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Frontiers in Neural Circuits 2014During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional...
During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca(2+) imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.
Topics: Animals; Biological Clocks; Calbindins; Calcium; Connexins; Cyclic Nucleotide Phosphodiesterases, Type 6; Disease Models, Animal; Excitatory Amino Acid Transporter 5; Green Fluorescent Proteins; Mice; Mice, Transgenic; Neurons; Neurotransmitter Agents; Phosphoproteins; Protein Kinase C-alpha; Retina; Retinitis Pigmentosa; Synapses; Gap Junction delta-2 Protein
PubMed: 25249942
DOI: 10.3389/fncir.2014.00108 -
Open Heart Oct 2020To determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease. (Meta-Analysis)
Meta-Analysis
Effects of adding ivabradine to usual care in patients with angina pectoris: a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis.
OBJECTIVE
To determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease.
METHODS
We conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published prior to June 2020. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane methodology, Trial Sequential Analysis, Grading of Recommendations Assessment, Development, and Evaluation, and our eight-step procedure. Primary outcomes were all-cause mortality, serious adverse events and quality of life.
RESULTS
We included 47 randomised clinical trials enrolling 35 797 participants. All trials and outcomes were at high risk of bias. Ivabradine compared with control did not have effects when assessing all-cause mortality (risk ratio [RR] 1.04; 95% CI 0.96 to 1.13), quality of life (standardised mean differences -0.05; 95% CI -0.11 to 0.01), cardiovascular mortality (RR 1.07; 95% CI 0.97 to 1.18) and myocardial infarction (RR 1.03; 95% CI 0.91 to 1.16). Ivabradine seemed to increase the risk of serious adverse events after removal of outliers (RR 1.07; 95% CI 1.03 to 1.11) as well as the following adverse events classified as serious: bradycardia, prolonged QT interval, photopsia, atrial fibrillation and hypertension. Ivabradine also increased the risk of non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16). Ivabradine might have a statistically significant effect when assessing angina frequency (mean difference (MD) 2.06; 95% CI 0.82 to 3.30) and stability (MD 1.48; 95% CI 0.07 to 2.89), but the effect sizes seemed minimal and possibly without any relevance to patients, and we identified several methodological limitations, questioning the validity of these results.
CONCLUSION
Our findings do not support that ivabradine offers significant benefits on patient important outcomes, but rather seems to increase the risk of serious adverse events such as atrial fibrillation and non-serious adverse events. Based on current evidence, guidelines need reassessment and the use of ivabradine for angina pectoris should be reconsidered.
PROSPERO REGISTRATION NUMBER
CRD42018112082.
Topics: Aged; Angina Pectoris; Cardiovascular Agents; Female; Humans; Ivabradine; Male; Middle Aged; Patient Safety; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33046592
DOI: 10.1136/openhrt-2020-001288 -
Neuro-ophthalmology (Aeolus Press) Feb 2019A 73-year-old female with a past medical history of breast cancer, who 10 years earlier experienced complete remission, complained of bilateral visual field...
A 73-year-old female with a past medical history of breast cancer, who 10 years earlier experienced complete remission, complained of bilateral visual field disturbances and photopsia, 2 months prior. Tumour recurrence and metastatic lesions were not found during the medical examination, but antibodies against recoverin were detected in her serum. Despite immunosuppressive treatment with prednisolone and plasmapheresis, rapid and diffuse degeneration of the patient's photoreceptors and deterioration of her visual field were observed. This is a rare case of cancer-associated retinopathy with a long interval (10 years) between the diagnosis of the malignancy and visual loss.
PubMed: 30723523
DOI: 10.1080/01658107.2018.1460761 -
BMJ Open Ophthalmology 2022To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.
Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review.
OBJECTIVE
To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.
METHODS AND ANALYSIS
Retrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Case 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed.
CONCLUSIONS
Immune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.
Topics: Antibodies, Monoclonal, Humanized; Autoimmune Diseases; Humans; Immunologic Factors; Immunotherapy; Ipilimumab; Melanoma; Nivolumab; Retinal Diseases; Retrospective Studies; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35047671
DOI: 10.1136/bmjophth-2021-000889 -
Documenta Ophthalmologica. Advances in... Dec 2013The purpose of the study is to report the clinical case of a 53-year-old woman whose presenting manifestation of primary intraocular lymphoma (PIOL) was unilateral...
PURPOSE
The purpose of the study is to report the clinical case of a 53-year-old woman whose presenting manifestation of primary intraocular lymphoma (PIOL) was unilateral retinal degeneration.
METHOD
A case report was created with review of clinical, imaging, electrophysiologic, and pathological investigations.
RESULTS
A 53-year-old woman with a distant history of ocular herpes simplex developed progressive central visual loss and intermittent photopsia over 4 years in her right eye. Ophthalmic examination revealed reduced visual acuity OD, central scotoma, and minimal ocular findings. Autofluorescence and infrared imaging revealed mild reflectance changes in the temporal macula, and spectral-domain optical coherence tomography identified mild disruptions of inner segment/outer segment junctions in the subfoveal region of the right eye. A mild window defect was seen on fluorescein angiography. Electrophysiology with multifocal electroretinogram (ERG) revealed evidence of unilateral macular dysfunction. Full-field ERGs revealed progressive global retinal dysfunction over 6 months, with unilateral decreases in amplitude and implicit time shifts, as seen in cases of autoimmune retinopathies. The eye eventually exhibited mild vitreous cellular infiltration on ophthalmoscopic examination, and vitrectomy diagnosed B cell non-Hodgkin's lymphoma. Further evaluation revealed no evidence of central nervous system or systemic disease, consistent with occult PIOL.
CONCLUSIONS
This case illustrates an atypical presentation of PIOL characterized by unilateral retinal disease presenting with symptoms and signs of macular dysfunction. Clinical and ERG features evolved into an acute zonal occult outer retinopathy (AZOOR)-like phenotype. PIOL should be considered in atypical cases of AZOOR with vitreal reactions, and some cases of AZOOR may be related to B cell lymphocyte disorders.
Topics: Electroretinography; Female; Flow Cytometry; Fluorescein Angiography; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Ophthalmoscopy; Retinal Neoplasms; Scotoma; Tomography, Optical Coherence; Visual Acuity; Visual Fields; Vitrectomy; White Dot Syndromes
PubMed: 24081663
DOI: 10.1007/s10633-013-9409-7 -
Journal of Clinical Medicine May 2023The global pandemic impact of the COVID-19 infection included clinical manifestations that affected several organs and systems, with various neuro-ophthalmological...
The global pandemic impact of the COVID-19 infection included clinical manifestations that affected several organs and systems, with various neuro-ophthalmological manifestations associated with the infection. These are rare and occur either secondary to the presence of the virus or by an autoimmune mechanism secondary to viral antigens. The manifestations are atypical, being present even in the absence of the systemic symptoms typical of a SARS-CoV-2 infection. In this article, we introduce a series of three clinical cases with neuro-ophthalmological manifestations associated with COVID infection that were shown in Ophthalmology Clinic of St. Spiridon Emergency Hospital. Case 1 is that of a 45-year-old male patient with no personal history of general pathology or ophthalmology, with binocular diplopia, painful red eyes, and lacrimal hypersecretion with a sudden onset of about 4 days. Based on the evaluations, a positive diagnosis of orbital cellulitis in both eyes is made. Case 2 is that of a 52-year-old female patient with general PPA (personal pathological antecedents) of SARS-CoV-2 infection 1 month prior to presentation with decreased visual acuity in the right eye and a positive central scotoma, preceded by photopsia and vertigo with balance disorders. The diagnosis is made at the right eye for retrobulbar optic neuritis and post-SARS-CoV-2 infection status. The last clinical case is that of a 55-year-old male patient known to have high blood pressure (HBP) with a sudden, painless decrease in VARE approximately 3 weeks post-SARS-CoV-2 immunization (Pfizer vaccine first dose). The diagnosis is made after consulting all the RE results for central retinal vein thrombosis. Conclusions: Although the cases were quickly and efficiently investigated and the treatment was administered adequately by a multidisciplinary team (cases 1 and 3), the evolution was not favorable in all three situations. Atypical neuro-ophthalmological manifestations can also be present in the absence of systemic symptoms typical of SARS-CoV-2 infection.
PubMed: 37297989
DOI: 10.3390/jcm12113795 -
Ophthalmic & Physiological Optics : the... Mar 2009Standardised patients (SPs) are the gold standard methodology for evaluating clinical care. This approach was used to investigate the content of optometric eyecare for a...
BACKGROUND
Standardised patients (SPs) are the gold standard methodology for evaluating clinical care. This approach was used to investigate the content of optometric eyecare for a presbyopic patient who presented with recent photopsia.
METHODS
A total of 102 community optometrists consented to be visited by an actor for a recorded eye examination. This actor received extensive training to enable accurate reporting of the content of the eye examinations, via an audio recording and a checklist completed for each clinical encounter. The actor presented unannounced (incognito) as a 59-year-old patient seeking a private eye examination and complaining of recent onset flashing lights. The results of each clinical encounter were recorded on a pre-designed checklist based on evidence-based reviews on photopsia, clinical guidelines and the views of an expert panel.
RESULTS
The presence of the symptom of photopsia was proactively detected in 87% of cases. Although none of the optometrists visited asked all seven gold standard questions relating to the presenting symptoms of flashing lights, 35% asked four of the seven questions. A total of 85% of optometrists asked the patient if he noticed any floaters in his vision and 36% of optometrists asked if he had noticed any shadows in his vision. The proportion of the tests recommended by the expert panel that were carried out varied from 33 to 100% with a mean of 67%. Specifically, 66% recommended dilated fundoscopy to be carried out either by themselves or by another eyecare practitioner, and 29% of optometrists asked the patient to seek a second opinion regarding the photopsia. Of those who referred, 70% asked for the referral to be on the same day or within a week.
CONCLUSION
SP encounters are an effective way of measuring clinical care within optometry and should be considered for further comparative measurements of quality of care. As in research using SPs in other healthcare disciplines, our study has highlighted substantial differences between different practitioners in the duration and depth of their clinical investigations. This highlights the fact that not all eye examinations are the same but inherently different and that there is no such thing as a 'standard sight test'. Future optometric continuing education could focus on history taking, examination techniques and referral guidelines for patients presenting with symptoms of posterior vitreous detachment, retinal breaks and secondary retinal detachment.
Topics: Adult; Aged; Aged, 80 and over; Clinical Competence; Delivery of Health Care; Humans; Middle Aged; Optometry; Patient Simulation; Presbyopia; Quality of Health Care; Surveys and Questionnaires; Vision Disorders
PubMed: 19236581
DOI: 10.1111/j.1475-1313.2008.00613.x -
The New England Journal of Medicine Aug 2012Vitreomacular adhesion can lead to pathologic traction and macular hole. The standard treatment for severe, symptomatic vitreomacular adhesion is vitrectomy. Ocriplasmin... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Vitreomacular adhesion can lead to pathologic traction and macular hole. The standard treatment for severe, symptomatic vitreomacular adhesion is vitrectomy. Ocriplasmin is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface.
METHODS
We conducted two multicenter, randomized, double-blind, phase 3 clinical trials to compare a single intravitreal injection of ocriplasmin (125 μg) with a placebo injection in patients with symptomatic vitreomacular adhesion. The primary end point was resolution of vitreomacular adhesion at day 28. Secondary end points were total posterior vitreous detachment and nonsurgical closure of a macular hole at 28 days, avoidance of vitrectomy, and change in best-corrected visual acuity.
RESULTS
Overall, 652 eyes were treated: 464 with ocriplasmin and 188 with placebo. Vitreomacular adhesion resolved in 26.5% of ocriplasmin-injected eyes and in 10.1% of placebo-injected eyes (P<0.001). Total posterior vitreous detachment was more prevalent among the eyes treated with ocriplasmin than among those injected with placebo (13.4% vs. 3.7%, P<0.001). Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo-injected eyes (P<0.001). The best-corrected visual acuity was more likely to improve by a gain of at least three lines on the eye chart with ocriplasmin than with placebo. Ocular adverse events (e.g., vitreous floaters, photopsia, or injection-related eye pain--all self-reported--or conjunctival hemorrhage) occurred in 68.4% of ocriplasmin-injected eyes and in 53.5% of placebo-injected eyes (P<0.001), and the incidence of serious ocular adverse events was similar in the two groups (P=0.26).
CONCLUSIONS
Intravitreal injection of the vitreolytic agent ocriplasmin resolved vitreomacular traction and closed macular holes in significantly more patients than did injection of placebo and was associated with a higher incidence of ocular adverse events, which were mainly transient. (Funded by ThromboGenics; ClinicalTrials.gov numbers, NCT00781859 and NCT00798317.).
Topics: Adult; Double-Blind Method; Eye Diseases; Fibrinolysin; Humans; Intravitreal Injections; Peptide Fragments; Retina; Retinal Perforations; Visual Acuity; Vitreous Body
PubMed: 22894573
DOI: 10.1056/NEJMoa1110823 -
Arquivos Brasileiros de Oftalmologia 2022A 38-year-old woman presented with photopsias and progressive but painless loss of vision in her right eye. Of note, she had received the first dose of inactivated...
A 38-year-old woman presented with photopsias and progressive but painless loss of vision in her right eye. Of note, she had received the first dose of inactivated COVID-19 vaccine (Sinovac/China National Pharmaceutical Group) 2 weeks prior to the onset of symptoms. Ophthalmic evaluation revealed a wreath-like foveal pattern and multiple gray-white dots throughout the posterior pole associated with discrete vitreous inflammatory reaction. Multimodal imaging analysis confirmed a diagnosis of multiple evanescent white dot syndrome. The patient underwent treatment with corticosteroids and, over the following weeks, her visual acuity improved to standard pattern.
Topics: Adult; COVID-19; COVID-19 Vaccines; Female; Fluorescein Angiography; Humans; Retinal Diseases; Vaccination; White Dot Syndromes
PubMed: 35298582
DOI: 10.5935/0004-2749.20220070 -
Case Reports in Ophthalmological... 2019Multimodal imaging techniques were performed in a patient with a newly emerged visual field defect; a missing retinal lesion on fundus examination made the diagnosis...
Multimodal imaging techniques were performed in a patient with a newly emerged visual field defect; a missing retinal lesion on fundus examination made the diagnosis challenging but infrared imaging showed a larger area of retinal abnormality temporal to the fovea. Indocyanine green angiography (IA) showed late hypofluorescence and there was mild hyperautofluorescence which is known from acute zonal occult outer retinopathy (AZOOR). Despite normal fluorescein angiography (FA) results, a perfusion loss in the outer retinal layer was detected by OCT-A. Similar OCT-A findings were recently described in patients with acute macular neuroretinopathy (AMN). . The methods included FA and IA, spectral domain optical coherence tomography (SD-OCT), near infrared imaging, and autofluorescence imaging (AF), as well as OCT-A. A 36-year-old patient who suffered from acute symptoms of photopsia and scotoma on her left eye. She had an influenzalike illness two weeks earlier. The scotoma could be verified by visual field testing. . The affected retinal zone showed mild fading of external limiting membrane (ELM) and a disorganisation of the ellipsoid zone (EZ) on SD-OCT. OCT-A revealed a large area of reduced perfusion in the outer retinal vascular layer. . OCT-A can help to detect reduced capillary network in patients with visual field defects and no visible fundus changes. This case seems to have features of different occult retinal disorders such as AZOOR and AMN.
PubMed: 31341688
DOI: 10.1155/2019/4349692