Ocular Histoplasmosis Syndrome
Ocular histoplasmosis syndrome (OHS) is a multifocal chorioretinitis presumed to be caused by infection with Histoplasma capsulatum early in life. Primary infection occurs after inhalation of the fungal spores. Hematogenous dissemination likely results in ocular disease. Initial infection is usually asymptomatic. The initial focal infection of the choroid may subside and leave an atrophic scar and depigmentation of the RPE. The choroiditis may disrupt Bruch membrane, choriocapillaris, and RPE, allowing proliferation of subretinal vessels years later. The syndrome is usually found in endemic areas such as the Ohio and Mississippi River valleys but may occur in nonendemic areas as well. Men and women are affected equally, and the vast majority of patients are of northern European descent.
The diagnosis is suggested by the clinical triad of multiple white, atrophic choroidal scars (so-called histo spots); peripapillary pigment changes; and macular CNV in the absence of vitreous cells. Histo spots may appear in the macula or periphery, are discrete and punched out, and are usually asymptomatic (Fig 11-23). Approximately 1.5% of patients from endemic areas exhibit typical peripheral histo spots, first appearing during adolescence. Linear equatorial streaks are present in 5% of patients (Fig 11-24). In contrast, metamorphopsia and a profound reduction in central vision herald macular CNV and bring the patient to the attention of the ophthalmologist. The mean age of patients presenting with maculopathy is 41 years. Funduscopy of active neovascular lesions reveals a yellow-green subretinal membrane typically surrounded by a pigment ring. There may be associated intraretinal or subretinal fluid and subretinal hemorrhage. Subretinal fibrosis may develop.
Figure 11-23 Fundus photograph from a patient with ocular histoplasmosis, showing peripapillary pigmentary scarring; midperipheral chorioretinal scars, or “histo spots” (some pigmented and fibrotic); and spontaneously regressed, nasal, juxtafoveal choroidal neovascular membrane in the absence of vitreous cells. Visual acuity, 20/25.
(Courtesy of Ramana S. Moorthy, MD.)
Figure 11-24 Ocular histoplasmosis. Fundus photograph showing linear equatorial streaks.
(Courtesy of E. Mitchel Opremcak, MD.)
Figure 11-25 Ocular histoplasmosis. Fundus photograph showing macular choroiditis (arrow) with multiple yellow elevated lesions.
(Courtesy of Ramana S. Moorthy, MD.)
The differential diagnosis includes entities associated with CNV, such as age-related macular degeneration, myopic degeneration, angioid streaks, choroidal rupture, undifferentiated CNV, MCP, and punctate inner choroidopathy. Granulomatous fundus lesions (toxoplasmosis, tuberculosis, coccidioidomycosis, syphilis, sarcoidosis, and toxocariasis) may mimic the scarring of OHS.
Over time, new choroidal scars develop in more than 20% of patients; however, only 3.8% of these cases progress to CNV. If histo spots appear in the macular area, the patient has a 15% chance of developing CNV within 5 years; if no spots are observed, the chances fall to 5%. Occasionally massive subretinal exudation and hemorrhagic retinal detachments may occur.
The early, acute granulomatous lesions of OHS are rarely seen but may be treated with oral or regional (periocular) corticosteroids (Fig 11-25). Early in a fluorescein angiography image, foci of active choroiditis hypofluoresce. These lesions hyperfluoresce in a staining pattern late in the imaging.
In contrast, areas of active CNV hyperfluoresce early and then hyperfluoresce in a leak pattern in later fluorescein angiography. Intravitreal vascular endothelial growth factor (VEGF) inhibitors have become mainline therapy for OHS-associated macular CNV. One large retrospective study suggests little benefit to combining VEGF inhibitor therapy with photodynamic therapy. See BCSC Section 12, Retina and Vitreous, for further detail about thermal laser photocoagulation, PDT, VEGF inhibitors, intravitreal corticosteroids, and submacular surgery for the treatment of CNV.
For discussions of the ocular manifestations of candidiasis, aspergillosis, cryptococcosis, and coccidioidomycosis, as well as their treatments, see Chapter 12 in this volume.
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Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.