Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012 Aug 15;2012(8):CD002219.
doi: 10.1002/14651858.CD002219.pub2.

Ivermectin for onchocercal eye disease (river blindness)

Henry O D Ejere  1 , Ellen Schwartz, Richard Wormald, Jennifer R Evans
Affiliations
Meta-Analysis

Ivermectin for onchocercal eye disease (river blindness)

Henry O D Ejere et al. Cochrane Database Syst Rev. .

Abstract

Background: It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. However, when given to everyone in communities where onchocerciasis is common, the effects of ivermectin on lesions affecting the eye are uncertain and data on whether the drug prevents visual loss are unclear.

Objectives: The aim of this review was to assess the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease. The secondary aim was to assess the effects of ivermectin on lesions affecting the eye in onchocerciasis.

Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 3), MEDLINE (January 1950 to April 2012), EMBASE (January 1980 to April 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 April 2012.

Selection criteria: We included randomised controlled trials with at least one year of follow-up comparing ivermectin with placebo or no treatment. Participants in the trials were people normally resident in endemic onchocercal communities with or without one or more characteristic signs of ocular onchocerciasis.

Data collection and analysis: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. As trials varied in design and setting, we were unable to perform a meta-analysis.

Main results: The review included four trials: two small studies (n = 398) in which people with onchocercal infection were given one dose of ivermectin or placebo and followed up for one year; and two larger community-based studies (n = 4941) whereby all individuals in selected communities were treated every six or 12 months with ivermectin or placebo, whether or not they were infected, and followed for two to three years. The studies provide evidence that treating people who have onchocerciasis with ivermectin reduces the number of microfilariae in their skin and eye(s) and reduces the number of punctate opacities. There was weaker evidence that ivermectin reduced the risk of chorioretinitis. The studies were too small and of too short a duration to provide evidence for an effect on sclerosing keratitis, iridocyclitis, optic nerve disease or visual loss. One community-based study in communities mesoendemic for the savannah strain of O.volvulus provided evidence that annual mass treatment with ivermectin reduces the risk of new cases of optic nerve disease and visual field loss. The other community-based study of mass biannual treatment of ivermectin in communities affected by the forest strain of O.volvulus demonstrated reductions in microfilarial load, punctate keratitis and iridocyclitis but not sclerosing keratitis, chorioretinitis, optic atrophy or visual impairment. The study was underpowered to estimate the effect of ivermectin on visual impairment and other less frequent clinical signs. The studies included in this review reported some adverse effects, in particular an increased risk of postural hypotension in people treated with ivermectin.

Authors' conclusions: The lack of evidence for prevention of visual impairment and blindness should not be interpreted to mean that ivermectin is not effective, however, clearly this is a key question that remains unanswered. The main evidence for a protective effect of mass treatment with ivermectin on visual field loss and optic nerve disease comes from communities mesoendemic for the savannah strain of O.volvulus. Whether these findings can be applied to communities with different endemicity and affected by the forest strain is unclear. Serious adverse effects were rarely reported. None of the studies, however, were conducted in areas where people are infected with Loa loa (loiasis).

PubMed Disclaimer

Conflict of interest statement

Jennifer Evans worked on one of the included trials ‐ Abiose 1993.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Abiose 1993 {published data only}
    1. Abiose A, Jones BR, Cousens SN, Murdoch I, Cassels‐Brown A, Babalola OE, et al. Reduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis. Lancet 1993;341(8838):130‐4. - PubMed
    1. Cousens SN, Cassels‐Brown A, Murdoch I, Babalola OE, Jatau D, Alexander NDE, et al. Impact of annual dosing with ivermectin on progression of onchocercal visual field loss. Bulletin of the World Health Organization 1997;75(3):229‐36. - PMC - PubMed
Dadzie 1989 {published data only}
    1. Dadzie KY, Awadzi K, Bird AC, Schulz‐Key H. Ophthalmological results from a placebo controlled comparative 3‐dose ivermectin study in the treatment of onchocerciasis. Tropical Medicine and Parasitology 1989;40(3):355‐60. - PubMed
Taylor 1988 {published data only}
    1. Newland HS, White AT, Greene BM, D'Anna SA, Keyvan‐Larijani E, Aziz MA, et al. Effect of single‐dose ivermectin therapy on human onchocerca volvulus infection with onchocercal ocular involvement. British Journal of Ophthalmology 1988;72(8):561‐9. - PMC - PubMed
    1. Taylor HR, Semba RD, Newland HS, Keyvan‐Larijani E, White A, Dukuly Z, et al. Ivermectin treatment of patients with severe ocular onchocerciasis. American Journal of Tropical Medicine and Hygiene 1989;40(5):494‐500. - PubMed
    1. White A, Newland HS, Taylor HR, Semba RD, Erttmann KD, Keyvan‐Larijani E, et al. Controlled trial and dose‐finding study of ivermectin for treatment of onchocerciasis. Journal of Infectious Diseases 1987;156(3):463‐70. - PubMed
Whitworth 1991a {published data only}
    1. Whitworth JAG, Gilbert CE, Mabey DM, Maude GH, Morgan D, Taylor DW. Effects of repeated doses of ivermectin on ocular onchocerciasis: community‐based trial in Sierra Leone. Lancet 1991;338(8775):1100‐3. - PubMed
    1. Whitworth JAG, Morgan D, Maude GH, Downham MD, Taylor DW. A community trial of ivermectin for onchocerciasis in Sierra Leone: adverse reactions after the first five treatment rounds. Transactions of the Royal Society of Tropical Medicine and Hygiene 1991;85(4):501‐5. - PubMed
    1. Whitworth JAG, Morgan D, Maude GH, Luty AJF, Taylor DW. A community trial of ivermectin for onchocerciasis in Sierra Leone: clinical and parasitological responses to four doses given at six‐monthly intervals. Transactions of the Royal Society of Tropical Medicine and Hygiene 1992;86(3):277‐80. - PubMed
    1. Whitworth JAG, Morgan D, Maude GH, Taylor DW. Community‐based treatment with ivermectin. Lancet 1988;ii:97‐8. - PubMed

References to studies excluded from this review

Gardon 2002 {published data only}
    1. Fobi G, Gardon J, Kamgno J, Aimard‐Favennec L, Lafleur C, Gardon‐Wendel N, et al. A randomized, double‐blind, controlled trial of the effects of ivermectin at normal and high doses, given annually or three‐monthly, against Onchocerca volvulus: ophthalmological results. Transactions of the Royal Society of Tropical Medicine and Hygiene 2005;99(4):279‐89. - PubMed
    1. Gardon J, Boussinesq M, Kamgno J, Gardon‐Wendel N, Demanga‐Ngangue, Duke BOL. Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet 2002;360(9328):203‐10. - PubMed

Additional references

Abiose 1994
    1. Abiose A, Murdoch I, Babalola OE, Cousens S, Liman I, Onyema J, et al. The distribution and aetiology of blindness and visual impairment in mesoendemic onchocercal communities in Kaduna State, Nigeria. British Journal of Ophthalmology 1994;78(1):8‐13. - PMC - PubMed
Abiose 1998
    1. Abiose A. Onchocercal eye disease and the impact of Mectizan treatment. Annals of Tropical Medicine and Parasitology 1998;92(Suppl 1):S11‐22. - PubMed
Abiose 2000
    1. Abiose A, Homeida M, Liese B, Molyneux D, Remme H. Onchocerciasis control strategies. Lancet 2000;356(9240):1523‐4. - PubMed
Akogun 2000
    1. Akogun OB, Akogun MK, Audu Z. Community‐perceived benefits of ivermectin treatment in north‐eastern Nigeria. Society for Science in Medicine 2000;50(10):1451‐6. - PubMed
Aziz 1982
    1. Aziz MA, Diallo S, Diop IM, Lariviere M, Porta M. Efficacy and tolerance of ivermectin in human onchocerciasis. Lancet 1982;2(8291):171‐3. - PubMed
Bird 1980
    1. Bird AC, Sheikh H, Anderson J, Fuglsang H. Changes in visual function and in the posterior segment of the eye during treatment of onchocerciasis with diethylcarbamazine citrate. British Journal of Ophthalmology 1980;64(3):191‐200. - PMC - PubMed
Boussinesq 1998
    1. Boussinesq M, Gardon J, Gardon‐Wendel N, Kamgno J, Ngoumou P, Chippaux JP. Three probable cases of Loa loa encephalopathy following ivermectin treatment for onchocerciasis. American Journal of Tropical Medicine and Hygiene 1998;58(4):461‐9. - PubMed
Burnham 1998
    1. Burnham G. Onchocerciasis. Lancet 1998;351(9112):1341‐6. - PubMed
Chijioke 1992
    1. Chijioke CP, Okonkwo PO. Adverse events following mass ivermectin therapy for onchocerciasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 1992;86(3):284‐6. - PubMed
Chippaux 1999
    1. Chippaux J, Boussinesq M, Fobi G, Lafieur C, Auduge A, Banos MJ, et al. Effect of repeated ivermectin treatments on ocular onchocerciasis: evaluation after six to eight dosings. Ophthalmic Epidemiology 1999;6(4):229‐46. - PubMed
Cooper 1996
    1. Cooper PJ, Guderian RH, Proano R, Taylor DW. Absence of cellular responses to a putative autoantigen in onchocercal chorioretinopathy. Cellular autoimmunity in onchocercal chorioretinopathy. Investigative and Ophthalmological Visual Science 1996;37(9):1717‐9. - PubMed
Cooper 1997
    1. Cooper PJ, Guderian RH, Proano R, Taylor DW. The pathogenesis of chorioretinal disease in onchocerciasis. Parasitology Today 1997;13:94‐8. - PubMed
De‐Sole 1989
    1. De‐Sole G, Remme J, Awadzi K, Accorsi S, Alley ES, Ba O, et al. Adverse reactions after large‐scale treatment of onchocerciasis with ivermectin: combined results from eight community trials. Bulletin of the World Health Organization 1989;67(6):707‐19. - PMC - PubMed
Diawara 2009
    1. Diawara L, Traore MO, Badji A, Bissan Y, Doumbia K, Goita SF, et al. Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal. PLoS Neglected Tropical Diseases 2009;3(7):e497. - PMC - PubMed
Gardon 1997
    1. Gardon J, Gardon‐Wendel N, Demanga N, Kamgno J, Chippaux JP, Boussinesq M. Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection. Lancet 1997;350(9070):2‐3. - PubMed
Glanville 2006
    1. Glanville JM, Lefebvre C, Miles JN, Camosso‐Stefinovic J. How to identify randomized controlled trials in MEDLINE: ten years on. Journal of the Medical Library Association 2006;94(2):130‐6. - PMC - PubMed
Goa 1991
    1. Goa KL, McTavish D, Clissold SP. Ivermectin: A review of its anti‐filarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs 1991;42(4):640‐58. - PubMed
Higgins 2005
    1. Higgins JPT, Green S, editors. Assessment of study quality. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]; Section 6. The Cochrane Library, Issue 3, 2005. Chichester, UK: John Wiley & Sons, Ltd.
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne, JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated September 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hise 2007
    1. Hise AG, Daehnel K, Gillette‐Ferguson I, Cho E, McGarry HF, Taylor MJ, et al. Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM. Journal of Immunology 2007;178(2):1068‐76. - PubMed
Hoerauf 2001
    1. Hoerauf A, Mand S, Adjei O, Fleischer B, Buttner DW. Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet 2001;357(9266):1415‐6. - PubMed
ISRCTN95189962
    1. ISRCTN95189962. Evaluation of the impact of large scale, community directed delivery of doxycycline for the treatment of onchocerciasis: the Anti‐Wolbachia (A‐WOL) trial. www.controlled‐trials.com/ISRCTN95189962/ (accessed 11 May 2012).
Johnson 1998
    1. Johnson G, Minassian DC, Weale R (Eds). The Epidemiology of Eye Disease. London: Chapman and Hall, 1998.
Kinnanom 2000
    1. Kinnanom KE, Engle RR, Poon BT, Ellis WY, McCall JW, Dzimianski MT. Anticancer agents suppressive for adult parasites of filariasis in Mongolian jirds. Proceedings of the Society for Experimental Biological Medicine 2000;224(1):45‐9. - PubMed
Murdoch 1997
    1. Murdoch IE, Jones BR, Cousens S, Liman I, Babalola OE, Dauda J, et al. Visual field constriction as a cause of blindness or visual impairment. Bulletin of the World Health Organization 1997;75(2):141‐6. - PMC - PubMed
NCT00790998
    1. NCT00790998. Study comparing moxidectin and ivermectin in subjects with Onchocerca Volvulus infection. clinicaltrials.gov/ct2/show/NCT00790998 (accessed 11 May 12).
Pond 1991
    1. Pond B. Mass Distribution of Ivermectin: A Handbook for Community Treatment of Onchocerciasis. The International Eye Foundation, 1991.
Remme 1990
    1. Remme J, Sole G, Dadzie KY, Alley ES, Baker RHA, Habbena JDF, et al. Large scale ivermectin distribution and its epidemiological consequences. Acta Leiden 1990;59(1‐2):177‐91. - PubMed
Review Manager 2011 [Computer program]
    1. The Cochrane Collaboration, The Nordic Cochrane Centre. Review Manager (RevMan). Version 5.1. Copenhagen: The Cochrane Collaboration, The Nordic Cochrane Centre, 2011.
Richards 2000
    1. Richards F, Hopkins D, Cupp E. Programmatic goals and approaches to onchocerciasis. Lancet 2000;355(9216):1663‐4. - PubMed
Rolland 1974
    1. Rolland A. Results of 2 eye examinations carried out with an interval of 6 years in 2 Upper Volta villages where onchocerciasis is endemic. Bulletin of the World Health Organization 1974;51(3):257‐61. - PMC - PubMed
Saint Andre 2002
    1. Saint Andre A, Blackwell NM, Hall LR, Hoerauf A, Brattig NW, Volkmann L, et al. The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Science 2002;295(5561):1892‐5. - PubMed
Stevenson 1999
    1. Stevenson P. Vision is failing for river‐blindness control in Ghana. Lancet 1999;354(9196):2143. - PubMed
Taylor 1990
    1. Taylor HR, Pacque M, Munoz B, Greene BM. Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection. Science 1990;250:116‐8. - PubMed
Taylor 2000
    1. Taylor M. Filarial nematodes: a bug's life?. Filarial Update 2000;2(1):10‐1.
Tekle 2012
    1. Tekle AH, Elhassan E, Isiyaku S, Amazigo UV, Bush S, Noma M, et al. Impact of long‐term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control. Parasites and Vectors 2012;5:28. - PMC - PubMed
Trpis 1990
    1. Trpis M, Childs JE, Fryauff DJ, Greene BM, Williams PN, Munoz BE, et al. Effect of mass treatment of of a human population with ivermectin on transmission of Onchocerca volvulus by Simulium yahense in Liberia, West Africa. American Journal of Tropical Medicine and Hygiene 1990;42(2):148‐56. - PubMed
White 1987
    1. White A, Newland HS, Taylor HR, Semba RD, Erttmann KD, Keyvan‐Larijani E, et al. Controlled trial and dose‐finding study of ivermectin for treatment of onchocerciasis. Journal of Infectious Diseases 1987;156(3):463‐70. - PubMed
White 2008
    1. White IR, Higgins JP, Wood AM. Allowing for uncertainty due to missing data in meta‐analysis‐Part 1: two‐stage methods. Statistics in Medicine 2008;27(5):711‐27. - PubMed
Whitworth 1991b
    1. Whitworth JA, Morgan D, Maude GH, McNicholas AM, Taylor DW. A field study of the effect of ivermectin on intestinal helminths in man. Transactions of the Royal Society of Tropical Medicine and Hygiene 1991;85(2):232‐4. - PubMed
Whitworth 1992
    1. Whitworth J. Treatment of onchocerciasis with ivermectin in Sierra Leone. Parasitology Today 1992;8(4):138‐40. - PubMed
WHO 1985
    1. World Health Organization. Ten years of onchocerciasis control in West Africa. OCP/GVA/85.1B 1985.
WHO 2000
    1. World Health Organization. Onchocerciasis (River blindness). Fact sheet No 95 Revised 2000.
Winthrop 2011
    1. Winthrop KL, Furtado JM, Silva JC, Resnikoff S, Lansingh VC. River blindness: an old disease on the brink of elimination and control. Journal of Global Infectious Diseases 2011;3(2):151‐5. - PMC - PubMed

References to other published versions of this review

Ejere 2001
    1. Ejere HOD, Schwartz E, Wormald R. Ivermectin for onchocercal eye disease (river blindness). Cochrane Database of Systematic Reviews 2001, Issue 2. [DOI: 10.1002/14651858.CD002219] - DOI - PubMed
Ejere 2009
    1. Ejere HOD, Schwartz E, Wormald R, Evans JR. Ivermectin for onchocercal eye disease (river blindness). Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD002219] - DOI

Publication types

MeSH terms