Discussion

The Retinoblastoma Centre in the Beijing Tongren hospital was inaugurated in August 2006. Since then, modern triple drug chemotherapy with focal consolidation (laser and cryotherapy) for the management of intraocular retinoblastoma was performed with more than 600 children treated until August 2009. Since the Tongren hospital was among the first centres in China to introduce the modern chemotherapy of retinoblastomas, patients travelled from all provinces of China to Beijing for treatment of their retinoblastoma. The present study which summarised these patient's clinical features found that the vast majority of eyes (501/595 or 84%) presented with an advanced stage of the tumour (Group D or E of the International Intraocular Retinoblastoma Classification). Only 94 (16%) eyes presented with less advanced disease stages, in which the prognosis after chemoreduction and consolidation therapy is considerably higher than in the groups D and E.1 In our study, we did not find any eyes of Group A in patients with a unilateral retinoblastoma and only five eyes in Groups B and C. In contrast, in patients with bilateral tumours, 23 eyes were diagnosed in Group A. The tumours in these eyes were probably found at a relatively low stage of the disease, since the fellow eye showed the more advanced retinoblastoma. Interestingly, patients with unilateral tumours as compared with patients with bilateral retinoblastomas had on average a higher tumour stage. In the group of patients with unilateral tumours, 98% of the eyes belonged to Group D and E, while in the group of patients with bilateral retinoblastomas, 62% of eyes were classified as Group D or E (table 3).

Comparison of the staging results of our study with the findings of studies from Korea and Iran shows that the patients from China had the lowest percentages for combined Groups A, B and C, and the highest percentage for Groups D and E, regardless of whether the patients presented with unilateral or bilateral disease (table 4).12 13 The results of our study may suggest that children in China were often diagnosed as having retinoblastoma in a relatively advanced stage of the disease. This may be due to several reasons. Some physicians, primarily seeing the children, in particular in rural and mountainous regions, may not be familiar with the clinical features of retinoblastoma and may delay the diagnosis. Parents may not have recognised that any abnormality in the pupillary reflex could be a serious disease, and only when the symptoms deteriorated did they take their children to the hospital. Some physicians may not have examined the ocular fundus when the children presented with strabismus. And last but not least, economic reasons or infrastructural problems in the healthcare system may have contributed to the situation. These thoughts may imply that future developments in the Chinese healthcare system may focus on the education of the general public and the primary care physicians to improve the diagnosis of retinoblastoma, so that children arrive at the treating hospital at an earlier stage of the disease. These teaching efforts could closely follow the policy statement of the American Academy of Paediatrics, to improve the detection of leucocoria.14

In our study, 56% of the patients were boys. This is the expected gender ratio in Chinese population in the age group of 0–4 years.15 These data are consistent with previous publications showing no significant difference between males and females in retinoblastoma.16–18 One-third of our patients (32%) initially presented with bilateral tumours. This percentage is similar to that for bilateral retinoblastomas reported from the UK (36%) and Korea (31%),12 16 and it is higher than the figure of 9% from developing countries such as Nepal,13 where unilateral tumours dominated. It has been suggested that the higher incidence of unilateral disease in those populations may reflect a maternal diet deficient in fruits and vegetables.19

The mean age at diagnosis of retinoblastoma in our study was 23 months, which was similar to the figure of 24 months from India,20 28 months from Iran,21 21 months from Korea12 and 26 months in Taiwan.2 In our study, 84% of the patients were diagnosed at an age of 3 years or less, while 4% of the children were older than 5 years at the time of diagnosis. The latter figure is less than the figure of 5% to 10% as reported in previous studies.2 22 In our series, the mean age at diagnosis was 27 months for patients with unilateral tumours and 15 months for patients with bilateral tumours. These data are similar to those from India (29 and 19 months),20 Taiwan (30 and 14 months),2 and the USA (23 and 13 months).23 In contrast, in a previous report from Australia,24 patients were diagnosed at an earlier age (21 months for unilateral and 5 months for bilateral disease). This may be attributed to the presence of a smaller population with better access to medical care in Australia or, in the case of the strikingly low age at diagnosis for bilateral disease, to greater family awareness of the disease risk in the case of a positive family history of retinoblastoma.

It is of interest to note that almost half (51%) of our patients diagnosed below 1 year of age had unilateral tumours. For these patients (figure 1), tight follow-up examinations for the fellow eye may be necessary and important, since tumours may still develop in the fellow during the follow-up. The low age at the diagnosis of these patients with unilateral retinoblastoma may not lead to assumption of an RB1 status and should not be used for genetic counselling purposes (Zhao J, Shi J, Murphree LA, et al. Older age at diagnosis in unilateral sporadic retinoblastoma patients does not eliminate individual risk for new germ line mutations. 2009 AAO Poster: PO507). It is equally important not to assume that an age at diagnosis of 4 or 5 years means that the child has non-heritable unilateral disease. Mosaicism can be found in older unilaterally affected patients.

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Figure 1

Histogram showing the distribution of unilateral versus bilateral retinoblastoma, treated at the beijing tongren hospital in the study period from August 2006 to August 2009, stratified by age at diagnosis

These data are consistent with many reports in that leucocoria was the most common presenting sign of retinoblastoma.12 20 23 Since leucocoria as a presenting sign leads to diagnosis at an earlier mean age than other signs, the significance of its presence should be taught to parents and physicians in a comprehensive early detection programme in China. The delay in the diagnosis of retinoblastoma with leucocoria as the presenting sign was 9 weeks and for strabismus 11 weeks (table 2). The finding that strabismus was associated with a relatively late age at the time of diagnosis may indicate that physicians relatively often diagnose strabismus in that age group and may not routinely perform a fundus examination in these children. This may imply the recommendation that all children with strabismus should have a careful ophthalmoscopic examination.

Potential limitations of our study should be mentioned. First, it was a retrospective hospital-based study with the possibility of a major bias by the referral of patients. The Beijing Tongren hospital, is, however, well known throughout all China, and parents of a child with a rare and life-threatening disease will not avoid major obstacles to find the best possible treatment for the child. Correspondingly, the patients in our study came from almost all provinces of China and may thus partially represent the situation in the country. Second, due to the profound and fast economic development of China, also the medical system has started to undergo major changes. The figures in our study on patients treated in the period from 2006 to 2009 may, therefore, no longer be valid in the near future.

In summary, the diagnosis of retinoblastoma occurs at a relatively advanced clinical stage of the disease in China. An intensified programme for earlier detection of retinoblastoma including educating parents and physicians may be warranted to improve clinical outcome with fewer enucleations.