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PURPOSE: To quantify morphological changes of the photoreceptors (PR) and retinal pigment epithelium (RPE) layers under pegcetacoplan therapy in geographic atrophy (GA) using deep learning-based analysis of optical coherence tomography (OCT) images. DESIGN: Post-hoc longitudinal image analysis SUBJECTS: Patients with GA due to age-related macular degeneration from two prospective randomized phase III clinical trials (OAKS and DERBY) METHODS: Deep learning-based segmentation of RPE loss and PR degeneration, defined as loss of the ellipsoid zone (EZ) layer on OCT, over 24 months on SD-OCT images MAIN OUTCOME MEASURES: Change in the mean area of RPE loss and EZ loss over time in the pooled sham arms and the monthly (PM)/every other month (PEOM) treatment arms RESULTS: 897 eyes of 897 patients were included. There was a therapeutic reduction of RPE loss growth by 22%/20% in OAKS and 27%/21% in DERBY for PM/PEOM compared to sham, respectively, at 24 months. The reduction on the EZ level was significantly higher with 53%/46% in OAKS and 47%/46% in DERBY for PM/PEOM compared to sham at 24 months. The baseline EZ-RPE difference had an impact on disease activity and therapeutic response. The therapeutic benefit for RPE loss growth increased with larger EZ-RPE difference quartiles from 21.9%, 23.1%, 23.9% to 33.6% for PM vs. sham (all p<0.01) and from 13.6% (p=0.11), 23.8%, 23.8% to 20.0% for PEOM vs. sham (p<0.01) in quartiles 1,2,3 and 4, respectively, at 24 months. Regarding EZ layer maintenance, the therapeutic reduction of loss increased from 14.8% (p=0.09), 33.3%, 46.6% to 77.8% (p<0.0001) between PM and sham and from 15.9% (p=0.08), 33.8%, 52.0% to 64.9% (p<0.0001) between PEOM and sham for quartiles 1-4 at 24 months. CONCLUSION: OCT-based AI analysis objectively identifies and quantifies PR and RPE degeneration in GA. Reductions in further PR degeneration consistent with EZ loss on OCT are even higher than the effect on RPE loss in phase 3 trials of pegcetacoplan treatment. The EZ-RPE difference has a strong impact on disease progression and therapeutic response. Identification of patients with higher EZ-RPE loss difference may become an important criterion for the management of GA secondary to AMD.
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PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Inhibidores de la Angiogénesis , Angiopoyetina 2 , Anticuerpos Biespecíficos , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Masculino , Femenino , Agudeza Visual/fisiología , Método Doble Ciego , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/uso terapéutico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/fisiopatología , Degeneración Macular Húmeda/diagnóstico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Angiopoyetina 2/antagonistas & inhibidores , Resultado del Tratamiento , Tomografía de Coherencia Óptica , Estudios de Seguimiento , Anciano de 80 o más Años , Angiografía con Fluoresceína , Relación Dosis-Respuesta a DrogaRESUMEN
PURPOSE: To evaluate the postoperative outcome of strabismus surgery performed in children aged 1-6 years by investigating the change of the preoperative angle of deviation (AOD), elevation in adduction, best-corrected visual acuity (BCVA) and refractive error. METHODS: Retrospective chart review of 62 children who received strabismus surgery between January 2018 and December 2021 at the Department of Ophthalmology and Optometry of the Medical University of Vienna. Age, sex, type of strabismus, AOD, BCVA, refractive error and visual acuity were evaluated with respect to the postoperative outcome. RESULTS: Mean follow-up was 13.55 ± 11.38 months with a mean age of 3.94 ± 1.97 years (range: 1.0-6.0) at time of surgery. 74.19% of patients (n = 46) had isolated or combined esotropia, 12.90% (n = 8) had isolated or combined exotropia and 12.90% (n = 8) had isolated strabismus sursoadductorius. Mean preoperative AOD of 15.69 ± 16.91°/15.02 ± 14.88° (near/distance) decreased to 4.00 ± 9.18°/4.83 ± 7.32° (near/distance) at final follow-up (p < 0.001). BCVA improved from 0.26 ± 0.26/0.25 ± 0.23 (left/right) to 0.21 ± 0.25/0.20 ± 0.23 (left/right) (p = 0.038). There was no significant change regarding refractive error (p = 0.109) or elevation in adduction (p = 0.212). Success rate which was defined as a residual AOD of less than 10° was 74.19% (n = 46). In 3.23% (n = 2) retreatment was necessary. CONCLUSION: Strabismus surgery in infants was shown to have a satisfactory outcome with a low retreatment rate. Surgical success rate was not linked to age, sex, type of strabismus or the preoperative parameters AOD, refractive error and visual acuity in this study.
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Músculos Oculomotores , Procedimientos Quirúrgicos Oftalmológicos , Estrabismo , Visión Binocular , Agudeza Visual , Humanos , Estudios Retrospectivos , Masculino , Femenino , Lactante , Agudeza Visual/fisiología , Procedimientos Quirúrgicos Oftalmológicos/métodos , Músculos Oculomotores/cirugía , Músculos Oculomotores/fisiopatología , Estrabismo/cirugía , Estrabismo/fisiopatología , Preescolar , Visión Binocular/fisiología , Estudios de Seguimiento , Resultado del Tratamiento , Niño , Periodo Posoperatorio , Movimientos Oculares/fisiología , Refracción Ocular/fisiologíaRESUMEN
PURPOSE: Neurovascular coupling impairment and inner retinal layer thinning are early detectable retinal changes in diabetes, and both worsen during progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyze associations between the retinal functional hyperemic response to light stimulation and the thickness of individual neuroretinal layers in eyes with early non-proliferative DR. METHODS: Thirty patients with type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non-proliferative DR and 14 healthy subjects were included in this cross-sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyzer. Individual layer thickness in the macula was analyzed from spectral domain optical coherence tomography. RESULTS: Flicker light-induced vessel dilation was significantly reduced in patients compared to healthy controls (veins: 3.0% vs. 6.1%, p < 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010), and negatively with hemoglobin A1c (HbA1c) levels (r=-0.41, p = 0.023) and age (r=-0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only GCL thickness (p = 0.017, ß = 0.42) and HbA1c (p = 0.045, ß=-0.35) remained significantly associated with the vascular flicker light response. CONCLUSION: The results indicate that thinner GCL and worse glycemic control both contribute to reduced retinal neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.
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PURPOSE: In this study, differences in retinal feature visualization of high-resolution optical coherence tomography (OCT) devices were investigated with different axial resolutions in quantifications of retinal pigment epithelium and photoreceptors (PRs) in intermediate age-related macular degeneration. METHODS: Patients were imaged with standard SPECTRALIS HRA + OCT and the investigational High-Res OCT device (both by Heidelberg Engineering, Heidelberg, Germany). Drusen, retinal pigment epithelium, and PR layers were segmented using validated artificial intelligence-based algorithms followed by manual corrections. Thickness and drusen maps were computed for all patients. Loss and thickness measurements were compared between devices, drusen versus nondrusen areas, and early treatment diabetic retinopathy study subfields using mixed-effects models. RESULTS: Thirty-three eyes from 28 patients with intermediate age-related macular degeneration were included. Normalized PR integrity loss was significantly higher with 4.6% for standard OCT compared with 2.5% for High-Res OCT. The central and parafoveal PR integrity loss was larger than the perifoveal loss (P < 0.05). Photoreceptor thickness was increased on High-Res OCT and in nondrusen regions (P < 0.001). Retinal pigment epithelium appeared thicker on standard OCT and above drusen (P < 0.01). CONCLUSION: Our study shows that High-Res OCT is able to identify the condition of investigated layers in intermediate age-related macular degeneration with higher precision. This improved in vivo imaging technology might promote our understanding of the pathophysiology and progression of age-related macular degeneration.
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Epitelio Pigmentado de la Retina , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/diagnóstico por imagen , Femenino , Masculino , Anciano , Anciano de 80 o más Años , Células Fotorreceptoras de Vertebrados/patología , Agudeza Visual/fisiología , Drusas Retinianas/diagnóstico , Drusas Retinianas/diagnóstico por imagen , Degeneración Macular/diagnóstico , Degeneración Macular/fisiopatología , Persona de Mediana EdadRESUMEN
BACKGROUND: /Objectives To compare two suturing techniques in patients undergoing upper eyelid blepharoplasty by using the FACE-Q™ Eye Module questionnaire to assess patient-reported outcomes and by blinded Likert-scale gradings of two experienced surgeons. METHODS: 90 patients undergoing bilateral blepharoplasty were randomly assigned to a suturing technique (running cutaneous or subcuticular closure) using Prolene 6.0. Patients completed the FACE-Q eye module questionnaire before surgery and 7 days and 3 months after surgery. Further, two trained oculoplastic surgeons assessed the outcome. FACE-Q ratings were RASCH-transformed, and linear models were fitted for appraisal and satisfaction results. Intraclass correlation coefficient (ICC) was calculated to assess the surgeons' rating agreement. RESULTS: There was no statistically significantly difference in patients' FACE-Q self-assessments regarding satisfaction with eyes and appraisal of upper eyelids between the two suturing techniques investigated, both 7 days and 3 months after blepharoplasty. The more content the patient at baseline, the less the increase in satisfaction after 3 months. There was good agreement between blinded graders in outcome assessment expressed by an ICC of 0.86. Dry-eye symptoms increased after surgery, independent of the suturing technique, patient age or sex. CONCLUSION: In conclusion, this study shows that post operative patient satisfaction is independent of suturing technique, but depends on baseline FACE-Q reports. These findings are valuable in patient communication and selection and are in line with observer-based assessments. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .
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Blefaroplastia , Humanos , Blefaroplastia/métodos , Proyectos Piloto , Párpados/cirugía , Satisfacción del Paciente , Evaluación de Resultado en la Atención de Salud , Estudios RetrospectivosRESUMEN
PURPOSE: To assess the characteristics and long-term outcomes of adult patients with dysthyroid optic neuropathy (DON) who underwent orbital decompression surgery and/or received intravenous (IV) methylprednisolone. METHODS: Retrospective chart review of 98 eyes of 49 patients who were diagnosed and treated with bilateral DON between 2007 and 2018 at the Department of Ophthalmology and Optometry and Oral and Maxillofacial Surgery of the Medical University of Vienna. RESULTS: The mean follow-up period was 4.1 ± 2.7 years. The most common presenting symptoms were eyelid and periorbital swelling (45%) representing active inflammation. Upgaze restriction was the most common clinical finding (73%). At time of diagnosis, the mean clinical activity score was 4 ± 1/4 ± 1 (right/left eye, respectively). Sixty-three percent (31/49) of the patients were treated both with IV methylprednisolone and underwent orbital decompression surgery, 22% (11/49) were treated with IV methylprednisolone alone and 14% (7/49) underwent surgical decompression only. Seventy-one percent (30/42) of the patients underwent 3-wall decompression. The mean reduction of proptosis in patients treated with both IV methylprednisolone and orbital decompression surgery was 4/5 mm. Mean of reduction in proptosis in patients receiving IV methylprednisolone only was 1/0 mm and in patients with surgical decompression only was 5/5 mm. Mean VA was 0.1 ± 0.5/0.1 ± 0.5 logMAR at baseline and 0.05 ± 0.7/0.05 ± 0.7 at final follow-up. In 92% (45/49), VA was preserved or improved at final follow-up. CONCLUSIONS: The majority of patients with DON were treated both with IV corticosteroids and 3-wall decompression surgery. Vision could be successfully preserved in most cases and reduction of proptosis was achieved, especially after orbital decompression surgery.
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Exoftalmia , Oftalmopatía de Graves , Enfermedades del Nervio Óptico , Adulto , Humanos , Oftalmopatía de Graves/complicaciones , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/tratamiento farmacológico , Estudios Retrospectivos , Descompresión Quirúrgica , Órbita/cirugía , Exoftalmia/cirugía , Metilprednisolona , Corticoesteroides/uso terapéutico , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/cirugíaRESUMEN
PURPOSE: To report on the morphological characteristics and regional distribution of multifocal macular neovascularization type 3 (mMNV3). METHODS: Twenty-two consecutive eyes of 21 patients with mMNV3 were included using multimodal imaging. The count and stage of lesions of all MNV types and the existence of exudate and hemorrhage were determined. Also, we addressed the regional distribution of MNV3 lesions between the superior-inferior and the nasal-temporal halves of the macula, and the range of the distance of the lesions from the central fovea. Furthermore, we explored the number of feeding vessels including the cilioretinal artery. RESULTS: We found 51 lesions in 22 eyes of 21 patients. They were bifocal in 16 (73%) eyes, trifocal in 5 (23%), and quadrifocal in one (4%). No lesion of MNV1 or 2 was found. Fifteen (68%), 2 (9%), and 16 (73%) eyes were associated with retinal hard exudate, subretinal pigment epithelium exudate, and intraretinal hemorrhage, respectively. Thirty (59%) lesions were located in the temporal half of the macula, whereas 21 (41%) were located nasally (p = 0.07). One (2%) lesion was closer than 500 µm, 49 (96%) between 500 and 1500 µm, and one (2%) between 1500 and 3000 µm. The lesions were supplied by one arteriole in one (4%) eye, two arterioles in 16 (73%) eyes, and 3 arterioles in 5 (23%) eyes. The CRA contributed as a feeding vessel in 5 (23%) eyes. CONCLUSION: The multifocal variant of MNV3 has specific morphological and topographical characteristics. Multimodal imaging allows the understanding of the pathomorphological condition in more detail.
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Neovascularización Retiniana , Angiografía con Fluoresceína , Humanos , Neovascularización Retiniana/diagnóstico , Vasos Retinianos , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To investigate the correlation of volumetric measurements of intraretinal (IRF) and subretinal fluid obtained by deep learning and central retinal subfield thickness (CSFT) based on optical coherence tomography in retinal vein occlusion, diabetic macular edema, and neovascular age-related macular degeneration. METHODS: A previously validated deep learning-based approach was used for automated segmentation of IRF and subretinal fluid in spectral domain optical coherence tomography images. Optical coherence tomography volumes of 2.433 patients obtained from multicenter studies were analyzed. Fluid volumes were measured at baseline and under antivascular endothelial growth factor therapy in the central 1, 3, and 6 mm. RESULTS: Patients with neovascular age-related macular degeneration generally demonstrated the weakest association between CSFT and fluid volume measurements in the central 1 mm (0.107-0.569). In patients with diabetic macular edema, IRF correlated moderately with CSFT (0.668-0.797). In patients with retinal vein occlusion, IRF volumes showed a moderate correlation with CSFT (0.603-0.704). CONCLUSION: The correlation of CSFT and fluid volumes depends on the underlying pathology. Although the amount of central IRF seems to partly drive CSFT in diabetic macular edema and retinal vein occlusion, it has only a limited impact on patients with neovascular age-related macular degeneration. Our findings do not support the use of CSFT as a primary or secondary outcome measure for the quantification of exudative activity or treatment guidance.
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Aprendizaje Profundo , Retinopatía Diabética , Edema Macular , Oclusión de la Vena Retiniana , Retinopatía Diabética/complicaciones , Humanos , Edema Macular/patología , Retina/patología , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológicoRESUMEN
PURPOSE: To explore the condition of fellow eyes of patients with macular neovascularization Type 3 (MNV3) and to verify whether the retinal-choroidal anastomosis (RCA) develops equally in all MNV types. METHODS: The contralateral eyes of 94 patients with MNV3, 96 patients with MNV1, and 96 patients with MNV2 were included. Multimodal imaging was performed. The MNV3 stage including the development of fibrosis and RCA over 24 months was determined. RESULTS: In the contralateral eyes of patients of the solitary (one lesion) MNV3 group, 32 eyes (42.1%) showed early/intermediate age-related macular degeneration, 25 eyes (33%) showed MNV3, and 11 eyes (14.5%) experienced fibrosis, of which 4 eyes (5.2%) had a RCA, 7 eyes (9.2%) had atrophy after resolved MNV3, and 1 eye (1.3%) developed MNV1. In the multifocal (more than one lesion) MNV3 group, 2 eyes (11.1%) showed early/intermediate age-related macular degeneration, 9 eyes (50%) showed 15 MNV3 lesions, and 4 eyes (22.2%) showed fibrosis, of which 2 eyes (11.1%) manifested with a RCA and 3 eyes (16.7%) showed atrophy after resolved MNV3. The number of eyes with a RCA accounted for 40% of all eyes with fibrosis. The count of simultaneous bilateral multifocal MNV3 was 5 (55.6%). In the MNV1 and MNV2 groups, no eye developed a RCA. The incidence of RCAs in the scarred eyes in MNV3 was significantly higher (P < 0.0001). CONCLUSION: Retinal-choroidal anastomosis is an exclusive clinical feature of MNV3. The development of the multifocal MNV3 is usually bilateral and simultaneous. The occurrence of fibrosis in MNV3 has decreased dramatically after the introduction of the antiangiogenic therapy.
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Fístula Arterio-Arterial/diagnóstico por imagen , Coroides/irrigación sanguínea , Arterias Ciliares/patología , Neovascularización Retiniana/diagnóstico por imagen , Vasos Retinianos/patología , Anciano , Anciano de 80 o más Años , Arterias Ciliares/diagnóstico por imagen , Colorantes/administración & dosificación , Estudios Transversales , Femenino , Fibrosis/diagnóstico , Angiografía con Fluoresceína , Estudios de Seguimiento , Atrofia Geográfica/diagnóstico , Humanos , Verde de Indocianina/administración & dosificación , Masculino , Persona de Mediana Edad , Imagen Multimodal , Retina/patología , Vasos Retinianos/diagnóstico por imagen , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To investigate the impact of baseline vitreomacular interface status on treatment outcomes in patients treated with three different anti-vascular endothelial growth factors for diabetic macular edema. METHODS: Post hoc analysis from patients enrolled in the DRCR.net Protocol T study. Optical coherence tomography images were analyzed at baseline and at the end of follow-up to identify the presence of complete vitreomacular adhesion, partial vitreomacular adhesion, vitreomacular traction syndrome, and complete posterior vitreous detachment. RESULTS: Six hundred and twenty-nine eyes were eligible for the study based on the study criteria. Complete adhesion eyes gained on average +3.7 more ETDRS letters compared with the complete posterior vitreous detachment group at the end of the 12 months follow-up ( P < 0.001). Baseline vitreomacular interface status had no significant influence on central subfield thickness at 12 months ( P = 0.144). There was no difference between the treatment arms based on effect of baseline vitreomacular interface status on best-corrected visual acuity gain. CONCLUSION: This study provides evidence that vitreomacular interface status affects functional outcomes in diabetic macular edema patients treated with anti-vascular endothelial growth factor injections. The presence of complete or partial vitreomacular adhesion at baseline may be associated with a larger treatment benefit than those with complete posterior vitreous detachment.
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Enfermedades de la Retina , Desprendimiento del Vítreo , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Desprendimiento del Vítreo/diagnóstico , Desprendimiento del Vítreo/tratamiento farmacológico , Desprendimiento del Vítreo/patología , Factores de Crecimiento Endotelial , Cuerpo Vítreo/patología , Inyecciones Intravítreas , Agudeza Visual , Tomografía de Coherencia Óptica , Enfermedades de la Retina/patología , Adherencias Tisulares/tratamiento farmacológico , Adherencias Tisulares/patologíaRESUMEN
PURPOSE: To characterize the spectrum of internal limiting membrane (ILM) disease in Alport syndrome using multimodal imaging, including widefield (WF) and ultra-widefield (UWF) modalities, and to report their relative prevalence according to the genetic pattern of inheritance. METHODS: Cross-sectional clinical study of patients diagnosed with Alport syndrome. All patients underwent UWF color photography and autofluorescence, WF-optical coherence tomography angiography and spectral-domain optical coherence tomography. Demographics, past medical and ophthalmic history, and genetic mutation history were collected. RESULTS: Forty-two eyes of 21 patients (11 men; age 36.6 ± 12.9 years) were included. Macular spectral-domain optical coherence tomography revealed ILM granularity, more frequent in X-linked Alport syndrome and corresponding to dot maculopathy on color fundus. Mid-peripheral spectral-domain optical coherence tomography scans revealed multilamellated ILM in eight eyes (19%), presumably progressive, which corresponded to a cavitary pattern on en-face OCT. En-face OCT revealed multiple areas of retinal nerve fiber layer dehiscence in the macula, overlapping with vascular lacunae on optical coherence tomography angiography, and a coarse arrangement of retinal nerve fiber layer above and below the temporal raphe in 20 eyes (52%). CONCLUSION: Multimodal imaging allowed for the detection/characterization of retinal findings (ILM granularity, progressive ILM lamellation, retinal nerve fiber layer dehiscence, vascular lacunae, and coarse arrangement of retinal nerve fiber layer toward the disc) as multifaceted manifestations of ILM disease in Alport syndrome.
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Membrana Basal/diagnóstico por imagen , Nefritis Hereditaria/complicaciones , Fibras Nerviosas/patología , Enfermedades de la Retina/diagnóstico por imagen , Células Ganglionares de la Retina/patología , Adolescente , Adulto , Membrana Basal/patología , Angiografía por Tomografía Computarizada , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Adulto JovenRESUMEN
BACKGROUND/PURPOSE: To apply an automated deep learning automated fluid algorithm on data from real-world management of patients with neovascular age-related macular degeneration for quantification of intraretinal/subretinal fluid volumes in optical coherence tomography images. METHODS: Data from the Vienna Imaging Biomarker Eye Study (VIBES, 2007-2018) were analyzed. Databases were filtered for treatment-naive neovascular age-related macular degeneration with a baseline optical coherence tomography and at least one follow-up and 1,127 eyes included. Visual acuity and optical coherence tomography at baseline, Months 1 to 3/Years 1 to 5, age, sex, and treatment number were included. Artificial intelligence and certified manual grading were compared in a subanalysis of 20%. Main outcome measures were fluid volumes. RESULTS: Intraretinal/subretinal fluid volumes were maximum at baseline (intraretinal fluid: 21.5/76.6/107.1 nL; subretinal fluid 13.7/86/262.5 nL in the 1/3/6-mm area). Intraretinal fluid decreased to 5 nL at M1-M3 (1-mm) and increased to 11 nL (Y1) and 16 nL (Y5). Subretinal fluid decreased to a mean of 4 nL at M1-M3 (1-mm) and remained stable below 7 nL until Y5. Intraretinal fluid was the only variable that reflected VA change over time. Comparison with human expert readings confirmed an area under the curve of >0.9. CONCLUSION: The Vienna Fluid Monitor can precisely quantify fluid volumes in optical coherence tomography images from clinical routine over 5 years. Automated tools will introduce precision medicine based on fluid guidance into real-world management of exudative disease, improving clinical outcomes while saving resources.
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Degeneración Macular , Degeneración Macular Húmeda , Algoritmos , Inhibidores de la Angiogénesis/uso terapéutico , Inteligencia Artificial , Preescolar , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Líquido Subretiniano , Tomografía de Coherencia Óptica/métodos , Factor A de Crecimiento Endotelial Vascular , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológicoRESUMEN
Age-related macular degeneration (AMD) is one of the main causes of visual impairment and blindness in patients over 60 years in developed countries. Whilst no effective form of therapy is available for the dry form of AMD, intravitreal application of anti-VEGF substances is able to prevent the progression of neovascular AMD (nAMD) in most cases. Aside from the drugs ranibizumab, aflibercept and brolucizumab, other agents such as bevacizumab are often used off-label in order to save expense. The treatment intervals have also been refined, so as to reduce the burden on patients and health care systems. After fixed injection intervals, the pro re nata-regimen has been developed. Each month, it is decided whether the patient receives intravitreal injections based on fixed criteria. In the treat and extend-protocol, patients receive injections on each visit, but the intervals between injections vary due to the clinical outcomes. The observe-and-plan regime allows scheduling of the injection intervals in blocks, for three consecutive injections at a time. However, results of real-world studies were not able to reproduce those obtained in the pivotal studies. A high number of visits and fear of the injection procedure impose a burden on patients, that is mostly accepted due to fear of vision loss. Caregivers also complain of loss of productivity and income from having to provide regular support to patients. Health care systems worldwide are affected by increasing treatment numbers and the costs involved. The treatment of nAMD constitutes an achievement for modern medicine. However, despite the challenges, it must be evaluated and reviewed repeatedly in order to provide the best therapy for patients.
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Inhibidores de la Angiogénesis , Humanos , Inyecciones Intravítreas , Degeneración Macular/terapia , Persona de Mediana Edad , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Agudeza VisualRESUMEN
Retinotopy experiments using population receptive field (pRF) mapping are ideal for assigning regions in the visual field to cortical brain areas. While various designs for visual stimulation were suggested in the literature, all have specific shortcomings regarding visual field coverage. Here we acquired high-resolution 7 Tesla fMRI data to compare pRF-based coverage maps obtained with the two most commonly used stimulus variants: moving bars; rotating wedges and expanding rings. We find that stimulus selection biases the spatial distribution of pRF centres. In addition, eccentricity values and pRF sizes obtained from wedge/ring or bar stimulation runs show systematic differences. Wedge/ring stimulation results show lower eccentricity values and strongly reduced pRF sizes compared to bar stimulation runs. Statistical comparison shows significantly higher pRF centre numbers in the foveal 2° region of the visual field for wedge/ring compared to bar stimuli. We suggest and evaluate approaches for combining pRF data from different visual stimulus patterns to obtain improved mapping results.
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Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Estimulación Luminosa/métodos , Retina/fisiología , Corteza Visual/fisiología , Campos Visuales/fisiología , Adulto , Femenino , Humanos , Masculino , Vías Visuales/fisiología , Adulto JovenRESUMEN
PURPOSE: To report the 96-week outcomes from HAWK and HARRIER. DESIGN: Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD). PARTICIPANTS: Treatment-naïve eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER). METHODS: After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w. MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w. RESULTS: Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, -174.8 µm vs. -148.7 µm; 95% confidence interval for treatment difference, -46.2 to -5.9 µm; P = 0.0115) and HARRIER (LS mean, -197.7 µm vs. -155.1 µm; 95% confidence interval for treatment difference, -62.0 to -23.3 µm; P < 0.0001). The proportions of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at 96w in HAWK were 31% (P = 0.0688) and 24% (P = 0.0002) for brolucizumab 3 mg and 6 mg and 37% for aflibercept, whereas in HARRIER, they were 24% for brolucizumab 6 mg (P < 0.0001) and 39% for aflibercept. At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile. CONCLUSIONS: Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Estudios de Seguimiento , Mácula Lútea/patología , Estudios Prospectivos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/administración & dosificación , Factores de Tiempo , Tomografía de Coherencia Óptica/métodos , Resultado del Tratamiento , Degeneración Macular Húmeda/diagnósticoRESUMEN
PURPOSE: To investigate associations between residual subretinal fluid (rSRF) volumes, quantified using artificial intelligence and treatment outcomes in a subretinal fluid (SRF)-tolerant treat-and-extend (T&E) regimen in neovascular age-related macular degeneration. METHODS: Patients enrolled in the prospective, multicenter FLUID study randomized in an SRF-tolerant T&E regimen were examined by spectral-domain optical coherence tomography and tested for best-corrected visual acuity (BCVA). Intraretinal fluid and SRF volumes were quantified using artificial intelligence tools. In total, 375 visits of 98 patients were divided into subgroups: extended intervals despite rSRF and extended intervals without fluid. Associations between BCVA change, SRF volume, subgroups, and treatment intervals were estimated using linear mixed models. RESULTS: In extended intervals despite rSRF, increased SRF was associated with reduced BCVA at the next visit in the central 1 mm (-0.138 letters per nL; P = 0.014) and 6 mm (-0.024 letters per nL; P = 0.049). A negative association between increased interval and BCVA change was found for rSRF in 1 mm and 6 mm (-0.250 and -0.233 letter per week interval, respectively; both P < 0.001). Extended intervals despite rSRF had significantly higher SRF volumes in the central 6 mm at the following visit (P = 0.002). CONCLUSION: Artificial intelligence-based analysis of extended visits despite rSRF demonstrated increasing SRF volumes associated with BCVA loss at the consecutive visit. This negative association contributes to the understanding of rSRF volumes on treatment outcomes in neovascular age-related macular degeneration.
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Inteligencia Artificial , Tolerancia a Medicamentos , Angiografía con Fluoresceína/métodos , Ranibizumab/administración & dosificación , Líquido Subretiniano/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Estudios Prospectivos , Líquido Subretiniano/efectos de los fármacos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular , Degeneración Macular Húmeda/diagnósticoRESUMEN
PURPOSE: To evaluate the change in the fovea's postoperative location after successful pars plana vitrectomy with combined epiretinal and internal limiting membrane peeling in patients with idiopathic epiretinal membranes (iERMs). METHODS: In this prospective study 32 eyes of 32 patients with iERMs were followed from baseline before until 3 months after surgery. Study measures included 4-m Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, enhanced-depth imaging-optical coherence tomography, and intraoperative fundus photographs. Foveal movement was assessed by measuring the change in the papillofoveal distance (∆PFD). RESULTS: Mean ∆PFD in the study eye was -124 µm (±138) and -272 µm (±213) one day and 3 months after surgery, respectively. Mean ∆PFD after 3 months was greater in the study than in the fellow eye (P < 0.001). ∆PFD at Month 3 did not correlate with the internal limiting membrane area peeled (P = 0.78). CONCLUSION: Foveal movement starts immediately after surgery and causes a statistically significant reduction in PFD after uneventful macular pucker surgery. ∆PFD correlates statistically significantly with baseline best-corrected visual acuity and baseline central retinal thickness. The internal limiting membrane peeling size had no significant effect on the amount of postoperative foveal dislocation.
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Membrana Epirretinal/cirugía , Fóvea Central/fisiopatología , Procedimientos Quirúrgicos Oftalmológicos/métodos , Tomografía de Coherencia Óptica/métodos , Anciano , Anciano de 80 o más Años , Membrana Epirretinal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To prospectively evaluate the outcomes of different subtypes of neovascular age-related macular degeneration during intravitreal aflibercept monotherapy. METHODS: Forty-four eyes of 44 patients with treatment-naïve polypoidal choroidal vasculopathy (PCV, n = 12), hemorrhagic choroidal neovascularization (hCNV, n = 12), pigment epithelium detachment (PED, n = 11), or retinal angiomatous proliferation (RAP, n = 9) were included and followed for 12 months. All patients received intravitreal aflibercept monotherapy. RESULTS: Mean visual acuity at baseline in PCV was 67 ± 16 Early Treatment Diabetic Retinopathy Study letters (20/50 Snellen equivalent), in hCNV 55 ± 21 (20/80), in RAP lesions 64 ± 11 (20/50), and in PED 74 ± 7 (20/32). At Month 12, visual acuity in PCV was 66 ± 16 (20/50), in hCNV 69 ± 17 (20/40), in RAP 68 ± 12 (20/50), and in PED 69 ± 18 (20/40). At the 12-month follow-up, visual acuity improved or was stable (±5 letters from baseline) in 84% of eyes (37/44 patients), with hCNV showing the greatest mean visual acuity gain. Mean central retinal thickness in patients with PCV was 523 ± 251 µm, in hCNV 497 ± 171, in RAP lesions 573 ± 132, and in PED 541 ± 158 and decreased to 310 ± 91 µm in PCV, 323 ± 75 µm in hCNV, 357 ± 173 µm in RAP lesions, and 422 ± 150 µm in PED. The mean area of atrophy increased from 2.0 ± 3.6 mm2 at baseline to 4.6 ± 8.6 mm2 at Month 12 (mean difference [95% confidence interval] -0.8 [-8.5 to 7.0], P = 0.8), with the greatest atrophy in patients with PED at Month 12. CONCLUSION: All subtypes of neovascular age-related macular degeneration showed anatomical improvement and stabilization of visual function during intravitreal treatment.
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Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Epitelio Pigmentado de la Retina/patología , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Femenino , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Masculino , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Resultado del Tratamiento , Degeneración Macular Húmeda/diagnósticoRESUMEN
PURPOSE: To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD). METHODS: Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates. RESULTS: One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was -2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875). CONCLUSION: The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.