ABSTRACT
Silicone oil (SO) emulsification is a significant concern in vitreoretinal surgery, leading to various complications. Despite the high prevalence of SO emulsification within the eye, there is currently no standardized method for its early detection. The recent introduction of widefield (WF) imaging and ultra-WF (UWF) imaging with navigated central and peripheral optical coherence tomography (OCT) techniques have shown promising results in providing high-resolution images of the peripheral vitreous, vitreoretinal interface, retina, and choroid. This enhanced visualization capability enables the early identification of emulsified SO droplets, facilitating a proactive therapeutic approach, and mitigating associated adverse events. This comprehensive literature review aims to provide an updated overview of the topic, focusing on the role of WFimaging and UWF imaging and navigated central and peripheral swept-source OCT (SS-OCT) in the early detection and management of SO emulsification. The review discusses the current understanding of SO emulsification, its associated complications, and the limitations of existing detection methods. In addition, it highlights the potential of WF and UWF imaging and peripheral OCT as advanced imaging modalities for improved visualization of SO emulsification. This review serves as a valuable resource for clinicians and researchers, providing insights into the latest advancements in the field of vitreoretinal surgery and the promising role of WF imaging and UWF imaging and navigated central and peripheral SS-OCT in the management of SO.
ABSTRACT
PURPOSE: To clarify the definition, prevalence and classification of different types of unexplained vision loss associated with silicone oil (SO) endotamponades (SO in situ (SOIS) or after removal of SO (ROSO)) in vitreoretinal surgery and identifying the most specific clinical findings and suggesting possible causes. METHODS: Review of the literature regarding randomized clinical trials (RCTs), retrospective case-control, cohort studies and case series evaluating the risk of using SO, published in English between 1994 and 2023, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. The search was supplemented using the Medline option 'Related Articles' and consulting review articles on the topic. RESULTS: Findings from reported clinical examinations in SOIS and ROSO are analyzed and finally different theories regarding the underlying pathophysiology are described. From the clinical point of view, findings have been found in OCT, OCTA, microperimetry and electrophysiological studies. Other clearly identifiable causes of vision loss related to the use of SO are listed and commented as differential diagnosis. Finally, the different physiopathological theories of the two types of causes of unexplained vision have been analyzed. CONCLUSION: Unexpected vision loss under or after SO tamponade (SOIS and ROSO) is a significant concern which is probably underestimated because it is not a clearly defined and known entity. The most frequently described changes were in the ganglion cell complex but this unexpected vision loss remains a serious and unexplained concern for vitreoretinal surgeons and should be identified by clinicians, addressed by manufacturers and reported to Health Authorities as a serious incident according to the new regulation.
ABSTRACT
PURPOSE: Patients with Retinitis Pigmentosa (RP) commonly experience sleep-related issues and are susceptible to stress. Moreover, variatiaons in their vision are often linked to anxiety, stress and drowsiness, indicating that stress and sleep deprivation lead to a decline in vision, and vision improves when both are mitigated. The objective of this study was to investigate the utility of salivary biomarkers as biochemical indicators of anxiety and sleep deprivation in RP patients. METHODS: Seventy-eight RP patients and 34 healthy controls were included in this observational study. Anxiety and sleep-quality questionnaires, a complete ophthalmological exam for severity grading and, the collection of salivary samples from participants were assessed for participants. The activity of biomarkers was estimated by ELISA, and statistical analysis was performed to determine associations between the parameters. Associations between underlying psychological factors, grade of disease severity, and biomarkers activity were also examined. RESULTS: Fifty-two (67%) of patients had a severe RP, and 26 (33%) had a mild-moderate grade. Fifty-eight (58,9%) patients reported severe levels of anxiety and 18 (23.,1%) a high level. Forty-six (59%) patients obtained pathological values in sleep-quality questionaries and 43 (55.1%) in sleepiness. Patients with RP exhibited significant differences in testosterone, cortisol, sTNFαRII, sIgA and melatonin as compared to controls and patients with a mild-moderate and advanced stage of disease showed greater differences. In covariate analysis, patients with a severe anxiety level also showed greater differences in mean salivary cortisol, sTNFαRII and melatonin and male patients showed lower IgA levels than female. CONCLUSIONS: The present findings suggest that salivary biomarkers could be suitable non-invasive biochemical markers for the objective assessment of sleep deprivation and anxiety in RP patients. Further research is needed to characterize the effects of untreated negative psychological states and sleep deprivation on increased variability of vision and disease progression, if any.
Subject(s)
Biomarkers , Retinitis Pigmentosa , Saliva , Sleep Deprivation , Humans , Male , Female , Saliva/chemistry , Saliva/metabolism , Biomarkers/metabolism , Biomarkers/analysis , Retinitis Pigmentosa/metabolism , Adult , Middle Aged , Sleep Deprivation/metabolism , Stress, Psychological/metabolism , Anxiety/metabolism , Case-Control Studies , Hydrocortisone/analysis , Hydrocortisone/metabolismABSTRACT
Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with TP53 being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in humanized Tp53 Arg72Pro knock-in mice. This work reports on the influence of the TP53 Arg72Pro polymorphism in bone microarchitecture, OPG expression, and apoptosis bone status. The results show that the proline variant of the TP53 Arg72Pro polymorphism (Pro72-p53) is associated with deteriorated bone tissue, lower OPG/RANK ratio, and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker that can be used to identify individuals with an increased risk of suffering metabolic bone alterations.
Subject(s)
Bone Diseases, Metabolic , Tumor Suppressor Protein p53 , Animals , Mice , Biomarkers , Bone and Bones , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/genetics , HumansABSTRACT
Introduction: Silicone oil (SO) is a crucial agent used as an intraocular tamponade in the treatment of complex vitreoretinal diseases. Despite its effectiveness, SO is prone to emulsification, which can lead to significant and sometimes irreversible complications in both the anterior and posterior segments of the eye. The detection and monitoring of SO emulsification are therefore of paramount importance. Traditional imaging modalities have limitations in visualizing SO, leading to the exploration of more advanced imaging techniques. This study introduces the application of dynamic infrared confocal scanning laser ophthalmoscopy (IRcSLO) for this purpose and evaluates its effectiveness. Case Presentation: We report on 2 patients who underwent pars plana vitrectomy with subsequent SO injection for the management of retinal detachment. Postsurgery, both patients were imaged using the Heidelberg Retina Tomography Spectralis IRcSLO. The focus was on the visualization of the SO status, including the presence and distribution of emulsified SO droplets. The IRcSLO imaging technique demonstrated its capability to effectively visualize emulsified SO droplets. Interestingly, this was also true for cases where the SO had been removed. The emulsified droplets were observed as micron-sized, spherical entities with a nonuniform distribution throughout the vitreous cavity. Conclusion: Dynamic IRcSLO has proven to be an effective imaging modality for visualizing the emulsification of SO, offering a novel perspective into the characterization of SO droplets. It facilitates the analysis of droplet count, motility, and precise localization within the vitreous cavity. The findings from the case presentations underscore the variability of SO emulsification patterns and the sensitivity of IRcSLO in detecting even minuscule emulsified droplets. This imaging technique has significant potential for future research, particularly in understanding the timing of emulsification, the factors contributing to it, and the development of possible preventive strategies. Additionally, it allows for a more in-depth analysis of the behavior of emulsified SO droplets across different SO viscosities, which could be instrumental in optimizing patient outcomes.
ABSTRACT
BACKGROUND: The medical community is beginning to recognize that retinitis pigmentosa (RP), due to its disabling progression, eventually leads to a reduction in the patient´s quality of life, a direct economic impact, and an increase in the burden on the health care system. There is no curative treatment for the origin of the disease, and most of the current interventions fail in reducing the associated negative psychological states, such as anxiety and depression, which lead to increased variability of vision and pose a continuous threat to the patient's independence. OBJECTIVE: The aim of this study is to assess the effect of oral melatonin (OM) administration alone and combined with short-wavelength light (SWL)-blocking filters on patients with RP and test their effectiveness in improving the level of stress and sleep problems in many of these patients. METHODS: We have developed a low-cost therapy protocol for patients with RP with sleep disorders and negative psychological stress. Patients will be randomized to receive a combined intervention with SWL-blocking filters and OM, SWL-blocking filters alone, or OM alone. There will also be a nonintervention arm as a control group. This study will be conducted across 2 retinal units in patients with RP with sleep disorders and high perceived stress and anxiety score reports. Patients will be assessed in the preintervention period, weekly during the 4 weeks of intervention, and then at 6 months postintervention. The primary outcomes are the differences in changes from baseline to postintervention in hormone release (α-amylase, cortisol, and melatonin) and sleep quality, as measured with the visual analog scale. Secondary outcome measures include clinical macular changes, as measured with optical coherence tomography and optical coherence tomography angiography; retinal function, as measured using the visual field and best-corrected visual acuity; sleep data collected from personal wearables; and several patient-reported variables, such as self-recorded sleep diaries, quality of life, perceived stress, and functional status. RESULTS: This project is still a study protocol and has not yet started. Bibliographic research for information for its justification began in 2020, and this working group is currently seeking start-up funding. As soon as we have the necessary means, we will proceed with the registration and organization prior to the preliminary phase. CONCLUSIONS: In this feasibility randomized clinical controlled trial, we will compare the effects of SWL blocking alone, administration of OM alone, and a combined intervention with both in patients with RP. We present this study so that it may be replicated and incorporated into future studies at other institutions, as well as applied to additional inherited retinal dystrophies. The goal of presenting this protocol is to aid recent efforts in reducing the impact of sleeping disorders and other psychological disorders on the quality of life in patients with RP and recovering their self-autonomy. In addition, the results of this study will represent a significant step toward developing a novel low-cost therapy for patients with RP and validating a novel therapeutic target. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/49196.
ABSTRACT
BACKGROUND: An effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®). METHODS: We conducted a prospective, non-randomized, clinical phase-II study (Eudra CT number 2016-003029-40; ClinicalTrials.gov Registry NCT03173638) that included 5 patients with acute unilateral NA-AION diagnosed within 2 weeks after symptom onset and who received an intravitreal injection of allogeneic BM-MSCs (0.05 ml; cell concentration: 1.5 × 106cells/mL). The patients underwent regular ophthalmological examinations and were followed for one year. RESULTS: In this trial, allogeneic BM-MSCs appeared to be safe as no patients developed signs of acute nor chronic intraocular inflammation or a significant change in intraocular pressure, although an epiretinal membrane was developed in one patient. A retrolental aggregate formed shortly after the injection spontaneously disappeared within a few weeks in another phakic patient, leaving a subcapsular cataract. Visual improvement was noted in 4 patients, and amplitudes of P100 on the visually evoked potentials recordings increased in three patients. The retinal nerve fiber layer and macular ganglion cell layer thicknesses significantly decreased during the follow-up. CONCLUSIONS: Besides the development of an epiretinal membrane in one patient, the intravitreal application of allogeneic BM-MSCs appeared to be intraocularly well tolerated. Consequently, not only NA-AION but also BM-MSCs deserve more clinical investigational resources and a larger randomized multicenter trial that would provide stronger evidence both about safety and the potential therapeutic efficacy of intravitreally injected allogeneic BM-MSCs in acute NA-AION. TRIAL REGISTRATION: Safety Assessment of Intravitreal Mesenchymal Stem Cells for Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NEUROSTEM). NCT03173638. Registered June 02, 2017 https://clinicaltrials.gov/ct2/show/NCT03173638 .
Subject(s)
Epiretinal Membrane , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cells , Optic Nerve Diseases , Humans , Inflammation , Prospective StudiesABSTRACT
PURPOSE: Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab. METHODS: Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-naïve patients and non-naïve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded. RESULTS: Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612 ± 0.75 logMAR and 256.16 ± 12.98 µm respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387 ± 0.54 logMAR, as well as CRT values which decreased to 245.43 ± 15.34 µm. In the 3 naïve patients, mean baseline BVCA and CRT values were 0.33 ± 0.29 and 874.67 ± 510.86 µm, respectively. At one month follow-up, mean BCVA improved to 0.30 ± 0.29 logMAR and mean CRT was 536.04 ± 36.15 µm. Overall, a significant improvement in BCVA of 0.21 ± 41 logMAR and 238.44 ± 114.9 µm was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed. CONCLUSION: Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.
ABSTRACT
Introduction: Ala®sil infusion was on the market for clinical use under the Medical Devices Directive (MDD) 93/42/EEC as an irrigating solution based on polydimethylsiloxane (PDMS). The product was withdrawn in 2016, and to the best of our knowledge, it did not cause any health damage. Methods: A bibliographic review and experimental analysis were conducted to evaluate whether this CE-marked product could have been used in patients under the current Medical Device Regulation (MDR) 2017/745. Analytical results from gas chromatography-mass spectrometry (GC-MS) and matrixassisted laser desorption ionization (MALDI) were performed. Citotoxicity studies were also carried out. Results: Only one study related to Ala®sil clinical use was found, describing a pilot series of five patients. The authors rated the product as not helpful in three out of the five cases for internal searching of retinal breaks and in four out of the five cases for drainage of subretinal fluid. No other scientific papers or documentation was found regarding Ala®sil's safety. Nevertheless, the product was introduced in the market after achieving the CE marking. GC-MS and MALDI showed that the polymer has a low molecular weight of 1,000 g/mol. Several linear and cyclic low-molecular-weight components (LMWCs) were identified as impurities ranging from L3 to D8, with a molecular weight below 600 g/mol. The Ala®sil sample was found to be cytotoxic after 24 h of cell culture but non-cytotoxic after 72 h, probably due to the cellular regeneration capacity of an immortalized cell line. Tissular cytotoxicity revealed an increased apoptosis rate but without morphological modifications. Discussion: Although Ala®sil cannot be classified as cytotoxic, this substance appears to increase retinal cell death processes. This study supports the notion that the MDDwas not functioning adequately to ensure the safety of medical devices. However, the current MDR 2017/745 imposes stricter standards to prevent the commercialization of medical devices without high-quality preclinical and clinical information, as well as precise clinical verification for their use, information not available for Ala®sil infusion.
ABSTRACT
Knowledge on the underlying mechanisms and molecular targets for managing the ocular complications of type 2 diabetes mellitus (T2DM) remains incomplete. Diabetic retinopathy (DR) is a major cause of irreversible visual disability worldwide. By using ophthalmological and molecular-genetic approaches, we gathered specific information to build a data network for deciphering the crosslink of oxidative stress (OS) and apoptosis (AP) processes, as well as to identify potential epigenetic modifications related to noncoding RNAs in the eyes of patients with T2DM. A total of 120 participants were recruited, being classified into two groups: individuals with T2MD (T2MDG, n = 67), divided into a group of individuals with (+DR, n = 49) and without (-DR, n = 18) DR, and a control group (CG, n = 53). Analyses of compiled data reflected significantly higher plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and significantly lower total antioxidant capacity (TAC) in the +DR patients compared with the -DR and the CG groups. Furthermore, the plasma caspase-3 (CAS3), highly involved in apoptosis (AP), showed significantly higher values in the +DR group than in the -DR patients. The microRNAs (miR) hsa-miR 10a-5p and hsa-miR 15b-5p, as well as the genes BCL2L2 and TP53 involved in these pathways, were identified in relation to DR clinical changes. Our data suggest an interaction between OS and the above players in DR pathogenesis. Furthermore, potential miRNA-regulated target genes were identified in relation to DR. In this concern, we may raise new diagnostic and therapeutic challenges that hold the potential to significantly improve managing the diabetic eye.
ABSTRACT
Sarcoidosis is a chronic multisystemic disease, which can be rarely associated with autoimmune disorders, such as antiphospholipid syndrome (APS). Although amaurosis fugax is an uncommon complication, its presentation can unmask a carotid artery dissection (CAD) in these diseases. In addition, central serous chorioretinopathy (CSC) has been related to vascular disorders too. We presented a case of a Caucasian middle-aged man, who developed CAD symptoms, such as amaurosis fugax in the right eye (RE) and headache. His medical history included arterial hypertension, hypothyroidism, and Lofgren's syndrome. On examination, retinal pigment epithelium (RPE) atrophy and subretinal fluid (SRF) in the macular area of the RE were observed. These findings were confirmed by optical coherence tomography (OCT), which also revealed an increase in choroidal thickness. However, these differed significantly from the contralateral eye. These clinical symptoms and imaging findings suggested a CSC in the RE, but not all clinical processes were justified. Subsequently, a CT angiography was performed and confirmed a significant occlusion in the right internal carotid artery and progressive sharpening of the lumen with an intimal flap due to a carotid dissection. In addition, the laboratory results were compatible with antiphospholipid syndrome (APS). To the authors' knowledge, the patient returned to the ED due to an anterior uveitis and he is currently asymptomatic with Cemidon and Adalimumab treatment. We described for the first time a case of carotid dissection and central serous chorioretinopathy in the context of two autoimmune-based pathologies, such as sarcoidosis and antiphospholipid syndrome. Abbreviations: APS = Antiphospholipid syndrome, BCVA = Best-corrected visual acuity, CAD = Carotid artery dissection, CNV = Choroidal neovascular membrane, CSC = Central serous chorioretinopathy, CT = Computed tomography, ED = Emergency Department, ICAD = Internal carotid artery dissection, LE = Left eye, OCT = Optical coherence tomography, RAPD = Relative afferent pupillary defect, RPE = Retinal pigment epithelium, RE = Right eye, SRF = Subretinal fluid.
Subject(s)
Antiphospholipid Syndrome , Central Serous Chorioretinopathy , Sarcoidosis , Amaurosis Fugax , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Carotid Arteries , Central Serous Chorioretinopathy/complications , Central Serous Chorioretinopathy/diagnosis , Fluorescein Angiography/methods , Humans , Male , Middle AgedABSTRACT
PURPOSE: It had been reported that mutations in CYP1B1 gene probably play an important role in the pathogenesis of primary open angle glaucoma (POAG) but the existing genetic association studies show contradictory results. Thus, the objective of our study was to perform a systematic review and meta-analysis to characterize more precisely the potential association between given polymorphisms in CYP1B1 gene and the risk of suffering POAG. METHODS: A systematic review of studies that related the risk of carrying CYP1B1 gene polymorphisms with POAG development was conducted. We selected 19 case-control studies including 3855 POAG patients and 4125 control subjects in our meta-analyses. A random effects model was used. Sensitivity analysis and assessment of bias were also included. RESULTS: The prevalence of CYP1B1 gene polymorphisms were significantly more frequent among POAG patients compared to all controls (OR = 2.91, 95% CI = 1.37 - 6.21; P = 0.006). Moreover, their prevalence was significantly higher in juvenile-onset patients than in adult-onset ones (OR = 2.27, 95% CI = 1.20-4.28; P = 0.001). CONCLUSION: The results of this meta-analysis uphold that being a carrier of polymorphic genetic variants in CYP1B1 gene would increase the risk of POAG, especially the juvenile onset.
Subject(s)
Cytochrome P-450 CYP1B1 , Glaucoma, Open-Angle , Adult , Case-Control Studies , Cytochrome P-450 CYP1B1/genetics , Genetic Association Studies , Glaucoma, Open-Angle/genetics , Humans , Mutation , Polymorphism, Single NucleotideABSTRACT
PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.
Subject(s)
COVID-19/diagnosis , Eye Infections, Viral/diagnosis , Retinal Vein Occlusion/diagnosis , SARS-CoV-2/isolation & purification , Adult , Aged , Angiogenesis Inhibitors/therapeutic use , COVID-19/virology , COVID-19 Nucleic Acid Testing , Dexamethasone/therapeutic use , Drug Implants , Eye Infections, Viral/drug therapy , Eye Infections, Viral/virology , Female , Fluorescein Angiography , Glucocorticoids/therapeutic use , Humans , Intravitreal Injections , Male , Middle Aged , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/virology , Retrospective Studies , SARS-CoV-2/genetics , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , COVID-19 Drug TreatmentABSTRACT
Silicone oil (SO) still represents the main choice for long-term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta-analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case-control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re-detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty-three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27-2.18) and the rate of retinal re-detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50-0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)-emulsification rate was non-significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so-called unexplained vision loss, which affects a significant percentage of eyes. Re-detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low- and high-viscosity silicones. All these data warrant more standardized prospective studies.
Subject(s)
Hypertension , Retinal Detachment , Vitreoretinal Surgery , Humans , Hypertension/complications , Retinal Detachment/etiology , Retrospective Studies , Silicone Oils/adverse effects , Vitrectomy/adverse effects , Vitreoretinal Surgery/adverse effectsABSTRACT
PURPOSE: Assess the mid and peripheral neuroretina and vitreoretinal interface using a novel Navigated Single-Capture 3D and Cross-Sectional Wide-Field Swept-Source Optical Coherence Tomography (WF SS-OCT) technology with correlation to Multi-Wavelength Ultra-Widefield Imaging (MW UWFI) and Histopathology reference. METHODS: Retrospective observational study. A total of 74 patients (148 eyes) were imaged using WF SS-OCT and Navigated Single-Capture twelve 23 mm cross-sectional radial scan pattern at 15° intervals. Image diagnosis included: congenital hypertrophy of the retinal pigment epithelium, choroidal nevus, ora serrata pearls, retinal tuft, lattice, snail track, cobblestone degeneration, retinal hole, retinal tear, degenerative retinoschisis, peripheral laser retinopexy, white without pressure, vitreous floaters, subclinical peripheral rhegmatogenous retinal detachment (RD), and tractional RD in proliferative diabetic retinopathy. WF SS-OCT images were correlated with MW UWFI and histopathological references where available. RESULTS: WF SS-OCT successfully imaged structural features in all diagnoses with significant improvement in diagnostic capability and increased the diagnosis of specific features such as vitreoretinal attachment, full thickness hole or tear and subretinal fluid. Histopathological correlation was available for five (5) different peripheral retinal pathologies imaged by both WF SS-OCT and MW UWFI and good anatomical correlation was observed in all diagnosis. CONCLUSIONS: Navigated Single-Capture 3D and Cross-Sectional WF SS-OCT provides detailed anatomic information of the mid and peripheral neuroretina and vitreoretinal interface, allowing early recognition of vision-threatening features that may influence clinical management, particularly in an era of telemedicine or when there is limited or no access to Indirect Ophthalmoscopy with 360° Scleral Indentation.
Subject(s)
Diabetic Retinopathy , Retinal Degeneration , Retinal Detachment , Retinal Perforations , Cross-Sectional Studies , Diabetic Retinopathy/diagnosis , Fluorescein Angiography/methods , Humans , Retina , Retinal Detachment/diagnosis , Retinal Perforations/diagnostic imaging , Retinal Perforations/surgery , Tomography, Optical Coherence/methodsABSTRACT
BACKGROUND: There are few clinical data on retinal involvement after acute exposure to high concentrations mercury and the available reports are based on a small number of patients suffering chronic exposure. The purpose of this paper is to report findings in workers acutely exposed to very high concentrations of mercury vapor with the aim of providing data on a possible direct retinal involvement. METHODS: Twenty-nine patients and 16 controls were evaluated in a comparative case series. Mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The correlations between variables also were studied. In addition, electrophysiological data from those patients with deeper VF defects (group 1) were compared with a normal control group. RESULTS: Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy. The VA was slightly affected in 48.27% (n = 14) of subjects. Loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n = 28) and 44.8% (n = 13), respectively. VF alterations were identified in 72.4% (n = 21) patients. No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP (p < 0.05). The reduced amplitude of the b wave at the ffERG, of the P50 at the PERG and of the P1 wave at the mfERG results (p < 0.05) suggested that the outer retina was involved. Significant negative correlations among blood mercury levels, VA, and ffERG were observed. CONCLUSIONS: In this case series, showed that acute exposure to mercury vapor had a hazardous effect on the visual system. Although neurologic and visual pathway involvement was clearly demonstrated, the differences found compared to control support the existence of a direct functional retinal damage and participation in impaired vision in mercury poisoning.
ABSTRACT
PURPOSE: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication. DESIGN: Cross-sectional study. PARTICIPANTS: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects. METHODS: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM). RESULTS: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (-2.57 (-1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm2), nerve branching density (2 (2.50) n/mm2), and dendritic cell density (9.1 (8.84) n/mm2) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels. CONCLUSIONS: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.
ABSTRACT
Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: "rho-Associated Kinas-es", "Diabetic Retinopathy", "Macular Edema", "Ripasudil", "Fasudil" and "Netarsudil". Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.
Subject(s)
Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Protein Kinase Inhibitors/therapeutic use , rho-Associated Kinases/antagonists & inhibitors , Animals , Diabetic Retinopathy/complications , Diabetic Retinopathy/physiopathology , Humans , Macular Edema/complications , Macular Edema/physiopathology , Protein Kinase Inhibitors/pharmacology , Retina/pathology , Signal Transduction/drug effects , Translational Research, Biomedical , rho-Associated Kinases/metabolismABSTRACT
The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce a localized retinal detachment to perform the subretinal placement of the transplanted cell; (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.
ABSTRACT
With the evolution of new genomic sequencing technologies an important amount of genomic data has been provided. As a consequence of this, many gene polymorphisms have been shown to be significantly associated with different disorders. Many strategies have been implemented to reveal the role of having more than one allele at a specific locus and their involvement in the illnesses. Site-directed mutagenesis is one of the most common strategies to understand the regulatory regions of genes and the relationship between the protein structure and its function. Here, we describe the analysis of lymphotoxin alpha expression in human retina and the generation of expression vectors to functional characterization of polymorphisms in the tumor necrosis factor locus using pCEFL-Flag expression vector and transfection assays in COS-1 cell line.