Retinoblastoma in patients with regressed retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a well-known clinical entity in premature babies. We report two patients (1 and 2) with regressed ROP who later presented with retinoblastoma (RB). To the best of our knowledge, there is only one such report in the literature so far. Two unrelated patients 1 and 2, born at 32 weeks gestation were screened for ROP at 34 weeks gestation. This showed Zone II Stage II ROP which regressed by 38 weeks of gestation on follow-up. Both patients were lost to follow-up by 40 weeks of gestation. They presented at four years of age with white reflex in the eye. Patient 1 was found to have unilateral and patient 2 bilateral RB. The occurrence of RB in these patients with regressed ROP is probably coincidental.

Retinopathy of prematurity (ROP) and retinoblastoma (RB) are both well documented in the pediatric population. While the incidence and severity of ROP is inversely related to the weight and gestational age at birth, the occurrence of RB has no such prerequisites. RB is a rare tumor but is highly malignant and if undetected can cause significant visual morbidity and mortality. The occurrence of RB in eyes with previous ROP has scant mention in the available literature. Whether some factor known to cause ROP can also predispose the eye to RB is not yet known. We report two cases of RB in eyes with previous ROP. We wish to highlight that regular follow-up of ROP patients at least on a yearly basis, will help in early diagnosis and treatment of other vision-threatening problems in these patients.

Case Reports

Case 1

A male neonate born at 31 weeks of post-conceptional age and birth weight 980 g was admitted to the neonatal ICU for care. There was no history of prolonged supplemental oxygen administration. First ROP screening at 33 weeks post conceptional age showed Stage I Zone II ROP, which later progressed to Stage II Zone II by 35 weeks. The ROP remained stable thereafter till 38 weeks, then regressed without treatment. The last visit at 40 weeks of post-conceptional age showed bilateral regressed Zone II ROP.

The parents noticed a white reflex in the child's left eye, when the child was four and a half years old [Fig. 1]. On examination, the left eye showed a Group D tumor by the International Classification of Intraocular Retinoblastoma [Fig. 2] and this eye was enucleated. The right eye on examination under general anesthesia, with intraoperative 360° scleral indentation, was normal. The enucleated left eye on histopathological examination showed scleral infiltration with malignant cells. Hence this patient underwent chemotherapy (CT) and external beam radio therapy (EBRT) to the left anophthalmic socket. At four years follow-up the child is doing well with no tumor recurrence in the left socket and normal vision in the right eye.

Figure 1

Clinical photograph of Case 1 showing leucocoria in the left eye

Figure 2

Fundus photograph of the left eye of Case 1 prior to enucleation showing large inferiorly located retinoblastoma

Case 2

A neonate was referred from the neonatal ICU (NICU) for ROP screening at 34 weeks post-conceptional age, whose gestational age was 32 weeks and birth weight was 1.4 kg. The child was treated in the NICU for respiratory infection and needed supplemental oxygen for two weeks. On examination, the child was found to have Zone II Stage II ROP, both eyes. The ROP started regressing after the 36th week and the child was discharged. A visit at 38 weeks showed regressing ROP. The patient was subsequently lost to follow-up.

After four years the child's parents reported to the Ophthalmology OPD with a history of bilateral white reflex in the child's eyes. On examination under general anesthesia, the right eye had Group B tumor by International Classification of Retinoblastoma. There were four tumors in the superotemporal quadrant and two in the inferonasal quadrant, with two of them being 6-10 mm in diameter. Another small tumor, 1-2 mm in diameter, was located 2 mm nasal to the fovea.

The left eye showed Group D tumor by International Classification of Retinoblastoma with multiple tumors in the superotemporal, nasal and inferonasal quadrants, two of which were greater than 10 mm in diameter with a height reaching more than half the vitreous cavity. One of them showed vitreous seeding close to the tumor.

As the left eye showed more advanced malignancy, the patient underwent left eye enucleation, and the enucleated eye on histopathological examination showed involvement of the cut end of the optic nerve with malignant cells. Hence antimetastatic chemotherapy and EBRT to the left socket was given. The right eye underwent chemoreduction and subsequent cryotherapy in three sessions [Fig. 3]. At four years follow-up the child is doing well with no tumor recurrence in the left socket and right eye, with normal vision in the right eye.

Figure 3

Fundus photograph of right eye of Case 2, showing regressed retinoblastoma with areas of retinal scarring surrounding the mass following cryotherapy

Discussion

Both the patients in this report had a similar stage of ROP that regressed spontaneously and both presented approximately four years later with advanced RB. The occurrence of RB in eyes that had previously developed ROP could be just a coincidence as stated in the case report by Benz et al.[1] The report by Benz et al, is the only other report in the literature of these two serious retinal conditions occurring in the same eyes. The timing of occurrence of the two conditions are, however, a little different. In the report by Benz et al., ROP and RB were detected simultaneously. This is in contrast to the patients in our report where ROP and RB were not related temporally, with RB lesions occurring many years after ROP in both patients. The increased survival of preterm babies with better neonatal care has resulted in ophthalmologists being able to examine these babies as they grow older.[23] The awareness among the parents of the possible occurrence of ocular abnormalities in premature babies, facilitated by regular screening and patient education for ROP, led the parents to report to the treating ophthalmologist early when the white reflex was noticed subsequently.

The occurrence of ROP and RB in the same eyes although rare and possibly coincidental, highlights the fact that these premature infants are not totally out of danger for developing other eye problems. In conclusion, we would like to emphasize that children with ROP should be followed up at least yearly to detect and treat other well-known ocular associations in premature infants including refractive errors, strabismus and rarely, glaucoma.[45]