Korean J Ophthalmol > Volume 26(1); 2012 > Article
Woo, Kim, Park, Lee, and Hwang: Resolution of Recalcitrant Uveitic Optic Disc Edema Following Administration of Methotrexate: Two Case Reports


A 13-year-old male and a 15-year-old female presented with optic disc edema associated with chronic recurrent uveitis. While the ocular inflammation responded to high doses of oral prednisolone, the disc edema showed little improvement. After oral administration of methotrexate, the disc edema and ocular inflammation were resolved, and the dose of oral corticosteroid could be reduced.

Optic disc edema or papillitis is commonly associated with chronic anterior uveitis in children, and its prevalence has been reported to be 21% [1]. However, there have been few reports regarding the treatment for recalcitrant uveitic disc edema, especially in children [2]. Methotrexate, a member of the antimetabolite class, has been used as an immunosuppressive agent that is effective against ocular inflammatory disease [3]. Here, we report two cases of children with chronic recurrent uveitis and disc edema that did not respond to oral corticosteroid but that showed significant improvement following administration of methotrexate.

Case Report

Case 1

A 13-year-old male patient presented with bilateral optic disc edema accompanied by idiopathic chronic anterior uveitis that had been ongoing for two months. At that time, his visual acuity was 20 / 25 in the right eye and 20 / 40 in the left eye, and there was no macula edema on funduscopic examination or optical coherence tomography. He had been taking 30 mg (0.52 mg/kg) of oral prednisolone daily. We could not find any neurologic or systemic abnormalities to explain the disc edema. For six months, he had taken oral prednisolone and could not taper it due to the recurrence of ocular inflammation. In addition, the disc edema had not subsided, even with a high dose of oral prednisolone (60 mg [1.05 mg/kg] per day). Thereafter, we added oral methotrexate 10 mg (0.18 mg/kg) per week to the daily dose of prednisolone 30 mg (0.52 mg/kg). After 3 weeks of methotrexate, the disc edema and ocular inflammation were alleviated, and his vision improved to 20 / 20 in both eyes (Fig. 1A and 1B). The disc edema and inflammation recurred during the oral prednisolone tapering period. However, a daily low-to-moderate dose of prednisolone (10-20 mg) combined with a weekly dose of methotrexate 15 mg (0.26 mg/kg) alleviated the ocular inflammation and disc edema (Fig. 1C and 1D). After 18 months of methotrexate and tapering the dose of oral prednisolone, the patient achieved stable vision without optic disc edema or ocular inflammation.

Case 2

A 15-year-old female patient presented with optic disc edema in the right eye and bilateral idiopathic panuveitis (Fig. 2A and 2B) with no associated neurologic or systemic abnormalities. Despite continued daily administration of oral prednisolone 30 mg (0.44 mg/kg) for 4 months, the disc edema persisted. We added a daily dose of cyclosporine 150 mg (2.21 mg/kg) to her medications. Although the anterior chamber inflammation had improved significantly, the disc edema persisted. We then prescribed a weekly dose of methotrexate, starting at 7.5 mg (0.11 mg/kg) and increasing to 15 mg (0.22 mg/kg), while reducing the prednisolone dose to 10 mg (0.15 mg/kg) per day and discontinuing the cyclosporine. The disc edema resolved dramatically one month after the initiation of methotrexate (Fig. 2C and 2D). The dose of oral prednisolone was tapered while increasing the dose of methotrexate to 20 mg weekly without recurrence of disc edema or ocular inflammation. After one year of methotrexate, the patient had good visual acuity in both eyes, and the intraocular inflammation was controlled without optic disc edema.


Optic disc edema from various causes may result in irreversible axonal damage and progressive visual field loss [4]. Although there have been reports of resolution of optic disc edema after successful treatment of anterior uveitis [2,5], there is no definite treatment guideline for uveitic disc edema in children who do not respond to corticosteroids. While corticosteroids are one of the traditional treatment regimens of uveitis, chronic oral intake by children can lead to serious side effects, i.e., cataract, glaucoma, and growth retardation in prepubescent children. Recent studies have reported that methotrexate is moderately effective for controlling ocular inflammation and for achieving corticosteroid-sparing objectives as a monotherapy or in combination with other agents in both adults and children [3,6,7].
For long-term treatment with methotrexate, caution should be exercised regarding the systemic and ocular side effects. Elevated liver enzymes, nausea, fatigue, cytopenia, stomatitis, bone marrow suppression and liver cirrhosis have been reported as systemic side effects of methotrexate [8-12]. Ocular side effects include irritation and dry eye [13], as well as the rare occurrence of toxic optic neuropathy, which can be reversed by the intake of folic acid [14-17]. Thus, regular ophthalmic and systemic examination is mandatory during methotrexate intake.
In our cases of steroid-refractory uveitic optic disc edema in children, methotrexate had a beneficial effect on the resolution of optic disc edema and controlled intraocular inflammation while sparing the corticosteroid. We are unaware of previous reports showing the efficacy of methotrexate reducing recalcitrant uveitic disc edema in children. Therefore, we think that this report is a significant reference regarding the effect of methotrexate in the treatment of pediatric uveitis accompanying disc edema.

Conflicts of interest

No potential conflict of interest relevant to this article was reported.


1. Holland GN, Denove CS, Yu F. Chronic anterior uveitis in children: clinical characteristics and complications. Am J Ophthalmol 2009;147:667-678.
crossref pmid
2. Kozak I, Robbins SL, Freeman WR. Bilateral papillitis associated with bilateral anterior uveitis in a child. J Pediatr Ophthalmol Strabismus 2007;44:374-376.
crossref pmid
3. Gangaputra S, Newcomb CW, Liesegang TL, et al. Methotrexate for ocular inflammatory diseases. Ophthalmology 2009;116:2188-2198.
crossref pmid
4. Rebolleda G, Mu?oz-Negrete FJ. Follow-up of mild papilledema in idiopathic intracranial hypertension with optical coherence tomography. Invest Ophthalmol Vis Sci 2009;50:5197-5200.
crossref pmid
5. Monheit BE, Read RW. Optic disk edema associated with sudden-onset anterior uveitis. Am J Ophthalmol 2005;140:733-735.
crossref pmid
6. Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2005;32:362-365.
7. Malik AR, Pavesio C. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis. Br J Ophthalmol 2005;89:806-808.
crossref pmid pmc
8. Walker AM, Funch D, Dreyer NA, et al. Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum 1993;36:329-335.
crossref pmid
9. Hoekstra M, van Ede AE AE, Haagsma CJ, et al. Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis 2003;62:423-426.
crossref pmid pmc
10. Van Ede AE, Laan RF, Blom HJ, et al. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998;27:277-292.
crossref pmid
11. Salaffi F, Manganelli P, Carotti M, et al. Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature. Clin Rheumatol 1997;16:296-304.
crossref pmid
12. Ohosone Y, Okano Y, Kameda H, et al. Toxicity of low-dose methotrexate in rheumatoid arthritis: clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis. Ryumachi 1997;37:16-23.
13. Doroshow JH, Locker GY, Gaasterland DE, et al. Ocular irritation from high-dose methotrexate therapy: pharmacokinetics of drug in the tear film. Cancer 1981;48:2158-2162.
crossref pmid
14. Johansson BA. Visual field defects during low-dose methotrexate therapy. Doc Ophthalmol 1992;79:91-94.
crossref pmid
15. Balachandran C, McCluskey PJ, Champion GD, Halmagyi GM. Methotrexate-induced optic neuropathy. Clin Experiment Ophthalmol 2002;30:440-441.
crossref pmid
16. Clare G, Colley S, Kennett R, Elston JS. Reversible optic neuropathy associated with low-dose methotrexate therapy. J Neuroophthalmol 2005;25:109-112.
crossref pmid
17. Sbeity ZH, Baydoun L, Schmidt S, Loeffler KU. Visual field changes in methotrexate therapy. Case report and review of the literature. J Med Liban 2006;54:164-167.
Fig. 1
Case 1. Fundus photographs of case 1. (A,B) At presentation, bilateral severe disc edema and vascular tortuosity were observed. (C,D) Three weeks after administration of methotrexate, disc edema and vascular tortuosity were resolved.
Fig. 2
Case 2. A fundus photograph (A) and fluorescein angiography (B) of the right eye revealing disc edema and choroiditis. (C,D). One month after administration of methotrexate, the disc edema and fluorescein leakage from the optic disc were resolved.

Editorial Office
SKY 1004 Building #701
50-1 Jungnim-ro, Jung-gu, Seoul 04508, Korea
Tel: +82-2-583-6520    Fax: +82-2-583-6521    E-mail: kos@ophthalmology.org                

Copyright © 2024 by Korean Ophthalmological Society.

Developed in M2PI

Close layer
prev next