Laboratory Studies

Although the diagnosis of presumed ocular histoplasmosis syndrome is clinical, certain ancillary tests help in confirming it. Other than fluorescein angiography (FA), most patients do not require ancillary testing.

HLA typing B7 and DRw2 may be indicated.

Complement fixing antibodies are only positive in 16-68% of patients with POHS.

Lymphocyte stimulation assay by Histoplasma antigens may be indicated.

Focal calcifications in the liver or the spleen may be present.

Imaging Studies

FA is essential in diagnosing and managing the maculopathy associated with POHS with photodynamic therapy or laser photocoagulation. The typical angiographic pattern is early hyperfluorescence with late leakage. According to its location relative to the center of the fovea, CNV has been classified as extrafoveal (200-1500 µm), juxtafoveal (1-199 µm), and subfoveal (under the center of the fovea).

Since the advent of anti-VEGF therapy for CNV secondary to the POHS, optical coherence tomography imaging is of paramount importance in the diagnosis and follow-up.^[22]Any signs of continued exudation, such as intraretinal or subretinal fluid, is usually an indication for continued anti-VEGF treatment.

Chest radiography findings usually reveal calcifications of the hilar areas.

Other Tests

Skin testing should not be performed on patients with a maculopathy; some report that it may exacerbate this condition.

Histologic Findings

Few cases report H capsulatum isolated from the human eye. In most cases, isolation of the organism in either atrophic scars or CNV is not possible. Histologically, the peripapillary and peripheral spots are seen as areas where there is partial loss of the RPE and the photoreceptor cell layer. The Bruch membrane often presents with focal breaks in it. Sometimes, the overlying inner retina shows cystic degeneration. These areas often are surrounded by a lymphocytic choroidal infiltrate.

In the macular area, most CNV develops adjacent to an atrophic histo spot, although de novo neovascularization can occur. The new capillaries and fibroblasts originate from the choroid and grow through a defect in the Bruch membrane into the subretinal space, not the sub-RPE space (type 2 CNV). Reactive hyperplastic RPE is present at the advancing edge of CNV.

Specimens obtained during surgical excision of CNV reveal that the most common cellular components are vascular endothelium and RPE; they were present in more than 85% of samples. Fibrocytes and macrophages have been identified in more than 50% of specimens. Extracellular components include collagen and fibrin.

Treatment & Management

Woods AC, Wahlen HE. The probable role of benign histoplasmosis in the etiology of granulomatous uveitis. Am J Ophthalmol. 1960 Feb. 49:205-20. [QxMD MEDLINE Link].
Rhee P, Dev S, Mieler WF. The development of choroidal neovascularization in pregnancy. Retina. 1999. 19(6):520-4. [QxMD MEDLINE Link].
Comstock GW, Vicens CN, Goodman NL, Collins S. Differences in the distribution of sensitivity to histoplasmin and isolations of Histoplasma capsulatum. Am J Epidemiol. 1968 Sep. 88(2):195-209. [QxMD MEDLINE Link].
Ganley JP. Epidemiologic characteristics of presumed ocular histoplasmosis. Acta Ophthalmol Suppl. 1973. 119:1-63. [QxMD MEDLINE Link].
Asbury T. The status of presumed ocular histoplasmosis: including a report of a survey. Trans Am Ophthalmol Soc. 1966. 64:371-400. [QxMD MEDLINE Link].
Schlaegel TF Jr, Weber JC, Helveston E, Kenney D. Presumed histoplasmic choroiditis. Am J Ophthalmol. 1967 May. 63(5):919-25. [QxMD MEDLINE Link].
Xu TT, Reynolds MM, Hodge DO, Smith WM. Epidemiology and Clinical Characteristics of Presumed Ocular Histoplasmosis in Olmsted County, Minnesota. Ocul Immunol Inflamm. 2022 Jul. 30 (5):1039-1043. [QxMD MEDLINE Link].
Hawkins BS, Ganley JP. Risk of visual impairment attributable to ocular histoplasmosis. Washington County Follow-up Eye Study Group. Arch Ophthalmol. 1994 May. 112(5):655-66. [QxMD MEDLINE Link].
Watzke RC, Klein ML, Wener MH. Histoplasmosis-like choroiditis in a nonendemic area: the northwest United States. Retina. 1998. 18(3):204-12. [QxMD MEDLINE Link].
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.
Sinha R, Raju S, Garg SP, Venkatesh P, Talwar D. Presumed ocular histoplasmosis syndrome in India. Ocul Immunol Inflamm. 2007 Jul-Aug. 15(4):315-7. [QxMD MEDLINE Link].
Suttorp-Schulten MS, Bollemeijer JG, Bos PJ, Rothova A. Presumed ocular histoplasmosis in The Netherlands--an area without histoplasmosis. Br J Ophthalmol. 1997 Jan. 81(1):7-11. [QxMD MEDLINE Link].
Amaro MH, Muccioli C, Abreu MT. Ocular histoplasmosis-like syndrome: a report from a nonendemic area. Arq Bras Oftalmol. 2007 Jul-Aug. 70(4):577-80. [QxMD MEDLINE Link].
Laghmari M, Lezrek O. [Presumed ocular histoplasmosis syndrome (POHS)]. Pan Afr Med J. 2014. 18:268. [QxMD MEDLINE Link].
Smith RE, Ganley JP. An epidemiologic study of presumed ocular histoplasmosis. Trans Am Acad Ophthalmol Otolaryngol. 1971 Sep-Oct. 75(5):994-1005. [QxMD MEDLINE Link].
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. 1996 Jun. 114(6):677-88. [QxMD MEDLINE Link].
Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991 Aug. 109(8):1109-14. [QxMD MEDLINE Link].
Macular Photocoagulation Study Group. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. 1994 Apr. 112(4):500-9. [QxMD MEDLINE Link].
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. 1993 Jan. 111(1):19-20. [QxMD MEDLINE Link].
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. 1995 Jan. 113(1):56-61. [QxMD MEDLINE Link].
Chheda LV, Ferketich AK, Carroll CP, Moyer PD, Kurz DE, Kurz PA. Smoking as a risk factor for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome. Ophthalmology. 2012 Feb. 119 (2):333-8. [QxMD MEDLINE Link].
Hatef E, Turkcuoglu P, Ibrahim M, et al. Importance of proper diagnosis for management: multifocal choroiditis mimicking ocular histoplasmosis syndrome. J Ophthalmic Inflamm Infect. 2011 Jun. 1(2):55-63. [QxMD MEDLINE Link]. [Full Text].
Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA. Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome. Am J Ophthalmol. 2003 Oct. 136(4):739-41. [QxMD MEDLINE Link].
Holekamp NM, Thomas MA, Pearson A. The safety profile of long-term, high-dose intraocular corticosteroid delivery. Am J Ophthalmol. 2005 Mar. 139(3):421-8. [QxMD MEDLINE Link].
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. 2007 Dec. 245(12):1873-5. [QxMD MEDLINE Link].
Schadlu R, Blinder KJ, Shah GK, et al. Intravitreal bevacizumab for choroidal neovascularization in ocular histoplasmosis. Am J Ophthalmol. 2008 May. 145(5):875-8. [QxMD MEDLINE Link].
Cionni DA, Lewis SA, Petersen MR, et al. Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis. Ophthalmology. 2012 Feb. 119(2):327-32. [QxMD MEDLINE Link].
Wood EH, Whitted RJ, Stone TW, Isernhagen RD, Wood WJ, Holcomb DM, et al. PRN Ranibizumab in the Treatment of Choroidal Neovascularization Secondary to Ocular Histoplasmosis. Ophthalmic Surg Lasers Imaging Retina. 2018 Jan 1. 49 (1):20-26. [QxMD MEDLINE Link].
Walia HS, Shah GK, Blinder KJ. Treatment of CNV secondary to presumed ocular histoplasmosis with intravitreal aflibercept 2.0 mg injection. Can J Ophthalmol. 2016 Apr. 51 (2):91-6. [QxMD MEDLINE Link].
Toussaint BW, Kitchens JW, Marcus DM, Miller DM, Kingdon ML, Holcomb D, et al. INTRAVITREAL AFLIBERCEPT INJECTION FOR CHOROIDAL NEOVASCULARIZATION DUE TO PRESUMED OCULAR HISTOPLASMOSIS SYNDROME: The HANDLE Study. Retina. 2018 Apr. 38 (4):755-763. [QxMD MEDLINE Link].
Dudenhoefer NE, Noble CW, Petersen MR, Foster RE, Riemann CD, Sisk RA, et al. INTRAVITREAL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO OCULAR HISTOPLASMOSIS: Ten-Year Follow-Up. Retina. 2022 Aug 1. 42 (8):1568-1573. [QxMD MEDLINE Link].
Rosenfeld PJ, Saperstein DA, Bressler NM, et al. Photodynamic therapy with verteporfin in ocular histoplasmosis: uncontrolled, open-label 2-year study. Ophthalmology. 2004 Sep. 111(9):1725-33. [QxMD MEDLINE Link].
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. 2004 Nov. 122(11):1597-611. [QxMD MEDLINE Link].
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.
Alam S, Zawadzki RJ, Choi S, et al. Clinical application of rapid serial fourier-domain optical coherence tomography for macular imaging. Ophthalmology. 2006 Aug. 113(8):1425-31. [QxMD MEDLINE Link]. [Full Text].
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. 1998 Sep. 105(9):1598-605. [QxMD MEDLINE Link].
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. 1980 Jan. 89(1):77-83. [QxMD MEDLINE Link].
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. 1997 Aug. 115(8):991-6. [QxMD MEDLINE Link].
Callanan D, Fish GE, Anand R. Reactivation of inflammatory lesions in ocular histoplasmosis. Arch Ophthalmol. 1998 Apr. 116(4):470-4. [QxMD MEDLINE Link].
Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999 Jul 9. 285(5425):245-8. [QxMD MEDLINE Link].
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. 2007 May. 91(5):649-54. [QxMD MEDLINE Link].
Gass JD. Stereoscopic Atlas of Macular Diseases. Diagnosis and Treatment. 4th ed. St Louis: Mosby Year Book Inc; 1997. 130-147.
Godfrey WA, Sabates R, Cross DE. Association of presumed ocular histoplasmosis with HLA-B7. Am J Ophthalmol. 1978 Jun. 85(6):854-8. [QxMD MEDLINE Link].
Grossniklaus HE, Green WR. Histopathologic and ultrastructural findings of surgically excised choroidal neovascularization. Submacular Surgery Trials Research Group. Arch Ophthalmol. 1998 Jun. 116(6):745-9. [QxMD MEDLINE Link].
Holekamp NM, Thomas MA, Dickinson JD, Valluri S. Surgical removal of subfoveal choroidal neovascularization in presumed ocular histoplasmosis: stability of early visual results. Ophthalmology. 1997 Jan. 104(1):22-6. [QxMD MEDLINE Link].
Khalil MK. Histopathology of presumed ocular histoplasmosis. Am J Ophthalmol. 1982 Sep. 94(3):369-76. [QxMD MEDLINE Link].
Melberg NS, Thomas MA, Dickinson JD, Valluri S. Managing recurrent neovascularization after subfoveal surgery in presumed ocular histoplasmosis syndrome. Ophthalmology. 1996 Jul. 103(7):1064-7;discussion 1067-8. [QxMD MEDLINE Link].
Oliver A, Ciulla TA, Comer GM. New and classic insights into presumed ocular histoplasmosis syndrome and its treatment. Curr Opin Ophthalmol. 2005 Jun. 16(3):160-5. [QxMD MEDLINE Link].
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 May. 83(5):535-9. [QxMD MEDLINE Link].
Prasad AG, Van Gelder RN. Presumed ocular histoplasmosis syndrome. Curr Opin Ophthalmol. 2005 Dec. 16(6):364-8. [QxMD MEDLINE Link].
Shah GK, Blinder KJ, Hariprasad SM, et al. Photodynamic therapy for juxtafoveal choroidal neovascularization due to ocular histoplasmosis syndrome. Retina. 2005 Jan. 25(1):26-32. [QxMD MEDLINE Link].
Smith RE, Dunn S, Jester JV. Natural history of experimental histoplasmic choroiditis in the primate. I. Clinical features. Invest Ophthalmol Vis Sci. 1984 Jul. 25(7):801-9. [QxMD MEDLINE Link].
Wilkes MF, Miller DM, Mitchell MD, Zanke B, Petersen MR, Sisk RA, et al. Investigation of choroidal neovascularization risk alleles in ocular histoplasmosis. Ophthalmology. 2014 Jul. 121 (7):1487-8.e1. [QxMD MEDLINE Link].
Ramaiya KJ, Blinder KJ, Ciulla T, Cooper B, Shah GK. Ranibizumab versus photodynamic therapy for presumed ocular histoplasmosis syndrome. Ophthalmic Surg Lasers Imaging Retina. 2013 Jan-Feb. 44 (1):17-21. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

Lihteh Wu, MD Ophthalmologist, Costa Rica Vitreo and Retina Macular Associates

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, Club Jules Gonin, Macula Society, Pan-American Association of Ophthalmology, Retina Society

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Bayer; Quantel Medical, Roche<br/>Received income in an amount equal to or greater than $250 from: Bayer Health; Quantel Medical, Roche.

Coauthor(s)

Dhariana Acón, MD Ophthalmologist, Caja Costarricense Seguro Social, Hospital de Guapiles, Costa Rica

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

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

Disclosure: Nothing to disclose.

Steve Charles, MD Founder and CEO of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine

Disclosure: Received royalty and consulting fees for: Alcon Laboratories.

Chief Editor

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Association of Immunologists, American College of Rheumatology, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, American Uveitis Society, Association for Research in Vision and Ophthalmology, Massachusetts Medical Society, Royal Society of Medicine, Sigma Xi, The Scientific Research Honor Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Aldeyra Therapeutics (Lexington, MA); Bausch & Lomb Surgical, Inc (Rancho Cucamonga, CA); Eyegate Pharma (Waltham, MA); Novartis (Cambridge, MA); pSivida (Watertown, MA); Xoma (Berkeley, CA); Allakos (Redwood City, CA)<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alcon (Geneva, Switzerland); Allergan (Dublin, Ireland); Mallinckrodt (Staines-upon-Thames, United Kingdom)<br/>Received research grant from: Alcon; Aldeyra Therapeutics; Allakos Pharmaceuticals; Allergan; Bausch & Lomb; Clearside Biomedical; Dompé pharmaceutical; Eyegate Pharma; Mallinckrodt pharmaceuticals; Novartis; pSivida; Santen; Aciont<br/>Stock for: Eyegate Pharma.

Additional Contributors

Russell P Jayne, MD 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, American Society of Retina Specialists

Disclosure: Nothing to disclose.

Acknowledgements

Teodoro Evans, MD Consulting Surgeon, Vitreo-Retinal Section, Clinica de Ojos, Costa Rica

Disclosure: Nothing to disclose.