RESUMEN
The blood supply in the retina ensures photoreceptor function and maintains regular vision. Leber's hereditary optic neuropathy (LHON), caused by the mitochondrial DNA mutations that deteriorate complex I activity, is characterized by progressive vision loss. Although some reports indicated retinal vasculature abnormalities as one of the comorbidities in LHON, the paracrine influence of LHON-affected retinal ganglion cells (RGCs) on vascular endothelial cell physiology remains unclear. To address this, we established an in vitro model of mitochondrial complex I deficiency using induced pluripotent stem cell-derived RGCs (iPSC-RGCs) treated with a mitochondrial complex I inhibitor rotenone (Rot) to recapitulate LHON pathologies. The secretomes from Rot-treated iPSC-RGCs (Rot-iPSC-RGCs) were collected, and their treatment effect on human umbilical vein endothelial cells (HUVECs) was studied. Rot induced LHON-like characteristics in iPSC-RGCs, including decreased mitochondrial complex I activity and membrane potential, and increased mitochondrial reactive oxygen species (ROS) and apoptosis, leading to mitochondrial dysfunction. When HUVECs were exposed to conditioned media (CM) from Rot-iPSC-RGCs, the angiogenesis of HUVECs was suppressed compared to those treated with CM from control iPSC-RGCs (Ctrl-iPSC-RGCs). Angiogenesis-related proteins were altered in the secretomes from Rot-iPSC-RGC-derived CM, particularly angiopoietin, MMP-9, uPA, collagen XVIII, and VEGF were reduced. Notably, GeneMANIA analysis indicated that VEGFA emerged as the pivotal angiogenesis-related protein among the identified proteins secreted by health iPSC-RGCs but reduced in the secretomes from Rot-iPSC-RGCs. Quantitative real-time PCR and western blots confirmed the reduction of VEGFA at both transcription and translation levels, respectively. Our study reveals that Rot-iPSC-RGCs establish a microenvironment to diminish the angiogenic potential of vascular cells nearby, shedding light on the paracrine regulation of LHON-affected RGCs on retinal vasculature.
RESUMEN
Purpose: The purpose of this study was to conduct a large-scale genome-wide association study (GWAS) and construct a polygenic risk score (PRS) for risk stratification in patients with dry eye disease (DED) using the Taiwan Biobank (TWB) databases. Methods: This retrospective case-control study involved 40,112 subjects of Han Chinese ancestry, sourced from the publicly available TWB. Cases were patients with DED (n = 14,185), and controls were individuals without DED (n = 25,927). The patients with DED were further divided into 8072 young (<60 years old) and 6113 old participants (≥60 years old). Using PLINK (version 1.9) software, quality control was carried out, followed by logistic regression analysis with adjustments for sex, age, body mass index, depression, and manic episodes as covariates. We also built PRS prediction models using the standard clumping and thresholding method and evaluated their performance (area under the curve [AUC]) through five-fold cross-validation. Results: Eleven independent risk loci were identified for these patients with DED at the genome-wide significance levels, including DNAJB6, MAML3, LINC02267, DCHS1, SIRPB3P, HULC, MUC16, GAS2L3, and ZFPM2. Among these, MUC16 encodes mucin family protein. The PRS model incorporated 932 and 740 genetic loci for young and old populations, respectively. A higher PRS score indicated a greater DED risk, with the top 5% of PRS individuals having a 10-fold higher risk. After integrating these covariates into the PRS model, the area under the receiver operating curve (AUROC) increased from 0.509 and 0.537 to 0.600 and 0.648 for young and old populations, respectively, demonstrating the genetic-environmental interaction. Conclusions: Our study prompts potential candidates for the mechanism of DED and paves the way for more personalized medication in the future. Translational Relevance: Our study identified genes related to DED and constructed a PRS model to improve DED prediction.
Asunto(s)
Síndromes de Ojo Seco , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndromes de Ojo Seco/genética , Síndromes de Ojo Seco/epidemiología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Adulto , Herencia Multifactorial/genética , Anciano , Factores de Riesgo , Medición de Riesgo/métodos , Polimorfismo de Nucleótido Simple , Taiwán/epidemiología , Puntuación de Riesgo GenéticoRESUMEN
This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Degeneración Macular , Desprendimiento de Retina , Degeneración Macular Húmeda , Humanos , Anciano , Anciano de 80 o más Años , Resultado del Tratamiento , Estudios de Seguimiento , Estudios Retrospectivos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Tomografía de Coherencia Óptica , Agudeza Visual , Inyecciones Intravítreas , Desprendimiento de Retina/etiología , Trastornos de la Visión/complicaciones , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Degeneración Macular/complicaciones , China , Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/complicacionesRESUMEN
INTRODUCTION: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. OBJECTIVES: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. METHODS: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. RESULTS: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. CONCLUSION: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.
RESUMEN
OBJECTIVES: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). METHODS: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. RESULTS: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). CONCLUSIONS: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.
Asunto(s)
Antirreumáticos , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hidroxicloroquina , Enfermedades de la Retina , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Enfermedades de la Retina/genética , Enfermedades de la Retina/inducido químicamente , Antirreumáticos/efectos adversos , Anciano , Adulto , Agudeza Visual , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Asunto(s)
Inhibidores de la Angiogénesis , Angiopoyetina 2 , Anticuerpos Biespecíficos , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Masculino , Femenino , Agudeza Visual/fisiología , Método Doble Ciego , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/uso terapéutico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/fisiopatología , Degeneración Macular Húmeda/diagnóstico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Angiopoyetina 2/antagonistas & inhibidores , Resultado del Tratamiento , Tomografía de Coherencia Óptica , Estudios de Seguimiento , Anciano de 80 o más Años , Angiografía con Fluoresceína , Relación Dosis-Respuesta a DrogaRESUMEN
INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.
RESUMEN
Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.
RESUMEN
Rhegmatogenous retinal detachment (RRD) is a significant cause of vision loss and requires appropriate surgical intervention. There are several approaches available, including observation, laser demarcation, pneumatic retinopexy, scleral buckling, and pars plana vitrectomy, which are chosen based on patient condition, surgeon experience, and national health insurance policies. Despite the various options, there is still no consensus on the optimal intervention. To address this, the Taiwan Retina Society assembled an expert committee with 11 experienced retina specialists to review the current evidence and develop a guideline with seven recommendations for managing RRD patients. Additionally, a survey was conducted with six questions to assess treatment patterns in Taiwan, which included input from the expert committee and an open poll at the 2023 Congress of the Taiwan Retina Society. This report provides a comprehensive summary of the current knowledge and expert consensus on the treatment of RRD, discussing the characteristics of current approaches and providing an overview of current treatment patterns in Taiwan. These findings aim to provide ophthalmologists with the best possible treatment for RRD.
Asunto(s)
Desprendimiento de Retina , Humanos , Consenso , Retina , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Taiwán , Resultado del Tratamiento , VitrectomíaRESUMEN
PURPOSE: To compare the efficiency and safety of internal limiting membrane (ILM) peeling between the Sharkskin forceps and End-grasping forceps in various macular diseases. METHODS: It is a prospective cohort block-randomized study conducted in a tertiary medical center. Seventy subjects with macular hole, epiretinal membrane, vitreomacular traction syndrome, or myopic foveoschisis, receiving pars plana vitrectomy and ILM peeling surgery were equally divided into Sharkskin forceps group and End-grasping forceps group. The duration of ILM peeling, the number of attempts to initiate peeling, and peeling-related retinal damage were evaluated by recorded video and optical coherence tomography. RESULTS: In the Sharkskin group, the authors demonstrated significantly fewer attempts to initiate ILM peeling compared with End-grasping group, with an average of 1.9 and 3.1 attempts ( P = 0.0001) and a lower incidence of retinal microstructural damage (20% vs. 45%, P < 0.0001). Moreover, the mean depth of inner retinal injury at the initiating site exhibited distinct difference postoperatively at 3 months between the Sharkskin group then the End-grasping group (4.3 vs. 30.0 µ m, P = 0.001). CONCLUSION: Sharkskin forceps provide better efficiency and outcome in ILM peeling in patients with various vitreomacular interface diseases, including reduced risk of retinal injury and fewer attempts to initiate ILM flap.
Asunto(s)
Membrana Epirretinal , Lesiones Oculares , Perforaciones de la Retina , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Membrana Basal/cirugía , Retina , Membrana Epirretinal/cirugía , Perforaciones de la Retina/cirugía , Lesiones Oculares/complicaciones , Vitrectomía/métodos , Tomografía de Coherencia ÓpticaRESUMEN
Significance: For research on retinitis pigmentosa in humans, the Royal College of Surgeons (RCS) rat is commonly used as the primary animal model since the disease process is similar. Therefore, it is necessary to understand how the disease develops and determine whether the treatment is effective. Aim: In this study, structural and microvascular change of retinal degeneration in RCS rats was assessed non-invasively on specific dates over 3.5 months. Approach: Using a high-resolution spectral domain (SD) optical coherence tomography angiography (OCTA), the retinal degeneration in RCS rats, from day 14 until day 126, was qualitatively and quantitatively analyzed. Results: Aside from the thinning of the retina thickness starting from 2 weeks of age, blood vessels in the deep layer of the retina also began to degenerate at about 4 weeks of age. Hole structures appeared at the inner nuclear layer and the inner plexiform layer by the age of 10 weeks. Observations of abnormal angiogenesis in the choroid began by 12 weeks of age. Conclusions: We conducted a longitudinal study of retina degeneration structure and vascular changes in an RCS rat model using a supercontinuum laser based high-resolution SD-OCTA. Combined with OCTA, OCT leads to a better understanding of photoreceptor pathology as retinal degeneration by identifying tissue and vessel loss.
Asunto(s)
Degeneración Retiniana , Cirujanos , Humanos , Ratas , Animales , Recién Nacido , Lactante , Degeneración Retiniana/diagnóstico por imagen , Degeneración Retiniana/patología , Tomografía de Coherencia Óptica/métodos , Estudios Longitudinales , Retina/diagnóstico por imagen , Retina/patología , Angiografía con Fluoresceína/métodosRESUMEN
PURPOSE: To assess the 1-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema from Asian and non-Asian countries. DESIGN: Global, multicenter, randomized, double-masked, active comparator-controlled, phase III trials. METHODS: Subgroup analysis of patients from Asian (N=144) and non-Asian (N=1747) countries randomized to faricimab 6.0 mg every 8 weeks (Q8W), faricimab per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W in the YOSEMITE/RHINE (NCT03622580/NCT03622593) trials. Primary endpoint: best-corrected visual acuity (BCVA) changes from baseline at 1 year, averaged over weeks 48, 52, and 56. RESULTS: Mean BCVA change from baseline at 1 year in the Asian country subgroup was similar between arms: faricimab Q8W (n=50), +10.9 (95% CI: 8.6-13.2); faricimab PTI (n=48) +10.0 (7.7-12.4) letters; aflibercept Q8W (n=46) +9.0 (6.6-11.4) letters. BCVA gains in the non-Asian country subgroup (n=582, 584, 581) were +11.3 (10.5-12.1), +11.2 (10.5-12.0), and +10.7 (9.9-11.5) letters, respectively. At 1 year, 49% of Asian country patients in the faricimab PTI arm achieved Q16W dosing (vs. 52% non-Asian) and 78% achieved ≥Q12W dosing (vs. 72% non-Asian). Anatomic improvementswere generally greater with faricimab versus aflibercept and similar between the Asian and non-Asian country subgroups. Faricimab was well tolerated, with no new safety signals. CONCLUSIONS: Vision, durability, anatomic, and safety outcomes were generally similar between the Asian and non-Asian country subgroups, suggesting that global YOSEMITE/RHINE results may be generalized to the Asian population. These data support the benefit-risk profile of faricimab for treating Asian patients with diabetic macular edema.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs). METHODS: Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study. RESULTS: There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed. CONCLUSIONS: GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.
Asunto(s)
Hemangioma Cavernoso , Radiocirugia , Masculino , Femenino , Humanos , Resultado del Tratamiento , Radiocirugia/efectos adversos , Estudios de Cohortes , Hemangioma Cavernoso/diagnóstico por imagen , Hemangioma Cavernoso/radioterapia , Hemangioma Cavernoso/cirugía , Estudios de Seguimiento , Estudios RetrospectivosRESUMEN
Purpose: Retinal detachment (RD) is a sight-threatening ocular disease caused by separation of the neurosensory retina from the underlying retinal pigment epithelium layer. Its genetic basis is unclear because of a limited amount of data. In this study, we aimed to identify genetic risk loci associated with RD in participants without diabetes mellitus and to construct a polygenic risk score (PRS) to predict the risk of RD. Methods: A genome-wide association study was conducted using data from the Taiwan Biobank to identify RD risk loci. A total of 1533 RD cases and 106,270 controls were recruited, all of whom were Han Chinese. Replication studies were performed using data from the UK Biobank and Biobank Japan. To construct the PRS, a traditional clumping and thresholding method was performed and validated by fivefold cross-validation. Results: Two novel loci with significant associations were identified. These two genes were TMEM132D (lead single nucleotide polymorphism [SNP]: rs264498, adjusted-P = 7.18 × 10-9) and VIPR2 (lead SNP: rs3812305, adjusted-P = 8.38 × 10-9). The developed PRS was effective in discriminating individuals at high risk of RD with a dose-response relationship. The quartile with the highest risk had an odds ratio of 1244.748 compared to the lowest risk group (95% confidence interval, 175.174-8844.892). Conclusions: TMEM132D and VIPR2 polymorphisms are genetic candidates linked to RD in Han Chinese populations. Our proposed PRS was effective at discriminating high-risk from low-risk individuals.
Asunto(s)
Desprendimiento de Retina , Humanos , Desprendimiento de Retina/genética , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Retina , Receptores de Tipo II del Péptido Intestinal Vasoactivo , Proteínas de la Membrana/genéticaRESUMEN
Pars plana vitrectomy (PPV) is the main treatment modality for patients with severe diabetic retinopathy. With the development of systems for microincision, wide-angle viewing, digitally assisted visualization, and intraoperative optical coherence tomography, contemporary PPV for diabetic retinopathy has been performed on a wider range of indications than previously considered. In this article, we reviewed, in conjunction with our collective experiences with Asian patients, the applications of new technologies for PPV in eyes with diabetic retinopathy and highlighted several important procedures and entities not generally reiterated in the literature, in order for vitreoretinal surgeons to optimize their approaches when facing the challenges imposed by the complications in diabetic eyes.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Desprendimiento de Retina , Humanos , Vitrectomía/métodos , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/cirugía , Agudeza Visual , Ojo , Tomografía de Coherencia Óptica , Desprendimiento de Retina/cirugía , Diabetes Mellitus/etiología , Diabetes Mellitus/cirugíaRESUMEN
INTRODUCTION: Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is related to the pathogenesis of various retinopathies including age-related macular degeneration (AMD). Oxidative stress is the major factor that induces degeneration of RPE cells associated with the etiology of AMD. OBJECTIVES: Sodium iodate (NaIO3) generates intracellular reactive oxygen species (ROS) and is widely used to establish a model of AMD due to the selective induction of retinal degeneration. This study was performed to clarify the effects of multiple NaIO3-stimulated signaling pathways on EMT in RPE cells. METHODS: The EMT characteristics in NaIO3-treated human ARPE-19 cells and RPE cells of the mouse eyes were analyzed. Multiple oxidative stress-induced modulators were investigated and the effects of pre-treatment with Ca2+ chelator, extracellular signal-related kinase (ERK) inhibitor, or epidermal growth factor receptor (EGFR) inhibitor on NaIO3-induced EMT were determined. The efficacy of post-treatment with ERK inhibitor on the regulation of NaIO3-induced signaling pathways was dissected and its role in retinal thickness and morphology was evaluated by using histological cross-sections and spectral domain optical coherence tomography. RESULTS: We found that NaIO3 induced EMT in ARPE-19 cells and in RPE cells of the mouse eyes. The intracellular ROS, Ca2+, endoplasmic reticulum (ER) stress marker, phospho-ERK, and phospho-EGFR were increased in NaIO3-stimulated cells. Our results showed that pre-treatment with Ca2+ chelator, ERK inhibitor, or EGFR inhibitor decreased NaIO3-induced EMT, interestingly, the inhibition of ERK displayed the most prominent effect. Furthermore, post-treatment with FR180204, a specific ERK inhibitor, reduced intracellular ROS and Ca2+ levels, downregulated phospho-EGFR and ER stress marker, attenuated EMT of RPE cells, and prevented structural disorder of the retina induced by NaIO3. CONCLUSIONS: ERK is a crucial regulator of multiple NaIO3-induced signaling pathways that coordinate EMT program in RPE cells. Inhibition of ERK may be a potential therapeutic strategy for the treatment of AMD.
RESUMEN
PRCIS: We report a case of a 45-year-old woman who developed serous retinal detachment, hypotony, and retinal necrosis after Xen gel stent implantation. ABSTRACT: A 45-year-old woman developed sudden blurring of vision 4 days after Xen gel stent replacement surgery. Persistent hypotony, uveitis, and serious retinal detachment rapidly progressed despite medical and surgical treatments. Retinal necrosis, optic atrophy, and total blindness developed within 2 months. Although infectious and autoimmune-related uveitis were ruled out through negative culture and blood test results, acute postoperative infectious endophthalmitis could not be completely excluded in this case. However, toxic retinopathy related to mitomycin- C was suspected eventually.
Asunto(s)
Implantes de Drenaje de Glaucoma , Glaucoma de Ángulo Abierto , Desprendimiento de Retina , Uveítis , Femenino , Humanos , Persona de Mediana Edad , Presión Intraocular , Glaucoma de Ángulo Abierto/cirugía , Mitomicina , Stents/efectos adversos , NecrosisRESUMEN
PURPOSE: To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making. METHODS: A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated. RESULTS: The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane. CONCLUSION: The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.
Asunto(s)
Membrana Epirretinal , Humanos , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Estudios Transversales , Retina/diagnóstico por imagen , Pronóstico , Agudeza Visual , Vitrectomía/métodos , Tomografía de Coherencia Óptica/métodos , Estudios RetrospectivosRESUMEN
There have been recent advances in basic research and clinical studies in polypoidal choroidal vasculopathy (PCV). A recent, large-scale, population-based study found systemic factors, such as male gender and smoking, were associated with PCV, and a recent systematic review reported plasma C-reactive protein, a systemic biomarker, was associated with PCV. Growing evidence points to an association between pachydrusen, recently proposed extracellular deposits associated with the thick choroid, and the risk of development of PCV. Many recent studies on diagnosis of PCV have focused on applying criteria from noninvasive multimodal retinal imaging without requirement of indocyanine green angiography. There have been attempts to develop deep learning models, a recent subset of artificial intelligence, for detecting PCV from different types of retinal imaging modality. Some of these deep learning models were found to have high performance when they were trained and tested on color retinal images with corresponding images from optical coherence tomography. The treatment of PCV is either a combination therapy using verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF), or anti-VEGF monotherapy, often used with a treat-and-extend regimen. New anti-VEGF agents may provide more durable treatment with similar efficacy, compared with existing anti-VEGF agents. It is not known if they can induce greater closure of polypoidal lesions, in which case, combination therapy may still be a mainstay. Recent evidence supports long-term follow-up of patients with PCV after treatment for early detection of recurrence, particularly in patients with incomplete closure of polypoidal lesions.
Asunto(s)
Inhibidores de la Angiogénesis , Enfermedades de la Coroides , Humanos , Masculino , Inhibidores de la Angiogénesis/uso terapéutico , Coroides/patología , Vasculopatía Coroidea Polipoidea , Inteligencia Artificial , Angiografía con Fluoresceína/métodos , Factores de Riesgo , Tomografía de Coherencia Óptica/métodos , Estudios Retrospectivos , Enfermedades de la Coroides/diagnóstico , Enfermedades de la Coroides/terapia , Inyecciones IntravítreasRESUMEN
Induced pluripotent stem cells (iPSCs) can be differentiated into mesenchymal stem cells (iPSC-MSCs), retinal ganglion cells (iPSC-RGCs), and retinal pigmental epithelium cells (iPSC-RPEs) to meet the demand of regeneration medicine. Since the production of iPSCs and iPSC-derived cell lineages generally requires massive and time-consuming laboratory work, artificial intelligence (AI)-assisted approach that can facilitate the cell classification and recognize the cell differentiation degree is of critical demand. In this study, we propose the multi-slice tensor model, a modified convolutional neural network (CNN) designed to classify iPSC-derived cells and evaluate the differentiation efficiency of iPSC-RPEs. We removed the fully connected layers and projected the features using principle component analysis (PCA), and subsequently classified iPSC-RPEs according to various differentiation degree. With the assistance of the support vector machine (SVM), this model further showed capabilities to classify iPSCs, iPSC-MSCs, iPSC-RPEs, and iPSC-RGCs with an accuracy of 97.8%. In addition, the proposed model accurately recognized the differentiation of iPSC-RPEs and showed the potential to identify the candidate cells with ideal features and simultaneously exclude cells with immature/abnormal phenotypes. This rapid screening/classification system may facilitate the translation of iPSC-based technologies into clinical uses, such as cell transplantation therapy.