Pseudoretinoblastoma: Distribution based on gender, age, and laterality

Purpose To investigate the distribution of pseudoretinoblastoma (PSRB) cases based on gender, age, and laterality Materials and Methods The clinical records of 607 patients (851 eyes) who were referred for diagnosis of retinoblastoma or simulating conditions between October 1998 and May 2021 were retrospectively evaluated. Patients were stratified by age as follows: ≤1 year, >1–3 years, >3–5 years, and >5 years. Results Of 190/607 PSRB patients, 129 (67.9%) were males and 61 (32.1%) females (p = 0.001). The 3 most common diagnoses in males were Coats disease (20.2%), persistent fetal vasculature (PFV, 14.0%), and chorioretinal coloboma (6.2%). In females, the 3 most common diagnoses included PFV (21.3%), retinal dysplasia, congenital glaucoma, and combined hamartoma (each 6.6%). PFV was the most common diagnosis in ≤1 year old patient group (26.6%). Coats disease and PFV were the most common diagnoses in >1–3 years old patient group (each 16.7%). Coats disease was the most common diagnosis in >3–5 years old (30.8%) and >5 years old patient groups (13.1%). PSRBs were unilateral in 121/190 (63.7%) patients. Coats disease usually presented unilaterally (p < 0.001) while PFV, optic nerve head drusen, and retinopathy of prematurity as bilateral diseases (p = 0.019, p = 0.001, and p = 0.001 respectively). Discussion PSRB diagnoses show differences depending on gender, age, and laterality. In our study, the most common PSRB lesions were Coats disease in males and PFV in females. PFV was the most frequent diagnosis in ≤3 years and Coats disease in >3 years of age groups. Coats disease and PFV were the most common unilateral and bilateral PSRB diagnoses respectively.


Materials and methods
The clinical records of 607 patients (851 eyes) who were referred with the diagnosis of RB or simulating conditions between October 1998 and May 2021 were retrospectively evaluated. The study was conducted in accordance with the Declaration of Helsinki and all families signed the informed consent form. Approval from the Ethics Committee of Ankara University Faculty of Medicine was obtained (Approval number: İ5-379-21). All patients except for a few older children underwent eye examination under general anesthesia. Older ones had office examinations. All examinations were performed by the same ocular oncology specialist (AKG). Anterior segment examination and photography, intraocular pressure measurement, determination of corneal parameters, funduscopy and fundus drawings, RetCam wide-field fundus photography, fluorescein angiography, B-mode ultrasonography, ultrasound biomicroscopy, optical coherence tomography, computed tomography, and magnetic resonance imaging were done as necessary.
Presenting features including white colour in the centre of the eye (leukocoria), strabismus, decreased vision (defined as absence of fix and follow vision or ≤20/200 Snellen visual acuity in older children), and involuntary eye movements were recorded. Referring diagnoses by the outside ophthalmologists as RB vs PSRB were noted. Patients were grouped by age as follows: ≤1 year old, >1-3 years old, >3-5 years old, and >5 years old. The frequency of each PSRB lesion was analysed according to gender, age, and laterality. The study period was divided into two equal periods for analysis of the distribution of PSRB cases.

Statistical analysis
SPSS for Windows 11.5 (SPSS Inc, Chicago, IL, USA) was used for all statistical analyses. Kolmogorov-Smirnov test was used to assess the normality assumption for age. Comparison of age between RB and PSRB patients was done with Mann-Whitney U test. Pearson's chi-square/ Fisher's exact test was performed for associations between categorical variables including symptoms, age group, gender, and laterality. Laterality of common PSRB diagnoses in comparison to the whole group were analysed. A two-sided p-value ≤0.05 was considered statistically significant.
In all PSRB cases, the correct diagnosis was made on clinical examination and ancillary testing without the need for enucleation. Enucleation was done in 17/190 (8.9%) PSRB cases due to blind painful eye, total retinal detachment (RD), VH, and intraocular tumour other than RB. Histopathological examination findings were consistent with phthisis bulbi in 5 eyes, RD in 5 eyes, Coats disease in 2 eyes, retinal dysplasia in 2 eyes, microphthalmia in 2 eyes, and medulloepithelioma in 1 eye. No eye was mistakenly enucleated for RB and proved to be a PSRB diagnosis.
In a study evaluating the accuracy of RB referring diagnoses, Maki et al. found PSRB lesions in 14 of 48 (29.2%) patients presenting with leukocoria, in 12 of 24 (50.0%) patients with esotropia, in 6 of 6 (100%) patients with microphthalmia, and in 4 of 12 (33.3%) patients with other findings including erythema, epiphora/tearing, poor visual acuity, nystagmus, and orange pupil. 6 Shields et al. reported that the most common presenting symptom in PSRB patients was decreased vision (76%). 7 Ghassemi et al. noted strabismus (39.2%) and leukocoria (39.1%) as the most common symptoms in PSRB patients. 8 The most common symptom was strabismus in our PSRB patients (19.5%). PSRB conditions were detected in 16.3%, 38.9%, and 84.2% of patients who had symptoms of white colour in the centre of the eye, strabismus, and decreased vision respectively. The rate of PSRB was 35.4% in patients who were referred with RB diagnosis by the outside ophthalmologists. PSRB diagnoses were more common (84.2%) compared to RB diagnosis (15.8%) in patients presenting with decreased vision. This situation could be related to the fact that 29.7% (124/417) of children with RB and 45.8% (87/190) of children with PSRB were >3 years old at presentation, at an age when crude vision determination is possible. Previous studies reported male preponderance (64-69%) in PSRB patients. [5][6][7][8] Similarly, males outnumbered females in our series (67.9% vs 32.1%, p = 0.001). In our study, the most common PSRB diagnoses in males and females were Coats disease (20.2%) and PFV (21.3%), respectively. PSRB diagnoses including PFV, ONHD, chorioretinal coloboma, FEVR, ROP, optic disc hypoplasia, RD, microphthalmia, retinal capillary hemangioblastoma, juvenile xanthogranuloma, phthisis bulbi, choroidal osteoma, Axenfeld-Rieger syndrome, congenital cataract, and subretinal hemorrhage were more likely to be encountered in males. Diagnoses including congenital glaucoma, retinal dysplasia, combined hamartoma, leukemic infiltration of the retina, and iris stromal cyst were more likely to be encountered in females.
Shields et al. reported that the most frequent lesions simulating RB in patients ≤1 year and >1 year age groups were PFV and Coats disease, respectively. 7 The median age of PSRB patients was 24 months at baseline in their series. 7 In our study, PFV was the most common diagnosis in ≤1 year old patient group (26.6%). In >1-3 years old patient group, PFV and Coats disease were the most frequent lesions (16.7%, for each diagnosis). In >3-5 years old and >5 years old patient groups, Coats disease was the most common diagnosis (30.8% and 13.1% respectively). The median patient age at baseline was greater in patients with PSRB compared to patients with RB (34.5 months vs 24 months, p˂0.001). Of PSRB patients, 41.6% were in the ≤1 year old, 12.6% were in the >1-3 years old, 13.7% were in the >3-5 years old, and 32.1% were in the >5 years old groups. While RB frequency was statistically higher than PSRB frequency in the >1-3 years old group (p = 0.001), PSRB frequency was statistically higher than RB frequency in the >5 years old group (p = 0.001).
In our series, the rate of PSRB diagnosis among patients referred with suspicion of RB was lower in the first study period compared to the second period (17.3% vs 43.5%, p˂0.001). This may be related to the fact that awareness of ophthalmologists to earlier diagnosis of RB increased during the recent years so that many cases with suspicion of RB or simulating conditions were promptly referred to our service. The most frequent PSRB diagnoses were Coats disease (24.5%) and PFV (17.0%) respectively in the first and second halves of our study.