For many years, the risk of dissemination, seeding and extraocular spread has been the biggest obstacle for surgical intervention in patients with retinoblastoma. Honavar et al. reported an unfavourable outcome in 75% of patients with retinoblastoma who underwent PPV in 2001(12). With the rapid development of local chemotherapy treatments in recent years, this situation may come to an end. Several studies have reported on the combined use of IViC and PPV for advanced retinoblastoma in small sample cases (9, 10, 13). Recently, Zhao et al. reported on planned PPV with IViC in 21 cases of refractory retinoblastoma, with eye preservation achieved in 85.7% (18/21) of the cases with a median of 5.1 years of follow-up(9). In our study, eye preservation was achieved in 100% of the cases during an average follow-up of 42.7 months, without any seeding through the surgical tracts or metastasis. These encouraging results revealed that the combined use of IViC (both preoperatively and intraoperatively) significantly improved the safety of a surgical intervention for retinoblastoma. Moreover, to reduce the risk of surgical incision seeding, some safety measures should be taken, such as using a minimally invasive incision and applying strictly water-tight sutures, cryotherapy and subconjunctival injections of anti-tumour drugs at the incision sites. In general, we believe that IViC-assisted endoresection by PPV can be carefully considered as a supplementary therapy in the refractory cases when standard therapies have failed prior to second eye enucleation.
IViC-assisted endoresection should be performed with strict control of the indications and contraindications. We suggest that only previously treated (IVC/IAC/IViC) refractory ICRB group D cases with obvious vitreous and/or subretinal seeding should be considered for this form of treatment. The direct and definite removal of tumour is the significant advantage of endoresection, so it is especially helpful for cases with a high burden of vitreous and/or subretinal seeding. The IViC-assisted endoresection by PPV can reduce the tumour size and its resulting burden while facilitating extensive and uniformed distribution of the chemotherapeutic drug in the vitreous cavity, which further enhances the efficiency of the drug and reduces the amount of treatment required and the retinal toxicity of repeated IViC(6).
The contraindication of endoresection for retinoblastoma is any sign of tumour metastasis in the anterior segment or extraocular metastasis, which suggests that ICRB group E cases should be excluded. In the study by Zhao et al., the retinoblastoma was not controlled by one-time use of PPV in 4 patients, all of whom demonstrated tumour metastases in the anterior chamber of the eyes, and only one eye was preserved(9). This result is consistent with the findings reported in many previous studies that anterior chamber tumour metastasis is a danger sign that implies poor prognosis and a high risk of recurrence and extraocular metastasis(14, 15). Moreover, in these eyes, PPV may greatly increase the risk of iatrogenic seeding because the incision is very close to the anterior segment of the eye. Consequently, we also suggest lens-preserving PPV even when there is partial opacity of the lens, in order to minimise disturbance to the anterior segment during surgery and lower the risk of iatrogenic seeding to the anterior segment. It should be noted that secondary cataract might develop due to silicone tamponade or chemotherapeutic drug toxicity after PPV. In our opinion, cataract surgery should be cautiously considered at least 6 months after PPV when there is no sign of tumour recurrence or metastasis.
Although many preventive measures have been used, the tumour can still recur. In our study, two cases had single or multiple focal subretinal tumour recurrence. Fortunately, the recurrent tumours could be eradicated by repeated IViC, laser coagulation or a second PPV. The relatively good prognosis was mostly attributed to the absence of recurrent vitreous seeding. We assumed the silicone oil tamponade helped confine the tumour as a focal lesion of the retina, thus limiting intravitreal tumour seeding. Therefore, intravitreal silicone oil tamponade is recommended during PPV to prevent tumour dissemination, especially vitreous seeding. Since the tumour may recur a long time after surgery (e.g. in case 8, tumour recurrence was observed 12 months after PPV), we suggest that the silicone oil tamponade time should be prolonged appropriately, unless any oil-related complications occur.
In addition to eradicating intraocular tumours, IViC-assisted PPV can also help address the sight-threatening vitreoretinal complications of retinoblastoma, such as vitreous haemorrhage and persistent retinal detachment. In our study, 4 of the11 eyes had pre-surgical retinal detachment, and all of them achieved successful anatomical retinal reattachment after PPV. This is especially crucial for monocular patients who have no other alternative for retaining visual function and who require eye preservation. In our study,10 of the 11 monocular patient had improved vision after PPV; in 4 cases, the patient’s vision had improved to ≥20/200. The favourable visual function outcomes also proved the value and good prospect of this treatment strategy.
However, this study has some limitations. Like any new technique, it is difficult to conduct a randomised controlled trial for treating retinoblastoma, as it is a relatively rare disease. The follow-up period in this study was also relatively short, with a mean of 42.7 months (ranging from 12 months to 83 months). Since retinoblastoma could recur years later, further follow-up is required to evaluate the long-term effects of this treatment method. We also used topotecan instead of melphalan because topotecan was the only chemotherapy drug currently approved in mainland China for the treatment of retinoblastoma.