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Journal of Clinical Medicine May 2024Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision... (Review)
Review
Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.
PubMed: 38792322
DOI: 10.3390/jcm13102778 -
Journal of Neuroinflammation May 2024Behcet's disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet's uveitis (BU) is a... (Review)
Review
Behcet's disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.
Topics: Humans; Behcet Syndrome; Uveitis; Animals
PubMed: 38778397
DOI: 10.1186/s12974-024-03123-6 -
Journal of Vitreoretinal Diseases 2024To assess the severity, progression, and treatment burden of diabetic retinopathy (DR) in patients after bariatric surgery compared with controls. A retrospective...
To assess the severity, progression, and treatment burden of diabetic retinopathy (DR) in patients after bariatric surgery compared with controls. A retrospective cohort study was performed of patients with type 2 diabetes and DR seen at the Duke Eye Center between 2014 and 2023. Clinical data included hemoglobin A (HbA), diagnostic stage of DR, diabetic macular edema (DME) or vitreous hemorrhage (VH), visual acuity (VA), and treatment burden at baseline and follow-up. Generalized estimating equation analysis was used to account for the correlation between 2 eyes of the same patient. Sixteen patients who had bariatric surgery were matched by age, sex, and duration of diabetes with 60 control patients managed medically during the same time period. The HbA level, severity of DR, presence of DME or VH, VA, and treatment burden were not significantly different (all > .05) at the baseline examination. On average, patients were followed for 6 years. The HbA level at the follow-up was significantly lower in the bariatric surgery group (6.4% vs 8.5%; < .001). At the follow-up, the treatment burden was reduced in the bariatric surgery group compared with the control group ( = .04). There was a clear trend toward reduced progression of DR and treatment burden in the bariatric surgery group over the follow-up. Bariatric surgery may improve glycemic control, stabilize DR progression, and reduce the treatment burden, which may have a significant impact on quality of life for patients with DR.
PubMed: 38770070
DOI: 10.1177/24741264241231185 -
Journal of Translational Medicine May 2024Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels,...
BACKGROUND
Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA mC methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA mC methylation, on the progression of DR.
METHOD
Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2.
RESULTS
The levels of both NSUN2 and RNA mC methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA mC reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing.
CONCLUSIONS
NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA mC methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.
Topics: Animals; Humans; Male; Diabetic Retinopathy; Disease Progression; Gene Expression Regulation; Gene Knockdown Techniques; Methylation; Methyltransferases; Mice, Inbred C57BL; Mucin-1; RNA Methylation
PubMed: 38764010
DOI: 10.1186/s12967-024-05287-4 -
Cureus Apr 2024The ventricular migration of vitreous silicone oil (SiO) is rare and can easily be mistaken for intraventricular hemorrhage or a ruptured colloid cyst. We report here...
The ventricular migration of vitreous silicone oil (SiO) is rare and can easily be mistaken for intraventricular hemorrhage or a ruptured colloid cyst. We report here the case of an adult male who was misdiagnosed with a ruptured colloid cyst and was subsequently found to have ventricular migration of vitreous SiO. A 57-year-old male presented unresponsive following a respiratory arrest and underwent a head computed tomography (CT) scan that demonstrated multiple ovoid hyperdensities in the ventricular system, which was concerning for a ruptured colloid cyst. He was transferred to our institution for neurosurgical evaluation. Magnetic resonance imaging (MRI) was performed and demonstrated widespread abnormal diffusion restriction throughout the cortex and basal ganglia, consistent with anoxic brain injury secondary to hypoxic respiratory arrest. The MRI also demonstrated an abnormal signal in areas corresponding with the previously identified intraventricular lesions, which did not layer posteriorly. Given that the MRI sequence signals of the lesions in the ventricular system matched perfectly with the signals of the somewhat deflated SiO within the globe, these multiple ovoid lesions on imaging were most consistent with the migration of SiO from the vitreous body of the right globe into the ventricular system. This case demonstrates a diagnostic error that can occur in emergent settings because of the broad differential diagnosis for cerebral ventricular hyperdensities. A ruptured colloid cyst was considered the reason for transfer, with the anticipation of neurosurgical intervention, but further imaging demonstrated that this was an incidental finding in this patient who presented in extremis. Awareness of this rare clinical condition can prevent overutilization of resources and unnecessary interventions.
PubMed: 38738078
DOI: 10.7759/cureus.58043 -
Journal of Cutaneous and Aesthetic... 2024A 25-year-old aesthetician was operating Q-switch pulse (SPECTRA) cosmetic laser machine of 1,064 nm wavelength, for the purpose of skin bleaching. The probe suddenly...
A 25-year-old aesthetician was operating Q-switch pulse (SPECTRA) cosmetic laser machine of 1,064 nm wavelength, for the purpose of skin bleaching. The probe suddenly slipped over the plastic sheet that had been placed to avoid COVID-19 exposure after which she complained of sudden loss of vision. She was diagnosed as having vitreous hemorrhage in her right eye and was treated conservatively for one month. She then complained of central scotoma and was diagnosed to have developed a full-thickness macular hole, for which she was advised vitrectomy surgery. The purpose of this case report is to emphasize the importance of taking precautions during the COVID-19 era and while doing that making sure how to handle the machines so as not to inflict any accidental injury to the operating physician. Macular Holes following skin bleaching with Nd:YAG laser occurring in operating aesthetician is rare as compared to that occurring in the patients.
PubMed: 38736866
DOI: 10.4103/JCAS.JCAS_74_21 -
BMJ Case Reports May 2024Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or...
Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or in the early postnatal period. Although typically benign, this disease is associated with other systemic abnormalities, including rare ocular alterations, such as congenital glaucoma, cataracts and retinopathy.This manuscript describes a female infant, who presented with generalised livedo reticularis, a band of alopecia and cutaneous atrophy in the temporal region above the coronal suture. The patient was diagnosed with cutis marmorata telangiectatica congenita by a paediatrician, and an ophthalmological evaluation was requested. A funduscopy examination in both eyes showed temporal and superior retina with avascular areas with new vessels, venous dilations and shunts, and no retinal detachments. Given these findings, we performed retinal photocoagulation laser treatment with excellent results.This case report highlights the importance of early ophthalmological evaluation of children with this disease to prevent secondary complications, such as vitreous haemorrhage and tractional retinal detachment.
Topics: Humans; Female; Livedo Reticularis; Telangiectasis; Skin Diseases, Vascular; Infant; Laser Coagulation; Retinal Vessels; Retina
PubMed: 38719246
DOI: 10.1136/bcr-2023-257810 -
Die Ophthalmologie Apr 2024
PubMed: 38687381
DOI: 10.1007/s00347-024-02040-6 -
POCUS Journal 2024In acute care environments, accurately assessing complications of intracranial pathology can be challenging. Ocular complications in acute intracranial disease are not...
In acute care environments, accurately assessing complications of intracranial pathology can be challenging. Ocular complications in acute intracranial disease are not consistently evaluated despite their high morbidity. We report on a case of monocular diplopia in a 63-year-old man with subacute traumatic brain injury with localized subarachnoid hemorrhage. Ocular point of care ultrasound (POCUS) identified features of vitreous hemorrhage in one globe, leading to a diagnosis of Terson syndrome and a timely referral to ophthalmology. This finding was made on the medical floor days after the initial presentation during rehabilitation when ophthalmoscopy was not possible, and vitreous hemorrhage had not been identified on presentation. Terson syndrome is a seldom discussed but important complication of intracranial hemorrhage generally associated with poor patient outcomes. Ocular POCUS can provide a useful alternative in assessing ocular complications of acute intracranial disease on the medical floor, particularly when the practicalities of performing ophthalmoscopy are challenged.
PubMed: 38681167
DOI: 10.24908/pocus.v9i1.16660