123I metaiodobenzylguanidine (MIBG) scintigraphy of retinoblastoma: preliminary experience.

123I metaiodobenzylguanidine (MIBG) is a radiopharmaceutical used for imaging neural crest tumours. The possibility of using 123I MIBG for imaging retinoblastomas has been assessed in this pilot study. Ten patients were studied, nine with clinically and histologically proved retinoblastomas and one with Coats's disease. 123I MIBG scintigraphy correctly identified the neoplasm in eight patients but gave a negative result in two, one of whom had Coats's disease and the other a retinoblastoma which proved to be extensively necrotic on histological examination. These preliminary results suggest that 123I MIBG scintigraphy may have a role in differentiating retinoblastomas from lesions that simulate them.     

Retinoblastoma as a diagnostic problem in a 16-years-old boy (author's transl)]

A secondary glaucoma due to an intraocular tumour with retinal detachment in a 16-years-old patient whose brother had died of suspected leucaemia illustrates the difficulties in the clinical diagnosis at this age. Although the ophthalmoscopical appearance was that of Coats's lesion a malignant melanoma of the choroid could not be ruled out. The histopathological examination revealed a retinoblastoma.     

Lactate dehydrogenase levels in aqueous humor and serum in retinoblastoma

The lactate dehydrogenase (LDH) levels were measured in the aqueous humor and serum of 16 patients (20 eyes) with retinoblastoma. The enzyme activity in the aqueous humor and serum did not show any correlation with each other. Age of presentation, age of enucleation, sex and disease duration had no correlation with the enzyme level either in the serum or aqueous humor. The stages of retinoblastoma were classified in Stages I to V: eyes with Stages I to III were included in Group 1, and those with Stages IV and V were in Group 2. The differences in LDH levels in the aqueous humor and in the aqueous to serum LDH ratio were highly significant (P less than 0.001) by Wilcoxon's nonparametric test between Groups 1 and 2. A considerable rise in the aqueous humor LDH level was observed without any alterations in the serum levels in Group 2 as compared to Group 1; hence the aqueous/serum ratio was increased in the former group. The LDH level in the aqueous humor and the aqueous/serum ratio can be a diagnostic tool in retinoblastoma of Stages IV and V. Though the lower aqueous levels of LDH do not rule out the presence of the disease, the higher levels are definitely helpful for diagnosis of retinoblastoma.     

Phthisis bulbi in retinoblastoma

Background: Phthisis bulbi is a relatively uncommon and atypical clinical presentation of retinoblastoma. Design: Retrospective study conducted at a tertiary care hospital. Participants: Eighteen consecutive retinoblastoma patients with primary phthisis bulbi. Methods: Retrospective analysis of clinical, imaging and histopathological features of all retinoblastoma patients with primary phthisis bulbi, treated at our centre between January 2005 and December 2009. Main outcome Measure: Clinical and histopathology features. Results: Eighteen (3.5%) retinoblastoma patients developed primary phthisis bulbi. The median age of presentation was 1.5 years. The median duration of symptoms before presentation was 6 months. In total, 15 out of 18 (83%) cases had bilateral disease. Among these, 80% (12/15) had advanced intraocular disease in the fellow eye. Most common first symptom was white reflex. History of orbital inflammation was present in 12/18 cases. Computed tomographic scan of orbit showed intraocular mass with calcific densities in 16 eyes. In two cases, hyperdense mass was seen without any calcification. On histopathology, residual viable tumour cells with characteristics of poorly differentiated retinoblastoma were found in 67% (12/18) eyes. High‐risk factors were present in six cases with microscopic residual disease in three cases. Conclusions: This is the largest case series of retinoblastoma patients with primary phthisis bulbi. Phthisis bulbi in retinoblastoma may be associated with bilateral disease in most cases and advanced intraocular disease in the fellow eye in a significant number of cases. Regression is incomplete in majority of these cases; therefore, enucleation must definitely be done in all cases of retinoblastoma presenting with phthisis bulbi.     

Electrophoretic assessment of aqueous and serum neurone-specific enolase in retinoblastoma and ocular malignant melanoma.

The isoenzyme pattern of enolase was examined in the aqueous humour and serum of patients with retinoblastoma (10 aqueous, 8 sera), malignant melanoma (4 aqueous, 25 sera), and normal subjects undergoing cataract surgery (25 aqueous, 30 sera). The assay we used allowed assessment of all three major isoenzymes, including the gamma gamma isoenzyme (neurone-specific enolase). No enolase was detectable in normal aqueous; alpha alpha isoenzyme was present in the aqueous of one patient with malignant melanoma, while aqueous from all patients with retinoblastoma contained both alpha alpha and gamma gamma. Normal serum contained only an alpha alpha band, while serum from patients with retinoblastoma contained alpha alpha, alpha gamma, and gamma gamma bands (7 sera, 87.5%), or alpha alpha only (1 patient, 12.5%). All sera from patients with malignant melanoma contained the alpha alpha band, with low levels of gamma gamma in 16 (60%). In a single patient with Coats's disease alpha alpha was present in the serum, but no enolase was detected in aqueous. Increased amounts of gamma-containing isoenzymes of enolase are found in both serum and aqueous from patients with retinoblastoma. In malignant melanoma there is often an increase in serum gamma gamma enolase. The assessment of aqueous and serum enolase patterns may be of value in the diagnosis of retinoblastoma and malignant melanoma.     

Coat''s disease: clinical, angiographic, histopathological findings and clinical management.

Twenty-four consecutive patients with Coats's disease are reported. In 9 cases the blind eye was enucleated because of total exudative detachment of the retina or because of untreatable secondary glaucoma. No treatment had been given. Fifteen patients between 22 months and 52 years of age were managed by argon laser or xenon photocoagulation and/or cryocoagulation. The number of treatment sessions varied from 1 to 9 per patient and totalled 49 sessions. Fluorescein angiography was performed in all cases. In most eyes the arterial system seemed to be more damaged than the venous side. Many arterioles ended in macroaneurysm-like dilatations surrounded by avascular areas or complete vascular closure in more advanced cases. In 11 out of 14 eyes the vision improved after treatment or remained unchanged. The follow-up varied from 1 to 8 years. Persistent and aggressive long-term treatment of Coats's disease is recommended because the prognosis without treatment is poor.     

Unilateral vs. bilateral retinoblastoma. Correlations between age at diagnosis and stage of ocular disease

Retrospective analysis of 358 cases of retinoblastoma for correlation between age and intraocular stage at the time of diagnosis revealed: in both early and advanced stages of intraocular disease, bilateral retinoblastoma presents at an earlier age than does unilateral retinoblastoma; support for the Knudson "two-hit" hypothesis of retinoblastoma genetics, the existence of a positive family history for retinoblastoma does not guarantee an earlier age at diagnosis compared to sporadic disease; and for any age at diagnosis, unilateral or bilateral disease, Group V is the most common intraocular stage found.     

Late presentation of a unilateral sporadic retinoblastoma in a 16-year-old girl

BACKGROUND: Retinoblastoma is the commonest intraocular tumour of childhood with the majority of cases being diagnosed before 5 years of age. Late presentation of retinoblastoma is rare. CASE HISTORY: A healthy 16-year-old Caucasian girl presented with a 1-day history of blurred vision in the left eye. Examination revealed an inferonasal mass in the left retina with an overlying haemorrhage and vitreous seeding. Imaging studies revealed a 5-mm densely calcified opacity. Other investigations, including cerebral spinal fluid examination, bone marrow aspirate trephine, toxocara serology and serum protein studies, were normal. After considering the differential diagnoses such as toxocariasis and Coat's disease, a diagnosis of late-presenting retinoblastoma was made. The patient subsequently underwent enucleation with a primary orbital implant. The diagnosis was confirmed histopathologically. CONCLUSION: Late presentation of retinoblastoma is uncommon but can be a cause of acute visual impairment in the non-paediatric age group. Retinoblastoma should be considered in the differential diagnosis of a fundal mass in any age group.     

High resolution magnetic resonance imaging of retinoblastoma

BACKGROUND/AIMS: Diagnosis of retinoblastoma is mainly based on indirect ophthalmoscopy, but additional imaging techniques are indispensable for the staging of the disease. A new high resolution magnetic resonance imaging (MRI) technique for the examination of the eye was evaluated. A new surface coil with a diameter of 5 cm allows a field of view of 60 mm with an in-plane resolution of 0.8 mm. We compared preoperative MRI scans with the histology after enucleation in 21 cases of retinoblastoma. Parameters studied were appearance of retinoblastoma, choroidal and scleral infiltration, extraocular extension, optic nerve infiltration, and vitreous seeding. RESULTS: All retinoblastomas could be visualised as hypointense to vitreous on T2 weighted images and slightly hyperintense to vitreous on plain T1 weighted images with a moderate enhancement after contrast application. Histology revealed seven cases with infiltration of the optic disc or optic nerve. Preoperative MRI scans depict juxtapapillary tumour masses, but it was impossible to differentiate between a juxtapapillary retinoblastoma, a prelaminar infiltration of the optic disc, or a just postlaminar optic nerve infiltration. In five of 14 cases with a proved tumour infiltration of the choroid, MRI scans showed an inhomogeneous contrast enhancement of the choroid in enhanced T1 weighted sequences beneath the retinoblastoma. Whether this sign is specific for a choroidal infiltration or is just an artefact remains unclear. High resolution MRI scans did not allow the exclusion of this form of intraocular tumour extension. All nine cases with proved vitreous seeding were not detected by MRI scans. None of these cases showed scleral infiltration or orbital tumour extension. Therefore, it is not possible to judge the rank of this technique in detecting orbital tumour growth. CONCLUSION: The new MRI technique is of limited value in visualisation of prelaminar or postlaminar infiltration of the optic nerve. Advanced choroidal infiltration might be visualised by contrast enhanced T1 weighted MRI scans, but the available spatial resolution did not allow the exclusion this critical form of tumour growth by MRI scans. Nevertheless, high resolution MRI with the new surface coil has superior contrast and spatial resolution compared to computed tomograph (CT) or other available imaging techniques. MRI cannot replace CT in detecting tumour calcification but with increasing experience with this new technique it should be possible to renounce CT scans in the majority of cases of retinoblastoma.     

Genetic profile of 81 retinoblastoma patients from a referral hospital in southern India

PURPOSE: To determine chromosomal abnormalities and inheritance pattern in patients with retinoblastoma from a referral hospital in southern India. MATERIALS AND METHODS: Eighty-one retinoblastoma patients from 78 families were included in this study. Peripheral venous blood was taken for chromosomal analysis and pedigree was ascertained for segregation analysis. RESULTS: Male to female ratio was 1.7:1, 55.56% were bilateral retinoblastoma, the mean age of onset was 12.37 months in bilateral and 33.07 months in unilateral cases (p=0.048). Majority (90.12%) had sporadic inheritance and 6.17% had autosomal dominant inheritance. In chromosomal abnormalities, 8.33% had 13q14 deletion, three cases had de novo balanced translocations. CONCLUSION: The age of onset of the disease was much earlier in the bilateral cases compared to unilateral cases. Sporadic inheritance was predominant while only a small percentage of patients had autosomal dominant inheritance. The percentage of patients with 13q14 deletion was higher than reported in the literature and three novel chromosomal translocations were observed. This is one of the largest series of cases reported from India.     

Full-field electroretinography under general anesthesia in retinoblastoma

Purpose

To investigate the electrical responses of the retina in retinoblastoma (RB), by recording full-field electroretinography (ERG) under general anesthesia.

Methods

The ERG was recorded using Ephios hand-held portable ERG system, according to International Standards for Clinical Electrophysiology of Vision. Forty-eight eyes of 43 cases and 33 eyes of 33 controls were enrolled. The cases were classified based on international intraocular retinoblastoma classification (IIRC). Forty-eight eyes of cases were divided into 30 cases with active RB and 18 cases with regressed RB.

Results

The amplitudes of a- and b-waves were decreased as compared to controls in all subgroups. The implicit times of all RB patients from group A to C differed statistically from controls (p value < 0.05) except for single-flash rod response. The ERG waveforms in group E eyes were non-recordable. The comparison of ERG parameters between active and regressed groups (IIRC groups A and B) was statistically insignificant. Single case follow-up of unilateral RB after systemic chemotherapy showed improvement in amplitudes compared to baseline parameters.

Conclusions

Reduced amplitudes and delayed implicit times were noted in advanced disease. The ERG of RB cases did not follow any specific pattern of waveform. ERG appears to be a dynamic parameter to observe changes following treatment for RB. Although ERG is not a diagnostic test for RB, it can be used as a complementary test to assess the residual retinal function in RB eyes.     

Retinoma and phtisis bulbi: benign expression of retinoblastoma]

Systematic investigation of families of children suffering from retinoblastoma reveals more and more cases of retinoma or phthisis bulbi, cases which used to be called "spontaneous regression". Between 1975 and 1991, we have in this way discovered 11 cases (7%) certain to be carrying retinoma or phthisis bulbi, and a further 5 cases where the same diagnosis is highly probable. Of the 11 certain cases, 5 are unilateral, 6 bilateral, and 8 present family history of the disease. Of the total number of 17 eyes, 16 present retinoma, 1 phthisis bulbi. On clinical examination, all (100%) showed characteristic lesions in the form of greyish homogenous elevated masses in the vitreous cavity. 11 presented calcifications (69%) and in 14 disturbance of the pigment epithelium occurred (87%). The average follow-up is 4 years. Of the 11 patients, 8 are of procreating age and have up to now 25 offsprings. Amongst these, 15 have retinoblastoma (60%), 2 retinoma and phthisis bulbi (8%). All except one of the retinoblastoma cases are bilateral. This study would appear to show that retinoma occurs with a higher frequency than that which is usually given. The figures show clearly that retinoblastoma and retinoma derive from the same genetic disturbances, possibly at different times during cell maturation, and consequently require the same investigation and follow-up.     

Significance of carcinoembryonic antigen in retinoblastoma.

The role of estimating the serum carcinoembryonic antigen (CEA) in the diagnosis and prognosis of retinoblastoma cases has been evaluated. Although the mean serum CEA titre in children with retinoblastoma was higher than that in control children (p = 0.01), the serum CEA level itself was found not to be a useful marker in the diagnosis of retinoblastoma. A significant correlation of serum CEA titre with progression or regression of the disease observed during therapy in most cases indicated that serial assays of serum CEA may be important in the follow-up of cases with retinoblastoma. The lower CEA values in aqueous humour and subretinal fluid from eyes with retinoblastoma than in the serum suggests that the tumour does not secrete the CEA.     

A Study of Immunoactivity of Retinal S—Antigen in Retinoblastoma

Purposese:To study retinal S-antigen expression in human retinoblastoma and as-sess if there is a correlation between S-antigen immunoactivity and degree of retinoblastoma cell differentiations.Methods:Ten cases of Chinese retinoblastoma parafin-embedded tissues were ap-plied for this thudy.A strain of monoclonal antibody,MabA9C6,Which defines an epitope in S-antigen retained in fixed-tissue sections,was used to study S-antigen expression in 10 cases of retinoblastomas.S-antigen was localized by the biotina-vidin indirect immunoperoxidase technique and purified MabA9C6 ascites fluid was used with1100dilution.The whole procedure could be finished within a few hours.Results:The S-antigen immunosctivity was observed in different pattterns:the“normal”photorecepto elements incorporated in 3cases of growing tumors;3of 4Fleurettes and E-W rosettes;and scattered tumor cells in50%of the cases.Conclusions:The result suggests that the expression of S-antigen in retinoblas-toma may be used to assess the degree of tumor differentiation as anothe tumor marker in retinoblastoma.     

Activity of topotecan in retinoblastoma

PURPOSE: To report our experience with topotecan in children with relapsed/refractory metastatic and intraocular retinoblastoma. PATIENTS AND METHODS: Topotecan was administered intravenously as a 30-min infusion at a dose of 2 mg/m2/d for five consecutive days and repeated after three weeks. If obvious progression was detected by physical examination in patients with overt extraocular disease or if progressive disease was noted after fundoscopic examination in patients with intraocular disease, a second cycle was not administered. Response was evaluated at Week 6. RESULTS: Nine patients (6 extraocular, 3 intraocular) were treated from November 1998 to March 2002. A total of 16 cycles were administered. In patients with extraocular disease, there were three partial responses, two cases of stable disease, and one case of progressive disease. Two patients with relapsed/resistant intraocular disease had partial response. allowing local therapy to be performed, and the third patient had progressive disease. The drug was well-tolerated. No patient developed fever or documented infections. No other serious toxicity was found. CONCLUSION: Topotecan is active in extraocular and relapsed/resistant intraocular retinoblastoma. The role of this drug in the treatment of retinoblastoma should be explored in further studies.     

Retinoblastoma in older children

A review of 400 consecutive patients with retinoblastoma who presented to the Ocular Oncology Service at Wills Eye Hospital showed that 34 (8.5%) patients were older than 5 years of age at the time of initial diagnosis. The tumor was active in 26 (76%) cases and inactive (retinoma) in 8 (24%). An evaluation of the 26 patients with active retinoblastoma showed several unique features. At the time of diagnosis, their median age was 6 years and the oldest was 18 years. In 20 (77%) cases, the patient volunteered symptoms that prompted the eye examination; the presenting symptoms included leukocoria (9 cases), decreased vision (9 cases), strabismus (4 cases), pain (1 case), floaters (1 case), and no symptoms (2 cases). All of the 26 patients (100%) had unilateral sporadic retinoblastoma. Misdiagnosis before referral was common in these older children with active retinoblastoma. Five patients (19%) had prior vitrectomy for presumed vitreous hemorrhage or endophthalmitis while the retinoblastoma was unsuspected clinically, one patient (4%) had cryotherapy for presumed Coats disease, and one (4%) was observed for 7 months for presumed vitreous hemorrhage. The clinician should seriously consider the possibility of retinoblastoma in children who present with signs of unexplained vitreous hemorrhage or endophthalmitis, even if they are older than 5 years of age.     

Ultrasonic evaluation of retinoblastoma

Seventeen children presenting with leucocoria were subjected to complete investigations. Careful A and B mode ultrasonography allowed us to make the correct diagnosis of retinoblastoma in 11 eyes of 9 patients, which was confirmed by histopathology or by response to radiotherapy. The diagnosis of retinoblastoma was not missed ultrasonographically in any of the eyes studied. The "V/W" configuration and absence of vascular pulsations on A mode; the "mixed" pattern and absence of choroidal excavation and orbital shadowing on B mode were found to be essential echographic features in characterizing the tumor and in differentiating it from other conditions including vitreous hemorrhage. The ultrasonographic features of early extraocular extension of retinoblastoma are discussed. Careful ultrasonic evaluation of leucocoria would seem to be invaluable in obviating the possibility of misdiagnosis in such problematic cases.     

Multinational clinical and pathologic registry of retinoblastoma

? Background: The Retinoblastoma International Collaborative Study is a multinational prospective clinical and pathologic registry designed to collect baseline clinical information, data on methods of treatment, and information on the subsequent clinical course of children with retinoblastoma. ? Methods: 206 children with newly diagnosed retinoblastoma were evaluated in the participating clinical centers between 1 July 1987 and 31 December 1989. All of the children underwent comprehensive baseline assessment of multiple clinical variables prospectively according to a standard protocol. The recorded values were tabulated and analyzed. ? Results: The 206 children with retinoblastoma included 99 boys (48.1%) and 107 girls (51.9%). The mean age at diagnosis was 21.2 mo in the total study group. One hundred twenty-seven of the 206 children (61.7%) had unilateral disease, while 79 (38.3%) had bilateral involvement. The mean age at diagnosis in the bilateral cases (14.6 mo) was substantially less than in the unilateral ones (23.5 mo). The great majority of patients (approximately 75%) had advanced disease (group V in both Reese-Ellsworth and Essen prognosis classifications) in the affected eye (unilateral cases) or the more severely affected eye (bilateral cases). ? Conclusions: This study shows that there is a dedicated group of international ophthalmologists and other physicians who are willing to participate in multicenter cooperative clinical studies of retinoblastoma and that a relatively large group of children with this ocular malignancy can be enrolled within this framework during a reasonably short time for the purposes of future studies.     

Sarcoma and familial retinoblastoma

Background: Retinoblastoma is the most common malignant ocular tumour of childhood. It results from mutations in the retinoblastoma gene, RB1, which may be sporadic or heritable. Only 10?25% of patients have a family history of retinoblastoma and can be assumed to have a heritable RB1 mutation. A small proportion of the remaining patients may have a heritable mutation despite the lack of relatives with retinoblastoma. Heritable RB1 mutations are associated with an increased risk of sarcoma. Described herein are three patients with a past history of retinoblastoma, no family history of retinoblastoma, and a first‐degree relative with sarcoma. Mutation analyses were performed on DNA samples from these patients to test for heritable RB1 mutations. Methods: A genomic DNA analysis of RB1 gene. Results: Heritable mutations in the RB1 gene were identified in two of the three cases. In these two cases, Bayesian risk calculation indicated that the chance of the affected relatives having the familial RB1 mutation was greater than 90%. In the case without an identified mutation, Bayesian risk analysis indicated that the chance of there being an unidentified familial RB1 mutation was low (16%) but could still be clinically significant in managing the family. Conclusion: The risk of non‐ocular malignancies and the availability of genetic testing for heritable RB1 mutations have important clinical implications for the management of children with retinoblastoma.     

Is screening for primitive neuroectodermal tumors in patients with unilateral retinoblastoma necessary?

Retinoblastoma is the most common childhood intraocular tumor, occurring in 1 of 18,000 live births. Retinoblastoma may occur as a germinal mutation or a somatic mutation. Forty percent of retinoblastoma cases are caused by a germline mutation and include those patients with a positive family history of the disease. Children with hereditary forms usually have multifocal, bilateral retinoblastoma, whereas children with the somatic form have unilateral, unifocal disease. However, up to 15% of cases of sporadic unilateral retinoblastoma may be hereditary. It is important to recognize that this subgroup of unilateral patients remains at risk for the development of second tumors as well as second primary tumors of the intracranial midline, or "trilateral retinoblastoma." We report a case of a 2-month-old child with unilateral retinoblastoma in whom pinealoblastoma subsequently developed.