Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of ß-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

Infectious Keratitis After Keratorefractive Surgery: Update and Review of the Literature.

OBJECTIVES: To summarize the clinical manifestations, microbiological profile, treatment, and prognosis of corneal infections after different keratorefractive surgery. METHODS: To obtain relevant studies, English-language databases, including PubMed, Ovid Embase, Web of Science, and CLNAHL, were searched from January 1979 to March 2022. The fundamentals of the literature, clinical characteristics, pathogens, and treatments were retrieved for each included article. RESULTS: Eighty-four studies involving 306 infectious eyes were included in this review. Risk factors of potential infection included a history of blepharitis, contact lens usage, and contaminated surgical instruments. The mean onset time was 22.9±38.7 days (range: 1 day to 3 years). The most common organism isolated from infectious keratitis after keratorefractive surgery were Staphylococcus aureus , followed by Mycobacterium and coagulase-negative Staphylococcus . Most of the infections after refractive procedures were sensitive to medical treatment alone, and the ultimate best-corrected visual acuity after medical treatment was as follows: 20/20 or better in 82 cases (37.0%), 20/40 or better in 170 cases (76.5%), and worse than 20/40 in 52 cases (23.5%). Surgical interventions including flap lift, flap amputation, ring removal, and keratoplasty were performed in 120 eyes (44.5%). CONCLUSIONS: Most infections after keratorefractive surgery occur within a week, whereas more than half of the cases after laser-assisted in situ keratomileusis happen after about a month. Gram-positive cocci and mycobacterium are the most common isolates. Infections after LASIK, intracorneal ring (ICR) implantation, and small incision lenticule extraction, which primarily occur between the cornea layers, require irrigation of the tunnels or pocket with antibiotics.

Combination of UHPLC-Q Exactive-Orbitrap MS, Bioinformatics and Molecular Docking to Reveal the Mechanism of Huan-Lian-Jie-Du Decoction in the Treatment of Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients' quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC-Q Exactive-Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb-Compound-Target network was constructed and enrichment analysis was used. In addition, a protein-protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb-Compound-Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.

Effect of artificial tears on dynamic optical quality in patients with dry eye disease.

BACKGROUND: In clinical practice, fluctuating vision or decreased quality of vision is a common complaint in DED patients. Our study was designed to investigate the change in dynamic optical quality in dry eye patients after the use of artificial tears. METHODS: Fifty-nine patients with dry eye disease (DED) and 31 control subjects were included in this prospective case-control study. There was no significant difference in age and sex between these two groups (P = 0.342, P = 0.847, respectively). Clinical evaluation of the ocular surface included Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), lipid layer thickness (LLT), and Schirmer I test. DED patients were divided into two groups, mild (31 patients) and severe (28 patients). The optical quality of the tear film was measured with the Optical Quality Analysis System (OQAS) using the mean objective scatter index (mean OSI), standard deviation of objective scatter index (SD-OSI) and modulation transfer function cut-off (MTF cut-off). After baseline examinations, one drop of artificial tears (ATs, carboxymethylcellulose ophthalmic solution, 0.5%) was instilled in both eyes, and optical quality parameters were measured again at 5 and 30 min following application of ATs. RESULTS: At baseline, the mean OSI was higher in the DED group (0.95 ± 0.54) than in controls (0.54 ± 0.23, P < 0.001). The SD-OSI was also significantly increased in DED patients (0.44 ± 0.71) compared to control subjects (0.12 ± 0.06, P = 0.003). Five minutes after AT instillation, mean OSI and SD-OSI decreased significantly in severe DED patients (P = 0.044; P = 0.018), remained unchanged in mild DED patients, and increased in the control group (P = 0.019; P < 0.001). Thirty minutes after AT instillation, no significant difference in optical quality parameters was observed among the three groups. CONCLUSION: The effect of ATs on optical quality in patients with DED may differ according to the severity of the disease. Measurement of optical quality might be a promising tool to evaluate the effects of various ATs and possibly individualize treatment in DED patients.

Local Immunosuppression in Wuzhishan Pig to Rhesus Monkey Descemet's Stripping Automated Endothelial Keratoplasty: An Innovative Method to Promote the Survival of Xenografts.

INTRODUCTION: Corneal xenotransplantation is an effective solution for human corneal shortage. We investigated the feasibility and efficacy of different postoperative protocols on xeno-Descemet's stripping automated endothelial keratoplasty (DSAEK) grafts. METHODS: Thirty rhesus monkeys were randomly divided into three groups: control group (C) and only Descemet's membrane (DM) stripping, DSAEK 1 (D1) and DSAEK 2 (D2) groups, DM stripping followed by endothelial keratoplasty. Betamethasone 3.5 mg was subconjunctivally injected in groups control and D1 postoperatively, whereas rhesus monkeys in group D2 received topical 0.1% tacrolimus and topical steroids. All groups were evaluated by slit lamp, anterior segment optical coherence tomography, and laser scanning confocal microscopy for at least 9 months. RESULTS: Twenty-four monkeys met the inclusion criteria. Nine months after the DSAEK surgery, most corneas were transparent. Graft rejection was observed in 25% and 28.57% of the cases in group D1 and group D2 (p > 0.05), respectively. Corneal endothelium densities in DSAEK groups were 2,715.83 ± 516.20/mm2 (D1) and 2,220.00 ± 565.13/mm2 (D2) (p > 0.05). CONCLUSIONS: Xenogeneic corneal endothelial grafts can survive and function in rhesus monkey eyes for a prolonged period of time with subconjunctival steroid or topical tacrolimus and steroid treatment. Furthermore, topical drugs are more suitable for clinical use.

Predicting Unplanned Health Care Utilization and Cost: Comparing Patient-reported Outcomes Measurement Information System and Claims.

OBJECTIVES: There is little literature describing if and how payers are utilizing patient-reported outcomes to predict future costs. This study assessed if Patient-reported Outcomes Measurement Information System (PROMIS) domain scores, collected in routine practice at neurology clinics, improved payer predictive models for unplanned care utilization and cost. STUDY DESIGN: Retrospective cohort analysis of private Health Plan-insured patients with visits at 18 Health Plan-affiliated neurology clinics. METHODS: PROMIS domains (Anxiety v1.0, Cognitive Function Abilities v2.0, Depression v1.0, Fatigue v1.0, Pain Interference v1.0, Physical Function v2.0, Sleep Disturbance v1.0, and Ability to Participate in Social Roles and Activities v2.0) are collected as part of routine care. Data from patients' first PROMIS measures between June 27, 2018 and April 16, 2019 were extracted and combined with claims data. Using (1) claims data alone and (2) PROMIS and claims data, we examined the association of covariates to utilization (using a logit model) and cost (using a generalized linear model). We evaluated model fit using area under the receiver operating characteristic curve (for unplanned care utilization), akaike information criterion (for unplanned care costs), and sensitivity and specificity in predicting top 15% of unplanned care costs. RESULTS: Area under the receiver operating curve values were slightly higher, and akaike information criterion values were similar, for PROMIS plus claims covariates compared with claims alone. The PROMIS plus claims model had slightly higher sensitivity and equivalent specificity compared with claims-only models. CONCLUSION: One-time PROMIS measure data combined with claims data slightly improved predictive model performance compared with claims alone, but likely not to an extent that indicates improved practical utility for payers.

Lipoid Proteinosis presenting as beaded papules of the eyelid: report of three cases.

BACKGROUND: Lipoid proteinosis (LP) is a rare multisystem inherited disease. We report here in three LP cases with beaded papules of the eyelid. Their clinical presentations, histological characteristics, and genetic findings are described and discussed. CASE PRESENTATION: A 12-year-old boy reported to our hospital with a complaint of ocular irritation, redness, and tearing for two years. He had a history of hoarseness since childhood. His younger brother (5 years old) also complained of hoarseness. Another patient, a 26-year-old woman, described many beaded papules on the edge of her eyelids since age 11 years. She additionally reported hoarseness since 4 years of age. Careful slit-lamp examination in these cases revealed waxy beaded papules on the margins of both eyelids and mild conjunctival congestion. Physical examination showed irregular, rugged scars on their facial skin. Genetic analysis showed the mutation located in exon 6 of the ECM1 gene. CONCLUSIONS: Three LP cases first diagnosed by ophthalmologists are presented. The presence of eyelid papules should prompt the ophthalmologist to pay close attention to the patient's voice. If there is a definite history of hoarseness, these patients should undergo gene sequence analysis. If necessary, otorhinolaryngology and dermatology consults may help confirm the diagnosis. Treatment is primarily symptomatic to improve patients' quality of life.

[Design and Implementation of User-oriented Auxiliary Treatment Instrument for Meibomian Gland Dysfunction].

Dry eye is a common ophthalmic disease caused by eye maladjustment due to meibomian gland dysfunction (MGD), which is often accompanied by symptoms such as increased tear film osmotic pressure and ocular surface inflammation. In the treatment of dry eye patients, dredging gland obstruction caused by meibomian gland secretion is an effective treatment method. Based on electrothermal effect and hyperelasticity of the silicone, an auxiliary treatment instrument for MGD is designed, which can improve the blood circulation of the glands through heat compress and massage to achieve the purpose of dredging the meibomian glands. The therapy device can display the temperature and pressure during the treatment in real time, so that the surgeon can grasp the progress of the treatment in real time. The therapy device constructs a user-oriented interactive interface based on parametric modeling method, which can be customized by 3D printing according to the user's eyeball geometric parameters. The designed therapeutic device was finally tested on New Zealand white rabbits. The experimental results show that the therapeutic device has significant effectiveness and safety, as well as clinical application prospects.

Autologous Serum Eye Drops versus Artificial Tear Drops for Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the efficacy of autologous serum (AS) eye drops and artificial tears (AT) in dry eye disease (DED). METHODS: Five databases (PubMed, Science Direct, the Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang Database) were searched for randomized controlled trials (RCTs). Efficacy was evaluated in terms of the Ocular Surface Disease Index (OSDI), Schirmer I test, tear break-up time (TBUT), and fluorescein and rose bengal staining of ocular surface. The estimated effects of AS or AT were expressed as a proportion with the 95% confidence interval and plotted on a forest plot. RESULTS: Seven RCTs with 267 subjects were included in the meta-analysis. For most of the studies, subjects' age was around 50 years old, and the mostly treatment duration was within 8 weeks. The follow-up results showed that the OSDI after AS treatment was lower than that after the AT treatment: the mean difference (MD) was -10.75 (95% CI, -18.12; -3.39) points. There was no difference on the Schirmer I test after treatment between the two groups: the MD was 1.68 (95% CI, -0.65; 4.00) mm. The TBUT of the AS group was longer than that of the AT group, with an MD of 4.53 (95% CI, 2.02; 7.05) s. There was no statistically significant difference on fluorescein staining score of the ocular surface between the AS group and the AT group, the MD was -2.53 (95% CI, -6.08; 1.03) points. The rose bengal staining score of the AS group was slightly lower than that of the AT group after treatment: the MD was -0.78 (95% CI, -1.34; -0.22) points. CONCLUSION: AS could be an effective treatment for DED, improving OSDI, TBUT, and rose bengal staining score. Further RCTs with large samples and long-term follow-up are still needed to determine the exact role of AS in the management of DED.

[Three-dimensional Reconstruction of Retinal Vessels Based on Binocular Vision].

In robot-assisted eye surgery, such as retinal vascular bypass surgery, precise positioning of operating points is required. In this study, a binocular vision-based 3D reconstruction method is proposed to locate the incision points on retinal vessels. Vessels in the image were extracted by CLAHE algorithm to remove the influence of background, then stereo matching was performed. Finally, the retinal vessel image was reconstructed by using the principle of parallax in binocular vision. Experimental results show that this method can accurately locate the incision points on retinal vessels and meet the requirements of ophthalmic surgery.

Porcine endothelial grafts could survive for a long term without using systemic immunosuppressors: An investigation of feasibility and efficacy of xeno-Descemet's stripping automated endothelial keratoplasty from WZS-pig to rhesus monkey.

BACKGROUND: In current non-human primate models, full-thickness porcine grafts could not achieve long-term survival without using potent systemic immunosuppressors. Moreover, the thickness disparity in xeno-PKP proved to be hard to manipulate and may cause several complications which also could prevent the grafts from long survival. Considering the advantages of Descemet's stripping automated endothelial keratoplasty (DSAEK) derived from its ultrathin graft and lower rejection rate, we hypothesize xeno-DSAEK may overcome these imperfections in xeno-PKP. The aim of this study was to explore the feasibility and efficacy of xeno-DSAEK and to investigate the possibility of long-term survival of porcine DSAEK grafts only using local immunosuppressors. METHODS: Nine rhesus monkeys were divided into two groups. In the DSAEK group (n = 7), Descemet's membrane stripping was performed to establish the bullous keratopathy model followed by the endothelial graft transplant. In the control group (n = 2), only DM stripping was performed. Betamethasone 3.5 mg was injected subconjunctivally every 10 days for a total of 10 times in the DSAEK group. After the surgery, all grafts were evaluated by slit lamp microscopy for at least 6 months. In addition, anterior segment optical coherence tomography (AS-OCT) and confocal laser microscopy (CLM) were hired to evaluate the graft attachment and survival. To investigate the rejection mechanism for xeno-DSAEK, pathological and immunity examinations, including immunohistochemistry, immunofluorescence, T-cell subgroups, cytokine concentration, and anti-GAL antibodies, were performed and compared between the survived and rejected grafts. RESULTS: In the control group, the corneal opacity gradually increased with the development of corneal swelling and neovascularization. In the DSAEK group, five recipients (n = 5/7) re-established their transparencies within 30 days after xeno-DSAEK, and four grafts survived >180 days (>180, >180, >298, >270) only by injecting betamethasone subconjunctivally, whereas two grafts (n = 2/7) rejected in 30 days. The AS-OCT and CLM showed the survived grafts attached firmly to the host beds, and the endothelial cell density was adequate (>2000cells/mm2 ) to maintain the graft function at post-operative month 6. The immunohistochemistry showed predominantly T cells (CD4+ and CD8+) and macrophages infiltrated in the rejected grafts, although a few B cells (CD20+) were also observed. Moreover, immunofluorescence demonstrated donor-specific antibody (IgG) and complement (C3c) were also involved in the immune rejection. However, T-cell subgroups and cytokine concentrations (except for IL-6) showed no significant differences between the rejected and survived grafts. CONCLUSION: Xeno-DSAEK is feasible and effective, and the technique may reduce the complications common to xeno-PKP. More importantly, the porcine DSAEK grafts could survive for a long term without using systemic immunosuppressors and exhibit promising future for clinical practice.

The feasibility and efficacy of preparing porcine Descemet's membrane endothelial keratoplasty (DMEK) grafts by two techniques: An ex-vivo investigation for future xeno-DMEK.

BACKGROUND: Descemet's membrane endothelial keratoplasty (DMEK) might be a promising technique for future xeno-corneal transplantation due to its ultrathin graft, extremely low rejection occurrence, suture-free graft fixation, and minimal immunosuppressive regime usage. The aim of this study is to explore the feasibility and efficacy of preparing porcine DMEK grafts by 2 techniques and investigate the graft ultrastructure. METHODS: Two mainstream techniques, mechanical stripping technique and liquid bubble technique, were modified to prepare the porcine DMEK grafts. In all, 40 corneas harvested from WZS-pigs (aged 10-12 months) were subjected to the techniques (20 corneas for each technique). The success rate, time consumption, and endothelial cell density (ECD) before and after preparation were recorded and compared between the 2 techniques. And the ultrastructure of the porcine DEMK graft was investigated by transmission electron microscope. In addition, 9 WZS-pigs with different ages were sacrificed to explore the correlation between the thickness of Descemet's membrane and porcine age. RESULTS: After modifying several technical details, the porcine DMEK grafts were successfully prepared by either mechanical stripping technique or liquid bubble technique, and the mark technique to distinguish the 2 sides of the graft was also explored. In all, 13 DMEK grafts (65%) were prepared successfully by the mechanical stripping technique, whereas 14 successful cases (70%) were prepared by the liquid bubble technique. The success rates between the 2 techniques showed no significant difference (P = .847). However, the mechanical stripping technique was significantly time-consuming when compared with the liquid bubble technique (P < .0001). The ECDs reduced significantly after preparation no matter what techniques were used (P < .0001), but the ECD after the liquid bubble preparation was significantly higher than the ECD after mechanical stripping (P = .032). The ECD reduction positively correlated to the time consumption for both mechanical stripping technique (P = .0014, R2  = 0.621) and liquid bubble technique (P = .013, R2  = 0.412). The ultrastructure showed the graft was comprised of stromal residuals, non-banded layer, and endothelial layer. Unlike human Descemet's membrane (DM), anterior banded layer was not observed. The thickness of porcine DM increased with the age, and a significant positive correlation between them was found (P < .0001, R2  = 0.949), and the predict equation was Y = 0.3764*X + 7.378 (Y indicates the thickness, whereas X indicates the age). CONCLUSIONS: Porcine DMEK grafts could be prepared either by mechanical stripping technique or liquid bubble technique, and the liquid bubble technique seems superior over the mechanical stripping technique regarding time consumption and ECD preservation. Although there are several technical barriers to overcome, xeno-DMEK might be a promising direction for future xeno-corneal transplantation.

Expression of cytokines in aqueous humor from fungal keratitis patients.

BACKGROUND: Although a series of reports on corneal fungal infection have been published, studies on pathogenic mechanisms and inflammation-associated cytokines remain limited. In this study, aqueous humor samples from fungal keratitis patients were collected to examine cytokine patterns and cellular profile for the pathogenesis of fungal keratitis. METHODS: The aqueous humor samples were collected from ten patients with advanced stage fungal keratitis. Eight aqueous humor samples from patients with keratoconus or corneal dystrophy were taken as control. Approximately 100 µl to 300 µl of aqueous humor in each case were obtained for examination. The aqueous humor samples were centrifuged and the cells were stained and examined under optical microscope. Bacterial and fungal cultures were performed on the aqueous humor and corneal buttons of all patients. Cytokines related to inflammation including IL-1ß, IL-6, IL-8, IL-10, TNF-α, and IFN-γ were examined using multiplex bead-based Luminex liquid protein array systems. RESULTS: Fungus infection was confirmed in these ten patients by smear stains and/or fungal cultures. Bacterial and fungal cultures revealed negative results in all aqueous humor specimens. Polymorphonuclear leukocytes were the predominant infiltrating cells in the aqueous humor of fungal keratitis. At the advanced stages of fungal keratitis, the levels of IL-1ß, IL-6, IL-8, and IFN-γ in the aqueous humor were significantly increased when compared with control (p<0.01). The levels of IL-10 and TNF-α also showed an ascending trend but with no statistical significance. CONCLUSIONS: High concentration of IL-1ß, IL-6, IL-8, and IFN-γ in the aqueous humor was associated with fungal keratitis.

[Clinical evaluation of a thermodynamic treatment system for meibomian gland dysfunction].

OBJECTIVE: To evaluate the effectiveness and safety of a single thermodynamic treatment system (LipiFlow) for meibomian gland dysfunction (MGD). METHODS: Retrospective series case study. Forty-eight subjects with meibomian gland dysfunction were analyzed before and after 12 minutes LipiFlow system treatment. All subjects were examined before, 4 weeks and 12 weeks after this treatment. Subjective symptoms, lipid layer thickness (LLT), expressible meibomian gland, tear break-up time, meibomian gland assessment and ocular surface staining were measured. Statistical analysis was performed using SPSS 11.5 software. Analysis included those independent sample two-tailed t-tests for comparison of the mean change from baseline to 4 weeks and baseline to 12 weeks after Lipiflow treatment. Statistically significant difference was based on α=0.05 (P<0.05). RESULTS: A total of 48 cases completed the 12-week follow-up. MGD patients with LipiFlow treatment had a significant reduction in the Ocular Surface Disease Index (OSDI) scores with 45.36±19.34 before treatment, 23.82±11.94 at 4 weeks (t=2.009, P=0.035) and 25.66±14.12 at 12 weeks (t=1.976 P=0.038). LipiFlow resulted in a higher number of expressible glands from 2.91±1.13 (baseline) to 6.27±2.37 (4 weeks, t=3.505, P<0.001) and 5.15±2.08 (12 weeks, t=2.004, P= 0.027) and change of secretion quality from 6.18±2.48 (baseline) to 13.55±3.46 (4 weeks,t=2.698,P=0.005) and 12.67±3.41 (12 weeks,t=2.403,P=0.009). In addition, a single thermodynamic treatment increase the LLT from (42.13±9.67)nm (baseline) to (59.02±16.39)nm (4 weeks, t=2.971, P=0.002) and (54.65±12.52)nm (12 weeks, t=2.021, P=0.021). The rate of partial blink was relieved from 0.37±0.30 (baseline) to 0.15±0.14 (4 weeks, t=3.428, P=0.035) and 0.12±0.13 (12 weeks, t=1.986, P=0.026). BUT was increased from (4.73± 2.34)s (baseline) to (9.32 ± 2.18)s (4 weeks, t=3.385, P<0.001) and (9.91 ± 3.01)s (12 weeks, t=3.253, P< 0.001). There were no unanticipated or serious device-related adverse events reported. Compared with baseline, there was no statistically significant difference in BCVA, corneal staining and intraocular pressure (P=0.141, 0.376, 0.421). CONCLUSION: The LipiFlow system was a safety and effectiveness treatment of MGD in the 12-week study.

Reis-Bücklers corneal dystrophy: a reappraisal using in vivo and ex vivo imaging techniques.

PURPOSE: To characterize the phenotype of Reis-Bücklers corneal dystrophy (RBCD) using in vivo and ex vivo imaging techniques. METHODS: Five RBCD patients with penetrating keratoplasty (PK) were enrolled. Before surgery, all patients underwent a complete ophthalmological examination including slitlamp biomicroscopy, in vivo confocal microscopy (IVCM) and anterior segment (AS) optical coherence tomography (OCT). After PK, corneal buttons were examined by light and transmission electron microscopy (TEM). Correlations between in vivo and ex vivo images were analyzed. RESULTS: In all cases, irregular geographic-like subepithelial gray-white opacities were observed in the central and mid-peripheral cornea. AS-OCT images of the cornea of all patients revealed hyperreflective homogeneous and continuous deposits concentrated at the level of Bowman's layer and anterior stroma. Using IVCM, a highly reflective irregular amorphous material was observed from intermediate epithelial cells to the anterior stroma. Sparse deposits of highly reflective material were also detected in the posterior stroma. TEM showed in all specimens basal epithelial cells containing small vesicles with rod-shaped dense material. CONCLUSIONS: IVCM and AS-OCT may be a useful adjunct to biomicroscopy for the diagnosis and management of RBCD. The correlations between the different in vivo and ex vivo imaging techniques emphasize the hypothesis of an epithelial origin for RBCD.

[Mechanism study on trans-lamina cribrosa pressure difference correlated with optic neuropathy in glaucoma].

Glaucomatous optic neuropathy is among the most common causes of blindness worldwide. Elevated intraocular pressure (IOP) has long being considered to be the major risk factors for the development and progression of glaucomatous optic nerve damage. However, numerous studies have shown that a relatively large number of patients with typical glaucomatous optic neuropathy, in whom the IOP measurements have always been in the normal range (<21 mmHg, 1 mmHg = 0.133 kPa). Thus, the role of IOP in the pathogenesis of POAG becomes vague and controversial. Based on prospective clinical observations, Beijing iCOP (Intracranial and Intraocular Pressure) Study has found that the orbital cerebrospinal fluid pressure (CSF-P) may be of importance for the physiology and patho-physiology of the optic nerve head and may play a role in the pathogenesis of glaucomatous optic neuropathy. A low CSF-P in the retrobulbar region of the orbit may act as the counter-pressure against IOP and theoretically have a similar effect as an increased IOP on the trans-lamina cribrosa pressure difference which may be more relevant to the glaucomatous optic neuropathy than IOP alone. Moreover, an experimental and chronic reduction in CSF-P in monkeys was associated with the development of optic nerve damage morphologically typical for glaucomatous optic neuropathy. The findings support the hypothesis the CSF-P may play a role in the pathogenesis of glaucomatous optic neuropathy.

[Perioperative ocular surface evaluation and management in meibomian gland dysfunction patients undergoing cataract surgery].

Meibomian gland dysfunction (MGD) is one of the most common conditions in the elderly. Most of MGD patients undergoing cataract surgery were found to have significant dry eye symptoms and ocular surface disease. The severe cases with ocular surface disease are also at higher risk of postoperative complications, namely infections and corneal ulcers. To improve the operation effect and achieve the best visual outcome and life quality in cataract patients, it is important to evaluate the ocular surface and meibomian glands in MGD patients preoperatively, pay attention to the intraoperative care and detect the postoperative complications carefully and use medicine properly.

[Evaluation of the diagnostic value for meibomian gland dysfunction examinations].

OBJECTIVE: To evaluate the sensitivity and specificity of clinical examinations in meibomian gland dysfunction (MGD). METHODS: A prospective case-controlled study. Fifty-two patients with MGD and 32 healthy age- and sex-matched control subjects were included from January to August 2013. All subjects were underwent the examinations sequentially as follows: evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index (OSDI); lid margin and ocular surface examination by slit lamp microscrope; infrared meibomian photography; cornea sensation testing using the Cochet-Bonnet esthesiometer; tear film break-up time (BUT); corneal and conjunctival staining (Oxford scale); and Schirmer I test. One eye of each subject was included in the study. The parameters between MGD group and the control group were compared using the independent-samples T test. Spearman's correlation analysis was used to analyze the correlation of each parameter of MGD group. Receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate MGD from normal eyes. RESULTS: OSDI score, lid margin abnormality score, miss rate of meibomian glands and corneal and conjunctival staining score were obviously higher in MGD group (36.13 ± 14.71, 2.37 ± 0.937, (52.64 ± 17.23) %, 1.06 ± 1.75) than those in control group(5.22 ± 11.97, 0.94 ± 0.564, (23.97 ± 6.36) %, 0.03 ± 0.18) (t = 10.019, 7.808, 8.796, 3.293, respectively; P < 0.01). BUT, schirmer I value and corneal sensitivity score were significantly lower in MGD group (4.57 ± 2.13, 6.04 ± 7.09, 5.77 ± 0.38) than those in control group (13.31 ± 2.54, 12.56 ± 6.99, 5.98 ± 0.07) (t = -16.97, -4.119, -3.018, respectively; P < 0.01). AUC value of BUT was the largest (0.995), and the followings were the miss rate of meibomian (0.944), OSDI (0.925) and lid margin abnormalities (0.811). The sensitivity and the specificity of BUT were 90.4% and 100.0%; the miss rate of meibomian were 76.9% and 100.0%; OSDI were 97.4% and 87.1%; and lid margin abnormalities were 79.5% and 79.4%. The diagnostic value of these four parameters were better than the rest ones. CONCLUSION: BUT and the miss rate of meibomian have great value in diagnosis of MGD. Patients considered MGD can be performed these examinations to confirm the diagnosis.

Ferroptosis as a Potential Therapeutic Target for Reducing Inflammation and Corneal Scarring in Bacterial Keratitis.

Purpose: Bacterial keratitis (BK) is a serious ocular infection that can cause severe inflammation and corneal scarring, leading to vision loss. In this study, we aimed to investigate the involvement of ferroptosis in the pathogenesis of BK. Methods: Transcriptome analysis was performed to evaluate ferroptosis-related gene expression in human BK corneas. Subsequently, the ferroptosis in mouse models of Pseudomonas aeruginosa keratitis and corneal stromal stem cells (CSSCs) were validated. The mice were treated with levofloxacin (LEV) or levofloxacin combined with ferrostatin-1 (LEV+Fer-1). CSSCs were treated with lipopolysaccharide (LPS) or LPS combined Fer-1. Inflammatory cytokines, α-SMA, and ferroptosis-related regulators were evaluated by RT-qPCR, immunostaining, and Western blot. Iron and reactive oxygen species (ROS) were measured. Results: Transcriptome analysis revealed significant alterations in ferroptosis-related genes in human BK corneas. In the BK mouse models, the group treated with LEV+Fer-1 exhibited reduced inflammatory cytokines (MPO, TNF-α, and IFN-γ), decreased corneal scarring and α-SMA expression, and lower Fe3+ compared to the BK and LEV groups. Notably, the LEV+Fer-1 group showed elevated GPX4 and SLC7A11 in contrast to the BK and LEV group. In vitro, Fer-1 treatment effectively restored the alterations of ROS, Fe2+, GPX4, and SLC7A11 induced by LPS in CSSCs. Conclusions: Ferroptosis plays a crucial role in the pathogenesis of BK. The inhibition of ferroptosis holds promise for mitigating inflammation, reducing corneal scarring, and ultimately enhancing the prognosis of BK. Consequently, this study provides a potential target for innovative therapeutic strategies for BK, which holds immense potential to transform the treatment of BK.

Corneal Epithelial Dendritic Cells: An Objective Indicator for Ocular Surface Inflammation in Patients with Obstructive Meibomian Gland Dysfunction?

PURPOSE: To examine whether corneal epithelial dendritic cells (CEDC) could serve as an indicator to distinguish obstructive meibomian gland dysfunction (MGD) with or without ocular surface inflammation (OSI). METHODS: We performed a case-control study on patients with diagnosed obstructive MGD between August 2017 and November 2019. RESULTS: 30 MGD cases and 25 healthy controls were recruited. The classification of MGD patients with and without OSI was based on the tear pro-inflammatory cytokine levels. Compared with the MGD without OSI and the control group, a higher CEDC density was detected in the MGD with OSI subgroup. The presence of >15.6 cells/mm2 CEDC had a sensitivity of 73% and specificity of 75% for the diagnosis of MGD with OSI. CONCLUSIONS: OSI is not present in all patients with obstructive MGD. Evaluation of CEDC density in the central cornea may help identify whether MGD is concomitant with OSI.