Zusammenfassung
Cidofovir ist ein Virustatikum aus der Gruppe der Nukleotidanaloga mit Wirksamkeit gegen Herpesviren. Hauptindikation ist derzeit die Behandlung der CMV-Retinitis. Neuere Untersuchungen belegen eine zusätzliche Wirksamkeit von Cidofovir bei durch JC-Virus-Reaktivierung verursachter progressiver multifokaler Leukoenzephalopathie (PML). Schwerwiegendste okuläre Komplikation bei Verabreichung von Cidofovir stellt die chronische, therapieresistente Hypotonia bulbi dar, welche durch sekundäre Komplikationen (Makulafalten, Netzhaut-/Aderhautablösung) zu ausgeprägter, permanenter Visusminderung führen kann. Die Entstehung der Drucksenkung ist nicht endgültig geklärt. Eine Behandlung derselben ist nur in Einzelfällen beschrieben worden und in der Effizienz nicht ausreichend gesichert. Als einzig sichere Option bei Auftreten einer Hypotonie verbleibt der Therapiewechsel von Cidofovir auf alternative Substanzen. Zur frühzeitigen Erkennung ophthalmologischer Komplikationen bei Cidofovirtherapie ist eine regelmäßige Kontrolle durch den Augenarzt notwendig.
Abstract
Cidofovir, a nucleotid analogue virostatic drug is effective in the treatment of herpes virus infections. However, cytomegaly infection is the prime indication due to its adverse effects. There is growing evidence suggesting cidofovir's effectiveness against progressive multifocal leukoencephalopathy (PML) caused by a reactivation of JC-virus. Chronic ocular hypotension which seems to be therapy refractory and anterior uveitis are considered to be the most serious ocular complications of cidofovir. Secondary side effects such as macular folds, retinal or choroidal detachment can result in a permanent loss of vision. Little is known about the pathology of reduced intraocular pressure and only few reports deal with therapeutical attempts to compensate this complication. Abandoning cidofovir presently remains the only therapeutic option. To avoid serious damage it is of utmost importance to monitor all patients undergoing cidofovir administration for signs of anterior uveitis and ocular hypotension.
Schlüsselwörter
Cidofovir - Hypotonia bulbi - Uveitis anterior - progressive multifokale Leukoenzephalopathie (PML) - CMV-Retinitis
Key words
Cidofovir - ocular hypotension - anterior uveitis - progressive multifocal leukoencephalopathy (PML) - cytomegalovirus retinitis
Literatur
-
1
Accorinti M, Ciapparoni V, Pirraglia M P, Pivetti-Pezzi P.
Treatment of severe ocular hypotony in AIDS patients with cytomegalovirus retinitis and cidofovir-associated uveitis.
Ocul Immunol Inflamm.
2001;
9 (3)
211-217
-
2
Akler M E, Johnson D W, Burman W J, Johnson S C.
Anterior uveitis and hypotony after intravenous cidofovir for the treatment of cytomegalovirus retinitis.
Ophthalmology.
1998;
105 (4)
651-657
-
3
Ambati J, Wynne K B, Angerame M C, Robinson M R.
Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis.
Br J Ophthalmol.
1999;
83 (10)
1153-1158
-
4
Bainbridge J W, Raina J, Shah S M, Ainsworth J, Pinching A J.
Ocular complications of intravenous cidofovir for cytomegalovirus retinitis in patients with AIDS.
Eye.
1999;
13 (Pt 3a)
353-356
-
5
Banker A S. et al .
Intraocular pressure and aqueous humor dynamics in patients with AIDS treated with intravitreal cidofovir (HPMPC) for cytomegalovirus retinitis.
Am J Ophthalmol.
1997;
124 (2)
168-180
-
6
Berger J R.
Progressive multifocal leukoencephalopathy.
Curr Treatm Opt Neurol.
2000;
2 (4)
361-368
-
7 Bienz K A. Erreger viraler Infektionskrankheiten. In: Kayser FH (Hrsg) Medizinische Mikrobiologie. Stuttgart; Thieme 1993: 342-344
-
8
Cardenas R L, Chen K H, Sack K.
The effects of cidofovir on progressive multifocal leukoencephalopathy: an MRI case study.
Neuroradiology.
2001;
43 (5)
379-382
-
9
Chavez de la Paz E. et al .
Anterior nongranulomatous uveitis after intravitreal HPMPC (cidofovir) for the treatment of cytomegalovirus retinitis. Analysis and prevention.
Ophthalmology.
1997;
104 (7)
539-544
-
10
Cochereau I. et al .
Uveitis in patients treated with intravenous cidofovir.
Ocul Immunol Inflamm.
1999;
7 (3 - 4)
229-233
-
11
Conway B, Halliday R C, Brunham R C.
Human immunodefiency virus associated progressive multifocal leukoencephalopathy: apparent response to 3'-azido-3'-deoxythymidine.
Rev Infect Dis.
1990;
12 (3)
479-482
-
12
Davis J L, Taskintuna I, Freeman W R, Weinberg D V, Feuer W J, Leonard R E.
Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis.
Arch Ophthalmol.
1997;
115 (6)
785-786
-
13
De Luca A. et al .
Cidofovir added to HAART improves virological and clinical outcome in AIDS-associated progressive multifocal leukoencephalopathy.
AIDS.
2000;
29, 14 (14)
117-121
-
14
Garweg J G.
Anterior segment involvement in HIV-related eye disease after the commencement of highly active antiretroviral therapy (HAART).
Klin Monatsbl Augenheilkd.
2000;
216 (2)
61-67
-
15
Gasnault J. et al .
Prolonged survival without neurological improvement in patients with AIDS-related progressive multifocal leukoencephalopathy on potent combined antiretroviral therapy.
J Neurovirol.
1999;
5 (4)
421-429
-
16
Gonzalez H, Bolgert F, Camporo P, Leblond V.
Progressive multifocal leukoencephalitis (PML) in three patients treated with standard-dose fludarabine (FAMP).
Hematol Cell Ther.
1999;
41
183-186
-
17
Haider S, Nafziger D, Gutierrez J A, Brar I, Mateo N, Fogle J.
Progressive multifocal leukoencephalopathy and idiopathic CD4+lymphocytopenia: a case report and review of reported cases.
Clin Infect Dis.
2000;
31 (4)
E20-22
-
18
Happe S. et al .
Cidofovir (vistide) in therapy of progressive multifocal leukoencephalopathy in AIDS. Review of the literature and report of 2 cases.
Der Nervenarzt.
1999;
70 (10)
935-943
-
19
Happe S. et al .
Progressive multifokale Leukoenzephalopathie im Verlauf der AIDS-Erkrankung.
Der Nervenarzt.
2000;
71
96-104
-
20
Holzapfel C. et al .
Progressive multifocal leukoencephalopathy (PML) as an opportunistic infection in chronic lymphatic leukaemia (CLL). Review of the literature and case report.
Der Nervenarzt.
2002;
73 (6)
543-547
-
21
Houston S, Roberts N, Mashinter L.
Failure of cidofovir therapy in progressive multifocal leukoencephalopathy unrelated to human immunodeficiency virus.
Clin Infect Dis.
2001;
32 (1)
150-152
-
22
Inui K. et al .
Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a patient with HIV infection.
Brain Dev.
1999;
21 (6)
416-419
-
23
Jacobson M A, Wilson S, Stanley H, Holtzer C, Cherrington J, Safrin S.
Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.
Clin Infect Dis.
1999;
28 (3)
528-533
-
24
Kersten A J, Althaus C, Best J, Sundmacher R.
Cystoid macular edema following immune recovery and treatment with cidofovir for cytomegalovirus retinitis.
Graefe's Arch Clin Exp Ophthalmol.
1999;
237 (11)
893-896
-
25
Kirsch L S, Arevalo J F, Chavez de la Paz E, Munguia D, Clerq E de, Freeman W R.
Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with aquired immune deficiency syndrome.
Ophthalmology.
1995;
102 (4)
533-542
-
26
Labetoulle M, Goujard C, Frau E, Offret H, Delfraissy J F, Gasnault J.
Cidofovir ocular toxicity is related to previous ocular history.
AIDS.
2000;
31, 14 (5)
622-623
-
27
Ledergerber B. et al .
AIDS-related opportunistic illnesses occuring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study.
JAMA.
1999;
282 (23)
2220-2226
-
28
Martinez de la Casa J M, Matilla-Rodero M, Castillo A, Garcia Feijoo J, Garcia Sanchez J.
Ocular complications after treatment with intravenous cidofovir for cytomegalovirus retinitis.
Arch Soc Esp Oftalmol.
2001;
76 (4)
213-220
-
29 Pharmacia & Upjohn GmbH .Zusammenfassung der Merkmale des Arzneimittels Vistide. Anforderung: Bundesverband der Pharmazeutischen Industrie e. V., Stand der Information 17. Juni 1999
-
30
Plosker G L, Noble S.
Cidofovir: a review of its use in cytomegalovirus retinitis in patients with AIDS.
Drugs.
1999;
58 (2)
325-345
-
31
Portilla J, Boix V, Roman F, Reus S, Merino E.
Progressive multifocal leukoencephalopathy treated with cidofovir in HIV-infected patients receiving highly active anti-retroviral therapy.
J Infect.
2000;
41 (2)
182-184
-
32
Rougier M B. et al .
Anterior uveitis and cidofovir.
J Fr Ophtalmol.
2001;
24 (5)
491-495
-
33
Segarra-Newnham M, Vodolo K M.
Use of cidofovir in progressive multifocal leukoencephalopathy.
Ann Pharmacother.
2001;
35 (6)
741-744
-
34
Tantisiriwat W. et al .
Progressive multifocal leukoencephalopathy in patients with AIDS receiving highly active antiretroviral therapy.
Clin Infect Dis.
1999;
28 (5)
1152-1154
-
35
Taskintuna I. et al .
Adverse events and autopsy findings after intravitreous cidofovir (HPMPC) therapy in patients with acquired immune deficiency syndrom (AIDS).
Ophthalmology.
1997;
104 (11)
1827-1836
-
36
Taskintuna I. et al .
An animal model for cidofovir (HPMPC) toxicity: intraocular pressure and histopathologic effects.
Exp Eye Res.
1997;
64 (5)
795-806
-
37
Tseng A L, Mortimer C B, Salit I E.
Iritis associated with intravenous cidofovir.
Ann Pharmacother.
1999;
33 (2)
167-171
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