Efficiency and Safety of Tocilizumab for the Treatment of Thyroid Eye Disease: A Systematic Review.

PURPOSE: To review existing literature concerning the effectiveness and safety of tocilizumab (TCZ) for managing thyroid eye disease. METHODS: A systematic search was conducted across the PubMed and Embase databases to identify studies on TCZ therapy, from inception to May 2023. The search included the keywords "Graves orbitopathy," "thyroid ophthalmopathy," "thyroid eye disease," "thyroid-associated orbitopathy," "thyroid-associated ophthalmopathy," "Graves ophthalmopathy," "endocrine ophthalmopathy," and "Tocilizumab." Only articles written in English, Spanish, or French were considered. RESULTS: Among the 1,013 articles initially screened, a total of 29 fulfilled the eligibility criteria and were selected. Most studies were case reports or case series, and only one randomized clinical trial was found. TCZ has been used mainly in glucocorticoid-resistant or relapsing cases, with a dosage ranging from 4 or 8 mg/kg every 4 weeks when intravenous or a weekly subcutaneous dose of 162 mg. Treatment duration is usually adjusted to the clinical response. TCZ is mostly effective in reducing inflammatory signs during the active phase of thyroid eye disease, with an improvement of at least 3 points in clinical activity score and an overall relapsing rate of 8.2%. Numerous studies have shown marked reductions in proptosis; although the only available randomized controlled trial reported a nonstatistically significant improvement 6 months after treatment, a recent meta-analysis indicated that TCZ seems to be the most effective treatment for reducing proptosis. No severe side effects related to intravenous or subcutaneous TCZ administration were reported. DISCUSSION: Despite these promising findings, randomized clinical trials to directly compare the efficacy and safety of TCZ and other currently available therapeutic options are needed.

Upper Eyelid Contour Changes After Müller's Muscle Conjunctiva Resection.

PURPOSE: To analyze the upper eyelid contour after Müller's muscle conjunctiva resection (MMCR) performed by four different surgeons. METHODS: Comparative cross-sectional analysis of the pre- and postoperative contours of a control group and four groups of upper lids (n = 88) of 65 patients who underwent MMCR at four international centers. The procedure employed was essentially the same as described by Putterman but performed with different instruments to entrap the posterior lamella. Multiple medial and lateral margin lid distances were measured on Bézier lines expressing the pre- and postoperative lid contours. RESULTS: Preoperatively, two groups had significant lateral and medial ptosis. After MMCR, the lateral segment of the lid's contour was corrected in all groups. In the two groups with more pronounced ptosis, the nasal lid contour was undercorrected. CONCLUSIONS: In MMCR, regardless of the instrument used to entrap the posterior lamella, the amount of medial tissue resection is essential to avoid postoperative nasal undercorrection. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Müllerotomy with anterior graded Müller muscle disinsertion for Graves upper eyelid retraction: validation of surgical outcomes using Bézier curves.

PURPOSE: To assess with Bézier curves the outcomes of Müllerotomy with anterior graded Müller muscle disinsertion for the treatment of Graves upper eyelid retraction (UER). METHODS: Eighty-six eyelids of 52 inactive GO patients operated from November 2018 to June 2021 were included in this study. All measurements were performed on Bézier curves adjusted to the upper lid contour with a previously validated algorithm. Lid contour was classified regarding grade of superposition (GS) as excellent (GS > 90%), good (GS 85-90%) or poor (< 85%). Surgical success was defined as complete or partial if postoperative grade of asymmetry was < 10% with an excellent or good lid contour, respectively. RESULTS: The mean age was 51 ± 10.4 years with a range from 31 to 78 years and a mean follow-up of 14.4 ± 7.4 months. There was a significant improvement of median GS (p < 0.0001) from preoperative (74.3%; 10.7 IQR) to postoperative values (91.7%; 6.3 IQR). A normalization of postoperative contour peak (- 0.69; 1.27 SD) and MPLD90 (4.2 mm; 0.8 SD) was noticed (p < 0.0001). Postoperative lid contour was excellent in 62 (72%), good in 16 (19%) and poor in 8 eyelids (9%). Surgical success was achieved in 42 patients (81%), from which 34 (81%) were complete. Reintervention was required in 14 eyelids (16%). CONCLUSIONS: Measuring surgical outcomes with Bézier curves allows an automated, complete and objective assessment, giving more consistency to our data compared to previous reports. Müllerotomy with graded Müller muscle disinsertion is a safe and effective procedure for Graves UER, offering predictable results.

Effect of Rim-Off Deep Lateral Orbital Decompression on Interpalpebral Fissure Shape.

PURPOSE: The purpose of this study is to compare the palpebral fissure shape after rim-off deep lateral decompression with and without restoration of the lateral orbital rim. METHODS: Retrospective cross-sectional quantitative analysis of the palpebral fissure images of 17 patients (25 eyes) who underwent rim-off deep lateral orbital decompression without repositioning of the rim (G1) and of 20 patients (34 eyes) operated with rim restoration. Quantification of palpebral fissure images included MRD 1 and MRD 2 , two lateral mid-pupil lid margin (MPD) distances, the width of the palpebral fissure, and the height and shape of the lateral canthus. RESULTS: Proptosis reduction did not differ significantly between G1 and G2. In both groups, decompression reduced the mean values of the MRD 1 and MRD 2 , the lateral height of the upper eyelid, and the height and angle of the lateral canthus. The palpebral fissure width and lateral height of the lateral lower eyelid were not affected. There was no significant difference between the mean changes of G1 and G2. Multivariate analysis showed that the lateral canthus decrease was correlated with changes in MRD 1 and MRD 2 . CONCLUSIONS: Small changes in palpebral fissure shape after deep lateral decompression are not dependent on the presence or absence of the lateral rim.

Childhood proliferative fasciitis of the orbit mimicking sarcoma: a case report.

Proliferative fasciitis (PF) is a benign fibroblastic reaction with histological and clinical characteristics that overlap with those of malignant soft tissue tumors; thus, it is referred to as a pseudosarcomatous reaction. It continues to be an important cause of diagnostic error and overtreatment. The childhood PF subtype has some distinct histological and immunohistochemical characteristics that make differential diagnosis with malignant tumors even harder, especially with sarcoma. These proliferations generally occur in the lower limbs, and the periorbital region is a rare location of appearance. Here, we describe a case of childhood subtype PF in a 16-year-old girl located in the periorbital area. To the best of our knowledge, this is the first reported case of childhood subtype PF in the periorbital area, and the third case if PF subtypes are not taken into account.

Upper Eyelid Contour Changes After Orbital Decompression in Graves Orbitopathy.

PURPOSE: To evaluate the effect of orbital decompression on the upper eyelid contour. METHODS: A paired cross-sectional analysis of the upper eyelid contour was performed for 103 eyes of 66 patients who underwent orbital decompression. A control group of 26 normal subjects was also included. The eyelid contour of all participants were measured with Bézier lines adjusted to the eyelid contour and 9 midpupil eyelid margin (MPD) distances from a horizontal line bisecting the pupil. One central, corresponding to the margin reflex distance (MRD 1), and 8 equally distributed medially and laterally at 20% of the interval between the lines. Patients were classified as with flare if the height of the most lateral MPD relative to the MRD 1 was above the upper limit of the controls. RESULTS: Preoperatively 63 of the 103 contours were classified as flare + (F+). After decompression MRD1 showed a mean decrease of 0.4 mm and the location of the contour shifted 0.8 mm medially. These changes were not correlated with proptosis reduction. Orbital decompression decreased the lateral curvature of the contours especially for the F+ lids. In 40% of the F+ eyelids the flare sign disappeared after decompression. CONCLUSIONS: Orbital decompression affects the lateral eyelid contour and diminishes the amount of lateral eyelid retraction surgery necessary to correct the flare sign. In 40% of the patients, the eyelid contour is normalized with proptosis reduction only.

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures.

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves' disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.

Orbital myopericytoma: an unusual tumor in an unusual location.

A 71-year-old male with a 4-month history of bulging, tearing, and redness in the right eye presented with vision loss, proptosis, conjunctival hyperemia, and chemosis. Magnetic resonance imaging showed a right intraconal solid mass with extraconal extension, hyper-intense in T2 sequences with heterogeneous contrast enhancement. Complete excision of the mass was performed through a lateral orbitotomy. Histological analysis revealed a neoplasm with high vessel density, solid growth of oval cells, a concentric proliferation of the wall of small vessels, and a weak and patchy positivity for smooth muscle actin. These findings were consistent with the diagnosis of myopericytoma. After surgery, visual acuity improved in the affected eye and after 18 months of follow-up there have been no signs of recurrence.

Frontalis Suspension Using Autologous Fascia Lata in Children Under 3 Years Old.

PURPOSE: To analyze functional results and complications of the use of autologous fascia lata in frontalis suspension in children under 3 years old and to confirm its technical viability. METHODS: A retrospective review of 8 patients (12 eyes) who underwent frontalis suspension using autologous fascia lata sling. RESULTS: Twelve eyes of 8 patients were analyzed, with an average age of 1.8 ± 0.6 years. Preoperatively, the mean margin-to-reflex distance 1 was -0.17 ± 0.577 mm. Postoperatively the mean margin-to-reflex distance 1 was 2.66 ± 0.492 mm without any graft donor site or corneal complications. No recurrence was recorded in the follow-up period (mean follow-up period 28.5 ± 32.33 months). CONCLUSIONS: Autologous fascia lata is an eligible material in frontalis suspension in children under 3 years old, despite the traditional oculoplastic dogma that advises against.

Nerve Sheath Myxoma Involving the Medial Rectus Muscle: A Case Report.

A 63-year-old man reported a 2-year history of painless OS proptosis. The first MRI, performed in the institution of origin, resulted in a diagnosis of hemangioma versus orbital pseudotumor. Examination revealed proptosis and mild chemosis. Ancillary tests were normal, and oral prednisone was initiated without remarkable changes. Later, an incisional biopsy identified the lesion as an intramuscular myxoma of the left rectus, and a new MRI was ordered. It described a fusiform thickening of the medial rectus with and exophytic growth below the inferior rectus and upward toward the superior oblique. Due to the localization of the lesion, a combined transcaruncular and swinging eyelid approach with a lateral orbitotomy was performed. Histopathological examination revealed a proliferation of stromal origin composed of myxoid matrix with fusocellular and stellate-shaped cells. Cells were S-100, CD34, and CD56 positive and negative for epithelial membrane antigen, CD68, CD10, actin, and desmin. Results were consistent with a left medial rectus nerve sheath myxoma.

Oscillopsia After Isolated Lateral Wall Decompression Versus Balanced or 3-Wall Decompression.

PURPOSE: To assess the incidence of postoperative masticatory oscillopsia after orbital decompression, comparing results between isolated lateral wall and balanced or 3-wall orbital decompression. METHODS: An observational retrospective study was performed, involving 161 consecutive patients who underwent orbital decompression between 2008 and 2018. Patients' clinical data were registered, and archives were revised for data compilation. Patients were divided into 2 groups according to the type of surgery: "lateral" group included patients who underwent isolated lateral wall decompression and "lateral plus" group involved patients with balanced or 3-wall decompression. Exclusion criteria were secondary decompressions, those not including lateral wall and asymmetrical surgeries, so analysis was performed among 131 remaining patients. Oscillopsia was self-reported and was registered as present or not. Diplopia was evaluated according to Paridaens grading system. RESULTS: Statistical analysis among the 131 patients with lateral wall decompression (isolated or in combination) was performed. Seven patients referred oscillopsia, 5 among "lateral" group, while 2 reported oscillopsia on "lateral plus" group (p = 0.001). The authors found no differences on new-onset or worsening of diplopia between groups (p = 1). CONCLUSIONS: Oscillopsia was significantly higher after isolated lateral wall decompression than after balanced or 3-wall decompression, while no differences were found between groups according to diplopia status. Transmission of temporal muscle contraction to the orbit seems to be the cause of the oscillopsia. The authors postulate that the absence of orbital floor or medial wall may act as a dampener for the temporalis muscle contractions, allowing the orbital contents to be expanded through them, and avoiding oscillopsia.

Influence of LASEK on Schiøtz, Goldmann and dynamic contour Tonometry.

PURPOSE: Our purpose was to assess the effect of LASEK surgery on ocular rigidity and to compare its effect on intraocular pressure (IOP) readings with Goldmann applanation tonometry (GAT), Schiøtz indentation tonometry (ST) and dynamic contour tonometry (DCT). METHODS: Prospective, observational, single-masked cohort study. One eye per patient from 31 consecutive subjects who underwent LASEK refractive surgery to correct myopia, as well as from 108 non-operated myopic patients, were included. IOP was measured using GAT, DCT, and ST. The coefficient of ocular rigidity (Ko) was obtained from the regression line of the three readings obtained with each weight of the ST. Linear multiple regression analysis was performed with dummy variables to assess the effect of age, central corneal thickness (CCT), and previous refractive surgery on IOP values. RESULTS: Age, CCT, and LASEK surgery explained 23% of the IOP readings with GAT, 11% with DCT, and had no significant influence on ST readings. The IOP readings obtained with GAT and DCT, but not with ST, were significantly different between LASEK and control groups. Significant differences in Ko were observed between LASEK (0.014 mmHg/µL ±0.007) and control groups (0.021 mmHg/µL ±0.013) (P = 0.001). Ko values were not related with age or CCT, in either LASEK or control groups. CONCLUSIONS: ST readings seems to be less affected by LASEK surgery than the other tonometers evaluated. There is a difference in the ocular rigidity between the control and the LASEK eyes that it is not correlated with CCT, so it seems that ST can detect changes in the biomechanical behavior of the LASEK operated corneas.

Choroidal thickening in a case of carotid cavernous fistula.

A 47-year-old woman was diagnosed with dural carotid cavernous fistula (CCF) in her right eye (RE). Scans of the choroid using Spectralis optic coherence tomography (OCT) demonstrated significant asymmetry in subfoveal choroidal thickness (RE 451 µm, left eye (LE) 367 µm). This asymmetry disappeared after the fistula was embolizated through the ophthalmic artery (RE 341 µm; LE 340 µm). This case suggests that OCT should be considered as an ancillary test in the diagnosis of CCF.

Reconstructive subperiosteal midface lift: A three nonvisible incision approach.

This article describes our surgical technique for subperiosteal midface elevation in patients with paralytic lower eyelid malposition or cicatricial inferior eyelid retraction. Nineteen patients with paralytic lower eyelid malposition and 15 patients with cicatricial inferior eyelid retraction underwent a subperiosteal midface lift (n = 34). The procedure was performed under local anesthesia through three nonvisible incisions. A transconjunctival incision allows preseptal dissection to the orbital rim, followed by a subperiosteal dissection of the midface. An oral incision is useful to achieve complete subperiosteal dissection and to perform the distal periostomy, which allows complete release of the midface soft tissues. A temporal incision provides access to the temporal fascia for fixation of the elevated tissues and gives the surgeon the possibility of removing redundant skin from the scalp instead of the lower eyelid. Additional posterior lamellar grafting was performed in 24 patients. There was a statistically significant reduction in the distance from the pupil centre to the lower eyelid (margin reflex distance, MRD2) 1 month after surgery (preoperative MRD2 9.62 ± 4.52 mm, postoperative MRD2 5.28 ± 2.62 mm). The ectropion and lower eyelid retraction was resolved in all patients, except for one recurrence. Midfacial elevation is a safe and effective surgical technique in the treatment of static lower eyelid malposition after chronic facial nerve palsy or posttraumatic or iatrogenic lower eyelid retraction.

Orbital Decompression for the Treatment of Spontaneous Globe Luxations.

AIMS: To describe the results of orbital decompression in patients with spontaneous globe luxations and to evaluate predisposing factors for this condition. METHODS: The clinical records of patients who underwent orbital decompression for the treatment of spontaneous globe luxations between 2010 and 2013 were reviewed. Data collected were age, gender, predisposing factors, preoperative and postoperative exophthalmometry, duration of follow-up, presence of diplopia before and after surgery and intra- and postoperative complications. RESULTS: Seven patients underwent orbital decompression after spontaneous globe luxation during the study period. Six patients underwent bilateral decompression. Two patients underwent a three-wall decompression, four of them medial and lateral decompression and one patient medial decompression. The predisposing factors for globe luxation were Graves' orbitopathy, malar hypoplasia, high myopia, floppy eyelid syndrome and orbital fat hypertrophy in the context of obesity. After orbital decompression, none of the patients reported new globe luxations. No intraoperative complications were observed. None of the patients developed de novo diplopia. DISCUSSION: Orbital decompression is an effective method for the prevention of new episodes in patients with spontaneous globe luxations. It has good aesthetic and functional results and addresses the exophthalmos present in most cases.

External dacryocystorhinostomy and transnasal canthopexy: new details of combined surgery.

PURPOSE: To describe the authors' modified combined surgical technique for external dacryocystorhinostomy and transnasal canthopexy. METHODS: A retrospective medical record review was performed including patients with late posttraumatic telecanthus and nasolacrimal duct obstruction treated by their combined dacryocystorhinostomy-transnasal canthopexy technique. In this technique, the bony window is extended superiorly and posteriorly further than in standard dacryocystorhinostomy, to allow pulling the canthus though the window, but at the same time not disturbing the suture of the dacryocystorhinostomy anastomosis. The lacrimal sac opening is performed under the canthal tendon, and only an anterior anastomosis is performed. Silicone intubation was performed only in cases with evidence of canalicular disease, marked sac inflammation or atrophic sac. The wires are fixed to the contralateral orbit, passed through the 2 middle holes of a 4-hole straight 1,7 mm microplate. The microplate is placed on the contralateral side to avoid in-fracture of the contralateral orbital bones from the pressure exerted by the transnasal wires. RESULTS: Combined external dacryocystorhinostomy-transnasal canthopexy surgery was performed on 13 eyelids of 11 consecutive patients for correction of medial telecanthus and nasolacrimal duct obstruction. Proper canthal position and lacrimal pathway patency were achieved in all cases after a mean follow up of 14.6 months. CONCLUSIONS: Combined dacryocystorhinostomy-transnasal canthopexy surgery with superior and posterior enlargement of the bony window avoided crossing of the wires and flaps and achieved a high success rate in the reconstruction of the lacrimal drainage pathway. This technique proved to be effective in the treatment of posttraumatic telecanthus with nasolacrimal duct obstruction.

Long-term cicatrization analysis in periocular incisions for oculoplastic surgery performed with cold blade and Colorado needle.

PURPOSE: To compare the degree of satisfaction of patients and observers about scars secondary to skin incisions in oculoplastic surgery performed with cold blade versus Colorado microcautery needle. METHODS: A cross-sectional noninferiority comparative study was performed. Eighty patients undergoing surgery for blepharoptosis repair, lateral tarsal strip, or dacryocystorhinostomy with cold blade or Colorado needle between January 2011 and July 2011 were included. Groups were paired by sex and surgery type. Scars were assessed between January 2012 and July 2012 using 2 validated scales (Patient and Observer Scar Assessment Scale [POSAS] and Vancouver Scar Scale [VSS]) by the patient and 2 trained observers. Sample size was predetermined, and 38 patients were needed in each group to detect differences of at least 8 points in the POSAS with 90% power. RESULTS: Patients operated with Colorado needle were 7.3 years older than those operated with cold blade (p = 0.007). No statistically significant differences between both techniques were observed either in the individual items or in the composite scores, correcting for age (POSAS, p = 0.518; VSS, p = 0.367). Multiple linear regression analysis showed that patients undergoing dacryocystorhinostomy had significantly lower scores in OSAS (p= 0.034) and VSS (p = 0.034), independent of the other variables in the model. No association between the surgical instrument and the final score was observed for any of the analyzed scales. CONCLUSIONS: Esthetic results of periocular scars secondary to skin incisions performed with cold blade or Colorado needle are clinically similar in Spanish patients. Esthetic result of dacryocystorhinostomy scars showed lower scores in OSAS and VSS.

Iatrogenic diplopia [corrected].

Diplopia is a very disturbing condition that has been reported as a complication of several surgical procedures. The following review aims to identify the ocular and nonocular surgical techniques more often associated with this undesirable result. Diplopia is reported as an adverse outcome of some neurosurgical procedures, dental procedures, endoscopic paranasal sinus surgery, and several ophthalmic procedures. The most common patterns and some recommendations in order to prevent and treat this frustrating outcome are also given.