Fig. 10.1
Color fundus photograph of a patient with peripapillary atrophy and macular choroidal neovascular membrane secondary to POHS. There was no vitritis on physical exam
- 1.
Multiple white atrophic chorioretinal scars (also known as histo spots)
- 2.
Peripapillary atrophy
- 3.
Absence of vitritis
Histo spots are discrete, focal; atrophic choroidal scars found in the posterior pole and the peripheral retina. They appear to be “punched out” of the inner choroid with central pigmentation, ring of pigmentation, or diffuse pigmentation. They may indicate former areas of subclinical CNV that have regressed spontaneously. Linear streaks that are parallel to the ora serrata may be found in around 5 % of patients [21]. These streaks may simply be the coalescence of small linear histo spots. The scars may remain stable but in some patients, they have been documented to grow in size or number [22, 23].
Peripapillary atrophy is more commonly associated with macular scars. About a third of patients with peripheral histo spots will have peripapillary chorioretinal scars versus over two-thirds of patients with macular scarring. The peripapillary atrophy may represent a ring of granulomas that formed during the active stage of the disease [20, 24].
POHS may only be diagnosed in the absence of vitreous cells or anterior inflammation. Pigmented cells should not be confused with inflammatory cells. The lack of cells may be attributed to patients presenting after the active inflammatory stage has passed. Another theory is that since POHS is mainly a choriodopathy, the cells do not reach the vitreous.
These classic POHS findings may or may not be associated with CNV. Active disciform lesions may look like a green-gray subretinal lacy discoloration with surrounding pigment, usually in the macula. It may be related to chorioretinal scars that have a break in Bruch’s membrane. CNV usually occurs at the edge of an old scar. A scar in the macula or peripapillary region appears more predisposed to progressing to CNV. However, CNV can also form in the macula where there was previously no scar. If advanced, CNV appears as a white disciform scar with fibrovascular tissue. Rarely, as with age-related macular degeneration, CNV may result in vitreous hemorrhage due to a break in the retina [25].
Diagnostic Procedures
POHS is usually a clinical diagnosis, but fluorescein angiography (FA) can assist in the diagnosis. In areas of chorioretinal atrophy, staining and window defects versus late leakage can be seen with CNV. Defects in the retinal pigment epithelium and patchy loss of the choriocapillaris can be seen. Krill et al. described histo lesions as being hypofluorescent initially but then acquiring a more hyperfluorescent appearance late in the disease [26]. FA can be useful in locating areas of neovascularization if laser treatment is employed for CNV.
The histoplasmin skin antigen test can help determine if the patient has been exposed to H. capsulatum. However, since up to two-thirds of patients in endemic areas have a positive skin test, this testing is not routinely performed if the clinical findings are classic.
Differential Diagnosis
Diseases causing granulomas such as tuberculosis, coccidiomycosis, cryptococcosis, and sarcoidosis, should be considered. Careful examination for vitreous inflammation can help distinguish POHS from these other diseases.
Other causes of chorioretinitis must also be considered, including multifocal chorioretinitis, serpiginous choroiditis, birdshot chorioretinopathy, multiple evanescent white dot syndrome, acute multifocal placoid pigment epitheliopathy, toxoplasmosis, toxocariasis, rubella, Vogt-Koyanagi-Harada syndrome, and Behçet syndrome. Most commonly, multifocal choroiditis may be confused with POHS, but again, the absence of vitreous cells in POHS is the key distinguishing feature [27]. PIC lesions may also appear very similar to the chorioretinal scars of POHS, but the PIC scars tend to be small and confined to the posterior pole [28].
Management
Indications
POHS without CNV is monitored with biomicroscopy and the Amsler grid. Since there is no solid evidence of the organism being present in the eye, antifungal treatment such as amphotericin B is not beneficial [29, 30]. When CNV develops in the macula, it is treated similarly as age-related macular degeneration. Peripapillary CNV may be monitored unless it causes prolonged serous or hemorrhagic detachment close to the fovea.
Laser Therapy
The Macular Photocoagulation Study (MPS) evaluated laser photocoagulation for extrafoveal (>200 μm from the center of the foveal avascular zone), juxtafoveal (1–200 μm from the center of the foveal avascular zone), and peripapillary CNV. The MPS found that untreated eyes had 3.6 times the risk of laser treated eyes of losing six or more lines of visual acuity. However, the major complication of this treatment was a permanent scotoma from the laser, limiting its use for subfoveal lesions. Furthermore, 26 % of extrafoveal CNV and 33 % of juxtafoveal CNV recurred at the border of the treatment scar [31, 32].
The Verteporfin for Ocular Histoplasmosis Study examined the use of photodynamic therapy. This looked at photodynamic therapy for subfoveal CNV. The study found that 45 % of patients experienced improved vision, 18 % lost vision, and 9 % of patients suffered severe vision loss at the 2-year follow up. No serious adverse side effects were reported [33, 34].
Surgery
Submacular surgery has been explored for the treatment of subfoveal CNV. Thomas and Kaplan first described techniques to remove subfoveal CNV in POHS patients [35]. Using a small retinotomy with the creation of a neurosensory retinal detachment allowed access to the fibrovascular membrane. There was a significant improvement in their patients without recurrence of CNV. However, these dramatic findings were not duplicated by subsequent studies that employed a larger population and longer follow up. It has been speculated that surgery to remove membranes in POHS patients is more successful than surgery in patients with age-related macular degeneration, because POHS CNV lesions are not as deeply located. The retinal pigment epithelium may also recover and proliferate better given this more superficial location and the fact that most patients are younger than those with age-related macular degeneration. However, as with any vitreoretinal surgery, the risks include cataract, retinal detachment, and lesion recurrence [36–38].
Steroids
In 1977, Schlaegel et al. recommended high dose oral corticosteroids for acute exacerbations of macular CNV. With the advent of anti-VEGF treatment, this practice is not commonly used [39].
Anti-VEGF Agents
Most recently, anti-vascular endothelial growth factor (anti-VEGF) agents such as bevacizumab and ranibizumab have been used in patients with POHS given the success of these treatments for age-related macular degeneration. A recent retrospective study of POHS-associated CNV found that the average visual acuity improved from 20/53 to 20/26 in 54 eyes treated over a 26-month period. The average number of injections was 4.5 over one year [40]. Anti-VEGF agents are now considered first line treatment for patients with POHS and CNV. Risks of anti-VEGF injections include endophthalmitis, subconjunctival hemorrhage, cataract formation, retinal tears, and increased intraocular pressure [41].
Prognosis
Patient with histo spots in one eye have an 8–24 % chance of developing CNV in the fellow eye over 3 years [31, 32]. Complications of CNV include disciform scarring, resulting in loss of central vision. The visual acuity has been reported to be about 20/200 in about half of patients untreated. Spontaneous recovery has been reported but may have been secondary to the development of eccentric vision [42]. However, when CNV is identified early, anti-VEGF treatments can maintain good visual acuity. Patients should be counseled appropriately on their risk of developing macular disease [43].
Prevention
There is no current primary prevention. Patients with clinical signs of POHS should be screened for CNV with routine dilated fundoscopic exams. Patients should monitor disease activity at home with the Amsler grid.
Conclusion
POHS is a choroidopathy, typically characterized by atrophic chorioretinal scars, peripapillary atrophy, and the absence of vitritis. The ocular manifestations are presumably secondary to a complex and poorly defined interaction between the fungal organism H. capsulatum and the host immune response. Patients without CNV require monitoring without treatment. When CNV develops in the macula, intraocular anti-VEGF agents are the preferred option for therapy.
References
1.
Nussenblatt RB, Whitcup SM, Palestine AG. Ocular histoplasmosis. In Nussenblatt RB et al., editors. Uveitis: fundamentals and clinical practice, 2nd ed. St. Louis: Mosby; 1996.
