You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
retinal astrocytoma associated with tuberous sclerosis complex is a relatively static lesion with little potential for aggressive behavior .
aggressive retinal astrocytoma associated with tuberous sclerosis complex is a rare variant of this usually benign astrocytoma , and the tumor enlarges progressively , leading to complications , including exudative retinal detachment , vitreous hemorrhage , and neovascular glaucoma.1,2 it has been reported that aggressive retinal astrocytoma can be treated with laser photocoagulation , photodynamic therapy , or intravitreal bevacizumab injection.27 herein , we report the case of a patient with aggressive retinal astrocytoma and macular edema who was initially treated with intravitreal bevacizumab injection . however , after six monthly intravitreal bevacizumab injections , vitreous hemorrhage developed which necessitated vitrectomy with endophotocoagulation .
the surgically removed epiretinal membrane and biopsied retinal tumor expressed vascular endothelial growth factor ( vegf ) despite preceding intravitreal bevacizumab injection .
a 24-year - old male presented to our clinic complaining of visual disturbance in his right eye . at 8 years of age
he had mental retardation , a medical history of epilepsy , and obvious facial angiofibromas .
the best - corrected visual acuity ( bcva ) was 0.09 in the right eye and 1.2 in the left eye .
, fundus examination demonstrated an elevated lesion in the superior aspect of the optic disc accompanied with marked neovascular vessels on the surface , retinal hemorrhage , and macular edema ( figure 1a ) .
spectral - domain optical coherence tomographic ( oct ) imaging through the fovea showed a serous retinal detachment ( figure 1c ) .
an aggressive retinal astrocytoma was suspected , and six monthly intravitreal bevacizumab injections ( 1.25 mg ) were performed after informed consent following institutional review board approval .
fundus examination demonstrated marked regression of neovascular vessels , retinal hemorrhage , and exudative change ( figure 2a ) .
oct imaging through the fovea showed disappearance of the serous retinal detachment ( figure 2c ) .
oct imaging through the elevated lesion showed an epiretinal membrane and retinal tumor located on the retinal surface ( figure 2d ) .
two months later , dense vitreous hemorrhage developed , and the bcva decreased to hand motion .
three days after additional intravitreal bevacizumab injection to prevent intraoperative bleeding , vitrectomy with endophotocoagulation was performed .
after the epiretinal neovascular membrane was peeled off , a soft , gelatinous , light grey mass without signs of calcification was found on the retinal surface .
histopathologic analysis of the retinal tumor revealed plump spindle - shaped cells with round or slightly elongated nuclei ( figure 3 ) .
the retinal tumor was intensely immunoreactive for vimentin , glial fibrillary acidic protein ( gfap ) , and neuron - specific enolase , being consistent with a diagnosis of astrocytoma1 ( figure 4a  c ) . despite the preceding intravitreal bevacizumab injections
immunohistochemical analysis of the surgically removed epiretinal membrane demonstrated coexpression of vegf and von willebrand factor , indicating the presence of vegf in the vascular endothelial cells ( figure 5 ) . a vitreous sample was obtained during vitrectomy , and we also measured the vegf concentration in the vitreous fluid by enzyme - linked immunosorbent assay ( ge healthcare , little chalfont , uk ) .
the vitreous vegf concentration measured by enzyme - linked immunosorbent assay was at undetectable levels .
fundus examination revealed photocoagulation scars corresponding to retinal astrocytoma , and oct imaging showed no serous macular detachment ( figure 6 ) .
shields et al1 reported four patients with aggressive retinal astrocytoma associated with tuberous sclerosis complex .
all cases had multiple tumors in the fundus . in every case , only one larger tumor near the optic disc showed progressive growth and retinal detachment , whereas all other tumors remained static .
shields et al1 reported that aggressive retinal astrocytoma was composed of two types of cells , ie , plump spindle cells and giant cells occasionally with vacuolated cytoplasm . all tumors coexpressed neuron - specific enolase and gfap . in general the giant cells were immunoreactive for neuron - specific enolase but were negative or only minimally reactive for gfap .
the tumor cells were also strongly immunoreactive for s-100 protein and vimentin . in our present case ,
histopathologic analysis of the biopsied retinal tumor revealed plump spindle - shaped cells and intense immunoreactivity for vimentin , gfap , and neuron - specific enolase ( table 1 ) .
mennel et al2 published an evidence - based review evaluating the incidence of symptomatic retinal astrocytoma . according to their analyses ,
symptomatic changes were described in 11 case reports published over a period of three decades .
the symptomatic alterations were caused by an enlarged tumor with leakage , macular edema , accumulating lipoid exudates , serous retinal detachment ( eight eyes ) , and vitreous hemorrhage ( four eyes ) .
interventional studies showed slow resorption of subretinal fluid after argon laser photocoagulation ( two eyes ) , although recurrent laser applications induced choroidal neovascularization and destruction of the neurosensory retina ( one eye ) .
vitrectomy was used to remove a vitreous hemorrhage in one patient . in one case , complete resorption of subretinal fluid and an increase in visual acuity
saito et al3 reported that macular edema secondary to aggressive retinal astrocytoma resolved after intravitreal bevacizumab injection in two cases .
similarly , macular edema regressed remarkably after monthly intravitreal bevacizumab injections in our present case .
these results suggest that vegf derived from retinal astrocytoma causes macular edema and that intravitreal bevacizumab injection is effective for resolving the macular edema temporarily .
it has been shown that hamartomas associated with tuberous sclerosis complex involving organs other than the eyes ( kidney , brain , and skin ) are highly angiogenic and may express vegf.3,8,9 as far as we know , there are no reports regarding vegf expression in the tumor of aggressive retinal astrocytoma , although the vitreous vegf concentration has been reported to be high in aggressive retinal astrocytoma ( table 1).3 in the present study , we showed vegf expression in both retinal tumor and epiretinal membrane .
therefore , vegf derived from aggressive retinal astrocytoma may play a potential role in the pathogenesis of macular edema , exudative retinal detachment , and epiretinal neovascular membrane secondary to tuberous sclerosis complex .
saito et al3 reported that macular edema recurred after intravitreal bevacizumab injection in one of two cases and that recurrent edema was successfully treated by additional laser photocoagulation to the tumors . in the other case
, the small tumor size might have been one of the causes of no recurrence of macular edema after intravitreal bevacizumab injection . in our case ,
several intravitreal bevacizumab injections led to an undetectable vitreous vegf concentration . despite the preceding intravitreal bevacizumab injections , the surgically removed epiretinal membrane and biopsied retinal tumor expressed vegf .
these results suggest that intravitreal bevacizumab injection is effective for reducing the vitreous vegf concentration but insufficient for completely inhibiting vegf activity in the tumor .
the clinical course and immunohistochemical analyses in our patient indicate that intravitreal bevacizumab monotherapy may have been insufficient to treat aggressive retinal astrocytoma with macular edema , and that laser photocoagulation or photodynamic therapy for the tumor should be considered following intravitreal bevacizumab injection .
however , we can not clarify whether combined therapy of intravitreal bevacizumab injection and laser photocoagulation or photodynamic therapy is more effective than photodynamic therapy alone or not .
aggressive retinal astrocytoma shows progressive enlargement of the tumor accompanied by total exudative retinal detachment and neovascular glaucoma.1 without adequate treatment , enucleation eventually becomes necessary because of blindness and ocular pain.1 therefore , precise diagnosis and prompt treatment are important . in our present case ,
final visual acuity remained at 0.2 , presumably because of longstanding macular edema at the initial visit .
when we follow up patients with tuberous sclerosis complex , detecting initial or recurrent macular edema by performing oct in the early stages is mandatory for preventing a poor visual prognosis.3
we report the case of a patient with an aggressive retinal astrocytoma accompanied with macular edema and neovascular vessels , who was initially treated with intravitreal bevacizumab injections . 
 a 24-year - old male presented to our clinic complaining of visual disturbance in his right eye . at 8 years of age 
 , he had been diagnosed as having tuberous sclerosis complex . 
 fundus examination demonstrated a retinal tumor accompanied with marked neovascular vessels on the surface , retinal hemorrhage , and macular edema . 
 after six monthly intravitreal bevacizumab injections , fundus examination demonstrated marked regression of the macular edema and neovascular vessels . 
 two months later , a vitreous hemorrhage developed which necessitated pars plana vitrectomy . after additional intravitreal bevacizumab injection for preventing intraoperative bleeding , vitrectomy with endophotocoagulation for the tumor was performed . 
 the vitreous sample was obtained during vitrectomy , and we measured the vascular endothelial growth factor concentration by enzyme - linked immunosorbent assay . 
 the surgically removed epiretinal neovascular membrane and biopsied retinal tumor expressed vascular endothelial growth factor , although several intravitreal bevacizumab injections led to a vitreous vascular endothelial growth factor concentration of undetectable levels . 
 the clinical course and immunohistochemical analyses indicate that intravitreal bevacizumab monotherapy may have been insufficient to treat the aggressive retinal astrocytoma with macular edema and that laser photocoagulation or photodynamic therapy for the tumor should be considered following intravitreal bevacizumab injection in such cases .