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Bony orbital development after early enucleation in humans.

AIM: To analyse the extent of bony orbital volume reduction after enucleation in humans. METHODS: Volumetric studies on bony orbital volumes based on three dimensional reconstructions acquired from high resolution computed tomograph (CT) scans were performed in 29 patients with acquired anophthalmia and four patients before enucleation (controls). Eight patients (follow up 25-52 years) were enucleated in childhood aged between 0.4 and 8 years (group I), 21 in adulthood aged between 15 and 53 years. Fifteen of these patients (group IIa) had long standing anophthalmia (follow up 7-53 years), six patients (group IIb) were enucleated 9 months to 4 years before CT. RESULTS: Bony orbital volumes were reduced in all patients with long standing anophthalmia. The median percentage reduction in enucleated orbits was 7.0% in group I, 3.8% in group IIa, and 1.9% in group IIb. In patients with long standing anophthalmia (I and IIa) the reductions were statistically significantly different (p <0.01) from zero. There was some evidence of a correlation between orbital volume reduction and age at enucleation (rho = 0.36, p = 0.09, Spearman rank correlation coefficient) and a statistically significant correlation between volume reduction and time interval since enucleation (rho = -0.5, p = 0.003). Clinically none of the patients showed significant facial asymmetry. CONCLUSIONS: These data provide strong evidence that enucleation both in children and adults is associated with a reduction of bony orbital volume and that this decrease in volume is associated with increasing time. However, the reduction is smaller than generally assumed and does not cause obvious facial asymmetry. It is more related to the time interval since enucleation than the age at enucleation, which makes a mechanism of volume adaptation more likely than just retardation of growth.

Adolescent↗

Leukoregulin upregulation of prostaglandin endoperoxide H synthase-2 expression in human orbital fibroblasts.

Human orbital fibroblasts from patients with severe thyroid-associated ophthalmopathy are particularly susceptible to the actions of a variety of proinflammatory molecules. In this study, we demonstrate that the inductions of prostaglandin endoperoxide H synthase-2 (PGHS-2), interleukin (IL)-1alpha, and IL-1beta by leukoregulin, a product of activated T lymphocytes, are far more robust in orbital fibroblasts than those observed in dermal fibroblasts. These actions of leukoregulin are mediated through an intermediate induction of IL-1alpha. In contrast, leukoregulin also induces IL-1-receptor antagonist (IL-1ra) expression in orbital fibroblasts, but this induction is considerably greater in dermal fibroblasts (2.3- vs. 8.5-fold). Interrupting the effects of IL-1alpha, either with a neutralizing antibody or with exogenous IL-1ra, can block the induction of PGHS-2 by leukoregulin. Leukoregulin increases PGHS-2 gene transcription in orbital fibroblasts but exerts the major effect on cyclooxygenase expression by enhancing the stability of mature PGHS-2 mRNA. The cytokine triggers nuclear translocation of nuclear factor-kappaB (NF-kappaB) p50/p50 homodimers and p50/p65 heterodimers, and an inhibitor of this transcriptional factor, pyrrolidinedithiocarbamate, can attenuate the PGHS-2 induction. Thus differential inducibility of the members of the IL-1 family of genes in orbital fibroblasts would appear to underlie, at least in part, the differences in PGHS-2 induction observed in orbital and dermal fibroblasts. NF-kappaB plays an important role in mediating the effects of leukoregulin on PGHS-2 expression.

Anti-Inflammatory Agents↗

Early transvaginal biometry of fetal orbits: a cross-sectional study.

OBJECTIVE: To construct nomograms of orbital diameters in early pregnancy by transvaginal sonography. DESIGN: A prospective cross-sectional study. METHODS: The study was performed on 923 consecutive normal singleton pregnancies from 10 to 16 weeks of gestation, using transvaginal high-resolution ultrasound technique. The interocular distance (IOD), binocular distance (BOD), as well as the orbital diameter (OD) at each gestational age (GA, days), were recorded. The distribution of the residuals for the different orbital measurements are also described. RESULTS: The increase in each of the ocular parameters studied could be accurately described by a linear model. The regression equation for orbital measurements as a function of GA was: for IOD, y = 0.153 GA (days) - 6.73 (r2 = 0.82); for BOD, y = 0.387 GA (days) - 16.85 (r2 = 0.80), and for OD, y = 0.132 GA (days) - 6.435 (r2 = 0.79). IOD and OD demonstrate a normal distribution of the residuals with uniform variance. CONCLUSION: The presented data obtained in early pregnancy by transvaginal scan offer normative measurements of the orbital diameter which may be useful in the prenatal diagnosis of congenital syndromes that include, among other manifestations, orbit maldevelopment and growth disturbances.

Adult↗

Computer-assisted image-guided orbit surgery.

PURPOSE: Modern stereotaxy utilizes preoperative computed tomography (CT) and magnetic resonance imaging (MRI) to provide accurate localization information which can be very helpful in orbital surgery. The purpose of this report is to evaluate the usefulness of stereotactic surgery and application of this procedure in the orbit. METHODS: Interventional case series of three patients with orbital tumors. All patients had tumor resection with the utilization of two frameless stereotactic systems: Cygnus and Stealth Station. RESULTS: The applications of image-guided stereotactic surgery proved to be beneficial in three extensive orbital tumors, including optic nerve glioma, recurrent pleomorphic adenoma of lacrimal gland, and secondary orbital meningioma. CONCLUSIONS: The interactive nature of image guidance can be useful in orbital surgery to orient the surgeon to the exact location within the surgical field and to determine the tumor margins.

Adenoma, Pleomorphic↗

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↗

Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture.

Graves' ophthalmopathy (GO), in which orbital tissues are infiltrated with activated T lymphocytes and hyaluronan, can manifest an overabundance of adipose tissue in the human orbit. Little is known about adipogenesis in this anatomic region. We have investigated whether orbital fibroblasts in culture possess the capacity to undergo adipocytic differentiation. Orbital tissue from patients with or without GO was placed in primary culture, and proliferating fibroblasts were sub-passaged. Confluent fibroblasts were subjected to a differentiation protocol, involving a serum-free defined medium supplemented with insulin, triiodothyronine, carbaprostacyclin, thyrotropin, dexamethasone, and isobutylmethylxanthine. Control cells were maintained in serum-free medium supplemented only with insulin. After approximately 14 days, light microscopy revealed characteristic morphologic changes of adipocyte differentiation, including cell rounding and lipid droplet accumulation. Oil Red O staining could be demonstrated in those cells. Scanning electron microscopy revealed that the cells undergoing adipogenesis contain multiple, discrete lipid droplets. The overall percentage of fibroblasts undergoing differentiation was somewhat variable, but no more than 5-10%. The adipocytes arise in close proximity to each other, and often at the periphery of the culture surface. In contrast, dermal fibroblasts and perimysial fibroblasts from extraocular muscle fail to differentiate. We conclude that a subpopulation of orbital fibroblasts is capable of adipocyte differentiation. These in vitro observations may represent the in vivo process that contributes to excess orbital adipose tissue volume in GO.

Adipocytes↗

Orbital scintigraphy with [111In-diethylenetriamine pentaacetic acid-D-phe1]-octreotide predicts the clinical response to corticosteroid therapy in patients with Graves' ophthalmopathy.

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.

Adult↗

Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor.

Although the autoantigen involved in Graves' hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves' ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens. GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals' cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens. These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.

Adipocytes↗

The superior orbital fissure: a microanatomical study.

The superior orbital fissure (SOF) is a small (3 x 22 mm), but functionally very important, region. The microsurgical anatomy of the SOF was studied on five adult, formalin-fixed cadavers. The vascular structures of three of them were injected with latex. The SOF contains the third, fourth, and sixth nerves, the ophthalmic branch of the fifth nerve, and the superior orbital vein. It is divided by the two tendons of the lateral rectus muscle: the superior part contains the fourth nerve, the frontal and the lacrimal branches of the ophthalmic division of the fifth nerve, and the superior orbital vein; the inferior part contains the superior and inferior branches of the third, the nasociliary, and the sixth nerves. In regard to surgical access to lesions involving the SOF, the question is often raised as to whether the dissection should be started from the cranial or the orbital side. The following procedure is recommended: 1) frontotemporo-orbital craniotomy; 2) resection of the lesser wing of the sphenoid bone, of the anterior clinoid, and of the superolateral part of the orbital roof and opening of the dura along the Sylvian fissure, with an extension to the frontal lobe and another extension to the temporal lobe; 3) incision of the periorbita in its superolateral part and identification of the frontal nerve; and 4) dissection of the frontal nerve in an anteroposterior direction. The fourth nerve will be found medially and inferiorly to the frontal nerve. The third nerve will be found inferomedially to the frontal nerve in the SOF, and the sixth nerve will be found inferiorly to the inferior branch of the third nerve.

Adult↗

The radiation dose to the lens in radiology of the orbit.

This paper describes research into measurement and reduction of the radiation dose to the lens during various examinations, namely skull and orbit, optic canal and optic strut, superior and inferior orbital fissure, localisation of foreign bodies in the eye, calcifications, orbital fractures, macrodacryography and orbital venography. Using rare-earth screens and high-sensitivity films, without an antiscattering grid, and with an added filtration of 0.5 mm Cu, it is possible to reduce the radiological risk during all investigations involving skull, orbit and eyeballs, while maintaining a good image quality. Particularly in those examinations with direct magnification (macrodacryography and venography, foreign bodies in the eye, orbital fractures), the dose to the lens is very low: less than 0.2 mGy/radiograph.

Eye Diseases↗

The use of real-time orbital ultrasound in Graves' ophthalmopathy: a comparison with computed tomography.

Evaluation of the severity of orbital involvement and likelihood of the development of optic neuropathy in Graves' disease can be clinically difficult. We describe the use of real-time orbital ultrasound scanning to measure the medial rectus muscle width in 20 patients with Graves' ophthalmopathy and 21 normal individuals. The normal reference interval (to 2 SDs) was 1.75 to 4.07 mm. Significantly (p less than 0.001; Mann Whitney U-test) larger values were observed in the patients compared with controls, and there was good correlation between medial rectus width and a clinical index of disease severity in individual eyes (p less than 0.001; Spearman rank correlation coefficient). Comparison of the medial rectus measurements obtained using orbital computed tomography and ultrasound showed positive correlation at the p less than 0.001 significance level. Computed tomographic medial rectus measurements also correlated with horizontal and vertical muscle indices for that orbit. We suggest that real-time ultrasound of medial rectus width, using widely available equipment, provides an accurate, simple and non-invasive means of evaluating the orbits of patients with Graves' disease. Repeated measurements may be of value in identifying patients at high risk of visual failure, and in following prospectively the orbital response to therapy in patients with Graves' ophthalmopathy.

Adult↗

Evaluation of and access to posterior orbital tumors.

Head and neck surgeons enter the peripheral orbit for the therapy and/or biopsy of the most common expanding lesions, i.e., thyroid ophthalmopathy, direct extension of paranasal disease, pseudotumor and metastases. It is in this space between the bony orbital walls and the extraocular muscle cone that a majority of primary orbital neoplasms occur. The four basic approaches to posterior orbital tumors are: lateral orbitotomy through the temporal fossa with a modified Kronlein procedure, medial orbitotomy utilizing a Lynch incision and lacriminal sac mobilization, superior orbitotomy via a Naffziger frontotemporal crainotomy, and inferior exposure/decompression through the maxillary sinus. Case examples of the former two approaches are presented. None of these standard procedures allows full exposure of the posterior orbit. A combined cranio-facial-orbital access to this region utilizing a modified maxillectomy and frontotemporal craniotomy is detailed.

Adolescent↗

Expression of cyclooxygenase-2 in orbital fibroadipose connective tissues of Graves' ophthalmopathy patients.

OBJECTIVE: The aim of this study is to evaluate the expression of cycloocygenase-2 (COX-2) in orbital fibroadipose connective tissue in Graves' ophthalmopathy (GO) patients, and investigate the associations between COX-2 expression and GO characteristics. METHODS: The orbital fibroadipose connective tissues of 23 cases demonstrating moderate or severe GO, and eight control subjects without any history of thyroid or autoimmune disease were analyzed for COX-2 mRNA expression. Real-time relative quantitative PCR was performed to assess transcripts of COX-2 using the LightCycler. The disease activity was evaluated by the clinical activity score (CAS). The clinical features of GO were evaluated by total eye score (TES) and the cases were divided into two groups; type 1 cases included higher degrees of proptosis with orbital fat volume increase, and type 2 cases included cases with compressive neuropathy and limited extraocular muscle functions. RESULTS: The mean +/- s.d. disease duration was 5.7 +/- 7.1 years. The mean +/- s.d. CAS and TES of cases were 1.60 +/- 1.04 and 7.5 +/- 1.8 respectively. The mean +/- s.d. expression of COX-2 was 0.023 +/- 0.013 and 0.010 +/- 0.002 in GO cases and controls (P = 0.008), and 0.015 +/- 0.073 and 0.029 +/- 0.135 in type 1 and type 2 cases respectively (P = 0.007). COX-2 expression showed a statistically significant positive correlation with TES (r = 0.634, P = 0.001), and a negative correlation with the disease duration (r = -0.621, P = 0.002). CONCLUSIONS: COX-2 is expressed at higher levels in orbital fibroadipose tissues of GO cases. This showed a positive correlation with increasing severity of orbital disease suggesting possible relation with COX-2 expression and orbital inflammation in GO.

Actins↗

Incidental asymptomatic orbital calcifications.

OBJECTIVE: To use modern computed tomography (CT) imaging to quantify the incidence of asymptomatic incidental orbital calcifications and describe their histological features. MATERIALS AND METHODS: One hundred orbital CT scans were reviewed. In addition, patients who had orbital calcification(s) detected on a brain CT scan were examined by the ophthalmology service. RESULTS: Of the orbital CT scans, 2% had bilateral drusen of the optic nerve head, 3% had calcified scleral plaques anterior to the medial or lateral rectus muscles, and 3% had bilateral ossification of the trochlear apparatus. Routine brain CT scans detected asymptomatic calcifications of the sclera and dura surrounding the proximal optic nerves. CONCLUSION: Incidental asymptomatic orbital calcifications are commonly encountered on modern high-resolution CT images of the brain and orbit. This article should help the clinician to confidently distinguish these densities from foreign bodies or pathological calcifications.

Adolescent↗

Intracranial extension of inflammatory pseudotumor of the orbit. Case report.

Orbital pseudotumors are inflammatory lesions of the orbit of unknown etiology, which initially mimic an orbital neoplasm. Involvement of the other orbit is uncommon, and extension into the paranasal sinus rare. Intracranial extension of pseudotumor of the orbit is previously unreported. This is a case report of a patient with pseudotumor of the orbit with intracranial extension. The literature of the subject is reviewed.

Aged↗

A four-wall orbital decompression for dysthyroid orbitopathy.

A new surgical technique is described for the relief of the ocular manifestations of dysthyroid orbitopathy. Surgical decompression of the orbit was reserved for patients who failed to respond to medical treatment. Eleven patients (nine women and two men) were followed for periods from 3 to 48 months. Visual loss was the commonest presentation and the main indication for surgery. All patients had failed to respond to medical therapy, consisting of steroid and/or radiation therapy. Three patients had previously undergone orbital decompressions with limited success. Six patients had preoperative visual acuity of worse than 20/200. Preoperative exophthalmos ranged from 24 to 35 mm (normal 16 mm). The orbits were approached by a bifrontal scalp flap with exposure of the temporal and infratemporal fossae. The orbital roof was approached transcranially. The posterior wall of the frontal sinus was removed together with the mucous lining. To maximize the decompression, the periosteum surrounding the orbital contents was incised, allowing the contents to prolapse through the newly created windows into the maxillary antrum, temporal fossa, anterior cranial fossa, and nose. During the past 3 years, 22 orbits in 11 patients have been decompressed by this technique. Symptomatic relief was obtained in all but one patient who still had significant exophthalmos with keratitis, but did have a dramatic improvement in vision. The decrease in exophthalmos ranged from 1 to 13 mm (mean 7 mm). The most dramatic improvement was in vision, with postoperative acuity of 20/20 to 20/30 in all but two patients. There were no deaths and no major morbidity.

Adult↗

Transcranial approach to the orbit: microsurgical anatomy.

An anatomical study of three microsurgical intraorbital routes to the optic nerve and orbital apex, which can be reached through a fronto-orbital craniotomy, was conducted on cadaver specimens. The structures that could be exposed via the medial, central, or lateral approaches directed through the orbital roof were defined. The medial approach, directed through the space between the superior oblique and the levator muscles, provides good access to all parts of the intraorbital optic nerve. The central approach, between the levator and the superior rectus muscles, provides the shortest route to the optic nerve. Two variants of the central approach were examined. In the first, the levator muscle and frontal nerve are retracted medially and the superior rectus muscle laterally. This variant provides access to only the midportion of the intraorbital segment of the optic nerve. In the second variant, the frontal nerve is retracted laterally together with the superior rectus muscle. This variant provides access to the posterior two-thirds of the intraorbital portion of the optic nerve. The lateral approach is directed between the levator and lateral rectus muscles. This approach also has two variants, depending on whether the superior ophthalmic vein is retracted medially or laterally. The variant in which the superior ophthalmic vein is retracted medially with the levator and superior rectus muscles provides access to the lateral side of the optic nerve except in the region adjacent to the superior orbital fissure. The variant in which the superior ophthalmic vein is retracted laterally together with the lateral rectus muscle provides excellent access to the optic nerve in the region of the superior orbital fissure. It is an ideal approach for lesions that involve both the cavernous sinus and orbit.

Abducens Nerve↗

Quantification of increased exposure resulting from orbital rim and orbitozygomatic osteotomy via the frontotemporal transsylvian approach.

OBJECT: Use of orbital rim and orbitozygomatic osteotomy has been extensively reported to increase exposure in neurosurgical procedures. However, there have been few attempts to quantify the extent of additional exposure gained by these maneuvers. Using a novel laboratory technique, the authors have attempted to measure the increase in the "area of exposure" that is gained by removal of the orbital rim and zygomatic arch via the frontotemporal transsylvian approach. METHODS: The authors dissected five cadavers bilaterally. The area of exposure provided by the frontotemporal transsylvian approach was determined by using a frameless stereotactic device. With the tip of a microdissector placed on targets deep within the exposure, the position of the end of the microdissector handle was measured in three-dimensional space as the microdissector was rotated around the periphery of the operative field. This maneuver was performed via the frontotemporal approach alone as well as with orbital rim and orbitozygomatic osteotomy approaches. After data manipulation, the areas of exposure corresponding to the polygons used to define these handle positions were calculated and directly compared. On average, the area of exposure provided by the frontotemporal transsylvian approach was increased 26 to 39% (p<0.05) by adding orbital rim osteotomy and an additional 13 to 22% (not significant) with removal of the zygomatic arch. CONCLUSIONS: Significant and consistent increases in surgical exposure were obtained by using orbital osteotomy, whereas zygomatic arch removal produced less consistent gains. Both maneuvers may be expected to improve surgical access. However, because larger and more consistent gains were afforded by orbital rim removal, the threshold for removal of this portion of the orbitozygomatic complex should be lower.

Brain Mapping↗