Basic Concept of Ophthalmology and Visual Disorder

The eye is a complex sensory organ that is responsible for vision. Within the protective sheath, each eye has receptors, a lens system for focusing light on receptors, and a nervous system for transmitting impulses from the receptors to the brain. Visual dysfunction can be caused by abnormal eye movements or changes in visual acuity, refraction, color vision, or accommodation. Visual dysfunction may also be a secondary effect of other neurological disorders. This narrative review aims to describe the structure of the eye in general and visual disturbances caused by the aging process and disorders of the protective structure of the eye.

Failed remyelination of the non-human primate optic nerve leads to axon degeneration, retinal damages and visual dysfunction.

White matter disorders of the CNS such as MS, lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery. Most of these strategies are developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined non-human primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculo-motor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This non-human primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair pro-myelinating/neuroprotective therapies to the clinic for myelin disorders such as MS.

The Effect of Insight Questions Inventory and Visual Support Strategies on Carer-Reported Quality of Life for Children With Cerebral Palsy and Perceptual Visual Dysfunction in Nigeria: A Randomized Controlled Trial

Structured clinical history question inventories have previously been used to try and elicit symptoms of perceptual visual dysfunction (PVD) in children with cerebral palsy (CP) in different settings. Earlier studies have suggested that PVD may affect quality of life and specific habilitational strategies, linked to inventory responses, may improve quality of life. Through an RCT, based on a community based sample of children with CP in Cross River State, Nigeria, we aimed to determine if a structured history inventory such as the Insight question inventory (IQI) and associated tailored visual support strategies (IQI VSS) for the management of those children who have PVD, can improve quality of life and is superior to standard therapy. Children with CP were recruited by the key informant method and confirmed by clinical examination. The parent reported IQI was used to identify children with PVD. Primary outcome measures were both Pediatric Quality of Life 4.0 Generic (PedsQL 4.0 Generic) and Pediatric Quality of Life 3.0 Cerebral Palsy (PedsQL 3.0 CP) scale scores. Children were enrolled with a parallel arm allocation to either IQI and IQI VSS or to standard therapy for CP. Children were followed up for 6 weeks with weekly phone call session and the questionnaires repeated at the end of the 6 weeks’ period. Results show that the children in the treatment group (n = 191) showed no significantly different change between baseline and follow up in quality of life (PedsQL 4.0 Generic p = 0.943: and PedsQL-CP 3.0 p = 0.287), compared to the control group. There was suggestion of a better improvement (p = 0.035) in the PedsQL 3.0 CP subscale of speech and communication for the intervention group. The use of IQI VSS for the treatment of PVD in children with CP in this population does not show any superiority over current standard CP management in terms of overall quality of life. However, there was some evidence of improvement in quality of life in the area of speech and communication. Further research and refinement of these management method is required.Clinical Trial Registration:www.ClinicalTrials.gov, identifier [PACTR20161200188] 6396.

A mutant wfs1 zebrafish model of Wolfram syndrome manifesting visual dysfunction and developmental delay

Wolfram syndrome (WS) is an ultra-rare progressive neurodegenerative disorder defined by early-onset diabetes mellitus and optic atrophy. The majority of patients harbour recessive mutations in the WFS1 gene, which encodes for Wolframin, a transmembrane endoplasmic reticulum protein. There is limited availability of human ocular and brain tissues, and there are few animal models for WS that replicate the neuropathology and clinical phenotype seen in this disorder. We, therefore, characterised two wfs1 zebrafish knockout models harbouring nonsense wfs1a and wfs1b mutations. Both homozygous mutant wfs1a−/− and wfs1b−/− embryos showed significant morphological abnormalities in early development. The wfs1b−/− zebrafish exhibited a more pronounced neurodegenerative phenotype with delayed neuronal development, progressive loss of retinal ganglion cells and clear evidence of visual dysfunction on functional testing. At 12 months of age, wfs1b−/− zebrafish had a significantly lower RGC density per 100 μm2 (mean ± standard deviation; 19 ± 1.7) compared with wild-type (WT) zebrafish (25 ± 2.3, p < 0.001). The optokinetic response for wfs1b−/− zebrafish was significantly reduced at 8 and 16 rpm testing speeds at both 4 and 12 months of age compared with WT zebrafish. An upregulation of the unfolded protein response was observed in mutant zebrafish indicative of increased endoplasmic reticulum stress. Mutant wfs1b−/− zebrafish exhibit some of the key features seen in patients with WS, providing a versatile and cost-effective in vivo model that can be used to further investigate the underlying pathophysiology of WS and potential therapeutic interventions.

Optical Coherence Tomography to Monitor Rebound Intracranial Hypertension with Increased Papilledema after Lumbar Puncture

Objective: We report that lumbar puncture (LP) with removal of cerebrospinal fluid (CSF) induced rebound intracranial hypertension with increased papilledema as monitored by optical coherence tomography (OCT). Background: Severe papilledema causes visual field loss and central vision damage if untreated. Fundoscopy is a key to diagnose papilledema, but is not sensitive enough to monitor therapeutic effects. Methods: OCT was applied to follow a 24-year-old woman with headache, visual dysfunction, severe bilateral papilledema, and elevated CSF opening pressure. She was first treated with serial LP, which led to symptom deterioration, increased CSF pressure, and increased the retinal nerve fiber layer (RNFL) thickness. She was then successfully treated with acetazolamide and furosemide. Results: OCT showed reduction of RNFL thickness directly after LP with CSF removal, accompanied with reduced CSF pressure. Increased RNFL thickness accompanied with worsened headache, visual dysfunction, and increased CSF pressure was observed on the next day after LP. Less than 24 h after start of medication, the symptoms had reversed and RNFL thickness was reduced. The patient was symptom-free 2 weeks after starting on medical treatment. Papilledema had vanished on fundoscopy 6 weeks after the therapy, and RNFL thickness was normalized at 3 months of follow-up. Conclusion: This case provides evidence that OCT is an objective and sensitive tool to monitor papilledema and its response to therapy, and thereby important to help in correct clinical decision-making.