The association of pre-photorefractive keratectomy Schirmer-1 test value with postoperative corneal epithelial thickness, ocular surface discomfort, and visual acuity

ABSTRACT Purpose: To investigate the association of pre--photorefractive keratectomy Schirmer-1 test value with post--photorefractive keratectomy central corneal epithelial thickness, ocular surface disease index score, and uncorrected distance visual acuity. Methods: Patients were categorized according to preoperative Schirmer-1 value: the normal Schirmer Group (n=54; Schirmer-1 test value, >10 mm) and the low Schirmer Group (n=52; Schirmer-1 test value, between 6 and 10 mm). We analyzed ablation depth, visual acuity, result of Schirmer-1 test (with anesthesia), tear film break-up time, ocular surface disease index score, central corneal epithelial thickness, and spherical equivalent refraction. Results: We found significant differences between the groups in Schirmer-1 test value, tear film break-up time, and ocular surface disease index score, both preoperatively and postoperatively (p<0.001). The preoperative central corneal epithelial thicknesses of the two groups were similar (p>0.05). After photorefractive keratectomy, the Schirmer-1 test value and spherical equivalent refraction decreased in both groups (p<0.05), and ocular surface disease index scores and central corneal epithelial thickness values increased in the low Schirmer Group (p<0.001) but not in the normal Schirmer Group (p>0.05). The postoperative central corneal epithelial thicknesses of the low Schirmer Group were significantly higher than those of the normal Schirmer Group (p<0.001). Postoperative uncorrected distance visual acuity did not differ significantly between the two groups (p>0.05). Conclusions: In patients with low Schirmer-1 test values before photorefractive keratectomy, the corneal epithelium thickened and ocular surface complaints increased during the postoperative period. However, changes in the corneal epithelium did not affect the postoperative uncorrected distance visual acuity. To reduce postoperative problems on the ocular surface in these patients, we recommend that dry eye be treated before photorefractive keratectomy.

Pigment deposits in the retrolental space of Berger: a rare feature of pigment dispersion syndrome? / Depósitos de pigmento no espaço de Berger: uma característica rara de síndrome de dispersão pigmentar?

ABSTRACT Pigment dispersion syndrome is associated with clinical features such as Krukenberg's spindles, trabecular pigmentation, Scheie's stripe and Zentmayer's ring. Another less common feature of this syndrome is retrolental pigment deposits due to anterior hyaloid detachment or a defect in the Wieger's ligament. We present two cases of pigment deposits on the posterior lens capsule. In both cases, there is bilateral dispersion of pigment throughout the anterior segment. The retrolental deposits are unilateral in the first case and bilateral in the second. Both patients report a history of ocular trauma. This is a possible important clinical sign of pigment dispersion syndrome, rarely described.

RESUMO A síndrome de dispersão pigmentar associa-se a sinais clínicos característicos como fuso de Krukenberg, hiperpigmentação da malha trabecular, linha de Scheie e anel de Zentmeyer. Um sinal menos comum dessa síndrome é o depósito de pigmento posterior ao cristalino, que ocorre por um descolamento da hialoide anterior ou um defeito no ligamento de Wieger. Apresentamos dois casos de depósitos de pigmento posterior à cápsula posterior do cristalino. Em ambos os casos, existia dispersão bilateral de pigmento por todo o segmento anterior. No primeiro caso, os depósitos eram unilaterais e, no segundo, estavam presentes em ambos os olhos. Este pode corresponder a um sinal potencialmente importante da síndrome de dispersão pigmentar, raramente descrito.

Research progress on the mechanism of subthreshold micropulse laser photocoagulation in central serous chorioretinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Central serous chorioretinopathy(CSC)is a common macular degeneration that primarily affects young patients. While the disease may resolve on its own to some extent, delayed or inadequate treatment can result in recurrence and progression to chronic CSC. This can lead to complications such as retinal pigment epithelium(RPE)atrophy and choroidal neovascularization, ultimately causing irreversible damage to central vision. Subthreshold micropulse laser photocoagulation(SMLP)is a type of laser therapy that differs from traditional lasers in that it does not cause damage or thermal injury to RPE cells and photoreceptors. SMLP has become widely used in clinical treatment of CSC due to its effectiveness, safety, and reproducibility, particularly in cases where verteporfin is not available in photodynamic therapy(PDT). The purpose of this review is to explain the mechanism of SMLP in CSC and summarize the effector cells, cytokines, and mechanisms of action involved in its treatment. This will provide a theoretical basis for promoting and rationalizing the use of SMLP in clinical practice.

Observation of corneal cell in diabetic patients using in vivo confocal microscopy / 国际眼科杂志(Guoji Yanke Zazhi)

In vivo confocal microscopy of the cornea is a non-invasive, rapid, and comprehensive technique for real-time, dynamic observation of all layers of the cornea. Confocal microscopy allows the examination of the morphology and cell density in the different layers of the cornea through direct visualization. With the increasing prevalence of diabetes, ocular complications have become common and have garnered more interest and in-depth research from clinical and scientific communities. This paper provides a comprehensive review of research progress made using in vivo confocal microscopy to observe various layers of cornea tissue in diabetic patients.

Research progress of microRNA in oxidative stress and lipid metabolism of non-exudative age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone / Uma variante bolhosa da coriorretinopatia serosa central tratada com espironolactona oral

ABSTRACT We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

RESUMO Relatamos o caso de um homem de 39 anos apresentando perda visual no olho direito há seis semanas. A melhor acuidade visual corrigida foi conta-dedos no olho direito e 20/30 no esquerdo. A fundoscopia demonstrou descolamento de retina direito inferiormente com extensão à fóvea e descolamento macular seroso à esquerda. Após estudos de imagem multimodal, o paciente foi diagnosticado com uma variante bolhosa de coriorretinopatia serosa central e tratado com espironolactona oral associada à fotocoagulação a laser adjuvante. As alterações retinianas resolveram após seis meses. A acuidade visual final foi 20/20 em ambos os olhos.

Histological Techniques for the Study of the Dentogingival Junction: A Scoping Review Using the Anatomical Quality Assurance Checklist (AQUA) / Técnicas Histológicas para el Estudio de la Unión Dentogingival: Una Revisión de Alcance Utilizando el Anatomical Quality Assurance Checklist (AQUA)

SUMMARY: The dentogingival junction (DGJ) is an adaptation of the oral mucosa composed of epithelial and connective tissues intimately related with the mineralised tissues of the tooth. The histological evidence available is mainly based on studies in animals, separate evaluations of hard and soft tissues, and studies using conventional histological techniques that eliminate the enamel from preparations. The aim of this study was to carry out a review of the existing evidence on histological techniques available for study of the tooth and periodontium in conjunction in humans. A scoping review was carried out of the available literature referring to study of the tooth and the periodontium in conjunction in humans, in the Web of Science (WoS), EMBASE, Scopus and SciELO databases, using the terms "Histological Techniques"[Mesh]) and "Epithelial Attachment"[Mesh]. One hundred and fifty-nine articles were found, of which 54 were selected for full- text reading. Ten were finally included in the qualitative synthesis, and we applied the Anatomical Quality Assurance (AQUA) checklist for analysis the methodological quality of the selected articles. The results showed that the only articles with a low risk of bias in all five domains according to the AQUA criteria corresponded to Silva et al. (2011) and Agustín-Panadero et al. (2020). Finally, we conclude that the quality of the histological sections to observe tissues that simultaneously contain the tooth and the periodontium, is conditioned by the selected technique and by the care required in certain specific tasks during the histological processing of the samples.

La unión dentogingival (DGJ) es una adaptación de la mucosa oral compuesta por tejidos epitelial y conectivo íntimamente relacionados con los tejidos mineralizados del diente. La evidencia histológica disponible se basa principalmente en estudios en animales, evaluaciones separadas de tejidos duros y blandos y estudios utilizando técnicas histológicas convencionales que eliminan el esmalte de las preparaciones. El objetivo de este estudio fue realizar una revisión de la evidencia existente sobre las técnicas histológicas disponibles para el estudio del diente y el periodonto en conjunto en humanos. Se realizó un scoping review de la literatura disponible referente al estudio del diente y el periodonto en conjunto en humanos, en las bases de datos Web of Science (WoS), EMBASE, Scopus y SciELO, utilizando los términos "Histological Techniques"[Mesh]) y "Epithelial Attachment"[Mesh]. Se encontraron 159 artículos, de los cuales 54 fueron seleccionados para lectura de texto completo. Diez fueron finalmente incluidos en la síntesis cualitativa, y se aplicó la lista de verificación Anatómica Quality Assurance (AQUA) para el análisis de la calidad metodológica de los artículos seleccionados. Los resultados mostraron que los únicos artículos con bajo riesgo de sesgo en los cinco dominios según los criterios AQUA correspondían a Silva et al. (2011) y Agustín-Panadero et al. (2020). Finalmente, concluimos que la calidad de los cortes histológicos para observar los tejidos que contienen simultáneamente el diente y el periodonto, está condicionada por la técnica seleccionada y por el cuidado requerido en ciertas tareas específicas durante el procesamiento histológico de las muestras.

Clinical outcomes of epithelial ingrowth following laser in situ keratomileusis with mechanical debridement and compressed heating air flow: a case series / Resultado visual do tratamento do crescimento epitelial após laser in situ ceratomileuse através da remoção mecânica e aplicação de ar comprimido aquecido: série de casos

ABSTRACT Purpose: To describe the clinical outcomes of manual scraping of epithelial ingrowth followed by compressed heating air flow after laser in situ keratomileusis (LASIK). Methods: We underwent a retrospective, noncomparative, and interventional case series. Twenty eyes of 17 patients were included in this study. Each patient with a history of LASIK underwent epithelial removal with mechanical debridement followed by compressed heating air flow. Our primary outcome was the recurrence of epithelial ingrowth after 3 months of follow-up, while our secondary outcomes were uncorrected distance visual acuity, corrected distance visual acuity, and complications after surgery. Results: Ten patients (58.8%) were male, and eight eyes of seven (41.2%) patients underwent primary LASIK surgery, while12 eyes of 10 patients had flap-lift retreatment LASIK; sixteen eyes (80.0%) underwent mechanical microkeratome LASIK and four (20.0%) underwent femtosecond laser-assisted LASIK. Mean age at surgical removal of epithelial ingrowth was 37.0 years ± 9.3 years (range 24 to 55 years). There was recurrence of ingrowth in two eyes (10%) after 3 months of follow-up. The mean corrected distance visual acuity of patients before surgery was 0.07 ± 0.09 logMAR, and after the last follow-up was 0.02 ± 0.04 logMAR (p=0.06). The odds ratio of presenting with epithelial ingrowth after LASIK enhancement compared to primary LASIK was 29.41. Conclusion: Manual scraping followed by compressed heating air flow is a safe and effective treatment of clinically significant epithelial ingrowth after LASIK. At the last follow-up, no eye lost any line in corrected distance visual acuity.

RESUMO Objetivo: Descrever os resultados clínicos do tratamento do crescimento epitelial através da técnica de remoção manual seguido da utilização de um compressor de ar comprimido aquecido após a cirurgia de laser in situ keratomileusis (LASIK). Métodos: Vinte olhos de 17 pacientes foram incluídos no estudo. Cada paciente havia sido submetido a cirurgia de LASIK com presença de crescimento epitelial e foi submetido a tratamento cirúrgico para sua retirada. O objetivo primário foi identificar a presença de crescimento epitelial recorrente ao final de 3 meses de seguimento. Os objetivos secundários foram as medidas de acuidade visual sem correção, acuidade visual com correção, e complicações pós-operatórias. Resultados: Dez pacientes (58,8%) eram homens e 7 mulheres. Oito olhos de sete (41,2%) pacientes apresentavam cirurgia de LASIK primária e 12 olhos de 10 pacientes tinham cirurgia de LASIK com retratamento; dezesseis olhos (80%) utilizaram microcerátomo manual e quatro (20%) laser de femtosegundo. A média de idade no momento da cirurgia de remoção do epitélio era de 37,0 anos ± 9,3 (DP) (variando de 24 a 55 anos). Ocorreu recidiva do crescimento epithelial em dois olhos (10%) após 3 meses de seguimento. A acuidade visual sem correção antes da cirurgia era de 0,07 ± 0,09 logMAR, e após a cirurgia passou para 0,02 ± 0,04 logMAR (p=0,06). A chance (odds ration) de aparecimento do crescimento epithelial após uma reoperação de LASIK é 29,41 vezes maior do que no LASIK primário. Conclusão: A técnica de remoção epitelial manual seguida da utilização de ar comprimido aquecido é segura e efetiva no tratamento do crescimento epitelial após LASIK. Ao final do último acompanhamento, nenhum olho apresentou perda de linhas de visão.

Ca-125: A Useful Marker to Distinguish Pulmonary Tuberculosis from Bacterial Pneumonia

Background: Ca-125 is a large molecular-weight glycoprotein synthesized by different cells originating from the coelomic epithelium. Although classically it has been used to monitor the course of ovarian epithelial cancer, there are other established circumstances associated with high serum Ca -125 levels and pulmonary tuberculosis is one of them. Diagnosing pulmonary tuberculosis, which is not bacteriologically positive often very challenging. Because many procedures are available for such cases but they are of limited use because some of them are lengthy or expensive or need sophisticated equipment, highly skilled personnel, etc. Serum CA-125 is a rapid, relatively inexpensive investigation. Objective: The present study aimed to assess the role of CA-125 in distinguishing pulmonary TB from bacterial pneumonia. Methods: This analytical cross-sectional study was conducted in the Department of Medicine, Dhaka Medical College Hospital for the period of March 2018 to September 2020.100 pulmonary tuberculosis patients were taken in group I, and 100 bacterial pneumonia patients were taken in group II according to selection criteria. Informed written consent was taken from each of the participants. All were subjected to detail clinical and demographic history along with thorough physical examination. Relevant investigations were done including serum CA-125. All final data were collected in the semi-structured and pretested case record form. After data collection, data were checked for errors, and analysis was done. Results: In this study, the mean CA-125 value was 62.29 (SD±31.51) IU/mL in group I(pulmonary tuberculosis). In group II (bacterial pneumonia) mean value was 22.95(±8.25) IU/mL. The mean value of CA-125 was significantly higher (p-value <0.001) in group I patients compared to group II. About 59.0% of patients in group I had a high level of serum CA-125 which had a significant difference from group II (p<0.001). ROC analysis of CA-125 in the diagnosis of patients with active pulmonary tuberculosis showed a cut-off value of ?31.7 IU/mL had sensitivity, specificity, PPV, NPV, PLR, NLR, and accuracy of 72%, 87%, 84.7%, 75.7%, 5.54%, 0.321%, and 79.5% respectively. Conclusion: This study’s findings stated that serum CA-125 may be a useful marker in distinguishing PTB from bacterial pneumonia. Therefore, further study with a more generalized study population is recommended.

Factors affecting the epithelial integrity of human donor corneas

Purpose: To evaluate various factors affecting the integrity of human donor corneal epithelium. Methods: Donor corneal buttons were evaluated for epithelial defect (ED) and exposure. The slit?lamp photographs were taken on day 01, and the data such as age and gender of the donor, cause of death, refrigeration of cadavers, death?to?preservation time (DPT), experience of technician, and distance from site of collection to eye bank were collected. Results: A total of 100 consecutive corneal buttons belonging to 56 donors were evaluated. The median age of donors was 50 years. Males constituted 45 (80.4%). The mean DPT was 9.7 ± 5.3 hours. After death, 34 donors (60.7%) were refrigerated before the collection/retrieval. Most of the corneas (80%) were recovered by technicians having an experience of 0–5 years. Thirty?one donors (55.3%) were located at 1–50 km from the eye bank. The mean area of exposure was 15 ± 4.3 mm2. The mean area of ED was 28.7 ± 5.9 mm2. ED was significantly associated with refrigeration of cadavers and longer DPT. On multivariate analysis, only DPT was found to be significantly associated (P = 0.006; odds ratio [OR] = 1.54 ± 0.24) with the presence of ED. After transplantation, only two corneas had persistent epithelial defects and were treated successfully using various interventions. Conclusion: Integrity of donor corneal epithelium is mainly influenced by the refrigeration of cadavers and DPT.

Does corneal epithelial thickness show the severity of psoriasis? SD-OCT study

Abstract Background Previous studies have generally focused on dry eye test abnormalities and ocular involvements such as uveitis, and blepharitis in psoriasis. Psoriasis area severity ındex (PASI), which is used to assess psoriasis severity, is a time-consuming and complex tool. Objective To evaluate the relationship between disease severity and central corneal epithelial thickness (CCET) in psoriasis. Methods 175 eyes of 175 psoriasis patients and 57 eyes of 57 healthy individuals as a control group was included in this study. Psoriasis patients were divided into three subgroups according to PASI score as < 10 mild, 10‒20 moderate and > 20 severe. CCET was measured by spectral domain-optical coherence tomography (SD-OCT), and mean values were recorded. Mean CCET values were compared between the psoriasis groups and the control group. Additionally, the relationship between PASI score and CCET was examined. Results The mean CCET value was 58.06 ± 3.1 μm in the mild group, 60.10 ± 5.0 μm in the moderate group, 65.75 ± 6.3 μm in the severe group and 56.16 ± 3.1 μm in the control group. It was determined that the mean CCET value was significantly higher in all psoriasis groups compared to the control group (p < 0.001). The mean CCET value was significantly higher in the moderate psoriasis group than in the mild psoriasis group (p = 0.018), and in the severe psoriasis group compared to the moderate psoriasis group (p < 0.001). There was a strong positive correlation between PASI score and CCET (p < 0.001, r = 0.519). Study limitations Cross-sectional design and a relatively small number of participants. Conclusions There is a strong positive correlation between psoriasis severity and CCET. Contactless measurement of CCET by SD-OCT can be an indicator of psoriasis severity.

Influencing factors of corneal epithelial punctate staining in patients wearing orthokeratology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the influencing factors of punctate staining of corneal epithelium in patients wearing orthokeratology.METHOD: Data of 280 cases wearing orthokeratology were collected, including 185 cases in the group without corneal staining and 95 cases in the group with corneal staining. All patients were examined for general distant vision, intraocular pressure, slit lamp, fundus examination after mydriasis, comprehensive optometry, corneal topography, corneal thickness, corneal endothelium, axial length, Schirmer Ⅰtest(SⅠt)before wearing lenses, meibomian gland loss score before wearing lenses, eccentric distance, interleukin-2(IL-2)in tear, tumor necrosis factor-α(TNF-α)content analysis and so on. The influencing factors of corneal epithelium punctate staining were analyzed by univariate and multivariate Logistic regression.RESULTS: There were significant differences in preoperative diopter, preoperative meibomian gland deletion score, IL-2, TNF-α and lens sediment between the two groups(all P&#x003C;0.05). Logistic regression analysis showed that diopter before wearing lenses was a protective factor for corneal epithelium punctate staining. Before wearing lenses, the loss of meibomian gland score, IL-2, TNF-α and lens deposits were the risk factors of corneal epithelium punctate staining. In the detection of corneal epithelium punctate staining, the comprehensive advantage of lens deposits was obvious, the specificity of lens deposits was higher, and the sensitivity of IL-2 was the highest. CONCLUSIONS: Before wearing lenses, diopter is the protective factor of corneal epithelium punctate staining, and the loss of meibomian gland score, IL-2, TNF-α and lens deposits are the risk factors of corneal epithelium punctate staining.

Effects and mechanisms of ferroptosis on high glucose-induced retinal pigment epithelial cells injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effects and mechanisms of ferroptosis on high glucose(HG)-induced retinal pigment epithelium(RPE)cells injury, and to provide new ideas for the treatment of diabetic retinopathy(DR).METHODS: The ARPE-19 cell lines cultured in vitro were divided into normal control group(NC group), high glucose group(HG group), and high glucose+Ferrostatin-1 group(Fer-1 group). The cell viability of each group was detected by CCK-8 assay. The expressions of interleukin 6(IL-6), IL-1β and monocyte chemotactic protein-1(MCP-1)were detected using ELISA kits. The levels of malondialdehyde(MDA), glutathione(GSH), glutathione peroxidase 4(GPX4)and iron content were detected using the corresponding assay kits. The mitochondrial changes in ARPE-19 cells were observed by transmission electron microscopy. The expressions of ferroptosis-related proteins including long-chain lipoyl CoA synthase 4(ACSL4)and GPX4, as well as vascular endothelial growth factor(VEGF)were detected by Western blotting and immunofluorescence staining.RESULTS: Compared with NC group, the cell viability of HG group decreased significantly, the expression levels of inflammatory factors in cell supernatant increased, the contents of MDA and iron significantly increased, GSH and GPX4 significantly decreased(all P&#x003C;0.01), the mitochondria of ARPE-19 cells shrunk, the expression of proteins ACSL4 and VEGF increased, while the expression of GPX4 decreased(all P&#x003C;0.01). Compared with HG group, the cell viability of Fer-1 group significantly increased, the expression levels of inflammatory factors in cell supernatant decreased, MDA and iron contents significantly decreased, GSH contents and GPX4 viability significantly increased(all P&#x003C;0.05), the morphology of mitochondria in ARPE-19 cells improved, the expression of ACSL4 and VEGF decreased, while the expression of GPX4 increased(all P&#x003C;0.05).CONCLUSION: Ferroptosis is involved in the injury of RPE induced by HG. Inhibiting ferroptosis can improve cell viability, reduce inflammation and oxidative stress, and alleviate HG-induced RPE cells injury.

Corneal epithelial remodeling following stromal lenticule addition keratoplasty combined with corneal collagen cross-linking for the treatment of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the epithelial remodeling of femtosecond laser-assisted stromal lenticule addition keratoplasty combined with corneal collagen cross-linking(SLAK-CXL)in patients with progressive keratoconus, investigate the remodeling rules of corneal epithelial and influencing factors, and provide clinical data for further refractive correction.METHODS: Retrospective and observational study. A total of 28 keratoconus patients(29 eyes)who received SLAK-CXL from September 2020 to October 2021 were included. Preoperative and postoperative visual acuity, intraocular pressure(IOP), diopter, keratometry and corneal epithelial thickness(CET)were recorded. The trend of CET change was observed. The factors affecting CET were analyzed according to the thickness and depth of the lenticule.RESULTS: Flattest meridian keratometry(Kf)and steepest meridian keratometry(Ks)at 1mo postoperatively were significantly larger than those preoperatively(P&#x003C;0.05). The thinnest corneal thickness(TCT)at 1, 2, 6mo and 1a postoperatively were significantly larger than preoperative(P&#x003C;0.05). The CET changed with time, with the central CET showing a larger variation tendency. The CET of superior, superior nasal, nasal, superior temporal in paracentral area were thinned, the CET of superior, temporal, superior temporal in midperipheral area were thinned, while the CET of superior nasal was thickened in peripheral area at 1, 2, 6mo and 1a postoperatively. The variation of CET was not correlated with the thickness or depth of lenticule at 1a postoperatively(P&#x003E;0.05).CONCLUSIONS: It is firstly found that the corneal morphology has changed after SLAK-CXL. CET decreases and then increases and then decreases again. At 1a postoperatively, the CET of the central and paracentral areas is thinner, while the CET of the midperipheral and peripheral areas is thicker. The degree of epithelial remodeling is not correlated with lenticule thickness or depth.

Progress on the function and mechanism of pigment epithelium derived factor receptors in the occurrence and development of diabetic retinopathy / 中华眼底病杂志

Endogenous pigment epithelium derived factor (PEDF) shows great potential as a drug target for the treatment of diabetes retinopathy (DR) due to its anti-angiogenesis, anti-inflammatory, neuroprotective and neurotrophic effects. PEDF plays a biological role by combining with receptor proteins on cell membrane surface and regulating a variety of signaling pathways. Low density lipoprotein receptor related protein 6 plays a role in inhibiting oxidative stress reaction, inflammatory reaction, and neovascularization of DR. Adipose triglyceride lipase, laminin receptor, plexin domain containing 1 (PLXDC) 1, PLXDC2 and F 1-adenosine triphosphate synthase have the effect of promoting endothelial cell apoptosis, among which PLXDC1 also has neuroprotective effect. By clarifying the receptor that PEDF acts on, exploring the affinity between the receptor and PEDF, the difference in the expression level of each receptor in the process of disease, and the specific function that PEDF plays after binding with specific receptors, we can develop fusion protein drugs for the active domain of high affinity of receptors, have a clearer understanding of the pathogenesis of DR, and take PEDF or PEDF receptor as the target to consolidate the theoretical basis for the development of new therapeutic drugs and strategies for DR.

Overexpression of SARS-CoV-2 spike protein mediates growth inhibition in human retinal pigment epithelial cells / 中华眼底病杂志

Objective:To observe the inhibition of SARS-CoV-2 spike protein (S-protein) on the proliferation of human retinal pigment epithelium (RPE) cells.Methods:SARS-CoV-2 S-protein gene fragment expression plasmid (p3xflag-S) was constructed and transfected into human RPE, HEK293 cells. DNA sequencing was used for identification, and the expression of Flag-S was detected by Western blot. HEK293 cells were divided into the cells 1, 2, 3 and 4 and transfected with GFP11 plasmid and vector, GFP1-10 plasmid and vector, transfected with GFP11 and pCMV-HA-ACE2 plasmid, GFP1-10 and p3xflag-S plasmid. Cell 1 was co-cultured with cell 2 (control group 1), cell 2 with cell 3 (control group 2), cell 3 with cell 4 (observation group), and cell 1 mixed with cells 2, 3 and 4 (control group 3). Bright-field microscopy and fluorescence microscopy were used to observe cell fusion. RPE cells were divided into control group and overexpression S-protein group. The cell cycle was detected by flow cytometry; the cell proliferation level was detected by Counting Kit 8 (CCK-8); and the S-protein expression level in RPE cells was detected by Western blot. The Student’s t-test was performed for comparison between groups. Results:DNA sequence assay showed that S-protein cDNA was fused with flag-tagged protein. Western blot assay showed that S-protein-related expression was elevated in transfected HEK293 cells compared with untransfected p3xflag-S cells. Large, multinucleated fused cell clusters were visible under bright-field microscopy; multiple nuclear with distinct green fluorescence were visible in the fused cells under fluorescence microscopy. Western blot assay showed elevated S-protein-related expression in transfected p3xflag-S plasmid RPE cells compared to untransfected p3xflag-S plasmid RPE cells. CCK-8 results showed that the proliferative capacity of RPE cells in the S-protein overexpression group was significantly reduced compared with the control group, with statistically significant differences ( t=22.70, 16.75, 23.38; P<0.000 1). The results of flow cytometry showed that the G1 phase cells in the control and overexpression S-protein groups were 41.1 % and 67.0%, respectively; compared with the control group, the G1 phase cells in the overexpression S-protein group were significantly higher, and the difference was statistically significant ( t=4.76, P=0.018). The apoptosis rate was significantly increased in the S-protein overexpression group compared with the control group, and the difference was statistically significant ( t=4.91, P=0.008). Conclusion:Overexpression of the SARS-CoV-2 spike protein reduced the proliferation of human RPE cells.

Inhibitory effect of miR-497 on the repair of diabetic mice corneal epithelial damage by targeting wnt3a / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of miR-497 on the corneal epithelial healing in diabetic mice and its possible mechanism.Methods:Forty healthy clean-grade wild-type C57BL/J6 mice were randomly divided into a blank control group and a model control group, with 20 mice in each group.Another 20 CRISPR/Cas9-mediated miR-497 knockout mice and miR-497 overexpression mice were taken as miR-497 knockout and miR-497 overexpression groups, respectively.The diabetes model was constructed by continuous intraperitoneal injection of streptozotocin (STZ) to the mice in model control, miR-497 knockout and miR-497 overexpression groups, and the mice in blank control group were injected with an equal amount of citrate buffer, followed by 8-week normal feeding.After the establishment of diabetes model, the corneal epithelial injury model was further constructed by scraping off part of the corneal epithelium with a central diameter of 2 mm.The corneal epithelial defect area of mice in 0, 12, 24 and 36 hours after corneal epithelial injury was observed by corneal fluorescein sodium staining.The expression of Wnt3a and β-catenin proteins in mice corneal tissues was detected by Western blot.The expression of miR-497 as well as the mRNA expression levels of cell proliferation-associated factor genes CyclinD1, c-Myc, and Ki-67 mRNA was detected by real-time quantitative fluorescence PCR.The targeting relationship between miR-497 and wnt3a was detected by a dual luciferase reporter gene assay.Human corneal epithelial cells (HCEC) were cultured in vitro and transfected with miR-497 mimics, miR-497 mimics negative control, miR-497 inhibitor, and miR-497 inhibitor negative control by Lipo8000 as miR-497 mimics group, mimics negative control group, miR-497 inhibitor group, andmiR-497 inhibitor negative control group, respectively, all of which were cultured in high glucose medium containing 25% glucose.Another two groups of HCEC were taken and cultured in medium containing 5% and 25% glucose as control and high glucose groups, respectively.The cell proliferation viability was determined by CCK8 method.The use and care of animals complied ith the ARVO statement.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (2019K-K010). Results:Eight weeks after STZ injection, the blood glucose of mice was significantly higher and the weight was significantly lower in each diabetic model group than those of blank control group (all at P<0.05). At 12, 24 and 36 hours after the corneal epithelial injury, the percentages of corneal epithelial defect area observed by slit-lamp microscopy in model control group were significantly higher than those in blank control group and miR-497 knockout group and lower than those in miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expressions of wnt3a and β-catenin proteins in the corneal tissues of model control group were significantly lower than those of blank control group and miR-497 knockout group, but higher than those of miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expressions of CyclinD1, c-Myc and Ki-67 mRNA in model control group were lower than those in miR-497 knockout group, but higher than those in miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expression of miR-497 in model control group, miR-497 knockout group and miR-497 overexpression group was 1.00±0.02, 0.63±0.06 and 1.48±0.03, respectively, with a statistically significant difference ( F=19.62, P<0.01). The luciferase activity of miR-497-5p mimics group in wild-type wnt3a transfected cells was lower than that of miR-497-5p negative control group and empty vector group, and the differences were statistically significant (all at P<0.05). In the mutant wnt3a transfected cells, there was no significant difference in the luciferase activity among various groups ( F=0.73, P=0.59). The cell proliferation A value of high glucose group was 0.59±0.03, which was significantly lower than 0.59±0.03 of normal control group and 0.88±0.08 of miR-497 inhibitor group, but significantly higher than 0.48±0.11 of miR-497 mimics group (all at P<0.05). Conclusions:The silencing of miR-497 may promote the repair of diabetic corneal epithelial defects by targeting wnt/β-catenin pathway.

Interpretation of Expert Consensus on the Identification, Diagnosis and Treatment of Neurotrophic Keratopathy / 中华实验眼科杂志

Neurotrophic keratopathy (NK) is a relatively rare degenerative corneal disease.Over time, it can cause varying degrees of ocular surface damage, leading to corneal ulcers, perforations and even blindness.The best opportunity to reverse ocular surface damage is in the earliest stage of NK.However, patients experience few typical symptoms and diagnosis is often delayed.In 2021, BMC Ophthalmology published the Expert Consensus on the Identification, Diagnosis and Treatment of Neurotrophic Keratopathy in Volume 21.Through the interpretation of the consensus, this paper hopes to further improve ophthalmologists' understanding of the screening and treatment of NK, and optimize the management norms of NK diagnosis and treatment.

Clinical efficacy evaluation of accelerated epithelium-off corneal collagen cross-linking on corneal ectasia after keratorefractive surgery / 中华实验眼科杂志

Objective:To investigate the efficacy and safety of accelerated epithelium-off corneal collagen cross-linking (CXL) in the treatment of corneal ectasia after keratorefractive surgery.Methods:An observational case series study was performed.Twelve patients (22 eyes) diagnosed with corneal ectasia after keratorefractive surgery in the First Affiliated Hospital of Army Medical University were enrolled from January 2016 to December 2018.All the patients received accelerated epithelium-off CXL and were followed up for 12 months.Before and 1 week, 1, 3, 6, and 12 months after the operation, the uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (LogMAR) unit were measured.The sphericity, cylindricity, and spherical equivalent were examined by Topcon auto refractor.The maximum keratometry (Kmax) of the front surface, mean keratometry (Km) of the front surface, Km of the back surface, symmetry index of front surface (SIf), symmetry index of back surface (SIb), thinnest corneal thickness (TCT), total aberrations, total high-order aberrations, coma aberration, trefoil aberration and spherical aberration were detected by the Sirius analyzer.The depth of corneal demarcation lines was determined by optical coherence tomography.The intraocular pressure was measured by the non-contact tonometry.The corneal endothelial cell density was assayed by the endothelial cell densitometry.The inflammatory reaction and haze were observed with a slit lamp at different time points after surgery.This study adhered to the Declaration of Helsinki.The study protocol was approved by the First Affiliated Hospital of Army Medical University (No.KY2020063). Written informed consent was obtained from each patient before entering the cohort.Results:Among the 22 eyes of 12 cases, 3 eyes of 2 cases (13.64%) underwent small incision lenticule extraction, and 19 eyes of 10 cases (86.36%) underwent excimer laser in situ keratomileusis.The UCVA (LogMAR), BCVA (LogMAR), cylindricity and spherical equivalent before the operation were 0.61±0.42, 0.24±0.23, (-2.83±2.39)D, (-3.60±2.66)D, which were significantly worse than 0.45±0.31, 0.12±0.15, (-2.11±1.67)D, (-3.12±2.31)D at 12 months after the operation ( t=4.054, 4.956, -3.728, -2.742; all at P<0.05). The front surface Kmax, front surface Km and SIf at 12 months after the operation were (48.37±5.80), (41.49±3.04), (5.36±4.07)D, which were significantly lower than (49.61±5.97), (41.66±2.97), (5.85±4.18)D before the operation ( t=5.949, 2.278, 2.719; all at P<0.05). There was no significant difference in sphericity, Km of the back surface, SIb, TCT, total aberrations, total high-order aberrations, coma aberration, trefoil aberration, spherical aberration, intraocular pressure and endothelial cell density between before and 12 months after the operation (all at P>0.05). Grade 0.5-2 haze occurred in 8 eyes of 4 patients one month postoperatively.After administration of prednisolone acetate eye drops, haze decreased or disappeared 3 months postoperatively, with UCVA and BCVA unchanged.A corneal demarcation line with a depth of (285.40±51.61)μm was found in 11 eyes of 6 cases at 1 month after operation. Conclusions:Accelerated epithelium-off CXL can significantly improve visual acuity, reduce corneal astigmatism and corneal curvature, as well as effectively prevent the progress of corneal ectasia.

Inhibitory effects of N-acetylcysteine and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans-retinoic acid / 中华实验眼科杂志

Objective:To observe the effect of the antioxidant N-acetylcysteine (NAC) and selective endoplasmic reticulum stress response inhibitor salubrinal on the apoptosis of retinal pigment epithelial cells induced by all-trans-retinoic acid (ATRA).Methods:Human ARPE-19 cell line was used as the experimental cell line, and was divided into normal control group cultured with complete medium, model control group cultured with complete medium containing 10 μmol/L ATRA, NAC treatment group cultured with complete medium containing 10 μmol/L ATRA+ 5 mmol/L NAC, salubrinal group cultured with complete medium containing 10 μmol/L ATRA+ 40 μmol/L salubrinal, NAC+ salubrinal group cultured with complete medium containing 10 μmol/L ATRA+ 5 mmol/L NAC+ 40 μmol/L salubrinal.After 24-hour culture, apoptosis rate, multicaspase level and reactive oxygen species (ROS) level of ARPE-19 cells were detected by flow cytometry.The expressions of vascular endothelial growth factor A (VEGF-A), C/EBP-homologous protein (CHOP), cleaved-caspase 3 in cells were detected by Western blot.Results:There were significant differences in the apoptosis rate, multicaspase and ROS levels among the five groups ( F=113.23, 602.41, 160.39; all at P<0.001). The apoptosis rate, multicaspase and ROS levels of normal control group, NAC treatment group, salubrinal group and NAC+ salubrinal group were significantly lower than those of model control group (all at P<0.05). There were significant differences in the expression levels of VEGF-A, CHOP and cleaved-caspase 3 among the five groups ( F=24.62, 36.35, 60.25; all at P<0.001). The protein expression levels of VEGF-A, CHOP and cleaved-caspase 3 of normal control group, NAC treatment group, salubrinal group and NAC+ salubrinal group were significantly lower than those of model control group (all at P<0.05). Conclusions:ATRA can induce RPE cells to produce oxidative stress and endoplasmic reticulum stress injury, which leads to apoptosis.NAC and salubrinal can effectively reduce the RPE cell apoptosis by inhibiting stress response.