Composition and diversity of meibum microbiota in meibomian gland dysfunction and the correlation with tear cytokine levels.

Meibomian gland dysfunction (MGD) leads to meibum stasis and pathogenic bacteria proliferation. We determined meibum microbiota via next-generation sequencing (NGS) and examined their association with tear cytokine levels in patients with MGD. This cross-sectional study included 44 moderate-severe patients with MGD and 44 healthy controls (HCs). All volunteers underwent assessment with the ocular surface disease index questionnaire, Schirmer without anesthesia, tear break-up time, Oxford grading of ocular surface staining, and lid and meibum features. Sample collection included tears for cytokine detection and meibum for 16S rRNA NGS. No significant differences were observed in the α-diversity of patients with MGD compared with that in HCs. However, Simpson's index showed significantly decreased α-diversity for severe MGD than for moderate MGD (p = 0.045). Principal coordinate analysis showed no significant differences in ß-diversity in meibum samples from patients with MGD and HCs. Patients with MGD had significantly higher relative abundances of Bacteroides (8.54% vs. 6.00%, p = 0.015) and Novosphingobium (0.14% vs. 0.004%, p = 0.012) than the HCs. Significantly higher interleukin (IL)-17A was detected in the MGD group than in the HC group, particularly for severe MGD (p = 0.008). Although Bacteroides was more abundant in the MGD group than in the HC group, it was not positively correlated with IL-17A. The relationship between core meibum microbiota and tear cytokine levels remains unclear. However, increased Bacteroides and Novosphingobium abundance may be critical in MGD pathophysiology.

Ocular surface microbiome in diabetes mellitus.

This cross-sectional, age- and gender-matched study included 20 eyes of non-diabetic subjects (non-DM group) and 60 eyes of type 2 diabetes mellitus (DM group). Subgroups of DM were classified by diabetic retinopathy (DR) staging into no DR (DM-no DR), non-proliferative DR (DM-NPDR), proliferative DR (DM-PDR), and by glycemic control (well-controlled DM; HbA1c < 7%, poorly controlled DM; HbA1c ≥ 7%). Conjunctival swabs were performed for ocular surface microbiome analysis using conventional culture and next-generation sequencing analysis (NGS). A higher culture-positive rate was found in DM (15%) than in non-DM group (5%) (p value = 0.437). Pathogenic organisms and antibiotic-resistant strains were detected in the DR groups (DM-NPDR and DM-PDR). The NGS analysis showed that potentially pathogenic bacteria such as Enterobacteriaceae, Neisseriaceae, Escherichia-Shigella, and Pseudomonas predominated in DM, especially in DR. There was dissimilarity in the ocular surface microbiome between DM and non-DM groups. The subgroup analysis showed that the DR group had significantly different microbial community from DM-no DR and non-DM groups (p value < 0.05). The microbial community in the poorly controlled DM was also significantly different from well-controlled DM and non-DM groups (p < 0.001). Using the NGS method, our study is the first to signify the importance of DR and glycemic control status, which affect the changes in the ocular surface microbiome.

Thoracolumbar Burst Fracture without Neurological Deficit: Review of Controversies and Current Evidence of Treatment.

Thoracolumbar burst fracture without neurological deficit is a common spinal injury. The ideal classification for the diagnosis and the optimal management strategies, including conservative management, surgical approach, implant constructs, need for spinal fusion, and implant removal, are controversial and currently being investigated. This article reviews the current literature to provide updated evidence on these topics. Posterior ligamentous complex integrity plays an important role in the classification and decision-making process of treatment. A brace is not necessarily required in conservatively treated patients. Regarding surgical management, current evidence advocates posterior-only short segment instrumentation with intermediate screw. Cementoplasty is another option for vertebral augmentation at the fractured level. Spinal fusion is not necessary for this type of injury. Minimally invasive surgery techniques provide equivalent outcomes and can safely replace open approaches. Implant removal after stabilization may provide some benefits, especially in younger patients.

Clinical parameters and biological markers associated with acute severe ocular complications in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions with high mortality rates. Its sequelae, such as blindness, persist even after recovery. Patients with SJS/TEN should be accurately diagnosed and receive appropriate treatment as soon as possible. Therefore, identifying the factors for severity prediction is necessary. We aimed to clarify the clinical parameters and biological markers that can predict acute severe ocular complications (SOCs) in SJS/TEN. This retrospective cross-sectional study enrolled 47 patients with SJS/TEN who were divided into two groups according to ocular severity at acute onset: non-severe ocular complications group (n = 27) and severe ocular complications group (n = 20). Multivariate logistic regression analysis revealed that disease severity (body surface area detachment ≥ 10%) was a predictive factor for acute SOCs, and older age (≥ 60 years) was marginally significantly predictive of SOCs. Serum biomarker levels of S100A8/A9 and granulysin were marginally significant and tended to increase in the SOC group. Therefore, during the early acute stage, focusing on disease severity, patient age, and serum inflammatory biomarkers (S100A8/A9 and granulysin) might help predict SOC progression in patients with SJS/TEN who need prompt and aggressive ocular management to prevent severe ocular sequelae.

Alteration of corneal biomechanical properties in patients with dry eye disease.

PURPOSE: To evaluate the association between symptoms and signs of dry eye diseases (DED) with corneal biomechanical parameters. METHODS: This cross-sectional study enrolled 81 participants without history of ocular hypertension, glaucoma, keratoconus, corneal edema, contact lens use, diabetes, and ocular surgery. All participants were evaluated for symptoms and signs of DED using OSDI questionnaire, tear film break-up time (TBUT), conjunctival and corneal staining (NEI grading) and Schirmer test. Corneal biomechanical parameters were obtained using Corvis ST. Mixed-effects linear regression analysis was used to determine the association between symptoms and signs of DED with corneal biomechanical parameters. Difference in corneal biomechanical parameter between participants with low (Schirmer value ≤10 mm; LT group) and normal (Schirmer value >10mm; NT group) tear production was analyzed using ANCOVA test. RESULTS: The median OSDI scores, TBUT, conjunctival and corneal staining scores as well as Schirmer test were 13±16.5 (range; 0-77), 5.3±4.2 seconds (range; 1.3-11), 0±1 (range; 0-4), 0±2 (ranges; 0-9) and 16±14 mm (range; 0-45) respectively. Regression analysis adjusted with participants' refraction, intraocular pressure, and central corneal thickness showed that OSDI had a negative association with highest concavity radius (P = 0.02). The association between DED signs and corneal biomechanical parameters were found between conjunctival staining scores with second applanation velocity (A2V, P = 0.04), corneal staining scores with second applanation length (A2L, P = 0.01), Schirmer test with first applanation time (A1T, P = 0.04) and first applanation velocity (P = 0.01). In subgroup analysis, there was no difference in corneal biomechanical parameters between participants with low and normal tear production (P>0.05). The associations were found between OSDI with time to highest concavity (P<0.01) and highest displacement of corneal apex (HC-DA, P = 0.04), conjunctival staining scores with A2L (P = 0.01) and A2V (P<0.01) in LT group, and Schirmer test with A1T (P = 0.02) and HC-DA (P = 0.03), corneal staining scores with A2L (P<0.01) in NT group. CONCLUSIONS: According to in vivo observation with Corvis ST, patients with DED showed more compliant corneas. The increase in dry eye severity was associated with the worsening of corneal biomechanics in both patients with low and normal tear production.

Clinical Characteristics, Histopathology, and Treatment Outcomes of Pythium Keratitis: A Retrospective Cohort Study.

PURPOSE: To identify factors associated with the prognosis in Pythium keratitis. PATIENTS AND METHODS: The medical records of 25 patients (26 eyes) diagnosed with Pythium keratitis at a referral institution were reviewed. The demographic and clinical characteristics, treatment, microbiological diagnosis, histopathological features, and outcomes were recorded. The histopathological specimens were reviewed. The patients were divided into a globe removal group and a globe salvage group. Univariate analysis was used to identify factors associated with poor outcomes. RESULTS: Fifteen eyes (57.7%) were removed. Patients in the globe removal group were on average 16.4 years older (95% CI 6.98 to 25.88) than those in the globe salvage group, received the first medication (either topical antifungals or antibiotics) later than one day after the onset of symptoms (RR = 2.75, 95% CI 1.18 to 6.42), and had a maximal diameter of the infiltration area ≥6 mm (RR = 3.14, 95% CI 1.17 to 8.45). The globe removal group showed satellite, multifocal, or total corneal infiltration patterns (RR = 2.82, 95% CI 1.03 to 7.74) and a hypopyon (RR = 3.43, 95% CI 1.26 to 9.35) as risk factors. The histopathological examination showed a higher density of Pythium in the globe removal group than the globe salvage group (median 376 (interquartile range 323, 620) versus 107 (interquartile range 16, 260) hyphae per high power field; P = 0.035). CONCLUSION: The risk of globe removal in patients with Pythium keratitis increased with age, delayed initial topical antifungal or antibiotic treatment, advanced disease at presentation, and dense Pythium hyphae infiltration of the cornea. Early recognition and treatment are critical to successfully eradicate the infection.

The Ocular Microbiome in Stevens-Johnson Syndrome.

The ocular surface microbiome is an essential factor that maintains ocular surface homeostasis. Since the ocular surface is continuously exposed to the external environment, its microbiome, tears, and local immunity are vital for maintaining normal conditions. Additionally, this microbiome helps prevent pathogen colonization, which commonly leads to opportunistic infection. The abnormal ocular surface microbiome has previously been reported in several conditions, including dry eyes, allergy, blepharitis, graft-versus-host disease (GVHD), and Stevens-Johnson syndrome (SJS). Several approaches were applied to identify the ocular microbiome, including conventional culture techniques and molecular sequencing techniques. By using 16s rRNA sequencing, alterations in the type, proportion, and composition of bacterial communities, described by alpha (α)-and beta (ß)-diversity, were observed in SJS patients compared to the healthy group. Conventional culture techniques indicated a higher number of positive bacterial cultures in the SJS group, with a predominance of gram-positive cocci and gram-positive bacilli. Besides, there are increased variations and multiple detections of bacterial genera. Taken together, SJS causes structural changes in the ocular surface and significantly affects its microbiome. Further studies into the area of temporal relationship, metagenomics, proteomics, and metabolomics analysis of the microbiome will lead to a better understanding of this disease. Finally, the treatment using prebiotics and probiotics to re-establish the normal ocular ecosystem and bring back a healthy ocular surface await confirmation.

Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects.

Stevens - Johnson syndrome (SJS) has manifestation through the exfoliation of epidermis and mucosal tissue. Ocular surface is usually affected in acute and chronic stage. The patients are usually suffered from chronic ocular sequelae including symblepharon, limbal stem cell deficiency, etc. Furthermore, ocular microbiome may also be altered in SJS. This is prospective, age and sex matched analytical study which including 20 chronic SJS patients and 20 healthy subjects for specimen collection from inferior conjunctiva for microbiome analysis by conventional cultures and Next-Generation Sequencing (NGS) methods. Significant higher proportion of positive-cultured specimen was demonstrated in SJS group (SJS group 60%, healthy 10%, p-value = 0.001). In addition, NGS which providing high-throughput sequencing has demonstrated the greater diversity of microbial species. The higher proportion of pathogenic microorganisms including Pseudomonas spp., Staphylococcus spp., Streptococcus spp., Acinetobacter spp. was shown in SJS group. Ocular surface in SJS is usually occupied by more diverse microorganisms with increased proportion of pathogenic species. This condition may affect chronic inflammation and opportunistic infections in SJS group. In order to prevent and treat infection in these patients, appropriate antibiotics based on bacterial examination should be considered as the first-line treatment in the SJS patients.