Summary of doctor of medicine thesis researching the effectiveness of lengthening levator muscle surgery to treat moderate and severe eyelid retraction

In Vietnam, there has not been any research mentioning the surgery method to lengthen levator muscle using orbital septum flap.. In order to contribute to improving the surgical efficien

In 2002, Lai CS et al reported a clinical case on a new technique for treating UER by using an orbital septum flap as a spacer to lengthen the levator muscle In 2013, author Watanabe A et al conducted a multi-center study applying the technique of Lai CS on 12 patients experiencing upper eyelid retraction The results showed that 70% of patients achieved good results

In Vietnam, there has not been any research mentioning the surgery method to lengthen levator muscle using orbital septum flap Previous author's reports did not mention the factors related to the long-term outcome and effectiveness of surgery In order to contribute to improving the surgical

efficiency of treating UER, we conduct research on the topic "Researching the effectiveness of lengthening levator muscle surgery to treat moderate and severe eyelid retraction" with two sections

1 Evaluate the results of lengthenning upper levator muscle surgery to treat moderate and severe eyelid retraction

2 Analysis of factors related to surgical results

THESIS’S NOVEL CONTRIBUTION

This is the first study on the use of a flap to the orbital septum to lengthen the levator muscle to treat cases of moderate and severe UER in a study with a large-enough number of patients The follow-up time is long enough to comprehensively evaluate the outcome of surgery

Determine the relation to the outcome of the surgery: history of treatment

of eyes, position of eyelid retraction

STRUCTURE OF THE THESIS

The thesis consists 135 pages, including Introduction (2 pages), 4 chapters: Chapter 1: Overview (27 pages), Chapter 2: Subjects and research methods (15 pages), Chapter 3: Research results (40 pages), Chapter 4: Discussion (47 pages), Conclusion (2 page), novel contribution (1 page), Proposal (1 page) There are also: references, appendices, tables, charts, illustrations of the results

CHAPTER 1: OVERVIEW 1.1 Anatomy of eyelid physiology

Eyelid is a complex structure that plays an important role in maintaining visual function Eyelids are limited to orbital organizations in the orbital septum

1.1.2 Eyelid anatomy

* Orbicularis ocular muscle

The eyelid part of the orbicularis ocular muscle contributes to the skin crease of the eyelids what dominates by nerves VII

* Orbital septum

From the eyelid septum membrane, the orbital septum moves towards the front, through the orbicularis ocular muscle of the anterior fat pad of the muscle This position is usually 3 - 5 mm from the margin of the tarsal

* Muller's muscle

The smooth muscles governed by the sympathetic nervous system exist in both the upper and lower eyelids Muller's muscles are 8 to 12 mm long, 0.5 – 1.0 mm thick

* Vascular and nerve

- Artery: eyelid artery system is separated from two main sources: eyelid artery and facial artery

- Vein: there are two veins in the eyelids: shallow vein network and deep vein network

- Lymph: includes superficial lymphatic plexus and deep lymphatic plexus

- Nerve: Motor nerves (the branches of the nerve III, VII), sensory nerves

(branch V1, V2), sympathetic nerves

1.2 The pathology of UER

1.2.1 Definition

Upper eyelid retraction (UER) is defined as an elevation beyond the normal position of the upper eyelid margin in the primary visual position (normally, in a straight forward position, the eyelid margin covers the upper edge of the cornea, 2 mm from the 12-hour-angle edge of the cornea)

1.2.2 Cause

UER is the consequence of many causes with one or more different pathogenetic mechanisms and in many cases the exact cause cannot be identified Barley divides the causes of UER into 3 groups:

1.2.2.1 Muscular causes

The Muller's muscle inflammation and fibrosis process ranges from a sparse to a dense level that causes changes from muscle atrophy, fat infiltration or fibrosis to increase muscle size Similarly, the levator muscle also has changes including striated muscle atrophy, fat infiltration, collagen proliferation and mast cell infiltration

1.2.2.2 Neurological causes

Common in congenital UER or common in the posterior brainstem syndrome, neuropathic regeneration III, myasthenia gravis that causes UER in the opposite side (Herring Law), orbicularis ocular muscle weakness due to paralysis VII

- Von Graefe sign: This is an abnormally related change in the eyelid movement

- Lagophthalmos: is a condition where the eyes are not closed properly when the patient closes the eyes or when sleeping

- Incomplete blinking (Stellwag sign)

- Regular or irregular eyelid retraction: Eyelid retraction occurs in the center 1/3 or in the lateral 1/3

- Over-reaction of the levator muscle - superior rectus due to reaction with inferior rectus

- Proptosis due to increased orbital septum volume, the eyeball is pushed forward, the eyelids shrink back on the eyeball

1.2.3.3 Subclinical characteristics

- CT Scan

- The tests of thyroid hormone FT3, increasing FT4 , decreasing TSH Tests for anti-thyroglobuline antibody, anti-TPO, increasing anti-receptor of TSH (TrAb) TrAb increases the specificity for Basedow's illness

1.2.4 Diagnosis

1.2.4.1 Definitive diagnosis

UER is definitively diagnosed based on the following factors:

- Functional symptoms: Having symptoms such as blurred vision, redness

of the eyes, dizziness, and watery eyes

- Physical signs:

+ MRD1 > 4 mm

+ PFH > 10 mm

+ Lid lag > -1 mm

+ Upper sclera show on varying degrees

+ May lose the physiological contour of the eyelids margin (C 2 mm), often is a sign of lateral flare

+ Lagophthalmos

1.2.4.2 Differential diagnosis

- UER due to eyelid drooping at the opposite according to Hering’s Law

- Vertical strabismus in upgaze causing sclera show

1.2.4.3 Diagnosis of degree of eyelid retraction

Elner et al classify eyelid retraction according to the distance from the corneal reflex to the eyelid margin in the primary position (MRD1 index)

- Mild UER: MRD1< 5 mm

- Moderate UER: MRD1 = 5 – 7 mm

- Severe UER: MRD1 > 7 mm

1.2.5 Treatment of upper Eyelid retraction

1.2.5.1 Medical treatment

Medical eye treatments include:

* Use Guanethidine eye drops

This is a sympatholytic drug that is used to lower eyelids However, the use

of this drug has many limitations due to side effects

* Botulinum toxin A (Botox) injection method

Some authors have used the Botox injection method under conjunctiva for UER patients with very positive results

* Steroid injection method

Steroid injections around the eyeball or under the conjunctiva may be considered when total and oral routes are not applicable

* Method of using Hyaluronic Acid (HA) filler

This is an aesthetic improvement method However, this method also has limitations

1.2.5.2 Surgical treatments

* The method of cutting or reversing the levator muscle with Muller's muscle cutting

For severe eyelid retraction this surgery is not enough to adjust the

position of the upper eyelid to normal level

* Methods of using spacers

The spacers is relatively hard, and there is no feeding circuit, so the results are quite limited in improving the aesthetics and there are risks of removal or rejection of the spacer

* Methods of using flaps

Rotating the flap with different lengths, depending on the degree of extending the wall needed is determined by the cooperation of the patient

1.3 Surgery to lenghthen the upper levator muscle by using rotation orbital septum flap

1.3.1 Summary of research history

In 2002, Lai CS et al first described the technique of using the orbital septum flap to form a natural cartilage to lengthen the upper levator muscle

In 2013, author Watanabe A and his colleagues performed this technique on

10 patients with 12 eyes with upper eyelid retraction due to Basedow and used orbital septum flap as a material to lenghthen the levator muscle

1.3.2 Indication

Surgery is indicated for cases of moderate and severe eyelid retraction, lateral flare, patients who have not had eyelid surgery, patients with Basedow eyelid retraction have been stabilized for at least 6 months

In Vietnam, there are many authors who perform surgery to extend the upper levator muscle with many different materials at major ophthalmic centers such as Hospital 108, Hospital 103, National Hospital of Ophthalmology, Ho Chi Minh Hospital of Ophthalmology The materials used in this surgery are relatively diverse, including lip mucosa membrain, ear cartilage, palate cartilage However, there have been no studies using the flap

of the orbital septum to extend the upper levator muscle

CHAPTER 2 SUBJECTS AND METHODS OF THE STUDY

2.1 Researched subject group

The subjects of the study were patients with moderate and severe Eyelid retraction who were examined, diagnosed and treated at Vietnam National Eye Hospital from October 2016 to October 2019

2.2 Method of research

2.2.1 Research design

Non-controlled clinical trial study

2.2.2 Sample size

Apply the following formula to calculate the sample size:

Therein:

+ n = minimum number of eyes to be studied

+ z = 1.96 (according to the table corresponding to 95% CI value)

+ p = 90,6 % According to Schaefer's success rate of 90.6 (2007)

+ q= 1-p

+ : error in research (choose  = 6.3%.)

According to the above calculation formula, the result is: n = 45 In fact, the study had 46 eyes of 43 patients

Methods of selecting samples: Select the eligible patients one after another

* Processing data by statistical algorithms, using SPSS 15.0 software

2.2.4 Research facilities

* Equipment for examination: Snellen vision table, millimeter measure,

Hertel proptosis ruler, eye examination microscopy, ophthalmoscope, Volk

ophthalmoscopes, cameras, medical records

* Surgical equipment: Eyelid surgery kits, bipole electric burners, surgical microscopes, shock-proof kits

+ MRD1: Measure the distance from the pupil's reflected light to the

eyelid margin at 12 o'clock in a straight looking position

+ MRD1 difference (MRD1) = MRD1 (UER eye) - MRD1 (normal

eye)

Or if the other eye is abnormal:  MRD1 = MRD1 (UER eye) – 3,5 mm

+ Palpebral fissure height_ PFH : The height of the skin crease is

measured from the midpoint of the free margin of the upper eyelid to the midpoint of the free margin of the lower eyelid

+ PFH difference (PFH): PFH = PFH (UER eye) – PFH (normal eye)

Or if the other eye is abnormal:  PFH = PFH (UER eye) – 10

+ Skin crease height assessment (SC): The height of the crease is

measured from the free margin of the eyelids to the crease when the eye looks downwards

+ Skin crease difference: ( SC) = SC (normal eye) – SC (UER eye) + Curvature assessment (C): This index is measured by the distance from

the highest point of the upper eyelid margin to the center point between the eyelid and the center of the cornea

+ Sclera show assessment: sclera show index is calculated from the edge

of the cornea to upper eyelid margin at 12 o'clock when the eyes are in a straight looking position

+ Lagophthalmos assessment: Ask the patient to close his eyes to sleep

gently and assess whether the eyelids are completely closed

+ Lid lag (loss of synergy between eyelid and eyeball): Lid lag is

calculated by the difference of the MRD1 in the downward and straight looking positions

+ Proptosis assessment: The Hertel ruler is placed parallel to the plane

across the 2 cornea vertices allows the measurement of the proptosis

+ Difference proptosis:  proptosis = UER eye's proptosis - normal eye's proptosis

+Levator function assessment (LF): Use a millimeter ruler to measure

the amplitude of the movement of the upper eyelid in the center when maximally looking down and maximally looking up as the forehead muscle has been blocked at the reflection in the pupil at 12 o'clock when the eye is fully downward-looking

+ Assess position of retraction: medial 1/3, center 1/3, lateral 1/3

2.2.5.3 Subclinical

- CT scan to determine the mobility condition and the nerve condition

- Tests to evaluate thyroid function: FT3, FT4, TSH, TrAb, thyroid ultrasound

- General tests prepared for surgery

2.2.5.4 Surgery

* Surgical steps

The steps are as follows:

- Posture of the patient: Lying on the back, disinfected, lying on surgical towels which allows to sit up, local anesthesia with Dicain solution

- Mark the skin incision on the expected skin crease or under the crease of the opposite eye For cases where the 2 eyes do not have creases, the height of the crease is expected based on the standard Asian creases (5-7 mm) If the patient has retraction in both eyes and needs surgery for both eyes, the incision of the skin crease can be used according to the old skin creases

- Local anesthetic under the eyelids with a 2% Lidocaine solution mixed with Epinephrine 1: 100,000

- Incise the skin with knife number 15 with the length of skin incision from 25 - 30 mm Hemostasis under the skin

- The anatomy reveals and separates the septum of the levator muscle from the orbicularis ocular muscle and the tarsal Continue to separate the levator muscle from the conjunctiva and remove the Muller's muscle

- From the position of the skin incision, surgery up to 5 mm to reach the orbital septum From here, we need to dissect the orbital septum and turn over the flap by 180 degree so that the edge the flap goes down and connected to the levator muscle The width of the orbital septum flap is fixed based on the length of the upper eyelid tarsal with a size of about 20 mm However, the height of the flap of the orbital septum can be adjusted according to the degree

- Suture the skin, creating eyelids with nylon 7.0

- Fixed two stitches which pull down the cheeks with tape

- Apply antibiotic ointment, and compress-patch the eye

* Care and Post-operative follow-up

- Medicine: Pain relief, antibiotic, anti-edematous, antibiotic ointment

- Apply cold compress for 48 hours, change the dressing daily, cut the stitches after 7 days, maintain 2 fixed stitches pulling down the cheek for 1 week with adhesive tape

* Follow-up

- Visit again after 1 week, 1 month, 3 months, 6 months and 12 months

* Detect complications and handle complications if any

- Bleeding: mild: Use bandage, hemostatic drug, severe: Open the incision

to remove the hematoma

- Infected: antibiotics combined with immunotherapy

- Injury of the eyeball: Treatment depends on each injury

- Granulomas: Removing granulomas under surgery

- Occur again periodically: Re-surgery after 6 months if indicated

2.2.6 Research variables and indicators

The research results were collected through research records and evaluated and categorized according to Mourits and Sasim's research Results are evaluated at 1 month, 3 months, 6 months and 12 months before and after surgery Research variables and indicators are categorized as follows:

Table 2.1: Methods to evaluate variables and research indicators

Variable name Variable

type

Methods and tools for data collection

Goal 1

Ruler Research medical records

Illness duration Quantitative

Duration of disease stability Quantitative

History of eye treatment Qualitative

History of systemic disease Qualitative

Position of UER Qualitative

Damage to the ocular surface Qualitative

Lagophthalmos condition Quantitative

Proptosis difference Quantitative

Size of orbital septum flap Quantitative

2.2.7 Methods to evaluate overall results

In the surgical evaluation criteria, the upper eyelid position index (MRD1), the C index, the PFH difference, the crease height, the crease height difference and the patient satisfaction level are the criteria that affect the overall outcome of surgery,

In which MRD1 and eyelid contour C are the other main criteria, the remainders are sub-criteria [95] The criteria related to the general outcome of surgery are categorized and evaluated according to the following score level:

Table 2.2: Evaluate research criteria

Critera 3 points 2 points 1 points

Table 2.3: Assess the level of patient satisfaction

Criteria 3 points 2 points 1 points

Satisfaction level Very satisfied Satisfied Not satisfied

Evaluate general results according to the above criteria with 3 levels: Good, medium and poor based on the results of the overall scores of each research indicator according to Mourit and Sasim's classification as follows:

Table 2.4: Evaluate the results according to the levels

Class: Good Average Poor

Total

score

15 12-14 < 12 and at least 1 main indicator

is poor Evaluation after surgery, results are good and average is considered successful, poor results are considered failure

2.3 Data processing and analysis

Data collected from research records will be processed using medical statistical methods using SPSS 16.0 software

CHAPTER 3 RESEARCH RESULTS

Our study was conducted on 43 patients with 46 moderate-to-severe UER eyes who were examined and treated with extending levator muscle surgery Orbital septum flap at Vietnam National Eye Hospital since October 2016 to October 2019 Through data analysis we have obtained the following results:

3.1 Characteristics off the researched subjects

3.1.1 Patient characteristics

In the study, 43 patients including 41.80% The average age is 33.35 32.5 years old Age group 17 - 50 has the highest proportion, accounting for 86.04%

3.1.2 Eye characteristics

7/46 eyes studied were caused by thyroid related to orbitopathy (15.22%), 7 congenital UER eyes (15.22%), 69.56% temporarily idiopathic 11 patients with a history of pathology (diabetes, hypertension ) accounted for 25.58% 74.42% of study patients had no previous medical history 13.04% of eyes had a history of previous eye surgery

Visual acuity of the group under 20/70 accounts for the highest proportion with 86.96% The subjective symptoms for patients who visit and receive treatment include 3 blurred vision (6.50%), 2 red eyes (4.30%), 4 teary eyes (8.70%) and 5 limited mobility (10.90%) 69.57% of patients come for aesthetics treatment 28.30%, eyes had slight damage to the surface of the eyeball (superficial keratitis, fibrous keratitis, dry eye) The average duration of illness was 68 months The median duration of stable treatment was 61 months

The study was conducted on 10 severe UER eye (21.74%) and 36 medium UER eye (78.26%) 36 eyes had UER in the central position (center 1/3)

The average MRD1 and PFH of the two groups was 5.97 ± 0.85 mm and 12,65  1,41 mm, respectively The group of severe UER had the largest sclera show of 2.30 ± 0.95 mm, which is higher than the level of moderate UER, of 1.53 ± 0.56 mm The sclera show degree of 1.70 ± 0.73

mm The eyelid curvature of the severe group was 1.20 ± 2.53 mm The average lid lag of the 2 groups was 2.26 ± 1.07 The levator function and skin crease are and 5.38 ± 0.89 mm 14,24  2,12 mm, respectively