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Pregnant woman presents with floaters and decreased vision

Examination of the left eye featured anterior vitreous cell, multiple vitreous opacities and retinal lesions involving the macula.

A 32-year-old pregnant woman at 31 weeks’ gestational age was referred to the New England Eye Center for a 1-week history of floaters and decreased vision in the left eye. She complained of 1 day of photophobia and left eye pain.

Ocular history was unremarkable. Medical history included prior cesarean section, hepatitis C and spinal desmoid tumors resected and treated with doxorubicin. She had a history of intravenous drug use and stated the last episode was 8 months before presentation. She lived in a rural area with exposure to many animals including cats, dogs and horses and had removed ticks from her skin over the past year.

Examination

Initial exam showed a best corrected visual acuity of 20/20 in the right eye and 20/100 in the left eye. Pupils were equal and brisk with no evidence of an afferent pupillary defect. Confrontation visual fields and extraocular movements were full bilaterally. IOP was 8 mm Hg in the right eye and 6 mm Hg in the left eye.

Anterior segment exam of the right eye was normal. Slit lamp biomicroscopy of the left eye was significant for diffuse conjunctival injection with 4+ cell and 2+ flare in the anterior chamber. The cornea, iris and lens were all noted to be normal. Posterior examination of the left eye revealed 2+ anterior vitreous cell, multiple vitreous opacities and retinal lesions involving the macula (Figure 1). There were no peripheral lesions or evidence of vasculitis. Funduscopic exam of the right eye was normal. OCT confirmed the presence of vitreous debris and a pre-retinal infiltrate (Figure 2).

Figure 1. Color fundus photographs of the right and left eyes. The right eye is normal. The left eye shows a hazy view with multiple vitreous opacities and pre-retinal lesions.

Images: Tirpack A, Baumal C

Figure 2. OCT images of the right (above) and left (below) eyes. The right eye is normal. The image of the left eye reveals vitreous debris and a pre-retinal infiltrate with underlying shadowing.

What is your diagnosis?

Unilateral panuveitis

The differential diagnosis for unilateral panuveitis is broad but can be categorized into infectious, inflammatory and neoplastic syndromes.

Infectious considerations include endogenous endophthalmitis, specifically bacterial or fungal, given the patient’s history of intravenous drug abuse. The clinical appearance was most consistent with fungal endophthalmitis given the “fluffy” vitreous opacities. Other infectious entities include syphilis, tuberculosis, toxoplasmosis, CMV retinitis, herpes simplex virus or herpes zoster virus. Syphilis and tuberculosis can present in varied forms and should always be considered in the differential of panuveitis. Toxoplasmosis, a commonly identified cause of posterior uveitis, is typically a unilateral granulomatous uveitis with retinitis adjacent to a chorioretinal scar. The retinal findings in our patient were not consistent with toxoplasmosis. CMV retinitis typically presents with retinal necrosis and hemorrhages, neither of which our patient demonstrated. While acute retinal necrosis, caused by herpes simplex and herpes zoster viruses, can present with panuveitis, areas of retinal necrosis and retinal vasculitis are usually appreciated on exam.

Sarcoidosis should always be considered in cases of panuveitis given its variable presentation. Primary intraocular lymphoma can present similarly to uveitis; however, these patients typically do not have pain, conjunctival injection or anterior chamber inflammation.

Diagnosis and management

Given the patient’s history of intravenous drug abuse and clinical picture, there was concern for underlying infectious etiology. On the day of presentation, she underwent vitreous tap and intravitreal injection of vancomycin and amphotericin in the left eye. Vitreous fluid was sent for Gram stain, routine bacterial culture and fungal culture. Given the concern for systemic illness, she was admitted to the obstetrics service, and infectious disease was consulted. Blood cultures, urine cultures, complete blood count, HIV, PPD, Lyme titers, toxoplasmosis titers, RPR/FTA-ABS and a transthoracic echocardiogram were ordered. There was concern for possible underlying autoimmune etiology in the setting of pregnancy; therefore, a chest X-ray, ACE, ANA and HLA-B27 were ordered. She was started on empiric intravenous vancomycin, ceftazidime and voriconazole at the time of admission.

Vitreous culture grew Candida dubliniensis, sensitive to fluconazole. Initial blood cultures grew coagulase-negative Staphylococcus in one of two bottles, which was suspected to be contaminant. Subsequent blood cultures were negative. Fungal blood cultures were negative. Chest X-ray, echocardiogram, and the remaining infectious and inflammatory blood work were all negative. Intravenous antibiotics were discontinued, and the patient was transitioned to oral voriconazole upon discharge.

Of particular interest in this case was the use of systemic antifungal agents in the setting of pregnancy. Voriconazole is the gold standard for treatment of fungal endophthalmitis given its excellent intraocular penetration. However, it has been shown to be teratogenic. Amphotericin was considered as an alternative therapy in this case but was determined to be inferior due to lower intraocular penetration. After discussions among the infectious disease, ophthalmology and obstetrics services and informed discussion with the patient, it was decided to initiate treatment with voriconazole because the patient was in her third trimester and the majority of fetal development was complete.

Her vision at the time of discharge, 5 days after initial presentation, was 20/300 in the left eye. The patient had improvement in pain and photophobia. Anterior and posterior inflammation was stable from presentation. Posterior exam revealed consolidation of vitreous opacities. The right eye exam remained normal. She continues to followup with her local ophthalmologist.

Discussion

Endogenous endophthalmitis must always be considered in the differential diagnosis of new onset vision loss with associated intraocular inflammation. It is thought that approximately 5% of all cases of endophthalmitis are endogenous. Risk factors include immunocompromised state, indwelling catheters or devices, and intravenous drug use. It has been shown that a diagnosis of endophthalmitis is initially missed in nearly half of cases. Physicians must have a high level of suspicion for endogenous endophthalmitis, particularly in younger individuals who are otherwise seemingly healthy. Clinical signs of endophthalmitis include fever, anterior segment inflammation, vitritis and retinal infiltrates.

Bacteria and fungi are the most commonly isolated pathogens in culture-proven endophthalmitis. Candida albicans is the most commonly isolated fungal species. It has been shown that Candida is a common pathogen in cases of endophthalmitis with known intravenous drug abuse. Candida endophthalmitis most commonly presents as “fluffy” white chorioretinal lesions with overlying vitreous opacities. C. dubliniensis, our patient’s causal pathogen, is a less common source of endogenous endophthalmitis. It has only been reported in North America a handful of times. This species was first described in cases of oral candidiasis in HIV patients. It is generally thought to be a less virulent species than the closely related C. albicans.

Successful treatment of endogenous endophthalmitis requires rapid diagnosis and initiation of treatment. Present standard of care typically involves intravitreal and systemic antibiotics and/or antifungal agents. Vancomycin and ceftazidime are the most commonly used intravitreal antibiotics. Clinical worsening despite adequate local and systemic delivery of antibiotics and antifungals necessitates pars plana vitrectomy. It is well documented throughout the literature that visual outcomes of infectious endophthalmitis are poor. Early detection and initiation of treatment are imperative. A high index of suspicion among providers is essential, particularly when seeing patients with known intravenous drug abuse.

A 32-year-old pregnant woman at 31 weeks’ gestational age was referred to the New England Eye Center for a 1-week history of floaters and decreased vision in the left eye. She complained of 1 day of photophobia and left eye pain.

Ocular history was unremarkable. Medical history included prior cesarean section, hepatitis C and spinal desmoid tumors resected and treated with doxorubicin. She had a history of intravenous drug use and stated the last episode was 8 months before presentation. She lived in a rural area with exposure to many animals including cats, dogs and horses and had removed ticks from her skin over the past year.

Examination

Initial exam showed a best corrected visual acuity of 20/20 in the right eye and 20/100 in the left eye. Pupils were equal and brisk with no evidence of an afferent pupillary defect. Confrontation visual fields and extraocular movements were full bilaterally. IOP was 8 mm Hg in the right eye and 6 mm Hg in the left eye.

Anterior segment exam of the right eye was normal. Slit lamp biomicroscopy of the left eye was significant for diffuse conjunctival injection with 4+ cell and 2+ flare in the anterior chamber. The cornea, iris and lens were all noted to be normal. Posterior examination of the left eye revealed 2+ anterior vitreous cell, multiple vitreous opacities and retinal lesions involving the macula (Figure 1). There were no peripheral lesions or evidence of vasculitis. Funduscopic exam of the right eye was normal. OCT confirmed the presence of vitreous debris and a pre-retinal infiltrate (Figure 2).

Figure 1. Color fundus photographs of the right and left eyes. The right eye is normal. The left eye shows a hazy view with multiple vitreous opacities and pre-retinal lesions.

Images: Tirpack A, Baumal C

Figure 2. OCT images of the right (above) and left (below) eyes. The right eye is normal. The image of the left eye reveals vitreous debris and a pre-retinal infiltrate with underlying shadowing.

What is your diagnosis?

Unilateral panuveitis

The differential diagnosis for unilateral panuveitis is broad but can be categorized into infectious, inflammatory and neoplastic syndromes.

Infectious considerations include endogenous endophthalmitis, specifically bacterial or fungal, given the patient’s history of intravenous drug abuse. The clinical appearance was most consistent with fungal endophthalmitis given the “fluffy” vitreous opacities. Other infectious entities include syphilis, tuberculosis, toxoplasmosis, CMV retinitis, herpes simplex virus or herpes zoster virus. Syphilis and tuberculosis can present in varied forms and should always be considered in the differential of panuveitis. Toxoplasmosis, a commonly identified cause of posterior uveitis, is typically a unilateral granulomatous uveitis with retinitis adjacent to a chorioretinal scar. The retinal findings in our patient were not consistent with toxoplasmosis. CMV retinitis typically presents with retinal necrosis and hemorrhages, neither of which our patient demonstrated. While acute retinal necrosis, caused by herpes simplex and herpes zoster viruses, can present with panuveitis, areas of retinal necrosis and retinal vasculitis are usually appreciated on exam.

Sarcoidosis should always be considered in cases of panuveitis given its variable presentation. Primary intraocular lymphoma can present similarly to uveitis; however, these patients typically do not have pain, conjunctival injection or anterior chamber inflammation.

Diagnosis and management

Given the patient’s history of intravenous drug abuse and clinical picture, there was concern for underlying infectious etiology. On the day of presentation, she underwent vitreous tap and intravitreal injection of vancomycin and amphotericin in the left eye. Vitreous fluid was sent for Gram stain, routine bacterial culture and fungal culture. Given the concern for systemic illness, she was admitted to the obstetrics service, and infectious disease was consulted. Blood cultures, urine cultures, complete blood count, HIV, PPD, Lyme titers, toxoplasmosis titers, RPR/FTA-ABS and a transthoracic echocardiogram were ordered. There was concern for possible underlying autoimmune etiology in the setting of pregnancy; therefore, a chest X-ray, ACE, ANA and HLA-B27 were ordered. She was started on empiric intravenous vancomycin, ceftazidime and voriconazole at the time of admission.

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Vitreous culture grew Candida dubliniensis, sensitive to fluconazole. Initial blood cultures grew coagulase-negative Staphylococcus in one of two bottles, which was suspected to be contaminant. Subsequent blood cultures were negative. Fungal blood cultures were negative. Chest X-ray, echocardiogram, and the remaining infectious and inflammatory blood work were all negative. Intravenous antibiotics were discontinued, and the patient was transitioned to oral voriconazole upon discharge.

Of particular interest in this case was the use of systemic antifungal agents in the setting of pregnancy. Voriconazole is the gold standard for treatment of fungal endophthalmitis given its excellent intraocular penetration. However, it has been shown to be teratogenic. Amphotericin was considered as an alternative therapy in this case but was determined to be inferior due to lower intraocular penetration. After discussions among the infectious disease, ophthalmology and obstetrics services and informed discussion with the patient, it was decided to initiate treatment with voriconazole because the patient was in her third trimester and the majority of fetal development was complete.

Her vision at the time of discharge, 5 days after initial presentation, was 20/300 in the left eye. The patient had improvement in pain and photophobia. Anterior and posterior inflammation was stable from presentation. Posterior exam revealed consolidation of vitreous opacities. The right eye exam remained normal. She continues to followup with her local ophthalmologist.

Discussion

Endogenous endophthalmitis must always be considered in the differential diagnosis of new onset vision loss with associated intraocular inflammation. It is thought that approximately 5% of all cases of endophthalmitis are endogenous. Risk factors include immunocompromised state, indwelling catheters or devices, and intravenous drug use. It has been shown that a diagnosis of endophthalmitis is initially missed in nearly half of cases. Physicians must have a high level of suspicion for endogenous endophthalmitis, particularly in younger individuals who are otherwise seemingly healthy. Clinical signs of endophthalmitis include fever, anterior segment inflammation, vitritis and retinal infiltrates.

Bacteria and fungi are the most commonly isolated pathogens in culture-proven endophthalmitis. Candida albicans is the most commonly isolated fungal species. It has been shown that Candida is a common pathogen in cases of endophthalmitis with known intravenous drug abuse. Candida endophthalmitis most commonly presents as “fluffy” white chorioretinal lesions with overlying vitreous opacities. C. dubliniensis, our patient’s causal pathogen, is a less common source of endogenous endophthalmitis. It has only been reported in North America a handful of times. This species was first described in cases of oral candidiasis in HIV patients. It is generally thought to be a less virulent species than the closely related C. albicans.

Successful treatment of endogenous endophthalmitis requires rapid diagnosis and initiation of treatment. Present standard of care typically involves intravitreal and systemic antibiotics and/or antifungal agents. Vancomycin and ceftazidime are the most commonly used intravitreal antibiotics. Clinical worsening despite adequate local and systemic delivery of antibiotics and antifungals necessitates pars plana vitrectomy. It is well documented throughout the literature that visual outcomes of infectious endophthalmitis are poor. Early detection and initiation of treatment are imperative. A high index of suspicion among providers is essential, particularly when seeing patients with known intravenous drug abuse.