Download Intravitreal injection of melphalan in the treatment of retinoblastoma

Intravitreal injection of melphalan in the treatment of retinoblastoma with vitreous cavity
seeding
SUN Yabin 1, HUI Peng 1, Kharbuja Punyaram2, BI Mingchao 1, LI Songhe 1, TENG Siying 1, SONG E 1
1
Departments of Ophthalmology,
2
General Surgery, The First Hospital of Jilin University, Changchun,
130021, China
Correspondence to:
SONG E, 71 Xinmin street, Changchun, Jilin, China 130021; Phone: +86-0431-88782351; Fax: +86-0431-88782992,
E-mail: [email protected]
Abstract
Background
The safety and efficacy of the intravitreal injection of melphalan for retinoblastoma with vitreous cavity seeding is
unclear due to limited published works. We report a case with favorable clinical and electroritinography after 12
months of intravitreal injection of melphalan for retinoblastoma with vitreous cavity seeding.
Method
Clinical case report of 6 years old, male was diagnosed with left eye Retinoblastoma, earlier received 4 courses of
cyrotherapy, 17 cycles of chemotherapy, 2 courses of selective intra-arterial chemotherapy and laser
photocoagulation. During follow up on 2011 February, we found vitreous cavity seeding of retinoblastoma in left eye.
We did Intravitreal injection of melphalan with anterior chamber puncture every two weeks for six times of each
dose of 20μg/0.05ml.Every time during procedure we aspirated 0.05ml of aqueous fluid by 32G syringe needle from
corneoscleral junction and sent for clinical laboratory test and did cryotherapy at the injection site.
Result
After 3rd melphalan injection, vitreous cavity retinoblastoma seeding started decreasing, completely disappeared
after 4th injection, and aspirated aqueous fluid showed no metastatic cells after 6th injection ,visual acuity : left eye
was 0.1, intraocular pressure: 11mmHg . 12 months follow up showed no sign of recurrence of vitreous body tumor
seeding.
Conclusion
Intravitreal injection of melphalan for recurrent vitreous seeds from retinoblastoma is effective and could
be another step for treatment and may preserve the eye. However large clinical trials are necessary to
establish as standard treatment for retinoblastoma.
Key Words
retinoblastoma; intravitreal injection; melphalan
MATHOD
Male Child, 6 years old, admitted for whitening of left pupil for 6 years, extensively pretreated with 4 courses
of cryotherapy in Beijing Tongren Hospital, 17 cycles of Chemotherapy, 2 courses of selective intra-arterial
chemotherapy in Guangzhou Children Hospital, and laser photocoagulation during follow up. In February of 2011,
he was found to have vitreous cavity seeding of retinoblastoma and got admitted in our hospital. Ophthalmologic
examination: visual acuity: Left eye: 0.1, intraocular pressure (IOP) 12mmHg, the anterior segment was normal, 3
spots of whitish tumor like seeding was seen at upper temporal region of vitreous cavity (Fig 1) about 1/2PDX1/2PD,
around 10 spots of grayish white satellite lesions and 3 floating scattered lesions were seen at subretinal area, 5D
above optical disc a yellow whitish tumor was seen, diameter of 6PD×5PD, superficially calcified, avascular (Fig 2).
At bottom area of macular region, grey white cloudy lesions were seen and then diagnosed as “retinoblastoma (left
eye)”. From 2011 May to 2011 July, intravitreal injection of melphalan with anterior chamber puncture procedure
(left) was done. It was given every two weeks for six times each dose of 20μg/0.05ml, and total dose of 120μg.
RESULT
After the 3rd melphalan injection, the retinoblastoma seeding in vitreous cavity started decreasing (Fig 3) and
completely disappeared after the 4th injection. In all the 6 injection, the pathology report of aspirated aqueous fluid
showed no metastatic tumor cells. Ophthalmic examination: visual acuity after the 6th injection: left eye was 0.1,
intraocular pressure: 11mmHg of the left eye, and no seeding of tumor in vitreous body was seen. Twelve months
follow up showed no sign of recurrence of vitreous body tumor seeding.
DISCUSSION
According to Reese-Ellsworth Classification for Retinoblastoma, Retinoblastoma with vitreous seeding is Grade
5B and has poor prognosis and initially proposed for enucleation but with the advances of conservative treatment
with external beam radiation therapy(ERBT), systemic chemotherapy, medical treatment has shifted to eye
preservation therapy. Especially, chemotherapy combined with local treatment for retinoblastoma has been proposed
as conservative treatment [1-2]. Moreover, many published literature has proved that chemotherapy combined with
local treatment for children with Grade V retinoblastoma could be avoided for enucleation by 46% [5] .But the lack of
blood supply to vitreous body seeding with retinoblastoma, the chemotherapy drugs could not reach the vitreous
body through blood-retinal barrier. So, this has been one of the important limiting factors in the treatment of children
with retinoblastoma with vitreous seeding. Melphalan proved to be one of the 12 kinds of chemosensitive drugs for
anti retinoblastoma cell colony formation [4]. Ueda M et al [2] by in vitro experiments showed that intravitreal
application of melphalan is safe and the effective dose is 4μg/ml. Subsequently Yukitoshi et al [5] through animal
experiments that the intravitreal injection of 5μg/ml melphalan appears to be nontoxic to the retina and the ERG and
histopathology showed no obvious change in retina and proved to be effective dose of melphalan treatment for
retinoblastoma with vitreous seeding. Meanwhile Kaneko et al [6] has successfully performed intracavitary
administration of melphalan in children with retinoblastoma with vitreous seeding. Out of 41 cases intravitreal
injection of melphalan in children with Retinoblastoma from 1994 to 2001, the method successfully preserved eye of
56.1% (23/41), while 43.9% (18/41) had to undergo enucleation, at the same time no extraocular side effects occurred.
This further indicates the necessity of eye preservation in children with retinoblastoma. Till date there is no any
published report about use of intravitreal injection of melphalan therapy for retinoblastoma with vitreous body
seeding.
In our department, with reference to the Kaneko surgical methods and dose, while injecting intravitreal melphalan
32G needle was used, and the injection point after procedure was condensed by cryotherapy as the injecting point may
the potential point for retinoblastoma cell transfer. After 6 courses of intravitreal melphalan injection, 12 months
follow up did not show any recurrence of tumor, disappeared vitreous seeding of retinoblastoma and no new invasions
were seen, no tumor growth at the puncture site (Fig 4-7), no significant change in vision. ERG assessment for dose
toxicity to retina not done yet as the child did not cope up, but there was no significant change in OCT (Fig 8), as there
is roughly association between human vision and retinal dose toxicity. Thus, we can see for vitreous cavity seeding
with retinoblastoma, intravitreal injection of melphalan is safe, effective eradication of the vitreous cavity tumor cells.
So the children with vitreous seeding retinoblastoma have wider therapeutic options of eye preservation. Children with
the calcified tumor, intravitreal injection of melphalan can inhibit tumor vascular supply to the fundus of
retinoblastoma is not yet observed in this case, still large number of clinical trials evidence is needed for support.
Fig 1: Three spots of whitish tumor like seeding were seen at upper temporal region of vitreous cavity,
around 10 spots of grayish white satellite lesions, three floating scattered lesions were seen
Fig 2: the main tumor of retinoblastoma
Fig 3: Vitreous cavity seeding with slight remaining at temporal top as irregular gray burr-like opacity.
Fig 4: Retinoblastoma after 6 course of procedure
Fig 5: After 1 month follow up, the vitreous cavity seeding disappeared and no new seeds were seen.
Fig 6: After 3 months follows up，the main tumor of retinoblastoma
Fig 7: After 3 months follow up, no new seeds recurrence in the vitreous cavity
A
B
C
Fig 8A: OCT during intravitreal injection of melphalan
Fig 8B: OCT after 1 months post intravitreal injection of melphalan
Fig 8C: OCT after 3 months post intravitreal injection of melphalan
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