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1.
Acta Ophthalmol ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706195

RESUMO

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

2.
Eye (Lond) ; 38(5): 847-852, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37865725

RESUMO

OBJECTIVE: To evaluate the effect of changing slab position on the correlation between choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) and yearly enlargement rate (yER) of GA. METHODS: OCT and OCTA images obtained on Cirrus HD-OCT device were collected from patients with GA. Each patient underwent OCTA scan at baseline and two OCT scans, one at baseline and one after at least 12 months. GA was delineated on en-face fundus image to calculate yER. OCTA images were generated from three 10 µm thick slabs 11, 21 and 31 µm posterior to RPE-fit line. 100 µm-wide concentric rings were generated around GA to calculate FD% in each ring which was correlated with yER. RESULTS: For the 11-21 µm slab, FD% was not significantly correlated with yER for any of the rings (p > 0.05). For the 21-31 and 31-41 µm slab, FD% of rings located in the 600 µm region around GA was significantly correlated with yER (p < 0.05). However, in all slab locations, there was no significant correlation between yER and CC FD% of rings located beyond the 600 µm region (p > 0.05). CONCLUSIONS: Slab selection for quantification of CC FD% may have a significant impact on quantitative results in eyes with GA.


Assuntos
Atrofia Geográfica , Humanos , Tomografia de Coerência Óptica/métodos , Fundo de Olho , Corioide , Angiofluoresceinografia/métodos
3.
BMC Ophthalmol ; 23(1): 465, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974114

RESUMO

BACKGROUND: Choroidal effusion is a common complication of glaucoma surgery. Although most cases of choroidal effusions resolve spontaneously with observation or medical management alone as intraocular pressure normalizes, surgical drainage might be needed in severe or persistent cases. Herein, we report a case of spontaneous resolution of long-standing severe choroidal effusion after Ahmed glaucoma valve implantation. CASE PRESENTATION: An 85-year-old man with uncontrolled primary open-angle glaucoma and medical history of chronic kidney disease underwent uneventful Ahmed glaucoma valve implantation. On postoperative day 8, transient hypotony occurred, and large 360° peripheral choroidal detachments developed. Although the intraocular pressure increased to normal levels on postoperative day 15, choroidal effusion did not resolve. Fundus examination over 8 months showed that the large choroidal effusion persisted despite a well-controlled intraocular pressure. Laboratory test performed at preoperatively and follow-up period revealed persistently elevated potassium and creatinine levels. On postoperative 9 months, the lesion resolved spontaneously without any surgical intervention. We found that the patient's creatinine level was normalized, pre-existing hyperkalemia was corrected, and accordingly his general condition was improved. CONCLUSIONS: Considering the underlying medical condition may be helpful in patients with persistent choroidal effusion of an unclear etiology following glaucoma filtering surgery.


Assuntos
Efusões Coroides , Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto , Glaucoma , Masculino , Humanos , Idoso de 80 Anos ou mais , Glaucoma de Ângulo Aberto/cirurgia , Creatinina , Complicações Pós-Operatórias , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma/cirurgia , Pressão Intraocular , Efusões Coroides/diagnóstico , Efusões Coroides/etiologia , Drenagem , Resultado do Tratamento , Estudos Retrospectivos
4.
Sci Rep ; 13(1): 11730, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474669

RESUMO

We investigated predictors of visual outcomes and injection interval in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) treated with a treat-and-extend (TAE) regimen. All 48 patients in a multicenter study were followed for 52 weeks and received three monthly intravitreal aflibercept injections before the TAE regimen, with treatment intervals adjusted by 4 weeks, up to a maximum of 16 weeks. Various laboratory biomarkers and optical coherence tomography parameters were evaluated. Patients were classified into the extension failure group if they had ≥ 1 treatment interval decreased due to an increase in the central macular thickness compared to the previous visit and 18 patients were assigned to this group. In multivariate logistic analyses, presence of microaneurysms and prominent middle limiting membrane (p-MLM) sign, increased initial external limiting membrane (ELM) disruption, and higher total cholesterol were correlated with inhibiting a sustained extension in the injection interval (P = 0.015, P = 0.032, P = 0.037, P = 0.009, respectively). Therefore, in the patients with ME secondary to BRVO with these risk factors, early consideration of frequent injection may improve treatment outcome.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Inibidores da Angiogênese , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Edema Macular/diagnóstico , Resultado do Tratamento , Injeções Intravítreas , Tomografia de Coerência Óptica/efeitos adversos , Estudos Retrospectivos
5.
Front Oncol ; 13: 1178762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37182165

RESUMO

Background: Cancer recurrence remains a significant problem, and most postoperative recurrences of non-small cell lung cancer (NSCLC) develop within 5 years after resection. We present a rare case of ultra-late recurrence of NSCLC accompanying choroidal metastasis with KIF13A-RET fusion 14 years after the definitive surgery. Case description: A 48-year-old female patient who had never-smoked presented with decreased visual acuity. She had been treated with right upper lobe lobectomy followed by adjuvant chemotherapy 14 years prior. Fundus photographs revealed bilateral choroidal metastatic lesions. Positron emission tomography-computed tomography (PET-CT) scans showed extensive bone metastases and focal hypermetabolism in the left uterine cervix. An excision biopsy of the uterus showed primary lung adenocarcinoma with immunohistochemistry of TTF-1+. Plasma next-generation sequencing (NGS) identified the presence of KIF13A-RET fusion. After 6 months of selpercatinib therapy, PET-CT revealed a partial response for bone and uterine metastasis and stable disease for choroidal lesions. Conclusion: In this case report, we are reporting a rare case of ultra-late recurrence of NSCLC in a patient with choroidal metastasis. Furthermore, the diagnosis of NSCLC with RET fusion was based on liquid-based NGS rather than tissue-based biopsy. The patient showed a good response to selpercatinib, which supports the efficacy of selpercatinib as a treatment for RET-fusion-positive NSCLC with choroidal metastasis.

6.
Sci Rep ; 12(1): 16626, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198738

RESUMO

We investigated the influence of scan direction on subfoveal choroidal vascularity index (CVI) measurements using spectral-domain optical coherence tomography (SD-OCT) in young healthy subjects. Seventy-eight eyes of 41 healthy volunteers were included. Choroidal structures were obtained using SD-OCT with enhanced depth imaging (EDI) through radial scans at the center of the macula. The subfoveal choroidal images in the horizontal (0°), 45°, vertical (90°) and - 45° directions were recorded and CVIs were analyzed according to their respective directions using image binarization. Additionally, subfoveal choroidal thickness (SFCT), and axial eye length were measured. The SFCT and subfoveal CVI showed a negative correlation but were only significant for the 45° scan (Pearson's r = - 0.262, P = 0.021). The axial eye length and subfoveal CVI had no significant correlation in any direction (all P > 0.05). In the Bland-Altman plot, the subfoveal CVI measurement showed high agreement among the four scan directions. When the SFCT was ≥ 300 µm, there was no difference in the measured values of the subfoveal CVI among the four scan directions; however, when the SFCT was < 300 µm, there was a significant difference in subfoveal CVI among the scan directions (one-way analysis of variance, F = 4.685, P = 0.004). In subfoveal CVI measurement, it is considered that the horizontal (0°) scan can represent the vertical (90°) or oblique (45°, - 45°) scans. However, when the SFCT is thinner, the subfoveal CVI in each direction of radial scan may vary significantly. Hence, caution is required in the interpretation.


Assuntos
Macula Lutea , Tomografia de Coerência Óptica , Corioide/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Cintilografia , Tomografia de Coerência Óptica/métodos
7.
Graefes Arch Clin Exp Ophthalmol ; 259(10): 2879-2886, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33914158

RESUMO

PURPOSE: To evaluate the functional and anatomical outcomes of a treat-and-extend (TAE) regimen with aflibercept for treatment-naive macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: This was a prospective, multicenter, noncomparative, open-label clinical trial. Forty-eight eyes of 48 patients received three monthly intravitreal aflibercept injections prior to the TAE regimen. However, if the best-corrected visual acuity (BCVA) was ≥ 20/20 and the central macular thickness (CMT) was < 250 µm during the loading phase, the patient immediately proceeded to the TAE regimen. The treatment interval was adjusted by 4 weeks based on changes in CMT. The primary outcome was the mean change in BCVA from baseline to 52 weeks. RESULTS: The mean change in BCVA was 23.6 ± 14.2 letters. The proportion of patients with BCVA gain ≥ 15 letters was 77.1% at 24 weeks and 72.9% at 52 weeks. The mean reduction in CMT was 326.2 ± 235.6 µm at 24 weeks and 324.2 ± 238.0 µm at 52 weeks. The mean number of injections was 6.7 ± 1.2 (range: 6-11, all patients received three monthly intravitreal aflibercept injections) over 52 weeks, and 34 patients (70.8%) reached the maximal extension interval of 16 weeks at 52 weeks. CONCLUSIONS: The TAE regimen using aflibercept for ME secondary to BRVO, which has a treatment interval of up to 16 weeks, showed comparable efficacy to the fixed-dosing regimen along with reduced treatment burden.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Inibidores da Angiogênese/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Resultado do Tratamento , Acuidade Visual
8.
Retina ; 41(2): 393-401, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33475272

RESUMO

PURPOSE: To evaluate the choriocapillaris (CC) flow deficit (FD) in eyes with hyporeflective cores (HCs) inside drusen in eyes with intermediate age-related macular degeneration. METHODS: Intermediate age-related macular degeneration subjects underwent optical coherence tomography and optical coherence tomography angiography using a Cirrus HD-optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). All B-scans were inspected for the presence of drusen with an HC that was defined as dark, condense materials inside drusen. Drusen regions delineated in the manufactures advanced retinal pigment epithelium elevation map were superimposed to the compensated CC optical coherence tomography angiography images. Quantitative analysis of CC FD% was performed under drusen with and without HCs, 150-µm-wide ring region around drusen with and without HCs, drusen-free region, and whole macula. RESULTS: Fifty eyes were included in this cross-sectional study. Twenty eyes had drusen with HCs. Thirty eyes without HCs were matched for age and sex. The CC FD% of whole macula was significantly greater in eyes with an HC than those without it (46.3% vs. 42.9%; P = 0.001). In eyes with HCs, regional CC FD% was the greater under drusen (59.8%) and in a 150-µm-wide ring surrounding drusen with HCs (53.0%) than corresponding regions for drusen without HCs (52.5% and 47.3%, respectively) (P < 0.005 in all, Bonferroni correction). The CC FD% in macular regions remote from drusen was 43.2%. CONCLUSION: Intermediate age-related macular degeneration eyes with HCs demonstrated more impaired CC flow, compared with those without this featured. The CC was also more severely impaired directly below these drusen with HCs. These findings highlight that the appearance of HCs may be an indicator of a more advanced disease phenotype.


Assuntos
Corioide/patologia , Angiofluoresceinografia/métodos , Degeneração Macular/diagnóstico , Fluxo Sanguíneo Regional/fisiologia , Drusas Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Corioide/fisiopatologia , Estudos Transversais , Feminino , Seguimentos , Fundo de Olho , Humanos , Degeneração Macular/complicações , Degeneração Macular/fisiopatologia , Masculino , Estudos Prospectivos , Drusas Retinianas/etiologia , Drusas Retinianas/fisiopatologia
9.
Int J Ophthalmol ; 13(7): 1152-1155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685405

RESUMO

AIM: To introduce a novel technique for transscleral fixation of the posterior chamber intraocular lens (PC-IOL) that requires no sutures on the IOL haptics. METHODS: Instead of suturing polypropylene onto the IOL haptics, the method simply winds the thread on the haptics. Fifteen eyes of 15 patients underwent this technique and were followed up for more than 18mo. Surgical outcomes and post-operative complications were evaluated and compared with those of the conventional transscleral fixation method. RESULTS: Postoperative cylinder was significantly lower in the thread winding group than in the conventional transscleral fixation method group (-1.02±0.46 diopters vs -1.57±0.77 diopters; P=0.01). Further, no postoperative complications, such as optic capture, IOL dislocation, and hyphema, were detected in the thread winding group. CONCLUSION: We believe that our thread winding technique is better than previously reported methods because it is simple, mechanically stable, and free from suture-related complications.

10.
Graefes Arch Clin Exp Ophthalmol ; 258(11): 2353-2362, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32666252

RESUMO

PURPOSE: To evaluate the choriocapillaris (CC) flow deficit (FD) beneath drusen associated with overlying intraretinal hyperreflective foci (HRF). METHODS: Patients with intermediate age-related macular degeneration (AMD) who had structural spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) using the Cirrus HD-OCT with AngioPlex software were retrospectively evaluated. A 6 × 6-mm-volume scan was used for the SD-OCT and OCTA. Post-imaging processing steps included generation of drusen map, identification of HRF, and generation of a signal-compensated CC slab prior to binarization and CC FD computation. The CC OCTA image was aligned with the drusen + HRF map to define regions of interest for CC FD measurement. The CC was quantified below drusen with and without overlying HRF and within a 150-µm-wide ring surrounding the drusen (unaffected by potential HRF-related shadowing), and across the entire 6 × 6 macular region. RESULTS: Fifty-three eyes with intermediate AMD were included, 25 eyes with HRF, and 28 eyes with no HRF. The mean ± SD FD% over the whole 6 × 6 macular region was 41.1 ± 3.4 in eyes with HRF compared with 39.5 ± 3.5 in eyes without HRF (p = 0.001). The mean ± SD CC FD% below drusen with HRF (54.4 ± 9.3) was significantly greater than below drusen without HRF (49.6 ± 9.5; p = 0.001). There was a strong positive correlation between the quantity of HRF and the extent of the CC FD (Pearson correlation = 0.81). CONCLUSION: Choriocapillaris flow deficits appear to be more severe in eyes with HRF and in particular directly below HRF. As HRF are thought to represent a higher risk or more advanced feature of intermediate AMD, these findings highlight the relationship between the severity of CC FD and overall severity of AMD.


Assuntos
Degeneração Macular , Drusas Retinianas , Corioide , Angiofluoresceinografia , Humanos , Degeneração Macular/diagnóstico , Drusas Retinianas/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica
11.
Am J Ophthalmol ; 219: 21-32, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32454035

RESUMO

PURPOSE: To evaluate the impact of processing technique and slab selection on the repeatability of choriocapillaris (CC) flow deficit (FD) measurements as assessed using optical coherence tomography angiography (OCTA) DESIGN: Prospective, cross-sectional study. METHODS: Healthy subjects were imaged with 4 consecutive 3 × 3-mm OCTA using a swept-source OCT (PLEX elite 9000; Carl Zeiss Meditec). OCTA images were generated using the Max projection, and three 10-µm-thick slabs starting 11, 21, and 31 µm posterior to the automatically segmented retinal pigment epithelial band. The resultant images were binarized using the Phansalkar method with a 43.94-µm radius and then the CCFD% was computed. The intraclass correlation coefficient (ICC) and coefficient of variation (CV) were computed for the 4 acquisitions to assess the repeatability of the CCFD%. This entire analysis was repeated after separately modulating several parameters: (1) Sum instead of the Max projection, (2) retinal pigment epithelial fit instead of the retinal pigment epithelial band as the offset reference, (3) 14.65 and 87.88 µm radius values instead of 43.94 µm. RESULTS: Twenty-four healthy eyes (mean age; 36.4 years) were enrolled. The CCFD% in the 11-21-, 21-31-, and 31-41-µm slabs generated by the Max algorithm and the retinal pigment epithelial band showed high repeatability values (ICCs = 0.963, 0.975, and 911; CVs = 0.05, 0.05, and 0.05, respectively). As most of the cases were confounded with the hypointense region when the 11-21-µm slab was used, however, this slab could not be included in the subsequent analyses. Those values in the 21-31- and 31-41-µm slabs were higher than those of the corresponding slabs by the Sum algorithm (ICC = 0.916 and 0.776; CV = 0.15 and 0.19, respectively) or by the retinal pigment epithelial fit (ICC = 0.907 and 0.802; CV = 0.06 and 0.06, respectively). The Phansalkar radius of 43.94 µm had the highest ICC numerically, but this was not statistically significantly greater than for a radius of 14.65 µm (ICC = 0.960 and 0.911, respectively) or a radius of 87.88 µm (ICC = 0.958 and 0.897, respectively). Regardless of which parameter was modulated, the 21-31-µm slab was the most repeatable. CONCLUSIONS: In normal eyes, en face CC OCTA images generated using the Max projection and a 10-µm-thick slab offset of 21 µm below the instrument-generated retinal pigment epithelial band yielded the most repeatable CCFD%. These findings have implications for the design of standardized processing algorithms for quantitative CC assessment.


Assuntos
Corioide/irrigação sanguínea , Artérias Ciliares/fisiologia , Adulto , Algoritmos , Velocidade do Fluxo Sanguíneo , Corioide/diagnóstico por imagem , Estudos Transversais , Feminino , Angiofluoresceinografia , Fundo de Olho , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos , Fluxo Sanguíneo Regional/fisiologia , Reprodutibilidade dos Testes , Tomografia de Coerência Óptica
12.
Graefes Arch Clin Exp Ophthalmol ; 258(6): 1173-1180, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32144487

RESUMO

PURPOSE: To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Patients with high myopia (≥ - 6D; axial length ≥ 26.5 mm), moderate myopia (≥ - 3D, < - 6D), and age-matched healthy subjects presenting to the Shanghai General Hospital and Doheny-UCLA Eye Centers were enrolled in this prospective, multicenter study. Any subjects with evidence of macular abnormalities suggestive of pathologic myopia were excluded. SS-OCTA at both sites was performed using a Zeiss PLEX Elite instrument with a 6 × 6 mm scan pattern centered on the fovea. Two repeated volume scans were acquired for image averaging. The instrument pre-defined en face slab of the superficial and deep retinal capillary microvasculature was used to isolate and display the superficial and deep retinal capillaries. A slab spanning from 21 to 31 µm deep to the RPE fit line was used to isolate and display the CC. The OCTA images were exported for averaging using Image J. Littmann's method and the Bennett formula were applied to adjust for the impact of magnification in the high and moderate myopia groups. The resultant images were then binarized. Though projection artifact removal software was used, regions below the large superficial retinal vessels were excluded for quantitative analyses of the deep retinal capillary plexus and the CC. Vessel density (VD) and vessel length density (VLD) of the superficial and deep retinal capillary plexus (SCP, DCP) and CC flow deficit (FD) were analyzed, quantified, and compared between different groups. RESULTS: Twenty-five eyes of 25 patients with high myopia, 25 eyes of 25 patients with moderate myopia, and 25 eyes of 25 normal age-matched controls were included in this study. The VD of the SCP was lower in the high myopia group compared with the emmetropic control groups (p < 0.05), but the VD of the DCP demonstrated no significant difference among the three groups (p > 0.05). The VLDs of the SCP were lower in the high and moderate myopia groups compared with the control group (p < 0.05), while the VLD of the DCP was lower in the high myopia group compared with the moderate myopia and emmetropic control group (p < 0.05). The CC FD% in the high myopia group was significantly greater than both the control and moderate myopia subjects (p < 0.05). Of note, the severity of the CC flow deficit was not correlated with choroidal thickness (p > 0.05). CONCLUSION: The retinal microvasculature may demonstrate alterations in highly myopia eyes. The CC in macular regions shows greater impairment in eyes with high myopia compared with eyes with lesser degrees of myopia, and these deficits are already present in the absence of features of pathologic or degenerative myopia. The threshold of CC FD leading to myopic maculopathy remains to be defined.


Assuntos
Corioide/patologia , Miopia/patologia , Vasos Retinianos/patologia , Adulto , Capilares/patologia , Corioide/irrigação sanguínea , Feminino , Angiofluoresceinografia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Microvasos , Pessoa de Meia-Idade , Miopia/classificação , Tamanho do Órgão , Estudos Prospectivos , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Adulto Jovem
13.
Circ Res ; 126(6): 767-783, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32078435

RESUMO

RATIONALE: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive. Dll4 signaling is important for various vascular contexts, but its role in the maintenance of vascular barrier in central nervous system remains unknown. OBJECTIVE: To find a TJ-independent regulatory mechanism selective for transcytosis and identify its dysregulation as a cause of pathological leakage. METHODS AND RESULTS: We studied transcytosis in the adult mouse retina with low vascular permeability and employed a hypertension-induced retinal edema model for its pathological implication. Both antibody-based and genetic inactivation of Dll4 or Notch1 induce hyperpermeability by increasing transcytosis without junctional destabilization in arterial endothelial cells, leading to nonhemorrhagic leakage predominantly in the superficial retinal layer. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blocking-driven vascular leakage. Ang II (angiotensin II)-induced hypertension represses arterial Sox17 and Dll4, followed by transcytosis-driven retinal edema, which is rescued by a gain of Notch activity. Transcriptomic profiling of retinal endothelial cells suggests that Dll4 blocking activates SREBP1 (sterol regulatory element-binding protein 1)-mediated lipogenic transcription and enriches gene sets favorable for caveolae formation. Profiling also predicts the activation of VEGF (vascular endothelial growth factor) signaling by Dll4 blockade. Inhibition of SREBP1 or VEGF-VEGFR2 (VEGF receptor 2) signaling attenuates both Dll4 blockade-driven and hypertension-induced retinal leakage. CONCLUSIONS: In the retina, Sox17-Dll4-SREBP1 signaling axis controls transcytosis independently of TJ in superficial arteries among heterogeneous regulations for the whole vessels. Uncontrolled transcytosis via dysregulated Dll4 underlies pathological leakage in hypertensive retina and could be a therapeutic target for treating hypertension-associated retinal edema.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Barreira Hematorretiniana/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Retinopatia Hipertensiva/metabolismo , Transcitose , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Artérias/metabolismo , Proteínas de Ligação ao Cálcio/genética , Cavéolas/metabolismo , Células Endoteliais/metabolismo , Proteínas HMGB/metabolismo , Homeostase , Camundongos , Camundongos Endogâmicos C57BL , Receptor Notch1/genética , Receptor Notch1/metabolismo , Fatores de Transcrição SOXF/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Junções Íntimas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
14.
J Ophthalmol ; 2016: 9810270, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27293879

RESUMO

Purpose. To evaluate the real-world efficacy and safety of the dexamethasone implant (DEX implant) in patients with diabetic macular edema (DME). Methods. Retrospective, multicenter, and noncomparative study of DME patients who were treated with at least one DEX implant. A total of 186 eyes from 165 patients were included. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and number of retreatments were collected. Data at baseline and monthly for 6 months were analyzed. Results. The average baseline BCVA and CRT were 0.60 LogMAR and 491.6 µm, respectively. The mean BCVA improved until 3 months and then decreased up to 6 months of follow-up (0.53, 0.49, and 0.55 LogMAR at 1, 3, and 6 months; p = 0.001, <0.001, and 0.044, resp.). The change of mean CRT was similar to BCVA (345.0, 357.7, and 412.5 µm at 1, 3, and 6 months, p < 0.001, <0.001, and <0.001, resp.). 91 eyes (48.9%) received additional treatment with anti-VEGF or DEX implant. The average treatment-free interval was 4.4 months. In group analyses, the DEX implant was more effective in pseudophakic eyes, DME with subretinal fluid (SRF), or diffuse type. Conclusions. Intravitreal dexamethasone implants are an effective treatment for patients with DME, most notably in pseudophakic eyes, DME with SRF, or diffuse type. A half of these patients require additional treatment within 6 months.

15.
Can J Ophthalmol ; 50(5): 367-72, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26455972

RESUMO

OBJECTIVE: To report the clinical outcomes of transscleral fixation using a single-piece foldable acrylic intraocular lens (IOL) with eyelets at the optic-haptic junction (enVista; Bausch & Lomb). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Sixty eyes of 60 patients who underwent transscleral fixation with an enVista IOL were reviewed. METHODS: Preoperative patient status, postoperative visual and refractive outcomes, and postoperative complications were analyzed. RESULTS: The study included 60 eyes of 60 patients (52 males, 8 females) with a mean age of 56.65 ± 15.57 years. At final follow-up visit, the mean follow-up was 11.40 ± 4.24 months. The mean uncorrected visual acuity (logMAR) improved from 1.95 ± 0.90 to 0.85 ± 0.77 (p < 0.001), and best corrected visual acuity (logMAR) improved from 1.11 ± 1.13 to 0.64 ± 0.70 (p = 0.006). The mean spherical equivalent improved significantly from 6.90 ± 6.10 to 0.21 ± 2.10 D postoperatively (p < 0.001). Complications included transient ocular hypertension (15%), transient hypotony (7%), and hyphema (5%), but no serious complications were observed. In all cases, the IOL remained stable and well centred. CONCLUSIONS: Transscleral fixation using a foldable acrylic IOL with eyelets at the optic-haptic junction can be a safe and effective alternative technique to manage cases with broken capsular bag or weak zonular support.


Assuntos
Implante de Lente Intraocular/métodos , Lentes Intraoculares , Esclera/cirurgia , Técnicas de Sutura , Resinas Acrílicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Facoemulsificação , Complicações Pós-Operatórias , Desenho de Prótese , Refração Ocular/fisiologia , Estudos Retrospectivos , Acuidade Visual/fisiologia
16.
Optom Vis Sci ; 92(4 Suppl 1): S55-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25738839

RESUMO

PURPOSE: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare ocular manifestation of syphilis, and its natural course is not well understood. We herein present two unusual cases of ASPPC in which there was almost total resolution of the fundus and optical coherence tomography (OCT) findings during the early presentation before treatment was initiated. CASE REPORTS: Patient 1: A 44-year-old man presented with a 4-day history of decreased visual acuity in his left eye. Dilated fundus examination revealed a yellowish subretinal placoid lesion in the posterior pole, and OCT images showed subretinal fluid and irregular or granular hyperreflectivity of the retinal pigment epithelium. Ten days later, the yellowish placoid lesion had dramatically improved and the OCT findings showed absence of the subretinal fluid and hyperreflective lesion without any treatment. Patient 2: A 35-year-old man presented with a 3-day history of decreased visual acuity in his right eye. Dilated fundus examination showed a yellow submacular placoid lesion, and OCT images showed a small amount of subretinal fluid with disruption of the inner segment/outer segment junction. Four days after presentation, the fundus and OCT findings had markedly resolved without definitive treatment. In both cases, serologic test results confirmed the diagnosis of syphilis, and the patients were referred to the Department of Infectious Disease for systemic antibiotic treatment. After treatment, the patients' visual acuities were improved, but the disruption of the inner segment/outer segment junction on OCT images remained. CONCLUSIONS: In patients with ASPPC, fundus and OCT findings can spontaneously recover during the early clinical course before treatment.


Assuntos
Coriorretinite/diagnóstico , Infecções Oculares Bacterianas/diagnóstico , Sífilis/diagnóstico , Adulto , Antibacterianos/uso terapêutico , Coriorretinite/tratamento farmacológico , Coriorretinite/microbiologia , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Angiofluoresceinografia , Fundo de Olho , Humanos , Infusões Intravenosas , Masculino , Penicilina G/uso terapêutico , Sífilis/tratamento farmacológico , Sífilis/microbiologia , Sorodiagnóstico da Sífilis , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia
17.
Int Ophthalmol ; 34(4): 979-81, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24493356

RESUMO

We report a rare case of peripheral ulcerative keratitis (PUK) associated with Behçet's disease. A 34-year-old female presented with right ocular pain persisting for 8 months. The patient had been treated for previously diagnosed Behçet's disease. The corrected visual acuity was 20/32 in the right eye. Ocular examination revealed mild conjunctival hyperemia and a deep ulcerative lesion with perilesional haziness in the peripheral cornea. Autoimmune screening and corneal culture were negative. One month following treatment with topical and systemic immunosuppressants, the symptom had resolved. Slit-lamp examination showed a healed corneal lesion, and visual acuity improved to 20/20. Despite its rare occurrence, PUK can develop in patients with Behçet's disease. Therefore, patients presenting PUK require examination for Behçet's disease using a systemic evaluation.


Assuntos
Síndrome de Behçet/complicações , Úlcera da Córnea/etiologia , Adulto , Feminino , Humanos , Acuidade Visual
18.
Curr Eye Res ; 39(6): 634-41, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24206188

RESUMO

PURPOSE: To investigate whether carnosine can increase retinal ganglion cell (RGC) survival in ischemic mouse retina. METHODS: Retinal ischemia was induced by constant elevation of intraocular pressure (100-110 mmHg) for 60 min in C57BL/6 J mice pretreated with carnosine (1000 mg/kg) or saline. Hypoxia inducing factor-1 alpha (HIF-1α), glial fibrillary acidic protein (GFAP), and dynamin-related protein-1 (Drp-1) expressions were assessed at 6, 12, and 24 h after retinal ischemia. Bax and Bcl-2 expressions were also analyzed at 12 h after retinal ischemia. RGC survival was assessed by retrograde FluoroGold labeling at 2 weeks after retinal ischemia. RESULTS: The expression of HIF-1α, GFAP, and Drp-1 was increased within 24 h after ischemic injury. Carnosine treatment effectively decreased the elevated expression of HIF-1α, GFAP, and Drp-1 in ischemic mouse retina. In ischemic retina treated with carnosine, Bax expression was decreased, whereas Bcl-2 expression was increased compared with ischemic retina treated with saline. Carnosine treatment also protected against RGC loss in ischemia mouse retina. CONCLUSIONS: Our findings showed that carnosine treatment significantly decreased RGC loss through decreased expression of HIF-1α, GFAP, Drp-1, and Bax, and increased expression of Bcl-2 in ischemic mouse retina. We suggest that carnosine can be an effective endogenous neuroprotective molecule in the prevention of RGC loss in ischemic retina.


Assuntos
Carnosina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Doenças Retinianas/tratamento farmacológico , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Western Blotting , Carnosina/administração & dosagem , Contagem de Células , Sobrevivência Celular/efeitos dos fármacos , Dinaminas/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Proteína Glial Fibrilar Ácida , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Doenças Retinianas/metabolismo , Células Ganglionares da Retina/metabolismo , Proteína X Associada a bcl-2/metabolismo
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