Abstract
Introduction: The aim of the study was to standardize the endoscopic deep medial orbital decompression surgery for better relief of optic nerve compression in dysthyroid optic neuropathy (DON). Methods: A total of 128 eyes from patients received the standardized endoscopic deep medial orbital decompression surgery were recruited in this study. The efficacy of the procedure was assessed at a 1-month follow-up by the best-corrected visual acuity (VA), visual field (VF), and visual evoked potential (VEP). Clinical data were collected to explore the factors that affected visual recovery. Oxygen saturation of retinal blood vessels, retinal thickness, and vessel density were measured to demonstrate the potential recovery mechanisms. Results: After surgery, the ratio of extraocular muscle volume in the orbital apex to orbital apex volume significantly decreased from 44.32 ± 22.31% to 36.82 ± 12.02% (p < 0.001). 96.87% of eyes’ final VA improved; average VA improved from 0.93 ± 0.73 to 0.50 ± 0.60 at 1 week (p < 0.001) and 0.40 ± 0.53 at 1 month (p < 0.001). Postoperatively, VF and VEP also improved, the oxygen saturation of retinal arteries increased, and the retinal thickness was reduced. Preoperative VA, visual impairment duration, and clinical activity score evaluation were associated with visual recovery. Conclusion: In this study, we standardized the endoscopic deep medial orbital decompression, of which key point was to relieve pressure in the orbital apex and achieved satisfactory visual recovery in DON patients.
Introduction
Dysthyroid optic neuropathy (DON) is the most common cause of visual loss in thyroid eye disease (TED) [1‒3]. The most widely accepted mechanism is that the enlarged extraocular muscle (EOM) compresses the optic nerve or restricts the blood supply to the optic nerve, causing optic nerve ischemia or inhibiting axonal flow [4]. According to the latest clinical practice guidelines, DON is the indication for surgical decompression in TED, particularly if treatment with steroids or irradiation has proven ineffective [5]. Accurate and timely identification and release of optic nerve compression are critical to the treatment of DON.
Currently, orbital decompression surgery consists of four main approaches: transorbital, transcranial, transantral, and transnasal. The transnasal approach is becoming increasingly popular as it can avoid the complications caused by external approaches and provides sufficient decompression to the orbital apex, which was difficult to approach in conventional surgery [6, 7]. However, at present, this surgery is still varied and lacks consensus regarding how to reach the correct anatomical site [8, 9].
In our preliminary study, we compared the differences in orbital parameters between DON and non-DON patients through computed tomography (CT) scans and found the primary site causing DON was in the orbital apex, where the enlarged EOM compressed the optic nerve [10]. This evidence suggests that an effective surgery should be able to relieve the compression of the optic nerve in the orbital apex.
Therefore, we proposed a more accurate procedure for endoscopic deep medial orbital decompression to standardize the procedure of endoscopic deep medial orbital decompression in DON to achieve better efficacy. The decompression procedure’s effectiveness was validated through orbital apex structure changes, visual acuity (VA), visual evoked potential (VEP), and visual field (VF). In addition, we attempted to explain the mechanism by which surgery relieves optic nerve compression and improves vision through changes in retinal oxygen saturation and retinal nerve fiber layer (RNFL) thickness. This lays the groundwork for the enhancement and standardization of the surgery and its possible mechanism.
Materials and Methods
Ethical Approval
This prospective clinical research was conducted in accordance with the principles outlined in the Declaration of Helsinki and approved by the Ethics Committee of Zhongshan Ophthalmic Center (Guangzhou, China, 2017KYPJ101). Before the study, written informed consent was obtained from all participating individuals. Participants also provided written informed consent for the publication of their photo used in the manuscript.
Participates
A total of 128 TED patients were recruited for this prospective study. Every TED diagnosis was based on clinical features according to Bartley’s criteria, and all operations were performed by the same senior ophthalmologist (Professor Rong Lu) at Zhongshan Ophthalmic Center (ZOC) from January 2016 to May 2021 [11]. The inclusion criteria were as follows: (1) a confirmed diagnosis of TED and at least one eye with DON (TED classification VI, American Thyroid Association, 1977), no relief or recurrence after steroid therapy; (2) No thyroid disease or euthyroid after treatment in hyperthyroidism, hypothyroidism; (3) age 20 years or older; (4) not in the gestation period; (5) no history of other ocular disorders, trauma, or surgery; (6) no other severe nonophthalmic complications detected upon systemic examination; and (7) not participating in other clinical trials. Only one eye from each patient was used for statistical purposes. For patients who needed surgery on both eyes, we randomly selected one eye to be included in the analysis. And for patients with DON and abnormal thyroid function, the treatment strategy we adopt is to first perform medical treatment to control thyroid function, and then perform glucocorticoid pulse therapy or surgical treatment after thyroid function is well controlled.
The diagnostic criteria for DON were as follows: (1) decreased best-corrected VA (i.e., VA < 0.8) caused by TED, of which orbital apical crowding can be observed on CT images, instead of other diseases; (2) the presence of a relative afferent pupillary defect, as defined by the criteria; (3) abnormality in terms of VEP; and (4) in the VF examination, mean deviation was less than 5.0 decibels.
Endoscopical Deep Medial Orbital Decompression and the Postoperative Management
The standardized deep medial orbital decompression surgery was carried out under general anesthesia. Nasal vasoconstriction and decongestion were achieved using mucosal injections of 1% lidocaine with 1:10,0000 epinephrine and a saturated cotton pad infiltrated with the above solution. Intranasal endoscopic spheno-ethmoidectomy was undertaken using a 0° endoscope (Karl Storz, Tuttlingen, Germany). The procedure was as follows (Fig. 1a–d):
- 1.
Transnasal endoscopic spheno-ethmoidectomy exposed the entire medial orbital wall, including the deep medial wall of the orbital apex.
- 2.
The medial orbital wall was thinned using a microdrill, and then the entire medial orbital bone, i.e., posterior to the optic canal, anterior to the maxillary line, superior to the ethmoid roof, and inferior to the inferomedial strut, was removed.
- 3.
The standardized transnasal deep medial orbital decompression not only decompressed the classic medial orbital wall but also precisely decompressed the orbital apex. The medial wall was finely resected to the junction of the medial lesser wing of the sphenoid bone and the optic canal next to the orbital apex, not full length of the optic canal, fully exposing the area of annulus of Zinn.
- 4.
A tip endoscopic knife (12-sickle blade) was used to incise the periosteum from the area of the annulus of Zinn to the maxillary line, horizontally, parallel with the medial rectus, and generally along the location of the superior and inferior border of the medial rectus muscle, respectively. As the surface layer of the area of the annulus of Zinn was extended from the orbital septum, we only incised the periosteum instead of the full thickness of the annulus of Zinn carefully to make sure that the EOMs were not injured. The appearance after the incision is shown in Figure 1c.
- 5.
Orbital fat was removed with a manual cutting instrument; the amount of fat we remove is mainly determined based on the preoperative protopsis.
Schematic diagram of deep medial orbital decompression. a Schematic representation of the anatomical structures: the medial wall of the orbit (the area between yellow lines), the optic nerve canal (the area between blue dotted lines), and the junction between the medial lesser wing of the sphenoid bone and the optic canal (black arrow). b Thinning and removing the medial orbital wall of the orbital apex (the blue trapezoid area), the junction between the medial lesser wing of the sphenoid bone, and the lateral bone wall of the optic canal, not all the optic canal. Then, incising the periosteum on the area of annulus of Zinn relieves optic nerve compression. c Horizontal incision of the orbital septum (the area between dashed black lines). d Removal of the orbital fat using a manual cutting instrument.
Schematic diagram of deep medial orbital decompression. a Schematic representation of the anatomical structures: the medial wall of the orbit (the area between yellow lines), the optic nerve canal (the area between blue dotted lines), and the junction between the medial lesser wing of the sphenoid bone and the optic canal (black arrow). b Thinning and removing the medial orbital wall of the orbital apex (the blue trapezoid area), the junction between the medial lesser wing of the sphenoid bone, and the lateral bone wall of the optic canal, not all the optic canal. Then, incising the periosteum on the area of annulus of Zinn relieves optic nerve compression. c Horizontal incision of the orbital septum (the area between dashed black lines). d Removal of the orbital fat using a manual cutting instrument.
The postoperative management was as follows: intravenous broad-spectrum antibiotics and 80 mg of methylprednisolone sodium succinate for injection (Solu-Medrol) were given to patients for 3 days. Follow-up visits were performed at 1 day (P1D), 3 days (P3D), 1 week (P1W), 2 weeks (P2W), and 1 month (P1M) postoperatively. At each follow-up visit, VA, Goldmann applanation tonometer, slit lamp, and funduscopic examinations were conducted. At P1M, VEP and VF were conducted to evaluate visual function. Also, a CT scan, optical coherence tomography angiography (OCT-A), and retinal oximeter were performed again at P1M.
Volume Measurements of Orbital Tissue
The measurement method is consistent with the published literature [10]. We focused on comparing orbital parameters found in previous studies that reflect compression of the orbital apex. EMV-OA/OAV is the ration of EOM volume in orbital apex (EMV-OA) and orbital apex volume (OAV).
Ophthalmologic Examination
The primary endpoint was VA changes at 1 month postoperative, and the secondary endpoint was VEP and VF at 1 month postoperative. To evaluate the safety of the treatment, we tracked the complications after the surgery, including rhinorrhagia following surgery, severe bleeding, leakage of cerebrospinal fluid rhinorrhea, or death throughout the follow-up period.
VA and Visual Function
To evaluate vision changes after surgery, VA was measured before and after the surgery at different follow-up visits. All the VA values were subjective and obtained after sufficient correction of refractive errors through eyeglasses. The improved degree of VA (IDVA): IDVA = (LogMar VA after treatments – logMAR VA before treatments)/(−0.12* –LogMar VA before treatments), where *20/15 (LogMar = −0.12) was considered to be the perfect vision [12]. To evaluate vision function changes, the VEP (RETI-Port, Roland Consult, Brandenburg, Germany) and VF (The Humphrey VF analyzer, Carl Zeiss Meditec Dublin, CA, USA) were measured before and 1 month after surgery.
Exophthalmometric Examination
All the exophthalmometric examinations used Hertel exophthalmometric examination and were conducted by the same examiner.
CAS Evaluation
All the CAS evaluation was conducted by the same senior ophthalmologist.
Oxygen Saturation of Retinal Blood Vessels (SO2)
SaO2 using Oxymap T1 retinal oximeter (Oxymap ehf., Reykjavik, Iceland) was measured before and 1 month after treatment. Oxymap T1 is a noninvasive instrument used for measuring in vivo oxygen saturation of retinal arteries (SaO2) and veins (SvO2), as well as the differences between the arteries and veins (AVD) using the published method [13].
Optical Coherence Tomography Angiography (OCT-A)
All subjects were examined under a single OCT-A system (AngioVue; Optovue, Inc., Fremont, CA, USA), which was able to visualize and quantify the microvasculature in the retina. The scanning includes vessel density indices and the thickness of the retinal RNFL of the optic nerve head area automatedly. The scanning parameters were as published in the literature [13].
Other Examination
Other examinations include postoperative nasal endoscopy, general condition, vital signs records, etc.
Statistical Analysis
Statistical analyses were performed using SPSS 26 for Mac. Descriptive statistics were calculated for clinical data. The data were expressed as means ± standard deviations. Mann-Whitney U test, Kruskal-Wallis test, and univariate analysis were used for correlation analysis, and the indicators with statistical significance in correlation analysis were analyzed by linear regression for multivariate analysis, and p < 0.05 indicated statistical significance. Paired/unpaired t test, rank sum test (Mann-Whitney U test), or Wilcoxon signed rank sum test were used to differentiate between two data depending on the distribution (Shapiro-Wilk test; α = 0.05) and homogeneity of variance (F test; α = 0.05). All statistical tests were two-sided, and p < 0.05 was considered statistically significant.
Results
Basic Characteristics of Participants
The characteristics of 128 participants are listed in Table 1 and they were not significantly different.
Clinical characteristics of participants
. | Mean ± SD (%) or n (%) . | Min–max . |
---|---|---|
Age, years | 53.16±10.35 | 26–77 |
Sex | - | - |
Male | 60 (47.2) | - |
Female | 68 (52.7) | - |
CAS evaluation | 2.64±1.24 | 1–6 |
TED course, months | 16±17.5 | 1–108 |
VA impairment history, months | 8.62±7.13 | 1–48 |
History of thyroid disease | Hypothyroidism 14 (10.9) | - |
Hyperthyroidism 87 (68.0) | ||
No thyroid disease and euthyroid 27 (21.1) | ||
I131 treatment history | 21 (16.4) | - |
History of glucocorticoid pulse therapy | 97 (75.7) | - |
. | Mean ± SD (%) or n (%) . | Min–max . |
---|---|---|
Age, years | 53.16±10.35 | 26–77 |
Sex | - | - |
Male | 60 (47.2) | - |
Female | 68 (52.7) | - |
CAS evaluation | 2.64±1.24 | 1–6 |
TED course, months | 16±17.5 | 1–108 |
VA impairment history, months | 8.62±7.13 | 1–48 |
History of thyroid disease | Hypothyroidism 14 (10.9) | - |
Hyperthyroidism 87 (68.0) | ||
No thyroid disease and euthyroid 27 (21.1) | ||
I131 treatment history | 21 (16.4) | - |
History of glucocorticoid pulse therapy | 97 (75.7) | - |
Deep Medial Orbital Decompression Can Significantly Retract the Eyeball and Relieve Orbital Apex Congestion
Figure 2a, b showed the effect of postoperative eyeball regress. The average exophthalmos was 19.97 ± 3.16 mm before the operation, and it was 16.51 ± 2.51 mm after the operation, showing a significant statistical difference (p < 0.001).
Deep medial orbital decompression relieves orbital apex congestion. a Deep medial orbital decompression could retract the eye. b Statistical difference between preoperative and postoperative proptosis. c Preoperative and postoperative computed tomography (CT) scans showed the enlarged muscle pressing on the optic nerve, which was relieved by surgery (blue arrow shows the optic nerve). d–f Pre- and postoperational comparison of orbital apex parameters.
Deep medial orbital decompression relieves orbital apex congestion. a Deep medial orbital decompression could retract the eye. b Statistical difference between preoperative and postoperative proptosis. c Preoperative and postoperative computed tomography (CT) scans showed the enlarged muscle pressing on the optic nerve, which was relieved by surgery (blue arrow shows the optic nerve). d–f Pre- and postoperational comparison of orbital apex parameters.
From the preoperative and postoperative CT comparison, the orbital apex crowding was relieved after surgery (Fig. 2c). Using a CT scan, the OV value increased from 23.19 ± 2.79 cm3 to 28.69 ± 2.54 cm3 (p < 0.001) postoperatively, while EMV/OV decreased from 22.41 ± 8.61 to 19.28 ± 3.68% (p = 0.01). This demonstrated that orbital decompression could increase OV while relieving intraorbital compression, which is consistent with the objective of surgical design (Table 2; Fig. 2d, e).
Orbital parameters change pre-surgery and post-surgery
. | Pre . | Post . | p value . |
---|---|---|---|
OV, cm3 | 23.19±2.79 | 28.69±2.54 | <0.001* |
EMV, cm3 | 5.27±2.33 | 5.58±1.91 | 0.44 |
EMV/OV, % | 22.41±8.61 | 19.28±3.68 | 0.01* |
OAV, cm3 | 2.65±1.48 | 5.26±1.52 | <0.001* |
EMV-OA, cm3 | 1.36±1.19 | 1.77±1.13 | 0.15 |
EMV-OA/OAV, % | 44.32±20.31 | 36.82±12.02 | <0.001* |
. | Pre . | Post . | p value . |
---|---|---|---|
OV, cm3 | 23.19±2.79 | 28.69±2.54 | <0.001* |
EMV, cm3 | 5.27±2.33 | 5.58±1.91 | 0.44 |
EMV/OV, % | 22.41±8.61 | 19.28±3.68 | 0.01* |
OAV, cm3 | 2.65±1.48 | 5.26±1.52 | <0.001* |
EMV-OA, cm3 | 1.36±1.19 | 1.77±1.13 | 0.15 |
EMV-OA/OAV, % | 44.32±20.31 | 36.82±12.02 | <0.001* |
OV, orbital volume; EMV, extraocular muscle volume; OAV, orbital apex volume; EMV-OA, extraocular muscle volume in orbital apex.
*The difference was statistically significant.
More importantly, for DON patients, OAV increased from 2.65 ± 1.48 to 5.26 ± 1.52 cm3 (p < 0.001), whereas EMV-OA/OAV decreased from 44.32 ± 20.31 to 36.82 ± 12.02% (p < 0.001). This strongly suggests that deep orbital decompression alleviated orbital apex congestion significantly (Table 2; Fig. 2d, e).
Additionally, we compared the EMV-OAV/OAV with non-DON patients using data published [10]. We discovered that there was no significant difference between the DON patients postoperatively and the non-DON patients (p = 0.3383) (shown in Fig. 2f). Postoperative DON patients exhibited comparable EMV-OAV/OAV values with non-DON patients from our previous study. This demonstrated that the operation successfully resected the anatomical structure, as we expected.
Visual Acuity Improved after Deep Orbital Decompression Surgery
We analyzed VA changes before and after deep orbital decompression surgery to confirm the effect of deep orbital decompression on optic nerve function. The mean VA increased from 0.93 ± 0.73 to 0.50 ± 0.60 (LogMar) at P1W (p < 0.001) and 0.40 ± 0.53 at P1M (p < 0.001) (Fig. 3a). Figure 3b showed the percentage of patients with improved vision at different time points. It could be seen that at P1M, 96.87% of eyes (123 eyes) VA improved. These results showed the postoperative VA improved gradually.
Visual acuity (VA) improvement post-surgery. a Mean VA at different time points. b The proportion of VA improvement at different time points. c Scatter plot of initial VA versus IDVA. d Scatter plot of VA impairment history versus IDVA. e Histogram of different CAS evaluation IDVA means.
Visual acuity (VA) improvement post-surgery. a Mean VA at different time points. b The proportion of VA improvement at different time points. c Scatter plot of initial VA versus IDVA. d Scatter plot of VA impairment history versus IDVA. e Histogram of different CAS evaluation IDVA means.
Analysis of Factors Affecting Final VA
Considering that factors may impact VA recovery, we analyzed the participants’ sex, age, clinical activity score (CAS) evaluation, TED course, VA impairment history, exophthalmos, initial VA, thyroid dysfunction, I131 treatment history, and history of glucocorticoid pulse therapy to multifactor analysis (Fig. 3c–e; Tables 3-5). The results showed that CAS evaluation, VA impairment history, and initial VA significantly impact the degree of VA improvement. IDVA was positively correlated with CAS evaluation, and initial VA, and negatively correlated with the VA impairment history.
Comparison of IDVA in different clinical features
. | IDVA . | Z/H value . | p value . |
---|---|---|---|
Sex | 0.326 | ||
Male | 0.44±0.26 | −0.982 | |
Female | 0.48±0.27 | ||
Glucocorticoid pulse therapy | 0.864 | ||
Yes | 0.46±0.27 | −0.171 | |
No | 0.46±0.26 | ||
I131 treatment history | 0.992 | ||
Yes | 0.47±0.28 | −0.010 | |
No | 0.46±0.26 | ||
History of thyroid disease | 0.639 | ||
No | 0.53±0.32 | 0.895 | |
Hypothyroidism | 0.43±0.28 | ||
Hyperthyroidism | 0.46±0.26 |
. | IDVA . | Z/H value . | p value . |
---|---|---|---|
Sex | 0.326 | ||
Male | 0.44±0.26 | −0.982 | |
Female | 0.48±0.27 | ||
Glucocorticoid pulse therapy | 0.864 | ||
Yes | 0.46±0.27 | −0.171 | |
No | 0.46±0.26 | ||
I131 treatment history | 0.992 | ||
Yes | 0.47±0.28 | −0.010 | |
No | 0.46±0.26 | ||
History of thyroid disease | 0.639 | ||
No | 0.53±0.32 | 0.895 | |
Hypothyroidism | 0.43±0.28 | ||
Hyperthyroidism | 0.46±0.26 |
Correlation analysis of IDVA with different variables
. | Age . | CAS evaluation . | TED course . | VA impairment history . | Exophthalmos . | Initial VA . |
---|---|---|---|---|---|---|
IDVA | −0.169 | 0.234 | −0.160 | −0.222 | 0.167 | 0.302 |
p value | 0.058 | 0.008 | 0.072 | 0.012 | 0.061 | 0.001 |
. | Age . | CAS evaluation . | TED course . | VA impairment history . | Exophthalmos . | Initial VA . |
---|---|---|---|---|---|---|
IDVA | −0.169 | 0.234 | −0.160 | −0.222 | 0.167 | 0.302 |
p value | 0.058 | 0.008 | 0.072 | 0.012 | 0.061 | 0.001 |
Multivariate analysis of influencing IDVA
. | Unstandardized coefficient B . | Standard error . | Standardized coefficient β . | t value . | p value . |
---|---|---|---|---|---|
CAS evaluation | 0.038 | 0.018 | 0.180 | 2.120 | 0.036 |
VA impairment history | −0.009 | 0.003 | −0.230 | −2.762 | 0.007 |
Initial VA | 0.079 | 0.031 | 0.217 | 2.564 | 0.012 |
Constant | 0.360 | 0.062 | - | 5.768 | <0.001 |
. | Unstandardized coefficient B . | Standard error . | Standardized coefficient β . | t value . | p value . |
---|---|---|---|---|---|
CAS evaluation | 0.038 | 0.018 | 0.180 | 2.120 | 0.036 |
VA impairment history | −0.009 | 0.003 | −0.230 | −2.762 | 0.007 |
Initial VA | 0.079 | 0.031 | 0.217 | 2.564 | 0.012 |
Constant | 0.360 | 0.062 | - | 5.768 | <0.001 |
Visual Function Improved after Deep Orbital Decompression Surgery
The VEP results indicated that visual function was restored following surgery (Fig. 4a–d). After surgery, the mean value of P100-wave latency was found to be increased (p = 0.006) at the 60’ spatial frequencies, though the changes at the 30’ and 15’ spatial frequencies were not significant. Preoperatively, the mean P100-wave amplitude was 6.20 ± 4.35 mV, 7.02 ± 4.17 mV, and 5.84 ± 5.16 mV, respectively, at the 60’, 30’, and 15’ spatial frequencies. Likewise, the amplitude of the P100 wave was 12.29 ± 14.18 mV, 9.45 ± 4.20 mV, and 9.67 ± 7.41 mV postoperatively, representing a significant increase (p = 0.03, p = 0.01, p = 0.02, respectively).
Visual evoked potential (VEP) and visual field (VF) changes pre- and postoperatively. a Preoperative VEP result. b Postoperative VEP shows decreased latency and increased frequencies. c, d Comparison of VEP of latency and amplitude before and after the operation. e Comparison of VF before and after the operation. f Preoperative VF showed a large VF defect. g Postoperative VF shows improvement of VF defect.
Visual evoked potential (VEP) and visual field (VF) changes pre- and postoperatively. a Preoperative VEP result. b Postoperative VEP shows decreased latency and increased frequencies. c, d Comparison of VEP of latency and amplitude before and after the operation. e Comparison of VF before and after the operation. f Preoperative VF showed a large VF defect. g Postoperative VF shows improvement of VF defect.
The VF examinations were performed to evaluate visual function (Fig. 4e–g). Additionally, significant improvement in the VF was observed following surgery. Before surgery, the mean VF defect value was −16.83 ± 9.83, while the mean VF defect value after surgery was −5.89 ± 4.29 (p < 0.001).
SaO2 Improved and the Increased RNFL Thickness Is Alleviated after Deep Orbital Decompression Surgery
The oxygen saturation of retinal arteries (SaO2) and veins (SvO2) and the differences between the arteries and veins (AVD) reflect changes in blood supply around the optic disc (Fig. 5a, b). We found that the DON group’s preoperative SaO2 was 89.63 ± 4.02%. However, the DON group’s postoperative SaO2 significantly increased to 94.42 ± 6.16% (p = 0.04). The SvO2 and AVD had no significant changes postoperatively. This may indicate that orbital decompression surgery improves blood supply around the optic disc.
SaO2 and RNFL change pre- and postoperatively. a The schematic diagram of SaO2 examination result. b Comparison of SaO2 pre- and postoperation. c The schematic diagram of the OCT-A examination result. d Comparison of RNFL of latency and amplitude pre- and postoperation.
SaO2 and RNFL change pre- and postoperatively. a The schematic diagram of SaO2 examination result. b Comparison of SaO2 pre- and postoperation. c The schematic diagram of the OCT-A examination result. d Comparison of RNFL of latency and amplitude pre- and postoperation.
We further examined changes in the thickness of RNFL around the optic disc and the density of blood vessels through an OCT-A scan (Fig. 5c, d). We found that the preoperative DON peripapillary RNFL was 143.93 ± 26.70 μm. The preoperative DON temporal RNFL was 89.86 ± 11.16 μm. In the comparison of DON pre- and postoperative RNFL thickness, we found that the peripapillary, temporal, and nasal reproduced thinning. The DON postoperative peripapillary, temporal, and nasal RNFL were 131.43 ± 21.03 μm, 83.29 ± 9.03 μm, 155.29 ± 24.74 μm. Significantly lower than preoperative 143.93 ± 26.70, 89.86 ± 11.16, 181.07 ± 53.91 (p = 0.04, p = 0.01, p = 0.04). There were no significant changes in the thickness of the RNFL and the density of blood vessels in other parts.
Surgical Complications and Safety
We tracked the complications after the surgery; 25 patients experienced mild rhinorrhagia following surgery, but this resolved spontaneously within 48 h. Diplopia was present in 39.06% (50/128) of patients before surgery. One month after the surgery, 13.3% patients (17/128) had new-onset diplopia or aggravated diplopia (increase of squint degree is greater than 10°), whose mean squint degree increased by 20.53 ± 8.11°. Other serious problems, such as leakage of cerebrospinal fluid rhinorrhea, severe bleeding, or death, were not observed.
Discussion
DON is a serious complication of TED that can cause varying degrees of visual impairment [14]. Orbital decompression surgery is the recommended surgery for DON. However, there is no consensus on transnasal orbital decompression surgery regarding how to reach the correct anatomical site [2, 5, 8, 15–19].
At the base of our preliminary study [10], we noticed that the differences between the DON patients and non-DON patients were mainly concentrated in the orbital apex, which indicated that orbital apex congestion, especially the pressure from the medial wall, was the primary cause of DON. In this study, we propose and emphasize the importance of deep orbital decompression (up to the orbital apex and the orbital part of the optic canal) in patients with DON. Additionally, we speculate incision of the periosteum on the area of the annulus of Zinn, which was a dense ring of fibrous connective tissue in the orbital apical, might help relieve orbital apex pressure. Thus, during the surgery, we incised the periosteum on the area of the annulus of Zinn, to relieve the pressure in the orbital apex. The reason we did not open the optic nerve sheath is that, we believe for DON patients, the pressure on the optic nerve is from the EOM at the orbital apex to the optic nerve, that is, from the outside to the inside of the optic nerve; therefore, we only incised the periosteum instead of the full thickness of the annulus of Zinn and did not open the optic nerve sheath, focused on the relieving the pressure on the orbital apex. We can see that EMV-OA/OAV was significantly improved after surgery. This indicated that the surgical procedure achieved our original goal. Accordingly, VA and visual function after the operation were significantly improved. During the surgery, we removed the orbital fat, not just prolapse into the nasal cavity, to better relieve exophthalmos. As for fat removal, before the operation, we communicated with the patient to understand the patient’s expectations for eyeball retraction. During the operation, we would expose both eyes pay close attention to the exophthalmos and changes in orbital pressure, as well as the coordination with the fellow eye, if the fellow eye has been operated on or is in a mild condition. The patient’s expectations should be met as much as possible without causing serious complications, and the surgeon judged based on experience.
In addition, in our study of factors affecting VA recovery, we found that initial VA, visual impairment duration, and CAS evaluation affected the degree of visual recovery. Of these, the CAS evaluation affects the final VA recovery. We speculate that this may be due to the inability of the CAS evaluation system to distinguish between reflux obstruction due to orbital apex compression and true inflammatory activity. In our case, if it is in the active stage before surgery, glucocorticoid pulse therapy is often performed. Therefore, all patients treated surgically were not in the active stage. In our study, we first consider glucocorticoid pulse therapy; unless the patient refuses glucocorticoid pulse therapy or there is no significant improvement within 2 weeks, surgical treatment is considered. Therefore, we tried to rule out the interference of glucocorticoid on the surgical effect. The high CAS evaluation of the cases may be due to the obstruction of reflux caused by orbital apex compression, which prompts some correlation between the CAS evaluation and orbital apex compression and thus the degree of visual recovery. Another thing to note is the positive relationship between LogMar VA and IDVA. The higher the LogMar value, the worse the vision and the better the IDVA. Although there are cases (Fig. 3d) where the initial VA is too poor and cannot be improved after surgery, generally speaking, to some extent, patients with poor vision have more room for recovery. The reason we used the VA at 1 month after surgery as the primary endpoint is that we found most patients’ VA had significantly improved at 1 month after surgery.
Additionally, we found by retinal oximeter that the arterial oxygen saturation around the optic disc was significantly improved after surgery. It could be that the compression of the optic nerve is likely to compress the ophthalmic artery at the same time, resulting in a decrease in blood oxygen content. The classic theory is that retinal edema occurs when the retina is deficient in blood supply and hypoxia, which may be the reason for the thickening of the RNFL. These are also consistent with other experimental results [20, 21] and need to be further explored.
However, this study still has some limitations; no comparison with conventional treatment strategies was made, nor did we compare the same surgical methods performed by different doctors. Large randomized controlled trials and longer observation times are required in the future to compare this method with conventional treatment strategies. Moreover, we adopted the incising periosteum on the area of the annulus of Zinn, which was not widely reported as a standard approach. How many risks and benefits such an operation brings needs further research. In addition, since sub‐clinical DON is not an infrequent entity, we did not include sub‐clinical DON in our study [21].
In summary, we emphasize the importance of deep orbital decompression and successful surgical outcomes. We found that initial VA, visual impairment duration, and CAS evaluation affected the degree of visual recovery. These provided a theoretical foundation for surgeons to standardize and expand the benefits of endoscopic medial orbital decompression surgery.
Conclusions
In patients with DON, endoscopic deep medial orbital decompression should reach the orbital apex and optic nerve canal, which helps to achieve better visual improvement and standardize the surgery. Initial VA, visual impairment duration, and CAS evaluation preoperatively affected the degree of visual recovery.
Acknowledgments
We thank all the participates and Zhongshan Ophthalmic Center for the support of this study.
Statement of Ethics
This prospective clinical research was conducted in accordance with the principles outlined in the Declaration of Helsinki and approved by the Ethics Committee of Zhongshan Ophthalmic Center (Guangzhou, China, 2017KYPJ101). Before the study, written informed consent was obtained from all participating individuals. Participants also provided written informed consents for the publication of their photo used in the manuscript.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This research was supported by the National Natural Science Foundation of China (Grant No. 81670823). Project supported by the Natural Science Foundation of Guangdong Province, China (Grant No. 2019A1515010361) and ophthalmic tumor treatment platform of Zhongshan Ophthalmic Center (Grant No. 303010406).
Author Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Cheng Li, Yang Gao, Zhihui Zhang, and Xi Lv. The first draft of the manuscript was written by Cheng Li. Yuekun Bao, Yujun Ma, Rongxin Chen, Chao Cheng, Jinmiao Li, and Yaoming Liu commented on previous versions of the manuscript. Ling Jin reviewed the statistical methods and Guangwei Luo provided VEP data analysis. Jianbo Shi and Rong Lu read and approved the final manuscript.
Additional Information
Cheng Li, Yang Gao, Zhihui Zhang, and Xi Lv contributed equally to this work.
Data Availability Statement
Data are not publicly available due to ethical reasons. Further inquiries can be directed to the corresponding author.