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Man presents with bilateral chorioretinal lesions
Both eyes showed 'punched-out' chorioretinal lesions dotting the peripapillary retina and macula.
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Source: James Constans, MD, and Lana Rifkin, MD
A 29-year-old white man with no significant medical history and a ocular history of contact lens use was referred to the uveitis clinic for a second opinion regarding bilateral chorioretinal lesions that were found on a routine comprehensive exam. He endorsed intermittent dry eye sensation, occasional blurred vision, and a long-standing and unchanged presence of intermittent floaters in both eyes. He was otherwise asymptomatic with no changes in vision, new floaters or flashes.
Examination
On examination, best corrected visual acuity was 20/20 in both eyes. Confrontational visual fields were full bilaterally. Both pupils were equal in size and reactive to light without afferent pupillary defect. Extraocular movements were full bilaterally, and IOPs were normal. Slit lamp examination of the anterior segment was unremarkable. Dilated fundoscopic examination revealed diffuse and scattered retinal pigment epithelial mottling limited to the macula in both eyes with a flat choroidal nevus along the temporal macula in the right eye. There was no vitritis or haze. Inactive-appearing “punched-out” chorioretinal lesions were seen dotting the peripapillary retina and macula bilaterally (Figure 1).
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Chorioretinal lesions
A detailed review of systems was negative, revealing no recent skin changes or history of rashes. There was no history of breathing difficulties, nor back or joint pain. Further inquiry of the patient’s medical and family history revealed a personal history of gingival recession, childhood varicella infection, as well as a recent sinus infection occurring 3 months before presentation. There was no history of cold sores or herpes zoster infection. Likewise, there was no history of trauma or personal/family history of systemic inflammatory conditions. Travel history revealed a trip to France approximately 9 months prior and a previous short-term residence in Kentucky many years before relocation to his current home in Massachusetts. Systemic workup had been initiated by the referring physician, including serum FTA-Abs and QuantiFERON Gold, both of which were negative.
Cross-sectional OCT imaging through the lesions revealed outer retinal atrophy (Figure 2). Fluorescein angiography demonstrated window defect-like late staining of the lesions, although no early hyperfluorescence or leakage (Figure 3). Indocyanine green angiography demonstrated hypocyanescence that remained consistent throughout the course of the study (Figure 4).
Given the clinical picture and workup described above, a narrow differential diagnosis was formulated to include presumed ocular histoplasmosis syndrome (POHS), followed by punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP).
Diagnosis
POHS represents a constellation of chorioretinal findings, often subclinical, related to exposure to the dimorphic fungus Histoplasma capsulatum. While this fungus is considered to be the world’s leading cause of endemic mycosis, its reported clinical activity remains primarily limited to the Ohio and Mississippi river valleys within the United States, with further case reports mostly concentrated to the countries of India, Mexico, the United Kingdom and the Netherlands.
Ocular findings most commonly include peripapillary atrophy (PPA) and characteristic chorioretinal scarring, with the potential for formation of choroidal neovascularization (CNV) — importantly, never appearing with concomitant vitritis. There is no gender predilection, although it is most commonly found in Caucasians. Acute lesions appear white or gray in coloration and are smaller in size than their chronic counterparts. Chronic lesions take on a more characteristic atrophic and “punched-out” appearance. They are often round in shape, with variable pigmentation and random orientation, and can involve the central or peripheral retina.
In cases of untreated CNV, extrafoveal location is associated with a 44% risk of severe vision loss over 5 years compared with the 75% risk over 2 to 3 years associated with subfoveal location.
These lesions can be further characterized by their appearance on ophthalmic imaging modalities. On fluorescein angiography, peripapillary atrophy and chronic chorioretinal scars typically appear hyperfluorescent with progressive scleral staining. POHS-related CNV demonstrates similar findings to those seen with other etiologies of neovascularization, most notably with prominent filling of new vessels during the early arterial phase followed by progressive and expanding borders of leakage over time. A “lacy” pattern CNV has been attributed to POHS more commonly than in other etiologies of neovascularization. Subretinal pigment epithelial CNV can also be visualized with the use of indocyanine green angiography, in which the membranes present as localized regions of hypercyanescence. Fundus autofluorescence and infrared imaging provide further assistance in distinguishing these lesions, with characteristic hypoautofluorescence and hyperreflective irregularity, respectively. Finally, OCT imaging taken through regions of chronic scarring demonstrates a loss of the normal hyperreflective band seen in the outer retina, corresponding to the punched-out atrophy characteristic of these lesions.
Given the coloration and atrophic appearance of these lesions, the differential diagnosis of POHS is often accompanied by other inflammatory chorioretinopathies, including multifocal choroiditis with panuveitis, punctate inner choroidopathy, birdshot chorioretinopathy, acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and multiple evanescent white dot syndrome (MEWDS). Furthermore, one should also consider evaluating for infectious or inflammatory etiologies commonly known for their varied presentation, including tuberculosis, sarcoidosis and syphilis. Finally, the presence of CNV necessitates further workup in an effort to distinguish POHS from other potential causes of CNV, such as choroidal rupture with CNV, myopic CNV and age-related macular degeneration, although these conditions are not typically associated with the aforementioned atrophic scarring.
MCP may present with yellow-gray chorioretinal lesions or punched-out-appearing scars, with the potential to develop CNV in approximately 35% of cases. Unlike POHS, it is typically associated with anterior uveitis and vitritis. Similarly, PIC often presents with the scattered appearance of small yellow-white retinal lesions, although unlike MCP, these often occur in the absence of anterior uveitis or vitritis. Additionally, these lesions are most commonly seen within the arcades, and subsequent development of CNV occurs in roughly 40% of cases. PPA may be commonly seen in MCP as well as POHS, although it is typically limited in extent with the former compared with the circumferential presentation seen in the latter. PPA is not characteristic of PIC. Both PIC and MCP are more common in females, whereas POHS has no gender predilection. The lesions are often thought to be largest in diameter in MCP, followed by POHS and then PIC. Additionally, these three conditions often appear similarly on ocular imaging modalities, making it more difficult to differentiate one from another, particularly among those individuals living in areas endemic to histoplasmosis.
MEWDS also presents with multiple small gray-white retinal lesions, usually unilateral, although they are typically limited to the posterior pole and do not demonstrate atrophic scarring. The lesions found in APMPPE are placoid, yellow-white in appearance and usually limited to the posterior pole. They resolve spontaneously over 2 to 6 weeks and leave shallow pigmented scars in their wake. Finally, birdshot chorioretinopathy is characterized by the bilateral presence of numerous cream-colored lesions typically involving the nasal fundus, although they can extend further. These lesions often present with indistinct margins and a notable lack of pigmentation. It is not uncommon to find associated anterior uveitis, vitritis, vasculitis, disc edema and rarely CNV.
Discussion and follow-up
The constellation of this patient’s relative lack of symptoms at presentation, negative laboratory testing and characteristic appearance of atrophic, pigmented chorioretinal lesions was felt to best represent either inactive PIC or POHS. Further consideration of his time spent in Kentucky, a region within the Ohio River Valley, lent further support to the diagnosis of POHS. Given a lack of evidence that prophylactic immunomodulatory therapy prevents future development of CNV in either PIC or POHS, no further treatment was recommended at this time.
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- For more information:
- James Constans, MD, and Lana Rifkin, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Aubrey R. Tirpack, MD, and Astrid C. Werner, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.