Volume 81, Issue 5 , Pages 221-233, May 2010
Retinal astrocytic hamartoma
Article Outline
Abstract
Background
Retinal astrocytic hamartomas are glial tumors of the retinal nerve fiber layer that arise from retinal astrocytes. Classically they appear as a cream-white, well-circumscribed, elevated lesion that may present as multiple or solitary sites. A lesion is commonly seen with a multilobulated, “mulberry” appearance, but can also appear flat and semitranslucent. It is most frequently associated with tuberous sclerosis (TS) but may also be found rarely in patients with neurofibromatosis. Although the finding may point toward a systemic association, it can also be found incidentally on retinal examination as an isolated presentation.
Case Reports
Two cases of solitary retinal astrocytic hamartomas without systemic complications discovered at routine examination are presented. Both patients were found to have a raised, multilobulated retinal lesion consistent with the appearance of a retinal astrocytic hamartoma. In both cases, the patients had no personal or family history of seizures or any signs of unusual dermatologic lesions. B-scan ultrasonography, fluorescein angiography, and magnetic resonance imaging (MRI) were performed as necessary.
Conclusion
A retinal astrocytic hamartoma is typically associated with TS but can also present as a spontaneous, idiopathic lesion. Prompt referral to rule out TS or other systemic associations, particularly in young children, is important. Neuroimaging, along with other diagnostic tests, may ensure the proper management and rule out need for further evaluation. Spontaneous lesions without systemic association can initially be monitored closely to rule out possible progression. Once stability has been established, annual follow-up with a primary care eye practitioner is appropriate.
Keywords: Astrocytic hamartoma, Astrocytoma, Phakomatoses, Tuberous sclerosis
Retinal astrocytic hamartomas are benign tumors of the retinal nerve fiber layer. Although these lesions may be found in isolation without systemic involvement, most often they are found in association with tuberous sclerosis (TS). TS, originally known as Bourneville's disease, was first identified in the 19th century as reports based on clinical and pathological findings appeared.1, 2, 3, 4 Although the diagnostic triad of “epilepsy, idiocy, and adenoma sebaceum” did not include astrocytic hamartomas, patients with TS commonly began to present with the retinal lesions.1
Dutch scientist Jan Van der Hoeve first described the lesions as retinal hamartomas in the early 20th century.2, 3 It was during this time that he also introduced the name phakomata (from the Greek word phakos meaning mother's spot).5 This name would later become phakomatoses, the all-encompassing name for congenital syndromes that manifest with central nervous system and cutaneous disorders.6
Case report 1
A 45-year-old white man presented for a comprehensive eye examination with an initial complaint of blurred near vision without spectacles. Through +1.75 over-the-counter readers, he reported his near vision to be clear and comfortable. The patient also reported 3 episodes, over a 4-year history, of a brilliant rainbow scotoma starting at 5 o'clock and radiating clockwise, eventually involving most of his visual field. Each episode lasted from 10 minutes to a few hours and was visually debilitating for the duration. He did not recall any eliciting factors but remembered that it occurred when going from a light to dark room. The patient also mentioned the persistent image with his eyes closed, but could not determine from which eye the image originated. He denied any neurologic symptoms including dysphasia, paresthesia, paresis, or paralysis. He also denied headaches, including migraines, or a history of a cerebral vascular accident.
The patient stated his last eye examination was approximately 20 years prior. He reported a positive history of tobacco use for 27 years but discontinued use 3 years prior. He also reported a history of illicit drug use as a younger man. He discontinued this drug activity 15 years prior, shortly after being diagnosed with hepatitis C, but continued to use marijuana up to 5 times every day. He was uncertain about a history of seizures, as he reported a single episode in which his friend saw him in convulsions after heavy marijuana use. Although the patient denied any family history of significant systemic conditions, he did report a positive history of seizures in his sister that was well controlled after surgical intervention. He denied any known unusual dermatologic lesions for himself and family members.
Further medical history included mild chronic obstructive pulmonary disease, erectile dysfunction, depression, anxiety, and facial lipomas. Medications included sildenafil citrate as needed for erectile dysfunction and valproic acid for mood. The patient reported a history of trauma with a glass bottle to his forehead around 20 years prior but denied any long-term effects.
Entering visual acuities were 20/20 in the right eye (O.D.) and 20/30 in the left eye (O.S.). He was correctable to 20/20 through +0.75 O.D. and 20/20- through +1.00-0.50×0.85 O.S. Pupils were equal in size and reactive to light, with no afferent pupillary defect. Confrontation visual fields and extraocular muscles were full in each eye, with no visual field defect or muscle restrictions. Anterior segment slit lamp biomicroscopy found clear lids, lashes, and cornea in both eyes (OU). The patient's bulbar and palpebral conjunctiva were healthy, and he had flat irides and deep and quiet anterior chambers bilaterally. Intraocular pressures were 15 mmHg O.D. and 16 mmHg O.S. at 1:52 pm by Goldmann applanation tonometry. Dilated fundus examination found a cup-to-disc ratio of 0.25 OU, and both nerves noted to be pink and round with symmetrical rim tissue and no apparent thinning. The fundus of the right eye was unremarkable (see Figure 1A). The left eye evaluation revealed an oval, raised, multilobulated, white/yellow lesion approximately 1 disc diameter by 1.5 disc diameters in size (see Figure 1B). The lesion was inferior temporal to the optic nerve head, approximately 1 disc diameter away, along the vascular arcades. No overlying serous detachment was noted. Differential diagnosis included astrocytic hamartoma, lymphoma, amelanotic melanoma, amelanotic nevus, or metastasis. The patient was referred for an ophthalmic B-scan ultrasound, retinal consultation, and brain magnetic resonance imaging (MRI) with and without contrast. With the retinal lesion and unusual visual symptoms, our objective was to rule out any similar lesions within the cortical areas.
Figure 1
Posterior pole, case 1. A, Normal fundus O.D. B, Retinal astrocytic hamartoma O.S.
He returned to clinic for baseline visual field testing. At that visit the patient reported he had begun to notice intermittent headaches but no new episodes of rainbow scotoma. The anterior segment evaluation was again unremarkable, with Goldmann applanation tonometry readings of 16 mmHg O.D. and 15 mmHg O.S. at 3:10 pm. The retinal lesion remained stable in size and appearance. Baseline Humphrey visual field 24-2 sita-standard testing showed a localized, absolute defect in the paracentral superotemporal quadrant O.S., corresponding with the anatomic location of the lesion. The visual field O.D. was full with excellent reliability OU (see Figures 2A,B).
Figure 2
Humphrey visual field, case 1. A, Normal O.D. B, Absolute defect in the paracentral superotemporal quadrant O.S., corresponding with the anatomical location of the lesion.
Upon consultation, the retinal specialist confirmed the diagnosis of astrocytic hamartoma and believed it to be spontaneous, based on the age at presentation and lack of seizure history or other associated systemic findings. Fundus photography, B-scan ultrasonography, and fluorescein angiography (FA) were also performed. On photography with red-free filter, the mulberry appearance was more apparent, and no other localized defects of the retinal nerve fiber layer were noted (see Figure 3). The B-scan showed a solid mass with highly reflective granular internal echoes and acoustic shadowing (see Figure 4). The FA showed the lesion diffusely stained without signs of leakage or subretinal neovascularization in late stages (see Figure 5, Figure 6).
Figure 3
Red-free photograph of retinal astrocytic hamartoma highlighting calcified bodies and mulberry appearance, case 1.
Figure 4
B-scan ultrasound scan of retinal astrocytic hamartoma shows high reflectivity with acoustic shadowing, case 1.
Figure 5
Early phase fluorescein angiography of retinal astrocytic hamartoma shows hyperfluorescence, case 1.
Figure 6
Late-phase fluorescein angiography of retinal astrocytic hamartoma shows staining without leakage, case 1.
The patient was seen for an MRI of the brain with and without contrast enhancement. The findings showed that the ventricles and sulci were normal for the patient's age. There were no areas of mass effect or hemorrhage, and there were no extra-axial blood or fluid collections. There was no evidence of cortical infarction within the deep gray nuclei, brainstem, or cerebellum. The radiologist's impression was that it was a normal MRI of the brain.
With the supportive diagnostic testing results, the final diagnosis was a spontaneous retinal astrocytic hamartoma with no systemic associations. Additionally, with no apparent parietal or temporal lobe lesions found on the MRI to explain his transient visual complaint, it was concluded that the visual symptoms were most likely related to past history of hallucinogenic drug use. The symptoms could also be attributed to ocular migraine without headache. The patient was then followed up at 6 months with dilated fundus examination to evaluate for change or growth in the lesion. The patient continues to be followed up yearly with retinal photos with stability of the lesion noted for 5 years now.
Case report 2
A 50-year-old man presented to the clinic for a comprehensive eye examination, referred by his primary care provider to rule out any signs of anterior uveitis associated with his previous diagnosis of ankylosing spondylitis. The patient had no visual or ocular complaints, including any signs of eye pain or sensitivity to light. The patient, however, did report a history of laser-assisted in situ keratomileusis (LASIK) surgery in the left eye only during the late 1990s. His medical history included ankylosing spondylitis, chronic obstructive pulmonary disease, and gastro-esophageal reflux disorder. Medications included cyclobenzaprine hydrochloride and naproxen for pain, formoterol fumarate and ipratropium bromide for breathing, and omperazole for stomach acid.
Entering visual acuities were 20/40 O.D. and 20/50 O.S. without correction. He was correctable to 20/20 through -1.00-1.50×100 O.D. and 20/20 through +0.50-2.50×170 O.S. Pupils were equal in size and reactive to light, with no afferent pupillary defect. Confrontation visual fields and extraocular muscles were full in each eye, with no visual field defect or muscle restrictions. Anterior segment slit lamp biomicroscopy showed mild meibomitis OU. The patient's bulbar and palpebral conjunctiva were healthy with no signs of circumlimbal injection OU. The right cornea appeared clear; however, in the left eye there appeared to be a nasal flap hinge with grade 2 epithelial ingrowth, a probable complication after the LASIK procedure. He had flat irides and deep and quiet anterior chambers without any signs of cells or flare bilaterally. Intraocular pressures were 16 mmHg OU at 9:06 am by Goldmann applanation tonometry. The lens appeared to have mild nuclear sclerosis OU. Dilated fundus examination found a cup-to-disc ratio of 0.25 OU, both nerves noted to be pink and round with symmetrical rim tissue and no apparent thinning. The fundus of the right eye was unremarkable; however, in the left eye there was an elevated glistening yellow lobulated “mulberry”-like lesion inferior to the optic nerve head 1 disc diameter in size, which was consistent with the appearance of astrocytic hamartoma (see Figures 7A,B). The patient was then questioned regarding any personal or family history of seizures or any unusual dermatologic lesions that may point toward the diagnosis of associated TS; however, the patient denied any such complications. A retinal specialist was also consulted, and, considering the patient's age and history, no further testing was recommended. The lesion was photo documented, and the diagnosis of a solitary astrocytic hamartoma without systemic association was made. The patient was informed that there was no evidence of any active inflammation, such as anterior uveitis related to ankylosing spondylitis, and was told to return to clinic if he noticed any changes in vision, eye pain, or sensitivity to light. The patient was then scheduled to return to the clinic in 4 months to check the stability of the lesion and for a baseline Humphrey visual field (HVF) 24-2 sita standard.
Figure 7
Posterior pole, case 2. A, Normal fundus O.D. B, Retinal astrocytic hamartoma O.S.
At the follow-up visit, the patient reported no changes since his last examination. The anterior segment appeared stable from the previous examination as did the retinal lesion O.S. when compared with the previous fundus photo. Baseline HVF 24-2 sita standard showed a full and reliable field OU; however, the blind spot O.S. was slightly enlarged, possibly correlating with the approximate location of the astrocytic hamartoma adjacent to the optic nerve (see Figures 8A,B). The patient was then scheduled to return to the clinic in 6 months for a dilated fundus examination to evaluate for change or growth in the lesion. Six months later, the lesion remained stable, and yearly examinations can now be performed for routine follow-up care.
Figure 8
Humphrey visual field, case 2. A, Normal O.D. B, Increased blind spot O.S. corresponding with the anatomic location of the lesion.
Discussion
Composition/pathophysiology
A hamartoma is defined as a focal growth that resembles a neoplasm but results from the imperfect maturation of an organ.1, 7, 8 They may arise at the heart, thyroid, kidney, or other sites throughout the body.4, 9 Astrocytic hamartomas, so named for their histologic appearance of astrocytes, are likewise considered congenital anomalies of tissue formation and development10 that arise from tissue normally found at the site of origination.7
Histopathologic analysis shows that the lesions are composed of several types of glial cells, including fibrous astrocytes, large gemistocytic astrocytes, and Mueller cells.11, 12 Long fibrous astrocytes with small, round or oval nuclei and elongated cytoplasmic processes make up the majority of the smaller retinal lesions.13, 14, 15 Large retinal astrocytic hamartomas are composed of a mixture of the cell types.11 They are also likely to contain calcospherites, which are spherical masses of calicium salts combined with organic matter in areas of calicification within the cytoplasm.12, 15 When performing DNA testing, astrocytic hamartoma have a specific staining pattern that indicates that the lesions are nonmalignant.12
Astrocytic tumors are the most frequent primary brain tumors in humans.16 They are comprised of a wide range of neoplasms that vary in location and presentation.17 Although astrocytic tumors are typically benign, they can induce morbidity.11, 16 For example, subependymal giant cell astrocytomas of the brain can have malignant growth that leads to necrosis of surrounding tissue.11 Cerebral giant cell astrocytic hamartomas, as well as subependymal astrocytomas, may cause increased intracranial pressure and lead to optic atrophy, causing vision loss.18, 19 In some cases as well, intracranial lesions may compress different areas of the brain resulting in nystagmus.20 Although these intracranial lesions may cause an array of complications, there has been no indication in the literature covering true metastasis of retinal astrocytic hamartomas.
Retinal astrocytic hamartomas, otherwise known as retinal astrocytomas, can arise from any location in the retina, including the macula and optic nerve head.21 They are characterized by their descriptive features, location, potential to grow, extent of invasiveness, and systemic associations.22 The retinal lesions are considered indolent low-grade tumors that typically show little to no growth.11 Retinal astrocytic hamartomas are often associated with TS, but can be found as spontaneous, idiopathic presentations as well.12, 14
Clinical presentation
Retinal astrocytic hamartomas can have 3 basic clinical presentations.13, 23, 24 The most commonly seen is a flat, semitranslucent, soft lesion of the nerve fiber layer with poorly defined borders; however, this is more frequently found in the peripheral retina. The second type appears as an elevated, nodular, opaque white lesion with well-defined borders, generally seen in the posterior pole. The third is seen as an intermediate lesion with combined features of the first 2 and may vary in presentation.3, 11, 12, 15, 21, 23 Because of calcification frequently associated with the lesions, they typically autofluoresce in observation with red-free filter,13 making the lesion appear more prominent.21
It is a common belief that the nodules in the second type can eventually take on a mulberry appearance, indicating increased calcification of the lesion.3, 7, 18 In addition to calcification, the lesion can develop cysts of serous exudates and blood.13, 18 Although the mulberry appearance is generally seen in older individuals, it has been noted in infants as well.3, 7
Astrocytic hamartomas can occur at any location in the visual pathway, but present more commonly at the optic nerve head or chiasm.9, 21 In many cases, patients are asymptomatic.
Retinal astrocytic hamartomas are most commonly seen superficially near the optic disc but can also be found out into the periphery.25 Leukocoria may be present if the lesion is located in the posterior pole.26 Patients may present with reduced vision or new-onset strabismus. The degree of symptoms will depend on the degree of macular involvement.8 When the optic nerve becomes involved, visual acuity is often reduced to less than 20/200.7
Progression and complications
Retinal astrocytic hamartomas, with or without systemic association, are typically benign and demonstrate little to no progression in their clinical course.12, 14 Calcification has been observed, but overall the appearance remains stable.18 In a study performed at the Mayo Clinic, 37 lesions were followed up with in patients with TS. Only 3 lesions showed progression or new calcification over 6 to 34 years. This indicates that although lesions can evolve, it is not common.3
Complications are seldom seen, as the retinal lesions typically remain stable and grow minimally over time.11, 18, 27 Shields et al.19 reported that although astrocytic hamartomas are generally stationary, some lesions may show progression. The studies found that while smaller peripheral lesions remained stable, those located around the optic disc had greater tendency to progress.19
Infrequently, the lesions show rapid, progressive growth, providing a risk of complication.28 Rapid growth can lead to exudative retinal detachment and necrosis of the tumor or surrounding tissue.2, 11, 18 It may also cause vascular disruption and proliferation via disturbance of the retinal circulation. This may lead to a central retinal vein occlusion and neovascular glaucoma.11 Even less likely, vitreous seeding, in which part of the tumor breaks off and disperses into the vitreous, and vitreous hemorrhage may occur.2, 3, 11, 15, 18, 23 Although vitreous hemorrhage rarely occurs and has been reported mainly in association with TS, a case of recurrent vitreous hemorrhage in sporadic retinal astrocytic hamartoma as well as a case of sporadic retinal astrocytic hamartoma associated with exudation have been reported.25, 29
Exudation of the retina may occur in retinal astrocytic hamartoma because of the vascularity of the lesion. Coppeto et al.30 described a case in which the astrocytic hamartoma hemorrhaged, developed a secondary inflammatory response, and underwent necrosis in a young woman with TS. Neovascularization of the iris then occurred with a secondary neovascular glaucoma, which led to the need for enucleation.30 Gunduz et al.11 described a similar case in a young girl.
While these progressive processes may be visually debilitating, progression may also be beneficial in some cases. Iaccheri et al.31 reported a case in which a patient with a retinal astrocytic hamartoma had an associated cystoid macular edema. The patient was followed up with optical coherence tomography imaging, which showed the increasing calcification of the lesion over time. The progression, calcification, and solidification of the lesion over time assisted in regressing the cystoid macular edema and improved the patient's visual acuity.31
Although there are reported cases of progressing hamartomas, there is also a scarcity of published cases reported that demonstrate spontaneous regression.18, 25, 32 A more recent article by Demirci et al.24 suggests that these cases may have been misdiagnosed findings of retinal astrocytic hyperplasia, which may be caused by inflammation, trauma, or congenital malformations. Therefore, evaluating the lesions and reviewing the patient's medical and ocular history is critical to determine if further evaluation is warranted.
Systemic associations
Tuberous sclerosis is a rare disease that belongs to a family of diseases named phakomatoses, which are characterized by congenital malformations of ectodermal structures.33 The associated findings of phakomatoses include benign cerebral tuberous astrocytic tumors, seizures, mental retardation, shagreen patches, subungal fibromas, café-au-lait spots, and vitiligo.10 Tuberous sclerosis is inherited by autosomal dominant pattern or sporadically due to a mutation.2, 4, 9 There is no race or sex predilection known.4, 9
Although retinal astrocytic hamartomas are not part of the definitive triad of mental retardation, adenoma sebaceum, and seizures, they are commonly seen in more than one half of patients with TS.3, 4, 7, 11, 13, 15, 18 The retinal lesion is present in up to 80% within the first 2 to 6 years of life7, 21 and can be the first clinical sign of TS.11
In TS, it is believed that astrocytic hamartomas arise as glial cells that replace the retinal pigment epithelium.10 Other retinal findings in patients with TS may include retinal pigment clumping and punched out chorioretinal lesions within the posterior pole that extend out to the midperiphery.3, 23 Further ocular findings may consist of coloration changes in the palpebral and bulbar conjunctiva, strabismus, optic atrophy, and ocular coloboma adenoma sebaceum of the adnexa, which are benign epithelial tumors presenting as multiple teleangetatic papules.9, 13, 15 Epilepsy and mental retardation may occur as a result of cortical hamartomas, which can be observed with radiologic assessment.4, 13
A retinal astrocytic hamartoma less commonly presents in another disease of the phakomatoses, neurofibromatosis.13, 18 Neurofibromatosis is one of the most common autosomal dominant central nervous system disorders,34 affecting 1 in 3,000 people.35 Multiple cell types and systems of the body are involved, which lead to a wide range of clinical presentations and neuroimaging findings.33, 36 Such findings include hamartomas of the cerebellum, basal ganglia and brain stem, optic pathway gliomas, vascular dysplasia, and nerve sheath tumors. In general, however, most diagnoses of neurofibromatosis can be made on a clinical basis, based on the presence of pathognomonic dermatologic lesions.35 Further retinal findings in patients with neurofibromatosis may include multiple retinal capillary hemangiomas and combined hamartomas of the retina and retinal pigment epithelium. These findings can lead to complications of neovascular glaucoma, vitreous hemorrhage, and retinal detachment.9
In general, a retinal astrocytic hamartoma in patients with TS and neurofibromatosis have a bilateral, multifocal presentation. In addition to an astrocytic hamartoma of the optic nerve head and posterior pole, these patients usually have multiple lesions found more peripherally and extending into the anterior retina.21
The case history is important in determining whether TS or neurofibromatosis is involved. Personal or family history of seizures, mental retardation, or unusual dermatologic lesions should be investigated. In patients who appear to have a systemic association, referral to a specialist is indicated for proper medical care and genetic counseling.
Spontaneous lesions
Although it was originally believed that the finding of astrocytic hamartoma established a diagnosis of TS,5 it has since been shown that single lesion presentations without systemic association do exist. A small number of spontaneous retinal astrocytic hamartomas without any systemic association has been demonstrated in the literature.11, 12, 13, 15, 18, 21, 37
General clinopathologic features of retinal astrocytic hamartoma vary, depending on whether there is a systemic association (see Table 1). Spontaneous lesions more commonly present as a single unilateral lesion and tend to be found more posteriorly near the optic nerve head.21 Spontaneous lesions appear in patients with a mean age of 27 years as compared with the mean age of 14.5 years in patients with systemic association. Therefore, younger patients who present with astrocytic hamartoma are more likely to have a systemic disease.2 However, cases of infants who present with spontaneous lesions unassociated with systemic findings have been reported.7 In general, there is no sex predilection in patients with systemic disease; however, patients who present with spontaneous lesions without systemic association are twice as likely to be male.2
Table 1. Features of astrocytic hamartoma in spontaneous vs. systemic association2, 7, 9, 12, 13, 14, 15, 21
| Spontaneous lesions | Systemic association | |
|---|---|---|
| Number of lesions | Single | Multiple |
| Laterality | Unilateral | Bilateral |
| Location | Posterior pole | Posterior pole and periphery |
| Age of onset | Infancy to geriatric, mean age 27 | Children, mean age 14.5 |
| Gender | Male>Female | No predilection |
| Progression | Rare | Rare |
| Complications | Rare | Rare |
| Other ocular findings | None | Adnexal adenoma sebaceum, conjunctival coloration changes, strabismus, optic atrophy, ocular coloboma, retinal capillary hemangiomas, combined hamartomas of the retina and retinal pigment epithelium |
| Extraocular hamartomas | None | CNS lesions |
Diagnosis
Retinal astrocytic hamartomas can be diagnosed based on their clinical appearance and with the support of further diagnostic testing. Ocular ultrasonography is a useful tool to assess the composition of the lesion, the extent of invasion, and to detect an overlying serous retinal detachment. A B-scan will demonstrate focal calcification of the lesion25 and acoustic shadowing behind the lesion.38 An A-scan will show high internal reflectivity universal to calcified lesions.14
Retinal angiography is also useful in the further evaluation of the retinal lesion. A low number of astrocytic hamartoma vessels have abnormalities, including irregular swelling, enlargement, or extensive calcification.14, 38 For this reason, the vessels are characteristically permeable to fluorescein,13 thus FA demonstrates delayed and gradual increasing hyperfluorescence throughout the angiography.13, 23, 39 Indocyanine green angiography (ICG) is performed less routinely. It has been shown to demonstrate hypocyanescence, most likely because of the masking effect of the astrocytic hamartomas overlying the retina, which become more distinct during the late phase. Although ICG does reveal a distinct pattern with the evaluation of a retinal astrocytic hamartoma, it does not provide any new information and therefore is simply recommended as adjunct testing to FA.23
Optical coherence tomography (OCT) also may aid in the diagnosis of many retinal lesions.40, 41 Retinal astrocytic hamartomas typically will show a distinctive feature on the OCT, which includes a gradual conversion from normal retinal tissue into an optically hyperreflective mass with retinal disorganization, distinguishing moth-eaten spaces, and posterior shadowing. 41, 42 Although the OCT has minimal optical penetration of the choriocapillaris, this disadvantage can aid in ruling out tumors such as choroidal melanomas by demonstrating normal adjacent tissue to the observed lesion.40, 43 OCT can also help in detecting complications, such as an overlying retinal detachment,44 monitoring for progression of the lesion, and assisting in understanding the mechanism of the changes surrounding the lesion.45 One study conducted by Shields et al.41 followed OCT evaluations in 44 children with intraocular tumors and mimicking lesions, including astrocytic hamartoma. The study concluded that the OCT is well-tolerated and useful in identifying intraocular lesions and might be more useful in detecting more subtle ocular findings than clinical examination or ultrasonography.41
In patients that present with retinal astrocytic hamartomas, neuroimaging should be one of the first considerations in a workup to rule out systemic associations with the phakomatoses, especially in the younger population. Contrast tomography (CT) will demonstrate hypodensity of the lesion with variable contrast enhancement. MRI with and without gadolinium contrast is more useful than a CT in seeing anatomic origin and lesion extension. Neuroimaging in patients with TS or neurofibromatosis will show calcified lesions that may be evident throughout the brain.35
Management/treatment
Before much was known about astrocytic hamartomas, many eyes were treated unnecessarily with irradiation and enucleation.41, 46 When CT was first used in the 1970s as a safe and noninvasive method for evaluation of astrocytic lesions, it changed the way physicians could manage the retinal lesions.46 Early diagnosis and management is important for prompt referral of systemic association. Additionally, misdiagnosis may alter the course of treatment.
Treatment choices are determined by the expected visual outcome, as patients with retinal astrocytic hamartomas have very little risk of complication. Initial management with close observation and photodocumentation is appropriate, watching for increased size, progression, or complications.3 Subsequent annual follow-up remains the most accepted form of management. In the rare case of an exudative retinal detachment secondary to an astrocytic hamartoma, argon laser photocoagulation may reduce the lesion and result in the resolution of the detachment. Depending on the extent of this area, final visual acuity may be permanently affected.44
Differential diagnoses
Retinoblastoma is a significant differential. The appearance may be very similar with subtle differences (see Table 2). Retinoblastomas are more likely to have dilated, tortuous vessels and a chalky-white appearance to the calcified lesion. On the other hand, astrocytic hamartomas are not usually associated with dilated vessels, and the calcification tends to be more glistening cream or yellow in color.14, 26 It is also prudent to consider the age of onset. Although the average age of diagnosis in patients with TS is 14.5 years,2 the average age of diagnosis of retinoblastoma is 2 years.7
Table 2. Astrocytic hamartoma associated with TS vs. retinoblastoma 2, 7, 14, 17, 26, 30, 38, 47
| Astrocytic hamartoma | Retinoblastoma | |
|---|---|---|
| Clinical appearance | Calcification appears glistening or yellow in color -no association with dilated vessels | Chalky-white appearance to the calified lesion -dilated tortuous vessels |
| Systemic/ocular findings | Systemic and ocular findings | Ocular findings |
| Age of diagnosis | 14.5 years old | 2 years old |
| Gender | Male>Female | No predilection |
| Fluoroscein angiography | Delayed hyperfluorescence with late staining | Quick and progressive hyperfluorescence with late staining |
| Ultrasonography (A and B scan) | High reflectivity and acoustic shadowing | High reflectivity and acoustic shadowing |
| Optical coherence tomography | Gradual transition between hamartoma and normal retina | Abrupt disruption toward uninvolved retina |
Retinoblastoma may show similar signs, but demonstrates subtle differences with diagnostic testing.13 In FA evaluation, quick and progressive hyperfluorescence with late staining is seen within retinoblastoma, whereas an astrocytic hamartoma generally shows a more delayed hyperfluorescence with a similar late staining.14 On OCT imaging the retinoblastoma will show an abrupt transition into the uninvolved retina, whereas the retinal astrocytic hamartoma will show a gradual transition.47 However, ultrasonography evaluation with A-scan and B-scan can be noncontributory, as both lesions demonstrate high reflectivity and acoustic shadowing because of calcification.14, 38
In the rare case in which the differential diagnosis is particularly challenging, fine-needle aspiration biopsy (FNAB) has been shown to be diagnostically useful.14 Although a biopsy of the lesion will provide a more definitive diagnosis, it has been shown to contribute to the risk of complication.30 This method is not recommended in easily identifiable cases of retinoblastoma or astrocytic hamartoma because the loose, easily fragmented tumor could be theoretically disseminated with manipulation.14 Earlier biopsy of the retinal tumor has been performed with vitrectomy instrumentation, but this can lead to hemorrhaging and vitreous seeding.30
Retinal astrocytic hamartomas have been mistaken as intraocular malignancies, leading to unnecessary enucleation.21 This occurs more often in the rare cases of aggressive astrocytic hamartomas, where rapid growth and complications develop.15, 37 An amelanotic choroidal melanoma can usually be ruled out, as the clinical appearance of this lesion is deeper in the retina without association of retinal blood vessels.13
More recent publications illustrate a mimicking retinal lesion called astrocytic hyperplasia. These lesions originate from reactive gliosis, caused by congenital malformation, trauma, and inflammation. They appear as well-defined, yellow-white lesions located in the nerve fiber layer and are very similar in appearance to the “mulberry”-type astrocytic hamartoma and may disappear spontaneously.24, 48
Additional differential diagnoses include choroidal osteoma, juxtapapillary choroiditis, drusen of the optic nerve, myelinated nerve fibers, glioma, and meningiomas of the optic nerve.2 There have also been few cases reported in which astrocytic hamartoma was mistaken for toxoplasmosis and toxocara canis.30, 43
Conclusion
Spontaneous retinal astrocytic hamartomas with no other related findings can be presumed to be benign and monitored for growth and invasive behavior. Diagnostic testing such as OCT, ultrasound scan, and FA will assist in proper diagnosis. Misdiagnosis may result in unwarranted treatment such as irradiation or enucleation. Prompt referral to rule out TS or other systemic associations, particularly in young children, is important. Once neuroimaging has been obtained and systemic associations have been ruled out, observation is the best form of management. Initially, observation every 3 to 6 months will rule out any growth or change in appearance that may cause concern. If the lesion remains stable, annual follow-up is the standard of care. When TS or other phakomatoses are suspected, the patient should be referred immediately for genetic counseling and management of the systemic condition.
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- Vitreous hemorrhage complicating retinal astrocytic hamartoma. Surv Ophthalmol. 1981;26:31–38
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- . Tuberous sclerosis complex and its founders. Neurol Neurosurg Psychiatry. 2004;75(5):770
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- . Combined hamartoma of the retina and retinal pigment epitheleum. Optometry and Vision Science. 1993;70:860–862
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PII: S1529-1839(10)00063-1
doi:10.1016/j.optm.2009.12.009
Published by Elsevier Inc.
Volume 81, Issue 5 , Pages 221-233, May 2010
