Presumed Ocular Histoplasmosis Syndrome 

  • Author: Lihteh Wu, MD; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: Feb 19, 2010
 

Background

Presumed ocular histoplasmosis syndrome (POHS) is a distinct clinical entity that is characterized by peripheral atrophic chorioretinal scars, peripapillary scarring, and maculopathy.[1] This condition is believed to be secondary to exposure to Histoplasma capsulatum, although this fungus rarely has been isolated or cultured from an eye with the typically associated clinical findings.

Epidemiologic findings link the fungus to this condition. Based on skin tests in the United States, a similar geographic distribution of the fungal infection and POHS exists. Histoplasmin skin testing may exacerbate the ocular condition. Visual loss in POHS is secondary to the development of macular choroidal neovascularization (CNV).

Next

Pathophysiology

H capsulatum is a dimorphic pathogenic fungus that often grows in soil around old chicken houses and areas harboring bats, such as caves. Large numbers of spores are dispersed into the air when contaminated soil is disturbed (eg, spelunking, raking). Exposure occurs when spores are inhaled.

In a normal host, the initial infection is usually asymptomatic or feels like influenza. In a few patients, a chronic cavitary pulmonary disease may follow. In immunocompromised patients, a progressive, life-threatening, disseminated form can occur. Following initial infection, hematogenous spread to the rest of the body, including the eye, can occur. A focal granulomatous choroiditis is thought to occur. This phase seldom is observed in humans.

In an experimental nonhuman primate model, inoculation of the organism via the carotid artery results in an active choroiditis. These foci are observed as discrete, round, yellowish choroidal lesions. Six weeks following inoculation of the organisms, isolating the organisms by any histologic techniques was not possible. The inflammatory response probably destroyed the invading organisms. With time, the lesions resolve, leaving the typical "punched-out" atrophic scars that disrupt the Bruch membrane (see Physical). Reexposure to the histoplasmin antigen may account for the enlargement of old scars and the emergence of new scars.

Visual loss in POHS is secondary to the development of CNV. Pigment epithelium derived factor (PEDF) was found to have an inhibitory effect on ocular neovascularization. Another peptide, vascular endothelium growth factor (VEGF), is a well-known ocular angiogenic factor. The balance between antiangiogenic factors (eg, PEDF) and angiogenic factors (eg, VEGF) may determine the growth of CNV. This CNV usually grows in the subretinal space in a sheetlike fashion, not in the sub–retinal pigment epithelium (RPE) space. As the CNV grows, reactive hyperplastic RPE tries to surround and envelop the CNV. If successful, the CNV usually involutes.

Why CNV arises is unclear. Based on a case of a pregnant woman who developed a macular detachment during the third trimester, some propose that a type of vascular decompensation caused the CNV.[2] A lymphocytic choroidal infiltrate usually is found near histo spots. Some hypothesize that an allergic reaction to Histoplasma antigens is an important stimulus for CNV growth. A few propose that the infectious granuloma secondary to the fungus is responsible for CNV growth. Others state that damage to the Bruch membrane by itself is a strong stimulus for CNV.

Previous
Next

Epidemiology

Frequency

United States

Presumed ocular histoplasmosis syndrome occurs in endemic areas of the United States, including the Ohio and Mississippi River Valleys (Indiana, Ohio, Illinois, Kentucky, Tennessee, and Mississippi) and parts of the mid-Atlantic region (Maryland, West Virginia, and Virginia). Approximately, 200,000-500,000 new infections occur annually.[3]

In an endemic area, 90% of patients with POHS had a positive histoplasmin skin test. In Maryland, 4% of those infected with histoplasmosis had POHS.[4, 5, 6]

Peripheral atrophic scars were present in 2% of people living in endemic areas; disciform scars were found in 0.1% of people.[7]

A clinical entity indistinguishable from POHS has been reported in a series of 10 patients from a nonendemic area, the Pacific Northwest. These patients tested negative to a lymphocyte stimulation assay with H capsulatum. Unlike series from the Midwest, all patients were female; 50% of them were myopic. The authors speculate that an atypical mycobacteria might be responsible for this entity.[8]

International

H capsulatum is endemic in the Caribbean, Central America, and South America. No reports of POHS from these areas have appeared in the literature. However, certain areas of India are endemic for systemic histoplasmosis.[9] Three cases of POHS were recently described in India.[10]

Patients with clinical findings indistinguishable from POHS have been reported in areas where H capsulatum is not found. These reports suggest that other agents can cause similar fundus findings as POHS. In the Netherlands and the United Kingdom, a clinical syndrome indistinguishable from POHS has been described. In the Dutch series by Suttorp-Schulten et al, a large number of female and myopic patients were reported.[11] Given that H capsulatum is not found in Europe, some European colleagues have proposed to change the name from POHS to multifocal choroidopathy. Other cases from Brazil have also been described.[12]

Mortality/Morbidity

  • POHS is an uncommon cause of visual loss.
  • The incidence and the prevalence in the blind population in Tennessee were reported to be 2.8% and 0.5%, respectively.

Race

  • Histoplasmin skin testing reveals that African Americans and Caucasians living in endemic areas are infected equally by H capsulatum. No difference is apparent between the prevalence of peripheral histo spots between these 2 groups. Caucasian patients are more likely than African Americans to develop macular CNV.
  • Some reports suggest an increased prevalence of POHS in patients with human leukocyte antigen B7 (HLA-B7) and human leukocyte antigen DRw2 (HLA-DRw2). Patients with HLA-DRw2 are more likely to have peripheral histo spots and disciform scarring, whereas patients with HLA-B7 are more likely to have peripheral histo spots.

Sex

  • No apparent gender predilection exists in the Midwest and the mid-Atlantic series according to Smith et al.[13]
  • In the series from the Netherlands by Suttorp-Schulten et al and in the series from the Pacific Northwest by Watzke et al, women seemed to be affected to a greater degree.[11, 8]

Age

  • Presumed ocular histoplasmosis syndrome usually affects patients aged 20-50 years; the average age is 35 years.
Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Lihteh Wu, MD  Consulting Surgeon, Department of Ophthalmology, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica

Lihteh Wu, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Pan-American Association of Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

Coauthor(s)

Teodoro Evans, MD  Retina Fellow, St Michael's Hospital, University of Toronto, Canada

Disclosure: Nothing to disclose.

Specialty Editor Board

Russell P Jayne, MD  Consulting Vitreoretinal Surgeon, The Retina Center at Las Vegas

Russell P Jayne, MD is a member of the following medical societies: American Medical Association, American Society of Cataract and Refractive Surgery, and American Society of Retina Specialists

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD  Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Steve Charles, MD  Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians & Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong

Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society

Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

References

  1. Woods AC, Wahlen HE. The probable role of benign histoplasmosis in the etiology of granulomatous uveitis. Am J Ophthalmol. Feb 1960;49:205-20. [Medline].

  2. Rhee P, Dev S, Mieler WF. The development of choroidal neovascularization in pregnancy. Retina. 1999;19(6):520-4. [Medline].

  3. Comstock GW, Vicens CN, Goodman NL, Collins S. Differences in the distribution of sensitivity to histoplasmin and isolations of Histoplasma capsulatum. Am J Epidemiol. Sep 1968;88(2):195-209. [Medline].

  4. Ganley JP. Epidemiologic characteristics of presumed ocular histoplasmosis. Acta Ophthalmol Suppl. 1973;119:1-63. [Medline].

  5. Asbury T. The status of presumed ocular histoplasmosis: including a report of a survey. Trans Am Ophthalmol Soc. 1966;64:371-400. [Medline].

  6. Schlaegel TF Jr, Weber JC, Helveston E, Kenney D. Presumed histoplasmic choroiditis. Am J Ophthalmol. May 1967;63(5):919-25. [Medline].

  7. Hawkins BS, Ganley JP. Risk of visual impairment attributable to ocular histoplasmosis. Washington County Follow-up Eye Study Group. Arch Ophthalmol. May 1994;112(5):655-66. [Medline].

  8. Watzke RC, Klein ML, Wener MH. Histoplasmosis-like choroiditis in a nonendemic area: the northwest United States. Retina. 1998;18(3):204-12. [Medline].

  9. Goswami RP, Pramanik N, Banerjee D, Raza MM, Guha SK, Maiti PK. Histoplasmosis in eastern India: the tip of the iceberg?Trans R Soc Trop Med Hyg. 1999;93:540–542.

  10. Sinha R, Raju S, Garg SP, Venkatesh P, Talwar D. Presumed ocular histoplasmosis syndrome in India. Ocul Immunol Inflamm. Jul-Aug 2007;15(4):315-7. [Medline].

  11. Suttorp-Schulten MS, Bollemeijer JG, Bos PJ, Rothova A. Presumed ocular histoplasmosis in The Netherlands--an area without histoplasmosis. Br J Ophthalmol. Jan 1997;81(1):7-11. [Medline].

  12. Amaro MH, Muccioli C, Abreu MT. Ocular histoplasmosis-like syndrome: a report from a nonendemic area. Arq Bras Oftalmol. Jul-Aug 2007;70(4):577-80. [Medline].

  13. Smith RE, Ganley JP. An epidemiologic study of presumed ocular histoplasmosis. Trans Am Acad Ophthalmol Otolaryngol. Sep-Oct 1971;75(5):994-1005. [Medline].

  14. Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA. Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome. Am J Ophthalmol. Oct 2003;136(4):739-41. [Medline].

  15. Holekamp NM, Thomas MA, Pearson A. The safety profile of long-term, high-dose intraocular corticosteroid delivery. Am J Ophthalmol. Mar 2005;139(3):421-8. [Medline].

  16. Adan A, Navarro M, Casaroli-Marano RP, Ortiz S, Molina JJ. Intravitreal bevacizumab as initial treatment for choroidal neovascularization associated with presumed ocular histoplasmosis syndrome. Graefes Arch Clin Exp Ophthalmol. Dec 2007;245(12):1873-5. [Medline].

  17. Schadlu R, Blinder KJ, Shah GK, et al. Intravitreal bevacizumab for choroidal neovascularization in ocular histoplasmosis. Am J Ophthalmol. May 2008;145(5):875-8. [Medline].

  18. Macular Photocoagulation Study Group. Five-year follow-up of fellow eyes of individuals with ocular histoplasmosis and unilateral extrafoveal or juxtafoveal choroidal neovascularization. Macular Photocoagulation Study Group. Arch Ophthalmol. Jun 1996;114(6):677-88. [Medline].

  19. Rosenfeld PJ, Saperstein DA, Bressler NM, et al. Photodynamic therapy with verteporfin in ocular histoplasmosis: uncontrolled, open-label 2-year study. Ophthalmology. Sep 2004;111(9):1725-33. [Medline].

  20. Hawkins BS, Bressler NM, Bressler SB, et al. Surgical removal vs observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic: I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9. Arch Ophthalmol. Nov 2004;122(11):1597-611. [Medline].

  21. Almony A, Thomas MA, Atebara NH, Holekamp NM, Del Priore LV. Long-term follow-up of surgical removal of extensive peripapillary choroidal neovascularization in presumed ocular histoplasmosis syndrome. Ophthalmology. 2008;115(3):540-545.e5.

  22. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. Aug 1991;109(8):1109-14. [Medline].

  23. Macular Photocoagulation Study Group. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. Apr 1994;112(4):500-9. [Medline].

  24. Fine SL, Wood WJ, Isernhagen RD, et al. Laser treatment for subfoveal neovascular membranes in ocular histoplasmosis syndrome: results of a pilot randomized clinical trial. Arch Ophthalmol. Jan 1993;111(1):19-20. [Medline].

  25. Macular Photocoagulation Study Group. Laser photocoagulation for neovascular lesions nasal to the fovea. Results from clinical trials for lesions secondary to ocular histoplasmosis or idiopathic causes. Macular Photocoagulation Study Group. Arch Ophthalmol. Jan 1995;113(1):56-61. [Medline].

  26. Alam S, Zawadzki RJ, Choi S, et al. Clinical application of rapid serial fourier-domain optical coherence tomography for macular imaging. Ophthalmology. Aug 2006;113(8):1425-31. [Medline].

  27. Atebara NH, Thomas MA, Holekamp NM, Mandell BA, Del Priore LV. Surgical removal of extensive peripapillary choroidal neovascularization associated with presumed ocular histoplasmosis syndrome. Ophthalmology. Sep 1998;105(9):1598-605. [Medline].

  28. Baskin MA, Jampol LM, Huamonte FU, Rabb MF, Vygantas CM, Wyhinny G. Macular lesions in blacks with the presumed ocular histoplasmosis syndrome. Am J Ophthalmol. Jan 1980;89(1):77-83. [Medline].

  29. Berger AS, Conway M, Del Priore LV, Walker RS, Pollack JS, Kaplan HJ. Submacular surgery for subfoveal choroidal neovascular membranes in patients with presumed ocular histoplasmosis. Arch Ophthalmol. Aug 1997;115(8):991-6. [Medline].

  30. Callanan D, Fish GE, Anand R. Reactivation of inflammatory lesions in ocular histoplasmosis. Arch Ophthalmol. Apr 1998;116(4):470-4. [Medline].

  31. Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. Jul 9 1999;285(5425):245-8. [Medline].

  32. Essex RW, Tufail A, Bunce C, Aylward GW. Two-year results of surgical removal of choroidal neovascular membranes related to non-age-related macular degeneration. Br J Ophthalmol. May 2007;91(5):649-54. [Medline].

  33. Gass JD. Stereoscopic Atlas of Macular Diseases. In: Diagnosis and Treatment. 4th ed. St Louis: Mosby Year Book Inc; 1997:130-147.

  34. Godfrey WA, Sabates R, Cross DE. Association of presumed ocular histoplasmosis with HLA-B7. Am J Ophthalmol. Jun 1978;85(6):854-8. [Medline].

  35. Grossniklaus HE, Green WR. Histopathologic and ultrastructural findings of surgically excised choroidal neovascularization. Submacular Surgery Trials Research Group. Arch Ophthalmol. Jun 1998;116(6):745-9. [Medline].

  36. Holekamp NM, Thomas MA, Dickinson JD, Valluri S. Surgical removal of subfoveal choroidal neovascularization in presumed ocular histoplasmosis: stability of early visual results. Ophthalmology. Jan 1997;104(1):22-6. [Medline].

  37. Khalil MK. Histopathology of presumed ocular histoplasmosis. Am J Ophthalmol. Sep 1982;94(3):369-76. [Medline].

  38. Melberg NS, Thomas MA, Dickinson JD, Valluri S. Managing recurrent neovascularization after subfoveal surgery in presumed ocular histoplasmosis syndrome. Ophthalmology. Jul 1996;103(7):1064-7;discussion 1067-8. [Medline].

  39. Oliver A, Ciulla TA, Comer GM. New and classic insights into presumed ocular histoplasmosis syndrome and its treatment. Curr Opin Ophthalmol. Jun 2005;16(3):160-5. [Medline].

  40. Ongkosuwito JV, Kortbeek LM, Van der Lelij A, et al. Aetiological study of the presumed ocular histoplasmosis syndrome in the Netherlands. Br J Ophthalmol. May 1999;83(5):535-9. [Medline].

  41. Prasad AG, Van Gelder RN. Presumed ocular histoplasmosis syndrome. Curr Opin Ophthalmol. Dec 2005;16(6):364-8. [Medline].

  42. Shah GK, Blinder KJ, Hariprasad SM, et al. Photodynamic therapy for juxtafoveal choroidal neovascularization due to ocular histoplasmosis syndrome. Retina. Jan 2005;25(1):26-32. [Medline].

  43. Smith RE, Dunn S, Jester JV. Natural history of experimental histoplasmic choroiditis in the primate. I. Clinical features. Invest Ophthalmol Vis Sci. Jul 1984;25(7):801-9. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.