Ophthalmic Surgery, Lasers and Imaging Retina

Brief Report 

The Role of Intravitreal Trimethoprim/Sulfamethoxazole in the Treatment of Toxoplasma Retinochoroiditis

Animesh Jindal, MD; Himadri Choudhury, MS; Avinash Pathengay, FRCS; Abhishek Bawdekar, MS; Thomas Albini, MD; Harry W. Flynn, MD

Abstract

The authors evaluate the role of intravitreal trimethoprim/sulfamethoxazole in the treatment of toxoplasma retinochoroiditis (TRC) in four patients. Intravitreal injection of trimethoprim/sulfamethoxazole 1.28 mg/0.08 mL with dexamethasone 400 µg/0.1 mL was injected weekly or biweekly. After the initiation of treatment, a reduction in intraocular inflammation was observed clinically and on optical coherence tomography within 1 week. Three patients regained visual acuity of 20/20, and one patient improved to 20/40 with residual macular scarring. No evidence of retinal toxicity was noted on full-field electroretinogram. Intravitreal trimethoprim/sulfamethoxazole and dexamethasone combination may be an alternative treatment strategy in patients with TRC.

[Ophthalmic Surg Lasers Imaging Retina. 2015;46:137–140.]

From the L V Prasad Eye Institute, Visakhapatnam, India (HC, AJ, AP, AB); and the Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida (TA, HWF).

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Avinash Pathengay, FRCS, LV Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam530 040, Andhra Pradesh, India; 91 0891 3989 2020; email: avinash@lvpei.org.

Received: July 09, 2014
Accepted: August 20, 2014

Abstract

The authors evaluate the role of intravitreal trimethoprim/sulfamethoxazole in the treatment of toxoplasma retinochoroiditis (TRC) in four patients. Intravitreal injection of trimethoprim/sulfamethoxazole 1.28 mg/0.08 mL with dexamethasone 400 µg/0.1 mL was injected weekly or biweekly. After the initiation of treatment, a reduction in intraocular inflammation was observed clinically and on optical coherence tomography within 1 week. Three patients regained visual acuity of 20/20, and one patient improved to 20/40 with residual macular scarring. No evidence of retinal toxicity was noted on full-field electroretinogram. Intravitreal trimethoprim/sulfamethoxazole and dexamethasone combination may be an alternative treatment strategy in patients with TRC.

[Ophthalmic Surg Lasers Imaging Retina. 2015;46:137–140.]

From the L V Prasad Eye Institute, Visakhapatnam, India (HC, AJ, AP, AB); and the Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida (TA, HWF).

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Avinash Pathengay, FRCS, LV Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam530 040, Andhra Pradesh, India; 91 0891 3989 2020; email: avinash@lvpei.org.

Received: July 09, 2014
Accepted: August 20, 2014

Introduction

Toxoplasma gondii, an obligate intracellular parasite, is the commonest cause of infectious posterior uveitis in immunocompetent individuals.1,2 Acute toxoplasma retinochoroiditis (TRC) may be asymptomatic or associated with visual loss due to intense vitritis, direct involvement of the macula or optic nerve, or complications like epiretinal membranes and retinal detachment.3–5 Although the disease may be self-limiting in most immunocompetent individuals, antitoxoplasma medication is often used to decrease sight-threatening inflammation and/or reduce recurrence.6 Classic treatment for ocular toxoplasmosis includes pyrimethamine, sulfadiazine, and systemic corticosteroid.7 However, this regimen may be associated with adverse effects like leukopenia and thrombocytopenia. Alternative therapeutic regimens include quadruple drug therapy (classic regimen plus clindamycin), trimethoprim and sulfamethoxazole, spiramycin, minocycline, azithromycin, atovaquone, and clarithromycin.8,9

Intravitreal clindamycin has also been used successfully in the treatment of TRC.10 It has also been reported that local treatment may be more effective than systemic therapy in the treatment of immunoglobulin G (IgG)-positive and immunoglobulin M (IgM)-negative cases.11 Intravitreal co-trimoxazole has been found to be nontoxic in rabbit eyes up to a dose of 1,600 µg/0.1 mL (in trimethoprim concentration).12 We report clinical outcomes of four patients with TRC who were treated with intravitreal co-trimoxazole and dexamethasone.

Patients and Methods

This was a retrospective, noncomparative, interventional case series. Four patients with active vision-threatening toxoplasma retinochoroiditis were included. Institutional review board approval was obtained.

All patients presented with a duration of symptoms ranging from 2 to 3 weeks. Presenting visual acuity ranged from 20/25 to 20/400. All patients had a focal active yellowish-white retinochoroiditis lesion. An old pigmented scar was noted near the active lesion in three patients. All patients had grade 1 to 2 vitreous haze. All patients had positive IgG and negative IgM serum antitoxoplasma antibody titers. Intravitreal injections of trimethoprim/sulfamethoxazole 1.28 mg/0.08 mL (reported in trimethoprim concentration) with dexamethasone 400 µg/0.1 mL were administered in all four patients, and the response was observed. Two patients underwent biweekly injections because of the close proximity of the lesion to the center of the fovea, requiring an early response. The other two patients received weekly injections. The patients were examined every 3 days for the first 3 weeks and weekly thereafter. At every visit, best corrected visual acuity and clinical and optical coherence tomography (OCT) evidence of resolution of TRC was studied. Full-field electroretinogram (ERG) was performed at the end of 6 weeks.

Results

A reduction in intraocular inflammation was observed in all patients within 1 week after the first injection. There was a reduction in vitritis, and the borders of the lesion became better defined. OCT imaging showed a reduction in intraretinal and/or subretinal fluid from baseline. Visual acuity improved in all patients; three patients regained 20/20 acuity, and one patient improved to 20/40 with residual macular scarring. The patients were observed closely, and complete resolution of retinochoroiditis was noted at 6 weeks in all patients. Full-field ERG was performed at the 6-week follow-up visit and was unremarkable and comparable with the normal fellow eye in all patients. Profiles of patients, disease characteristics, and the results of treatment are summarized in Table 1.

Demographic Profile, Clinical Features, and Treatment Outcomes in Patients Who Received Intravitreal Cotrimoxazole/Dexamethasone for TRC

Table:

Demographic Profile, Clinical Features, and Treatment Outcomes in Patients Who Received Intravitreal Cotrimoxazole/Dexamethasone for TRC

Discussion

Vision-threatening TRC is usually treated with systemic antibiotics along with oral prednisolone. Corticosteroids are added to reduce the inflammation when the reduction of inflammation is likely to restore vision. There are numerous antibiotic regimens, but none of them have been demonstrated to be superior to the others in the treatment of TRC.6,13 Treatment is most commonly continued for 4 to 6 weeks. The combination of sulfadiazine and pyrimethamine is the most commonly used oral treatment. Co-trimoxazole (trimethoprim/sulfamethoxazole) alone or in combination with clindamycin may also be used. However, all these regimens may have systemic side effects, and up to 26% of immunocompetent and 40% of immunocompromised patients have to discontinue treatment.13,14 If lesions close to the optic nerve or macula do not show a prompt response to systemic treatment or the patient is unable to tolerate the medication, permanent vision loss may occur. Local therapy in the form of intravitreal clindamycin along with dexamethasone has been used successfully in the treatment of TRC. An intravitreally delivered drug, by bypassing ocular barriers, can deliver a high concentration of the drug directly to the intraocular tissues while avoiding systemic complications. It has also been shown that local therapy may be more effective than systemic therapy in serum IgG-positive and IgM-negative cases.8

In our series, we chose local therapy with co-trimoxazole over clindamycin because co-trimoxazole is a combination of two drugs, trimethoprim and sulfamethoxazole. Co-trimoxazole (80 mg trimethoprim and 400 mg sulfamethoxazole per 5 mL of injection) blocks two consecutive steps in the biosynthesis of tetrahydrofolic acid.15 Many organisms resistant to sulfamethoxazole but moderately susceptible to trimethoprim exhibit a synergistic response, and in vitro resistance develops more slowly than with either drug alone.15 The safety of intravitreal co-trimoxazole has been demonstrated in rabbit eyes.12 In the current series, full-field ERG was normal after 6 weeks of treatment.

Our case series demonstrates the efficacy of combination therapy with intravitreal trimethoprim/sulfamethoxazole and dexamethasone in the treatment of TRC. To our knowledge, this is the first successful use of intravitreal trimethoprim/sulfamethoxazole in TRC. In conclusion, intravitreal trimethoprim/sulfamethoxazole may be an effective alternative to systemic therapy or intravitreal clindamycin.

References

  1. Jones JL, Dargelas V, Roberts J, et al. Risk factors for Toxoplasma gondii infection in the United States. Clin Infect Dis. 2009;15:878–884. doi:10.1086/605433 [CrossRef]
  2. Bonfioli AA, Orefice F. Toxoplasmosis. Semin Ophthalmol. 2005;20:129–141. doi:10.1080/08820530500231961 [CrossRef]
  3. Gilbert RE, Dunn DT, Lightman S, et al. Incidence of symptomatic toxoplasma eye disease: aetiology and public health implications. Epidemiol Infect. 1999;123:283–289. doi:10.1017/S0950268899002800 [CrossRef]
  4. Perkins ES. Ocular toxoplasmosis. Br J Ophthalmol. 1973;57:1–17. doi:10.1136/bjo.57.1.1 [CrossRef]
  5. Rothova A. Ocular involvement in toxoplasmosis. Br J Ophthalmol. 1993;77:371–377. doi:10.1136/bjo.77.6.371 [CrossRef]
  6. Kim SJ, Scott IU, Brown GC, et al. Interventions for toxoplasma retinochoroiditis: a report by the American Academy of Ophthalmology. Ophthalmology. 2013;120(2):371–378. doi:10.1016/j.ophtha.2012.07.061 [CrossRef]
  7. Dodds EM. Ocular Toxoplasmosis: Clinical Presentations, Diagnosis and Therapy. Focal Points: Clinical Modules for Ophthalmologists. San Francisco, CA: American Academy of Ophthalmology; 1999:1–14.
  8. Rothova A, Bosch-Driessen LE, van Loon NH, Treffers WF. Azithromycin for ocular toxoplasmosis. Br J Ophthalmol. 1998;82:1306–1308. doi:10.1136/bjo.82.11.1306 [CrossRef]
  9. Stanford MR, See SE, Jones LV, Gilbert RE. Antibiotics for toxoplasmic retinochoroiditis: an evidence-based systematic review. Ophthalmology. 2003;110:926–931; quiz 31–32. doi:10.1016/S0161-6420(03)00083-6 [CrossRef]
  10. Kishore K, Conway MD, Peyman GA. Intravitreal clindamycin and dexamethasone for toxoplasmic retinochoroiditis. Ophthalmic Surg Lasers. 2001;32(3):183–192.
  11. Soheilian M, Ramezani A, Azimzadeh A, et al. Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisolone in treatment of ocular toxoplasmosis. Ophthalmology. 2011;118(1):134–141. doi:10.1016/j.ophtha.2010.04.020 [CrossRef]
  12. Fiscella R, Peyman GA, Kimura A, Small G. Intravitreal toxicity of cotrimoxazole. Ophthalmic Surg. 1988;19(1):44–46.
  13. Holland GN, Lewis KG. An update on current practices in the management of ocular toxoplasmosis. Am J Ophthalmol. 2002; 134:102–114. doi:10.1016/S0002-9394(02)01526-X [CrossRef]
  14. Engstrom RE Jr, Holland GN, Nussenblatt RB, Jabs DA. Current practices in the management of ocular toxoplasmosis. Am J Ophthalmol. 1991;111:601–610 doi:10.1016/S0002-9394(14)73706-7 [CrossRef]
  15. Clark MA, Finkel R, Rey JA, Whalen K. Lippincott’s Illustrated Reviews: Pharmacology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.

Demographic Profile, Clinical Features, and Treatment Outcomes in Patients Who Received Intravitreal Cotrimoxazole/Dexamethasone for TRC

Pt. No.Age/SexPresenting VALocation of RetinitisMedia Haze GradeNo. Injections ReceivedInjection RegimenInjection-related ComplicationsDuration of Follow-upPost-treatment Media Haze GradeFinal VA
112 y/M20/400parafoveal25biweeklynone23 weeks020/20
224 y/M20/100pparafoveal15biweeklynone15 weeks020/40
314 y/M20/25pInfero-nasal to optic disc23weeklynone15 weeks020/20
441 y/F20/40Infero-temporal to optic disc23weeklynone15 weeks020/20
Fundus photographs of the left eye of case 1. (A) Focal retinochoroiditis at presentation (day 0). (B) One day after the first injection (day 1). (C) Three days after the second injection (day 5). At the last follow-up, 3 weeks after the fifth injection (day 35). (EH) Corresponding OCTs on days 0, 1, 5, and 35, respectively. Subretinal fluid and increased retinal thickness noted at presentation resolved over time.

Figure.

Fundus photographs of the left eye of case 1. (A) Focal retinochoroiditis at presentation (day 0). (B) One day after the first injection (day 1). (C) Three days after the second injection (day 5). At the last follow-up, 3 weeks after the fifth injection (day 35). (EH) Corresponding OCTs on days 0, 1, 5, and 35, respectively. Subretinal fluid and increased retinal thickness noted at presentation resolved over time.

10.3928/23258160-20150101-27

Sign up to receive

Journal E-contents