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PubMed1998

Treatment of strabismus and nystagmus with botulinum toxin type A. An evaluation of effects and complications.

PURPOSE: Injection of botulinum toxin type A into eye muscles leads to a temporary paralysis and the effects have been evaluated in strabismus or nystagmus. METHOD: A total of 112 patients with different types of concomitant and paralytic strabismus and acquired nystagmus were treated with botulinum toxin, according to well-established indications. RESULTS: The lasting effects of the injections on strabismic angle were largest in esotropia, consecutive exotropia and abducens palsy, and amounted to, on an average, 12 prism diopters or 6 degrees. The larger the strabismus the better was the effect. Repeated injections reduced the angle further. In complex nystagmus forms retrobulbar injections could be used. The side effects were mostly due to spread of botulinum toxin to the levator, producing ptosis (8%), or the inferior rectus muscle, causing vertical strabismus (10%). On an average 42% of the patients were later operated for strabismus and nystagmus. CONCLUSION: Injection of botulinum toxin A into eye muscles is a valuable adjunct to surgery in the treatment of strabismus and nystagmus.

Adult↗
PubMed1979

The organization of the electromotor nucleus and extraocular motor nuclei in the stargazer (Astroscopus y-graecum).

The organization of the oculomotor and electromotor systems was examined in the stargazer, a teleost. The electromotor system in these animals is a derivative of the oculomotor system. The extraocular motor nuclei and nerves consist of approximately equal numbers of motoneurons and axons (about 100 per muscle). In contrast, electromotor axons appear to branch several times within the intracranial portion of the IIIrd nerve. The topographical organization of the motoneurons was examined using retrograde transport of horseradish peroxidase injected into the electric organ or eye muscles. Electromotor and oculomotor neurons form distinct populations. Each electric organ receives a strong ipsilateral and a weak contralateral innervation. Individual eye muscles receive unilateral innervations with the expected laterality. Within the oculomotor nucleus there is some topographical separation of motoneurons innervating each muscle. Antidromic field potentials confirm the identity of the electromotor nucleus.

Animals↗
PubMed1992

Nature and significance of orbital autoantigens and their corresponding autoantibodies in thyroid-associated ophthalmopathy.

There is now considerable evidence that the pathogenesis of thyroid-associated ophthalmopathy is closely linked to the presence of a shared autoantigen(s) in the thyroid and the eye muscle, against which cytotoxic mechanisms are directed. Although the orbital connective tissue is certainly involved in the orbital inflammatory process, a 64 kDa membrane protein expressed by both the eye muscle and the thyroid and recognized consistently by antibodies in the sera of TAO patients, seems to be the most likely target candidate. While its presence in non ocular skeletal muscle is not as well established, more recent data tend to suggest the existence of a 64 kDa molecule in the three tissues. The availability of a cDNA encoding a 572 amino acid protein corresponding to a MW of 63-64 kDa, which may be the same molecule, will allow us to determine more clearly the structural characteristics of the different molecules proposed as targets. The role of the corresponding autoantibodies in the pathogenesis of the eye disease is far less well defined. Whether they play a role in the induction of the ophthalmopathy or only represent helpful markers remains to be clarified.

Autoantibodies↗
PubMed1985

Morphology and permeability properties of blood capillaries in extraocular muscles of macaque monkeys.

Extrinsic eye muscles are very different from other skeletal muscles with regard to the morphology of their fibers and response to drugs. In addition, they are provided with an unusually rich blood supply. Since it had been previously reported that the capillaries of extraocular muscles are, at least in part, of the fenestrated type, a feature unusual for skeletal muscles, we have analyzed the morphology of these vessels in macaque monkeys and tested their permeability properties with horseradish peroxidase (HRP). Our study of the blood capillaries in the superior rectus muscle and levator palpebrae superioris in Macaca mulatta and M. fascicularis has demonstrated that these vessels are morphologically similar to the capillaries of other skeletal muscles. Furthermore, when HRP is introduced intravenam, it is transported out of the vessels by a vesicular transcellular mechanism. When HRP is injected in the interstitial spaces of the muscles, it is returned to the lumen by an identical vesicular transcellular transport. Thus, a bidirectional movement of macromolecules can take place across the walls of these vessels, and such a movement is not different from that previously reported for other skeletal muscles.

Animals↗
PubMed1975

Partition coefficient of 133Xe between blood and eye tissues.

The relative solubility coefficient of 133Xe and the tissue-blood partition coefficient for the aqueous humour vitreous body, conjunctiva and external eye muscles of the rabbit were determined in vitro at 37 degrees C and at various haematocrit values. The partition coefficient for haematocrit 40 was: for the aqueous humour 0,49 ml/ml, for the vitreous body 0,50 ml/ml, for the conjunctiva 0,81 ml/g and for the external eye muscles 0,77 ml/g. It was found that the solubility of 133Xe in rabbit erythrocytes is about 50 per cent higher than that in human red cells. The consequences of this fact for the precision of blood flow measurements by the method of tissue clearance are discussed.

Animals↗
PubMed1988

Ultrastructural observations on muscle spindles in extraocular muscles of pig.

Human and some mammals such as the sheep, goat and domestic and wild pigs have more or less muscle spindles in the extrinsic eye muscles, especially the domestic pigs having abundant muscle spindles (Matsuyama, 1987). The muscle spindles play a large role in maintaining the stable visual posture of the eyeballs. To define the morphological properties of the muscle spindles relative to the eye movement, the ultrastructure of the spindles was investigated in 6 extraocular muscles of the pigs by electron microscopy. The muscle spindles in the pig extraocular muscles consist of 4 to 5 intrafusal muscle fibers, one of which is nuclear bag fiber and 3 to 4 are nuclear chain fibers. The outer capsule is thin, composing of few layers, and the inner capsule ramifying to enwrap the individual fiber, accompanied by the medullated and unmedullated nerve fibers and blood capillaries. The nuclear bag fiber, 14 micron in diameter, is innervated by the atypical annulospiral sensory terminals and the chain fiber by the typical annulospiral terminal packed with mitochondria and microvesicles. The intrafusal fibers are innervated by the flower-spray sensory terminals anchoring deeply into the sarcoplasma, having abundant neurotubules and few mitochondria. The gamma motor end-plates have a relatively smooth synaptic cleft with a width of 70 nm and synaptic boutons containing few synaptic vesicles, sometimes, revealing a shallow fold of postsynaptic sarcolemma and abundant synaptic vesicles. The alpha motor end-plates reveal a relatively smooth synaptic cleft with a width of 80 nm, sometimes with a rough postsynaptic infolding, and boutons containing few synaptic vesicles and small-sized mitochondria. The satellite cells are innervated by the sensory terminals in various ways. The muscle spindles in the pig extraocular muscles are found to be much simpler in structure than those in the other antigravity muscles of the body. Their ultrastructure seems to reflect the morphological adaptation relative to the eyebal movement.

Animals↗
PubMed1994

[Exophthalmometry and thyroid disease. The value of the Hertel measurement evaluated by a group of patients with thyroid diseases and a control group].

Exophthalmometry values from routine referrals to a hospital eye clinic are analysed, including adult patients with and without thyroid disease. In thyroid disease without eye motility complaints (n = 90) the median exophthalmometry value was 18 mm (range 12-28 mm). Thyroid patients with eye muscle involvement (diplopia, n = 47) had significantly higher values (median 22 mm, range 15-31 mm) but did not differ significantly from a subgroup of 51 patients without thyroid disease, but with "big eyes" as a (presumably) physiological finding (median value 20 mm, range 16-25 mm). The above three categories were all excluded from the control group (n = 203) which had 16 mm as median value, range 11-23 mm. Mean values were 16.0 +/- 1.8 mm in the females and 16.5 +/- 2.3 mm in the male controls. A side difference in exophthalmometry value > or = 2 mm appeared in 34% of thyroid patients with eye muscle involvement. This appeared in only a few per cent in the three other groups. Due to the wide overlap between groups, the solitary exophthalmometry reading is of limited diagnostic value, while the importance of exophthalmometry is evident when following the individual patient with orbital disease.

Adolescent↗
PubMed1988

Affinity purification of orbital membrane antigens for the study of the pathogenesis of Graves' ophthalmopathy.

We characterized 22 human monoclonal antibodies (MCAB) reactive with human orbital antigens. Most of these monoclonal antibodies had variable degrees of reactivity with eye muscle, orbital connective tissue, thyroid, and extra-thyroid tissue preparations when tested in an enzyme-linked immunosorbent assay (ELISA). Eight of the MCABs, selected on the basis of their reactivity with human eye muscle or orbital connective tissue antigens, were used to affinity purify orbital membrane antigens. All purified fractions were tested in the ELISA for reactivity with the MCAB used for their purification. Four of the purified antigens with a high reactivity were not proteins. To increase the specificity of the reactivity of serum autoantibodies with affinity-purified antigens, we developed a competitive binding ELISA in which the MCAB-immunoglobulin was directly labeled with alkaline phosphatase. We tested the serum of 24 patients with Graves' ophthalmopathy, 10 patients with a history of Graves' hyperthyroidism and no eye disease, 14 patients with Hashimoto's thyroiditis without eye disease, 8 patients with other nonautoimmune thyroid disorders, and 20 normal subjects for reactivity with an affinity-purified nonprotein orbital antigen. The levels of serum autoantibodies against this antigen in patients with Graves' ophthalmopathy were significantly higher than those in normal subjects or patients with Graves' hyperthyroidism with no eye disease. Although unlikely to be of primary pathogenetic significance, it is possible that levels of this antibody in patients with Graves' ophthalmopathy may reflect the extent of orbital inflammation and, therefore, be useful as a clinical marker.

Adult↗
PubMed2006

[Graves' orbitopathy].

Graves' orbitopathy or thyroid associated orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease with autoimmune mechanism which is still incompletely understood. The epidemiologic data provided evidence that severe, infiltrative orbitopathy is present in 3-5% of patients, and the quality of life is impaired even in individuals with mild form of this disease. The anti-TSH receptor and anti-eye muscle autoantibodies have been proved to be involved into pathomechanism of orbitopathy. The accumulation of glucose-aminoglycan and proinflammatory cytokines in retro-orbital fibroblasts are responsible for enlargement of eye muscle and the retro-orbital tissues resulting in inflammation of periorbital tissues and proptosis. Management of orbitopathy can be either medical and surgical. The medical therapy relies on the use of high dose systemic glucocorticoids or retro-orbital irradiation, either alone or in combination. Recent randomized clinical trials have confirmed that glucocorticoids are more effective in intravenous than oral use. Retro-orbital radiotherapy is an effective and safe therapy for orbitopathy and the side effects are avoidable. Somatostatin analogs are not so effective as it has been waited in previous studies. The high dose intravenous immunoglobulins and pentoxifylline therapy are favorable, however, prospective randomized trials have been not yet made. The manifestation of orbitopathy includes both unavoidable (genetic background) and avoidable (smoking, cytokine therapy, iodine exposure, radioiodine therapy) risk factors. Cigarette smoking must be given up by all patients with Graves' disease. Pentoxifylline therapy is advisable for all patients with Graves'diseases, especially for those who have genetic susceptibility to autoimmune disorders and not able to give up cigarette smoking.

Graves Disease↗
PubMed1978

Co-activation of the M. transversus auris with eye movements (Wilson's oculo-auricular phenomenon) and with activity in other cranial nerves.

Extreme lateral gaze induces a perceptible backward movement of the upper part of the pinna (Wilson, 1908). In 29 subjects (15 normal controls and 14 patients with peripheral eye-muscle or facial paresis) electromyographic (EMG) investigation of the transverse auricular muscle with simultaneous electronystagmographic (ENG) recording of the various ocular movements was carried out. Tonic activity was detected in the transverse auricular muscle during extreme horizontal eye movements, but was detected in only a few subjects during convergent or vertical movement of the eyes, or in the primary position. Investigation of the other cranial nerves revealed that EMG activity of the transverse auricular muscle is also occasionally present during chewing, coughing, swallowing, straining, inspiration, and vestibular stimulation.

Cranial Nerves↗
PubMedDate not supplied

Necrotizing scleritis following strabismus surgery for thyroid ophthalmopathy.

Necrotizing scleritis with inflammation of the right eye developed after bilateral eye muscle surgery for thyroid ophthalmopathy. Debilitating pain, delay in onset, and involvement of the sclera distinguish this condition from anterior segment ischemia. The surgery may have acted as a nonspecific trigger in an eye at risk for scleritis. Necrotizing scleritis has occurred infrequently after other types of eye surgery but, to our knowledge, has not been previously reported as a complication of eye muscle surgery.

Aged↗
PubMed1995

Thyroid stimulating antibody in sera of Graves' ophthalmopathy patients as a possible marker for predicting the efficacy of methylprednisolone pulse therapy.

Nine patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone pulse therapy and followed up by ophthalmological assessment, magnetic resonance imaging, and thyroid-associated autoantibody (thyroid stimulating antibody (TSAb), TSH binding inhibitor immunoglobulins (TBII), and anti-eye muscle antibody (EMAb)). Ophthalmological assessment was performed by the ophthalmopathy index (OI) which was made on the basis of the system recommended by the American Thyroid Association Committee. EMAb was expressed as the ratio of density of the 64 kDa band of eye muscle membrane to that of 92 kDa non-specific band found with all normal sera when assessed by western blotting. Five patients with mild ophthalmopathy (OI < 4) did not show progressive improvement in OI. Three of 4 patients with severe eye disease (OI > 4) showed a progressive and distinct improvement in OI. These 3 patients had high TSAb levels before methylprednisolone pulse therapy. One patient with severe ophthalmopathy did not respond to this pulse therapy; this patient's TSAb was negative. A significant positive correlation was observed between the activity of TSAb before treatment and the improvement in OI (delta OI) (r = 0.86, P < 0.01, n = 9). The relationship between delta OI and EMAb did not reach significance. These results suggest that TSAb in sera of GO patients can be a useful marker for predicting the efficacy of methylprednisolone pulse therapy.

Adolescent↗
PubMed1998

Analysis of the IgG autoantibody repertoire in endocrine ophthalmopathy using the MegaBlot technique.

PURPOSE: Normal sera contain a large number of naturally-occurring autoantibodies which can complicate the differentiation of disease-associated autoantibodies from the complex background of "autoimmune noise" (i.e. naturally-occurring autoantibodies). The aim of this study was to analyze the human IgG autoantibody repertoire of sera from patients suffering from endocrine ophthalmopathy and to compare those to sera from healthy subjects using the recently developed MegaBlot technique. This new method allows the simultaneous global and quantitative screening for reactivities of antibodies with a large number of antigens. METHODS: Sera (n = 17: endocrine ophthalmopathy; n = 10: healthy subjects) were tested against Western blots of SDS-PAGE preparations of proteins from human extraorbital eye muscle. Digital image analysis was performed (ScanPacK, Biometra, Germany). The blots were subsequently analyzed by our new MegaBlot technique. RESULTS: Both the sera of patients suffering from endocrine ophthalmopathy and the sera of healthy subjects revealed reactivities of antibodies against eye muscle proteins (up to 15 bands/blot). The MegaBlot procedure could differentiate between the banding patterns of patients suffering from endocrine ophthalmopathy and healthy subjects. The staining patterns of both groups were significantly different (p < 0.02). A 64 kDa protein was recognized by autoantibodies in the sera of both healthy subjects and patients suffering from endocrine ophthalmopathy. CONCLUSIONS: This study shows that naturally-occurring antibodies in sera of healthy subjects recognize many antigenic proteins, but despite that, the MegaBlot technique can differentiate between the complex staining patterns of both groups. Our new method can be a valuable tool in the evaluation of autoantibody repertoires in autoimmune diseases such as endocrine ophthalmopathy and can help to find and to identify the disease-associated autoantibodies.

Adult↗
PubMed1981

Graves' ophthalmopathy.

Graves' ophthalmopathy usually occurs in association with hyperthyroidism. Its occasional occurrence in the absence of thyroid disease suggests, however, that it may be a separate autoimmune disorder. While the evidence supporting an autoimmune pathogenesis is considerable for the ophthalmopathy, it is not so impressive as that for Graves' hyperthyroidism: orbital antibodies have not been convincingly demonstrated and autoantigens have not been identified. On the other hand, in patients with Graves' ophthalmopathy the orbital tissues and eye muscle membranes are infiltrated with lymphoid cells and show evidence of cell-mediated immune reactions. Although there is some evidence that binding of thyroid stimulating hormone fragments and thyroglobulin-antithyroglobulin immune complexes to eye muscle membranes may be important in the pathogenesis of the ophthalmopathy, this needs to be confirmed. The mechanism for the association of hyperthyroidism and ophthalmopathy is unknown, but the association likely reflects an influence of thyroid hormones on the immune system. In view of the autoimmune pathogenesis the logical treatment of Graves' ophthalmopathy appears to be immunosuppression.

Autoantibodies↗
PubMed1994

[Is treatment with corticotherapy or radiotherapy effective for involvement of ocular motility and for reduction of exophthalmos in Basedow's disease?].

It is acknowledged that high-dose corticotherapy, radiotherapy, or surgical decompression of the orbit are often efficient in dysthyroid optic neuropathy. Corticotherapy and radiotherapy are also given to patients with dysfunction of eye-muscle motility and/or proptosis in the absence of visual loss. The latter indication has been retrospectively evaluated in 13 patients. The limited character of our series is partially explainable by strict inclusion criteria (objective evaluation of muscle dysfunction and proptosis). We failed to demonstrate any significant functional improvement after oral corticotherapy and/or radiotherapy. It thus appears that our study sheds doubt on the actual efficacy of these treatments in patients presenting with not very evolutive involvement of eye-muscle motility. A larger study aimed at comparing the benefits and drawbacks of these treatments is consequently to be encouraged.

Adult↗
PubMed2002

Kestenbaum and artificial divergence surgery for abnormal head turn secondary to nystagmus. Specific and nonspecific effects of artificial divergence.

Recommendations concerning the kind and dosage of eye muscle surgery for nystagmus vary in the literature. The present paper is an evaluation of the effects of Kestenbaum and artificial divergence surgery on abnormal head posture in a retrospective study. Exclusively patients with surgery for nystagmus-related horizontal head-turn (HT), with binocular vision and without previous eye muscle surgery were considered. Of the 78 patients, aged 3 to 68 years, 52 had a HT to the left side; 47 patients were male. In the Kestenbaum group (n = 31), the preoperative HT of 30 degrees (20-40) (median, 0.1-0.9 quantile) was reduced to 10 degrees (0-30) by surgery of 14 mm (10-20) on each eye. Four patients received further surgery. In the artificial divergence group (n = 27), the HT of 30 degrees (25-40) was reduced to 5 degrees (0-20) by recess-resect surgery of 10 mm (7-12) on the adducted eye. Seven patients needed further surgery. In the combined Kestenbaum plus artificial divergence group (n = 20), the HT of 30 degrees (25-40) was reduced to 7 degrees (-5-15) by surgery of 29 mm (21-37) on both eyes together. No further surgery was necessary. Kestenbaum surgery had a similar effect/dose ratio as recess-resect surgery for strabismus. If a test with base-out prisms suggests that artificial divergence is promising, this concept is preferable. It can be integrated into Kestenbaum surgery.

Adolescent↗
PubMed1988

Human orbital tissue and thyroid membranes express a 64 kDa protein which is recognized by autoantibodies in the serum of patients with thyroid-associated ophthalmopathy.

A 64 kDa protein has been identified in the membrane fraction of human eye muscle, orbital connective tissue and thyroid, by testing sera of patients with thyroid-associated ophthalmopathy in SDS-polyacrylamide gel electrophoresis and Western blotting. Antibodies to this membrane antigen seem characteristic of the early stage of ophthalmopathy. In the thyroid this newly recognized protein seems different from previously known membrane antigens. A thyroid antibody reactive with a 64 kDa membrane antigen in eye muscle could explain the very frequent association of ophthalmopathy with autoimmune thyroid disease.

Adult↗