Presumed Ocular Histoplasmosis Syndrome Treatment & Management

Updated: Mar 13, 2023
  • Author: Lihteh Wu, MD; Chief Editor: C Stephen Foster, MD, FACS, FACR, FAAO, FARVO  more...
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Medical Care

Corticosteroid therapy

A few anecdotal cases of oral steroids inducing involution of recent-onset subfoveal CNV have been reported.

A small series reported on the benefits of an intravitreal injection of 4 mg of triamcinolone acetonide in eyes with subfoveal or juxtafoveal CNV secondary to POHS. [23]

Sustained-release steroid implants have been used on a compassionate basis in refractory patients with stabilization or improvement of vision in 6 of 7 cases. However, concomitant submacular surgery was performed in 4 cases. [24]

Antifungal therapy

Antifungals are not beneficial.

Anti-VEGF therapy

Vascular endothelial growth factor (VEGF) has been shown to be a key molecular player in the pathogenesis of CNV. In the current era of anti-VEGF therapy, the extraordinary results obtained in CNV secondary to age-related macular degeneration have been extrapolated to other causes of CNV with apparent good results. [25, 26] Currently available anti-VEGF agents include bevacizumab, ranibizumab, and pegaptanib sodium.

In a small retrospective case series of 28 eyes with a relatively short follow-up of 22 weeks, intravitreal bevacizumab was shown to improve the visual acuity in 71% of eyes. In 14%, the visual acuity remained the same, and, in another 14%, the visual acuity decreased despite treatment. [26]

A large retrospective comparative case series compared intravitreal bevacizumab (117 eyes) with combination therapy consisting of intravitreal bevacizumab and verteporfin photodynamic therapy (34 eyes). At the end of 2 years of follow up, no difference in visual outcome was noted between the treatment strategies. Approximately 30% of eyes gained at least 3 lines of best-corrected visual acuity over baseline. Subgroup analysis revealed that in juxtafoveal CNV, no difference in the burden of injections was noted between the groups. However, in the subfoveal group, there were statistically significantly fewer injections in the combination group. [27]  

A prospective open-label study compared 2 different treatment regimens of ranibizumab. In one group, 11 eyes received a loading dose of 3 consecutive monthly injections of ranibizumab and were then followed on a monthly basis with prn injections. The other group of 10 eyes received a single injection at baseline and were retreated prn during their monthly monitoring. There were no differences between the groups in terms of number of injections, gains in visual acuities, and improvements in central macular thickness. The gains in visual acuity were an average of 2 lines and were achieved with an average of 5.7 injections. [28]

Aflibercept has also been shown to be effective in the management of CNV secondary to ocular histoplasmosis. In a small prospective study, patients received 3 consecutive monthly 2-mg aflibercept injections followed by bimonthly injections. At the end of the study (12 months’ follow-up), the average gain in best corrected visual acuity was 12.4 ETDRS letters, and the mean central subfoveal thickness decreased by 34.6 microns. [29] A larger study compared 19 eyes that underwent the same loading dose of 3 monthly aflibercept injections followed by bimonthly injections with 20 eyes that were injected once at baseline and then received monthly follow-up with prn injections. At 1 year of follow-up, both groups sustained similar improvements in visual acuity and central macular thickness. The prn group required fewer injections. [30]

Combination Therapy 

A retrospective comparative case series demonstrated that after 10 years of follow up, both monotherapy with an anti-VEGF agent or combination therapy of an anti-VEGF plus photodynamic therapy are effective. However combination therapy appeared to reduce the injection burden and increase the treatment free interval. [31]


Surgical Care

Laser photocoagulation

The Macular Photocoagulation Study (MPS), a multicenter prospective randomized clinical trial, demonstrated that laser photocoagulation is indicated in the treatment of extrafoveal and juxtafoveal CNV secondary to POHS. [16]

The goal of treatment is to obliterate the entire area of CNV.

Prior to laser treatment, a fluorescein angiogram that shows the exact borders of the lesion is essential.

Despite its marginal benefits, the MPS recommended laser treatment of peripapillary CNV. Alternatively, pars plana vitrectomy and excision of the peripapillary CNV may be considered. Most surgeons recommend removal of recent subfoveal CNV but not peripapillary lesions.

Pilot studies of laser photocoagulation of subfoveal CNV were inconclusive.

Photodynamic therapy

Photodynamic therapy (PDT): Subfoveal CNV secondary to POHS is a labeled indication for PDT by the US Food and Drug Administration. An open-label, uncontrolled clinical study reported the median improvement of visual acuity of 6 letters after a mean of 3.9 PDT treatments in a 2-year follow-up with no serious ocular or systemic effects reported. [32]

Submacular surgery

Given that most CNV secondary to POHS grow in the subretinal space, uncontrolled studies have recommended surgical excision of subfoveal CNV via pars plana vitrectomy. The goal is to remove the CNV but to leave the underlying RPE and choriocapillaris intact.

The Submacular Surgery Trial (SST), a randomized multicenter prospective trial sponsored by the National Eye Institute (NEI), reported on the modest benefit in eyes with CNV secondary to POHS with a baseline visual acuity of 20/100 or worse. [33]

A case series of 45 eyes with extensive peripapillary CNV that were ineligible for laser photocoagulation by the Macular Photocoagulation Study criteria underwent surgical removal. Of these 45 eyes, in 23 eyes the CNV extended subfoveally. In this subgroup, the median visual acuity improved from 20/200 to 20/50. Almost 80% (18/23) of eyes achieved stable or improved visual acuity from baseline. Only 22% (5/23) of eyes experienced a loss of more than 2 lines of visual acuity from baseline. Close to 50% (11/23) of eyes achieved a visual acuity of ≥ 20/40. In the remaining 17 eyes where CNV remained extrafoveal, 88% (15/17) of eyes had an improvement or stability in visual acuity. Only 12% (2/17) of eyes showed a loss of ≥ 2 lines of visual acuity. The median visual acuity improved from 20/60 to 20/20. This suggests that surgical extraction in selected cases of extensive peripapillary CNV secondary to POHS might be beneficial. [34]

Photocoagulating atrophic scars

Photocoagulating atrophic scars to prevent CNV formation is not recommended.



Refer to a vitreoretinal specialist.



After 5 years of follow-up care, the MPS reported that 26% and 33% of patients had recurrent or persistent CNV following laser photocoagulation to an extrafoveal or juxtafoveal CNV, respectively. [16, 17] ​ These recurrences tended to be toward the foveal side and were associated with visual loss. In most cases, photocoagulation of recurrent CNV is indicated.

Laser treatment of peripapillary CNV may be complicated by thermal damage to the papillomacular bundle.

Surgical excision of CNV may be complicated by retinal detachment, postvitrectomy cataract, macular pucker, and macular hole. Recurrence of CNV following excision is observed in 58% of cases by 24 months of follow-up. [33]  How to effectively manage these recurrences is unclear.


Long-Term Monitoring

Most persistent and recurrent leakage occurs during the first 18 months following laser treatment.

Clinical examination cannot replace FA during the first 18 months following laser treatment.

Two weeks following laser photocoagulation, monitor a patient with a repeat FA. Pay special attention to the borders of the laser treatment zone to detect any persistence. If no leakage is detected, repeat the FA 4 weeks later. If no leakage is detected again, obtain another FA 4-6 weeks later.