To report the first patient with ocular toxoplasmosis treated with a slow-release biodegradable intravitreal clindamycin implant.
A 39-year-old human immunodeficiency virus (HIV)-positive woman with recurrent toxoplasmic retinochoroiditis and vitritis for whom oral medication was medically contraindicated was treated with an intravitreal slow-release clindamycin implant and three monthly intravitreal injections of clindamycin and dexamethasone. Serial ophthalmologic examinations demonstrated gradual, complete resolution of posterior uveitis and healing of the retinochoroidal lesion with cicatricial changes, as well as gradual improvement of cells in the anterior chamber. There was no significant change in electroretinography waves after treatment with the implant. The presence of the implant, or part of it, was detectable in the vitreous cavity for 4 months. To date, the patient has been monitored for 30 months, and there has been no reactivation of ocular toxoplasmosis.
The slow-release clindamycin implant was safe for intravitreal use in this patient and may have contributed to the long-term control of toxoplasmosis chorioretinitis.
Toxoplasmosis is caused by the protozoan Toxoplasma gondii , and is the most common cause of infectious posterior uveitis. It can be transmitted by ingestion of the protozoan through contaminated foods and fluids, or by the transplacental route, organ transplantation, or blood transfusion. About one-third of the world’s population may be infected with toxoplasmosis. T. gondii seropositivity can range from 10% to 90% and may be asymptomatic or may manifest with various clinical signs and symptoms depending on the immunological status of the patient. ,
The prevalence of posterior uveitis caused by toxoplasmosis is about 17.7% in southern Brazil, and in the United States 2% of T. gondii -infected patients have ocular signs of the disease. , Ocular toxoplasmosis usually occurs as focal exudative retinochoroiditis, although it can also manifest in an atypical manner as punctate outer retinitis, Jensen neuroretinitis, or even as a necrotizing condition.
In most cases, the treatment of ocular toxoplasmosis consists of orally administered drugs. The traditional regimen is a combination of sulfadiazine, pyrimethamine, and folinic acid, with or without the use of oral steroids, although sometimes just sulfamethoxazole/trimethoprim is administered. Clindamycin and azithromycin are alternatives for patients who are allergic to other treatment regimens. However, oral treatments may induce undesirable side effects. Helfenstein M et al. reported a 24.3% rate of adverse reactions to the classic regimen (sulfadiazine, pyrimethamine and folinic acid) which led to discontinuation of the medication; reported adverse events included elevated creatinine (5.4%), increased hepatic enzyme levels (5.4%), vomiting (5.4%), skin rashes (5.4%, and facial edema (2.7%). A retrospective study reported a 40% incidence of adverse effects related to the medications commonly used (sulfadiazine, pyrimethamine, sulfamethoxazole-trimethoprim, clindamycin, and atovaquone), among them skin rashes, diarrhea, gastrointestinal bleeding, epigastric pain, leukopenia, and thrombocytopenia. Thus, other therapeutic options have been proposed. Kishore K et al. reported resolution of the inflammatory process with improved visual acuity among patients with ocular toxoplasmosis treated with intravitreal injections of 1.0 mg clindamycin in 0.1 mL and 1.0 mg of dexamethasone in 0.1 mL. However, multiple injections of these agents may be required to control the disease, thereby increasing the risk of complications.
Clindamycin is a medication belonging to the lincosamide group and is considered to be a bacteriostatic agent that penetrates the intracellular medium and inhibits the synthesis of bacterial proteins. It affects apicoblast translation, rendering the microorganisms more vulnerable to opsonization and phagocytosis, which facilitates their digestion by leukocytes.
We report herein a case of an immunosuppressed and sulfa drug-intolerant patient with posterior uveitis due to toxoplasmosis, who was medically unable to be treated with the medication regimen traditionally used to treat ocular toxoplasmosis and, therefore, was treated with a slow-release intravitreal clindamycin implant, the safety of which was demonstrated by Fernandes-Cunha et al.
A 39-year-old woman presented with a one-week history of reduced visual acuity, conjunctival injection, photophobia and pain in the left eye which had not improved after four days of treatment with dexamethasone and tropicamide eyedrops and oral sulfamethoxazole/trimethoprim prescribed by her primary eye doctor. Her visual acuity was 20/20 in the right eye (OD) and 20/200 in the left eye (OS). Slit-lamp biomicroscopy of the right eye was unremarkable and, in the left eye, revealed mild conjunctival injection, anterior chamber cells (ACC) 2+/4+, and fine diffuse keratic precipitates (KP). Dilated funduscopic examination was unremarkable in the right eye and, in the left eye, revealed mild vitritis and a yellow-white retinochoroidal lesion with overlying exudation occupying the entire posterior pole. Serological IgM and IgG tests were positive for toxoplasmosis. Therefore, oral sulfamethoxazole 800mg/trimethoprim 160mg every 12 hours, oral prednisone 40 mg once daily and topical dexamethasone and tropicamide were continued. In addition to toxoplasmosis, serological investigation demonstrated human immunodeficiency virus (HIV)-positivity, with a CD4 count of 143 cells/mm³ and a viral load of 126,305 copies/ml. Other common causes of retinochoroiditis in Brazil, such as syphilis and tuberculosis, were excluded with laboratory testing. Anti-retroviral treatment was initiated 30 days after initiation of ocular toxoplasmosis treatment and monitored by infectious disease specialists, and serial ophthalmologic examinations over the subsequent 45 days demonstrated gradual improvement in visual acuity (20/100 in OS), anterior (absence of anterior chamber reaction) and posterior segment inflammation (absence of vitritis), and retinochoroiditis (hypochromic lesion without exudation). After 45 days of treatment, prophylactic sulfamethoxazole/trimethoprim, three days per week, was prescribed.
One month after prophylactic medication use, the patient presented with pharmacodermia (face, neck, chest and abdomen skin eruptions and erythema) and her clinical situation worsened, with reactivation of the chorioretinal lesion in the left eye. At this time, her visual acuity in the left eye was hand motion. Optical coherence tomography (OCT) was unremarkable in the right eye and, in the left eye, revealed disorganization of retinal architecture, increased central subfield thickness (548 μm), and the presence of hyperreflective points on the retinal surface suggestive of inflammatory cells ( Fig. 1 A and B). Treatment with the typical anti-toxoplasmosis oral medications was contraindicated due to elevated liver enzymes and adverse skin effects. The patient also could not afford oral clindamycin. Intravitreal injections of clindamycin (1 mg) and dexamethasone (1 mg) were performed in the same setting. Forty-five days after this single intravitreal procedure, Best-corrected visual acuity (BCVA) improved to 20/1600 and there was partial improvement of eye fundus findings.