Management of Corneal Haze After Photorefractive Keratectomy.

Photorefractive keratectomy (PRK) is a safe and popular corneal surgery performed worldwide. Nevertheless, there is potential risk of corneal haze development after surgery. Proper management of post PRK haze is important for good visual outcome. We performed a comprehensive review of the literature on the various risk factors and treatments for PRK haze, searching the PubMed, Google Scholar, SCOPUS, ScienceDirect, and Embase databases using relevant search terms. All articles in English from August 1989 through April 2023 were reviewed for this study, among which 102 articles were chosen to be included in the study. Depending on the characteristics of and examination findings on post PRK haze, different management options may be preferred. In the proposed framework, management of PRK haze should include a full workup that includes patient's subjective complaints and loss of vision as well as visual acuity, biomicroscopy, anterior segment optical coherence tomography, epithelial mapping, and Scheimpflug densitometry. Topical steroid treatment for haze should be stratified based on early- or late-onset haze. Mechanical debridement or superficial phototherapeutic keratectomy (PTK) may be used to treat superficial corneal haze. Deep PTK and/or PRK can be used to treat deep corneal haze. Mitomycin-C and topical steroids are prophylactic post-surgery agents to prevent recurrence of haze.

A Literature Review of the Incidence, Management, and Prognosis of Corneal Epithelial-Related Complications After Laser-Assisted In Situ Keratomileusis (LASIK), Photorefractive Keratectomy (PRK), and Small Incision Lenticule Extraction (SMILE).

Our purpose is to provide a comprehensive investigation into the incidence, treatment modalities, and visual prognosis of epithelial-related complications in corneal refractive surgeries, including laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE). A systematic search of multiple databases was conducted by two independent examiners using various search terms related to epithelial-related complications and corneal refractive surgeries. A total of 91 research articles were included, encompassing a sample size of 66,751 eyes across the three types of surgeries. The average incidence of epithelial-related complications varied across the different types of corneal refractive surgeries. LASIK had an average incidence of 4.9% for epithelial defects, while PRK and SMILE had lower rates of 3.3% and 3.9%, respectively. Our findings indicate that SMILE has a lower incidence of epithelial defects compared to LASIK, potentially due to the less invasive nature of lenticule incision in SMILE. Visual prognosis after epithelial complications (EC) is generally favorable, with various supportive care and surgical interventions leading to significant improvements in postoperative visual acuity and full recovery. Understanding the incidence rates and management approaches for epithelial-related complications can guide clinicians in enhancing patient safety, refining surgical techniques, and optimizing postoperative outcomes in corneal refractive surgeries.

Assessment of Pupil Size and Angle Kappa in Refractive Surgery: A Population-Based Epidemiological Study in Predominantly American Caucasians.

Purpose This retrospective study aims to establish normative values for pupil size, angle kappa, higher-order aberration, and astigmatism type in a largely Caucasian population in Utah, United States, utilizing the NIDEK OPD-Scan III system (Gamagori, Japan). Methods This study included 716 patients (1432 eyes) grouped based on spherical equivalence and age. Measurements were conducted under mesopic and photopic conditions. Statistical analysis involved Pearson's correlation and linear regression using the generalized estimating equation. NIDEK OPD-Scan III measured mesopic and photopic pupil size and angle kappa. The subjects were then grouped based on their spherical equivalence in diopters (D) and age in decades. The spherical equivalence groups were defined: >-6 D, -5.99 to -3 D, -2.99 to -0.25 D, -0.24 to 0.24 D, and >0.25 D (range 0.25-5.75 D). The higher-order aberration groups were based on the reason for the visit: laser-assisted in situ keratomileusis, photorefractive keratectomy, and small incision lenticule extraction as one group; cataract evaluation; and keratoconus. Astigmatism measurements were grouped into with-the-rule (WRT), against-the-rule (ATR), and oblique astigmatism, with further subgrouping into a young cohort (20-40 years) and an old cohort (>65 years).  Results Among 716 participants, 49.2% were men; the mean age was 42.1±15.5 (range 7-88 years). The average spherical equivalence for myopia eyes was -3.28±2.34 D, and 1.51±1.46 D for hyperopia eyes. The mean mesopic pupil size was 5.68 ± 1.09 mm; the photopic pupil size was 4.65±1.09 mm. Pearson's correlation coefficient for mesopic pupil size versus age was -0.551, and -0.42 for photopic pupil (p < 0.001); sphere vs mesopic pupil size was -0.200, and -0.173 for photopic pupil (p < 0.001). The regression analysis for mesopic pupil size versus age revealed a 0.39 mm decrease in average pupil size per decade increase in age, and 0.25 mm decrease per decade for photopic pupil. The regression analysis for mesopic pupil size versus sphere revealed a 0.22 mm decrease in average pupil size per 3D increase in sphere, and a 0.16 mm decrease 3 D increase in sphere for the photopic pupil. The mean mesopic angle kappa was 0.33 ± 0.15 mm; photopic angle kappa was 0.31±0.15 mm. Pearson's correlation coefficient for mesopic angle kappa vs spherical equivalence was 0.32, and 0.296 for photopic angle kappa (p <0.001 for both). Regression analysis for mesopic angle kappa vs spherical equivalence demonstrated a 0.051 mm increase in angle kappa per 3 D increase in spherical equivalence, and a 0.048 mm increase for photopic angle kappa (p < 0.001 for both). Among the higher-order aberration groups, the keratoconus group exhibited the highest levels. In terms of astigmatism type, WRT astigmatism was the most common in the young cohort, while ATR astigmatism was most prevalent in the older cohort. Conclusions The results of this study reveal significant associations between pupil size and increasing age, as well as between pupil size and increasingly positive refractive errors. These findings hold particular clinical relevance to older patients and individuals with hyperopia, as they undergo photoablative corneal refractive surgery or multifocal intraocular lens implantation. Understanding the established normative values for pupil size, angle kappa, higher-order aberration, and astigmatism type can aid clinicians in making more informed decisions and improving patient outcomes.

Unilateral upper cervical cord infarction in Opalski's syndrome caused by spontaneous vertebral artery dissection.

We report a case of a man with concurrent unilateral upper cervical cord infarction in Opalski's syndrome due to spontaneous vertebral artery dissection.

Comparison of Corneal Power Difference Maps with Achieved Myopic Correction Using Scheimpflug Tomography After LASIK, PRK, and SMILE.

Purpose: To compare corneal power difference maps (∆maps) obtained from the Pentacam in patients with 1 year follow-up after LASIK, PRK, and SMILE with further stratification to low, moderate, and high myopia. Patients and methods: This retrospective study was comprised of patients who had preoperative and 1-year postoperative power maps that were obtained-front sagittal (SagF), refractive power (RP), true net power (TNP), and total corneal refractive power (TCRP)-for evaluation. Measurements were recorded and compared at the 4mm, 5mm and 6mm pupil and apex zones. Comparisons were made between each specific power ∆map and the surgically induced refractive change (SIRC). Further analysis of the ∆maps was performed based on degree of myopia (high, moderate, and low). Correlation and agreement were also assessed with regression and limits of agreement (LoA). Results: There were 172 eyes in the LASIK group, 187 eyes in the PRK group, and 46 eyes in the SMILE group. In the LASIK group, TNP ∆map at 5mm pupil zone had the least absolute mean difference with SIRC (0.007 ± 0.42D). In the PRK group, TNP ∆map at 5mm apex zone was most accurate compared to SIRC (0.066 ± 0.45D). In the SMILE group, TCRP ∆map at 4mm apex zone had the closest absolute value when compared to SIRC (0.011 ± 0.50D). There was good correlation and agreement for all three surgery groups, LASIK: r = 0.975, LoA -0.83D to +0.83D, PRK: r = 0.96, LoA -0.83D and +0.95D, and SMILE: r = 0.922, LoA -0.97 D to +0.99D. Conclusion: TNP ∆maps most accurately measured corneal power in the LASIK and PRK groups while TCRP ∆maps were most accurate in the SMILE group. The degree of myopia may change which ∆map is most accurate.

Bioinformatics exploration of potential common therapeutic targets for systemic and pulmonary arterial hypertension-induced myocardial hypertrophy.

Systemic and pulmonary arterial hypertension (PAH) can induce left and right ventricular hypertrophy, respectively, but common therapeutic targets for both left and right hypertrophy are limited. In this study, we attempt to explore potential common therapeutic targets and screen out potential target drugs for further study. Cardiac mRNA expression profiles in mice with transverse aortic constriction (TAC) and pulmonary arterial constriction (PAC) are obtained from online databases. After bioinformatics analyses, we generate TAC and PAC mouse models to validate the phenotypes of cardiac remodelling as well as the identified hub genes. Bioinformatics analyses show that there are 214 independent differentially expressed genes (DEGs) in GSE136308 (TAC related) and 2607 independent DEGs in GSE30922 (PAC related), while 547 shared DEGs are associated with the function of the extracellular matrix (ECM) or involved in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interactions, and ECM-receptor interactions. We identifyd Fn1, Il6, Col1a1, Igf1, Col1a2, Timp1, Col3a1, Cd44, Ctgf and Postn as hub genes of the shared DEGs, and most of them are associated with myocardial fibrosis. Those hub genes and phenotypes of cardiac remodelling are validated in our TAC and PAC mouse models. Furthermore, we identify dehydroisoandrosterone (DHEA), iloprost and 4,5-dianilinophthalimide (DAPH) as potential therapeutic drugs targeting both left and right ventricular hypertrophy and validate the effect of DHEA. These findings suggest that DHEA could be an effective drug for pressure overload-induced left or right ventricular hypertrophy by regulating the shared hub differentially expressed genes associated with fibrosis.

Diagnostic performance of angiography-derived fractional flow reserve analysis based on bifurcation fractal law for assessing hemodynamic significance of coronary stenosis.

OBJECTIVES: Blood flow into the side branch affects the calculation of coronary angiography-derived fractional flow reserve (FFR), called Angio-FFR. Neglecting or improperly compensating for the side branch flow may decrease the diagnostic accuracy of Angio-FFR. This study aims to evaluate the diagnostic accuracy of a novel Angio-FFR analysis that considers the side branch flow based on the bifurcation fractal law. METHODS: A one-dimensional reduced-order model based on the vessel segment was used to perform Angio-FFR analysis. The main epicardial coronary artery was divided into several segments according to the bifurcation nodes. Side branch flow was quantified using the bifurcation fractal law to correct the blood flow in each vessel segment. In order to verify the diagnostic performance of our Angio-FFR analysis, two other computational methods were taken as control groups: (i) FFR_s: FFR calculated by delineating the coronary artery tree to consider side branch flow, (ii) FFR_n: FFR calculated by just delineating the main epicardial coronary artery and neglecting the side branch flow. RESULTS: The analysis of 159 vessels from 119 patients showed that our Anio-FFR calculation method had comparable diagnostic accuracy to FFR_s and provided significantly higher diagnostic accuracy than that of FFR_n. In addition, using invasive FFR as a reference, the Pearson correlation coefficients of Angio-FFR and FFRs were 0.92 and 0.91, respectively, while that of FFR_n was only 0.85. CONCLUSIONS: Our Angio-FFR analysis has demonstrated good diagnostic performance in assessing the hemodynamic significance of coronary stenosis by using the bifurcation fractal law to compensate for side branch flow. CLINICAL RELEVANCE STATEMENT: Bifurcation fractal law can be used to compensate for side branch flow during the Angio-FFR calculation of the main epicardial vessel. Compensating for side branch flow can improve the ability of Angio-FFR to diagnose stenosis functional severity. KEY POINTS: • The bifurcation fractal law could accurately estimate the blood flow from the proximal main vessel into the main branch, thus compensating for the side branch flow. • Angiography-derived FFR based on the bifurcation fractal law is feasible to evaluate the target diseased coronary artery without delineating the side branch.

Regulating Zn Ion Desolvation and Deposition Chemistry Toward Durable and Fast Rechargeable Zn Metal Batteries.

The high Zn ion desolvation energy, sluggish Zn deposition kinetics, and top Zn plating pattern are the key challenges toward practical Zn anodes. Herein, these key issues are addressed by introducing zinc pyrovanadate (ZVO) as a solid zinc-ion conductor interface to induce smooth and fast Zn deposition underneath the layer. Electrochemical studies, computational analysis, and in situ observations reveal the boosted desolvation and deposition kinetics, and uniformity by ZVO interface. In addition, the anti-corrosion ability of Zn anodes is improved, resulting in high Zn stripping/plating reversibility. Consequently, the ZVO layer renders fast rechargeability and durable life in both Zn symmetric cells (1050 h at 10 mA cm-2 , 1 mAh cm-2 ) and Zn/V2 O5 batteries (79.1% capacity retention after 1000 cycles at 2 A g-1 ) with low electrode polarization. This work provides insights into the design of solid zinc-ion conductor interface to enhance the interface stability and kinetics of Zn metal anodes.

Revascularization of chronic total occlusion coronary artery and cardiac regeneration.

Coronary chronic total occlusion (CTO) contributes to the progression of heart failure in patients with ischemic cardiomyopathy. Randomized controlled trials demonstrated that percutaneous coronary intervention (PCI) for CTO significantly improves angina symptoms and quality of life but fails to reduce clinical events compared with optimal medical therapy. Even so, intervening physicians strongly support CTO-PCI. Cardiac regeneration therapy after CTO-PCI should be a promising approach to improving the prognosis of ischemic cardiomyopathy. However, the relationship between CTO revascularization and cardiac regeneration has rarely been studied, and experimental studies on cardiac regeneration usually employ rodent models with permanent ligation of the coronary artery rather than reopening of the occlusive artery. Limited early-stage clinical trials demonstrated that cell therapy for cardiac regeneration in ischemic cardiomyopathy reduces scar size, reverses cardiac remodeling, and promotes angiogenesis. This review focuses on the status quo of CTO-PCI in ischemic cardiomyopathy and the clinical prospect of cardiac regeneration in this setting.

Images of the month 1: Recurrent ischaemic stroke secondary to Eagle syndrome.

We present a case of a man who experienced recurrent ischaemic stroke secondary to an elongated styloid process compressing the cervical carotid artery.

Clinical Presentation and Outcomes of Acute Disseminated Encephalomyelitis in Adults Worldwide: Systematic Review and Meta-Analysis.

Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disorder that is often misdiagnosed. To improve early diagnosis, we performed a systematic review and meta-analysis of clinical features, outcomes for ADEM in adults. Methods: The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies reporting the clinical features of adults with ADEM between January 1990 and May 2021. A random-effects meta-analysis model was used to pool data on clinical features and functional outcomes. Results: Twelve studies examining 437 adults with ADEM met the inclusion criteria. Overall, the clinical features and diagnostic findings observed in more than two-thirds of the patients were white matter lesions [87.1%, 95% confidence interval (CI)=75-95.6], polyfocal onset (80.5%, 95% CI=50.5-98.9) and pyramidal signs (68.7%, 95% CI =40.0-91.9). The mortality rate was 7.8% (95% CI = 3.3-13.5), and the risk of residual deficits was 47.5% (95% CI = 31.8-63.4). Conclusions: Adults with ADEM had worse outcomes than children. Clinicians should maintain high clinical suspicion for patients presenting with certain clinical features and diagnostic findings.

Promoting Construction Industrialisation with Policy Interventions: A Holistic Review of Published Policy Literature.

By adopting the concept of 'factory assembly followed by onsite installation,' construction industrialisation (CI) plays an increasingly important role in sustainable urban development. CI can enhance construction quality and efficiency while reducing environmental impacts. To promote the CI, several policy interventions have been developed and implemented in different countries and regions. This study reviews the global CI promoting regulations and policies to provide a comprehensive insight into its interrelationship and development tendency. The research selects 105 publications related to practical CI policy from widely utilised databases (i.e., Web of Science and Scopus). Based on the annual publication trend analysis, geospatial distribution, and citation analysis, seven interrelated critical CI policy formulation themes are identified and examined: regulatory policies, standardised policies, promotional policies, urban design and planning policies, technological policies, managerial and educational policies, and sustainability policies. In addition, internal correlations and mutual influence among these seven classified policies are explored and discussed, which helps scholars enhance their grasp of current CI policy research and guide future research. This review provides the research community and industrial practitioners with a comprehensive understanding of various CI-promoting policies and a roadmap to CI-promoting policy development and evaluation.

Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity.

It has been reported that growth differentiation factor 11 (GDF11) protects against myocardial ischemia/reperfusion (IR) injury, but the underlying mechanisms have not been fully clarified. Considering that GDF11 plays a role in the aging/rejuvenation process and that aging is associated with telomere shortening and cardiac dysfunction, we hypothesized that GDF11 might protect against IR injury by activating telomerase. Human plasma GDF11 levels were significantly lower in acute coronary syndrome patients than in chronic coronary syndrome patients. IR mice with myocardial overexpression GDF11 (oe-GDF11) exhibited a significantly smaller myocardial infarct size, less cardiac remodeling and dysfunction, fewer apoptotic cardiomyocytes, higher telomerase activity, longer telomeres, and higher ATP generation than IR mice treated with an adenovirus carrying a negative control plasmid. Furthermore, mitochondrial biogenesis-related proteins and some antiapoptotic proteins were significantly upregulated by oe-GDF11. These cardioprotective effects of oe-GDF11 were significantly antagonized by BIBR1532, a specific telomerase inhibitor. Similar effects of oe-GDF11 on apoptosis and mitochondrial energy biogenesis were observed in cultured neonatal rat cardiomyocytes, whereas GDF11 silencing elicited the opposite effects to oe-GDF11 in mice. We concluded that telomerase activation by GDF11 contributes to the alleviation of myocardial IR injury through enhancing mitochondrial biogenesis and suppressing cardiomyocyte apoptosis.

Characterizing a long-term chronic heart failure model by transcriptomic alterations and monitoring of cardiac remodeling.

The long-term characteristics of transcriptomic alterations and cardiac remodeling in chronic heart failure (CHF) induced by myocardial infarction (MI) in mice are not well elucidated. This study aimed to reveal the dynamic changes in the transcriptome and cardiac remodeling in post-MI mice over a long time period. Monitoring C57BL/6 mice with MI for 8 months showed that approximately 44% of mice died of cardiac rupture in the first 2 weeks and others survived to 8 months with left ventricular (LV) aneurysm. The transcriptomic profiling analysis of cardiac tissues showed that the Integrin and WNT pathways were activated at 8 months after MI while the metabolism-related pathways were inversely inhibited. Subsequent differential analysis at 1 and 8 months post-MI revealed significant enrichments in biological processes, including consistent regulation of metabolism-related pathways. Moreover, echocardiographic monitoring showed a progressive increase in LV dimensions and a decrease in the LV fractional shortening during the first 4 weeks, and these parameters progressed at a lower rate till 8 months. A similar trend was found in the invasive LV hemodynamics, cardiac morphological and histological analyses. These results suggested that mouse MI model is ideal for long-term studies, and transcriptomic findings may provide new CHF therapeutic targets.

Antihypertrophic Memory After Regression of Exercise-Induced Physiological Myocardial Hypertrophy Is Mediated by the Long Noncoding RNA Mhrt779.

BACKGROUND: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5 to 6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. METHODS: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning [EHP] group) and sedentary mice (control group) then underwent transverse aortic constriction or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated with echocardiography, invasive left ventricular hemodynamic measurement, and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay, and comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot were used to investigate the role of Mhrt779 involved in the antihypertrophic effect induced by EHP. RESULTS: At 1 and 4 weeks after transverse aortic constriction, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after transverse aortic constriction, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction revealed that the long noncoding myosin heavy chain-associated RNA transcript Mhrt779 was one of the markedly upregulated lncRNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with transverse aortic constriction and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. Using chromatin immunoprecipitation assay and quantitative polymerase chain reaction, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779. Comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot showed that Mhrt779 can bind SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (Brg1) to inhibit the activation of the histone deacetylase 2 (Hdac2)/phosphorylated serine/threonine kinase (Akt)/phosphorylated glycogen synthase kinase 3ß(p-GSK3ß) pathway induced by pressure overload. CONCLUSIONS: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779/Brg1/Hdac2/p-Akt/p-GSK3ß.

Excessive fibroblast growth factor 23 promotes renal fibrosis in mice with type 2 cardiorenal syndrome.

Cardiorenal syndrome (CRS) has a high mortality, but its pathogenesis remains elusive. Fibroblast growth factor 23 (FGF23) is increased in both renal dysfunction and cardiac dysfunction, and FGF receptor 4 (FGFR4) has been identified as a receptor for FGF23. Deficiency of FGF23 causes growth retardation and shortens the lifespan, but it is unclear whether excess FGF23 is detrimental in CRS. This study sought to investigate whether FGF23 plays an important role in CRS-induced renal fibrosis. A mouse model of CRS was created by surgical myocardial infarction for 12 weeks. CRS mice showed a significant increase of circulatory and renal FGF23 protein levels, as well as an upregulation of p-GSK, active-ß-catenin, TGF-ß, collagen I and vimentin, a downregulation of renal Klotho expression and induction of cardiorenal dysfunction and cardiorenal fibrosis. These changes were enhanced by cardiac overexpression of FGF23 and attenuated by FGF receptor blocker PD173074 or ß-catenin blocker IGC001. In fibroblasts (NRK-49F), expression of FGFR4 rather than Klotho was detected. Recombinant FGF23 upregulated the expression of p-GSK, active-ß-catenin, TGF-ß, collagen I and vimentin proteins. These changes were attenuated by FGFR4 blockade with BLU9931 or ß-catenin blockade with IGC001. We concluded that FGF23 promotes CRS-induced renal fibrosis mediated by partly activating FGFR4/ß-catenin signaling pathway.

A virtual COVID-19 ophthalmology rotation.

The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.