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1.
Artículo en Inglés | MEDLINE | ID: mdl-38197587

RESUMEN

OBJECTIVE: Giant Cell arteritis (GCA) is a large vessel vasculitis, typically involving the aorta and its branches with predilection for the scalp arteries. Intracranial involvement is still part of ongoing research. We assess inflammation of the intracranial arteries on 3D-black-blood magnetic resonance imaging (3D-CS-BB-MRI) in patients with GCA and age-matched controls. METHODS: 105 patients with 3D-CS-BB-MRI of the brain were included in this retrospective dual-center case-control study; 55 with diagnosed GCA and 50 age-matched controls. High-resolution 3D-CS-BB-MRI was performed on a 3 Tesla MR scanner with a post-contrast 3D-compressed-sensing (CS) MR pulse sequence, specifically a T1-weighted sampling perfection, application-optimized contrasts using different flip angle evolution (SPACE) pulse sequence with whole-brain coverage and isotropic resolution of 0.55 mm3. Two neuroradiologists blinded to clinical data independently scored the cerebral arteries qualitatively for inflammation; circumferential vessel wall thickening and contrast enhancement were scored positive for vasculitis. RESULTS: 8 of 55 GCA patients (14.5%) showed inflammation of at least one intracranial artery. The internal carotid artery (ICA) was affected in 6/55 (10.9%), the vertebral artery in 4/55 (7.3%) and the basilar artery and posterior cerebral artery in 1/55 (1.8%). All patients with inflammatory changes reported headaches and none showed any focal neurological deficit. Besides headache and general weakness, there was no significant correlation between inflammation of the intracranial arteries and clinical symptoms. No age-matched control patient showed inflammatory changes of the intracranial arteries. CONCLUSION: High-resolution 3D-CS-BB-MRI revealed inflammatory changes of intracranial arteries in 14.5% of GCA patients with the intradural ICA as the most frequently affected vessel.

2.
Haematologica ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38572568

RESUMEN

Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides a unique therapeutic option for patients ineligible for CAR-T and bispecific antibody therapy, and/or patients progressing on anti-CD38 treatment where CAR-T and bispecifics might be kept in reserve. Wider use of the drug can be challenged by its distinct ocular side effect profile, including corneal microcysts and keratopathy. While dose reduction has been the most effective way to reduce these toxicities, the underlying mechanism of this BCMA off-target effect remains to be characterized. In this study, we provide the first evidence for soluble BCMA (sBCMA) in lacrimal fluid and report on its correlation with tumor burden in myeloma patients. We confirm that corneal cells do not express BCMA, and show that sBCMA-belantamab complexes may rather be internalized by corneal epithelial cells through receptor-ligand independent pinocytosis. Using an hTcEpi corneal cell-line model, we show that the pinocytosis inhibitor EIPA significantly reduces belantamab-specific cell killing. As a proof of concept, we provide detailed patient profiles demonstrating that, after belantamab-induced cell killing, sBCMA is released into circulation, followed by a delayed increase of sBCMA in the tear fluid and subsequent onset of keratopathy. Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies.

3.
Graefes Arch Clin Exp Ophthalmol ; 262(2): 537-543, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37831170

RESUMEN

PURPOSE: To investigate changes in distal outflow tract vessels caused by VEGF-A and their impact on outflow. METHODS: We compared VEGF-A perfused porcine anterior segments with and without trabecular meshwork (TM) to control eyes. In the first experiment (n=48), we analyzed live changes of the outflow tract with spectral-domain optical coherence tomography (SD-OCT) over 3 h and reconstructed them in 3D. In a second experiment (n=32), we measured the intraocular pressure (IOP) variation in response to VEGF-A over 48 h and computed the outflow facility. RESULTS: VEGF-A increased the vessel volume of the distal outflow tract by 16.8±10.6% while control eyes remained unchanged (0.5±6.8%). Volume changes occurred within the first 100 min before plateauing at 140 min. VEGF-A enhanced the outflow facility in eyes without TM by 38.6±25.5% at 24 h as compared to controls (p<0.05). CONCLUSION: VEGF-A dilated vessels of the distal outflow tract and increased the outflow facility even after TM removal, pointing to a regulatory mechanism independent of proximal structures.


Asunto(s)
Humor Acuoso , Factor A de Crecimiento Endotelial Vascular , Animales , Porcinos , Humor Acuoso/fisiología , Factor A de Crecimiento Endotelial Vascular/farmacología , Malla Trabecular , Presión Intraocular
4.
Klin Monbl Augenheilkd ; 241(1): 69-74, 2024 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-37995716

RESUMEN

BACKGROUND: There is a great demand for suitable models to test novel surgical and therapeutic approaches in glaucoma therapy. To address this need and to provide further alternatives to in vivo animal models, we aimed at modifying an established in vitro porcine eye perfusion model. METHODS: Two weaknesses of the previously established porcine anterior segment model include media leakage during perfusion and setup disintegration due to mechanical instability. To overcome these, we slightly modified the previously used custom-made perfusion dishes and incorporated new components into the model setup. To prevent fluid leakage, we secured the anterior segments more firmly to the perfusion trays using a compression ring, steel screws, and nuts. Customised mounts were used to stabilise the perfusion dish and pressure transducer as a single unit. The mounts were made of polylactide (PLA) and printed using a 3D printer. RESULTS: The use of steel screws and nuts allowed tighter clamping of the anterior segments and prevented medium leakage. Our PLA custom mounts stabilised the entire assembly and facilitated handling during experiments and improved comparability between tested eyes. They also prevented accidental detachment of the pressure transducers, which resulted in more stable pressure curves. Our PLA mounts tolerated incubation temperatures of up to 37 °C and disinfection with enzymatic detergents and 70% ethanol without showing signs of deformation or degradation after four months of regular usage. CONCLUSION: Modifications introduced to an established in vitro perfusion model improved its efficacy and reproducibility. Our adjusted model is an example of how many models can be optimised through critical analysis, thereby saving resources and providing reliable results in the long run.


Asunto(s)
Glaucoma , Malla Trabecular , Porcinos , Animales , Reproducibilidad de los Resultados , Glaucoma/cirugía , Modelos Animales de Enfermedad , Poliésteres/metabolismo , Acero
5.
Eur Radiol ; 33(4): 2529-2535, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36394601

RESUMEN

OBJECTIVE: Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls. METHODS: In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms. RESULTS: Eighteen of 56 GCA patients (32%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures. CONCLUSIONS: BB-MRI revealed inflammatory findings in the orbits in up to 32% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms. KEY POINTS: • Up to 32% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI. • Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI. • Features of inflammation of intraorbital structures are independent of clinically reported symptoms.


Asunto(s)
Arteritis de Células Gigantes , Humanos , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico por imagen , Estudios de Casos y Controles , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Inflamación/patología , Arterias Temporales/patología
6.
Int Ophthalmol ; 43(12): 5071-5078, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37874441

RESUMEN

PURPOSE: To compare two approaches for the implantation of the PRESERFLO microshunt: an anterior approach (A) with a 6-8-mm peritomy and a posterior approach (P) with a 3-mm incision. METHODS: We retrospectively analyzed 126 patients who received a PRESERFLO microshunt. We compared intraocular pressure (IOP), surgical time, medication count, and postoperative complications over nine months. RESULTS: The baseline IOP was similar in A (21.8 ± 8.5 mm Hg) and P (23.9 ± 8.1 mm Hg) (p = 0.08). Surgical duration was significantly shorter in P (10 ± 0.4 min) than in A (26 ± 0.8 min) (p < 0.001). Postoperative IOP levels were comparable in A (10.8 ± 5.9 mm Hg) and P (10.6 ± 4.5 mm Hg) at 30 days (p = 0.62) and throughout the study (all intra-group p-values > 0.08). The preoperative medication count was 3.2 ± 1.3 drops in A and 3.3 ± 1.0 drops in P (p = 0.4). Postoperative values were 0.2 ± 0.6 in A and 0.3 ± 0.7 in P at nine months. There were no significant differences in complications and surgical revisions between groups (p-values > 0.05). CONCLUSION: Both techniques achieved satisfactory IOP and medication count reductions and had similar safety profiles, but the posterior incision technique was 2.6 times faster than the anterior incision technique.


Asunto(s)
Glaucoma de Ángulo Abierto , Humanos , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/complicaciones , Estudios Retrospectivos , Presión Intraocular , Tonometría Ocular , Implantación de Prótesis
7.
Graefes Arch Clin Exp Ophthalmol ; 260(10): 3349-3356, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35501491

RESUMEN

PURPOSE: To determine whether 24-h IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion, and progression parameters. METHODS: We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (Tmax), average IOP(Tavg), IOP variation (IOPvar), and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was also conducted to check for various inter-eye relationships. RESULTS: Two hundred seventeen eyes were included. The average IOP was 14.8 ± 3.5 mmHg, with a 24-h variation of 5.2 ± 2.9 mmHg. A total of 52% of eyes with RNFL progression data showed disease progression. There was no significant difference in Tmax, Tavg, and IOPvar between progressors and non-progressors (all p > 0.05). Except for Tavg and the temporal RNFL, there was no correlation between disease progression in any quadrant and Tmax, Tavg, and IOPvar. Twenty-four-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. CONCLUSION: In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.


Asunto(s)
Glaucoma , Presión Intraocular , Progresión de la Enfermedad , Glaucoma/diagnóstico , Humanos , Retina
8.
Int J Mol Sci ; 23(5)2022 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-35269767

RESUMEN

Transforming growth factor ß (TGFß) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGFß receptor type 2 (Tgfbr2) is upregulated in retinal neurons and Müller cells during retinal degeneration. In this study we investigated if this upregulation of TGFß signaling would have functional consequences in protecting retinal neurons. To this end, we analyzed the impact of TGFß signaling on photoreceptor viability using mice with cell type-specific deletion of Tgfbr2 in retinal neurons and Müller cells (Tgfbr2ΔOC) in combination with a genetic model of photoreceptor degeneration (VPP). We examined retinal morphology and the degree of photoreceptor degeneration, as well as alterations of the retinal transcriptome. In summary, retinal morphology was not altered due to TGFß signaling deficiency. In contrast, VPP-induced photoreceptor degeneration was drastically exacerbated in double mutant mice (Tgfbr2ΔOC; VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGFß signaling in retinal neurons and Müller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.


Asunto(s)
Degeneración Retiniana , Factor de Crecimiento Transformador beta , Animales , Modelos Animales de Enfermedad , Células Ependimogliales/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismo , Retina/metabolismo , Degeneración Retiniana/genética , Degeneración Retiniana/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
9.
Graefes Arch Clin Exp Ophthalmol ; 258(12): 2775-2780, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32960322

RESUMEN

PURPOSE: To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. METHODS: Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. RESULTS: A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. CONCLUSION: T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.


Asunto(s)
Glaucoma de Ángulo Abierto , Trabeculectomía , Glaucoma de Ángulo Abierto/cirugía , Humanos , Presión Intraocular , Tonometría Ocular , Malla Trabecular/cirugía
10.
Graefes Arch Clin Exp Ophthalmol ; 258(10): 2151-2161, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32583283

RESUMEN

INTRODUCTION: Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. METHODS: Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. RESULTS: The mean duration of the MH prior to SR-fluid application was 17 months (6-96 months). The mean age of the patients at the time of surgery was 72 years (54-88). The mean preoperative aperture diameter of the opening was 1212 µm (239-4344 µm), base diameter 649 µm (SD 320 µm). The mean preoperative BCVA prior to surgery was 0.1 (0.01-0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02-0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. CONCLUSION: Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.


Asunto(s)
Perforaciones de la Retina , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Líquido Subretiniano/diagnóstico por imagen , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza Visual , Vitrectomía
11.
Klin Monbl Augenheilkd ; 237(2): 192-201, 2020 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-31049909

RESUMEN

PURPOSE: To investigate the effect of Selective Retina Therapy (SRT) on inflammatory key factors such as complement factor-C3 (CC3), tumor growth factor-beta2 (TGF-ß2), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). MATERIALS AND METHODS: Porcine RPE-Bruch's membrane-choroid explants were irradiated with two SRT laser systems, SRTYLF and SRTYAG (Nd : YLF laser, wave length 527 nm, pulse duration 1.7 µs and Nd : YAG laser, wave length 532 nm, pulse duration 2.4 - 3 µs). Laser irradiation was performed on a spot size of 200 × 200 µm, 30 pulses, with a repetition rate of 100 Hz, and a radiant exposure of 140 (threshold RPE death) and 180 mJ/cm2 per pulse (above threshold RPE death). Explants were cultivated in modified Ussing chambers and culture viability was assessed by calcein-AM cell staining. Secretion of inflammatory factors was analyzed by ELISA. Protein expression of tissue explants was assessed by Western blot. RESULTS: Regeneration of RPE was observed after 4 days. One day after SRT with 140 mJ/cm2 per pulse the secretion of basal CC3 decreased in ELISA. Following 180 mJ/cm2 radiant exposure, the level of IFN-γ decreased at day 4. CONCLUSION: SRT does not induce the release of the pro-inflammatory factors analyzed in this in-vitro study.


Asunto(s)
Coagulación con Láser , Láseres de Estado Sólido , Retina , Animales , Coroides , Porcinos
12.
Ophthalmologica ; 238(3): 124-132, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28719903

RESUMEN

PURPOSE: To evaluate retinal layer thickness with optical coherence tomography (OCT) in eyes with macula-off retinal detachment after silicone oil (SiO) or gas endotamponade. PROCEDURES: Cross-sectional study of 40 eyes with macula-off rhegmatogenous retinal detachment that underwent vitrectomy. 20 eyes received SiO tamponade and 20 matched eyes received gas. 33 healthy fellow eyes served as controls. Macular spectral domain OCT was performed with automated layer detection in the 5 inner subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. RESULTS: Comparing the SiO group with the gas group, the ganglion cell layer showed a significant thinning in all fields of the inner ring of the ETDRS map, the inner plexiform layer in the nasal, superior and temporal quadrants, and the outer plexiform layer in the nasal quadrant. CONCLUSIONS: Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade.


Asunto(s)
Endotaponamiento/métodos , Mácula Lútea/patología , Desprendimiento de Retina/cirugía , Aceites de Silicona/administración & dosificación , Tomografía de Coherencia Óptica/métodos , Vitrectomía/métodos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Desprendimiento de Retina/diagnóstico , Agudeza Visual
13.
Graefes Arch Clin Exp Ophthalmol ; 254(8): 1465-1471, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27278374

RESUMEN

PURPOSE: We aimed to investigate frequency, time course and pathophysiology of vision loss in eyes with macula-on rhegmatogenous retinal detachment operated with vitrectomy and silicone oil tamponade. PATIENTS AND METHODS: Fifteen eyes of 15 patients who had been operated with 5,000 centistoke silicone oil between 2006 and 2014 were included in a retrospective case series. Examinations included logMAR best corrected visual acuity (BCVA), visual field testing (VF), spectral domain optical coherence tomography (OCT), electrophysiology, and fluorescein angiography. RESULTS: Vision loss was seen in eight (53 %) eyes of 15 patients with symptomatic central scotoma, which was confirmed by VF (5/6). Preoperative median BCVA of these patients was 0.15 (0.5 to 0), prior to oil removal 0.7 (1.0 to 0.5), and 6 weeks post oil removal 1.0 (1.5 to 0.2). BCVA recovered in five patients to a median of 0.15 (0.5 to 0.1), and it remained 1.0 in three (20 %) out of 15 eyes. OCT revealed significant thinning of the foveal and parafoveal combined nerve fiber, ganglion cell and inner plexiform layers in affected eyes (mean 58.3 µm +/-13, horizontal scan through fovea, 500 µm radius) compared to their healthy fellow eyes (mean 84.5 µm +/-12.3; p < 0.01, n = 6 patients, 12 eyes) and compared to eyes with no vision loss under silicone oil. CONCLUSIONS: We find persisting vision loss in three out of 15 patients treated for macula-on rhegmatogenous retinal detachment with silicone oil tamponade. Thinning of inner retinal layers possibly evoked by silicone oil tamponade might be a pathophysiological explanation for vision loss in these patients.


Asunto(s)
Ceguera/etiología , Complicaciones Posoperatorias , Desprendimiento de Retina/cirugía , Aceites de Silicona/administración & dosificación , Vitrectomía/efectos adversos , Anciano , Ceguera/diagnóstico , Ceguera/fisiopatología , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Desprendimiento de Retina/diagnóstico , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía/métodos
14.
Graefes Arch Clin Exp Ophthalmol ; 252(11): 1737-45, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25047875

RESUMEN

PURPOSE: Localized application of hyperthermia is a potential treatment for retinal diseases. Vascular endothelial growth factor (VEGF) derived from the retinal pigment epithelium (RPE) is implicated in a variety of retinal pathologies. As it has been recently shown that hyperthermia may induce VEGF in the RPE, the aim of this study was to investigate hyperthermia-induced VEGF secretion and the pathways of hyperthermal VEGF upregulation in the RPE. MATERIAL AND METHODS: The human RPE cell line (Arpe-19) was exposed to 40°, 42°, 45° and 50 °C for one, five and 15 min. Cell viability was evaluated using a trypan blue exclusion assay, VEGF secretion was evaluated by an enzyme-linked immunosorbent assay ELISA) and VEGF expression was investigated using a Western blot. Involvement of mitogen-activated protein kinase (MAPK) pathways (ERK1/2, JNK, p38) and transient receptor potential vanilloid (TRPV) channels on VEGF induction was investigated using commercially available inhibitors (U0126, SB203580, SP600125, ruthenium red). Expression and phosphorylation of MAPKs was investigated using a Western blot. RESULTS: Hyperthermia induces time- and temperature-dependent cell death in human RPE cells. VEGF expression and secretion is induced by hyperthermia in a time- and temperature-dependent manner mediated by p38 and to a lesser degree by JNK. TRPV channels seem to play a minor role in regulation of hyperthermia-induced VEGF secretion. CONCLUSIONS: Hyperthermia induces temperature-dependent secretion of VEGF in the RPE, which is mediated by p38 and, to a lesser extent, JNK. This may lead to undesired effects from hyperthermal treatment of retinal diseases.


Asunto(s)
Hipertermia Inducida , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Western Blotting , Línea Celular , Supervivencia Celular , Inhibidores Enzimáticos/farmacología , Ensayo de Inmunoadsorción Enzimática , Humanos , MAP Quinasa Quinasa 4/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
Ophthalmologie ; 120(10): 1029-1036, 2023 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-37340244

RESUMEN

BACKGROUND: This study was an analysis of fluorescein angiography (FAG) and indocyanine green angiography (ICGA) at a university eye hospital. The primary objective of the study was to analyze adverse drug reactions (ADRs) and their severity (mild, moderate, severe). The secondary objective was to investigate the indications of FAG and ICGA before and during the COVID-19 pandemic. METHODS: A retrospective analysis of all FAG and ICGA at the University Eye Hospital in Würzburg from January 2016 to the end of December 2021 was performed. The ADRs, gender, age, examination time points and indications were evaluated. The ADRs were classified into mild, moderate, and severe, following the definition of Kornblau et al. [1] RESULTS: A total of 4900 examinations from 4193 patients were analyzed. An FAG was performed slightly more frequently in men (54.8%) than in women (45.2%) and the mean age was 63.2 ± 16.9 years (median: 65 years). The ADRs occurred in only 1.65% of all FAG, of which 1.27% were mild and 0.39% were moderate. No severe ADRs occurred. The most common ADR was nausea at 59.26%. No ADR occurred in ICGA. The annual number of FAGs averaged 816.7 ± 91.1 and was relatively constant throughout the period except for a significantly reduced number in 2016 (compared with 2018, 2019, and 2021). The most common indication for FAG was venous retinal occlusion at 22.93% (N = 774), showing a significant increase in 2021 compared to 2018-2020. An ICGA was performed in 4.18% of cases, with the most common indication being uveitis at 31.82% (N = 63). CONCLUSION: Compared to other studies very few ADRs occurred and no life-threatening ADR occurred in any case. Venous retinal occlusions were very common indications for FAG, probably due to the frequent need for repeated examinations in this condition. Briefly, during the first lockdown (18 March-8 May 2020), a decrease in angiographies was observed, but over a longer period, no significant differences were seen compared with the prepandemic period.

16.
Clin Ophthalmol ; 17: 3113-3122, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37881783

RESUMEN

Purpose: To analyse single-operation anatomical success (SOAS) of primary rhegmatogenous retinal detachment (RRD) repair by junior vitreoretinal surgeons guided by preoperative individual case selection by an experienced mentor vitreoretinal surgeon. Methods: Retrospective, single institute, observational study, included all patients who underwent standard pars plana vitrectomy (PPV) or combined encircling band (CB) and PPV and gas tamponade in the treatment of RRD from November 2021 to December 2022 were included. Preoperative selection for the surgery decision, whether standard PPV or combined CB & PPV was undertaken through the senior surgeon; according to the location and extensions of the RRD, number of retinal tears (RT) and lens status. We excluded patients with tractional retinal detachment, RD with proliferative vitreoretinopathy stage C, giant tears, trauma, previous scleral buckle, schisis RD and RD requiring silicone oil. The primary outcome measure was to evaluate the single-operation anatomic success (SOAS). Secondary outcome measures evaluated whether there was a statistical significant difference between both procedures. Results: Eighty-two eyes were included in the study. Forty-five eyes were selected for combined CB&PPV and 37 eyes for standard PPV. SOAS was achieved in 40 eyes (88.8%) in combined group and 35 eyes (94.5%) in standard PPV group. There was no statistically significant difference in the success rate between both operations, p = 0.65. Conclusion: Structured preoperative selection of standardized surgical techniques according to the degree of complexity of RD together with close supervision enables junior vitreoretinal surgeons in training to achieve re-attachment rates of more than 80% with both types of surgeries.

17.
J Curr Glaucoma Pract ; 17(1): 9-14, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37228309

RESUMEN

Aim: To compare ab interno trabeculectomy by trabecular meshwork (TM) excision to plasma-mediated ablation in primary open-angle glaucoma (POAG) patients. Methods: Retrospectively collected data of TrabEx+ (TEx) (n = 56) and Trabectome (T) (n = 99) patients were compared by coarsened exact matching to reduce confounding and matched based on baseline intraocular pressure (IOP) and age. The primary outcomes were IOP and the number of glaucoma medications. Complications and the need for additional glaucoma surgery were assessed. Patients were followed for up to 1 year. Results: A total of 53 TEx could be matched to T. Baseline IOP was 16.5 ± 4.6 mm Hg in both; age was 73.7 ± 8.8 and 71.5 ± 9.9 years in TEx and T, respectively. TEx was taking more medications than T (p < 0.001). IOP was reduced to 14.8 ± 4.3 in TEx and to 13.4 ± 3.4 in T at 6 months, and to 14.9 ± 6.0 (p = 0.13) in TEx and to 14.1 ± 3.8 mm Hg (all p < 0.05) in T at 12 months. Medications were reduced at both 6 and 12 months (p < 0.05). No differences were seen between TEx and T at 6 and 12 months. In TEx, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline IOP considered low for ab interno trabeculectomy, IOP and medications were reduced further at 6 and 12 months. IOP reduction did not reach significance in TEx at 12 months. The intergroup comparison did not reveal any significant differences. Both had a low complication rate. Clinical significance: This study investigated subtle differences between a plasma-ablative device, the T, and an excisional device, the TEx, by applying coarsened exact matching. IOP and medications were reduced in both groups at 6 and 12 months, although IOP reduction did not reach significance in TEx at 12 months. The intergroup comparison did not reveal any significant differences, with both devices having a low complication rate. How to cite this article: Dakroub M, Verma-Fuehring R, Strzalkowska A, et al. Coarsened Exact Matching of Excisional to Plasma-ablative Ab Interno Trabeculectomy. J Curr Glaucoma Pract 2023;17(1):9-14.

18.
Clin Ophthalmol ; 17: 769-777, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36919033

RESUMEN

Purpose: To evaluate the morphological macular changes and fluid dynamics under brolucizumab treatment in eyes refractory to previous anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) compared with treatment-naive eyes. Methods: Retrospective study of all eyes treated with brolucizumab for nAMD between 2020 and 2021 with a fixed injection regimen and one year follow-up. Treatment-naive eyes (TN) were compared with eyes refractory to previous treatment with bevacizumab, ranibizumab, or aflibercept (RT). The primary outcome measure was change of best-corrected visual acuity (BCVA). Secondary outcome measures included foveal central thickness (FCT), presence of intra- or subretinal fluid (IRF, SRF) and presence of pigment epithelial detachment (PED) at any time point during treatment in both groups. Results: Seventeen TN eyes and 17 RT eyes were included. Mean BCVA and mean FCT in TN eyes had significantly improved after 3 months and continued to improve during treatment (p<0.05 and p=0.001, respectively). In RT eyes, mean BCVA did not change significantly while mean FCT had improved after 3 months of treatment and remained stable thereafter. SRF or PED were more frequent in RT eyes compared with TN eyes (p=0.003 and p=0.005, respectively). Conclusion: After 3 months of treatment, the BCVA increased significantly only in TN eyes, while the FCT was significantly reduced in both groups. IRF appears to be similarly seen in both groups after the loading phase; however, SRF and PED appear to be more frequent in the RT eyes compared with TN eyes.

19.
Transl Vis Sci Technol ; 12(7): 8, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37418250

RESUMEN

Purpose: Systemic chloroquine/hydroxychloroquine (CQ/HCQ) can cause severe ocular side effects including bull's eye maculopathy (BEM). Recently, we reported higher quantitative autofluorescence (QAF) levels in patients with CQ/HCQ intake. Here, QAF in patients taking CQ/HCQ in a 1-year follow-up is reported. Methods: Fifty-eight patients currently or previously treated with CQ/HCQ (cumulative doses 94-2435 g) and 32 age- and sex-matched healthy subjects underwent multimodal retinal imaging (infrared, red free, fundus autofluorescence [FAF], QAF [488 nm], and spectral-domain optical coherence tomography (SD-OCT). For analysis, custom written FIJI plugins were used for image processing, multimodal image stacks assembling, and QAF calculation. Results: Thirty patients (28 without BEM and 2 with BEM, age range = 25-69 years) were followed up (370 ± 63 days). QAF values in patients taking CQ/HCQ showed a significant increase between baseline and follow-up examination: 282.0 ± 67.9 to 297.7 ± 70.0 (QAF a.u.), P = 0.002. An increase up to 10% was observed in the superior macular hemisphere. Eight individuals (including 1 patient with BEM) had a pronounced QAF increase of up to 25%. Compared to healthy controls, QAF levels in patients taking CQ/HCQ were significantly increased (P = 0.04). Conclusions: Our study confirms our previous finding of increased QAF in patients taking CQ/HCQ with a further significant QAF increase from baseline to follow-up. Whether pronounced QAF increase might predispose for rapid progression toward structural changes and BEM development is currently investigated in ongoing studies. Translational Relevance: In addition to standard screening tools during systemic CQ/HCQ treatment, QAF imaging might be useful in CQ/HCQ monitoring and could serve as a screening tool in the future.


Asunto(s)
Antirreumáticos , Hidroxicloroquina , Humanos , Recién Nacido , Lactante , Hidroxicloroquina/efectos adversos , Cloroquina/efectos adversos , Antirreumáticos/efectos adversos , Estudios de Seguimiento
20.
Graefes Arch Clin Exp Ophthalmol ; 250(9): 1315-20, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22527309

RESUMEN

BACKGROUND/AIM: To determine the complication rate and risk factors for intraoperative complications in resident-performed phacoemulsification surgery at a tertiary care center during the first 100 surgeries. METHODS: Retrospective chart review of the first 100 performed phacoemulsification cases of six consecutive residents. Posterior capsule tear, vitreous loss, and dislocation of lenticular fragments into the vitreous were defined as intraoperative complications. Patient characteristics considered risk factors for surgery were identified and correlated with the occurrence of intraoperative complications. RESULTS: Complications occurred in 23 of 600 operations (3.8 %). Surgery was complicated by posterior capsular tear in 23 eyes (3.8 %) with vitreous loss in 17 eyes (2.8 %) and loss of lenticular fragments into the vitreous in seven eyes (1.2 %). Eyes with dense nuclear sclerosis (p = 0.002) and white cataracts (p = 0.019) were associated with a statistically significantly greater incidence of posterior capsular tears and vitreous loss (p = 0.007 and p = 0.027 respectively). An intraocular lens was implanted in 591 eyes as intended. CONCLUSIONS: Residents achieve an acceptable complication rate during their initial 100 phacoemulsification cases.


Asunto(s)
Competencia Clínica/normas , Educación de Postgrado en Medicina/normas , Internado y Residencia , Complicaciones Intraoperatorias , Oftalmología/educación , Facoemulsificación/efectos adversos , Anciano , Femenino , Humanos , Curva de Aprendizaje , Implantación de Lentes Intraoculares , Subluxación del Cristalino/etiología , Masculino , Facoemulsificación/educación , Cápsula Posterior del Cristalino/lesiones , Estudios Retrospectivos , Factores de Riesgo , Cuerpo Vítreo/patología
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