Compressive Optic Neuropathy Research Articles

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface.

Teprotumumab, a monoclonal antibody that blocks the insulin-like growth factor-1 receptor, has recently been approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Since its approval, aside from data on the safety and clinical efficacy of teprotumumab from Phase-2 and Phase-3 trials, only a handful of reports have been published regarding its use in the wider population. In this review, we briefly describe the mechanism of action of teprotumumab and review the literature to provide an overview of published clinical experience. This information was used to provide recommendations for patient selection, management of patient expectations, infusion details and site options, tips to optimize the authorization process, and how to monitor and mitigate side effects. A systemic review of the literature was performed regarding teprotumumab, focusing on its mechanisms of action and published reports on its use on patients with TED. A review of Embase, Medline (PubMed), Web of Science, and Google Scholar was conducted. Clinical experience following the approval of teprotumumab has confirmed its efficacy in reducing inflammation and proptosis in patients with acute TED (<2 years). The reduction in proptosis occurs due to a reduction in orbital fat and muscle volume. Furthermore, there is evidence for its use in patients with compressive optic neuropathy. There are also reports that show its efficacy in reducing proptosis, inflammation, and diplopia in patients with chronic TED (>2 years). Teprotumumab was associated with side effects, such as muscle spasm, hearing loss, and hyperglycemia. To date, 2 case reports have shown a possible association with flares of inflammatory bowel disease. Teprotumumab is a powerful therapeutic option for the treatment of TED. Clinical experience following FDA approval has demonstrated efficacy in treating patients with acute and chronic TED. It is the only therapeutic option that has been shown to reduce orbital soft tissue expansion in TED. However, it is expensive, and sometimes, obtaining insurance authorization can be time consuming and difficult. Further work will reveal its full side effect profile and help to establish its role in the armamentarium used to treat TED.

Diagnostic assessment of glaucoma and non-glaucomatous optic neuropathies via optical texture analysis of the retinal nerve fibre layer.

The clinical diagnostic evaluation of optic neuropathies relies on the analysis of the thickness of the retinal nerve fibre layer (RNFL) by optical coherence tomography (OCT). However, false positives and false negatives in the detection of RNFL abnormalities are common. Here we show that an algorithm integrating measurements of RNFL thickness and reflectance from standard wide-field OCT scans can be used to uncover the trajectories and optical texture of individual axonal fibre bundles in the retina and to discern distinctive patterns of loss of axonal fibre bundles in glaucoma, compressive optic neuropathy, optic neuritis and non-arteritic anterior ischaemic optic neuropathy. Such optical texture analysis can detect focal RNFL defects in early optic neuropathy, as well as residual axonal fibre bundles in end-stage optic neuropathy that were indiscernible by conventional OCT analysis and by red-free RNFL photography. In a diagnostic-performance study, optical texture analysis of the RNFL outperformed conventional OCT in the detection of glaucoma, as defined by visual-field testing or red-free photography. Our findings show that optical texture analysis of the RNFL for the detection of optic neuropathies is highly sensitive and specific.

Metabolic disorders in hereditary optic neuropathies

To compare the content of folic acid, vitamin B12 and homocysteine in the blood serum of patients with Leber's hereditary optic neuropathy (LHON) and autosomal recessive optic neuropathy (ARON), optic neuropathy of other genesis, and the comparison group. The study involved 58 patients with LHON and ARON, the control group of 49 patients with ischemic, inflammatory, traumatic and compressive optic neuropathies, and the comparison group of 20 healthy volunteers. A decrease in blood folic acid levels was revealed (4.0±1.6 ng/mL) in patients with HON compared to the control group (p=1.3·10-8) and the comparison group (p=1·10-17). The content of vitamin B12 in patients with HON was 380.8±168.1 pg/mL, which was significantly lower than in the comparison group (p=0.0001). The homocysteine content was 14.1±5.6 μmol/L in patients with HON, which was significantly higher than in the control group (p=0.0007) and the comparison group (p=0.000003). At the same time, an increase in homocysteine level of more than 10 µmol/L was revealed in 75% of patients with HON. Similar metabolic disorders were found in groups with various mutations in mitochondrial and nuclear DNA. Patients with HON showed marked decrease in the levels of folic acid and vitamin B12, as well as hyperhomocysteinemia. It is very important to identify the causes of metabolic disorders in order to determine the role of folate deficiency in the development of HON, as well as the possibility of its pharmacological treatment.

Compression optic and oculomotor neuropathy caused by misdiagnosed sphenoid sinus mucocele

We herein describe the case of a 60-year-old man who complained of headache and inability to open his left eye. Four years ago, he was admitted to a hospital because of the loss of vision in his left eye. Without adequate radiological examination, he was misdiagnosed with ischemic optical neuropathy and treated with glucocorticoid and neurotrophic drugs, but his vision did not improve. After sphenoidostomy under local anesthesia in time, his headache disappeared and his left eye could be opened immediately. We herein report this case to emphasize the relationship between the optic and oculomotor neuropathy and paranasal sinus disease.

Two Patients of Unilateral Compressive Optic Neuropathy and Homonymous Hemianopia After Intracerebral Hemorrhage with Midline Shift

Two Patients of Unilateral Compressive Optic Neuropathy and Homonymous Hemianopia After Intracerebral Hemorrhage with Midline Shift

Endoscopic optic nerve decompression in traumatic optic neuropathy: our experience in a tertiary care centre

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Traumatic optic neuropathy (TON) a vision threatening disorder requires early diagnosis and prompt treatment. High dose steroid injections, optic nerve decompression or combined therapy are the available current treatment options. This study aims to determine the visual outcome with transnasal endoscopic optic nerve decompression in patients with TON having no improvement in vision despite high dose steroids.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A prospective study was conducted at the department of ENT, government medical college Kozhikode; on patients who presented with loss of vision following history of trauma. All patients suspected of compressive optic neuropathy received injection methyl prednisolone (30 mg/kg/day) with assessment of vision and HRCT scan. Patients with deterioration or no improvement in vision despite high steroid therapy were taken up for trans-nasal endoscopic optic nerve decompression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; In our study 19 patients with TON underwent trans-nasal endoscopic optic nerve decompression. 11(57.9%) patients had improvement of vision, 7 (36.8%) patients had no improvement of vision and 1 (5.3%) patient had worsening of vision. The visual improvement was seen in 8 (80%) patients when treatment was initiated within 7 days and in only 3(33.3%) patients when treatment was initiated after 7 days. The visual acuity at presentation and time interval between trauma and intervention are factors that determine better visual outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The decreased visual acuity in TON requires prompt treatment. High dose steroid must be started at once when it is suspected or diagnosed. The timely surgical intervention with trans-nasal endoscopic optic nerve decompression is a relatively safe and effective technique enabling better visual prognosis.&lt;/p&gt;

Successful Treatment of Bilateral Compressive Optic Neuropathy With Teprotumumab

Successful Treatment of Bilateral Compressive Optic Neuropathy With Teprotumumab

The Role of Oxidative Stress and Therapeutic Potential of Antioxidants in Graves' Ophthalmopathy.

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO.

Orbital Radiation for Thyroid Eye Disease: A Report by the American Academy of Ophthalmology

To review the current literature on the safety and efficacy of orbital radiation for the management of thyroid eye disease (TED). A literature search was conducted last in February 2021 of the PubMed database to identify all articles published in the English language on original research that assessed the effect of orbital radiation on TED. The search identified 55 articles, and 18 met the inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study, and all of them were rated level III. Two large retrospective studies demonstrated the efficacy of radiation treatment, with or without corticosteroid use, in preventing or treating compressive optic neuropathy (CON). Three studies highlighted the role of orbital radiation therapy (RT) to facilitate the tapering of corticosteroids. Several other studies showed a possible role for RT to improve diplopia and soft tissue signs. Although no level I or level II evidence exists, the best available evidence suggests that orbital radiation, used with or without corticosteroids, is efficacious in preventing CON, improving motility restriction, and decreasing clinical activity in TED. Orbital radiation also may facilitate a corticosteroid taper. Together, these studies show that RT seems to modify the active phase of TED. Short-term risks of orbital radiation are minor, but long-term outcome data are lacking.

Neuro-Ophthalmological Optic Nerve Cupping: An Overview

Optic nerve cupping or enlargement of the cup-to-disc ratio is widely recognized as a feature of glaucoma, however it may also occur in non-glaucomatous optic neuropathies. The most well-recognized non-glaucomatous optic neuropathies that cause cupping include compressive optic neuropathies, arteritic anterior ischemic optic neuropathies, hereditary optic neuropathies, and optic neuritis. Cupping is thought to consist of two main components: prelaminar and laminar thinning. The former is a shallow form of cupping and related to loss of retinal ganglion cells, whereas the latter involves damage to the lamina cribrosa and peripapillary scleral connective tissue. Differentiating glaucomatous and non-glaucomatous optic nerve cupping remains challenging even for experienced observers. Classically, the optic nerve in non-glaucomatous causes has pallor of the neuroretinal rim, but the optic nerve should not be examined in isolation. The patient’s medical history, history of presenting illness, visual function (visual acuity, color vision and visual field testing) and ocular examination also need to be considered. Ancillary testing such as optical coherence tomography of the retinal nerve fiber layer and ganglion cell layer-inner plexiform layer may also be helpful in localizing the disease. In this review, we review the non-glaucomatous causes of cupping and provide an approach to evaluating a patient that presents with an enlarged cup-to-disc ratio.

An atypical case of compressive optic neuropathy and cranial nerve 6th palsy caused by a cholesterol granuloma

An atypical case of compressive optic neuropathy and cranial nerve 6th palsy caused by a cholesterol granuloma

Anomalous Course of the Internal Carotid Artery Resulting in Optic Nerve Compression

Compression of the optic nerve by the internal carotid artery can occur due to their proximity as they exit the cavernous sinus. This report details a case of unilateral compressive optic neuropathy resulting from an anomalous course of the internal carotid artery. It presents optical coherence tomography scans, Humphrey visual field results, and magnetic resonance images, as well as reviews other causes of optic neuropathy that can have a similar clinical presentation.

Relationship between Serum Thyroid-stimulating Hormone Receptor Autoantibodies and Activity and Severity of Thyroid Eye Disease

Purpose: To study the relationship between the levels of serum thyroid-stimulating hormone (TSH)-receptor autoantibodies (TRAbs) and thyroid eye disease (TED) activity and severity scores.Methods: A cross-sectional study was performed. The medical records of 315 patients diagnosed with TED between March 2014 and December 2019 were reviewed. The clinical activity score (CAS) was used to assess TED activity and a modified NOSPECS score was used for severity grading. The serum TRAb level was measured using two assays: a TSHR binding inhibitory immunoglobulin (TBII) assay and thyroid stimulating immunoglobulin (TSI) bioassay.Results: The TBII and TSI assay results were significantly positively correlated with the CAS (R = 0.113 and 0.211, respectively; &lt;i&gt;p&lt;/i&gt; &lt; 0.05), modified NOSPECS score (R = 0.173 and 0.316, respectively; &lt;i&gt;p&lt;/i&gt; &lt; 0.05), and proptosis (R = 0.136 and 0.167, respectively; &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Both assays demonstrated significant differences in the level of TRAb between patients with and without compressive optic neuropathy or corneal epithelial defects.Conclusions: The levels of TRAbs according to both TBII and TSI assays showed significant correlations with clinical signs of corneal involvement, optic neuropathy, and TED activity and severity.

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease.

Thyroid eye disease (TED; also known as thyroid-associated ophthalmopathy) is an autoimmune condition with disabling and disfiguring consequences. Teprotumumab is the first and only medication approved by the United States Food and Drug Administration for the treatment of TED. We review the efficacy and safety of teprotumumab in TED, highlighting results from the 2 randomized, double-masked, placebo-controlled trials. Post-approval case reports of teprotumumab use in patients with compressive optic neuropathy (CON) and inactive TED were similarly favorable to those from the trials. The preliminarily results of teprotumumab for CON and inactive TED should be investigated in formal clinical trials. Teprotumumab should be avoided in pregnancy. Evidence also suggests that teprotumumab may exacerbate pre-existing inflammatory bowel disease, worsen hyperglycemia, and be associated with hearing impairment. Patients at risk for these adverse events need to be closely monitored with baseline and periodic assessments.

Population-Based Incidence and Outcomes of Compressive Optic Neuropathy

Prior studies on compressive optic neuropathy (CON) have come from large tertiary centers, which may contain referral bias toward more severe or atypical disease. To our knowledge, there are no studies to determine the population-based etiologies and clinical outcomes of compressive optic neuropathy (CON). This study aims to bridge that gap using the Rochester Epidemiology Project database. Retrospective, population-based cohort. Medical records of all residents living in Olmsted County, Minnesota, from January 1, 2000, through December 31, 2018, were screened for CON. Demographic and clinical information were collected before and after treatment. Twenty-three patients had a confirmed diagnosis of CON during our study period, which provided an overall incidence of 1.14 per 100 000 per year. Average age at onset of CON was 51 years (SD 24), and 39% were male. The most common etiologies were pituitary adenoma and meningioma. There was significant improvement in visual fields (P < .003) but not in visual acuity (P=.08) after patients underwent treatment for CON. There was also a significant relationship between the time until treatment and the degree of visual field improvement at follow-up (Pearson correlation rho=-0.58, P < .047). To our knowledge, this study provides the first population-based incidence of CON. The finding that earlier treatment leads to better visual outcomes stresses the importance of having CON on the differential diagnosis of patients with optic neuropathy.

Isolated intracranial Rosai–Dorfman disease presenting as compressive optic neuropathy

A 56-year-old female presented with bilateral progressive painless loss of vision. Examination showed a relative afferent pupillary defect in the left eye with temporal disc pallor and visual field loss. MRI (magnetic resonance imaging) brain revealed a suprasellar mass for which mass excision via frontotemporal craniotomy was done. Histopathology examination of the mass revealed foamy histiocytes with emperipolesis, S-100 marker was positive. Thus, a diagnosis of Rosai–Dorfman disease (RDD) was made. Our case describes a rarely found isolated intracranial RDD presenting as compressive optic neuropathy and vision loss in an elderly female.

Peripapillary Microvascularization Analysis Using Swept-Source Optical Coherence Tomography Angiography in Optic Chiasmal Compression.

Purpose To evaluate the vessel density (VD) of the radial peripapillary capillary (RPC) network using swept-source optical coherence tomography angiography (SS-OCTA) “en face” images of eyes with chiasmal compression caused by brain tumors before and after decompressive surgery compared with healthy controls. Methods A cross-sectional study was conducted in 12 patients with chiasmal compression confirmed by neuroimaging. Sixteen healthy participants were also included. All patients with chiasmal compression underwent a neuro-ophthalmological examination one week before and 6 months after brain surgery, including static automated perimetry as well as measurement of the thickness of the retinal nerve fiber layer (RNFL) and the ganglion cell complex (GCC) with spectral-domain optical coherence tomography (SD-OCT). Based on this neuro-ophthalmological examination, the presence of an optic neuropathy (ON) was evaluated. Peripapillary VD was obtained in four sectors on a 6 × 6 mm SS-OCTA image using the Cirrus Plex Elite 9000. Results Baseline average VD was significantly lower in patients with chiasmal compression and ON than in controls (median: 55.62; interquartile range (IQR): 2.96 vs. 58.53; IQR: 2.02; p=0.003). This decrease was also found in the temporal, superior, and nasal sectors. Average postoperative VD was decreased in patients with chiasmal compression compared with average preoperative VD (median: 56.16; IQR: 4.07 vs. 57.48; IQR: 3.83; p=0.004). Preoperative VD was significantly correlated with RNFL, GCC thickness, and visual field defects. Conclusions The VD of the RPC network was decreased in chiasmal compressive ON, and it was further decreased at 6 months after decompressive surgery.

Detection of Optic Disc Abnormalities in Color Fundus Photographs Using Deep Learning.

To date, deep learning-based detection of optic disc abnormalities in color fundus photographs has mostly been limited to the field of glaucoma. However, many life-threatening systemic and neurological conditions can manifest as optic disc abnormalities. In this study, we aimed to extend the application of deep learning (DL) in optic disc analyses to detect a spectrum of nonglaucomatous optic neuropathies. Using transfer learning, we trained a ResNet-152 deep convolutional neural network (DCNN) to distinguish between normal and abnormal optic discs in color fundus photographs (CFPs). Our training data set included 944 deidentified CFPs (abnormal 364; normal 580). Our testing data set included 151 deidentified CFPs (abnormal 71; normal 80). Both the training and testing data sets contained a wide range of optic disc abnormalities, including but not limited to ischemic optic neuropathy, atrophy, compressive optic neuropathy, hereditary optic neuropathy, hypoplasia, papilledema, and toxic optic neuropathy. The standard measures of performance (sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC-ROC)) were used for evaluation. During the 10-fold cross-validation test, our DCNN for distinguishing between normal and abnormal optic discs achieved the following mean performance: AUC-ROC 0.99 (95 CI: 0.98-0.99), sensitivity 94% (95 CI: 91%-97%), and specificity 96% (95 CI: 93%-99%). When evaluated against the external testing data set, our model achieved the following mean performance: AUC-ROC 0.87, sensitivity 90%, and specificity 69%. In summary, we have developed a deep learning algorithm that is capable of detecting a spectrum of optic disc abnormalities in color fundus photographs, with a focus on neuro-ophthalmological etiologies. As the next step, we plan to validate our algorithm prospectively as a focused screening tool in the emergency department, which if successful could be beneficial because current practice pattern and training predict a shortage of neuro-ophthalmologists and ophthalmologists in general in the near future.

Bruch Membrane Opening Minimum Rim Width and Retinal Nerve Fiber Layer Helps Differentiate Compressive Optic Neuropathy From Glaucoma

To compare optical coherence tomography-measured Bruch membrane opening minimum rim width (MRW), peripapillary retinal nerve fiber layer (pRNFL) measurements, and MRW:pRNFL ratios in eyes with compressive optic neuropathy (CON) and glaucoma and controls, and evaluate the ability of these parameters to differentiate CON from glaucoma. Prospective, cross-sectional study. Setting: Single-center tertiary hospital and outpatient clinic. One hundred fifteen eyes of 77 participants, 34 with CON from chiasmal lesions, 21 with glaucoma, and 22 healthy controls. Optical coherence tomography-measured MRW, pRNFL, and MRW:pRNFL ratios for each optic disc sector and global average. MRW, pRNFL, and MRW:pRNFL ratios compared using generalized estimated equations. Area under the receiver operating characteristic curve and positive and negative likelihood ratios were calculated. MRW and pRNFL measurements were significantly reduced in CON and glaucoma compared with controls. In glaucoma, MRW was thinner than in CON in the global, inferotemporal, superonasal, inferonasal, and vertical average measurements, but a significant overlap was observed in many parameters. MRW:pRNFL ratios increased the ability to discriminate between CON and glaucoma, as shown by the high area under the receiver operating characteristic curve, high positive likelihood ratios, and low negative likelihood ratios, especially in the nasal disc sector and the nasal and temporal average. MRW measurements alone cannot reliably distinguish CON from glaucoma, but the combination of MRW, pRNFL, and MRW:pRNFL ratios significantly improves accuracy. When comparing the 2 conditions, MRW:pRNFL ratios yielded higher area under the receiver operating characteristic curve and positive and negative likelihood ratios, suggesting this parameter may be helpful in clinical practice.

Extrathyroidal Manifestations of Thyroid Disease: Graves Eye Disease.

Graves disease is an autoimmune disorder caused by the breakdown of immune tolerance to thyroid antigens against the TSH receptor. In approximately 25% of patients, an inflammatory condition, Graves eye disease (GED), affects the orbital soft tissues. About 60% of patients develop mild symptoms including fat expansion and inflammation of the levator muscle complex with resultant proptosis, eyelid retraction, and exposure of the globe. The remaining patients experience enlargement of one or more of the extraocular muscles, leading to conjunctival and eyelid edema and congestion, restricted ocular movement with resultant diplopia, and optic nerve compression leading to compressive optic neuropathy.