From the Western Eye Hospital, Imperial College NHS Healthcare Trust, London, United Kingdom.
Supported by the NIHR Biomedical Research Centre Funding Scheme.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Kevin Gregory-Evans, MD, FRCS, FRCOphth, Imperial College NHS Healthcare Trust, Western Eye Hospital, 171, Marylebone Road, London NW1 5QH, United Kingdom.
Choroidal (subretinal) neovascularization in children is rare,1 so building a significant evidence base on which to establish future clinical practice is challenging. In the absence of large prospective studies, it is likely that clinical decisions will rely on smaller retrospective case series. In this context, we report a rare case of subretinal neovascularization in a child also exhibiting optic disc drusen. Many management dilemmas were raised by this case and we demonstrate for the first time a successful treatment with intravitreal ranibizumab2,3 that will aid clinicians in the future when confronted with similar cases.
An 11-year-old boy presented with reduced vision in his left eye over a 1-month period. Best-corrected visual acuity was 20/20 in the right eye with a +0.25 sph/−0.75 cyl at 180° spectacle lens and 20/100 in the left eye with a +0.75 sph/−0.75 cyl at 180° spectacle lens. Funduscopy revealed bilateral optic disc drusen associated with hemorrhage, exudates, and subretinal fibrosis within the maculopapular bundle in the left eye. This lesion appeared to extend to include the fovea (Fig. 1A). Fluorescein angiography (Figs. 1B and 1C) and optical coherence tomography (OCT) (Figs. 2A and 2B) revealed a classic choroidal neovascular membrane but with significant surrounding masking due to blood, retinal thickening, and intraretinal fluid.
Figure 1. Color Fundus and Fluorescein Angiogram Images from the Left Eye at Presentation (A, B, C) and After 3 Months of Treatment (D, E, F). B and E = Early Fluorescein Angiogram Images; D and F = Late Fluorescein Angiograms. Images Show Marked Improvement in Clinical Appearance and Less Leakage at 3 Months. An Area of Retinal Pigment Epithelial Atrophy Has Appeared Around the Lesion.
Figure 2. Horizontal, High-Definition Optical Coherence Tomography Images (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) Taken Through the Center of the Optic Nerve Head (A, C, E) and Through the Center of the Fovea (B, D, F) at Initial Presentation (A, B), 3 Months Later (C, D), and 6 Months Later (E, F). Images Show Marked Reduction in Swelling and a Foveal Pit by 3 Months, Signifying Improvement in Retinal Architecture with Time.
Several treatment options were considered, and a short course of intravitreal ranibizumab was agreed on after discussion with the patient and family. Under general anesthesia, the patient underwent three intravitreal ranibizumab injections at monthly intervals. At the end of this treatment period, the patient reported significant visual improvement. Best-corrected visual acuity had improved to 20/30 and there had been marked improvement in retinal architecture with a foveal pit now identifiable on OCT imaging (Fig. 2D). Fluorescein angiography showed markedly less leakage surrounded by an area of retinal pigment epithelium depigmentation replacing the hemorrhage and retinal fluid (Figs. 1E, 1F, 2C, and 2D)
An additional 3 months of follow-up saw visual acuity improve to 20/20 with normalization of foveal architecture (Figs. 2E and 2F) but with a small, elevated fibrous scar forming nasal to the fovea (Fig. 3). During this observation period, no adverse ocular or systemic complications were seen.
Figure 3. Color Fundus Photograph of the Left Eye 6 Months After Presentation Showing Resolution of Retinal Edema and a Dense Scar Nasal to the Fovea Surrounded by an Area of Retinal Pigment Epithelial Depigmentation.
This case raised several management challenges. First, the reason for choroidal neovascularization in children is often obscure. In a retrospective review of published reports, Sivaprasad and Moore1 concluded that the most common causes are chorioretinal inflammation, traumatic choroidal rupture, angioid streaks, high myopia, and retinal dystrophies. Subretinal neovascularization has been associated with optic nerve head drusen in several reports,4–6 including in children.4,7,8 However, it is unclear why this optic neuropathy should predispose to hemorrhagic maculopathy. In the absence of relevant history (eg, a history of trauma or family history of eye disease) or clinical signs (eg, angioid streaks), it is most likely that this case does represent a case of subretinal neovascularization secondary to optic nerve head drusen.
Second, several treatment options are now available for subretinal neovascularization. A variable natural history means that non-intervention can be an option in some cases. Although there are no natural history outcome reports for children with choroidal neovascularization associated with optic nerve head drusen, Wise et al.5 has recommended intervention in most adult cases. However, Harris et al.6 found that six of seven eyes with choroidal neovascularization associated with optic nerve head drusen retained visual acuities of 20/40 or better without any therapy. Surgical removal of neovascular complexes has also been reported in such cases in adults and children,9–11 but follow-up studies have suggested a recurrence rate as high as 25%.1 Photodynamic therapy with verteporfin has also been reported in adult12 and pediatric cases.13 As yet there have been no reports of anti-vascular endothelial growth factor use in pediatric cases of choroidal neovascularization despite superior outcomes when this treatment modality is used in adults.3
The presence of significant subretinal fibrosis and declining vision led us to exclude non-intervention and surgical excision, and the relatively large area of fibrosis and blood masking part of the lesion also suggested that this was not an ideal case for photodynamic therapy. We therefore opted for a short course of anti-vascular endothelial growth factor therapy.
The optimal regimen for ranibizumab use in adults is still the focus of considerable research, with most clinicians currently adopting an initial “induction course” followed by a variable dosing strategy guided by changes in serial OCT imaging.14 Without contradictory data, it would seem logical to follow the same regimen in children. However, a particular concern is the issue of side effects. Although well-documented in adults, it is unclear how this extrapolates to pediatric practice. For instance, it is not known whether systemic levels of ranibizumab after intravitreal injection will have effects on normal growth in the child.1 The long-term prognosis in this case is therefore uncertain. In particular with respect to vision, the emergence of an area of retinal pigment epithelium depigmentation, which presumably resulted from chronic retinal hemorrhage causing iron-related toxicity of hemoglobin, and fibrin-mediated retinal damage may affect vision in the longer term.
A short course of intravitreal ranibizumab in a rare case of choroidal neovascularization secondary to optic nerve head drusen has resulted in a prolonged improvement in visual acuity. This case adds to the evidence base accumulating for the use of ranibizumab and other anti-vascular endothelial growth factor agents in cases of choroidal neovascularization secondary to causes other than age-related macular degeneration and in particular supports a role for the use of these drugs in a pediatric setting.
- Sivaprasad S, Moore AT. Choroidal neovascularisation in children. Br J Ophthalmol. 2008;92:451–454. doi:10.1136/bjo.2007.124586 [CrossRef]
- Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–1431. doi:10.1056/NEJMoa054481 [CrossRef]
- Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432–1444. doi:10.1056/NEJMoa062655 [CrossRef]
- Gass JDM. Choroidal neovascular membranes: their visualisation and treatment. Trans Am Acad Ophthalmol Otolaryngol. 1973;77: OP310–OP320.
- Wise GN, Henkind P, Alterman M. Optic disc drusen and subretinal haemorrhage. Trans Am Acad Ophthalmol Otolaryngol. 1974;78:OP212–OP219.
- Harris MJ, Fine SL, Owens SL. Hemorrhagic complications of optic nerve drusen. Am J Ophthalmol. 1981;92:70–76.
- Brown SM, Del Monte MA. Choroidal neovascular membrane associated with optic nerve head drusen in a child. Am J Ophthalmol. 1996;121:215–217.
- Hoover DL, Robb RM, Peterson RA. Optic disc drusen in children. J Pediatr Ophthalmol Strabismus. 1988;25:191–195.
- Mateo C, Moreno JG, Lechuga M, Adan A, Corcostegui B. Surgical removal of peripapillary choroidal neovascularization associated with optic nerve drusen. Retina. 2004;24:739–745. doi:10.1097/00006982-200410000-00009 [CrossRef]
- Jain K, Shafiq AE, Devenyi RG. Surgical outcome for removal of subfoveal choroidal neovascular membranes in children. Retina. 2002;22:412–417. doi:10.1097/00006982-200208000-00003 [CrossRef]
- Sullu Y, Yildiz L, Erkan D. Submacular surgery for choroidal neovascularization secondary to optic nerve drusen. Am J Ophthalmol. 2003;136:367–370. doi:10.1016/S0002-9394(03)00187-9 [CrossRef]
- Chaudhry NA, Lavaque AJ, Shah A, Liggett PE. Photodynamic therapy for choroidal neovascular membrane secondary to optic nerve drusen. Ophthalmic Surg Lasers Imaging. 2005;36:70–72.
- Silva R, Torrent T, Loureiro R, Travassos A, de Abreu JR. Bilateral CNV associated with optic nerve drusen treated with photodynamic therapy with verteporfin. Eur J Ophthalmol. 2004;14:434–437.
- Dadgostar H, Waheed N. The evolving role of vascular endothelial growth factor inhibitors in the treatment of neovascular age-related macular degeneration. Eye. 2008;22:761–767. doi:10.1038/eye.2008.86 [CrossRef]