|Year : 2020 | Volume
| Issue : 1 | Page : 1-8
Vision-related quality of life in children cured of retinoblastoma
Samar S Hammad, Sherif Elwan, Azza M.A Said, Yousra A.T Farweez
Department of Ophthalmology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||03-Nov-2019|
|Date of Acceptance||02-Dec-2019|
|Date of Web Publication||15-May-2020|
MD Azza M.A Said
10th Fawzy Elmoteay Street, Heliopolis, Cairo 11736
Source of Support: None, Conflict of Interest: None
Purpose The aim was to assess visual functions in patients with retinoblastoma (Rb) after treatment and complete cure and the effect of this on quality of life by means of visual functioning questionnaire-39 (VFQ-39).
Patients and methods A cross-sectional study was carried out in the period from July 2017 to February 2018 in Ophthalmology Department, Ain Shams University Hospital, Retinoblastoma Clinic. A total of 30 patients were recruited at least after 1 year of complete cure from Rb. They were classified into two groups: group I included unilateral cases (15 patients), and group II included bilateral cases (15 patients). All children were subjected to detailed history, and ophthalmological examination included best-corrected visual acuity (BCVA), binocular and color vision assessment, and dilated fundus examination. Scoring of VFQ-25 and VFQ-39 subscales was conducted by the parents.
Results Mean overall vision-related quality of life scores were 90.5±10.45 (range: 60.9–100) and 89.1±8.59 (range: 76.1–100) in groups I and II, respectively, with no difference of statistical significance being found between them (P=0.86), with marked affection of mental health in group II. A highly statistically significant negative correlation was found between each of BCVA (logMAR) and duration of therapy and the mean total score (r: −0.57, P=0.001, and (r: −0.41, P=0.04, respectively).
Conclusion High scores regarding VFQ-25 and VFQ-39 subscales were achieved in older children with Rb, with no difference between unilateral and bilateral cases. BCVA and duration of therapy had a big influence on the results.
Keywords: quality, retinoblastoma, visual functions
|How to cite this article:|
Hammad SS, Elwan S, Said AM, Farweez YA. Vision-related quality of life in children cured of retinoblastoma. J Egypt Ophthalmol Soc 2020;113:1-8
|How to cite this URL:|
Hammad SS, Elwan S, Said AM, Farweez YA. Vision-related quality of life in children cured of retinoblastoma. J Egypt Ophthalmol Soc [serial online] 2020 [cited 2020 May 29];113:1-8. Available from: http://www.jeos.eg.net/text.asp?2020/113/1/1/284340
| Introduction|| |
Retinoblastoma (Rb) in the pediatric age group is by far the most frequent primary intraocular malignancy . It accounts for 3% of all malignant tumors in childhood. For children younger than 15 years, it is the most common ocular malignancy, usually occurring in infancy, even in utero. It can also be observed in older children or young adults .
It is a fatal malignancy except if it is diagnosed early. The early discovery and treatment can salvage one or both eyes, and even retain part or full vision , as in developed countries where the likelihood of disease-free survival has been higher than 80–90%. With increase in populations, especially in Asia and Africa, Rb has gained importance rapidly, and there is much progress worldwide to combat this ocular malignancy. This increasing importance can be attributed to the fact that in developing countries this tumor is one of the most common malignancies in pediatric oncology services .
There is a paradigm shift in management of this tumor in the recent years. Understanding of the disease has contributed to trials of new treatment modalities with higher survival rates . Owing to the severe influence of the late effects of Rb and its treatment, it is important to evaluate health-related quality-of-life (QOL) of Rb survivors specifically vision-related aspects .
Since the WHO definition of health , in addition to traditional clinical measures, the effect of a disease or treatment on the patient’s life has been measured using well-being or QOL assessments. In fact, measurements of health-related QOL (HR-QOL) are now a standard part of health intervention clinical trials .
Preservation of vision is the third most important goal after saving life and eye in patients with Rb. It is important to measure the effect of visual impairment and visual symptoms on various aspects of life, including physical, social, and psychological aspects .
Vision in those patients correlates with the tumor location . The visual outcome of patients with macular Rb depends on the size of the tumor and wither the fovea is involved or not. In 90% of eyes with extramacular tumors, and in 24% of eyes with macular tumors, visual acuity 20/40 or better can be reached. Overall, half the eyes may achieve a final visual acuity of 20/40 or better, and two-thirds have visual acuity of 20/200 or better .
Rb affects the visual system at an age when the central nervous system continues to develop; variations in visual performance in patients with Rb may be owing to changes in the primary visual cortex triggered by disease or treatment .
The Visual Functioning Questionnaire-25 (VFQ-25) tests the most critical vision-targeted health status of people with chronic eye diseases. Because of this aim, it examines the effect of visual impairment and visual symptoms on traditional health areas such as feelings and social aspects in addition to task-oriented fields relevant to everyday visual functioning; it measures the influence of visual disability and visual symptoms on generic health areas such as emotions and social aspects. The VFQ-25 consists of a base of 25 vision-targeted questions, representing 11 vision-related constructs plus a single general health rating concern. Additional questions that users add to a particular sub-scale were optional items. Inclusion of these may be helpful if a particular subscale represents the primary domain of vision-targeted HR-QOL, which is considered most important for the condition being studied. VFQ-39 subscales (VFQ-25+ optional items) will result in an average of these items .
The aim of the study was to assess visual functions in Rb survivors after treatment and complete cure and to report the effects of these on their QOL using VFQ-39 subscales.
| Patients and methods|| |
A cross-sectional study was conducted in Retinoblastoma Clinic, Ophthalmology Department, Ain Shams University Hospital, starting from July 2017 through February 2018. A total of 30 patients were recruited at least 1 year of complete cure from Rb. They were classified into two groups:
- Group I: unilateral cases (15 patients).
- Group II: bilateral cases (15 patients).
This study followed the tenets of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Humans. Written informed consents were obtained from all parents.
Data regarding detailed history about the disease and the treatment modalities used were taken from parents, including age at time of presentation, complaint, laterality, family history, consanguinity, duration of treatment, and duration of follow-up after complete regression of the tumor. Full ophthalmological examination was performed for all patients. Binocular vision assessment using Worth’s four dot test was done. Patients who underwent enucleation of one eye were not examined using this test. Color vision assessment was done using pseudoisochromatic 38 plates (Ishihara test). Fundus examination with full pupillary dilatation was done to determine number, site, size, and type of tumor regression.
The VFQ-25 was administered in an interviewer format with the parents and took around 15 min to be administered. We used the Arabic version of VFQ-25, which was developed according to the WHO translation guidelines for research instruments. Adequate reliability and validity of this Arabic version to be used for the assessment of ophthalmic disorders was achieved .
This questionnaire generates vision-targeted subscales. Scoring of VFQ-25 and VFQ-39 subscales was performed in this study in a two-step process according to Mangione et al. .
SPSS 13 software (SPSS Inc., Chicago, Illinois, USA) was used to analyze the data. The Kolmogorov–Smirnov test was used to evaluate data normality. Nonparametric quantitative data were expressed as median and interquartile range (IQR) and 95% confidence interval. The Mann–Whitney U-test was used to compare variables between two groups. Parametric continuous variables were expressed as mean and SD. To compare quantitative variables of two groups, independent sample t-test was used. Qualitative variables were described in the form of numbers and percentages. χ2 and Fisher’s exact tests were used to compare between qualitative data. Spearman’s correlation coefficient was used to correlate variables. The level of significance was set at P less than or equal to 0.05.
| Results|| |
This study included 30 patients completely cured from Rb, comprising 16 (53%) males and 14 (47%) females. Their age ranged from 6.0 to 19.0 years (median was 10.0 years and IQR was 4.25).
Patients were classified into two groups:
- Group I: 15 patients had a unilateral disease. Right eye was involved in eight (53%) patients, and left eye in seven (47%) patients. Overall, 11/15 patients (73.3%) underwent enucleation of the diseased eye. Thus, from the 30 eyes in this group, 11.0 eyes (37%) were enucleated and 19 eyes (63%) were preserved.
- Group II: 15 patients had bilateral disease. Overall, 12 (80%) patients underwent enucleation of one eye, and three (20%) patients had both eyes preserved.
[Table 1] demonstrates the demographic data of each study group. There was no statistically significant difference between the study groups regarding age at time of study and at presentation, sex, family history, consanguinity, and follow-up duration, except the duration of therapy was longer in study group II (P=0.01).
There was a statistically significant difference regarding the treatment modalities (P=0.02), where in the unilateral cases, five (33.3%) patients underwent enucleation of the diseased eye, four (26.7%) patients received transpupillary thermotherapy (TTT) combined with systemic chemotherapy with eye preservation ([Figure 1]), four (26.7%) patients had TTT combined with systemic chemotherapy followed by enucleation, and two (13.3%) patients received TTT combined with systemic chemotherapy and external beam radiotherapy followed by enucleation. So the total number of patients in group I who had unilateral enucleation with the other eye completely free was 11 (73.3%) patients.
|Figure 1 (a) Fundus view of left eye of one of our unilateral retinoblastoma cases showing single mass, central, type IV regression; and (b) another unilateral retinoblastoma cases showing single mass, approaching the fovea, combined type I and type IV regression in the right eye. Both children were completely cured by transpupillary thermotherapy and systemic chemotherapy.|
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However, of the 15 patients in the bilateral group, seven (46.7%) patients had TTT combined with systemic chemotherapy followed by enucleation in one eye, and received TTT combined with systemic chemotherapy for the other eye, four (26.7%) patients had enucleation of one eye and TTT combined with systemic chemotherapy for the other eye ([Figure 2]), three (20%) patients received TTT combined with systemic chemotherapy for both eyes (no enucleation of either eye), and only one (6.7%) patient received TTT combined with systemic chemotherapy followed by enucleation in one eye, and received TTT combined with systemic chemotherapy and external beam radiotherapy for the other eye. The total number of patients in group II who had one eye enucleated was 12 (80%) patients.
|Figure 2 Fundus view of right eye of one of our bilateral patient underwent enucleation of the left eye, to the right eye, showing three masses. (a) One upper temporal, type IV regression; (b) one upper nasal, type 1 regression; and (c) one lower nasal mass, combined type 1 and type IV regression. This eye was treated by transpupillary thermotherapy with systemic chemotherapy.|
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[Table 2] shows ophthalmological examination of the remaining eyes of the two study groups regarding tumor numbers, site, size, and types of regression.
Regarding binocular vision assessment of those who had both eyes preserved using Worth’s 4 dot test, only 4/7 patients could be tested [had best-corrected visual acuity (BCVA) (logMAR) <1.7].
Two (6.7%) patients saw only three green lights, which was interpreted as right suppression. One belonged to the bilateral group. This patient’s BCVA (logMAR) was 0.78 OD and 0.3 OS, and fundus examination revealed OD two masses: upper nasal, type 4 regression, 3 DD in size, and OS two masses: lower temporal, type 4 regression, endophytic, and 1 DD in size.
The other one belonged to the unilateral group. This patient’s BCVA (logMAR) was 1.47 OD and 0.0 OS, and fundus examination revealed a single mass: type 1 regression, 8 DD in size, central OD, and completely free left eye.
One patient of the unilateral patients saw four lights: one red at the top, two green on either side, one mixed at the bottom, interpreted as normal retinal correspondence (no deviation). This patient’s BCVA (logMAR) was 0.0 OD and 0.78 OS, and fundus examination revealed completely free right eye and single mass: type 1 regression, 3 DD in size, and lower nasal left eye.
The other one of the unilateral group saw five lights (two red and three green) but not at the same time; the patient kept switching between the two responses, which was interpreted as alternating suppression. This patient’s BCVA (logMAR) was 0.48 OD and 0.0 OS, and fundus examination revealed completely free left eye and single mass of type 1 regression about 6 DD in size, with endophytic lower temporal in his right eye. All patients in this study had normal color vision.
Mean QOL scores were 90.5±10.45 (r: 60.9–100) in group I and 89.1±8.59 (r: 76.1–100) regarding group II, with no statistically significant difference between them (P=0.86) using independent sample t-test. [Table 3] demonstrated median and IQR of scores of VFQ-39 with marked affection of mental health in group II (37.5±20.0) compared with group I (score: 85.0±25.0).
|Table 3 Median and interquartile range of scores of visual functioning questionnaire −39|
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There was a highly statically significant negative correlation between BCVA (logMAR) and mean QOL score, so the worse the BCVA the worse mean QOL score (r: −0.57; P=0.001).
The duration after starting treatment till the end of treatment showed a statistically significant negative correlation (r: −0.41; P=0.04), as those who had longer duration experienced poor mean QOL score than those with shorter duration.
| Discussion|| |
Few studies in the world used HR-QOL in patients with Rb but even these studies were not especially concerned with the vision-related aspects. This is the first study to our knowledge in Africa and Middle East concerned with QOL in patients with Rb, where disease presentation is often late and has different social support systems as compared with the west.
In the present study, no difference was found regarding the overall QOL between unilateral and bilateral cases, and this result was comparable to van Dijk et al. .
A total of 46 children with Rb between the ages of 2 and 18 were assessed using questionnaires relating to children’s participation (CFFS) and HRQOL (CHQ and PedsQL) by their parents, and the children were administered the PedsQL . They reported that the overall HRQOL of those patients was comparable to that of the normal children. However, a detailed analysis of the questionnaire subscales shows poor general health and emotional QOL as reported by the parents. Their results were similar to Sheppard et al.  who described the QOL and intelligence quotient of patients with Rb were poor in relation to the normal population, and their sample included 54 children aged from 8 to 16 years, and they used the PedsQL TM 4.0 questionnaire.
Lower scores on mental health were reported in bilateral cases compared with the unilateral group in this study. This was comparable to the results of the two studies conducted by van Dijk et al. , in addition to the results of Ek et al.  and Sheppard et al. . The risk factors for this result were hereditary disease, intensive treatment, and single-parent family. Although the overall QOL of RB survivors is not different from the general population, it was considered that parents perceive their children’s general health as poorer and report more emotional and behavioral problems .
QOL of 50 patients with Rb in a cross-sectional study was analyzed using parent proxy report of PedsQL 4.0 generic core scale . They reported that all domains were worse in those patients and found nothing could predict the results. They referred the difference between studies regarding results of HR-QOL to several factors: factors related to study design such as small sample size, use of different assessment tools, parent proxy report versus child’s self-report questionnaire, and variability in sociodemographics in different regions, in addition to disease-related factors such as stage, involvement of bilateral eyes, and therapies received.
In the present study, the age at first presentation of Rb did not affect QOL, contradicting a study , which concluded that lower diagnostic age (<18 months) predicted better QOL owing to younger patients, as they may have no memories of treatment-related stress and morbidities.
A study was conducted on Chinese children with Rb measuring and comparing their QOL after enucleation with healthy individuals. They found that longer survival time of children with cancer, monocular vision following enucleation, older age at diagnosis greater than 18 months in addition to poor ocular prosthesis satisfaction all associated with worse QOL . They recommend more attention and care to the health, social, and school development of children with Rb.
Comparing the different treatment modalities used for patients with Rb, it was found that these types of treatment did not affect the QOL even enucleation, which used to be thought of as a stigma and an obstacle in treating patients with Rb in the developing countries . There was no difference between who did or did not receive enucleation or radiation; however, patients who had bilateral disease and those who received chemotherapy seemed to have less HR-QOL score than normal, especially in community-related activities. They stated that children with bilateral Rb usually received chemotherapy and/or irradiation; thus, there is an overlap between groups, which needs further studies to evaluate the separate effects of laterality and treatment modality .The visual problems were associated with vision-targeted HR-QOL in adult patients with Rb, as reported by the patients themselves, commonly between those with a history of bilateral disease or enucleation. However, overall QOL was largely preserved in this cohort treated for ocular tumors at a very young age .
The duration of receiving treatment till complete regression is what had an actual effect on the QOL. In this study, those who received treatment for a longer duration had worse QOL than those who received treatment for a shorter duration.
BCVA of both eyes in those patients was an important factor affecting their QOL. Better BCVA had good QOL than those with worse BCVA. This result was in line with van Dijk et al. , in which patients with Rb with a normal vision reported better physical well-being than visually impaired Rb survivors.
Finally, this study showed that Rb survivors can have good QOL. Most participants were living full lives and regular activities. They seemed to spend little time reflecting on early childhood illness.
A number of study limitations should be considered when interpreting the results of this study. First, the small number of cases limits the study’s statistical power. Second, it is conceivable that some of the nonparticipating Rb survivors experienced a different HR-QOL. Nonetheless, it is not clear whether this would lead to better or worse outcomes. For example, patients who feel good may have disregarded the value of the study, or on the contrary, parents of nonparticipating survivors may have refused to participate to prevent their child from facing their disease again, which may imply significant parental concerns or worse coping strategies. For example, patients who feel good might disregard the importance of the study, and on the contrary, parents of nonparticipating survivors may have refused participation to avoid their child being confronted with their disease again, which might suggest serious concern of the parents, or worse coping strategies and a poorer QOL. Third, survivors who were lost to follow-up after treatment completion may also have different QOL. Rb survivors’ QOL is affected by the duration of receiving treatment since the first diagnosis till complete regression of Rb. The longer the duration, the worse their QOL is expected to be.
Their QOL is also affected by their BCVA; the worse the vision, the worse their QOL. These two items should be taken into consideration in making the decision of the course of treatment in patients with Rb: how to reach complete regression with preserving the BCVA possible and how to minimize the time the child spends under treatment.
The findings of this study also indicate a need for further deep assessment of the emotional and physical well-being of this population, in addition to designing appropriate intervention programs which will enhance their participation in daily activities as well as their QOL.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol 2009; 93:1129–1131.
Balmer A, Zografos L, Munier F. Diagnosis and current management of retinoblastoma. Oncogene 2006; 25:5341–5349.
Patil S, Deogade S, Bahetwar S. A prosthetic approach for rehabilitation of a pediatric patient with retinoblastoma. Int J Pedod Rehabil 2017; 2:85–89. [Full text]
Houston SK, Murray TG, Wolfe SQ, Fernandes CE. Current update on retinoblastoma. Int Ophthalmol Clin 2011; 51:77–91.
Shields CL, Shields JA. Diagnosis and management of retinoblastoma. Cancer Control 2004; 11:317–327.
Batra A, Kumari M, Paul R, Patekar M, Dhawan D, Bakhshi S. Quality of Life Assessment in Retinoblastoma: a cross-sectional study of 122 survivors from India. Pediatr Blood Cancer 2016; 63:313–317.
van Dijk J, Huisman J, Moll AC, Schouten-van Meeteren AY, Bezemer PD, Ringens PJ et al.
Health-related quality of life of child and adolescent retinoblastoma survivors in the Netherlands. Health Qual Life Outcomes 2007; 5:65–72.
Huurre TM, Aro HM. Psychosocial development among adolescents with visual impairment. Eur Child Adolesc Psychiatry 1998; 7:73–78.
Ek U, Seregard S, Jacobson L, Oskar K, Af Trampe E, Kock E. A prospective study of children treated for retinoblastoma: cognitive and visual outcomes in relation to treatment. Acta Ophthalmol Scand 2002; 80:294–299.
Demirci H, Shields CL, Meadows AT, Shields JA. Long-term visual outcome following chemoreduction for retinoblastoma. Arch Ophthalmol 2005; 123:1525–1530.
Huttenlocher PR, de Courten C, Garey LJ, Van der Loos H. Synaptogenesis in human visual cortex–evidence for synapse elimination during normal development. Neurosci Lett 1982; 33:247–252.
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol 2001; 119:1050–1058.
Abdelfattah NS, Amgad M, Salama AA, Israel ME, Elhawary GA, Radwan AE et al.
Development of an Arabic version of the National Eye Institute Visual Function Questionnaire as a tool to study eye diseases patients in Egypt. Int J Ophthalmol. 2014; 7:891–897.
Weintraub N, Rot I, Shoshani N, Pe’er J, Weintraub M. Participation in daily activities and quality of life in survivors of retinoblastoma. Pediatr Blood Cancer 2011; 56:590–594.
Sheppard L, Eiser C, Kingston J. Mothers’ perceptions of children’s quality of life following early diagnosis and treatment for retinoblastoma (Rb). Child Care Health Dev 2005; 31:137–142.
van Dijk J, Imhoff SJ, Moll C, Ringens PJ, Cohen-Kettenis PT, Rijmen F, Huisman J. Quality of life of adult retinoblastoma survivors in the Netherlands. Health Qual Life Outcomes 2007; 5:30–36.
Batra A, Kain R, Kumari M, Paul R, Dhawan D, Bakhshi S. Parents’ perspective of quality of life of retinoblastoma survivors. Pediatr Blood Cancer 2016; 63:1287–1289.
Zhang L, Gao T, Shen Y. Quality of life in children with retinoblastoma after enucleation in China. Pediatr Blood Cancer 2018; 65:e27024.
Friedman DN, Chou JF, Francis JH, Sklar CA, McCabe MYL, Robison LL et al.
Vision-targeted health-related quality of life in adult survivors of retinoblastoma. JAMA Ophthalmol 2018; 136:637–641.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]