Measuring contrast sensitivity in patients with Graves' ophthalmopathy complicated by ocular hypertension and suspect glaucoma or dysthyroid optic neuropathy

The present study compares contrast sensitivity functions of patients with uncomplicated Graves' ophthalmopathy, patients with ophthalmopathy and elevated intraocular pressure or suspect glaucoma, and patients with dysthyroid optic neuropathy (DON). Aim of the study was to investigate the clinical potential for the contrast sensitivity functions (CSF) in distinguish between the groups. Contrast sensitivity measurements were obtained from twenty-seven subjects with endocrine ophthalmopathy. Group I included patients with uncomplicated ophthalmopathy (n=20 eyes); group II included patients with ophthalmopathy, intraocular pressure 24 mmHg with and without early visual field defects, and no evidence of apical crowding on coronal computed tomography scan (n=14 eyes); group III included patients with DON (n=12 eyes). Contrast thresholds were determined for stationary and 6.87 Hz phase-alternating gratings at eight spatial frequencies from 0.18 to 15.7 c/deg. Data from each group was compared with data from age-matched normal subjects. Observers with uncomplicated ophthalmopathy had normal CSFs. Eyes affected with DON showed contrast sensitivity disruption at overall intermediate-high spatial frequencies. Eyes with elevated intraocular pressure or suspect glaucoma had pronounced sensitivity loss in the low frequency range (0.18-0.70 c/deg) as compared to eyes with DON. This study shows that CSF detects visual function abnormalities noninvasively in patients with complicated Graves' ophthalmopathy. Results also indicate that the clinical potential for CSF in distinguish between patients suffering from ophthalmopathy complicated by ocular hypertension or suspect glaucoma and patients with DON improves when a temporal modulation of 6.87 Hz and gratings of low spatial frequency (< 1 c/deg) are used.     

Visual evoked potentials in patients with Graves' ophthalmopathy complicated by ocular hypertension and suspect glaucoma or dysthyroid optic neuropathy

The study compared visual evoked potentials of patients with uncomplicated Graves' ophthalmopathy, patients with ophthalmopathy and elevated intraocular pressure or suspect glaucoma, and patients with dysthyroid optic neuropathy (DON). The aim of the study was to investigate the clinical potential for the visual evoked potentials (VEP) in the differential diagnosis among the groups. The VEPs were obtained from 43 subjects with endocrine ophthalmopathy. Group I included patients with uncomplicated ophthalmopathy (30 eyes); group II included patients with ophthalmopathy, intraocular pressure 23 mmHg with and without early visual field defects, and no evidence of apical crowding on coronal computed tomography scan (28 eyes); group III included patients with DON (28 eyes). Amplitude and latency of major component of pattern VEP were obtained at three visual angles (60', 30', 15'). Data from each group was compared with data from age-matched normal subjects. Disturbances of VEP were found mainly in patients of Group II and Group III. Control Group had normal VEP. About the differential diagnosis between Group II and Group III the most important parameter was the N75-P100 amplitude for 15' of pattern stimulation. Only for this visual angle, Group II and Group III had not overlapped N75-P100 amplitude. This study shows that VEP detect visual function abnormalities noninvasively in patients with complicated Graves' ophthalmopathy. Results also indicate the clinical potential for VEP in the differential diagnosis between patients suffering from ophthalmopathy complicated by ocular hypertension or suspect glaucoma and patients with dysthyroid optic neuropathy.     

Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO) survey

BACKGROUND: This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. RESULTS: Graves' hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. CONCLUSION: Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.     

Dysthyroid optic neuropathy. The crowded orbital apex syndrome

The authors have reviewed the clinical presentation, visual fields, color vision testing, visual-evoked potentials, and computed tomographic (CT) findings of 58 patients (95 eyes) with dysthyroid optic neuropathy. The authors compared these findings to a control group of 60 patients (119 eyes) with thyroid eye disease who underwent CT scanning and did not exhibit evidence of optic neuropathy. Clinically, dysthyroid optic neuropathy is an insidious disease; when compared with the usual Graves' orbitopathy patient, the optic neuropathy group presented at a later age and with a later onset of thyroid eye disease. The patients in this group were more likely to be male and/or diabetic, and often presented with desaturation of color vision. Asymmetrical extraocular muscle restriction and vertical tropias were more frequent in the optic neuropathy group. The most sensitive indicators of optic nerve dysfunction appeared to be visual-evoked potentials and color vision. Computed tomographic studies confirmed that apical orbital crowding was a characteristic feature of optic neuropathy. These findings should alert the clinician to a more aggressive approach to these patients.     

Contrast sensitivity function in Graves' ophthalmopathy and dysthyroid optic neuropathy.

Contrast sensitivity function was measured by a computer automated method on 38 eyes with dysthyroid optic neuropathy and 34 eyes with Graves' ophthalmopathy only. The results were compared with 74 healthy control eyes. Disturbances of contrast sensitivity functions were found in both groups when compared with controls. The eyes affected with dysthyroid optic neuropathy showed pronounced loss of contrast sensitivity in the low frequency range, which facilitates differentiation between the two groups.     

Management of patients with dysthyroid optic neuropathy treated with intravenous corticosteroids and/or orbital decompression surgery

Graefe's Archive for Clinical and Experimental Ophthalmology - To assess the characteristics and long-term outcomes of adult patients with dysthyroid optic neuropathy (DON) who underwent...     

Using frequency-doubling perimetry to detect optic neuropathy in patients with Graves’ orbitopathy

Purpose  to test the ability of frequency-doubling technology (FDT) perimetry to detect dysthyroid optic neuropathy (DON). Methods  Fifteen eyes of 15 patients with DON and 15 healthy control eyes were studied. Eligible eyes had a diagnosis of DON based on visual field abnormalities on standard automated perimetry and had visual acuity better than 20/30. FDT testing was performed using both the C-20-5 screening test and the C-20 full-threshold test. Normal and DON eyes were compared with regard to FDT mean sensitivity. Results  Sensitivity ranges were 40.0%–86.7% for the screening test, and 53.3%–100.0% (total deviation) and 20.0–93.3 (pattern deviation) for the C-20 threshold test. The corresponding specificity ranges were 86.7–100.0, 33.3–93.3, and 26.7–100.0, respectively. The best sensitivity/specificity ratios were for one abnormal point depressed <5% in the screening test (86.7%/86.7%), one point depressed <1% in the total deviation analysis (80.0%/86.7%), and one point depressed <2% in the pattern deviation analysis (80.0%/86.7%). DON eyes presented significantly lower than normal average sensitivity in the central, pericentral, and peripheral areas. Conclusions  FDT perimetry is a useful screening tool for DON in eyes with normal or only slightly reduced visual acuity.     

甲状腺相关眼病图形视觉诱发电位的研究

目的了解图形视觉诱发电位(P-VEP)在甲状腺相关眼病视神经病变(DON)早期诊断中的应用价值.方法随机选取39例甲状腺相关眼病(TAO)和30例正常对照进行P-VEP检查.结果P-VEP的改变主要为P1振幅(PA)的降低(P＜0.05).结论P-VEP比较敏感地反映TAO视神经功能的变化,可作为DON早期诊断的敏感指标.     

Results of transmedial-canthal ethmoidal decompression for severe dysthyroid optic neuropathy

PURPOSE: To study the effects of ethmoidal wall (one-wall) decompression using a transmedial-canthal approach (transmedial-canthal ethmoidectomy) for the treatment of dysthyroid optic neuropathy. METHODS: The ethmoidal wall and air cells were completely removed using a transmedial-canthal approach in 6 eyes of 4 patients (mean age = 55 years; age range, 46-69 years) with dysthyroid optic neuropathy. Similar surgery was performed on 2 contralateral eyes in 2 of the patients for cosmetic reasons. The preoperative corrected visual acuity in the 6 eyes ranged from hand motion to 20/100. Centrocecal scotomas were detected using automatic static threshold perimetry in the 6 eyes. RESULTS: After transmedial-canthal ethmoidectomy, the corrected visual acuity improved to better than 20/20 in the 6 eyes, and the centrocecal scotomas had almost completely resolved. There were no major complications, such as cerebrospinal fluid leakage or diplopia associated with the surgery. There were no relapses during an average follow-up period of 29 months. CONCLUSIONS: These findings suggest that transmedial-canthal ethmoidectomy is an effective and safe therapy for dysthyroid optic neuropathy.     

Visual evoked potentials in diagnosis and monitoring of optic neuropathy in the course of thyroid ophthalmopathy

PURPOSE: To evaluate the usefulness of pattern visual evoked potentials (PVEP) in early diagnosis and monitoring of dysthyroid optic neuropathy (DON). MATERIAL AND METHODS: We recorded PVEP (UTAS E--1000) in 74 patients with thyroid ophthalmopathy (TO) including 12 patients with clinically evident DON--group I, 13 patients with subclinical DON (prolongation of latency of P100 wave in PVEP)--group II, and 49 patients without clinical or electrophysiological signs of DON--group III. Thirty six healthy subjects served as controls. The latencies of P100 and N75 waves were examined. In 50 TO patients we recorded changes in PVEP before and after treatment. RESULTS: The mean LP100 and LN75 were significantly longer in TO patients compared to control group. In groups I and II they were also significantly longer in comparison to group III. We observed prolongation of LP100 above the upper limit of normal values in all patients with clinically evident DON and in 13/62 (21%) cases without clinical signs of optic nerve dysfunction. The prolongation of LP100 was present in 16/21 (76.2%) eyes in group I and in 15/26 (57.7%) eyes in group II. Prolongation of LN75 was less frequent: group I--5/21 (23.8%), group II--2/26 (7.7%). After treatment in patients with clinically evident DON the latencies of both waves were significantly shorter in comparison to values obtained before therapy. In group II statistically significant differences were observed only in LP100. The percentage of eyes with prolonged latencies was significantly smaller after treatment (group I: LP100--3/23 (13.0%), LN75--1/23 (4.3%); group II: LP100--2/18 (11.1%), LN75--no prolongation was observed). CONCLUSIONS: PVEP is an useful method in diagnosis and monitoring of dysthyroid optic neuropathy. It can reveal even asymptomatic optic nerve dysfunctions. Detection of subclinical neuropathy using PVEP enables early--thus more effective--treatment. The most important factor in PVEP evaluation is the latency of P100 wave, the latency of N75 wave is less useful.     

Transcaruncular orbital decompression for dysthyroid optic neuropathy

PURPOSE: To determine the efficacy of transcaruncular approach orbital apex decompression for treatment of dysthyroid optic neuropathy. METHODS: In this retrospective noncomparative interventional case series, charts for all patients undergoing orbital decompression surgery for dysthyroid optic neuropathy performed by one author between October 1999 and September 2001 were included in the study. Primary outcome measures included visual acuity, static perimetry, pupillary testing, and color plate testing before and after surgery. Records were also reviewed for changes in extraocular motility and proptosis after surgery and for surgical complications. RESULTS: Sixteen consecutive patients (6 unilateral, 10 bilateral, for a total of 26 cases) underwent orbital apex decompression for dysthyroid optic neuropathy through a transcaruncular approach. In each orbit, the optic neuropathy was refractory to oral corticosteroid therapy. Preoperative visual acuity remained stable or improved in each case. Preoperative Humphrey visual field testing revealed an average mean deviation of -10.3 +/- 6.5 (range, +0.76 to -25.45). Average postoperative mean deviation was -2.79 +/- 2.4 (range, +0.94 to -9.82). Before surgery, 7 of 23 eyes (30%) had full color plates. After surgery, 22 of 23 eyes (96%) had full color plates. Follow-up ranged from 2 to 26 months (mean, 10 months). New-onset diplopia developed in 2 of 10 (20%) patients without preexisting diplopia. CONCLUSIONS: Transcaruncular approach orbital apex decompression effectively treats dysthyroid optic neuropathy.     

Results of orbital decompression in Taiwan

Orbital decompression was performed on 116 orbits with Graves' ophthalmopathy. The indications for decompression were dysthyroid optic neuropathy (DON), recalcitrant corneal exposure (EXP) and disfiguring exophthalmos (COS). All cases but one (in the DON group) had improved or unchanged vision. The average retinal sensitivity improvement in the DON group was 6.7 +/- 6.1 dB and 85% had a significant retinal sensitivity improvement (>5 dB). The average retroplacement effect was 4.4 +/- 2.1 mm and only five cases (7%) had postoperative asymmetry of more than 2 mm by Hertel's exophthalmometry. The most frequent sequela was diplopia, which tended to occur in more severely myopathic eyes. In our series, 21% (10/48 cases without preoperative diplopia) developed diplopia after decompressive surgery. Hypoglobus is another complication, noted in two cases, which was successfully repositioned. In conclusion, decompressive surgery is a safe and effective procedure to restore vision and reduce exophthalmos in Graves' ophthalmopathy. Careful evaluation of clinical parameters, individualization of surgical goals and intraoperative titration of the retroplacement effect are the key to optimal results.     

Reduced choroidal peripapillary capillaries in thyroid-associated ophthalmopathy with early stage of dysthyroid optic neuropathy

AIM: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroid-associated ophthalmopathy (TAO) could be an early sign to detect dysthyroid optic neuropathy (DON). METHODS: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography (OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries (RPC), retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. RESULTS: Whole choroidal RPC was significantly reduced in DON (48.24%±0.4978%) compared to normal (50.33%±0.3173%) and TAO without DON (49.16%±0.5463%; P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field (VF) defect in DON (r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed. CONCLUSION: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.     

Changes in peripapillary blood vessel density in Graves’ orbitopathy after orbital decompression surgery as measured by optical coherence tomography angiography

The purpose is to evaluate the utility of optical coherence tomography (OCT) angiography in the evaluation of Graves’ orbitopathy (GO) and response to orbital decompression in patients with and without dysthyroid optic neuropathy (DON). This was a single-center, prospective case series in a cohort of 12 patients (24 orbits) with GO and ±DON, (6 orbits) who underwent bilateral orbital decompression. All patients underwent pre- and postoperative OCT angiography of the peripapillary area. Vessel density indices were calculated in a 4.5 mm × 4.5 mm ellipsoid centered on the optic disk using split-spectrum amplitude decorrelation angiography algorithm, producing the vessel density measurements. Mean change in vessel density indices was compared between pre- and postoperative sessions and between patients with and without DON. Patient 1, a 34-year-old male with GO and unilateral DON OD, showed a significant reduction in blood vessel density indices oculus dexter (OD) (DON eye) after decompression while a more modest reduction was found oculus sinister (OS) with the greatest change noted intrapapillary. Patient 2, a 50-year-old male with DON OU, showed worsening neuropathy following decompression OD that was confirmed by angiographic density indices. Patient 3, a 55-year-female with DON, showed a reduction in blood vessel density OD and increased density OS. Patients without DON showed overall less impressive changes in indices as compared to those with DON. Using OCT angiography, response to surgical treatment in GO orbits, more so in orbits with DON, can be demonstrated and quantified using vessel density indices with reproducibility.     

CT scan evidence of dysthyroid optic neuropathy

PURPOSE: To determine the utility of CT imaging in identifying patients with dysthyroid optic neuropathy. METHODS: Orbital CT scans of 12 randomly selected patients with dysthyroid optic neuropathy and 15 control subjects with Graves orbitopathy were retrospectively reviewed by two investigators blinded to the clinical data. The clinical diagnosis of optic neuropathy was made by one author before obtaining CT images and was based on clinical features. RESULTS: Optic nerve crowding (P<0.001) and intracranial fat prolapse (P<0.05) were the imaging features independently related to optic neuropathy. A muscle index greater than 50% had excellent sensitivity (100%) but did not have high specificity (47%) for dysthyroid optic neuropathy. Superior ophthalmic vein dilation and proptosis did not show significant relations with optic neuropathy. CONCLUSIONS: This study suggests that patients with Graves orbitopathy who have severe optic nerve crowding, intracranial fat prolapse, and/or muscle index greater than 50% present on orbital CT scans are more likely to have coexisting optic neuropathy.     

Quantification of optic nerve length and tortuosity in thyroid eye disease

ObjectiveTo objectively quantify the length and tortuosity of optic nerves (ONs) in patients with thyroid eye disease (TED), in relation to the occurrence of dysthyroid optic neuropathy (DON).Patients and MethodsAll patients seen by 2 of the senior authors over a period of 12 years were screened for study entry. The primary outcome was the quantitative measurement of ON tortuosity and length in relation to the occurrence of DON. Image analysis involved the creation of a 3-dimensional reconstruction of the ON from the anterior clinoid process to the posterior globe using image analysis software. A centreline was created through the middle of the reconstruction, and the length of the ON was calculated as the length of this centreline. Tortuosity was calculated by creating a ratio between the straight-line length of the ON and the actual length (centreline length).ResultsThe final sample included 50 patients who contributed 100 orbits, of which 26 orbits had DON. There were no differences in the Hertel exophthalmometry readings between patients with and without DON (p = 0.56). There was no significant relationship between the length (p = 0.39) and tortuosity (p = 0.82) of the ON and occurrence of DON.ConclusionThere is no significant relationship between the length and tortuosity of the ON and development of DON in patients with TED.     

Apoptosis in orbital fibroadipose tissue and its association with clinical features in Graves' ophthalmopathy

PURPOSE: To evaluate the rate of apoptosis in orbital fibroadipose tissue in Graves' ophthalmopathy (GO) patients and investigate its associations with disease characteristics. METHODS: Orbital tissue samples were obtained during decompression surgery from 25 GO patients. Disease activity was evaluated using the Clinical Activity Score, while the clinical features of GO were evaluated using the Total Eye Score (TES). Tissue samples of 12 patients without any thyroid or autoimmune disease were studied as controls. The rate of apoptosis was evaluated with a terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay, and ultrastructural features of apoptosis were evaluated with electron microscopy. RESULTS: The rate of apoptosis in orbital fibroadipose tissue was significantly higher in GO cases than in the control group (p < 0.001) and significantly correlated with TES (r: 0.545; p = 0.005). The rate of apoptosis was 7.9% +/- 6.5%, and 22.0% +/- 7.8% in type 1 and type 2 cases, respectively (p = 0.001). The rate of apoptosis was 21.6% +/- 7.5% in eyes showing dysthyroid optic neuropathy (DON) and 6.7% +/- 5.4% in eyes without DON (p = 0.005). CONCLUSIONS: The rate of apoptosis was high in the orbital fibroadipose tissue of GO cases and was related to the clinical features of the disease.     

糖尿病性视神经病变的OCT图像特点分析

目的：回顾分析糖尿病性视神经病变( diabetic optic neuropathy, DON )的相干光断层成像( optical coherence tomography,OCT)的特点。
　　方法：回顾性系列病例研究。选择2013-12/2015-10西安交通大学医学院第二附属医院眼科门诊和内分泌科会诊期间诊断为2型糖尿病且伴有眼底病变的患者175例350眼的临床资料,记录患者的全身检查情况和疾病史,阅读所有患者的彩色眼底照相、荧光素眼底血管造影( fluorescein fundus angiography,FFA)、OCT的影像结果,并进行分析统计。
　　结果：通过FFA 检查视乳头具有异常荧光表现,确定有DON的有49例90眼,占25.7%。 OCT结果显示DON 90眼中15眼(16.7%)表现为视神经形态大致正常;20眼(22.2%)表现为视杯凹陷变小或消失,筛板前组织肿胀,同时伴有盘周神经纤维层水肿;26眼(28.9%)表现为视杯深陷,杯盘比变大;18眼(20.0%)表现为视盘内或视盘表面组织增生;11眼(12.3%)玻璃体视乳头牵拉,视盘边缘抬高。在FFA中有相同荧光表现的DON患眼,在OCT检查可表现出不同的组织形态。
　　结论：FFA从视神经的血循环状态变化定义DON,而OCT可以发现FFA所不能显示的视神经组织形态的变化,从而更清晰视神经病变的位置和原因,为治疗提供依据。OCT无创、快捷、费用低、可重复性强等优点有利于DON患者的复查及治疗效果追踪。     

Methylprednisolone pulse therapy in severe dysthyroid optic neuropathy

Five patients with severe dysthyroid optic neuropathy were treated with intravenous methylprednisolone (1 g daily for 3 consecutive days). Before administration, visual acuity of the more severely affected eyes of each patient was counting fingers at 5 feet, 8/200, 20/400, 20/200, and 20/80. Immediately after completion of pulse therapy, visual acuity improved to 20/25 in four patients and 20/30 in one. Remissions were maintained with oral prednisone and external beam irradiation of the orbit. Pulse methylprednisolone therapy appears to be beneficial in the initial management of severe dysthyroid optic neuropathy.     

Ultrasonographic measurement of the optic nerve sheath diameter in dysthyroid optic neuropathy

BackgroundThe aim of this study is to evaluate the optic nerve sheath diameter (ONSD) in eyes with dysthyroid optic neuropathy (DON) and its relationship with clinical characteristics and disease severity.MethodsPatients diagnosed as thyroid-associated ophthalmopathy (TAO), with or without DON, and healthy participants were recruited. Vertical and horizontal sectional images of the optic nerve were collected by B-scan ultrasonography. ONSDs at 3 mm and 6 mm behind the eyeball were measured independently by two researchers. Multivariate regression analysis was performed to evaluate the association of ONSD with demographic and ocular parameters in TAO patients. Areas under the receiver operating characteristic curves (AUROCs) were applied to evaluate the diagnostic accuracy of ONSD for DON.ResultsA total of 47 healthy eyes, 36 TAO eyes without DON, and 33 eyes with DON were studied. ONSDs at 3 mm and 6 mm of DON eyes were significantly higher than those in non-DON and healthy eyes (all P < 0.05). There was no significant difference in ONSDs between clinically active and inactive eyes (both P > 0.05). DON occurrence showed a positive association with both ONSDs at 3 mm (β = 0.49, 95% CI: 0.14–0.83, P = 0.007) and 6 mm (β = 0.58, 95% CI: 0.20–0.96, P = 0.003). ONSDs at 3 mm and 6 mm showed a desirable diagnostic capacity to distinguish DON from non-DON eyes (AUROC was 0.77 and 0.75, respectively).ConclusionsAn increase in ONSD is evident in DON eyes independent of clinical activity. Ultrasound-based ONSD has sufficient ability to distinguish DON from non-DON eyes.Subject terms: Eye diseases, Biomarkers