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Purpose: To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS)., Design: Retrospective, comparative case series., Participants: Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010., Intervention: Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT)., Main Outcome Measures: Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals., Results: A total of 117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT treatment. For all patients, the average pretreatment logarithm of minimum angle of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB injections per year. There was no significant difference in initial VA, VA at 12 months, VA at 24 months, or number of eyes with a 3-line gain between the IVB monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3 lines or more, and 81.2% (84/104) of subjects had maintained or improved their starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32) follow-up. There was no increase in the proportion of subjects losing 3 lines or more over 3 years of follow-up., Conclusions: There is no significant difference in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The use of IVB alone or in combination with PDT results in significant visual stabilization in the majority of patients with CNV secondary to POHS., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Presumed ocular histoplasmosis syndrome classically presents with atrophic choroidal scars, which are thought to progress into choroidal neovascularization in a small proportion of patients. The pathophysiology of the disease, including its underlying etiology, continues to be controversial and subject to ongoing research. Even more important is the controversy that surrounds the optimal treatment for choroidal neovascularization in patients with presumed ocular histoplasmosis, in particular that of subfoveal localization., Recent Developments: Intense efforts oriented toward defining the most beneficial therapeutic modality have resulted in some well-designed, large studies that evaluated submacular surgery, photodynamic therapies, and anti-angiogenic therapies, as well as small pilot studies exploring new therapeutic approaches for choroidal neovascularization., Summary: Important results obtained by these studies were recently made public, and the conclusions that may be drawn from them, as well as an update on findings concerning presumed ocular histoplasmosis etiology, epidemiology, and pathophysiology are presented in this report.

Objective: To evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS)., Design: Open-label, 3-center, uncontrolled clinical study., Participants: Ocular histoplasmosis syndrome patients with subfoveal CNV (N = 26) with a greatest linear dimension no larger than 5400 microm with classic or occult CNV extending under the geometric center of the fovea, and best-corrected visual acuity letter score of approximately 20/40 to 20/200., Methods: The methods were similar to those described in the 1-year results with follow-up examinations every 3 months continuing through the second year. During the second year, additional therapy was recommended if fluorescein angiography showed leakage at a scheduled visit., Main Outcome Measurements: Visual function measurements included the changes from baseline in visual acuity and contrast sensitivity scores. Lesion size and leakage from classic and occult CNV were assessed at month 12 and month 24. Safety assessments also were made., Results: A 24-month examination was completed in 22 of the 26 enrolled participants (85%). At the 24-month examination, median improvement from baseline in visual acuity of the 22 patients evaluated was 6 letters; median contrast sensitivity improved by 3.5 letters. At the 24-month examination, 10 patients (45%) gained 7 or more letters of visual acuity from baseline, whereas 4 patients (18%) lost 8 or more letters, including 2 patients (9%) who lost at least 15 letters. There was absence of fluorescein angiographic leakage from classic CNV in 17 of the 20 evaluable lesions (85%), and leakage from occult CNV was absent in all eyes. No serious ocular adverse events were reported, and no serious systemic event was considered to be associated with treatment., Conclusions: Median visual acuity improved and fluorescein angiographic leakage decreased after verteporfin therapy in this small, uncontrolled clinical study of patients with subfoveal CNV resulting from OHS. Verteporfin therapy seemed to be relatively safe in these patients. The selected cases feature fluorescein angiographic examples of CNV that are important in determining when to apply verteporfin therapy.

Objective: To evaluate the safety and effect on visual acuity of photodynamic therapy with verteporfin (Visudyne, Novartis AG) in patients with subfoveal choroidal neovascularization (CNV) secondary to the ocular histoplasmosis syndrome (OHS)., Design: Open-label, three-center, noncomparative prospective case series., Participants: OHS patients with subfoveal CNV lesions no larger than 5400 micro m in greatest linear dimension (GLD) with classic or occult CNV extending under the geometric center of the foveal avascular zone and best-corrected visual acuity letter score of 73 to 34 (approximate Snellen equivalent 20/40-20/200)., Methods: Twenty-six patients received verteporfin (6 mg/m(2)) infused IV over 10 minutes. Fifteen minutes after the start of infusion, a laser light at 689 nm delivered 50 J/cm(2) at an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 micro m larger than the GLD of the lesion. At 3-month follow-up examinations, retreatment with the same regimen was applied if angiography showed fluorescein leakage. Safety assessments were also made., Main Outcome Measures: Visual function measurements were the changes from baseline in visual acuity and contrast sensitivity scores and the proportion of patients who, based on best-corrected visual acuity scores, (1) gained 7 or more letters, (2) lost 8 or more letters, and (3) lost 15 or more letters., Results: One patient was omitted from the study at the month 3 examination for not meeting the visual acuity eligibility requirements at baseline. By the month 12 examination, but excluding any retreatment at that visit, patients had received an average of 2.9 treatments of a maximum of 4 possible treatments. The month 12 median improvement from baseline in visual acuity of the remaining 25 patients was 7 letters, and median contrast sensitivity improved by 2 letters. Median visual acuity improvement was also 7 letters when three patients, who failed to meet all photographic eligibility requirements at baseline, were excluded. At the month 12 examination, 14 (56%) patients gained 7 or more letters of visual acuity from baseline, whereas 4 (16%) patients lost 8 or more letters, of which 2 (8%) lost 15 or more letters. No serious systemic or ocular adverse events were reported., Conclusions: Median visual acuity improved after verteporfin therapy for at least 1 year in a small uncontrolled prospective case series of patients with subfoveal CNV caused by OHS. Verteporfin therapy seemed to be safe and well tolerated in these patients. Two-year data from this study will provide important, additional information on the safety and effect of verteporfin therapy for the treatment of subfoveal CNV secondary to OHS.

Background: Active inflammation has not been traditionally associated with the ocular histoplasmosis syndrome., Objective: To investigate the occurrence of presumed inflammatory chorioretinal lesions in patients with the ocular histoplasmosis syndrome., Methods: Patients seen with acute symptoms and a clinical picture of ocular histoplasmosis were observed prospectively between August 13, 1993, and December 2, 1997. Symptoms, visual acuity, and fluorescein sodium angiography were used to document changes in inflammatory loci., Results: Twelve patients were seen with active inflammatory lesions. Eleven had resolution of the loci with lessening of symptoms and improvement in acuity and angiographic findings. A typical subretinal neovascular membrane developed in 1 patient 8 months after the onset of symptoms., Conclusions: Inflammatory chorioretinal lesions can reactivate in the ocular histoplasmosis syndrome. In most of these patients, neovascularization did not develop and visual acuity was preserved.

Purpose: To compare 15-year incidence rates of visual impairment and vision-threatening conditions between cases with ocular histoplasmosis and controls residing in the same endemic community., Methods: Controls and cases with and without disciform lesions who were between 30 and 69 years of age when selected, interviewed, and examined in 1970 were reinterviewed and reexamined in 1985., Results: Of the 252 cases and controls examined in 1970, 216 were still alive in 1985. Of these, 202 (94%) were interviewed; 197 (91%) underwent visual acuity measurement; and 173 (80%) were examined by a study ophthalmologist. Both in 1970 and in 1985, cases with disciform macular lesions of ocular histoplasmosis had a higher prevalence of both unilateral and bilateral visual impairment and blindness. Although prevalence of visual impairment and blindness in 1985 was similar among controls and cases of ocular histoplasmosis without disciform lesions, this group of cases had about twice the incidence of visual impairment as that of controls. However, the 95% confidence intervals on estimates of relative risks were broad and included unity. No new disciform lesions attributable to ocular histoplasmosis were found in 28 eyes of 18 cases free of them in 1970 or among 148 controls., Conclusions: The 15-year risk of visual impairment and blindness appears to be somewhat higher among adults aged 30 years and older who have only peripheral atrophic scars characteristic of ocular histoplasmosis than among individuals without such scars who live in the same endemic community. Adults who already have a disciform lesion attributed to ocular histoplasmosis in one eye are at low risk of development of a disciform lesion in the fellow eye later in life.

We used computerized electroretinography (E.R.G.) flash to study 12 patients: five pseudohistoplasmosis (P.S.H.) and seven chronic idiopathic retinal vasculitis (C.I.R.V.), compared with 12 healthy controls. We found a moderate correlation in controls between white computer averaged b-wave amplitude and b-wave obtained with other wavelengths (over 600 nm red, over 550 nm orange, and under 500 nm blue), in scotopic (white/orange r = 0.41, P < 0.05; white/red r = 0.45, P < 0.05; white/blue r = 0.48, P < 0.02) and photopic conditions (white/orange r = 0.6, P < 0.01). For P.S.H. there was a highly significant correlation between white and all wavelengths in photopic (white/orange r = 1, white/red r = 0.96, P < 0.0001) and scotopic conditions (white/orange r = 0.97, P < 0.0001; white/red r = 0.96, P < 0.0001; white/blue r = 0.96). In vasculitis, as in controls, we found no white/red correlation and only in vasculitis we could not find a scotopic white/blue correlation. We conclude that these situations are electrophysiologically different. The closer correlation in P.S.H. suggests more efficient phototransduction and in C.I.R.V. there may also be a rod-selective dysfunction.