Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis.

Ligneous conjunctivitis is a rare, autosomal recessive, membranous conjunctivitis characterized by a deficiency in type 1 plasminogen. The absence of normal plasmin activity results in the formation of fibrin-rich, membranous material that typically manifests on the palpebral conjunctiva. Surgical treatment often causes irritation of the conjunctiva and accelerated recurrence of pseudomembranes. In this interventional case report, the authors document the results of treatment with topical plasminogen following conjunctival pseudomembrane excision in a 32-year-old woman. The patient underwent pseudomembrane excision in the OS followed immediately by hourly topical application of plasminogen eye drops. The plasminogen was prepared from pooled human plasma purchased under Food and Drug Administration approval from DiaPharma. Follow-up evaluation at 1 week, 1 month, and 5 months showed no evidence of recurrent pseudomembranous change. Adjunctive topical plasminogen application appears to be an effective and safe method of controlling pseudomembrane recurrence in patients with ligneous conjunctivitis.

High-resolution ultrasound as an effective and practical tool to analyze eyebrow profile expansion in thyroid-associated periorbitopathy.

PURPOSE: Clinical, radiographic, and molecular studies have shown that patients with thyroid-associated orbitopathy exhibit volumetric expansion of eyebrow tissues. This clinicopathologic entity has been termed thyroid-associated periorbitopathy. The goal of this study was to determine whether high-resolution ultrasonography could be used to reliably quantify thyroid-associated periorbitopathy. METHODS: Institutional review board approval was obtained. The internal case-control study consisted of 12 subjects with unilateral-asymmetric thyroid-associated orbitopathy. High-resolution ultrasonography using a 15-MHz probe (Logiq p6) was performed by a single operator. Measurements were obtained 0.5 cm cephalad to the superior orbital rim at the midpupillary sagittal level. For each subject and tissue layer thickness (total tissue, dermis fat, retro-orbicularis oculi fat), the measured values on the less affected side were subtracted from those on the more severely diseased side. Summary statistics were used to analyze results. RESULTS: High-resolution ultrasonography effectively demonstrated asymmetric expansion of total eyebrow tissue (p < 0.0001) and retro-orbicularis oculi fat (p = 0.0003). No significant difference in dermis fat thickness was found between the 2 sides (p = 0.2). Hertel exophthalmometry measurements were statistically different between the 2 sides (p = 0.002). CONCLUSIONS: This study demonstrates that high-resolution ultrasonography independently confirms previously published studies of retro-orbicularis oculi fat expansion in patients with thyroid-associated orbitopathy. Compared with CT, MRI, and tissue biopsy, high-resolution ultrasonography is a more practical and cost-effective way to quantify and track thyroid-associated periorbitopathy over time. With its potential for real-time tissue assessment, high-resolution ultrasonography may be best suited for future studies of the dynamic relationship between globe and periorbital structures.

Aesthetic considerations in upper eyelid retraction surgery.

PURPOSE: Classically, the aesthetic outcomes of eyelid retraction surgery in patients with thyroid-associated orbitopathy have been described in reference to eyelid margin position and marginal reflex distance. A critically important component of upper eyelid contour is the tarsal platform show (TPS). With this study, the authors aimed to assess the hypothesis that modification of the tarsal platform in posterior eyelid retraction surgery has a significant effect on the final aesthetic outcome. METHODS: In a retrospective, observational, case-cohort study, the authors reviewed the medical records of 36 patients with thyroid-associated orbitopathy who underwent primary eyelid retraction surgery by 1 surgeon. Patients who underwent eyelid retraction surgery at the time of orbital decompression were excluded. The surgical technique consisted of posterior approach conjunctival release of Müeller muscle and graded recession of the levator aponeurosis. To address lateral flare, dissection was carried toward the lateral orbital rim with spreading of the lateral horn of the levator aponeurosis. Outcome measures were millimeters of TPS, millimeters of brow fat span, and symmetry of the eyelid margin position. Randomized preoperative and postoperative standardized photographs were evaluated in masked fashion by 4 surgeons to grade cosmetic outcomes. RESULTS: Fifteen patients (24 eyelids) met the inclusion criteria. Mean follow-up period was 6 months (range, 3-12). Mean TPS increased from 2.27 mm (standard deviation, 1.9 mm) to 4.77 mm (standard deviation, 1.7 mm; p < 0.05). Mean brow fat span remained unchanged, from 13.22 mm (standard deviation, 2.2 mm) to 13.25 mm (standard deviation, 1.9; p > 0.05). Evaluation of the aesthetic outcomes (eyelid contour, eyelid symmetry, and TPS) by 4 masked observers characterized the relevance of TPS in the postoperative aesthetics of eyelid contour and symmetry. CONCLUSIONS: In upper eyelid retraction surgery, the ability to control the TPS has a significant impact on the final aesthetic outcome. Posterior approach eyelid retraction surgery can control eyelid contour and can represent an ideal surgical approach in carefully selected patients. However, it has limited ability to control upper orbital volume and eyebrow and orbital fat (brow fat span). This can result in relative overelongation of the TPS. Factors such as ethnic characteristics, bony asymmetry, brow fat span, and premorbid TPS influence cosmetic outcomes achieved by the anterior or posterior approach. For optimal aesthetic results in eyelid retraction surgery, the decision for anterior versus posterior approach should be individualized.

Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-κB.

PURPOSE: CD40-CD40 ligand (CD40L) interactions appear to play pathogenic roles in autoimmune disease. Here we quantify CD40 expression on fibrocytes, circulating, and bone marrow-derived progenitor cells. The functional consequences of CD40 ligation are determined since these may promote tissue remodeling linked with thyroid-associated ophthalmopathy (TAO). METHODS: CD40 levels on cultivated fibrocytes and orbital fibroblasts (GOFB) from patients with Graves' disease (GD), as well as fibrocyte abundance, were determined by flow cytometry. CD40 mRNA expression was evaluated by real-time PCR, whereas response to CD40 ligation was measured by Luminex and RT-PCR. Protein kinase B (Akt) and nuclear factor (NF)-kappa B (NF-κB) signaling were determined by Western blot and immunofluorescence. RESULTS: Basal CD40 expression on fibrocytes is greater than that on GOFB. IFN-γ upregulates CD40 in both cell types and its actions are mediated at the pretranslational level. Fibrocytes produce high levels of cytokines, including interleukin-6 (IL-6), TNF-α, IL-8, MCP-1, and RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted) in response to CD40L. IL-6 induction results from an increase in steady state IL-6 mRNA, and is mediated through Akt and NF-κB activation. Circulating CD40(+)CD45(+)Col1(+) fibrocytes are far more frequent in vivo in donors with TAO compared with healthy subjects. CONCLUSIONS: Particularly high levels of functional CD40 are displayed by fibrocytes. CD40L-provoked signaling results in the production of several cytokines. Among these, IL-6 expression is mediated through Akt and NF-κB pathways. The frequency of circulating CD40(+) fibrocytes is markedly increased in patients with TAO, suggesting that this receptor might represent a therapeutic target for TAO.

Thyroid-associated periorbitopathy: eyebrow fat and soft tissue expansion in patients with thyroid-associated orbitopathy.

OBJECTIVE: To compare soft tissue and fat volumes in the supraorbital area of healthy patients and patients with thyroid-associated orbitopathy (TAO) using 3-dimensional reconstruction software. METHODS: The superiolateral orbital area was delineated on a bony framework. Three-dimensional reconstruction and volumetric calculation of the retro-orbicularis oculi fat (brow fat), galeal fat (including the retro-orbicularis oculi fat), and soft-tissue muscle were performed. RESULTS: We analyzed 100 computed tomographic scans from 48 patients with TAO and 52 control subjects. All patients showed an age-related increase of fat volumes. The mean total eyebrow volume was greater in patients with TAO vs healthy control subjects (P < .001). Galeal fat (P = .02) and retro-orbicularis oculi fat (P = .01) volumes were significantly higher in patients with TAO vs control subjects. Soft-tissue muscle volume decreased with age in healthy females but remained constant in the aging female group with TAO. Both total volume and brow thickness did not appear to change with age in healthy patients but exhibited an increase in the female population with TAO. CONCLUSIONS: This study brings into focus the clinicopathologic entity of thyroid-associated periorbitopathy. Three-dimensional evaluation of computed tomographic scans can provide information on volumetric changes in the eyebrow profile of patients with TAO. Further investigation of the biologic and morphologic changes of eyebrow fat and soft tissue in patients with TAO may help better characterize, classify, and guide their treatment.

Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production.

CONTEXT: The molecular basis for anatomically dispersed clinical manifestations in Graves' disease (GD) eludes our understanding. Bone marrow-derived, pluripotent fibrocytes represent a subset of peripheral blood mononuclear cells and infiltrate the orbital and thyroid tissues in GD. These cells may be involved in the pathogenesis of thyroid-associated ophthalmopathy (TAO). OBJECTIVE: The objective of the study was to quantify fibrocyte display of functional cell surface TSH receptor (TSHR), identify the profile of chemokines they express after TSHR activation, and determine whether circulating TSHR(+) peripheral blood fibrocytes are more frequent in situ in patients with TAO. DESIGN/SETTING/PARTICIPANTS: Using a newly developed technique, fibrocytes were directly identified in peripheral blood from 31 patients with TAO and 19 healthy subjects receiving care at a multidisciplinary academic center. MAIN OUTCOME MEASURES: The frequency in situ of fibrocytes (collagen 1(+), CD45(+), CD34(+), CD14(+), CD86(+) peripheral blood mononuclear cells) was assessed by multiparameter flow cytometry and correlated to clinical disease activity and smoking status. Levels of TSHR-displaying fibrocytes and their response to TSH and TSHR-activating antibody, M22, were measured by flow cytometry, Luminex, and real-time PCR. RESULTS: The levels of TSHR expression by fibrocytes are substantially higher than those found in orbital fibroblasts. Moreover, the frequency of TSHR(+) fibrocytes in patients with TAO was greater than that in healthy subjects in situ. Their abundance is not influenced by disease activity or smoking history. These cells produce high levels of several cytokines and chemokines including IL-8, regulated upon activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 when treated with TSH or M22. TSH induces IL-8 production at the pretranslational level. This induced cytokine can be detected in intact fibrocytes ex vivo. CONCLUSIONS: Frequency of circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and they express proinflammatory chemokines in response to TSH. Because they infiltrate both orbit and thyroid in GD, they may represent the link between systemic immunoreactivity and organ-specific autoimmunity.

A three-dimensional construct of the aging eyebrow: the illusion of volume loss.

BACKGROUND: The eyebrows and eyebrow fat pads, key structures in upper facial aesthetics, are particularly vulnerable to age-related changes. OBJECTIVES: In this study, the authors compare the impact of aging on the eyebrows and eyebrow fat pad volume in men and women through three-dimensional (3D) volumetric analysis. METHODS: Electronic medical records of patients seen at the Jules Stein Eye Institute in the Division of Orbital and Ophthalmic Plastic Surgery between 2005 and 2010 were reviewed. Patients were included if they had undergone investigative imaging of the orbit for unilateral pathology. Computed tomography (CT) scans of patients with Graves disease diagnosis, extensive orbital trauma, and/or previous eyebrow surgery were excluded. A total of 52 CT scans (24 men and 28 women) were retained for analysis. A 3D reconstruction software was used to analyze the scans and calculate volumes of the retroorbicularis oculi fat (ROOF), galeal fat (ROOF and subcutaneous fat), and soft tissue muscles. RESULTS: Galeal and brow fat volumes showed a significant positive trend toward enlargement in women (P values of .01 and .05, respectively). Although men showed a tendency toward fat enlargement with age, this was not statistically significant. Soft tissue-muscle volume decreased significantly in aging women (9.32 mm(3)/y) (P = .02). Data indicated that soft tissue volume in men tended to increase with age (3.92 mm(3)/y) but not significantly (P = .36). Neither total volume nor brow thickness appeared to change significantly in women (P = .56, P = .73). In men, total volume and brow thickness showed weak evidence of increasing with age (P = .12, P = .22). Linear regressions of Hertel measurements with and without sex interaction showed no statistically significant trend between the amount of proptosis and the galeal or brow fat. CONCLUSIONS: Although overall eyebrow volume does not change with age, the relative contribution of fat and soft tissue to the total volume does seem to change. This pattern also differs between males and females. As women age, the fat volume increases and the soft tissue volume decreases. In men, the shift from soft tissue volume to fat volume is less pronounced. Although many clinicians have been drawn to the concept of fat volume deflation as a key element of facial aging, this study does not support this perspective in the eyebrow fat pad. An increasingly refined understanding of the dynamics of facial aging is mandatory for clinical diagnosis and will likely provide the framework from which to develop more innovative treatment options.

Exposure to Euphorbia lathyris latex resulting in alkaline chemical injury: a case report.

INTRODUCTION: We report the case of a patient with extreme pain following accidental exposure to the latex of Euphorbia lathyris. CASE PRESENTATION: A 76-year-old Caucasian woman attended the ophthalmology department with acute severe bilateral eye pain. This occurred immediately after having pulled a weed out of her garden with her bare hands. She recalled having subsequently rubbed her eyes. The offending plant, was brought into hospital and was identified as the Caper Spurge (Euphorbia lathyris). Her ocular pH was alkaline (pH 9). After copious irrigation, the pH normalised. She was treated with topical steroids, cycloplegics, lubricants and opioid oral analgesia. Three days later, she was symptom-free and her vision had returned to normal. CONCLUSION: Exposure to Caper spurge latex is a rare cause of keratoconjunctivitis. It can, however, potentially lead to corneal ulceration, anterior uveitis and rarely blindness. Treatment remains largely empirical. Exposure to the milky latex can result in extreme pain requiring prompt treatment. The use of goggles and gloves is recommended when handling this plant.

Ocular metastases from HER2 positive breast carcinoma and the response to combination therapy with Paclitaxel and Trastuzumab: a case report.

PURPOSE: Breast cancer is the most common tumour to metastasize to the uveal tract. The mean survival period after diagnosis of metastasis to the eye, ranges from 10 to 32 months. However, recent advances in therapy including the use of monoclonal antibody therapy, will hopefully improve treatment outcomes and prolong survival rates. METHODS: We report a case of a 45 year old woman with a HER2 positive breast cancer, who developed two metastatic lesions in the left choroid, and the left optic nerve sheath. She underwent treatment with a combination of chemotherapy (Paclitaxel) and anti-HER2 monoclonal antibodies (Trastuzumab). RESULTS: Nine months after treatment, a B-scan showed resolution of the superior choroidal focus, as well as absence of blood flow within the optic nerve sheath. The inferonasal lesion was still present but the dimensions were reduced. CONCLUSION: The patient underwent a combined treatment of chemotherapy and Trastuzumab to increase the response rate. Trastuzumab is a humanized monoclonal antibody, which binds to the extracellular segment of the HER2/neu receptor. Nine months following the therapy her vision was stable, whilst one focus of the tumour in the affected eye, had regressed. The favourable response highlights the significant impact of this new therapy, as an alternative to external beam radiotherapy in patients with ocular metastasis from HER2 (+) breast cancer.

Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report.

INTRODUCTION: We report a case of optic atrophy, necrotizing anterior scleritis and keratitis presenting in a patient with Streptococcal Toxic Shock Syndrome. CASE PRESENTATION: A 43-year-old woman developed streptococcal toxic shock syndrome secondary to septic arthritis of her right ankle. Streptococcus pyogenes (b-haemolyticus Group A) was isolated from blood cultures and joint aspirate. She was referred for ophthalmology review as her right eye became injected and the pupil had become unresponsive to light whilst she was in the Intensive Therapy Unit (ITU). The iris appeared atrophic and was mid-dilated with no direct or consensual response to light. Three zones of sub-epithelial opacification where noted in the cornea. There where extensive posterior synechiae. Indirect ophthalmoscopy showed a pale right disc. The vision was reduced to hand movements (HM). A diagnosis of optic atrophy was made secondary to post-streptococcal uveitis. She subsequently developed a necrotizing anterior scleritis. CONCLUSION: This case illustrates a previously unreported association of optic atrophy, necrotizing anterior scleritis and keratitis in a patient with post-streptococcal uveitis. This patient had developed Streptococcal Toxic Shock Syndrome secondary to septic arthritis. We recommend increased awareness of the potential risks of these patients developing severe ocular involvement.

Vitreous and subretinal haemorrhage: an unusual complication of retinal racemose haemangioma.

Racemose haemangioma of the retina is a rare, usually unilateral developmental abnormality: an arteriovenous communication with variable alterations in capillary and arteriolar networks. Herein a case of a 57-year-old man with a vitreous and subretinal haemorrhage in the left eye is described.

An unusual presentation of hydatid cyst within the soft tissues of the back: re-investigation of the undiagnosed lung opacity.

BACKGROUND: Echinococcosis is a zoonotic infection, affecting humans in a characteristic geographic distribution. The disease most commonly involves the liver and the lung and a soft tissue localization is very rare. METHODS: A case of a 68-year-old man, who presented with a cystic lesion on his back, which was presumed to be a lipoma or a sebaceous cyst. Surgical excision of the lesion was performed. RESULTS: Histopathology revealed a hydatid cyst and with further investigations, we identified the nature of a previously undiagnosed opacity in the right lung field. Although the patient previously presented with symptoms of hydatid cyst rupture (productive cough with haemoptysis), echinococcosis was not under consideration. CONCLUSIONS: This unusual case serves to demonstrate that echinococcosis, though rare, should be considered in the differential diagnosis of cystic lesions in every anatomic location, especially when they occur in endemic areas. We overview the diagnosis and treatment of this parasitic infection.