Person: Méndez Hernández, Carmen Dora
Loading...
First Name
Carmen Dora
Last Name
Méndez Hernández
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Oftalmología
Identifiers
10 results
Search Results
Now showing 1 - 10 of 10
Item CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix(Human Genetics, 2020) Bonet Fernández, Juan Manuel; Aroca Aguilar, José Daniel; Corton Pérez, Marta; Ramírez Sebastián, Ana Isabel; Alexandre Moreno, Susana; García Antón, María Teresa; Salazar Corral, Juan José; Ferre Fernández, Jesús José; Atienzar Aroca, Raquel; Villaverde Montero, Cristina; Iancu, Ionut; Tamayo Durán, Alejandra; Méndez Hernández, Carmen Dora; Morales Fernández, Laura; Rojas López, Blanca; Ayuso García, Carmen; Coca Prados, Miguel; Martínez De La Casa Fernández-Borrella, José María; García Feijoo, Julián; Escribano, JulioAbnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients’ features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene.Item Comparision of intraocular pressure measured using the new icare 200™ rebound tonometer and the Perkins™ applanation tonometer in healthy subjects and in patients with primary congenital glaucoma(Archivos de la Sociedad Española de Oftalmología (English Edition), 2021) Pérez García, Pilar; Morales Fernández, Laura; Sáenz Francés, Federico; Méndez Hernández, Carmen Dora; García Feijoo, Julián; Santos Bueso, Enrique; Martínez De La Casa Fernández-Borrella, José MaríaObjective: To compare intraocular pressure (IOP) measurements obtained using the Icare 200™ (IC200) rebound tonometer and the hand-held version of the Goldmann Applanation Tonometer (Perkins™ tonometer, GAT) in patients with primary congenital glaucoma (PCG) and in healthy subjects. Material and methods: A total of 42 eyes of healthy subjects (G1) and 40 patients with PCG (G2) were analysed. The following clinical data were collected: gender, age, Cup/Disc ratio, central corneal thickness (CCT). IOP was determined in the examination room using the IC200 and GAT tonometers, in the same order. Agreement between both tonometers was determined using the intraclass correlation coefficient (ICC) and Bland-Altman plot. A linear regression analysis was used to establish the IOP was affected by the studied variables. Results: Mean IOP between both tonometers (IC200 minus GAT) was: G1 = 15.91 (2.57) mmHg vs. 15.06 (2.12) mmHg (mean difference, MD = 0.84 (0.50) mmHg; P < .101) and G2=20.10 (6.37) vs.19.12 (5.62) (MD = 0.98 (1.36); P = 0.474). Excellent agreement was found between IC200 and GAT in both groups (ICC = G1: 0.875 (95% CI; 0.768−0.933; P < .001); G2: 0.924 (95% CI; 0.852−0.961; P < .001), and there was a statistically significant correlation between the IOP difference measured with IC200 and GAT and CCT in G1 (B=0.021; 95% CI; 0.005–0.037; P = .008), but was not statistically significant in G2. Conclusions: There was excellent agreement between the IC200 and GAT tonometers, both in healthy subjects and PCG, with a trend to overestimate IOP when measured with IC200. There was no influence by CCT on IOP measurements in patients with PGC.Item Agreement between rebound (Icare ic200) and applanation tonometry (Perkins) in patients with primary congenital glaucoma(Acta Ophthalmologica, 2020) Morales Fernández, Laura; Pérez García, Pilar; Sáenz Francés, Federico; Molero Senosiain, Mercedes; García Sáenz, Sofía; Méndez Hernández, Carmen Dora; Santos Bueso, Enrique; García Feijoo, Julián; Martínez De La Casa Fernández-Borrella, José MaríaPurpose: To examine agreement between intraocular pressure (IOP) measurements made using the rebound tonometer Icare ic200 (RT200) and the Perkins handheld applanation tonometer (PAT) in patients with primary congenital glaucoma (PCG). The impacts of several covariables on measurements using the two devices were also assessed. Materials and Methods: Intraocular pressure measurements were made in a single session in 86 eyes of 86 patients with PCG (46 under anaesthesia, 40 in the office). The order was RT200 then PAT. The variables age, central corneal thickness (CCT), corneal state and anaesthesia were recorded in each patient. Data were compared by determining interclass correlation coefficients (ICC) for each tonometer and representing the differences detected as Bland–Altman plots. Effects of covariables were assessed through univariate and multivariate regression. Results: Mean IOP difference between tonometers (RT200 minus PAT) was 1.26 mmHg (95%: 0.22–2.31). Absolute agreement (ICC) was 0.73 (95% CI: 0.62–0.82). Lower and upper limits of agreement (95%) were −8.06 mmHg (95% CI: −9.87 to −6.25) and 10.59 mmHg (95% CI: 8.77–12.40), respectively. The tonometers showed systematic differences (a = −4.63 mmHg; 95% CI: −9.11 to −1.44) and proportional differences; for each mmHg increase in PAT‐IOP, the RT200 reading increased by 1.28 mmHg (b = 1.28; 95% CI: 1.12–1.53). None of the variables tested as predictors were able to explain differences between the tonometers. Conclusions: Despite the good overall agreement between both tonometers, caution should be taken in high values of IOP, considering the interchangeability of its readings as systematic and proportional differences appear to exist between both methods.Item Evaluation of a Novel Αb Εxterno MicroShunt for the Treatment of Glaucoma(Advances in Therapy, 2022) Burgos Blasco, Bárbara; García Feijoo, Julián; Perucho González, Lucía; Güemes Villahoz, Noemi; Morales Fernández, Laura; Méndez Hernández, Carmen Dora; Martínez De La Casa Fernández-Borrella, José María; Konstas, Anastasios GeorgiosThe surgical management of glaucoma has been revolutionized by the introduction of minimally invasive glaucoma surgery (MIGS). The various MIGS options aim to meaningfully lower intraocular pressure with a better safety profile than traditional glaucoma surgery. The key clinical attributes and the emerging potential of an ab externo MicroShunt (PreserFlo™) are reviewed in the context of published evidence and clinical experience. This novel MicroShunt consists of an 8.5-mm-long tube that is implanted in the eye via an ab externo approach enabling aqueous humor drainage into the sub-Tenon's space through the formation of a bleb, similar in appearance to that created by trabeculectomy. The efficacy and safety of this procedure, the concomitant use of antimetabolites, the impact of tube positioning, and its future value in clinical practice are critically reviewed. Recent evidence has demonstrated the MicroShunt to be less effective than traditional filtration surgery, but with a significant improvement in safety. Cumulative data suggest that the new implant provides tangible clinical benefits to selected patients with glaucoma in need of further intraocular pressure (IOP) lowering. Future research should delineate the precise role of this and other MIGS options in the rapidly evolving glaucoma treatment algorithm.Item Efficacy and safety of the PreserFlo implant with mitomycin C in childhood glaucoma after previous failed glaucoma surgeries(Graefe's Archive for Clinical and Experimental Ophthalmology, 2023) Burgos Blasco, Bárbara; García Feijoo, Julián; Ginés Gallego, Cristina; Perucho González, Lucía; Fernández Vigo, José Ignacio; Martínez De La Casa Fernández-Borrella, José María; Sáenz Francés, Federico; Morales Fernández, Laura; Méndez Hernández, Carmen DoraPurpose: This study aims to evaluate the efficacy and safety of the PreserFlo MicroShunt (Santen, Osaka, Japan) in lowering intraocular pressure (IOP) in childhood glaucoma patients with previous failed glaucoma surgeries. Methods: This is a prospective case review of consecutive PreserFlo procedures performed in childhood glaucoma patients after failed surgeries. Age, sex, diagnosis, and previous glaucoma surgeries, as well as visual acuity, IOP, and treatment in the preoperative visit and all follow-up visits were collected. Outcome measures included IOP reduction from baseline, mean IOP change from baseline at month 6, medication use at 6 months, complications, adverse events, and need for further procedures. Results: Fourteen patients were included, 8 (57%) males and 6 (43%) females; the mean age was 27.5 ± 13.5 years. Nine patients (64%) had at least two trabeculectomies, and 6 patients (43%) had at least one trabeculectomy and a glaucoma drainage implant. The mean IOP change from baseline was 11.3 ± 4.9 mmHg at 12 months. At 12 months, 12 patients (86%) presented ≥ 20% IOP lowering from baseline, and 11 patients (79%) presented ≥ 30%. The mean medication count decreased from 3.9 ± 0.7 (baseline) to 0.7 ± 1.3 (12 months). No intraoperative complications were reported. No adverse events were noted. No secondary filtration surgery was required, although bleb needling was required in one case, 1 month after the surgery. Conclusions: PreserFlo with MMC can be used successfully to treat uncontrolled IOP in childhood glaucoma cases with previous failed surgeries. Larger studies with longer follow-up are needed to further explore the role of the device in resistant childhood glaucoma cases.Item Clinical outcomes of combined Preserflo Microshunt implantation and cataract surgery in open-angle glaucoma patients(Scientific reports, 2021) Martínez De La Casa Fernández-Borrella, José María; Sáenz Francés, Federico; Morales Fernández, Laura; Perucho González, Lucía; Méndez Hernández, Carmen Dora; Fernández Vidal, Ana M.; García Sáenz, Sofía; Sánchez Jean, Rubén; García Feijoo, JuliánTo assess the effectiveness and safety of the Preserflo Microshunt (PMS) implantation combined with cataract surgery in open-angle glaucoma (OAG) patients. Retrospective, open-label study conducted on insufficiently controlled OAG patients, who underwent a PMS implant procedure with mitomycin-C 0.2%, either alone or in combination with cataract surgery, and were followed for at least 12 months. Success was defined as an intraocular pressure (IOP) ≤ 18 mmHg and a reduction of at least 20% without (complete) or with (qualified) hypotensive medication. Fifty-eight eyes were included in the study, 35 eyes underwent PMS alone and 23 underwent PMS + Phaco. In the overall study sample, mean IOP was significantly lowered from 21.5 ± 3.3 mmHg at baseline to 14.6 ± 3.5 mmHg at month 12 (p < 0.0001). The IOP was significantly reduced in both groups; p < 0.0001 each, respectively. Ocular hypotensive medication was significantly reduced (p < 0.0001) in both groups. No significant differences were observed in IOP lowering or medication reduction between groups. At month 12, 62.1% eyes were considered as complete success and 82.8% eyes as qualified success. The most common adverse events were device close-to-endothelium, conjunctival fibrosis, and wound leakage. PMS, either alone or in combination with phacoemulsification, may be considered as a valuable option for treating OAG patients.Item Charles Bonnet syndrome in a child with congenital glaucoma(Archivos de la Sociedad Española de Oftalmología, 2017) Santos Bueso, Enrique Miguel; Serrador García, Mercedes; Sáenz Francés, Federico; Méndez Hernández, Carmen Dora; Morales Fernández, Laura; Martínez De La Casa Fernández-Borrella, José María; García Feijoo, Julián; Porta-Etessam, JesúsCase report: The case is presented of a 12 year-old boy with congenital glaucoma and low visual acuity diagnosed with Charles Bonnet syndrome. This consisted of the acute onset of complex, repetitive, persistent, and with visual hallucinations (people, brooms and coffeemakers) of self-limited evolution without treatment. The patient was diagnosed with congenital glaucoma at 3 years of age, and subjected to a trabeculectomy in right eye, and trabeculectomy and keratoplasty in his left eye. Discussion: Charles Bonnet syndrome symptoms have been described in adults, but their presence in children is poorly reflected in literature, with unknown characteristics and prevalence.Item Retinal nerve fiber layer thickness in children with primary congenital glaucoma measured by spectral domain optical coherence tomography(Journal of American Association for Pediatric Ophthalmology and Strabismus, 2019) Perucho González, Lucía; Martínez De La Casa Fernández-Borrella, José María; Sáenz Francés, Federico; Morales Fernández, Laura; Méndez Hernández, Carmen Dora; Sánchez Jean, Rubén; García Feijoo, JuliánPurpose: To evaluate retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) in a population of children diagnosed with primary congenital glaucoma (PCG). Methods: In this cross-sectional study, 59 eyes of 59 children diagnosed with PCG and 87 eyes of 87 healthy children were evaluated by SD-OCT to measure the RNFL. The global average peripapillary RNFL thickness and sectional RNFL thickness were evaluated in both groups. Differences in global average and sectional thickness were analyzed. Results: Mean age in the PCG group was 9.61 ± 3.23 years; in the control group, 8.47 ± 2.99 years (P = 0.0516). There were statistically significant differences (P < 0.007) in all sectors between both groups. Conclusions: SD-OCT is a promising tool for evaluating the eyes of children diagnosed with PCG. Future research should examine the test–retest variability of SD-OCT parameters and their ability to diagnose progression in these children.Item Structural and biomechanical corneal differences between patients suffering from primary congenital glaucoma and healthy volunteers(Acta Ophthalmologica, 2017) Perucho González, Lucía; Sáenz Francés, Federico; Morales Fernández, Laura; Martínez De La Casa Fernández-Borrella, José María; Méndez Hernández, Carmen Dora; Santos Bueso, Enrique Miguel; Brookes, John L.; García Feijoo, JuliánPurpose: To determine whether a set of ocular morphometric and biomechanical variables are able to discriminate between healthy volunteers and patients suffering from primary congenital glaucoma (PCG). Methods: Case-control study in which 66 patients with PCG and 94 age-matched healthy subjects were evaluated using ocular response analyser (ORA) to record corneal biomechanical properties. Topographic corneal variables were obtained using the Pentacam in both groups. To determine the ability to discern between both groups, a multivariate binary logistic model was constructed. The outcome was the diagnosis of PCG and the predictors; the corneal variables analysed along with their first-term interactions. Sensitivity and specificity of this model along with the area under the receiver characteristic operating curve (AUC of ROC) were determined. Results: The best model to discriminate between both groups included the following predictors: corneal hysteresis (CH), corneal resistance factor (CRF), posterior maximum elevation (PME), anterior maximum elevation (AME) and central corneal thickness (CCT). This model, for a cut-point of 50%, presents a sensitivity of 86.67%, a specificity of 86.89% and an AUC of the ROC curve of 93.16% [95% confidence interval (CI): 88.97-97.35]. The adjusted odds ratios of those predictors which showed a significant discriminating capacity were as follows: for CH, 0.27 (95% confidence interval: 0.15-0.46); for CRF, 2.13 (95% CI: 1.33-3.40); for PME, 1.06 (95% CI: 1.01-1.12); and for AME, 1.35 (95% CI: 1.10-1.66). Conclusion: Corneal hysteresis (CH), CRF, PME and AME are able to discern between patients with PCG and healthy controls. This fact suggests that there are structural and biomechanical differences between these groups.Item The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease(2024) Tevar, Ángel; Aroca Aguilar, José Daniel; Bonet Fernández, Juan Manuel; Atienzar Aroca, Raquel; Campos Mollo, Ezequiel; Morales Fernández, Laura; Leal Palmer, Iñaki; Coca Prados, Miguel; Escribano, Julio; Méndez Hernández, Carmen Dora; Martínez De La Casa Fernández-Borrella, José María; García Feijoo, JuliánChildhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual impairment with poorly understood genetic basis. Our goal was to identify gene variants associated with these glaucoma types by assessing the mutational burden in 76 matrix metalloproteinase-related genes. We studied 101 childhood glaucoma patients with no identified monogenic alterations using next-generation sequencing. Gene expression was assessed through immunohistochemistry. Functional analysis of selected gene variants was conducted in cultured cells and in zebrafish. Patients presented a higher proportion of rare variants in four metalloproteinase-related genes, including CPAMD8 and ADAMTSL4, compared to controls. ADAMTSL4 protein expression was observed in the anterior segment of both the adult human and zebrafish larvae's eye, including tissues associated with glaucoma. In HEK-293T cells, expression of four ADAMTSL4 variants identified in this study showed that two variants (p.Arg774Trp and p.Arg98Trp) accumulated intracellularly, inducing endoplasmic reticulum stress. Additionally, overexpressing these ADAMTSL4 variants in zebrafish embryos confirmed partial loss-of-function effects for p.Ser719Leu and p.Arg1083His. Double heterozygous functional suppression of adamtsl4 and cpamd8 zebrafish orthologs resulted in reduced volume of both the anterior eye chamber and lens within the chamber, supporting a genetic interaction between these genes. Our findings suggest that accumulation of partial functional defects in matrix metalloproteinases-related genes may contribute to increased susceptibility to early-onset glaucoma and provide further evidence supporting the notion of a complex genetic inheritance pattern underlying the disease.