|Ahead of print publication
Seven-year follow-up of a pediatric patient with combined hamartoma of retina and retinal pigment epithelium complicating with preretinal neovascularization and vitreous hemorrhage treated with intravitreal injections of bevacizumab
Tsung-Ying Tsai1, Kuan-Jen Chen2, An-Ning Chao2
1 Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan
2 Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
|Date of Submission||23-Aug-2022|
|Date of Acceptance||09-Oct-2022|
|Date of Web Publication||21-Dec-2022|
No. 5, Fuxing Street, Guishan District, Taoyuan 33305
Source of Support: None, Conflict of Interest: None
We report a case of successful management of intravitreal injections of anti-vascular endothelial growth factor antibody bevacizumab in two unusual complications, preretinal neovascularization and vitreous hemorrhage, secondary to a combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). A male pediatric patient suffered from decreased vision in the right eye at 5-year-old. His ophthalmologic examination revealed a CHRRPE involving the superior area of the optic disc and macula in the right eye. The patient's family history and neurological examinations of tuberous sclerosis were absent. While no lesion growth was observed over time, preretinal vascularization and recurrent nonclearing hemorrhage occurred 2 years after the initial presentation. The patient was successfully managed with two intravitreal injections of bevacizumab. No recurrences of vitreous hemorrhage were observed at a 7-year post-treatment follow-up. Intravitreal injections of bevacizumab were safe and effective in the management of uncommon complications of preretinal neovascularization and vitreous hemorrhage of CHRRPE in a pediatric patient in long-term follow-up.
Keywords: Bevacizumab, combined hamartoma of the retina and retinal pigment epithelium, retinal neovascularization, vitreous hemorrhage
|How to cite this URL:|
Tsai TY, Chen KJ, Chao AN. Seven-year follow-up of a pediatric patient with combined hamartoma of retina and retinal pigment epithelium complicating with preretinal neovascularization and vitreous hemorrhage treated with intravitreal injections of bevacizumab. Taiwan J Ophthalmol [Epub ahead of print] [cited 2023 Jan 28]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=364566
| Introduction|| |
Combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) is a rare, benign intraocular tumor first described by Gass as a pigmented, elevated grayish lesion involving retina, retinal pigment epithelium, with vitreoretinal interface changes, and vascular tortuosity. CHRRPE is usually diagnosed in children, commonly with symptoms of strabismus or reduced visual acuity. CHRRPE can sometimes associated with retinal manifestations of neurofibromatosis., The differential diagnosis of these retinal tumors from retinoblastoma is paramount in the pediatric age. To the best of our knowledge, only six cases of vitreous hemorrhage related to CHRRPE have been reported to date.,,,, Here, we describe a male pediatric patient who developed two unusual complications of a CHRRPE (preretinal neovascularization and vitreous hemorrhage). This uncommon clinical scenario was successfully managed with intravitreal injections of the anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab.
| Case Report|| |
The patient was initially referred to our clinic in 2011, when he was aged 5 years, because of decreased vision in his right eye that was found in routine school eye examination. His best-corrected vision was 20/200 OD and 20/20 OS. The results of anterior segment examination were unremarkable for both eyes. Fundus examination of the right eye [Figure 1]a revealed an ill-defined gray-whitish, elevated lesion with basal diameter approximately 8 mm located along the superior temporal arcade, with involvement of the optic disc and extension toward the macula. Intraretinal telangiectasias at the fovea were also evident. A retinal examination of the left eye was unremarkable. The results of intravenous fluorescein angiography revealed early blocked fluorescence and late leakage occurring both at the lesion level and in abnormal vessels [Figure 1]b. On spectral domain optical coherence tomography (OCT), an elevated mass characterized by marked disorganized retinal layers and hyporeflective shadowing of the underlying retinal tissue was identified. An epiretinal membrane with disorganization of retinal layers was also evident [Figure 1]c. A B-scan ultrasonography showed that the tumor was minimally elevated (2 mm) and had no evidence of calcifications [Figure 1]d. The results of a thorough neurological examination and brain magnetic resonance imaging findings were unremarkable; the diagnosis of both neurofibromatosis and tuberous sclerosis complex was ruled out.
|Figure 1: Clinical images of the right eye at initial presentation (a). A fundus photograph revealed a grey-whitish retinal and subretinal mass in the posterior pole (b). Fluorescein angiography demonstrated blocked hypofluorescence in the early phase followed by hyperfluorescence during the late phase (c). Spectral domain OCT identified an elevated mass within a full layer disorganized retina structures (d). B-scan ultrasonography revealed a slightly elevated lesion located inferiorly to the optic disc. OCT: Optical coherence tomography|
Click here to view
The lesion remained stable during the first 2 years of follow-up from the initial examination, after which the patient noticed increasing floaters and decreased vision. On eye examination, preretinal neovascularization and vitreous hemorrhages were identified. Treatment with an intravitreal injection of bevacizumab (Avastin®, Genentech/Roche; 0.625 mg/0.025 mL) was attempted 1 month after for nonclearing Grade 2 vitreous hemorrhage. Preretinal vascularization partially regressed and the vitreous hemorrhage was temporarily resolved [Figure 2]a. However, vitreous hemorrhage recurred within the next 2 months, for which a second injection of bevacizumab (1.25 mg/0.05 mL) was given. The treatment led to significant regression of preretinal vascularization and vitreous hemorrhage resolved in 1 month. His visual acuity gradually returned to 20/200. The preretinal neovascularization was replaced by fibrotic scar-like tissue over a 6-month period. At a 7-year posttreatment follow-up, the patient's visual acuity remained stable and no recurrence of vitreous hemorrhage, reduced subretinal exudation were observed [Figure 2]b and [Figure 2]c.
|Figure 2: (a) A fundus photography obtained 2 years after one intravitreal bevacizumab injection with partial regression of superficial retinal vascularization in the macula and vitreous hemorrhage in the right eye (b). Seven years after, the second injection of bevacizumab, a significant resolution of retinal hemorrhages and vitreous hemorrhage (c). Swept source OCT showing inner retinal disorganization (maxi peaks) and altered ellipsoid layer. OCT: Optical coherence tomography|
Click here to view
| Discussion|| |
The diagnosis of CHRRPE is based on ophthalmological findings and imaging results. In our pediatric patient, the tumor appeared as a gray-whitish nodular lesion located within the sensory retina in the juxtapapillary region and macula. The ophthalmological and imaging findings of our case were compatible with a diagnosis of CHRRPE. While the early vascular filling phase of fluorescein angiography revealed the presence of intratumoral well-defined fine blood vessels, diffuse intense staining was observed in the late phase. The results of B-scan ultrasonography showed the presence of a noncalcified, nodular mass. In addition, OCT revealed certain features demonstrated that the tumor had inner retinal disorganization (maxi peaks) and disruption of ellipsoid zone.
The optimal management of retinal astrocytic hamartoma has not yet been established. In general, the therapeutic approach should be tailored at the individual level and may be limited to watchful waiting in patients with small asymptomatic lesions. Different treatment modalities have been proposed for symptomatic growing hamartomas including cryotherapy, laser photocoagulation, photodynamic therapy, as well as pars plana vitrectomy although results have not been entirely consistent.,
Our pediatric patient was successfully treated with intravitreal injections of bevacizumab. This choice was prompted by a few case reports showing the clinical usefulness of intravitreal anti-VEGF antibodies for the treatment of vascular leakage, macular edema, and vitreous hemorrhage in patients with CHRRPE. Compared with other complex therapeutic procedures, the intravitreal injection of bevacizumab represents a safe and less costly alternative. Notably, the same approach has been successfully used for treating retinopathy of prematurity (ROP). The dose initially injected into our patient was in accordance with that previously utilized for ROP (0.625 mg). After relapse of vitreous hemorrhage, the second injection was switched to a higher dose (1.25 mg) in line with that used for diabetic retinopathy and age-related macular degeneration. This approach ultimately proved to be successful.
In summary, the pediatric patient presented in this report developed two unusual complications (preretinal neovascularization and vitreous hemorrhage) of a CHRRPE. Intravitreal injections of bevacizumab were safe and effective in the management of this uncommon clinical scenario.
Ethics approval and consent to participate: Approved by Institutional Review Board of Chang Gung Memorial Hospital 103-2476c.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the parents have given their consent for images and other clinical information to be reported in the journal. The parents understand that name and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
The authors declare that there are no conflicts of interests of this paper.
| References|| |
Gass JD. An unusual hamartoma of the pigment epithelium and retina simulating choroidal melanoma and retinoblastoma. Trans Am Ophthalmol Soc 1973;71:171-83.
Shields CL, Schoenberg E, Kocher K, Shukla SY, Kaliki S, Shields JA. Lesions simulating retinoblastoma (pseudoretinoblastoma) in 604 cases: Results based on age at presentation. Ophthalmology 2013;120:311-6.
Tsai P, O'Brien JM. Combined hamartoma of the retina and retinal pigment epithelium as the presenting sign of neurofibromatosis-1. Ophthalmic Surg Lasers 2000;31:145-7.
Destro M, D'Amico DJ, Gragoudas ES, Brockhurst RJ, Pinnolis MK, Albert DM, et al
. Retinal manifestations of neurofibromatosis. Diagnosis and management. Arch Ophthalmol 1991;109:662-6.
Kahn D, Goldberg MF, Jednock N. Combined retinal-retina pigment epithelial hamartoma presenting as a vitreous hemorrhage. Retina 1984;4:40-3.
Wang CL, Brucker AJ. Vitreous hemorrhage secondary to juxtapapillary vascular hamartoma of the retina. Retina 1984;4:44-7.
Moschos M, Ladas ID, Zafirakis PK, Kokolakis SN, Theodossiadis GP. Recurrent vitreous hemorrhages due to combined pigment epithelial and retinal hamartoma: Natural course and indocyanine green angiographic findings. Ophthalmologica 2001;215:66-9.
Helbig H, Niederberger H. Presumed combined hamartoma of the retina and retinal pigment epithelium with preretinal neovascularization. Am J Ophthalmol 2003;136:1157-9.
Diana C. Complications of combined retinal and retinal pigment epithelium hamartoma involving the optic disc in a child, treated with Avastin – A review of the literature and case presentation. Rom J Ophthalmol 2015;59:255-62.
Gupta R, Fung AT, Lupidi M, Pappuru RR, Nayak S, Sahoo NK, et al
. Peripapillary versus macular combined hamartoma of the retina and retinal pigment epithelium: Imaging characteristics. Am J Ophthalmol 2019;200:263-9.
Ledesma-Gil G, Essilfie J, Gupta R, Fung AT, Lupidi M, Pappuru RR, et al
. Presumed natural history of combined hamartoma of the retina and retinal pigment epithelium. Ophthalmol Retina 2021;5:1156-63.
Mennel S, Hausmann N, Meyer CH, Peter S. Photodynamic therapy for exudative hamartoma in tuberous sclerosis. Arch Ophthalmol 2006;124:597-9.
van der Sommen CM, van Romunde SHM, van Overdam K. Surgery for combined hamartoma of the retina and retinal pigment epithelium. Case Rep Ophthalmol 2021;12:778-83.
Wu WC, Lien R, Liao PJ, Wang NK, Chen YP, Chao AN, et al
. Serum levels of vascular endothelial growth factor and related factors after intravitreous bevacizumab injection for retinopathy of prematurity. JAMA Ophthalmol 2015;133:391-7.
[Figure 1], [Figure 2]