Optic Nerve Compression Research Articles

Multimodal therapy of cavernous sinus meningioma: Impact of surgery and 68Ga-DOTATATE PET-guided radiation therapy on tumor control and functional outcome.

BackgroundFunctional preservation in patients with WHO grade I meningioma involving the cavernous sinus (CSM) is crucial for long-term tumor control. Concise data on the functional outcome of an interdisciplinary, multimodal treatment are scarce. We analyzed functional outcome and tumor control in CSM patients following maximal safe resection (MSR), fractionated stereotactic radiotherapy (FSRT), or combination of them, retrospectively.MethodsPatients with WHO grade I CSM treated between 2003 and 2017 were included. Prior to FSRT, a 68Ga-DOTATATE PET/CT was performed for radiation planning. Progression-free survival (PFS) was analyzed using Kaplan–Meier method and log-rank test was performed to test differences between groups. Visual function was analyzed at baseline and follow-up.ResultsEighty-five patients were included. MSR alone was performed in 48 patients (group A), MSR followed by FSRT in 25 patients (group B), and FSRT alone in 12 patients (group C). Intracranial tumor volumes were higher in A and B compared to C (median 9.2/10.8/4.3 ccm for A/B/C, P = .023). Median follow-up was 47/46/45 months and PFS at 5 years 55.7%, 100%, and 100% in A/B/C, respectively (P < .001). Optic nerve compression was more common in A (91.7%) and B (84.0%) than C (16.7%), P < .001. Post-therapeutic new onset or deterioration of double vision was observed in 29% (A), 17% (B), and 0% (C).ConclusionPersonalized treatment strategies for CSM are essential to control space-occupying or functionally compromising lesions. The additional potential side effect of radiotherapy seems to be justified under the aspect of longer tumor control with low functional risk. Without space-occupying effect of CSM, FSRT alone is reasonably possible.

NFB-03. TRAMETINIB FOR ORBITAL PLEXIFORM NEUROFIBROMAS IN YOUNG CHILDREN WITH NF1

Plexiform neurofibromas (PN) in NF1 are diagnosed in early childhood and may grow rapidly during this period. In 10% of patients they involve the orbital-periorbital area and may cause visual problems including glaucoma and visual loss from amblyopia (deprivational, strabismic, or refractive), optic nerve compression or keratopathy. Ptosis, proptosis and facial disfigurement lead to social problems and decreased self-esteem. Complete surgical removal is usually impossible and there is a tendency for regrowth after debulking. Recently inhibitors of the RAS/MAPK pathway have been investigated for their activity in PN. We describe 5 young children with NF1 and PN of the orbital area treated with the MEK inhibitor trametinib followed clinically and by volumetric MRI. Treatment was initiated at mean age 26.8 months (SD ±12.8) and continued for median 25 months (range 17– 48). Reasons for initiating treatment were visual compromise and progressive tumor growth. Doses were as recommended. One child reported decreased orbital pain after one week and another, with involvement of the masseters, had increased ability to chew food. Toxicities were mostly to skin and nails grades 1–2 as expected. Additionally, 60% had debulking surgery of preseptal eyelid tumor in first year of medical treatment. Volumetric MRI measurements showed reduction of 8–26% at 1 year from baseline with a maximal reduction of 45% in two patients at 22 & 45 months. No change in visual function was recorded following treatment initiation. In conclusion, trametinib may decrease tumor size in young children with orbital PN and may prevent progressive disfigurement.

Principles of Protection of the Eye and Vision in Orbital Surgery.

Orbital surgery can result in damage to ocular and orbital structures, leading to a range of structural and visual sequelae, including corneal abrasions, globe malposition, diplopia, and blindness. Vision loss in particular is the most feared and devastating complication, occurs with an overall incidence of 0.84%, and can occur secondary to direct injury, optic nerve compression, or ischemic events. Different types of orbital surgery and surgical approaches carry their own hazards, and it is important to be mindful of these risks in addition to having a thorough understanding of individual risk factors and anatomical variations for each patient. Although universal guidelines for preserving vision in orbital surgery do not yet exist, there are concrete steps that every surgeon can take at the preoperative, intraoperative, and postoperative stages to minimize the risk of injury and maximize the likelihood of preserving the eye and visual function.

Dysthyroid optic neuropathy: evaluation and management.

Dysthyroid optic neuropathy (DON) is a serious complication of Graves orbitopathy (GO) from optic nerve dysfunction that may result in permanent loss of vision. This paper reviews the current knowledge of DON, including its pathogenesis and epidemiology, clinical and radiologic features, and management choices and outcomes. Literature review and author retrospective case series. Over 90% of DON cases are related to nerve compression by enlarged extraocular muscles (EOM) while the remainder are caused by stretching of the optic nerve without compression. DON's incidence is 5-8% of GO cases. Risk factors include advancing age, male gender, smoking and diabetes mellitus, and these cases should be referred promptly to an ophthalmologist or GO clinic to rule out DON and for ongoing care. Clinical features of DON may include reduction in central and colour vision (unexplained by other ocular disorders), afferent pupil defect and/or optic disc edema. Since most cases are associated with enlarged EOM, restricted motility and soft tissue venous congestion are common. Visual fields and optical coherence tomography (OCT) help confirm the diagnosis while CT or MRI Scans show apical optic nerve compression or proptosis with optic nerve stretch. Standard therapy includes iv/oral corticosteroids (CS) with partial response in most cases, but often relapse with tapering. Radiotherapy may delay or avoid surgery and may prevent the onset of DON when combined with CS in high-risk individuals. The benefits of newer biologic targeted therapy are not clear. Orbital decompression surgery often has positive outcomes, even in cases of severe vision loss or delayed surgery. The most common surgical complication is worsening strabismus, which may worsen visual function and quality of life. In rare cases, permanent vision loss from DON may occur despite full therapy. Although DON may cause vision loss, most cases are reversible if recognized and managed in a timely manner.

Subclinical dysthyroid optic neuropathy: tritan deficiency as an early sign of dysthyroid optic neuropathy

PurposeThe aim of this research was to investigate the subclinical findings of dysthyroid optic neuropathy (DON) and to look for early indicators for optic nerve compression in patients with Graves’...

Long-Term Visual Disturbance Affected by Infraorbital Cell Mucocele and Fully Recovered after Surgical Management: A Case Report

Mucocele of the paranasal sinuses is a benign, expansible, and cystic mass filled with mucous collection. Infraorbital cells are extramural ethmoid cells that develop into the roof of the maxillary sinus and the base of the orbital cavity. Although infraorbital cells are asymptomatic in most cases, inflammation or mucocele in those cells may cause various symptoms including facial pain, hypoesthesia, and secondary rhinosinusitis. They sometimes invade the orbital cavity, which may cause ophthalmic symptoms such as visual disturbance, orbital swelling, and orbital pain. Most of the cases with ophthalmic symptoms are related to sphenoethmoidal cell mucocele. Delayed treatment of more than two days is known to have a poor prognosis for visual disturbances caused by acute optic nerve compression. We describe a case of 61-year-old man who complained of visual disturbance related to infraorbital cell mucocele and fully recovered right after surgical management.

Immunoglobulin G4-Related Ophthalmic Disease: A Case Report

The authors reported a rare case with immunoglobulin (Ig) G4-related ophthalmic disease presented with chronic progressive bilateral complete ophthalmoplegia and blindness from orbital apex syndrome. MRI brain and orbit demonstrated ill-defined infiltrative lesions at bilateral orbital apexes, bilateral optic canals, and bilateral Meckel’s caves, causing optic nerve compression and possibly optic neuropathy with generalized leptomeningeal enhancement at dura, cavernous sinus, and parotid gland. Lumbar puncture revealed few small lymphocytes, rare monocytes, very rare neutrophils with degenerative cells in background, and negative for malignancy. Serology titers for IgG subclass 4 (IgG4) had resulted in 5.959 grams per deciliter (g/dL). A dural biopsy revealed aggregate histiocytes with chronic inflammation and focal foreign body type giant cells. Motility improvement was achieved in the patient after systemic corticosteroids treatment. IgG4 serology should be considered for workup when patients present with chronic idiopathic orbital inflammation. Keywords: IgG4-related ophthalmic disease, Ophthalmoplegia, Orbital apex syndrome

Subperiosteal Orbital Hemorrhage: An Unusual Complication During Labor

Subperiosteal orbital hemorrhage in the postpartum period has been rarely reported. The authors herein present a female patient who developed acute-onset vertical diplopia, proptosis, mild retro-orbital pain, and restriction of upgaze immediately after labor. Neuroimaging revealed a subperiosteal hematoma along the right orbital roof. Diplopia, motility limitation, and retro-orbital pain gradually resolved in the following weeks. Subperiosteal orbital hematomas are a rare complication of labor, with only 12 cases reported so far. They result from straining during labor, which increases central and orbital venous pressure by means of the Valsalva-maneuver. In order to evaluate ocular motility and exclude optic nerve compression, an urgent ophthalmological examination is required.

Hypoxia-Preconditioned Placenta-Derived Mesenchymal Stem Cells Rescue Optic Nerve Axons Via Differential Roles of Vascular Endothelial Growth Factor in an Optic Nerve Compression Animal Model

Human placenta-derived stem cells (hPSCs) with the therapeutic potential to recover from optic nerve injury have been reported. We have recently demonstrated that hPSCs have protective abilities against hypoxic damage. To improve the capacity of hPSCs, we established a hypoxia-preconditioned strain (HPPCs) using a hypoxic chamber. The hPSCs were exposed to short-term hypoxic conditions of 2.2% O2 and 5.5% CO2. We also performed in vivo experiments to demonstrate the recovery effects of HPPCs using an optic nerve injury rat model. Naïve hPSCs (and HPPCs) were injected into the optic nerve. After 1, 2, or 4weeks, we analyzed changes in target proteins in the optic nerve tissues. In the retina, GAP43 expression was higher in both groups of naïve hPSCs and HPPCs versus sham controls. Two weeks after injection, all hPSC-injected groups showed recovery of tuj1 expression in damaged retinas. We also determined GFAP expression in retinas using the same model. In optic nerve tissues, HIF-1α levels were significantly lower in the HPPC-injected group 1week after injury, and Thy-1 levels were higher in the hPSC-injected group at 4weeks. There was also an enhanced recovery of Thy-1 expression after HPPC injection. In addition, R28 cells exposed to hypoxic conditions showed improved viability through enhanced recovery of HPPCs than naïve hPSCs. VEGF protein was a mediator in the recovery pathway via upregulation of target proteins regulated by HPPCs. Our results suggest that HPPCs may be candidates for cell therapy for the treatment of traumatic optic nerve injury.

The outcomes of conservatively observed asymptomatic nonfunctioning pituitary adenomas with optic nerve compression.

The authors investigated the natural history of asymptomatic nonfunctioning pituitary adenomas (NFPAs) with optic nerve compression. This study retrospectively analyzed the natural history of asymptomatic NFPAs with documented optic nerve compression on MRI diagnosed between 2000 and 2016 from 2 institutions. The patients were followed up with regular endocrinological, ophthalmological, and radiological evaluations, and the endpoint was new endocrinopathy or neurological deficits. The study comprised 81 patients. The median age at diagnosis was 58.0 years and the follow-up duration was 60.0 months. As the denominator of overall pituitary patients, 2604 patients were treated with surgery after diagnosis at the 2 institutions during the same period. The mean initial and last measured values for tumor diameter were 23.7 ± 8.9 mm and 26.2 ± 11.4 mm, respectively (mean ± SD). Tumor growth was observed in 51 (63.0%) patients; however, visual deterioration was observed in 14 (17.3%) patients. Ten (12.3%) patients experienced endocrine deterioration. Fourteen (17.3%) patients underwent surgery for either visual deterioration (in 12 patients) or endocrine dysfunction (in 2 patients). After surgery, all patients experienced improvements in visual or hormonal function. The actuarial rates of treatment-free survival at 2, 3, and 5 years were 96.1%, 93.2%, and 85.6%, respectively. In the multivariate analysis, initial cavernous sinus invasion (HR 4.985, 95% CI 1.597-15.56; p = 0.006) was the only independent risk factor for eventual treatment. The neuroendocrinological deteriorations were not frequent and could be recovered by surgery with early detection on regular follow-up in asymptomatic NFPAs with documented optic nerve compression on MRI. Therefore, conservative management could be an acceptable strategy for these tumors. Careful follow-up is required for tumors with cavernous sinus invasion.

SAT-236 Unusual Presentation of a Stable Pituitary Macroadenoma with Pituitary Apoplexy Causing SIADH and Pan-hypopituitarism

We are reporting a case of SIADH hyponatremia and pan-hypopituitarism in an otherwise stable appearing non-functional pituitary macroadenoma on MRI that suddenly developed apoplexy.Patient is a 52-year-old hispanic male with a history of a pituitary adenoma diagnosed initially on 06/2017 during MRI head for chronic headaches. MRI Pituitary on 07/2018 showed “well-circumscribed lesion” measuring approximately 12.7 x 14.8 x 13.4 mm in AP. Hormonal work up was normal in 06/2017, 01/2018, and 07/2018. In 07/2018 labs showed: IGF-1 247 ng/mL (65–222), ACTH 28 pg/mL (7–69), random cortisol 8.58 microg/dL (3.09–22.4), TSH 2.3 mIU/mL (0.4–5.5), fT4 1.06 ng/dL (0.8–1.8), LH 4.6 mIU/mL (0.98–79.7), FSH 6.2 MIU/mL (1–18), prolactin 2.92 ng/mL (2.1–24), and testosterone 310 ng/dL (87–814). Oral glucose tolerance test was done and showed: GH was 0.34 ng/mL at baseline and 1.01 ng/mL after 75 g oral glucose (equivocal result). Repeat IgF1 was normal after that.Subsequently, patient was admitted on 09/24/2018 with severe headaches, nausea, vomiting, polyuria, and polydipsia. He was hypotensive and tachycardic and was found to be hyponatremic with a Na of 124, lowest at 119 where hypertonic saline was given at that point. Urine output was 1.5 L in 24 hours while he was on an 0.8 L fluid restriction, and then 6 L the following day while he was on 1.5 L fluid restriction, serum osmolality was 251, urine osmolality was 1003, urine specific gravity was >1.030. Nephrology agreed to the diagnosis of SIADH.Blood work on 09/24 showed: random cortisol 0.67 microg/dL, TSH 0.19 mIU/mL, free T4: 0.63 ng/dL, ACTH 11 pg/mL, LH 2.4 mIU/mL, FSH 4.7 MIU/mL, testosterone 13 ng/dl. Patient was started on Levothyroxine 125 mcg and hydrocortisone stress dose. MRI brain was done and showed a pituitary macro-adenoma, measuring approximately 14 x 11 x 11 mm with no significant change in size since 6/30/2017, without optic nerve compression, no hemorrhage was mentioned. Work up for other causes of panhypopituitarism, i.e. hemochromatosis was done and was negative: Ferritin: 258 ng/mL (22–322). CT abdomen and pelvis was also done and showed normal adrenal glands. We thought about granulomatous infiltrative diseases like sarcoidosis since 1–25 (OH) vitamin D was high at 120 pg/mL (19.9–79.3). CT neck and chest was done but was negative for sarcoidosis or lymphadenopathy. Patient was seen outpatient by neurosurgery in 1/2019 and a repeat MRI was done which reported resolution of cystic and blood material from a pituitary adenoma, and per neurosurgery there is resolution of a pituitary cystic adenoma with apoplexy that now looks like a partial empty sella. Patient currently continues to be pan-hypopituitary requiring hydrocortisone, levothyroxine and testosterone replacement. SIADH has resolved.An otherwise non-functioning stable pituitary macroadenoma on MRI, can suddenly present as symptomatic apoplexy with SIADH and pan-hypopituitarism.

Long‐term outcomes of children with extracutaneous juvenile xanthogranulomas in Japan

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis in children. The mortality and morbidity of JXG with extracutaneous lesions remain unclear. Data of patients aged<18 years who were diagnosed with JXG between 2001 and 2010 were retrospectively collected through a nationwide survey. Twenty patients (11 male and nine female) had extracutaneous lesions. The median observation time was 10 years (range, 0-17). Six patients presented with symptoms at birth. The median age at diagnosis was 8.5 months (range, 0 month-13 years). Fifteen patients underwent treatment for JXG, including chemotherapy (n=11), and five did not receive treatment. All patients except one survived; 17 were disease-free and two survived with disease. One newborn-onset patient with liver, spleen, and bone marrow involvement died of the disease. Permanent sequelae included central diabetes insipidus, growth hormone deficiency, and panhypopituitarism detected at diagnosis in three, one, and two patients, respectively. Four patients had visual impairment (optic nerve compression and intraocular invasion in two each), three had epilepsy, one had mental retardation, and one had a skin scar. Eight patients who had intracranial lesions were older at diagnosis, and had a higher frequency of disease-related comorbidities and permanent sequelae than those without intracranial involvement. Patients with extracutaneous JXG had good outcomes, although those with intracranial lesions had serious permanent sequelae. Effective and safe treatment regimens for patients with intracranial JXG need to be developed.

SUN-286 Lymphocytic Hypophysitis Mimicking Tolosa Hunt Syndrome

Introduction:Lymphocytic hypophysitis often presents with headache, hypopituitarism and visual disturbance, the latter from optic nerve compression. Rarely, it can present with diplopia from cranial nerves III, IV and VI (3.7%) and cavernous sinus involvement (1).Clinical Case:A 40 year old woman presented with left eye pain, blurry vision, ptosis and diplopia for 2 days, preceded by headache for 2 weeks. Exam was remarkable for left eye ptosis, mild proptosis, downward and outward gaze and inability to adduct her left eye. Endocrinological exam revealed free T4 0.67 ng/dL (Nl 0.70 - 1.48), TSH 0.67 ng/dL (Nl 0.70–1.48), estradiol <10 pg/mL, LH 1.0 mIU/mL, FSH 6.9 mIU/mL, prolactin 23.3 ng/ml (Nl 5.2–26.5) and IGF-1 95 ng/mL (Nl 52–328). Cortisol was not assessed as patient was already on steroids. Work-up revealed atypical ANCA (1:320) but normal C-ANA (<1:20), P-ANCA (<1:20), and the rest of immune work-up was negative including ACE, ESR, CRP, ANA, serine protease and myeloperoxidase. No systemic manifestations were present concerning for systemic autoimmune disease. CSF exam was unrevealing including a normal ACE level. MRI revealed an enlarged pituitary gland with suprasellar extension containing a focal area of T2 hyperintensity and slight T2 hypointensity at the posterior aspect of the gland. There was a midline, thickened infundibulum, enhancement of both cavernous sinuses and narrowing of right internal carotid artery without occlusion. Endoscopic endonasal transsphenoidal biopsy of pituitary lesion confirmed diagnosis of lymphocytic hypophysitis and did not meet criteria for IgG4 hypophysitis. After 4 weeks of prednisone, she had significant symptomatic improvement and repeat MRI showed decreased pituitary size but persistent abnormal enhancement of the pituitary gland and cavernous sinuses.Conclusion:The atypical and variable clinical and radiological findings of lymphocytic hypophysitis can mimic other inflammatory, infiltrative lesions, pituitary tumor with apoplexy and Tolosa Hunt Syndrome. Tolosa Hunt syndrome is an idiopathic granulomatous inflammation of the cavernous sinus involving cranial nerves II to VI and often presenting with painful ophthalmoplegia. Pituitary involvement and carotid artery narrowing have been observed (2). Our case highlights a patient with cranial nerve III palsy and significant cavernous sinus involvement, clinically concerning for Tolosa Hunt syndrome, but confirmed by biopsy to be lymphocytic hypophysitis. There are no specific serum markers to distinguish lymphocytic hypophysitis from other entities and when uncertain, diagnosis is best established by biopsy.

MON-LB49 Atypical Presentation for a 5.5-cm Macroprolactinoma: Unilateral Visual Loss and Only Partial Hypopituitarism; Asymptomatic Hypogonadism

Background: Macroprolactinoma is an uncommon pituitary tumor which presents mainly in males. The usual presentation is headache, bitemporal hemianopia, and signs/symptoms of hypogonadism. Ours is a case report of 5.5 –cm macroprolactinoma presented with unilateral optic nerve atrophy and asymptomatic hypogonadism. Clinical case: A 50-year-old male with past medical history of type 2 diabetes mellitus and essential hypertension presented with progressive blurred vision of the left eye for 6 months. He was able to perceive color but had difficulty reading. There was occasional headache with left periorbital pain. He was seen by an optometrist and was found to have left optic disc atrophy with suspicion of glaucoma. Subsequent visual field test showed entire left and right superior temporal loss. MRI of the pituitary showed 5.5 x 5.6 x 5.3 cm enhancing mass centered in the sellar/suprasellar region. There was significant mass effect with compression of the optic chiasm, temporal lobe and brainstem. The patient reported mood changes, normal libido, but loss of morning erection. He has family history of pituitary macroadenoma with left optic nerve compression. On physical examination, there were left visual field defect and decreased visual acuity. There were no signs of Cushing’s syndrome, hypothyroidism, acromegaly, or hypogonadism. Laboratory tests showed prolactin of >200 ng/ml and 16,610 ng/ml after dilution (male <13), total testosterone 92 ng/dl (240-950) and free testosterone 1.20 mg/dl (4.26-16.40). Surprisingly, other pituitary hormones were normal: AM cortisol 20.3 µg/dl (6-27), GH 0.24 ng/ml (0.01-0.97), IGF-1 58 ng/ml (40-259), FSH 4 IU/l (1-18), LH 3 IU/l (1.3-9.6), TSH 1.38 µIU/ml (0.34-3), and free T4 0.8 ng/dl (0.6-1.6). The patient underwent surgery with partial resection. Pathology revealed lactotroph adenoma. Postoperative prolactin level was 11,900 ng/ml. Medical treatment with cabergoline 0.25 mg twice weekly has been started. Conclusion: Even though profoundly hypogonadal by labs, the presentation for this 5.5-cm prolactinoma was acute vision loss. The highly elevated prolactin level correlates with the size of macroadenoma. The typical presentation of local mass effect is bitemporal hemianopia, but in our case the patient presented with unilateral optic nerve atrophy. Despite a 5.5-cm lesion, there is partial hypopituitarism; hypogonadism. Based on the size, one would have expected panhypopituitarism. Given a family history of macroadenoma, there might be genetic predisposition. Molecular testing is planned.

ENT Disorders Presenting with Ophthalmological Manifestations:An Overview

Background: It is important to diagnose the condition early and manage aggressively. It is often difficult to cure orbital cellulitis due to late treatment and may cause blindness if left untreated because of optic nerve compression. Both orbital abscess and cavernous sinus thrombosis may lead to intracranial spread of infection, such as meningitis or cerebral abscess with high morbidity and possible mortality.Subjects and Methods:A total number of 124 cases of ophthalmological manifestation caused by various ENT diseases, mostly paranasaltumourextensions; nasopharyngeal tumour and furunculosis of nose were analyzed in a retrospective study in relation to their age, sex, clinical,radiological and histopathologicalprofile.Results: Direct nasal endoscopy(DNE), Fibre optic Flexible nasopharyngoscopy was Useful. HRCT scan was considered as the most dependable investigating tool. Different modalities of medical and surgical treatment have been adopted according to location and nature of diseases.Conclusion: Aclose co-operationand team effort required between otorhinolaryngologist and ophthalmologist to overcome this kind of challenges.

Successful Management of a Complex Case of Recurrent Sphenoid Sinus Mucocele with Fungal Sinusitis and Optic Nerve Compression

Successful Management of a Complex Case of Recurrent Sphenoid Sinus Mucocele with Fungal Sinusitis and Optic Nerve Compression

VISUAL IMPAIRMENT IN NASOPHARYNGEAL CARCINOMA

Introduction:&#x0D; he most common complaint in almost half of nasopharyngeal carcinoma (NPC) patients is a lump in the neck. Neurological symptoms occur less frequently, whereas blindness occurs in only less than one percent of cases.&#x0D; Case report:&#x0D; A 47-year-old male had complained about headache, nasal voice, and blindness in the right eye since a month ago. An examination found a mass in the right nasal cavity, right neck lymph nodes enlargement, damage to the right oculomotor (III), trochlear (IV), and abducens (VI) nerve, and right optic nerve (II). On funduscopy, the right macular reflex decreased. On CT scan there was a right nasopharyngeal mass extending to intracranial and right intraorbital spaces.&#x0D; Conclusion:&#x0D; There was a direct infiltration of NPC into surrounding and intracranial structures. Unilateral blindness might be caused by expansion to middle cerebral fossa and orbita. It could also be caused by optic nerve compression from surrounding tumor tissue.

Accidental Closantel Poisoning in Sheep in the State of Rio Grande do Sul - Brazil

Background: Verminosis is one of the major health problems in sheep flocks, and is one of the main causes of death in sheep worldwide. Closantel is an antiparasitic drug commonly used in sheep; however, its safety margin is narrow, and this drug may induce intoxication in animals submitted to high doses. Lesions occur mainly in the eyes, and are characterized by edema and compression of the optic nerve, retinopathy, and severe degeneration of ganglia cells. Clinical signs are pupil dilation, which often lead to permanent blindness. This work aims to report an outbreak of sheep mortality due to closantel intoxication, associated with inadequate anthelmintic administration practices.Case: An on-site visit was conducted to a sheep farm, located in the municipality of Osório, Rio Grande do Sul (RS), in which high mortality was reported. The flock consisted of approximately 300 Texel sheep, managed in an extensive grazing system. Lambs and adult animals were affected. According to the information provided by the farm owner, many animals presented clinical signs of haemonchosis, and a closantel dose of 20 mg / lamb was administered in all sheep, regardless of body weight. Lambs weighted on average 13 kg. After closantel administration, several sheep presented neurologic signs and died. At the clinical examination, sheep presented pallor of ocular mucous membranes, as well as submandibular edema. Also, 20 lambs showed signs of blindness, disorientation and bumping into objects, as well as hypothermia and lack of response to the menace reflex. Three 30 to 45-day-old male lambs that died spontaneously were submitted for necropsy. Grossly, only mild ascites was noted. Histopathological examination of the retina showed degeneration and fragmentation of photoreceptor layer as well as depletion of the inner nuclear layer, associated with pyknosis and karyorrhexis. There was also a reduction in the number of ganglia cells in the ganglion cell layer and atrophy and vacuolization in the outer plexiform layer. In the optic nerve, multifocal mild to moderate vacuolization was observed. Diffuse perineural and perivascular edema were observed in the brain, predominantly in the grey matter. In the encephalon of one of the lambs, multifocal vacuolization was observed, which was also evidenced at the junction of the white and gray matter of the telencephalon, and in the white matter of the cerebellum. In the trigeminal ganglia, moderate multifocal vacuolization was noted in the perikaryon of neurons. Furthermore, the spinal cord had moderate multifocal vacuolization at the junction of white and gray matter.Discussion: The diagnosis of closantel intoxication in sheep was based on the clinical history and histopathological findings. The association of these data is crucial to suspect and confirm the diagnosis of this type of intoxication. Closantel is an anthelmintic drug widely used in sheep, and in correct doses may be very effective, but when used in doses higher than recommended may lead to irreversible lesions. The optical damage is derived from edema which leads to degeneration of ganglia cells and injury to the optic nerve. Another proposed mechanism is related to optic nerve compression causing rupture and edema of retinal structures. Lesions tend to be dose related, and poisoning usually occurs when treating groups of animals based on the weight of the heaviest animal. Clinical signs of blindness and pupil dilatation are usually seen. There is no effective treatment for reversion of this condition; therefore, prevention based on correct calculation of anthelmintic dose is pivotal. The epidemiological examination, clinical signs and anatomopathological examination were extremely important to make the final diagnosis of this intoxication.

PRELIMINARY STUDY ON THE BLOCKADE OF AXONAL TRANSPORT BY ACTIVATED ASTROCYTES IN OPTIC NERVE HEAD UNDER CHRONIC OCULAR HYPERTENSION

Glaucoma is considered a group of neurodegenerative diseases that damage the optic disc and result in a reduction of the field of vision. High intraocular pressure-induced deformation of optic nerve head (ONH) may compress the optic nerve and affect axonal transport. This study aims to show experimental observations: the activated astrocytes under high intraocular pressure play an important role in compression of optic nerve and block of axonal transport. Four-week duration of ocular hypertension (more than 20[Formula: see text]mm Hg) rats induced by cauterizing of three episcleral vessels and administering a fluorouracil subconjunctival injection in the right eye were enrolled and the left eyes of all the rats were used as a self-control. The axonal transport of the optic nerve was examined by a confocal laser scanning microscope after intravitreally injecting rhodamine-[Formula: see text]-isothiocyanate. The morphology of the optic nerve head was examined by hematoxylin–eosin (HE) staining, immunofluorescence staining and transmission electron microscopy (TEM). The results showed transport of rhodamine-[Formula: see text]-isothiocyanate was blocked in the experimental group, and fluorescent dye accumulated around the ONH. The nucleus counts of the coronal section kidney-shaped area showed that the number of cell nucleus in experimental eye was more than that of the control according to the results of HE staining. The increased collagen fibers in ONH were observed. The density of the glial fibrillary acidic protein in experimental eyes was a little bit higher than that in the control group by quantify analysis of the expression. The obvious changes of microstructure of the ONH also were found according to the images of TEM. It can be concluded that the activated astrocytes might squeeze the optic nerve, likely leading to optic nerve distortion and axonal flow blockage.

Microbial Keratitis in Thyroid Eye Disease: Clinical Features, Microbiological Profile, and Treatment Outcome.

To report the incidence, clinical features, microbiologic profile, and risk indicators in the development of microbial keratitis in Thyroid Eye Disease (TED). All patients who were diagnosed to have TED and developed microbial keratitis between the years 2009 to 2017 at the Ophthalmic Plastic Surgery service, LV Prasad Eye Institute were included in this retrospective interventional study. The clinical features, microbiological profile, and treatment outcome of the infection were studied. Possible risk factors leading to the development of microbial keratitis were studied. A total of 1,000 patients of TED were evaluated in the 10-year period. Of the 1,000, 13 patients (14 eyes, 1.4%) were diagnosed with microbial keratitis. The average age at presentation was 44 years (range 1969 years). Of the 13 patients, 10 (77%) were men, 12 (92%) were hyperthyroid, and 12 (92%) were active (average clinical activity score 3) at presentation. Average exophthalmometry value in the involved eye was 24.75mm, and severe eyelid retraction (>2mm scleral show) was noted in 13 of 14 eyes. None of the patients had optic nerve compression. Moderate motility restriction (2 in all gazes) was noted in 6 eyes, and severe motility restriction (4 in all gazes) in 8 eyes. At presentation, 11 (85%) had visual acuity of counting fingers at 1 meter or less, The mean follow up from the time of presentation was 18.3 months (range 566 months). Majority of the eyes (8/14) presented with severe infection (panophthalmitis with microbial keratits = 1, total corneal infiltrate with/without melt = 4, severe thinning/perforation = 4). Microbiological work up of 14 eyes revealed presence of gram-negative bacteria in 5 eyes which included Escherichia coli, Pseudomonas sp., and Acinetobacter sp., and gram-positive bacteria in 4 eyes including Streptococcus pneumoniae, Corynebacterium sp., and Staphylococcus sp. Three eyes revealed a mixed infection of E. coli with Alternaria sp, and E. coli with Corynebacterioum amycolatum while 1 had Corynebacterium pseudodiptheriticum, and S. pneumoniae. Two eyes of the bilateral case showed no growth. Antibiotic susceptibility revealed 6 of the 7 gram-negative isolates were multidrug resistant, whereas the gram-positive isolates were susceptible to most drugs tested. Surgical procedures required were tarsorrhaphy in 7 eyes, tissue adhesive with bandage contact lens in 4, evisceration in 4, levator recession in 2, 3-wall orbital decompression in 2, and penetrating keratoplasty in 1 eye. The visual acuity at presentation was counting fingers or worse in 10/14 eyes. Posttreatment, 10 eyes achieved resolution of infiltrate (with visual improvement in 2), and 4 required evisceration. In the authors large series of TED, microbial keratitis was noted in 1.3% of patients presenting to a tertiary eye center. Majority presented with advanced diseases and ended with a poor outcome. Gram-negative isolates showed multidrug resistance. An association with early phase of active TED (CAS 3 or more), severe eyelid retraction, and moderate-severe motility restriction is suggested.Microbial Keratitis occurs in 1.3% cases of Thyroid Eye Disease. It is more common in men, and in active disease. The microbiological spectrum and possible clinical risk factors are presented.