Application of anterior scleral thickness measurement in different ocular conditions using anterior segment optical coherence tomography, a systemic review

来源期刊： Eye Science | 2024年12月第1卷第4期： 328-342 发布时间：2024-12-20 收稿时间：2024/12/17 9:22:11 阅读量：51

作者：: 孟丽慧,

于仟仪,

杨景元,

陈有信,

关键词：: anterior scleral thickness anterior segment optical coherence tomography ocular disorder clinical implication; anterior scleral thickness anterior segment optical coherence tomography ocular disorder clinical implication

DOI：: 10.12419/es24090202

Received date：: 2024-09-02
Accepted date：: 2024-10-16
Published online：: 2024-12-20

Purpose: To conduct a review to systematically evaluate the use of anterior segment opticalcoherence tomography (AS-OCT) in measuring anterior scleral thickness across diverse ocularconditions and its clinical implications. Methods: Literature search was conducted across electronicdatabases, including PubMed, Scopus, and Embase, to identify relevant studies. The risk of biaswas assessed, and the main characteristics of each studies were analyzed. We calculated theoverall mean anterior scleral thickness using the data which have measurement at the same locations. Results: A total of 32 studies were included that utilized AS-OCT to measure anterior scleralthickness in both healthy subjects and individuals with ocular disorders such as myopia, keratoconus, scleritis, and others , The review found that anterior scleral thickness is signiicantly influenced by age, diurnal variation, and specific ocular conditions. For example, myopic eyes mayexhibit thinner sclera, particularly along certain meridians, while conditions like scleritis showecincreased scleral thickness due to inflammation, However, some studies have inconsistent resultsAdditionally, AS-OCT proved effective in detecting subtle variations in anterior scleral thickness. which could be linked to the progression of ocular diseases. Conclusions: Anterior scleral thicknessvaries considerably depending on age, time of day, and ocular health, making it a valuable parameterin the assessment of eye conditions. AS-OCT's ability to measure these variations non-invasivelybroadens its application in both clinical practice and research, offering new insights into thebiomechanical properties of the sclera and their implications for ocular diseases.

HIGHLIGHTS

•Anterior scleral thickness is affected by age, daily variations, and ocular diseases, making it crucial for assessing eye health.

•AS-0CT provides a non-invasive method to measure anterior scleral thickness as an indicator of ocular health, which is an area with limited systemic reviews and signifcant research potential.

•AS-0CT may enhance clinical evaluation and research on ocular biomechanics, aiding in disease monitoring and progression understanding.

INTRODUCTION

The sclera is a crucial component of the eye.forming around 85% of the outer tunic of the humaneyeball. It is a connective tissue that consists of irregularlyarranged lamellae of collagen fibrils interspersed withproteoglycans and glycoproteins, serving as a protectivelayer that maintains the shape ofthe eyeball and providesan attachment point for the extraocular muscles.^[1] It canalso influence the biomechanical characteristics of manyintraocular tissues, such as the cornea. A variety ofoculardisorders affect the sclera, such as scleritis, myopia, andcentral serous chorioretinopathy (CSC).^[2-4]The seleralthickness may change with different ocular conditionsNowadays, limited imaging techniques are available forcomprehensively analyzing the whole structure of thesclera. Ultrasound biomicroscopy and anterior segmentoptical coherence tomography (AS-OCT) can be usedto visualize the anterior segment, including the anteriorsclera.^[5]At present, OCT can also visualize the sclera othe posterior pole in highly myopic eyes.

The advent of AS-OCT has revolutionized the evaluation of anterior ocular structures, including theanterior sclera.^[6] AS-OCT offers high-resolution, non-invasive imaging that allows for precise measurementof anterior scleral thickness in vivo. Initially, the ASOCT was developed for the assessment of the corneaand anterior chamber. AS-OCT has expanded its utilityto include detailed visualization of the sclera, providingclinicians with valuable insights into the structuralintegrity and pathology of the eye. The growing body ofresearch utilizing AS-OCT underscores its importancein advancing our understanding of ocular biomechanicsand pathology, Recently, researchers have utilized AS.OCT to investigate the anterior scleral thickness not onlyin healthy eyes, but also in certain ocular disorders suchas keratoconus, myopia, CSC and others.^[3-4,7]Given thecritical role of the sclera in maintaining the structuralintegrity of the globe and regulating choroidal venousflow and intraocular pressure, changes in scleral structurecan serve as indicators of susceptibility to various oculardiseases.^[8-9] These changes are often reflected in scleralthickness measurements. Compared to ultrasoundbiomicroscopy, AS-OCT, with its superior axial resolution of 10 um, offers a more effective and precisetool for evaluating these conditions.^[4,10]

The purpose of this systematic review is to identifand summarize the current literature regarding to theanterior scleral thickness measurement in different ocularconditions. By systematically evaluating the availableevidence, we aim to better understand the anterior scleralchanges in certain ocular diseases and to suggest futuredirections of research.

METHODS

Search strategy

A comprehensive literature search was conductedacross electronic databases, including PubMed, Scopusand Embase, to identify studies on measurement ofanterior scleral thickness using AS-OCT across differentocular conditions. The search strategy employed acombination of Medical Subject Headings (MeSH) termsand keywords related to "scleral thickness", "opticalcoherence tomography" and "anterior segment OCT" The search was limited to articles published in Englishand included studies from the inception of the databasesuntil January 2024. Bibliographies of selected articleswere also reviewed to identify any additional relevantstudies.

The inclusion criteria and exclusion criteria

The inclusion criteria were as follows: 1) useof AS-OCT to measure anterior scleral thickness; 2) quantitative measurements of anterior scleral thickness; and 3) full-text available.

The exclusion criteria were as follows: 1) involvedanimal subjects or cadaveric eyes; 2) used imagingtechniques other than AS-OCT; 3) no information aboutanterior scleral thickness; 3) case reports, reviews, editorials, or conference abstracts without full text.

Data extraction and risk of bias assessment

Data extraction was performed independentlyby two authors (Lihui Meng and Qianyi Yu) using astandardized data extraction form, The extracted dataincluded study characteristics (author, year of publication, country), population characteristics (age, sex, ocularcondition), AS-OCT parameters (device used), outcomes(mean anterior scleral thickness, standard deviation, measurement locations) and main study conclusions. Discrepancies between reviewers were resolved throughdiscussion or consultation with the corresponding author(Youxin Chen).

For risk of bias assessment, we used the Newcastle-Ottawa Scale (NOS) and the JBl Critical AppraisalChecklist for analytical cross-sectional studies to assess(as shown in supplementary file 1 and 2). The NOSincluded the following items: 1) the representativenessof the sample; 2) risk of bias in the measurementof exposures; 3) risk of bias in the measurement ofoutcomes; 4) risk of bias due to confounding factors. And the JBI Checklist included eight items includinginclusion criteria, study subjects, exposure, objective, confounding factors, strategies to deal with confoundingfactors, outcome measurement and statistical analysis.

Data synthesis

We did not perform any meta-analysis becauseof the heterogeneity of these studies. In our study,heterogeneity primarily arose from differences inthe sample characteristics (such as age, gender, andcomorbidities), variations in study equipment (differentAS-OCT devices), and inconsistencies in measurementlocations. Additionally, the analytical techniquesemployed in the included studies varied, which couldhave influenced the comparability of results. Given these factors, the variability between studies was substantial. and a meta-analysis would not have been appropriate. We summarized anterior scleral thickness in differentocular conditions in different studies and their mainfindings. Besides, we selected studies which have samelocation measurement in healthy eyes and CSC subjects, calculating the overall mean values (μ_overall) and SD (σ_overall) via the following formulas:

Ni is the sample size of subgroup i.
μi is the mean value of subgroup i.
n is the total number ofsubgroups.

oi is the sample size of subgroup i.

RESULTS

The screening process was presented in Figure 1. Wepotentially publicationsinitially identified 745 potentially publications related to the anteriorscleral thickness using AS-OCT. After removing theduplicates and reviewing the titles and abstracts, 78 full-text articles were assessed for eligibility. Eventually, 32studies were included in this systematic review.

Main characteristics ofincluded studies

Except healthy subjects, this review included 11 different types ofocular disorders or conditions, includingmyopia, keratoconus, exotropia, retinal vein occlusion, CSC, scleritis or episcleritis, glaucoma, fuchs endothelialdystrophy, nanophthalmos, cycloplegia and intravitrealinjections. Researchers investigated the associationsbetween anterior scleral thickness with age, measurementlocations, diurnal variations, different disorders and localtherapies ( Table 1).

Table 1. Summary of main characteristics of incuded studies.

Publication year

Nationality

Disease

Sample size

Age(years)

Gender(M:F)

Study design

OCT device

Study findings

Zinkernagel et al

2015

Switzerland

Repeated Intravitreal Injections

35 (70 eyes)

76 (range 61-87)^

15:20

Retrospective interventional cross-sectional study

SD-AS OCT (Heidelberg)

Intravitreal injections may lead to thinner sclera when applied repeatedly in the same quadrant.

Pekel et al

2015

Turkey

High Myopia

62 (62 eyes)

(30.5±13.2)vs(30.9±10.6)*

20:42

Cross-sectional comparative study

SD-AS OCT (Heidelberg)

The thickness of anterior wall structures of myopia patients is not statistically different with healthy controls.

Schlatter et al

2015

Switzerland

Keratoconus

55 (62 eyes)

(30.8±8.5)vs(30.7±6.3)

42:13

Comparative case-control study

SD-AS OCT (Heidelberg)

The anterior scleral stroma thickness in keratoconus patients is similar to that in healthy controls.

Ebneter et al

2015

Switzerland

53 (53 eyes)

48.6 (median: 47, range 18-92)

25:28

Observational case series

SD-AS OCT (Heidelberg)

The anterior scleral thickness increases with age and varies significantly between quadrants.

Buckhurst et al

2015

United Kingdom

74 (74 eyes)

27.7±5.3

28:46

Cross-sectional study

Visante AS-OCT (Zeiss)

Significant variations in AST occur depending on meridian and distance from the SS.

Read et al

2016

Australia

19 (19 eyes)

21.5±2.3

9:10

Longitudinal study

SD-AS OCT (Heidelberg)

This study provides the first evidence of diurnal variations occurring in the thickness of the anterior sclera and conjunctiva.

Woodman-Pieterse et al

2018

Australia

Myopia and emmetropes

40 (40 eyes)

21±2

20:20

Longitudinal study

SD-AS OCT (Heidelberg)

There is significant thinning of the anterior sclera during accommodation. These changes were more prominent in myopes.

Ha et al

2019

Korea

Exotropia

76 (76 eyes)

11.6±6.6

30:46

Retrospective chart review

Cirrus high-definition OCT (Zeiss)

The scleral thickness at 1.0-0.5 mm anterior to OMR insertion site was thicker that than at the OMR insertion site.

Adiyeke et al

2020

Turkey

CRVO

67 (134 eyes)

(62.2±11.6)vs(57.9±13.8)

32:35

Case-control study

SD-AS OCT (Heidelberg)

Thicknesses of sclera and lamina cribrosa are increased in the CRVO, which may play a role in the pathogenesis of the disease.

Dhakal et al

2020

India

Myopia

95 (95 eyes)

23.7±3.9

37:58

Cross-sectional study

SS-AS OCT (Topcon)

The relative significant thinning of the anterior sclera along the inferior meridian with increasing degree of myopia compared with the other three meridians.

Kaya et al

2020

Turkey

Systemic Lupus Erythematosus

91 (91 eyes)

(37.9±12.5)vs(38.45±13.76)

12:79

Cross-sectional study

SD-AS OCT (Heidelberg)

Scleral thickness is thicker in SLE patients compared to healthy controls.

Imanaga et al

2021

Japan

Central Serous Chorioretinopathy

87 (100 eyes)

(48.0±10.7)vs(49.0±7.9)

67:20

Retrospective comparative study

SD-AS OCT (Heidelberg)

Scleral thickness is greater in CSC eyes than in control, and thick sclera may have a role in the pathogenesis of CSC.

Hau et al

2021

Singapore

Scleritis or Episcleritis

37 (37 eyes)

(42±10.0)vs(40±8.7)

19:18

Prospective study

AS OCT (Optovue)

The degree of vascularity and tissue thickness were different between episcleritis, scleritis and controls.

Sung et al

2021

Korea

Myopia

79 (79 eyes)

27.03±2.70

51:28

Cross-sectional study

SD-AS OCT (Heidelberg)

Scleral thicknesses are influenced significantly by axial length, central corneal thickness, intraocular pressure, and Bruch’s membrane opening area in myopic eyes.

Niyazmand et al

2021

Australia

Myopia

45 (45 eyes)

24.8±4.6

20:25

Cross-sectional study

SD-AS OCT (Heidelberg)

The biomechanical forces acting on the eye led to nasal anterior scleral thickening and forward movement of the nasal scleral surface.

Lee et al

2021

Korea

Central Serous Chorioretinopathy

30 (30 eyes)

(50.27±14.42)vs(54.73±11.82)

24:6

Prospective case control study

SD-AS OCT (Heidelberg)

Scleral thickness of the study group were significantly greater than those of the control group. Choroidal thickness was positively correlated with scleral thickness.

Park et al

2021

Korea

Primary Open‑Angle Glaucoma

54 (54 eyes)

51.35±13.27

Prospective observational study

SD-AS OCT (Heidelberg)

There were no significant changes in AST after using the DTFC drugs, the AST showed a significant reduction after using PG analogues. These might be related with the increased uveoscleral outflow.

Fernández-Vigo et al

2021

Spain

596 (596 eyes)

42.6±17.2

258:338

Cross-sectional study

SS-AS OCT (Topcon)

The CTT dimensions were then correlated with age, sex, refractive error and AST.

Imanaga et al

2022

Japan

Central Serous Chorioretinopathy

158 (158 eyes)

(50.2±10.9)vs(55.1±12.7)

130:28

Retrospective cross-sectional study

SD-AS OCT (Heidelberg)

A thick choroid and thick sclera appeared to be related to the presence of LOF in CSC.

Wang et al

2022

Canada

Repeated Intravitreal Injections

79 (158 eyes)

73 (range 34–94)

30:49

Cross-sectional study

Compared to injecting naive eyes, multiple intravitreal injections at the repeated scleral quadrant results in scleral thinning.

Burguera-Giménez et al

2022

Spain

50 (50 eyes)

29.02±9.58

14:36

Cross-sectional prospective nonrandomized study

Casia 2 (AS SS-OCT; Tomey)

Scleral thickness is associated with the biomechanical corneal response metrics. Significant meridional variances in scleral thickness occur and prove that AST is associated with AL, CCT and IOP.

Li et al

2023

China

High Myopia

76 (76 eyes)

(34.8±13.3)vs(39.1±12.5)

32:44

Cross-sectional study

Casia SS-1000 (AS SS-OCT; Tomey)

AST and SS length were not significantly different between high myopia and control groups.

Zhou et al

2023

China

Myopia

93 (93 eyes)

30.2±8.8

37:56

Cross-sectional study

CIRRUS HD-OCT 5000 (Zeiss)

The AST is negatively correlated with AL and positively correlated with age. Compared with emmetropic eyes, the AST is thinner in highly myopic eyes.

Mohapatra et al

2022

India

Central Serous Chorioretinopathy

100 (100 eyes)

(39.72±8.4)vs(36.16±8.4)

92:8

Prospective case-control study

CIRRUS HD-OCT 5000 (Zeiss)

There is a significant increase in posterior scleral thickness in patients with CSCR while AST is not affected.

Korkmaz et al

2023

Turkey

Fuchs endothelial dystrophy

62 (62 eyes)

(62.5±13.2)vs(64±8.1)

10:52

Prospective cross-sectional study

SS-AS OCT (Topcon)

In patients with FED, scleral thickness was significantly higher.

Aichi et al

2023

Japan

Central Serous Chorioretinopathy

115 (230 eyes)

50.7±12.1

99:16

Retrospective comparative study

SD-AS OCT (Heidelberg)

The affected and fellow eyes showed no significant difference in scleral thickness.

Fernández-Vigo et al

2023

Spain

113 (113 eyes)

(38.7±12.3)vs(41.8±11.7)

50:63

Cross-sectional study

SS-AS OCT (Topcon)

CTT and AST measurements were thicker in the temporal quadrant of Hispanic patients compared to Caucasians.

Yildiz et al

2023

Turkey

Keratoconus

71 (71 eyes)

(25.3±4.9)vs(26.5±2.3)

45:26

Cross-sectional study

SS-AS OCT (Topcon)

Structural features of the cornea, sclera, and lamina cribrosa with similar collagen content may be similarly affected in patients with keratoconus.

Fernández-Vigo et al

2023

Spain

Nanophthalmos

58 (106 eyes)

Cross-sectional comparative study

SD-AS OCT (Heidelberg)&SS-AS OCT (Zeiss)

Significant anatomical differences are found in nanophthalmic eyes, but no relevant differences in the AST were observed.

Korkmaz et al

2023

Turkey

Cycloplegia

25 (25 eyes)

30.6±12.4

8:17

Prospective cross-sectional study

SS-AS OCT (Topcon)

After cycloplegia, there was a significant thinning of AST posterior to SS and a slight increase in AST at the SS.

Burguera-Giménez et al

2023

Spain

Keratoconus

111 (111 eyes)

(32.3±12.0)vs(29.0±9.6)

47:64

Prospective non-randomized case-control study

Casia 2 (AS SS-OCT; Tomey)

KC eyes presented significant thickness variations among eccentricities over the paracentral sclera.

Teeuw et al

2023

Netherland

107 (214 eyes)

51.6±18.5

48:59

Comprehensive prospective imaging study

SD-AS OCT (Heidelberg)

The mean AST of the inferior quadrant was the
largest, followed by the nasal, temporal
and superior quadrants. The averaged scleral thickness increased 0.96μm per age year.

Age of all participants
*(Age of patient group)vs(Age of control group)
SD-AS OCT Spectral domain anterior segment optical coherence tomography
AST Anterior scleral thickness
SS Scleral spur
OMR Original medial rectus
CRVO Central retinal vein occlusion
CSC Central Serous Chorioretinopathy
SLE Systemic lupus erythematosus
DTFC Dorzolamide/timolol fixed combination
PG Prostaglandin
CTT Conjunctival and Tenon’s capsule thickness
AL Axial length
IOP Intraocular pressure
LOF Loculation of fluid
FED Fuchs endothelial dystrophy

Figure 1 Screening process ofthe included studies

Risk of bias assessment

As shown in Supplementary file 1 and 2, twoevaluation scales, the NOS and the JBI Critical AppraisalChecklist for analytical cross-sectional studies werecomprehensively considered. The detailed qualityevaluation results can be seen in Supplementary file 1 and 2.

Anterior scleral thickness in healthy eyes

Based on the literature, it is evident that anteriorseleral thickness was significantly associated with age, measurement locations and diurnal changes. Ebneterfound a significant association of increasing anteriorscleral thickness with age ( P < 0.0001, Pearson r = 0.704). Besides, they found that the thickness varies significantlybetween quadrants ( P < 0.0001), with the mean anteriorscleral thickness ( 2 mm from the scleral spur) of 571μm, 511 μm, 475 μm, and 463 μm in the inferonasal.inferotemporal, superotemporal and superonasal quadrant respectively^[11]. Buckhurst reported that significantvariations in anterior scleral thickness were associatedwith meridian and distance from scleral spur, In theirstudy,Meridian superionasal sclera was the thinnest( 662±57 μm) and inferior area was the thickest ( 806±60 μm). And anterior scleral thickness at 1 mm ( 682±48 μm) was the thinnest and at 6 mm (818±49 μm) thethickest ( P < 0.001).^[12] Teuw et al found that the meananterior scleral thickness of the inferior quadrant wasthe largest (596+64 μm), followed by the nasal ( 567±76 μm), temporal ( 516±67 μm) and superior ( 467±52 μm) quadrants ( P < 0.001). Besides, they found thataveraged anterior seleral thickness increased 0.96 μm per year.^[13] We summarized the results of seven studies ( 21.88%) which have same measurement locations andcalculated the overall mean anterior scleral thickness( Table 2 and Figure 2). In addition, Read et al reported the diurnal variations in the thickness of the anteriorsclera.Over a 24-hour period, anterior seleral thicknesshad a small magnitude thinning close to midday, and alarger magnitude thickening immediately after wakingin the morning ( P < 0.01).^[14] And Fernández-Vigo et alfound the anterior scleral thickness was higher in thetemporal quadrant of Hispanic patients compared toCaucasians, which they thought might be associatedwith the pathogenesis of different ocular disorders.Anterior scleral thickness values were larger in thetemporal quadrant in the Hispanie group ( 2 mm fromthe scleral spur: 559.8+80,8 μm and 3 mm from thescleral spur: 591.6+83.0 μm) compared to the Caucasiangroup ( 520.7+50.1 μm and 558.9+54.7 μm respectively; P ≤ 0.022).^[15] As for different gender, we summarized twostudies ( 6.25%) which reported anterior scleral thicknessin male and female subjects respectively ( as shown in Table 3). The findings showed that female tended to havethinner anterior scleral thickness than the male subjects, though in diferent measurement locations.

Table 2. Anterior scleral thickness of healthy eyes (included in the calculation)

First author

Publication year

Nationality

Sample size (Healthy)

Age (Healthy)

Gender (M:F,healthy)

OCT device

0mm-SS-T (μm)

1mm-SS-T (μm)

2mm-SS-T (μm)

3mm-SS-T (μm)

0mm-SS-N (μm)

1mm-SS-N (μm)

2mm-SS-N (μm)

3mm-SS-N (μm)

Buckhurst

2015

United Kingdom

74 (74 eyes)

27.7±5.3

28:46

Visante AS-OCT (Zeiss)

731±64

666±57

659±61

673±65

698±63

674±63

690±62

712±57

Adiyeke

2020

Turkey

35 (70 eyes)

57.9±13.8

18:17

SD-AS OCT (Heidelberg)

702.0±30.8

659.0±28.4

649.0±22.2

655.0±24.9

665.3±24.2

651.9±21.7

655.9±26.7

682.8±21.9

Fernández-Vigo

2021

Spain

596 (596 eyes)

42.6±17.2

258:338

SS-AS OCT (Topcon)

556.5±60.7

522.4±65.7

513.3±67.3

548.8±71.9

546.8±63.4

558.4±71.5

574.4±71.6

590.1±76.6

Burguera-Giménez

2022

Spain

50 (50 eyes)

29.02±9.58

14:36

Casia 2 (AS SS-OCT; Tomey)

522±65

497±63

513±71

525±51

531±58

532±65

2023

China

42 (42 eyes)

39.1±12.5

18:24

SS-OCT

767.48±104.28

558.43±87.99

560.29±84.29

589.29±91.62

690.76±68.69

524.98±59.00

554.88±47.07

564.26±55.06

Fernández-Vigo

2023

Spain

53 (53 eyes) Hispanic

38.7±12.3

24:29

SS-AS OCT (Topcon)

536.1±77.9

559.8±80.8

591.6±83.0

589.3±68.3

611.3±78.8

613.0±75.0

60 (60 eyes) Caucasian

41.8±11.7

26:34

SS-AS OCT (Topcon)

535.5±56.0

520.7±50.1

558.9±54.7

565.8±75.1

577.5±74.5

589.8±76.4

Fernández-Vigo

2023

Spain

30 (60 eyes)

SS-AS OCT (Zeiss)

670±100

704±89

691±118

687±98

740±94

767±120

30 (60 eyes)

SD-AS OCT (Heidelberg)

691±99

666±87

691±74

682±99

707±84

719±69

Korkmaz

2023

Turkey

25 (25 eyes)

30.6±12.4

8:17

Casia 2 (AS SS-OCT; Tomey)

718.4±40.1

522.5±24.7

527.2±39.9

697.5±46.0

512.3±34.4

529.6±34.2

Burguera-Giménez

2023

Spain

50 (50 eyes)

29.0±9.6

14:36

SD-AS OCT (Heidelberg)

522±65

497±63

513±71

525±51

531±58

532±65

1mm-SS-T: Anterior scleral thickness at a temporal distance of 1mm from the scleral spur

1mm-SS-N: Anterior scleral thickness at a nasal distance of 1mm from the scleral spur

Figure 2 The overall mean temporal/nasal anterior scleral thickness in healthy eyes

Table 3. Anterior scleral thickness of eyes in two gender

First author

Publication year

Nationality

Disease

Sample size

Age

Gender

0~6mm-SS-S (μm)

0~6mm-SS-T (μm)

0~6mm-SS-I (μm)

0~6mm-SS-N (μm)

0~6mm-SS-4q (μm)

0~2mm-LB-4q (μm)

Zhou

2023

China

Myopia

93 (93 eyes)

30.2±8.8

Male (n=37)

495±42

603±48

575±62

569±67

559±50

Female (n=56)

489±34

589±46

573±59

562±55

552±38

Teeuw

2023

Netherland

No

107 (214 eyes)

51.6±18.5

Male (n=48)

552±57

Female (n=59)

524±44

0~6mm-SS-S: Average anterior scleral thickness at a superior distance of 0~6mm from the scleral spur

0~6mm-SS-T: Average anterior scleral thickness at a temporal distance of 0~6mm from the scleral spur

0~6mm-SS-I: Average anterior scleral thickness at a inferior distance of 0~6mm from the scleral spur

0~6mm-SS-N: Average anterior scleral thickness at a nasal distance of 0~6mm from the scleral spur

0~6mm-SS-4q: Average anterior scleral thickness of 4 quadrant at a distance of 0~6mm from the scleral spur

0~2mm-LB-4q: Average anterior scleral thickness of 4 quadrant at a distance of 0~2mm from the limbus

Anterior scleral thickness in different ocularconditions

Scleritis and episcleritis

Inflammatory conditions like scleritis andepiseleritis show signifcant changes in scleral structure.Hau et al found the degree of vascularity and thickness ofsclera and episclera were different between episcleritis,scleritis and controls using AS-OCT or AS-OCTA.^[16]AS-OCT may potentially be a useful tool in evaluatingpatients with scleral inflammation. And several studieshave investigated the conjunctival and scleral complex thickness in scleral inflammatory diseases.^[2] We did not include them since they had no information about isolated anterior scleral thickness.

Myopia

50% studies proposed that myopic eyes often exhibited thinner sclera when compared to emmetropicand hypertropic eyes. For example, Dhakal et al foundthat the relative thinning of the anterior sclera alongthe inferior meridian with inereasing myopie degreecompared to other meridians (r = 0.27; P = 0.008).^[17]The anterior scleral thickness can also be influenced by axial length, corneal thickness, intraocular pressure andeven Bruch’s membrane opening area^[18] This thinningis associated with the elongation of the eye in myopia,contributing to the biomechanical instability ofthe sclera.However, the other 50% of publications did not findsignificant differences. For example, Pekel et al and Li et al found that the thickness of anterior wall struetures of myopic eyes has no statistical diference with healthyeyes.^[3,19]

Keratoconus

In Keratoconus, anterior scleral thickness tendsto be abnormal. Yildiz et al found that structuralfeatures of the cornea, sclera, and lamina cribrosa might be similarly affected in patients with keratoconusdue to similar collagen content of them.^[7]Burguera-Giménez et al reported that keratoconus eyes presentedsignificant thickness variations among eccentricitiesover the paracentral selera. The anterior scleral thicknesssignificantly varied with scleral eccentricity over thetemporal meridian (P = 0.009) in healthy controls, whereasin KC eyes, this variation was over the nasal (P = 0.001), temporal (P = 0.029) and inferior (P = 0.006) meridians.^[20] However, Schlatter et al reported that the anterior scleralstroma thickness in keratoconus eyes is similar to that inhealthy subjects.^[20]

Central serous chorioretinopathy

In CSC (Table 4 and Figure 3), 60% of the studiesWasfound that anterior scleral thickness was greater thancontrols and thought that thick sclera might have a role inmi ghtthe pathogenesis of CSC.^[4,21] For example, lmanaga etal found that anterior scleral thickness was significantlygreater in CSC eyes than in normal control eyes at thesuperior (429.4±50.3 μm vs. 395.2±55.4 μm; P =0.005),temporal (447.7±45.7μm vs. 396.5±64.1 μm; P <0.001),inferior (455.7±81.2 μm vs. 437.8±46.9 μm; P = 0.022), and nasal (454.9±44.7 μm vs. 416.6±51.2 μm; P = 0.001) points. 4 Besides, the anterior scleral thickness may alsohave a positive association with choroidal thickness.Lee et al found a positive association between subfovealchoroidal thickness and the sub-lateral rectus musclescleral thickness (r = 0.394, P = 0.031).^[21] However, Mohapatra et al found that there is a significant inerease in posterior scleral thickness in CSC but no significantdifferences in anterior scleral thickness. ^[22] Aichi et al also found no significant differences between CSC and controls.^[23]

Figure 3 The overall mean anterior scleral thickness in different meridians in CSC eyes

^{Other ocular conditions}

Some local therapies of the eye may lead to scleralchanges.For example, intravitreal injections may leadto thinner sclera if repeating in the same quadrant,^[24-25]Zinkemagel et al reported that eyes with more than 30injections had thinner average anterior seleral thicknessin the inferotemporal quadrant ( 568.46±66 μm) thanthe fellow eyes ( 590.6±75 μm, P = 0.003).^[25] Wang et alreported that injected eyes had a mean anterior scleral thickness of 588±95 μm versus 618±85 μm in fellownaive eyes ( P < 0.001).^[24]The anterior seleral thicknessshowed a signifcant reduction after using Prostaglandinanalogues ( P < 0.05), which might be associated with theinerease uveoscleral outflow.^[26] And Korkmaz foundthat after cyeloplegia, there was a significant thinning ofanterior scleral thickness posterior to scleral spur in nasaland temporal quadrants ( P < 0.05) and a slight increasein anterior scleral thickness at the scleral spur but nosignificant difierences.^[27]

In retinal vascular diseases, such as retinal veinocclusion, Adiyeke et al found that thickness of selerain CRVO eyes were significantly increased at scleralspur in all quadrants (P < 0.05).^[28] Also, in other cornealdiseases, such as Fuchs endothelial dystrophy, sclera wassignificantly thicker at 6 mm posterior to the seleral spurin all quadrants (P < 0.05).^[29]

Noteworthy, AS-OCT has been applied in somesystemic diseases’ researches. For example, Kaya et alinvestigated the anterior scleral thickness in patients withsystemic lupus erythematosus (SLE), and found that inSLE patients, the anterior sclera thickness is thicker atall distances compared with controls (P < 0.05).^[30] Thisbroadens the application scope of AS-OCT.

Table 4. Anterior scleral thickness of eyes with central serious chorioretinopathy (included in the calculation)

First author

Publication year

Nationality

Disease

Sample size (CSC)

Age (CSC)

Gender (M:F, CSC)

6mm-SS-S (μm)

6mm-SS-T (μm)

6mm-SS-I (μm)

6mm-SS-N (μm)

Imanaga

2021

Japan

Central Serous Chorioretinopathy

40 (47 eyes)

48.0±10.7

33:7

429.4±50.3

447.7±45.7

455.7±81.2

454.9±44.7

Imanaga

2022

Japan

Central Serous Chorioretinopathy (loculation of fluid (LOF))

98 (98 eyes)

86:12

426.2±63.0

445.7±55.9

459.2±62.3

445.4±59.3

Central Serous Chorioretinopathy (non-loculation of fluid (non-LOF))

60 (60 eyes)

44:16

395.1±52.1

414.9±47.4

428.8±49.6

414.3±55.9

Aichi

2023

Japan

Central Serous Chorioretinopathy

115 (230 eyes)

46.4±18.3

54:46

410.3±58.4

434.3±52.9

447.9±59.5

434.9±59.1

CSC Central Serous Chorioretinopathy

6mm-SS-S: Anterior scleral thickness at a superior distance of 6mm from the scleral spur

6mm-SS-T: Anterior scleral thickness at a temporal distance of 6mm from the scleral spur

6mm-SS-I: Anterior scleral thickness at a inferior distance of 6mm from the scleral spur

6mm-SS-N: Anterior scleral thickness at a nasal distance of 6mm from the scleral spur

DISCUSSION

In this systematic review, we provided a comprehensive overview of the curent understanding of anterior scleral thickness across various ocular conditionsusing AS-OCT. These studies collectively examined11 ocular disorders as well as healthy eyes. Variationsin anterior scleral thickness can indicate the preseneeand progression of ocular conditions. For instance.thinner sclera in myopic eyes suggests biomechanicalalterations, while increased thickness in conditions like active seleritis may reflects inflammatory responses.Additionally, age and diurnal variations further impactseleral measurements, ofering insights into their dynamicnature. The precision of AS-OCT in detecting thesesubtle changes enhances its utility in monitoring ocularhealth, potentially aiding early diagnosis and trackingdisease progression in clinical settings. The findingsunderscore the importance of anterior scleral thickness tobe a potential biomarker in ocular health.

It is regarded that the anterior scleral thickness ispositively with age, This might be due to age-relatedchanges in seleral collagen and biomechanies.^[11,13] Theobserved regional variations in anterior scleral thickness.such as the thicker inferior quadrant compared to otherquadrants, suggested that these variations could be linkedto the different mechanical stresses exerted on the seleraby ocular movements and external forces.^[13]The diurnalvariations reported by Read et al indicated that the selera was not static throughout the day, which might be due tophysiological changes in ocular blood flow, intraocularpressure and other metries fuctuating with the cireadianrhythm,^[14] The ethnic differences revealed by Femández.Vigo et al., with Hispanie patients showing highertemporal quadrant thickness compared to Caucasians, suggest that genetie or environmental factors may alsoinfluence scleral structure.^[31] This finding may explainthe phenomenon to some extent that different ethics havequite different epidemiology in certain ocular disorders.Males had thicker anterior scleral thickness compared tofemales, but the significance of this phenomenon is notknown and could perhaps represent an anthropologicaldifference between two genders.^[2]

The sclera has tight associations with other ocularstructures, such as the cornea, choroid and ciliary muscle.The anterior scleral thickness is associated with thebiomechanical corneal response metrics, Although themeasurement profiles did not differ between keratoconus and control groups in some studies, the inferior-superiorasymmetry differences demonstrated scleral changesover the vertical meridian in keratoconus, which needfurther investigation.^[7,20,32] According to Korkmaz study,inhibition of forward inward movement of the ciliarybody by cycloplegia can affect anterior scleral thicknessvia causing a change in the mechanical force of theciliary muscle on the sclera.^[27] In CSC, the associationbetween choroidal changes and anterior scleral thicknesshas been observed.^[21]

The association between myopia and reducedanterior scleral thickness is well-documented in thereviewed studies, The thinning of the sclera, particularlyalong certain meridians, reflects the biomechanicalalterations associated with axial elongation in myopiceyes. This thinning compromises the structuralintegrity of the sclera, potentially exacerbating myopicprogression and increasing the risk of myopia-relatedcomplications.^[33] However, the inconsistencies reportedby Pekel et al. suggest that anterior scleral thicknesschanges in myopia may not be uniform and coulddepend on additional factors such as the degree ofmyopia, axial length, and individual variations in seleralcomposition.^[3,34]

In inflammatory conditions like scleritis andepiscleritis, the significant thickening of the scleraobserved in the reviewed studies underscores the utility ofAS-OCT in diagnosing and monitoring these conditions.AS-OCT was instrumental in identifying necrosisand scleral nodules in subclinical cases, and differentsubtypes of scleritis indicate different pathogenesis.Moreover, complete resolution of scleral inflammationcan be followed by OCT.^[35]The ability of AS-OCTto detect subtle changes in scleral strueture makes it avaluable tool in distinguishing between different types ofscleral inflammation and in assessing the effectiveness of therapeutic interventions.

The findings related to CSC suggest a potential rolefor inereased anterior scleral thickness in the pathogenesisof the disease, possibly due to its association withchoroidal thickness. However, the lack of consensus, asseen in the studies by Mohapatra et al. and Aichi et al. indicates that further investigation was required to elucidatethe exact relationship between anterior scleral thicknessand CSC.^[22-23,36] The potential influence of other factors, such as intraocular pressure and choroidal circulation, should also be considered in future studies.

The impact of local therapies, such as intravitrealinjections and the use of prostaglandin analogues, cycloplegia on anterior scleral thickness further broadensthe clinical relevance of anterior scleral thicknessmeasurements. The observed thinning of the sclerafollowing repeated injections or chronic medication usesuggests that these interventions may have unintendedeffects on scleral integrity, which could influencetreatment outcomes, particularly in patients requiringlong-term therapy, This may remind clinicians to monitoranterior scleral thickness in patients undergoing suchtreatments to prevent adverse effects.

The variations in anterior scleral thicknessobserved in conditions like retinal vein occlusion, Fuchsendothelial dystrophy, and systemic diseases like SLEsuggest that scleral changes are not confined to ocularpathologies but may also reflect systemic health. Thethicker sclera in SLE patients, as reported by Kaya et al, implies that systemic inflammatory or autoimmuneprocesses could impact scleral structure, providinga potential link between systemic health and ocular manifestations.^[30] This finding opens new avenues forresearch into the role of anterior scleral thickness as amarker for systemie disease.

Strengths of our systematic review include that this topic was the first time to report. And we followedthe strict protocol in the synthesis process. However,there was significant variability in the standards usedacross studies, particularly in relation to diagnostictools and measurement techniques. For example, AS-OCT equipment from different manufacturers can yieldslightly varying results due to differences in resolutionscanning protocols, or imaging software. Additionally, measurement techniques are often not uniformly appliedacross studies, which can lead to inconsistencies inthe data. Standardization of these tools and methodswould not only enhance the accuracy and consistencyof measurements but also facilitate better comparabilityacross studies. Establishing standardized protocols for AS-OCT imaging, measurement analysis, and reporting could significantly improve the reproducibility ofresearch findings and lead to more robust conclusionsin future studies. Our analysis was limited due to thehigh risk of bias and heterogeneity of included studies,which preclude the further statistical analysis and poolingdata for meta-analysis. Specifically, variations in patientcharacteristics (e.g., age, gender, comorbidities andethnicities) and study equipment (e.g., SD-OCT vs. SS-OCT) could introduce bias or lead to divergent findings.To better understand the robustness of the conclusions, it would be useful to evaluate how such heterogeneitymight affect the outcomes with large sample size in thefuture.

To advance future research in this area, severalcritical steps should be taken to tackle the deficienciesidentified in the current literature. These steps include 1) measuring same locations in cohort studies; 2)conducting research in a large sample size andmaximizing the representativeness; 3) use design suchas matching, and analytic strategies (multivariableadjustment, propensity score matching, or inverse probability weighting)to control for potentialconfounding factors; 4) conducting subgroup analyses orsensitivity tests to assess the consistency of results acrossdifferent settings or groups; 5) promoting well-designedstudies to investigate anterior scleral thickness in diferentage group, gender group and different ocular conditions.

^{In conclusion, this systematic review underscoresthe significant role of anterior scleral thickness inocular health and disease, as well as the growingimportance of AS-OCT in clinical practice. Continuedresearch into anterior scleral thickness, with a focus onstandardization, longitudinal analysis, and multimodalimaging, will further advance our understanding ofscleral biomechanics and its implications for ocular andsystemic health.}

Correction notice

^None

Acknowledgement

None

Author Contributions

(I)Conception and design: Lihui Meng and Qianyi Yu
(II)Administrative support: Jingyuan Yang and YouxinChen
(III)Provision of study materials or patients: Allauthors
(IV)Collection and assembly of data: Lihui Meng andQianyi Yu
(V)Data analysis and interpretation: Lihui Meng and Qianyi Yu
(VI)Manuscript writing: All authors
(VII)Final approval of manuscript: All authors

Funding

This work was supported by the National Postdoetoral Researcher Funding Program, National NaturalScicnee Foundation of China (82271112).

Confiet of Interests

None of the authors has any conflicts of interest to disclose. All authors have declared in the completed the ICMJE uniform disclosure form.^{Patient consent for publication

None

Ethical Statement

None

Provenance and Peer Review

This article was a standard submission to our journal. The article has undergone peer review with our anonymous review system.

Data Sharing Statement

None

Open Access Statement

This is an Open Access article distributed inaccordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 InternationalLicense (CC BY-NC-ND 4.0), which permits thenon-commercial replication and distribution of thearticle with the strict proviso that no changes oredits are made and the original work is properlycited (including links to both the formal publicationthrough the relevant DOl and the license).}

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1、This work was supported by the National Postdoctoral Researcher Funding Program, National Natural Science Foundation of China (82271112).()