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Recurrence of meningiomas after surgery and radiotherapy deserves specific attention because of the lack of active third-line therapies. Somatostatin receptors are usually overexpressed on the cell membrane of meningiomas, and this has led the way to a radionuclide theranostic approach. Diagnoses with 68Ga-DOTA-octreotide and peptide receptor radionuclide therapy (PRRT) with 90Y/177Lu-DOTA-octreotide are currently possible options within experimental protocols or as compassionate use in small patient groups. Methods: From October 2009 to October 2021, 42 meningioma patients with radiologic recurrence after standard therapies were treated with 90Y-DOTATOC (dosage of 1.1 or 5.5 GBq) or with 177Lu-DOTATATE (dosage of 3.7 or 5.5 GBq) in a mean of 4 cycles. All patients showed intense uptake at diagnostic 68Ga-DOTATOC PET/CT or in an 111In-octreotide scan. Results: Of 42 patients treated, 5 patients received 90Y-DOTATOC with a cumulative activity of 11.1 GBq and 37 patients received 177Lu-DOTATATE with a cumulative activity of 22 GBq. The disease control rate was 57%. With a median follow-up of 63 mo, median progression-free survival was 16 mo, and median overall survival was 36 mo. Retreatment 177Lu-PRRT was performed in 6 patients with an administered median activity of 13 GBq in a mean of 5 cycles. With a 75.8-mo follow-up, median progression-free survival and overall survival were 6.5 and 17 mo, respectively. Only 1 patient discontinued the treatment because of grade 3 platelet toxicity. A rapidly transient grade 2 neutropenia was recorded in 1 retreated patient. Conclusion: PRRT in patients with advanced meningiomas overexpressing somatostatin receptor 2 was active and well tolerated, showing a 57% disease control rate. Furthermore, PRRT could represent a potential retreatment option. Further studies, also in combination with other treatments, are warranted.
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Purpose: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Methods: Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. Results: At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Conclusions: Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.
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Electrorretinografía , Terapia Genética , Miosina VIIa , Tomografía de Coherencia Óptica , Síndromes de Usher , Agudeza Visual , Campos Visuales , Humanos , Masculino , Femenino , Adulto , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual/fisiología , Persona de Mediana Edad , Campos Visuales/fisiología , Adulto Joven , Adolescente , Síndromes de Usher/genética , Síndromes de Usher/fisiopatología , Síndromes de Usher/terapia , Síndromes de Usher/diagnóstico , Terapia Genética/métodos , Niño , Pruebas del Campo Visual , Europa (Continente) , Angiografía con Fluoresceína , Estudios de Seguimiento , Anciano , Estudios Longitudinales , Progresión de la Enfermedad , Miosinas/genética , Retina/diagnóstico por imagen , Retina/fisiopatología , Retina/patologíaRESUMEN
PURPOSE: To assess the efficacy of voretigene neparvovec (VN) treatment by objective fixation stability and chromatic pupillometry testing in clinical practice. DESIGN: Retrospective cohort study with longitudinal follow-up. SUBJECTS: Twelve patients (aged 7-34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes. METHODS: Patients treated at the same center with VN were evaluated over a 12-month posttreatment follow-up by subjective and objective tests. Furthermore, patients treated with VN who developed atrophy were compared with those who did not. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), full-field stimulus threshold test (FST), semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over a 12-month follow-up. RESULTS: Significant improvements of BCVA (P < 0.001), SKVF (P < 0.05), and FST (P < 0.001) were already observed 45 days after treatment and were maintained at the 12-month timepoint. Fixation stability, assessed by microperimetry, improved significantly (P < 0.05) after treatment. Chromatic pupillometry showed significant improvements (P < 0.05) at the 6- and 12-month timepoints. The increase in maximum pupillary constriction significantly (P < 0.001) correlated with higher retinal sensitivity in FST. Four patients developed multifocal retinal atrophy in both eyes, detected at the 6-month timepoint, but this atrophy was not generally associated with worse visual function outcomes. CONCLUSIONS: This study explores objective outcomes in order to demonstrate the efficacy of VN treatment in addition to the tests normally performed in clinical practice. Our findings show a significant improvement of retinal function both in subjective assessments, such as BCVA, SKVF, and FST, and in objective measurements of fixation stability and maximum pupillary constriction. Moreover, the significant correlation between maximum pupillary constriction and light sensitivity thresholds corroborates the introduction of chromatic pupillometry as an objective test to better assess treatment outcomes in patients with inherited retinal dystrophies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.
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Distrofias Retinianas , Agudeza Visual , Campos Visuales , cis-trans-Isomerasas , Humanos , Masculino , Femenino , Adolescente , Estudios Retrospectivos , Niño , Adulto , Agudeza Visual/fisiología , Adulto Joven , Estudios de Seguimiento , Campos Visuales/fisiología , cis-trans-Isomerasas/genética , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/fisiopatología , Distrofias Retinianas/genética , Distrofias Retinianas/terapia , Resultado del Tratamiento , Terapia Genética/métodos , Pruebas del Campo VisualRESUMEN
BACKGROUND: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. CASES PRESENTATION: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. CONCLUSIONS: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.
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Anemia Megaloblástica , Sordera , Diabetes Mellitus , Pérdida Auditiva Sensorineural , Humanos , Niño , Adulto , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/genética , Tiamina/uso terapéutico , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/tratamiento farmacológico , Diagnóstico Precoz , Sordera/complicaciones , Sordera/tratamiento farmacológicoRESUMEN
Inherited retinal diseases (IRDs) are a group of clinically and genetically heterogeneous disorders that may be complicated by several vitreoretinal conditions requiring a surgical approach. Pars plana vitrectomy (PPV) stands as a valuable treatment option in these cases, but its application in eyes with such severely impaired chorioretinal architectures remains controversial. Furthermore, the spreading of gene therapy and the increasing use of retinal prostheses will end up in a marked increase in demand for PPV surgery for IRD patients. The retinal degeneration that typically affects patients with hereditary retinal disorders may influence the execution of the surgery and the expected results. Considering the importance of PPV application in IRD-related complications, it is fundamental to try to understand from the literature what is adequate and safe in posterior eye segment surgery. Use of dyes, light toxicity, and risk of wounding scar development have always been themes that discourage the execution of vitreoretinal surgery in already impaired eyes. Therefore, this review aims to comprehensively summarize all PPV applications in different IRDs, highlighting the favorable results as well as the potential precautions to consider when performing vitreoretinal surgery in these eyes.
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Optical coherence tomography angiography (OCT-A) is a valuable imaging technique, allowing non-invasive, depth-resolved, motion-contrast, high-resolution images of both retinal and choroidal vascular networks. The imaging capabilities of OCT-A have enhanced our understanding of the retinal and choroidal alterations that occur in inherited retinal diseases (IRDs), a group of clinically and genetically heterogeneous disorders that may be complicated by several vascular conditions requiring a prompt diagnosis. In this review, we aimed to comprehensively summarize all clinical applications of OCT-A in the diagnosis and management of IRDs, highlighting significant vascular findings on retinitis pigmentosa, Stargardt disease, choroideremia, Best disease and other less common forms of retinal dystrophies. All advantages and limitations of this novel imaging modality will be also discussed.
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OBJECTIVE: Clinical trials offer new and potentially more effective therapeutic options for cancer patients and a potential cost-saving opportunity, especially considering that trial drugs are provided free-of-charge. The aim of this study was to analyse drug-related cost savings in clinical trials in a cancer institute over a 3 year period. The cost savings relate to the pharmaceutical expenditure of our centre, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori". METHODS: We conducted a retrospective analysis of patients taking part in interventional clinical cancer trials approved by a local independent Ethics Committee between 1 January 2018 and 31 December 2020. The standard of care (SOC) was identified as the standard treatment that would have been offered to a patient if he/she had not been enrolled in the study. The sum of SOC costs of all patients represents the potential cost avoidance during the study period. Results were stratified by year, trial promoter, trial phase and tumour type. The same approach was used to perform a secondary analysis of compassionate use programmes. RESULT: In the 3 year analysis, 1,257 patients were treated with experimental therapies in 244 clinical trials, of which 157 were profit and 87 academic. Results showed an overall cost savings of 13,266,518, more than 50% of which (7,035,009) was related to phase III studies. Profit clinical trials generated 9,069,764 (68.4%) of the drug cost savings compared with 4,196,754 (31.6%) of academic studies. The stratification for tumour type was 3,552,592 (26.8%) genitourinary cancer, 3,268,074 (24.6%) melanoma, 2,574,127 (19.4%) haematological malignancies, 2,330,791 (17.6%) lung cancer, 728,149 (5.5%) gastrointestinal cancer, 557,608 (4.2%) rare tumours and 255,178 (1.9%) breast cancer. The secondary analysis on compassionate use included 122 patients involved in 28 different access programmes and revealed cost savings of 1,649,550. CONCLUSION: The results of our analysis point to the benefits of participating in and planning clinical trials for the public healthcare sector.
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Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Medicina Estatal , Gastos en Salud , Estudios Retrospectivos , Antineoplásicos/uso terapéuticoRESUMEN
Purpose: To report a case of peripapillary pachychoroid syndrome (PPS) successfully treated with navigated subthreshold micropulse laser (SML). Observations: A 65-year-old male was referred to our retina service complaining a worsening vision in the left eye (LE) over the past 6 months. A complete ophthalmological evaluation including best corrected visual acuity (BCVA) measurement, spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) was performed. SD-OCT showed a thicker nasal choroid and peripapillary intraretinal cysts in both eyes, and macular subretinal fluid (SRF) in the LE. FA illustrated a bilateral peripapillary hyperfluorescent areas, with some macular focal leaking points in the left eye. A diagnosis of PPS was made, and considering the worldwide shortage of verteporfin, Navigated 577-nm SML was performed in the LE on the leaking areas shown on the FA. At the 3- and 6- months follow-up the SRF reabsorbed and BCVA improved from 20/32 to 20/20. Conclusions and importance: SML can be considered an efficacious treatment option in patients with PPS. Prospective studies with longer follow-up in a bigger cohort are needed to confirm the optimal treatment strategy in PPS.
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Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular diagnosis for 2036 patients (from 1683 unrelated families). We identified a total of 1319 causative sequence variations in 132 genes, including 353 novel variants, and 866 possibly actionable genotypes for therapeutic approaches. ABCA4 was the most frequently mutated gene (n = 535; 26.3% of solved cases), followed by USH2A (n = 228; 11.2%) and RPGR (n = 102; 5.01%). The other 129 genes had a lower contribution to IRD pathogenesis (e.g. CHM 3.5%, RHO 3.5%; MYO7A 3.4%; CRB1 2.7%; RPE65 2%, RP1 1.8%; GUCY2D 1.7%). Seventy-eight genes were mutated in five patients or less. Mitochondrial DNA variants were responsible for 2.1% of cases. Our analysis confirms the complex genetic etiology of IRDs and reveals the high prevalence of ABCA4 and USH2A mutations. This study also uncovers genetic associations with a spectrum of clinical subgroups and highlights a valuable number of cases potentially eligible for clinical trials and, ultimately, for molecular therapies.
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Enfermedades de la Retina , Humanos , Epidemiología Molecular , Estudios Retrospectivos , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/genética , Retina , Italia/epidemiología , Proteínas del Ojo/genética , Transportadoras de Casetes de Unión a ATP/genética , Proteínas de la Membrana/genética , Proteínas del Tejido NerviosoRESUMEN
Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis. In vitro studies were conducted in two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3-Bbs10-/-cells) and over-expressed. The CKD status affected plasmatic metabolite fingerprinting in both patients with BBS and controls. Specific phosphatidylcholine and acylcarnitines discriminated eGFR decline only in patients with BBS. IMCD3-Bbs10-/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane and citrate synthase staining. Mass-Spectrometry-based analysis revealed that human BBS10 interacted with six mitochondrial proteins, in vitro. In conclusion, renal dysfunction correlated with abnormal phosphatidylcholine and acylcarnitines plasma levels in patients with BBS; in vitro, Bbs10 depletion caused mitochondrial defects while human BBS10 interacted with several mitochondria-related proteins, suggesting an unexplored role of this protein.
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To report quantitative retinal changes assessed by spectral-domain optical coherence tomography (SD-OCT) in children treated with voretigene neparvovec (VN) at a single center in Italy. Retrospective review of six consecutive pediatric patients with biallelic RPE65-related dystrophy treated bilaterally with VN. SD-OCT scans were analyzed to extract Early Treatment Diabetic Retinopathy Study (ETDRS) thickness maps of the whole retina and the outer nuclear layer (ONL). Changes in visual function were assessed by best-corrected visual acuity (BCVA) and retinal morphology at Days 30/45 and 180. BCVA significantly improved at Day 30/45 and 6 months (both P < 0.001). Central foveal retinal thickness and central foveal ONL thickness tended to increase (6.4 ± 19.2 µm; P = 0.080 and 3.42 ± 7.68 µm; P = 0.091, respectively). ONL thickness of the internal ETDRS-ring significantly increased at day 30/45 (4.7 ± 8.4 µm; P < 0.001) and day 180 (5.0 ± 5.7 µm; P = 0.009). Intra-operative foveal detachment was not associated with a higher function gain in terms of BCVA, but with a mild thinning of foveal ONL after treatment. The improvement of BCVA and thickening of the ONL layer suggest that improvement of visual acuity could be related to partial recovery of retinal morphology in the perifoveal ring.
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Retina , Distrofias Retinianas , Humanos , Niño , Retina/diagnóstico por imagen , Fóvea Central/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Distrofias Retinianas/genética , Distrofias Retinianas/terapia , Estudios RetrospectivosRESUMEN
OBJECTIVES: Although inherited retinal disorders (IRDs) related to the gene encoding the retinal pigment epithelium 65kD protein (RPE65) significantly impact the vision-related quality of life (VRQoL), their emotional and social aspects remain poorly investigated in Italy. Narrative Medicine (NM) reveals the more intimate aspects of the illness experience, providing insights into clinical practice. DESIGN AND SETTING: This NM project was conducted in Italy between July and December 2020 and involved five eye clinics specialised in IRDs. Illness plots and parallel charts, together with a sociodemographic survey, were collected through the project's website; remote in-depth interviews were also conducted. Narratives and interviews were analysed through NVivo software and interpretive coding. PARTICIPANTS: 3 paediatric and 5 adult patients and eight caregivers participated in the project; 11 retinologists globally wrote 27 parallel charts; 5 professionals from hospital-based multidisciplinary teams and one patient association member were interviewed. RESULTS: Findings confirmed that RPE65-related IRDs impact VRQoL in terms of activities and mobility limitations. The emotional aspects emerged as crucial in the clinical encounter and as informative on IRD management challenges and real-life experiences, while psychological support was addressed as critical from clinical diagnosis throughout the care pathway for both patients and caregivers; the need for an IRDs 'culture' emerged to acknowledge these conditions, and therefore, promoting diversity within society. CONCLUSIONS: The project was the first effort to investigate the impact of RPE65-related IRDs on the illness experience through NM, concomitantly addressing the perspectives of paediatric and adult patients, caregivers and healthcare professionals and provided preliminary insights for the knowledge of RPE65-related IRDs and the clinical practice.
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Medicina Narrativa , Enfermedades de la Retina , Adulto , Cuidadores/psicología , Niño , Emociones , Humanos , Calidad de Vida/psicología , Trastornos de la VisiónRESUMEN
Anti-vascular endothelial growth factor nowdays represents the standard of care for diabetic macular edema (DME). Nevertheless, the burden of injections worldwide has created tremendous stress on the healthcare system during the COVID-19 pandemic. The aim of this study was to investigate the effects of the oral administration of Curcuma longa and Boswellia serrata (Retimix®) in patients with non-proliferative diabetic retinopathy (DR) and treatment-naïve DME < 400 µm, managed during the COVID-19 pandemic. In this retrospective study, patients were enrolled and divided into two groups, one undergoing observation (Group A, n 12) and one receiving one sachet a day of Retimix® (Group B, n 49). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured by spectral-domain optical coherence tomography were performed at baseline, then at one and six months. A mixed-design ANOVA was calculated to determine whether the change in CMT and BCVA over time differed according to the consumption of Retimix®. The interaction between time and treatment was significant, with F (1.032, 102.168) = 14.416; η2 = 0.127; p < 0.001, indicating that the change in terms of CMT and BCVA over time among groups was significantly different. In conclusion, our results show the efficacy of Curcuma longa and Boswellia serrata in patients with non-proliferative DR and treatment-naïve DME in maintaining baseline CMT and BCVA values over time.
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Since prostate cancer is the most commonly diagnosed malignancy in men, the theranostic approach has become very attractive since the discovery of urea-based PSMA inhibitors. Different molecules have been synthesized starting from the Glu-urea-Lys scaffold as the pharmacophore and then optimizing the linker and the chelate to improve functional characteristics. This article aimed to highlight the quality aspects, which could have an impact on clinical practice, describing the development of an Investigational Medicinal Product Dossier (IMPD) for clinical trials with [177Lu]Lu-PSMA-I&T in prostate cancer and other solid tumors expressing PSMA. The results highlighted some important quality issues of the final preparation: radiolabeling of PSMA-I&T with lutetium-177 needs a considerably longer time compared with the radiolabeling of the well-known [177Lu]Lu-PSMA-617. When the final product was formulated in saline, the stability of [177Lu]Lu-PSMA-I&T was reduced by radiolysis, showing a decrease in radiochemical purity (<95% in 24 h). Different formulations of the final product with increasing concentrations of ascorbic acid have been tested to counteract radiolysis and extend stability. A solution of 20 mg/mL of ascorbic acid in saline prevents radiolysis and ensures stability over 30 h.
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Glutamato Carboxipeptidasa II , Neoplasias de la Próstata , Antígenos de Superficie , Ácido Ascórbico/uso terapéutico , Dipéptidos/química , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/química , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Control de Calidad , Radiofármacos/química , Radiofármacos/uso terapéutico , UreaRESUMEN
The latest technological developments have radically impacted the daily practice of ophthalmologists, thanks to the advent of novel diagnostic tools that facilitate an early diagnosis and allow a better management of ocular disorders [...].
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PURPOSE: Retinol dehydrogenase 5 (RDH5)-related fundus albipunctatus can present with phenotypic variability. Our purpose was to investigate new clinical characteristics and multimodal imaging findings in patients from different ethnic origins, carrying different mutations. METHODS: Multicenter international retrospective case series of 18 patients with genetically confirmed RDH5-related fundus albipunctatus. Patients' files were reviewed for fundus images, visual acuity, macular optical coherence tomography scans, near-infrared images, fundus autofluorescence, electroretinogram, and genetic mutations. Imaging and electroretinogram findings. RESULTS: All eyes (n = 36, 100%) showed small circular findings seen on near-infrared images, termed as the "target sign," correlating to the yellowish dots seen clinically and to the distinct hyperreflective linear lesions on optical coherence tomography at the level between external limiting membrane and retinal pigment epithelium. Perifoveal atrophy with foveal sparing was seen in 4 eyes of 2 patients (both RDH5-c.160C>T, p.R54X mutation). Fundus autofluorescence revealed small hyperautofluorescent dots (n = 16, 44.4%). Scotopic electroretinograms were significantly reduced in all cases with an electronegative pattern, 66.7% displayed cone dysfunction. CONCLUSION: Our results show distinct imaging findings present in all patients with fundus albipunctatus independent of ethnicity or genetic mutation. Our results can facilitate the current algorithm to diagnose RDH5-related fundus albipunctatus and allow for targeted genetic testing.
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Ceguera Nocturna , Distrofias Retinianas , Oxidorreductasas de Alcohol , Electrorretinografía , Etnicidad , Angiografía con Fluoresceína , Humanos , Imagen Multimodal , Ceguera Nocturna/diagnóstico , Ceguera Nocturna/genética , Enfermedades de la Retina , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
BACKGROUND: To investigate the anatomical and functional results in eyes with peripapillary pachychoroid syndrome (PPS) undergoing photodynamic therapy (PDT). METHODS: A total of 25 eyes from 23 patients with PPS treated with PDT were retrospectively evaluated in this multicentric study. Main outcome measure was the proportion of eyes that achieved treatment success, defined as a decrease in both subretinal fluid (SRF) height and central subfield thickness (CST), at 3 months after PDT compared to baseline. Secondary outcomes were the change in CST, SRF, and best-corrected visual acuity (BCVA) 3 months after treatment and predictive factors for treatment success. When available, data between 3 and 12 months were also reviewed. RESULTS: Treatment success was achieved in 16 eyes (64%). In the total cohort, CST decreased significantly from 356 ± 118 µm at baseline to 282 ± 90 µm and 270 ± 91 µm at 1 and 3 months, respectively (p < 0.001). Maximal SRF height decreased significantly from 102 ± 83 µm at baseline to 38 ± 46 µm and 32 ± 42 µm at 1 and 3 months, respectively (p < 0.001), and remained stable at month 6 (29 ± 44 µm) and month 12 (23 ± 35 µm). BCVA improved significantly from baseline to month 3 (p = 0.021). CONCLUSIONS: PDT can be considered an efficacious treatment option in patients with PPS. Prospective data with longer follow-up in a bigger cohort are needed in order to determine the optimal treatment algorithm in this relatively novel disease.
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Fotoquimioterapia , Porfirinas , Angiografía con Fluoresceína , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Proyectos Piloto , Estudios Prospectivos , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Verteporfina/uso terapéutico , Agudeza VisualRESUMEN
PURPOSE: Timely detection and multidisciplinary management of RPE65-related inherited retinal disorders (IRDs) can significantly improve both disease management and patient care. Thus, this Narrative Medicine (NM) project aimed to investigate the evolution of the care pathway and the expectations on genetic counseling and gene therapy by patients, caregivers, and healthcare professionals. PATIENTS AND METHODS: This project was conducted between July and December 2020, involving five Italian eye clinics specialized in IRDs, targeted pediatric and adult patients, their caregivers, attending retinologists and multidisciplinary healthcare professionals. Narratives and parallel charts, together with a sociodemographic survey, were collected through the project webpage. In-depth interviews were conducted with Patient Association (PA) members and multidisciplinary healthcare professionals. All data were entered into the Nvivo Software for coding and analysis. RESULTS: Three pediatric and five adult patients with early-onset RPE65-related IRDs as well as eight caregivers were enrolled; 11 retinologists globally wrote 27 parallel charts; in-depth interviews were done with five multidisciplinary healthcare professionals and one PA member. Early diagnosis remains challenging, and patients reported to have changed up to 10 healthcare professionals before accessing their specialized center. Despite the oftentimes lack of awareness of patients and caregivers on the purpose of genetic testing, participants generally consider gene therapy as a therapeutic chance and a historic breakthrough for the management of RPE65-related IRDs. Well-organized networks to support the patient's referral to specialized centers - as well as a proper communication of the clinical and genetic diagnosis and the multidisciplinary approach - emerge as crucial aspects in facilitating an early diagnosis and management and a timely initiation of the rehabilitation pathway. CONCLUSION: The project investigated the RPE65-related IRDs care pathway while integrating the different perspectives involved through NM. The analysis explored the patient's pathway in Italy and confirmed the need for a well-organized network and multidisciplinary care while highlighting several preliminary areas of improvement in the management of RPE65-related IRDs.
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In the last few decades, the incidence and prevalence of neuroendocrine tumors has been increasing. The theragnostic approach, that allows the diagnosis and treatment of different neoplasms with the same ligand, is a typical nuclear medicine tool. Applied for years, is also pivotal in neuroendocrine tumors (NETs) where it has improved the diagnostic accuracy and the therapeutic efficacy with impact on patient's survival. Theragnostic also allows the identification of important prognostic factors such as tumor location and burden, presence of liver metastases and intensity of somatostatin receptors (SSTR) expression to consider in new and possibly combined studies to ameliorate patient's outcome. Moreover, the possibility to evaluate receptor expression even in non-NET malignancies has de facto widened the possible indications for PRRT. We believe that this innovative therapeutic approach will be implemented in next years by radiomics and biological tumors characterization to better address PRRT applications.