Abstract
Purpose
To evaluate progressive changes in retinal nerve fibre layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL) and visual function in thyroid eye disease (TED) patients with and without orbital decompression.
Methods
Sixty TED patients (105 eyes) were included. All patients were divided into mild, moderate-to-severe and dysthyroid optic neuropathy (DON) groups. Orbital decompression was performed in the moderate-to-severe and DON groups. Optic coherence tomography (OCT), visual field (VF) and best-corrected visual acuity (BCVA) were performed pre- and postoperatively. Preoperative follow-up was performed in the mild group and in part of the moderate-to-severe and DON groups.
Results
After decompression, the thickness of GCL/IPL and RNFL significantly decreased in DON group (p < 0.05), with varying degrees of decrease in eyes with optic disc swelling, atrophy and normal appearance. The mean GCL/IPL thickness significantly decreased in moderate-to-severe group (p < 0.05), the mean RNFL thickness slightly decreased with no statistical significance (p = 0.07). During the preoperative follow-ups, the mean GCL/IPL thickness significantly decreased (p = 0.04), whereas the mean RNFL thickness tended to increase (p = 0.13) in DON group. The thickness of GCL/IPL and RNFL did not change significantly in the mild and moderate-to-severe groups (p > 0.05). BCVA and VF did not change significantly in any group (p > 0.05) preoperatively.
Conclusion
Swelling and degeneration of retinal ganglion cells (RGCs) may coexist in DON eyes, leading to continuous changes in the RNFL and GCL/IPL thickness either before or after decompression. Slight swelling and degeneration of RGCs may exist in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.
Subject terms: Optic nerve diseases, Eye manifestations, Thyroid diseases
Introduction
Thyroid eye disease (TED) is the most common orbital disease [1]. The majority of patients exhibit mild-to-moderate symptoms, and approximately 3–7% develop vision-threatening complications, such as dysthyroid optic neuropathy (DON) [2]. DON is typically evaluated clinically in terms of visual acuity (VA), color vision, pupillary reaction and visual field [3]. In recent years, optical coherence tomography (OCT) has emerged as a reliable and sensitive tool for assessing the anatomy of the optic nerve. The thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer/inner plexiform layer (GCL/IPL) have been shown to change not only in DON patients but also in patients without definitive DON [4, 5], which indicates that structural damage might occur earlier than functional impairment. We previously reported that the thickness of the RNFL and GCL/IPL became thinner in patients with moderate-to-severe TED [6].
Orbital decompression surgery is a crucial treatment for DON [7, 8]. This surgery relieves optic nerve compression secondary to increased orbital soft tissue and leads to improvements in visual function. Conversely, the thickness of the RNFL decreases after decompression in DON patients, which is probably due to the resolution of edema and persistent atrophy [9, 10].
However, the progressive changes in retinal ganglion cells (RGCs) and visual function in TED patients with different severities either before or after their surgery unclear, and this information may aid in understanding the pathological changes of the optic nerve in this disease. In this study, we analyzed the postoperative changes in the GCL/IPL, RNFL and visual function in different severities of TED. We also analyzed the changes in the GCL/IPL, RNFL and visual function when TED eyes were not subjected to surgery.
Patients and methods
Sixty patients diagnosed with TED were recruited at Eye & ENT Hospital, Fudan University, from January 2018 to January 2020. The study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Fudan University. Informed consent was obtained from all patients in the study.
The patients were classified into three groups based on their disease severity: (1) mild group, (2) moderate-to-severe group, and (3) DON group. The mild and moderate-to-severe groups were defined according to the European Group on Graves’ Orbitopathy (EUGOGO) criteria. DON was diagnosed based on the following: decreased VA, a relative afferent pupillary defect (RAPD), abnormal color vision (Ishihara plates), compatible visual field (VF) defects, disc swelling or atrophy and orbital apex crowding based on radiological evidence. If bilateral severities were different, then only the more serious eye would be assigned to the corresponding groups.
The exclusion criteria included age younger than 18 years, history of ocular surgery or ocular trauma, evident refractive error (spherical: >−3 D or > +2 D, cylindrical: >±2 D), evident exposure keratopathy that could affect vision, and other ophthalmopathies that could affect OCT measurements (e.g., glaucoma, optic nerve diseases, retinal diseases, obvious media opacities, and obvious strabismus).
The following clinical data were obtained from the patients: sex, age, disease duration, corticosteroid treatment, clinical activity score (CAS), best corrected VA (logMAR), intraocular pressure (IOP) (Goldmann applanation tonometry), slit-lamp and fundus examinations, Hertel exophthalmometry, Humphrey perimetry and OCT measurements.
Ophthalmic examinations and OCT measurements were performed pre- and postoperatively in the eyes with orbital decompression surgery, and a reevaluation was performed in some eyes during the follow-up period before surgery.
Surgical technique
All decompression surgeries were performed by a single surgeon (J.Q.). Deep lateral wall decompression was performed through an eyelid crease incision. The lacrimal gland fossa, the greater wing of the sphenoid bone, and, for some patients, the basin region was removed, and the periorbita was incised. Medial wall decompression was performed through a transcaruncular incision. Medial and posterior ethmoidectomy were performed, and the periorbita was incised. For inferior wall decompression, a small region of the posteromedial orbital floor was removed. The extent of osteotomy was individualized based on the degree of proptosis. For some patients, inferolateral intraconal fat was removed, yielding volumes ranging from 0.5 to 1.5 ml.
OCT measurement
Patients underwent OCT scanning with a Cirrus HD-OCT device (Carl Zeiss Meditec, Inc., Germany). The peripapillary RNFL thickness was obtained using the Optic Disc Cube 200 × 200 protocol, and the GCL/IPL thickness was obtained using the Macular Cube 512 × 128 protocol. The included scans had to demonstrate a signal strength ≥6, no movement artifacts or segmentation errors, and good centring on the fovea.
Visual field examination
Humphrey visual field analysis was performed using the 30-2 SITA-standard protocol (Humphrey Field Analyzer 750i, Carl Zeiss Meditec Inc. Dublin). Only reliable visual fields were considered (<20% false positives or false negatives; fixation losses <20%), and the mean deviation (MD) was recorded.
Statistical analysis
The analyses were performed using SPSS 19. Mean values are presented with standard deviations. Paired t tests and Wilcoxon signed-ranks tests were used to analyse the changes in OCT measurements and ophthalmic examinations between different visits. Student’s t test and nonparametric test were used to analyse the difference between the cases with and without prior steroid treatment. All differences with a value of p < 0.05 were considered statistically significant.
Results
Patient characteristics
Sixty TED patients (105 eyes) were included in the study. The general characteristics of the patients are listed in Table 1. The interval between prior steroid treatment and the current evaluation was 9.8 ± 7.9 months (range, 6–24 months) and 4.2 ± 3.2 months (range, 0.5–12 months) in the moderate-to-severe and DON groups, respectively. Four patients with moderate-to-severe TED did not demonstrate evident DON before or during their steroid treatment. No patient received radiation therapy prior to treatment.
Table 1.
General characteristics of the TED patients.
| Mild | Moderate-to-severe | DON | |
|---|---|---|---|
| Patients (eyes) | 9 (18) | 24 (43) | 27 (44) |
| Age (years) | 37.2 ± 10.9 | 42.1 ± 12.1 | 53.7 ± 8.8 |
| Male/female | 3/6 | 6/18 | 13/14 |
| Disease duration (months) | 17.8 ± 17.1 | 22 ± 16.7 | 15.8 ± 13.3 |
| Previous steroid treatment number (%) | 0 (0%) | 4 (16.7%) | 18 (66.7%) |
| CAS | 0.3 ± 0.5 | 0.7 ± 0.7 | 1.6 ± 0.9 |
CAS clinical activity score.
Changes after orbital decompression surgery
Twenty-nine eyes in the moderate-to-severe group and 34 eyes in the DON group undergoing orbital decompression surgery were included for analysis. OCT measurements and ophthalmic examinations were performed pre- and postoperatively (Table 2).
Table 2.
The changes of ophthalmic parameters in TED eyes before and after orbital decompression surgery.
| Moderate-to-severe group (n = 29) | DON group (n = 34) | |||||
|---|---|---|---|---|---|---|
| Mean follow-up period | 3.9 ± 3.3 months | 2.6 ± 1.6 months | ||||
| Pre-op | Post-op | p value | Pre-op | Post-op | p value | |
| GCL/IPL (μm) | ||||||
| Mean | 83.2 ± 4.3 | 82.0 ± 4.6 | <0.001 | 77.6 ± 11.6 | 73.7 ± 11.9 | <0.001 |
| S | 82.9 ± 5.7 | 82.7 ± 5.8 | 0.08 | 77.2 ± 13.3 | 73.5 ± 13.4 | 0.001 |
| ST | 80.9 ± 5.5 | 79.9 ± 5.5 | 0.056 | 75 ± 15.7 | 72.1 ± 13.2 | 0.019 |
| SN | 85.2 ± 6.1 | 83.6 ± 6 | 0.002 | 79.4 ± 11.3 | 75.1 ± 13.2 | <0.001 |
| I | 81.9 ± 5.2 | 80.6 ± 6.1 | 0.03 | 76.1 ± 13.1 | 72.4 ± 10.7 | 0.004 |
| IT | 82.7 ± 5.6 | 81.8 ± 6.5 | 0.03 | 76.8 ± 16.1 | 74.9 ± 12 | 0.143 |
| IN | 83.7 ± 5.4 | 83.3 ± 6.3 | 0.21 | 77.4 ± 12.7 | 74 ± 11.5 | 0.007 |
| RNFL (μm) | ||||||
| Mean | 98.9 ± 6.9 | 97.5 ± 7.8 | 0.07 | 128.2 ± 66.1 | 107.3 ± 24.7 | 0.015 |
| S | 121.7 ± 15.2 | 122.5 ± 15.5 | 0.33 | 166.9 ± 109.2 | 134.8 ± 41.7 | 0.021 |
| T | 72.8 ± 72.9 | 72.3 ± 13.7 | 0.37 | 86.7 ± 46.6 | 72.9 ± 18.1 | 0.048 |
| I | 131.4 ± 15.4 | 127 ± 17.7 | 0.052 | 165.5 ± 72.6 | 142.8 ± 39.5 | 0.017 |
| N | 69.7 ± 9.1 | 68.8 ± 11.3 | 0.4 | 94.4 ± 49.2 | 78.5 ± 15.6 | 0.02 |
| Proptosis (mm) | 21.0 ± 2.4 | 17.1 ± 2.1 | <0.001 | 21.7 ± 2.3 | 17.3 ± 2.2 | <0.001 |
| VA (LogMAR) | 0.02 ± 0.03 | 0.01 ± 0.03 | 0.08 | 0.44 ± 0.38 | 0.26 ± 0.3 | <0.001 |
| MD (dB) | −1.5 ± 1.1 | −1.2 ± 1.2 | 0.19 | −11.1 ± 8.3 | −5.9 ± 6.5 | <0.001 |
| IOP (mmHg) | 16.8 ± 4.8 | 16.4 ± 4.2 | 0.46 | 18.9 ± 5.1 | 17.6 ± 4.2 | 0.012 |
Statistically significant p-values are in bold.
OCT optic coherence tomography, TED thyroid eye disease,Pre-op preoperative, Post-op postoperative, DON dysthyroid optic neuropathy. GCL/IPL ganglion cell layer/inner plexiform layer, RNFL retinal nerve fibre layer, S superior, T temporal, I inferior, N nasal, ST supero-temporal, SN superonasal, IT infero-temporal, IN inferonasal, VA visual acuity, MD mean deviation, IOP intraocular pressure.
In the 34 eyes with DON, the mean thickness of the GCL/IPL and RNFL significantly decreased after decompression surgery (p < 0.05). BCVA and MD showed significant improvement postoperatively (p < 0.001). IOP significantly decreased (p = 0.012). Additionally, the mean thickness of GCL/IPL decreased in the eyes with optic disc swelling, atrophy and normal appearance (p < 0.05); the mean thickness of RNFL significantly decreased in the eyes with optic disc swelling and normal appearance (p < 0.05), there was a minimal decrease in the eyes with optic disc atrophy but the difference was not statistically significant (p = 0.15) (Table 3).
Table 3.
The changes of OCT parameters in DON eyes with different optic disc appearance before and after orbital decompression surgery.
| Swelling | Atrophy | Normal | |||||||
|---|---|---|---|---|---|---|---|---|---|
| n = 17 | n = 6 | n = 11 | |||||||
| Pre-op | Post-op | p-value | Pre-op | Post-op | p-value | Pre-op | Post-op | p-value | |
| Mean GCL/IPL (μm) | 80.9 ± 8 | 75.8 ± 10.1 | <0.001 | 64.4 ± 12.8 | 62.6 ± 13.3 | 0.02 | 78 ± 10.6 | 75.2 ± 11.9 | 0.03 |
| Mean RNFL (μm) | 151.5 ± 58.1 | 118.1 ± 26.1 | 0.02 | 81.5 ± 2.3 | 79.8 ± 3.2 | 0.15 | 102.5 ± 8.8 | 98.2 ± 7.9 | 0.002 |
Statistically significant p-values are in bold.
In the 29 eyes with moderate-to-severe TED, the mean GCL/IPL thickness significantly decreased postoperatively (p < 0.001). The mean RNFL thickness also decreased, but the difference did not reach statistical significance (p = 0.07). BCVA, MD and IOP did not change significantly postoperatively (p > 0.05).
The preoperative parameters and the changes in GCL/IPL and RNFL thickness had no significant difference between patients with or without prior steroid treatment in both groups (all p > 0.1).
Progressive changes after orbital decompression surgery
Nineteen eyes received a second postoperative follow-up over a relatively long period, including 13 eyes with DON and 6 eyes with moderate-to-severe TED.
In the 13 eyes with DON, the mean duration of the two follow-ups was 2.3 ± 0.5 months (range, 1–3 months) and 6.6 ± 3.1 months (range, 4–12 months). The mean thickness of the RNFL and GCL/IPL continued to decrease after surgery. The mean RNFL thickness significantly decreased from 142.8 ± 84.4 μm preoperatively to 117.6 ± 34.1 μm (p = 0.008) and 102.9 ± 15.2 μm (p = 0.001) postoperatively. The mean GCL/IPL thickness significantly decreased from 79 ± 10.9 μm preoperatively to 73.4 ± 13.1 μm (p = 0.002) and 69.8 ± 15.8 μm (p = 0.021) postoperatively. The logMAR VA significantly improved from 0.46 ± 0.4 preoperatively to 0.26 ± 0.3 (p < 0.001) and 0.16 ± 0.3 (p = 0.012) postoperatively. The MD significantly improved from −14.1 ± 7 dB preoperatively to −7.1 ± 6 dB (p = 0.006) at the first postoperative follow-up and then demonstrated a trend for improvement, ultimately reaching −5.2 ± 3.9 dB (p = 0.09) (Fig. 1A–D). Compared with the eyes with optic disc atrophy, the continuous thinning of RNFL and GCL/IPL were more significant in those with optic disc swelling, which tended to get stable later.
Fig. 1. Progressive changes in ophthalmic parameters after orbital decompression surgery.
A–D changes in the mean thickness of RNFL and GCL/IPL, mean deviation, and visual acuity (logMAR) in the DON group. E, F changes in the mean thickness of RNFL and GCL/IPL in the moderate-to-severe group.
In the 6 eyes with moderate-to-severe TED, the mean duration of the two follow-ups was 7.2 ± 4.1 months (range, 2–10 months) and 14.8 ± 6.5 months (range, 10–23 months). The mean GCL/IPL thickness significantly decreased from 83.8 ± 5.6 μm preoperatively to 82 ± 6.4 μm (p = 0.03) at the first follow-up but showed no significant decrease at the second follow-up (82.3 ± 6.1 μm, p = 0.53). The mean RNFL thickness was 98 ± 4 μm preoperatively and 97 ± 3.7 μm and 96.8 ± 2.3 μm postoperatively; neither of the changes was statistically significant (p > 0.05) (Fig. 1E, F). Additionally, the logMAR VA and MD did not significantly change during the follow-up period (p > 0.1).
Changes before orbital decompression surgery
The changes in ophthalmic parameters were evaluated in 42 eyes before their decompression surgery. In total, 18 eyes with mild TED and 14 eyes with moderate-to-severe TED did not undergo orbital decompression surgery during the study period; 10 eyes with DON were reexamined before the surgery (Table 4).
Table 4.
Changes of ophthalmic parameters in TED eyes without orbital decompression surgery.
| Mild group (n = 18) | Moderate-to-severe group (n = 14) | DON group (n = 10) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean follow-up period | 4.9 ± 2.9 months | 3.3 ± 3.6 months | 1.8 ± 1.5 months | ||||||
| First-visit | Second-visit | p-value | First-visit | Second-visit | p-value | First-visit | Second-visit | p-value | |
| GCL/IPL (μm) | |||||||||
| Mean | 86.8 ± 5.6 | 86.4 ± 5.2 | 0.14 | 81.6 ± 4.9 | 81.4 ± 4.4 | 0.3 | 79 ± 7 | 75 ± 9 | 0.04 |
| S | 86.6 ± 5.8 | 85.8 ± 5.7 | 0.08 | 82.1 ± 5.5 | 81.8 ± 5.2 | 0.8 | 80.1 ± 6.8 | 75.7 ± 9.1 | 0.027 |
| ST | 85.8 ± 6 | 84.9 ± 5.3 | 0.08 | 79.3 ± 6 | 79.1 ± 6.1 | 0.21 | 78.1 ± 6.5 | 74.4 ± 8 | 0.022 |
| SN | 89.3 ± 6.4 | 89 ± 6 | 0.71 | 84 ± 5.2 | 82.9 ± 4.8 | 0.83 | 80.3 ± 7.6 | 76.3 ± 10.6 | 0.097 |
| I | 86 ± 5.9 | 85.9 ± 5.7 | 0.82 | 78.8 ± 5.9 | 78.6 ± 3.9 | 0.89 | 78.1 ± 7.5 | 73.6 ± 10 | 0.054 |
| IT | 87 ± 5.7 | 86.9 ± 5.2 | 0.3 | 80.8 ± 4.8 | 80.2 ± 5.1 | 0.42 | 78.6 ± 7.9 | 74.7 ± 9.9 | 0.029 |
| IN | 87.5 ± 6 | 86.9 ± 5.9 | 0.25 | 81.1 ± 5.4 | 80.7 ± 5.1 | 0.36 | 80.1 ± 7.4 | 75.9 ± 10.4 | 0.083 |
| RNFL (μm) | |||||||||
| Mean | 104.2 ± 7.4 | 103.6 ± 7.1 | 0.38 | 98.7 ± 7.3 | 97.7 ± 6.5 | 0.51 | 103.9 ± 11.1 | 106.4 ± 11.9 | 0.13 |
| S | 132.3 ± 8.9 | 130.8 ± 7.9 | 0.42 | 126.3 ± 12 | 125.2 ± 10.2 | 0.68 | 120.7 ± 11.5 | 129.3 ± 20.1 | 0.12 |
| T | 77 ± 12.9 | 77.1 ± 10.9 | 0.9 | 69.7 ± 12.1 | 69.4 ± 9.7 | 0.94 | 72.6 ± 11.2 | 70.9 ± 9.5 | 0.41 |
| I | 136.6 ± 13.4 | 136.5 ± 13.1 | 0.86 | 128.4 ± 11.1 | 128.2 ± 10 | 0.97 | 142.3 ± 25.8 | 145.1 ± 24 | 0.28 |
| N | 71.2 ± 9.5 | 70.7 ± 11.2 | 0.67 | 70.2 ± 8.4 | 69.1 ± 10.8 | 0.64 | 76.1 ± 8.4 | 78.4 ± 8.9 | 0.2 |
| Proptosis (mm) | 15.3 ± 2.4 | 15.4 ± 2.5 | 0.68 | 18.2 ± 2.2 | 18.4 ± 1.9 | 0.29 | 21.6 ± 1.8 | 21.4 ± 1.7 | 0.36 |
| VA (LogMAR) | 0 | 0 | N/A | 0.1 ± 0.23 | 0.08 ± 0.14 | 0.33 | 0.31 ± 0.35 | 0.35 ± 0.34 | 0.48 |
| MD (dB) | −1.8 ± 1.3 | −1.7 ± 1.5 | 0.39 | −3.6 ± 1.4 | −3.3 ± 2.3 | 0.67 | −13.4 ± 7.5 | −15.8 ± 12.4 | 0.6 |
| IOP (mmHg) | 15.7 ± 2.3 | 15.8 ± 2.2 | 0.85 | 16.3 ± 5 | 16.9 ± 4.6 | 0.42 | 18.7 ± 3.3 | 18 ± 4 | 0.39 |
Statistically significant p-values are in bold.
OCT optic coherence tomography, TED thyroid eye disease, DON dysthyroid optic neuropathy, GCL/IPL ganglion cell layer/inner plexiform layer, RNFL retinal nerve fibre layer. S superior, T temporal, I inferior, N nasal, ST supero-temporal, SN superonasal, IT infero-temporal, IN inferonasal, VA visual acuity, MD mean deviation, IOP intraocular pressure.
The thickness of the GCL/IPL and RNFL did not significantly change in the eyes with mild or moderate-to-severe TED before they were subject to surgery (p > 0.05). In the eyes with DON, the mean GCL/IPL thickness significantly decreased during the follow-up period (p = 0.04), whereas the mean RNFL thickness increased but not to a statistically significant degree (p = 0.13).
The initial parameters and changes in GCL/IPL and RNFL thickness had no significant difference between patients with or without prior steroid treatment in the moderate-to-severe and DON groups (all p > 0.1).
No significant difference was found in proptosis, logMAR VA, MD or IOP in the three groups during the follow-up period (p > 0.1).
Discussion
Compression of the optic nerve by increased orbital soft tissue is considered a main cause of neuropathy in TED. Blocking and damaging optic nerve axons will lead to varying degrees of visual dysfunction. OCT provides a useful tool for quantifying the anatomic changes in RGCs. Specifically, the cell bodies of RGCs are located in the GCL, and their axons constitute the RNFL [11].
Orbital decompression surgery is a well-established treatment for DON; it can relieve optic nerve compression and is generally required in patients who are refractory to drug treatment [12]. It has been widely demonstrated that visual functions improve after orbital decompression in DON patients [7, 8], which likely results from the restoration of signal conduction. The RNFL always becomes thinner postoperatively in eyes with DON [9, 10]. Our results are consistent with those of previous reports. Damage to the RGCs is a continuous process: the persistent axonal conduction block and subsequent retrograde degeneration. RNFL thickness may be affected by axonal swelling and retrograde degeneration simultaneously in patients with DON. After orbital decompression, the RNFL thickness exhibited a marked decrease in the eyes with optic disc swelling, mainly due to the recovery of axoplasmic transport and the subsidence of axonal swelling. A tiny decrease in the RNFL thickness was observed in the eyes with optic disc atrophy, mainly due to the prolonged process of axonal degeneration. For the eyes with a normal optic disc appearance, we speculated that the resolution of axonal swelling and the prolonged axonal degeneration both play a role in the thinning of RNFL.
In our study, the GCL/IPL thickness also decreased after orbital decompression in DON group. For the eyes with different optic disc appearances, the changes in GCL/IPL thickness were consistent with those in RNFL thickness. The results might indicate that swelling and/or degeneration were present not only in the axons of RGCs but also in their bodies. Additionally, repeated follow-up was performed in some eyes with DON, the thickness of the RNFL and GCL/IPL decreased continuously over a relatively long postsurgical period. These may indicate that the resolution of swelling and/or persistence of degeneration was a slow and continuous process after surgery [13]. A similar result was reported in patients with chiasmal compressive optic neuropathy who underwent decompression surgery [13].
Structural damage may occur earlier than functional impairment in compressive neuropathy. The thickness of the RNFL and GCL/IPL has been reported to decrease in TED patients who have no clinical sign of DON, especially in patients with moderate-to-severe TED [4–6]. This reduction might indicate underlying damage to the optic nerve. In this study, additionally, the thickness of the GCL/IPL exhibited a small but significant decrease after orbital decompression in eyes with moderate-to-severe TED. These results might indicate that slight atrophy accompanied by minimal oedema occurs in the RGCs of these eyes and the oedema was relieved after decompression surgery. Unlike the changes in DON eyes, repeated follow-up revealed that the thickness of the RNFL and GCL/IPL did not decrease continuously and even exhibited a small increasing tendency in some eyes with moderate-to-severe TED. This finding might indicate that the retrograde degeneration was slight and that delayed restoration of the RGCs may occur after surgery.
In our study, the preoperative changes in the RNFL, GCL/IPL and visual functions were evaluated in some eyes. Within the follow-up period, the GCL/IPL thickness decreased and the RNFL thickness tended to increase in DON eyes, indicating that RGCs damage progressed continuously prior to surgery, although visual function exhibited no obvious change. The thickness of the GCL/IPL and RNFL did not significantly change in eyes with moderate-to-severe TED, which may indicate that the changes in RGCs were minimal, chronic and relatively stable during the follow-up period. We speculated that the damage of RGCs is absent in eyes with mild TED.
There were still some limitations in our study. First, the sample size was small. Second, the follow-up duration was relatively short. The remyelination and restoration of axoplasmic flow might occur months to years after decompression surgery; therefore, the long-term changes in the RNFL and GCL/IPL thickness in patients with mild and moderate-to-severe TED are unclear.
In conclusion, for eyes with DON, RGC damage may be progressive before surgery, although changes in visual function are not obvious. In addition, the decreased swelling and persistent degeneration in RGCs may continue for a relatively long period of time after orbital decompression surgery. For eyes with moderate-to-severe TED, although the GCL/IPL, RNFL and visual function remained stable before surgery, the thickness of GCL/IPL and RNFL showed a small decrease postoperatively and then remained relatively stable. These findings may indicate that slight oedema and underlying degeneration may be present in RGCs in eyes with moderate-to-severe TED.
Summary table
What was known before
The thickness of the RNFL decreases after decompression in DON patients due to the resolution of oedema and persistent atrophy.
The thickness of the RNFL and GCL/IPL may become thinner in patients with moderate-to-severe TED.
What this study adds
The thickness of the RNFL and GCL/IPL has progressive changes in DON patients either before or after decompression.
Chronic mild swelling and degeneration of RGCs may be present in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.
Author contributions
All authors conceived of and participated in the study design. All authors participated in the eye examinations and data collection. JQ performed the orbital decompression surgeries. JG and RQM drafted the manuscript. LG and XFL performed the statistical analysis. KX, JWC and JQ did critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.
Funding
National Natural Science Foundation of China [grant numbers 82000940, 81800867 and 81970835]. The Shanghai Committee of Science and Technology, China [grant number 20Y11911200].
Data availability
All data generated or analysed during this study are included in this published article.
COMPETING INTERESTS
The authors declare no competing interests.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Jie Guo, Ruiqi Ma, Lu Gan.
References
- 1.Lazarus JH. Epidemiology of Graves’ orbitopathy (GO) and relationship with thyroid disease. Best Pr Res Clin Endocrinol Metab. 2012;26:273–9. doi: 10.1016/j.beem.2011.10.005. [DOI] [PubMed] [Google Scholar]
- 2.Blandford AD, Zhang D, Chundury RV, Perry JD. Dysthyroid optic neuropathy: update on pathogenesis, diagnosis, and management. Expert Rev Ophthalmol. 2017;12:111–21. doi: 10.1080/17469899.2017.1276444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91:455–8. doi: 10.1136/bjo.2006.094607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Sen E, Berker D, Elgin U, Tutuncu Y, Ozturk F, Guler S. Comparison of Optic Disc topography in the cases with graves disease and healthy controls. J GLAUCOMA. 2012;21:586–9. doi: 10.1097/IJG.0b013e31822e8c4f. [DOI] [PubMed] [Google Scholar]
- 5.Wu Y, Tu Y, Wu C, Bao L, Wang J, Lu F, et al. Reduced macular inner retinal thickness and microvascular density in the early stage of patients with dysthyroid optic neuropathy. Eye Vis. 2020;7:1–12. doi: 10.1186/s40662-020-00180-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Guo J, Li X, Ma R, Gan L, Qian J. The changes of retinal nerve fiber layer and ganglion cell layer with different severity of thyroid eye disease. Eye. 2021;36:129–34. doi: 10.1038/s41433-021-01453-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Choe CH, Cho RI, Elner VM. Comparison of lateral and medial orbital decompression for the treatment of compressive optic neuropathy in thyroid eye disease. Ophthal Plast Reconstr Surg. 2011;27:4–11. doi: 10.1097/IOP.0b013e3181df6a87. [DOI] [PubMed] [Google Scholar]
- 8.Liao SL, Chang TC, Lin LLK. Transcaruncular orbital decompression: an alternate procedure for graves ophthalmopathy with compressive optic neuropathy. AM J Ophthalmol. 2006;141:810–8. doi: 10.1016/j.ajo.2005.12.010. [DOI] [PubMed] [Google Scholar]
- 9.Park K, Kim Y, Woo KI. Changes in optical coherence tomography measurements after orbital wall decompression in dysthyroid optic neuropathy. Eye. 2018;32:1123–9. doi: 10.1038/s41433-018-0051-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Rajabi MT, Ojani M, Esfahani HR, Tabatabaei SZ, Rajabi MB, Hosseini SS. Correlation of peripapillary nerve fiber layer thickness with visual outcomes after decompression surgery in subclinical and clinical thyroid-related compressive optic neuropathy. J Curr Ophthalmol. 2019;31:86–91. doi: 10.1016/j.joco.2018.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Micieli JA, Newman NJ, Biousse VR. The role of optical coherence tomography in the evaluation of compressive optic neuropathies. Curr Opin Neurol. 2019;32:115–23. doi: 10.1097/WCO.0000000000000636. [DOI] [PubMed] [Google Scholar]
- 12.Saeed P, Rad ST, Bisschop PHLT. Dysthyroid Optic Neuropathy. Ophthal Plast Reconstr Surg. 2018;34:60–7. doi: 10.1097/IOP.0000000000001146. [DOI] [PubMed] [Google Scholar]
- 13.Moon CH, Hwang SC, Ohn Y, Park TK. The time course of visual field recovery and changes of retinal ganglion cells after optic chiasmal decompression. Invest Ophthalmol Vis Sci. 2011;52:7966–73. doi: 10.1167/iovs.11-7450. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analysed during this study are included in this published article.