A 76-year-old female with past medical history of hyperlipidemia and hypertension presents for second opinion on vitritis. She initially presented 2 months prior to an ophthalmologist who treated her for anterior uveitis. She eventually was referred to a retina specialist, who identified retinal whitening that could indicate retinal artery occlusion and subsequent development of vitritis. She was referred to our uveitis clinic, and on presentation her visual acuity was counting fingers and 20/25. Intraocular pressure was 25 and 12. Her anterior chamber demonstrated granulomatous keratic precipitates and 2+ cell.

The clinical picture was concerning for acute retinal necrosis given the panuveitis with vitritis, large areas of retinal whitening, and arteritis (Figure 1). There was a focal area of thinning in the macula concerning for a branch retinal artery occlusion. Tap and inject was performed with foscarnet and clindamycin. Aqueous fluid was sent for HSV, VZV, CMV, and Toxoplasma gondii PCR. Treatment with valacyclovir was initiated at 2 g 3 times daily and she was started on difluprednate every 2 hours. The toxoplasma PCR was highly positive, so valacyclovir was discontinued and the patient—who was allergic to sulfa drugs—was started on atovaquone 750 mg twice a day. She received 3 more injections of clindamycin, each 1 week apart (Figure 2). Oral prednisone was initiated at this time. After 5 weeks of treatment, vitritis had improved and lesions were resolving with well-granulated borders (Figure 3).

She returned to clinic 3 weeks later and was found to have a total retinal detachment (Figure 4). She had noticed a mild decline in vision; in clinic, her visual acuity measured light perception. She was taken to the operating room for repair. The retina was flattened and treated with laser and silicone oil tamponade.

DISCUSSION

Ocular toxoplasmosis is often described with the pathognomonic “fog in the headlights” appearance. This refers to the exam finding of a whitish-yellow retinochoroiditis adjacent to an inactive pigmented scar with a dense vitritis and haze. Rarely, primary acquired toxoplasmosis can cause an infectious retinitis that mimics acute retinal necrosis (ARN), a viral retinitis. This phenomenon has been well documented in immunocompromised patients with AIDS, lymphoma or other hematologic malignancy, autoimmune disease, organ or bone marrow transplant recipients, or those on chronic immunosuppressive therapy (including steroids). Though not classically recognized as an immuno-compromised state, age has also been identified as a risk factor for this atypical fulminant presentation of toxoplasmosis retinochoroiditis, as was the case in our patient. While this presentation is rare, it should be in the back of your mind when seeing “classic” cases of ARN.

DIAGNOSIS

Acute retinal necrosis often presents with the following clinical characteristics: 1 or more foci of retinal necrosis with discrete borders located in the peripheral retina; rapid progression; circumferential spread; evidence of occlusive vasculopathy with arterial involvement; and a prominent inflammatory reaction in both the vitreous and anterior chamber. As demonstrated in our case, an atypical presentation of toxoplasmosis can masquerade as ARN. However, there are other entities that we need to think of when we see these findings on exam. Additional diagnoses that may explain these findings include syphilis, tuberculosis, Behçet’s disease, sarcoidosis, and even sympathetic ophthalmia.

In patients with diffuse necrotizing retinitis vitreous, tap and inject is recommended. The sensitivity and specificity for aqueous viral PCR testing is quite high, but for aqueous toxoplasma PCR testing it is lower. Reports on vitreous PCR sensitivity and specificity area have yielded variable results, but if one can obtain vitreous, there appears to be a higher sensitivity. Samples should be tested for HSV, VZV, CMV, and T. gondii PCR. Most reference laboratories can do testing on as little as 50 μl of fluid. I recommend communicating with your lab and the reference lab of choice in advance so that they know they are handling a precious aqueous or vitreous sample.

Serum testing for toxoplasmosis can be deceiving. The window for IgM antibodies can be short and missed, and patients may have positive IgG years after exposure. The clinical picture should be consistent with ocular toxoplasmosis regardless of the serum results. Other serologic testing should be done to test for syphilis, tuberculosis, and sarcoidosis. A full medical and social history should be performed along with a review of systems to make sure nothing is missed.

TREATMENT

For cases of a toxoplasmosis diffuse retinitis, I like to treat with systemic medication and recommend considering adjuvant intravitreal clindamycin. Since the diagnosis is usually not known at first presentation, consider empiric treatment for both viral and toxoplasmosis necrotizing retinitis. Patients can be started on 1 g to 2 g of valacyclovir 3 times a day and concomitant treatment for ocular toxoplasmosis. At the time of tap, consider foscarnet (and/or ganciclovir) and clindamycin. Dosing for foscarnet is 2.4 mg and the dosing for clindamycin is 1 mg.

For treatment of toxoplasmosis, Bactrim DS (sulfamethaxole/trimethoprim) has become a first-choice therapy due to availability and low side-effect profile. Classic triple therapy is pyrimethamine, sulfadiazine, and folinic acid ± corticosteroids; quadruple therapy includes the addition of clindamycin. For patient that are sulfa-allergic, alternatives include atovoquone (750 mg twice a day) or azithromycin (500 mg daily). For pregnant patients, spiramycin is recommended; however, this can be difficult to obtain in the United States.

In patients with atypical retinitis, as in our case, consider adjuvant intravitreal clindamycin 1 mg ± 400 μg of dexamethasone until the borders are no longer active.

COMPLICATIONS

Despite aggressive treatment, patients can develop some devastating complications. Our patient developed both an artery occlusion and a retinal detachment. Retinal detachment tends to result from a tear at the border of an area of retinal necrosis that is thinned. Prophylactic laser can be applied to the posterior border of the healed or active necrosis, but it is controversial. Artery occlusions occur as a result of the associated arteritis. Sometimes patients can develop secondary neovascularization of the retina from this, which would require panretinal photocoagulation.

PEARLS

Ocular toxoplasmosis can present as a multifocal necrotizing retinitis even in seemingly immunocompetent patients. Toxoplasmosis should be on the differential when seeing cases of acute retinal necrosis. Consider PCR testing of ocular fluid for toxoplasma DNA and injection of intravitreal clindamycin in these cases. Empiric treatment with both Bactrim DS and valacyclovir in a newly diagnosed case of necrotizing retinitis is a reasonable choice. NRP

FURTHER READING

1. de-la-Torre A, Stanford M, Curi A, Jaffe GJ, Gomez-Marin JE. Therapy for ocular toxoplasmosis. Ocul Immunol Inflamm. 2011;19(5):314-320. doi:10.3109/09273948.2011.608915
2. Johnson MW, Greven GM, Jaffe GJ, Sudhalkar H, Vine AK. Atypical, severe toxoplasmic retinochoroiditis in elderly patients. Ophthalmology. 1997;104(1):48-57. doi:10.1016/s0161-6420(97)30362-5
3. Fardeau C, Romand S, Rao NA, et al. Diagnosis of toxoplasmic retinochoroiditis with atypical clinical features. Am J Ophthalmol. 2002;134(2):196-203. doi:10.1016/s0002-9394(02)01500-3
4. Montoya JG, Parmley S, Liesenfeld O, Jaffe GJ, Remington JS. Use of the polymerase chain reaction for diagnosis of ocular toxoplasmosis. Ophthalmology. 1999;106(8):1554-1563. doi:10.1016/S0161-6420(99)90453-0
5. Smith JR, Cunningham ET Jr. Atypical presentations of ocular toxoplasmosis. Curr Opin Ophthalmol. 2002;13(6):387-392. doi:10.1097/00055735-200212000-00008