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Eye (London, England) Jun 2024Pterygium, an ocular surface disorder, manifests as a wing-shaped extension from the corneoscleral limbus onto the cornea, impacting vision and causing inflammation.... (Review)
Review
Pterygium, an ocular surface disorder, manifests as a wing-shaped extension from the corneoscleral limbus onto the cornea, impacting vision and causing inflammation. With a global prevalence of 12%, varying by region, the condition is linked to UV exposure, age, gender, and socioeconomic factors. This review focuses on key genes associated with pterygium, shedding light on potential therapeutic targets. Matrix metalloproteinases (MMPs), especially MMP2 and MMP9, contribute to ECM remodelling and angiogenesis in pterygium. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and is elevated in pterygium tissues. B-cell lymphoma-2, S100 proteins, DNA repair genes (hOGG1, XRCC1), CYP monooxygenases, p53, and p16 are implicated in pterygium development. A protein-protein interaction network analysis highlighted 28 edges between the aforementioned proteins, except for VEGF, indicating a high level of interaction. Gene ontology, microRNA and pathway analyses revealed the involvement of processes such as base excision repair, IL-17 and p53 signalling, ECM disassembly, oxidative stress, hypoxia, metallopeptidase activity and others that are essential for pterygium development. In addition, miR-29, miR-125, miR-126, miR-143, miR-200, miR-429, and miR-451a microRNAs were predicted, which were shown to have a role in pterygium development and disease severity. Identification of these molecular mechanisms provides insights for potential diagnostic and therapeutic strategies for pterygium.
PubMed: 38907016
DOI: 10.1038/s41433-024-03186-y -
Bilateral Aggressive Mooren Ulcer in the Setting of Bilateral Pterygia and Pregnancy: A Unique Case.Cornea Jun 2024To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy.
PURPOSE
To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy.
METHODS
A 39-year-old woman of Black African ethnicity, 36-week pregnant, presented to the eye casualty with bilateral nasal corneal ulcer and associated melt around preexisting pterygia. A detailed workup including microbial evaluation, culture and sensitivity, polymerase chain reaction for herpes simplex virus, varicella zoster virus, and cytomegalovirus, inflammatory blood profile, autoimmune markers, and human leucocyte antigen (HLA) screening was undertaken. Treatment was initiated in a stepwise approach.
RESULTS
Infections and systemic autoimmune and rheumatologic conditions were ruled out. A diagnosis of bilateral Mooren ulcer was made by exclusion. The peripheral blood was positive for HLA DQ2. As the condition seemed refractory to medical management (topical steroids and intravenous pulse methylprednisolone followed by oral prednisolone and topical cyclosporine), urgent bilateral conjunctival resection with multilayered amniotic membrane transplantation was performed to reduce the inflammatory stimulus and keratolysis. Stabilization of the condition warranted the need for systemic immunosuppressive agents. Using a multidisciplinary approach, in liaison with Obstetricians and Rheumatologists, the patient was planned for an earlier elective Cesarean section and commencement of oral mycophenolate mofetil postpartum, which aided in successful control of the disease.
CONCLUSIONS
Mooren ulcer could follow an aggressive course during pregnancy, especially in the setting of preexisting pterygium. The complex hormonal and immunological changes during pregnancy and the delivery of inflammatory mediators directly onto the cornea by pterygium could contribute to the severity. A well-planned, stepwise, and multidisciplinary management is pivotal for the treatment of this condition.
PubMed: 38900823
DOI: 10.1097/ICO.0000000000003591 -
Evidence-based Complementary and... 2024are the principal causative factor in the etiological factors of chronic, active, or type B gastritis; peptic and duodenal ulcers; stomach carcinoma; and epithelial...
BACKGROUND
are the principal causative factor in the etiological factors of chronic, active, or type B gastritis; peptic and duodenal ulcers; stomach carcinoma; and epithelial tissue lymphoid malignancies. It infects more than half of the population worldwide. To reduce production, pharmacological therapy of diseases typically involves using threefold treatment methods. However, as a result of such therapy, antimicrobial resistance is commonly developed. Alternative therapeutics for diseases are thus of particular interest.
METHODS
Thyme essential oils (EOs) obtained from Jalas plants in Iran were tested for antibacterial activity against obtained from 320 poultry specimens in this investigation. Antibacterial activity was measured using inhibition zones, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs). The impact of Jalas essential oils on isolate , , and gene expression was evaluated using a quantitative real-time PCR method ( < 0.05).
RESULTS
The chemical content of these EOs varied significantly according to chromatographic examination. Thymol, carvacrol, and terpinene-4-ol are the most abundant components in these EOs. was recognized as a species with a 175-bp PCR product of 16S rRNA in 20/20 (100%). According to PCR results, all 20 (100%) isolates belonged to . The EOs inhibited in a dose-dependent manner, with Jalas being the most effective, followed by pterygium EOs in decreasing order. At 8 mg/mL of Jalas EOs, IZs against were 27.4 ± 0.42 mm, and at 8 mg/mL of pterygium, IZs against were 1 ± 0.02. Jalas essential oils were used to treat all bacteria, and the findings showed that Jalas had a substantial inhibitory impact on the expression of , , and virulence-related genes ( < 0.05).
CONCLUSIONS
In a dose-dependent manner, the EOs of Jalas EO demonstrated a high degree of antimicrobial property against bacteria. The most efficient EOs were those from Jalas with relative concentrations of thymol and carvacrol, followed by the coumarin-dominated pterygium EO with reduced antibacterial activity.
PubMed: 38887601
DOI: 10.1155/2024/3627074 -
Ophthalmology Science 2024To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia.
A Phase IIa Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CBT-001 Ophthalmic Solution in Patients With Primary or Recurrent Pterygium.
PURPOSE
To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia.
DESIGN
Phase II clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial.
PARTICIPANTS
Patients with primary or recurrent pterygia.
MAIN OUTCOME MEASURES
The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety.
METHODS
In stage 1, 24 eyes of 24 patients received 1 drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up.
RESULTS
In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, the mean change from baseline in pterygium vascularity scores was -0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle ( < 0.001; 95% confidence interval: -1.12, -0.40). Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 ( ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation.
CONCLUSIONS
CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38883924
DOI: 10.1016/j.xops.2024.100502 -
Cureus Jun 2024Purpose To evaluate clinical outcomes of primary pterygium excision surgery and analyze risk factors for pterygium recurrence. Setting Eye Treatment Centre, Cornea and...
Purpose To evaluate clinical outcomes of primary pterygium excision surgery and analyze risk factors for pterygium recurrence. Setting Eye Treatment Centre, Cornea and External Diseases Service, Whipps Cross Hospital, London, United Kingdom. Methods Retrospective case series of eyes undergoing primary pterygium excision between August 2017 and July 2022. Patients who underwent "pterygium excision" documented in the electronic patient record system were identified. Patients with recurrent pterygium and those lost-to-follow-up were excluded. The duration of follow-up, type of surgery performed (primary conjunctival closure, conjunctival autograft, and amniotic membrane transplantation), recurrences with respect to the type of surgery performed, and postoperative complications were collected and analyzed. Results In total, 83 eyes (from 79 patients) were included. The mean age of our patient cohort was 59.3 ± 5.9 years. The most common ethnic distribution was Black Caribbean (15.7%). Conjunctival autograft was performed in 76 eyes (91.6%), primary conjunctival closure was performed in five eyes (6%) and amniotic membrane transplantation was performed in two eyes (2.4%). The recurrence rate with conjunctival autograft was 1.3% with a median time to recurrence of 2.98 months. Recurrence was significantly more common in patients below the age of 40 years (p=0.03). Recurrence was not significantly associated with gender (p=0.23), ethnicity (p=0.17), or grade of surgeon (p=0.38). Conclusion Our findings demonstrate the effectiveness of conjunctival autograft with fibrin glue fixation for the surgical management of primary pterygium. Recurrence was found to be significantly more common in patients under the age of 40 years old. However, recurrence was not associated with ethnicity, gender, or surgeon grade.
PubMed: 38882219
DOI: 10.7759/cureus.62440 -
Graefe's Archive For Clinical and... Jun 2024To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence.
PURPOSE
To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence.
METHODS
This prospective randomized clinical trial was conducted on patients who were candidates for pterygium surgery. A total of 75 patients were included in the study from December 2021 to December 2022, of which 64 patients (one eye each) were examined and analyzed based on the inclusion criteria. Then the patients were randomly assigned to control groups, intra-operative MMC (32 patients) and the intervention group, IFN-α2b drops after the operation (32 patients). All patients underwent pterygium surgery using the rotational conjunctival flap method.
RESULTS
In terms of pterygium grading, 8 (12.5%), 25 (39.06%), and 31 (48.44%) eyes were in grades 1, 2, and 3, respectively. The average size of the pterygium was 3.6 ± 0.7 mm. The grade and size of pterygium had the same distribution in the two groups. There was no statistically significant difference between the two groups in the level of post-operative clinical inflammation. The present study showed no significant difference in complications between the two groups (p = 0.999). The recurrence rate in the control group was 9.4% (3 eyes), and 0% (no recurrence) in the intervention group (p = 0.119).
CONCLUSIONS
interferon-alpha 2b group did not show a statistically significant difference in preventing pterygium recurrence compared to the mitomycin C group. The post-surgery administration of IFN-α 2b drops can effectively prevent pterygium recurrence with a comparable and even more compelling effect than MMC during surgery.
PubMed: 38878067
DOI: 10.1007/s00417-024-06548-0 -
Journal of Ophthalmic Inflammation and... Jun 2024To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear...
OBJECTIVE
To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test.
DESIGN
Prospective, single-center study.
PARTICIPANTS
400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls.
METHODS
The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group.
RESULT
Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency.
CONCLUSION
The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.
PubMed: 38874736
DOI: 10.1186/s12348-024-00413-1 -
Neurology Jul 2024
Topics: Humans; Arthrogryposis; Female; Pregnancy; Myasthenic Syndromes, Congenital; Adult; Abnormalities, Multiple; Malignant Hyperthermia; Skin Abnormalities
PubMed: 38870465
DOI: 10.1212/WNL.0000000000209602 -
Clinical Genetics Jun 2024Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births....
Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.
PubMed: 38856159
DOI: 10.1111/cge.14570 -
European Journal of Pharmaceutics and... Jun 2024Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate...
Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. Given the toxicity and poor water solubility of celastrol, we fabricated celastrol-loaded nanomicelles hydrogel hybrid to attenuate subconjunctival fibrosis around silicone implant. The results in vitro demonstrated that celastrol-nanodrug suppressed TGF-β1-induced fibroblast activation and extracellular matrix deposition in human pterygium fibroblasts by inhibiting the TGF-β1/Smad2/3-YAP/TAZ signaling. Further, the results in vivo showed that the celastrol-nanodrug reduced subconjunctival fibrosis in the rabbit model of silicone implantation. These findings suggested that celastrol could serve as a promising therapy for controlling subconjunctival fibrosis. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. We used celastrol-loaded nanomicelles hydrogel hybrid as a sustained-release drug. A rabbit model of subconjunctival fibrosis following silicone implantation was used for in vivo study and TGF-β1-induced human pterygium fibroblast (HPF) activation as an in vitro model. The effects of celastrol on inhibiting TGF-β1-induced migration and proliferation of HPFs were evaluated by scratch wound assay and CCK-8, respectively. Immunofluorescence and western blotting were used to examine the effect of celastrol on the expression of α-SMA, collagen I, fibronectin, and the targets of the Hippo signaling pathway. We found that in vivo celastrol treatment reduced the expression of YAP and TAZ in subconjunctival tissue. Moreover, celastrol alleviated collagen deposition and subconjunctival fibrosis at 8weeks. No obvious tissue toxicity was observed in the rabbit models. Mechanistically, celastrol significantly inhibited TGF-β1-induced proliferation and migration of HPFs. Pretreatment of HPFs with celastrol also suppressed the TGF-β1-induced protein expression of α-SMA, collagen I, fibronectin, TGF-βRII, phosphorylated Smad2/3, YAP, TAZ, and TEAD1. In conclusion, celastrol effectively prevented subconjunctival fibrosis through inhibiting TGF- β1/Smad2/3-YAP/TAZ pathway. Celastrol could serve as a promising therapy for subconjunctival fibrosis.
PubMed: 38851459
DOI: 10.1016/j.ejpb.2024.114352