• Presumed ocular histoplasmosis syndrome (POHS) is an inflammatory condition associated with systemic infection by the fungus Histoplasma capsulatum. It may be unilateral or bilateral.
– POHS is most common in the Ohio and Mississippi River valleys, where H. capsulatum is endemic.
Elderly patients with coexisting age-related macular degeneration should be monitored closely due to the increased risk of choroidal neovascular membrane (CNVM).
Incidence of new cases of POHS is difficult to determine but has been approximated at 2 per 100,000 per year in an endemic area.
• The prevalence ranges from 1.6% to 5.3% in endemic areas based on epidemiologic data from the 1960s and 1970s.
• In endemic regions, up to 70% of the population demonstrate exposure to H. capsulatum and react positively to histoplasmin antigen skin testing (1).
• Exposure to H. capsulatum is the major risk factor for developing POHS.
– 4.4% of those who are skin test positive to H. capsulatum have clinical findings consistent with POHS (1).
The HLA subtypes DRw2 and B7 have been associated with POHS. This suggests that POHS is possibly an immune-mediated response to an infectious trigger (1).
Avoiding exposure to H. capsulatum by avoiding sites of possible contamination such as excavation sites, old buildings being demolished, bird habitats, and bat-infested caves may prevent infection.
• Focal infection of the choroid with H. capsulatum and/or a chronic reaction to immunogenic remnants of the organism causes the choroidal lesions in POHS.
– Very little pathologic evidence exists implicating H. capsulatum in POHS.
• H. capsulatum has been implicated by epidemiologic studies and antigen skin testing in the U.S.
• However, a study in the Netherlands found no immunologic evidence to support a relationship between the clinical findings of POHS and H. capsulatum or other endemic organisms (2).
COMMONLY ASSOCIATED CONDITIONS
CNVM, which can be vision threatening
• Patients are typically young or middle-aged and may be asymptomatic.
• Patients should be questioned about time spent in endemic areas.
• POHS may be unilateral or bilateral.
• The classic findings for POHS are as follows:
– Multiple, focal, discrete, atrophic choroidal scars in the macula or periphery (termed “punched-out” lesions or “histo spots”) can result from previous choroiditis or CNVM.
– Linear atrophic lesions may also be seen (“histo streaks”).
– Peripapillary atrophy (chorioretinal atrophy adjacent to the optic nerve)
– No cellular reaction in the anterior chamber or vitreous cavity
• Active and/or regressed CNVM may be seen in association with POHS. A fibrovascular disciform scar may also be seen as a remnant of prior CNVM.
– The development of CNVM is more likely in eyes with macular “histo spots.”
• Active areas of choroiditis may be seen.
DIAGNOSTIC TESTS & INTERPRETATION
• Laboratory testing is not generally indicated in patients with POHS, since it is a clinical diagnosis.
• Skin testing with histoplasmin antigen is generally no longer performed.
• In patients with ocular disease only, serum and/or urine antigen testing for H. capsulatum is unlikely to yield positive results.
• Serum antibodies to H. capsulatum can be detected in patients with a history of exposure to the organism.
• Imaging tests are indicated to confirm the presence of CNVM.
– Fundus photographs
– Fluorescein angiogram
– Ocular coherence tomography
– Indocyanine green angiography
Follow-up & special considerations
Patients with POHS should be followed at least yearly for early detection of CNVM.
One study detected products of H. capsulatum DNA via polymerase chain reaction in 1 eye with POHS (3).
• Multifocal choroiditis with panuveitis
– Clinically similar to POHS but can be differentiated by the presence of a cellular reaction.
• Pathologic myopia
• Age-related macular degeneration
• Angioid streaks
• Idiopathic CNVM
• Other fungal choroiditis
• Bacterial choroiditis
• Viral choroiditis
• Medication is not indicated for most cases of POHS.
• Patients with choroiditis may be treated with oral or periocular steroid.
Issues for Referral
• Patients with any suspicion of CNVM should be evaluated by a retinal specialist.
– Immunocompromised patients may develop disseminated histoplasmosis. Such cases should be referred to an infectious disease specialist.
• Thermal laser has been shown to be beneficial in CNVM secondary to POHS (1)[A].
– However, thermal laser to subfoveal or juxtafoveal lesions can cause a central scotoma, so alternative therapies should be explored.
• Photodynamic therapy can be beneficial for treatment of CNVM due to POHS. Patients typically require only 1 or 2 treatments and have good 2-year maintenance of treatment benefit (4)[A].
• Intravitreal bevacizumab has resulted in an increase in vision in 71% of eyes treated for CNVM due to POHS. Intravitreal bevacizumab should be considered especially in patients with subfoveal CNVM in whom other treatment modalities may lead to central scotoma (5)[A].
• In patients with extension of peripapillary CNVM into the subfoveal space, pars plana vitrectomy with removal of the CNVM may be beneficial. In a retrospective review, 15/17 patients had stabilization or improvement of their vision after a year or more (6)[B].
• The submacular surgery trial found that there was a benefit to surgery in patients with vision worse than 20/100, but this was before anti-VEGF therapy. There was a 58% recurrence rate.
In patients with disseminated histoplasmosis, a complete medical evaluation to determine organ involvement should be performed. Intravenous antifungals should be initiated.
Disseminated histoplasmosis may occur in immunocompromised patients. These patients require hospitalization and aggressive management.
Patients need regularly scheduled follow-up visits at least yearly. In patients with evidence of previous or active CNVM, more frequent follow-up is indicated.
Patients should monitor their central vision daily with an Amsler grid. Any changes should be evaluated immediately.
Patients should be educated on the need for regular follow-up and daily Amsler grid monitoring.
Visual prognosis can be good, as long as glaucoma and any posterior segment complications are controlled.
Permanent visual loss can occur secondary to CNVM.
1. Prasad AG, Van Gelder RN. Presumed ocular histoplasmosis syndrome. Curr Opin Ophthalmol 2005;16:364–368.
2. Ongkosuwito JV, Kortbeek LM, Van Der Lelij A, et al. Aetiological study of the presumed ocular histoplasmosis syndrome in the Netherlands. Br J Ophthalmol 1999;83:535–539.
3. Spencer WH, Chan CC, Shen DF, et al. Detection of Histoplasma capsulatum DNA in lesions of chronic ocular histoplasmosis syndrome. Arch Ophthalmol 2003;121:1551–1555.
4. Postelmans L, Pasteels B, Coquelet P, et al. Photodynamic therapy for subfoveal classic choroidal neovascularization related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like). Ocul Immunol Inflamm 2005;13:331–333.
5. Schadlu R, Blinder KJ, Shah GK, et al. Intravitreal bevacizumab for choroidal neovascularization in ocular histoplasmosis. Am J Ophthalmol 2008;145:875–878.
6. Almony A, Thomas MA, Atebara NH, et al. Long-term follow-up of surgical removal of extensive peripapillary choroidal neovascularization in presumed ocular histoplasmosis syndrome. Ophthalmology 2008;115:540–545.
7. Hawkins BS, Bressler NM, Bressler SB, et al. Submacular Surgery Trials Research Group. Surgical removal versus observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trial Group H Trial: SST Report No. 9. Arch Ophthalmol 2004;122(11):1597–1611.