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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-04-2016 | Neurophthalmology

Levodopa as a possible treatment of visual loss in nonarteritic anterior ischemic optic neuropathy

Authors: Deanna P. Lyttle, Lenworth N. Johnson, Edward A. Margolin, Richard W. Madsen

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 4/2016

Abstract

Purpose

To determine the clinical effectiveness and potential neuroprotection of levodopa in improving visual acuity, visual field, and retinal nerve fiber layer (RNFL) thickness in eyes affected by NAION.

Method

Retrospective cohort study involving 59 eyes of 59 participants with NAION who were evaluated within 15 days of NAION onset. Participants received 25 mg carbidopa/100 mg levodopa three times daily with meals for 12 weeks (levodopa group) or were untreated (control group). Best-corrected visual acuity converted to logMAR, mean deviation (MD) threshold sensitivity on automated perimetry, and mean RNFL thickness on optical coherence tomography (OCT) were assessed. The primary outcome was the categorization of eyes into improved visual acuity (by 0.3 logMAR difference), worsened visual acuity (by 0.3 logMAR difference), or no change in visual acuity. The proportions in each category were compared between the levodopa and control groups.

Results

Among participants with 20/60 or worse initial visual acuity, levodopa-treated participants had significant improvement (P < 0.0001) in the mean change from initial to final logMAR visual acuity of −0.74 ± 0.56 (95 % CI, −0.98 to −0.50), while the mean change for the control group at −0.37 ± 1.09 (95 % confidence interval estimate, −1.00 to +0.26) was not significant (P = 0.23). A significant difference between groups was observed (P = 0.0086) such that 19/23 (83 %) in the levodopa group improved and none got worse, as compared with 6/14 (43 %) in the control group improving while four (29 %) worsened. The change in visual field MD and RNFL thickness on OCT showed no significant difference at P = 0.23 and P = 0.75 respectively. No levodopa-treated participant had any adverse event from the levodopa.

Conclusions

Treatment within 15 days of onset of NAION with levodopa improved central visual acuity by an average of 6 lines on Snellen acuity chart. Levodopa may promote neuroprotection of the maculopapular retinal ganglion cell fibers in NAION.

Johnson LN, Arnold AC (1994) Incidence of nonarteritic and arteritic anterior ischemic optic neuropathy: population-based study in the State of Missouri and Los Angeles County. J Neuro-Ophthalmol 14:38–44CrossRef

Hattenhauer MG, Leavitt JA, Hodge DO, Grill R, Gray DT (1997) Incidence of nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 123:103–107CrossRefPubMed

The Ischemic Optic Neuropathy Decompression Trial (IONDT) Research Group (1995) Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful: results of the Ischemic Optic Neuropathy Decompression Trial. JAMA 273:625–632CrossRef

Newman NJ, Scherer R, Langenberg P, Kelman S et al (2002) The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol 134:317–328CrossRefPubMed

Johnson LN (2003) Chlamydia pneumoniae Seropositivity and the risk of nonarteritic anterior ischemic optic neuropathy (NAION). Ophthalmology 110:1067–1069CrossRefPubMed

Johnson LN (1998) Nonarteritic anterior ischemic optic neuropathy. J Am Optom Assoc 69:422–423PubMed

Johnson LN, Krohel GB, Allen SD, Mozayeni R (1996) Recurrent herpes labialis as a potential risk factor for nonarteritic anterior ischemic optic neuropathy. J Natl Med Assoc 88:369–373PubMedPubMedCentral

Johnson LN, Kuo HC, Arnold AC (1993) Human Leukocyte Antigen (HLA-A29) as a potential risk factor for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 115:540–541CrossRefPubMed

Burde RM (1993) Optic disk risk factors for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 116:759–764CrossRefPubMed

10.

Kerr NM, Chew SS, Danesh-Meyer HV (2009) Non-arteritic anterior ischaemic optic neuropathy: a review and update. J Clin Neurosci 16:994–1000CrossRefPubMed

11.

Mojon DS, Hedges TR 3rd, Ehrenberg B, Karam EZ et al (2002) Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol 120:601–605CrossRefPubMed

12.

Beck RW, Servais GE, Hayreh SS (1987) Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology 94:1503–1508CrossRefPubMed

13.

Deramo VA, Sergott RC, Augsburger JJ, Foroozan R et al (2003) Ischemic optic neuropathy as the first manifestation of elevated cholesterol levels in young patients. Ophthalmology 110:1041–1046CrossRefPubMed

14.

Fry CL, Carter JE, Kanter MC et al (1993) Anterior ischemic optic neuropathy is not associated with carotid artery atherosclerosis. Stroke 24:539–542CrossRefPubMed

15.

Johnson LN, Botelho PJ, Kuo HC (1994) Is smoking a risk factor for NAION? Ophthalmology 101:1322–1324CrossRefPubMed

16.

Müller M, Wessel K, Mehdorn E, Kompf D et al (1993) Carotid artery disease in vascular ocular syndromes. J Clin Neuroophthalmol 13:175–180PubMed

17.

Hayreh SS, Jonas JB, Zimmerman MB (2007) Nonarteritic anterior ischemic optic neuropathy and tobacco smoking. Ophthalmology 114:804–809CrossRefPubMed

18.

Knox DL, Kerrison JB, Green WR (2000) Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc 98:203–222PubMedPubMedCentral

19.

Odette JD, Okorodudu DO, Johnson LN (2011) Early diabetes mellitus or hypertension is not significantly associated with severity of visual loss in nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol 129:1106–1107CrossRefPubMed

20.

Botelho PJ, Johnson LN, Arnold AC (1996) The effect of aspirin on the visual outcome of nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 121:450–451CrossRefPubMed

21.

Aptel F, Khayi H, Pépin JL, Tamisier R et al (2015) Association of nonarteritic ischemic optic neuropathy with obstructive sleep apnea syndrome. Consequences for obstructive sleep apnea screening and treatment. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2015.0893, Published online April 30, 2015 PubMed

22.

Hayreh SS, Zimmerman MB, Podhajsky P, Alward WL (1994) Nocturnal arterial hypotension and its role in optic nerve head and ocular ischemic disorders. Am J Ophthalmol 117:603–624CrossRefPubMed

23.

Hayreh SS (2001) Blood flow in the optic nerve head and factors that may influence it. Prog Retin Eye Res 20:595–624CrossRefPubMed

24.

Levin LA, Louhab A (1996) Apoptosis of retinal ganglion cells in anterior ischemic optic neuropathy. Arch Ophthalmol 114:488–491CrossRefPubMed

25.

Nork TM, Kim CBY, Shanmuganayagam D, Van Lysel MS et al (2006) Measurement of regional choroidal blood flow in rabbits and monkeys using fluorescent microspheres. Arch Ophthalmol 124:860–868CrossRefPubMed

26.

Alm A, Bill A (1987) Ocular circulation. In: Moses RA, Hart WH Jr (eds) Adler’s physiology of the eye clinical application, 8th edn. Mosby, St. Louis, pp 183–203, Fig 6–11, pg 191

27.

Parsa CF, Hoyt WF (2015) Nonarteritic anterior ischemic optic neuropathy (NAION): a misnomer. Rearranging pieces of a puzzle to reveal a nonischemic papillopathy caused by vitreous separation. Ophthalmology 122:439–442CrossRefPubMed

28.

Atkins EJ, Bruce BB, Newman NJ, Biousse V (2010) Treatment of nonarteritic anterior ischemic optic neuropathy. Surv Ophthalmol 55:47–63CrossRefPubMedPubMedCentral

29.

Nicholson JD, Leiba H, Goldenberg-Cohen N (2014) Translational preclinical research may lead to improved medical management of non-arteritic anterior ischemic optic neuropathy. Front Neurol 5:1–5

30.

Golan S, Waisbourd M, Kesler A (2011) Nonarteritic anterior ischemic optic neuropathy — an update. J Clin Exp Ophthalmol S3:001,1–10

31.

Parisi V, Coppola G, Ziccardi L, Gallinaro G et al (2008) Cytidine-5′-diphosphocholine (citicoline): a pilot study in patients with non-arteritic ischaemic optic neuropathy. Eur J Neurol 15:465–474CrossRefPubMed

32.

Johnson LN, Gould TJ, Krohel GB (1996) Effect of levodopa and carbidopa on recovery of visual function in patients with nonarteritic anterior ischemic optic neuropathy of longer than six months duration. Am J Ophthalmol 121:77–83CrossRefPubMed

33.

Johnson LN, Guy ME, Krohel GB, Madsen RW (2000) Levodopa may improve vision loss in recent onset nonarteritic anterior ischemic optic neuropathy. Ophthalmology 107:521–526CrossRefPubMed

34.

Johnson LN, Aminlari A, Sassani JW (1993) Effect of intermittent versus continuous patient monitoring on reliability indices during automated perimetry. Ophthalmology 100:76–84CrossRefPubMed

35.

Knight OJ, Chang RT, Feuer WJ, Budenz DL (2009) Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology 116:1271–1277CrossRefPubMedPubMedCentral

36.

Contreras I, Noval S, Rebolleda G, Munoz-Negrete FJ (2007) Follow-up of nonarteritic anterior ischemic optic neuropathy with optical coherence tomography. Ophthalmology 114:2338–2344CrossRefPubMed

37.

Rebolleda G, Perez-Lopez M, Casas-Llera P, Contreras I et al (2013) Visual and anatomical outcomes of non-arteritic anterior ischemic optic neuropathy with high-dose systemic corticosteroids. Graefes Arch Clin Exp Ophthalmol 251:255–260CrossRefPubMed

38.

Bellusci C, Savini G, Carbonelli M, Carelli V et al (2008) Retinal nerve fiber layer thickness in nonarteritic anterior ischemic optic neuropathy: OCT characterization of the acute and resolving phases. Graefes Arch Clin Exp Ophthalmol 246:641–647CrossRefPubMed

39.

Razeghinejad MR, Rahat F, Bagheri M (2010) Levodopa-carbidopa may improve vision loss in indirect traumatic optic neuropathy. J Neurotrauma 27:1905–1909CrossRefPubMed

40.

Gottlob I, Stangler-Zuschrott E (1990) Effect of levodopa on contrast sensitivity and scotomas in human amblyopia. Invest Ophthalmol Vis Sci 31:776–780PubMed

41.

Leguire LE, Rogers GL, Bremer DL, Walson PD et al (1993) Levodopa/carbidopa for childhood amblyopia. Invest Ophthalmol Vis Sci 34:3090–3095PubMed

42.

Gottlob I, Charlier J, Reinecke RD (1992) Visual acuities and scotomas after one week levodopa administration in human amblyopia. Invest Ophthalmol Vis Sci 33:2722–2728PubMed

43.

Repka MX, Kraker RT, Beck RW, Atkinson SC et al (2010) A pilot study of levodopa dosage as treatment for residual amblyopia in children 8 to <18 years old. Arch Ophthalmol 128:1215–1217CrossRefPubMedPubMedCentral

44.

Pediatric Eye Disease Investigator Group (PEDIG), Repka MX, Kraker RT, Dean TW, Beck RW et al (2015) A randomized trial of levodopa as treatment for residual amblyopia in older children. Ophthalmology 122:874–881CrossRef

45.

Simsek T, Eryilmaz T, Acaroglu G (2005) Efficacy of levodopa and carbidopa on visual function in patients with non-arteritic anterior ischaemic optic neuropathy. Int J Clin Pract 59:287–290CrossRefPubMed

46.

Ghanbari H, Dehghani A (2000) Levodopa plus carbidopa: is it effective in nonarteritic anterior ischemic optic neuropathy management? J Res Med Sci 5:60

47.

Johnson LN, Harris Lyttle DP, Petroski GF (2014) Visual recovery and OCT changes following treatment of nonarteritic anterior ischemic optic neuropathy with levodopa, allopurinol and tetracycline. Invest Ophthalmol Vis Sci 55:6220

48.

Levin LA (2007) Axonal loss and neuroprotection in optic neuropathies. Can J Ophthalmol 42:403–408CrossRefPubMed

49.

Mora-Ferrer C, Neumeyer C (2009) Neuropharmacology of vision in goldfish: a review. Vis Res 49:960–969CrossRefPubMed

50.

Ventura AL, de Mello FG, de Melo Reis RA (2013) Methods of dopamine research in retina cells. Methods Mol Biol 964:25–42CrossRefPubMed

51.

Vaarmann A, Kovac S, Holmström KM, Gandhi S et al (2013) Dopamine protects neurons against glutamate-induced excitotoxicity. Cell Death Dis 4, e455CrossRefPubMedPubMedCentral

52.

Harnois C, Di Paolo T (1990) Decreased dopamine in the retinas of patients with Parkinson’s disease. Invest Ophthalmol Vis Sci 31:2473–2475PubMed

53.

Yavas GF, Yilmaz O, Küsbeci T, Oztürk F (2007) The effect of levodopa and dopamine agonists on optic nerve head in Parkinson disease. Eur J Ophthalmol 17:812–816PubMed

54.

Kashii S, Takahashi M, Mandai M, Shimizu H et al (1994) Protective action of dopamine against glutamate neurotoxicity in the retina. Invest Ophthalmol Vis Sci 35:685–695PubMed

55.

Olanow CW (2009) Can we achieve neuroprotection with currently available anti-parkinsonian interventions? Neurology 72(Suppl2):S59–S64CrossRefPubMed

56.

Nair VD, Olanow CW, Sealfon SC (2003) Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines. Biochem J 373:25–32CrossRefPubMedPubMedCentral

Title: Levodopa as a possible treatment of visual loss in nonarteritic anterior ischemic optic neuropathy
Authors: Deanna P. Lyttle
Lenworth N. Johnson
Edward A. Margolin
Richard W. Madsen
Publication date: 01-04-2016
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 4/2016
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-015-3191-z

At a glance: The STEP trials

Springer Medicine

Levodopa as a possible treatment of visual loss in nonarteritic anterior ischemic optic neuropathy

Abstract

Purpose

Method

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Method

Results

Conclusions

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