Background: Congenital hereditary endothelial dystrophy (CHED) is characterized by blindness at birth or in early infancy resulting from bilateral corneal opacification, and is linked to mutation in the Slc4a11 gene. A Slc4a11 knockout (KO) mouse, generated by gene deletion (Vithana et al. Nat Genet 2006), was acquired in order to study this disease. To confirm the phenotype of this Slc4a11 KO mouse model as a function of age, using the wild type (WT) mouse as a control.
Methods: Genotyping was performed by PCR (REDExtract-N-AmpTM Tissue PCR Kit, Sigma-Aldrich, Oakville, ON). Slc4a11 WT and KO mice populations aged from 5 to 50 weeks were studied (n=5 animals per age group; 5-year age intervals). Slit lamp examination, anterior segment-ocular coherence tomography (OCT930SR; Thorlabs, Inc., Newton, NJ), corneal endothelial cell staining, and scanning (SEM) and transmission (TEM) electron microscopy were used to assess the morphological and cellular differences between the two groups. The expression of basolateral membrane transporter NaBC1 within the corneal endothelium was also assessed using immunohistochemistry.
Results: Diffuse and progressive corneal opacification was observed at the slit lamp in the Slc4a11 KO mice, starting at 10 weeks. The central corneal thickness (CCT) also increased progressively as a function of time. In comparison, Slc4a11 WT corneas remained clear over the entire study period. Early TEM results showed vacuole degeneration of the corneal endothelium in the 15-week KO mouse, which was not seen in the same age WT mouse.
Conclusions: The corneal phenotype of this Slc4a11 KO mouse is representative of the clinical manifestations of CHED in human subjects, confirming the usefulness of this model for studying pathophysiology and therapeutic alternatives for Slc4a11-associated corneal dystrophies.
Background: Decrease of ocular blood flow has been linked to the pathogenesis of ocular diseases such as glaucoma and age-related macular degeneration. Current methods that measure the pulsatile blood flow have major limitations, including the assumption that ocular rigidity is the same in all eyes. Our group has recently developed a new method to measure the pulsatile choroidal volume change by direct visualization of the choroid with OCT imaging and automated segmentation. Our goal in this study is to describe the distribution of PCBF in a healthy Caucasian population.
Methods: Fifty-one subjects were recruited from the Maisonneuve-Rosemont Hospital Ophthalmology Clinic and underwent PCBF measurement in one eye. The distribution of PCBF in healthy eyes was assessed.
Results: The distribution of PCBF among the healthy eyes was found to be 3.94±1.70 μL with this technique.
Conclusions: This study demonstrates the normal range of PCBF values obtained in a healthy Caucasian population. This technique could be used for further investigation of choroid pulsatility and to study glaucoma pathophysiology.
Abstract: Pediatric neuro-ophthalmology is a subspecialty within neuro-ophthalmology. Pediatric neuro-ophthalmic diseases must be considered separate from their adult counterparts, due to the distinctive nature of the examination, clinical presentations, and management choices. This manuscript will highlight four common pediatric neuro-ophthalmic disorders by describing common clinical presentations, recommended management, and highlighting recent developments. Diseases discussed include pediatric idiopathic intracranial hypertension (IIH), pseudopapilledema, optic neuritis (ON) and optic pathway gliomas (OPG). The demographics, diagnosis and management of common pediatric neuro-ophthalmic disease require a working knowledge of the current research presented herein. Special attention should be placed on the differences between pediatric and adult entities such that children can be appropriately diagnosed and treated.
Abstract: Pathologic myopia is the major cause of the loss of the best-corrected visual acuity (BCVA) worldwide, especially in East Asian countries. The loss of BCVA is caused by the development of myopic macula patchy, myopic traction macula patchy, and myopic optic neuropathy (or glaucoma). The development of such vision-threatening complications is caused by eye deformity, characterized by a formation of posterior staphyloma. The recent advance in ocular imaging has greatly facilitated the clarification of pathologies and pathogenesis of pathological myopia and myopia-related complications. These technologies include ultra-wide field fundus imaging, swept-source optical coherence tomography, and 3D MRI. In addition, the new treatments such as anti-VEGF therapies for myopic choroid all neovascularization have improved the outcome of the patients. Swept-source OCT showed that some of the lesions of myopic maculopathy were not simply chorioretinal atrophy but were Bruch’s membrane holes. Features of myopic traction maculopathy have been analyzed extensively by using OCT. The understanding the pathophysiology of complications of pathologic myopia is considered useful for better management of this blinding eye disease.
Abstract: Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral granulomatous panuveitis associated with serous retinal detachments and vitritis, and can be associated with extraocular manifestations of meningismus, poliosis, vitiligo, hearing loss, and headaches. It is mediated by CD4+ T cells that target melanocytes in the eye, ear, meninges, and skin. It classically presents in 4 different phases: prodromal, uveitic, convalescent, and recurrent. There have been considerable advances in our understanding of the disease in recent years, and options for treatment have also expanded beyond systemic corticosteroids though these remain the mainstay of therapy in patients with VKH. This brief review will focus on updates in the diagnosis and treatment of VKH, specifically advances in imaging techniques including the use of optical coherence tomography angiography (OCTA) and enhanced depth imaging (EDI) optical coherence tomography (OCT). OCT parameters that are diagnostically predictive of acute VKH compared to other exudative maculopathies include the presence of subretinal membranous structures, a high retinal detachment, subretinal hyperreflective dots, and RPE folds. Evaluations of choroidal thickness using EDI-OCT demonstrate predominant involvement of the outer choroid in the acute inflammatory phase of VKH, consistent with histopathological analysis. OCTA may emerge as an alternative to fluorescein angiography (FA) and indocyanine angiography (ICGA) but is limited at this time due to its small field of view. While the mainstay of treatment of acute VKH continues to be systemic corticosteroids, biological response modifiers (BRMs) such as adalimumab and infliximab have been shown to be effective in the management of adult and pediatric VKH with one benefit being a faster onset of action compared to conventional immunosuppression. Literature Search: A literature search was done in PubMed using the words “Vogt Koyanagi Harada” “imaging” “diagnosis” “treatment” “therapy “posterior uveitis”.
Abstract: Idiopathic intracranial hypertension (IIH) is a condition in which elevated pressure in the cerebrospinal fluid can lead to optic nerve head (ONH) dysfunction and subsequent visual impairment. Physicians are currently limited in their ability to monitor and manage this condition, as clinical symptoms and exam findings are often delayed in response to changes in intracranial pressure. In order to find other biomarkers of disease, researchers are using imaging modalities such as optical coherence tomography (OCT) to observe microscopic changes in the eye in this condition. OCT can create 2-dimensional and 3-dimensional high definition images of the retina of the ONH and has been used to study various conditions such as glaucoma and multiple sclerosis. Numerous studies have used OCT in IIH as well, and they have shown that certain retinal layers and the ONH change in thickness and shape in both the short and long term with intracranial pressure changes. OCT is a promising modality for clinical and scientific evaluation of IIH as it is a noninvasive and practical tool to obtain in depth images. This review will discuss how OCT can be used to assess a patient with IIH, both before and after treatment, along with its limitations and future applications.
