Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: One-year results of an uncontrolled, prospective case series

doi:10.1016/S0161-6420(02)01103-X

Ophthalmology

Volume 109, Issue 8, August 2002, Pages 1499-1505

Presented in part at the annual meeting of the American Academy of Ophthalmology, Dallas, Texas, October, 2000.

https://doi.org/10.1016/S0161-6420(02)01103-X Get rights and content

Abstract

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 μm 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/m²) infused IV over 10 minutes. Fifteen minutes after the start of infusion, a laser light at 689 nm delivered 50 J/cm² at an intensity of 600 mW/cm² over 83 seconds using a spot size with a diameter 1000 μm 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.

Section snippets

Patients and methods

The VOH Study was designed as an open-label, multicenter study to investigate the safety and effect of verteporfin therapy on subfoveal CNV secondary to OHS. The design of the study was reviewed by the authors, the institutional review boards of the participating centers, and the independent data and safety monitoring committee used in the TAP Investigation.18 Certification and monitoring of the clinical centers and study personnel were also similar to the procedures described for the TAP

Results

Twenty-six patients were enrolled in the study; one patient with OHS was subsequently excluded from further study participation after the month 3 examination for failure to meet the inclusion/exclusion criteria (the patient’s baseline best-corrected visual acuity letter score was 20). The demographic baseline characteristics for the 26 patients are shown in Table 2. The mean baseline visual acuity score was 56 letters (median, 56 letters), and the mean contrast sensitivity score was 29 letters

Discussion

The month 12 results from the VOH Study show that median visual acuity improved after verteporfin therapy with no serious adverse events. Compared with previous studies, which evaluated verteporfin therapy for AMD, no additional safety concerns were identified. There was no vision loss in most of these patients for 1 year, and approximately 50% of patients experienced some improvement in vision. To our knowledge, similar favorable vision outcomes have never been reported in OHS patients.4, 24

Verteporfin in Ocular Histoplasmosis (VOH) study group

Participating clinics, investigators, clinic coordinators, vision examiners, photographers, and central resource groups in the VOH Study Group as of July 2000.

References (24)

M.L Lewis et al.
Follow-up study of presumed ocular histoplasmosis syndrome
Ophthalmology
(1980)
R.J Olk et al.
Subfoveal and juxtafoveal subretinal neovascularization in the presumed ocular histoplasmosis syndrome. Visual prognosis
Ophthalmology
(1984)
N.M Holekamp et al.
Surgical removal of subfoveal choroidal neovascularization in presumed ocular histoplasmosis. Stability of early visual results
Ophthalmology
(1997)
M Kramer et al.
Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys
Ophthalmology
(1996)
B.S Hawkins et al.
Ocular histoplasmosis
L.B Edwards et al.
An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States
Am Rev Respir Dis
(1969)
Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Results of a randomized clinical trial. Macular Photocoagulation Study Group
Arch Ophthalmol
(1987)
Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group
Arch Ophthalmol
(1991)
Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group
Arch Ophthalmol
(1994)
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)

R.C Kleiner et al.

Subfoveal neovascularization in the ocular histoplasmosis syndrome. A natural history study

Retina

(1988)

S.L Fine et al.

Laser treatment for subfoveal neovascular membranes in ocular histoplasmosis syndromeresults of a pilot randomized clinical trial

Arch Ophthalmol

(1993)

Cited by (77)

Age-related macular degeneration masqueraders: From the obvious to the obscure
2021, Survey of Ophthalmology
Citation Excerpt :
The Verteporfin in Ocular Histoplasmosis Study analyzed the use of PDT in 26 patients with subfoveal CNV secondary to POHS. At 12 months, 56% of patients gained at least 7 letters.106 Intravitreal anti-VEGF agents have shown efficacy in treating CNV secondary to POSH, with ranibizumab and bevacizumab being the most used.
Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide with increasing prevalence owing to increased life expectancy. Intravitreal injections of antivascular endothelial growth factor agents are commonly used in exudative AMD and oral antioxidant medication for nonexudative AMD; however, many disorders mimic exudative and nonexudative AMD, and misdiagnosis can seriously affect the management of these patients. We summarize the demographics and clinical and imaging characteristics of each of the conditions that masquerade as AMD. As some of the conditions have features of AMD, a short update on the classical features of AMD is also included.
Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis
2021, Laboratory Investigation
Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease with poor clinical outcomes. Podocyte loss via apoptosis is one important mechanism underlying the pathogenesis of FSGS. Recently, Yes-associated-protein (YAP), a key downstream protein in the Hippo pathway, was identified as an activator for multiple gene transcriptional factors in the nucleus to control cell proliferation and apoptosis. To investigate the potential role of YAP in the progression of FSGS, we examined kidney samples from patients with minimal change disease or FSGS and found that increases in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in human FSGS. Utilizing an established mT/mG transgenic mouse model and primary cultured podocytes, we found that YAP was distributed uniformly in nucleus and cytoplasm in the podocytes of control animals. Adriamycin treatment induced gradual nuclear exclusion of YAP with enhanced phospho-YAP/YAP ratio, accompanied by the induction of podocyte apoptosis both in vivo and in vitro. Moreover, we used verteporfin to treat an Adriamycin-induced FSGS mouse model, and found YAP inhibition by verteporfin induced nuclear exclusion of YAP, thus increasing podocyte apoptosis and accelerating disease progression. Therefore, our findings suggest that YAP nuclear distribution and activation in podocytes is an important endogenous anti-apoptotic mechanism during the progression of FSGS.
An increase in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in focal segmental glomerulosclerosis (FSGS). YAP inhibition by verteporfin induces nuclear exclusion of YAP, thus increasing the podocyte apoptosis and accelerating disease progression. Therefore, this study suggests that YAP activation and nuclear distribution in podocytes is an endogenous anti-apoptotic mechanism during the progression of FSGS.
Whitcup and Nussenblatt’s Uveitis: Fundamentals and Clinical Practice
2021, Whitcup and Nussenblatt's Uveitis: Fundamentals and Clinical Practice
Ocular histoplasmosis syndrome
2015, Survey of Ophthalmology
Citation Excerpt :
These results were maintained at 24 months, with 45% of patients gaining ≥7 letters and 18% losing ≥8 letters. At 24 months, no leakage was observed in 17 of 20 classic CNV lesions.118,123 Smaller clinical studies obtained similar results.78,113,117,135
Ocular histoplasmosis syndrome (OHS) is a chorioretinal disorder with a distinct fundus appearance that is commonly found in regions endemic for Histoplasma capsulatum. Choroidal neovascularization (CNV) secondary to OHS is considered one of the principal causes of central vision loss among young adults in endemic areas. Although there is no consensus regarding its pathogenesis, evidence points to Histoplasma capsulatum as the most probable etiology. Once considered an intractable hemorrhagic maculopathy, CNVs are now treatable. Extrafoveal CNVs are successfully treated with laser photocoagulation. Subfoveal and juxtafoveal CNVs are managed with anti-vascular endothelial growth factor therapy, photodynamic therapy, or a combination of both. Modern imaging technologies such as spectral-domain optical coherence tomography have improved our diagnostic abilities, making it easier to monitor disease activity and CNV regression. We review the epidemiology, pathogenesis, clinical manifestations, differential diagnosis, and current treatment of this disease.
Choroidal neovascularization in pathological myopia
2012, Progress in Retinal and Eye Research
Myopic choroidal neovascularization (CNV) is one of the leading causes of visual impairment worldwide. The clinical and socioeconomic impact of myopic CNV in Asian countries is particularly significant due to rising trend in the prevalence and severity of pathological myopia. The exact pathogenesis of myopic CNV remains unclear and there is paucity of information with respect to incidence and risk factors for myopic CNV from prospective studies. Furthermore, there are no recognized measures that may prevent or delay the development of CNV in eyes with pathological myopia. Advances have been made in the diagnosis and characterization of myopic CNV over the years. Until recently, treatment modalities for myopic CNV were limited to thermal laser photocoagulation and photodynamic therapy with verteporfin, both these modalities primarily aim at prevention of further visual loss. In the last 5 years, inhibitors of vascular endothelial growth factor (VEGF) have been used successfully and may improve vision to some extent. Nevertheless, the long-term safety and efficacy of anti-VEGF agents remains unknown. Furthermore, the risk of developing chorioretinal atrophy remains the key factor in determining the final visual outcome. This review article summarizes the current literature on myopic CNV, highlighting new evolving diagnostic and treatment modalities, prognostic factors influencing visual outcome, and areas of future research.
Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis
2012, Ophthalmology
To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS).
Retrospective, comparative case series.
Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010.
Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT).
Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals.
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.
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.
Proprietary or commercial disclosure may be found after the references.

View all citing articles on Scopus

^☆: Supported by Novartis Ophthalmics AG, Bülach, Switzerland, and QLT Inc., Vancouver, British Columbia, Canada.

³: Reprint requests to Medical Affairs, Novartis Ophthalmics Inc., 11695 Johns Creek Parkway, Duluth, GA 30097.

¹: Neil M. Bressler has been a paid consultant of Novartis Ophthalmics and QLT Inc. (the terms of this agreement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies); David A. Saperstein has indicated support for scientific presentations at meetings and travel expenses; Troy A. Reaves is an employee of Novartis Ophthalmics.

^∗: See page 1504.

View full text

Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: One-year results of an uncontrolled, prospective case series3☆,

Abstract

Objective

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Section snippets

Patients and methods

Results

Discussion

Verteporfin in Ocular Histoplasmosis (VOH) study group

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ocular histoplasmosis

An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States

Am Rev Respir Dis

Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Results of a randomized clinical trial. Macular Photocoagulation Study Group

Arch Ophthalmol

Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group

Arch Ophthalmol

Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group

Arch Ophthalmol

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

Subfoveal neovascularization in the ocular histoplasmosis syndrome. A natural history study

Retina

Laser treatment for subfoveal neovascular membranes in ocular histoplasmosis syndromeresults of a pilot randomized clinical trial

Arch Ophthalmol

Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: One-year results of an uncontrolled, prospective case series³ ☆,