Mussa Adil Butt MBBS BSc (Hons)1
1The Princess Alexandra Hospital, Harlow, United Kingdom
Introduction
Presumed ocular histoplasmosis syndrome (POHS) is an inflammatory condition that continues to be cause for debate. Although the evidence is not robust, it is thought to be associated with infection with the fungus Histoplasma capsulatum. Although H. capsulatum is endemic to specific regions within the United States (US), there have been reports of cases in India, United Kingdom and Mexico[1].
The diagnosis is clinical and is dependent on the presence of characteristic signs on funduscopic examination. Choroidal neovascularisation (CNV) and the resulting loss of visual acuity is the most devastating complication of the disease. Numerous therapies have been suggested to help prevent disease progression, however, their efficacy is varied and therefore POHS remains a challenge for ophthalmologists[2].
Aetiology and Pathogenesis
As the name implies, there is only a ‘presumed’ association between the fungus H. capsulatum and the syndrome. The evidence supporting this relationship is heavily based on epidemiological studies. Areas with a high prevalence of H. capsulatum, Ohio and Mississippi in the US, have shown the highest incidence of POHS[3]. Furthermore, associations between POHS and a positive histoplasmin skin test have been used to reinforce the claim that the fungus is the causative agent. Although this test is no longer administered routinely[4]. However, there have been reports of cases in the Netherlands, that meet the clinical diagnostic criteria but then have not been able to isolate H. capsulatum, calling into question the original understanding of aetiology[5].
The most accepted theory proposes that inhaled H. capsulatum spores replicate in alveolar macrophages and result in choroidal seeding through haematogenous dissemination[3]. The resulting choroidal neovascularisation is also a topic of debate. It is thought that disruption of Bruch’s membrane may stimulate neovascularisation, but how the fungus results in this dysfunction is not clear[6].
Diagnosis
POHS is a clinical diagnosis secondary to the discovery of an agreed triad of components on fundoscopic examination in the absence of vitreal inflammation. These are chorioretinal peripapillary atrophy, chorioretinal scars and choroidal neovascularization[7]. However, many patients remain asymptomatic and therefore undiagnosed, until CNV compromises their visual acuity and they are seen by an ophthalmologist[8]. These patients usually complain of metamorphopsia, decreased vision and scotomas[9]. Choroidal scars have been found in 20% of patients under monitoring, however 3.8% progress to CNV. The link between this progression is unclear and as asymptomatic patients with scars are rarely identified there are no strong conclusions from previous studies[10].
Management
The presence of choroidal scars in asymptomatic patients has led to the agreement that treatment at this stage is not necessary. However, progression to CNV results in a direct effect on patients’ visual acuity and is, therefore, the focus of treatment. Previously, the use of antifungal medication was attempted however, as the role of H. capsulatum in the disease is unclear and the efficacy of treatment was minimal, it was abandoned[11]. Systemic corticosteroids were used previously as a result of their immunosuppressive properties. However, their efficacy in halting disease progression was poor following haemorrhage from vessels and as the side effects of long term systemic use became known, their use was also abandoned[12]. As our understanding of the process of neovascularization has improved, studies have explored the role of the inflammatory system in this pathway, highlighting a possible use for intravitreal steroid use[13]. The use of photodynamic therapy, consisting of the intravenous infusion of a photosensitive drug and subsequent activation using light of a specific wavelength has shown occlusion of treated vessels. It demonstrates a significant benefit of selectively targeting CNV without harm to the overlying retinal tissue[14]. Vascular endothelial growth factor (VEGF) has been shown to play a fundamental role in the induction of CNV making it a valuable target for treatment. Anti-VEGF treatments have been created for the use of CNV in age-related macular degeneration (AMD), which will likely be adopted to treat CNV as a result of POHS[15].
Conclusion
POHS has proven to be a controversial topic in the field of ophthalmology. Despite multiple studies, our understanding of this condition has not progressed greatly. As a complex condition with unclear aetiology, the focus is placed on the management of its main complication, visual loss due to CNV. As our understanding of the pathogenesis of CNV has expanded, new treatment modalities have become available. POHS-related CNV management will likely be similar to AMD-related CNV management which is a more prevalent ophthalmic health concern.
Bibliography
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