Ocular Surface最新文献

Purpose

To study the outcomes of minor salivary gland transplantation for severe dry eye disease secondary to chronic Steven Johnson Syndrome.

Methods

It was an ambispective, interventional case series conducted at Rajendra Prasad Centre for Ophthalmic Sciences, Delhi, India from 2022 to 2023 evaluating the outcomes of minor salivary gland transplantation with anchorage of the minor salivary glands to superior rectus muscle in twenty cases of severe dry eye disease secondary to chronic Steven-Johnson Syndrome. The pre-operative clinical parameters were compared to those at post-operative 1 year follow-up.

Results

At 1 year follow-up, there was an improvement in mean Schirmer-1 value (p = 0.0004), hyperemia score (p = 0.0004), keratinization score (p = 0.04), corneal epithelial defect score (p = 0.0004), corneal opacification score (p = 0.001), corneal neovascularization score (p = 0.001), palisades of Vogt score (p = 0.007), corneal keratinization score (p = 0.04) and corneal conjunctivalization score (p = 0.08).

Conclusion

The minor salivary gland transplantation is a viable management option for cases with severe dry eye disease secondary to chronic Steven Johnson Syndrome with clinical improvement in corneal and conjunctival parameters of the ocular surface.

Purpose

To critically appraise the evidence on the efficacy and recanalization rates of permanent punctal occlusion via thermal or surgical means in managing dry eye disease (DED).

Methods

In PubMed, Scopus, and Cochrane databases, two authors systematically reviewed the literature for prospective studies on punctal cautery or surgical occlusion (excluding punctal plugs) for DED. The studied outcomes were changes in tear volume, tear film stability, punctal recanalization rates, and patient symptomatology.

Results

Nine studies (all single-arm) had 150 subjects (96 females). Five studies were on thermal punctal cauterization, and four used surgical occlusion techniques. One hundred eighty puncta were operated for eyes not responding to maximal lubricants or recurrent plug extrusion. DED etiologies were Sjogren's syndrome (78), cicatricial ADDE (27), graft-versus-host disease (12), and non-SS DED (50). Follow-up ranged from 3 to 24 months. At the final follow-up, improvements in Schirmer I and TBUT were 2.5 mm and 0.8s with thermal and 2.1 mm and 0.6s with surgical methods, respectively (P = 0.17 for Schirmer, P = 0.18 for TBUT). Punctal recanalization rates varied between thermal (0–38.7 %) and surgical (5–9%) techniques (p = 0.22). Different cautery devices show different recanalization rates; disposable thermal cautery tips directly inserted into the punctum had lesser recanalization than radiofrequency monopolar cautery. Most patients reported subjective improvement following the procedure, but no quantification measure was given in the studies. None of the published studies had a comparison group for performing a meta-analysis.

Conclusion

Based on non-comparative studies, thermal or surgical punctal occlusion improves tear volume in DED with similar recanalization rates; however, randomized controlled trials are needed to ascertain the real effects of punctal cautery on DED.

Background-aim

PAX6 is a key regulator of eye development and epithelial homeostasis in the cornea. When deficient, chronic corneal inflammation, neovascularization and limbal stem cell deficiency can occur. Here we investigated the potential of duloxetine, a generic serotonin reuptake inhibitor that can upregulate PAX6 in vitro, for its in vivo activity in the context of corneal inflammation.

Methods

Duloxetine tolerance was tested in a human limbal stem cell line and isogenic CRISPR-knockout PAX6^+/− cells. C57BL/6-Wildtype mice were administered duloxetine eye drops at concentrations of 1 μM - 2 mM and tested for toxicity and corneal PAX6 expression. In LPS-induced corneal inflammation in mice, duloxetine's effect on PAX6 expression, corneal opacification and inflammatory responses were evaluated by in vivo corneal imaging, immunostaining, and whole-transcriptome microarray analysis.

Results

No toxicity was observed in vitro for duloxetine concentrations up to 10μΜ. In vivo, duloxetine drops were well-tolerated up to 50 μM. Duloxetine drops at 10μΜ significantly upregulated PAX6 protein levels in the cornea by 30 % within 2 days. In the LPS model, duloxetine resulted in a sustained 33 % PAX6 protein upregulation in the cornea at 7 days, and in reduced opacity within 2 days, accompanied by a significant dampening of IL-17A signaling, neutrophil degranulation, microglial activation, macrophage markers, and MMP expression, despite non-significant changes in total inflammatory cell infiltration.

Conclusion

Short-term administration of a repurposed generic drug, duloxetine, upregulates PAX6 protein levels in the cornea of mice and exerts an anti-inflammatory activity by dampening innate immune responses.

Purpose

While meibomian gland dysfunction (MGD) is widely recognized as a major cause of evaporative dry eye disease, little is known about normal gland differentiation and lipid synthesis or the mechanism underlying gland atrophy and abnormal lipid secretion. The purpose of this study was to use single-cell and spatial transcriptomics to probe changes in cell composition, differentiation, and gene expression associated with two murine models of MGD: age-related gland atrophy in wild-type mice and altered meibum quality in acyl-CoA wax alcohol acyltransferase 2 (Awat2) knockout (KO) mice. Methods: Young (6 month) and old (22 month) wild type, C57Bl/6 mice and young (3 month) and old (13 month) Awat2 KO mice were used in these studies. For single-cell analysis, the tarsal plate was dissected from the upper and lower eyelids, and single cells isolated and submitted to the UCI Genomic Core, while for the spatial analysis frozen tissue sections were shipped to Resolve Biosciences on dry ice and sections probed in duplicate using a meibomian gland specific, 100 gene Molecular Chartography panel.

Results

Analysis of gene expression patterns identified the stratified expression of lipogenic genes during meibocyte differentiation, which may control the progressive synthesis of meibum lipids; an age-related decrease in meibocytes; and increased immune cell infiltration. Additionally, we detected unique immune cell populations in the Awat2 KO mouse suggesting activation of psoriasis-like, inflammatory pathways perhaps caused by ductal dilation and hyperplasia.

Conclusion

Together these findings support novel mechanism controlling gland function and dysfunction.

Purpose

The aim of this study was to develop and validate a method to generate phenol red thread tests (PRTT) due to the lack of availability of commercial PRTT.

Methods

White cotton thread was dyed with phenol red (pH indicator) for 48 h, dried, cut, and sterilized. To validate its wicking ability, the thread was inserted into solutions of varying pH, flanking the pH of healthy tears, for different time intervals. To assess its diagnostic utility, PRTTs were performed in vivo on wildtype and a murine model of evaporative dry eye, acyl-coA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mice.

Results

Two batches of PRTT were produced that had a similar appearance and function to the commercial product. In vitro testing revealed no significant differences in the wicking kinetics at any time point across the pH solutions for batch 1 and only one difference for batch 2 (pH 7.4 vs 7.8 at 5 s, P = 0.029). When comparing both batches, similar wicking kinetics were found with only two significant differences identified (pH 7.6 at 40 s and pH 7.8 at 35 s, P < 0.01). In vivo, our PRTT yielded similar measurements to the commercial PRTT in wildtype and Awat2 KO mice and detected a significant increase in aqueous tear volume in the Awat2 KO mice (commercial: P = 0.015, our PRTT: P = 0.002).

Conclusion

Our method provides a reproducible diagnostic test that performs similarly to its commercial counterpart in a relevant dry eye model indicating that it can serve as a valid and reliable replacement.

Meibomian gland (MG) dysfunction and glaucoma are very prevalent ocular conditions that significantly impact patients’ quality of life. A growing number of clinical and experimental studies have reported an association between the use of topical eye drops to reduce intraocular pressure and the development or exacerbation of MG dysfunction. Studies investigating the impact of glaucoma eyedrops on MG diagnostic parameters have shown variable results, particularly regarding the morphology and function of MG and tear film instability. Herein, we corroborated the findings of greater changes in morphological and functional variables related to MG in patients treated with antiglaucoma eye drops through a systematic review and meta-analysis.

Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.

Ocular surface disease (OSD) is a complex condition that can cause a range of symptoms (e.g, dryness, irritation, and pain) and can significantly impact the quality of life of affected individuals. Iatrogenic OSD, a common finding in patients with glaucoma who receive chronic therapy with topical ocular antihypertensive drugs containing preservatives such as benzalkonium chloride (BAK), has been linked to damage to the ocular surface barrier, corneal epithelial cells, nerves, conjunctival goblet cells, and trabecular meshwork. Chronic BAK exposure activates inflammatory pathways and worsens symptoms, compromising the success of subsequent filtration surgery in an exposure-dependent manner.

In eyes being treated for glaucoma, symptomatic treatment of OSD may provide some relief, but addressing the root cause of the OSD often necessitates reducing or, ideally, eliminating BAK toxicity. Strategies to decrease BAK exposure in patients with glaucoma encompass the use of preservative-free formulations or drugs with alternative and less toxic preservatives such as SofZia®, Polyquad, potassium sorbate, or Purite®. Though the benefits of these alternative preservatives are largely unproven, they might be considered when financial constraints prevent the use of preservative-free versions. For patients receiving multiple topical preserved drugs, the best practice is to switch to nonpreserved equivalents wherever feasible, regardless of OSD severity. Furthermore, nonpharmacological approaches, including laser or incisional procedures, should be considered.

This review explores the effects of BAK on the ocular surface and reviews strategies for minimizing or eliminating BAK exposure in patients with glaucoma in order to significantly improve their quality of life and prevent complications associated with chronic exposure to BAK.

Vernal keratoconjunctivitis (VKC) is a chronic severe ocular allergic inflammation mostly observed in children and young adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, however long-term inflammation may remarkably reduce the visual function due to complications and poor therapeutic responses.

Lack of responsiveness to a drug or treatment is relatively common in VKC and it is not only due to corneal involvement, which is considered the main sign of severity. The concept of refractory may be relative to multiple factors including the clinical condition, systemic co-morbidities, previous or concomitant drugs or regiments, compliance, patient's psychological condition or expectations, type of exposome and environmental conditions, doctor's experience and expectations, or timing of clinical evaluation. In this narrative review, the authors propose a definition of refractory VKC based on revised literature and clinical experience and consider potential new treatments for refractory patients and surgical management in case of complications.