Visual Outcomes of Adding Erythropoietin to Methylprednisolone for Treatment of Retrobulbar Optic Neuritis


Purpose: To compare the short-term visual function results and safety of erythropoietin as an add-on to the standard corticosteroid therapy in retrobulbar optic neuritis (RON).

Methods: In this prospective pilot study, adult patients with isolated RON with less than 10 days of onset were enrolled. Patients were consecutively assigned to standard intravenous methylprednisolone treatment either in combination with intravenous erythropoietin (20,000 units/day for three days) (group-1) or alone (group-2). Primary outcome measure was best-corrected visual acuity (BCVA), which was assessed up to 120 days from the day the treatment was begun. Systemic evaluations were performed during and after treatment.

Results: Sixty-two patients with RON (mean age = 26.6 ± 5.77 years; range = 18–40 years) were enrolled into the study (group-1, n = 35; group-2, n = 27). BCVA three months after the treatment was 0.19 ± 0.55 logMAR and 0.11 ± 0.32 logMAR in group-1 and group-2, respectively (95% CI: –0.61–0.16; P = 0.62). Change in BCVA after three months was 2.84 ± 3.49 logMAR in group-1 and 2.46 ± 1.40 logMAR in group-2 (95% CI: –0.93–1.91; P = 0.57). Pace of recovery was not significantly different between the groups. No complications were detected among patients.

Conclusion: Intravenous erythropoietin as an add-on did not significantly improve the visual outcome in terms of visual acuity, visual field, and contrast sensitivity compared to traditional intravenous corticosteroid. This pilot study supports the safety profile of intravenous human recombinant erythropoietin, and it may help formulate future investigations with a larger sample size.


Contrast Sensitivity; Erythropoietin; Optic Neuritis; Optic Neuroprotection; Optic Nerve Regeneration; Visual Acuity; Visual Function

1. Toosy AT, Mason DF, Miller DH. Optic neuritis. Lancet Neurol 2014;13:83–99.

2. Hickman SJ, Toosy AT, Jones SJ, Altmann DR, Miszkiel KA, MacManus DG, et al. A serial MRI study following
optic nerve mean area in acute optic neuritis. Brain 2004;127:2498–2505.

3. Matsunaga Y, Kezuka T, An X, Fujita K, Matsuyama N, Matsuda R, et al. Visual functional and histopathological
correlation in experimental autoimmune optic neuritis. Invest Ophthalmol Vis Sci 2012;53:6964–6971.

4. Beck RW, Cleary PA. Optic neuritis treatment trial. Oneyear follow-up results. Arch Ophthalmolo 1993;111:773–

5. Steinsapir KD, Goldberg RA, Sinha S, Hovda DA. Methylprednisolone exacerbates axonal loss following optic
nerve trauma in rats. Restor Neurol Neurosci 2000;17:157–163.

6. Brück W, Stadelmann C. Inflammation and degeneration in multiple sclerosis. Neurol Sci 2003;24:S265–S267.

7. Beck RW, Gal RL, Bhatti MT, Brodsky MC, Buckley EG, Chrousos GA, et al. Visual function more than 10 years after optic neuritis: Experience of the optic neuritis treatment trial. Am J Ophthalmol 2004;137:77–83.

8. Hickman SJ, Dalton CM, Miller DH, Plant GT. Management of acute optic neuritis. Lancet 2002;360:1953–1962.

9. Diem R, Hobom M, Maier K, Weissert R, Storch MK, Meyer R, et al. Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway. J Neurosci 2003;23:6993–7000.

10. Kashkouli MB, Pakdel F, Sanjari MS, Haghighi A, Nojomi M, Homaee MH, et al. Erythropoietin: A novel treatment for traumatic optic neuropathy-a pilot study. Graefes Arch Clin Exp Ophthalmol 2011;249:731–736.

11. Kashkouli MB, Yousefi S, Nojomi M, Sanjari MS, Pakdel F, Entezari M, et al. Traumatic optic neuropathy treatment trial (TONTT): Open label, phase 3, multicenter, semiexperimental trial. Graefes Arch Clin Exp Ophthalmol 2018;256:209–218.

12. Pakdel F, Sanjari MS, Kashkouli MB, Pirmarzdashti, N, Haghighi A, Moddareszade M. Erythropoietin in
recurrent anterior ischaemic optic neuropathy. Neuroophthalmology 2012;36:249–252.

13. Pakdel F, Sanjari MS, Naderi A, Pirmarzdashti N, Haghighi A, Kashkouli MB. Erythropoietin in treatment of methanol optic neuropathy. J Neuroophthalmol 2018;38:167–171.

14. Sühs KW,Hein K, Sättler MB, Görlitz A, Ciupka C, Scholz K, et al. A randomized, double-blind, phase 2 study of
erythropoietin in optic neuritis. Ann Neurol 2012;72:99–210.

15. Sun TS, Wei SH. Preliminary report of contrast sensitivity in idiopathic optic neuritis patients after recovery. Zhonghua Yan Ke Za Zhi 2009;45:1068–1073.

16. Quinn TA, Dutt M, Shindler KS. Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis. Front Neurol 2011;2:50.

17. Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI, et al. Quantifying axonal loss after optic
neuritis with optical coherence tomography. Ann Neurol 2006;59:963–969.

18. Weishaupt JH, Rohde G, Pölking E, Siren AL, Ehrenreich H, Bähr M. Effect of erythropoietin axotomy-induced apoptosis in rat retinal ganglion cells. Invest Ophthalmol Vis Sci 2004;45:1514–1522.

19. Juul S. Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage. Acta Paediatr Suppl 2002;91:36–42.

20. Jehle T, Meschede W, Dersch R, Feltgen N, Bach M, Lagrèze WA. Erythropoietin protects retinal ganglion cells
and visual function after ocular ischemia and optic nerve Compression. Ophthalmologe 2010;107:347–353.

21. Mammis A, McIntosh TK, Maniker AH. Erythropoietin as a neuroprotective agent in traumatic brain injury Review. Surg Neurol 2009;71:527–531.

22. Feng Q. Beyond erythropoiesis: The anti-inflammatory effects of erythropoietin. Cardiovasc Res 2006;71:615–617.

23. Sun Y, Calvert JW, Zhang JH. Neonatal hypoxia/ischemia is associated with decreased inflammatory mediators after erythropoietin administration. Stroke 2005;36:1672–1678.

24. Katavetin P, Tungsanga K, Eiam-Ong S, Nangaku M. Antioxidative effects of erythropoietin. Kidney Int Suppl

25. Sättler MB, Merkler D, Maier K. Neuroprotective effects and intracellular signaling pathways of erythropoietin
in a rat model of multiple sclerosis. Cell Death Differ 2004;2:S181–S192.

26. Abri Aghdam K, Soltan Sanjari M, Ghasemi Falavarjani K. Erythropoietin in ophthalmology: A literature review. J Curr Ophthalmol 2016;28:5–11.

27. Fishbane S, Besarab A. Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets.Clin J Am Soc Nephrol 2007;2:1274–1282.

28. Zhu X, Perazella MA. Nonhematologic complications of erythropoietin therapy. Semin Dial 2006;19:279–284.