Elsevier

Ophthalmology

Volume 115, Issue 11, November 2008, Pages 1957-1964.e3
Ophthalmology

Original article
Intravitreal Ranibizumab Therapy for Retinal Capillary Hemangioblastoma Related to von Hippel-Lindau Disease

https://doi.org/10.1016/j.ophtha.2008.04.033Get rights and content

Purpose

To evaluate the effect of intravitreal ranibizumab on retinal capillary hemangioblastomas (RCHs) associated with von Hippel-Lindau (VHL) disease that are not amenable or responsive to standard therapy.

Design

Prospective, noncomparative, interventional case series.

Participants

Five patients with VHL-associated RCH with exudative changes and visual loss.

Methods

Monthly intravitreal injections of ranibizumab (0.5 mg) were given over a course of 6 months for a total of 7 injections, with additional injections considered until week 52. The final study visit was designated as 8 weeks after the final study injection.

Main Outcome Measures

The primary outcome was the change in best-corrected visual acuity (BCVA) of ≥15 letters at the final visit compared with baseline. Secondary outcomes included change in lesion size, exudation as assessed clinically and by fluorescein angiography, change in retinal thickness as evaluated by optical coherence tomography, and adverse event assessments.

Results

Patients received an average of 10.0±3.1 injections over an average period of 47±14 weeks, including follow-up. Mean change in BCVA was a decrease of 9±20 letters, with 1 patient gaining ≥15 letters, and 2 patients losing ≥15 letters. Changes in both lesion size and exudation were variable.

Conclusions

Intravitreal ranibizumab, delivered as monotherapy every 4 weeks, had minimal beneficial effects on most VHL-related RCHs. Possible treatment efficacy was demonstrated in the patient with the smallest lesion with less exudation. Future prospective studies are needed to determine the potential role of an antiangiogenic agent, possibly in combination with other therapies for the treatment of such advanced ocular tumors associated with VHL.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Patients and Methods

This study was an open-label, nonrandomized, prospective, pilot study of intravitreal injections of ranibizumab in patients with RCHs associated with VHL disease with either severe ocular disease or disease not amenable to standard therapy. The diagnosis of VHL disease was made both clinically according to the criteria of Melmon and Rosen21 and genetically by the detection of a disease-causing mutation in the germline sequence of the VHL gene. Inclusion criteria included having best-corrected

Patient 1

A 33-year-old man with systemic VHL disease with renal, pancreatic, cerebellar, and endolymphatic sac involvement, also had severe bilateral ocular disease related to RCHs. Extensive RCH involvement in his left eye had resulted in enucleation 4 years before study enrollment. The right eye had a large juxtapapillary lesion that had been treated with argon laser photocoagulation 12 years prior, resulting in a small centrocecal scotomatous field defect. Visual acuity immediately posttreatment was,

Results

Demographics and ocular characteristics of the 5 patients in this prospective treatment study are given in Table 1.

Active exudative activity related to the RCHs was evident in all study eyes at baseline. Visual acuities at baseline ranged from 20/25 to 20/500 (79 to 18 letters; average, 54±26 letters). After 7 initial injections, patients were assessed for treatment benefit. In 2 patients (patients 1 and 4), treatment benefit was not apparent and injections were stopped. In the remaining

Discussion

In this study, we evaluated the effects of intravitreal ranibizumab (0.5 mg) in 5 patients in treating advanced retinal disease associated with VHL-related RCHs. To our knowledge, this is the first report of the use of ranibizumab and the second prospective study on the use of anti-VEGF therapy for this indication. Aberrantly high levels of VEGF secreted by tumor cells lacking the VHL protein are thought to promote the formation and growth of hemangioblastomas.8 Originally termed vascular

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  • Cited by (0)

    Manuscript no. 2008-109.

    Financial Disclosure(s): No conflicting relationship exists for any author.

    Supported by the Intramural Research Program of the National Institutes of Health, Division of Epidemiology and Clinical Research, National Eye Institute.

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