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

Refe

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

Refe

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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

Refe

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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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Refe

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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.