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International Journal of Molecular... Jul 2022Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene () cause a rare autosomal recessive retinal dystrophy and its disease course is not well...
Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene () cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone-rod or rod-cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease.
Topics: Autoimmune Diseases; Cone-Rod Dystrophies; Electroretinography; Humans; Membrane Proteins; Mutation; Pedigree; Phenotype; Retinal Dystrophies; Tomography, Optical Coherence
PubMed: 35806404
DOI: 10.3390/ijms23137398 -
ESC Heart Failure Apr 2024A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data... (Observational Study)
Observational Study
AIMS
A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF.
METHODS AND RESULTS
This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%).
CONCLUSIONS
Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies.
Topics: Adult; Aged; Humans; Male; Middle Aged; Adrenergic beta-Antagonists; Benzazepines; Cardiovascular Agents; China; Heart Failure; Ivabradine; Prospective Studies; Quality of Life; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Vision Disorders; Female
PubMed: 38193606
DOI: 10.1002/ehf2.14581 -
European Journal of Ophthalmology May 2024To review all studies reporting the occurrence of white dot syndromes (WDSs) following SARS-COV-2 infection. (Review)
Review
PURPOSE
To review all studies reporting the occurrence of white dot syndromes (WDSs) following SARS-COV-2 infection.
METHODS
On May 12, 2023, we registered our protocol on PROSPERO [registration number: CRD42023426012]. Five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct were searched up to May 2023. We included all studies that reported the symptoms of WDSs following SARS-COV-2 infection. The data was extracted using a uniform Excel extraction sheet. All statistical tests were conducted with a 95% confidence interval and a 5% error margin. A p-value of less than 0.05 was considered statistically significant. The publication bias of included studies was assessed using JBI Critical Appraisal Checklist for Case Reports and IHE Quality Appraisal Checklist for Case Series studies.
RESULTS
This review included thirty-two studies involving forty-eight patients. Acute macular neuroretinopathy was the most common disease (70.8%) followed by multiple evanescent white dot syndrome (14.6%) with 58.3% of WDS after their first SARS-COV-2 infection, and paracentral acute middle maculopathy (4.1%). They were mostly unilateral (56.2%). The presenting symptoms were blurred vision (70.8%), visual field disturbance (68.7%), and photopsia (20.8%). About 35.4% of the patients improved by their treatment and future complications were persistent scotoma (4.2%) and macular edema (2.1%).
CONCLUSION
White dot syndromes are very rare entities. Our findings suggest a possible association between white dot syndrome onset and SARS-COV-2 infection. We recommend ophthalmologists should be aware of this suggested association to deliver better management and patients' care.
PubMed: 38751139
DOI: 10.1177/11206721241255402 -
Future Oncology (London, England) Jun 2019ALK inhibitors are a new group of tyrosine kinase inhibitors, highly efficient in the treatment of non-small-cell lung carcinoma. However, these targeted therapies can... (Meta-Analysis)
Meta-Analysis Review
ALK inhibitors are a new group of tyrosine kinase inhibitors, highly efficient in the treatment of non-small-cell lung carcinoma. However, these targeted therapies can induce various adverse effects, including ocular toxicity. To date, few articles reporting ophthalmological side effects of ALK inhibitors have been published. In this review, we aim to describe the different side effects and to collect information regarding the causes behind the discrepancy between the reported rates of visual disorders. Frequent ocular side effects of ALK inhibitors included flashes, post-flashbulb effect, stripes, photopsia, accommodation disorder, presbyopia, reduced visual acuity and blurred vision. Optic neuropathy, vitreous floaters, diplopia, cataract and macular edema were also reported.
Topics: Anaplastic Lymphoma Kinase; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Eye Diseases; Humans; Lung Neoplasms; Molecular Targeted Therapy; Orbital Diseases; Protein Kinase Inhibitors
PubMed: 31140869
DOI: 10.2217/fon-2018-0608 -
BMJ Case Reports Aug 2015
Topics: Adult; Humans; Light; Male; Retinal Neoplasms; Retinoblastoma
PubMed: 26243747
DOI: 10.1136/bcr-2015-211018 -
Cureus Dec 2022We report on a case of multiple evanescent white dot syndrome (MEWDS) following the simultaneous administration of the human papillomavirus and meningococcal (conjugate)...
We report on a case of multiple evanescent white dot syndrome (MEWDS) following the simultaneous administration of the human papillomavirus and meningococcal (conjugate) vaccines and two recurrences of MEWDS following the administration of the second dose of the human papillomavirus (HPV) vaccine and the COVID-19 vaccine and COVID-19 viral infection. A 17-year-old Hispanic female presented with a one-week history of photopsia and blurred vision in her left eye following the simultaneous administration of the human papillomavirus and meningococcal (conjugate) vaccines. Upon a comprehensive examination, her best-corrected visual acuity was 20/20 in the right eye and 20/100 in the left eye. A left fundus examination revealed multiple white dots in the macula and nasal periphery, consistent with a diagnosis of MEWDS. Ancillary testing, including fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and optical coherence tomography, supported the diagnosis. One month following her initial diagnosis, the patient's symptoms had resolved without any therapy, and a fundus examination revealed multiple relatively ill-defined brown-colored subretinal lesions in the nasal midperiphery, corresponding to the location of the previous MEWDS lesions. Subsequently, she received the second dose of the HPV vaccine and then developed a mild COVID-19 infection. Four months after the initial presentation, she received the first dose of the BNT162b2 COVID-19 vaccine, followed by the second dose a month later. Eight months following her initial presentation, she presented with photopsia in the right eye. Her visual acuity remained 20/20 in the right eye and improved to 20/20 in the left eye, and white dots were identified nasal to the disk and surrounding the peripapillary region; the contralateral MEWDS diagnosis was confirmed by the previously mentioned ancillary tests. At her one-month follow-up, she presented new onset photopsia of the right eye. Her visual acuity remained 20/20 in both eyes, and a fundus examination revealed white lesions suggestive of active MEWDS temporal to the macula and brown-colored spots nasal to the disk, suggestive of recovering MEWDS, nasally. The aforementioned testing confirmed the coexistence of new and resolving lesions; nonetheless, the patient's symptoms resolved without any therapy, and she received the third dose of the BNT162b2 COVID-19 vaccine 11 months after her initial presentation. Our case suggests that vaccines may serve as immunological triggers of MEWDS. Recurrent MEWDS may occur when an individual is exposed to a powerful immune challenge, such as receiving a wide array of vaccinations in a short period of time. We believe this case constitutes a previously undescribed finding of multiple relatively ill-defined brown-colored subretinal lesions present in late MEWDS.
PubMed: 36628035
DOI: 10.7759/cureus.32300 -
Journal of Cancer Research and Clinical... Mar 2022Fluid-conducting extracellular matrix patterns known as vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma and other cancers. We...
PURPOSE
Fluid-conducting extracellular matrix patterns known as vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma and other cancers. We investigate the correlations between VM, presenting symptoms, mortality, and the area density of periodic acid-Schiff positive histological patterns (PAS density).
METHODS
Sixty-nine patients that underwent enucleation for uveal melanoma between 2000 and 2007 were included. Clinicopathological parameters presenting symptoms and outcomes were collected. Histological tumor sections were evaluated for VM and PAS density was quantified with digital image analysis.
RESULTS
Thirty-four patients (49%) presented with blurred vision. 18 (26%) with a shadow in the visual field, 7 (10%) with photopsia and/or floaters, and 2 (3%) with metamorphopsia. Nine patients (13%) had no symptoms at all. Median follow-up was 16.7 years (SD 2.6). A shadow in the visual field, but no other symptom, was positively correlated with the presence of VM (φ 0.70, p < 0.001) and greater PAS density (p < 0.001). In multivariate regression, retinal detachment (RD), presence of VM, and PAS density ≥ median were independent predictors of a shadow, but not tumor distance to the macula, tumor apical thickness, tumor diameter, or ciliary body engagement. The presence of VM was associated with significantly shorter cumulative disease-specific survival (Wilcoxon p = 0.04), but not PAS density ≥ median, presenting symptoms or RD (p > 0.28).
CONCLUSION
Tumors from uveal melanoma patients that report a visual field shadow are likely to display VM and greater PAS density, likely explaining the previously reported association between this symptom and poor prognosis.
Topics: Female; Follow-Up Studies; Humans; Male; Melanoma; Middle Aged; Neovascularization, Pathologic; Prognosis; Retrospective Studies; Survival Rate; Uveal Neoplasms
PubMed: 34775516
DOI: 10.1007/s00432-021-03851-9 -
Case Reports in Neurology 2021Migraine with aura may be confused with a stroke. Magnetic resonance imaging is an important tool for the differential diagnosis. Cerebral hypoperfusion has been...
Migraine with aura may be confused with a stroke. Magnetic resonance imaging is an important tool for the differential diagnosis. Cerebral hypoperfusion has been described in classic migraine, mainly during the aura. A 47-year-old male had an unremarkable past medical history. After sneezing, he developed a left hemi hypoesthesia, bitemporal vision loss, photopsia, and some distortion in the position of letters and words. This lasted <1 h, and it was followed by a severe headache. A magnetic resonance angiography was performed during the headache. It showed a left hemispheric hypoperfusion that did not correlate with the symptoms described by the patient. It is believed that during the aura, cerebral blood flow decreases, leading to hypoxia and decreased cellular energy generation, and these metabolic alterations define the symptoms of the patient. In our case, we documented brain hypoperfusion during the headache in the ipsilateral brain hemisphere to the symptoms, which has no clinical correlation. This condition could be due to spasm in the capillary arteries, and it may persist and influence the clinical manifestations during the headache phase in migraine with aura. A state of generalized cerebral hyperperfusion has been suggested, and there may be a coexistence of both phenomena for some period. This may open a new line of research regarding the pathophysiology and vascular changes of migraine with aura.
PubMed: 34899251
DOI: 10.1159/000519508 -
Survey of Ophthalmology 2022Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's... (Meta-Analysis)
Meta-Analysis Review
Ocriplasmin for treatment of vitreomacular traction and macular hole: A systematic literature review and individual participant data meta-analysis of randomized, controlled, double-masked trials.
Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.
Topics: Female; Fibrinolysin; Humans; Intravitreal Injections; Peptide Fragments; Retinal Diseases; Retinal Perforations; Tomography, Optical Coherence; Traction; Treatment Outcome; Vision Disorders; Visual Acuity; Vitreous Body; Vitreous Detachment
PubMed: 34480895
DOI: 10.1016/j.survophthal.2021.08.003 -
Ophthalmology Oct 2015To assess the character and cause of photopsias in vitreoretinal patients.
PURPOSE
To assess the character and cause of photopsias in vitreoretinal patients.
DESIGN
Cross-sectional study.
PARTICIPANTS
A total of 169 consecutive patients (217 eyes) with vitreoretinal disease presenting with a history of photopsias.
METHODS
A total of 217 eyes with photopsias in 169 patients were evaluated. Photopsia assessment included (1) laterality (unilateral, bilateral but not simultaneous, bilateral, and simultaneous); (2) morphology (flash, zig-zag, strobe, scintillating scotoma, twinkling, other); (3) color (white, silver, yellow, combination, other); (4) location (temporal, central, other); (5) duration (quick, prolonged, constant, other); (6) frequency; (7) diurnal appearance (day, night, both); (8) stimuli (turning head or eyes, hypoglycemia, hyperglycemia, other); and (9) associated systemic or ocular signs and symptoms (headache, numbness, weakness, vertigo, syncope, diplopia, hypotension, floaters, other).
MAIN OUTCOME MEASURES
Clinical photopsia features correlated with the causes of photopsias.
RESULTS
Thirty-two photopsia causes were identified. The top 16 included posterior vitreous detachment (PVD) in 39.7% of eyes; retinal tear in 8.9% of eyes; neovascular age-related macular degeneration (AMD) in 7.9% of eyes; rhegmatogenous retinal detachment (RRD) in 7.5% of eyes; classic and ophthalmic migraine in 6.5% of eyes; hypoglycemia in 2.8% of eyes; vertebrobasilar insufficiency in 2.8% of eyes; non-AMD choroidal neovascularization in 2.3% of eyes; retinitis pigmentosa in 1.9% of eyes; severe cough in 1.9% of eyes; central serous chorioretinopathy in 1.4% of eyes; intraocular lens reflections in 0.9% of eyes; blue field entoptic phenomenon in 0.9% of eyes; Charles Bonnet syndrome in 0.9% of eyes; digitalis in 0.9% of eyes; and metastatic adenocarcinoma to the brain in 0.9% of eyes. The photopsias associated with PVD are typically quick (96%), with lightning/flash morphology (96%), white (87%), temporally located (86%), associated with new-onset floaters (85%), preferentially seen in dark (90%) rather than lighted environments (29%), and often initiated by head/eye movements (60%). Retinal detachment had a similar profile, but with more nontemporal photopsias (40%) (P = 0.01). The photopsias from neovascular AMD are more centrally located (83%), quick and repetitive (79%), seen in light (73%) and dark (63%) environments, have no inciting stimuli (84%), and are more likely to be nonwhite (40%).
CONCLUSIONS
A pointed history for photopsias can reveal a cause that may not initially seem apparent. Thus, the history can play a key role in management decisions.
Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Eye Diseases; Female; Humans; Male; Middle Aged; Perceptual Disorders; Phosphenes; Retinal Diseases; Vision Disorders; Vitreous Body
PubMed: 26249730
DOI: 10.1016/j.ophtha.2015.06.025