The ICRB defines Group D eyes as having significant tumour burden including large tumours with diffuse subretinal and/or vitreous seeding. Salvage of Group D eyes is particularly challenging with advanced Group D presentation being treated with enucleation [8]. Pakistan contributes a sizeable to the impact of RB in the Asia Pacific region [9] and lacks adequate resources to tackle it. This study looked at the outcomes of being diagnosed with Group D RB at a centre where specialist treatment was available involving a multidisciplinary approach. Specialist treatment for RB is limited in this part of the world and coupled with poor socio-economic factors, leads to a higher mortality rate when compared to the developed world.
The most common presentation in our patients was leukocoria followed by strabismus which are the two most common presenting complaints of RB documented in medical literature [10]. Genetic testing is a scant resource in the developing world, therefore, based on verbal confirmation during history taking, it was found that two patients (13.33%) had a positive family history for RB. This may imply that hereditary RB is not as prevalent in this region when compared to sporadic presentation, this is consistent with the findings of Kalsoom et al. [11].
The mean age of diagnosis in our study was 32 months compared to 21 months in high income countries including the U.K., U.S and France [12], 20 months in Tehran [13] but similar to those reported in India [14]. This increased age of diagnosis is a critical factor in determining patient outcomes. With increased age correlating to an advanced stage of disease, poorer rates of successful treatment and hence higher mortality. This study highlights this, where patients that required enucleation were found to be of an older age compared to the patients with eyes salvaged. Many patients referred to this centre are from rural areas where early detection is near impossible and coupled with financial strains incurred in travelling further deters patients from receiving prompt treatment. This could advocate for the increased age of presentation when compared to our western counterparts. Our results highlight the importance of early diagnosis and the necessity of early referral to specialist centres in Pakistan.
In our study, 14 patients had bilateral intraocular RB with the majority having advanced Group D or E disease. It is worth mentioning that the study cohort majorly comprised of bilateral disease with only one patient with unilateral presentation. However, a study by Supawan et al did not find any significance of pathological risk factors based on gender, and laterality [15].
IVC along with focal therapy remains to be the mainstay of treatment in group D RB eyes [16]. It is widely accepted that despite numerous emerging protocols for Group D eyes, they are still a challenge to treat. The role of laser therapy in treatment of RB is often overlooked and understated despite being an integral part of the treatment regime. Laser is in fact, the most readily available and inexpensive resource available to low income, developing countries [17]. Our success rates using local consolidative therapy raise a question towards the need for a standardised training programme rather than the consultant’s personal experiences in the treatment of RB. Standardization of laser therapy in line with a protocol may improve its reproducibility in a standard patient cohort. This has previously been discussed by Soliman et al. [18].
We treated a small cohort of 15 Group D eyes with the intention of globe salvage spanning over nine years in which we were able to achieve globe salvage of 11 eyes with IVC coupled with local consolidative therapy. This led to achieving an overall globe salvage rate of 73% which is consistent with the findings of Fabian et al.; a similar study conducted in the U.K. at a larger scale [7]. These findings are also similar to those of Kaliki et al which reported that systemic chemotherapy was the main treatment modality used, giving a globe salvage rate of 58% [19]. Another study by Khaqan et al reported a very comparable globe salvage rate of 72.73% with IVC, laser and/or cryotherapy along with IViC melphalan [20]. In addition to this, a review article by Yet et al also reported the use of systemic chemotherapy with VEC with local consolidative therapy in selected Group D patients and reported salvage rates as high as 87% in China [21]. These comparable studies strengthen the success rates achieved in our study with systemic IVC with local consolidative therapy as a treatment regime for Group D RB.
Out of the four patients that received intravitreal melphalan in adjunct to systemic chemotherapy, three had to undergo secondary enucleation. This is consistent with the findings of Palwasha et al who found no additional benefit with intravitreal melphalan in terms of globe salvage [22]. However, a study by Saima et al reported promising results with intravitreal melphalan in a similar demographic. This difference may be due to a low sample size of patients treated with intravitreal melphalan or the nature of the vitreous seeds. It is reported that vitreous clouds have a better outcome with intravitreal melphalan [23]. In our study, we found that multiple vitreous seeds and those of a large cotton ball appearance are more resistant to intravitreal melphalan. Furthermore, it has been observed that vitreous seeds associated with a non-resolving tumour mass and/or exudative retinal detachment render treatment futile and inevitably result in enucleation [24]. This was also the case in our study where three quarters of the patients treated with intravitreal melphalan were offered secondary enucleation due to associated exudative retinal detachment and non-resolving tumour mass.
There have been various studies on the salvage rates of Group D RB worldwide, but this study is among the few that have been conducted in Pakistan. Discrepancies in reporting of globe salvage rates may occur due to different classification systems used in various studies [25]. Therefore, it is essential to mention the classification used in order to compare findings.
Newer treatment modalities and protocols have increased globe salvage rates, as seen in the developed world where the use of intra-arterial chemotherapy was reported to be superior to IVC [26]. The results of this study show that this progress in increased globe salvage has translated to low income countries as well, given that specialist treatment centres are available.
Limitations
There are several limitations to this study, firstly, patients undergoing primary enucleation were excluded from the study which could imply selection bias. Secondly, visual acuity before or after treatment was not considered, this was partly due to incomplete medical records. Furthermore, the timespan for follow-up is severely truncated due to various factors including incomplete contact information and missed appointments. Also, the study cohort was particularly small in comparison to other studies which hinders the generalisation of these findings. Given the low sample size of our study, it is far from significant in terms of representation of the region. However, the results do show a great deal of promise with an overall globe salvage rate of 72% and no recorded deaths or signs of metastatic spread in the study period. These findings are a step towards better management of the burden of RB in Pakistan.