RESUMEN
PURPOSE: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed. RESULTS: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only. CONCLUSIONS: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted.
Asunto(s)
Retinopatía Diabética , Predisposición Genética a la Enfermedad , Edema Macular , Polimorfismo de Nucleótido Simple , Receptor TIE-2 , Humanos , Masculino , Edema Macular/genética , Retinopatía Diabética/genética , Femenino , Persona de Mediana Edad , Receptor TIE-2/genética , Anciano , Genotipo , Haplotipos , China/epidemiología , Pueblo Asiatico/genética , Estudios de Casos y ControlesRESUMEN
PURPOSE: To evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV). DESIGN: A case-control genetic association study. METHODS: This study enrolled 217 CSCR, 341 nAMD, 288 PCV patients, and 1380 controls. The CSCR patients were classified into those with focal or diffuse leakage, with or without pigment epithelial detachment (PED), and with or without macular neovascularization (MNV). Associations between 11 variants from 8 genes, ADAMTS9, ANGPT2, ARMS2, CFH, NR3C2, PGF, TNFRSF10A and VIPR2, and diseases/subtypes were analyzed by logistic regression analysis adjusted for age and sex, and inter-phenotype comparison by heterogeneity test. RESULTS: The CFH rs800292-A conferred a protective effect for CSCR with MNV (OR=0.44, P = 0.002) and a risk effect for CSCR without MNV (OR=1.31, P = 0.023). CSCR patients carrying rs800292-G had a 3.23-fold of increased risk towards developing secondary MNV (P = 1.45 ×10-4). CFH rs3753394, rs800292 and rs1329428 showed similar effects among CSCR with MNV, nAMD and PCV, but opposite effects on CSCR without MNV. TNFRSF10A rs13278062-T was associated with overall CSCR but not with CSCR subtypes, nAMD or PCV. Moreover, CFH and ARMS2 SNPs showed heterogeneous effects in CSCR without MNV against CSCR with MNV, nAMD and PCV. CONCLUSIONS: Genetic associations of CSCR with MNV resembled nAMD and PCV compared to CSCR without MNV, indicating differential genetic effects on neovascularization and choroidopathy. Further investigation of the functional roles of CFH, ARMS2, and TNFRSF10A in CSCR, nAMD and PCV should help elucidate the mechanisms of these maculopathies.
Asunto(s)
Coriorretinopatía Serosa Central , Neovascularización Coroidal , Degeneración Macular , Humanos , Genotipo , Coriorretinopatía Serosa Central/genética , Vasculopatía Coroidea Polipoidea , Polimorfismo de Nucleótido Simple , Degeneración Macular/genética , Neovascularización Coroidal/genética , Angiografía con FluoresceínaRESUMEN
PURPOSE: To compare the anatomic and functional outcomes of half-dose photodynamic therapy (PDT) and yellow 577-nm subthreshold micropulse laser (SMLT) in treating patients with chronic central serous chorioretinopathy (CSCR). DESIGN: Prospective, double-masked, randomized, controlled clinical trial. PARTICIPANTS: Patients with chronic CSCR confirmed by clinical features and multimodal imaging. METHODS: Eligible patients were randomized (1:1) to receive half-dose PDT or SMLT. The same treatment was repeated if persistent subretinal fluid (SRF) was observed. Treatment responses were evaluated 1 month after treatment and every 3 months until the end point at 12 months. MAIN OUTCOME MEASURES: The primary outcome measure was the complete resolution of SRF on OCT scan at month 12. Secondary outcomes included the changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) as measured by OCT, retinal sensitivity as measured by microperimetry, and vision-related quality of life using the National Eye Institute 25-Item Visual Function Questionnaire. RESULTS: Between April 2017 and October 2020, 68 patients were recruited. At 1 month after treatment, SRF resolved in 8 (24.2%) of 33 patients receiving SMLT and in 20 (58.8%) of 34 patients receiving half-dose PDT. This increased to 23 (82.1%) of 28 patients in the SMLT group and 30 (90.9%) of 33 patients in the half-dose PDT group at 12 months of follow-up. Kaplan-Meier survival curves showed significantly faster resolution of SRF in the half-dose PDT group than the SMLT group (P = 0.016). Both groups showed significant improvement in BCVA (-0.12 ± 0.21, P = 0.005 for SMLT; -0.13 ± 0.12, P < 0.001 for half-dose PDT), CMT (-154.2 ± 105.6, P < 0.001 for SMLT; -140.8 ± 94.0, P < 0.001 for half-dose PDT), and retinal sensitivity (5.70 ± 5.02, P < 0.001 for SMLT; 6.05 ± 3.83, P < 0.001 for half-dose PDT) at 12 months compared with baseline. There was no significant difference between the 2 treatment groups at each time point in all investigations except BCVA at 3 months (P = 0.03). CONCLUSIONS: When comparing half-dose PDT to subthreshold SMLT, this study has shown both treatments to be viable options, with half-dose PDT achieving faster anatomic success and functional improvement. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMEN
Purpose: Central serous chorioretinopathy (CSCR) is a leading cause of central vision impairment in the working-age population with male predilection. Knowledge about the genetic basis of CSCR and its male predilection remained limited. This study aimed to evaluate the association patterns of multiple gene variants in chronic CSCR (cCSCR) in Chinese patients. Methods: This case-control genetic association study included 531 patients with cCSCR and 2383 controls from two independent Chinese cohorts. Nine single-nucleotide polymorphisms (SNPs) of six genes, namely CFH, NR3C2, GATA5, VIPR2, TNFRSF10A, and ARMS2, were genotyped in all subjects. The main outcome measures were the association of individual single-nucleotide polymorphism (SNP) with cCSCR, the sex-stratification effects of individual SNP, and joint effects of different SNPs on cCSCR. Results: Association results in the two cohorts were consistent with low heterogeneities. In the combined analysis, SNPs CFH rs800292 (odds ratio [OR] = 1.25, P = 0.0020), CFH rs1329428 (OR = 1.23, P = 0.0037), and TNFRSF10A rs13278062 (OR = 1.43, P = 0.0014) were significantly associated with cCSCR. In stratification analysis by sex, 3 SNPs in CFH, rs3753394, rs800292, and rs1329428, were associated with cCSCR in male patients, but not in female patients. Joint analysis revealed that subjects homozygous for the risk alleles of CFH rs800292 and TNFRSF10A rs13278062 had over 4-fold of increased risk of cCSCR when compared with subjects homozygous for the non-risk alleles (OR = 4.06, P = 2.30 × 10-5). Conclusions: This study revealed main and joint effects of SNPs in CFH and TNFRSF10A on cCSCR, and suggested CFH as a potential genetic factor underlying the male predilection of cCSCR. Further replication in other study populations is needed.
Asunto(s)
Coriorretinopatía Serosa Central , Humanos , Masculino , Femenino , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/genética , Factor H de Complemento/genética , Genotipo , Estudios de Casos y Controles , Estudios de Asociación Genética , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: To address the problem of teaching noncore specialties, for which there is often limited teaching time and low student engagement, a flipped classroom case learning (FCCL) module was designed and implemented in a compulsory 5-day ophthalmology rotation for undergraduate medical students. The module consisted of a flipped classroom, online gamified clinical cases, and case-based learning. METHOD: Final-year medical students in a 5-day ophthalmology rotation were randomized to the FCCL or a traditional lecture-based (TLB) module. The outcomes of subjective assessments (student-rated anonymous Likert scale questionnaire, scale 1 to 5, and course and teaching evaluation, scale 1 to 6) and objective assessments (end-of-rotation and post-MBChB multiple-choice questions, scale 0 to 60) were compared between the 2 groups. RESULTS: Between May 2021 and June 2022, 216 students (108 in each group) completed the study. Compared with the TLB students, the students in the FCCL group rated various aspects of the course statistically significantly higher, including feeling more enthusiastic and engaged by the course and more encouraged to ask questions and participate in discussions (all P < .001). They also gave higher ratings for the instructional methods, course assignments, course outcomes, and course workload ( P < .001). They gave higher course and teaching evaluation scores to the tutors (5.7 ± 0.6 vs 5.0 ± 1.0, P < .001). The FCCL group scored higher than the TLB group on the end-of-rotation multiple-choice questions (53.6 ± 3.1 vs 51.8 ± 2.8, P < .001). When 32 FCCL students and 36 TLB students were reassessed approximately 20 weeks after the rotation, the FCCL group scored higher (40.3 ± 9.1) than the TLB group (34.3 ± 10.9, P = .018). CONCLUSIONS: Applying the FCCL module in ophthalmology teaching enhanced medical students' satisfaction, examination performance, and knowledge retention. A similar model may be suitable for other specialties.
Asunto(s)
Oftalmología , Estudiantes de Medicina , Humanos , Oftalmología/educación , Facultades de Medicina , Aprendizaje , Encuestas y Cuestionarios , Aprendizaje Basado en Problemas/métodos , CurriculumRESUMEN
Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: "Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy". Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.
Asunto(s)
Retinopatía Diabética , Edema Macular , Uveítis , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Factores de Crecimiento Endotelial/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Uveítis/tratamiento farmacológico , Inflamación , Inyecciones Intravítreas , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.
Asunto(s)
Diabetes Mellitus Experimental , Retinopatía Diabética , Animales , Ratones , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Microglía/metabolismo , Necroptosis/fisiología , Enfermedades Neuroinflamatorias , Proteínas Quinasas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Background: The mechanism of diabetic macular edema (DME) was explored by comparing the intraocular metabolite profiles of the aqueous humor of patients with DME to those of diabetic patients without DME using untargeted metabolomic analysis. Methods: Aqueous samples from 18 type 2 diabetic patients with DME and 18 type 2 diabetic patients without DME used as controls were analyzed using liquid chromatography-mass spectrometry (LCMS). The two groups of patients were age and gender matched and had no systemic diseases other than diabetes mellitus (DM). The metabolites were analyzed using orthogonal partial least square discriminant analysis. Results: The metabolite profiles in DME patients differed from those in DM controls. This indicates the following metabolic derangements in DME: (a) a higher amount of oxidized fatty acids but a lower amount of endogenous antioxidants (oxidative stress); (b) higher levels of ß-glucose and homocysteine but a lower level of sorbitol (hyperglycemia); (c) a higher amount of prostaglandin metabolites (inflammation); (d) higher amounts of acylcarnitines, odd-numbered fatty acids, and 7,8-diaminononanoate (respiration deterioration); (e) a higher amount of neurotransmitter metabolites and homovanillic acid (neuronal damage); (f) a lower amount of extracellular matrix (ECM) constituents (ECM deterioration); and (g) a higher amount of di-amino peptides (microvascular damage). Conclusions: The change in the metabolic profiles in the aqueous humor of DME patients compared to DM controls without DME indicates that DME patients may have less capability to resist various stresses or damaging pathological conditions, such as oxidative stress, mitochondrial insufficiency, inflammation, and ECM deterioration.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Edema Macular , Humanos , Retinopatía Diabética/metabolismo , Humor Acuoso/metabolismo , Antioxidantes , Ácido Homovanílico/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Inflamación/metabolismo , Homocisteína , Sorbitol/análisis , Sorbitol/metabolismo , Prostaglandinas/análisis , Prostaglandinas/metabolismo , Ácidos Grasos/metabolismo , Glucosa/metabolismoRESUMEN
BACKGROUND: Due to the variety of clinical presentation, some tumors may be concealed and easily misdiagnosed, leading to delays in management. We report a series of patients who initially presented to an Ophthalmic Clinic with ocular symptoms and were subsequently diagnosed with extraocular tumors. METHODS: Patients who presented to the ophthalmic outpatient clinic at the Joint Shantou International Eye Center with ocular symptoms between April 2013 and December 2019 and were subsequently diagnosed with intracranial or systemic tumors were reviewed retrospectively. Clinical data, including ocular symptoms and signs, ophthalmic and systemic imaging examinations, and the results of tumor biopsies were collected and analyzed. RESULTS: Twenty-three patients were included in this study, of which 16 were female (69.6%) and 7 were male (30.4%). Chief complaints at the first visit included visual loss (n=20), proptosis (n=2), and diplopia (n=1). Ocular examination revealed disc pallor (n=8) and swelling (n=3), choroidal mass with or without chorioretinal detachment (n=5), and proptosis (n=2). Visual field (VF) examination was performed in 11 patients of which hemianopia (n=4) and non-specific field loss (n=7) were noted. Brain CT or MRI, together with histopathological findings from surgical biopsies confirmed the diagnosis of the intracranial tumors in 18 cases, including pituitary adenoma (n=7), meningioma (n=2), oligodendroglioma (n=1), sellar tumor (n=1), suprachiasmatic arteriovenous aneurysm (n=1), orbital glioma (n=1), multiple intracranial tumors (n=1), and sphenoid ossifying fibroma (n=1). Nasopharyngeal carcinoma (NPC) (n=3) was diagnosed with brain MRI and nasal endoscopy. Five patients were confirmed as choroidal metastasis secondary to lung cancer (n=3), hepatoma (n=1), and breast cancer (n=1). CONCLUSIONS: Patients with extraocular tumors may present initially to an ophthalmologist with ocular symptoms. It is important to identify and appropriately manage these patients to avoid unnecessary delays in future treatment.
RESUMEN
PURPOSE: The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis. METHODS: This study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed. RESULTS: Two SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities. CONCLUSION: This study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.
Asunto(s)
Neovascularización Coroidal/genética , Predisposición Genética a la Enfermedad/genética , Pólipos/genética , Receptor TIE-2/genética , Degeneración Macular Húmeda/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Coroides/irrigación sanguínea , Neovascularización Coroidal/diagnóstico , Femenino , Angiografía con Fluoresceína , Frecuencia de los Genes , Técnicas de Genotipaje , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Pólipos/diagnóstico , Agudeza Visual/fisiología , Degeneración Macular Húmeda/diagnósticoRESUMEN
BACKGROUND: Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are sight-threatening maculopathies with both environmental and genetic risk factors. We have previously shown relative risks posed by genes of the complement pathways to neovascular AMD and PCV. METHODS: In this study, we investigated the haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement component 5 (C5) gene in 708 unrelated Chinese individuals: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Six tagging SNPs in C5 were genotyped. Univariate single SNP association analysis, haplotype-based association analysis and gene-gene interaction analysis between C5 and other AMD-associated genes were performed. RESULTS: The results revealed none of the six tagging SNPs of the C5 gene had a significant association with neovascular AMD or PCV (P > 0.05). We also found insignificant haplotype-based association, and no significant SNP-SNP interaction between C5 and other genes (including C2-CFB-RDBP-SKIV2L, SERPING1, CETP, ABCG1, PGF, ANGPT2, CFH and HTRA1) for neovascular AMD and PCV. CONCLUSIONS: This study showed no statistical significance in the genetic association of C5 with neovascular AMD or PCV in a Hong Kong Chinese population. Further studies in large samples from different populations are warranted to elucidate the role of C5 in the genetic susceptibility of AMD and PCV.
RESUMEN
PURPOSE: Intronic variants in the placental growth factor (PGF) gene have been associated with neovascular age-related macular degeneration (AMD). This study is to discover and characterize rare variants in the PGF gene for neovascular AMD. METHODS: The promoter region, coding sequences and splicing regions of the PGF gene were sequenced in a Hong Kong southern Chinese cohort of 235 neovascular AMD patients and 435 controls. A detected 18 base-pair deletion variant in the promoter region of PGF was analyzed in a Shantou southern Chinese cohort of 189 neovascular AMD patients and 846 controls. The transcription activity of this disease-associated promoter variant was determined in human ARPE-19â¯cells by promoter-luciferase analysis. RESULTS: A novel 18-base-pair deletion mutation in the promoter region of PGF was identified in 3 (1.28%) patients and 1 (0.23%) control subject (ORâ¯=â¯5.61; 95% CI 0.58-54.26) in the Hong Kong cohort, and in 2 (1.06%) patients and 2 (0.24%) controls (ORâ¯=â¯4.51; 95% CI: 0.63-32.25) in the Shantou cohort. In the combined southern Chinese sample, this deletion had a significant association with neovascular AMD (Pâ¯=â¯0.026; ORâ¯=â¯5.08, 95% CI: 1.21-21.36). The 18-base-pair deletion was predicted to alter the transcription factor binding sites in the PGF promoter, and higher luciferase expression was detected in ARPE-19â¯cells transfected with the deletion variant plasmid than those transfected with wild type plasmid (Pâ¯=â¯0.0002). CONCLUSIONS: This study identified a rare, functional promoter variant in the PGF gene that increases PGF transcription activity and confers a 5-fold risk to neovascular AMD.
Asunto(s)
Neovascularización Coroidal/genética , Variación Genética/genética , Factor de Crecimiento Placentario/genética , Regiones Promotoras Genéticas/genética , Degeneración Macular Húmeda/genética , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Secuencia de Bases , Línea Celular , Neovascularización Coroidal/diagnóstico , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Activación Transcripcional , Agudeza Visual , Degeneración Macular Húmeda/diagnósticoAsunto(s)
Oftalmopatías , Degeneración Macular , Calcio , Suplementos Dietéticos , Humanos , MineralesRESUMEN
There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME.
Asunto(s)
Edema Macular/terapia , Retinitis Pigmentosa/complicaciones , Corticoesteroides/uso terapéutico , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Humanos , Coagulación con Láser/métodos , Edema Macular/etiología , Esteroides/uso terapéutico , Vitrectomía/métodosRESUMEN
Dysthyroid optic neuropathy (DON) is the commonest cause of blindness in thyroid associated orbitopathy (TAO). While diagnosis remains clinical, objective tests for eyes with early or equivocal findings are lacking. Various electrophysiological studies (EPS) have been reported, yet the types and parameters useful for DON remain inconclusive. We performed a systematic literature search in MEDLINE, EMBASE and the Cochrane databases via the OVID platform up to August 20, 2017. 437 records were identified for screening and 16 original studies (1327 eyes, 787 patients) were eligible for review. Pattern visual evoked potential (pVEP) was the most frequently studied EPS. Eyes of TAO patients with DON showed delayed P100 latencies, decreased P100 amplitudes or delayed N75 latencies during pVEP, compared to those without or healthy controls. Due to study heterogeneity, no quantitative analysis was possible. This review highlights the most common type (pVEP) and useful parameters (P100 latency and amplitude) of EPS, and supports further research on them using standardized testing conditions.
Asunto(s)
Potenciales Evocados Visuales , Ojo/fisiopatología , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/fisiopatología , Electrorretinografía , Humanos , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/fisiopatología , Agudeza VisualRESUMEN
Angiopoietin 2 (ANG2) is a proangiogenic cytokine which may have an implication in neovascular age related macular degeneration (nAMD). In 24 eyes of 24 subjects presenting with treatment naïve nAMD and 26 eyes of 26 control patients, aqueous humor samples were collected at the time of intervention (intravitreal injection of anti-vascular endothelial growth factor or cataract extraction). Best corrected visual acuity (BCVA) with and central macular thickness (CMT) using optical coherence tomography (OCT) were measured before each injection in the nAMD group. Aqueous cytokine levels were determined by immunoassay using a multiplex array (Quansys Biosciences, Logan, UT). Levels of ANG2 in the aqueous were significantly higher in nAMD patients than those of the control group (p < 0.0001), so were hepatocyte growth factor (HGF), interleukin-8 (IL-8) and tissue inhibitor of metalloproteinase 1 (TIMP 1), all with p < 0.001. ANG2 correlated with worse BCVA (r = 0.44, p-value = 0.027) and greater CMT (r = 0.66, p-value < 0.0001) on optical coherence tomography (OCT). ANG2 is upregulated in patients with nAMD and correlates with severity of disease at presentation.
Asunto(s)
Angiopoyetina 2/metabolismo , Humor Acuoso/metabolismo , Degeneración Macular/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Estudios de Casos y Controles , Femenino , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Interleucina-8/metabolismo , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Agudeza VisualRESUMEN
Purpose: We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). Methods: A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed. Results: In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction. Conclusions: This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.
Asunto(s)
Angiopoyetina 2/genética , Neovascularización Coroidal/genética , ADN/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Degeneración Macular Húmeda/genética , Anciano , Angiopoyetina 2/metabolismo , Coroides/irrigación sanguínea , Coroides/patología , Neovascularización Coroidal/epidemiología , Neovascularización Coroidal/metabolismo , Factor H de Complemento/genética , Factor H de Complemento/metabolismo , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Genotipo , Hong Kong/epidemiología , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Retina/patología , Degeneración Macular Húmeda/epidemiología , Degeneración Macular Húmeda/metabolismoRESUMEN
Polypoidal choroidal vasculopathy is a relatively common type of degenerative macular disease among the Chinese population. This study aims to describe the therapeutic responses to combination therapy with photodynamic therapy, intravitreal aflibercept and intravitreal dexamethasone in patients with polypoidal choroidal vasculopathy. A prospective series of 17 eyes of 13 patients suffering from treatment-naïve polypoidal choroidal vasculoapathy were recruited. All cases received triple therapy with photodynamic therapy, intravitreal aflibercept and intravitreal dexamethasone and one year outcomes were reported. The baseline visual acuity was 0.65logMAR +/- 0.38 (Snellen 20/80 to 20/100). The visual acuity at 1 week, 3 months, 6 months and one year after treatment were significantly improved to 0.522logMAR+/- 0.365 (P < 0.04) (Snellen 20/70), 0.363logMAR+/-0.382 (Snellen 20/50;P < 0.001), 0.377logMAR +/- 0.440 (Snellen 20/50;p = 0.005), and 0.35logMAR +/- 0.407 (Snellen 20/40;P < 0.001), respectively. The baseline central foveal thickness (CFT) on optical coherence tomography (OCT) was 394.7 +/- 70.6 µm. CFT at 6 months and 1 year after treatment were significantly reduced to 259 +/- 54 µm (p = 0.004) and 271 +/- 49.7 µm(p = 0.016), respectively. Triple therapy with photodynamic therapy, intravitreal aflibercept and intravitreal dexamethasone is an effective treatment for polypoidal choroidal vasculopathy. The majority of cases responded well with significant responses observed as early as 1 week after initiation of therapy.
Asunto(s)
Antiinflamatorios/administración & dosificación , Dexametasona/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Fotoquimioterapia/métodos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Quimioterapia Combinada/métodos , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: We investigated the association of the ATP-binding cassette, subfamily G, member 1 (ABCG1) gene with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) in independent Chinese and Japanese cohorts. METHODS: A total of 12 haplotype-tagging single-nucleotide polymorphisms (SNPs) and the SNP rs57137919 in the ABCG1 gene were first analyzed in a Hong Kong Chinese cohort of 235 nAMD, 236 PCV, and 365 controls, using TaqMan genotyping assays. Two SNPs (rs57137919 and rs225396) that showed a disease-association were genotyped in a Shantou Chinese cohort of 189 nAMD, 187 PCV, and 670 controls, and an Osaka Japanese cohort of 192 nAMD, 204 PCV, and 157 controls, totaling 2435 subjects. Association analysis was performed in individual cohorts, followed by a pooled analysis of the data from all three cohorts. RESULTS: In the Hong Kong cohort, SNP rs57137919 was associated with PCV (odds ratio [OR] = 1.35). A tagging SNP rs225396 was associated with nAMD (OR = 1.28) and PCV (OR = 1.32). In the Osaka cohort, SNP rs225396 was associated with nAMD (OR = 1.42) and PCV (OR = 1.74). In the pooled analysis involving the 3 study cohorts, rs225396 showed an enhanced association with nAMD (P = 0.01, OR = 1.21, I2 = 14%) and PCV (P = 0.0001, OR = 1.35, I2 = 46%). CONCLUSIONS: In this study, we have newly identified a haplotype-tagging SNP, rs225396, in ABCG1 to be associated with PCV and nAMD in Chinese and Japanese cohorts. This provides new evidence to support ABCG1 as a susceptibility gene for PCV and nAMD. Further replication in other populations should be warranted.