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

^{Other ocular conditions}

Some local therapies of the eye may lead to scleral changes. For example, intravitreal injections may lead to thinner sclera if repeating in the same quadrant,^[24-25] Zinkemagel et al.^[25] reported that eyes with more than 30injections had thinner average anterior scleral thickness in the inferotemporal quadrant ( 568.46±66 ) μm than the fellow eyes ( 590.6±75 ) μm, P = 0.003. Wang et al.^[24] reported that injected eyes had a mean anterior scleral thickness of ( 588±95 ) μm versus ( 618±85 ) μm in fellow naive eyes ( P < 0.001). The anterior scleral thickness showed a significant reduction after using Prostaglandin analogues ( P < 0.05), which might be associated with the increase uveoscleral outflow.^[26] And Korkmaz found that after cyeloplegia, there was a significant thinning of anterior scleral thickness posterior to scleral spur in nasal and temporal quadrants ( P < 0.05) and a slight increase in anterior scleral thickness at the scleral spur but no significant differences.^[27]

In retinal vascular diseases, such as retinal vein occlusion, Adiyeke et al.^[28] found that thickness of sclera in CRVO eyes were significantly increased at scleral spur in all quadrants (P < 0.05). Also, in other corneal diseases, such as Fuchs endothelial dystrophy, sclera was significantly thicker at 6 mm posterior to the scleral spur in all quadrants (P < 0.05).^[29]

Noteworthy, AS-OCT has been applied in some systemic diseases’ researches. For example, Kaya et a investigated the anterior scleral thickness in patients with systemic lupus erythematosus (SLE), and found that inSLE patients, the anterior sclera thickness is thicker at all distances compared with controls (P < 0.05).^[30] This broadens the application scope of AS-OCT.

DISCUSSION

In this systematic review, we provided a comprehensive overview of the current understanding of anterior scleral thickness across various ocular conditions using AS-OCT. These studies collectively examined11 ocular disorders as well as healthy eyes. Variations in anterior scleral thickness can indicate the presented progression of ocular conditions. For instance. Thinner sclera in myopic eyes suggests biomechanical alterations, while increased thickness in conditions like active scleritis may reflects inflammatory responses. Additionally, age and diurnal variations further impact scleral measurements, offering insights into their dynamic nature. The precision of AS-OCT in detecting these subtle changes enhances its utility in monitoring ocular health, potentially aiding early diagnosis and tracking disease progression in clinical settings. The findings underscore the importance of anterior scleral thickness to be a potential biomarker in ocular health.

It is regarded that the anterior scleral thickness is positively with age, This might be due to age-related changes in scleral collagen and biomechanics.^[11,13] The observed regional variations in anterior scleral thickness such as the thicker inferior quadrant compared to other quadrants, suggested that these variations could be linked to the different mechanical stresses exerted on the sclera by ocular movements and external forces.^[13] The diurnal variations reported by Read et al indicated that the sclera was not static throughout the day, which might be due to physiological changes in ocular blood flow, intraocular pressure and other metrics fluctuating with the circadian rhythm,^[14] The ethnic differences revealed by Femández. Vigo et al., with Hispanic patients showing higher temporal quadrant thickness compared to Caucasians, suggest that genetic or environmental factors may also influence scleral structure.^[31] This finding may explain the phenomenon to some extent that different ethics have quite different epidemiology in certain ocular disorders. Males had thicker anterior scleral thickness compared to females, but the significance of this phenomenon is not known and could perhaps represent an anthropological difference between two genders.^[2]

The sclera has tight associations with other ocular structures, such as the cornea, choroid and ciliary muscle. The anterior scleral thickness is associated with the biomechanical corneal response metrics, Although the measurement profiles did not differ between keratoconus and control groups in some studies, the inferior-superior asymmetry differences demonstrated scleral changes over the vertical meridian in keratoconus, which need further investigation.^[7,20,32] According to Korkmaz study, inhibition of forward inward movement of the ciliary body by cycloplegia can affect anterior scleral thickness via causing a change in the mechanical force of the ciliary muscle on the sclera.^[27] In CSC, the association between choroidal changes and anterior scleral thickness has been observed.^[21]

The association between myopia and reduced anterior scleral thickness is well-documented in the reviewed studies, The thinning of the sclera, particularly along certain meridians, reflects the biomechanical alterations associated with axial elongation in myopic eyes. This thinning compromises the structural integrity of the sclera, potentially exacerbating myopic progression and increasing the risk of myopia-related complications.^[33] However, the inconsistencies reported by Pekel et al. suggest that anterior scleral thickness changes in myopia may not be uniform and could depend on additional factors such as the degree of myopia, axial length, and individual variations in scleral composition.^[3,34]

In inflammatory conditions like scleritis and episcleritis, the significant thickening of the sclera observed in the reviewed studies underscores the utility of AS-OCT in diagnosing and monitoring these conditions.AS-OCT was instrumental in identifying necrosis and scleral nodules in subclinical cases, and different subtypes of scleritis indicate different pathogenesis. Moreover, complete resolution of scleral inflammation can be followed by OCT.^[35] The ability of AS-OCT to detect subtle changes in scleral structure makes it a valuable tool in distinguishing between different types of scleral inflammation and in assessing the effectiveness of therapeutic interventions.

The findings related to CSC suggest a potential role for inereased anterior scleral thickness in the pathogenesis of the disease, possibly due to its association with choroidal thickness. However, the lack of consensus, as seen in the studies by Mohapatra et al. and Aichi et al. indicates that further investigation was required to elucidate the exact relationship between anterior scleral thickness and 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 intravitreal injections and the use of prostaglandin analogues, cycloplegia on anterior scleral thickness further broadens the clinical relevance of anterior scleral thickness measurements. The observed thinning of the sclera following repeated injections or chronic medication use suggests that these interventions may have unintended effects on scleral integrity, which could influence treatment outcomes, particularly in patients requiring long-term therapy, This may remind clinicians to monitor anterior scleral thickness in patients undergoing such treatments to prevent adverse effects.

The variations in anterior scleral thickness observed in conditions like retinal vein occlusion, Fuchs endothelial dystrophy, and systemic diseases like SLE suggest that scleral changes are not confined to ocular pathologies but may also reflect systemic health. The thicker sclera in SLE patients, as reported by Kaya et al, implies that systemic inflammatory or autoimmune processes could impact scleral structure, providing a potential link between systemic health and ocular manifestations.^[30] This finding opens new avenues for research into the role of anterior scleral thickness as a marker for systemic disease.

Strengths of our systematic review include that this topic was the first time to report. And we followed the strict protocol in the synthesis process. However, there was significant variability in the standards used across studies, particularly in relation to diagnostic tools and measurement techniques. For example, AS-OCT equipment from different manufacturers can yield slightly varying results due to differences in resolution scanning protocols, or imaging software. Additionally, measurement techniques are often not uniformly applied across studies, which can lead to inconsistencies in the data. Standardization of these tools and methods would not only enhance the accuracy and consistency of measurements but also facilitate better comparability across studies. Establishing standardized protocols for AS-OCT imaging, measurement analysis, and reporting could significantly improve the reproducibility of research findings and lead to more robust conclusions in future studies. Our analysis was limited due to thehigh risk of bias and heterogeneity of included studies, which preclude the further statistical analysis and pooling data for meta-analysis. Specifically, variations in patient characteristics (e.g., age, gender, comorbidities and ethnicities) 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 heterogeneity might affect the outcomes with large sample size in the future.

To advance future research in this area, several critical steps should be taken to tackle the deficiencies identified in the current literature. These steps include 1) measuring same locations in cohort studies; 2)conducting research in a large sample size and maximizing the representativeness; 3) use design such as matching, and analytic strategies (multivariable adjustment, propensity score matching, or inverse probability weighting)to control for potential confounding factors; 4) conducting subgroup analyses or sensitivity tests to assess the consistency of results across different settings or groups; 5) promoting well-designed studies to investigate anterior scleral thickness in differentiate group, gender group and different ocular conditions.

In conclusion, this systematic review underscores the significant role of anterior scleral thickness in ocular health and disease, as well as the growing importance of AS-OCT in clinical practice. Continued research into anterior scleral thickness, with a focus on standardization, longitudinal analysis, and multimodal imaging, will further advance our understanding of scleral biomechanics and its implications for ocular and systemic health.

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