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1.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139354

RESUMO

This study aimed to (1) determine whether the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 is increased in tobacco smokers, which potentially increases their susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and (2) assess whether eye rinsing can reduce susceptibility. This prospective study included 20 eyes of 10 smokers and 18 eyes of nine healthy non-smokers (control) for reverse-transcription polymerase chain reaction. This study also included 28 eyes of 14 smokers and 16 eyes of eight healthy non-smokers (control) for enzyme-linked immunosorbent assay. Tear and impression cytology samples were collected from the right eye of each patient. The left eye was then rinsed for 30 s, and after 5 min, the tear and impression cytology samples were collected in the same manner. The expression of the ACE2 gene was significantly higher in the conjunctiva of smokers (n = 17; median 3.07 copies/ng of total RNA) than in those of non-smokers (n = 17; median 1.92 copies/ng of total RNA, p = 0.003). Further, mRNA expression and protein levels of ACE2 were weakly correlated in smokers (r = 0.49). ACE2 protein levels in Schirmer's strip samples were significantly reduced from 5051 to 3202 pg/mL after eye washing (n = 10; p = 0.001). Ocular surface cells are susceptible to SARS-CoV-2 infection. Smoking may be a risk factor for SARS-CoV-2 infection, and eye rinsing may reduce the risk of infection.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Túnica Conjuntiva/metabolismo , COVID-19/metabolismo , COVID-19/prevenção & controle , Estudos Prospectivos , RNA/metabolismo , SARS-CoV-2/metabolismo , Fumantes , Olho/metabolismo
2.
FASEB J ; 34(8): 10778-10800, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32619061

RESUMO

Chronic graft-vs-host disease (cGVHD) is a multifactorial inflammatory disease that affects patients undergoing hematopoietic stem cell transplantation. Multiple organs, including the lacrimal glands (LGs), are negatively affected by cGVHD and lose function due to the resultant fibrosis. An abnormal immune response is thought to be a major factor in the development of chronic ocular GVHD, which is currently treated primarily with immunosuppressive therapies. However, all the treatments yield unsatisfactory outcomes, and additional treatment strategies are needed. To meet this unmet medical need, we aimed to elucidate an additional pathway of chronic ocular GVHD. Our findings suggest a potential association between chronic ocular GVHD pathogenesis and stress-induced cellular senescence through the senescence-associated secretory phenotype (SASP). Senescent cells produce cytokines and chemokines, such as IL-6 and CXCL9. Indeed, senescent cell accumulation was presumably associated with cGVHD development in LGs, as evidenced by the improvement in LGs after the selective elimination of senescent cells (senolysis) with ABT-263. Results in the sclerodermatous cGVHD mouse model suggest that inhibiting the major components of the SASP, including IL-6 and CXCL9, with senolytics is a potential novel strategy for treating cGVHD-affected LGs. Taken together, our results indicate a potential association between the SASP and cGVHD development in LGs and suggest that targeted senolytic treatment may be a new therapeutic option for this disease.


Assuntos
Senescência Celular/fisiologia , Olho/patologia , Doença Enxerto-Hospedeiro/patologia , Animais , Quimiocina CXCL9/metabolismo , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Olho/metabolismo , Feminino , Fibrose/metabolismo , Fibrose/patologia , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C
3.
BMC Ophthalmol ; 21(1): 164, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827493

RESUMO

BACKGROUND: Chronic ocular graft-versus-host disease (oGVHD) is an ocular comorbidity of graft-versus-host disease (GVHD) that usually occurs concurrently with systemic manifestations. Failure to detect and treat oGVHD in its early stages may lead to progression of ocular signs and symptoms leading to oGVHD that is refractory to conventional treatment. CASE PRESENTATION: We report the clinical course of a 19-year-old male and a 59-year-old female with severe and progressive chronic oGVHD without concurrent systemic signs of chronic graft-versus-host disease (cGVHD). Although their systemic conditions had been stable, both suffered from severe oGVHD and were referred to our clinic. Both cases exhibited marked improvement in conjunctival inflammation and fibrotic changes after amniotic membrane transplantation (AMT). Both cases underwent keratoplasty eventually to stabilize ocular surface conditions and to improve visual function. CONCLUSIONS: We reported the clinical outcomes of 2 cases of chronic oGVHD without concurrent systemic comorbidities that were treated with AMT. The clinician should be aware that cGVHD may persist in target organs even in the absence of concurrent systemic comorbidities following seemingly successful systemic treatment. A multidisciplinary team approach is essential in the early detection and therapeutic intervention for chronic oGVHD.


Assuntos
Síndromes do Olho Seco , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Âmnio , Doença Crônica , Comorbidade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Sensors (Basel) ; 21(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669487

RESUMO

This study assessed the anterior chamber depth (ACD) and iridocorneal angle using a portable smart eye camera (SEC) compared to the conventional slit-lamp microscope and anterior-segment optical coherence tomography (AS-OCT). This retrospective case-control study included 170 eyes from 85 Japanese patients. The correlation between the ACD evaluations conducted with the SEC and conventional slit-lamp was high (r = 0.814). The correlation between the Van-Herick Plus grade obtained using two devices was also high (r = 0.919). A high kappa value was observed for the Van-Herick Plus grading (Kappa = 0.757). A moderate correlation was observed between the ACD measured using AS-OCT and the slit-lamp image acquired with the conventional slit-lamp microscope and SEC (r = 0.609 and 0.641). A strong correlation was observed between the trabecular-iris angle (TIA) measured using AS-OCT and Van-Herick Plus grade obtained with the conventional slit-lamp microscope and SEC (r = 0.702 and 0.764). Strong correlations of ACD evaluation and high kappa value of the Van-Herick Plus grading indicated the adequate subjective assessment function of the SEC. Moderate correlations between the ACD objective measurement and evaluation and strong correlation between the TIA and Van-Herick Plus grade suggested the good objective assessment function of the SEC. The SEC demonstrated adequate performance for ACD evaluation and angle estimation.


Assuntos
Câmara Anterior , Microscopia , Câmara Anterior/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Iris , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica
5.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063118

RESUMO

Mesenchymal stem cells (MSCs) have been widely used in therapeutic applications for many decades. However, more and more evidence suggests that factors such as the site of origin and pre-implantation treatment have a crucial impact on the result. This study investigates the role of freshly isolated MSCs in the lacrimal gland after allogeneic transplantation. For this purpose, MSCs from transgenic GFP mice were isolated and transplanted into allogeneic and syngeneic recipients. While the syngeneic MSCs maintained a spherical shape, allogeneic MSCs engrafted into the tissue as spindle-shaped cells in the interstitial stroma. Furthermore, the MSCs produced collagen type I in more than 85% to 95% of the detected GFP+ MSCs in the recipients of both models, supposedly contributing to pathogenic fibrosis in allogeneic recipients compared to syngeneic models. These findings indicate that allogeneic MSCs act completely differently from syngeneic MSCs, highlighting the importance of understanding the exact mechanisms behind MSCs.


Assuntos
Transplante de Medula Óssea , Colágeno Tipo I/biossíntese , Células-Tronco Mesenquimais/metabolismo , Animais , Aparelho Lacrimal/citologia , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Transplante Homólogo , Transplante Isogênico
6.
Int J Mol Sci ; 22(7)2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916809

RESUMO

Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model.


Assuntos
Antibacterianos/farmacologia , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/tratamento farmacológico , Administração Oral , Aloenxertos , Animais , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Interleucina-6/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia
7.
Ann Allergy Asthma Immunol ; 122(4): 387-392.e1, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30639466

RESUMO

BACKGROUND: Severe atopic keratoconjunctivitis (AKC) is a relatively rare disease, and some cases are refractory to conventional steroid treatment. OBJECTIVE: To examine the efficacy of 0.1% tacrolimus ophthalmic suspension in treating severe AKC during a 1-year follow-up. METHODS: This was a single-center, retrospective clinical study. Sixty eyes from 30 patients with severe AKC who were treated with 0.1% tacrolimus ophthalmic suspension 4 times per day, were included. The mean age of the patients was 21.5 ± 13.7 years. The severity of objective signs was observed at baseline (before treatment), at 2 weeks, and at 1, 2, 3, 6, and 12 months after treatment initiation. Ten objective signs of palpebral conjunctiva, bulbar conjunctiva, limbus, and cornea were assessed using 4 grades (0 = normal; 1+ = mild; 2+ = moderate; 3+ = severe). Safety was assessed based on the incidence and the severity of adverse events. RESULTS: The total score of the 10 clinical signs significantly decreased from baseline 2 weeks after initiating tacrolimus eye drop treatment, except at 2 months. The mean total score of clinical signs was 13.6 ± 6.6 at the beginning of treatment, and decreased to 5.4 ± 4.8 12 months after initiation. Treatment was gradually tapered, with increasing intervals between applications. Additional medications were required to provide relief in 18 patients during follow-up. No patient discontinued treatment due to adverse drug effects. Herpes keratitis was observed in 3 cases during follow-up. However, these cases were completely controlled. CONCLUSION: The 0.1% tacrolimus ophthalmic suspension is effective for the treatment of severe AKC refractory to standard conventional treatments throughout a full year.


Assuntos
Conjuntivite Alérgica/tratamento farmacológico , Imunossupressores/administração & dosagem , Ceratoconjuntivite/tratamento farmacológico , Tacrolimo/administração & dosagem , Adolescente , Adulto , Criança , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Soluções Oftálmicas , Estudos Retrospectivos , Índice de Gravidade de Doença , Tacrolimo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
8.
Eye Contact Lens ; 45(2): 124-131, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30005054

RESUMO

OBJECTIVES: To evaluate corneal higher-order aberrations (HOAs) in eyes with corneal scar after traumatic perforation and their correlation with visual acuity. METHODS: This retrospective consecutive case study included 40 eyes of 40 consecutive patients (mean age, 39.2±21.6 years), treated for traumatic corneal perforation at Tokyo Dental College, and 18 normal control eyes. Higher-order aberrations of anterior and posterior corneal surfaces and total cornea were analyzed by swept-source optical coherence tomography. Correlations between corneal HOAs and visual acuity were analyzed. RESULTS: Higher-order aberrations within 4-mm diameter were significantly larger in eyes with corneal perforation (anterior surface, 0.51±0.54 µm; posterior surface, 0.20±0.14; and total cornea, 0.52±0.50) as compared to normal controls (0.10±0.02, 0.02±0.01, and 0.09±0.02, respectively; all P<0.001). Higher-order aberrations within 6-mm diameter were significantly larger in eyes with corneal perforation (anterior surface, 1.15±1.31; posterior surface, 0.31±0.23; and total cornea, 1.09±1.28) as compared to normal controls (0.21±0.06, 0.06±0.01, and 0.19±0.06, respectively; all P<0.001). The most common topography pattern observed was the minimal change pattern (37.5%), followed by asymmetric pattern (30.0%). Visual acuity significantly correlated with corneal HOAs (anterior surface: R=0.646, P<0.001; posterior surface: R=0.400, P=0.033; and total cornea: R=0.614, P<0.001). CONCLUSIONS: Corneal scar after traumatic perforations not only induces corneal opacity, but also increases corneal HOAs, which indicates a direct effect on visual acuity.


Assuntos
Cicatriz/diagnóstico , Córnea/patologia , Perfuração da Córnea/complicações , Topografia da Córnea/métodos , Aberrações de Frente de Onda da Córnea/diagnóstico , Refração Ocular/fisiologia , Tomografia de Coerência Óptica/métodos , Adulto , Cicatriz/etiologia , Cicatriz/fisiopatologia , Perfuração da Córnea/diagnóstico , Aberrações de Frente de Onda da Córnea/etiologia , Aberrações de Frente de Onda da Córnea/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual
10.
Int J Mol Sci ; 19(11)2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30423813

RESUMO

Various cytokines, including interferon (IFN)-γ and IL-17, are augmented, and autoreactive T cells and B cells are activated in the immune pathogenesis of Sjögren's syndrome (SS). In particular, IFNs are involved in both the early stages of innate immunity by high level of type I IFN in glandular tissue and sera and the later stages of disease progression by type I and type II IFN producing T cells and B cells through B cell activating factor in SS. Genetically modified mouse models for some of these molecules have been reported and will be discussed in this review. New findings from human SS and animal models of SS have elucidated some of the mechanisms underlying SS-related dry eye. We will discuss IFN-γ and several other molecules that represent candidate targets for treating inflammation in SS-related dry eye.


Assuntos
Síndromes do Olho Seco/metabolismo , Interferons/metabolismo , Síndrome de Sjogren/metabolismo , Animais , Modelos Animais de Doenças , Síndromes do Olho Seco/microbiologia , Síndromes do Olho Seco/terapia , Humanos , Microbiota , Modelos Biológicos , Síndrome de Sjogren/microbiologia , Síndrome de Sjogren/terapia
11.
Cureus ; 16(2): e53358, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38435205

RESUMO

Pheochromocytoma or paraganglioma (PPGL) originating from chromaffin cells can produce diverse hormones in addition to catecholamines, including adrenocorticotropic hormone (ACTH). In pheochromocytoma, high levels of ACTH might not result in pigmentation as typically observed in Addison's disease, and patients might not exhibit the symptoms of Cushing's syndrome, despite ACTH-dependent hypercortisolism. A 63-year-old male patient with hypertension was admitted to our facility, and computed tomography (CT) revealed a large right adrenal tumor. Despite high plasma ACTH (700-1300 pg/mL) and serum cortisol (90-100 µg/dL) levels, no physical pigmentation or Cushingoid symptoms were observed. Urinary metanephrine and normetanephrine levels reached as high as 16.0 mg and 3.2 mg, respectively. 123I-metaiodobenzylguanidine (MIBG) scintigraphy was negative. Low-dose dexamethasone paradoxically increased ACTH and cortisol levels, indicating the potential positive feedback regulation of both hormones by glucocorticoids. The patient was diagnosed with an ACTH-producing pheochromocytoma and underwent successful laparoscopic surgery to remove the adrenal tumor under the intravenous administration of a high-dose α-blocker and hydrocortisone. The levels of ACTH, cortisol, and urinary metanephrine/normetanephrine returned close to normal after tumor removal. We report a rare case of pheochromocytoma with extremely high ACTH/cortisol production but without pigmentation or Cushingoid symptoms. We also reviewed previous reports of ACTH-producing PPGL regarding the paradoxical regulation of ACTH/cortisol by glucocorticoids, pigmentation, Cushingoid symptoms, and negativity of 123I-MIBG scintigraphy.

12.
Cureus ; 16(7): e65153, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39176324

RESUMO

Chichijima Island, part of the Ogasawara Islands in Tokyo, is a remote island with a population of approximately 2,000, served by a few resident general practitioners (GPs). This case report discusses the application of teleophthalmology in managing pediatric ocular trauma on this remote island. A pediatric patient sustained an ocular injury from a badminton shuttlecock and was initially examined by a resident GP using a recordable slit-lamp microscope. The ocular images were transmitted to a mainland ophthalmologist through a telemedicine system. The specialist provided remote consultation and recommended further examination and treatment, leading to the patient's transfer to the mainland. The successful management of this case underscores the critical role of telemedicine in enhancing healthcare delivery in isolated regions. With advancements in medical technology, teleophthalmology is expected to become increasingly vital in providing specialized care in remote and underserved areas. The case highlights the importance of telemedicine in improving access to specialized medical expertise, ensuring timely and effective patient care, and potentially reducing the need for patient transfers to more equipped healthcare facilities.

13.
Cureus ; 16(8): e66321, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39246965

RESUMO

Laser iridotomy (LI) is an effective treatment for patients with pupillary block mechanisms. Here, we report a case of LI performed on a patient with primary angle closure (PAC) and elevated intraocular pressure (IOP), who was unsuitable for other treatments due to specific social circumstances. The patient, a 97-year-old female residing in a private nursing home, had a medical history notable only for mild dementia and was wheelchair-bound. She had not undergone ophthalmologic evaluation for over 50 years. The patient presented with intermittent tenderness and redness in the left eye. Therefore, an ophthalmologist visited the nursing home. Examination revealed visual acuity of 20/200 in the right eye and 20/100 in the left eye, IOP of 24 mmHg in the right eye and 26 mmHg in the left eye, no conjunctival hyperemia, shallow anterior chambers, and nuclear sclerosis grade 4 cataracts in both eyes. Fundus examination was challenging due to lens opacity, and both optic nerve papillae appeared pale. Given her history of episodic eye pain and hyperemia, PAC was diagnosed. Treatment options, including eye drops and cataract surgery, were discussed. However, the patient opted for LI due to her advanced age and inability to attend frequent follow-up visits. LI was successfully performed on both eyes during her visit to the clinic. One week post-procedure, IOP decreased to 12 mmHg bilaterally, with no complications. This case demonstrates that LI can be a viable option for managing PAC and high IOP in patients who are not candidates for surgery or eye drops due to social constraints.

14.
Bioengineering (Basel) ; 11(3)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38534547

RESUMO

Ophthalmological services face global inadequacies, especially in low- and middle-income countries, which are marked by a shortage of practitioners and equipment. This study employed a portable slit lamp microscope with video capabilities and cloud storage for more equitable global diagnostic resource distribution. To enhance accessibility and quality of care, this study targets corneal opacity, which is a global cause of blindness. This study has two purposes. The first is to detect corneal opacity from videos in which the anterior segment of the eye is captured. The other is to develop an AI pipeline to detect corneal opacities. First, we extracted image frames from videos and processed them using a convolutional neural network (CNN) model. Second, we manually annotated the images to extract only the corneal margins, adjusted the contrast with CLAHE, and processed them using the CNN model. Finally, we performed semantic segmentation of the cornea using annotated data. The results showed an accuracy of 0.8 for image frames and 0.96 for corneal margins. Dice and IoU achieved a score of 0.94 for semantic segmentation of the corneal margins. Although corneal opacity detection from video frames seemed challenging in the early stages of this study, manual annotation, corneal extraction, and CLAHE contrast adjustment significantly improved accuracy. The incorporation of manual annotation into the AI pipeline, through semantic segmentation, facilitated high accuracy in detecting corneal opacity.

15.
Ocul Surf ; 32: 198-210, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499288

RESUMO

PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.


Assuntos
Senescência Celular , Doença Enxerto-Hospedeiro , Disfunção da Glândula Tarsal , Glândulas Tarsais , Animais , Feminino , Masculino , Camundongos , Compostos de Anilina/farmacologia , Transplante de Medula Óssea/métodos , Senescência Celular/fisiologia , Doença Crônica , Modelos Animais de Doenças , Doença Enxerto-Hospedeiro/patologia , Imuno-Histoquímica , Disfunção da Glândula Tarsal/metabolismo , Glândulas Tarsais/patologia , Glândulas Tarsais/metabolismo , Camundongos Endogâmicos BALB C , Sulfonamidas/farmacologia
16.
Invest Ophthalmol Vis Sci ; 65(10): 38, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39189995

RESUMO

Purpose: To identify molecular signatures specific for ocular graft-versus-host disease (GVHD) by proteomic analysis of corneas from mice with GVHD. Methods: We identified differentially expressed proteins (DEPs) in corneal samples from GVHD model mice and syngeneic control mice 4 weeks after bone marrow transplantation. Data-independent acquisition analysis was performed on individual samples, and the roles of DEPs in biological pathways related to GVHD were evaluated via bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Three important signaling pathways were upregulated in the cornea in mice with GVHD: (1) the necroptosis pathway, (2) the mitogen-activated protein kinase (MAPK) pathway, and (3) as previously reported, the neutrophil extracellular trap (NET) pathway. In those signaling pathways, we identified new upregulated molecules, including (1) receptor-interacting protein kinase 1 (RIPK1), RIPK3, interferon regulatory factor 9, the interferon-induced double-stranded RNA-activated protein kinase lipoxygenase, and high mobility group box1 (HMGB1) which are damage-associated molecular patterns (DAMPs) in the necroptosis pathway; (2) the sequentially upregulated interleukin 1 (IL-1) receptor-associated kinase (IRAK), an evolutionarily conserved signaling intermediate in the Toll pathway (ECSIT), and p38, which is downstream of the IL-1 receptor and increased CDC42/Rac (Rac2), a Rho family GTPase in the MAPK pathway; and (3) the integrin components CR3 and macrophage-1 antigen (MAC-1), which are DAMPs, and the pyroptosis-related protein gasdermin D (GSDMD) in the NET pathway. Conclusions: These novel molecules may help researchers elucidate the pathogenesis of GVHD and identify new therapeutic targets for corneal changes in patients with ocular GVHD.


Assuntos
Córnea , Modelos Animais de Doenças , Doença Enxerto-Hospedeiro , Camundongos Endogâmicos C57BL , Necroptose , Proteômica , Transdução de Sinais , Regulação para Cima , Animais , Camundongos , Necroptose/fisiologia , Doença Enxerto-Hospedeiro/metabolismo , Córnea/metabolismo , Córnea/patologia , Transdução de Sinais/fisiologia , Feminino , Transplante de Medula Óssea
17.
Diagnostics (Basel) ; 14(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38337832

RESUMO

PURPOSE: We aimed to evaluate the feasibility of using a novel device, the Smart Eye Camera (SEC), for assessing tear meniscus height (TMH) after fluorescein staining and the agreement of the results with measurements obtained using standard slit lamp examination. METHODS: TMH was assessed using both SEC and conventional slit lamp examination. The images were analyzed using the software ImageJ 1.53t (National Institutes of Health, Bethesda, MD, USA). A common measurement unit scale was established based on a paper strip, which was used as a calibration marker to convert pixels into metric scale. A color threshold was applied using uniform parameters for brightness, saturation, and hue. The images were then binarized to black and white to enhance the representation of the tear menisci. A 2 mm area around the upper and lower meniscus in the central eye lid zone was selected and magnified 3200 times to facilitate manual measurement. The values obtained using SEC were compared with those obtained with a slit lamp. RESULTS: The upper and lower TMH values measured using the SEC were not statistically different from those obtained with a slit lamp (0.209 ± 0.073 mm vs. 0.235 ± 0.085, p = 0.073, and 0.297 ± 0.168 vs. 0.260 ± 0.173, p = 0.275, respectively). The results of Bland-Altman analysis demonstrated strong agreement between the two instruments, with a mean bias of -0.016 mm (agreement limits: -0.117 to 0.145 mm) for upper TMH and 0.031 mm (agreement limits: -0.306 to 0.368 mm) for lower TMH. CONCLUSIONS: The SEC demonstrated sufficient validity and reliability for assessing TMH in healthy eyes in a clinical setting, demonstrating concordance with the conventional slit lamp examination.

18.
J Ophthalmol ; 2024: 2562064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39041004

RESUMO

Background: Phacoemulsification has proven to be a breakthrough technique in cataract surgery. Its popularity has grown dramatically as procedures and equipment have advanced, improving both safety and efficiency. This study presents long-term outcomes from phacoemulsification surgeries performed at the Evangelical Church Winning All (ECWA) Eye Hospital, a tertiary eye care center. Method: This prospective clinical cohort study followed standard practices for operations performed under local anesthesia. Ophthalmologists evaluated long-term outcomes and predictors of improved visual acuity after phacoemulsification cataract surgery. The visual recovery of the patients over time was evaluated, and the factors that influence the gains in vision were identified. Results: A total of 177 patients were subjected to treatment at our facilities during the study period. There were 116 male and 61 female patients, which resulted to a male-to-female ratio of 1 : 0.53. The average age of the patients was 59.18 years with a standard deviation of 11.38 years. Of the 259 eyes treated, 249 eyes (96.1%) achieved a high success rate with visual acuity of 6/6 - 6/18. Ten (10) eyes (3.9%) had moderate acuity between <6/18 and 6/60. Follow-up examinations over five years after phacoemulsification showed poor vision outcomes among old patients. The primary factor that affected improvement in visual acuity among patients was amblyopia, present in 30% of cases. Posterior capsular opacification and macular edema collectively accounted for 20% of poor vision cases, while optic atrophy, glaucoma, and retinal hemorrhage each represented approximately 10% of poor vision cases. Conclusions: The phacoemulsification approach demonstrated a highly effective restoration of vision for the vast majority, while long-term data analysis indicated the potential for age-related variability in postoperative visual gains.

19.
Indian J Ophthalmol ; 71(6): 2416-2420, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37322651

RESUMO

Purpose: Diseases affecting the cornea are a major cause of corneal blindness globally. The pressing issue we are facing today is the lack of diagnostic devices in rural areas to diagnose these conditions. The aim of the study is to establish sensitivity and accuracy of smartphone photography using a smart eye camera (SEC) in ophthalmologic community outreach programs. Methods: In this pilot study, a prospective non-randomized comparative analysis of inter-observer variability of anterior segment imaging recorded using an SEC was performed. Consecutive 100 patients with corneal pathologies, who visited the cornea specialty outpatient clinic, were enrolled. They were examined with a conventional non-portable slit lamp by a cornea consultant, and the diagnoses were recorded. This was compared with the diagnoses made by two other consultants based on SEC videos of the anterior segment of the same 100 patients. The accuracy of SEC was accessed using sensitivity, specificity, PPV, and NPV. Kappa statistics was used to find the agreement between two consultants by using STATA 17.0 (Texas, USA). Results: There was agreement between the two consultants to diagnosing by using SEC. Above 90% agreements were found in all the diagnoses, which were statistically significant (P-value < 0.001). More than 90% sensitivity and a negative predictive value were found. Conclusion: SEC can be used successfully in the community outreach programs like field visits, eye camps, teleophthalmology, and community centers, where either a clinical setup is lacking or ophthalmologists are not available.


Assuntos
Oftalmologia , Telemedicina , Humanos , Oftalmologia/métodos , Smartphone , Estudos Prospectivos , Relações Comunidade-Instituição , Projetos Piloto , Telemedicina/métodos , Fotografação/métodos
20.
Sci Rep ; 13(1): 22046, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086904

RESUMO

In ophthalmology, the availability of many fundus photographs and optical coherence tomography images has spurred consideration of using artificial intelligence (AI) for diagnosing retinal and optic nerve disorders. However, AI application for diagnosing anterior segment eye conditions remains unfeasible due to limited standardized images and analysis models. We addressed this limitation by augmenting the quantity of standardized optical images using a video-recordable slit-lamp device. We then investigated whether our proposed machine learning (ML) AI algorithm could accurately diagnose cataracts from videos recorded with this device. We collected 206,574 cataract frames from 1812 cataract eye videos. Ophthalmologists graded the nuclear cataracts (NUCs) using the cataract grading scale of the World Health Organization. These gradings were used to train and validate an ML algorithm. A validation dataset was used to compare the NUC diagnosis and grading of AI and ophthalmologists. The results of individual cataract gradings were: NUC 0: area under the curve (AUC) = 0.967; NUC 1: AUC = 0.928; NUC 2: AUC = 0.923; and NUC 3: AUC = 0.949. Our ML-based cataract diagnostic model achieved performance comparable to a conventional device, presenting a promising and accurate auto diagnostic AI tool.


Assuntos
Catarata , Doenças do Nervo Óptico , Humanos , Inteligência Artificial , Catarata/diagnóstico , Algoritmos , Doenças do Nervo Óptico/diagnóstico
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