Retinal capillary hemangioblastoma (RCH) is a vascular tumor that may be seen sporadically or as a manifestation of von Hippel-Lindau (VHL) syndrome.1 It can be the earliest manifestation of VHL and may lead to severe visual impairment due to retinal edema, subretinal exudation, fibrovascular proliferation, and retinal detachment (RD).2 Conventional therapeutic procedures, including laser photocoagulation or cryotherapy, have been reported as effective treatment modalities in controlling small and middle-sized RCHs; however, cases with vitreous hemorrhage, exudative or tractional RD, as well as those complicated with any stage of proliferative vitreoretinopathy (PVR), often require vitreoretinal surgery.3 Herein, we report a patient with genetically confirmed VHL syndrome who developed a combined tractional exudative and rhegmatogenous retinal detachment after a single, uneventful cryotherapy session of a RCH lesion.
A 15-year-old female with genotypically confirmed VHL syndrome was referred to our clinic for evaluation. Best-corrected visual acuity (BCVA) was 20/20 in both eyes. Dilated funduscopy and fluorescein angiography (FA) revealed RCHs with their characteristic afferent and efferent feeder retinal vessels located in the superotemporal quadrant in the right and left eyes, respectively (Figures 1A–1C). Laser photocoagulation was scheduled but not performed due to the development of new spinal cord hemangioblastomas requiring prompt irradiation. Seven months after the first examination, the patient returned for follow-up evaluation. Ocular examination including ultra-widefield color photography and FA revealed enlargement of lesions in both eyes with a contracted hyaloid overlying the lesion in the left eye (Figures 1D and 1E). Considering the growth of the RCH and the development of preretinal fibrosis, cryotherapy treatment was applied in both eyes under anesthesia.
(A) Ultra-widefield imaging of the right fundus demonstrating the peripheral retinal capillary hemangioblastoma (RCH) located on the superior quadrant. (B) Fluorescein angiography depicting a marked filling pattern between a feeder artery and draining vein. (C) A small RCH located on the superotemporal quadrant in the left eye (white arrow). (D, E) Enlargement of the angioma in the left eye over 7 months with associated vitreous condensation and contraction. Note the increased vessel tortuosity on superior quadrant (arrowhead). (F) Combined tractional, rhegmatogenous, and exudative retinal detachment in the affected eye. (G) Retina was successfully attached after pars plana vitrectomy surgery combined with scleral buckling and silicone oil injection. (H, I) Histopathologic features of the retinal hemangioblastoma on hematoxylin and eosin stain, which is composed of vacuolated stromal cells and blood vessels. There are elements of chronic stromal inflammation (H, ×10; I, ×20).
One month after the procedure, the patient presented with sudden visual loss in her left eye to hand motions level. Retinal examination revealed a near total RD in the affected eye (Figure 1F). A retinal break was present underneath the contracted fibrovascular membrane, with partial avulsion of the RCH from the retina. Prominent subretinal fluid was present contributing to the bullous appearance of the RD. The patient underwent pars plana vitrectomy with excision of the lesion and all fibrosis, combined with encircling scleral buckling and radial sponge placement to support the retinal break given its posterior location (Figure 1G). Six months after the surgery and removal of silicone oil tamponade, BCVA improved to 20/50.
Concurrently, the right eye also developed a marked exudative macula splitting RD (Figure 2A) that was initially treated with intense topical corticosteroid treatment. However, due to the development of focal preretinal fibrovascular proliferation and clinically apparent vitreous traction, a radial scleral sponge was placed, which aided in the gradual resolution of the exudative RD (Figure 2B). BCVA remained 20/20 on last follow-up visit.
(A) Ultra-widefield imaging of the right fundus after the cryotherapy treatment showing a prominent exudative retinal detachment involving the superior part of macula, as seen on spectral-domain optical coherence tomography (inlet). (B) Gradual resolution of the subretinal fluid 6 months after treatment.
Histopathologically, the lesion was attached to fragments of neurosensory retinal tissue and was composed of vacuolated stromal cells and blood vessels (Figure 1H). Elements of chronic inflammation were present in the stroma, including lymphocytes and plasma cells (Figure 1H, I).
The case presented herein underscores several key features in the management of RCH secondary to VHL syndrome. First, timely treatment of small or middle-sized lesions with laser photocoagulation or cryotherapy is usually preferred before their enlargement, as the rate of intraocular complications such as lipid and serous exudation increases with tumor enlargement. Not all such lesions enlarge, but there are no reliable clinical features predictive of growth. Risk / benefit considerations favor treating retinal lesions in VHL when they are small. Along these lines, Krivosic et al. demonstrated that tumors larger than 1 disc diameter require more laser treatment sessions compared to smaller tumors for their control.4
Adverse reactions after laser and cryotherapy applications have been reported, including persistence of macular edema and the occurrence of RD arising from retinal tears adjacent to the area of the induced chorioretinal scar.4 Exudative RD after laser,4 cryotherapy, or photodynamic therapy5 have been reported, as well. It is likely that the high flow vascular lesion together with the extensive breakdown in blood-retinal barrier induced by the treatment contribute to the extravasation of serous fluid leading to an exudative RD. Preoperative administration of oral or periocular steroids has been advocated, but no large series exist to authoritatively speak to their efficacy.2 In our patient, topical steroid treatment was employed initially, but the development of focal preretinal fibrosis prompted the decision to support the lesion with a radial element, which subsequently lead to the resolution of the RD.
Rapid worsening of vitreoretinal traction is a rare complication following treatment of RCH lesions resulting in tractional and rhegmatogenous RDs.4 The tractional component is prominent in such cases, since RCHs secondary to VHL syndrome are mostly diagnosed in young patients with formed vitreous. Therefore, the risk of new retinal breaks occurring in the immediate follow-up period after laser photocoagulation or cryotherapy is slightly increased in these patients.6 Consistent with previous observations, the retinal tear in our patient was located at the posterior base of the angioma, between the afferent and efferent vessels.7 The proliferative glial tissue of the RCH has been implicated in the occasional development of preretinal fibrosis associated with tractional RD in larger angiomas.8
Vitreoretinal surgery is considered for the treatment of severe cases complicated with dense vitreous hemorrhage, exudative or tractional RD, and any stage of PVR.6,12 Gaudric et al. published one of the largest case series on complicated RCHs, where retinectomy for tumor removal was performed in nine eyes compared to laser endo-photocoagulation only, or combined with transscleral cryotherapy in 14 eyes.13 A higher rate of PVR with poorer visual outcomes was observed in the retinectomy group.13 In our case, the contracted vitreous over the RCH avulsed the lesion from the retina and, thus, a retinectomy was not necessary (See supplemental video below). Avci et al. attributed their considerably lower rates of PVR to the limited retinectomies in cases requiring endoresection of RCHs.14 Finally, important points to consider during vitrectomy are effective closure of feeder and draining vessels with either endodiathermy12 or intraoperative ligation,15 as well as removal of posterior hyaloid and epiretinal membranes to avoid postoperative vitreous hemorrhage and PVR.15
In summary, rapid worsening of vitreoretinal traction after cryotherapy may lead to complicated RDs in the immediate post-treatment period of a RCH with pre-existing traction, requiring complex vitreoretinal interventions. From the published series in the literature, there are currently no known risk factors that may predispose patients to these complications, which appear to represent idiosyncratic reactions to the treatment applied.
- Wong WT, Chew EY. Ocular von Hippel-Lindau disease: Clinical update and emerging treatments. Curr Opin Ophthalmol. 2008;19(3):213–217. doi:10.1097/ICU.0b013e3282fb7c04 [CrossRef]
- Chew EY. Ocular manifestations of von Hippel-Lindau disease: Clinical and genetic investigations. Trans Am Ophthalmol Soc. 2005;103:495–511.
- Singh AD, Nouri M, Shields CL, Shields JA, Perez N. Treatment of retinal capillary hemangioma. Ophthalmology. 2002;109(10):1799–1806. doi:10.1016/S0161-6420(02)01177-6 [CrossRef]
- Krivosic V, Kamami-Levy C, Jacob J, Richard S. Laser photocoagulation for peripheral retinal capillary hemangioblastoma in von Hippel-Lindau disease. Ophthalmology Retina. 2017:59–67. doi:10.1016/j.oret.2016.08.004 [CrossRef]
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- Chan CC, Collins ABD, Chew EY. Molecular pathology of eyes with von Hippel-Lindau (VHL) Disease: A review. Retina. 2007;27(1):1–7. doi:10.1097/01.iae.0000244659.62202.ee [CrossRef]
- Miyazawa A, Inoue M, Hirakata A, Okada AA, Iihara K, Fujioka Y. Expression of inhibin alpha by stromal cells of retinal angiomas excised from a patient with von Hippel-Lindau disease. Jpn J Ophthalmol. 2009;53(5):501–505. doi:10.1007/s10384-009-0699-y [CrossRef]
- Jakobiec FA, Font RL, Johnson FB. Angiomatosis retinae. An ultrastructural study and lipid analysis. Cancer. 1976;38(5):2042–2056. doi:10.1002/1097-0142(197611)38:5<2042::AID-CNCR2820380529>3.0.CO;2-O [CrossRef]
- Chan CC, Vortmeyer AO, Chew EY, et al. VHL gene deletion and enhanced VEGF gene expression detected in the stromal cells of retinal angioma. Arch Ophthalmol. 1999;117(5):625–630. doi:10.1001/archopht.117.5.625 [CrossRef]
- Yeh S, Wilson DJ. Pars plana vitrectomy and endoresection of a retinal vasoproliferative tumor. Arch Ophthalmol. 2010;128(9):1196–1199. doi:10.1001/archophthalmol.2010.194 [CrossRef]
- Gaudric A, Krivosic V, Duguid G, Massin P, Giraud S, Richard S. Vitreoretinal surgery for severe retinal capillary hemangiomas in von hippel-lindau disease. Ophthalmology. 2011;118(1):142–149. doi:10.1016/j.ophtha.2010.04.031 [CrossRef]
- Avci R, Yilmaz S, Inan UU, Kaderli B, Cevik SG. Vitreoretinal surgery for patients with severe exudative and proliferative manifestations of retinal capillary hemangioblastoma because of Von Hippel-Lindau disease. Retina. 2017;37(4):782–788. doi:10.1097/IAE.0000000000001240 [CrossRef]
- van Overdam KA, Missotten T, Kilic E, Spielberg LH. Early surgical treatment of retinal hemangioblastomas. Acta Ophthalmologica. 2017;95(1):97–102. doi:10.1111/aos.13223 [CrossRef]