Abstract: Optical coherence tomography (OCT) is an ocular imaging technique that can complement the neuro-ophthalmic assessment, and inform our understanding regarding functional consequences of neuroaxonal injury in the afferent visual pathway. Indeed, OCT has emerged as a surrogate end-point in the diagnosis and follow up of several demyelinating syndromes of the central nervous system (CNS), including optic neuritis (ON) associated with: multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Recent advancements in enhanced depth imaging (EDI) OCT have distinguished this technique as a new gold standard in the diagnosis of optic disc drusen (ODD). Moreover, OCT may enhance our ability to distinguish cases of papilledema from pseudopapilledema caused by ODD. In the setting of idiopathic intracranial hypertension (IIH), OCT has shown benefit in tracking responses to treatment, with respect to reduced retinal nerve fiber layer (RNFL) measures and morphological changes in the angling of Bruch’s membrane. Longitudinal follow up of OCT measured ganglion cell-inner plexiform layer thickness may be of particular value in managing IIH patients who have secondary optic atrophy. Causes of compressive optic neuropathies may be readily diagnosed with OCT, even in the absence of overt visual field defects. Furthermore, OCT values may offer some prognostic value in predicting post-operative outcomes in these patients. Finally, OCT can be indispensable in differentiating optic neuropathies from retinal diseases in patients presenting with vision loss, and an unrevealing fundus examination. In this review, our over-arching goal is to highlight the potential role of OCT, as an ancillary investigation, in the diagnosis and management of various optic nerve disorders.
Background: To present a surgical technique using a rigid intraocular lens as endocapsular supporting device in manual small incision cataract surgery (MSICS) for treating mild-moderate subluxated cataracts.
Methods: In our technique, a single-piece rigid polymethyl methacrylate (PMMA) lens was implanted in the bag following the nucleus removal, with its axis vertical to the zonular dialysis. This endocapsular-implanted IOL stretched the bag and provided sufficient stability and lens centration. This technique was performed in 19 eyes with subluxated cataracts, with zonulysis of ≤120 degree and nuclear sclerosis of grade ≤3. Mean follow-up time was 9.8 months.
Results: All eyes had endocapsular IOL implantation during surgery. Intraoperative extension of the dialysis did not occur in any eye. The IOL was placed in the bag in all but 1 case, in which dislocation of the IOL haptic into the vitreous occurred. Though the IOL was slightly decentered in 3 cases, it kept stable. All patients were asymptomatic.
Conclusions: This approach provides a simplified and practical strategy for surgically managing subluxation with mild-moderate zonular loss.
Abstract: Between 2011 and 2013, two large-scale cohort epidemiology studies were launched in Shanghai: the SCALE study, which aimed to provide ocular public health services to cover the entire youth population in Shanghai, and the SCES, which was based on sample surveys and aimed to provide information on the prevalence and incidence of visual impairment and different types of refractive errors. A total of 910,245 children and adolescents were finally enrolled in the SCALE study; three possible methods for monitoring refractive error without mydriasis were tested, and the agreement between the refractive outcomes of three commonly used autorefractors were examined to ensure the accuracy of the results of the SCALE study. A total of 8,627 children were enrolled in the SCES, and the baseline prevalence of different refractive errors, different behaviors associated with 1 year myopic shifts, and the different patterns of 2-year myopia progression between internal migrant and local resident school children have been analyzed. In some subset samples of the SCALE study and the SCES, several refraction components such as choroidal thickness (ChT) and crystalline lens power were also measured, to further elucidate the relationships between the refraction components and myopia as well as the mechanism of myopia incidence and development. The three methods used in Shanghai to prevent and intervene with childhood myopia: increasing outdoor time, low concentration atropine, and use of orthokeratology lens are also addressed in this review.
Abstract: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular, bulbar and limb skeletal muscles. There are two major clinical types of MG. Ocular MG (OMG) affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body. Patients with OMG have painless fluctuating extra ocular muscles weakness, diplopia and ptosis accompanied by normal visual acuity and pupillary function. Frequently, patients with OMG develop generalized MG over 24 months. Pure OMG is more often earlier in onset (<45 years) than generalized MG. It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors. Diagnosis is based on clinical manifestations, laboratory findings, electrophysiological evaluation and pharmacologic tests. Therapeutic strategies for MG consist of symptom relieving medications (e.g., acetylcholine esterase inhibitors), immunosuppressive agents, and surgical intervention (e.g., thymectomy).
Background: To compare objective electrophysiological contrast sensitivity function (CSF) in patients implanted with either multifocal intraocular lenses (MIOLs) or monofocal intraocular lenses (IOLs) by pattern reversal visual evoked potentials (prVEP) measurements.
Methods: Fourty-five cataract patients were randomly allocated to receive bilaterally: apodized diffractive-refractive Alcon Acrysof MIOL (A), full diffractive AMO Tecnis MIOL (B) or monofocal Alcon Acrysof IOL (C). Primary outcomes: 1-year differences in objective binocular CSF measured by prVEP with sinusoid grating stimuli of 6 decreasing contrast levels at 6 spatial frequencies. Secondary outcomes: psychophysical CSF measured with VCTS-6500, photopic uncorrected distance (UDVA), and mesopic and photopic uncorrected near and intermediate visual acuities (UNVA and UIVA respectively).
Results: Electrophysiological CSF curve had an inverted U-shaped morphology in all groups, with a biphasic pattern in Group B. Group A showed a lower CSF than group B at 4 and 8 cpd, and a lower value than group C at 8 cpd. Psychophysical CSF in group A exhibited a lower value at 12 cpd than group B. Mean photopic and mesopic UNVA and UIVA were worse in monofocal group compared to the multifocal groups. Mesopic UNVA and UIVA were better in group B.
Conclusions: Electrophysiological CSF behaves differently depending on the types of multifocal or monofocal IOLs. This may be related to the visual acuity under certain conditions or to IOL characteristics. This objective method might be a potential new tool to investigate on MIOL differences and on subjective device-related quality of vision.
Background: Visual deficits, caused by ocular disease or trauma to the visual system, can cause lasting damage with insufficient treatment options available. However, recent research has focused on neural plasticity as a means to regain visual abilities. In order to better understand the involvement of neural plasticity and reorganization in partial vision restoration, we aim to evaluate the partial recovery of a visual deficit over time using three behavioural tests. In our study, a partial optic nerve crush (ONC) serves as an induced visual deficit, allowing for residual vision from surviving cells.
Methods: Three behavioural tests—optokinetic reflex, object recognition, and visual cliff—were conducted in 9 mice prior to a bilateral, partial ONC, then 1, 3, 7, 14, 21, and 28 days after the ONC. The optokinetic reflex test measured the tracking reflex in response to moving sinusoidal gratings. These gratings increase in spatial frequency until a reflex is no longer observed, i.e., a visual acuity threshold is reached. The object recognition test examines the animal’s exploratory behaviour in its capacity to distinguish high versus low contrast objects. The visual cliff test also evaluates exploratory behaviour, by simulating a cliff to observe the animal’s sense of depth perception. All three tests provide an estimate of the rodent’s visual abilities at different levels of the visual pathway.
Results: The partial optic nerve crush resulted in a total loss of visual acuity as measured by the optokinetic reflex. The deficit did not show improvement during the 4 following weeks. Despite the visual cliff test showing a non-significant decrease in deep end preference 1-day post ONC, though this was not the case for subsequent test occasions. The object recognition test showed no significant trends.
Conclusions: In conclusion, the optokinetic reflex test showed a significant loss of function following the visual deficit, but no recovery. However, a complimentary pilot study shows visual recovery using lighter crush intensities. The spatial visual function does not seem to be affected by the ONC, suggesting that the object recognition and visual cliff tests, in their current design, may rely on somatosensory means of exploration.
Background: Zellweger spectrum disorder (ZSD) is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome assembly. Retinopathy leading to blindness is one of the major handicaps faced by affected individuals, but treatment for this is supportive only. To test whether we could improve visual function in ZSD, we performed a proof-of-concept trial for PEX1 gene augmentation therapy using the Pex1-G844D mouse model, which bears the equivalent to a common human mutation. This model exhibits a gradual decline in scotopic ffERG response, an always residual photopic ffERG response, diminished visual acuity, and cone and bipolar cell anomalies.
Methods: We administered subretinal injections of a PEX1-containing viral vector (AAV8.CMV.hPEX1.HA) to 2 mouse cohorts of 5 or 9 weeks of age. A GFP-containing vector was used as a control in the contralateral eye of each animal. Efficient expression of the virus was confirmed by retinal histology/immunohistochemistry, and its ability to recover peroxisome import was confirmed in vitro. Preliminary ffERG and optokinetic (OKN) analyses were performed on a subset of animals at 8, 16, and 20 weeks after gene delivery. Final ffERG and OKN measures were performed when each cohort reached 32 weeks of age (23 or 27 weeks post injection).
Results: Preliminary ffERG and OKN analyses at 8 weeks post injection showed mildly better retinal response and visual acuity, respectively, in the PEX1-injected eyes, as did ffERG analysis when each cohort reached 25 weeks of age (16 or 20 weeks after gene delivery). This effect was more pronounced in the cohort treated at 5 weeks of age, when ffERG response is highest in Pex1-G844D mice. At 32 weeks of age, the ffERG response in the PEX1-injected eyes was double that of GFP-injected eyes, on average, though there was no change in OKN. Furthermore, in PEX1-injected eyes the photopic ffERG response improved over time, and the decline in scotopic b-wave amplitude was ameliorated compared to un-injected eyes.
Conclusions: AAV8.CMV.hPEX1.HA was subretinally delivered into the left eye of 5- and 9-week-old Pex1-G844D retina. Successful expression of the protein with no gross histologic side effect was observed. Neither the injection, nor exposure to the AAV8 capsid or the transgenic protein negatively altered the ERG or OKN response. At 5–6 months after gene delivery, therapeutic vector-treated eyes showed improved ERG compared to control eyes, on average, in both the “prevention” and “recovery” cohorts. This implies clinical potential of gene delivery to improve vision in patients with ZSD. Retinal immunohistochemistry (to visualize retinal cell types) and biochemical analyses will be performed on treated and untreated retinas, and may inform the mechanism of ERG improvement.
Background: Diabetic macular edema (DME) is a leading cause of severe visual impairments in older and the working-age population. An important target of current therapy is vascular endothelial growth factor (VEGF), which plays a role in the pathogenesis of DME by inducing angiogenesis and increasing vascular permeability. Currently available anti-VEGF agents include off-label use of Bevacizumab, which has been shown to be effective in the treatment of DME. However, many patients with DME do not respond or demonstrate only a partial response to this agent. As of November 2016, the Canadian Health authorities approved Aflibercept as an anti-VEGF agent for treatment of DME, and the patients who are non-responders to Bevacizumab are switched to this non-off label medication. We aimed to investigate the anatomical and functional visual changes associated with response to Aflibercept in a real-life Canadian population of Bevacizumab non-responders.
Methods: A retrospective review of chronic DME patients refractory to bevacizumab treatment who were switched to Aflibercept was done. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), central subfield thickness (CST), average macular thickness, and total macular volume were extracted at the visit prior to switching to Aflibercept (baseline) as well as the first, second and third follow-up visits after switching. Anatomical and functional visual changes were compared using Generalized Estimating Equations and the association between variables was tested using Pearson correlation test with significance set at P<0.05.
Results: Twenty-six eyes with mean age of 63 were included. Average CST at baseline was 421.5±116.1 μm and the number of Bevacizumab injections received prior to switching was 15.3±8.0. No significant changes were observed in terms of BCVA and IOP, from baseline to any of the follow-ups. Switching to Aflibercept significantly improved CST, average macular thickness, and total macular volume. From baseline to the first follow-up visit, CST decreased from 421.5±116.1 to 333.0±91.2 μm (P=0.001) and average macular thickness reduced from 344.6±74.9 to 322.2±60.5 μm (P=0.008). Similarly, total macular volume decreased from 12.4±2.7 to 11.6±2.2 μm3, measured at baseline and the first follow-up (P=0.007). No further improvements were observed from the first follow-up to the subsequent ones. The median CST value at baseline (378 μm) was used to classify the patients into low and high CST groups. We observed that those with higher CST at baseline (>378 μm) showed a trend for improvements in visual acuity (P=0.058). Pearson correlation test confirmed the association between higher CST at baseline and better visual outcomes in response to switching to Aflibercept (P=0.018).
Conclusions: Our data evidenced significant anatomical improvements in macula, which did not translate to immediate functional vision improvements. Bevacizumab non-responders with higher CST might also gain visual acuity and benefit functionally from switching to Aflibercept.
