Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

Low vision devices for age-related macular degeneration: a systematic review.

PURPOSE: Age-related macular degeneration (AMD) is a degenerative condition impacting central vision. Evaluating the effectiveness of low vision devices provides empirical evidence on how devices can rehabilitate and overcome deficits caused by AMD. This evidence could help to facilitate discussion on necessary future improvements to vision enhancement technology. METHODS: A systematic review of the literature was conducted on low vision device use in AMD populations. Relevant peer-reviewed research articles from six databases were screened. RESULTS: The findings of thirty-five studies revealed a significant positive impact of low vision devices leading to improvements in visual acuity, reading performance, facial recognition, and more. While the studies were found to have moderate risks of bias, a GRADE assessment of the evidence suggested the certainty of the evidence was low-moderate. DISCUSSION: Simple hand-held low vision devices (e.g., magnifiers) appear to currently have greater preferential support than newer visual enhancement technology (e.g., head mounted devices). Financial, comfort or usability reasons may influence preferences more than performance-based findings. However, there is a lack of studies examining newer technologies in AMD populations, which future research should address. Moreover, given the presence of bias across the studies and limited controlled experiments, confidence in the results may be low. CONCLUSIONS: Most studies indicated that low vision devices have positive impacts on reading and visual performance. But, even though they are reported to be a valuable asset to AMD populations, more rigorous research is required to draw conclusive evidence. IMPLICATIONS FOR REHABILITATIONLow vision devices can improve patient outcomes (e.g., vision, reading ability) for age-related macular degeneration populations.A multidisciplinary combination of low vision devices and rehabilitative services (i.e., eccentric viewing training, counselling, education) may enhance quality of life.

Evaluating the effectiveness of multidisciplinary low-vision rehabilitation.

PURPOSE: To objectively evaluate the changes in vision-specific quality of life (QoL) after multidisciplinary low-vision rehabilitation at the Royal Society for the Blind Low-Vision Clinic. METHODS: The standard care model at the Royal Society for the Blind Low-Vision Clinic is optical management at the initial assessment, with subsequent referral to multidisciplinary services as required. Participants completed the Impact of Vision Impairment Questionnaire (IVI) and Veterans Affairs Low-Vision Visual Functioning Questionnaire (VA LV VFQ-48) before initial assessment, at 30 days (to assess the outcome of optical management) and at 3 months follow-up (to assess the outcome of multidisciplinary services). RESULTS: Seventy-one participants completed the study. Using the VA LV VFQ-48, an improvement (p < 0.05) was seen at 30 days follow-up in overall visual ability, and the reading, visual information, and visual motor subscores. However, at 3 months follow-up, all subscores were not significantly different from pre-rehabilitation levels. In contrast, for the IVI, there was no improvement in both the overall score and the mobility subscale at 30 days follow-up, but a significant improvement at 3 months follow-up. Greater improvements in visual function were seen for those with low vision (<20/60-20/200) compared with those with blindness, those aged >85 years compared with those aged 80 to 85 and <80 years, and those without glaucoma (visual motor subscore). CONCLUSIONS: The VA LV VFQ-48 and IVI demonstrated improvements in QoL after low-vision rehabilitation. The timing of the observed changes varied between the two questionnaires, reflecting the different content of these instruments and the timing of delivery of multidisciplinary services, but also suggests that continued rehabilitation may be warranted to maintain a patient's QoL.

Efficacy of intravenous tissue-type plasminogen activator in central retinal artery occlusion: report from a randomized, controlled trial.

BACKGROUND AND PURPOSE: Central retinal artery occlusion is caused by a platelet-fibrin thrombus or embolic occlusion and is a stroke of the eye. Observational studies suggest that thrombolytics may restore ocular perfusion and visual function. We hypothesized that intravenous tissue-type plasminogen activator (tPA) administered within 24 hours of symptom onset might restore ocular perfusion and visual function. METHODS: A placebo-controlled, randomized trial of intravenous tPA versus intravenous saline was performed in patients with clinically defined central retinal artery occlusion within 24 hours of symptom onset. tPA was administered at a total dose of 0.9 mg/kg, with 10% given as a 1-minute bolus and the remainder over 1 hour. An improvement of visual acuity of 3 lines or more was considered significant. RESULTS: Twenty-five percent (2 of 8) of the tPA group experienced the primary outcome at 1 week after tPA versus none of the placebo group. One patient had an intracranial hemorrhage. The visual acuity improvement of these 2 patients was not sustained at 6 months. In both patients, tPA was administered within 6 hours of symptom onset. CONCLUSIONS: Although essentially a negative study, it does add to the evidence base of reperfusion in central retinal artery occlusion by showing that the time window for intervention is likely to be <6 hours. Reocclusion is a potential problem and may require adjuvant anticoagulation. Future studies should concentrate on determining the efficacy of thrombolytics in the <6-hour time window. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: 83102.

Bilateral occipital lobe infarction with altitudinal field loss following radiofrequency cardiac catheter ablation.

BACKGROUND: Bilateral stroke following radiofrequency catheter ablation is an unusual complication and may result in bilateral altitudinal visual field defects. Bilateral altitudinal visual field defects usually result from prechiasmal pathology causing damage to both retinas or optic nerves and rarely from bilateral symmetric damage to the post chiasmal visual pathways. CASE PRESENTATION: A 48-year-old man complained of visual disturbance on wakening following radiofrequency catheter ablation. The patient had a CHADS score of 1 pre-operatively and no complications were noted intra-operatively. Examination revealed a bilateral superior altitudinal defect and MRI of the brain showed multifocal areas of infarction predominantly involving the occipital lobes which correlated to with the visual deficits. CONCLUSION: While the risk of thromboembolism and perioperative stroke during radiofrequency catheter ablation is small, it is not insignificant.

Traumatic vertebral artery dissection presenting with incomplete congruous homonymous quadrantanopia.

BACKGROUND: To describe a rare presentation of vertebral artery dissection (VAD) as a small but congruous incomplete homonymous hemianopia demonstrating use of visual field testing in the diagnosis. CASE PRESENTATION: A 30 year old woman had been unwell for 4 months with difficulty focusing, vertigo, dizziness and a feeling of falling to the right. A small but congruous right inferior homonymous quadrantanopia was found on examination leading to further investigation that uncovered a vertebral artery dissection and multiple posterior circulation infarctions including a left occipital stroke matching the field defect. CONCLUSIONS: We describe an atypical case of VAD presenting with a small congruous quadrantanopia. This is a rare but significant condition that predisposes to multiple thromboembolic infarction that may be easily misdiagnosed and a high index of suspicion is required to make the diagnosis.

Patients' knowledge and perception on optic neuritis management before and after an information session.

BACKGROUND: Patients' understanding of their condition affect the choice of treatment. The aim of this study is to evaluate patients' understanding and treatment preferences before and after an information session on the treatment of acute optic neuritis. METHODS: Participants were asked to complete a questionnaire consisting of 14 questions before and after an information session presented by a neuro-ophthalmologist. The information session highlighted the treatment options and the treatment effects based on the Optic Neuritis Treatment Trial in plain patient language. The information session stressed the finding that high dose intravenous steroid therapy accelerated visual recovery but does not change final vision and that treatment with oral prednisone alone resulted in a higher incidence of recurrent optic neuritis. RESULTS: Before the information session, 23 (85%) participants knew that there was treatment available for ON and this increased to 27 (100%) after the information session. There were no significantly change in patients knowledge of symptoms of ON and purpose of treatment before and after the information session. Before the information session, 4 (14%) respondents reported they would like to be treated by oral steroid alone in the event of an optic neuritis and 5 (19%) did not respond. After the education session, only 1 patient (4%) indicated they would undergo treatment with oral steroid alone but 25 (92%) indicated they would undergo treatment with intravenous steroid treatment, alone or in combination with oral treatment. Results indicated that there were significant differences in the numbers of participants selecting that they would undergo treatment with a steroid injection (n = 22, p = 0.016). CONCLUSIONS: In this study, patients have shown good understanding of the symptoms and signs of optic neuritis. The finding that significant increases in the likelihood of patients engaging in best practice can be achieved with an information session is very important. This suggests that patient knowledge of available treatments and outcomes can play an important role in implementing and adopting guideline recommendations.

Clinical characteristics and outcome of current standard management of central retinal artery occlusion.

BACKGROUND: To investigate the visual outcomes in acute central retinal artery occlusion (CRAO) with current standard therapy at two university teaching hospitals. METHODS: Retrospective analysis of two cohorts of CRAO patients from John Hopkins Hospital (JHH; USA), and Flinders Medical Centre (FMC; Australia), treated with current standard therapy. The outcome measures were visual acuity, and subsequent ocular and systemic ischaemic events. RESULTS: The mean follow-up period was 11.2 +/- 13.1 months in the JHH cohort and 35.4 +/- 34.9 months in the FMC cohort. The frequency distribution of vascular risk factors and the incidence of subsequent ischaemic events were similar for the patients from both institutions. All patients from JHH were treated as inpatients, whereas 79% of patients from FMC were treated as outpatients. More patients in the JHH cohort underwent paracentesis, ocular massage or were treated with intraocular hypotensive agents (76%) than in the FMC cohort (26%); however, there was no significant difference in visual outcome between the two cohorts (P = 0.114). CONCLUSION: Despite differences in management of CRAO between two institutions in different countries, visual outcomes were similar. This suggests a lack of efficacy of current standard treatment in acute CRAO.

Isolated unilateral abducens cranial nerve palsy: a rare presentation of pituitary apoplexy.

PURPOSE: To describe a rare presentation of pituitary apoplexy as unilateral abducens nerve palsy demonstrating the various presentations of the condition. METHODS: Case report. RESULTS: A 48-year-old man presented with isolated right abducens nerve palsy. Magnetic resonance imaging showed a large pituitary macroadenoma with evidence of recent bleed into the right cavernous sinus and surrounding the right internal carotid artery. CONCLUSIONS: Pituitary apoplexy may present subtly with an isolated sixth nerve palsy but the condition is critical and high index of suspicion needs to be governed.

Visual field defects after stroke--a practical guide for GPs.

BACKGROUND: Visual field defect after stroke can result in significant disability and reduction in quality of life. Visual rehabilitation aims to maximise the residual vision and decrease functional disability. Understanding the rehabilitation options available, and where to refer patients with visual defects after a stroke, can help patients, and their families, in the rehabilitation process. OBJECTIVE: This article provides a review of the functional disability from visual field loss and discusses the various forms of visual rehabilitation. DISCUSSION: Optical therapy, eye movement therapy and visual field restitution are the rehabilitation therapies currently available. Rehabilitation needs to cater to each patient's specific needs. Any patient recognised as having a visual field defect after stroke needs prompt referral for further assessment and consideration for visual rehabilitation.

Arterial Occlusions to the Eye: From Retinal Emboli to Ocular Ischemic Syndrome.

: Abstract: A loss or lack of blood supply to the eye can result in acute loss of vision. The site of ischemia may be at the level of the retinal arterioles, the central retinal artery, or further back at the ophthalmic and internal carotid artery. Recognizing the symptoms and signs are important to help prevent permanent ischemic and irreversible blindness. The objective of this review article is to provide the general ophthalmologists with information on how to recognize the symptoms and to best manage these patients. The management is to investigate for the cause of the transient monocular visual loss and to apply secondary prevention to address atherosclerotic risk factors to prevent further ischemic events like a stroke.

Vision-related quality of life in patients with complete homonymous hemianopia post stroke.

PURPOSE: The aim is to determine the characteristics of vision-specific quality of life restriction using the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and Veterans Affairs Low Vision Visual Function Questionnaire (VA LV VFQ-48) in patients with complete homonymous hemianopia (HH) post stroke. METHOD: Prospective cohort study of patients with complete HH compared to age- and gender-matched subjects with normal visual fields. RESULTS: In the NEI VFQ-25, scores on five subscales were significantly reduced after multiple logistic regression accounting for vision and comorbidities. The five subscales are vision-specific social functioning, vision-specific mental health, vision-specific dependency, driving, and peripheral vision. In the VA LV VFQ-48 postregression analysis, mobility is the only domain that is significantly affected in the people with HH. CONCLUSION: Identification of the significant areas of visual difficulties and their effects on quality of life is important as it can help better address the patients' rehabilitation needs. The current study identifies the need for orientation and mobility training as well as independent living rehabilitation in patients with HH to help address the difficulties in their vision-specific quality of life and maximize their residual vision.

Optic neuritis--more than a loss of vision.

BACKGROUND: Optic neuritis is an acute inflammation of the optic nerve that results in painful loss of vision. Patients often present to a general practitioner, and early recognition is important as treatment may improve the speed of vision recovery. OBJECTIVE: This article provides information on the signs and symptoms of optic neuritis and discusses appropriate referral, investigations and management. DISCUSSION: Optic neuritis is the presenting symptom in up to one-fifth of people with multiple sclerosis. Diagnosis of optic neuritis is based on history and examination, therefore obtaining pertinent information and performing proper ophthalmic examination is essential. Prompt recognition and appropriate referral is important to facilitate investigations such as magnetic resonance imaging of the brain that can help predict risk in the development of multiple sclerosis.

Multiple sclerosis presenting with homonymous hemianopia.

Ophthalmic manifestations are a prominent feature of multiple sclerosis (MS). Optic neuritis accounts for 18% of initial MS symptoms and 40-70% of all patients with MS have at least one episode of optic neuritis during their disease course.

Visual compensation in cervical dystonia.

Introduction: Visual-spatial processing can be affected in people with cervical dystonia (CD). These impairments have almost exclusively been observed in laboratory studies, but the impact of visuo-spatial impairments on daily activities is unclear. Here, we investigated how people living with CD visually explore the environment. Method: 21 participants (10 patients and 11 controls) walked a designated course searching for targets while their eye movements were tracked by the means of eye tracking glasses. In addition, all participants performed an extensive battery of spatial neglect tests. Results: People with CD visually compensated for their lateral head position. That is, they made more eye movements towards the side opposite their lateral head position. No evidence for or against spatial asymmetries were detected in a range of behavioral measures (target detection, standard neglect battery tests) on a group level. Yet, single patients showed a neglect-like pattern. One patient with a right torticollis failed to detect most left-sided targets when walking. Conclusion: In general, participants seem to adequately compensate for the deviated head posture when judging spatial stimuli. However, the insufficient spatial exploration in one patient with a valid driving license should raise awareness in clinicians to potential visuo-spatial problems in people living with CD. An interesting question arising from our findings is whether people with CD and marked visuo-spatial deficits would benefit from scanning training, as is employed in stroke rehabilitation.

Local intraarterial fibrinolysis administered in aliquots for the treatment of central retinal artery occlusion: the Johns Hopkins Hospital experience.

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in acute visual loss with poor spontaneous recovery. Current standard therapies do not alter the natural history of disease. Several open-label clinical studies using continuous infusion of thrombolytic agents have suggested that local intraarterial fibrinolysis (LIF) is efficacious in the treatment of central retinal artery occlusion. The aim is to compare the visual outcome in patients with acute central retinal artery occlusion of presumed thromboembolic etiology treated with LIF administered in aliquots with that of patients treated with standard therapy. METHODS: We conducted a single-center, nonrandomized interventional study of consecutive patients with acute central retinal artery occlusion from July 1999 to July 2006. RESULTS: Twenty-one patients received LIF and 21 received standard therapy. Seventy-six percent of subjects in the LIF group had a visual acuity improvement of one line or more compared with 33% in the standard therapy group (P=0.012, Fisher exact). Multivariate logistic regression controlling for gender, history of prior stroke/transient ischemic attack, and history of hypercholesterolemia showed that patients who received tissue plasminogen activator were 36 times more likely to have improvement in visual acuity (P=0.0001) after adjusting for these covariates. Post hoc analysis showed that patients who received tissue plasminogen activator were 13 times more likely to have improvement in visual acuity of 3 lines or more (P=0.03) and 4.9 times more likely to have a final visual acuity of 20/200 or better (P=0.04). Two groin hematomas were documented in the LIF group. No ischemic strokes, retinal or intracerebral hemorrhages were documented. CONCLUSIONS: LIF administered in aliquots is associated with an improvement in visual acuity compared with standard therapy and has few side effects.

Management of acute central retinal artery occlusion.

Central retinal artery occlusion (CRAO) is considered to be an acute stroke of the eye that results in profound visual loss. Spontaneous recovery rates are poor. Most CRAOs are caused by thromboembolism in the central retinal artery. Current standard therapies for CRAO that aim to restore perfusion to the retina and optic nerve head have not been shown to alter the natural course of the disease. Thrombolytic therapy for acute management of CRAO has shown promise in nonrandomized studies with regard to improving visual outcomes. A randomized controlled trial will be required to confirm the efficacy of thrombolytic therapy before it can be recommended for use in CRAO in daily clinical practice.

Third cranial nerve palsy caused by intracranial extension of a sino-orbital natural killer T-cell lymphoma.

Natural killer/T-cell lymphomas (NKTLs) are rare destructive lesions that usually involve the nasal cavity or paranasal sinuses. Orbital and intracranial involvement is rare. A 53-year-old man with systemic lupus erythematosus who was receiving chronic low-dose prednisone treatment developed proptosis of the right eye. Biopsy of a sino-orbital lesion suggested nonspecific inflammation. Clinical and imaging manifestations resolved with a higher dose of prednisone, but when the prednisone dose was tapered, the patient developed a complete right third cranial nerve palsy. Imaging showed return of the original lesion, now with intracranial extension and enhancement of the right third cranial nerve. Repeat biopsy showed features consistent with NKTL. Biopsy of this lesion in its early stage may misleadingly suggest a primary inflammatory disorder because of a paucity of neoplastic cells, a large number of inflammatory cells recruited by the innate natural killer (NK) cell immune response, and extensive necrosis caused by angiodestructive tumor cells.

A novel deletion in the FTL gene causes hereditary hyperferritinemia cataract syndrome (HHCS) by alteration of the transcription start site.

Hereditary hyperferritinemia cataract syndrome (HHCS) is characterized by distinctive cataracts and high serum ferritin in the absence of iron overload. It is caused by mutations in the iron response element (IRE) of the Ferritin Light Chain (FTL) gene. Here we investigate the genetics of HHCS in a three generation Australian kindred with typical HHCS ocular lens morphology and high ferritin levels. Initial sequencing of the IRE failed to detect any mutations. Sequencing of the entire gene including the promoter region revealed a novel 25 bp deletion upstream of the IRE abolishing the transcription start site. In lymphoblastoid cells, the deletion allele was transcribed from an alternate start site within the lower stem of the IRE and mutation carriers had high cellular L-ferritin levels. This novel deletion in the promoter encompassing the transcription start site of the FTL gene is responsible for HHCS in this kindred. The initial primers for amplifying the IRE similar to those used by other researchers failed to detect this mutation. Therefore the genomic region assessed in HHCS cases for diagnosis should be expanded to include mutations of this type.

Double vision in a patient with thyroid disease: what's the big deal?

A 70-year-old woman with a 46-year history of Graves disease had significant thyroid related orbitopathy (TRO) requiring previous bilateral orbital decompressions and one previous strabismus procedure for an exotropia of 60 PD. At the initial neuro-ophthalmology assessment, she had an exotropia of 20 PD and was scheduled for further surgery, but at the time of a second assessment a few weeks later, her strabismus had markedly changed. Accordingly, the patient underwent a neostigmine bromide test that demonstrated evidence of co-existing myasthenia gravis.