RESUMEN

Purpose: To evaluate progression rate estimation in long-term Stargardt disease microperimetry data by accounting for floor effect. Design: Cohort study. Subjects: Thirty-seven subjects (23 females, 14 males) with biallelic ABCA4 pathogenic or likely pathogenic variants and more than >2 years of longitudinal microperimetry data. Methods: Cross-sectional and longitudinal microperimetry data (Grid A: 18° diameter, Grid B: 6° diameter; Macular Integrity Assessment microperimeter, dynamic range 0-36 decibels [dB]) was extracted from patients with biallelic mutation in the adenosine triphosphate-binding cassette subfamily A member 4 (ABCA4) gene. For each eye, mean sensitivity (MS) and responding point sensitivity (RPS) rates were extracted. Floor censored sensitivity (FCS) progression rate, which accounts for the floor effect at each locus by terminating calculation when scotoma was observed in 2 consecutive visits, was also calculated. In a subset of eyes with ≥1 scotomatous locus at baseline (Grid A), sensitivity progression of loci around the scotoma (edge of scotoma sensitivity [ESS]) was examined against other progression parameters. Paired t test compared progression rate parameters across the same eyes. Main Outcome Measures: Microperimetry grid parameters at baseline and progression rates. Results: A total of 37 subjects with biallelic ABCA4 mutations and >2 years of longitudinal microperimetry data were included in the study. In Grid A, at baseline, the average MS and RPS were 16.5 ± 7.9 and 19.1 ± 5.7 dB, respectively. Similar MS (18.4 ± 7.6 dB) and RPS (20.0 ± 5.5 dB) values were found at baseline for Grid B. In Grid A, overall, MS, RPS, and FCS progression rates were -0.57 ± 1.05, -0.74 ± 1.24, and -1.26 ± 1.65 (all dB/year), respectively. Floor censored sensitivity progression rate was significantly greater than the MS or RPS progression rates. Similar findings were observed in Grid B (MS -1.22 ± 1.42, RPS -1.44 ± 1.44, FCS -2.16 ± 2.24, all dB/year), with paired t test again demonstrated that FCS had a significantly faster rate of decline than MS or RPS. In patients with progression data in both grids, MS, RPS, and FCS progression rates were significantly faster in the smaller Grid B. In 24 eyes with scotoma at baseline, fastest rate of decline was ESS combined with FCS compared with other progression parameters. Conclusions: Incorporation of FCS can reduce confound of floor effect in perimetry analysis and can in turn detect a faster rate of decline. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

RESUMEN

We present a case of a 75-year-old Asian woman with Guillain-Barré syndrome (GBS) who underwent a 1-month comprehensive rehabilitation training program supplemented by robot-assisted gait training (RAGT). GBS can lead to fatigue and prolonged bed rest, thereby further debilitating older patients. Although exercise intervention is recommended for GBS, a consensus regarding the appropriate intensity has yet to be established. Individualized strategies are required because older patients experience varying levels of fatigue and frailty. We used a technological adjunct to support comprehensive rehabilitation for GBS reconditioning in an older patient. To the best of our knowledge, research involving the use of an exoskeleton robotic device in the geriatric population with GBS is limited. Our case demonstrates the feasibility and safety of RAGT for improving lower limb muscle power and scores on the Barthel Index, Clinical Frailty Scale, and Instrumental Activities of Daily Living Scale at discharge from a geriatric ward.

Asunto(s)

Síndrome de Guillain-Barré , Robótica , Humanos , Anciano , Femenino , Síndrome de Guillain-Barré/rehabilitación , Síndrome de Guillain-Barré/complicaciones , Robótica/métodos , Marcha/fisiología , Terapia por Ejercicio/métodos , Caminata/fisiología

Asunto(s)

Maltrato a los Niños , Errores Diagnósticos , Femenino , Humanos , Masculino , Maltrato a los Niños/diagnóstico , Diagnóstico Diferencial

RESUMEN

PURPOSE: To report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy. METHODS: A 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)]. RESULTS: Visual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction. CONCLUSIONS: This case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted.

RESUMEN

Usher syndrome (USH) is the most common cause of inherited deaf-blindness. Here, we produced the LEIi020-A and LEIi020-B induced pluripotent stem cell (iPSC) lines from dermal fibroblasts derived from a patient with USH1B caused by inheritance of homozygous c.496del variants in MYO7A using episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, LIN28, mir302/367 microRNA and shRNA for TP53. Both iPSC lines expressed pluripotency markers, demonstrated trilineage differentiation potential and displayed a 46,XY karyotype. These cell lines represent a valuable resource for the production of retinal and otic tissues to support research into the pathogenesis and treatment of USH1B.

Asunto(s)

Homocigoto , Células Madre Pluripotentes Inducidas , Factor 4 Similar a Kruppel , Miosina VIIa , Síndromes de Usher , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Síndromes de Usher/genética , Síndromes de Usher/patología , Línea Celular , Diferenciación Celular , Masculino , Fibroblastos/metabolismo

RESUMEN

PURPOSE: To describe visual function and retinal features of female carriers of choroideremia (CHM), using multimodal imaging and microperimetry. DESIGN: Cross-sectional cohort study. PARTICIPANTS AND CONTROLS: Choroideremia carriers seen in Australia (Melbourne or Perth) or the United Kingdom (Oxford or Cambridge) between 2012 and 2023. Healthy age-matched controls seen in Melbourne, Australia, between 2022 and 2023. METHODS: Participants had visual acuity, fundus-tracked microperimetry, OCT, and fundus autofluorescence imaging performed. Choroideremia carriers were either genetically or clinically confirmed (i.e., obligate carriers). Choroideremia carriers were grouped according to their retinal phenotype and compared with healthy controls. Statistical analyses were performed on StataBE (v18.0). MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), average retinal sensitivity, volume of macular hill of vision (HoV), inner retinal thickness, and photoreceptor complex (PRC) thickness. RESULTS: Eighty-six eyes of 43 CHM carriers and 60 eyes of 30 healthy controls were examined using multimodal imaging and microperimetry. Median age was 54 and 48.5 years for CHM carriers and controls, respectively (P = 0.18). Most CHM carriers (86%) were genetically confirmed. Choroideremia carriers and controls had strong intereye correlation between eyes for BCVA and average retinal sensitivity (P < 0.001). Low-luminance visual acuity and macular HoV tests were sensitive tests to detect changes in CHM carriers with mild phenotypes (i.e., fine and coarse). Choroideremia carriers with geographic or male-pattern phenotypes had reduced BCVA, LLVA, retinal sensitivity, and retinal thinning, compared with healthy controls. Retinal thickening of the inner retina was observed in the central 1°, despite generalized thinning of the PRC in the central 7°, indicating retinal remodeling in CHM carriers, compared with controls. There were no genotype-phenotype correlations observed. CONCLUSIONS: Female carriers of CHM with severe retinal phenotypes (i.e., geographic or male pattern) have significantly decreased visual function and retinal structural changes when compared with age-matched controls and those carriers with milder phenotypes. Low-luminance visual acuity and volumetric measures of the macular HoV were found to be the most sensitive functional tests to detect milder retinal disease (fine and coarse phenotypes) in CHM carriers. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

RESUMEN

Purpose: To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA). Methods: Photothrombotic BRVOs were created in both eyes of four groups of nine pigs (2, 6, 10, and 20 days). In each group, six pigs received intravitreal injections of BEV in one eye and TA in the fellow eye, with three pigs serving as untreated BRVO controls. Three untreated pigs served as healthy controls. Expression of mRNA of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), dystrophin (DMD), potassium inwardly rectifying channel subfamily J member 10 protein (Kir4.1, KCNJ10), aquaporin-4 (AQP4), stromal cell-derived factor-1α (CXCL12), interleukin-6 (IL6), interleukin-8 (IL8), monocyte chemoattractant protein-1 (CCL2), intercellular adhesion molecule 1 (ICAM1), and heat shock factor 1 (HSF1) were analyzed by quantitative reverse-transcription polymerase chain reaction. Retinal VEGF protein levels were characterized by immunohistochemistry. Results: In untreated eyes, BRVO significantly increased expression of GFAP, IL8, CCL2, ICAM1, HSF1, and AQP4. Expression of VEGF, KCNJ10, and CXCL12 was significantly reduced by 6 days post-BRVO, with expression recovering to healthy control levels by day 20. Treatment with BEV or TA significantly increased VEGF, DMD, and IL6 expression compared with untreated BRVO eyes and suppressed BRVO-induced CCL2 and AQP4 upregulation, as well as recovery of KCNJ10 expression, at 10 to 20 days post-BRVO. Conclusions: Inflammation and cellular osmohomeostasis rather than VEGF suppression appear to play important roles in BRVO-induced retinal neurodegeneration, enhanced in both BEV- and TA-treated retinas. Translational Relevance: Inner retinal neurodegeneration seen in this acute model of BRVO appears to be mediated by inflammation and alterations in osmohomeostasis rather than VEGF inhibition, which may have implications for more specific treatment modalities in the acute phase of BRVO.

Asunto(s)

Inhibidores de la Angiogénesis , Bevacizumab , Citocinas , Modelos Animales de Enfermedad , Inyecciones Intravítreas , Oclusión de la Vena Retiniana , Triamcinolona Acetonida , Animales , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Triamcinolona Acetonida/farmacología , Triamcinolona Acetonida/administración & dosificación , Triamcinolona Acetonida/uso terapéutico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Citocinas/metabolismo , Citocinas/genética , Porcinos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Regulación de la Expresión Génica/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/genética , Canales de Potasio de Rectificación Interna

RESUMEN

Introduction: Stereotactic radiotherapy (SRT) is used for choroidal melanoma (CM) abutting the optic nerve. Visual acuity (VA) deterioration to ≤6/60 is common. We report a pilot study of reduced-dose SRT using 2 Gy/day, aiming to preserve vision without compromising survival. Method: 60 Gy SRT was delivered in 30 fractions over 6 weeks. Liver metastasis surveillance was annual ultrasound. The primary endpoint was 5-year metastasis-free survival (5yMFS). Secondary endpoints were 2-year freedom from local progression (2yFFLP), VA, enucleation rate, and radiation toxicity. Results: Twenty adults aged ≤70 years with T1-T2M0 CM without diabetes mellitus were enrolled. Median follow-up was 5.1 years. About 85% and 90% of tumours were ≤3 mm of the macula and optic disc, respectively. Median tumour height was 2.2 mm (range 1.0-4.4 mm), and median basal diameter was 8.2 mm (range: 4.3-15.0 mm). 5yMFS was 88% (95% CI: 61-97), and the 2yFFLP rate was 90% (95%: CI 66-97). There were three enucleations for disease progression. Final VA in retained eyes was ≥6/7.5 in 6 (30%), 6/9 to 6/12 in 5 (25%), 6/15 to 6/48 in 2 (10%), and ≤6/60 in 4 (20%) eyes. Retinopathy was the main cause of vision loss besides tumour progression. Conclusion: Meaningful vision was preserved 5 years after SRT, despite high-risk tumour locations for vision loss. 2yFFLP and 5yMFS were acceptable. This dose fractionation warrants further investigation.

RESUMEN

The human induced pluripotent stem cell (iPSC) line LEIi019-A was generated from a patient with early-onset pattern dystrophy caused by a heterozygous mutation NM_001270525.1:c.259G>A (p.Glu87Lys) in OTX2. Patient-derived dermal fibroblasts were reprogrammed using episomal plasmids containing reprogramming factors OCT4, SOX2, KLF4, MYCL, LIN28, TP53 shRNA and miR-302/367. The iPSC line expressed pluripotency markers, displayed a normal 46,XY karyotype and demonstrated the ability to differentiate into the three primary germ layers, retinal organoids and retinal pigment epithelial cells.

Asunto(s)

Células Madre Pluripotentes Inducidas , Factor 4 Similar a Kruppel , Factores de Transcripción Otx , Distrofias Retinianas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Factores de Transcripción Otx/genética , Factores de Transcripción Otx/metabolismo , Distrofias Retinianas/genética , Distrofias Retinianas/patología , Línea Celular , Diferenciación Celular , Masculino , Mutación

RESUMEN

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Asunto(s)

Electrorretinografía , Periferinas , Fenotipo , Distrofias Retinianas , Agudeza Visual , Humanos , Periferinas/genética , Persona de Mediana Edad , Adulto , Masculino , Femenino , Adolescente , Distrofias Retinianas/genética , Distrofias Retinianas/fisiopatología , Distrofias Retinianas/diagnóstico , Anciano , Agudeza Visual/fisiología , Niño , Adulto Joven , Preescolar , Tomografía de Coherencia Óptica , Mutación , Angiografía con Fluoresceína , Estudios de Asociación Genética , Estudios Retrospectivos , Análisis Mutacional de ADN , ADN/genética , Linaje

RESUMEN

BACKGROUND/OBJECTIVES: Artificial intelligence can assist with ocular image analysis for screening and diagnosis, but it is not yet capable of autonomous full-spectrum screening. Hypothetically, false-positive results may have unrealized screening potential arising from signals persisting despite training and/or ambiguous signals such as from biomarker overlap or high comorbidity. The study aimed to explore the potential to detect clinically useful incidental ocular biomarkers by screening fundus photographs of hypertensive adults using diabetic deep learning algorithms. SUBJECTS/METHODS: Patients referred for treatment-resistant hypertension were imaged at a hospital unit in Perth, Australia, between 2016 and 2022. The same 45° colour fundus photograph selected for each of the 433 participants imaged was processed by three deep learning algorithms. Two expert retinal specialists graded all false-positive results for diabetic retinopathy in non-diabetic participants. RESULTS: Of the 29 non-diabetic participants misclassified as positive for diabetic retinopathy, 28 (97%) had clinically useful retinal biomarkers. The models designed to screen for fewer diseases captured more incidental disease. All three algorithms showed a positive correlation between severity of hypertensive retinopathy and misclassified diabetic retinopathy. CONCLUSIONS: The results suggest that diabetic deep learning models may be responsive to hypertensive and other clinically useful retinal biomarkers within an at-risk, hypertensive cohort. Observing that models trained for fewer diseases captured more incidental pathology increases confidence in signalling hypotheses aligned with using self-supervised learning to develop autonomous comprehensive screening. Meanwhile, non-referable and false-positive outputs of other deep learning screening models could be explored for immediate clinical use in other populations.

Asunto(s)

Algoritmos , Biomarcadores , Aprendizaje Profundo , Retinopatía Diabética , Hallazgos Incidentales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Retinopatía Diabética/diagnóstico , Fondo de Ojo , Fotograbar/métodos , Anciano , Hipertensión/diagnóstico , Adulto

RESUMEN

Amidst rapid advancements in ocular gene therapy, understanding patient perspectives is crucial for shaping future treatment choices and research directions. This international cross-sectional survey evaluated knowledge, attitudes, and perceptions of ocular genetic therapies among potential recipients with inherited retinal diseases (IRDs). Survey instruments included the Attitudes to Gene Therapy-Eye (AGT-Eye), EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and Patient Attitudes to Clinical Trials (PACT-22) instruments. This study included 496 participant responses (89% adults with IRDs; 11% parents/guardians/carers) from 35 countries, with most from the United States of America (USA; 69%) and the United Kingdom (11%). Most participants (90%) indicated they would likely accept gene therapy if it was available, despite only 45% agreeing that they had good knowledge of gene therapy. The main sources of information were research registries (60% of participants) and the internet (61%). Compared to data from our recently published Australian national survey of people with IRDs (n = 694), USA respondents had higher knowledge of gene therapy outcomes, and Australian respondents indicated a higher perceived value of gene therapy treatments. Addressing knowledge gaps regarding outcomes and financial implications will be central to ensuring informed consent, promoting shared decision-making, and the eventual clinical adoption of genetic therapies.

Asunto(s)

Terapia Genética , Humanos , Terapia Genética/métodos , Adulto , Masculino , Estudios Transversales , Encuestas y Cuestionarios , Femenino , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Enfermedades de la Retina/terapia , Enfermedades de la Retina/genética , Adulto Joven , Adolescente , Anciano , Estados Unidos

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This case report describes an 8-year-old girl who received oral sirolimus as an adjuvant therapy for pulse dye laser of her port-wine stain and as an off-label treatment of exudative retinal detachment secondary to diffuse choroidal hemangioma.

Asunto(s)

Neoplasias de la Coroides , Sirolimus , Síndrome de Sturge-Weber , Humanos , Síndrome de Sturge-Weber/tratamiento farmacológico , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/complicaciones , Neoplasias de la Coroides/tratamiento farmacológico , Neoplasias de la Coroides/diagnóstico , Sirolimus/administración & dosificación , Administración Oral , Hemangioma/tratamiento farmacológico , Hemangioma/diagnóstico , Femenino , Masculino , Angiografía con Fluoresceína , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico

RESUMEN

Inherited retinal diseases (IRDs) are a heterogeneous group of blinding genetic disorders caused by pathogenic variants in genes expressed in the retina. In this study, we sought to develop a method for rapid evaluation of IRD gene variant pathogenicity by inducing expression of retinal genes in patient-derived fibroblasts using CRISPR-activation (CRISPRa). We demonstrate CRISPRa of CRB1 expression in fibroblasts derived from patients with retinitis pigmentosa, enabling investigation of pathogenic mechanisms associated with specific variants. We show the CRB1 c.4005 + 1G>A variant caused exon 11 skipping in CRISPR-activated fibroblasts and retinal organoids (ROs) derived from the same RP12 patient. The c.652 + 5G>C variant was shown to enhance exon 2 skipping in CRISPR-activated fibroblasts and differentially affected CRB1 isoform expression in fibroblasts and ROs. Our study demonstrates an accessible platform for transcript screening of IRD gene variants in patient-derived fibroblasts, which can potentially be applied for rapid pathogenicity assessments of any gene variant.

Asunto(s)

Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Virulencia , Edición Génica , Expresión Génica , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo

RESUMEN

OCT is a widely used clinical ophthalmic imaging technique, but the presence of speckle noise can obscure important pathological features and hinder accurate segmentation. This paper presents a novel method for denoising optical coherence tomography (OCT) images using a combination of texture loss and generative adversarial networks (GANs). Previous approaches have integrated deep learning techniques, starting with denoising Convolutional Neural Networks (CNNs) that employed pixel-wise losses. While effective in reducing noise, these methods often introduced a blurring effect in the denoised OCT images. To address this, perceptual losses were introduced, improving denoising performance and overall image quality. Building on these advancements, our research focuses on designing an image reconstruction GAN that generates OCT images with textural similarity to the gold standard, the averaged OCT image. We utilize the PatchGAN discriminator approach as a texture loss to enhance the quality of the reconstructed OCT images. We also compare the performance of UNet and ResNet as generators in the conditional GAN (cGAN) setting, as well as compare PatchGAN with the Wasserstein GAN. Using real clinical foveal-centered OCT retinal scans of children with normal vision, our experiments demonstrate that the combination of PatchGAN and UNet achieves superior performance (PSNR = 32.50) compared to recently proposed methods such as SiameseGAN (PSNR = 31.02). Qualitative experiments involving six masked clinical ophthalmologists also favor the reconstructed OCT images with PatchGAN texture loss. In summary, this paper introduces a novel method for denoising OCT images by incorporating texture loss within a GAN framework. The proposed approach outperforms existing methods and is well-received by clinical experts, offering promising advancements in OCT image reconstruction and facilitating accurate clinical interpretation.

RESUMEN

Migraine is one of the world's most debilitating disorders, and it has recently been shown that changes in the retina can be a potential biomarker for the disease. These changes can be detected by optical coherence tomography (OCT), which measures retinal thickness, and optical coherence tomography angiography (OCTA), which measures vessel density. We searched the databases Google Scholar, ProQuest, Scopus, and Web of Science for studies in English using OCT and OCTA in migraineurs, using the search terms "optical coherence tomography," "OCT," "optical coherence tomography angiography," "OCTA" and "migraine." We found 73 primary studies, 11 reviews, and 8 meta-analyses pertaining to OCT and OCTA findings in migraineurs. They showed that migraineurs had reduced retinal thickness (via OCT), retinal vessel density, and greater foveal avascular zone area (via OCTA) than controls. OCTA changes reflect a perfusion compromise occurring in migraineurs as opposed to in healthy controls. OCT and OCTA deficits were worse in migraine-with-aura and chronic migraine than in migraine-without-aura and episodic migraine. Certain areas of the eye, such as the fovea, may be more vulnerable to these perfusion changes than other parts. Direct comparison between study findings is difficult because of the heterogeneity between the studies in terms of both methodology and analysis. Moreover, as almost all case-control studies were cross-sectional, more longitudinal cohort studies are needed to determine cause and effect between migraine pathophysiology and OCT/OCTA findings. Current evidence suggests both OCT and OCTA may serve as retinal markers for migraineurs, and further research in this field will hopefully enable us to better understand the vascular changes associated with migraine, perhaps also providing a new diagnostic and therapeutic biomarker.

RESUMEN

Retinitis pigmentosa 11 is an untreatable, dominantly inherited retinal disease caused by heterozygous mutations in pre-mRNA processing factor 31 PRPF31. The expression level of PRPF31 is linked to incomplete penetrance in affected families; mutation carriers with higher PRPF31 expression can remain asymptomatic. The current study explores an antisense oligonucleotide exon skipping strategy to treat RP11 caused by truncating mutations within PRPF31 exon 12 since it does not appear to encode any domains essential for PRPF31 protein function. Cells derived from a patient carrying a PRPF31 1205C>A nonsense mutation were investigated; PRPF31 transcripts encoded by the 1205C>A allele were undetectable due to nonsense-mediated mRNA decay, resulting in a 46% reduction in PRPF31 mRNA, relative to healthy donor cells. Antisense oligonucleotide-induced skipping of exon 12 rescued the open reading frame with consequent 1.7-fold PRPF31 mRNA upregulation in the RP11 patient fibroblasts. The level of PRPF31 upregulation met the predicted therapeutic threshold of expression inferred in a non-penetrant carrier family member harbouring the same mutation. This study demonstrated increased PRPF31 expression and retention of the nuclear translocation capability for the induced PRPF31 isoform. Future studies should evaluate the function of the induced PRPF31 protein on pre-mRNA splicing in retinal cells to validate the therapeutic approach for amenable RP11-causing mutations.

Asunto(s)

Oligonucleótidos Antisentido , Precursores del ARN , Retinitis Pigmentosa , Humanos , Precursores del ARN/genética , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/uso terapéutico , Sistemas de Lectura Abierta , Mutación , Codón sin Sentido , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Linaje

RESUMEN

Quantitative assessment of retinal microvasculature in optical coherence tomography angiography (OCTA) images is important for studying, diagnosing, monitoring, and guiding the treatment of ocular and systemic diseases. However, the OCTA user community lacks universal and transparent image analysis tools that can be applied to images from a range of OCTA instruments and provide reliable and consistent microvascular metrics from diverse datasets. We present a retinal extension to the OCTA Vascular Analyser (OCTAVA) that addresses the challenges of providing robust, easy-to-use, and transparent analysis of retinal OCTA images. OCTAVA is a user-friendly, open-source toolbox that can analyse retinal OCTA images from various instruments. The toolbox delivers seven microvascular metrics for the whole image or subregions and six metrics characterising the foveal avascular zone. We validate OCTAVA using images collected by four commercial OCTA instruments demonstrating robust performance across datasets from different instruments acquired at different sites from different study cohorts. We show that OCTAVA delivers values for retinal microvascular metrics comparable to the literature and reduces their variation between studies compared to their commercial equivalents. By making OCTAVA publicly available, we aim to expand standardised research and thereby improve the reproducibility of quantitative analysis of retinal microvascular imaging. Such improvements will help to better identify more reliable and sensitive biomarkers of ocular and systemic diseases.

Asunto(s)

Mácula Lútea , Vasos Retinianos , Reproducibilidad de los Resultados , Angiografía con Fluoresceína/métodos , Microvasos , Tomografía de Coherencia Óptica/métodos

RESUMEN

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical manifestations of WD are complex and variable, with Kayser-Fleischer ring (K-F ring) and the sunflower cataract being the most common ocular findings. Visual impairment is rare in patients with WD. We report the case of a 17-year-old female with bilateral optic atrophy associated with WD and summarize the clinical features of previously reported cases of optic neuropathy in WD, Clinicians should be aware that WD is a rare cause of optic neuropathy and that optic neuropathy in patients with WD may need to be recognized and screened.

Asunto(s)

Degeneración Hepatolenticular , Atrofia Óptica , Enfermedades del Nervio Óptico , Femenino , Humanos , Adolescente , Degeneración Hepatolenticular/complicaciones , Degeneración Hepatolenticular/diagnóstico , Cobre , Enfermedades del Nervio Óptico/complicaciones , Atrofia Óptica/complicaciones

Asunto(s)

Oftalmología , Humanos , Edición