bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal maculo‐papillary OCT and hippocampal and others cerebral areas MRI in subjects with a family history of Alzheimer's disease and allelic characterization for ApoE ɛ4
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , Salobrar‐Garcia Elena , Elvira‐Hurtado Lorena , Fernández‐Albarral José A. , Lozano María Pilar Rojas , Ramirez Ana Isabel , Salazar Juan Jose , Marcos‐Dolado Aberto , Fuertes Miguel Yus , Barabash Ana , Ramírez‐Toraño Federico , De Hoz Rosa , Ramirez Jose Manuel
Published: December 2022

Purpose: In addition to advanced age, genetic inheritance is another predisposing factor for the development of Alzheimer's disease (AD). Retinal changes already exist in preclinical stages, so the aim of this study was to analyse possible retinal changes in subjects at high risk of developing AD using OCT and correlate them with brain areas analysed by magnetic resonance imaging (MRI).

Methods: Macular and peripapillary OCT and brain MRI were performed in 64 cognitively healthy subjects. 30 controls were subjects with no family history of AD and carrying no ApoE ɛ4 allele (FH− ApoE ɛ4−), while 34 subjects had an affected first‐degree relative and at least one ɛ4 allele (FH+ ApoE ɛ4+).

Results: We observed in the FH+ ApoE ɛ4+ group compared to the control group a significant volume reduction in the following macular areas: (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL); (iii) inner nuclear layer (INL) and (iv) outer plexiform layer (OPL). Moreover, in the FH+ ApoE ɛ4+ group the retinal sectors that showed a statistically significant decrease in volume correlated with brain areas that are affected in the early stages of AD, such as the lingual gyrus, the hippocampal region and the entorhinal cortex. In the same group, no statistically significant changes in thickness were found in the peripapillary retinal nerve fibre layer (pRNFL) compared to the control group. However, correlations of these sectors with brain areas involved in this pathology were also found.

Conclusions: In cognitively healthy subjects at high genetic risk of developing sporadic forms of AD, there are significant correlations between the changes observed in the retina and brain areas closely related to AD, such as the lingual gyrus, the hippocampal area and the entorhinal cortex.
Corneal fine‐needle diathermy with intrastromal and subconjunctival injection of bevacizumab in a child with corneal neovascularization of herpetic origin
Authors: Rivasés Guillermo Pérez , El Bakkali Ismael Bakkali , De Rivas Marta Orejudo , Arias Pablo Cisneros , Moscarda Eva Josefina Nuñez , Claveria Julia Aramburu , Fernandez Miguel Castillo , Martinez Marta Suñer , Millán Patricia Ramiro , Puyuelo Javier Ascaso
Published: December 2022

Purpose: Corneal neovascularization (CNV) in the paediatric population has a variety of etiologies including bacterial ulcers, herpes keratitis, exposure keratopathy, blepharokeratoconjunctivitis and corneal anaesthesia. Monotherapy with antiangiogenic agents or corneal fine‐needle diathermy (FND) alone do not completely resolve CNV; however, the combined treatment of these two seems to offer better results.

Methods: We present the results of FND with adjuvant injection of intrastromal and subconjunctival Bevacizumab in a child with CNV of herpetic origin.

Results: A 3‐year‐old patient who has been treated in our hospital for corneal involvement in the left eye (LE) due to herpetic keratitis of weeks of evolution comes to our consultation. Examination under general anaesthesia reveals in LE an inferior paracentral corneal leukoma with partial involvement of the visual axis and CNV that enters through the limbus from 5 to 8 h and begins to involve corneal stroma; no epithelial lesions, no corneal oedema or inflammatory activity in the anterior segment. After not improvement, it was decided to perform FND of lower CNV in conjunction with an intrastromal injection and another subconjunctival injection of Bevacizumab. Subsequently, it remains stable with topical and oral antiherpetic treatment, and topical corticosteroid therapy. At 3 months, the CNV reactivated, for which FND + intrastromal and subconjunctival bevacizumab was performed again. Finally, at 2 months, the patient is asymptomatic with VA LE of 1.0, with 2 corneal leukomas without CNV or epithelial lesions, and continues to be treated with oral acyclovir at prophylactic doses.

Conclusions: FND of CNV together with adjuvant treatment with intrastromal and subconjunctival Bevacizumab is a good choice in children to treat those active corneal neovascularizations that do not respond to corticosteroid.

References

1. Yeung SN, Lichtinger A, Kim P, Amiran MD, Slomovic AR. Combined use of subconjunctival and intracorneal bevacizumab injection for corneal neovascularization. Cornea. 2011; 30(10): 1110–4.

2. Koenig Y, Bock F, Kruse FE, Stock K, Cursiefen C. Angioregressive pretreatment of mature corneal blood vessels before keratoplasty: Fine‐needle vessel coagulation combined with Anti‐VEGFs. Cornea. 2012; 31(8): 887–92.
Evaluation of intravitreal injection of blank microspheres in a new chronic glaucoma rat model
Authors: Aragón Alba , Garcia‐Herranz David , Rodrigo Maria Jesus , Perié Manuel Subías , Mendez‐Martínez Silvia , Arias Lorena , Munuera Ines , García‐Feijoó Julián , Pablo Luis E. , Garcia‐Martin Elena , Vanrell Rocío Herrero , Bravo‐Osuna Irene
Published: December 2022

Purpose: To evaluate the intravitreal injection of PLGA/VitE non‐loaded microspheres as a potential platform to deliver neuroprotective active compounds in a chronic glaucoma animal model. In this model, a gradual increase in intraocular pressure (IOP) is observed due to physical and pharmacological damage to the trabecular meshwork by the intracameral injection of fibronectin‐loaded PLGA microspheres.

Methods: Microspheres (Ms) employed to create the animal model were made by a double water‐in‐oil‐in‐water emulsion technique where fibronectin was included in the inner aqueous phase (F‐Ms). PLGA/VitE blank Ms (B‐Ms) were made by a single oil‐in‐water emulsion. Ms were characterized regarding mean particle size, particle size distribution and morphology. In vivo studies were carried out in Long‐Evans rats divided into two groups: control (n = 30) and treated (n = 20). To create the model, both groups received a single intracameral injection of F‐Ms suspension (10% w/v) in the right eye (RE). Two weeks later, a suspension of B‐Ms (5% w/v) was intravitreally injected into the RE (treated group). Clinical signs and IOP were assessed in both groups for 12 weeks.

Results: Ms were spherical with a smooth surface and some porous in the case of F‐Ms and with a typical “golf‐ball like” surface in the case of B‐Ms. Size distribution was unimodal with an average size of 16.45 ± 0.37 μm for F‐Ms and 29.95 ± 0.42 μm for B‐Ms. Both ocular injections were well tolerated. In all cases, IOP values significantly increased over time (p < 0.05) with a rise of 6–7 mmHg at 12 weeks. No significant differences were found between the IOP in the treated and the control group.

Conclusions: Intravitreal injections of B‐Ms were well tolerated and did not affect the IOP increase of the animal model. These findings underline the suitability of the glaucoma animal model created by the intracameral injection F‐Ms for the evaluation of treatments based on intravitreal injection of PLGA/VitE‐based microsystems.
Inter‐Observer variability in MRI‐based target volume delineation of uveal melanoma
Authors: Beenakker Jan‐Willem , Jaarsma‐Coes Myriam , Klaassen Lisa , Verbist Berit , Vu Khanh , Klaver Yvonne , Rodrigues Myra , Nabarro Claire , Luyten Gre , van Herk Marcel , Rasch Coen
Published: December 2022

Purpose: Several efforts are being undertaken towards MRI‐based treatment planning for ocular proton therapy for uveal melanoma (UM). The inter‐observer variability of the gross target volume (GTV) on MRI is one of the important parameters to design safety margins for a reliable treatment. Therefore, this study assessed the inter‐observer variation in tumour delineation of UM on MRI.

Methods: Six observers delineated the tumour in 10 different UM patients using the Big Brother contouring software. Patients were scanned at 3 T MRI with a surface coil and tumours were delineated separately on contrast enhanced 3DT1 (T1gd) and 3DT2‐weighted scans with a resolution of 0.8 mm isotropic for the acquisition voxels (1). Volume difference and overall local variation were analysed for each patient. Additionally the local variation was analysed for four interfaces: sclera, vitreous, retinal detachment, and tumour‐choroid interface.

Results: The average tumour contour was significantly larger on T1gd (0.57 cm3) compared to T2 (0.51cm3, p = 0.01). A not significant higher interobserver variation was found on T1gd (0.4 1 mm) compared to T2 (0.35 mm). The largest variations were found at the tumour‐choroid interface, due to peritumoral enhancement (T1gd: 0.62 mm and T2: 0.5 2 mm). As a result, a larger part of this tumour‐choroid interface appeared to be included on T1gd based GTVs compared to T2, explaining the smaller volumes on T2.

Conclusions: The interobserver variation of 0.4 mm on MRI are low with respect to the voxel size of 0.8 mm. We recommend to delineate based on the T1gd‐weighted scans, as choroidal tumour extensions might be missed.

Reference

1. Ferreira, et al. MR imaging characteristics of uveal melanoma with histopathological validation. Neuroradiology. 2022; 64:171. doi: 10.1007/s00234‐021‐02825‐5.
Horizontal diplopia with right abducens palsy and gaze evoked nystagmus due to pontine lesion in human immunodeficiency virus related cerebral toxoplasmosis
Authors: Damanik Hidris , Wulandari Lely Retno , Vierlia Wino Vrieda
Published: December 2022

Purpose: This case report will discuss about the diagnostic approach in a rare case of horizontal diplopia with Human Immunodeficiency Virus (HIV) related Cerebral Toxoplasmosis.

Methods: The diagnosis was based on history taking, ophthalmologic examinations, vestibular‐ocular reflex (VOR) test, convergence test, nystagmus test, cerebellar function test, serological findings and magnetic resonance imaging (MRI) of head and orbita.

Results: A 30 years old man with the main complaint binocular horizontal diplopia since 2 months ago, accompanied by headache, disorder of coordination, balance, speech and also impaired of memory and concentration. There was history of head injury and promiscuity. Visual acuity of both eyes 6/6 with best corrected visual acuity. There were abduction deficit on right eye, abducting nystagmus on left eye, no vestibular‐ocular reflex, no convergence insufficiency and no dysfunction of cerebellar. Immunoglobulin‐G antibodies Toxoplasma >650.0 IU/ml, Cluster Determinant 4 (CD4) T cell 55 cells/μl, and HIV reactive in serological findings. MRI of head and orbita revealed a lesion on pontine tegmentum. Patient was diagnosed with horizontal diplopia with right abducens palsy and gaze evoked nystagmus due to pontine lesion in HIV related cerebral toxoplasmosis.

Conclusions: History taking and ophthalmologic examinations are important steps to establish the diagnosis. VOR test can determine the lesion in supranuclear, nuclear or infranuclear. Serological tests and MRI of head and orbita may be helpful in confirming the diagnosis and finding the cause of binocular horizontal diplopia.
Choroidal haemangioma and its multimodal diagnosis: A case report
Authors: Rivasés Guillermo Pérez , El Bakkali Ismael Bakkali , De Rivas Marta Orejudo , Arias Pablo Cisneros , Moscarda Eva Josefina Nuñez , Clavería Julia Aramburu , Fernandez Miguel Castillo , Martinez Marta Suñer , Floria Olivia Esteban , Puyuelo Javier Ascaso
Published: December 2022

Purpose: To describe the clinical manifestations and diagnosis of choroidal haemangioma with the aid of different multimodal images, as well as its usefulness for making a differential diagnosis.

Methods: A case of a patient who comes due to blurred vision is described, who underwent different complementary tests of multimodal images: optical coherence tomography (OCT), fluorescein angiography (FA), indocyanine green angiography (ICGA), autofluorescence (AF), ultrasound eye exam and retinography to achieve the accurate diagnosis.

Results: We present the case of a 50‐year‐old patient who debuted with recently‐onset blurred vision in the left eye (LE). In the eye fundus of LE, a yellow‐orange temporal‐inferior lesion of 3 disc diameter (DD) with neurosensory detachment of 4 DD that affects the fovea is observed. An OCT is performed that shows a choroidal mass associated with subretinal and intraretinal fluid with hyperrefringent points, the B‐scan ultrasound shows a hyperechoic lesion in the posterior pole, and both ICGA and FA reveal a hyperfluorescent pattern in all its phases, being the choroidal vessels of better visualization in the latter phase (without double vascularization pattern). AF shows hyperautofluorescence. After the definitive diagnosis of choroidal haemangioma, he was referred for treatment with Argon laser with favourable results.

Conclusions: Choroidal haemangioma is a rare benign vascular tumour that occurs in middle‐aged adults and can be circumscribed (CCH) or diffuse depending on its extension. For the diagnosis of intraocular tumours it is very important to make a good differential diagnosis with the help of multimodal images: OCT, FA, ICGA, AF, Ultrasound and retinography; in order to differentiate it from similar posterior pole lesions with worse prognosis. CCH itself is benign and asymptomatic, and its treatment consists of observation; but it can present inflammatory signs with subretinal fluid and affect the macular area and therefore a more invasive treatment is indicated.

References.

1. Singh AD, Kaiser PK, Sears JE. Choroidal hemangioma. Ophthalmol Clin North Am. 2005;18(1):151–61, ix.

2. Berry M, Lucas LJH. Circumscribed choroidal hemangioma: A case report and literature review. J Optom. 2017;10(2):79–83.
The effect of preserved glaucoma eye drops exposure on glaucoma surgery prevalence and surgical failure in a French nationwide study between 2009 and 2017
Authors: Chamard Chloé , Bron Alain , Fouad Fayssoil , Debourdeau Eloi , Villain Max , Baudouin Christophe , Daien Vincent
Published: December 2022

Purpose: Preservatives induce trabecula toxicity and conjunctival fibrosis. This may negatively affect the management of glaucoma by inducing uncontrolled intraocular pressure or excessive healing after surgery.

Methods: To evaluate the association between preserved glaucoma eye drops exposure and the occurrence of glaucoma surgery as well as surgical failure. A retrospective analysis of French National database was conducted between January 1st 2009 and December 31st 2017 and followed until December 31st 2018. Patients were categorized as 0% preservative exposure, 100% preservative exposure and mixed exposure. The occurrence of glaucoma surgery was the main outcome and surgical failure the secondary outcome.

Results: A total of 664 494 patients (57% women; median age, 66 years [interquartile range, IQR, 18.0 years]) with first glaucoma eye drops claim were included. Among them, 8467 (1.3%) individuals had glaucoma surgery with a median delay of 2 years (IQR, 3.3 years). The occurrence of glaucoma surgery was respectively 1.8 times higher (hazard ratio [HR], 1.8 [95% CI, 1.73–1.97], p = <0.001) for 100% preserved group, 2.7 times higher (HR, 2.7; [95% CI, 2.46–2.89]; p = <0.001) for mixed exposure compared to 0% preservatives group. Among patients with glaucoma surgery, 2671 (31.5%) individuals had surgical failure with a median delay of 6 months (IQR, 14.0 months). The risk of surgical failure increased by 1.5‐fold for 100% preserved group and low mixed group (HR = 1.5; [95% CI, 1.1–2.1]; HR = 1.5; [95% CI, 1.0–2.1], respectively) and by 1.7‐fold for high mixed group (HR = 1.7; [95% CI, 1.2–2.5]), compared to 0% preservatives group.

Conclusions: An increased risk of glaucoma surgery and its failure was observed in patients treated with preserved glaucoma eye drops. This suggests the interest to initiate glaucoma treatment with preservative‐free eye drops to decrease trabecular toxicity and conjunctival fibrosis.
Clinical manifestations, laboratory characteristics, and treatment outcomes of ocular syphilis: A case series
Authors: Ferreira Catarina , Teixeira Sofia , Fonseca Sofia
Published: December 2022

Purpose: To describe the clinical and laboratory findings, ocular complications, and visual prognosis of patients with syphilis‐associated uveitis.

Methods: Retrospective observational case series of patients diagnosed with ocular syphilis between January 2012 and April 2022 at a single tertiary referral centre in Portugal. Medical records of patients presenting with syphilis‐associated uveitis were reviewed.

Results: Eighteen eyes from 10 consecutive patients were included. All patients were male and median age at diagnosis was 51 years (range 20–83). HIV coinfection was present in 3 patients, with two of these being newly diagnosed on presentation. All patients had a reactive serum treponema pallidum haemagglutination test and median serum rapid plasma reagin titre was 1:260 (range 1:1–1:520), with no significant difference between HIV‐positive and HIV‐negative patients (p = 0.222). A lumbar puncture was performed in seven patients, confirming the diagnosis of neurosyphilis in six patients. Bilateral involvement occurred in eight patients. The most frequent form of intraocular inflammation was posterior uveitis (33.3%), followed by panuveitis (27.8%) and anterior uveitis (27.8%). All patients were treated with intravenous penicillin, showing partial or complete resolution of the ocular findings. Visual acuity improved significantly from presentation to the last visit (0.7 logMAR, range 0–2; and 0.2 logMAR, range 0–0.7, respectively; p = 0.004). Five eyes (27.8%) had ocular complications from syphilis‐associated uveitis, including epiretinal membrane formation and cystoid macular oedema, with significantly worse visual prognosis (p < 0.001).

Conclusions: Ocular syphilis is re‐emerging as a prominent cause of uveitis. In our series, patients were characteristically middle‐aged men with posterior segment involvement. A relevant proportion of patients had HIV co‐infection. Despite good visual prognosis with standard treatment, ocular complications may compromise visual recovery.
Germline variants in cancer predisposition genes in patients with uveal melanoma
Authors: Repo Pauliina , Salminen Eveliina , Järvinen Reetta‐Stiina , Hiltunen Juho , Al‐Jamal Rana'a , Täll Martin , Raivio Virpi , Kivelä Tero , Turunen Joni
Published: December 2022

Purpose: Patients with uveal melanoma (UM) have an increased risk of other primary tumours; up to 12% of patients belong to families with other cancers.[1] ~2% of unselected patients and 25% of patients with a family history of UM harbour a pathogenic germline variant in the BAP1 gene.[2] Additionally, 12 other genes might contribute to UM susceptibility [3] whereas 75% of patients with familial UM remain without a genetic explanation for UM susceptibility.

Methods: We sequenced 312 consecutively enrolled patients with UM for germline variants in 15 genes driving UM tumorigenesis or having a BAP1 association using next‐generation sequencing. Additional 191 cancer‐associated genes were analysed from 108 high‐risk patients who had another cancer, UM at <45 years of age, or either bilateral or familial UM.

Results: 6.5% (7/108; 95% CI 2.6–12.9) of the high‐risk patients had a pathogenic or likely pathogenic germline variant in AR, CHEK2, DDX41, RAD50, RET, or SDHB and 8.3% (9/108; 95% CI 3.9–15.2) harboured a cancer‐associated VUS in BMPR1A or CHEK2. Germline variants in UM drivers other than BAP1 did not contribute to UM predisposition.

Conclusions: Germline variants in known cancer genes are relatively frequent in selected patients with UM. The family history of cancer should be obtained and the threshold to offer genetic counselling should be low.

References

1. Abdel‐Rahman, M.H., et al., Cancer family history characterization in an unselected cohort of 121 patients with uveal melanoma. Fam Cancer, 2010. 9(3): p. 431–8.

2. Repo, P., et al., Population‐based analysis of BAP1 germline variations in patients with uveal melanoma. Hum Mol Genet, 2019. 28(14): p. 2415–2426.

3. Abdel‐Rahman, M.H., et al., Whole Exome Sequencing Identifies Candidate Genes Associated with Hereditary Predisposition to Uveal Melanoma. Ophthalmology, 2019.
Relationship of APOE ε4 allele and BDNF Val66Met polymorphism to retinal structural and vascular OCTA parameters in aging cohort: Optic nerve decline and cognitive change study
Authors: Sheriff Samran , Shen Ting , Saks Danit , Chitranshi Nitin , Schulz Angela , Graham Stuart , Gupta Vivek
Published: December 2022

Purpose: To investigate the relationship between the APOE (Apolipoprotein ε4) allele and brain‐derived neurotrophic factor (BDNF) Val66Met polymorphism on retinal structural and vascular characteristics in healthy aging subjects.

Methods: 109 healthy participants (mean age 67.1 (±9.0) years) were recruited. Participants were classified as either APOE carriers or non‐carriers based on the presence or absence of the ε4 allele and cohorts established based on their BDNF genotype (Val/Val, Met/Met and Val/Met). Baseline assessment included ophthalmological examination and retinal imaging including OCT (optical coherence tomography) and OCTA (optical coherence tomography angiography) with 3 T Wide Bore MRI imaging to assess brain volumetric measures. Cognitive function was evaluated using a battery of neuropsychological assessments. The relationship between carriers of APOE ε4 allele and Met carriers between these ocular parameters were analysed using the generalized estimating equation (GEE) models and data adjusted for age, sex and inter‐eye differences as within‐subject variables (p < 0.05).

Results: 20 subjects (22%) were identified as APOE ε4 carriers and 44 subjects (41%) were identified as Met Carriers. Temporal RNFL thickness was decreased in APOE ε4 carriers (p < 0.01). Vessel density between carriers and non‐carriers was not significantly different at either the superficial or deep level, however, the FAZ (foveal avascular zone) area was found to be smaller in ε4 carriers in both superficial (p < 0.01) and deep layers (p < 0.003). The BDNF Met allele carriage had significant association with reduction of the entorhinal cortex volume in the healthy aging cohort (p = 0.012). No association was found with cognitive performances.

Conclusions: Our results indicate possible associations between reduced FAZ area and reduced temporal RNFL thickness with the APOE ε4 allele, and that carriage of BDNF Val66Met polymorphism may be associated with some specific regions of cortical volume loss. Further studies could further characterize this association.
Choroidal neovascularization (CNV) due to non‐age‐related macular degeneration (AMD) causes: Multimodal imaging and treatment outcome in a retrospective case series
Authors: Kabanarou Stamatina , Bitzanakis Nikolaos , Mamareli Vasiliki , Makryllou Sophia Ioanna , Garvanou‐Xirou Christina , Gkizis Ilias , Xirou Tina
Published: December 2022

Purpose: To present the management (clinical evaluation, fundus imaging and treatment outcome) of patients with non‐AMD related CNV.

Methods: We retrospectively reviewed the medical records of a case series with non‐AMD related CNV patients that were referred to our clinic since January 2021 and treated with intravitreal injections of anti‐VEGF (ranibizumab or aflibercept). The following data were retrieved: demographic data, best‐corrected visual acuity (BCVA) at the initial and final visit, number of injections and side‐effects, fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and OCT‐angiography imaging results.

Results: We included nine eyes of nine patients (seven females and two males, median age: 59 years, range 19–72): five myopic, three with idiopathic CNV, one with angioid streaks (AS). Median BCVA at presentation was 0.7 (range 0.1–0.8). FFA revealed a classic CNV in all cases (subfoveal: eight cases, extrafoveal: one case). OCT‐angiography confirmed the presence of an active CNV in six out of nine cases. In OCT, there was minimal fluid (five out of nine cases), subretinal fluid (two cases) or both subretinal and intraretinal fluid (two cases). The median number of injections was three (range 1–14) with no reported adverse events. An improvement in BCVA was documented in all cases after treatment. On the final recorded visit, OCT showed minimal/no fluid in all patients while in OCT‐angiography the CNV showed signs of inactivity in the majority cases.

Conclusions: Multimodal imaging is useful in the diagnosis, follow‐up and management of cases with non‐AMD related CNV. Most of them demonstrated minimal signs of exudative disease and required less number of anti‐VEGF injections compared to neovascular AMD cases.
Respiratory comorbidities. Looking ahead to new glaucoma risk factors
Authors: Pinazo‐Duran Maria Dolores , Sala‐Grau Nuria , Millá‐Griñó Elena , Andrés‐Blasco Irene , Bolarin‐Guillen Jose M. , Gallego‐Martinez Alex , Garcia‐Medina Jose J. , Cruz‐Espinosa Javier , Benitez‐Del‐Castillo Javier , Hernández‐Martínez F. Javier , Zanon‐Moreno Vicente
Published: December 2022

Purpose: Open‐Angle glaucoma (OAG) continues being the first cause of irreversible blindness worldwide. Recent advances in biotechnology did not cover all needs for avoiding glaucoma neurodegeneration (GND) and its high socioeconomic burden. Revisiting OAG risk factors, (including respiratory comorbidities), is mandatory to optimize OAG managing.

Methods: A total of 412 participants were recruited in a prospective nationwide study (Spain and Portugal) according to strict inclusion/exclusion criteria, and classified into: OAG patients (n = 214) and ocular hypertension (OHT) subjects (n = 198). Sociodemographic, personal characteristics/lifestyle, and comorbid respiratory disorders were recorded. Among the latter asthma, chronic obstructive pulmonar disease (COPD) and sleep apnea/hypopnea syndrome (SAHS). Statistical processing was done by RStatistics v4.1.2 and RStudio v2021.09.1.

Results: Mean age and gender distribution were: 62 years and 49% men (OAG group) and 61 years and 61% men (HTO group). Univariant analysis reflected that smoking and COPD (p < 0.001) were significantly different between groups. Logistic regression of all variables showed that asthma (p = 0.003) and COPD (p = 0.035) were the most statistically significant characteristics between groups. When eliminating the outlier variables, the logistic regression displayed that asthma (p = 0.002) and COPD (p = 0.05) were the most discriminative parameters between groups. The SAHS did not show statistical significance.

Conclusions: Data from this population strongly indicated that in addition to traditional OAG risk factors, asthma, COPD, and smoking habit can be considered detrimental to the OAG course.
Use of freeze‐dried amniotic membrane of umbilical cord (hAM‐UC) as scleral patch after conjunctival tumour excision surgery
Authors: Nahon‐Esteve Sacha , Barnouin Laurence , Caujolle Jean Pierre
Published: December 2022

Purpose: In ocular oncology, scleral thinning is a complication that can occur after conjunctival tumour excision surgery. Scleral thinning depends on the tumour invasion of the sclera and on individual anatomical variations. Ocular surface repair surgery can use autologous, allogeneic or even xenogeneic graft. A monocenter, open and prospective clinical trial was conducted to evaluate the safety of a freeze‐dried hAM‐UC used as a patch to reinforce the sclera thinned by tumour excision surgery. This product has been tested in rabbit model in trabeculectomy versus autograft and has shown an egal kinetic of scleral reconstruction.

Methods: Patients aged 18 years and older with a risk of scleral thinning after conjunctival tumour excision surgery were included. The main objective of this study was to assess the tectonic effect of the implant including clinical tolerance using a composite score. Secondary objectives were the evaluation of the scleral thickness recovery by swept‐source optical coherence tomography (OCT) at 15 days, 1, 3 and 6 months.

Results: Twelve patients were implanted during surgical management of conjunctival tumour. Clinical tolerance was good throughout the study. Tectonic recovery was achieved with a minimal score for local reactions after 3 months. OCT images showed good integration of the graft and recovery of the ocular surface. At 6 months, all patients, including the 5 patients with invasive malignant conjunctival tumour treated by proton‐therapy one month after implantation, had sclera thickness at physiological level.

Conclusions: The use of a freeze‐dried human amniotic membrane of umbilical cord is a promising option in the tumour of the conjunctiva.
Corneal stroma densitometry evolution in a clinical model of cellular therapy for advanced keratoconus
Authors: Alio Jorge , El Zarif Mona , del Barrio Jorge Alio
Published: December 2022

Purpose: To report the corneal stromal densitometry (CD) evolution studied by Scheimpflug tomography, anterior segment optical coherence tomography (AS‐OCT), and confocal microscopy changes, in keratoconus patients included in a clinical experience of advanced cell therapy using autologous humans adipose‐derived adult stem cells (ADASCs), and corneal decellularized or ADASCs‐recellularized human donor corneal laminas in advanced keratoconus.

Methods: Interventional prospective, consecutive, randomized, comparative series of cases. Fourteen keratoconic patients were randomly distributed into three groups for three types of surgical interventions: group 1 (G‐1), autologous ADASCs implantation (n = 5); group 2 (G‐2), decellularized human corneal stroma (n = 5); and, group 3 (G‐3), autologous ADASCs + decellularized human corneal stroma (n = 4). Participants were assessed with Scheimpflug‐based Oculus Pentacam CD module, AS‐OCT (Visante, Carl Zeiss), and confocal microscopy (HRT3 RCM Heidelberg).

Results: The central and total CD were statistically significantly higher in G‐2 compared with G‐1, and G‐3 compared with G‐1 at the studied annular zones centered on the corneal apex (0–2 mm, 2–6 mm, and 6–10 mm). There was statistical significance higher in G‐3 compared with G‐2 at the central corneal stroma at (0–2 mm, 2‐6 mm). The confocal microscopy findings, as well as the AS‐OCT reflected the densitometry changes.

Conclusions: The intrastromal implantation of ADASCs produced very subtle changes in CD at the level of the central corneal stroma. However, the intrastromal implantation of decellularized corneal laminas increases it slightly, but with lower values than the implantation of recellularized laminas with ADASCs.
Oxygen‐dependent regulation of β3‐adrenoceptor in the retina: Another piece in the puzzle of the pathological neovascularization
Authors: Amato Rosario
Published: December 2022

Purpose: Hypoxia‐inducible factor (HIF)‐1 is the major transcriptional regulator involved in the adaptive responses to hypoxia in health and disease. In the retina, HIF‐1 controls the hypoxia‐driven vascular proliferation by inducing the overexpression of neoangiogenic factors. The HIF‐1‐mediated neoangiogenesis is strongly promoted by β‐adrenoceptors overstimulation following the hypoxia‐driven surge of catecholamines. Among them, β3‐adrenoceptor (β3‐AR) appears strictly linked to hypoxia, resulting overexpressed in proliferating vessels parallelly with increased HIF‐1. However, whether β3‐AR undergoes HIF‐1 direct regulation remains to be established.

Methods: The mouse model of oxygen‐induced retinopathy (OIR) was used to test the influence of the HIF‐1 stabilization with DMOG on the oxygen‐dependent modulation of β3‐AR expression in the retina. Hence, the mouse β3‐AR gene was analysed to search for putative HIF binding sites (HBSs), which then underwent in silico simulations to predict their suitability for the binding with HIF‐1. Finally, the oxygen‐dependent physical interaction of the best scored HBS with HIF‐1 was tested using ChIP‐qPCR in retinas of OIR mice and correlated with the β3‐AR gene expression.

Results: In OIR retinas, β3‐AR expression inversely correlated with the oxygen tension. The inhibition of HIF‐1 drop under hyperoxia abolished the oxygen‐dependent β3‐AR modulation, indicating that β3‐AR expression might depend on HIF‐1 levels. The β3‐AR gene analysis and the HIF‐1 docking simulations revealed 6 possible HBS, of which HBS#1 resulted the most suitable region for HIF‐1 binding. The ChIP‐qPCR analysis on OIR retinas demonstrated the actual oxygen‐dependent HIF‐1/HBS#1 physical interaction, which correlated with the β3‐AR gene transactivation.

Conclusions: This evidence allows to establish the β3‐AR as a member of the HIF‐1 target genes, thus paving the way to the further characterization of its role in oxygen‐dependent retinal abnormalities.
Comparing the efficacy of idroflog vs conventional artificial tears in patients with dry eye disease after cataract surgery
Authors: Giannaccare Giuseppe , Borselli Massimiliano , Rossi Costanza , Mancini Alessandra , Vaccaro Sabrina , Scalzo Giovanna Carnovale , Scorcia Vincenzo
Published: December 2022

Purpose: To examine the changes of ocular surface parameters in patients with dry eye disease (DED) instilling Idroflog eye drop (sodium hyaluronate 2 mg/ml plus hydrocortisone sodium phosphate 10 mcg/ml) versus conventional tear substitutes.

Methods: This study was performed at the University Magna Græcia of Catanzaro between September 2021 and April 2022. Twenty patients (11 males, 9 females) affected by mild–moderate DED occurring after cataract surgery were included: 10 patients were treated with Idroflog (group 1) whereas 10 patients with conventional tear substitutes (Thealoz duo n = 4; Systane ultra n = 4, Hyalistil n = 2). Patients were examined at baseline (T0), day 15 (T1) and day 45 (T2) by means of Keratograph for the evaluation of: non‐invasive breakup time (NIBUT) class (0: >10 s; I: 6–10 s; II 3–6 s; III < 3 s), tear meniscus height (TMH) and bulbar redness. Subjective symptoms of ocular discomfort were scored at the same time points. Intraocular pressure (IOP) was measured at T0 and T2 in both groups.

Results: In group 1, a statistically significant reduction of OSDI score and NIBUT class was found at T2 compared to T0 (respectively, 15.9 ± 7.4 vs. 23.8 ± 8.7; p < 0.001 and 1.05 ± 0.75 at 0.55 ± 0.60; p = 0.027); conversely, mean values of TMH were significantly higher at T2 compared to T0 (0.52 ± 0.45 vs. 0.35 ± 0.22 mm; p = 0.027). Redness variation was not statistically significant (p = 0.30). Concerning group 2, only OSDI score improved significantly (from 25.98 ± 12.91 at T0 vs. 17.23 ± 8.36 at T2; p = 0.038). Conversely, no statistically significant changes were detected at T2 compared to T0 for NIBUT class (p = 0.96), TMH (p = 0.23) and bulbar redness (p = 0.87). No changes of IOP was found in both groups throughout the entire study (p = 0.91 in group 1 and p = 0.88 in group 2).

Conclusions: Ocular discomfort symptoms improved in both groups after 45 days of treatment. Unlike conventional tear substitutes, Idroflog eye drop allowed also the improvement of the main signs of DED.
Macular and peripapillary microvascular changes in open angle glaucoma and ocular hypertension: A longitudinal study using optical coherence tomography angiography (OCT‐A)
Authors: del Mar Schilt‐Catafal Maria , Pérez‐Torregrosa Vicente T. , Duch‐Samper Antonio M.
Published: December 2022

Purpose: To investigate prospectively macular and peripapillary microvascular changes in patients with glaucoma and ocular hypertension.

Methods: A 12‐month prospective longitudinal study was performed with 124 open‐angle‐glaucoma‐eyes (GE), 111 ocular‐hypertension‐eyes (OHE) and 98 gender and age matched control‐eyes (CE). Glaucomatous progression was defined as a decrease of ≥5 μm in average or ≥7 μm in a sector of RNFL thickness. OMAG OCT microangiography (Angioplex, HD OCT, Cirrus 5000, Zeiss) was used to analyse optic disc and macular regions. The statistical analysis was performed using Mann–Whitney‐Test with the SPSS version 23.0 statistical package (SPSS Inc., IL).

Results: Among OHE and GE groups, 21.7% of eyes showed progression, being the decrease of Peripapillary Flux Index (PFI), Macular Vessel Density (MVD) and Macular Capillary Perfusion Density (MPD) greater (−0.0067; −0.696 mm/mm2 and −1.56%) compared to non‐progressive eyes (+0.0038; 0.527 mm/mm2 and 1.55%) being the nasal and inferior sectors for PFI, and the superior and temporal sectors for both MVD and MPD, the ones that showed greater differences [p = 0.015 and p < 0.001 for the last two]. Furthermore, Peripapillary Perfusion Density (PPD) showed non‐significant greater decrease (−0.347) compared to non‐progressive eyes (−0.324) [p = 0.775]. Characteristics as increased vertical cup to disc ratio (CDV) (0.64 vs. 0.57), elevated intraocular pressure (IOP) (18.25 vs. 15.40 mmHg), thinner central corneal thickness (CCT) (520.18 vs. 541.67 μm) and lower ocular perfusion pressure (OPP) (47.81 vs. 48.95 mmHg) were significantly different in those progressive OHE and GE [p < 0.05 for all]. Nevertheless, minimum ganglion cell layer thickness (GCLM) was only significantly lower in progressive GE (58.51 vs. 73.98 μm) [p = 0.036].

Conclusions: Data showed that when glaucomatous progression took place, stronger microvascular changes occurred in the macular and peripapillary areas, as greater decrease of MVD, MPD and PFI, especially in superior and temporal sectors for the macular area, and in nasal and inferior sectors for the peripapillary area. Nevertheless, further research with larger population and larger follow‐up is needed to obtain stronger results.
development of e‐Health technologies for big data analysis in contact lens
Authors: Chikri Youssef Marrakchi , Alonso Jose Manuel Lopez , Garzón Nuria , Gonzalez‐Perez Mariano
Published: December 2022

Purpose: Development of an App for e‐health in Optometry to study the comfort of contact lenses. Within this objective is the study of blinking (frequency, duration, quality, speed, etc.) from videos collected by the application.

Methods: HTML5, CSS3 and JavaScript are used with Angular and Ionic libraries for a hybrid application on Web, IOS and Android (mobile phones). It connects with nearby free access weather stations, collecting only environmental pollution data. From videos of the patient face taken at that moment, programs in the MATLAB environment are used to locate the eyes (Viola‐Jones algorithms) and give the frequency and duration of the blinks. Using PIV (Particle Image Velocimetry) techniques, information is also acquired on the speed and quality of the blink. In addition, adding patient questionnaires, it is expected to collect joint data for later analysis in the MATLAB environment with an online server and various Big Data techniques.

Results: The application collects data and videos. It allows the analysis of the number of blinks, their frequency and duration in a simple way, having been tested with several MATLAB algorithms. PIV techniques also allow the characterization of blink process, allowing a better characterization of the influence of contact lenses on blinking showing some differences.

Conclusions: The characterization of the comfort and fit of contact lenses depends on a large number of factors, so the development of an application that collects both physical and behavioural data is of great importance. Hence, it is important to have an instrument that collects data in real time on a large number of patients for subsequent analysis using statistical techniques.
Managing recurrent macular holes with ready‐to‐use freeze‐dried disks of human amniotic membranes
Authors: Mathis Thibaud , De Smet Marc , Barnouin Laurence , Laurent Kodjikian
Published: December 2022

Purpose: Primary Macular Holes (MH) have a closure rate of 85%–90%. However, for large or recurrent MH, there is an ongoing debate regarding the best technique. Recent studies have highlighted the use of amniotic membrane in the treatment of recurrent MH. For this purpose, easy‐to‐use small disks of freeze‐dried and sterile human amniotic membrane (hAM) can be proposed. A phase II open and prospective clinical trial was conducted to evaluate the efficacy of a hAM in the closure of recurrent MHs.

Methods: Patients between 18 and 75 years old with full thickness MHs of all etiologies that failed to close after previous pars plana vitrectomy were included. Small disks of 3 mm or 5 mm diameter of virally inactivated, freeze‐dried and sterile hAM, with intensive microbiological controls was proposed for this study. After inclusion, all patients underwent vitrectomy and hAM placement on the MH. Closure of recurrent MH (primary objective), clinical tolerance, functional restoration and impact of hAM on the retina area (secondary objectives) were assessed in the 6 months following the surgery.

Results: Ten eyes of 10 patients with large recurrent MH of 412–1324 μm (mean = 715 μm) were treated in the study. Closure was complete in six eyes (60%). For two patients (20%), MH closed partially before recurring. Best corrected visual acuity improved for four of the six eyes who achieved complete MH closure (67%). No safety issue related to the hAM were reported. hAM can be persistent on MH after 6 months.

Conclusions: Early results of the study suggest that freeze‐dried hAM is a safe and effective option for the treatment of recurrent MH.
The relationship of retinal vessel calibres with cardiovascular risk factors in apparently healthy young eyes
Authors: El Youssfi Asmae Igalla , Hidalgo‐Saiz Beatriz , Cedrun‐Sanchez Juan , Alonso José Manuel López , Puell María
Published: December 2022

Purpose: Although retinal vascular calibre has been linked to increased cardiovascular (CV) risk, it remains unclear whether retinal vascular morphologic changes are already evident in young adults and correlate with modifiable CV risk factors. The purpose of this study was to explore the relationship of retinal arteriolar and venular calibre with CV risk factors and ocular parameters in healthy young subjects.

Methods: A cross‐sectional study was performed in 52 apparently healthy subjects (mean 21.6 ± 2.2 years of age). Retinal vascular calibres were measured from fundus photographs using semi‐automated imaging software and expressed as central retinal arteriolar (CRAE) or venular (CRVE) equivalent and arterio‐venous ratio (AVR). CV risk factors and ocular parameters were assessed. Forward stepwise multiple linear regression analysis was used to detect the independent relationship between retinal vascular calibre and CV and ocular parameters.

Results: Means for CRAE and CRVE were 191 ± 15.4 μm and 209 ± 15.8 μm respectively. The mean CRAE but not CRVE was significantly higher in women than in men (p = 0.009). Systolic blood pressure (SBP) and spherical equivalent were significant contributing factors to CRAE (SBP: p < 0.001; SE: p = 0.021). However, CRVE was not significantly predicted by CV risk factors or ocular parameters. SBP was the only one independent contributor to AVR (p = 0.018).

Conclusions: In young adults, higher SBP was found to be related to narrower retinal arterioles, but not to retinal venules. Sex and other confounding CV or ocular factors had no effect on the relationship of SBP and retinal vessel calibre.
Assessing the impact of long‐term idebenone treatment on various visual acuity outcomes in Leber's hereditary optic neuropathy (LHON): Results, according to primary mitochondrial DNA mutation, from the prospective, natural history‐controlled LEROS study
Authors: Tomasso Livia , Carelli Valerio , Yu‐Wai‐Man Patrick , Klopstock Thomas ,   the LEROS Study Group
Published: December 2022

Purpose: In LEROS, visual acuity (VA) outcomes in idebenone‐treated patients with LHON were compared to an external, matched, natural history (NH) cohort. Here, we report results from a cumulative frequency analysis to understand the impact of idebenone on carriers of each of the primary mitochondrial DNA (mtDNA) mutations.

Methods: Patients with LHON and a confirmed primary mtDNA mutation (11 778, 14 484 or 3460) were enrolled and stratified by time since onset: acute (≤1 year) and chronic (>1 but ≤5 years). Data from 181 patients treated up to 24 months were compared to retrospective data from the NH cohort (372 patients), matched by time since onset. In a cumulative frequency analysis, VA change was assessed from baseline to month 24. A change of ≥0.2 logMAR was considered a clinically relevant recovery or worsening, depending on the direction of change.

Results: For carriers of the 11 778 mutation, VA outcomes were observed, in treated versus untreated eyes, as follows: recovery: 38.3% (23/60) vs. 14.9% (7/47) [acute], 24.4% (20/82) vs. 13.7% (7/51) [chronic]; worsening: 24.4% (10/41) vs. 66.7% (20/30) [acute], 4.4% (2/45) vs. 31.6% (6/19) [chronic]. For 14 484 carriers VA outcomes were as follows: recovery: 74.3% (26/35) vs. 70.0% (7/10) [acute], 90.9% (10/11) vs. 16.7% (3/18) [chronic]; worsening: 2.9% (1/35) vs. 22.2% (2/9) [acute], 0.0% (0/8) vs. 16.7% (3/18) [chronic]. For 3460 carriers, outcomes were as follows: recovery: 34.6% (9/26) vs. 61.1% (11/18) [acute], and 30.4% (7/23) vs. 20.8% (5/24) [chronic]; worsening: 76.5% (13/17) vs. 30.0% (3/10) [acute], and 0.0% (0/15) vs. 13.0% (3/23) [chronic].

Conclusions: Idebenone can improve the ratio of positive to negative VA outcomes in a large proportion of patients with LHON, although these benefits seem to manifest to varying degrees dependent on disease stage and/or causative mtDNA mutation. Carriers of the most prevalent mutation, 11 778, saw a consistent treatment benefit regardless of disease stage.
Investigating the use of translational readthrough inducing drugs in keratocytes from a mouse model of brittle cornea syndrome
Authors: Stanton Chloe , Findlay Amy , Drake Camilla , Vitart Veronique
Published: December 2022

Purpose: Brittle Cornea Syndrome (BCS) is a rare recessive condition characterized by extreme thinning of the cornea. The collagen‐rich corneal stroma accounts for 90% of corneal thickness in humans, and is a major determinant of visual acuity. BCS results from homozygous loss‐of‐function mutations in ZNF469 (BCS1) or PRDM5 (BCS2). Our mouse model of BCS1, caused by a premature termination codon (PTC) mutation in Zfp469, showed that the stroma is thinner due to of decreased type 1 collagen expression1. To elucidate disease mechanisms and test potential therapies, we established a primary keratocyte disease‐in‐a‐dish model of BCS1. Translational readthrough inducing drugs (TRIDs) can restore full‐length proteins truncated by PTC and are a potential treatment for 20% of BCS patients with PTC mutations. Primary keratocytes from our BCS1 mouse model were treated with TRIDs to assess their efficacy in improving the BCS phenotype in vitro.

Methods: Zfp469BCS1/BCS1 keratocytes were treated with TRIDs PTC124 (ataluren), amlexanox, gentamicin, geneticin or vehicle‐only, for 2 or 5 days. Following treatment, Zfp469 and Col1a1 mRNA levels were evaluated by RT‐qPCR. Changes to keratocyte cell‐derived matrices were assessed using immunostaining or the collagen dye CNA35.

Results: Zfp469BCS1/BCS1 keratocytes express 40% more Zfp469 mRNA than wildtype cells; this was unchanged by treatment with amlexanox, geneticin or gentamicin. PTC124 decreased expression of Zfp469 by 50%. Expression of Col1a1, a key component of the stromal matrix, was significantly decreased by PTC124 treatment (<65% relative to vehicle‐only Zfp469BCS1/BCS1 keratocytes). Collagen deposition, visualized using CNA35 dyes, was decreased by PTC124 treatment in BCS and wildtype keratocytes.

Conclusions: BCS is a devastating condition. Extreme thinning of the corneal stroma, as a result of impaired collagen production by keratocytes, makes the cornea prone to rupture. This causes irreversible sight loss. There is currently no treatment for BCS. Our initial work suggests that TRIDs may not restore functional full‐length Zfp469 in primary keratocytes and are unlikely to be of therapeutic benefit in BCS.

Reference

1. Stanton CM et al. A mouse model of brittle cornea syndrome caused by mutation in Zfp469. Dis Model Mech. 2021;14(9):dmm049175.