Evaluation of Choroidal and Macular Thickness in Patients with Inactive Thyroid Eye Disease Using Optical Coherence Tomography

Introduction

Thyroid eye disease (TED) is an autoimmune disease characterized orbital adipose tissue proliferation, inflammation of the orbital connective tissue and extraocular muscles enlargement resulting cause an enhancement in orbital tissue volume. TED is observed in roundly 30% of patients with Graves disease and 2% of patients is observed with thyroiditis.1 Although most patients with TED have mild symptoms, about 3 to 5% patients may develop a more severe form. Clinical signs of TED include dry eye, exposure keratopathy, proptosis, diplopia and decreased visual acuity.2-4 Some studies on retinal changes in TED patients have recently appeared, including publications on choroidal thickness and its association with macular degeneration.5-9 TED patients were evaluated according to the Mourits et al. developed Clinical Activity Classification System (CAS) classified as active and inactive in 1989.

Corresponding Author: Ömer Özer, omerozer92@gmail.com, Received: 27.10.2023, Accepted: 26.02.2024, Available Online Date: 30.06.2024 Cite this article as: Özer Ö, Güçlü ES, Bektas FM, Baysal Z. Evaluation of Choroidal and Macular Thickness in Patients with Inactive Thyroid Eye Disease Using Optical Coherence Tomography. J Cukurova Anesth Surg. 2024; 7(2): 64-7.

https://doi.org/10.36516/jocass.1381884 Copyright © 2024 This is an open access article distributed under the terms of the Creative Commons Attribution-Non-Commercial-No Derivatives License 4.0 (CC-BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

A total of seven parameters are queried in this evaluation system. In this scoring system, each parameter is assigned a score, and if the overall score is three or more, the disease is considered to be in the active phase. Criteria; 1) Spontaneous bulbar or retrobulbar pain for the last four weeks, 2) Pain with looking up or down, 3) Redness of the eyelids, 4) Redness of the conjunctiva, 5) Swelling in the caruncle or plica, 6) Swelling of the eyelids and 7) Conjunctival swelling.10

In this study, we aimed to estimate the choroidal and macular thickness (according to clinical activity score) in cases with TED who weren’t in the active complaint period and to compare them with healthy controls.

Materials and methods

This retrospective study included 40 eyes of 40 patients (group 1) admitted to the Endocrinology and Ophthalmology Outpatient Mersin City Hospital between 01 February 2019 and 01 February 2022. Forty healthy controls (group 2) of similar age group were included. Written informed consent was obtained from all participants. This study approved from the Clinical Studies Ethics Committee of Mersin City Hospital (2021 / 799 – 29/12/2021). The study was conducted in agreement with the Declaration of Helsinki.

Subfoveal, temporal, nasal, choroidal thickness evaluation and central foveal thickness evaluation of the right eyes of all participants were performed, independently, by an educated technician using Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) spectral-domain optical coherence tomography (SD-OCT). Similar measurements were compared with an equal number of controls.

Exclusion criteria: Greater than (- 5.00) diopters myopia (D) or greater than (+ 3.00) diopters (D) hyperopia, anomaly of optic disc, vitreoretinal interface disease, retinal vascular and degenerative diseases, corneal and lens opacity, previous ocular surgery, neurologic diseases, use of cardiovascular drugs, amblyopia, diplopia, uveitis, enlarged extraocular muscles confirmed by orbital magnetic resonance imaging (MRI) and keratitis. A detailed history was taken from all patients and comprehensive ophthalmologic examination with slit lamp biomicroscopy, intraocular pressure measurement and fundus examination was performed.

The level of proptosis was evaluated with Hertel exophthalmometer. All patients were also evaluated using orbital MRI to observe extraocular muscle involvement.

Statistical Analysis

Statistical analysis of this study data was performed with SPSS 24.0 package program (IBM Corp, Armonk, NY, USA). Categorical variables were epitomized as number, percentage and continuous variables as mean ± standard deviation (minimum – maximum). Normal distribution of continuous variables was checked by Shapiro-Wilk test. Student's t test, was used to compare the means of two independent groups for the variables that conformed to normal distribution. Connection between categorical variables were investigated by Chi-Square analysis. Statistical significance level was taken as p < 0.05 for all comparisons.

Results

In this study, the mean age of the 40 patients (group 1) was 52.1 ± 14.2 years (37–66 years), while the mean age of the 40 healthy controls (group 2) was 51.2 ± 13.4 years (37–66 years). Group 1 consisted of 17 males (42.5%) and 23 females (57.5%). Group 2 consisted of 21 males (52.5%) and 19 females (47.5%). Both groups were similar in terms of demographics (p=0.166 and p=0.371, respectively) (Table 1).

Demographic data of study participants

The clinical profile of group 1 showed hyperthyroidism in 25 (62.5%), euthyroidism in 7 (17.5%) and hypothyroidism in 8 (20%) patients. In addition, thyroid function tests revealed a mean thyroid stimulating hormone (TSH) level of 3.3 ± 1.8 (1.5 – 5.1) mIU/L, a mean free thyroxine (T4) level of 1.6 ± 0.6 (1.0 – 2.2) ng/dl, and a mean free triiodothyronine (T3) level of 4.4 ± 1.2 (3.2 – 5.6) ng/dL. (Table 2)

The mean clinical activity score for group 1 was 1.25 ± 0.47 and the mean Hertel ophthalmometry was 21.6 ± 2.4 (19.2 – 24.0) millimeters. Mean intraocular pressure (IOP) was 16.3 ± 3.9 (12.4 – 20.2) mm Hg. The mean of IOP in the group 2 was 15.8 ± 3.1 (12.7 – 18.9) mm Hg. This difference was not statistically significant (p=0.253).

Clinical profiles and thyroid function tests of the patients

TSH: Thyroid Stimulating Hormone, T4: thyroxine, T3: triiodothyronine

In group 1, mean foveal thickness was 285.3 ± 15.2 (270.1 – 300.5) μm, mean subfoveal choroid thickness was 285.42 ± 81 (204.4 – 366.4) μm, mean temporal choroid thickness was 265.6 ± 57.5 (208.1 – 323.1) μm, mean nasal choroidal thickness was 232.1 ± 71.7 (160.4 – 302.8) μm.

In group 2, the mean foveal thickness was 288 ± 16.1 (272.1 – 304.1) μm, the mean subfoveal choroid thickness was 251.1 ± 57.4 (193.7 – 308.5) μm. The mean temporal choroid thickness was 233.7 ± 51.3 (182.4 – 285.0) μm, and the mean nasal choroid thickness was 221.1 ± 59.9 (172.2 – 281.0) μm. There is a statistically significant difference between subfoveal choroidal thickness and temporal choroidal thickness between both groups (p=0.014 and p=0.008, respectively). (Table 3)

Central foveal and choroidal thickness of the participants

FT: Foveal thickness CT: Choroidal thickness

Discussion

Thyroid eye disease is an autoimmune disease involving many factors. Inflammatory events occur more frequently during the active phase, whereas fibrosis of the orbital tissue predominates during the inactive phase [8]. Studies have shown that changes in choroidal thickness occur in orbital inflammatory and systemic diseases due to choroidal inflammatory cell infiltration, increased exudate, increased vascular leakage, and altered orbital blood flow.5-7 In TED patients, orbital fibroblasts overexpressing thyroid-stimulating hormone receptors and insulin-like growth factor-1 receptors play an important role in orbital inflammation, extracellular matrix production, and adipocyte and myofibroblast differentiation. plays. Inflammatory cells normally infiltrate the orbital adipose tissue and extraocular muscles, and under the influence of inflammatory mediator cytokines, cause orbital stromal edema and extraocular muscle hypertrophy. It has been reported that orbital venous drainage is reduced in TED patients and that the reason for orbital venous flow reduction is elevated retroorbital pressure above normal venous pressure. It has been hypothesized that compression exerted by blood flow within the orbital space, restricted by reduced orbital venous outflow, may be associated with increased choroidal thickness.14-16 We found that the intraocular pressure values ​​in the patient group were higher than those in the control group. In the same study, foveal thickness was thinner in the patient group compared to the control group. In our study, the difference in intraocular pressure between patient and control groups was not significant.11 In our study, foveal thickness and intraocular pressure were similar between patient and control groups. Elongation of the optic nerve and sclera, with or without muscle involvement, can increase the measured intraocular pressure when the thyroid gland is active or inactive. Macular thickness can be affected by changes in intraocular pressure. Ganglion cell damage in the macula was confirmed in a study by Wu et al. Demonstrated in patients with high intraocular pressure [13]. Macular thickness increases within a month due to the reduction in intraocular pressure after glaucoma filtration surgery. They hypothesized that this was due to the physiological response of the retina to a sudden drop in intraocular pressure. As no differences in intraocular pressure were observed in our study, there are no differences in foveal thickness.

Sen et al. the Graves' disease group was found to have higher intraocular pressure values ​​than the control group (p=0.01).12 Similarly, Wu et al. found higher intraocular pressure values ​​in the patient group compared to the control group.13 The reason the results differ from the literature is that the number of patients included in the study was relatively small and patients were inactive. In a study by Ozcan et al., subfoveal choroidal thickness was higher in the patient group than in the control group. Most patients in this patient group were clinically inactive, and it was reported that the increased subfoveal choroidal thickness may be due to the venous occlusion observed in the patient group.8 In another study, Charshukan et al. They found that subfoveal choroidal thickness increases in active TED patients compared with controls, whereas subfoveal choroidal thickness does not change in non-active TED patients compared with controls.2 In our study, similar to other literature studies, we found that the inactive TED group had higher subfoveal choroidal thickness than the healthy control group. Increased choroidal thickness in our study has been linked to venous occlusion, periorbital and retroorbital tissue inflammation, vascular macro- and microanatomical alterations due to proptosis, and consequent possible ischemic causes in the pathogenesis of TED. It is hypothesized that it is due to. Limitations of this study include the small number of patients, the lack of automation in the measurements of foveal and choroidal thickness, the lack of subgrouping of patients according to different clinical findings, and the lack of IOP and foveal thickness. and lack of correlation analysis with foveal thickness. It does not evaluate the best visual acuity.

Conclusion

In conclusion, foveal thickness in patients with thyroid eye disease did not differ from that in healthy controls, but subfoveal and temporal choroidal thicknesses were thicker than in healthy controls. Large-scale, long-term studies are needed on the causes and long-term effects of these differences.

Statement of ethics

This study approved from the Clinical Studies Ethics Committee of Mersin City Hospital (2021 / 799 – 29/12/2021).

Conflict of interest statement

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Funding source

The authors received no financial support for the research, authorship, and/or publication of this article.

Author Contributions

All authors contributed equally to the article. All authors read and approved the final manuscript.