Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease

William Seiple, Danna Jennings, Richard B Rosen, Leona Borchert, Lee Canale, Nora Fagan, Mark Forrest Gordon, William Seiple, Danna Jennings, Richard B Rosen, Leona Borchert, Lee Canale, Nora Fagan, Mark Forrest Gordon

Abstract

Background. Parkinson's disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and ropinirole in patients with early idiopathic PD with ≤6 months' prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole (n = 121) or ropinirole (n = 125) for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus ropinirole was 1.07 (95% CI: 0.71-1.60). Mean changes from baseline in Unified Parkinson's Disease Rating System parts II+III total scores (pramipexole: 1 year, -4.1 ± 8.9, and 2 years, -0.7 ± 10.1, and ropinirole: 1 year, -3.7 ± 8.2, and 2 years, -1.7 ± 10.5) and Hoehn-Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300.

Conflict of interest statement

Dr. Seiple discloses receiving fees from Boehringer Ingelheim for leading the ERG Reading Center and reading all ERG data during the conduct of the study. Dr. Jennings has nothing to disclose. Dr. Rosen discloses receiving fees from Boehringer Ingelheim for Expert Panel participation in reviewing all COA components during the conduct of the study. Dr. Borchert, Ms. Fagan, and Dr. Gordon disclose employment by Boehringer Ingelheim. Ms. Canale discloses employment by Boehringer Ingelheim at the time the study was conducted.

Figures

Figure 1
Figure 1
Subject disposition. Among the 55 patients who failed screening, 45 did not meet inclusion/exclusion criteria, 1 was lost to follow-up, 6 withdrew consent (for reasons not involving adverse events), and 3 had other reasons. aFor reasons other than adverse events. bThe FAS includes all patients from the treated set who had a baseline and at least 1 postbaseline comprehensive ophthalmology assessment (COA). AE: adverse event and FA: full analysis set.

References

    1. Archibald N. K., Clarke M. P., Mosimann U. P., Burn D. J. The retina in Parkinsons disease. Brain. 2009;132(5):1128–1145. doi: 10.1093/brain/awp068.
    1. Armstrong R. A. Visual symptoms in Parkinson's disease. Parkinson's Disease. 2011;2011:9. doi: 10.4061/2011/908306.908306
    1. Nguyen-Legros J. Functional neuroarchitecture of the retina: hypothesis on the dysfunction of retinal dopaminergic circuitry in Parkinson's disease. Surgical and Radiologic Anatomy. 1988;10(2):137–144. doi: 10.1007/BF02307822.
    1. Harnois C., Di Paolo T. Decreased dopamine in the retinas of patients with Parkinson's disease. Investigative Ophthalmology and Visual Science. 1990;31(11):2473–2475.
    1. Inzelberg R., Ramirez J. A., Nisipeanu P., Ophir A. Retinal nerve fiber layer thinning in Parkinson disease. Vision Research. 2004;44(24):2793–2797. doi: 10.1016/j.visres.2004.06.009.
    1. Miyasaki J. M., Martin W., Suchowersky O., Weiner W. J., Lang A. E. Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2002;58(1):11–17. doi: 10.1212/wnl.58.1.11.
    1. Pahwa R., Factor S. A., Lyons K. E., et al. Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):983–995. doi: 10.1212/01.wnl.0000215250.82576.87.
    1. Ferreira J. J., Katzenschlager R., Bloem B. R., et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. European Journal of Neurology. 2013;20(1):5–15. doi: 10.1111/j.1468-1331.2012.03866.x.
    1. Boehringer Ingelheim Pharmaceuticals Inc. MirapexⓇ (pramipexole dihydrochloride) prescribing information, 2016, .
    1. GlaxoSmithKline, REQUIP® (ropinirole tablets) prescribing information, 2014, .
    1. UCB Inc. NeuproⓇ (Rotigotine Transdermal System) prescribing information, 2007, .
    1. Hardus P., Verduin W. M., Engelsman M., et al. Visual field loss associated with vigabatrin: quantification and relation to dosage. Epilepsia. 2001;42(2):262–267. doi: 10.1046/j.1528-1157.2001.15000.x.
    1. Van der Torren K., Graniewski-Wijnands H. S., Polak B. C. P. Visual field and electrophysiological abnormalities due to vigabatrin. Documenta Ophthalmologica. 2002;104(2):181–188. doi: 10.1023/A:1014615517996.
    1. Goetz C. G., Poewe W., Rascol O., et al. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Movement Disorders. 2004;19(9):1020–1028. doi: 10.1002/mds.20213.
    1. Fahn S., Elton R. Members of the UPDRS development committee. In: Fahn S., Marsden C. D., Calne D. B., Goldstein M., editors. Recent Developments in Parkinson's Disease. Vol. 2. Florham Park, NJ, USA: Macmillan Health Care Information; 1987. pp. 293–304.
    1. Gittings N. S., Fozard J. L. Age related changes in visual acuity. Experimental Gerontology. 1986;21(4-5):423–433. doi: 10.1016/0531-5565(86)90047-1.
    1. Erb C., Adler M., Stübiger N., Wohlrab M., Zrenner E., Thiel H.-J. Colour vision in normal subjects tested by the colour arrangement test ‘Roth 28-hue desaturated’. Vision Research. 1998;38(21):3467–3471. doi: 10.1016/s0042-6989(97)00433-1.
    1. Seiple W., Vajaranant T. S., Szlyk J. P., et al. Multifocal electroretinography as a function of age: the importance of normative values for older adults. Investigative Ophthalmology & Visual Science. 2003;44(4):1783–1792. doi: 10.1167/iovs.02-0518.
    1. Stemplewitz B., Keserü M., Bittersohl D., et al. Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease. Acta Ophthalmologica. 2015;93(8):e672–e677. doi: 10.1111/aos.12764.
    1. Bittersohl D., Stemplewitz B., Keserü M., Buhmann C., Richard G., Hassenstein A. Detection of retinal changes in idiopathic Parkinson's disease using high-resolution optical coherence tomography and heidelberg retina tomography. Acta Ophthalmologica. 2015;93(7):e578–e584. doi: 10.1111/aos.12757.
    1. Garcia-Martin E., Satue M., Otin S., et al. Retina measurements for diagnosis of Parkinson disease. Retina. 2014;34(5):971–980. doi: 10.1097/iae.0000000000000028.
    1. Steele J. C., Wresch R., Hanlon S. D., Keystone J., Ben-Shlomo Y. A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism-Dementia complex of Guam. Movement Disorders. 2015;30(9):1271–1275. doi: 10.1002/mds.26264.
    1. Yin F., Tian Z.-M., Liu S., et al. Transplantation of human retinal pigment epithelium cells in the treatment for Parkinson disease. CNS Neuroscience and Therapeutics. 2012;18(12):1012–1020. doi: 10.1111/cns.12025.
    1. Patil H., Saha A., Senda E., et al. Selective impairment of a subset of Ran-GTP-binding domains of Ran-binding protein 2 (Ranbp2) suffices to recapitulate the degeneration of the retinal pigment epithelium (RPE) triggered by Ranbp2 ablation. The Journal of Biological Chemistry. 2014;289(43):29767–29789. doi: 10.1074/jbc.m114.586834.
    1. Björnsson Ó. M., Syrdalen P., Bird A. C., Peto T., Kinge B. The prevalence of age-related maculopathy (ARM) in an urban Norwegian population: The Oslo Macular Study. Acta Ophthalmologica Scandinavica. 2006;84(5):636–641. doi: 10.1111/j.1600-0420.2006.00696.x.
    1. Jonasson F., Arnarsson A., Sasaki H., Peto T., Sasaki K., Bird A. C. The prevalence of age-related maculopathy in Iceland: reykjavik eye study. Archives of Ophthalmology. 2003;121(3):379–385. doi: 10.1001/archopht.121.3.379.
    1. Krishnan T., Ravindran R. D., Murthy G. V. S., et al. Prevalence of early and late age-related macular degeneration in India: the INDEYE study. Investigative Ophthalmology and Visual Science. 2010;51(2):701–707. doi: 10.1167/iovs.09-4114.
    1. Silvestri G., Williams M. A., McAuley C., et al. Drusen prevalence and pigmentary changes in Caucasians aged 18–54 years. Eye. 2012;26(10):1357–1362. doi: 10.1038/eye.2012.165.
    1. Jaffe M. J., Bruno G., Campbell G., Lavine R. A., Karson C. N., Weinberger D. R. Ganzfeld electroretinographic findings in parkinsonism: untreated patients and the effect of levodopa intravenous infusion. Journal of Neurology, Neurosurgery & Psychiatry. 1987;50(7):847–852. doi: 10.1136/jnnp.50.7.847.
    1. Schneider T., Zrenner E. The effect of fluphenazine on rod-mediated retinal responses. Documenta Ophthalmologica. 1987;65(3):287–296. doi: 10.1007/BF00149935.
    1. Li L., Dowling J. E. Effects of dopamine depletion on visual sensitivity of zebrafish. Journal of Neuroscience. 2000;20(5):1893–1903.
    1. Klein R., Klein B. E. K., Linton K. L. P., De Mets D. L. The Beaver Dam Eye Study: visual acuity. Ophthalmology. 1991;98(8):1310–1315. doi: 10.1016/s0161-6420(91)32137-7.
    1. Birch D. G., Anderson J. L. Standardized full-field electroretinography: normal values and their variation with age. Archives of Ophthalmology. 1992;110(11):1571–1576. doi: 10.1001/archopht.1992.01080230071024.
    1. Jaffe G. J., Alvarado J. A., Juster R. P. Age-related changes of the normal visual field. Archives of Ophthalmology. 1986;104(7):1021–1025. doi: 10.1001/archopht.1986.01050190079043.
    1. Brusini P. Ageing and visual field data. British Journal of Ophthalmology. 2007;91(10):1257–1258. doi: 10.1136/bjo.2007.117978.
    1. Spry P. G. D., Johnson C. A. Senescent changes of the normal visual field: an age-old problem. Optometry and Vision Science. 2001;78(6):436–441. doi: 10.1097/00006324-200106000-00017.
    1. Rudolph T., Frisén L. Influence of ageing on visual field defects due to stable lesions. British Journal of Ophthalmology. 2007;91(10):1276–1278. doi: 10.1136/bjo.2006.112508.
    1. Müller T., Kuhn W., Büttner T., Przuntek H. Distorted colour discrimination in Parkinson's disease is related to severity of the disease. Acta Neurologica Scandinavica. 1997;96(5):293–296.
    1. Price M. J., Feldman R. G., Adelberg D., Kayne H. Abnormalities in color vision and contrast sensitivity in Parkinson’s disease. Neurology. 1992;42(4):887–890. doi: 10.1212/wnl.42.4.887.
    1. Veselá O., Růžička E., Jech R., et al. Colour discrimination impairment is not a reliable early marker of Parkinson's disease. Journal of Neurology. 2001;248(11):975–978. doi: 10.1007/s004150170051.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren