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Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes. Among the ultra-rare and recently discovered genes is ARSG, coding for the lysosomal sulfatase Arylsulfatase G. This subtype was assigned as "USH IV" with a late onset of RP and usually late-onset progressive SNHL without vestibular involvement. Here, we describe nine new subjects and the clinical description of four cases with the USH IV phenotype bearing seven novel and two known pathogenic variants. Functional experiments indicated the complete loss of sulfatase enzymatic activity upon ectopic expression of mutated ARSG cDNA. Interestingly, we identified a homozygous missense variant, p.(Arg99His), previously described in dogs with neuronal ceroid lipofuscinosis. Our study expands the genetic landscape of ARSG-USH IV and the number of known subjects by more than 30%. These findings highlight that USH IV likely has been underdiagnosed and emphasize the need to test molecularly unresolved subjects with deafblindness syndrome. Finally, testing of ARSG should be considered for the genetic work-up of apparent isolated inherited retinal diseases.
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Objetivo: El objetivo principal del presente estudio consistió en determinar la prevalencia de los cambios en la interfase vitreomacular (IVM) mediante tomografía de coherencia óptica (OCT) en la población general. En segundo lugar, se describieron otros cambios de la OCT. Métodos: Las anomalías en la IVM se diagnosticaron mediante OCT y se distribuyeron de acuerdo con la clasificación del grupo International Vitreomacular Traction Study (estudio internacional de tracción vitreomacular, IVTS, por sus siglas en inglés) y se dividieron en 3 grados según John et al. [Retina 2014;34:442-446]. Resultados: La prevalencia calculada de anomalías vitreomaculares en la población belga de ≥50 años fue del 1,17% [intervalo de confianza (IC 0,38-3,62)] en el caso de tracción vitreomacular (TVM) focal de grado 1; del 0,39% (IC 0,05-2,76) en el caso de TVM focal de grado 2; del 8,17% (IC 5,33-12,53) en el caso de adhesión vitreomacular focal; y del 17,9% (IC 13,41-23,9) en el caso de adhesión vitreomacular difusa. Conclusiones: Se presentó la prevalencia de anomalías vitreomaculares en un estudio de cohortes belga. Estos resultados concuerdan en gran medida con los datos presentados previamente sobre la prevalencia de la TVM. Un conocimiento correcto sobre la epidemiología de las alteraciones en la IVM y un diagnóstico temprano permitirán una intervención satisfactoria.
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PURPOSE: To determine whether cone photoreceptors are impaired early in macular telangiectasia type 2 (MacTel 2) progression. METHODS: Eight patients with MacTel 2 lacking intraretinal cavitation underwent multimodal retinal imaging including adaptive optics. Cone packing metrics were determined in 5 sampling windows at different eccentricities from the fovea. Results were compared with a previously established normative database. RESULTS: In MacTel 2 eyes, cone density was significantly lower than normal at all eccentricities (P < 0.0001). Mean cone spacing and mean percentage of hexagonally organized cone photoreceptors were respectively significantly larger and lower than normal at all eccentricities (P = 0.0488 and P < 0.0001). In MacTel 2 patients, adaptive optics showed an irregular patchy disturbance of the cone mosaic corresponding to some fragmentation of the interdigitation zone on optical coherence tomography. The ellipsoid zone remained intact in the studied area. CONCLUSION: Adaptive optics showed that the macular cone density was lower than normal even outside the telangiectasia in MacTel 2 lacking intraretinal cavitation, although the ellipsoid zone remained intact on optical coherence tomography. These findings do not indicate that the cone density loss is causative of the disease as it might be secondary to Müller cell or rod loss in this area. However, cone density assessment could become a useful parameter to monitor disease progression.
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Imagen Multimodal , Células Fotorreceptoras Retinianas Conos/patología , Telangiectasia Retiniana/diagnóstico , Anciano , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oftalmoscopía , Telangiectasia Retiniana/clasificación , Telangiectasia Retiniana/fisiopatología , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: The primary objective of this study was to determine the prevalence of vitreomacular interface (VMI) changes on optical coherence tomography (OCT) in the general population. Second, other OCT changes were described. METHODS: Abnormalities in the VMI were diagnosed by OCT scan and graded according to the International Vitreomacular Traction Study (IVTS) Group classification and subdivided into 3 grades according to John et al. [Retina 2014;34:442-446]. RESULTS: The estimated prevalence of vitreomacular abnormalities within a Belgian population aged ≥50 years was 1.17% [confidence interval (CI 0.38-3.62)] for focal vitreomacular traction (VMT) grade 1; 0.39% (CI 0.05-2.76) for focal VMT grade 2; 8.17% (CI 5.33-12.53) for focal vitreomacular adhesion, and 17.9% (CI 13.41-23.9) for broad vitreomacular adhesion. CONCLUSION: The prevalence of vitreomacular abnormalities within a Belgian study cohort was reported. These results closely match previously reported data on the prevalence of VMT. Correct knowledge of the epidemiology of VMI disorders and early diagnosis will enable adequate intervention.
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Retina/patología , Perforaciones de la Retina/diagnóstico , Tomografía de Coherencia Óptica/métodos , Cuerpo Vítreo/patología , Desprendimiento del Vítreo/diagnóstico , Bélgica/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Prevalencia , Perforaciones de la Retina/epidemiología , Estudios Retrospectivos , Agudeza Visual , Desprendimiento del Vítreo/epidemiologíaRESUMEN
PURPOSE OF STUDY: This study assessed the effectiveness of a virtual interprofessional education (IPE) discharge planning simulation, focusing on collaborative patient education, and recommendations for hospital discharge. PRIMARY PRACTICE SETTING: An acute care hospital. METHODOLOGY AND SAMPLE: The study utilized a virtual IPE discharge planning simulation for health care students from six different programs. The simulation involved prebriefing, icebreaker, team meeting, patient interaction, and debriefing. Assessment included pre- and post-IPE surveys that included the Interprofessional Education Collaborative (IPEC) Competency Self-Assessment Tool, and video analysis using the Modified McMaster-Ottawa Rating Scale. RESULTS: Student participants from diverse health care programs ( n =143) included nursing ( n = 20), occupational therapy ( n = 21), physical therapy ( n = 42), physician assistant ( n = 38), respiratory therapy ( n = 3), and social work ( n = 19). All programs except respiratory therapy showed significant improvement in IPEC Competency scores post-IPE, with positive outcomes for understanding other professions' roles. Students' self-reported perceptions of team performance were rated highly in various categories. Video analysis demonstrated strong interrater reliability for team scores. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Effective hospital discharge planning is vital for cost reduction and patient care improvement. IPE emphasizes collaborative learning among health care students. Previous studies highlight positive outcomes from IPE discharge planning, including virtual formats. This virtual IPE discharge planning simulation significantly improved students' understanding and collaboration competencies, evident in increased IPEC scores across five professions.
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Educación Interprofesional , Grupo de Atención al Paciente , Alta del Paciente , Humanos , Alta del Paciente/normas , Educación Interprofesional/métodos , Conducta Cooperativa , Femenino , Masculino , Adulto , Relaciones Interprofesionales , Personal de Salud/educaciónRESUMEN
PURPOSE: To report a case of metastatic cutaneous melanoma to the choroid with rapid and complete resolution of associated choroidal elevation and subretinal fluid after initiation of combined targeted therapy. METHODS: We describe a case of a 41-year-old man diagnosed with a metastatic cutaneous melanoma to the choroid of his right eye, for which treatment with dabrafenib/trametinib was initiated. RESULTS: A 41-year-old man with a past medical history of a BRAF V600E/V600E2/V600D mutated invasive superficial spreading cutaneous melanoma presented with acute metamorphopsia and blurred vision in his right eye. Examination revealed a best-corrected visual acuity (BCVA) of 20/22 and 2 elevated choroidal lesions temporal to the fovea with subretinal exudation to the fovea on fundoscopy. On repeat examination 3 days later, his vision had further decreased to 20/50 with an increase of subretinal fluid. Treatment with BRAF/MEK-inhibitor dabrafenib/trametinib was initiated, with complete resolution of the choroidal masses and subretinal exudation and improvement of the BCVA to 20/22 after only 15 days. Follow-up 8 weeks after start of therapy showed stable fundoscopic and tomographic findings, with further improvement of BCVA to 20/17 and no ocular side effects. CONCLUSION: A case of metastatic cutaneous melanoma to the choroid with choroidal elevation and subretinal exudation to the fovea, for which treatment with dabrafenib/trametinib was initiated. Rapid and complete resolution of choroidal metastasis and the associated subretinal exudation after initiation of combined targeted therapy was seen, without any ocular side effects.
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Purpose: This retrospective observational study reports early results on a cohort of neovascular age-related macular degeneration (nAMD) patients switched to brolucizumab, a recently approved anti-vascular endothelial growth factor (anti-VEGF). Patients and Methods: We evaluated best-corrected visual acuity (BCVA), treatment interval, central subfield retinal thickness (CST) and the presence of intra-retinal (IRF), subretinal (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid on optical coherence tomography (OCT). Concurrently, patients were carefully examined for signs of intra-ocular inflammation (IOI) and other adverse events. Results: Seventeen patients (19 eyes) were included. The difference in BCVA at baseline compared to the last examination following brolucizumab injection was not statistically significant (Wilcoxon signed-rank test, p=0.247). Mean CST decrease was -5.16 ±48.28 µm (p=0.647). A morphological improvement in IRF was observed in four eyes, with a complete resolution in 50% (n=2) and a decrease in 50% (n=2). Regarding SRF (total n=15), resolution was seen in 46.67% (n=7), decrease in 26.67% (n=4) and stabilization in 13.33% (n=2). Increase in SRF was observed in 13.33% (n=2). Of 14 eyes with sub-RPE fluid, 7.14% (n=1) demonstrated a resolution, 42.86% (n=6) a decrease, 50% (n=7) a stabilization and none an increase in fluid. Mean treatment interval was increased by 4.08 ±1.40 weeks (p<0.001). Treatment was discontinued in seven eyes (41.18%), including four cases due to IOI. In all four cases, inflammation was mild and resolved under corticosteroid treatment. No cases of vasculitis were observed. Conclusion: This study provides additional data suggesting that brolucizumab is a beneficial alternative for patients refractory to other anti-VEGF therapies. It can provide a morphological reduction in fluid and prolong the treatment interval, while maintaining a stable BCVA and CST. However, as a higher occurrence of IOI is probable, patients should be informed, selected and monitored carefully. Signs of inflammation should be detected early and treated promptly.
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PURPOSE: To describe different ocular paraneoplastic syndromes in patients treated with Immune Checkpoint Inhibitors (ICI), its relation with different types of ICI and different types of tumors, and its implications for treatment. METHODS: A comprehensive review of the literature was performed. RESULTS: Patients treated with ICI can present with different ocular paraneoplastic syndromes, such as Carcinoma Associated Retinopathy (CAR), Melanoma Associated Retinopathy (MAR) and paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy (pAEPVM). In literature, the different types of paraneoplastic retinopathy are mostly related to different types of primary tumors, with MAR and pAEPVM seen in melanoma, and CAR in carcinoma. Visual prognosis is limited in MAR and CAR. CONCLUSION: Paraneoplastic disorders result from an antitumor immune response against a shared autoantigen between the tumor and ocular tissue. ICI enhance the antitumor immune response, which can lead to increased cross-reaction against ocular structures and unmasking of a predisposed paraneoplastic syndrome. Different types of primary tumors are related to different cross-reactive antibodies. Therefore, the different types of paraneoplastic syndromes are related to different types of primary tumors and are probably unrelated to the type of ICI. ICI-related paraneoplastic syndromes often lead to an ethical dilemma. Continuation of ICI treatment can lead to irreversible visual loss in MAR and CAR. In these cases overall survival must be weighed against quality of life. In pAEPVM however, the vitelliform lesions can disappear with tumor control, which may involve continuation of ICI.
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PURPOSE: To describe a case of bilateral Vogt-Koyanagi-Harada (VKH)-like uveitis during treatment with dabrafenib and trametinib and three months after discontinuation of nivolumab for malignant melanoma, and discuss the possible (synergistic) role(s) of mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors in its pathophysiology. METHODS: Retrospective case report with fluorescein angiography and optical coherence tomography. RESULTS: A 55-year old patient with metastatic melanoma presented with a complaint of gradually worsening blurry vision in the right eye during treatment with dabrafenib and trametinib, three months after discontinuation of nivolumab. Based on the clinical examination, optical coherence tomography and fluorescein angiography findings, and a thorough laboratory work-up, he was diagnosed with a bilateral VKH-like uveitis without extraocular manifestations. The uveitis responded well to oral corticosteroids. CONCLUSION: Vogt-Koyanagi-Harada-like uveitis is a rare adverse effect of MAPK inhibitors and immune checkpoint inhibitors. Similar pathogenetic mechanisms including a drug-induced autoimmunity targeted against benign and malignant melanocytes may underlie MAPK inhibitor-induced and immune checkpoint inhibitors-induced VKH-like uveitis. In our report, the patient developed a VKH-like uveitis during MAPK inhibition therapy, four months after discontinuation of nivolumab. It is difficult to delineate whether MAPK inhibition alone was responsible for this adverse effect, or whether, on the contrary, potentiation occurred as a result of immune modulation by previous treatment with an immune checkpoint inhibitor. Further cases are needed to further clarify this latter hypothesis.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Melanoma , Uveítis , Síndrome Uveomeningoencefálico , Masculino , Humanos , Persona de Mediana Edad , Nivolumab/efectos adversos , Síndrome Uveomeningoencefálico/inducido químicamente , Síndrome Uveomeningoencefálico/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico , Estudios Retrospectivos , Melanoma/tratamiento farmacológicoRESUMEN
AIM: To evaluate the MONA.health artificial intelligence screening software for detecting referable diabetic retinopathy (DR) and diabetic macular edema (DME), including subgroup analysis. METHODS: The algorithm's threshold value was fixed at the 90% sensitivity operating point on the receiver operating curve to perform the disease classification. Diagnostic performance was appraised on a private test set and publicly available datasets. Stratification analysis was executed on the private test set considering age, ethnicity, sex, insulin dependency, year of examination, camera type, image quality, and dilatation status. RESULTS: The software displayed an area under the curve (AUC) of 97.28% for DR and 98.08% for DME on the private test set. The specificity and sensitivity for combined DR and DME predictions were 94.24 and 90.91%, respectively. The AUC ranged from 96.91 to 97.99% on the publicly available datasets for DR. AUC values were above 95% in all subgroups, with lower predictive values found for individuals above the age of 65 (82.51% sensitivity) and Caucasians (84.03% sensitivity). CONCLUSION: We report good overall performance of the MONA.health screening software for DR and DME. The software performance remains stable with no significant deterioration of the deep learning models in any studied strata.
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In this report, we present a case of unilateral melanoma-associated retinopathy in a 72-year-old woman. The patient's main symptoms were decreased vision and positive dysphotopsia. Unilateral electronegative electroretinogram (ERG) was suggestive for melanoma retinopathy. PET-CT discovered metastatic disease, 3 years after the initial melanoma. A prompt treatment with corticosteroids was started, followed by immunotherapy. The central and peripheral vision of the patient improved, and the ERG showed normalization of the responses. This case highlights the importance of early recognition and individualized treatment strategies for melanoma-associated retinopathy.
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Background: A common carotid artery occlusion (CCAO) is very rare and the clinical features of CCAO have rarely been described. Since the blood supply of the eye and orbit is derived from the internal carotid artery, a CCAO may present with various ophthalmological symptoms, ranging from incidental findings to complete visual loss but also other neuro-ophthalmological abnormalities. Case report: A 61-year-old woman presented with acute monocular vision loss and an elevation deficit of the right eye. Fluorescein angiography showed delayed filling of both the retinal and choroidal vasculature, without occlusion/embolisms of the retinal arteries. Vascular imaging showed a right CCAO. Conclusion: CCAO has a variable presentation. In patients with acute unilateral visual loss a CCAO should be considered, especially when ocular motility deficits are present. Fluorescein angiography examination can aid in the localization and diagnosis of the vascular insult. Urgent referral for a systemic work-up is essential.
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Objective: Explore perceptions and preoccupations regarding use of medical cannabis against chronic musculoskeletal pain, among patients and physicians. Design: Qualitative study using interviews with patients and physicians, based on the Theory of Planned Behavior (TPB). Setting: The study was conducted in Quebec, Canada, in spring 2020. Subjects: We included 27 adult patients and 11 physicians (GPs, anesthesiologists, psychiatrists, and a rheumatologist); the mean age of patients was 48.2 years; 59.3% of patients and 36.4% of physicians were women; 59.3% of patients used no medical cannabis at the time of study; 45.5% of physicians had never authorized it. Methods: Semi-structured interviews were conducted, transcribed and for the qualitative analysis codes were developed in a hybrid, inductive and deductive approach. Guided by the TPB, facilitators and barriers, perceived benefits and harms, and perceived norms that may influence cannabis use or authorization were documented. Results: Although medical cannabis is an interesting avenue for the relief of chronic musculoskeletal pain, doctors and patients agreed that it remained a last line option, due to the lack of scientific evidence regarding its safety and efficacy. The norms surrounding medical cannabis also play an important role in the social and professional acceptance of this therapeutic option. Conclusion: Medical cannabis is seen as a last line option among interventions in the management of chronic pain, and attitudes and prior experiences play a role in the decision to use it. Study results may contribute to improved shared decision making between patients and physicians regarding this option.
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This case report describes full-thickness macular hole formation after intravitreal aflibercept injections for the treatment of macular neovascularization in neovascular age-related macular degeneration (AMD). Only limited case reports and case series have reported this possible adverse event after aflibercept injection. Possible mechanisms leading to the formation of a macular hole subsequent to intravitreal injection are focal tractional forces on the vitreoretinal interface due to globe deformation during needle insertion, vitreous syneresis, and vitreous incarceration at the injection site, and tangential shearing forces on the posterior surface of the retina due to contraction and rapid volume reduction of the neovascular membrane or a decrease in intra- or subretinal fluid. Furthermore, some reports suggest a toxic effect of the anti-vascular endothelial growth factor agent on a previously compromised retina as etiological factor. Macular hole formation may thus represent a rare adverse event of intravitreal aflibercept injection in patients with neovascular AMD, and it should be included in the differential diagnosis of post-injectional visual loss.
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PURPOSE: To report a case of bilateral Vogt-Koyanagi-Harada (VKH)-like granulomatous pan uveitis secondary to brentuximab vedotin (BV) administration to treat for classical Hodgkin lymphoma (CHL). OBSERVATIONS: A case of bilateral pan uveitis is described, following administration of BV, with features of VKH-like uveitis: presence of inflammatory cells in the anterior and posterior segment, multiple small serous detachments around the optic disc and retinal pigment epithelium (RPE) folds confirmed by optical coherence tomography (OCT) as well as hypocyanesent dark dots, disc hyperfluorescence and fuzzy vascular patterns seen on indocyanine green and fluorescein angiography. There were no systemic features of VKH disease. Further etiological investigation showed no clear infectious or inflammatory cause. The uveitis responded well to treatment with corticosteroids and cessation of BV. A relapse occurred a few months later when BV treatment was reinitiated, suggesting a probable adverse event to this drug, according to the Naranjo algorithm. CONCLUSIONS: We hypothesize that administration of BV can induce a VKH-like uveitis, caused by loss of function of protective CD30+ cells present in the uveal tract, possibly aggravated by collateral damage to surrounding CD30-cells and melanocytes, leading to a uveal immune reaction. It is therefore important for the clinicians using BV to be aware of this adverse event. Growing experience with immunotherapy will provide more clinical insights in these complex immune mechanisms in the future.
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PURPOSE: The purpose of this report was to describe a case with paracentral acute middle maculopathy after oral intake of sumatriptan. METHODS: Case presentation. RESULTS: One patient showed typical findings on fundoscopic examination and optical coherence tomography consistent with paracentral acute middle maculopathy following oral intake of sumatriptan. CONCLUSION: Sumatriptan may be a trigger for paracentral acute middle maculopathy.
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Degeneración Macular , Enfermedades de la Retina , Sumatriptán , Enfermedad Aguda , Administración Oral , Humanos , Degeneración Macular/inducido químicamente , Degeneración Macular/diagnóstico por imagen , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico por imagen , Sumatriptán/administración & dosificación , Sumatriptán/efectos adversos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To report on two cases with paraneoplastic acute exudative polymorphous vitelliform maculopathy within one month after the initiation of nivolumab. METHODS: Case report. RESULTS: Two patients with metastatic mucosal melanoma were diagnosed with acute exudative polymorphous vitelliform maculopathy within one month after the initiation of the checkpoint inhibitor nivolumab. Both cases showed a neurosensory retinal detachment and subretinal hyperautofluorescent material, which persisted after discontinuation of nivolumab and treatment with local and/or systemic corticosteroids. In one case, nivolumab was introduced again in a later stage in combination with surgical reduction of the tumor, eventually leading to resolution of the subretinal lipofuscin-rich fluid. CONCLUSION: The development of paraneoplastic acute exudative polymorphous vitelliform maculopathy in melanoma patients can be triggered by treatment with nivolumab. However, achieving tumor control, which may involve continuation of nivolumab, could be the key to success.