Person:
Martínez De La Casa Fernández-Borrella, José María

First Name

José María

Last Name

Martínez De La Casa Fernández-Borrella

URI

https://hdl.handle.net/20.500.14352/79989

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Óptica y Optometría

Department

Inmunología, Oftalmología y ORL

Area

Oftalmología

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 22

Corneal aberrations in primary congenital glaucoma and its visual correlation
(International Ophthalmology, 2024) Ly-Yang, Fernando; Morales Fernández, Laura; García Bella, Javier; Garcia Caride, Sara; Santos Bueso, Enrique Miguel; Saenz Frances, Federico; Fernández-Vigo López, José; García Feijoo, Julián; Martínez De La Casa Fernández-Borrella, José María
Primary congenital glaucoma (PCG) can cause permanent vision loss, and its prognosis is related to early detection and treatment. The main pathological defect consists of resistance to aqueous outflow through the trabecular meshwork due to abnormal development of tissue derived from the neural crest in the anterior chamber angle. Even after successful intraocular pressure (IOP) management in PCG poor visual outcomes still present a lifelong challenge. Vision loss in PCG is multifactorial, resulting from optic nerve damage, corneal scarring, and myopic astigmatism associated with anisometropic amblyopia. Although it is already known that children with PCG present with an altered corneal configuration, the knowledge of irregular astigmatism due to high-order aberrations (HOA) and due to the unequal expansion of the anterior segment, and its impact on visual outcomes, is not yet fully understood, to the best of our knowledge. Quality vision is influenced by the presence of aberrations in the eye's optical system, which can degrade the quality of the image projected onto the retina. Low-order aberrations (LOA), including myopia, hyperopia, and regular astigmatism, can be corrected by spectacles, while HOA cannot be corrected by ordinary means. Coma and spherical aberrations are the most visually significant HOAs, while trefoil and other HOAs have a lower impact on visual quality. The purpose of this article is to establish a quantitative correlation between HOA and visual acuity (VA) to measure the magnitude of the impact of the altered cornea on visual outcomes in PCG.
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, Julio
Abnormal 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.
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 María
Objective: 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.
Scheie's line as a first sign of pigment dispersion syndrome
(Archivos de la Sociedad Española de Oftalmología (English Edition), 2019) Santos Bueso, Enrique; García Sáenz, Sofía; Morales Fernández, Laura; Martínez De La Casa Fernández-Borrella, José María; Sáenz Francés, Federico
A 50 year old woman was diagnosed with pigment dispersion syndrome (PDS) in the right eye and pigmentary glaucoma in the left eye in a routine medical examination. A line of pigment was observed in the vitreo-lenticular interface (Scheie's line) of the left eye and with an intraocular pressure of 26 mmHg. The Scheie's line (SL) develops by the accumulation of detached iris pigment in PDS and accumulated in the ligament of Wieger that forms the vitreo-lenticular union. The SL is considered a pathognomonic sign of PDS.
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 María
Purpose: 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.
Tear and aqueous humour cytokine profile in primary open‐angle glaucoma
(Acta Ophthalmologica, 2020) Burgos Blasco, Bárbara; Vidal Villegas, Beatriz; Sáenz Francés, Federico; Morales Fernández, Laura; Perucho González, Lucía; García Feijoo, Julián; Martínez De La Casa Fernández-Borrella, José María
Purpose: To evaluate the concentrations of pro‐inflammatory cytokines in tear and aqueous humour of patients with primary open‐angle glaucoma (POAG), relative to healthy controls. Method: Tear and aqueous humour samples were collected from 29 healthy controls and 27 POAG patients. Twenty‐seven inflammatory cytokines were analysed: interleukin (IL)‐1β, IL‐1ra, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL9, IL‐10, IL‐12, IL‐13, IL‐15, IL‐17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony‐stimulating factor, granulocyte‐monocyte colony‐stimulating factor, interferon (IFN)‐γ, interferon gamma‐induced protein, monocyte chemo‐attractant protein‐1, macrophage inflammatory protein (MIP)‐1α, MIP‐1β, platelet‐derived growth factor, regulated on activation normal T cell expressed and secreted, tumour necrosis factor (TNF)‐α and vascular endothelial growth factor (VEGF). Results: In tear samples of glaucoma patients, an increase in IL‐4, IL‐12, IL‐15, FGF‐basic and VEGF was observed, as well as a decrease in MIP‐1a relative to the control group (p < 0.05). IL‐5, IL‐12, IL‐15, IFN‐γ and MIP‐1a were significantly higher in aqueous humour of glaucoma eyes (p < 0.05). A poor correlation between cytokine levels in tear and aqueous humour was observed. Conclusion: The different profiles of inflammatory marker expression of patients with POAG and healthy controls confirm the inflammatory activity of the pathology, indicating that some of them could be used as potential biomarkers of this disease.
Clinical Variability of Primary Congenital Glaucoma in a Spanish Family With Cyp1b1 Gene Mutations
(Journal of Glaucoma, 2015) Morales Fernández, Laura; Martínez De La Casa Fernández-Borrella, José María; García Bella, Javier; Méndez Hernández, Carmen D.; Saenz Frances, Federico; García Antón, Maite; Escribano, Julio; García Feijoo, Julián
Background: Primary congenital glaucoma (PCG) is a rare disease. In around a third of Spanish patients, the disease is attributed to mutations in the CYP1B1 gene inherited in an autosomal recessive manner. Such mutations are the main known genetic cause of PCG. Case Report: We describe the case of a family with 3 of 7 siblings diagnosed with PCG. In a genetic study of the CYP1B1 gene, 2 null mutations were identified in the affected siblings (R355fsX69/T404fsX38). Two of the 4 healthy siblings were heterozygous for mutation R355fsX69 and the remaining 2 had no mutations. The healthy parents were found to be heterozygous for mutations T404fsX38 (mother) and R355fsX69 (father). High variation in the expression of PCG was observed, especially in terms of disease onset and severity: Patient 1 in the eldest affected sibling, PCG was diagnosed at 8 years of age and is presently stable after 60 months of medical treatment; patient 2 the second affected child underwent surgery at 7 days of age. Today, at 104 months, she has undergone 2 operations on the right eye and 3 on the left eye; patient 3 the youngest sibling, the disease also manifested at birth and the boy underwent surgery at 4 days. Currently he is 84 months old, he has required 7 operations for glaucoma, 3 in the right eye and 4 in the left. Conclusions: This clinical case reveals the etiological relationship between CYP1B1 mutations and PCG. In addition, it indicates a highly variable clinical picture associated with a single disease genotype mainly affecting disease onset and progression.
Corneal Segmentation Analysis Increases Glaucoma Diagnostic Ability of Optic Nerve Head Examination, Heidelberg Retina Tomograph's Moorfield's Regression Analysis, and Glaucoma Probability Score
(Journal of Ophthalmology, 2015) Sáenz Francés, Federico; Jañez Escalada, Luis; Berrozpe Villabona, Clara; Borrego Sanz, Lara; Morales Fernández, Laura; Acebal Montero, Alejandra; Méndez Hernández, Carmen D.; Martínez De La Casa Fernández-Borrella, José María; Santos Bueso, Enrique Miguel; García Sánchez, Julián; García Feijoo, Julián
Purpose. To study whether a corneal thickness segmentation model, consisting in a central circular zone of 1 mm radius centered at the corneal apex (zone I) and five concentric rings of 1 mm width (moving outwards: zones II to VI), could boost the diagnostic accuracy of Heidelberg Retina Tomograph's (HRT's) MRA and GPS. Material and Methods. Cross-sectional study. 121 healthy volunteers and 125 patients with primary open-angle glaucoma. Six binary multivariate logistic regression models were constructed (MOD-A1, MOD-A2, MOD-B1, MOD-B2, MOD-C1, and MOD-C2). The dependent variable was the presence of glaucoma. In MOD-A1, the predictor was the result (presence of glaucoma) of the analysis of the stereophotography of the optic nerve head (ONH). In MOD-B1 and MOD-C1, the predictor was the result of the MRA and GPS, respectively. In MOD-B2 and MOD-C2, the predictors were the same along with corneal variables: central, overall, and zones I to VI thicknesses. This scheme was reproduced for model MOD-A2 (stereophotography along with corneal variables). Models were compared using the area under the receiver operator characteristic curve (AUC). Results. MOD-A1-AUC: 0.771; MOD-A2-AUC: 0.88; MOD-B1-AUC: 0.736; MOD-B2-AUC: 0.845; MOD-C1-AUC: 0.712; MOD-C2-AUC: 0.838. Conclusion. Corneal thickness variables enhance ONH assessment and HRT's MRA and GPS diagnostic capacity.
Corneal Properties in Primary Open Angle Glaucoma Assessed Through Scheimpflug Corneal Topography and Densitometry
(Journal of Glaucoma, 2020) Molero Senosiain, Mercedes; Morales Fernández, Laura; Sáenz Francés, Federico; Perucho González, Lucía; García Bella, Javier; García Feijoo, Julián; Martínez De La Casa Fernández-Borrella, José María
Purpose: To compare corneal topography and densitometry measurements in patients with primary open angle glaucoma (POAG) and healthy subjects. Patients and Methods: 200 eyes of 75 patients with POAG and 125 healthy controls underwent corneal topography and densitometry (Oculus Pentacam HR). The data compared in the two groups were: anterior chamber angle (ACA), depth (ACD) and volume (ACV), keratometry (K minimum, K maximum and K mean), central corneal thickness (CCT), central anterior elevation (CAE), anterior elevation apex (AEA), maximum anterior elevation (MAE) and posterior elevation apex (PEA). Densitometry measurements were made at three depths on a 12▒mm-diameter circle divided into 4 concentric rings (0-2▒mm, 2-6▒mm, 6-10▒mm and 10-12▒mm). The diagnostic capacity of the corneal variables was assessed through the areas under the receiver operator characteristics (ROC) curve (AUC). Results: The corneal density of practically all depth layers and total corneal density were significantly higher in the POAG than control group (P<0.05). Total corneal density was positively correlated with age (r=0.623; P<0.001) and also showed a good diagnostic capacity for glaucoma (AUC=0.617; IC 95% [0.541-0.697]; P<0.001). In a multiple linear regression designed to assess its relationship with age, gender, CCT and Km, age emerged as a significant confounder both in controls (coef. 0.315; P<0.001; 95% CI [0.246-0.384]) and patients (coef. 0.370; P<0.001; 95% CI [0.255-0.486]). Conclusion: Corneal densitometry measurements showed a good diagnostic capacity for POAG suggesting this type of examination could have clinical applications in the diagnosis and management of glaucoma.
Correlations between corneal and optic nerve head variables in healthy subjects and patients with primary open angle glaucoma
(International journal of ophthalmology, 2015) Sáenz Francés, Federico; Jañez Escalada, Luis; Borrego Sanz, Lara; Berrozpe Villabona, Clara; Martínez De La Casa Fernández-Borrella, José María; Morales Fernández, Laura; García Sánchez, Julián; Santos Bueso, Enrique Miguel; García Feijoo, Julián
AIM: To correlate corneal variables (determined using the Pentacam) with optic nerve head (ONH) variables determined using the Heidelberg retina tomograph (HRT) in healthy subjects and patients diagnosed with primary open angle glaucoma (POAG). METHODS: Measurements were made in 75 healthy eyes and 73 eyes with POAG and correlations examined through Pearson correlation coefficients between the two sets of variables in the two subject groups. The corneal variables determined were corneal volume (CVol), central corneal thickness (CCT), overall corneal thickness (OvCT), the mean thickness of a circular zone centered at the corneal apex of 1 mm radius (zone I) and the mean thickness of several concentric rings, also centered at the apex until the limbus, each of 1 mm width (zones II to VI respectively). The ONH variables were determined using the HRT. RESULTS: The following pairs of variables were correlated in the control group: CCT-disc area (DAr) (-0.48; P<0.0001), Zone I-DAr (-0.503; P<0.0001) and Zone II-DAr (-0.443; P<0.0001); and in the POAG group: CCT-cup-to-disc area ratio (CDRa) (-0.402; P<0.0001), Zone I-CDRa (-0.418; P<0.0001), Zone II-CDRa (-0.405; P=0.006), Zone I-cup shape measure (CSM) (-0.415; P=0.002), Zone II-CSM (-0.405; P=0.001), Zone IV-height variation contour (HVC) (0.378; P=0.002); Zone V-HVC (0.388, P<0.0001). CONCLUSION: AS-OCT-derived lens thickness measurement is valid and comparable to the results obtained by A-scan US. It can be used as a reliable noncontact method for measuring lens thickness in adults with or without significant cataract.