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1.
Am J Ophthalmol Case Rep ; 35: 102069, 2024 Sep.
Article En | MEDLINE | ID: mdl-38799226

Purpose: This case report highlights a possible association between netarsudil use and crystalline keratopathy. Observations: Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment. Conclusions and importance: Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.

2.
Gynecol Oncol ; 187: 145-150, 2024 May 21.
Article En | MEDLINE | ID: mdl-38776632

OBJECTIVES: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer. METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer. RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes. CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.

3.
Article En | MEDLINE | ID: mdl-38768759

INTRODUCTION: Suicide is the first cause of external death in Spain. International studies show frequent and varied health contacts in the months prior to suicide. There are hardly any studies on that phenomenon in this country. OBJECTIVE: To analyze health care use in the year prior to suicide between 2010 and 2018 in the Basque Country, as well as pharmacological prescriptions and psychiatric diagnoses received. METHODS: Retrospective descriptive study with all suicides registered by the Basque Institute of Legal Medicine (BILM) between 2010 and 2018. The records of the BILM and the Basque Health Service (Osakidetza) were cross-checked. RESULTS: 1526 suicides were analyzed. 74% had health contacts in the previous year. The use was higher in women (p<0.05) and in older ages (p<0001). Primary care was the most used specialty (58.8% the previous year and 7.1% the previous week), followed by Hospital Emergencies (50.3% and 10.2%) and Outpatient Medical Specialties (49% and 11.6%), especially Radiology. Outpatient psychiatry only contacted 29.6% that year, although it had the highest average number of visits (15.1 SD22.6). The most frequent diagnostic category among psychiatric patients was F30-39 (26.7%), with differences between sexes and ages. 49.7% received psychotropic drugs. CONCLUSIONS: The results are aligned with international evidence, which they also extend, and reinforce the need to extend prevention beyond psychiatric services. It seems advisable to increase proactivity in the search for risk by sensitizing and training different professional profiles, but also to work from non-health settings to improve assistance to highly vulnerable profiles (young men) with low health links.

4.
Pharmaceutics ; 16(5)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38794241

Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280-300 mOsm/L), had a pH close to neutral (7-8), medium surface-tension values (<56 MN/m-1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90-110% range in the compounded formulations containing normal saline solution when stored at 2-8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.

5.
Cell Death Dis ; 15(4): 249, 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38582872

Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.


Diazepam Binding Inhibitor , gamma-Aminobutyric Acid , Animals , Mice , Diazepam Binding Inhibitor/pharmacology
6.
Ophthalmol Ther ; 13(6): 1669-1682, 2024 Jun.
Article En | MEDLINE | ID: mdl-38635137

INTRODUCTION: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment. METHODS: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test. RESULTS: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit. CONCLUSIONS: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.

7.
Ophthalmol Glaucoma ; 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38636705

PURPOSE: Compare outcomes of tube shunt surgery (Tube) and trabeculectomy with mitomycin C (Trab-MMC) in patients with angle-closure glaucoma (ACG). DESIGN: Retrospective nonrandomized comparative study. PARTICIPANTS: A total of 80 eyes from 80 patients with ACG who underwent either Tube (N = 50) or Trab-MMC (N = 30) between January 2015 and January 2022 at Massachusetts Eye and Ear. METHODS: Reviewed and analyzed 390 visits from patient charts. MAIN OUTCOME MEASURES: Kaplan-Meier (KM) success rates, intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), adjusted hazard ratios (HRs), and complications. RESULTS: Baseline demographics were similar between both groups, except for a higher proportion of patients with pseudophakia and prior incisional ocular surgery in the Tube group. The Trab-MMC procedure had significantly higher KM complete success (CS) rates than the Tube procedure, but similar qualified success (QS) rates. Under QS, the cumulative probability of survival was 87% in the Tube group and 83% in the Trab-MMC group at year 1 (P = 0.77), and 75% in the Tube group and 58% in the Trab-MMC group at year 2 (P = 0.14). Under CS, the cumulative probability of survival was 13% in the Tube group and 59% in the Trab-MMC group at year 1 (P < 0.001), and 11% in the Tube group and 41% in the Trab-MMC group at year 2 (P < 0.001). Both Tube and Trab-MMC procedures resulted in significant patterns of IOP and medication reduction from baseline up to 2 years with mean IOP reduced to 12.6 ± 5.9 mmHg on 2.8 ± 1.4 medications after Tube and 12.1 ± 6.6 mmHg on 2.4 ± 1.7 medications after Trab-MMC. Patients who underwent Trab-MMC required less IOP-lowering medications at every follow-up visit up to year 1, but a similar number at year 2. No significant differences were found in IOP reduction, BCVA, or complication rates between groups. CONCLUSIONS: We demonstrate that Trab-MMC confers similar IOP reduction and QS rates to Tube placement in patients with ACG. Trab-MMC, however, demonstrated greater medication burden reduction up to 1 year, and more favorable CS rates up to 2 years, while still maintaining similar complication rates to Tube. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

8.
Chaos ; 34(3)2024 Mar 01.
Article En | MEDLINE | ID: mdl-38437871

This research addresses the challenge of characterizing the complexity and unpredictability of basins within various dynamical systems. The main focus is on demonstrating the efficiency of convolutional neural networks (CNNs) in this field. Conventional methods become computationally demanding when analyzing multiple basins of attraction across different parameters of dynamical systems. Our research presents an innovative approach that employs CNN architectures for this purpose, showcasing their superior performance in comparison to conventional methods. We conduct a comparative analysis of various CNN models, highlighting the effectiveness of our proposed characterization method while acknowledging the validity of prior approaches. The findings not only showcase the potential of CNNs but also emphasize their significance in advancing the exploration of diverse behaviors within dynamical systems.

9.
Article En | MEDLINE | ID: mdl-38394352

Aging is a multifactorial process characterized by an age-related decline in organismal fitness. This deterioration is the major risk factor for chronic diseases such as cardiovascular pathologies, neurodegeneration, or cancer, and it represents one of the main challenges of modern society. Therefore, understanding why and how we age would be a fundamental pillar to design strategies to promote a healthy aging. In the last decades, the study of the molecular bases of disease has been revolutionized by the discovery of different types of noncoding RNAs (ncRNAs) with regulatory potential. In this work, we will review the implication of ncRNAs in aging, with the aim to provide a first approach to the different aging-associated ncRNAs, their mechanism of action, and their potential relevance as therapeutic targets and disease biomarkers.


Longevity , MicroRNAs , Longevity/genetics , RNA, Untranslated/genetics , MicroRNAs/genetics
10.
Nature ; 626(8001): 1025-1033, 2024 Feb.
Article En | MEDLINE | ID: mdl-38418912

Reaction conditions that are generally applicable to a wide variety of substrates are highly desired, especially in the pharmaceutical and chemical industries1-6. Although many approaches are available to evaluate the general applicability of developed conditions, a universal approach to efficiently discover these conditions during optimizations is rare. Here we report the design, implementation and application of reinforcement learning bandit optimization models7-10 to identify generally applicable conditions by efficient condition sampling and evaluation of experimental feedback. Performance benchmarking on existing datasets statistically showed high accuracies for identifying general conditions, with up to 31% improvement over baselines that mimic state-of-the-art optimization approaches. A palladium-catalysed imidazole C-H arylation reaction, an aniline amide coupling reaction and a phenol alkylation reaction were investigated experimentally to evaluate use cases and functionalities of the bandit optimization model in practice. In all three cases, the reaction conditions that were most generally applicable yet not well studied for the respective reaction were identified after surveying less than 15% of the expert-designed reaction space.

12.
Ophthalmology ; 131(2): 240-248, 2024 Feb.
Article En | MEDLINE | ID: mdl-38069944

PURPOSE: To evaluate the current published literature on the utility of the 10-2 visual field (VF) testing strategy for the evaluation and management of early glaucoma, defined here as mean deviation (MD) better than -6 decibels (dB). METHODS: A search of the peer-reviewed literature was last conducted in June 2023 in the PubMed database. Abstracts of 986 articles were examined to exclude reviews and non-English-language articles. After inclusion and exclusion criteria were applied, 26 articles were selected, and the panel methodologist rated them for strength of evidence. Thirteen articles were rated level I, and 8 articles were rated level II. The 5 level III articles were excluded. Data from the 21 included articles were abstracted and reviewed. RESULTS: The central 12 locations on the 24-2 VF test grid lie within the central 10 degrees covered by the 10-2 VF test. In early glaucoma, defects detected within the central 10 degrees generally agree between the 2 tests. Defects within the central 10 degrees of the 24-2 VF test can predict defects on the 10-2 VF test, although the 24-2 may miss defects detected on the 10-2 VF test. In addition, results from the 10-2 VF test show better association with findings from OCT scans of the macular ganglion cell complex. Modifications of the 24-2 test that include extra test locations within the central 10 degrees improve detection of central defects found on 10-2 VF testing. CONCLUSIONS: Evidence to date does not support routine testing using 10-2 VF for patients with early glaucoma. However, early 10-2 VF testing may provide sufficient additional information for some patients, particularly those with a repeatable defect within the central 12 locations of the standard 24-2 VF test or who have inner retinal layer thinning on OCT scans of the macula. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Glaucoma , Ophthalmology , Humans , United States , Visual Fields , Scotoma/diagnosis , Retinal Ganglion Cells , Tomography, Optical Coherence/methods , Visual Field Tests , Glaucoma/diagnosis , Glaucoma/complications , Intraocular Pressure
13.
Clin Auton Res ; 34(1): 191-201, 2024 02.
Article En | MEDLINE | ID: mdl-38064009

PURPOSE: Guanfacine is an α2A-adrenergic receptor agonist, FDA-approved to treat attention-deficit hyperactivity disorder and high blood pressure, typically as an extended-release formulation up to 7 mg/day. In our dysautonomia clinic, we observed that off-label use of short-acting guanfacine at 1 mg/day facilitated symptom relief in two families with multiple members presenting with severe generalized anxiety. We also noted anecdotal improvements in associated dysautonomia symptoms such as hyperhidrosis, cognitive impairment, and palpitations. We postulated that a genetic deficit existed in these patients that might augment guanfacine susceptibility. METHODS: We used whole-exome sequencing to identify mutations in patients with shared generalized anxiety and dysautonomia symptoms. Guanfacine-induced changes in the function of voltage-gated Na+ channels were investigated using voltage-clamp electrophysiology. RESULTS: Whole-exome sequencing uncovered the p.I739V mutation in SCN9A in the proband of two nonrelated families. Moreover, guanfacine inhibited ionic currents evoked by wild-type and mutant NaV1.7 encoded by SCN9A, as well as other NaV channel subtypes to a varying degree. CONCLUSION: Our study provides further evidence for a possible pathophysiological role of NaV1.7 in anxiety and dysautonomia. Combined with off-target effects on NaV channel function, daily administration of 1 mg short-acting guanfacine may be sufficient to normalize NaV channel mutation-induced changes in sympathetic activity, perhaps aided by partial inhibition of NaV1.7 or other channel subtypes. In a broader context, expanding genetic and functional data about ion channel aberrations may enable the prospect of stratifying patients in which mutation-induced increased sympathetic tone normalization by guanfacine can support treatment strategies for anxiety and dysautonomia symptoms.


Autonomic Nervous System Diseases , Guanfacine , Humans , Guanfacine/therapeutic use , NAV1.7 Voltage-Gated Sodium Channel/genetics , Mutation , Anxiety/drug therapy , Anxiety/genetics , Adrenergic alpha-Agonists
14.
Am J Med Genet A ; 194(4): e63501, 2024 Apr.
Article En | MEDLINE | ID: mdl-38082334

Bladder exstrophy epispadias complex (BEEC) encompasses a spectrum of conditions ranging from mild epispadias to the most severe form: omphalocele-bladder exstrophy-imperforate anus-spinal defects (OEIS). BEEC involves abnormalities related to anatomical structures that are proposed to have a similar underlying etiology and pathogenesis. In general, BEEC, is considered to arise from a sequence of events in embryonic development and is believed to be a multi-etiological disease with contributions from genetic and environmental factors. Several genes have been implicated and mouse models have been generated, including a knockout model of p63, which is involved in the synthesis of stratified epithelium. Mice lacking p63 have undifferentiated ventral urothelium. MNX1 has also been implicated. In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. We also evaluated the DECIPHER database to identify copy number variants (CNVs) in genes in individuals with the search terms "bladder exstrophy" in an attempt to identify additional candidate genes within these regions. Several de novo variants were identified; however, a candidate gene is still unclear. This data further supports the multi-etiological nature of BEEC.


Anus, Imperforate , Bladder Exstrophy , Epispadias , Hernia, Umbilical , Scoliosis , Urogenital Abnormalities , Pregnancy , Female , Humans , Animals , Mice , Bladder Exstrophy/genetics , Bladder Exstrophy/pathology , Epispadias/genetics , Epispadias/pathology , Exome Sequencing , Urinary Bladder/pathology , Transcription Factors/genetics , Homeodomain Proteins/genetics
15.
Ophthalmol Glaucoma ; 7(1): 66-74, 2024.
Article En | MEDLINE | ID: mdl-37536395

PURPOSE: Compare outcomes of a gelatin stent (XEN45 Gel Stent [XGS]) placed either ab externo with open conjunctiva (AEO) or ab externo with closed conjunctiva (AEC) with or without cataract surgery in patients with glaucoma. DESIGN: Retrospective nonrandomized comparative study. PARTICIPANTS: A total of 86 eyes from 86 glaucoma patients who received XGS placed either AEO (N = 49) or AEC (N = 37) with or without cataract surgery between May 2019 and April 2022 at Massachusetts Eye and Ear. METHODS: Reviewed and analyzed 809 visits from patient charts from a level 3 triage center. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), medication burden, Kaplan-Meier (KM) success rates, 5-fluorouracil (5-FU) impact, and complications. RESULTS: Baseline demographics were similar between both groups, except for baseline IOP and glaucoma type. Both AEO and AEC procedures resulted in significant patterns of IOP and medication reduction from baseline up to 1 year. The AEO procedure had significantly higher KM qualified success (QS) rates than the AEC procedure, but similar complete success (CS) rates. Under QS, the cumulative probability of survival was 73% in the AEO group and 51% in the AEC group at month 6 and 62% in the AEO group and 20% in the AEC group at year 1. Under CS, the cumulative probability of survival was 41% in the AEO group and 37% in the AEC group at month 6 and 29% in the AEO group and 14% in the AEC group at year 1. The AEO procedure had significantly more IOP reduction than the AEC procedure at all postoperative time points beyond week 2, but similar medication burden reduction. At postoperative year 1 (POY1), the mean IOP was reduced to 10.72 ± 5.71 mmHg on 1.16 ± 1.68 medications after AEO and 17.03 ± 2.37 mmHg on 1.59 ± 1.21 medications after AEC. Phacoemulsification (phaco) was not a significant factor while 5-FU usage trended toward significance. Procedure time was longer for standalone XGS AEO. CONCLUSIONS: We demonstrate that both placements reduce medication and IOP from baseline, with AEO placement having more favorable XGS success rates and IOP control at the expense of longer procedure time and greater 5-FU usage. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Cataract , Glaucoma , Humans , Gelatin , Retrospective Studies , Glaucoma/surgery , Glaucoma/complications , Fluorouracil , Cataract/complications , Conjunctiva/surgery , Stents
16.
J Glaucoma ; 33(2): 116-125, 2024 02 01.
Article En | MEDLINE | ID: mdl-37853674

PRCIS: Ab externo with open conjunctiva placement may lead to improved gelatin stent (XEN Gel Stent; Allergan) success rate compared with ab interno with closed conjunctiva because it conferred more favorable intraocular pressure (IOP) and medication burden reduction based on our complete and qualified success criteria. PURPOSE: To compare outcomes of a gelatin stent (XEN 45 Gel Stent; Allergan) placed either ab interno with closed conjunctiva (AIC) or ab externo with open conjunctiva (AEO) with or without cataract surgery in patients with glaucoma. DESIGN: Retrospective, nonrandomized comparative study of 85 eyes from 85 glaucoma patients who received XEN 45 Gel Stent placed either AIC (N=32) or AEO (N=53) with or without cataract surgery between July 2018 and January 2022 at Massachusetts Eye and Ear. Patients were included if they were 18 years of age or above and had at least 30 days of follow-up without any disqualifying event. RESULTS: Baseline demographics were similar between both groups, except for the glaucoma type. Both AIC and AEO procedures resulted in significant patterns of IOP and medication reduction from baseline up to 1 year. At postoperative year (POY)1, mean IOP was reduced to 11.34±4 mmHg on 1.29±1.34 medications after AEO and 13.70±3.32 mmHg on 2±1.81 medications after AIC. The average IOP reduction was significantly greater in the AEO group at all postoperative time points beyond postoperative week 2. There were significant differences in the survival curves of AEO and AIC groups under both the complete success criteria and the qualified success criteria. Under the complete success criteria, the cumulative probability of survival at POY1 was 28.5% in the AEO group and 3.8% in the AIC group. Under the qualified success criteria, the cumulative probability of survival at POY1 was 60.3% in the AEO group and 21.9% in the AIC group. CONCLUSIONS: In our study, we demonstrate that both placements reduce IOP and medication from baseline, with AEO placement having more favorable success rates compared with AIC placement.


Cataract , Glaucoma Drainage Implants , Glaucoma, Open-Angle , Glaucoma , Humans , Infant , Intraocular Pressure , Glaucoma, Open-Angle/surgery , Gelatin , Retrospective Studies , Treatment Outcome , Glaucoma/surgery , Conjunctiva , Stents
17.
Curr Eye Res ; 49(4): 345-353, 2024 04.
Article En | MEDLINE | ID: mdl-38152876

PURPOSE: To determine the safety and feasibility of human autologous adipose tissue-derived adult mesenchymal stem cells (ASCs) for ocular surface regeneration in patients with bilateral limbal stem-cell deficiency (LSCD). METHODS: A phase IIa clinical trial was designed (https://Clinicaltrials.gov, NCT01808378) with 8 patients, 3 of whom had aniridia, 2 meibomian glands diseases, 2 multiple surgeries and 1 chronic chemical injury. The therapeutic protocol was as follows: 6-mm of central corneal epithelium was removed, 400,000 ASCs were injected into each limboconjunctival quadrant, 400,000 ASCs were suspended over the cornea for 20 min, and finally the cornea was covered with an amniotic membrane patch. RESULTS: No adverse events were detected after a mean of 86,5 months of follow-up. One year after surgery, 6 of the 8 transplants were scored as successful, five patients had improved uncorrected visual acuity (mean of 12 letters), two patients presented epithelial defects (also present at baseline) and the mean percentage of corneal neovascularization was of 28.75% (36.98%, at baseline). Re-examination 24 months after treatment disclosed preserved efficacy in 4 patients. At the last visit (after a mean of 86,5 months of follow up) epithelial defects were absent in all patients although improvement in all of the variables was only maintained in patient 3 (meibomian glands agenesia). CONCLUSION: ASCs are a feasible and conservative therapy for treating bilateral LSCD. The therapeutic effect differs between etiologies and diminishes over time.


Corneal Diseases , Epithelium, Corneal , Limbal Stem Cell Deficiency , Limbus Corneae , Mesenchymal Stem Cells , Adult , Humans , Cornea/surgery , Corneal Diseases/surgery , Stem Cell Transplantation/methods , Transplantation, Autologous/methods
18.
Ophthalmol Glaucoma ; 2023 Dec 04.
Article En | MEDLINE | ID: mdl-38056708

PURPOSE: To compare trabeculectomy with mitomycin C (trab-MMC) and XEN45 Gel Stent placed ab externo with open conjunctiva (XGS AEO) with or without cataract surgery in patients with glaucoma. DESIGN: Nonrandomized, retrospective, comparative study. SUBJECTS: A total of 204 eyes from 204 glaucoma patients who received XGS AEO or underwent trab-MMC with or without cataract surgery between July 2018 and August 2021 at Massachusetts Eye and Ear. METHODS: Visits from 204 patient charts were reviewed after either trab-MMC or XGS AEO from 2018 to 2021 from a level 3 triage center. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), medication burden, Kaplan-Meier success rates, 5-fluorouracil impact, and complications. RESULTS: One hundred fifty-seven patients underwent trab-MMC and 47 underwent XGS AEO. Groups had similar baseline intraocular pressure (IOP) and medications (meds). Intraocular pressure and meds decreased similarly at 1.5 years (11.2 mmHg vs. 7.4 mmHg, P = 0.62; 2.9 vs. 2.8 meds, P = 0.92, respectively for trab-MMC and XGS AEO). Success was defined as IOP reduction ≥ 20% with 5 mmHg ≤ IOP ≤ 18 mmHg for 2 consecutive visits. Complete success (CS) did not allow meds; qualified success (QS) allowed for ≤ baseline meds. When IOP fluctuations in the first 60 days were not counted as failures, CS was 43% for trab-MMC, about 8.5% higher than for XGS AEO (P < 0.01). Qualified success was similar between the groups (65%-67%). Procedure time was shorter for XGS AEO than trab-MMC (44 vs. 63 minutes, P < 0.01). CONCLUSIONS: XEN45 Gel Stent AEO may provide similar benefits to trab-MMC, especially for patients who tolerate some meds, with shorter procedure times. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

19.
Reumatol. clín. (Barc.) ; 19(9): 465-477, Nov. 2023. tab
Article Es | IBECS | ID: ibc-226599

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos para el manejo terapéutico de los pacientes con uveítis no infecciosas, no neoplásicas y no asociadas a enfermedad desmielinizante. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento, reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Subsecuentemente, se formularon las recomendaciones. Resultados: Se seleccionaron tres preguntas PICO, referentes a uveítis anteriores, no anteriores y complicadas con edema macular. Se formularon un total de 19 recomendaciones con base en la evidencia encontrada y/o en el consenso de expertos. Conclusiones: Se presenta el primer documento oficial de la Sociedad Española de Reumatología de recomendaciones para el tratamiento de las uveítis. Pueden aplicarse directamente al sistema sanitario español como herramienta de ayuda y homogenización terapéutica.(AU)


Objective: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. Methods: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. Results: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. Conclusions: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.(AU)


Humans , Uveitis/drug therapy , Uveitis/therapy , Macular Edema , Panuveitis , Uveitis, Intermediate
20.
Reumatol Clin (Engl Ed) ; 19(9): 465-477, 2023 Nov.
Article En | MEDLINE | ID: mdl-37839964

OBJECTIVE: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. METHODS: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. RESULTS: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. CONCLUSIONS: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.


Macular Edema , Uveitis , Humans , Macular Edema/complications , Uveitis/complications , Uveitis/therapy , Systematic Reviews as Topic , Practice Guidelines as Topic
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