Case Report
Silicone Oil Droplets in Vitreous after
Intravitreal Bevacizumab Injection
Haroon Tayyab, Asad
Aslam Khan, Muhammad Ali A Sadiq, Sana Jahangir, Suhail Sarwar
Pak J Ophthalmol 2018, Vol. 35, No. 2
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See end of article for authors affiliations
..
.. Correspondence to: Dr.
Haroon Tayyab Assistant
Prof. of Vitreoretina COAVS KEMU (Mayo Hospital Lahore) Email: haroontayyab79@gmail.com |
Intravitreal
injection of Bevacizumab for various retinal vascular disorders has become
the mainstay of treatment. The injection of Bevacizumab is usually dispensed
through local pharmacies after formulating from a larger vial under sterile
conditions. We report an interesting finding of silicone oil bubble in
vitreal cavity after intravitreal Bevacizumab injection. This is attributed
to the fact that the syringes used for dispensing bevacizumab are coated with
silicone oil that acts as a lubricant. These silicone oil droplets can lead
to floaters and other possible complications. We report two cases of such
occurrence and propose strategies to avoid this complication. Keywords: Bevacizumab, diabetic macular edema, silicone oil, ranibizumab. |
In last
one decade, intravitreal drug delivery in the form of anti-vascular endothelial
growth factor (anti-VEGF) has become the mainstay of treatment for
many retinal vascular disorders including diabetic retinopathy, diabetic
maculopathy and macular edema resulting from retinal vein occlusions1,2.
Also, the current recommended treatment for wet age related macular
degeneration (ARMD) is intravitreal anti-VEGF injections3. Given the
highly prevalent nature of conditions like diabetic maculopathy and wet ARMD,
it is no surprise to us that intravitreal injections of bevacizumab,
ranibizumab and aflibercept have become the most commonly performed
vitreoretinal intervention and second most commonly performed ophthalmic
surgical procedure. There have been many studies where local and systemic side
effects of intravitreal injections have been mentioned.4 An interesting finding after injection of bevacizumab
and ranibizumab is finding of silicone oil bubble in vitreous cavity. This can
be symptomatic in the form of a floater or an incidental finding during
detailed retinal examination. First of such reports was by Fruend and Richard F
Spaide in 20065. This peculiar finding has been infrequently but
persistently reported in western literature up till mid 20166. This
finding has been attributed to the fact that intravitreal injection syringes
are pretreated with silicone oil that acts as a lubricating agent for smooth
entry in the tissue7.
Here we
report our first few cases of intravitreal silicone oil bubble in patients who
had received Bevacizumab for diabetic macular edema. To date, local literature
has provided no such report about this interesting finding. The rationale of
reporting these cases is to discuss possible ocular implications and propose
remedy to this problem.
These
case reports are from the outdoor patient department (OPD) of Ophthalmology
Unit 3, Mayo hospital, Lahore from the period between October 2017 to February
2018. An informed consent was sought from both patients and hospital ethics
committee approval was obtained before proceeding with reporting of these
cases. While presenting these case series, the authors do not have any conflict
of interest to disclose.
Case 1
Our first case (October 2017) was a 54
year old male diabetic patient who had been on intravitreal Bevacizumab
injection for his diabetic macular edema in left eye. He had history of 7 such
injections in his right eye and presented to our outdoor patient department for
routine follow-up. His last injection was one week ago. He had no complaints of
floaters at the time of presentation. His best corrected visual acuity in left
eye was 20/80 and intraocular pressure was 15 mmHg. He had a history of
uneventful phacoemulsification with IOL implantion one year ago. A fundus
photograph was taken using Topcon Fundus camera (TRC-50DX Topcon Medical
Systems, Inc. Oakland, NJ. USA). The next follow-up of this patient was in
December 2017 by which time the silicone oil bubble was no more visible on slit
lamp examination. This patient has remained complication free and symptom free
to date as far as the silicone oil bubble was concerned (Fig. 1). B-scan was
performed and classic ringing bell sign due to silicone oil droplet was noted
(Fig. 2). The size of silicone oil droplet was noted to be 0.3 mm.
Fig.
1: Silicone oil bubble in
vitreous cavity after intravitreal Bevacizumab injection Left eye.
Case 2
The second case (February 2018) was a 60
year old female who presented to OPD and was scheduled to have her left eye
examination prior to intravitreal Bevacizumab injection for diabetic macular
edema. This was her third injection in left eye. Her best corrected visual
acuity was 20/200 and intraocular pressure was 17 mm Hg. She was phakic with no
history of ocular surgery apart from intravitreal Bevacizumab. We noted
intravitreal silicone oil bubble suspended in superior half of post vitreous
cavity but could not capture this finding on fundus camera due to very small
and indistinct appearance of this bubble on photography. Her last injection was
one month ago. She also remained symptom free.
Fig.
2: Ringing bell sign on B
scan. Size of silicone oil bubble is 0.3mm.
Fig.
3: Three distinct silicone oil
bubbles in vitreous cavity (marked in black circle).
Case 3:
Our third case was a 60 year old lady who
presented to us with traumatic crystalline dislocation after blunt trauma in
her right eye. On detailed fundus examination, she was found to have old
central retinal vein occlusion with subhyaloid hemorrhage for which she had
received 2 bevacizumab injections 8 months ago. She was also noted to have 2
silicone oil bubbles on her vitreous cavity. Her fundus photograph shows
silicone oil bubbles suspended in vitreous cavity (Fig. 3). She also did not
have any history of ocular surgery apart from mentioned intervention for her
CRVO.
DISCUSSION
The
most frequent anti-VEGF used in Pakistan is Bevacizumab. It is usually
dispensed by pharmacies in pre-formulated insulin syringes from a larger vial
under sterile conditions. The largest dispenser of Bevacizumab in the province
of Punjab, Pakistan is Shaukat Khanum Memorial Cancer Hospital and Research
Centre (SKMCH). We have not noted any clinical report about the presence of
silicone oil bubbles after intravitreal Bevacizumab injections in local
literature. This problem was recently reported by American Society of Retina
Specialists (ASRS) in 2016, where they attributed this finding to silicone oil lining
the syringe and needle that acts as a lubricating agent to facilitate movement6.
In our
clinical practice, lots of patients report of floaters after intravitreal
Bevacizumab injection but it was never attributed to silicone oil droplets.
Only recently that we started noting presence of silicone oil bubbles in
vitreous cavity after this intervention and thus reported the three cases. None
of our patients had any symptoms related to silicone oil bubble because on both
occasions the bubble was above and away from the nodal point; and on one
occasion the BCVA was decreased to an extent that floater may not have been
noted by the patient. In one of the largest case series reported in American
Journal of Ophthalmology, it was quoted that the rate of this finding was
0.026% per injection or 0.15% per patient (A total of 7 patients reported).6 With time the complaints
of patient decreased because the oil bubble rose superiorly to pars plicata
region of fundus and became un-noticeable to patient and ophthalmologist alike.
Polydimethylsiloxane (PDMS) is the most frequently used silicone oil to
lubricate the syringes and is density is less than vitreous (PDMS: 965 kg/m3; Vitreous
1000 kg/m3).
It
should be remembered that Bevacizumab is dispensed for intravitreal use in
insulin syringes that are manufactured
with the intent of subcuticular use especially in diabetic patients. We use
syringes manufactured by Becton Dickinson (BD) and Company (30 G; 12.7mm
length; U100 1 ml Insulin Syringe BD Ultra-Fine needle, Becton Dickinson and
Company, Franklin Lakes, NJ). BD states that needles and syringes are
lubricated with silicone oil during the manufacturing process to facilitate
smooth drug delivery and less leaching of drug with syringe and needle walls.
The lubricant most likely used is 365 Dow Corning surfactant that contains 2-3%
of silicone oil7. The Dow Corning company has claimed that there are
no adverse effects related to its surfactant and that this surfactant has also
been used in other products that have human contact including food industry8.
Kocabora
reported similar finding while using injections of Pegabtanib9. Pegabtanib
was packaged in a sterile, 1-mL, USP type 1, graduated, prefilled glass syringe
fitted with a sterile 27-gauge needle manufactured by BD (similar manufacturing
process).7 Ranibizumab is
drawn up with a 19-gauge filter needle (5-um filter) and injected intravitreal
using a 30-gauge 0.5-in needle (Precision Glide, Becton Dickinson and Company,
Franklin Lakes, NJ).
Since
these syringes are very commonly used in diabetic patients, there is compelling
evidence of presence of silicone oil in these syringes in diabetic literature.
A subcuticular granulomatous reaction induced by silicone oil was found in one
case series.10 Miller et
al documents the extrusion of silicone oil from these syringes after repeated flushing
with distilled water. In another report, silicone oil became incorporated in
insulin after repeated pumping of plunger in the syringe shaft9. The
efficacy of insulin has also been reported to be decreased after getting mixed
with silicone oil. This area still remains to be unexplored whether the
efficacy of anti-VEGFs is reduced after coming in contact with silicone oil.
Perhaps further insight into this problem will give us a better idea about the
interaction of anti-VEGFs and silicone oil.
We need
to review the methodology by which pharmacies dispense Bevacizumab despite no
adverse effects have been reported due to the problem of inadvertent silicone
oil injection in eye.
Since it
has been reported that repeated pumping of plunger can lead to release of
silicone oil from hub and syringe lining, it is suggested that the drug should
be withdrawn from the vial in the syringe with minimal manipulation of plunger.
We also recommend to perform Bevacizumab stability test after being packaged in
the syringe to ensure its efficacy and to avoid any potential degradation.
Syringes have been in use which incorporate silicone oil free surfactant as
lubricant but they are slightly more expensive6. The use of such
syringes can also be suggested to avoid this potential problem.
In my impression, the incidence of this
finding is more than what we have observed in our recent experience. Possible
reasons may include ignorance towards this potential problem, busy outdoor
patient department schedules, tiny size and innocuous nature of the droplet and
the likelihood of this droplet to rise up and become un-noticeable to the
examining ophthalmologist.
CONCLUSION
In
context of this interesting observation, we recommend following changes in the
process of dispensing and injecting Bevacizumab:
Education
of pharmacists to prepare intravitreal Bevacizumab with minimal manipulation of
plunger.
Use of
Silicon oil polymer free syringes (can be discussed with SKMCH).
Revision
of consent forms for patients where this problem is well explained to the
patients.
Authors Affiliation
Dr. Haroon Tayyab
Assistant Prof. of Vitreoretina - COAVS
KEMU (Mayo Hospital Lahore)
Prof. Dr. Asad Aslam Khan
Professor & Head Department of
Ophthalmology - KEMU (Mayo Hospital
Lahore)
Dr. Muhammad Ali A Sadiq
Assistant Prof. of Ophthalmology - KEMU
(Mayo Hospital Lahore)
Dr. Sana Jahangir
Assistant Prof. of Ophthalmology - Sharif
Medical & Dental College Lahore
Dr. Suhail Sarwar
Associate Prof. of Diagnostic Opthalmology
- COAVS KEMU (Mayo Hospital Lahore)
Role of Authors
Dr. Haroon Tayyab
Principle investigator, article write-up.
Prof. Dr. Asad Aslam Khan
Literature search
Dr. Muhammad Ali A Sadiq
Literature search, discussion.
Dr. Sana Jahangir
Photography, data maintenance.
Dr. Suhail Sarwar
B-Scan, photography.
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