·Clinical Research·
The
effect of intravenous high-dose glucocorticoids and orbital decompression
surgery on sight-threatening thyroid-associated ophthalmopathy
Yun Wen, Jian-Hua Yan
The State Key Laboratory of Ophthalmology,
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060,
Guangdong Province, China
Correspondence to: Jian-Hua Yan. Zhongshan Ophthalmic
Center, Sun Yat-sen University, 54 Xianlie Nan Road, Guangzhou 510060,
Guangdong Province, China. yanjh2011@126.com
Received:
Abstract
AIM: To report the effects of intravenous high-dose glucocorticoids (ivGC)
and orbital decompression (OD) surgery for treatment of sight-threatening
thyroid-associated ophthalmopathy (TAO).
METHODS: A retrospective review of medical records from
patients with sight-threatening TAO [definite or highly suspected dysthyroid
optic neuropathy (DON)] treated with ivGC (60 cases) and OD (25 cases) was
conducted at the Zhongshan Ophthalmic Center between January 2001 and January
2009. Patients were initially treated with ivGC (ivGC group). If no significant
improvement in visual function was obtained, they then received OD surgery (OD
group). The pre- versus post-treatment efficacies of either ivGC or OD in these
patients were assessed using several indices, including visual acuity,
intraocular pressure, ocular alignment, ocular motility, and exophthalmos.
RESULTS: Nighty-one eyes had definite DON while 79 were
considered to have highly suspected DON. In the ivGC group, 51 individuals
(85.0%) eventually demonstrated normal vision, while 10 patients (16.7%)
demonstrated a reduction in deviation (P<0.01), and 35 cases (58.3%)
showed slight improvements in ocular motility (P<0.01). In OD group,
visual acuity improved in 24 cases (96.0%, P<0.01) and all patients
showed varying reductions of exophthalmos (mean: 4.35±
CONCLUSION: Both ivGC and OD show good therapeutic efficacy in
the treatment of sight-threatening TAO. The presence of extremely poor eyesight
(≥0.5logMAR) was corrected in some patients with ivGC alone, thus sparing these
patients from subsequent OD surgery. In patients who were refractory to
steroids, subsequent OD surgery often provided satisfactory outcomes, however,
new-onset strabismus with diplopia was observed in 12.0% of these cases.
KEYWORDS: thyroid-associated ophthalmopathy;
dysthyroid optic neuropathy; glucocorticoids; orbital decompression; orbital
surgery
DOI:10.18240/ijo.2019.11.12
Citation:
Wen Y, Yan JH. The effect of intravenous high-dose glucocorticoids and orbital
decompression surgery on sight-threatening thyroid-associated ophthalmopathy. Int
J Ophthalmol
2019;12(11):1737-1745
INTRODUCTION
Thyroid-associated ophthalmopathy (TAO)
or thyroid orbitopathy is the most common cause of unilateral or bilateral
proptosis, accounting for approximately 39.3%-42.2% of all orbital diseases in
adults[1]. The majority of patients present with
mild thyroid orbitopathy, characterized by variable lid swelling, lid
retraction, and mild exophthalmos. These patients experience minimal
photophobia, tearing, ocular fatigue and other ocular discomforts. In these
cases, regular follow-up counseling and local preservative-free artificial
tears are recommended. In contrast to these mild cases, about 5%-6% of these
patients progress to develop severe orbitopathy[2],
which results in sight-threatening features including exophthalmos along with
significant soft tissue features and myopathy, exposure keratitis and even
optic neuropathy. Although small proportion of TAO patients are likely to
deteriorate as sight-threatening cases, once that happens, this disease could
seriously impact patient’s quality of life[3-4].
Dysthyroid optic neuropathy (DON) is
a condition that compression of the orbital apex leads to impairment of visual
function[5-6]. It is usually treated
with high-dose of glucocorticoids or orbital decompression (OD). Glucocorticoid
pulse therapy can reduce inflammation, while OD spares space for optic nerve
and relieve the pressure around it[7]. The EUGOGO
recommendation for patients with DON includes high-dose intravenous
corticosteroids (ivGC) combined with a subsequent application of OD if there is
little or no response to corticosteroids[8]. However,
published data are very rare for each treatment strategy. Therefore, managing
patients with DON remains a challenge for many clinicians, and protocols for
this condition continue to evolve.
In this study, we reviewed the case
records of previously untreated patients with definite or highly suspected DON
who were treated with ivGC and OD in a tertiary referral hospital in China over
the past 10y. From this review we found that ivGC, by itself, was very
effective in correcting extremely poor eyesight, more than 0.5 logMAR in
Logarithmic Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity
Chart, in some patients, thus sparing them from surgical treatment. In patients
who were refractory to steroids, OD often provided a satisfactory outcome
(mainly visual acuity improve by more than 2 lines). In some patients, who
experienced vision loss after successful OD, their vision was restored
following ivGC treatment.
SUBJECTS AND METHODS
Ethical Approval This retrospective study was performed in
compliance with the Declaration of Helsinki, and approved by the ethics
committee of the Zhongshan Ophthalmic Center. Informed consent was obtained
from the subjects.
Patients A retrospective analysis of medical
records was conducted for cases with severe TAO as treated by a single
ophthalmologist (Yan JH) at the Zhongshan Ophthalmic Center of Sun Yat-sen
University between January 2001 and January 2009.
Definite DON cases refer to those
with optic disc swelling, impairment of color vision, together with
radiological evidence of apical optic nerve compression. If optic disc swelling
was not present or could not be observed because of opaque refractive media,
highly suspected DON was diagnosed by the following two or more signs combined:
abnormal color vision, an increased latency showed in visual evoked potential
(VEP), visual field loss compatible with optic nerve stretch or apical muscle
crowding showed in radiological images, and presence of a relative afferent
pupillary defect (RAPD). Exclusion criteria were: 1) previous orbital radiation
therapy; 2) treated by ivGC or OD before; 4) failed to cooperate with follow-up
investigations.
Comprehensive ophthalmological
assessments were performed before therapy and at the follow-up period. For each
subject, the following data were recorded before treatments: 1) basic
information and medical history including gender, age, duration of thyroid
disease, previous treatment for thyroid disease, family history,
ophthalmological history and smoking habits; 2) best corrected visual acuity,
intraocular pressure (IOP), orbital pressure, slit-lamp examination of the
anterior segments, pupil examination, fundus examination, eyelid swelling,
eyelid retraction, von Graefe’s sign, lagophthalmus, conjunctival hyperemia,
swelling of the caruncle, ocular alignment and motility. Proptosis was assessed
by Hertel exophthalmometry. In addition, a major synoptophore examination and
prism cover test were included within our routine examinations for evaluating
the exact eye deviation and binocular vision. Color vision test (FM 100-hue
test), VEP and automated perimetry were performed to enable a comprehensive and
detailed assessment of each case. Diplopia was detected using red filter test.
Patients were asked to answer no diplopia, intermittent diplopia, or constant
diplopia in any gazing directions. Orbital magnetic resonance imaging (MRI) or
computed tomography (CT) was performed on all patients. The severity and
activity of TAO were evaluated using the NOSPECS, European Group on Graves
Ophthalmopathy (EUGOGO) and Clinical Activity Score (CAS) criteria,
respectively. In the follow-up, best corrected visual acuity, IOP, slit-lamp
examination of the anterior segments, fundus examination, proptosis assessment,
eye deviation, ocular movement, and CAS score of each patient were recorded.
Principle of Treatment Our steroid pulse therapy was based
on those of van Geest et al[9] and
Higashiyama et al[10]. Before receiving
treatment, all the patients were required to undergo a general physical
examination including routine blood and urine assays, blood biochemistry, liver
and kidney function tests, blood clotting index tests, electrocardiographic
examination, chest X-ray and thyroid function examination. Initially, an
intravenous high dose of steroids (0.5 or
Intravenous High-dose
Glucocorticoids Therapy The schedule for ivGC therapy
initially involved a daily dose of
Orbital Decompression Surgery When no significant improvements in
visual function, for example, less than 2 lines in visual acuity, were obtained
after administration of ivGC therapy (after 2 courses), patients received OD
while under general anesthesia. We waited for one week after the last steroid
dose and move the patient from the ivGC group to the surgical decompression.
Our commonly used surgical techniques consisted of decompression of the deep
lateral wall, both medial and inferior walls, balanced removal of the medial
and deep lateral walls and uniting the inferomedial with the lateral wall. In
all cases, adipose tissue removal was performed. Post-operative steroid therapy
consisted of intravenous injections of 10-15 mg/d dexamethasone or 60-80 mg/d
methylprednisolone for 3-5d, followed by oral prednisone at 40-60 mg/d, which
was then reduced by 5 mg per week over the following 8-12wk.
Statistical Analysis Statistical analysis was performed
to assess pre- versus postoperative results within these two groups as achieved
with use of paired samples t-tests for continuous variables such as IOP
and degree of exophthalmos. The Mann-Whitney U test or the Wilcoxon rank
sum test was used for an abnormal distribution or zero values. χ2
test was used for categorical data. The SPSS software version 24.0 (SPSS, Chicago,
IL, USA) was used for all statistical analyses. P<0.01 was required
for results to be considered statistically significant.
RESULTS
Population Characteristics Between January 2001 and January
2009, 142 severe TAO cases were included in our study. Finally, 85 patients
were brought into our analysis with relatively completed medical records and
matched the standard of diagnosis mentioned above. Their clinical
characteristics of are summarized in Table 1. Female (32 patients) account for
37.6% of the population, while male represented the majority of 62.4%. At that
time, 28 admitted that they were current smokers, including 26 males and 2
females. Graves’ disease was the predominant thyroid disease, which occupied
90.6% of the whole. Before the referral, more than half of our patients (60.0%)
were treated with antithyroid drugs in the local hospital. The number came with
37.6% of the patients who undergone thyroidectomy. Only two of our subjects
received radioiodine treatment. We have confirmed that our patients’
euthyroidism had all restored and stably maintained before we plan for their
ophthalmic therapy.
Table 1 Clinical characteristics of
the subjects n (%)
|
Parameters |
Number of the subjects |
|
Gender (F/M) |
32/53 |
|
Smoking habits |
|
|
Never smoked |
51 (28 females, 23 males) |
|
Past smokers |
6 (2 females, 4 males) |
|
Current smokers |
28 (2 females, 26 males) |
|
Thyroid diseases |
|
|
Graves’ disease |
77 (90.6) |
|
Hashimoto thyroiditis |
8 (9.4) |
|
Treatment for thyroid diseases
before visit us |
|
|
Antithyroid drug |
51 (60.0) |
|
Total thyroidectomy |
32 (37.6) |
|
Radioiodine treatment |
2 (2.4) |
|
Age (median) |
|
|
On diagnosis of thyroid disease |
51y |
|
At onset of eye symptoms |
52y |
|
On diagnosis of severe TAO |
55y |
TAO: Thyroid-associated
ophthalmopathy.
Clinical Features of Definite DON
and Highly Suspected DON Sixty-four patients (75.3%) were
diagnosed with definite DON, including 91 affected eyes. Seventy-night eyes were
considered to have highly suspected DON. In ivGC group, there are 16 subjects
diagnosed with bilateral definite DON and 9 patients with highly suspected
features in both eyes. In OD group, 11 patients were considered to have
bilateral definite DON. Clinical features of eyes with definite and highly
suspected DON are demonstrated in Table 2.
Table 2 Clinical features of eyes
with definite and highly suspected DON n (%)
|
Parameters |
Definite DON |
Highly suspected DON |
|
Number of eyes |
91 |
79 |
|
Impairment of color vision |
91 (100) |
18 (22.8) |
|
Visual field defects |
65 (71.4) |
48 (60.8) |
|
Abnormal VEP latency |
68 (74.7) |
63 (79.7) |
|
RAPD |
21 (23.1) |
13 (16.5) |
|
In ivGC group |
67 |
53 |
|
In OD group |
24 |
26 |
DON: Dysthyroid optic neuropathy;
VEP: Visual evoked potential; RAPD: Relative afferent pupillary defect; ivGC:
High-dose intravenous corticosteroids; OD: Orbital decompression.
High-dose Intravenous
Corticosteroids Results
General data A total of 60 cases (40 males and 20
females) comprised the ivGC group, with mean age of 49.67±13.83y (range:
19-82y). Primary ailments experienced by this group included decreased visual
acuity (81.7%), exophthalmos (86.7%), restricted ocular motility (81.7%),
double vision (76.7%), eye redness, swelling and pain (66.7%) and squint
(43.3%). In 7 cases (14 eyes) with normal visual acuity (20/20) in both eyes,
visual functional tests (pupil examination, color vision, or VEP) showed obvious
abnormalities. All cases were classified as active TAO (CAS score ≥3). By
EUGOGO assessment, 3 cases (5.0%) were considered as moderate-to-severe TAO and
57 cases (95.0%) as sight-threatening TAO. On the basis of NOSPECS
classification, 2 cases (3.3%) were classified as Grade 5 (corneal involvement)
and 58 cases (96.7%) were Grade 6 (sight loss). The relevant data of patients
in both groups are shown in Table 3.
Table 3 Baseline findings in both
ivGC group and OD group n (%)
|
Parameters |
IvGC group |
OD group |
|
Number of patients (eyes) |
60 (120) |
25 (50) |
|
Agea (range), y |
49.67±13.83 (19-82) |
49.16±8.24 (31-63) |
|
Gendera |
|
|
|
Male |
40 (67.7) |
13 (52.0) |
|
Female |
20 (33.3) |
12 (48.0) |
|
Visual acuityb, logMAR |
|
|
|
≤0.1 |
22 (18.3) |
1 (2.0) |
|
>0.1-0.3 |
56 (46.7) |
17 (34.0) |
|
>0.3-0.5 |
16 (13.3) |
12 (24.0) |
|
>0.5-1.0 |
14 (11.7) |
7 (14.0) |
|
>1.0 |
4 (3.3) |
2 (4.0) |
|
FC |
6 (5.0) |
9 (18.0) |
|
HM |
2 (1.7) |
2 (4.0) |
|
IOPb (mm Hg) |
21.37±5.93 |
19.45±6.11 |
|
11-21 |
76 (63.3) |
36 (72.0) |
|
>21 |
44 (36.7) |
14 (28.0) |
|
Pupil examinationb |
|
|
|
Pupil size |
|
|
|
Normal |
29 (24.2) |
11 (22.0) |
|
Dilated |
79 (65.8) |
33 (66.0) |
|
Pupillary light reflex |
|
|
|
Brisk |
8 (6.7) |
2 (4.0) |
|
Sluggish |
87 (72.5) |
38 (76.0) |
|
Nonreactive |
13 (10.8) |
4 (8.0) |
|
Unavailable data |
12 (10.0) |
6 (12.0) |
|
Color visionb (FM
100-hue test) |
|
|
|
Normal |
25 (20.8) |
6 (12.0) |
|
Mild decline in blue-green hues |
43 (35.9) |
19 (38.0) |
|
Obvious abnormality |
36 (30.0) |
11 (22.0) |
|
Unavailable data |
16 (13.3) |
14 (28.0) |
|
Visual field testb |
|
|
|
Normal |
18 (15.0) |
1 (2.0) |
|
Defect |
76 (63.3) |
37 (74.0) |
|
Peripheral & partial |
21 (17.5) |
11 (22.0) |
|
Peripheral & wide |
23 (19.2) |
7 (14.0) |
|
Central visual field related |
32 (26.7) |
19 (38.0) |
|
Unavailable data |
26 (21.7) |
12 (24.0) |
|
Visual evoked potentialb
(P100) |
|
|
|
Normal |
8 (6.7) |
0 |
|
Mildly abnormal |
37 (30.8) |
7 (14.0) |
|
Severe abnormal |
75 (62.5) |
43 (86.0) |
|
NOSPECSa (grade) |
|
|
|
Corneal involvement (Grade 5) |
2 (3.3) |
2 (8.0) |
|
Sight loss (Grade 6) |
58 (96.7) |
23 (92.0) |
|
EUGOGOa (grade) |
|
|
|
Moderate-to-severe |
3 (5.0) |
1 (4.0) |
|
Sight-threatening |
57 (95.0) |
24 (96.0) |
|
CAS scorea |
|
|
|
Inactive GO (CAS<3) |
0 |
2 (8.0) |
|
Active GO (CAS≥3) |
60 (100) |
23 (92.0) |
|
Follow-up period (range), y |
1.23±0.43 (1-2) |
2.32±1.65 (1-8) |
OD: Orbital decompression; FC:
Finger counting; HM: Hand motion; IOP: Intraocular pressure; GO: Graves’ ophthalmopathy.
aNumber of patients; bNumber of eyes.
Final follow-up results Patients were followed-up at an
average of 1.23±0.43y (range: 1-2y). All the patients became inactive after
steroid therapy.
Visual acuity and intraocular
pressure Fifty-one patients (85.0%)
demonstrated normal visual acuity (20/20) in both eyes at final follow-up.
Thirty-eight patients (63.3%) showed improved vision in both eyes for more than
2 lines (P<0.01), 23 eyes (19.2%) experienced either slight vision
improvement or remained the same and a mild decrease in vision was observed in
2 cases (3.3%). The IOP was normal in 59 cases (98.3%) and only 1 case showed a
mild increase in IOP (
Exophthalmos reduction There were no obvious changes of
exophthalmos in 35 cases (58.0%), while 42 eyes (35.0%) showed a mean reduction
of 1.78±
Improvements in diplopia Twelve patients (20.0%) mentioned
that the treatment provided relief from double vision. In general, significant
improvements were shown in ocular alignment and ocular motility. Ten cases
(16.7%) demonstrated a reduced deviation of 8-15 PD (P<0.01). Slight
improvements in ocular motility were seen in 35 cases (58.3%), with 5 cases
(8.3%) showing improvements of 75% in the direction of the previously
restricted area and the remaining cases improved 25%-50% in the previously
restricted direction (P<0.01).
Complications Eight patients (13.3%) demonstrated
a mild disorder of glycometabolism, with no diabetes. During the course of drug
treatment, 14 individuals (23.3%) experienced digestive symptoms and 19
patients (31.7%) showed a slight appearance of Cushing’s. No serious
complications such as hypokalemia, liver or kidney damage, depression,
osteoporosis, infection and blood hypertension were observed. Parameters before
and after treatment of the patients in both groups are shown in Table 4.
Table 4 Clinical parameters before
and after treatment
n
(%)
|
Parameters |
IvGC group |
P |
OD group |
P |
|||
|
Before treatment |
After treatment |
Before treatment |
After treatment |
||||
|
CAS scorea |
7 |
2 |
<0.01d |
6 |
2 |
<0.01d |
|
|
Inactive GO (CAS<3) |
0 |
60 (100) |
|
2 (8.0) |
25 (100) |
|
|
|
Active GO (CAS≥3) |
60 (100) |
0 |
|
23 (92.0) |
0 |
|
|
|
Decrease |
60 (100) |
|
23 (92.0) |
|
|||
|
No change |
0 |
|
2 (8.0) |
|
|||
|
Visual acuity, logMARb |
|
<0.01d |
|
<0.01d |
|||
|
Improve≥2 lines |
95 (79.2) |
|
26 (52.0) |
|
|||
|
No change<2 lines |
23 (19.2) |
|
22 (44.0) |
|
|||
|
Deteriorate≥2 lines |
2 (1.6) |
|
2 (4.0) |
|
|||
|
≤0.1 |
104 (86.7) |
|
18 (36.0) |
|
|||
|
>0.1-0.3 |
9 (7.5) |
|
14 (28.0) |
|
|||
|
>0.3-0.5 |
5 (4.2) |
|
8 (16.0) |
|
|||
|
>0.5-1.0 |
1 (0.8) |
|
5 (10.0) |
|
|||
|
>1.0 |
1 (0.8) |
|
4 (8.0) |
|
|||
|
FC |
0 |
|
1 (2.0) |
|
|||
|
HM |
0 |
|
0 |
|
|||
|
IOP (mm Hg)b |
21.37±5.93 |
15.59±2.14 |
< |
19.45±6.11 |
15.63±2.21 |
< |
|
|
Proptosis (mm)b |
21.13±2.66 |
20.50±2.72 |
< |
22.61±1.23 |
18.26±1.10 |
< |
|
|
Decrease≥2 |
27 (22.5) |
|
50 (100) |
|
|||
|
No change<2 |
93 (77.5) |
|
0 |
|
|||
|
Diplopiaa |
|
|
|
|
|||
|
Pre-existing |
46 (76.7) |
|
19 (76.0) |
|
|||
|
Improve |
12 (20.0) |
|
8 (32.0) |
|
|||
|
No change |
32 (53.3) |
|
9 (36.0) |
|
|||
|
Deteriorate |
2 (3.3) |
|
2 (8.0) |
|
|||
|
New-onset |
0 |
|
3 (12.0) |
|
|||
|
Complicationsa |
|
|
|
|
|||
|
Disorder of glycometabolism |
8 (13.3) |
|
2 (8.0) |
|
|||
|
Digestive symptoms |
14 (23.3) |
|
2 (8.0) |
|
|||
|
Appearance of Cushing’s |
19 (31.7) |
|
3 (12.0) |
|
|||
|
Upper eyelid retraction |
0 |
|
2 (8.0) |
|
|||
|
New-developed strabismus |
0 |
|
3 (12.0) |
|
|||
OD: Orbital decompression; FC: Finger
counting; HM: Hand motion; IOP: Intraocular pressure; GO: Graves’
ophthalmopathy. aNumber of patients; bNumber of eyes; cPaired-samples
t-test; dWilcoxon rank sum test. P<0.01 was
required for results to be considered statistically significant.
Orbital Decompression Results
General data A total of 25 cases (13 males and 12
females) comprised the OD group, with mean age of 49.16±8.24y (range: 31-63y).
Primary ailments included decreased visual acuity (98.0%), exophthalmos
(92.0%), restricted motility (80.0%), double vision (76.0%) and squint
(40.0%).Visual functional tests of all the patients showed obvious
abnormalities. Twenty-three cases (92.0%) were evaluated as active TAO (CAS
score ≥3) and 2 patients (8.0%) as inactive TAO with CAS scores of <3. By
EUGOGO assessment, one case (4.0%) was classified as moderate-to-severe TAO and
24 cases (96.0%) as sight-threatening TAO. According to NOSPECS classification,
2 cases (8.0%) were classified as Grade 5 (corneal involvement) and 23
individuals (92.0%) as Grade 6 (sight loss). A decompression of deep lateral
and inferior orbital walls were performed in 2 eyes (4.0%), balancing of deep
lateral and medial orbital walls in 4 eyes (8.0%), medial and inferior orbital
walls in 22 eyes (44.0%) and deep lateral orbital wall united with medial and
inferior orbital walls in 22 eyes (44.0%).
Final follow-up results Patients were followed-up at an
average of 2.32±1.65y (range: 1-8y). All 25 patients became inactive TAO at
final follow-up.
Visual acuity and intraocular
pressure Visual acuity improved in 24
patients (47 eyes, 94.0%) as assessed at final follow-up. The average increase
was 2.70±2.22 lines and 26 eyes (52.0%) increased their eyesight by more than 2
lines (P<0.01). However, the visual acuity decreased by 2 lines in 1
patient. All the patients showed normal IOP after surgeries (P<0.01).
Exophthalmos reduction All patients showed varying
reductions of exophthalmos (range: 3
Improvements in diplopia Overall, there were a certain degree
of improvements in double vision, for 8 cases (32.0%) declared that symptoms
greatly improved, and these patients revealed approximately an 8-15 PD
reduction in deviation. In contrast, 3 cases (12.0%) complained emerging double
vision and developed strabismus (approximately 10-15 PD) 6-48mo after OD
surgery, of which 1 case received decompression of the deep lateral and
inferior walls, 2 cases with a 3-wall decompression. However, ocular motility
improved in 12 cases (48.0%), with a 25%-50% improvement in the restricted
direction (P<0.01).
Complications Two patients (8.0%) showed increased
upper eyelid retraction after OD, which was corrected by subsequent
tarsorrhaphy. Newly-developed strabismus was observed in 3 cases (12.0%). No
other complications occurred in our case series.
DISCUSSION
To date, the management of very
severe TAO, especially DON is still a matter of controversy among
ophthalmologists[11]. Although a number of
studies have provided findings on the efficacy and safety of various treatments
for TAO, only a few studies with small sample size have been directed to the
reliable treatments for sight-threatening TAO[7,11]. As a result, many issues relating to the treatment
of this serious disease remained to be addressed. In addition, some studies are
advocating a comparatively low-dose ivGC plan and immediately OD surgery in
case of potentially life-threatening adverse effects when it comes to the
arrangement of moderate-to-severe TAO without clearly demarcating DON or
detailing the general conditions[8]. Currently, no
clear information regarding the optimal dose and administration protocol of
systemic high-dose ivGC therapy for these sight-threatening TAO is available.
Moreover, the specific indications for orbital decompression, details regarding
surgical techniques employed and surgical effects warrant further evaluation.
van Geest et al[9] reported results obtained from their severe TAO
patients who received intravenous
Patients in our study treated
steroid pulse therapy only showed obvious improvements in CAS scores, visual
acuity, ocular alignment and ocular motility, while changes in exophthalmos
were not so remarkable, effects which were similar to that reported in previous
studies. In specific, 41 cases (68.3% of ivGC group) showed severely impaired
visual functions, significant exophthalmos and obvious hypertrophy of
extraocular muscles. According to the recommended guidelines, these patients
should receive OD surgery. However, after ivGC therapy, they achieved
satisfactory results and were able to avoid surgical intervention. In this way,
ivGC therapy can be as effective as OD for recovery of optic nerve function in
some cases[16].
OD, as achieved through removal of
either the orbital wall or orbital fat, is a cornerstone in the treatment of
very severe TAO, especially those diagnosed with DON[6].
Bony decompression includes a balance of medial and lateral walls, deep lateral
wall, inferomedial wall, or “3-wall” (medial, lateral, inferior wall)
techniques. Fatty decompression is commonly used due to its lower complication
rate[8,17]. OD are required for
those patients who are unresponsive to ivGC or radiotherapy, and proves
effective for correcting exposure keratopathy, restoring optic nerve function
as well as for disfiguring exophthalmos[18]. The
specific surgical methods to be used for OD are selected by the surgeon
depending on the TAO severity. A deep lateral orbit wall combined with fatty
decompression are used for TAO patients with exophthalmos less than
In regard to diplopia and
strabismus, opinions vary. In most papers, diplopia is divided into
pre-existing diplopia and new-onset diplopia. Improvement rates in pre-existing
diplopia have been reported from 20% to 30%[22-23]. Conversely, some reports show that OD is ineffective
in relieving strabismus and diplopia (range from 3% to 25%)[24-25], and around 20% of these patients require further
strabismus surgery after OD at least 6mo later[26-28]. To compare diplopia changes after various OD
approaches is hampered by multiple factors: the preoperative conditions of the
patients[29] (diplopia in primary gaze or
secondary gaze), the criteria for detecting diplopia, subjective factors of the
patients, etc. It is said that balanced decompression considering the
involvement of extraocular muscles and technique to remodel the fat medially
and laterally, may contribute less worsening of diplopia and sometimes improve
the existing diplopia[30]. Our results indicated
that 32% of our patients treated with OD showed an improvement on diplopia.
This could be explained by 1) for patients who showed a hypertropia, we often
selected a decompression of the orbital floor; 2) adipose tissue removal was
performed in all cases attempting to rebalance the proptosis which may also
improve the deviation of the eyeball; 3) similar to ivGC therapy, patients who
received OD showed obvious reduction of swelling orbital tissues, which could
improve the pre-existing diplopia.
In this study, all patients in OD
group initially received ivGC, but were unresponsive to this ivGC therapy. In
line with previous reports, our study confirms the efficacy of OD in such
conditions. After OD surgeries, all the patients obtained a mean exophthalmos
reduction of 4.35±
The limitations of the present study
include the relatively small sample size, and that all patients were treated by
a single author which precludes effects that may result from individual
differences in surgical techniques of OD. As this was an uncontrolled
retrospective study it is vulnerable to some clinical data bias. While
comprehensive examinations of visual functions (visual acuity, visual field,
VEP and color vision) were performed prior to treatment in these cases, only
visual acuity examinations were performed at the final follow-up. Finally, the
fact that all patients were from south China may also limit the findings of
this study. Future work on this topic will require randomized controlled trials
in patients with sight-threatening TAO, especially those with DON. Comparing
two or more intravenous steroid administration protocols, different surgical
interventions for OD and information addressing the efficacy, safety and
quality of life in these patients.
In summary, we found that the
severely impaired eyesight in some patients with sight-threatening TAO could be
restored by ivGC alone, thus sparing them from surgical OD. Some patients, who
experienced vision loss after successful OD, showed a restoration of their
vision again in response to ivGC treatment. In those patients refractory to
steroids, OD often resulted in satisfactory outcomes, however, new-onset
strabismus was present in 12.0% of these patients following OD surgery. Based
on the findings of our review there exists compelling evidence that ivGC should
be considered as a first-line treatment for active sight-threatening TAO, while
subsequent OD is particularly effective in cases unresponsive to steroids.
ACKNOWLEDGEMENTS
Foundations: Supported by the National Natural Science
Foundation of China (No.81670885); the Science and Technology Program of
Guangdong Province, China (No.2013B020400003); the Science and Technology
Program of Guangzhou, China (No.15570001).
Conflicts of Interest: Wen Y, None; Yan JH, None.
REFERENCES