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Figure 1.
A 64-year-old man was referred with an enlarging iris melanoma and secondary neovascular glaucoma in his only seeing eye. A, The melanoma occupied the inferior portion of the iris and diffuse neovascularization on the entire iris surface was noted. B, Ultrasound biomicroscopy depicted a solid iris mass touching the endothelium.

A 64-year-old man was referred with an enlarging iris melanoma and secondary neovascular glaucoma in his only seeing eye. A, The melanoma occupied the inferior portion of the iris and diffuse neovascularization on the entire iris surface was noted. B, Ultrasound biomicroscopy depicted a solid iris mass touching the endothelium.

Figure 2.
Treatment involved intravitreal bevacizumab and plaque radiotherapy. A, Application of the radioactive plaque over the cornea for a total dose of 8000 cGy to the melanoma (the conversion of centigray to rad is 1:1). B, Fifteen months after treatment, the tumor remained regressed and the iris neovascularization completely resolved. A dense cataract is present. Cataract surgery is planned.

Treatment involved intravitreal bevacizumab and plaque radiotherapy. A, Application of the radioactive plaque over the cornea for a total dose of 8000 cGy to the melanoma (the conversion of centigray to rad is 1:1). B, Fifteen months after treatment, the tumor remained regressed and the iris neovascularization completely resolved. A dense cataract is present. Cataract surgery is planned.

1.
Shields  CLShields  JAMaterin  MGershenbaum  ESingh  ADSmith  A Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology 2001;108 (1) 172- 178
PubMedArticle
2.
Shields  CLMaterin  MAShields  JAGershenbaum  ESingh  ADSmith  A Factors associated with elevated intraocular pressure in eyes with iris melanoma. Br J Ophthalmol 2001;85 (6) 666- 669
PubMedArticle
3.
Folkman  J Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285 (21) 1182- 1186
PubMedArticle
4.
Lee  ESBaratz  KHPulido  JSSalomao  DR Expression of vascular endothelial growth factor in iris melanoma. Arch Ophthalmol 2006;124 (9) 1349- 1350
PubMedArticle
5.
Sahin  A Kiratli  HTezel  GGSoylemezoglu  FBilgic  S Expression of vascular endothelial growth factor a, matrix metalloproteinase 9 and extravascular matrix patterns in iris and ciliary body melanomas. Ophthalmic Res 2007;39 (1) 40- 44
PubMedArticle
6.
Hurwitz  HFehrenbacher  JNovotny  W  et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350 (23) 2335- 2342
PubMedArticle
7.
Varker  KABiber  JEKefauver  C  et al.  A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma [published online ahead of print May 30, 2007]. Ann Surg Oncol 2007;14 (8) 2367- 2376
PubMedArticle
8.
Davidorf  FHMouser  JGDerick  RJ Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina 2006;26 (3) 354- 356
PubMedArticle
Research Letters
April 1, 2008

Treatment of Iris Melanoma and Secondary Neovascular Glaucoma Using Bevacizumab and Plaque Radiotherapy

Arch Ophthalmol. 2008;126(4):578-579. doi:10.1001/archopht.126.4.578

Iris melanoma is uncommon, representing only 2% of all uveal melanomas.1 In a series of 169 consecutive patients with iris melanoma, Shields et al2 indicated that elevated intraocular pressure was found in 30% of cases. The main mechanism for the elevated pressure was mechanical obstruction of aqueous outflow from solid tumor or seeding. In that series, there were no eyes with secondary neovascular glaucoma. We report herein the unique association of neovascular glaucoma with chronic iris melanoma and discuss its management.

Report of a Case

A 64-year-old man was referred with a documented 12-year history of a slowly enlarging pigmented iris lesion in the left eye. The right eye had longstanding poor vision secondary to ocular histoplasmosis with a foveal scar diagnosed at age 15 years. At his initial visit, the visual acuities were 20/300 OD and 20/150 OS. On slitlamp examination of the left eye, a nodular, pigmented tumor with prominent intrinsic vascularity was noted in the inferior iris and measured 8 mm in the largest diameter and 1.9 mm in thickness, with corneal endothelial touch (Figure 1). There was no ciliary body component by ultrasound biomicroscopy. Associated ectropion uveae, cataract, and profound iris neovascularization of the entire iris were found. Intraocular pressures were 17 mm Hg OD and 24 mm Hg OS, despite using topical and oral antiglaucoma medications. Angle involvement with tumor seeding and neovascularization were noted on gonioscopy. Fundus examination showed bilateral peripheral histoplasmosis chorioretinal lesions with a large atrophic foveal scar in the right eye.

A diagnosis of enlarging iris melanoma in the left eye with secondary cataract and neovascular glaucoma was rendered. Due to contralateral amblyopia, enucleation was avoided, and because of extensive tumor seeding, surgical resection was not considered. Plaque radiotherapy combined with a single injection of 1.25 mg of intravitreal bevacizumab (0.05 mL at a concentration of 25 mg/mL) (Avastin; Genentech, Inc, San Francisco, California) was advised for treatment of the melanoma and resolution of the iris neovascularization. At the time of radiotherapy, fine-needle aspiration biopsy of the melanoma for genetic testing was performed.

Microsatellite array disclosed chromosome 3 monosomy. At 15 months' follow-up, the iris neovascularization and glaucoma were completely resolved with an intraocular pressure of 6 mm Hg while the patient was receiving no medications, and the residual melanoma scar remained regressed and flat (Figure 2).

Comment

The assumption that tumor growth and metastasis are angiogenesis dependent was initially proposed by Folkman3 in 1971. Recent research in tumor microvasculature has emphasized vascular endothelial growth factor (VEGF) as a mediator of tumor angiogenesis.4

Iris melanoma demonstrates VEGF expression.4,5 Lee et al4 reported an iris melanoma with VEGF expression using immunohistochemical staining of an anti-VEGF antibody. Sahin et al5 described weak VEGF expression (staining of < 25% of cells) in 2 of 3 iris melanomas using a similar technique.

Bevacizumab is a recombinant humanized anti-VEGF IgG1 monoclonal antibody approved as an antiangiogenic agent for the treatment of metastatic colorectal cancer in combination with chemotherapy.6 It has also been proven to increase survival rates when used in association with chemotherapy for the treatment of non–small-cell lung cancer. A phase 2 clinical trial of bevacizumab in patients with metastatic skin melanoma showed prolonged disease stabilization in 25% of the patients.7 From an ophthalmology standpoint, intravitreal bevacizumab has been used for age-related macular degeneration and iris neovascular glaucoma.8

The management of iris melanoma with elevated intraocular pressure is challenging and generally requires enucleation.2 In this case, the bevacizumab was used in combination with plaque radiotherapy, which resulted in rapid resolution of the neovascular glaucoma as well as the tumor. The precise effect of bevacizumab on the melanoma remains speculative.

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Article Information

Correspondence: Dr C. L. Shields, Ocular Oncology Service, Ste 1440, Wills Eye Institute, 840 Walnut St, Philadelphia, PA 19107 (carol.shields@shieldsoncology.com).

Financial Disclosure: None reported.

Funding/Support: This work was supported by the Retina Research Foundation of the Retina Society in Capetown, South Africa (Dr C. L. Shields), the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (Dr J. A. Shields), a donation from Michael, Bruce, and Ellen Ratner, New York, New York (Drs J. A. Shields and C. L. Shields), Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (Dr C. L. Shields), the LuEsther Mertz Retina Research Foundation, New York (Dr C. L. Shields), and the Eye Tumor Research Foundation, Philadelphia (Drs C. L. Shields and J. A. Shields).

References
1.
Shields  CLShields  JAMaterin  MGershenbaum  ESingh  ADSmith  A Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology 2001;108 (1) 172- 178
PubMedArticle
2.
Shields  CLMaterin  MAShields  JAGershenbaum  ESingh  ADSmith  A Factors associated with elevated intraocular pressure in eyes with iris melanoma. Br J Ophthalmol 2001;85 (6) 666- 669
PubMedArticle
3.
Folkman  J Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285 (21) 1182- 1186
PubMedArticle
4.
Lee  ESBaratz  KHPulido  JSSalomao  DR Expression of vascular endothelial growth factor in iris melanoma. Arch Ophthalmol 2006;124 (9) 1349- 1350
PubMedArticle
5.
Sahin  A Kiratli  HTezel  GGSoylemezoglu  FBilgic  S Expression of vascular endothelial growth factor a, matrix metalloproteinase 9 and extravascular matrix patterns in iris and ciliary body melanomas. Ophthalmic Res 2007;39 (1) 40- 44
PubMedArticle
6.
Hurwitz  HFehrenbacher  JNovotny  W  et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350 (23) 2335- 2342
PubMedArticle
7.
Varker  KABiber  JEKefauver  C  et al.  A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma [published online ahead of print May 30, 2007]. Ann Surg Oncol 2007;14 (8) 2367- 2376
PubMedArticle
8.
Davidorf  FHMouser  JGDerick  RJ Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina 2006;26 (3) 354- 356
PubMedArticle
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