J Korean Ophthalmol Soc.  2016 May;57(5):691-699. 10.3341/jkos.2016.57.5.691.

Effect of Mixed Injection of Botulinum Neurotoxin, Triamcinolone and 5-Fluorouracil in Graves' Upper Eyelid Retraction

• Sung YJ
• Park JS
• Lew H

• KMID: 2212709
• DOI: http://doi.org/10.3341/jkos.2016.57.5.691

Abstract

PURPOSE
The aim of this study is to evaluate the effects and complications of mixed injections of botulinum neurotoxin A (BoNT-A), triamcinolone acetonide, 5-fluorouracil (5-FU) in patients with Graves upper eyelid retraction.
METHODS
Twenty-four eyes of 17 patients with a mean age of 43.9 years showed symptoms of Grave's upper eyelid retraction (GUER). They received mixed injections of BoNT-A 4 IU/0.1 mL, triamcinolone acetonide 4 mg/0.1 mL and 5-FU 5 mg/0.1 mL via subconjunctival injection. The response to treatment and the presence of adverse effects were followed up for 9.0 ± 6.0 months and evaluated retrospectively.
RESULTS
Margin reflex distance 1 decreased significantly from 5.6 ± 1.2 mm to 4.7 ± 1.1 mm at 1 month after injection. Tarsal platform show increased significantly from 1.4 ± 1.3 mm to 1.8 ± 1.3 mm, and tear break up time increased significantly from 5.2 ± 3.1 seconds to 10.3 ± 7.8 seconds. When success was defined as the correction amount of GUER being larger than 1 mm, the success rate was 66.7%. Kaplan-Meier survival analysis showed that GUER correction effects last longer in patients with a duration of disease longer than 6 months. There were no severe adverse effects such as diplopia, blepharoptosis and intraocular pressure elevation.
CONCLUSIONS
Mixed injections of BoNT-A, triamcinolone acetonide and 5-FU, which compensate the side effects of solitary injection and enhances the anti-fibrotic effect, improves the eyelid position and tear film stability in the patients with GUER. It is an effective and safe method for treating GUER with long maintenance with less adverse effects.

Keyword

Botulinum neurotoxin A; 5-Fluorouracil; Graves upper eyelid retraction; Periocular injection; Triamcinolone

MeSH Terms

Blepharoptosis
Botulinum Toxins, Type A
Diplopia
Eyelids*
Fluorouracil*
Humans
Injections, Intraocular
Intraocular Pressure
Reflex
Retrospective Studies
Tears
Triamcinolone Acetonide
Triamcinolone*
Botulinum Toxins, Type A
Fluorouracil
Triamcinolone
Triamcinolone Acetonide

Figure

• 

  Figure 1. Morphologic outcome measurement. MRD1 = margin reflex distance; IPF = interpalpebral fissure; TPS = tarsal platform show; MLD = margin limbal distance.

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  Figure 2. Clinical outcomes after mixed injection of botulinum neurotoxin A (BoNT-A), triamcinolone and 5-fluorouracil (5-FU) in Graves’ upper eyelid retraction. MRD = margin reflex distance; IPF = interpalpebral fissure; TPS = tarsal platform show; MLD = margin-limbal distance; BUT = break-up time; TAO-QoL = thyroid associated ophthalmopathy quality of life questionnaire; LTMH = lower eyelid tear meniscus height. ∗p< 0.05, Wilcoxon signed-rank test.

• 

  Figure 3. Tear film stability before and after mixed injection of botulinum neurotoxin A (BoNT-A), triamcinolone and 5-fluorouracil (5-FU) in Graves’ upper eyelid retraction. 35 year-old female patient with Graves’ upper eyelid retraction (Case #9). Mixed injection of BoNT-A, triamcinolone and 5-FU was performed in the both upper eyelid. Margin reflex distance 1 (MRD1) decreased from 6.4 mm and 5.2 mm (A) to 3.8 mm and 3.9 mm (B) after 3 month. Spectralis optical coherence tomography shows lower eyelid tear meniscus height decrease after mixed injection (C, D). Keratogragh shows almost broken tear film of the left eye (E, red color) and recovered status after mixed injection (F, green color). OD = oculus dexter; OS = oculus sinister.

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  Figure 4. Kaplan-Meier Survival Analysis for Graves’ upper eyelid retraction Correction following mixed Injection of botulinum neurotoxin A (BoNT-A), Triamcinolone and 5-fluorouracil (5-FU).

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  Figure 5. Case series before and after mixed injection of botulinum neurotoxin A (BoNT-A), triamcinolone and 5-fluorouracil (5-FU) in Graves’ upper eyelid retraction. 43 year-old female patient with Graves’ upper eyelid retraction (Case #2, A, B). Mixed injection of BoNT-A, triamcinolone and 5-FU was performed in the both upper eyelid. Margin reflex distance 1 (MRD1) decreased from 6.2 mm and 6.8 mm (A) to 5.0 mm and 5.1 mm (B). 28 year-old female patient with Graves upper eyelid retraction of her right eye (Case #12, C, D). MRD1 decreased from 4.6 mm (C) to 3.4 mm (D). 40 year-old female patient with Graves upper eyelid retraction of her right eye (Case #17, E, F). MRD1 decreased from 5.2 mm (E) to 4.1 mm (F).

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