Outcomes of 320-degree intrastromal corneal ring segment implantation for advanced keratoconus.

PURPOSE: The purpose of this study is to investigate visual and tomographic outcomes and complications of long-arc length intrastromal corneal ring segment (ICRS) implantation for the treatment of advanced keratoconus. MATERIALS AND METHODS: This retrospective study enrolled 10 eyes of 9 subjects. All patients received 320-degree ICRS (320-ICRS) implantation with femtosecond laser-assisted technique based on their advanced grading with preoperative high keratometry (K) value, asphericity (Q), and astigmatism. Medical records and corneal tomography changes of consecutive patients were reviewed at baseline, 1, and 3 months after treatment. RESULTS: There are 6 female and 3 male patients with a mean age of 29.6 ± 7.8 years in this study. Mean K (Km) reduced from 59.01 ± 5.81 D preoperatively to 50.7 ± 5.3 and 50.2 ± 3.66 postoperatively (after 1 month and 3 months respectively, P < 0.001). The changes in mean K, K1, K2, and maximum K (Kmax) reading were all statistically significant (all P < 0.001). Mean uncorrected distance visual acuity (UCVA) improved from 20/400 to 20/200. Mean best-corrected distance visual acuity (BCVA) improved from 20/100 to 20/60. Both UCVA and BCVA showed a trend of improvement at postoperative month 3, though insignificant in BCVA (P = 0.114). Mean Q improved from -1.59 ± 0.62 preoperatively to -0.48 ± 1.08 and -0.11 ± 1.04 postoperatively (after 1 month and 3 months respectively, P = 0.016, 0.002). No intraoperative or postoperative complications were observed. CONCLUSIONS: The present results suggest that implanting a 320-ICRS is a safe and effective procedure for treating patients with advanced keratoconus. Preoperative corneal measurements and the selection of types and thickness of ICRS are important to prevent unpredictable results.

Bilateral keratitis associated with afatinib therapy.

This case discussed a significant ocular side effect, bilateral keratitis, which could be induced by afatinib, an irreversible epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We explored the disease progression of a 52-year-old, stage IV nasopharyngeal carcinoma male patient, who was under afatinib treatment and had experienced progressive bilateral eye dryness and tenderness on increasing afatinib from 40 mg every other day to 40 mg daily. Clinical examination noted bilateral visual acuity reduction, diffuse superficial punctate keratopathy in the right eye, and a central epithelial defect in the left eye. Seidel test results were negative for both eyes, with no corneal infiltration, lagophthalmos, anterior chamber cell precipitation, or retinal lesion. Symptoms subsequently resolved after reducing the frequency of afatinib used, along with intensive ocular hydration. In summary, this case highlighted afatinib's potential link to bilateral keratitis, and early afatinib dose adjustment with supportive medication could significantly reverse the condition.

Deciphering Early-Stage Molecular Mechanisms of Negative Pressure Wound Therapy in a Murine Model.

Negative Pressure Wound Therapy (NPWT) is a commonly employed clinical strategy for wound healing, yet its early-stage mechanisms remain poorly understood. To address this knowledge gap and overcome the limitations of human trials, we establish an NPWT C57BL/6JNarl mouse model to investigate the molecular mechanisms involved in NPWT. In this study, we investigate the intricate molecular mechanisms through which NPWT expedites wound healing. Our focus is on NPWT's modulation of inflammatory immune responses and the concurrent orchestration of multiple signal transduction pathways, resulting in shortened coagulation time and reduced inflammation. Notably, we observe a significant rise in dickkopf-related protein 1 (DKK-1) concentration during NPWT, promoting the differentiation of Hair Follicle Stem Cells (HFSCs) into epidermal cells, expediting wound closure. Under negative pressure, macrophages express and release DKK-1 cytokines, crucial for stimulating HFSC differentiation, as validated in animal experiments and in vitro studies. Our findings illuminate the inflammatory dynamics under NPWT, revealing potential signal transduction pathways. The proposed framework, involving early hemostasis, balanced inflammation, and macrophage-mediated DKK-1 induction, provides a novel perspective on enhancing wound healing during NPWT. Furthermore, these insights lay the groundwork for future pharmacological advancements in managing extensive wounds, opening avenues for targeted therapeutic interventions in wound care.

Sex Differences and Discordance Between Symptoms and Signs of Dry Eye Disease.

PURPOSE: To examine the initial presenting symptoms in relation to sex and identify predictors of discordance between symptoms and signs of dry eye disease (DED) in Taiwan. DESIGN: Retrospective cross-sectional study. METHODS: This clinic-based cohort from a tertiary referral center in Taiwan included 1229 patients diagnosed with DED at Keelung Chang Gung Memorial Hospital in Taiwan between August 1, 2011, and July 31, 2018. Initial presenting symptoms were cross-sectionally and retrospectively collected. The composite score, indicating the discordance between symptoms and signs, was derived from the difference between the DED symptom severity score and the DED sign severity score. RESULTS: Of 1229 patients, 975 (79.3%) were female, with a mean age of 56.7 ± 14.9 years. Initial presenting symptoms didn't show significant sex differences (all P > .05). In multivariate analysis, predictors of higher symptom severity score than sign severity score included being female (P = .011) and having a surgical history of cataract (P = .037), pterygium, or conjunctivochalasis (P = .014). Conversely, older age (P < .001) and artificial tear use (P < .001) were significant predictors of a lower symptom severity score than sign severity score. CONCLUSIONS: Strong predictors of incongruity between DED symptoms and signs include age, gender, surgical history for cataract, pterygium or conjunctivochalasis, and artificial tear use. Ophthalmologists should prioritize symptoms for female patients and postsurgery cases. In addition, the absence of symptoms should not dismiss DED possibility in older adult patients and those using artificial tears. Notably, early recognition and enhancement of postoperative care can improve patient satisfaction and quality of life.

Targeting Ca2+-dependent pathways to promote corneal epithelial wound healing induced by CISD2 deficiency.

Chronic epithelial defects of the cornea, which are usually associated with severe dry eye disease, diabetes mellitus, chemical injuries or neurotrophic keratitis, as well as aging, are an unmet clinical need. CDGSH Iron Sulfur Domain 2 (CISD2) is the causative gene for Wolfram syndrome 2 (WFS2; MIM 604928). CISD2 protein is significantly decreased in the corneal epithelium of patients with various corneal epithelial diseases. Here we summarize the most updated publications and discuss the central role of CISD2 in corneal repair, as well as providing new results describing how targeting Ca2+-dependent pathways can improve corneal epithelial regeneration. This review mainly focuses on the following topics. Firstly, an overview of the cornea and of corneal epithelial wound healing. The key players involved in this process, such as Ca2+, various growth factors/cytokines, extracellular matrix remodeling, focal adhesions and proteinases, are briefly discussed. Secondly, it is well known that CISD2 plays an essential role in corneal epithelial regeneration via the maintenance of intracellular Ca2+ homeostasis. CISD2 deficiency dysregulates cytosolic Ca2+, impairs cell proliferation and migration, decreases mitochondrial function and increases oxidative stress. As a consequence, these abnormalities bring about poor epithelial wound healing and this, in turn, will lead to persistent corneal regeneration and limbal progenitor cell exhaustion. Thirdly, CISD2 deficiency induces three distinct Ca2+-dependent pathways, namely the calcineurin, CaMKII and PKCα signaling pathways. Intriguingly, inhibition of each of the Ca2+-dependent pathways seems to reverse cytosolic Ca2+ dysregulation and restore cell migration during corneal wound healing. Notably, cyclosporin, an inhibitor of calcineurin, appears to have a dual effect on both inflammatory and corneal epithelial cells. Finally, corneal transcriptomic analyses have revealed that there are six major functional groupings of differential expression genes when CISD2 deficiency is present: (1) inflammation and cell death; (2) cell proliferation, migration and differentiation; (3) cell adhesion, junction and interaction; (4) Ca2+ homeostasis; (5) wound healing and extracellular matrix; and (6) oxidative stress and aging. This review highlights the importance of CISD2 in corneal epithelial regeneration and identifies the potential of repurposing venerable FDA-approved drugs that target Ca2+-dependent pathways for new uses, namely treating chronic epithelial defects of the cornea.

Efficacy and safety of topical cyclosporine 0.1% in moderate-to-severe dry eye disease refractory to topical cyclosporine 0.05% regimen.

PURPOSE: To evaluate the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) following prior treatment with 0.05% cyclosporine A anionic emulsion (CsA AE) in moderate to severe dry eye disease (DED). MATERIALS AND METHODS: We retrospectively identified patients with moderate-to-severe DED who had shown an inadequate response to twice-daily use of topical 0.05% CsA AE but showed a significant improvement after switching to 0.1% CsA CE daily. Dry eye parameters before and after CsA CE were evaluated by tear break-up time (TBUT), corneal fluorescein staining (CFS), cornea sensitivity, Schirmer's test without anesthetics, and Ocular Surface Disease Index questionnaire. RESULTS: Twenty-three patients, including ten patients with Sjogren syndrome and five patients with rheumatoid arthritis, were reviewed. After a 2-month course of treatment with topical 0.1% CsA CE, significant improvements were noted for CFS (P < 0.001), corneal sensitivity (P = 0.008), and TBUT (P = 0.01). Efficacy was similar in the autoimmune versus nonautoimmune group. 39.1% of patients reported treatment-related adverse events, while the majority was transient instillation pain. Visual acuity and intraocular pressure had no significant changes during the study. CONCLUSION: In patients with moderate to severe DED refractory to 0.05% cyclosporine, shifting to 0.1% cyclosporine showed improvement in objective signs but with lower treatment tolerability in the short term.

Orthokeratology compliance, digital device use, and myopia control among children with myopia during COVID-19 home confinement in Taiwan.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic profoundly impacts lifestyle habits and myopia control in children worldwide. This study investigated the changes in eyecare habits, orthokeratology compliance, axial length, and time interval of follow-up visits during home confinement in the COVID-19 pandemic in Taiwan. Methods: This investigation was part of a prospective study undertaken to evaluate the effectiveness of a mobile application. A semi-structured telephone interview was conducted with parents retrospectively to document eyecare habits and myopia control during the COVID-19 home confinement. Results: Thirty-three children with myopia participated in the follow-up of orthokeratology lenses for 2 years. The children's time viewing digital devices such as tablets and televisions significantly increased during the COVID-19 pandemic (P < 0.05). An analysis using McNemar's test found that the proportional growth of axial length <0.2 mm in 2021 was significantly higher than that in 2020 (77.42% vs. 58.06%, P < 0.05). In the multivariate logistic regression analysis, onset <10 years of age (P = 0.001) and parents with high myopia (P < 0.001) were independent risk factors for the growth of axial length ≥0.2 mm in 2021. Conclusion: The suspension of face-to-face classes and after-school tutorials benefited myopic axial elongation in children during COVID-19 home confinement. The use of digital devices and staying indoors may not be the exclusive reasons for myopia progression. Educating parents about the influence of extra learning classes after school on myopia progression would be prudent.

Retinal Neurodegeneration and Visual Acuity Decline in Patients with Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease (CKD) has been associated with accelerated retinal neurodegeneration. The purpose of this study is to evaluate the association between retinal neurodegeneration and the best-corrected visual acuity (BCVA) decline in patients with CKD. METHODS: Post hoc analysis of two prospective studies. Patients with CKD stage ≥ 3 were enrolled. Macular thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular ganglion cell complex (GCC) thickness were measured by optical coherence tomography. Eyes were classified into three groups: Group 1, no GCC defect; Group 2, GCC defect confined to parafoveal area; and Group 3, GCC defects extending beyond the parafoveal area. Each group was matched for age, sex, axial length, lens status, and cataract grading. RESULTS: A total of 120 eyes (40 eyes in each group) from 120 patients (age 63.0 ± 10.3 years) were included. The logMAR BCVA was 0.076 ± 0.101, 0.100 ± 0.127, and 0.196 ± 0.191 in Group 1, 2, and 3, respectively. Group 3, but not Group 2, had a significantly worse BCVA than Group 1. In simple linear regression, parafoveal inner retinal thickness, pRNFL thickness, presence of pRNFL defect, GCC thickness, GCC global loss volume, GCC focal loss volume, and GCC defect extending beyond parafoveal area were associated with BCVA. Central subfield retinal thickness (CRT), parafoveal full retinal thickness, and parafoveal outer retinal thickness were not associated with BCVA. In backward stepwise linear regression, age and GCC defects extending beyond the parafoveal area were factors associated with BCVA. Moreover, GCC defect extending beyond parafoveal area was connected with worse BCVA in both phakic and pseudophakic subgroups. CONCLUSIONS: GCC defect extending beyond parafoveal area could be an independent biomarker associated with decreased BCVA in patients with CKD. However, macular thinning measured by CRT or parafoveal full retinal thickness might have low discriminative power in determining BCVA.

Accelerated Peripapillary Retinal Nerve Fiber Layer Degeneration in Patients With Chronic Kidney Disease: A 2-Year Longitudinal Study.

Purpose: To evaluate the longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) in patients with chronic kidney disease (CKD). Methods: In this prospective cohort study, the CKD group consisted of patients with CKD stage ≥ 3. Age-matched healthy controls were enrolled at a 1:4 ratio. Spectral-domain optical coherence tomography was used to measure the pRNFL at baseline, 1 year, and 2 years. Within-group longitudinal changes and between-group comparisons were performed using linear mixed models. Results: Overall, 152 patients with CKD and 40 controls were included (mean ages, 62.8 ± 9.1 years vs. 63.0 ± 9.3 years; P = 0.931). The CKD group showed faster loss of pRNFL than the control group (-0.87 µm/y vs. -0.26 µm/y; P = 0.004). Subgroup analysis found that the rate of pRNFL change was -0.41 µm/y in stage 3a CKD, -0.74 µm/y in stage 3b, -0.98 µm/y in stage 4/5, and -1.38 µm/y in end-stage renal disease. Multiple linear regression analysis revealed that CKD stage (coefficient = -0.549; 95% confidence interval [CI], -0.966 to -0.131; P = 0.010), hypertension (coefficient = -1.557; 95% CI -3.013 to -0.101; P = 0.036), and rim area (coefficient = -1.505; 95% CI, -2.940 to -0.070; P = 0.040) were factors associated with the pRNFL change over 2 years. Conclusions: Patients with CKD experienced faster pRNFL loss than healthy controls did. Severity of CKD, hypertension, and rim area were independent factors associated with the loss of pRNFL. Translational Relevance: This study contributes to our understanding of retinal neurodegeneration in normal aging and in patients with chronic kidney diseases.

Tear function in patients with diabetes mellitus: A systematic review and meta-analysis.

Purpose: To examine tear function in patients with diabetes mellitus (DM). Design: Systematic review and meta-analysis. Method: We searched Embase and PubMed from database inception to March 16, 2022. We included observational studies that compared tear function between patients with and without DM. Tear function was measured using invasive tear breakup time (ITBUT) and Schirmer's 1 test. Pooled results are presented as standard mean difference (SMD) with 95% confidence interval (CI) based on random-effects models. Results: We included 59 studies (7,234 eyes) comparing the tear function between patients with and without DM. This meta-analysis indicated that patients with DM had worse tear function than those without DM (ITBUT: SMD: -0.98, 95% CI: -1.27 to -0.69; Schirmer's 1 test: SMD: -0.45, 95% CI: -0.64 to -0.26), and the results remained consistent in patients with different types of DM (e.g., type 1 DM and type 2 DM) and from different ethnic backgrounds (e.g., Asian vs. non-Asian). Patients with DM under poor glycemic control had worse tear function than those of the non-DM group (ITBUT: SMD: -1.26, 95% CI: -1.86 to -0.66; Schirmer's 1 test: SMD: -0.25, 95% CI: -0.48 to -0.02), whereas there were no significant differences in tear function between patients with DM under optimal glycemic control and non-DM groups. Conclusions: We found that patients with type 1 or type 2 DM had significantly reduced tear function. The level of tear function could be determined by glycemic control, and therefore, our findings suggest that glycemic control in patients with DM is critical for maintaining tear function. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42021250498.

Staphylococcus lugdunensis Endophthalmitis: Case Series and Literature Review.

Staphylococcus lugdunensis endophthalmitis is an uncommon intraocular infection with potentially visually devastating consequences. S. lugdunensis endophthalmitis have been reported following cataract surgery, trauma, intravitreal injections of anti-vascular endothelial growth factor agents and dexamethasone implant. We report four cases of postoperative S. lugdunensis endophthalmitis after cataract extraction (three patients) and combined pars plana vitrectomy and cataract extraction (one patient). The onset of presentation of endophthalmitis was acute (within 2 weeks) in two patients, subacute (2 to 6 weeks) in one patient, and chronic (more than 6 weeks) in one patient. All patients had presenting visual acuity (VA) of hand motions or worse and were treated with pars plana vitrectomy with intravitreal antibiotics. The final VA was 20/50 in two patients, 4/200 in one patient with pre-existing myopic maculopathy, and no light perception in one patient with retinal detachment. In antibiotic susceptibility testing, S. lugdunensis isolates were resistant to penicillin (3/4, 75%), but all were susceptible to vancomycin, oxacillin, teicoplanin, tigecycline, and sulfamethoxazole-trimethoprim. S. lugdunensis may be associated with acute or chronic endophthalmitis. Favorable visual outcomes can be achieved with prompt diagnosis and management.

Dry eye disease in patients with type II diabetes mellitus: A retrospective, population-based cohort study in Taiwan.

Purpose: To investigate the risk and protective factors of dry eye disease (DED) in patients with type II diabetes mellitus (DM). Design: A retrospective cohort study using Chang- Gung research database collecting data from 2005 to 2020. Methods: Patients with type II DM were included, and those with previous ocular diseases were excluded. Ten thousand twenty nine developed DED (DED group), and 142,491 didn't (non-DED group). The possible risk and protective factors were compared and analyzed using the logistic regression model. Results: A majority of the DED group were female with significantly higher initial and average glycated hemoglobin levels, and higher incidence of diabetic neuropathy and retinopathy. In conditional logistic regression model, advanced age was a risk factor. After adjusting for sex, age, and DM duration; average glycated hemoglobin level, diabetic neuropathy, retinopathy, and nephropathy with eGFR 30 ~ 59 and intravitreal injection, vitrectomy, pan-retinal photocoagulation, and cataract surgery were contributing factors of DED. Considering antihyperglycemic agents, DPP4 inhibitor, SGLT2 inhibitor, GLP-1 agonist, and insulin monotherapy and dual medications combining any two of the aforementioned agents were protective factors against DED compared with metformin alone. In the monotherapy group, SLGT2 inhibitor had the lowest odds ratio, followed by GLP1 agonist, DPP4 inhibitor, and insulin. Conclusions: DED in patients with DM is associated with female sex, advanced age, poor diabetic control, microvascular complications and receiving ocular procedures. GLP-1 agonist, SGLT-2 inhibitor, DPP4 inhibitor, and insulin are superior to metformin alone in preventing DM-related DED. A prospective randomized control trial is warranted to clarify our results.

Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients With Type 2 Diabetes in Taiwan.

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to improve low-grade systemic and tissue inflammation; however, the association between SGLT2 inhibitor use and the incidence of dry eye disease (DED) has not been explored. Objective: To investigate the association between SGLT2 inhibitor use and dry eye disease in patients with type 2 diabetes (T2D). Design, Setting, and Participants: A retrospective cohort analysis of the largest multi-institutional electronic medical records database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or glucagonlike peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Data analysis was performed from March 1 to May 31, 2022. Propensity scores with inverse probability of treatment weighting were generated to enable homogeneous comparisons between the 2 groups. Exposures: Treatment with SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures: Incident dry eye disease, which was defined by clinical diagnoses, plus the related drug prescription. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for the risk of DED. Results: A total of 10 038 and 1077 T2D patients newly receiving SGLT2 inhibitors (mean [SD] age, 59.5 [12.1] years; 5689 [56.7%] men) or GLP-1 RAs (mean [SD] age, 58.5 [41.2] years; 587 [54.5%] men), respectively, were included in the analysis. The incidence of DED was lower in patients newly receiving SGLT2 inhibitors (9.0 events per 1000 person-years) compared with those receiving GLP-1 RAs (11.5 events per 1000 person-years), yielding a hazard ratio of 0.78 (95% CI, 0.68-0.89). Subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitors in patients with T2D were similar across different age, sex, blood glucose level, and kidney function groups. Results from the sensitivity analyses (including the propensity score-matching approach, on-treatment analyses, and different follow-up periods of 1, 2, and 3 years) were similar to the main analyses. Conclusions and Relevance: The findings of this study suggest that patients with T2D newly receiving SGLT2 inhibitors may have a lower risk for DED compared with those receiving GLP-1 RAs. Prospective studies are needed to analyze these results.

Efficacy of Myopia Control and Distribution of Corneal Epithelial Thickness in Children Treated with Orthokeratology Assessed Using Optical Coherence Tomography.

The association between myopia control efficacy in children treated with orthokeratology and corneal epithelial thickness is still unknown. The aim of this study was to explore the corneal epithelial thickness and its association with axial length changes in children treated with orthokeratology. This retrospective cohort study enrolled children aged from 9 to 15 years who had received orthokeratology for myopia control and had been followed up for at least 1 year. Anterior segment optical coherence tomography was performed to generate wide epithelial thickness maps of the patients. Annual axial length changes were calculated from the axial length at 6 months after the initiation of orthokeratology lens wear and at final measurements. Corneal epithelial thickness data were obtained from 24 sectors and a central 2 mm zone of the wide epithelial thickness map. Associations between annual axial length changes and corneal epithelial thickness for each sector/zone of the wide epithelial thickness map, and orthokeratology treatment data were determined by generalized estimating equations. Finally, a total of 83 eyes of 43 patients (mean age 11.2 years) were included in the analysis. The mean annual axial length change was 0.169 mm; when regressing demographic and ortho-k parameters to mean annual axial length changes, age and target power were both negatively associated with them (ß = -14.43, p = 0.008; ß = -0.26, p = 0.008, respectively). After adjusting for age and target power, the annual axial length changes were positively associated with the corneal epithelium thickness of IT1, I1, SN2, and S2 sectors of the wide epithelial thickness map, and negatively with that of the I3 sector. In conclusion, we identified associations between annual axial length changes and the corneal epithelium thickness of certain sectors in children treated with orthokeratology. This may facilitate the design of orthokeratology lenses with enhanced efficacy for myopia control.

Relationship between Obstructive Sleep Apnea and Central Serous Chorioretinopathy: A Health Insurance Database Study.

PURPOSE: To evaluate the association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). METHODS: A retrospective, cohort, longitudinal study was conducted using the national health insurance database in Taiwan between 1996 and 2013. Patients diagnosed with OSA were enrolled after exclusion, and a control group with similar age, gender, and major systemic co-morbidities were included in a 1:1 ratio by propensity score matching. The primary outcome is the occurrence of CSCR, and patients with CSCR were categorized via severity for further analysis. The percentage of incident CSCR in the OSA group and control groups and the adjusted hazard ratios (aHR) of CSCR were determined by Cox proportional hazard regression. RESULTS: There were 13,084 patients enrolled in both the OSA group and control groups, respectively. The total event of CSCR was 50 (0.4%) in the OSA group and 25 (0.2%) in the control group (P < .001). Moreover, the OSA group has an increased aHR of 1.9 (P = .012) for developing CSCR. In the subgroup analysis, patients with OSA aged from 30 to 39 and 50 to 59 demonstrated higher risk of developing CSCR compared to the control group, and the presence of OSA would lead to a higher incidence of mild CSCR (all P < .05). CONCLUSIONS: OSA patients aged from 30 to 39 and 50 to 59 have a higher risk of developing CSCR, while the severity of CSCR will not be worsen by OSA.

Protective Effect of Pioglitazone on Retinal Ganglion Cells in an Experimental Mouse Model of Ischemic Optic Neuropathy.

The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL/6 mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-γ inhibitor) (1 mg/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 ± 4.9 cells/field) than in group 2 (24.0 ± 11.5 cells/field) and 3 (25.0 ± 7.7 cells/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 ± 2.6 cells/field; group 2: 15.6 ± 3.5 cells/field; and group 3: 14.8 ± 7.5 cells/field) and retinal thinning (group 1: 6.7 ± 5.7 µm; group 2: 12.8 ± 6.1 µm; and group 3: 15.8 ± 5.8 µm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A+ cells were significantly greater in group 2 (2382 ± 140 Brn3A+ cells/mm2, n = 7) than in group 1 (1920 ± 228 Brn3A+ cells/mm2; p = 0.03, n = 4), group 3 (1938 ± 213 Brn3A+ cells/mm2; p = 0.002, n = 4), and group 4 (2138 ± 126 Brn3A+ cells/mm2; p = 0.03, n = 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.

Retinal Vasculitis and Posterior Pole Preretinal Exudates in Exogenous Bacterial Endophthalmitis: Management and Visual Outcomes.

PURPOSE: To investigate the clinical settings and features, management, and visual outcomes of exogenous bacterial endophthalmitis with retinal vasculitis and posterior pole preretinal exudates. METHODS: Retrospectively reviewed records for 40 eyes of 40 patients. RESULTS: Retinal vasculitis was identified with focal type in eight eyes and diffuse type in 32 eyes. Posterior pole preretinal exudates were identified with discrete type in 23 eyes and condensed type in 17 eyes. Final VA was 20/200 or better in 23 of 40 eyes (57.5%). Multivariate linear regression revealed that condensed posterior pole preretinal exudates (P =.005) and ocular hypertension (P =.012) were the significant independent factors for poor visual outcomes. CONCLUSIONS: Condensed posterior pole preretinal exudates and ocular hypertension are critical prognostic factors for poor visual outcomes.

Impact of bisphosphonates and comorbidities on initial hip fracture prognosis.

The aim of this study is to investigate the impact of bisphosphonate treatment on the prognosis of patients with initial hip fracture. Patients aged fifty years and older with initial hip fracture were identified from the Taiwan National Health Insurance Research Database between 2002 and 2011. A multi-state model was established to evaluate the transition between "first to second hip fracture", "first hip fracture to death", and "second hip fracture to death". Transition probability and cumulative hazards were used to compare the prognosis of initial hip fracture in a bisphosphonate treated cohort versus non-treated cohort. In addition, Deyo-Charlson comorbidities, both vertebral and non-vertebral fractures, and cataracts were also included for analysis. After 10-year follow-up, there is decreased cumulative transition probability for both second hip fracture and mortality after both first and second hip fracture in the bisphosphonate treated cohort. Multivariable, transition-specific time-dependent Cox model revealed that bisphosphonate treatment significantly reduced risk for second hip fracture in the first 5 years of the treatment (HR 0.88; 95% CI 0.79-0.99; P: 0.034), first hip fracture mortality (HR 0.88; 95% CI 0.83-0.93; P < 0.001), and second hip fracture mortality in the first 2 years of the treatment (HR 0.78; 95% CI 0.65-0.95; P = 0.011). Female sex, both vertebral and non-vertebral fractures, cataracts, dementia in the first 2 years, and DM with complication were all significantly associated with risk of a second hip fracture. Cerebrovascular disease and hemiplegia comorbidities had less risk of a second hip fracture. The risk of mortality after both first and second hip fracture was significantly associated with congestive heart failure, renal disease, myocardial infarction, and moderate to severe liver disease. Our study demonstrated that bisphosphonate treatment and strict management of comorbidities after the initial hip fracture significantly decrease the risk for a second hip fracture and mortality.

Investigation of Possible Correlation Between Retinal Neurovascular Biomarkers and Early Cognitive Impairment in Patients With Chronic Kidney Disease.

Purpose: To investigate the association between retinal neurovascular biomarkers and early cognitive impairment among patients with chronic kidney disease (CKD). Methods: Patients with CKD stage ≥3 were evaluated using the standardized Mini-Mental State Examination (MMSE). Patients were classified as having a low (<24), middle (24 to 27), and high (>27) MMSE level. Retinal nerve fiber layer thickness, ganglion cell complex (GCC) thickness, GCC global loss volume, and GCC focal loss volume were measured using optical coherence tomography (OCT). Superficial vascular plexus vessel density, deep vascular plexus vessel density (DVP-VD), and size of the foveal avascular zone were obtained by OCT angiography. Results: The study enrolled 177 patients with a mean ± SD age of 64.7 ± 6.6 years. The mean ± SD MMSE score was 27.25 ± 2.30. Thirteen, 65, and 99 patients were classified as having a low, middle, and high MMSE level, respectively. The patients with a high MMSE level were younger, had more years of education, had less severe CKD, and had higher DVP-VD than patients with a low MMSE level. The multivariable regression revealed that age (coefficient, 0.294; 95% confidence interval [CI], 0.195-0.393; P = 0.041), years of education (coefficient, 0.294; 95% CI, 0.195-0.393; P < 0.001), estimated glomerular filtration rate (coefficient, 0.019; 95% CI, 0.004-0.035; P = 0.016), and DVP-VD (coefficient, 0.109; 95% CI, 0.007-0.212; P = 0.037) were independent factors associated with MMSE score. Conclusions: Retinal DVP-VD was associated with early cognitive impairment among patients with CKD. Translational Relevance: DVP-VD measured by OCT angiography may facilitate early detection of cognitive impairment.