Advances in Therapy

, Volume 36, Issue 9, pp 2493–2505 | Cite as

Effects of Macuprev® Supplementation in Age-Related Macular Degeneration: A Double-Blind Randomized Morpho-Functional Study Along 6 Months of Follow-Up

  • Mariacristina Parravano
  • Massimiliano Tedeschi
  • Daniela Manca
  • Eliana Costanzo
  • Antonio Di Renzo
  • Paola Giorno
  • Lucilla Barbano
  • Lucia ZiccardiEmail author
  • Monica Varano
  • Vincenzo Parisi
Brief Report



To evaluate the effects of Macuprev® supplementation on macular function and structure in intermediate age-related macular degeneration (AMD) along 6 months of follow-up.


In this double-blind, monocentric, randomized, and prospective study, 30 patients with intermediate AMD were enrolled and randomly divided into two age-similar groups: 15 patients (AMD-M group; mean age 68.50 ± 8.79 years) received 6-month oral daily supplementation with Macuprev® (Farmaplus Italia s.r.l., Italy, two tablets/day on an empty stomach, before meals; contained in total lutein 20 mg, zeaxanthin 4 mg, N-acetylcysteine 140 mg, bromelain 2500GDU 80 mg, vitamin D3 800 IU, vitamin B12 18 mg, alpha-lipoic acid 140 mg, rutin 157 mg, vitamin C 160 mg, zinc oxide 16 mg, Vaccinium myrtillus 36% anthocyanosides 90 mg, Ganoderma lucidum 600 mg) and 15 patients (AMD-P group; mean age 70.14 ± 9.87) received two tablets of placebo daily on an empty stomach, before meals. A total of 28 eyes, 14 from each AMD group, completed the study. Multifocal electroretinogram (mfERG) and spectral domain-optical coherence tomography (SD-OCT) were assessed at baseline and after 6 months.


At 6-month follow-up, AMD-M eyes showed a significant increase of mfERG response amplitude density (RAD) recorded from the central macular areas (ring 1, 0–2.5°; ring 2, 2.5–5°), whereas non-significant changes of retinal and choroidal SD-OCT parameters were found when values were compared to baseline. Non-significant correlations between functional and structural changes were found. In AMD-P eyes, non-significant differences for each mfERG and SD-OCT parameters were observed at 6 months.


In intermediate AMD, Macuprev® supplementation increases the function of the macular pre-ganglionic elements, with no associated retinal and choroidal ultra-structural changes.

Trial Registration identifier, NCT03919019.


Research for this study was financially supported by the Italian Ministry of Health and Fondazione Roma. Article processing charges were funded by Farmaplus Italia s.r.l., Italy.


Carotenoid and antioxidant supplementation Intermediate age-related macular degeneration mfERG OCT Ophthalmology 



We thank the participants of the study. The authors also acknowledge Dr. Valter Valli Fiore for his technical help in the electrophysiological evaluations.


Research for this study was financially supported by the Italian Ministry of Health and Fondazione Roma. Article processing charges were funded by Farmaplus Italia s.r.l., Italy.


All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.


Mariacristina Parravano, Massimiliano Tedeschi, Daniela Manca, Eliana Costanzo, Antonio Di Renzo, Paola Giorno, Lucilla Barbano, Lucia Ziccardi, Monica Varano, and Vincenzo Parisi have nothing to disclose.

Compliance with Ethics Guidelines

The study was registered at (NCT03919019) and was approved by the local ethics committee (Comitato Etico Centrale IRCCS Lazio, Sezione IFO/Fondazione Bietti, Rome, Italy—Registro Sperimentazioni Italiano approval number 59/17/FB). All procedures performed in this study were also in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Data Availability

All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.


  1. 1.
    Evans JR, Fletcher AE, Wormald RP, et al. Prevalence of visual impairment in people aged 75 years and older in Britain: results from the MRC trial of assessment and management of older people in the community. Br J Ophthalmol. 2002;86:795–800.CrossRefGoogle Scholar
  2. 2.
    Ferris FL 3rd, Wilkinson CP, Bird A, et al. Beckman initiative for macular research classification committee. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120:844–51.CrossRefGoogle Scholar
  3. 3.
    Jaffe GJ, Martin DF, Toth CA, et al. Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2013;120:1860–70.CrossRefGoogle Scholar
  4. 4.
    Hood DC. Assessing retinal function with the multifocal technique. Prog Retin Eye Res. 2000;19:607–46.CrossRefGoogle Scholar
  5. 5.
    Parisi V, Tedeschi M, Gallinaro G, et al. Carotenoids and antioxidants in age-related maculopathy Italian study: multifocal electroretinogram modifications after 1 year. Ophthalmology. 2008;115:324–33.CrossRefGoogle Scholar
  6. 6.
    Parisi V, Perillo L, Tedeschi M, et al. Macular function in eyes with early age-related macular degeneration with or without contralateral late age-related macular degeneration. Retina. 2007;27:879–90.CrossRefGoogle Scholar
  7. 7.
    Moschos MM, Nitoda E. The role of mf-ERG in the diagnosis and treatment of age-related macular degeneration: electrophysiological features of AMD. Semin Ophthalmol. 2018;33:461–9.CrossRefGoogle Scholar
  8. 8.
    Heinemann-Vernaleken B, Palmowski AM, Allgayer R, Ruprecht KW. Comparison of different high resolution multifocal electroretinogram recordings in patients with age-related maculopathy. Graefes Arch Clin Exp Ophthalmol. 2001;239:556–61.CrossRefGoogle Scholar
  9. 9.
    Rimayanti U, Kiuchi Y, Yamane K, et al. Inner retinal layer comparisons of eyes with exudative age-related macular degeneration and eyes with age-related macular degeneration and glaucoma. Graefes Arch Clin Exp Ophthalmol. 2014;252:563–70.CrossRefGoogle Scholar
  10. 10.
    Lee EK, Yu HG. Ganglion cell-inner plexiform layer and peripapillary retinal nerve fiber layer thicknesses in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2015;56:3976–83.CrossRefGoogle Scholar
  11. 11.
    Wood A, Binns A, Margrain T, et al. Retinal and choroidal thickness in early age-related macular degeneration. Am J Ophthalmol. 2011;152:1030–8.CrossRefGoogle Scholar
  12. 12.
    Schuman SG, Koreishi AF, Farsiu S, Jung SH, Izatt JA, Toth CA. Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography. Ophthalmology. 2009;116:488–96.CrossRefGoogle Scholar
  13. 13.
    Yang S, Zuo C, Xiao H, et al. Photoreceptor dysfunction in early and intermediate age-related macular degeneration assessed with mfERG and spectral domain OCT. Doc Ophthalmol. 2016;132:17–26.CrossRefGoogle Scholar
  14. 14.
    Cohen SY, Dubois L, Tadayoni R, Delahaye-Mazza C, Debibie C, Quentel G. Prevalence of reticular pseudodrusen in age-related macular degeneration with newly diagnosed choroidal neovascularisation. Br J Ophthalmol. 2007;91:354–9.CrossRefGoogle Scholar
  15. 15.
    Wilde C, Patel M, Lakshmanan A, Morales MA, Dhar-Munshi S, Amoaku WM. Prevalence of reticular pseudodrusen in eyes with newly presenting neovascular age-related macular degeneration. Eur J Ophthalmol. 2016;26:128–34.CrossRefGoogle Scholar
  16. 16.
    Laíns I, Wang J, Providência J, et al. Choroidal changes associated with subretinal drusenoid deposits in age-related macular degeneration using swept-source optical coherence tomography. Am J Ophthalmol. 2017;180:55–63.CrossRefGoogle Scholar
  17. 17.
    Keenan TD, Klein B, Agrón E, Chew EY, Cukras CA, Wong WT. Choroidal thickness and vascularity vary with disease severity and subretinal drusenoid deposit presence in non advanced age-related macular degeneration. Retina. 2019. Scholar
  18. 18.
    Yiu G, Chiu SJ, Petrou PA, et al. Relationship of central choroidal thickness with age-related macular degeneration status. Am J Ophthalmol. 2015;159:617–26.CrossRefGoogle Scholar
  19. 19.
    Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309:2005–15.CrossRefGoogle Scholar
  20. 20.
    Piermarocchi S, Saviano S, Parisi V, et al. Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study. Eur J Ophthalmol. 2011;22:216–25.Google Scholar
  21. 21.
    Parisi V, Ziccardi L, Centofanti M, et al. Macular function in eyes with open-angle glaucoma evaluated by multifocal electroretinogram. Invest Ophthalmol Vis Sci. 2012;53:6973–80.CrossRefGoogle Scholar
  22. 22.
    Hood DC, Bach M, Brigell M, et al. ISCEV standard for clinical multifocal electroretinography (2011 edition). Doc Ophthalmol. 2012;124:1–13.CrossRefGoogle Scholar
  23. 23.
    Berrow EJ, Bartlett HE, Eperjesi F. The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes. Doc Ophthalmol. 2016;132:123–35.CrossRefGoogle Scholar
  24. 24.
    Moschos MM, Dettoraki M, Tsatsos M, Kitsos G, Kalogeropoulos C. Effect of carotenoids dietary supplementation on macular function in diabetic patients. Eye Vis (Lond). 2017;4:23.CrossRefGoogle Scholar
  25. 25.
    Berrow EJ, Bartlett HE, Eperjesi F, Gibson JM. The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy—a randomised controlled trial. Br J Nutr. 2013;109:2008–14.CrossRefGoogle Scholar
  26. 26.
    Ma L, Dou HL, Huang YM, et al. Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. Am J Ophthalmol. 2012;154:625–34.CrossRefGoogle Scholar
  27. 27.
    Snodderly DM, Handelman GJ, Adler AJ. Distribution of individual macular pigment carotenoids in central retina of macaque and squirrel monkeys. Invest Ophthalmol Vis Sci. 1991;32:268–79.Google Scholar
  28. 28.
    Bone RA, Landrum JT, Fernandez L, Tarsis SL. Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci. 1988;29:843–9.Google Scholar
  29. 29.
    Curcio CA. Photoreceptor topography in ageing and age-related maculopathy. Eye (Lond). 2001;15:376–83.CrossRefGoogle Scholar
  30. 30.
    Curcio CA, Sloan KR, Kalina RE, Hendrickson AE. Human photoreceptor topography. J Comp Neurol. 1990;292:497–523.CrossRefGoogle Scholar
  31. 31.
    Obana A, Tanito M, Gohto Y, Okazaki S, Gellermann W, Bernstein PS. Changes in macular pigment optical density and serum lutein concentration in Japanese subjects taking two different lutein supplements. PLoS One. 2015;10:e0139257.CrossRefGoogle Scholar
  32. 32.
    Stahl W, Sies H. Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta. 2005;1740:101–7.CrossRefGoogle Scholar
  33. 33.
    Huang Y, Dou H, Huang F, et al. Changes following supplementation with lutein and zeaxanthin in retinal function in eyes with early age-related macular degeneration: a randomised, double-blind, placebo-controlled trial. Br J Ophthalmology. 2015;99:371–5.CrossRefGoogle Scholar
  34. 34.
    Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. J Am Med Assoc. 1994;272:1413–20.CrossRefGoogle Scholar
  35. 35.
    Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE. Macular pigment in donor eyes with and without AMD: a case–control study. Invest Ophthalmol Vis Sci. 2001;42:235–40.Google Scholar
  36. 36.
    Malinow MR, Feeney-Burns L, Peterson LH, Klein ML, Neuringer M. Diet-related macular anomalies in monkeys. Invest Ophthalmol Vis Sci. 1980;19:857–63.Google Scholar
  37. 37.
    Thomson LR, Toyoda Y, Langner A, et al. Elevated retinal zeaxanthin and prevention of light-induced photoreceptor cell death in quail. Invest Ophthalmol Vis Sci. 2002;43:3538–49.Google Scholar
  38. 38.
    Carver KA, Yang D. N-Acetylcysteine amide protects against oxidative stress-induced microparticle release from human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2016;57:360–71.CrossRefGoogle Scholar
  39. 39.
    Nakayama M, Aihara M, Chen YN, Araie M, Tomita-Yokotani K, Iwashina T. Neuroprotective effects of flavonoids on hypoxia-, glutamate-, and oxidative stress-induced retinal ganglion cell death. Mol Vis. 2011;17:1784–93.Google Scholar
  40. 40.
    Kim YS, Kim M, Choi MY, et al. Alpha-lipoic acid reduces retinal cell death in diabetic mice. Biochem Biophys Res Commun. 2018;503:1307–14.CrossRefGoogle Scholar
  41. 41.
    Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2012;14(11):CD00025440.Google Scholar
  42. 42.
    de Lencastre Novaes LC, Jozala AF, Lopes AM, et al. Stability, purification, and applications of bromelain: a review. Biotechnol Prog. 2016;32:5–13.CrossRefGoogle Scholar
  43. 43.
    Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci. 2016;73:1765–86.CrossRefGoogle Scholar

Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Mariacristina Parravano
    • 1
  • Massimiliano Tedeschi
    • 1
  • Daniela Manca
    • 1
  • Eliana Costanzo
    • 1
  • Antonio Di Renzo
    • 1
  • Paola Giorno
    • 1
  • Lucilla Barbano
    • 1
  • Lucia Ziccardi
    • 1
    Email author
  • Monica Varano
    • 1
  • Vincenzo Parisi
    • 1
  1. 1.IRCCS Fondazione BiettiRomeItaly

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