Clinical evaluation of radiotherapy for Graves' ophthalmopathy

Seventeen patients with moderately severe ophthalmopathy due to Graves' disease were treated by cobalt or supervoltage radiotherapy. All patients complained of diplopia. The mean proptosis value was 21.4 mm. Three patients (18%) showed good response, 7 (41%) moderate and 7 minimal or no response. Improvement was noted mainly in soft tissue changes and diplopia, while proptosis decreased in only 5 patients. All except one patient who had marked extraocular muscle involvement revealed by computed tomography responded to treatment. These data indicate that radiotherapy may be indicated in patients with progressive ophthalmopathy, especially in those who are associated with extraocular muscle enlargement.     

High voltage orbital radiotherapy and surgical orbital decompression in the management of Graves' ophthalmopathy

We report on 2 groups of patients with Graves' ophthalmopathy. A group of 21 patients was treated by high voltage (18 MV) orbital radiotherapy combined with mean doses of corticoids. The results were good or excellent in 12 patients (mean score 6.62 before and 4.0 after, soft tissues greater than proptosis greater than extraocular muscle involvement), without any complications from irradiation. Patients undergoing surgery initially presented less severe symptoms, even 7 patients treated after corticoid and/or radiotherapy failure. The results were satisfactory in all patients (mean score 5.1 before and 2.4 after, proptosis greater than soft tissues greater than extraocular muscle involvement). Both methods showed results within 3 months, and they can be combined.     

Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves' disease

Uveal autoantigen with coiled coil domains and ankyrin repeats (UACA) is an autoantigen in patients with panuveitis such as Vogt-Koyanagi-Harada disease. The prevalence of IgG anti-UACA antibodies in patients with uveitis is significantly higher than healthy controls, suggesting its potential role as an autoantigen. Originally, UACA was cloned from dog thyroid tissue following TSH stimulation. So, we presumed UACA could be a novel autoantigen in autoimmune thyroid diseases. We measured serum anti-UACA antibody titer using ELISA in patients with autoimmune thyroid diseases (Graves' disease, Hashimoto's thyroiditis, subacute thyroiditis, and silent thyroiditis). The prevalence of anti-UACA antibodies in Graves' disease group was significantly higher than that in healthy group (15% vs. 0%). Moreover, the prevalence of anti-UACA antibodies in Graves' ophthalmopathy was significantly higher than that in Graves' patients without ophthalmopathy (29% vs. 11%). Especially, 75% of severe ocular myopathy cases showed high UACA titer. Immunohistochemical analysis revealed that UACA protein is expressed in eye muscles as well as human thyroid follicular cells. Taken together, UACA is a novel candidate for eye muscle autoantigens in thyroid-associated ophthalmopathy.     

Orbital cobalt radiotherapy and systemic or retrobulbar corticosteroids for Graves' ophthalmopathy

Orbital radiotherapy and corticosteroids are two well-established medical treatments for severe Graves' ophthalmopathy. In this report we analyze the results obtained by the combination of orbital radiotherapy and systemic or retrobulbar corticosteroids in patients with severe Graves' ophthalmopathy. Orbital cobalt radiotherapy was carried out by a cobalt unit, delivering a total of 2,000 rads to each eye in 10 daily doses. Systemic corticosteroid treatment was started with 70-80 mg methylprednisolone/day for 2-3 weeks with subsequent progressive reduction of the dose until discontinuation of the drug after 5-6 months. Retrobulbar corticosteroid therapy was performed by 14 bilateral injections of 40 mg methylprednisolone acetate at 20- to 30-day intervals. Results were evaluated both on clinical grounds and by numerical scoring (ophthalmopathy index, OI). Excellent or good responses were obtained in the majority of 72 patients by combined treatment with orbital cobalt radiotherapy and systemic corticosteroids. Soft tissue changes, newly developed eye muscle dysfunction and optic neuropathy showed the most beneficial effects from treatment, whereas proptosis, corneal lesions and long-standing eye muscle abnormalities responded to a lesser extent. The results of a controlled clinical trial showed that the combined treatment was more effective than the administration of systemic methylprednisolone alone. Because relevant side effects of systemic corticosteroid therapy were observed in 4 cases, the clinical validity of retrobulbar corticosteroids in substitution for systemic corticosteroids was evaluated in 44 patients. Excellent or good responses were observed in 25% of these patients, slight responses being obtained in 55% and no change in 20%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the volume of intraorbital structures using the numerical segmentation image technique (NSI): the extraocular muscles

INTRODUCTION: In recent years the use of computer systems has allowed numerical analysis of medical images to be introduced and has speeded up the conversion of numerical data into clinically valuable information. The creation of a software application that could almost automatically calculate the volume of anatomical structures imaged by MRI has seemed possible. The aim of our study was to determine the clinical usefulness of an numerical segmentation image technique (NSI) software application in estimating the volume of extraocular muscles. MATERIAL AND METHODS: The study group was formed of 45 patients (90 orbits). All the patients underwent MRI examinations of the orbits by a 1.5 T scanner using a head coil. The degree of exophthalmos was determined clinically and radiologically in relation to the interzygomatic line. The quantitative assessment of all eye muscles was carried out using the NSI application, a new software program introduced by the authors. RESULTS: A close correlation between muscle volume and the degree of exophthalmos was revealed and confirmed by statistical analysis (r = 0.543, p = 3.13396E-08) in agreement with other papers. CONCLUSIONS: The NSI software program is an application which offers a reliable and precise estimation of eye muscle volume. It is therefore useful in the diagnosis of the pathological processes leading to exophthalmos. It has special clinical value for monitoring discrete volume changes of muscles during treatment.     

Plasma exchange therapy for severe Graves' ophthalmopathy

The authors report on the treatment of 11 Graves' disease patients with severe ophthalmopathy by the use of intensive plasma exchange followed by immunosuppression. Results were evaluated by comparing the ophthalmopathy index and the orbital CT scan performed before and after plasmapheresis. Favorable results were obtained in 91% of the patients. The best positive effects of plasmapheresis were observed for soft tissue involvement, proptosis, tonometry, and visual acuity. Furthermore, a significant reduction in the size and density of enlarged extraocular muscles was also found. Six months after withdrawal of immunosuppression, 4 patients presented a moderate recurrence of ophthalmopathy and were treated successfully by a second course of plasmapheresis, followed by short immunosuppression. In conclusion, the use of intensive plasma exchange associated with immunosuppression is an effective approach to the treatment of severe Graves' ophthalmopathy. It yields rapid and dramatic improvements that are maintained in most patients after withdrawal of immunosuppression. Recurrences are still responsive to the beneficial effects of this combined treatment.     

Paradoxical absence of M lines and downregulation of creatine kinase in mouse extraocular muscle.

The M lines are structural landmarks in striated muscles, necessary for sarcomeric stability and as anchoring sites for the M isoform of creatine kinase (CK-M). These structures, especially prominent in fast skeletal muscles, are missing in rodent extraocular muscle, a particularly fast and active muscle group. In this study, we tested the hypotheses that 1). myomesin and M protein (cytoskeletal components of the M lines) and CK-M are downregulated in mouse extraocular muscle compared with the leg muscles, gastrocnemius and soleus; and 2). the expression of other cytosolic and mitochondrial CK isoforms is correspondingly increased. As expected, mouse extraocular muscles expressed lower levels of myomesin, M protein, and CK-M mRNA than the leg muscles. Immunocytochemically, myomesin and M protein were not detected in the banding pattern typically seen in other skeletal muscles. Surprisingly, message abundance for the other known CK isoforms was also lower in the extraocular muscles. Moreover, total CK activity was significantly decreased compared with that in the leg muscles. Based on these data, we reject our second hypothesis and propose that other energy-buffering systems may be more important in the extraocular muscles. The downregulation of major structural and metabolic elements and relative overexpression of two adenylate kinase isoforms suggest that the extraocular muscle group copes with its functional requirements by using strategies not seen in typical skeletal muscles.     

一个常染色体显性遗传先天性眼外肌 纤维化家系A

为寻找疾病相关基因,通过随访调查、体检、病理检查等手段,发现了一眼外肌纤维化家系4代中有15人患有眼外肌纤维化综合征,主要表现先天性上眼睑下垂、下颌上举、头后仰、双眼固定下转位和被动牵拉试验阳性,眼外肌病理检查结果为肌纤维化和玻璃样变性,所有阳性体征者除眼球运动限制程度有区别外,其他眼部症状基本相同。遗传分析表明,该疾病属常染色体显性遗传。该家系可作为寻找眼外肌纤维化疾病相关基因的宝贵资源。Abstract: To discover novel disease genes, a family with congenital fibrosis of the extraocular muscle was studied by a follow-up investigation, eye examinations and histo-pathological examination. There were fifteen cases suffering from congenital general fibrosis syndrome in four generations. They have congenital blepharoptosis, head tilt, chin lift, primary gaze fixed in a hypo- and exotropic position. The diagnosis is confirmed with positive forced duction testing in the affected eye. Furthermore, fibrosis of the extraocular muscles and hyaline degeneration was confirmed by histo-pathological examination. Except for different levels of restriction of the eyeball movements , other eye symptoms in positive patients are substantially identical. The genetic analysis showed that this disease was caused by autosomal dominant inheritance. The pedigree may be precious resource candidate for discovering disease gene related with congenital fibrosis of the extraocular muscle.     

The properties of the extraocular muscles of the frog. II. Pharmacological properties of the isolated superior oblique and superior rectus muscles.

The pharmacological properties of the superior oblique and the superior rectus muscles of the frog's eye were investigated in comparison with those of a skeletal muscle (iliofibularis muscle) of the same animal. Acetylcholine causes sustained contractures of the extraocular muscles; this effect is increased by physostigmine and decreased or abolished by d-tubocurarine. Also the applications of succinylcholine, choline or caffeine are able to evoke contractures. There are no striking differences in pharmacological properties between extraocular and skeletal muscles of the frog. The time-course of the contractures and the sensitivity of the muscle preparations to the drugs which evoke contractures are identical in extraocular and iliofibularis muscles. In comparison with skeletal muscles there is no higher sensitivity of the extraocular muscles against curare-like drugs. The existence of adrenergic receptors could not be found neither in extraocular nor in skeletal muscles of the frog. It is concluded that in frogs no pharmacological differences exist between the muscle fibre types which compose the extraocular and the skeletal muscles.     

The development of extraocular muscle calcium homeostasis parallels visuomotor system maturation

Extraocular muscle is modulated by unique genetic and epigenetic factors to produce an atypical phenotype. As a prelude to regulation studies, we characterized the development of cation homeostasis in the predominately fast-twitch extraocular muscles. By atomic absorption spectroscopy, total muscle calcium content declined from birth to postnatal day 27 and, thereafter, stabilized at a low level in limb but increased dramatically in extraocular muscle (to 40x limb values). By ELISA, the slow isoform of sarcoplasmic reticulum Ca2+-ATPase predominated in neonatal eye muscle, but subsequently was largely replaced by the fast isoform. This replacement in eye muscle was completed later than in limb. Residual, slow Ca2+-ATPase likely resides in an unusual slow tonic fiber type characteristic of eye muscle. Maturation of the definitive extraocular muscle Ca2+-ATPase pattern paralleled myofiber Ca2+ and sarcoplasmic reticulum content. These data show that, like myosin heavy chain expression patterns, the development of cation homeostatic mechanisms in extraocular muscle parallels landmarks in the maturation of vision and eye movement control systems. Findings suggest that cation homeostasis in extraocular muscle may be susceptible to perturbations of the developing visual sensory system, as we have previously shown for myosin.     

Mechanisms of immune damage in Graves' ophthalmopathy

We have studied the role of immunologically mediated cytotoxicity in the orbital tissue damage of Graves' ophthalmopathy. Antibody-dependent cell-mediated cytotoxicity (ADCC) against eye muscle (EM) cells and orbital fibroblasts (OF) was demonstrated in a small proportion of patients, all of whom had severe, recent disease. Antibody-mediated (complement-dependent) cytotoxicity against OF was found in only a few patients. No patients showed lysis above background with EM targets. ADCC activity against OF was absorbed by preincubation of serum with thyroid cells, eye muscle cells, and orbital fibroblasts, as well as thyroid, eye muscle and orbital connective tissue membranes. Both EM and OF were able to express class II MHC HLA-DR antigens when stimulated by gamma interferon, phytohemagglutinin or activated T lymphocytes. DR-positive target cells were much more susceptible to lysis, in both ADCC and lymphocyte-mediated cytotoxicity, than DR negative cells. When DR-positive OF and EM were used as targets in ADCC assays, the degree of lysis determined as 51Cr release given by serum from patients with Graves' ophthalmopathy was enhanced, but only in those patients showing positive tests with DR-negative targets. Intrathyroidal T lymphocytes obtained from a patient with Graves' ophthalmopathy were more cytotoxic against DR-positive OF and EM than equal numbers of her peripheral blood T lymphocytes. Antibody-dependent cell-mediated cytotoxicity and lymphocyte-mediated cytotoxicity against orbital fibroblasts and eye muscle cells are thus associated with target cell HLA-DR antigen expression and are likely to be mechanisms for in vivo tissue damage in Graves' ophthalmopathy. The identity of the mononuclear cell subpopulation effecting cell-mediated cytotoxicity against orbital target cells, and the possible significance of reaction of cytotoxic antibodies against orbital, thyroid-shared antigens are unclear.     

Injection of methylprednisolone directly into the extraocular muscles of eyes with disturbed motility secondary to Graves' ophthalmopathy. Preliminary report

Aim of the study was to estimate the efficacy of 6-alpha-methylprednisolone injection into involved extraocular muscles in eyes with motility disturbances caused by endocrine ophthalmopathy. MATERIAL AND METHODS: For further evaluation we qualified 4 patients, 1 female and 3 males, aged: 60, 43, 42 and 64 years, with clinical activity score equal 4, with duration of Graves' ophthalmopathy of mean 2.1 years (0.16 - 5.5). Included were patients with movement restrictions in vertical plane and echographic findings of isolated extraocular muscle involvement (inferior rectus). Each of the patients received 20 mg 6-alpha-methylprednisolone into the muscle belly of inferior rectus, in one case injection was done in both eyes. RESULTS: In all cases we were able to archive lessening of the intraocular pressure in secondary position, with slight improvement in ocular motility and bigger range of duction free of diplopia. CONCLUSIONS: Visual function improvement found by the patients is the best evidence for application of 6-alpha-methylprednisolone into the extraocular muscles of patients with motility disturbances secondary to endocrine ophthalmopathy.     

布朗族成人的身体成分分析

本文采用生物阻抗分析法,研究了布朗族成人的体成分特点。我们在云南省测量了604例(男性248例,女性356例)布朗族成人19项身体成分指标,运用Excel 2003、Spss 19.0对其各项指标进行统计分析。结果显示,男性全身脂肪分布特征为躯干和下肢的脂肪率都大于上肢脂肪率,女性脂肪率从大到小依次为下肢、躯干、上肢;男、女性双侧下肢脂肪率和肌肉量接近,左上肢肌肉量低、脂肪率高;布朗族男性的身高、体质量、肌肉量、推定骨量、总能量代谢、水分率、内脏脂肪等级均大于女性,而体脂率、BMI小于女性。随着年龄的增长,布朗族成人身体肌肉量、骨量、下肢脂肪率、能量代谢等呈明显下降,而内脏脂肪等级明显增加。与云南汉族比较,布朗族成人的体脂率较低、肌肉较发达。     

Correlation between Extraocular Muscle Size Measured by Computed Tomography and the Vertical Angle of Deviation in Thyroid Eye Disease

The aim of this study was to investigate extraocular muscle (EOM) volume and cross-sectional area using computed tomography (CT), and to determine the relationship between EOM size and the vertical angle of deviation in thyroid eye disease (TED). Twenty-nine TED patients (58 orbits) with vertical strabismus were enrolled in the study. All patients underwent complete ophthalmic examination including prism, alternate cover, and Krimsky tests. Orbital CT scans were also performed on each patient. Digital image analysis was used to quantify superior rectus (SR) and inferior rectus (IR) muscle cross-sectional areas and volumes. Measurements were compared with those of controls. The correlation between muscle size and degree of vertical angle deviation was evaluated. The mean vertical angle of deviation was 26.2 ± 4.1 prism diopters. The TED group had a greater maximum cross-sectional area and EOM volume in the SR and IR than the control group (all p<0.001). Area and volume of the IR were correlated with the angle of deviation, but the SR alone did not show a significant correlation. The maximum cross-sectional area and volume of [Right IR + Left SR − Right SR − Left IR] was strongly correlated with the vertical angle of deviation (P<0.001). Quantitative CT of the orbit with evaluation of the area and volume of EOMs may be helpful in anticipating and monitoring vertical strabismus in TED patients.     

Properties of 3D rotations and their relation to eye movement control

Rotations of the eye are generated by the torques that the eye muscles apply to the eye. The relationship between eye orientation and the direction of the torques generated by the extraocular muscles is therefore central to any understanding of the control of three-dimensional eye movements of any type. We review the geometrical properties that dictate the relationship between muscle pulling direction and 3D eye orientation. We then show how this relation can be used to test the validity of oculomotor control hypotheses. We test the common modeling assumption that the extraocular muscle pairs can be treated as single bidirectional muscles. Finally, we investigate the consequences of assuming fixed muscle pulley locations when modeling the control of eye movements.     

Analysis of early results of combined treatment with glucocorticoids and telecobalt therapy for Graves' disease ophthalmopathy]

Early results of combined use of glucocorticoid administration and irradiation with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy associated with Graves' disease have been analyzed in a group of 33 patients including 28 women and 5 men of age between 25 and 66 years (mean age 47.3 years). The combined therapy was a modification of the original method of Bartalena et al. which consisted in the gradual increase of the initial dose of glucocorticoids and prolongation of the period of administration of the drug. The ophthalmic lesions were assessed by thorough ophthalmologic examination and classified according to Werner. The ophthalmopathy index was calculated according to Donaldson. Satisfactory results of treatment have been obtained in 32 patients, with 9 patients being completely relieved from any objective or subjective ophthalmic symptoms (very good results), and 23 patients having still small afflictions originating from the soft tissues of the eye socket, exophthalmos, diplopia during marginal vision and a decreased visual acuity (good results). The clinical recovery was mostly connected with the improvement in the condition of soft tissues of the eye socket, cornea and external ocular muscles and, to a smaller extent, exophthalmos which persisted to some degree and acuity of vision not always attaining normal values. In one person the results of treatment were unsatisfactory despite some improvement. Very good and good results obtained in 97% of patients indicate that the administration of glucocorticoids combined with the irradiation of retrobulbar tissues with radioactive cobalt can now be regarded as the most effective method of treatment of the progressive oedematous-infiltrative ophthalmopathy.     

Inflammatory and Noninflammatory Thyroid Eye Disease: Comparison of Disease Signs,Symptoms, and Quality of Life in Patients in the United States

ObjectiveThyroid eye disease (TED) is an autoimmune, inflammatory disease resulting in retro-orbital fat and extraocular muscle expansion. TED quiets (“inactivates”) as inflammation wanes; however, signs/symptoms often persist. Signs/symptoms of the disease and the impact on quality of life (QoL) were examined in noninflammatory and inflammatory TED.MethodsData of patients with moderate-to-severe TED were collected from treating physicians. Clinical activity score (CAS, 6/7 measures available) was used to classify TED as inflammatory (CAS ≥ 3) or noninflammatory (CAS = 0 or 1). QoL impact was scored as 1 = “not at all impaired” to 7 = “extremely impaired.” Patients with noninflammatory TED were further grouped into longer (>3 years) and shorter (≤3 years) disease courses.ResultsPatients with inflammatory (N = 307) and noninflammatory (N = 281) TED had comparable age (50.0 ± 13.3 years vs 48.3 ± 13.8 years), gender (66% men vs 64% women), TED duration (4.0 ± 4.9 years vs 4.6 ± 5.5 years), and proportion of smokers (15% vs 11%). The most common signs/symptoms of noninflammatory TED included ocular dryness/grittiness (77%), proptosis (56%), excessive tearing (43%), soft tissue edema (42%), conjunctival redness (24%) decreased vision (24%), and eye muscle involvement (22%; 14% had diplopia). All signs/symptoms were less frequently reported in these patients than in those with inflammatory TED. QoL was impacted by noninflammatory TED, although to a lesser degree than the inflammatory disease (3.6 ± 1.5 vs 4.7 ± 1.4). However, mental health issues were similarly reported. Patients with noninflammatory TED with a longer disease course (9.0 ± 6.0 years) had similar QoL impact, mental health diagnoses, and TED signs/symptoms as those with a shorter disease course (1.4 ± 1.0 years).ConclusionThe signs/symptoms of TED often chronically persist long after TED has “quieted,” continuing to impact a patient’s QoL and mental health. These data suggest that moderate-to-severe TED should be thought of as a robust symptomatic chronic disease, regardless of its inflammatory status.     

The effects of the extraocular muscles on eye impact force–deflection and globe rupture response

There are over 1.9 million eye injuries per year in the United States, with blunt impacts the cause of approximately one-half of all civilian eye injuries. No previous experimental studies have investigated the effects of the extraocular muscles on the impact response of the eye. A spring-powered blunt impactor was used to determine the effects that the extraocular muscles have on the force–deflection and injury response of the eye to blunt trauma. A total of 10 dynamic impact tests were performed at 8.2±0.1 m/s on five human cadaver heads. With the extraocular muscles left intact, the average peak force was found to be 271±51 N at 7.5±0.9 mm posterior translation; with the muscles transected, the average peak force was 268±26 N at 7.6±1.3 mm of posterior translation. From the data available from this study, the peak impact force and overall amount of translation during the impact are not affected by the extraocular muscles. Additionally, from the data presented in this study, the eyes with the extraocular muscles left intact do not rupture with a different injury pattern or display an increased risk for rupture than the eyes with the extraocular muscles transected. Therefore, it is believed that the effect of the extraocular muscles is not sufficient to drastically alter the response of the eye under dynamic impact. This information is useful to characterize the boundary conditions that dictate the eye response from blunt impact and can be used to define the biofidelity requirements for the impact response of synthetic eyes.     

Characteristics of Diabetic and Nondiabetic Patients With Thyroid Eye Disease in the United States: A Claims-Based Analysis

ObjectiveThyroid eye disease (TED) is a debilitating autoimmune disease characterized by ocular and periorbital tissue inflammation, proptosis, and visual impairment. The known risk factors for TED include radioactive iodine therapy, female sex, and smoking. The risk factors for severe TED include hyperthyroidism, male sex, smoking, and diabetes; however, little is known about how diabetes mellitus (DM) influences TED. This claims-based analysis examined TED characteristics in patients with and without diabetes.MethodsSymphony database (2010-2015 U.S. claims) was mined for patients with ≥1 Graves’ disease diagnosis code and ≥1 TED-associated eye code, including proptosis, strabismus, diplopia, lid retraction, exposure keratoconjunctivitis, and optic neuropathy (ON). DM status was determined based on type 1 or type 2 diabetes coding. Sight-threatening TED was defined as ≥1 ON or exposure keratoconjunctivitis code.ResultsA total of 51 220 patients were identified. Of them, 2618 (5.1%) and 12 846 (25.1%) had type 1 and type 2 DM, respectively. Patients with and without DM had similar characteristics, but patients with DM were more often men (type 1: 30.3%, type 2: 28.7% vs no DM: 20.5%; both P < .001) and older at the first TED code. In patients with DM, strabismus (25.4%, 22.6% vs 19.9%) and diplopia (38.6%, 37.9% vs 29.9%) occurred more often but proptosis occurred less often (42.3%, 46.3% vs 58.5%; all P < .001). Sight-threatening TED occurred more often in patients with DM because of higher ON rates.ConclusionPatients with TED and DM may have more extraocular muscle involvement. Furthermore, the higher prevalence of severe TED stemmed from higher ON rates, possibly associated with diabetes-related vasculopathies. These hypothesis-generating data warrant further exploration.     

Afferent signals from pigeon extraocular muscles modify the vestibular responses of units in the abducens nucleus.

Although the extraocular muscles contain stretch receptors it is generally believed that their afferents exert no influence on the control of eye movement. However, we have shown previously that these afferent signals reach various brainstem centres concerned with eye movement, notably the vestibular nuclei, and that the decerebrate pigeon is a favourable preparation in which to study their effects. If the extraocular muscle afferents do influence oculomotor control from moment-to-moment they should exert a demonstrable effect on the oculomotor nuclei. We now present evidence that extraocular muscle afferent signals do, indeed, alter the responses of units in an oculomotor nucleus (the abducens, VI nerve nucleus, which supplies the lateral rectus muscle) to horizontal, vestibular stimulation induced by sinusoidal oscillation of the bird. Such stimuli evoke a vestibulo-ocular reflex in the intact bird. The extraocular stretch receptors were activated by passive eye movement within the pigeon's saccadic range; such movements modified the vestibular responses of all 19 units studied which were all, histologically, in the abducens nucleus. The magnitude of the effects, purely inhibitory in 15 units, depended both on the amplitude and the velocity of the eye movement and most units showed selectivity for particular combinations of plane (e.g. horizontal versus vertical) and direction (e.g. rostral versus caudal) of eye movement. The results show that an afferent signal from the extraocular muscles influences vestibularly driven activity in the abducens nucleus to which it carries information related to amplitude, velocity, plane and direction of eye movement in the saccadic range. They thus strongly support the view that extraocular afferent signals are involved in the control of eye movement.