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Management of retinoblastoma during the Covid-19 pandemic: Experience at a tertiary care centre
Correspondence to NEIWETE LOMI; neiwete@gmail.com
[To cite: Gupta Y, Lomi N, Raj N, Kishore A, Tandon R. Management of retinoblastoma during the Covid-19 pandemic: Experience at a tertiary care centre. Natl Med J India 2026;39:150-3. DOI: 10.25259/NMJI_558_2023]
Abstract
Background
Covid-19 disease and the imposed lockdown adversely affected patient care at healthcare facilities worldwide. Children affected with retinoblastoma require uninterrupted care due to systemic immunosuppression and the chances of disease relapse. We evaluated the impact of Covid-19 on patients with retinoblastoma and report a strategy to mitigate this impact.
Methods
We reviewed records of patients attending the ophthalmic emergency from March 2020 to March 2021. Patients with retinoblastoma were categorized based on their urgency level, and managed as per the treatment protocol. The relevant demographic data, clinical profile, referral details, and management strategy used were recorded and analysed.
Results
Fifty patients with retinoblastoma were reviewed (males 31 [62%], mean age 3.33 years). After Covid-19 screening, an ophthalmic examination was done, and an ocular diagnosis was established. The categorization was: 1 emergent, 21 urgent, 26 semi-urgent, and 2 non-urgent patients. Of the 47 patients tested for Covid-19, two were positive and the intervention was deferred. An intervention was delivered in 41 patients (1 orbital biopsy, 9 enucleation, 27 focal therapy, 4 systemic chemotherapy), and 9 received no intervention. A 78.7% reduction in new patients was seen in attendance of the retinoblastoma clinic (p=0.02). All healthcare professionals used personal protective equipment. Teleconsultations were encouraged wherever possible. Support of non-governmental organizations was sought for patient mobilization.
Conclusion
The described model exemplifies a strategy to mitigate the impact of Covid-19 and lockdown on healthcare delivery to patients with retinoblastoma for a year.
INTRODUCTION
The first case of Covid-19 from India was reported on 30 January 2020 and the total number of confirmed cases in India was more than 6 900 000 by October 2020.1,2 The virus is transmitted via direct contact or droplet spread.3 Strategies like social distancing and case isolation were being practised for the control of Covid-19 infection. The government of India announced phase 1 of a nationwide lockdown at midnight on 24 March 2020.4 The lockdown was continued in 4 phases and extended from March 25 to May 4 in phase 2. The lockdown adversely affected access to healthcare resources. Only emergency services were provided, and patients with chronic diseases in need of regular follow-up were the most affected. Telemedicine was promoted during this period to help remote screening and avoid exposure of patients and healthcare workers (HCWs).5 Certain activities in the non-containment zones were permitted in a phased manner starting from June 1.6
Cancer and cancer therapy often lead to immuno-suppression, and for this reason, there is a greater risk for cancer patients in general during pandemics.7 Retinoblastoma, a common childhood tumour, is considered a high-risk category for Covid-19. Managing retinoblastoma patients is complex, as the care involves multidisciplinary support and repeated examinations under anaesthesia (EUA). This required dedicated attention and space in ophthalmology clinics to prevent the risk of exposure of patients, their parents, and the involved HCWs to Covid-19. The American Association of Ophthalmic Oncologists and Pathologists (AAOOP) formulated guidelines for the management and triage of ocular oncology cases during the pandemic.8,9 AAOOP described four levels of urgency (Table 1) in ocular oncology (emergent, urgent, semi-urgent, and non-urgent) and recommended ophthalmic oncologists to strike a balance between delayed care versus safety and resource conservation.8,9
| Emergent | Extraocular or Group E retinoblastomas with complications like intractable glaucoma or globe perforation |
| Urgent | Detailed ocular examinations under anesthesia (EUAs) for newly suspected retinoblastoma, enucleation for diagnosed non-globe salvageable group E retinoblastoma |
| Semi-urgent | EUA for retinoblastoma on active treatment (e.g. intravenous chemotherapy, intra-arterial chemo- therapy, intravitreal chemotherapy, plaque radio- therapy, cryotherapy, transpupillary thermotherapy, laser photocoagulation); regressing tumor requiring further focal therapy or those which completed treatment within past 6 months; EUA for screen- ing of siblings /children at high risk for retino- blastoma due to family history or germline mutations |
| Non-urgent | Regressed cases of retinoblastoma completed treat- ment for >6 months; screening of the normal eye in a child with other eye enulcleated for retinoblastoma |
We describe our experience of triage and management of patients with retinoblastoma during the Covid-19 lockdown and the outcomes with this strategy.
METHODS
In a retrospective cohort study, patients of retinoblastoma who attended the ophthalmic emergency from 24 March 2020, to 24 March 2021, were reviewed. The AAOOP guidelines were followed for the management of these patients.8,9 The cases were categorized based on urgency level, and managed accordingly. Demographic characteristics (age, sex, socioeconomic status, location, distance travelled in cases of physical visits), clinical profile (at each visit or EUA) viz. the stage of retinoblastoma, urgency level, intraocular pressure (IOP), fundus image, anterior segment details, mass lesion size on ultrasonography (USG) or MRI), referral details, and the management strategy used were retrieved.
The patients and parents/legally authorised representative (LAR) were screened in detail at their first contact point in the ophthalmic emergency room for symptoms suggestive of Covid-19, like sore throat, cough, or fever, contact with a Covid-19 positive patient, or any recent travel history, if their locality was included in the government-issued hotspot list, etc., and their declaration was recorded regarding these details. Any patient with positive screening at the ophthalmic facility (screening A) was referred to the screening area (screening B) of the main hospital, where evaluation by a physician was done, followed by reverse transcriptase polymerase chain reaction (RT-PCR) testing for Covid-19, if required, and further management of the systemic symptoms.
After initial history taking, the patients were evaluated by torch light, slit lamp (with breath shields attached), and fundoscopic examinations wherever possible, and further investigations like USG of the involved eye or MRI of the head and orbit if indicated. Examination of the fundus in an uncooperative child with an indirect ophthalmoscope (IO) was discouraged due to the high risk of aerosol generation in case the child cried, and since it increased the contact period between examiner and patient. HCWs in contact with the patient at any level were fully equipped with personal protective measures, including N95 masks, face shields, gloves, goggles, gowns, and shoe-covers.
During the pandemic, a modified set of protocols were followed. Patients were usually called on the day of the procedure directly to the operating room (OT) to reduce exposure from hospital stay unless the intervention was of a higher order, like an urgent enucleation, for which admission to the hospital a day prior to the procedure was mandatory for evaluation and detailed pre-anaesthetic check up. Covid-19 testing was done preferably within 48 hours of the procedure, and the child and parents were strictly counselled on the need to distance themselves from the rest of the community after testing, proper use of masks, social distancing, and the need to report to the nursing staff, in case any Covid-19 symptoms developed prior to the procedure. Patients for surgical intervention or EUA were classified based on the criteria in Table 1 (similar to AAOOP categories8,9) and were further managed on a case-by-case basis wherever required.
The study was approved by the Institute Ethics Committee (IEC) and adhered to the tenets of the Declaration of Helsinki.
RESULTS
We studied 50 children who presented to the emergency department with referrals from an ophthalmologist, suggestive of or already diagnosed with retinoblastoma, requiring an intervention (Table 2). The mean age of the patients was 3.33 years (youngest patient was a 6-month-old boy, and the oldest was a 7-year-old girl). Of these, 31 (62%) were boys, 33 (66%) had received chemotherapy during any period in their lifetime, with 18 (36%) on active chemotherapy. Most patients were residents of nearby states (Haryana: 27.3%, Uttar Pradesh: 22.2%, Punjab: 17.2%, Rajasthan: 15.5%, Madhya Pradesh: 12.2%, Delhi: 5.6%), and had difficulty reaching the hospital due to lockdown constraints. The most common mode of travel was public transport in 60% (n=30), while 26% used shared private transport (n=13) and the rest used personal transport (n=7); 74% resided in nearby Covid-19 hotspot areas, as designated by local authorities. Initial medical contact was self-reported by 74% (n=37) and 26% (n=13) called for a physical visit from a teleconsultation facility.
| Characteristic | Number |
|---|---|
| Number of patients | 50 |
| Male:Female | 31:19 |
| Mean age | 3.33 years |
| Categorization based on level of priority (AAOOP definitions8) | |
| Emergent | 1 |
| Urgent | 21 |
| Semi-urgent | 26 |
| Non-urgent | 2 |
| Planned for intervention | 41 |
| Orbital biopsy | 1 |
| Enucleation | 9 |
| Focal therapy | 27 |
| Systemic chemotherapy | 4 |
| No intervention (e.g. regressed retinoblastoma) | 9 |
| Postponed | 3 |
| Tested for Covid-19 | 47 |
| Positive for Covid-19 | 2 |
Covid-19 testing
Of 50 patients, 47 underwent Covid-19 RT-PCR tests, while 3 had to be postponed due to Covid-19-related travel restrictions. Two children tested Covid-19 positive and were advised to quarantine at home as they were asymptomatic and were rescheduled (after 2 weeks of resolution of fever and a negative Covid-19 RT-PCR report) and managed according to their presentation.
One patient had symptoms of upper respiratory tract infection with mild cough at the time of pre-anaesthetic checkup, and despite his RT-PCR test result being negative, the procedure was postponed due to high suspicion of Covid-19. One patient scheduled for enucleation was cancelled due to a low haemoglobin level (7.5 g/dl) around the planned date. The child was given a blood transfusion at the paediatric facility, and the procedure was rescheduled to a later date.
Clinical profile, triaging, and management
Thirteen patients required admission (Table 2) which included 9 enucleations (4 primary enucleations for unilateral group E retinoblastoma, 3 in patients following chemoreduction for extra ocular component in the form of optic nerve involvement, 2 patients with recalcitrant group D retinoblastoma) and 1 orbital biopsy in a suspected secondary orbital retinoblastoma who had undergone enucleation for extraocular retinoblastoma (EORB) 8 months ago. No patient had any perioperative complications. Patients were followed up with a histopathological examination (HPE) report of the enucleated specimen after 10–14 days of surgery. Two patients, who were found to have high-risk features (HRF) on HPE, were referred for adjuvant chemotherapy, and those with no HRF, were asked to follow up utilizing a telemedicine facility and a physical visit to the hospital only in case of emergencies.
Three patients presented with proptosis. Their MRI showed features of EORB. A referral to the paediatric oncology department was made for neoadjuvant chemotherapy.
Emergent cases. Of all the categories assigned, one patient who came under the emergent group (Table 2) had EORB with neovascular glaucoma with a presenting IOP of ~52 mmHg at admission.
Urgent cases. Twenty-one patients came under the urgent category, with 10 requiring immediate surgery (9 enucleations and 1 orbital biopsy), 3 with EORB requiring urgent referral to the paediatric oncology department for systemic chemotherapy, and 8 were posted for EUA in the urgent category due to active disease under treatment received intravitreal or periocular chemotherapy with or without transpupillary thermotherapy or cryotherapy. Five of 9 enucleations were done as a primary procedure for unilateral group E retinoblastoma diagnosed on screening EUAs.
Semi-urgent cases. A total of 26 patients were included in the semi-urgent category, with 19 requiring some form of intervention, like focal therapy or local chemotherapy, in the form of intravitreal or periocular injections for local tumour control. Five received transpupillary thermotherapy treatment, 3 received cryotherapy, 4 received intra-vitreal injection with cryotherapy of the injection site, and 4 received periocular chemotherapy with topotecan (2.5 mg/2.5 ml; 3 of them received additional cryotherapy). One patient was given a combination of intravitreal chemotherapy (topotecan 20 μg/0.1 ml) with periocular chemotherapy. Nine patients in this category did not require any intervention.
Non-urgent. Two patients fell in the non-urgent category. They were taken up for EUA. One was for screening EUA in a child whose other eye was enucleated for retinoblastoma. The other patient had presented with redness and pain in the eye with regressed retinoblastoma, and on EUA, it was found to be allergic conjunctivitis, and treated for the same.
When both the urgent and semi-urgent groups were combined, 27 (~57%) of 47 patients were given some form of local therapy to control the disease effectively and this obviated unnecessary visits to the paediatric oncology OPD.
Impact of Covid-19 on the number of registered retinoblastoma patients
A comparison of the number of new patients registered from March 2020 to March 2021 (17 patients), as compared to the previous year (80 patients; Fig. 1) showed a steep fall of 78.7% (p=0.02). The impact of these steep declines in follow-up during the lockdown period was seen with an increasing number of EORB/recurrent tumours in the ocular oncology clinic. When comparing different levels of lockdown and unlocking, we found a greater reduction in the number of new patients attending the retinoblastoma clinic during lock-down phases 3 and 4 (91.4% decline during 4–31 May 2020), compared with lockdown phases 1 and 2 (60.6% decline from 25 March 2020 to 4 May 2020). Also, unlock 1.0 (1–30 June 2020) saw the continuation of reduced clinic attendance, compared with the previous year’s attendance (85% decline).
- Chart showing the decrease in new retinoblastoma patients month-wise in 2020 compared to 2019 due to Covid-19
Impact on HCWs
Only 4 HCWs were identified as ‘high risk contacts.’ These were tested on day 7 after exposure and tested negative. They were isolated for 14 days from exposure or 5 days after resolution of fever, whichever was earlier.
Modified protocols in pandemic times
The functioning of OT also saw major changes during the pandemic period with minimal personnel allowed inside the OT (made possible by rotating staff in shifts), use of personal protective equipment with face shields for all staff, frequent cleaning of the surfaces and floors in the OT, and cleaning of the OT table after each case with a 10 minute interval between cases. All procedures were done under general anaesthesia, and the surgical team entered the OT only after completion of intubation and left the OT during extubation to minimize crowding and to reduce the number of HCWs exposed to high aerosol-generating procedures.
A few modifications were made in the surgical technique of enucleation as well. Gentle manipulation of tissues to avoid any spillage of blood or fluids, and the use of electrocautery/diathermy during the separation of extraocular muscles during enucleation was avoided. The options of focal therapy (periocular and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy) were encouraged, wherever possible, to avoid exposure of the child to other departments for intravenous chemotherapy, which may increase the chances of contracting Covid-19.
Parents of children referred for systemic chemotherapy were counselled about the need for proper treatment and the chances of contracting Covid-19 easily, as the child would be immunosuppressed and hence the need for taking utmost care in the hospital, while travelling, and at home.
Role of non-governmental organizations (NGOs)
Covid-19 testing of retinoblastoma patients requiring intervention was done with the help of Cankids, a national NGO. NGOs also helped in arranging transportation, accommodation, food, drugs, and travel passes to cross inter-state borders during the lockdown.
Role of teleconsultations
All patients who had day care procedures were asked to follow-up through teleconsultation on the next day, by sending a photograph of the eye using a smartphone or a video consultation. They were advised to visit the hospital only if needed, after the teleconsultation. Those who had procedures after admission were advised to follow-up once the day after the procedure, and through teleconsultation for scheduling dates of further follow-up visits/EUAs.
DISCUSSION
Ocular tumours are an emergency and cannot be neglected. Retinoblastoma patients are at an increased risk of contracting Covid-19 due to the malignancy itself and also due to chemotherapy, which can result in immune suppression that causes increased susceptibility to infection. It was important to consider such patients for an early intervention, as progression to advanced stages can be fatal due to the high risk of systemic metastasis. It was equally important to protect the HCWs. Triage of retinoblastoma patients helped in judicious utilization of resources. Once the tumour stage was determined, the follow-up visits were planned. Early stage of the disease could have a later follow-up compared with advanced stage of the disease, due to the pandemic.
Since management of retinoblastoma requires the interaction of patients with multiple departments, including ocular radiology, paediatric oncology, and radiotherapy, efforts were targeted towards limiting the number of unessential visits. Post-surgery (enucleation), the follow-up can be limited, and parents were advised to opt for tele-consultations, especially for tapering postoperative medications. Also, the patient was called directly for the scheduled EUA of the other eye, and the operated eye was evaluated in the same sitting, avoiding a follow-up to the clinic.
Considering that retinoblastoma presents mainly in children, a standardized approach was followed so that patient care was not compromised. Simultaneously, care was taken to minimize the spread of Covid-19 in hospital premises. The limitations of our study are bias due to catering to the healthcare needs of a particular catchment area, health-seeking behaviour, and the effect of the local trend of transmission of Covid-19. However, we describe a set of measures used at our facility to overcome the problems of Covid-19 disease and the imposed lockdown.
To conclude, Covid-19 significantly reduced the attendance of new retinoblastoma patients by 78%. Following standard operating procedures enabled us to manage retinoblastoma patients during Covid-19.
Conflicts of interest
None declared
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