Retinal Vasoproliferative Tumor Secondary to Retinitis Pigmentosa

Although these tumors are benign, it is important to identify and treat them to avoid visual compromise.

By Jideofor K. Ndulue, MD, MSPH; Christina Stathopoulos, MD; and Carol L. Shields, MD
 

Retinal vasoproliferative tumor (VPT) is a histopathologically benign vascularized glial tumor believed to result from the proliferation of blood vessels, glial tissue, and retinal pigment epithelium (RPE). VPT was first described in 1983 under the term presumed acquired retinal hemangioma.1-3 This tumor generally appears in the fourth and fifth decade of life with features of a peripheral yellow-red intraretinal mass most often located temporally or inferotemporally.4 VPTs are classified into primary (idiopathic, 80%) or secondary (20%) types.4

AT A GLANCE

• Retinal vasoproliferative tumors (VPTs) typically develop in individuals in their 30s and 40s.

• Primary VPTs are deemed idiopathic in otherwise healthy eyes, whereas secondary VPTs have been associated with preexisting congenital, inflammatory, vascular, traumatic, and dystrophic retinal conditions. Secondary forms are more often bilateral, multiple, and accompanied by poorer visual acuity.

• Both types of VPTs are benign, but either can compromise vision due to retinal exudation, retinal detachment, intraretinal edema, membrane formation, and vitreous hemorrhage.

• Management of VPTs depends on tumor features and patient symptoms.

Primary VPTs are deemed idiopathic in otherwise healthy eyes, whereas secondary VPTs have been associated with preexisting congenital, inflammatory, vascular, traumatic, and dystrophic retinal conditions.4 Secondary forms are more often bilateral, multiple, and accompanied by poorer visual acuity.4 Both types of VPTs are benign, but either can compromise vision due to retinal exudation, retinal detachment, intraretinal edema, membrane formation, and vitreous hemorrhage.4 Although these tumors are benign, it is important to identify and treat them to avoid visual compromise. In this report, we describe a patient with bilateral retinitis pigmentosa (RP) who developed secondary VPT.

CASE REPORT

A 39-year-old white woman who had been diagnosed with bilateral RP at age 26 was referred for evaluation of an intraocular mass. The lesion was initially considered to be a choroidal neovascular membrane (CNVM) and had been treated elsewhere with laser photocoagulation 8 months previously.

Figure 1. A 39-year-old woman with RP and retinal VPT misdiagnosed as neovascular membrane and treated at another center with laser photocoagulation. Fundus OS shows typical RP changes and a yellow-red mass located inferotemporally, posterior to the equator and surrounded by dense exudation. Note the minimally dilated feeding retinal vessels (A). Late-phase FA demonstrates diffuse leakage from the tumor (B).

At the time of presentation at our center, the patient’s visual acuity was 20/25 in the right eye (OD) and 20/30 in the left eye (OS). The anterior segment was unremarkable in each eye. Her fundus examination showed bilateral attenuated retinal vasculature and 360° bone-spicule pigmentation within the retina, compatible with the previous diagnosis of RP. Additionally, a peripheral elevated orange-red retinal mass was noted OS, surrounded by a shallow, dependent exudative retinal detachment and measuring 4.5 x 4.0 x 2.5 mm (Figure 1A). Fluorescein angiography (FA) demonstrated rapid filling of the tumor from a nondilated feeding retinal artery and late leakage (Figure 1B). B-scan ultrasonography showed a dense mass (Figure 2A), and spectral-domain optical coherence tomography (SD-OCT) showed normal foveal contour OD and a blunted foveal depression OS secondary to an epiretinal membrane (ERM) (Figure 2B). SD-OCT over the mass confirmed a full-thickness intraretinal mass with superficial intralesional cysts (Figure 2C). The clinical picture was compatible with an active secondary VPT in the setting of RP.

Management options were discussed with the patient, including surrounding laser photocoagulation, indocyanine green–enhanced transpupillary thermotherapy (ICG-enhanced TTT), verteporfin (Visudyne, Bausch + Lomb) photodynamic therapy (PDT), and cryotherapy. PDT was performed with standard settings and with simultaneous intravitreal anti-VEGF therapy. Four months later, the tumor had responded with slow involution, partial resolution of surrounding subretinal fluid and exudation, and thinning of the retinal feeder vessel.

Figure 2. Imaging of VPT in a patient with RP. B-scan ultrasonography discloses a dome-shaped retinal mass measuring 4.5 × 4.0 x 2.5 mm (A). SD-OCT displays a discrete blunted foveal contour secondary to an ERM (B). SD-OCT over the lesion demonstrates a full thickness retinal mass with two intralesional cystic spaces that could represent intralesional fluid or large vessels (C).

DISCUSSION

RP, which affects approximately 1 in 4,000 persons worldwide, refers to a group of inherited disorders in which degenerative abnormalities of the photoreceptors lead to progressive vision loss.5 Exudative vasculopathy manifesting as Coats-like disease, VPT, or CNVM complicates approximately 5% of RP cases.5,6 The pathophysiology of the different manifestations of related exudative vasculopathy might result from chronic retinal ischemia from attenuation of the retinal vessels or exudation from incompetent retinal vessels. Additionally, chronic damage in the RPE could provide access for secondary choroidal-retinal anastomoses through Bruch membrane defects.5,6

In a large series of 334 cases of VPT in 275 patients, 80% (n = 219) of patients had primary and 20% (n = 56) had secondary VPT (see infographic at right).4 In the 56 patients with secondary tumors, underlying ocular diseases included RP (n = 15, 22%), pars planitis (n = 14, 21%), Coats disease (n = 11, 16%), previous retinal detachment surgery (n = 8, 12%), and idiopathic peripheral retinal vasculitis (n = 4, 6%).4 A comparison of primary versus secondary VPT revealed significant differences, in that primary tumors occurred more often at older age (46 vs. 38 years) and with less frequency of visual symptoms (74% vs. 87%), visual acuity worse than 20/200 (15% vs. 28%), bilaterality (4% vs. 20%), and multifocality (5% vs. 15%).4

Secondary VPT demonstrated a classically dome-shaped retinal mass with a mean basal diameter of 7 mm, often located inferotemporally, anterior to the equator (n = 58, 72%).4 Associated ocular findings included intraretinal or subretinal exudation (n = 56, 68%), subretinal fluid (n = 42, 51%), retinal hemorrhage (n = 20, 24%), RPE alterations (n = 40, 50%), vitreous inflammation (n = 39, 48%), ERM (n = 15, 18%), retinal detachment (n = 7, 9%), retinoschisis (n = 3, 5%), and, rarely, retinal neovascularization (n = 1, 1%).4

Management of VPTs depends on tumor features and patient symptoms. Nonleaking VPTs in asymptomatic patients can remain stable, and these can be cautiously observed. However, vision-threatening findings such as secondary exudative retinal detachment or intraretinal exudation should prompt treatment. Treatment options are based on tumor size, location, and associated vitreoretinal findings and may include laser photocoagulation, ICG-enhanced TTT, verteporfin PDT, cryotherapy, plaque radiotherapy, and, in selected cases, local resection of the tumor.7-9 Eyes with extensive disease and neovascular glaucoma may require enucleation.6,9,10

Photocoagulation can be effective against small post-
equatorial tumors.11,12 Cryotherapy is reserved for fairly large tumors anterior to the equator. In addition to tumor control, cryotherapy can lead to release of ERM in 63% of cases.13 Intravitreal injection of an anti-VEGF agent has been used alone for treatment of small VPTs but has been equivocal in controlling the tumor and has shown response to edema.14 Intravitreal anti-VEGF therapy might benefit from additional focal treatment to assist in reducing tumor size and leakage.7,8 Sub-Tenon injection of triamcinolone acetate might minimize inflammatory response at the time of treatment.7,8 Radiotherapy with either iodine-125 or ruthenium-106 can demonstrate control of larger tumors, with tumor regression rates of 97% and 72% to 88%, respectively, reported.9,10,15 In a review of 39 VPTs treated with ruthenium-106, Brockman et al found that tumors greater than 7.5 mm in diameter had a greater risk of nonresponse, whereas tumor thickness was not a factor.15

VPT TREATMENT PEARLS

Clinicians should be aware of the possibility of VPT occurring in patients with RP. VPTs in the presence of exudative retinopathy should be treated or re-treated. For small to medium-sized lesions, intravitreal anti-VEGF therapy, in combination with PDT, can lead to tumor regression and counteract early PDT-related pathophysiologic alterations.

1. Shields JA, Decker WL, Sanborn GE, et al. Presumed acquired retinal hemangiomas. Ophthalmology. 1983;90(11):1292-1300.

2. Shields JA, Shields CL. Vasoproliferative tumor of the ocular fundus. In: Shields JA, Shields CL, eds. Intraocular Tumors: An Atlas and Textbook. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:418-426.

3. Poole Perry LJ, Jakobiec FA, Zakka FR, et al. Reactive retinal astrocytic tumors (so-called vasoproliferative tumors): histopathologic, immunohistochemical, and genetic studies of four cases. Am J Ophthalmol. 2013;155(3):593-608.

4. Shields CL, Kaliki S, Al-Dahmash S, et al. Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases. JAMA Ophthalmology. 2013;131(3):328-334.

5. Pagon RA. Retinitis pigmentosa. Surv Ophthalmol. 1988;33(3):137-177.

6. Fogle JA, Welch RB, Green WR. Retinitis pigmentosa and exudative vasculopathy. Arch Ophthalmol. 1978;96(4):696-702.

7. Shields CL, Douglass A, Higgins T, et al. Retinal hemangiomas: understanding clinical features, imaging, and therapies. Retina Today. 2015;10(5):61-67.

8. Shields CL, Shields JA. The American Society of Retina Specialists 2016 Founders Award Lecture. Retinal tumors: understanding clinical features, OCT morphology, and therapy. Journal of VitreoRetinal Diseases. 2017;1(1):10-23.

9. Heimann H, Bornfeld N, Vij O, et al. Vasoproliferative tumors of the retina. Br J Ophthalmol. 2000;84(10):1162-1169.

10. Cohen VM, Shields CL, Demirci H, Shields JA. Iodine I 125 plaque radiotherapy for vasoproliferative tumors of the retina in 30 eyes. Arch Ophthalmol. 2008;126(9):1245-1251.

11. Blasi MA, Scupola A, Tiberti AC, et al. Photodynamic therapy for vasoproliferative retinal tumors. Retina. 2006;26(4):404-409.

12. Mennel S, Barbazetto I, Meyer CH, et al. Ocular photodynamic therapy–standard applications and new indications. Part 2. Ophthalmologica. 2007;221(5):282-291.

13. Manjandavida FP, Shields CL, Kaliki S, Shields JA. Cryotherapy-induced release of epiretinal membrane associated with retinal vasoproliferative tumor: analysis of 16 cases. Retina. 2014;34(8):1644-1650.

14. Saito W, Kase S, Fujiya A, Dong Z, Noda K, Ishida S. Expression of vascular endothelial growth factor and intravitreal anti-VEGF therapy with bevacizumab in vasoproliferative retinal tumors. Retina. 2013;33(9):1959-1967.

15. Brockmann C, Rehak M, Heufelder J, et al. Predictors of treatment response of vasoproliferative tumors to ruthenium-106 brachytherapy. Retina. 2016;36(12):2384-2390.

Jideofor K. Ndulue, MD, MSPH
• ocular oncology intern, Wills Eye Hospital, Philadelphia, Pa.

Carol L. Shields, MD
• director of the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pa.
• member of the Retina Today editorial advisory board
carolshields@gmail.com

Christina Stathopoulos, MD
• research fellow, Wills Eye Hospital, Philadelphia, Pa.

No conflicting relationship exists for any author.

Support provided by Eye Tumor Research Foundation, Philadelphia, Pa. (CLS). The funders had no role in the design and conduct of the study, in the collection, analysis and interpretation of the data, and in the preparation, review or approval of the manuscript. Carol L. Shields, MD, has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

 

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About Retina Today

Retina Today is a publication that delivers the latest research and clinical developments from areas such as medical retina, retinal surgery, vitreous, diabetes, retinal imaging, posterior segment oncology and ocular trauma. Each issue provides insight from well-respected specialists on cutting-edge therapies and surgical techniques that are currently in use and on the horizon.