fluorescein angiography was performed to verify the diagnosis. Results: At baseline, mean VA in Snellen units was 0.6 ± 0.2 (logMAR 0.2 ± 0.7) in the treatment group and 0.7 ± 0.3 (logMAR 0.2 ± 0.5) in the control group. On OCT, mean neuroretinal or pigment epithelial detachment measured 288 ± 163 lm in the ketoconazole group and 225 ± 51 lm in the control group, respectively. Four weeks later, mean VA improved in both groups. On OCT, neuroretinal or pigment epithelial detachment decreased in both the treatment and control groups. The differences were not statistically significant. Conclusions: Although a pharmacological decrease in endogenous cortisol synthesis appears to be a rational approach in the treatment of CSCR, systemic ketoconazole at 200 mg ⁄ day was not associated with a significantly better outcome in this preliminary study. Localized impairment of metabo transport functions of the RPE, lea ing to a reversal of the direction ion secretion, has also been suggest (Spitznas 1986). The common fin pathway results in an accumulation extracellular fluid in the subretin and ⁄ or sub-RPE space. Central serous chorioretinopathy a disease characterized by sero detachment of the neurosensory reti secondary to one or more focal lesio of the RPE. It afflicts young and m dle-aged adults and concerns mo men than women. Symptoms are bl ring of vision (usually unilaterall metamorphopsia, micropsia, relat scotoma and colour desaturati (Bennett 1955; Gass 1967; Wang et 2008). The condition is subdivid into acute and chronic types. Acu CSCR appears predominantly young people and shows characteris changes starting with a focal po and resulting in an accumulation 200 mg/die Miglioramento ad un mese, ma non rispetto a gruppo di controllo Key words: central serous chorioretinopathy – CSC – CSCR – corticosteroids – ketoconazole KETOCONAZOLO (NIZORAL 200 mg) Dosaggio 600 mg/die per almeno un mese Effetti collaterali Epatotossicità, ginecomastia Esami da richiedere prima Funzionalità epatica KETOCONAZOLO (NIZORAL 200 mg) Interazioni farmacologiche nifedipina e chinidina: effetto antiipertensivo intensificato da ketoconazolo rifampicina e isoniazide: riducono i livelli ematici di ketoconazolo antiacidi anti H2: inibiscono l’assorbimento di ketoconazolo farmaci con metabolismo citocromo-dipendente: anticoagulanti orali, digossina, ciclosporina, metilprednisone, midazolam, ecc. KETOCONAZOLO (NIZORAL 200 mg) Dubbi Dosaggi >200 mg sono tossici? Un mese di terapia a 600 mg è troppo breve? Ancora scarsa evidenza e no studi con gruppo di controllo Terapia per tutti i pazienti con CRSC cronica? O solo per quelli con ipercortisolismo?