Physiological effects of inactivation and the roles of Elovl3/ELOVL3 in maintaining ocular homeostasis.

Recently, elongase of very long chain fatty acids-3 (ELOVL3) was demonstrated to play a pivotal role in physiology and biochemistry of the ocular surface by maintaining a proper balance in the lipid composition of meibum. The goal of this study was to further investigate the effects of ELOVL3 ablation in homozygous Elovl3-knockout mice (E3hom) in comparison with age and sex matched wild-type controls (E3wt). Slit lamp examination of the ocular surface of mice, and histological examination of their ocular tissues, highlighted a severe negative impact of Elovl3 inactivating mutation on the Meibomian glands (MG) and conjunctiva of mice. MG transcriptomes of the E3hom and E3wt mice were assessed and revealed a range of up- and downregulated genes related to lipid biosynthesis, inflammation, and stress response, compared with E3wt mice. Heat stage polarized light microscopy was used to assess melting characteristics of normal and abnormal meibum. The loss of Elovl3 led to a 8°C drop in the melting temperature of meibum in E3hom mice, and increased its fluidity. Also noted were the excessive accumulation of lipid material and tears around the eye and severe ocular inflammation, among other abnormalities.

Approach to the diagnosis and management of nutritional optic neuropathies.

PURPOSE OF REVIEW: Nutritional deficiency is an under-recognized cause of optic neuropathy. The purpose of this review is to discuss how to identify, diagnose, and appropriately manage patients with nutritional optic neuropathy. RECENT FINDINGS: Nutritional deficiencies have long been thought to be more prevalent in the developing countries. However, with the advent of bariatric surgery, restrictive/selective diets, and the increase in alcohol dependence, it is not uncommon to see nutritional optic neuropathies in the developed world. SUMMARY: Although nutritional optic neuropathy can cause severe and debilitating vision loss, it is often reversible when it is diagnosed and treated in a timely manner.

Paracentral Acute Middle Maculopathy in Pregnancy.

ABSTRACT: A 31-year-old previously healthy, pregnant woman presented with acute, unilateral, painless paracentral vision loss in the left eye. The results of neuroimaging studies were normal. Hypercoagulable workup was negative, and fundus examination showed no retinal emboli and no retinal vascular abnormalities. The patient had well-controlled blood pressure and did not have eclampsia/preeclampsia. Although a presumptive referral diagnosis of "optic neuritis" was made, optical coherence tomography (OCT) of the macula showed a hyperreflective band involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). Furthermore, OCT angiography (OCT-A) showed flow attenuation of the outer retinal capillary plexus, further supporting a diagnosis of PAMM in pregnancy. Clinicians should be aware of the benefit of OCT-A as a complement to macular OCT in the evaluation of acute monocular vision loss mimicking retrobulbar optic neuropathy, particularly when signs and findings of other retinal vasculopathy are absent. PAMM should be considered in pregnant patients with acute visual changes.

Postinfectious Optic Neuritis After Hand-Foot-Mouth Disease.

ABSTRACT: A 33-year-old man presented with acute painless loss of vision in his right eye after hand-foot-mouth disease (HFMD). Examination confirmed a right optic neuropathy. Neuroimaging and routine evaluations for alternative causes for an optic neuropathy were negative. He was treated with high dose corticosteroids and made an almost complete visual recovery. Postinfectious optic neuritis has been reported after a vast array of infections including: varicella zoster virus, influenza virus, herpes simplex virus, Epstein-Barr Virus, Lyme disease, and many others. Although Coxsackie virus infections are a known cause of HFMD and have been reported to cause maculopathy, to the best of our knowledge, this is the first reported case of optic neuritis after HFMD in the English language ophthalmic literature.

Optical Coherence Tomography Findings in the Junctional Scotoma of Traquair.

ABSTRACT: A 43-year-old woman presented with a right-sided visual field defect in the right eye. The visual acuity was normal and there was a right relative afferent pupillary defect. Formal visual field testing revealed a junctional scotoma of Traquair. The fundus examination showed optic atrophy in the right eye and optical coherence tomography demonstrated unilateral band atrophy. Neuroimaging revealed a sellar and suprasellar cystic pituitary adenoma for which she underwent a transsphenoidal drainage. We demonstrate the clinical and radiographic features of the junctional scotoma of Traquair and describe the differentiating features vs the junctional scotoma.

Compressive Optic Disc Edema and Contralateral Papilledema: Type 2 Foster Kennedy Variant Syndrome.

ABSTRACT: A 43-year-old woman presented with progressive anosmia, self-neglect, and lethargy for 1 year. Brain MRI demonstrated a mass that was compressing the optic nerve in the right eye and had a significant mass effect and cerebral edema producing increased intracranial pressure. Examination revealed the patient to have a variant of Foster Kennedy syndrome involving ipsilateral compressive optic neuropathy with superimposed optic disc edema and contralateral papilledema.

Neuro-Ophthalmic Manifestations of Mollaret Meningitis.

ABSTRACT: Mollaret meningitis (MM) refers to benign recurrent aseptic meningitis usually following herpes simplex virus 2 (HSV-2) infection. Neuro-ophthalmic manifestations associated with MM are rarely reported. We present a case of recurrent HSV-2 meningitis with the neuro-ophthalmic presentation of papilledema and sixth nerve palsy. To our knowledge, this is the first such description in the English language ophthalmic literature.

Paracentral Acute Middle Maculopathy Mimicking Retrobulbar Optic Neuropathy.

ABSTRACT: A 70-year-old woman presented with acute awareness of decreased color vision in her right eye. Fundus examination and a flash electroretinography (ERG) were both normal. A multifocal ERG (mfERG) however revealed foveal depression, and thinning of inner nuclear layer was noted on macular optical coherence tomography (OCT), and a diagnosis of resolved paracentral acute middle maculopathy was made. Clinicians should be aware of the complementary role of OCT and mfERG in unexplained acute central visual loss to distinguish retinal from neuro-ophthalmic etiologies. Structural ocular imaging with OCT shows features of inner, middle, and outer retinal localizations to the visual loss.

Orbital Compartment Syndrome After High-speed Air-Gasoline Blast Injury.

Orbital compartment syndrome is an ophthalmologic emergency that requires timely surgical intervention. The authors present a rare case of orbital compartment syndrome in a 30-year-old male injured by forceful entry of air-gasoline mixture into the orbit, secondary to inadvertent firing of the piston from running mechanical diagnostics on an automobile internal combustion engine. Orbital CT revealed extensive orbital emphysema with both pre- and postseptal involvement and diffuse chemical cellulitis. Serial exams revealed rapid deterioration of vision with elevated intraocular pressure and development of eyelid, corneal, and orbital edema; a relative afferent pupillary defect and optic nerve hypoperfusion. He was started on intravenous steroids and underwent an emergent lateral canthotomy with cantholysis, which temporarily reduced the intraocular pressure. However, a second rapid increase in soft tissue swelling resulted in another episode of ocular hypertension and compressive optic neuropathy, requiring emergent orbital bony decompression, which was followed by decreased intraocular and orbital pressure. The patient later developed progressive corneal opacification indicating delayed chemical injury. This was managed with a 10-day course of aggressive topical and systemic antiinflammatory agents with significant improvement in visual acuity. At last follow up, the vision was 20/30 and the corneal and eyelid edema had cleared.

Optic Perineuritis Distinguishing Arteritic Ischaemic from Amiodarone-Associated Optic Neuropathy.

Giant cell arteritis (GCA) is a common medium to large vessel vasculitis of the elderly that can lead to permanent vision loss. Neuroimaging in GCA may reveal optic nerve sheath enhancement, which is a cardinal finding of optic perineuritis (OPN). The clinical manifestations of GCA can mimic that of other ocular disorders including amiodarone-associated optic neuropathy (AAON). We report a case of biopsy-proven GCA in a patient initially suspected to have AAON. This patient presented with bilateral optic disc oedema in conjunction with subacute predominately monocular vision loss and enhancement of the corresponding optic nerve sheath on neuroimaging. Clinicians should recognise that clinical and neuroimaging findings of GCA can mimic a variety of ocular and orbital pathologies including idiopathic OPN and AAON.

On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice.

The purpose of this study was to examine the role of Elovl3 gene in meibogenesis and the impact of ELOVL3 protein ablation on the physiology of the mouse ocular surface and Meibomian glands (MGs). Elovl3 knockout, ELOVL3-ablated (E3hom) mice and their wild type littermates (E3wt) were studied side by side. E3hom mice had abnormal ocular phenotypes such as delayed eye opening, weeping eyes, crusty eyelids, eyelid edema, highly vascularized cornea and tarsal plates (TPs), slit eye, and increased tearing that resemble symptoms observed in human subjects with various forms of dry eye, MG dysfunction and blepharitis. Lipid profiling of E3hom TPs was conducted using chromatography and mass spectrometry. The analyses revealed that the lipid composition of E3hom TPs was strikingly different from that of their E3wt littermates. The mutation affected major classes of meibomian lipids - cholesteryl esters, wax esters, and cholesteryl esters of (O)-acylated w-hydroxy fatty acids. The studies illuminated the central role of ELOVL3 in producing C21:0-C29:0 fatty acids, including odd-chain and branched ones. Ablation of ELOVL3 leads to selective changes in the lipid composition of meibum, making E3hom mice instrumental in studying the mechanisms of the biosynthesis of meibum and modeling various pathologies of human ocular surface and adnexa.-Butovich, I. A., Wilkerson, A., Bhat, N., McMahon, A., Yuksel, S. On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice.

Comparative Transcriptomic and Lipidomic Analyses of Human Male and Female Meibomian Glands Reveal Common Signature Genes of Meibogenesis.

Meibum is a lipid secretion that is produced by holocrine Meibomian glands (MGs). MGs are a specialized type of sebaceous glands that are embedded in the human eyelids. Chemically, meibum and sebum are different. A detailed characterization of lipidome and transcriptome of MG is required to deconvolute a complex and poorly characterized array of biosynthetic reactions (termed meibogenesis) that lead to formation of meibum. Changes in the composition and quality of meibum have been linked to various ocular disorders, some of which are more prevalent in males, while others in females. To establish the role of gender in meibogenesis in humans, we characterized MG transcriptomes and lipidomes of females and males, and identified signature genes of meibogenesis in both genders. Specimens of MG tissues were subjected to mRNA microarray analyses. Chemical composition of meibum samples was assessed chromatographically and mass spectrometrically. Both targeted and untargeted approaches were used. About 290 signature genes of meibogenesis were identified. The analyses of their expression patterns demonstrated no major differences between the genders. Lipid profiling of major classes of meibomian lipids, such as wax esters, cholesteryl esters, free cholesterol, (O)-acylated omega-hydroxy fatty acids (OAHFA), cholesteryl esters of OAHFA, and triacylglycerols, also demonstrated only minor (and random) differences in these lipids. The results of transcriptomic analyses correlated well with lipidomic data. Taken together, our data imply that in males and females, meibogenesis proceeds in a similar fashion, yielding secretions with similar, highly conserved, compositions. This finding is important for designing novel, gender-independent diagnostic and therapeutic approaches to various MG-related diseases and pathological conditions.