Idiopathic Intracranial Hypertension in Female-to-Male Transgender Patients on Exogenous Testosterone Therapy.

PURPOSE: To present four female-to-male (FTM) transgender patients on testosterone therapy diagnosed with idiopathic intracranial hypertension (IIH). METHODS: The authors report 4 consecutive FTM transgender patients on exogenous testosterone diagnosed with IIH at a single institution. RESULTS: Patient 1 presented with progressive blurred vision and a central scotoma 10 weeks after starting testosterone cypionate injections for hormonal gender transition. Bilateral grade 5 papilledema was present; the patient underwent bilateral optic nerve sheath fenestration with improved vision and resolution of edema. Patient 2 presented with transient vision loss, pulsatile tinnitus, and blurred vision 13 months after starting testosterone cypionate injections. The patient had grade 4 and 3 disc edema of the right and left eyes, respectively. Patient 3 presented with headaches and pulsatile tinnitus and was on testosterone injections at an unknown dose. The examination revealed grade 1 and 2 disc edema of the right and left eyes, respectively. Patient 4 presented with decreased vision, transient visual obscurations, and daily migraines while using topical testosterone gel every other day. Color vision was reduced, and lumbar puncture revealed elevated intracranial pressure. All patients had neuroimaging findings consistent with increased intracranial pressure. CONCLUSIONS: Testosterone therapy plays an essential role in FTM hormonal transitioning and may play a role in IIH. Patients undergoing testosterone therapy for gender transition should be informed of the possibility of developing IIH while on treatment, with obesity possibly increasing this risk. Comprehensive eye examinations should be considered in these patients before initiating hormone therapy.

Papilledema and idiopathic intracranial hypertension due to the possible potentiation of ATRA by posaconazole in a case of acute promyelocytic leukemia.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) (pseudotumor cerebri) is a rare side effect of all-trans retinoic acid (ATRA). IIH cases have been observed after the concomitant use of ATRA with azole group antimicrobials such as fluconazole and voriconazole. Here, we discuss about the diagnosis and treatment process of the IIH emerging in a young acute promyelocytic leukemia (APL) case with the ATRA impact, which can be increased by posaconazole. CASE: A 19-year-old male patient was diagnosed with APL. Headache and blurred vision were developed on the 12th day of the AIDA (ATRA, 45 mg/m2/day, oral and idarubicin 12 mg/m2, on days 2, 4, 6, 8, intravenous) protocol and posaconazole proflaxis. He was diagnosed IIH along with the existing eye findings and imagings. MANAGEMENT & OUTCOME: ATRA treatment and posaconazole were interrupted. Systemic acetazolamide and dexamethasone treatment were initiated. After significant clinical response was observed, ATRA treatment was resumed without posaconazole and a similar clinical condition did not recur. DISCUSSION: The combined use of ATRA and azole group drugs increases the risk of developing IIH. Patients with APL who developed IIH during the concomitant use of ATRA and fluconazole or voriconazole have been reported. To the best of our knowledge, our case is the first APL case with a IIH who treated with ATRA-based therapy and used posaconazole. In case of development of side effects, drugs should be interrupted and this combination should be avoided if possible after appropriate approach and clinical improvement.

Ocular Adverse Effects of Amiodarone: A Systematic Review of Case Reports.

SIGNIFICANCE: Amiodarone is an excellent antiarrhythmic medication; however, it has numerous systemic and ocular adverse effects. PURPOSE: We aimed to improve our understanding of amiodarone and its ocular adverse effects by performing a systematic review and meta-analysis of published case reports. METHODS: This systematic review was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We used the MEDLINE database, primarily through PubMed, and used keywords (amiodarone, eye, eye diseases, visual/ocular adverse effects/manifestations) to identify case reports of ocular adverse effects after amiodarone use. The initial search resulted in 92 total case reports. However, after excluding nonrelevant case reports, 25 cases were selected for the final analysis. RESULTS: Among the patients in the 25 case reports, 18 were male (72%), and the median age was 66 ± 9.9 years. In 15 cases (60%), the patients reported halos around light and/or decrease in vision after amiodarone use. The most common ophthalmic examination findings were cornea verticillata/vortex keratopathy in 19 cases (76%), followed by different patterns of papilledema and retinal hemorrhages in 5 cases (20%). Discontinuation of amiodarone was the most common intervention, followed by application of topical heparin. Outcomes among case reports were variable. CONCLUSIONS: Cornea verticillata/vortex keratopathy was the most common ocular adverse effect in cases where amiodarone was administered. Early recognition of amiodarone-induced ocular adverse effects is imperative to prevent worsening keratopathy or uncommon adverse effects. Collaboration between physicians prescribing amiodarone-to recognize the ocular symptoms-and referral to eye care physicians are important.

Inhibition of Atypical Protein Kinase C Reduces Inflammation-Induced Retinal Vascular Permeability.

Changes in permeability of retinal blood vessels contribute to macular edema and the pathophysiology of numerous ocular diseases, including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Vascular endothelial growth factor (VEGF) induces retinal permeability and macular thickening in these diseases. However, inflammatory agents, such as tumor necrosis factor-α (TNF-α), also may drive vascular permeability, specifically in patients unresponsive to anti-VEGF therapy. Recent evidence suggests VEGF and TNF-α induce permeability through distinct mechanisms; however, both require the activation of atypical protein kinase C (aPKC). We provide evidence, using genetic mouse models and therapeutic intervention with small molecules, that inhibition of aPKC prevented or reduced vascular permeability in animal models of retinal inflammation. Expression of a kinase-dead aPKC transgene, driven by a vascular and hematopoietic restricted promoter, reduced retinal vascular permeability in an ischemia-reperfusion model of retinal injury. This effect was recapitulated with a small-molecule inhibitor of aPKC. Expression of the kinase-dead aPKC transgene dramatically reduced the expression of inflammatory factors and blocked the attraction of inflammatory monocytes and granulocytes after ischemic injury. Coinjection of VEGF with TNF-α was sufficient to induce permeability, edema, and retinal inflammation, and treatment with an aPKC inhibitor prevented VEGF/TNF-α-induced permeability. These data suggest that aPKC contributes to inflammation-driven retinal vascular pathology and may be an attractive target for therapeutic intervention.

Effect of acute and chronic aldosterone exposure on the retinal pigment epithelium-choroid complex in rodents.

Preclinical and clinical evidences show that aldosterone and/or mineralocorticoid receptor (MR) over-activation by glucocorticoids can be deleterious to the retina and to the retinal pigment epithelium (RPE)-choroid complex. However, the exact molecular mechanisms driving these effects remain poorly understood and pathological consequences of chronic exposure of the retina and RPE/choroid to aldosterone have not been completely explored. We aimed to decipher the transcriptomic regulation in the RPE-choroid complex in rats in response to acute intraocular aldosterone injection and to explore the consequences of systemic chronic aldosterone exposure on the morphology and the gene regulation in RPE/choroid in mice. High dose of aldosterone (100 nM) was intravitreously injected in Lewis rat eyes in order to yield an aldosterone dose able to induce a molecular response at the apical side of the RPE-choroid complex. The posterior segment morphology was evaluated in vivo using optical coherence tomography (OCT) before and 24 h after aldosterone injection. Rat RPE-choroid complexes were used for RNA sequencing and analysis. Uninephrectomy/aldosterone/salt (NAS) model was created in wild-type C57BL/6 mice. After 6 weeks, histology of mouse posterior segments were observed ex vivo. Gene expression in the RPE-choroid complex was analyzed using quantitative PCR. Acute intravitreous injection of aldosterone induced posterior segment inflammation observed on OCT. RNA sequencing of rat RPE-choroid complexes revealed up-regulation of pathways involved in inflammation, oxidative stress and RNA procession, and down-regulation of genes involved in synaptic activity, muscle contraction, cytoskeleton, cell junction and transporters. Chronic aldosterone/salt exposure in NAS model induces retinal edema, choroidal vasodilation and RPE cell dysfunction and migration. Quantitative PCR showed deregulation of genes involved in inflammatory response, oxidative stress, particularly the NOX pathway, angiogenesis and cell contractility. Both rodent models share some common phenotypes and molecular regulations in the RPE-choroid complex that could contribute to pachychoroid epitheliopathy in humans. The difference in inflammatory status relies on different intraocular or systemic route of aldosterone administration and on the different doses of aldosterone exposed to the RPE-choroid complex.

Heavy and standard silicone oil: intraocular inflammation.

PURPOSE: Proliferative vitreoretinopathy in the inferior retina remains clinically challenging. Heavier-than-water intraocular tamponades have been developed to improve inferior tamponading properties, and their chemical compositions have been substantially improved over the years, in parallel with developments in vitrectomy instrumentation and surgical techniques. Herein we present an updated review of the clinical use of standard formulations and HSO, focusing on analysis of the intraocular inflammation associated with endotamponade agents, and comparison of the adverse effects of these agents on the physical and biological properties of the eye. METHODS: A detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Fifty-eight articles matched our inclusion criteria that were included in this systematic review. RESULTS: Perfluorocarbon liquids and partially fluorinated alkanes are associated with tamponade emulsification, intraocular inflammation, and rises in intraocular pressure, but these associations are not as strong when these substances are mixed with a heavy silicone oil (HSO). Two recently approved heavy silicone oil tamponades, Oxane HD and Densiron 68, are now available for use in clinical practice. While the complication spectrum of the new generation of these HSOs seems to be similar to that of conventional silicone oil tamponades, they provide better support for the inferior retina and the posterior pole. CONCLUSION: Both regular and heavy silicone oils usually yield good success rates in cases of complicated retinal detachment. Decisions as to whether to utilize heavy or regular silicone oil should be made on a case-by-case basis.

Fulminant bilateral papilloedema during low-dose steroid taper in a child with systemic idiopathic arthritis treated with tocilizumab.

Systemic juvenile idiopathic arthritis (SJIA) is one of the most severe forms of arthritis that affects children younger than 16 years of age at onset. SJIA often requires corticosteroids to control the inflammation. However, long-term corticosteroid use may have adverse effects, including intracranial hypertension (IH). Biologic therapies have been used as corticosteroid sparing agents. We report the first case of a child with steroid-dependent SJIA treated with tocilizumab, an IL-6 receptor monoclonal antibody, who developed fulminant IH, bilateral papilloedema and vision loss when oral prednisone was weaned from 2 to 1 mg per day. Despite repeated lumbar punctures and high dose acetazolamide, he required urgent unilateral optic nerve sheath fenestration (ONSF). This endoscopic surgical intervention released the pressure exerted by the cerebrospinal fluid on the optic nerve and stopped the progression of vision loss. Nine weeks after the diagnosis of bilateral papilloedema, his vision was completely restored in one eye and partially recovered in the contralateral one. Long-term treatment with corticosteroids even at very low dose and tocilizumab may predispose to severe IH, papilloedema and vision loss. The role that tocilizumab might have played in this case in unclear. Early recognition and prompt treatment of papilloedema is crucial in avoiding permanent vision loss. Fulminant papilloedema in an immunocompromised child carries additional significant challenges. Early ONSF is a safe and effective intervention in refractory papilloedema. Children with severe papilledema secondary to IH should be managed by a multidisciplinary team in tertiary centres.

Sildenafil-related cerebral venous sinus thrombosis and papilledema: a case report of a rare entity.

We present a rare case of cerebral venous sinus thrombosis associated with long-term and high-dose use of sildenafil. A 29-year-old man was referred to our neuroophthalmology clinic for bilateral visual deterioration and severe headache. He had stage 2 papilledema and other clinical and neurological examinations were normal. He had used the drug for nearly 2 years, two to three times a day. All laboratory parameters including blood count cell, coagulation panels, and genetic tests including methylene-tetrahydrofolate reductase and factor V Leiden mutation were unremarkable. The brain magnetic resonance imaging result confirmed transverse cerebral venous sinus thrombosis (CVST). The opening pressure of cerebrospinal fluid (CSF) was 43 cm H2O with normal biochemistry and no cells. Clinicians must be aware of the possibility of CVST when the patient uses sildenafil.

Linezolid induced retinopathy.

PURPOSE: While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been investigated. Here, we report a case of retinopathy demonstrated by multifocal electroretinogram (mfERG) in a linezolid-treated patient. METHOD AND RESULTS: A 61-year-old man with extensively drug-resistant pulmonary tuberculosis treated with linezolid for 5 months presented with painless loss of vision in both eyes. The patient's best corrected visual acuity was 20/50 in the right eye and 20/100 in the left eye. Fundus examination revealed mild disc edema, and color vision was defective in both eyes. Humphrey visual field tests showed a superotemporal field defect in the right eye and central and pericentral field defect in the left eye. Optical coherence tomography (OCT) revealed only mild optic disc swelling. In mfERG, central amplitudes were depressed in both eyes. Four months after the cessation of linezolid, visual acuity was restored to 20/20 right eye and 20/25 left eye. The color vision and visual field had improved. The OCT and mfEFG findings improved as well. CONCLUSIONS: Although the clinical features were similar to linezolid-induced optic neuropathy, the mfERG findings suggest the possibility of a retinopathy through cone dysfunction.

Papillophlebitis associated with the use of oral contraceptive: a case report.

We present a 20-year-old female patient with papillophlebitis in the right eye. Minimal expansion of the blind spot and nasal peripheral defects in the right eye visual field were detected. The patient was using ethinyl estradiol-cyproterone acetate for ovarian cyst and menstrual irregularity. An improvement in the patient's visual field began within a week after cessation of ethinyl estradiol-cyproterone acetate. Ophthalmoscopic findings resolved completely in the sixth week. This situation suggests that female sex hormones or thromboembolic process caused by them may be responsible for the pathogenesis of papillophlebitis. But the exact mechanism in the pathogenesis of papillophlebitis is still controversial.

Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation.

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

Toxic optic neuropathy in the setting of docetaxel chemotherapy: a case report.

BACKGROUND: To describe the first reported case of toxic optic neuropathy secondary to docetaxel (Taxotere®) chemotherapy. CASE PRESENTATION: A 53-year-old female presented with predominantly unilateral visual loss, but extensive bilateral visual field defects and bilateral optic nerve head swelling 2 weeks after first dose of docetaxel (Taxotere®) and trastuzumab (Herceptin®) chemotherapy for a left sided node-positive, HER2 positive breast cancer. Extensive investigation ruled out other causes of optic neuropathy. She was treated with high dose corticosteroids intravenously for 1 week then a tapering oral dose over 8 weeks. Visual field defects gradually resolved and visual acuity improved. Docetaxel chemotherapy was discontinued but targeted therapy with trastuzumab continued without further complication. CONCLUSION: Docetaxel can cause a toxic optic neuropathy possibly due to an ischemic or neurotoxic mechanism at the optic nerve head. With cessation of docetaxel therapy and treatment with systemic corticosteroids, visual recovery can occur without significant residual visual deficit.

Bilateral optic neuropathy and permanent loss of vision after treatment with amiodarone.

Amiodarone is a commonly prescribed and one of the most effective anti-arrhythmic drugs available. However, its use is limited by serious toxic adverse effects including optic neuropathy. Previously, amiodarone-associated optic neuropathy has been reported at an incidence of 1.3%-1.8%. Nearly, one-third of patients with amiodarone-induced toxic optic neuropathy are asymptomatic and typically visual acuity improves after drug cessation. We describe the case of a 75-year-old woman who experienced severe optic neuropathy with bilateral optic disc edema and hemorrhages, irreversible loss of vision, and severe defects in visual fields after 1.5 months use of amiodarone. The optic disc edema resolved promptly after discontinuation of the drug, but the patient remained blind permanently. This is the first report of only 6.5 weeks of amiodarone treatment resulting in bilateral optic neuropathy with bilateral and irreversible loss of vision. To ideally establish a connection between amiodarone and optic neuropathy, re-exposure of the patient to the drug should reproduce the symptoms. As a limitation of the study, this was not done in the present case because it would have been unethical. The worldwide growth of the elderly population in number is expected to increase age-related conditions including cardiac diseases. The use of cardiovascular drugs, also anti-arrhythmic agents such as amiodarone, may increase. Thus, clinicians need to be aware of the possibility of drug-induced toxic optic neuropathy, especially if a patient receiving a regimen of amiodarone complains of visual problems.

Bilateral optic disc oedema and associated optic neuropathy in the setting of FOLFOX chemotherapy.

BACKGROUND: To report a case of bilateral optic disc oedema and associated optic neuropathy in the setting of FOLFOX chemotherapy. CASE PRESENTATION: A case of a 57-year-old male being treated with FOLFOX chemotherapy for stage 3B colorectal cancer, who developed bilateral optic disc oedema and associated left sided optic neuropathy is described. The patient presented following cycles 7, 8 and 9 of chemotherapy with a history of bilateral simultaneous intermittent inferior altitudinal field defects. These episodes progressed to bilateral optic nerve oedema and a subsequent left sided optic neuropathy. The patient's symptoms and oedema regressed with discontinuation of chemotherapy. CONCLUSION: This is the first report suggesting a vasospastic role of 5-fluoruracil in 5-FU associated optic neuropathy. It highlights that 5-FU may have the potential to cause arterial vasospasm outside the cardiac vasculature, resulting in end-organ optic nerve ischaemia.

Bilateral optic disc edema as a possible complication of cabozantinib use-a case report.

INTRODUCTION: Cabozantinib, which was approved by the Food and Drug Administration (FDA) in 2012, is a tyrosine kinase inhibitor widely used in the treatment of metastatic renal cell carcinoma (RCC) and medullary thyroid carcinoma. To date, no ocular adverse events have been reported by the FDA or on the package label. Here, we described a patient with metastatic RCC who developed bilateral optic disc edema after a 4-month course of cabozantinib. CASE DESCRIPTION: A 55-year-old ethnic Chinese male with RCC with multiple metastases presented to our department with progressive blurred vision in both eyes for 1 month. He started taking cabozantinib 60 mg once daily 5 months prior to this presentation. Poor visual acuity and bilateral disc edema were then noted. Cabozantinib was discontinued after that, and 3-day pulse steroid therapy with methylprednisolone 1 g/day was given. The optic disc edema subsided gradually with limited improvement in visual acuity. CONCLUSION: Bilateral optic edema should be considered as a complication associated with cabozantinib. We propose discontinuation of the treatment in cases such as that, and pulse steroid therapy should be considered if there is no contraindication.