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BACKGROUND AND OBJECTIVES: To develop and test VMseg, a new image processing algorithm performing automatic segmentation of retinal non-perfusion in widefield OCT-Angiography images, in order to estimate the non-perfusion index in diabetic patients. METHODS: We included diabetic patients with severe non-proliferative or proliferative diabetic retinopathy. We acquired images using the PlexElite 9000 OCT-A device with a photomontage of 5 images of size 12 x 12 mm. We then developed VMseg, a Python algorithm for non-perfusion detection, which binarizes a variance map calculated through convolution and morphological operations. We used 70% of our data set (development set) to fine-tune the algorithm parameters (convolution and morphological parameters, binarization thresholds) and evaluated the algorithm performance on the remaining 30% (test set). The obtained automatic segmentations were compared to a ground truth corresponding to manual segmentation from a retina expert and the inference processing time was estimated. RESULTS: We included 51 eyes of 30 patients (27 severe non-proliferative, 24 proliferative diabetic retinopathy). Using the optimal parameters found on the development set to tune the algorithm, the mean dice for the test set was 0.683 (sd = 0.175). We found a higher dice coefficient for images with a higher area of retinal non-perfusion (rs = 0.722, p < 10-4). There was a strong correlation (rs = 0.877, p < 10-4) between VMseg estimated non-perfusion indexes and indexes estimated using the ground truth segmentation. The Bland-Altman plot revealed that 3 eyes (5.9%) were significantly under-segmented by VMseg. CONCLUSION: We developed VMseg, an automatic algorithm for retinal non-perfusion segmentation on 12 x 12 mm OCT-A widefield photomontages. This simple algorithm was fast at inference time, segmented images in full-resolution and for the OCT-A format, was accurate enough for automatic estimation of retinal non-perfusion index in diabetic patients with diabetic retinopathy.
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Algoritmos , Retinopatía Diabética , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Procesamiento de Imagen Asistido por Computador/métodos , Vasos Retinianos/diagnóstico por imagen , Retina/diagnóstico por imagen , Retina/patología , Angiografía/métodos , Angiografía con Fluoresceína/métodosRESUMEN
PURPOSE: To assess the efficacy and safety of 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) in treating chronic postoperative cystoid macular edema (PCME) after pars plana vitrectomy. DESIGN: Retrospective multicentric case series in clinical settings. SUBJECTS: Patients with chronic PCME who underwent vitrectomy in tertiary care centers in France. All eyes had a documented good response to the DEX implant prior to FAc implantation. METHODS: Review of charts and OCT scans of patients treated with a FAc intravitreal implant. MAIN OUTCOME MEASURES: The primary endpoints were the best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary endpoints were the intraocular pressure (IOP); proportion of patients maintaining a BCVA ≥20/40; need for additional non-study treatment; differences between eyes that underwent a single and multiple surgeries and OCT biomarkers of better BCVA. RESULTS: Forty-nine eyes of 49 patients with a mean follow-up of 24.5 ± 3.9 months were included. The mean BCVA increased from 0.40 ± 0.26 logMAR at baseline to 0.32 ± 0.24 logMAR at month 24 (M24) (p=0.0035). The mean CRT decreased from 409.37 ± 139.43 µm at baseline to 340 ± 91 µm at M24 (p=0.0001). The mean IOP was 14.0 ± 4 mmHg at baseline and remained stable at 14.03 ± 4.1 mmHg at M24 (p=0.99). During the follow-up, the IOP exceeded 21 mmHg in 9 eyes. The IOP rise was controlled with topical therapy in all eyes except one, which required cyclophotocoagulation. The BCVA was ≥20/40 in 47% of eyes (95% CI: 34%-61%) at baseline and in 58% of eyes at M24 (95% CI: 41%-73%). At M18, the likelihood of achieving a BCVA ≥20/40 was higher in eyes with intact external limiting membrane and ellipsoid zone. Additional dexamethasone implant (DEXi) was injected in 14 eyes (28.57%). The treatment burden of 2.45 ± 1.35 DEXi/year was decreased to 0.57 ± 0.60 DEXi/year after FAc implantation (p=0.001). CONCLUSION: FAc implant improved the BCVA and reduced the CRT in eyes with chronic PCME after vitrectomy. The IOP rise could be anticipated by the previous response to corticosteroids. FAc implant in eyes with chronic PCME also allowed reducing the treatment burden.
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PURPOSE: To describe the retinal and vitreous changes in eyes showing myopic macular schisis (MMS) improvement when vitrectomy was not performed and identify triggering factors. DESIGN: Retrospective observational study. SUBJECTS: Patients with nonoperated MMS. METHODS: The records of patients with MMS who were followed without performing surgery for >6 months were retrospectively reviewed, and the eyes showing an anatomic improvement were included. Myopic macular schisis evolution was analyzed quantitatively (central foveal thickness [CFT], parafoveal thickness, maximum height) and qualitatively (presence/absence of foveal detachment, lamellar hole, epiretinal membrane, choroidal neovascularization, inner and outer retinoschisis, vitreous status) at baseline and at the final visit. An anatomic improvement was defined as a decrease in CFT by ≥50 µm. MAIN OUTCOME MEASURES: The rate of anatomic improvement of MMS without performing vitrectomy and the morphological changes observed in these cases. RESULTS: In a cohort of 74 nonoperated eyes with MMS, MMS improved in 14 eyes (19%) after a mean follow-up of 55 ± 38 months (range, 8-138). In these improved cases, the mean decrease in CFT was 153 ± 166 µm (range, 24-635; P = 0.005) and a complete resolution of MMS was observed in 9 eyes (64%). In 9 eyes (64%), the improvement was associated with visible vitreous changes in the macular area on the OCT scans. The mean visual acuity, which was already good at baseline (20/50, 0.4 ± 0.2 logarithm of the minimum angle of resolution), increased at the last visit (20/40, 0.3 ± 0.3 logarithm of the minimum angle of resolution) but without reaching significance. CONCLUSIONS: This long-term follow-up analysis showed that almost 20% of MMS in eyes without indication for surgery could improve over time. In most cases, the improvement was associated with an apparent resolution of vitreous tensions. 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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INTRODUCTION: An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution. METHODS AND ANALYSIS: A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms. ETHICS AND DISSEMINATION: The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients. TRIAL REGISTRATION NUMBER: NCT04624737.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Masculino , Femenino , Retinopatía Diabética/diagnóstico por imagen , Inteligencia Artificial , Estudios Prospectivos , Retina , AlgoritmosRESUMEN
BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.
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Inhibidores de la Angiogénesis , Retinopatía Diabética , Coagulación con Láser , Edema Macular , Oclusión de la Vena Retiniana , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Humanos , Edema Macular/etiología , Edema Macular/tratamiento farmacológico , Edema Macular/cirugía , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Coagulación con Láser/métodos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Francia , Resultado del Tratamiento , Estudios Multicéntricos como Asunto , Inyecciones Intravítreas , Factores de Tiempo , Estudios de Equivalencia como Asunto , Terapia CombinadaRESUMEN
Diabetic Retinopathy (DR), an ocular complication of diabetes, is a leading cause of blindness worldwide. Traditionally, DR is monitored using Color Fundus Photography (CFP), a widespread 2-D imaging modality. However, DR classifications based on CFP have poor predictive power, resulting in suboptimal DR management. Optical Coherence Tomography Angiography (OCTA) is a recent 3-D imaging modality offering enhanced structural and functional information (blood flow) with a wider field of view. This paper investigates automatic DR severity assessment using 3-D OCTA. A straightforward solution to this task is a 3-D neural network classifier. However, 3-D architectures have numerous parameters and typically require many training samples. A lighter solution consists in using 2-D neural network classifiers processing 2-D en-face (or frontal) projections and/or 2-D cross-sectional slices. Such an approach mimics the way ophthalmologists analyze OCTA acquisitions: (1) en-face flow maps are often used to detect avascular zones and neovascularization, and (2) cross-sectional slices are commonly analyzed to detect macular edemas, for instance. However, arbitrary data reduction or selection might result in information loss. Two complementary strategies are thus proposed to optimally summarize OCTA volumes with 2-D images: (1) a parametric en-face projection optimized through deep learning and (2) a cross-sectional slice selection process controlled through gradient-based attribution. The full summarization and DR classification pipeline is trained from end to end. The automatic 2-D summary can be displayed in a viewer or printed in a report to support the decision. We show that the proposed 2-D summarization and classification pipeline outperforms direct 3-D classification with the advantage of improved interpretability.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Vasos Retinianos/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Estudios TransversalesRESUMEN
OBJECTIVES: To assess the risk factors for resistance to first-line therapy and long-term response to dexamethasone intravitreal implant (Ozurdex®) of patients with macular oedema (MO) secondary to rhegmatogenous retinal detachment repair (RRDR). METHODS: This was a retrospective, consecutive cohort study conducted in patients who underwent RRDR between January 2014 and December 2020 in the Rothschild Foundation Hospital and experienced postoperative MO (POMO) with a follow-up of at least 18 months. RESULTS: Of the 1152 patients screened, 36 eyes (3.1%) experienced POMO. The mean follow-up duration was 45.2 months (18.0-80.5 months). Twenty-five eyes (69.4%) were resistant to first-line therapy and received at least one Ozurdex® injection (mean number: 2.7 [1-12]). The multivariate analysis showed an increased risk of resistance in patients who underwent perfluorocarbon liquid (PFCL)-assisted drainage (adjusted odds ratio: 8.65; 95% confidence interval: 1.97-15.33; p = 0.01). Significant differences in best-corrected visual acuity and central macular thickness were found between before Ozurdex® injection and the last follow-up visit: from 0.57 ± 0.47 LogMAR to 0.34 ± 0.32 LogMAR (p = 0.02) and from 483.0 ± 124.0 µm to 354.6 ± 96.5 µm (p = 0.001), respectively. The absence of serous retinal detachment and the presence of hyperreflective foci at baseline were associated with a higher resistance and a poorer response to Ozurdex®. Two patients (8%) experienced hypertony, that was well controlled with hypotonic drops. CONCLUSION: MO secondary to RRDR is challenging. Ozurdex® could be reasonably proposed as first-line treatment, at least when MO occurs following PFCL-assisted drainage, given the favourable long-term benefit/risk ratio.
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Edema Macular , Desprendimiento de Retina , Oclusión de la Vena Retiniana , Humanos , Glucocorticoides/uso terapéutico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/cirugía , Estudios Retrospectivos , Estudios de Cohortes , Implantes de Medicamentos/uso terapéutico , Inyecciones Intravítreas , Dexametasona/uso terapéutico , Factores de Riesgo , Oclusión de la Vena Retiniana/tratamiento farmacológicoRESUMEN
Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia, leads to nonproliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retina barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels, and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation remains unknown. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas expressed perilipin 2 (PLIN2), a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from patients with T2DM or with palmitate concentrations typical of those found in T2DM plasma, but not under high-glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induced capillary degeneration in ex vivo explants that was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study reveals a mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target for inhibition of lipid-activated MPs in DR.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Dislipidemias , Humanos , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Dislipidemias/metabolismo , Lípidos , Macrófagos/metabolismo , Perilipina-2/genética , Perilipina-2/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Retina/metabolismoRESUMEN
Purpose: To determine whether the nonperfusion index (NPI) measured on widefield (WF) optical coherence tomography angiography (OCTA) could be used as an alternative method for the diagnosis of proliferative diabetic retinopathy (PDR) and to study the relationship between the NPI and the location of new vessels (NV) in eyes with PDR. Methods: Fifty-one treatment-naïve eyes with either severe nonproliferative DR (NPDR) or PDR were imaged using ultra-wide-field imaging and wide-field OCTA. Results: The NPI was significantly higher in eyes with PDR (18.94% vs. 7.51%; P < 0.01). Using the NPI on the whole image to assess PDR status, the area under the curve was 0.770, but the area under the curve increased when the NPI of the most peripheral circle was used (area under the curve of 0.792). Four eyes with PDR (17%) had NV outside the OCTA image field, and their mean NPI (6.15 %) did not differ from that measured in severe NPDR eyes (7.51%; P = 0.67) and was lower than in other eyes with PDR (21.49%; P = 0.023). The presence of NV in a sector was associated with a higher NPI in the same sector (29.2% vs. 6.0%; P < 10-15). Conclusions: Although the NPI was significantly higher in eyes with PDR compared with severe NPDR eyes, its measurement on the whole wide-field OCTA image was not sensitive enough to replace the detection of NV for the diagnosis of PDR. Translational Relevance: Because the presence of new vessels was related to the local nonperfusion index in the same sector, the assessment of nonperfusion outside the optical coherence tomography angiography field is important in diabetic retinopathy.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/diagnóstico por imagen , Tomografía de Coherencia Óptica , Angiografía , OjoRESUMEN
Retromode scanning laser ophthalmoscopy imaging captures a pseudo-3-dimensional image of the ocular fundus. Retromode scanning laser ophthalmoscopy imaging was introduced first in 2008 using the Nidek F-10 scanning laser ophthalmoscope (F-10; Nidek Co., Gamagori, Japan). At that time, no major role was described for this imaging modality. The interest in retromode scanning laser ophthalmoscopy imaging is reemerging with the recent advent of the Mirante that combines scanning laser ophthalmoscopy and optical coherence tomography (Nidek Co., Gamagori, Japan) that can capture retromode images of the fundus. We summarize the findings and clinical implications of retromode imaging using the Nidek F-10 and the Mirante in retinal diseases with the aim of helping researchers direct their future studies.
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Enfermedades de la Retina , Humanos , Enfermedades de la Retina/diagnóstico por imagen , Oftalmoscopía/métodos , Fondo de Ojo , Tomografía de Coherencia Óptica/métodosRESUMEN
OBJECTIVE: To compare subjective levels of comfort and visual experiences related to microscope light in patients undergoing their first cataract surgery with topical anaesthesia using a digital microscope (the NGENUITY three-dimensional (3D) visualisation system) or a conventional microscope. METHODS AND ANALYSIS: A prospective, randomised, single-blinded, parallel-group, multicentre, interventional study. Patients (n=128) were randomly assigned to one of two treatment groups: the experimental group (n=63) had surgery using the digital microscope and the control group (n=65) had surgery with a conventional microscope. The primary outcome was patients' subjective experience of glare from the microscope light during surgery on a numerical scale from 0 to 10. Key secondary outcomes were patients' subjective levels of comfort and visual experiences related to the microscope light. RESULTS: The experimental group reported significantly lower levels of glare; median levels were 1.0 (0.0-4.0) for the experimental group vs 3.0 (0.0-6.0) for the control group (p=0.027). They also reported higher levels of comfort; median ratings were 8.0 (6.5-10.0) in the experimental group and 7.0 (5.0-9.0) in controls (p=0.026). There were no group differences in ratings of subjective pain or visual disturbances. Median microscope light intensity was lower in the experimental group than controls; 3425.0 (2296.0-4300.0) Lux vs 24 279.0 (16 000.0-26 500.0) Lux (p<0.0001), respectively. CONCLUSION: Compared with conventional microscopes, the NGENUITY 3D visualisation system allows surgeons to operate with lower levels of light exposure, resulting in significantly less glare and improved comfort in patients undergoing cataract surgery. TRIAL REGISTRATION NUMBER: NCT05085314.
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Extracción de Catarata , Catarata , Humanos , Estudios Prospectivos , Deslumbramiento , Método Simple CiegoRESUMEN
PURPOSE: To assess a new optical coherence tomography angiography (OCTA) technology and its contribution to retinal vascularization and choriocapillaris (CC) exploration. METHODS: A new module, named "Beam expander" (BE), which increases the lateral resolution of OCTA, was used in combination with a prototype software in the PLEX® Elite 9000 Swept-Source OCT instrument (ZEISS, Dublin, CA). This prospective study involved 22 healthy subjects imaged with and without BE. Qualitative analysis of superficial capillary plexus (SCP), deep capillary complex (DCC) retinal and CC angiograms were performed. Perfusion density (PD), vessel density (VD), and foveal avascular zone (FAZ) measurements were also compared. RESULTS: Qualitative analysis of single SCP and DCC retinal angiograms acquired with BE showed significantly better vessel sharpness (respectively, p = 0.0002, and p<0.0001), and greater peripheral image quality (p = 0.028 and p = 0.007) compared to standard OCTA images. Mean VD of whole retina single scans was significantly higher for BE angiograms compared to classic angiograms (28.16 ±1.29 mm-1 and 23.36 ±0.92 mm-1, respectively, p<0.0001). Repeatability of VD, PD and FAZ raw size were found to be similar between the two methods (intraclass correlation coefficient: 0.671, 0.604 and 0.994 with BE versus 0.764, 0.638 and 0.990 without BE). CC image quality was found to be significantly superior with BE, and flow deficits were more visible in all BE scans compared to standard scans. CONCLUSIONS: An increase in lateral resolution of the OCT beam resulted in higher quality of retinal and choriocapillaris OCTA images in healthy subjects. These results provide significant insights into the future OCTA imaging enhancements.
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Angiografía , Tomografía de Coherencia Óptica , Humanos , Estudios Prospectivos , Retina/diagnóstico por imagen , Coroides/diagnóstico por imagenRESUMEN
Early-onset osteoporosis (EOOP) has been associated with several genes, including LRP5, coding for a coreceptor in the Wnt pathway. Variants in LRP5 were also described in osteoporosis pseudoglioma syndrome, combining severe osteoporosis and eye abnormalities. Genomewide-association studies (GWAS) showed that LRP5 p.Val667Met (V667M) variant is associated with low bone mineral density (BMD) and increased fractures. However, despite association with a bone phenotype in humans and knockout mice, the impact of the variant in bone and eye remains to be investigated. Here, we aimed to evaluate the bone and ocular impact of the V667M variant. We recruited 11 patients carrying the V667M variant or other loss-of-function variants of LRP5 and generated an Lrp5 V667M mutated mice. Patients had low lumbar and hip BMD Z-score and altered bone microarchitecture evaluated by HR-pQCT compared with an age-matched reference population. Murine primary osteoblasts from Lrp5 V667M mice showed lower differentiation capacity, alkaline phosphatase activity, and mineralization capacity in vitro. Ex vivo, mRNA expression of Osx, Col1, and osteocalcin was lower in Lrp5 V667M bones than controls (all p < 0.01). Lrp5 V667M 3-month-old mice, compared with control (CTL) mice, had decreased BMD at the femur (p < 0.01) and lumbar spine (p < 0.01) with normal microarchitecture and bone biomarkers. However, Lrp5 V667M mice revealed a trend toward a lower femoral and vertebral stiffness (p = 0.14) and had a lower hydroxyproline/proline ratio compared with CTL, (p = 0.01), showing altered composition and quality of the bone matrix. Finally, higher tortuosity of retinal vessels was found in the Lrp5 V667M mice and unspecific vascular tortuosity in two patients only. In conclusion, Lrp5 V667M variant is associated with low BMD and impaired bone matrix quality. Retinal vascularization abnormalities were observed in mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Besides cystoid macular edema due to a blood-retinal barrier breakdown, another type of macular cystoid spaces referred to as non-vasogenic cystoid maculopathies (NVCM) may be detected on optical coherence tomography but not on fluorescein angiography. Various causes may disrupt retinal cell cohesion or impair retinal pigment epithelium (RPE) and Müller cell functions in the maintenance of retinal dehydration, resulting in cystoid spaces formation. Tractional causes include vitreomacular traction, epiretinal membranes and myopic foveoschisis. Surgical treatment does not always allow cystoid space resorption. In inherited retinal dystrophies, cystoid spaces may be part of the disease as in X-linked retinoschisis or enhanced S-cone syndrome, or occur occasionally as in bestrophinopathies, retinitis pigmentosa and allied diseases, congenital microphthalmia, choroideremia, gyrate atrophy and Bietti crystalline dystrophy. In macular telangiectasia type 2, cystoid spaces and cavitations do not depend on the fluid leakage from telangiectasia. Various causes affecting RPE function may result in NVCM such as chronic central serous chorioretinopathy and paraneoplastic syndromes. Non-exudative age macular degeneration may also be complicated by intraretinal cystoid spaces in the absence of fluorescein leakage. In these diseases, cystoid spaces occur in a context of retinal cell loss. Various causes of optic atrophy, including open-angle glaucoma, result in microcystoid spaces in the inner nuclear layer due to a retrograde transsynaptic degeneration. Lastly, drug toxicity may also induce cystoid maculopathy. Identifying NVCM on multimodal imaging, including fluorescein angiography if needed, allows guiding the diagnosis of the causative disease and choosing adequate treatment when available.
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Glaucoma de Ángulo Abierto , Degeneración Macular , Edema Macular , Telangiectasia Retiniana , Humanos , Edema Macular/diagnóstico , Angiografía con Fluoresceína , Tomografía de Coherencia Óptica/métodosRESUMEN
PURPOSE: To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study. METHODS: A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of ≥2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT. RESULTS: Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2% were men, 26.4% were Hispanic, and 73.6% were non-Hispanic White individuals; 41.1%, 23.4%, 9.1%, and 2.5% had ≥1, ≥2, ≥3, and 4 highly suggestive features. Results showed that 23.4% (95% CI, 17.6%-29.9%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8% vs 64.9%, P = .01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6% vs 28.2%, P = .006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6% and 29.9% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.
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Neovascularización Coroidal , Degeneración Macular , Pólipos , Desprendimiento de Retina , Masculino , Humanos , Anciano , Femenino , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/epidemiología , Estudios Retrospectivos , Estudios Transversales , Población Blanca , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Pólipos/diagnóstico , Pólipos/epidemiología , Coroides/irrigación sanguíneaRESUMEN
PURPOSE: To assess the sequence of anatomical resolution of myopic foveoschisis (MFS) after vitrectomy. DESIGN: Monocentric retrospective observational case series. SUBJECTS: The files of consecutive patients with MFS who underwent vitreoretinal surgery and were followed postoperatively for at least 6 months were reviewed. METHODS: Patients underwent pars plana vitrectomy for MFS. The central foveal thickness (CFT) was measured. The presence of a foveal involvement, and/or outer retinoschisis (ORS), with or without inner retinoschisis (IRS), and foveal detachment (FD) were analyzed. Anatomical success was defined as the resolution of foveal ORS and FD. MAIN OUTCOME MEASURES: The main outcome was the time to resolution of the different morphologic features of MFS after surgery. RESULTS: Thirty-nine eyes of 36 patients were included in the analysis. The mean follow-up was 14.8 ± 12.9 months (range, 6-84 months). Anatomical success was achieved in 82% of cases at the end of the follow-up and in > 80% of cases during the first year. The CFT was significantly decreased in 79% of cases at 3 months. Inner retinoschisis, present in 18 eyes (46%), resolved in all cases after a median time of 1 month. Foveal ORS, present in all cases, resolved in 82% of cases after a median time of 3 months. The FD, present in 23 eyes (59%), resolved in 91% of cases after a median time of 6 months. Extrafoveal ORS resolved in 59% of cases after a median time of 12 months. The mean best-corrected visual acuity significantly improved from 0.80 ± 0.64 logarithm of the minimum angle of resolution (logMAR) (Snellen Eq 20/148) to 0.48 ± 0.52 logMAR (Snellen Eq 20/70). CONCLUSIONS: Most MFS (80%) are completely resolved during the first year. The decrease in CFT and early resolution of IRS could be used as early biomarkers of surgical success.
Asunto(s)
Miopía Degenerativa , Retinosquisis , Humanos , Membrana Basal/cirugía , Fóvea Central , Miopía Degenerativa/complicaciones , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/cirugía , Retinosquisis/diagnóstico , Retinosquisis/cirugía , Estudios Retrospectivos , Tomografía de Coherencia Óptica , VitrectomíaRESUMEN
PURPOSE: The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts. METHODS: An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel. RESULTS: After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated. CONCLUSION: This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Desprendimiento de Retina , Inhibidores de la Angiogénesis/uso terapéutico , Técnica Delphi , Dexametasona , Diabetes Mellitus/tratamiento farmacológico , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Implantes de Medicamentos/uso terapéutico , Glucocorticoides , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Desprendimiento de Retina/tratamiento farmacológico , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza VisualRESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to describe the outcomes of a switch back to anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DME) eyes treated temporarily with a dexamethasone implant (DEXi), after an initial poor response to anti-VEGF. METHODS: The study involved a case series. RESULTS: Twenty-three eyes of 17 patients were included. All were poorly responsive to anti-VEGF and switched to a DEXi after a mean of 12 anti-VEGF injections. The mean best-corrected visual acuity (BCVA) increased from 0.25 ± 0.19 (decimals) to 0.29 ± 0.20 after switching to the DEXi (p = 0.11). BCVA remained stable (0.31 ± 0.23; p = 0.11) after switching back to anti-VEGF, one month after the last injection. The mean central macular thickness (CMT) decreased significantly from 517.0 ± 128.5 µm to 343.4 ± 118.9 µm (p < 0.001) after switching to the DEXi. In eyes receiving ≥3 anti-VEGF injections during the switch back, the CMT 1 month after the last anti-VEGF injection was significantly decreased compared to the CMT before the switch to the DEXi (mean change of - 95.55 ± 89.82 µm, p = 0.005). CONCLUSION: Switching back poorly responsive DME eyes to anti-VEGF after temporary DEXi therapy is associated with good anatomical and visual outcomes similar to those obtained with the DEXi, provided that at least 3 anti-VEGF injections are administered. The DEXi might restore retinal sensitivity to anti-VEGF.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Inhibidores de la Angiogénesis , Bevacizumab , Dexametasona , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Ranibizumab , Factor A de Crecimiento Endotelial Vascular , Agudeza VisualRESUMEN
AIM: To analyse the choroidal thickness (CT) and vessel pattern of myopic patients with dome-shaped macula (DSM) and their association with the DSM axis and serous retinal detachment (SRD). METHODS: Retrospective study. The CT and vessel pattern were assessed on optical coherence tomography (OCT), OCT-angiography and ultra-wide-field photography. RESULTS: 27 eyes of 18 subjects (mean age: 65 years) were included. Compared with the 11 eyes (41%) with horizontal DSM, the 16 eyes (59%) with vertical DSM had a shorter axial length (25.8±2 mm vs 28.3±2.5 mm; p=0.01), a higher mean macular bulge height (624.4±207 µm vs 255.4±160.3 µm; p=0.0001) and a thicker CT (183.1±91.1 µm vs 72±38.3 µm; p<0.001). Large choroidal vessels crossed the macular area in 75% of eyes with vertical DSM vs 27% of eyes with horizontal DSM (p=0.02), whereas a watershed zone framing the macula was more often seen in horizontal DSM (72% vs 25%, p=0.02). Thirteen eyes (48%) had an SRD that was not associated with the DSM axis, the mean bulge height, the CT or the vessel pattern. CONCLUSION: The presence of an SRD did not correlate with the DSM axis, the CT or the vessel pattern. However, the rate of large choroidal vessels crossing the macula was higher in vertical DSM than in horizontal DSM.