Retinoblastoma is the most common intraocular malignancy in children, originating from the embryonic retinal cells. It accounts for approximately 4% of all paediatric cancers worldwide. The disease is caused by mutations in the RB1 tumour-suppressor gene, which can occur sporadically or be inherited. Retinoblastoma typically manifests in children under five years of age, with the median age of diagnosis varying between unilateral and bilateral cases.  The global incidence is estimated at 1 in 20,000 live births,with India contributing to nearly one-third of cases worldwide. In developed countries, where advanced healthcare systems ensure early detection and treatment, survival rates for retinoblastoma exceed 90%.^[1] However, the scenario is significantly different in developing regions like Latin America, Africa, and Asia, where delayed diagnosis often leads to advanced-stage presentation.^[2-6]In India, retinoblastoma constitutes 33% of the global burden, with an estimated 1,500 new cases annually and a mortality rate of approximately 24%. A combination of factors, including limited access to healthcare, lack of awareness, socio-economic barriers, and cultural taboos, contributes to these dismal outcomes. The clinical presentation of retinoblastoma varies but typically includes leukocoria (a white pupillary reflex), strabismus, proptosis, or other signs of advanced ocular involvement. Early symptoms often go unnoticed by caregivers, leading to delayed consultations and subsequent progression to advanced disease.^[7] Timely referral to specialized centres is crucial for accurate diagnosis and treatment planning. However, in rural and underserved areas, patients frequently consult informal healthcare providers or general practitioners with limited expertise, further compounding diagnostic delays. Treatment for retinoblastoma depends on the stage at presentation. In early stages, vision-preserving options such as focal therapies, chemotherapy, or radiotherapy may be effective. However, advanced disease often necessitates enucleation or exenteration to prevent metastasis and ensure survival. Despite these interventions, long-term complications, including cosmetic disfigurement, impaired orbital growth, and psychosocial challenges, remain a concern for survivors. The current study was undertaken to address the limited data on retinoblastoma in the Indian context. It aims to analyse the demographic characteristics, clinical presentations, and treatment outcomes of patients treated at a regional cancer centre in Northwest India. By identifying key patterns and challenges, the study seeks to contribute to improving early detection, treatment strategies, and overall survival outcomes for children with retinoblastoma.

Aim: The aim was to evaluate demographic data, clinical presentations, diagnostic pathways, and treatment outcomes.

This study retrospectively analysed medical records of patients diagnosed with retinoblastoma at a regional cancer centre in Northwest India over a fifteen-year period, from January 2010 to November 2024.

Study Design and Data Collection: The study included 95 patients whose medical files were reviewed for relevant information. Data parameters included demographic characteristics (age, gender, locality, and family history), clinical symptoms at presentation, disease laterality (unilateral or bilateral), and the duration between symptom onset, diagnosis, and treatment initiation. Details regarding disease staging, referral sources, and treatment modalities were also documented.

Clinical Evaluation: All patients underwent a detailed ophthalmological examination, which comprised the following:

External Ocular Examination: Assessment of the eyelids, surrounding structures, and extraocular movements. Anterior Segment Assessment: Conducted using slit-lamp bio microscopy to evaluate the anterior segment for signs of tumour-related complications. Fundus EUA: After pupil dilation, the posterior segment was examined using indirect ophthalmoscopy to identify tumour characteristics such as size, number, and location. Imaging Studies: Ultrasonography and computed tomography (CT) scans were used to evaluate intraocular tumour size, extraocular extension, and orbital involvement. Histopathological Analysis: Tumour samples from enucleated or exenterated eyes were examined to assess differentiation, optic nerve invasion, and orbital spread. The International Retinoblastoma Staging System (IRSS) and the International Intraocular Retinoblastoma Classification (IIRC) were used to categorize the stage and severity of the disease at presentation. These systems provided a standardized framework for evaluating treatment needs and predicting outcomes. Treatment Modalities: The choice of treatment was guided by the stage of the disease and the availability of resources: Surgery: Enucleation or exenteration was performed for advanced or non-salvageable cases. Systemic Chemotherapy: Administered according to the OPEC protocol, which included vincristine, cyclophosphamide, cisplatin, and etoposide. 6 cycles of chemotherapy was given and further cycles were given in few cases. Radiotherapy: Employed to manage residual disease or extraocular extension. Referral for Specialized Therapies: Patients requiring advanced focal therapies, such as photocoagulation or cryotherapy, or intra-arterial chemotherapy and intravitreal chemotherapy were referred to higher centres due to limited local availability.

Statistical Analysis: Descriptive statistics were used to summarize the data, focusing on demographic profiles, clinical findings, and treatment outcomes. Outcome measures included rates of remission, relapse, and mortality across different treatment modalities

Patient Demographics

A total of 95 children diagnosed with retinoblastoma were analysed in this study. Of these, 80 (84.2%) presented with unilateral disease, while 15 (15.8%) had bilateral involvement. The median age at diagnosis was 3 years for unilateral cases and 2 years for bilateral cases. The study observed a male predominance, with a male-to-female ratio of 2:1. A family history of retinoblastoma was noted in 5% of cases (n=5). Most patients were from the state of Rajasthan (73.7%), followed by neighbouring states, including Punjab (12.6%) and Haryana (8.4%).

Figure 1: Leukocoria (white eye), the most common presenting symptom of retinoblastoma

Clinical Presentation

All 95 patients presented with noticeable symptoms, with no cases identified through screening. Leukocoria was the most common presenting symptom, observed in 75 patients (78.9%), followed by red eye (34.7%) and proptosis (21.1%). Less common symptoms included strabismus (12.6%), orbital swelling (8.4%), and fungating masses (4.2%). Some patients presented with systemic features such as weight loss or fever, indicative of metastatic disease. The median duration of symptoms before diagnosis was 9.1 months (range: 1–60 months), reflecting significant delays in recognition and diagnosis.

Table 2: Frequency of Presenting Symptoms and Their Duration (n=95)

Disease Staging

Disease staging was performed using the International Retinoblastoma Staging System (IRSS). Stage I disease, characterized by complete tumour resection without residual microscopic disease, was the most common (45.3%, n=43). Stage II (localized residual microscopic disease) was observed in 8 patients (8.4%), while Stage III (regional disease) was noted in 15 patients (15.8%). Advanced metastatic disease (Stage IV) was present in 18 cases (19.0%), highlighting the late-stage presentation in many patients. The intraocular classification (IIRC) revealed a substantial number of high-risk cases, with 12.6% in Group E, indicating very advanced intraocular disease.

Table 3: Stage-Wise Distribution of Patients According to the International Retinoblastoma Staging System (n=95)

Table4:Group-Wise Distribution of Patients of Stage I According to the International Intraocular Retinoblastoma Classification (n=43)

Referral Patterns and Time to Diagnosis

Analysis of referral patterns revealed that 50.5% of patients were referred by local ophthalmologists, while general practitioners accounted for 21.1% of referrals. Informal healthcare providers such as quacks contributed to 10.5% of referrals, and nurses referred 17.9% of cases. The median time from the onset of symptoms to diagnosis was shortest for patients initially consulting ophthalmologists (6.5 months), compared to 10 months for those consulting general practitioners and 18 months for those who first saw informal providers. The median time from diagnosis to initiation of treatment was 36.5 days (range: 0–180 days).

Table5:Time to Diagnosis and Treatment of Retinoblastoma (n=95)

Treatment Modalities

Treatment varied according to the stage of the disease and resource availability:

• Enucleation: Performed in 45 cases (47.4%), primarily in patients with advanced intraocular disease or poor response to conservative treatments.
• Chemotherapy: Administered in 31 cases (32.6%), which includes Intravenous,intra-arterial and intra vitreal.For intra-arterial and intra vitreal patients were referred to higher centre.
• Radiotherapy: Provided to 15 patients (15.8%), mainly for residual disease or extraocular spread.
• Photocoagulation and Cryotherapy: Limited to 4 cases (4.2%) due to the unavailability of these advanced modalities in the regional centre. These patients were referred to higher centre.

Table6:Treatment-Wise Distribution of Patients According to Laterality of Disease (1)(n=95)

Treatment Outcomes

The overall remission rate was 78.9% (n=75). Enucleation resulted in complete remission for 80% of cases (n=36), with a relapse rate of 11.1% (n=5) and mortality of 8.9% (n=4). Chemotherapy demonstrated the highest remission rate (83.8%, n=26), with a relapse rate of 12.9% (n=4) and mortality of 3.2% (n=1). Radiotherapy achieved remission in 73.3% of cases (n=11), but relapse and mortality rates were higher at 13.3% (n=2) each. Patients treated with photocoagulation had a remission rate of 50%, with one patient relapsing and another succumbing to the disease. Overall, relapse occurred in 12.6% (n=12) of patients, while mortality was observed in 8.4% (n=8).

Table7: Treatment Outcomes with Various Modalities (n=95)

Advanced Disease Outcomes   

Patients with metastatic or Stage IV disease had the poorest outcomes. Among these 18 patients, remission was achieved in 50% (n=9), while 33.3% (n=6) experienced relapse, and 16.7% (n=3) succumbed to the disease. These findings underscore the challenges associated with late-stage presentation and the need for more aggressive interventions.

Follow-Up and Long-Term Complications

Follow-up data revealed significant challenges, with some patients lost to follow-up after initial treatment. Among survivors, complications included cosmetic deformities (such as contracted sockets), psychosocial challenges, and a need for prosthetic eye fitting. A minority of patients reported impaired orbital growth and functional limitations, highlighting the importance of long-term multidisciplinary care.

Retinoblastoma is a significant cause of childhood cancer-related morbidity and mortality, particularly in developing countries like India, where access to healthcare is often limited.^[8-9] This study highlights the demographic and clinical characteristics, as well as treatment outcomes, of 95 retinoblastoma patients treated at a regional cancer centre. The findings underline the challenges associated with delayed diagnosis, advanced-stage presentation, and limited availability of specialized treatments.

Demographics and Clinical Presentation

The study revealed a predominance of unilateral disease (84.2%) compared to bilateral cases (15.8%), consistent with global data. The median age at diagnosis was 3 years for unilateral cases and 2 years for bilateral cases, aligning with previous studies that demonstrate earlier onset in bilateral cases, often associated with heritable forms of the disease. The male-to-female ratio of 2:1 reflects a potential gender disparity, possibly due to cultural or biological factors.This study shows a predilection for males (66.7%), which is similar to the literature from Mexico^[8] (52.4%), Mali^[10] (54.5%), Egypt^[11] (60.25), and Jordan^[12] (70.0%). Four patients (4.2%) had a family history of retinoblastoma which was comparable to 6.67% in Singapore^[13] and 4.8% in Iran^.[14] However, further research is needed to determine whether this difference is due to biological predisposition or gender biases in accessing healthcare.

Leukocoria emerged as the most common presenting symptom (78.9%), followed by red eye (34.7%) and proptosis (21.1%). The predominance of leukocoria as an early warning sign emphasizes the need for parental and healthcare provider awareness to ensure timely detection. Advanced symptoms, such as orbital proptosis and fungating masses, were seen in later stages, highlighting the challenges posed by delayed diagnosis and lack of screening programs.^[15,16]

Diagnostic Delays and Referral Patterns

The study identified significant delays in diagnosing retinoblastoma, with a median time of 8.7 months from symptom onset to diagnosis. Early diagnosis was more likely when ophthalmologists were the initial healthcare providers, as opposed to informal providers or general practitioners. However, a large proportion of patients first consulted non-specialized healthcare providers, contributing to delays in initiating appropriate treatment. These findings underscore the urgent need for widespread public awareness campaigns and improved referral systems to connect patients with specialized care earlier in the disease course.

Disease Staging and Treatment Approaches

A notable proportion of patients presented with advanced-stage disease, with 45.3% in Stage I and 19.0% in Stage IV. Late-stage presentation is a recurring challenge in resource-constrained settings, where healthcare infrastructure and awareness programs are often inadequate.^[17] Advanced disease at presentation often necessitates enucleation or exenteration, which, while life-saving, carries significant psychological and social implications for patients and families.

Treatment modalities included enucleation (47.4%), chemotherapy (32.6%), and radiotherapy (15.8%), with focal therapies such as photocoagulation and cryotherapy offered in selected cases. The use of chemotherapy, particularly in neoadjuvant settings, helped in reducing tumour size and improving operability, while radiotherapy played a crucial role in managing extraocular disease and residual tumours. However, the availability of advanced treatments such as intra-arterial chemotherapy or genetic counselling remains limited in many centres, necessitating referrals to higher tertiary institutions.

Outcomes and Challenges

The overall remission rate of 78.9% is encouraging but leaves room for improvement, particularly given the relapse (12.6%) and mortality (8.4%) rates. These outcomes reflect the challenges associated with advanced-stage presentation, poor follow-up compliance, and the limited availability of advanced therapeutic modalities in regional centres. Patients who received chemotherapy demonstrated the highest remission rates, underscoring its importance as a cornerstone of retinoblastoma management.

The study also highlights the psychosocial impact of retinoblastoma treatment, particularly in cases requiring enucleation or radiotherapy. Post-treatment complications, such as impaired orbital growth and cosmetic disfigurement, can have long-term consequences on survivors' quality of life. This underscores the need for comprehensive follow-up care that includes psychosocial support, rehabilitative services, and cosmetic reconstruction options.

Recommendations for Improvement

Addressing the challenges of retinoblastoma management requires a multifaceted approach. Public education campaigns should focus on recognizing early symptoms such as leukocoria and promoting timely consultations with specialized healthcare providers. Strengthening referral systems and integrating retinoblastoma screening into primary care settings can help reduce diagnostic delays. Moreover, investments in healthcare infrastructure are essential to ensure access to advanced treatments like focal therapies and intra-arterial chemotherapy at regional centres.

The establishment of a national retinoblastoma registry could aid in tracking cases, monitoring outcomes, and identifying gaps in care. Training programs for healthcare providers, particularly in rural areas, are critical to improving early detection and management capabilities. Finally, expanding access to genetic counselling and testing could help families understand the heritable nature of the disease and facilitate early interventions in siblings or offspring

Retinoblastoma continues to be a significant paediatric health challenge, particularly in regions with limited healthcare resources, such as India. This study sheds light on the demographic and clinical profiles of retinoblastoma patients, emphasizing the burden of late-stage presentations due to delays in diagnosis and limited access to specialized care.

The findings reveal that most cases involved unilateral disease, with leukocoria being the primary presenting symptom. However, delays in recognizing symptoms and initiating treatment often resulted in advanced disease stages, necessitating invasive procedures like enucleation and exenteration. Although vision-preserving treatments such as photocoagulation and chemotherapy were available for select cases, their use was constrained by the late stage of presentation and limited resources.

Treatment outcomes demonstrated the importance of timely intervention. Chemotherapy showed the highest remission rates, followed by enucleation and radiotherapy. However, advanced disease stages were associated with higher rates of recurrence and mortality, underlining the need for earlier detection and intervention to improve survival rates and reduce disease-related complications.

This study highlights the critical need for improved public awareness, early screening initiatives, and effective referral systems to facilitate timely diagnosis and treatment. A multidisciplinary approach involving paediatric oncologists, ophthalmologists, and specialized care centres is essential to optimize outcomes. Expanding access to advanced therapies and ensuring adequate follow-up care can further enhance the quality of life for survivors while minimizing treatment-related morbidity.

In summary, tackling the challenges associated with retinoblastoma requires a comprehensive strategy that includes public education, early diagnosis, and strengthening healthcare infrastructure. With early detection and timely, effective treatment, significant improvements can be made in survival rates, visual outcomes, and overall quality of life for affected children.

Acknowledgments: The authors would like to thank the doctors and support staff of the Department of Ophthalmology, Medical Oncology, and Radiation Oncology, Sardar Patel Medical College, Bikaner, Rajasthan, India.

Financial support and sponsorship: Nil.

Conflicts of interest:There are no conflicts of interest.

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