Correlation of Levator Palpebrae Superioris and Dry Eye Disease

doi:10.21203/rs.3.rs-4005099/v1

Download PDF

Research Article

Correlation of Levator Palpebrae Superioris and Dry Eye Disease

https://doi.org/10.21203/rs.3.rs-4005099/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Purpose: To evaluate the effect of levator palpebrae superioris in patients with dry eye disease.

Methods: 168 eyes of 84 patients (group 1= levator function ≤9 mm, 78 eyes; group 2= levator function >9 mm, 90 eyes) who have been diagnosed with ptosis were retrospectively enrolled. Levator function test, Ocular Surface Disease Index Questionnaire (OSDI), Schirmer I test, noninvasive tear break up time (NItBUT), corneal staining score, meibography, meibum quality and expressibility scores, tear meniscus height, and partial blinking rate (PBR) were examined.

Results: PBR and NItBUT in group 2 (9.29 ± 4.01 and 4.76 ± 2.39, respectively) were significantly worse than those in group 1 (5.88 ± 3.99 and 5.78 ± 2.94, respectively) (P<0.05). There was a significantly positive correlation between levator function and partial blinking rate (R=0.4114, P=0.0002). Meibum expressibility and lipid thickness in group 2 (0.48 ± 0.70 and 1.12 ± 0.33, respectively) were significantly better than those in group 1 (1.29 ± 0.65 and 1.39 ± 0.45, respectively) (P<0.05) (Figure 3). There was a significantly negative correlation between levator function and meibum expressibility grade (R=0.4114, P=0.0002) (Figure 2).

Conclusion: The eyes with good levator function showed shorter tear break-up time due to a higher partial blinking rate, but showed better lipid thickness due to better meibum expressibility compared with the eyes with fair levator function.

Levator palpebrae superioris

Dry eye disease

Tear break-up time

Meibum expressibility

The dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms. [1] Ptosis refers to a condition in which the upper eyelid droops and the gap between the upper eyelid and lower eyelid is small because the force of the levator palpebral muscle to open the eyes is weak. [2, 3] Depending on the time of occurrence, there are congenital ptosis that occurs from birth and acquired ptosis that occurs with age. Acquired ptosis is mainly when the function of the levator palpebral muscle weakens with age or there is a problem in the attachment site with the eyelid, causing the eyelid to droop downward. [4–6] The normal position is for the upper eyelid to slightly cover the upper part of the pupil when the eyes are opened, but in patients with ptosis, the upper eyelid droops down, covering more pupils than the normal position, and in severe cases, it can even cover the pupil. A dry eye disease could be a possible cause of aponeurogenic blepharoptosis. [2]

Although the degree of ptosis surgery varies, in most cases, since the eyes close less than before the surgery, dry eye symptoms may occur. [7–9] However, in most cases, the discomfort diminishes over time. [10] Frontalis sling surgery is the primary option for patients with weak levator action (less than 4mm). [11] Bell’s phenomenon reduces tear film instability and ocular surface damage in eyes with lagophthalmos caused by frontalis suspension surgery. [12] Compared to upper blepharoplasty, Muller muscle-conjunctival resection surgery can increase both the symptom and signs in dry eye. [9, 13] These differences result from the increase in ocular surface and corneal exposure, which produces an increase in evaporative and aqueous tear-deficient dry eye because of the loss of meibomian glands after Muller muscle-conjunctival resection surgery. [13]

There are many studies on dry eye and changes in tears that occur after ptosis surgery. However, to date, there has been no report on whether ptosis itself is related to the function of the meibomian glands or the severity of dry eyes. Recently, studies on dermatochalasis, dry eye, and meibomian gland function have been reported. In the study, it was reported that the degree of dermatochalasis showed a significant association with meibomian gland expression (MGE) and meiboscale grade. Schirmer test, tBUT and SPK did not show a significant difference. [14]

Therefore, the authors conducted a study to determine the degree of dry eye and meibomian gland function according to the function of the levator palpebral muscle.

Study Design and Patients

This retrospective study was performed in Seoul St. Mary’s Hospital at the Catholic University of Korea in Seoul, Korea. We retrospectively reviewed the medical records of 84 patients with ptosis. The data provided to us excluded all personal identifiers. This study was performed in accordance with the tenets of the Declaration of Helsinki. The Institutional Review Board (IRB)/Ethics Committee of Seoul St. Mary Hospital approved this study protocol (XC16MIMV0056H) and waived the informed consent because of the retrospective nature of the study. Those with a history of previous orbital surgery, blepharoplasty, or ocular trauma were excluded from the study.

Clinical Assessment

All patients completed a full ophthalmological examination and eyelid function test, including a slit-lamp examination. The grading of levator action consists of four cathegories (less than 4 mm – poor, 5 to 9 mm – fair, 9 to 11 mm – good, greater than 12 mm – excellent). [15] We divided patients into two groups according to fair or good levator function grades (group 1 = levator function ≤ 9 mm in more than one eye, 40 patients, or group 2 = levator function > 9 mm in both eyes, 44 patients) (Table 1). And we divided the eyes into two groups according to fair or good levator function grades (group 1 = levator function ≤ 9 mm, 78 eyes; group 2 = levator function > 9 mm, 90 eyes) (Table 2). Schirmer I tested without topical anesthetic and stained the cornea with fluorescein strips (fluorescein paper; Haag-Streit AG, Köniz, Switzerland). The corneal staining score was assigned a value ranging from zero to five points using the Sicca scoring. The noninvasive tear break up time (NItBUT) test, Ocular Surface Disease Index (OSDI) score, and tear-meniscus height were measured. Partial blinking rate was also examined by LipiView.

Table 1

Patients’s parameters according to the levator function
Parameter	Group 1 (Levator function ≤ 9)	Group 2 (Levator function > 9)
Number of eyes	40	44
F:M	30:10	28:12
Age, years (range)	73.45 ± 8.15 (55–81)	73.33 ± 6.44 (66–82)
OSDI score (range)	10.98 ± 9.36 (4–35)	7.28 ± 6.86 (2–25)
Tear Height, mm (range)	0.26 ± 0.21 (0.08–0.44)	0.29 ± 0.13 (0.12–0.44)
Schirmer I, mm (range)	11.02 ± 6.95 (5–30)	10.90 ± 5.75 (4–20)
NItBUT, sec (range)	5.68 ± 2.99 (1.5-11.85)	4.73 ± 2.27 (2.29–11.47)
Corneal Stain (range)	0.45 ± 0.76 (0–3)	0.58 ± 0.76 (0–3)
Meibomian gland dropout (range)	1.27 ± 0.62 (0–3)	1.11 ± 0.69 (0–3)
Meibum expressibility (range)	1.29 ± 0.65 (0–3)	*0.48 ± 0.70 (0–2)
Meibum quality (range)	1.26 ± 0.79 (0–3)	1.10 ± 0.79 (0–3)
Lid inflammation (range)	1.21 ± 0.78 (0–3)	1.10 ± 0.75 (0–3)
Lipid layer thickness (range)	1.39 ± 0.64 (0–2)	1.31 ± 0.77 (0–3)
Partial blinking rate (%) (range)	5.88 ± 8.99 (0–27)	9.29 ± 10.01 (0–38)
Meibum expressibility in group 2 was significantly better than that of group 1 (p < 0.05).
Group 1: Levator function < 9 in more than one eye
Group 2: Levator function ≥ 9 in both eye
OSDI: Ocular Surface Disease Index Questionnaire
NItBUT: Noninvasive tear break up time
Values are presented as mean ± SD. D; diopter

Table 2

Parameters of eyes according to the levator function
Parameter	Group 1 (Levator function ≤ 9)	Group 2 (Levator function > 9)
Number of eyes	78	90
Tear Height, mm (range)	0.26 ± 0.11 (0.09–0.50)	0.29 ± 0.13 (0.12–0.45)
Schirmer I, mm (range)	11.02 ± 6.95 (5–30)	10.90 ± 5.75 (5–26)
Corneal Stain (range)	0.45 ± 0.76 (0–3)	0.58 ± 0.77 (0–3)
Meibomian gland dropout (range)	1.27 ± 0.75 (0–3)	1.30 ± 0.77 (0–3)
Meibum quality (range)	1.18 ± 0.79 (0–3)	1.15 ± 0.81 (0–3)
Lid inflammation (range)	1.14 ± 0.77 (0–3)	1.15 ± 0.76 (0–2)
There was no statistical difference between the two groups (p > 0.05).
Group 1: Levator function < 9 in more than one eye
Group 2: Levator function ≥ 9 in both eye
Values are presented as mean ± SD. D; diopter

Measurement of the meibomian gland

A Lipiview (Johnson & Johnson Vision, Irvine, CA, USA) was used to measure meibomian gland grade and lipid layer thickness. Meibomian gland dropout was examined using infrared pictures of the upper and lower lid meibomian glands. Meibomian gland dropout was graded from 0 to 3, as reported earlier. [16] Meibum expression score (MES) and meibum quality score (MQS) were also examined, as reported earlier. [17]

Lipid layer thickness was captured by Keratograph 5M, which was graded from 0 to 3, as follows: 0, severely decreased lipid layer; 1, mildly to moderately decreased lipid layer; 2, normal lipid layer; and 3, hypersecretary lipid layer (Fig. 1).

Statistical Analysis

All statistical analyses were carried out using SPSS for Windows (version 21.0.1; SPSS Inc., Chicago, IL). The Wilcoxon signed rank test was used to compare the data before and after treatment. Comparisons among three groups were performed with one-way analysis of variance (ANOVA) with a Bonferroni post hoc comparison. The chi-square test was used for the comparison between groups of different proportions. P values < 0.05 were considered statistically significant. P values < 0.05 were considered statistically significant.

Patients’s parameters

We divided the patients into two groups according to fair or good levator function grades (group 1 = levator function ≤ 9 in more than one eye, 40 patients with 80 eyes, or group 2 = levator function > 9 mm in both eyes, 44 patients with 88 eyes).

The meibum expressibility grade in group 2 (0.48 ± 0.70) was significantly better than that in groups 1 (1.29 ± 0.65) and 2 (P < 0.05). There were no statistically significant differences between the two groups according to age, OSDI, tear height, Schirmer I, NItBUT, corneal stain, meibomian gland scores, lid inflammation grade, or lipid layer thickness grade, or partial blinking rate (P > 0.05) (Table 1).

Parameters of the eyes

We divided the eyes into two groups according to fair or good levator function grades (group 1 = levator function ≤ 9 mm, 78 eyes; group 2 = levator function > 9 mm, 90 eyes).

The partial blinking rate (%) and NItBUT (seconds) in group 2 (9.29 ± 4.01 and 4.76 ± 2.39, respectively) were significantly worse than those in group 1 (5.88 ± 3.99 and 5.78 ± 2.94, respectively) (P < 0.05) (Fig. 2). There was a statistically significant positive correlation between levator function and partial blinking rate (R = 0.4114, P = 0.0002) (n = 168 eyes) (Fig. 3).

The meibum expressibility grade and lipid thickness grade in group 2 (0.48 ± 0.70 and 1.12 ± 0.33, respectively) were significantly better than those in group 1 (1.29 ± 0.65 and 1.39 ± 0.45, respectively) (P < 0.05) (Fig. 4). There was a statistically significant negative correlation between levator function and meibum expressibility grade (R = 0.4114, P = 0.0002) (n = 168 eyes) (Fig. 5). A lower grade of meibum expressibility is better expressible.

There was no statistically significant difference between the two groups according to tear height, Schirmer I, corneal stain, meibomian gland dropout grade, meibum quality, or lid inflammation grade (P > 0.05) (Table 2).

Dry eye disease can be simply classified as an evaporative or aqueous-deficient type. Both inflammation and apoptosis play an important role in dry eye pathogenesis. [18] Treatment of DED is complicated because it is caused by a vicious cycle of tear film instability, hyperosmolarity, and ocular surface inflammation. [19]

Acquired aponeurogenic blepharoptosis can be induced by disinsertion or dehiscence of the levator aponeurosis. [4] Aponeurogenic ptosis can be caused by aging, continuous use of hard contact lens, intraocular surgery, or trauma. [20, 21] Moesen, I. et al. reported that increased eyelid friction, orbicularis tonus, and inflammation in the dry eye patient, may promote disinsertion of the levator aponeurosis after a prolonged period of time. [2] Patients with acquired aponeurogenic blepharoptosis were reported to have decreased aqueous tear production more often. Although low tear production may play a part in the etiology of acquired blepharoptosis, it could also be explained by a weakened reflex in blepharoptosis patients. [2] In our result, there was no statistically significant difference between the two groups according to tear height and Schirmer I. But those of group 2 (levator function > 9) were insignificantly increased compared with group 1 (P > 0.05) (Table 2). The reason why the tear production of both groups was not significantly different is that both groups had mild blepharoptosis (one group had fair and the other had good levator function in our result).

There were no changes in dry eye tests after blepharoplasty in patients without dry eye symptoms. [7] However, changes were prominent after ptosis surgery, especially Muller’s muscle-conjunctival resection (MMCR). [7, 8, 22] Zloto O. et al. also reported that MMCR leads to an increase both the symptom and signs of dry eye disease. [13] In patients with initial high tear volume, tear volume can decrease after the blepharoptosis surgery. [22] On the other hand, some physicians reported that the MMCR after upper eyelid blepharoplasty did not aggravate ocular surface scores or dry eye symptoms. [9, 23]

Age and mental activity influence spontaneous blinking, which complicatedly interacts with the ocular surface. [24] PBR and meibomian gland dropout rates measured with IDRA were reported to have a significant correlation with dry eye symptoms. [25] In our study, PBR and NItBUT in group 2 (9.29 ± 4.01 and 4.76 ± 2.39, respectively) were significantly worse than those in group 1 (5.88 ± 3.99 and 5.78 ± 2.94, respectively) (P < 0.05). There was a significantly positive correlation between levator function and partial blinking rate (R = 0.4114, P = 0.0002). Meibum expressibility and lipid thickness in group 2 (0.48 ± 0.70 and 1.12 ± 0.33, respectively) were significantly better than those in group 1 (1.29 ± 0.65 and 1.39 ± 0.45, respectively) (P < 0.05) (Fig. 3). There was a significantly negative correlation between levator function and meibum expressibility grade (R = 0.4114, P = 0.0002) (Fig. 2).

The reason why PBR in group 2 was higher than that in group 1 may be that the lid height of group 2 is higher than that of group 1. So we think NItBUT in group 2 was shorter than that in group 1 because evaporation increased due to higher PBR in group 2. Incomplete blinking is associated with decreased tBUT. [26] Patients with dry eye disease spent 4.5% of a minute with their eyes closed, while normal subjects spent 0.7% of a minute. [27]

And we also think the meibum expressibility in group 2 was better than that in group 1 because the lid closing pressure in group 2 may be higher than that in group 1 because of the higher gravity force of group 2 compared with that of group 1. So we think lipid thickness in group 2 was significantly better than that in group 1 because meibum expressibility in group 2 was better than that in group 1. The levator palpebrae superioris and orbicularis oculi are antagonistic muscles in eyelid motion. But motoneurons innervating the levator and orbicularis muscles were controlled by retrograde transport of WGA/HRP and HRP. [28] So we think that good levator function may have a correlation with good orbicularis muscle function.

To the best of our knowledge, there was no study about the levator palpebrae superioris function in patients with dry eye disease

In our study, there was a limitation that a multicenter clinical trial with a larger sample size and a longer follow-up period was required to observe the long-term study of levator palpebrae superioris function in patients with dry eye disease.

In conclusion, the eyes with good levator function showed shorter tear break-up time due to a higher partial blinking rate, but showed better lipid thickness due to better meibum expressibility compared with the eyes with fair levator function.

MES

Meibum expression score

MQS

meibum quality score

MMCR

Muller’s muscle-conjunctival resection

Ethics approval and consent to participate

This study was approved by the institutional review board at Seoul St. Mary’s Hospital (XC16MIMV0056H); the informed consent was waived. All clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

None

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1F1A1069218). The funding offered support in the design of the study and collection, analysis, interpretation of data, and publication fee.

Author Contribution

ECK was involved in analysis and interpretation of data and drafting the manuscript. ECK, HS, SEK, SY made contribution to acquisition of data and drafting. SY contributed to conception and design, analysis and interpretation of data, drafting and revising the manuscript. All authors read and approved the final manuscript.

Acknowledgements

None.

Availability of data and materials

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15(3):276–83.
Moesen I, van den Bosch W, Wubbels R, Paridaens D. Is dry eye associated with acquired aponeurogenic blepharoptosis? Orbit 2014, 33(3):173–177.
Lee YG, Son BJ, Lee KH, Lee SY, Kim CY. Clinical and Demographic Characteristics of Blepharoptosis in Korea: A 24-year Experience including 2,328 Patients. Korean J Ophthalmol. 2018;32(4):249–56.
Fujiwara T, Matsuo K, Kondoh S, Yuzuriha S. Etiology and pathogenesis of aponeurotic blepharoptosis. Ann Plast Surg. 2001;46(1):29–35.
Buttanri IB, Serin D. Levator Resection in the Management of Myopathic Ptosis. Korean J Ophthalmol. 2014;28(6):431–5.
Abrishami A, Bagheri A, Salour H, Aletaha M, Yazdani S. Outcomes of Levator Resection at Tertiary Eye Care Center in Iran: A 10-Year Experience. Korean J Ophthalmol. 2012;26(1):1–5.
Aydemir E, Aksoy Aydemir G. Changes in Tear Meniscus Analysis After Ptosis Procedure and Upper Blepharoplasty. Aesthetic Plast Surg. 2022;46(2):732–41.
George JL, Tercero ME, Angioï-Duprez K, Maalouf T. Risk of dry eye after mullerectomy via the posterior conjunctival approach for thyroid-related upper eyelid retraction. Orbit. 2002;21(1):19–25.
Rymer BL, Marinho DR, Cagliari C, Marafon SB, Procianoy F. Effects of Muller's muscle-conjunctival resection for ptosis on ocular surface scores and dry eye symptoms. Orbit. 2017;36(1):1–5.
Watanabe A, Kakizaki H, Selva D, Ohmae M, Yokoi N, Wakimasu K, Kimura N, Kinoshita S. Short-term changes in tear volume after blepharoptosis repair. Cornea. 2014;33(1):14–7.
Yoon JS, Lew H, Lee SY. Bell's phenomenon protects the tear film and ocular surface after frontalis suspension surgery for congenital ptosis. J Pediatr Ophthalmol Strabismus. 2008;45(6):350–5.
Zloto O, Matani A, Prat D, Leshno A, Ben Simon G. The Effect of a Ptosis Procedure Compared to an Upper Blepharoplasty on Dry Eye Syndrome. Am J Ophthalmol. 2020;212:1–6.
Wu WL, Chang SW. Dermatochalasis Aggravates Meibomian Gland Dysfunction Related Dry Eyes. J Clin Med 2022, 11(9).
Anderson RL, Dixon RS. Aponeurotic ptosis surgery. Arch Ophthalmol. 1979;97(6):1123–8.
Srinivasan S, Menzies K, Sorbara L, Jones L. Infrared imaging of meibomian gland structure using a novel keratograph. Optom Vis Sci. 2012;89(5):788–94.
Chan HH: Is the peripheral retina an important site for myopic development? [Liu, Wildsoet Y. C (2011) The effectof two-zone concentric bifocal spectacle lenses on refractive error development and eye growth in young chicks. Invest Ophthalmol Vis Sci 52(2):1078–1086]. Graefes Arch Clin Exp Ophthalmol 2011, 249(7):955–956.
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. (2007). Ocul Surf 2007, 5(2):75–92.
Baudouin C, Aragona P, Messmer EM, Tomlinson A, Calonge M, Boboridis KG, Akova YA, Geerling G, Labetoulle M, Rolando M. Role of hyperosmolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN group meeting. Ocul Surf 2013, 11(4):246–258.
Frueh BR. The mechanistic classification of ptosis. Ophthalmology. 1980;87(10):1019–21.
Paris GL, Quickert MH. Disinsertion of the aponeurosis of the levator palpebrae superioris muscle after cataract extraction. Am J Ophthalmol. 1976;81(3):337–40.
Watanabe A, Selva D, Kakizaki H, Oka Y, Yokoi N, Wakimasu K, Kimura N, Kinoshita S. Long-term tear volume changes after blepharoptosis surgery and blepharoplasty. Invest Ophthalmol Vis Sci. 2014;56(1):54–8.
Hamed Azzam S, Nama A, Hartstein M, Habib HJ, Mukari A. The Effect of Ptosis Surgery on Meibomian Glands and Dry Eye Syndrome. Ophthalmic Plast Reconstr Surg; 2023.
Su Y, Liang Q, Su G, Wang N, Baudouin C, Labbé A. Spontaneous Eye Blink Patterns in Dry Eye: Clinical Correlations. Invest Ophthalmol Vis Sci. 2018;59(12):5149–56.
Jeon YJ, Song MY, Kim KY, Hwang KY, Kwon YA, Koh K. Relationship between the partial blink rate and ocular surface parameters. Int Ophthalmol. 2021;41(7):2601–8.
Jie Y, Sella R, Feng J, Gomez ML, Afshari NA. Evaluation of incomplete blinking as a measurement of dry eye disease. Ocul Surf. 2019;17(3):440–6.
Ousler GW 3rd, Abelson MB, Johnston PR, Rodriguez J, Lane K, Smith LM. Blink patterns and lid-contact times in dry-eye and normal subjects. Clin Ophthalmol. 2014;8:869–74.
Porter JD, Burns LA, May PJ. Morphological substrate for eyelid movements: innervation and structure of primate levator palpebrae superioris and orbicularis oculi muscles. J Comp Neurol. 1989;287(1):64–81.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Correlation of Levator Palpebrae Superioris and Dry Eye Disease

Status:

Version 1

Abstract

Figures

Introduction

Methods

Measurement of the meibomian gland

Statistical Analysis

Results

Parameters of the eyes

Discussion

Abbreviations

Declarations

Ethics approval and consent to participate

Funding

Author Contribution

Acknowledgements

Availability of data and materials

References

Additional Declarations

Status:

Version 1