A 12-month-old girl born at 40 weeks gestation with a birth weight of 2,835 g and no significant medical or family history was referred for esotropia and retinal hemorrhage in the left eye. The patient was examined under anesthesia. Intraocular pressure was 14 mm Hg in both eyes and anterior segment examination was normal with no neovascularization of the iris. Posterior examination of the right eye was unremarkable (Figure 1A). On clinical examination, the left eye demonstrated macular grape-like aneurysms and tortuous vessels with intralesional hemorrhage, no exudates, and normal peripheral exam (Figure 1B). Wide-field fluorescein angiogram with transit of the left eye demonstrated a central hypofluorescent lesion consistent with blockage, aneurysms, and arborization of vessels in the early arteriovenous phase (Figure 1C). Mid to late venous phases revealed a slow-filling lesion with irregular pooling of fluoresce-in (hyperfluorescent superiorly and hypofluorescent inferiorly) and nonperfusion nasal to the lesion (Figures 1D–E). Mid-phase photograph of the post-equatorial fundus in the right eye was unremarkable (Figure 2A). Wide-field mid and late phase photographs both eyes demonstrated diffuse areas of nonperfusion with vessel tortuosity and anomalous courses, most notable inferiorly in the left eye (Figures 2C–H). Of note, no exudate or leakage was detected in either eye. The patient is being managed conservatively. Magnetic resonance imaging of the brain was recommended. The patient’s family was subsequently contacted several times but did not return for follow-up.
(A) Color fundus photograph of the right eye with a normal pediatric fundus. (B) Color fundus photograph of the left eye demonstrates a macular hemangioma with a grape-like configuration, vessel tortuosity, no exudates, and an intralesional hemorrhage. (C) Early arteriovenous phase of the left eye at 13 seconds. Angiogram demonstrates a central hypofluorescent lesion consistent with blockage from the intralesional hemorrhage (black arrow), aneurysms (yellow arrow), and arborization of vessels (circle). (D) Late venous phase photo of the left eye at 20 seconds with a slow-filling, central hypofluorescent lesion, circumlesional aneurysms, arborization of vessels, and nasal hypoperfusion. (E) Mid-phase photo of the left eye at 1:16 seconds with mixed hyperfluorescent and hypofluorescent caps and nasal hypoperfusion (arrows).
(A) Mid-phase fluorescein angiogram of the right eye at 1:33 seconds. (B) Mid-phase wide field fluorescein angiogram of the right eye at 1:40 seconds demonstrates peripheral nonperfusion and vessel drop-out (arrows) that are also noted in the superior quadrant (C) and inferonasal quadrants (D). (E) Mid-phase photograph of nasal quadrant in left eye demonstrates peripheral nonperfusion and vessel dropout (arrows) that is also noted in the temporal quadrant (F). (G) Mid-phase photograph of superior quadrant in left eye that demonstrates capillary nonperfusion and cessation of vessels (arrows) with vascular anomalies that are also revealed in the inferotemporal quadrant of the left eye (H).
Retinal cavernous hemangiomas are benign vascular anomalies characterized by saccular venous aneurysms with overlying glial proliferation.1 The earliest reports by Elwyn and Reese describe retinal cavernous hemangiomas as a precursor to Coats’ disease with capillary neoplasms and telengiectasia.1 Gass and Reese later describe this lesion as a separate clinical entity arising from a retinal vein.1,4
Cavernous hemangiomas present in the first three decades of life and predominantly in females.1 Clinical presentations range from decreased vision, floaters, and esotropia to seizures or incidental findings.2,4 Most lesions are nonprogressive, however, complications can include recurrent hyphemas, vitreous hemorrhages from glial traction,5 intralesional thrombosis,6,7 and secondary glaucoma.8 At the genetic level, this condition has an autosomal dominant or sporadic inheritance pattern with associated cerebral and cutaneous hemangiomas.9 KRIT1/CCM1 (retina) and CCM2/CCM3 genes (cerebral) have been linked to endothelial cell function and vascular permeability.10,11 Approximately 5% of familial cerebral hemangiomas have concurrent retinal hemangiomas with all three CCM genes being identified.12
The histological features of cavernous hemangiomas classically include large vascular channels with a non-fenestrated endothelial lining and glial tissue.6 In 1971, Gass described retinal vessels extending into the vitreous with no overlying internal limiting membrane, implicating a potential neovascular phenomenon.4 Retinal pigment epithelium and Bruch’s membrane changes are less common. Shields and colleagues recently reported RPE hyperplasia and osseous metaplasia in Bruch’s membrane,8 whereas Klein demonstrated areas of RPE and choroidal atrophy with pigment changes.13 The etiology of these associated changes is unclear but findings suggest a secondary stress reaction to surrounding lesional hemorrhages.
Classic fluorescein angiographic (FA) features reflect the histologic features with a slow, non-leaking filling phase and a hyperfluorescent (superior) and hypofluorescent (inferior) layering pattern secondary to plasma and erythrocyte sedimentation, respectively.1,6,8 Other associated anomalous findings are less reported. Messmer et al described an 18-year-old girl with an 8-clock hour peripheral hemangioma associated with an interconnecting shunt vessel and distal avascular retina.7 Giuffre reported a 28-year-old woman with a hemangioma superior to the disc with concurrent proximal telangiectatic capillaries and hard exudates.14 Neither case exhibited vascular anomalies or nonperfusion distinct from the lesion, however.
We present a case of a unilateral intralesional hemorrhagic macular cavernous hemangioma with bilateral peripheral vascular anomalies and nonperfusion distinct from the lesion. Although Coats’ disease is also a possibility, the lack of hard exudates, mixed hyperfluorescent and hypofluorescent filling, delayed filling, and no leakage may suggest otherwise. In addition to the classic FA findings, the macular hemangioma exhibited mixed developmental vascular features, including aneurysms, capillary nonperfusion, venous tortuosity, and arborization of vessels at the edges of the lesion. The capillary dropout was specific to the nasal portion of the lesion in contrast to non-perfusion associated with a distal lesion reported by Velasquez-Martin and colleagues in a macular hemangioma.15 The aneurysms, tortuosity, and nonperfusion may be isolated features. However, endothelial cell functional mutations and angiographic features may suggest a possible vascular endothelial factor driven mechanism.
Wide-field imaging of the periphery demonstrated separate bilateral vascular anomalies with nonperfusion. The peripheral anomalies may be incidental with previously unavailable wide-field angiography and the lack of normative data on pediatric peripheral retinal findings. However, the distal vessel tortuosity suggests otherwise. Most recently, Shapiro and colleagues17 described a range of peripheral retinal non-perfusion abnormalities in 24 pediatric eyes with optic disc anomalies, ten of which exhibited mild to moderate nonperfusion.16 Rojanaporn reported peripheral nonperfusion, peripheral vascular loops and “brushfire” retinal vessels at the vascular-avascular junction in four cases with morning glory discs.17 Although the optic disc was unremarkable in this case and genetics were unavailable, the macular and peripheral changes may represent a continuum of phenotypic features found either in cavernous hemangiomas or previously unrecognized congenital abnormalities associated with peripheral nonperfusion. Alternatively, the peripheral findings may be a separate clinical entity, such as a concurrent stage 1 familial exudative vitreoretinopathy.18
In conclusion, we present a novel case of a unilateral macular cavernous hemangioma with bilateral peripheral vascular anomalies and nonperfusion. The peripheral features may be incidental or represent previously unrecognized phenotypic variations. Histopathology, recent genetic analysis, and advanced wide-field angiographic findings may provide a better understanding of this rare, vision-threatening lesion and direct future therapies, including photodynamic and anti-vascular endothelial growth factor therapy.