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1.
J Clin Med ; 13(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38999475

ABSTRACT

Objective: The objective of this paper is to reconsider the significance of preoperative chest radiography (CXR) before ophthalmic surgery through investigation of imaging findings and usage status. Methods: This retrospective observational clinical study involved 1616 patients who underwent ophthalmic surgery at Saga University Hospital from 1 January 2019 to 31 December 2020. The patients' radiology reports were obtained from the electronic medical records, and their CXR findings, therapeutic interventions, and progress were investigated. Results: Among all patients, 539 (33.4%) had abnormal preoperative CXR findings. Of these patients, 74 (4.6%) had newly identified abnormal findings. In both patient groups, approximately 70% of patients with abnormal findings were aged ≥70 years, and interstitial shadows were the most common finding. Among all patients with abnormal findings, three (0.19%) received preoperative therapeutic interventions, and all surgeries were performed safely. Forty-three patients with abnormal findings were referred to our hospital or other hospitals for further investigation and treatment postoperatively. Among those patients, eight (0.5%) had primary lung cancer, seven underwent surgery, and one received chemoradiation. The other patients were also followed up and received appropriate therapeutic interventions. Conclusions: Before ophthalmic surgery, few patients required actual therapeutic interventions based on their CXR results. However, many abnormal findings were revealed in elderly patients, including some serious diseases. Furthermore, research has suggested that appropriate therapeutic intervention after ophthalmologic surgery may reduce the risk of a poor life prognosis. This study clearly shows that preoperative CXR is not only useful for perioperative systemic management but also ultimately benefits patients. It is also considered particularly meaningful for patients aged ≥70 years.

2.
Jpn J Ophthalmol ; 68(1): 57-63, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38017339

ABSTRACT

PURPOSE: To explore the clinical features of COVID-19-associated conjunctivitis with the objective of preventing the spread of infection. STUDY DESIGN: Retrospective cohort study. METHODS: From March 2020 to March 2021, we retrospectively reviewed 26 (9.8%) consecutive COVID-19 patients with conjunctivitis among 282 COVID-19 cases admitted to our hospital. Clinical symptoms, onset date of conjunctivitis, time to patient recovery, and eye drop intervention were investigated. In addition, risk factors for developing conjunctivitis were statistically examined among 206 inpatients available for within 5 days of the onset. A multivariate analysis of conjunctivitis risk factors was performed. RESULTS: Among the 282 COVID-19 patients, 4 (1.4%) had conjunctival hyperemia as the primary symptom. The median time of onset was 4 days after the COVID-19 onset. Hyperemia was observed in all cases, but other ocular symptoms were rare. The median duration of hyperemia was 3 days. A multiple logistic regression analysis revealed that a young age (p=0.005) and current smoking habit (p=0.027) were independent risk factors for conjunctivitis after COVID-19. CONCLUSIONS: COVID-19-associated conjunctivitis is rare in the elderly and strongly associated with a history of smoking. It often occurs in the early stages of infection, and while hyperemia is recognized as a clinical symptom, other ocular symptoms are rare or non-existent. Many cases recover within a short time.


Subject(s)
COVID-19 , Conjunctivitis , Eye Infections, Viral , Hyperemia , Humans , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Retrospective Studies , Hyperemia/diagnosis , Conjunctivitis/diagnosis , Conjunctivitis/epidemiology , Conjunctivitis/etiology , Eye Infections, Viral/diagnosis , Eye Infections, Viral/epidemiology
3.
Int Ophthalmol Clin ; 64(1): 153-161, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38146888
4.
Biomed Opt Express ; 14(8): 4112-4125, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37799706

ABSTRACT

A novel scanning protocol, ammonite scan, is proposed for widefield optical coherence tomography angiography (OCTA) and relative retinal blood flow velocity imaging in the human retina using variable interscan time analysis (VISTA). A repeated circle scan using a 400 kHz swept-source was employed to achieve an interscan time of 1.28 ms. The center of the repeated circular scan continuously moved spirally towards the peripheral region, ensuring an extended and adjustable scan range while preserving the short interscan time. Image artifacts due to eye movement were eliminated via extra motion-correction processing using data redundancy. The relative blood flow velocity in superficial and deep plexus layers was calculated from the VISTA image, and their ratio was used to explore the microvascular flow parameter in the healthy human eye.

5.
Jpn J Ophthalmol ; 67(6): 637-644, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37561308

ABSTRACT

PURPOSE: To customize a passive surgery support robot for ophthalmic surgery and preliminarily evaluate its performance. STUDY DESIGN: Prospective observational study. METHODS: The range of motion of the arm was analyzed during ophthalmic surgery and, based on this analysis, a commercially available passive robot was customized for surgical support for ophthalmic surgery; following which a prototype robot was constructed. To examine the effects on the brachial muscle during surgical operations with and without the prototype robot, surface electromyograms of the biceps and triceps were analyzed after performing continuous curvilinear capsulorrhexis (CCC) and suturing the sclerocorneal wound in a cataract surgery simulation. Six surgeons performed cataract surgery, and the degree of arm stability and muscle fatigue during surgery were evaluated using a visual analog scale. RESULTS: During surgery, the prototype robot enabled fixation of the elbow and wrist at any position within the surgeon's range of motion, expanding the range of motion of the hand and fingers and stabilizing operability. Surface electromyography showed a significant decrease in the mean amplitude value of the biceps brachii during both CCC and suturing (p < 0.0001). No significant difference was observed in the triceps brachii. The arm stability and muscle fatigue were improved by 83.3% on the visual analog scale with the prototype robot compared with that without protpotype robot. CONCLUSION: The use of a passive prototype robot may improve arm stability and reduce muscle fatigue during ophthalmic surgery.


Subject(s)
Cataract , Robotics , Humans , Muscle, Skeletal/physiology , Arm/physiology , Electromyography
6.
Retin Cases Brief Rep ; 17(6): 672-675, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-35333842

ABSTRACT

PURPOSE: The purpose of this study was to report a case of atypical endogenous fungal endophthalmitis caused by Candida rugosa , a rare species of nonalbicans Candida . METHODS: This report describes a case of a 45-year-old woman who presented with a reduced visual acuity in the right eye in addition to vitreous opacity during breast cancer treatment, which was suspected as fungal endophthalmitis from medical examination and history. Various tests were performed for diagnosis. RESULTS: Blood test results were normal, including the blood beta-D-glucan level, and blood cultures were negative. Diagnosis could not be made using systemic computed tomography and magnetic resonance imaging results. Therefore, a lesion sample was collected by using vitrectomy. C. rugosa was identified through DNA (extracted from the lesion sample) analysis using Basic Local Alignment Search Tool. The visual acuity of the right eye improved after vitrectomy. CONCLUSION: We encountered a rare case of atypical endogenous fungal endophthalmitis caused by C. rugosa . Clinicians sometimes encounter invasive candidiasis caused by rare nonalbicans Candida species. DNA analysis using Basic Local Alignment Search Tool is effective for diagnosing such cases.


Subject(s)
Candidiasis , Endophthalmitis , Eye Infections, Fungal , Female , Humans , Middle Aged , Candidiasis/diagnosis , Candidiasis/microbiology , Endophthalmitis/microbiology , Vitrectomy/methods , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/microbiology , DNA , Antifungal Agents/therapeutic use
9.
BMC Ophthalmol ; 20(1): 426, 2020 Oct 23.
Article in English | MEDLINE | ID: mdl-33097012

ABSTRACT

BACKGROUND: Neurofibromatosis type 1 (NF1) is a hereditary disease that causes neurofibromas generally, but it has been reported to sometimes be associated with various forms of blood vessel stenosis, occlusion and vascular abnormalities of unknown mechanism. However, a symptomatic case with simultaneous ophthalmic artery stenosis and internal carotid artery stenosis is an extremely rare pathogenesis in a child with NF1. In this report, we performed the diagnosis and observation using various imaging modalities for this rare pediatric case. CASE PRESENTATION: A 6-year-old girl diagnosed with NF1 presented with gradual visual loss in the right eye. Best corrected visual acuity (BCVA) was 20/40 OD and the intraocular pressure (IOP) was normal in both eyes. Retinal vascular abnormalities with tortuous vessels and optic disc pallor were observed in the right fundus. Widefield fluorescein angiography revealed multiple sites of neovascularization and a large non-perfusion area in the peripheral retina. Optical coherence tomography angiography showed retinal vascular abnormalities in the right eye and revealed differences in inner retinal thickness and blood flow signal between the left and right eyes. Laser speckle flowgraphy showed that chorioretinal blood flow was significantly decreased in the right eye. Cerebral angiography revealed the right ophthalmic artery was significantly narrowed throughout. In addition, Magnetic resonance angiography revealed that the right internal carotid artery was significantly narrowed in the ophthalmic segment. We diagnosed ophthalmic artery and internal carotid artery stenosis with retinal vascular abnormalities and ocular ischemic syndrome in NF1. Because IOP increased to 35 mmHg, due to neovascular glaucoma in addition to mild vitreous hemorrhage occurred, panretinal photocoagulation was performed after intravitreal bevacizumab injection. After treatments, IOP normalized, but BCVA decreased to 20/100 OD. Arterial spin labeling showed normal cerebral blood flow. The patient is currently being carefully monitored. CONCLUSIONS: We have described the diagnosis and treatment of ocular ischemic syndrome due to multiple arteries stenosis in a child with NF 1. Utilization of various imaging modalities was helpful in diagnosing the complicated pathogenesis. However, since direct intervention by neurosurgery is not possible in this case, it is expected that treatment will be extremely difficult in the future.


Subject(s)
Carotid Stenosis , Neurofibromatosis 1 , Carotid Artery, Internal/diagnostic imaging , Carotid Stenosis/complications , Carotid Stenosis/diagnosis , Child , Female , Fluorescein Angiography , Humans , Ischemia , Neurofibromatosis 1/complications , Neurofibromatosis 1/diagnosis , Retina
10.
Jpn J Ophthalmol ; 64(5): 455-461, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32809075

ABSTRACT

PURPOSE: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. STUDY DESIGN: Prospective clinical study. METHODS: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. RESULTS: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee's grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. CONCLUSION: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results.


Subject(s)
Benzenesulfonates , Cataract , Physicians , Staining and Labeling , Coloring Agents , Humans , Prospective Studies , Trypan Blue
11.
PLoS One ; 15(5): e0233464, 2020.
Article in English | MEDLINE | ID: mdl-32437414

ABSTRACT

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.


Subject(s)
DNA-Binding Proteins/genetics , Early Growth Response Protein 2/genetics , Genetic Predisposition to Disease , Oxygenases/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin/genetics , Transcription Factors/genetics , Uveomeningoencephalitic Syndrome/genetics , Adult , Alleles , Asian People/genetics , Carotenoids , Case-Control Studies , Female , Gene Frequency , Genome-Wide Association Study , HLA-DR4 Antigen/genetics , Humans , Japan , Male , Middle Aged
13.
J Med Case Rep ; 13(1): 249, 2019 Aug 11.
Article in English | MEDLINE | ID: mdl-31400769

ABSTRACT

BACKGROUND: Gonioscopy-assisted transluminal trabeculectomy is a novel and useful technique for ab interno trabeculotomy. However, gonioscopy-assisted transluminal trabeculectomy is difficult to perform in patients with corneal opacity or in patients with sequelae of cerebral infarction and cervical osteoarthritis with severe limitation of spinal mobility. This is because observing Schlemm's canal during surgery using gonioscopy is difficult. In this report, we introduce a new and beneficial surgical technique of transluminal trabeculotomy for these patients, using an ophthalmic endoscope for cases in which normal gonioscopy-assisted transluminal trabeculectomy is difficult. CASE PRESENTATION: Our patient was a 65-year-old Japanese man with cervical osteoarthritis with severe limitation of spinal mobility who showed primary open-angle glaucoma of the right eye. He had limited conversion of his head during surgery because of complications. Therefore, we performed transluminal trabeculotomy using an ophthalmic endoscope. Finally, ab interno trabeculotomy of 200 degrees was achieved by this method, and an average reduction in ocular pressure of 60% from baseline was achieved after surgery, with no major complications. CONCLUSIONS: This surgical technique may be useful as an alternative method for normal gonioscopy-assisted transluminal trabeculectomy in difficult cases.


Subject(s)
Glaucoma, Open-Angle/surgery , Trabeculectomy/instrumentation , Aged , Glaucoma, Open-Angle/pathology , Humans , Male , Patient Positioning
14.
Graefes Arch Clin Exp Ophthalmol ; 257(9): 1915-1924, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31321523

ABSTRACT

PURPOSE: In vivo microenvironments are critical to tissue homeostasis and wound healing, and the cornea is regulated by a specific microenvironment complex that consists of cell-cell interactions, air-liquid interfaces, and fluid flow stimulation. In this study, we aimed to clarify the effects of and the correlations among these three component factors on the cell kinetics of corneal epithelial cells. METHODS: Human corneal epithelial-transformed (HCE-T) cells were cocultured with either primary rat corneal fibroblasts or NIH 3T3 fibroblasts. We employed a double-dish culture method to create an air-liquid interface and a gyratory shaker to create fluid flow stimulation. Morphometric and protein expression analyses were performed for the HCE-T cells. RESULTS: Both the primary rat fibroblasts and the NIH 3T3 cells promoted HCE-T cell proliferation, and the presence of fluid flow synergistically enhanced this effect and inhibited the apoptosis of HCE-T cells. Moreover, fluid flow enhanced the emergence of myofibroblasts when cocultured with primary rat fibroblasts or NIH 3T3 cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by both fluid flow and cellular interaction between the HCE-T and NIH 3T3 cells. CONCLUSION: The cell-cell interaction and fluid flow stimulation in the air-liquid interface synergistically or independently regulated the behavior of HCE-T cells. Fluid flow accelerated the phenotypic change from corneal fibroblasts and NIH 3T3 cells to myofibroblasts. Elucidation of the multicomponent interplay in this microenvironment will be critical to the homeostasis and regeneration of the cornea and other ocular tissues.


Subject(s)
Corneal Injuries/metabolism , Epithelium, Corneal/metabolism , Mesenchymal Stem Cells/cytology , Wound Healing/physiology , Animals , Blotting, Western , Cell Differentiation , Cell Line , Cell Proliferation , Corneal Injuries/pathology , Disease Models, Animal , Epithelial Cells/metabolism , Epithelium, Corneal/pathology , Homeostasis , Humans , Immunohistochemistry , Rats , Rats, Wistar , Signal Transduction
15.
Sci Rep ; 9(1): 6329, 2019 04 19.
Article in English | MEDLINE | ID: mdl-31004111

ABSTRACT

The sclera as well as the cornea forms the principal part of the outer fibrous coat of the eye, with a primary function of protecting the intraocular contents and maintaining the shape of the globe. However, the exact morphometric arrangement of scleral fibroblasts remains unclarified. The aim of this study was to observe the three-dimensional structure of the mouse scleral fibroblasts by focused ion beam/scanning electron microscopy (FIB/SEM). Four eyes from C57BL/6J mice were fixed using a mixture of glutaraldehyde and formaldehyde. The sclera was cut out at the equatorial portion and the posterior pole, and postfixed with potassium ferrocyanide, osmium, thiocarbohydrazide, uranyl acetate and lead aspartate. Specimens were then dehydrated and embedded in an epoxy resin. Serial block face images were obtained using FIB/SEM. Three-dimensional image reconstruction and segmentation of the image stack were created using computer software (Amira v6.0.1, FEI). Scleral fibroblasts were arranged in collagenous layers. The cells frequently showed a cellular junction with the neighboring cells and formed cellular networks. Compared with equatorial fibroblasts, there was a more complicated cellular arrangement of the posterior scleral fibroblasts.


Subject(s)
Cornea/ultrastructure , Fibroblasts/ultrastructure , Imaging, Three-Dimensional , Microscopy, Electron, Scanning , Sclera/ultrastructure , Software , Animals , Male , Mice
16.
Jpn J Ophthalmol ; 63(2): 181-185, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30604110

ABSTRACT

PURPOSE: From an early stage, retinitis pigmentosa (RP) patients suffer from night blindness which causes nocturnal mobility difficulties. We created a wearable visual aid that uses a high-performance see-through display, and added a high-sensitivity camera with a complementary metal-oxide-semiconductor sensor. Here, we evaluate the device's efficacy for helping night-blindness sufferers walk in the dark. STUDY DESIGN: Prospective clinical study. METHODS: Twenty-eight subjects underwent binocular visual acuity testing in the dark without (power off) and with (power on) the device. The test was carried out in a darkened room. We recorded the number of trial errors and the time it took each subject to arrive at the goal both with and without the aid of our device. RESULTS: Our device effectively assists walking in RP patients with mobility problems in the dark. CONCLUSION: Binocular visual acuity in the dark was significantly improved with the aid of our device. In the walking test, the number of errors decreased greatly with the device, and the travel time was significantly shortened.


Subject(s)
Dark Adaptation/physiology , Night Blindness/rehabilitation , Retinitis Pigmentosa/complications , Sensory Aids , Visual Acuity , Walking , Adult , Aged , Equipment Design , Female , Humans , Male , Middle Aged , Night Blindness/etiology , Night Blindness/physiopathology , Prospective Studies , Retinitis Pigmentosa/physiopathology , Retinitis Pigmentosa/rehabilitation , Treatment Outcome , Vision Tests , Vision, Binocular/physiology
17.
Ocul Immunol Inflamm ; 27(5): 699-705, 2019.
Article in English | MEDLINE | ID: mdl-30395750

ABSTRACT

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.


Subject(s)
Armadillo Domain Proteins/genetics , Genetic Predisposition to Disease , Uveomeningoencephalitic Syndrome/genetics , Adult , Asian People/genetics , Case-Control Studies , Female , Gene Frequency , Genotype , Humans , Japan , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide
18.
Graefes Arch Clin Exp Ophthalmol ; 257(3): 557-565, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30569321

ABSTRACT

PURPOSE: This study was conducted in order to develop a novel noninvasive system for measurement and imaging of the arterial oxygen density ratio (ODR) in the retinal microcirculation. METHODS: We developed a system composed of two digital cameras with two different filters, which were attached to a fundus camera capable of simultaneously obtaining two images. Actual measurements were performed on healthy volunteer eyes (n = 61). A new algorithm for ODR measurement and pixel-level imaging of erythrocytes was constructed from these data. The algorithm was based on the morphological closing operation and the line convergence index filter. For system calibration, we compared and verified the ODR values in arterioles and venules that were specified in advance for 56 eyes with reproducibility. In 10 additional volunteers, ODR measurements and imaging of the arterial phase in the retinal microcirculation corresponding to changes in oxygen saturation of the peripheral arteries at normal breathing and breath holding were performed. RESULTS: Estimation of incident light to erythrocytes and pixel-level ODR calculation were achieved using the algorithm. The mean ODR values of arterioles and venules were 0.77 ± 0.060 and 1.02 ± 0.067, respectively. It was possible to separate these regions, calibrate at the pixel level, and estimate the arterial phase. In each of the 10 volunteers, changes in the arterial phase ODR corresponding to changes in oxygen saturation of the peripheral arteries were observed before and after breath holding on ODR images. The mean ODR in 10 volunteers was increased by breath holding (p < 0.05). CONCLUSIONS: We developed a basic system for arterial phase ODR measurement and imaging of the retinal microcirculation. With further validation and development, this may provide a useful tool for evaluating retinal oxygen metabolism in the retinal microcirculation.


Subject(s)
Fluorescein Angiography/instrumentation , Microcirculation/physiology , Oximetry/instrumentation , Regional Blood Flow/physiology , Retinal Vessels/metabolism , Arterioles/diagnostic imaging , Arterioles/metabolism , Equipment Design , Fundus Oculi , Healthy Volunteers , Humans , Oxygen/blood , Reproducibility of Results , Retinal Vessels/diagnostic imaging , Venules/diagnostic imaging , Venules/metabolism , Young Adult
19.
J Hum Genet ; 63(10): 1083-1091, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30054556

ABSTRACT

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.


Subject(s)
Genome-Wide Association Study , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics , Macular Degeneration , Otx Transcription Factors/genetics , Polymorphism, Genetic , Ranibizumab/administration & dosage , Suppressor of Cytokine Signaling Proteins/genetics , Aged , Aged, 80 and over , Asian People , Female , Humans , Japan , Macular Degeneration/drug therapy , Macular Degeneration/genetics , Male , Middle Aged
20.
Jpn J Ophthalmol ; 62(3): 398-406, 2018 May.
Article in English | MEDLINE | ID: mdl-29572578

ABSTRACT

PURPOSE: To investigate the roles of P2X7 receptors (P2RX7) in the pathogenesis of experimental autoimmune uveoretinitis (EAU). STUDY DESIGN: Experimental. METHODS: Either wild-type (P2rx7 +/+ ) or P2rx7-deficient (P2rx7 -∕- ) mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-20. Severity of EAU was evaluated clinically and histopathologically. The induction of IRBP-specific proliferation and cytokines in draining lymph nodes was assessed by enzyme-linked immunosorbent assays (ELISA). The frequency of activation markers was examined by flow cytometry. Furthermore, inhibitory roles of systemic administration of Brilliant Blue G (BBG), an antagonist for P2RX7, in EAU were also assessed in the wild-type mice. RESULTS: The severity of EAU in P2rx7 -∕- mice was reduced as compared with that in P2rx7 +/+ mice, both clinically and histopathologically. IRBP-specific proliferation in P2rx7 -∕- on day 16 was slightly decreased compared to that in P2rx7 +/+ mice. The induction of IRBP-specific interferon (IFN)-γ and interleukin (IL)-17 in P2rx7 -∕- mice on day 16 was lower than that in P2rx7 +/+ mice. The up-regulation of surface expression of activation markers such as CD25, CD44, and CD69 in response to TCR stimulation in P2rx7 -∕- mice was decreased as compared with that in P2rx7 +/+ mice. Furthermore, neutralization of P2RX7 in vivo by BBG suppressed EAU clinically and histopathologically. IRBP-specific IFN-γ and IL-17 induction in BBG-treated mice was significantly lower than that in vehicle-treated mice. CONCLUSION: The results suggest that P2RX7 is a novel preventative therapeutic target for uveitis as it suppresses the effector functions of both Th1 and Th17 cell responses.


Subject(s)
Autoimmune Diseases/immunology , Lymphocyte Activation/immunology , Receptors, Purinergic P2X7/immunology , T-Lymphocytes/immunology , Uveitis/immunology , Animals , Autoimmune Diseases/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Mice , Mice, Inbred C57BL , Uveitis/metabolism
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