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Prospective study with confocal and
histological confirmation of Ophthalmic
Viscoelastic Device deposition in the
corneal subepithelium
Brendon WH Lee, Jeremy Tan, Fiona Lau, Michelle Hui, Jenny
Norman, Chris Douglas, Ashish Agar, Minas Coroneo, Ian Francis
RANZCO Tasmania: Cornea Unplugged
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rence
The authors declare no financial relationships or conflicts of interest
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Ophthalmic Viscoelastic Devices (OVDs)
are an essential component of anterior
segment surgery
DOCS: Lee, et al.
Reported adverse effects of OVD
include:
•Postoperative raised IOP1
•Capsular block syndrome2,3
•Toxic anterior segment syndrome4-7
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DOCS: Lee, et al.
Corneal deposits observed near the
sideport incision on day 1 following
uneventful phaco
DOCS: Deposition of OVD in the
Corneal Subepithelium
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Corneal deposits seen on slit lamp examination
Fig 1A. Presumed OVD deposition within the corneal
epithelium below the healed sideport region.DOCS: Lee, et al.
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Corneal deposits seen on slit lamp examination
Fig 1B. Presumed OVD deposition within the corneal
epithelium below the healed sideport region (zoomed).DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
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rence
The authors declare no financial relationships or conflicts of interest.
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To study the incidence and possible aetiological
factors of DOCS
To confirm and assess the nature of DOCS using:
• Confocal microscopy
• Light microscopy
• Electron microscopy
• Mass spectrometry
Prospective, consecutive study
1
2
3
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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212 patients
1 excluded
Total: 211
Recruitment
Single surgeon
Phaco stop-and-chop
Viscoat®
Provisc®
Injected via sideport
Procedure
• Day 1
• Week 1
• Month 1
Samples
harvested
DOCS
Age
Gender
Nuclear sclerosis grade
Postop complications
Duration of surgery
Preop/postop CDVA
Parameters
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Refe
rence 211 patients:
• Age: 71
• 64% female
• NS: 2.37 (LOCS III)
• No postoperative
complications
Parameters:
• Visual Outcomes:
96% (203): 6/6
93% (196): 6/4
• Mean surgery
duration = 37.80
minutes (8.48 SD)
DOCS:
Overall incidence: 34%
Day 1 = 6.2%
Week 1= 27.5%
Month 1 = 15.2%
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Light microscopy of DOCS
Fig 2. Corneal epithelial specimen from left eye
(H&E staining, 400x).DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Confocal microscopy of DOCS
Fig 3. Corneal epithelial specimen demonstrating an intact
vacuole with surrounding meniscus effect of emulsified OVD.DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Confocal microscopy of probable DOCS entry pathway
Fig 4. Probable pathway of OVD ingress into corneal
subepithelium, traversing between epithelial cells.DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Refe
rence Electron microscopy
Mass spectrometry
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Repeated measures ANOVA
demonstrates a positive relationship
between postoperative time and initial
presence of DOCS on day 1:(F1.81,376.20 = 12.15, p ≤ 0.001)
More DOCS at one week (p < 0.001)
and one month (p = 0.001)
than at one day
Statistical Analysis for DOCS
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Spearman correlation
Positive for duration of surgery and presence of
DOCS but only for 2.2% of the variance
(r = 0.0148, p = 0.032, r2 = 0.022)
Binary logistic
regression model
No further significant
predictors (p 0.05)
Statistical Analysis for DOCS
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Historically, OVD deposition has been reported elsewhere:
• In the intrastromal cornea8-11
• Between Descemet’s membrane and corneal stroma12-14
• On anterior surface of posterior lens capsule15
No previous documentation of DOCS16
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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• The correlation of DOCS with duration of surgery is
likely due to:
1. More OVD used in longer, more difficult cases
2. Patients having Fuchs’ or EBM dystrophy
3. Longer phaco times17,18
• However, this correlation only explained 2.2% of cases
• Therefore, there are likely to be other mechanisms for
DOCS
• But, DOCS seems to be longstanding
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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1
2
3
DOCS: 15.2% of 211 phaco cases at 1 month
DOCS was confirmed by confocal and light
microscopy
Mechanism of DOCS is still unclear
4 DOCS had no adverse surgical or visual
outcomes
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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Thank you.
Brendon W. H. Lee (UNSW)
Email – brendon-lee@live.com.au
Thanks to A/Professor Ian Francis, Professor Minas
Coroneo, and Dr. Ashish Agar for their guidance.
Special thanks to Dr. Douglas and Dr. Norman for their
expertise.
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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1. Assia EL, et al. Removal of viscoelastic devices after experimental cataract surgery in vitro. J
Cataract Refract Surg. 1992;18(1):3-6.
2. Durak I, et al. Early postoperative capsular block syndrome. J Cataract Refract Surg.
2001;27(4):555-559.
3. Theng JT, et al. Capsular block syndrome: A case series. J Cataract Refract Surg.
2000;26(3):462:467.
4. Athomali TA. Viscoelastic substance in prefilled syringe as an etiology of Toxic Anterior Segment
Syndrome. Cutan Ocul Toxicol. 2016;35(3):237-241.
5. Mamalis N, et al. Toxic anterior segment syndrome. J Cataract Refract Surg. 2006;32(2):324-
333.
6. Eydelman MB, et al. The Food and Drug Administration’s Proactive toxic anterior segment
syndrome Program. Ophthalmology. 2012;119(7):1297-1302.
7. Leder HA, et al. An investigation of enzymatic detergents as a potential cause of toxic anterior
segment syndrome. Ophthalmology. 2012;119(7):e30-35.
8. Nevyas AS, et al. Acute Band Keratopathy Following Intracameral Viscoat. Arch Ophthalmol.
1987;105(7):958-964.
9. Ullman S, et al. Corneal opacities secondary to Viscoat. J Cataract Refract Surg.
1986;12(5):489-492.
10. Binder PS, et al. Calcific Band Keratopathy After Intraocular Chondroitin Sulfate. Arch
Ophthalmol. 1987;105(9):1243-1247.
11. Coffman MR, et al. Corneal subepithelial deposits after use of sodium chondroitin. Am J
Ophthalmol. 1986;102(2):279-280.
12. Ostberg A, et al. Management of detachment of Descement’s membrane caused by injection of
hyaluronic acid Ophthalmic Surg. 1989;20(12):885-886.
DOCS: Lee, et al.
Prospective study on the ocular
manifestations in inherited
epidermolysis bullosa
Brendon WH Lee, Jeremy CK Tan, Melissa Radjenovoic,
Lien Tat, Minas T Coroneo, Dedee F Murrell
Paediatric Symposium
Refe
rence
The authors declare no financial relationships or conflicts of interest.
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13. Chay E, et al. Descemet’s Membrane Dehiscence Resulting From Misdirected Viscoelastic During
Anterior Chamber Reformation. Eye Contact Lens. Doi: 10.1097/icl.0000000000000378.
2017.06.14.14. McConnell LK, et al. Inadvertent intrastromal injection of ophthalmic viscoelastic. J AAPOS.
2013;17(6):639-641.
15. Mathys KC, et al. Identification of unknown intraocular material after cataract surgery:
Evaluation of a potential cause of toxic anterior segment syndrome. J Cataract Refract Surg.
2008;34(3):465-469.
16. Bissen-Miyajima H. Ophthalmic viscosurgical devices. Curr Opin Ophthal. 2008;19(1):50-54.
17. Holst A, et al. Formation of free radicals using phacoemulsification. Curr Eye Res.
1993;12(4):359-365.
18. Cameron MD, et al. Identification of free radials produced during phacoemulsification. J
Cataract Refract Surg. 2001;27(3):463-470.
Acknowledgements:
Power point design to: https://powerpointschool.com/
Icon design from Authors: Smashicons, Freepik, Skyclick, Eucalyp, Prosymbols, accessible
from www.flaticon.com/
DOCS: Lee, et al.
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