Skip to main content
Erschienen in: Documenta Ophthalmologica 3/2006

01.11.2006 | Original Paper

Retinal function and histopathology in rabbits treated with Topiramate

verfasst von: S. Kjellström, A. Bruun, B. Isaksson, T. Eriksson, S. Andréasson, V. Ponjavic

Erschienen in: Documenta Ophthalmologica | Ausgabe 3/2006

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate retinal function and histopathology in rabbits treated orally with the anti-epileptic drug topiramate.

Methods

Six rabbits were treated with a daily oral dose of topiramate during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition. Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.

Results

After eight months of treatment the full-field ERG demonstrated normal rod function in treated and control rabbits, but the light adapted 30 Hz flicker b-wave amplitude was significantly reduced in the treated rabbits. This was the case for both the light adapted (Wilcoxon signed ranks test, P = 0.046) and the dark adapted (Wilcoxon signed ranks test, P = 0.028) 30 Hz flicker response from the treated rabbits. Retinal immunohistology revealed a severe accumulation of GABA in amacrine cells and in the inner plexiform layer in 4 of 6 treated rabbits compared to the controls.

Conclusions

Topiramate, orally administrated to rabbits, may cause a significant reduction of the retinal function demonstrated by the reduced b-wave amplitude in the full-field ERG, as well as changes in immunohistology characterized by a severe accumulation of GABA in the inner retina. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another anti-epileptic drug).
Literatur
1.
Zurück zum Zitat Roff Hilton EJ, Hosking SL, Betts T (2004) The effect of antiepileptic drugs on visual performance. Seizure 13:113–128CrossRef Roff Hilton EJ, Hosking SL, Betts T (2004) The effect of antiepileptic drugs on visual performance. Seizure 13:113–128CrossRef
2.
Zurück zum Zitat Czapinski P, Blaszczyk B, Czuczwar SJ (2005) Mechanism of action of antiepileptic drugs. Curr Top Med Chem 5:3–14PubMedCrossRef Czapinski P, Blaszczyk B, Czuczwar SJ (2005) Mechanism of action of antiepileptic drugs. Curr Top Med Chem 5:3–14PubMedCrossRef
3.
Zurück zum Zitat Eke T, Talbot JF, Lawden MC (1997) Severe persistent visual field constriction associated with vigabatrin. Brit Med J 314:180–181PubMed Eke T, Talbot JF, Lawden MC (1997) Severe persistent visual field constriction associated with vigabatrin. Brit Med J 314:180–181PubMed
4.
Zurück zum Zitat Harding GA (1997) Severe persistent visual field constriction associated with vigabatrin (letter). Brit Med J 314:1694PubMed Harding GA (1997) Severe persistent visual field constriction associated with vigabatrin (letter). Brit Med J 314:1694PubMed
5.
Zurück zum Zitat Wilson EA, Brodie MJ (1997) Severe persistent visual field constriction associated with vigabatrin (letter). Brit Med J 314:1693PubMed Wilson EA, Brodie MJ (1997) Severe persistent visual field constriction associated with vigabatrin (letter). Brit Med J 314:1693PubMed
6.
Zurück zum Zitat Steinhoff J, Freudenthaler N, Paulus W (1997) The influence of established and new epileptic drugs on visual perception. Epilepsy Res 29:34–47 Steinhoff J, Freudenthaler N, Paulus W (1997) The influence of established and new epileptic drugs on visual perception. Epilepsy Res 29:34–47
7.
Zurück zum Zitat Harding GF, Wild JM, Robertson KA et al (2000) Separating the retinal electrophysiological effects of vigabatrin: treatment versus field loss. Neurology 55:347–352PubMedCrossRef Harding GF, Wild JM, Robertson KA et al (2000) Separating the retinal electrophysiological effects of vigabatrin: treatment versus field loss. Neurology 55:347–352PubMedCrossRef
8.
Zurück zum Zitat Coupland SG, Zackon DH, Leonard BC, Ross TM (2001) Vigabatrin effect on inner retinal function. Ophthalmology 109:1493–1498CrossRef Coupland SG, Zackon DH, Leonard BC, Ross TM (2001) Vigabatrin effect on inner retinal function. Ophthalmology 109:1493–1498CrossRef
9.
Zurück zum Zitat Ponjavic V, Andréasson S (2001) Multifocal ERG and full-field ERG in patients on long-term vigabatrin medication. Doc Ophthalmol 102:63–72PubMedCrossRef Ponjavic V, Andréasson S (2001) Multifocal ERG and full-field ERG in patients on long-term vigabatrin medication. Doc Ophthalmol 102:63–72PubMedCrossRef
10.
11.
Zurück zum Zitat Ioannides-Demos LL, Proietto J, McNeil JJ (2005) Pharmacotherapy for obesity. Drugs 65:1391–1418PubMedCrossRef Ioannides-Demos LL, Proietto J, McNeil JJ (2005) Pharmacotherapy for obesity. Drugs 65:1391–1418PubMedCrossRef
12.
Zurück zum Zitat Kaplan LM (2005) Pharmacological therapies for obesity. Gastroenterol Clin North Am 35:91–104CrossRef Kaplan LM (2005) Pharmacological therapies for obesity. Gastroenterol Clin North Am 35:91–104CrossRef
13.
Zurück zum Zitat Li Z, Maglione M, Tu W et al (2005) Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 142:532–546PubMed Li Z, Maglione M, Tu W et al (2005) Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 142:532–546PubMed
14.
Zurück zum Zitat Halpern A, Mancini MC (2005) Diabesity: are weight loss medications effective? Treat Endocrinol 4:65–74PubMedCrossRef Halpern A, Mancini MC (2005) Diabesity: are weight loss medications effective? Treat Endocrinol 4:65–74PubMedCrossRef
15.
Zurück zum Zitat Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J (2005) Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane Database Syst Rev CD004096 Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J (2005) Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane Database Syst Rev CD004096
16.
Zurück zum Zitat Pederson KJ, Roerig JL, Mitchell JE (2003) Towards the pharmacotherapy of eating disorders. Expert Opin Pharmacother 4:1659–1678PubMedCrossRef Pederson KJ, Roerig JL, Mitchell JE (2003) Towards the pharmacotherapy of eating disorders. Expert Opin Pharmacother 4:1659–1678PubMedCrossRef
17.
Zurück zum Zitat Hedges DW, Reimherr FW, Hoopes SP et al (2003) Treatment of bulimia nervosa with topiramate in a randomized double-blind, placebo-controlled trial, part 2: improvement in psychiatric measures. J Clin Psychitry 64:1449–1454CrossRef Hedges DW, Reimherr FW, Hoopes SP et al (2003) Treatment of bulimia nervosa with topiramate in a randomized double-blind, placebo-controlled trial, part 2: improvement in psychiatric measures. J Clin Psychitry 64:1449–1454CrossRef
18.
Zurück zum Zitat Appolinarion JC, McElroy SL (2004) Pharmacological approaches in the treatment of binge eating disorder. Curr Drug Targets 5:301–307CrossRef Appolinarion JC, McElroy SL (2004) Pharmacological approaches in the treatment of binge eating disorder. Curr Drug Targets 5:301–307CrossRef
19.
Zurück zum Zitat De Bernardi C, Ferraris S, D´Inella P, Do F, Torre E (2005) Topiramate for binge eating disorder. Prog Neuropsychopharmacol Biol Psychiatry 29:339–341PubMedCrossRef De Bernardi C, Ferraris S, D´Inella P, Do F, Torre E (2005) Topiramate for binge eating disorder. Prog Neuropsychopharmacol Biol Psychiatry 29:339–341PubMedCrossRef
20.
Zurück zum Zitat Winkelman JW (2003) Treatment of nocturnal eating syndrome and sleep-related eating disorder with topiramate. Sleep Med 4:243–246PubMedCrossRef Winkelman JW (2003) Treatment of nocturnal eating syndrome and sleep-related eating disorder with topiramate. Sleep Med 4:243–246PubMedCrossRef
21.
Zurück zum Zitat Pappagallo M (2003) Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther 25:2506–2538PubMedCrossRef Pappagallo M (2003) Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther 25:2506–2538PubMedCrossRef
22.
Zurück zum Zitat Lewis DW, Dimond S, Scott D, Jones V (2004) Prophylactic treatment of pediatric migraine. Headache 44:230–237PubMedCrossRef Lewis DW, Dimond S, Scott D, Jones V (2004) Prophylactic treatment of pediatric migraine. Headache 44:230–237PubMedCrossRef
23.
Zurück zum Zitat Diamond M, Dahlof C, Papadopoulos G, Neto W, Wu SC (2005) Topiramate improves health-related quality of life when used to prevent migraine. Headache 45:1023–1030PubMedCrossRef Diamond M, Dahlof C, Papadopoulos G, Neto W, Wu SC (2005) Topiramate improves health-related quality of life when used to prevent migraine. Headache 45:1023–1030PubMedCrossRef
24.
Zurück zum Zitat Blumenfeld A (2005) Clinical approaches to migraine prophylaxis. Am J Manag Care 11:S55–61PubMed Blumenfeld A (2005) Clinical approaches to migraine prophylaxis. Am J Manag Care 11:S55–61PubMed
25.
Zurück zum Zitat Brown JS, Papadopoulos G, Neumnn PJ, Friedman M, Miller JD, Menzin J (2005) Cost-effectiveness of topiramate in migraine prevention: results from a pharmacoeconomic model of topiramate treatment. Headache 45:1012–1022PubMedCrossRef Brown JS, Papadopoulos G, Neumnn PJ, Friedman M, Miller JD, Menzin J (2005) Cost-effectiveness of topiramate in migraine prevention: results from a pharmacoeconomic model of topiramate treatment. Headache 45:1012–1022PubMedCrossRef
26.
Zurück zum Zitat Bussone G, Diener HC, Pfeil J, Schwlen S (2005) Topiramate 100md/day in migraine prevention: pooled analysis of double-blind randomized controlled trials. Int J Clin Pract 59:961–968PubMedCrossRef Bussone G, Diener HC, Pfeil J, Schwlen S (2005) Topiramate 100md/day in migraine prevention: pooled analysis of double-blind randomized controlled trials. Int J Clin Pract 59:961–968PubMedCrossRef
27.
Zurück zum Zitat D´Amico D, Grzzi L, Usai S, Moschiano F, Bussone G (2005) Topiramate in migraine prophylaxis. Neurol Sci 26:130–133CrossRef D´Amico D, Grzzi L, Usai S, Moschiano F, Bussone G (2005) Topiramate in migraine prophylaxis. Neurol Sci 26:130–133CrossRef
28.
29.
Zurück zum Zitat Brandes JL (2005) Practical use of topiramate for migraine prevention. Headache 45:66–73CrossRef Brandes JL (2005) Practical use of topiramate for migraine prevention. Headache 45:66–73CrossRef
30.
Zurück zum Zitat White HS (2005) Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache 45:S48–56PubMedCrossRef White HS (2005) Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache 45:S48–56PubMedCrossRef
31.
Zurück zum Zitat Campistol J, Campos J, Casa C, Herranz JL (2005) Topiramate in the prophylactic treatment of migraine in children. J Child Neurol 20:251–253PubMed Campistol J, Campos J, Casa C, Herranz JL (2005) Topiramate in the prophylactic treatment of migraine in children. J Child Neurol 20:251–253PubMed
32.
Zurück zum Zitat Wang PW, Ketter TA, Becker OV, Nowakowska C (2003) New anticonvulsant medication uses in bipolar disorder. CNS Spectr 8:941–947 Wang PW, Ketter TA, Becker OV, Nowakowska C (2003) New anticonvulsant medication uses in bipolar disorder. CNS Spectr 8:941–947
33.
Zurück zum Zitat Dunner DL (2005) Safety and tolerability of emerging pharmacological treatments for bipolar disorder. Bipolar Disord 7:307–325PubMedCrossRef Dunner DL (2005) Safety and tolerability of emerging pharmacological treatments for bipolar disorder. Bipolar Disord 7:307–325PubMedCrossRef
34.
Zurück zum Zitat Gajwani P, Fortshoff A, Muzina D et al (2005) Antiepileptic drugs in mood-disordered patients. Epilepsia 46:38–44PubMedCrossRef Gajwani P, Fortshoff A, Muzina D et al (2005) Antiepileptic drugs in mood-disordered patients. Epilepsia 46:38–44PubMedCrossRef
35.
36.
Zurück zum Zitat Janowsky DS, Kraus JE, Barnhill J, Elmir B, Davis JM (2003) Effects of topiramate on aggressive, self-injurious, and disruptive/destructive behaviors in the intellectually disabled, an open-label retrospective study. J Clin Psychopharmacol 23:500–504PubMedCrossRef Janowsky DS, Kraus JE, Barnhill J, Elmir B, Davis JM (2003) Effects of topiramate on aggressive, self-injurious, and disruptive/destructive behaviors in the intellectually disabled, an open-label retrospective study. J Clin Psychopharmacol 23:500–504PubMedCrossRef
37.
Zurück zum Zitat Gatto EM, Roca MC, Raina G, Micheli F (2003) Low doses of topiramate are effective in essential tremor: a report of three cases. Clin Neuropharmacol 26:294–296PubMedCrossRef Gatto EM, Roca MC, Raina G, Micheli F (2003) Low doses of topiramate are effective in essential tremor: a report of three cases. Clin Neuropharmacol 26:294–296PubMedCrossRef
38.
Zurück zum Zitat Fhager B, Meiri IM, Sjogren M, Edman A (2003) Treatment of aggressive behavior in dementia with the anticonvulsant topiramate: a retrospective pilot study. Int Psychogeriatr 15:307–309PubMedCrossRef Fhager B, Meiri IM, Sjogren M, Edman A (2003) Treatment of aggressive behavior in dementia with the anticonvulsant topiramate: a retrospective pilot study. Int Psychogeriatr 15:307–309PubMedCrossRef
39.
Zurück zum Zitat Asnis GM, Kohn SR, Henderson M, Brown NL (2004) SSRIs versus non SSRIs in post-traumatic stress disorder: an update with recommendations. Drugs 64:383–404PubMedCrossRef Asnis GM, Kohn SR, Henderson M, Brown NL (2004) SSRIs versus non SSRIs in post-traumatic stress disorder: an update with recommendations. Drugs 64:383–404PubMedCrossRef
40.
Zurück zum Zitat Nickel MK, Nickel C, Kpln P et al (2005) Treatment of aggression with topiramate in male borderline patients: a double-blind, placebo-controlled study. Biol Psychiatry 57:495–499PubMedCrossRef Nickel MK, Nickel C, Kpln P et al (2005) Treatment of aggression with topiramate in male borderline patients: a double-blind, placebo-controlled study. Biol Psychiatry 57:495–499PubMedCrossRef
41.
Zurück zum Zitat Tiihonen J, Hlonen P, Wahlbeck K et al (2005) Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychiatry 66:1012–1015PubMedCrossRef Tiihonen J, Hlonen P, Wahlbeck K et al (2005) Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychiatry 66:1012–1015PubMedCrossRef
42.
Zurück zum Zitat Arnone D (2005) Review of the use of topiramate for treatment of psychiatric disorders. Ann Gen Psychiatry 16:5CrossRef Arnone D (2005) Review of the use of topiramate for treatment of psychiatric disorders. Ann Gen Psychiatry 16:5CrossRef
43.
Zurück zum Zitat Anderson N, Oliver MN (2003) Oral topiramate effective for alcoholism. J Fam Pract 52:682–683, 687 Anderson N, Oliver MN (2003) Oral topiramate effective for alcoholism. J Fam Pract 52:682–683, 687
44.
Zurück zum Zitat Raguraman J, Priyadharshini RK, Chandrasekarn (2005) Effects of topiramate in alcohol dependence. Aust N Z J Psychiatry 39:736–737 Raguraman J, Priyadharshini RK, Chandrasekarn (2005) Effects of topiramate in alcohol dependence. Aust N Z J Psychiatry 39:736–737
45.
Zurück zum Zitat Johnson BA, Ait-Daoud N, Akhtar FZ, Jvors MA (2005) Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: a randomized controlled trial. Arch Intern Med 165:1600–1605PubMedCrossRef Johnson BA, Ait-Daoud N, Akhtar FZ, Jvors MA (2005) Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: a randomized controlled trial. Arch Intern Med 165:1600–1605PubMedCrossRef
46.
Zurück zum Zitat Book SW, Myrick H (2005) Novel anticonvulsants in the treatment of alcoholism. Expert Opin Investig Drugs 14:371–376PubMedCrossRef Book SW, Myrick H (2005) Novel anticonvulsants in the treatment of alcoholism. Expert Opin Investig Drugs 14:371–376PubMedCrossRef
47.
Zurück zum Zitat Rubio G, Ponce G, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F (2005) Effects of topiramate in the treatment of alcohol dependence. Pharmacopsychiatry 37:37–40 Rubio G, Ponce G, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F (2005) Effects of topiramate in the treatment of alcohol dependence. Pharmacopsychiatry 37:37–40
48.
Zurück zum Zitat Sofouglu M, Kosten TR (2005) Novel approaches to the treatment of cocaine addiction. CNS Drugs 19:13–25CrossRef Sofouglu M, Kosten TR (2005) Novel approaches to the treatment of cocaine addiction. CNS Drugs 19:13–25CrossRef
49.
Zurück zum Zitat Artemowitz B, Sobaniec W (2005) Neuroprotection possibilities in epileptic children. Rocz Akad Med Bialymst 50:91–95 Artemowitz B, Sobaniec W (2005) Neuroprotection possibilities in epileptic children. Rocz Akad Med Bialymst 50:91–95
50.
Zurück zum Zitat Al Ajlouni S, Shorman A, Daoud AS. The efficacy of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial. Seizure 2005: [Epub ahead of print] Al Ajlouni S, Shorman A, Daoud AS. The efficacy of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial. Seizure 2005: [Epub ahead of print]
51.
Zurück zum Zitat Hershey AD, Winner PK (2005) Pediatric migraine: recognition and treatment. J Am Osteopath Assoc 105:2S–8SPubMed Hershey AD, Winner PK (2005) Pediatric migraine: recognition and treatment. J Am Osteopath Assoc 105:2S–8SPubMed
52.
Zurück zum Zitat Gjörloff K, Andréasson S, Ehinger B (2004) Standardized full-field electroretinography in rabbits. Doc Ophthalmol 109:163–168PubMedCrossRef Gjörloff K, Andréasson S, Ehinger B (2004) Standardized full-field electroretinography in rabbits. Doc Ophthalmol 109:163–168PubMedCrossRef
53.
Zurück zum Zitat Ponjavic V, Gränse L, Kjellström S, Andréasson S, Bruun A (2004) Alterations in electroretinograms and retinal morphology in rabbits treated with Vigabatrin. Doc Ophthalmol 00:1–9 Ponjavic V, Gränse L, Kjellström S, Andréasson S, Bruun A (2004) Alterations in electroretinograms and retinal morphology in rabbits treated with Vigabatrin. Doc Ophthalmol 00:1–9
54.
Zurück zum Zitat Marmor MF, Holder GE, Seelinger MW, Yamamoto S (2004) International Society for Clinical Electrophysiology of Vision. Standard for clinical electroretinography (2004 update). Doc Ophthalmol 108:107–114PubMedCrossRef Marmor MF, Holder GE, Seelinger MW, Yamamoto S (2004) International Society for Clinical Electrophysiology of Vision. Standard for clinical electroretinography (2004 update). Doc Ophthalmol 108:107–114PubMedCrossRef
55.
Zurück zum Zitat Hauser W (1997) Incidence and prevalence. In: Engel J, Pedley T (eds) Epilepsy: a comprehensive textbook. Lippincott-Raven Publishers, Philadelphia, pp. 47–57 Hauser W (1997) Incidence and prevalence. In: Engel J, Pedley T (eds) Epilepsy: a comprehensive textbook. Lippincott-Raven Publishers, Philadelphia, pp. 47–57
56.
Zurück zum Zitat Fraunfelder FW, Fraunfelder F (2004) Adverse ocular drug reactions recently identified by the national registry of drug-induced ocular side effects. Ophthalmology 111:1275–1279PubMedCrossRef Fraunfelder FW, Fraunfelder F (2004) Adverse ocular drug reactions recently identified by the national registry of drug-induced ocular side effects. Ophthalmology 111:1275–1279PubMedCrossRef
57.
Zurück zum Zitat Foroozan R, Buono LM (2003) Clinical challenges: foggy visual field defect. Surv Ophthalmol 48:447–451PubMedCrossRef Foroozan R, Buono LM (2003) Clinical challenges: foggy visual field defect. Surv Ophthalmol 48:447–451PubMedCrossRef
58.
Zurück zum Zitat Vaphiades MS, Mason J (2003) Letter to the editor: foggy visual field defect. Surv Ophthalmol 49:266–267CrossRef Vaphiades MS, Mason J (2003) Letter to the editor: foggy visual field defect. Surv Ophthalmol 49:266–267CrossRef
Metadaten
Titel
Retinal function and histopathology in rabbits treated with Topiramate
verfasst von
S. Kjellström
A. Bruun
B. Isaksson
T. Eriksson
S. Andréasson
V. Ponjavic
Publikationsdatum
01.11.2006
Verlag
Springer-Verlag
Erschienen in
Documenta Ophthalmologica / Ausgabe 3/2006
Print ISSN: 0012-4486
Elektronische ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-006-9027-8

Weitere Artikel der Ausgabe 3/2006

Documenta Ophthalmologica 3/2006 Zur Ausgabe

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Die Verwendung von Ophthalmika in der Schwangerschaft und Stillzeit stellt immer eine Off-label-Anwendung dar. Ein Einsatz von Arzneimitteln muss daher besonders sorgfältig auf sein Risiko-Nutzen-Verhältnis bewertet werden. In der vorliegenden …

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Vitrektomie Originalie

Die endogene Endophthalmitis ist eine hämatogen fortgeleitete, bakterielle oder fungale Infektion, die über choroidale oder retinale Gefäße in den Augapfel eingeschwemmt wird [ 1 – 3 ]. Von dort infiltrieren die Keime in die Netzhaut, den …

Bakterielle endogene Endophthalmitis

Vitrektomie Leitthema

Eine endogene Endophthalmitis stellt einen ophthalmologischen Notfall dar, der umgehender Diagnostik und Therapie bedarf. Es sollte mit geeigneten Methoden, wie beispielsweise dem Freiburger Endophthalmitis-Set, ein Keimnachweis erfolgen. Bei der …

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Die bestmögliche Wundheilung der Kornea, insbesondere ohne die Ausbildung von lichtstreuenden Narben, ist oberstes Gebot, um einer dauerhaften Schädigung der Hornhaut frühzeitig entgegenzuwirken und die Funktion des Auges zu erhalten.   

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.