Grand Rounds at the New England Eye Center

Man presents with blurry vision, flashes, floaters and redness

The left eye had anterior chamber inflammation, vitritis, retinitis and retinal vasculitis.

A 53-year-old Caucasian man presented with a 3-week history of worsening blurry vision of the left eye associated with flashes, floaters and redness. He also complained of a recent fever that lasted 2 weeks and resolved on its own. He noted that he recently had a “sore” in his mouth that also resolved.

The patient had a medical history of hypertension and hyperlipidemia. His ocular history was significant only for refractive error. He denied any tobacco use and reported social alcohol use. He had no pets at home. He worked as a chef, often working with raw or undercooked meat. He noted that his wife recently had a cold sore, and he had chicken pox as a child.

Examination

Uncorrected visual acuity was 20/25 in the right eye and 20/50 in the left eye. Both pupils were equally round and briskly reactive with no afferent pupillary defect. IOP, confrontational visual fields and extraocular movements were normal in both eyes. Anterior segment examination was within normal limits in the right eye, and the left eye had diffuse keratic precipitates with 2+ cell and flare of the anterior chamber. Anterior vitreous was clear in the right eye, and there were 2+ anterior vitreous cells in the left eye with 2+ haze. Fundus examination of the right eye was within normal limits, while the left eye had a single discreet nasal patch of retinitis near the optic nerve with sheathing of arterioles emanating from the optic nerve nasally (Figure 1).

Figure 1. Mosaic photo of left eye showing a single discreet nasal patch of retinitis near the optic nerve with sheathing of arterioles emanating from the optic nerve nasally.

Images: Witkin D, Witkin A

Figure 2. OCT of the macula of the left eye (top). OCT through the patch of retinitis in the left eye (bottom).

OCT of the maculae of both eyes was within normal limits without intraretinal fluid or subretinal fluid, although there was a slight irregularity of the foveal retinal pigment epithelium in the left eye. OCT signal of the left eye was also attenuated by vitreous haze. OCT through the lesion of retinitis in the left eye showed diffuse hyperreflectivity involving all retinal layers without associated intraretinal or subretinal fluid (Figure 2). The patient was unable to tolerate fluorescein angiography due to vomiting and hypotension.

What is your diagnosis?

See answer on next page.

Retinitis with vitritis

The differential diagnosis for retinitis with vitritis includes infectious, inflammatory and other etiologies. Infectious causes include acute retinal necrosis or progressive outer retinal necrosis due to herpes simplex or varicella zoster viruses, Toxoplasma gondii, cytomegalovirus retinitis, syphilis, tuberculosis, Bartonella, Lyme and endogenous endophthalmitis. Inflammatory causes include Behçet’s disease and sarcoidosis. Although lower on the differential, neoplastic etiologies such as lymphoma must also be considered.

The anterior chamber was tapped, and fluid was sent for PCR for varicella zoster, herpes simplex 1 and 2, cytomegalovirus and toxoplasmosis. At the time of tap, foscarnet and clindamycin were injected into the vitreous. Blood tests were performed to check complete blood count, HIV, RPR, FTA-ABS, toxoplasma IgG and IgM, and herpes simplex 1 and 2. The patient was started on trimethoprim 160 mg and sulfamethoxazole 800 mg twice daily and valacyclovir 2 g three times daily for 3 days, then decreased to 1 g three times daily. He was also started on prednisolone acetate six times daily in the left eye, timolol twice daily in the left eye and atropine twice daily in the left eye.

Diagnosis and management

Serum testing showed that T. gondii IgM and IgG were both positive. PCR from aqueous fluid was also positive for T. gondii. This confirmed the diagnosis of primary toxoplasma infection. After the results were obtained, valacyclovir was discontinued, and trimethoprim-sulfamethoxazole was continued to complete a 30-day course. Prednisolone acetate was slowly tapered. At the patient’s 5-month follow-up visit, visual acuity was 20/25-1 in the right eye and 20/30-2 in the left eye. IOP was within normal limits in both eyes. Anterior chamber showed 2+ fine pigment in both eyes and trace cell in the left eye. Left eye had persistent central vitreous floaters. Fundus examination of the left eye showed no optic nerve edema or pallor and a 5 mm by 9 mm chorioretinal scar nasal to the optic nerve. There was stable sheathing of nasal arterioles with arteriolar plaques overlying the area of prior retinitis nasally and a small retinal hemorrhage on the nasal border. He continued to use prednisolone twice daily in the left eye at that time.

Discussion

T. gondii is an obligate intracellular protozoan parasite. There are two primary routes of infection: oral ingestion of oocysts from cat feces (primary host), or oral uptake of tissue cysts that persist in skeletal muscles of farm animals (intermediate hosts). Cysts are generally destroyed by cooking, so for the second route of infection, the person usually has to eat raw or undercooked meat. Most postnatal infections are clinically asymptomatic, and only about 2% of seropositive individuals have ocular toxoplasmosis. In general, the clinical course is more severe in immunocompromised patients. Seroprevalence is lower in the United States than in most countries. Worldwide, 22% of human T. gondii infections are secondary to ingestion of cysts in meat. It has been noted that animals raised outdoors or who have access to the outdoors have higher prevalence of T. gondii infection than animals raised in confinement.

Toxoplasma retinochoroiditis is typically unilateral, unifocal and larger than 1 disc diameter in size. It is generally associated with vitritis and can also present with granulomatous anterior chamber reaction and retinal vasculitis predominantly affecting arterioles. Most cases of toxoplasma retinochoroiditis represent reactivation of the disease, so there are often adjacent chorioretinal scars next to the area of active retinitis. The initial vision loss is often secondary to vitritis or macular involvement, and permanent vision loss can result from macular scarring. Usually, this is a self-limiting disease in immunocompetent adults. Trimethoprim-sulfamethoxazole, azithromycin, pyrimethamine-sulfadiazine, clindamycin, spiramycin and atovaquone have all been shown to be effective systemic treatments. Another possible first-line treatment that has been shown to be effective is intravitreal injection of clindamycin and dexamethasone together. There is also evidence that using trimethoprim-sulfamethoxazole every 2 to 3 days significantly reduces the risk of recurrence for at least 1 year after an active episode.

Summary

Primary Toxoplasma gondii infection can have a variable presentation and can mimic other infectious or inflammatory etiologies. It should be considered in all patients presenting with retinitis and vitritis. This patient was diagnosed by serum testing and aqueous fluid PCR, but he was treated empirically with oral trimethoprim-sulfamethoxazole and intravitreal clindamycin before definitive diagnosis. With treatment, his vision improved to 20/30. There may be a role for long-term trimethoprim-sulfamethoxazole as prophylaxis against recurrence of this infection.

A 53-year-old Caucasian man presented with a 3-week history of worsening blurry vision of the left eye associated with flashes, floaters and redness. He also complained of a recent fever that lasted 2 weeks and resolved on its own. He noted that he recently had a “sore” in his mouth that also resolved.

The patient had a medical history of hypertension and hyperlipidemia. His ocular history was significant only for refractive error. He denied any tobacco use and reported social alcohol use. He had no pets at home. He worked as a chef, often working with raw or undercooked meat. He noted that his wife recently had a cold sore, and he had chicken pox as a child.

Examination

Uncorrected visual acuity was 20/25 in the right eye and 20/50 in the left eye. Both pupils were equally round and briskly reactive with no afferent pupillary defect. IOP, confrontational visual fields and extraocular movements were normal in both eyes. Anterior segment examination was within normal limits in the right eye, and the left eye had diffuse keratic precipitates with 2+ cell and flare of the anterior chamber. Anterior vitreous was clear in the right eye, and there were 2+ anterior vitreous cells in the left eye with 2+ haze. Fundus examination of the right eye was within normal limits, while the left eye had a single discreet nasal patch of retinitis near the optic nerve with sheathing of arterioles emanating from the optic nerve nasally (Figure 1).

Figure 1. Mosaic photo of left eye showing a single discreet nasal patch of retinitis near the optic nerve with sheathing of arterioles emanating from the optic nerve nasally.

Images: Witkin D, Witkin A

Figure 2. OCT of the macula of the left eye (top). OCT through the patch of retinitis in the left eye (bottom).

OCT of the maculae of both eyes was within normal limits without intraretinal fluid or subretinal fluid, although there was a slight irregularity of the foveal retinal pigment epithelium in the left eye. OCT signal of the left eye was also attenuated by vitreous haze. OCT through the lesion of retinitis in the left eye showed diffuse hyperreflectivity involving all retinal layers without associated intraretinal or subretinal fluid (Figure 2). The patient was unable to tolerate fluorescein angiography due to vomiting and hypotension.

What is your diagnosis?

See answer on next page.

PAGE BREAK

Retinitis with vitritis

The differential diagnosis for retinitis with vitritis includes infectious, inflammatory and other etiologies. Infectious causes include acute retinal necrosis or progressive outer retinal necrosis due to herpes simplex or varicella zoster viruses, Toxoplasma gondii, cytomegalovirus retinitis, syphilis, tuberculosis, Bartonella, Lyme and endogenous endophthalmitis. Inflammatory causes include Behçet’s disease and sarcoidosis. Although lower on the differential, neoplastic etiologies such as lymphoma must also be considered.

The anterior chamber was tapped, and fluid was sent for PCR for varicella zoster, herpes simplex 1 and 2, cytomegalovirus and toxoplasmosis. At the time of tap, foscarnet and clindamycin were injected into the vitreous. Blood tests were performed to check complete blood count, HIV, RPR, FTA-ABS, toxoplasma IgG and IgM, and herpes simplex 1 and 2. The patient was started on trimethoprim 160 mg and sulfamethoxazole 800 mg twice daily and valacyclovir 2 g three times daily for 3 days, then decreased to 1 g three times daily. He was also started on prednisolone acetate six times daily in the left eye, timolol twice daily in the left eye and atropine twice daily in the left eye.

Diagnosis and management

Serum testing showed that T. gondii IgM and IgG were both positive. PCR from aqueous fluid was also positive for T. gondii. This confirmed the diagnosis of primary toxoplasma infection. After the results were obtained, valacyclovir was discontinued, and trimethoprim-sulfamethoxazole was continued to complete a 30-day course. Prednisolone acetate was slowly tapered. At the patient’s 5-month follow-up visit, visual acuity was 20/25-1 in the right eye and 20/30-2 in the left eye. IOP was within normal limits in both eyes. Anterior chamber showed 2+ fine pigment in both eyes and trace cell in the left eye. Left eye had persistent central vitreous floaters. Fundus examination of the left eye showed no optic nerve edema or pallor and a 5 mm by 9 mm chorioretinal scar nasal to the optic nerve. There was stable sheathing of nasal arterioles with arteriolar plaques overlying the area of prior retinitis nasally and a small retinal hemorrhage on the nasal border. He continued to use prednisolone twice daily in the left eye at that time.

Discussion

T. gondii is an obligate intracellular protozoan parasite. There are two primary routes of infection: oral ingestion of oocysts from cat feces (primary host), or oral uptake of tissue cysts that persist in skeletal muscles of farm animals (intermediate hosts). Cysts are generally destroyed by cooking, so for the second route of infection, the person usually has to eat raw or undercooked meat. Most postnatal infections are clinically asymptomatic, and only about 2% of seropositive individuals have ocular toxoplasmosis. In general, the clinical course is more severe in immunocompromised patients. Seroprevalence is lower in the United States than in most countries. Worldwide, 22% of human T. gondii infections are secondary to ingestion of cysts in meat. It has been noted that animals raised outdoors or who have access to the outdoors have higher prevalence of T. gondii infection than animals raised in confinement.

PAGE BREAK

Toxoplasma retinochoroiditis is typically unilateral, unifocal and larger than 1 disc diameter in size. It is generally associated with vitritis and can also present with granulomatous anterior chamber reaction and retinal vasculitis predominantly affecting arterioles. Most cases of toxoplasma retinochoroiditis represent reactivation of the disease, so there are often adjacent chorioretinal scars next to the area of active retinitis. The initial vision loss is often secondary to vitritis or macular involvement, and permanent vision loss can result from macular scarring. Usually, this is a self-limiting disease in immunocompetent adults. Trimethoprim-sulfamethoxazole, azithromycin, pyrimethamine-sulfadiazine, clindamycin, spiramycin and atovaquone have all been shown to be effective systemic treatments. Another possible first-line treatment that has been shown to be effective is intravitreal injection of clindamycin and dexamethasone together. There is also evidence that using trimethoprim-sulfamethoxazole every 2 to 3 days significantly reduces the risk of recurrence for at least 1 year after an active episode.

Summary

Primary Toxoplasma gondii infection can have a variable presentation and can mimic other infectious or inflammatory etiologies. It should be considered in all patients presenting with retinitis and vitritis. This patient was diagnosed by serum testing and aqueous fluid PCR, but he was treated empirically with oral trimethoprim-sulfamethoxazole and intravitreal clindamycin before definitive diagnosis. With treatment, his vision improved to 20/30. There may be a role for long-term trimethoprim-sulfamethoxazole as prophylaxis against recurrence of this infection.