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1.
Transl Vis Sci Technol ; 13(10): 14, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39377753

RESUMO

Purpose: Expansion of the suprachoroidal space (SCS) by a hydrogel injection has been shown to reduce intraocular pressure (IOP) in rabbits as a potential treatment for ocular hypertension in glaucoma. Here, we evaluate the safety and efficacy of this approach in hypertensive and normotensive eyes in nonhuman primates. Methods: A microneedle was used to inject a hyaluronic acid-based hydrogel or saline solution (control) into the SCS of cynomolgus monkey eyes that were either normotensive (n = 7 experimental; n = 2 control eyes) or had induced ocular hypertension (n = 6 experimental; n = 3 control eyes). IOP and the degree of SCS expansion were monitored over time by tonometry and ultrasound biomicroscopy, respectively. Safety was evaluated through slit lamp, fundus, and histology examinations. Results: In hypertensive eyes, SCS injection with hydrogel initially reduced IOP by 47.5 ± 16.7%, and IOP returned to baseline in 38 days. In normotensive eyes, hydrogel injection initially reduced IOP by 38.8 ± 8.1% and IOP gradually returned to baseline also in 39 days. Sham injections resulted in mild IOP reduction in hypertensive eyes and normotensive eyes. The hydrogel injections were well tolerated by clinical assessments. Conclusions: IOP was reduced in nonhuman primates for over one month by sustained SCS expansion. This procedure was safe and simple to perform. These data confirm the translational potential of this treatment method. Further optimization of the hydrogel may provide longer durations of IOP reduction. Translational Relevance: A microneedle injection of hydrogel into the suprachoroidal space may provide a non-surgical, non-pharmacologic treatment for ocular hypertension in glaucoma patients.


Assuntos
Ácido Hialurônico , Hidrogéis , Pressão Intraocular , Macaca fascicularis , Agulhas , Hipertensão Ocular , Animais , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Hipertensão Ocular/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/farmacologia , Hidrogéis/administração & dosagem , Modelos Animais de Doenças , Corioide/diagnóstico por imagem , Tonometria Ocular , Masculino , Injeções Intraoculares , Feminino , Microscopia Acústica , Glaucoma/tratamento farmacológico
2.
Sci Rep ; 14(1): 23545, 2024 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384883

RESUMO

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10-4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 µm (AA, 73.8%) and 31.1 µm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 µm (AA, 74.2%) and 28.2 µm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration.


Assuntos
Corioide , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Corioide/patologia , Idoso , Masculino , Feminino , Estudos Longitudinais , Idoso de 80 Anos ou mais , Degeneração Macular/genética , Degeneração Macular/patologia , Células Endoteliais da Veia Umbilical Humana , Estudos de Coortes , Predisposição Genética para Doença , Genótipo
3.
PLoS One ; 19(10): e0311505, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39392817

RESUMO

PURPOSE: This study investigated the differential gene expression of BMPs in chick retinal pigment epithelium (RPE) during recovery from short term exposure to optical defocus and form-deprivation (FD) treatments. METHODS: 14-day old White-Leghorn chicks wore either monocular +10 or -10 D lenses, or diffusers for 2 or 48 h, after which eyes were allowed unobstructed vision for up to 96 h. Over this recovery period, refractive errors and choroidal thickness (ChT) were tracked using retinoscopy and high-frequency A-scan ultrasonography. Real-time PCR was used to examine the expression of BMP2, 4, and 7 genes in RPE samples collected 0, 15 min, 2, 24, 48, and 96 h after the termination of treatments. Expression levels in treated eyes and their contralateral control eyes were compared. RESULTS: After the termination of the lens and diffuser treatments, eyes gradually recovered from induced shifts in refractive error. With all three treatments, ChT changes reached statistical significance after 48 h of treatment, be it thinning with the -10 D lens and diffuser treatments (-0.06 ± 0.03mm, p < 0.05; -0.11 ± 0.04 mm, p < 0.05, resp.), or thickening with the +10 D lens (0.31 ± 0.04 mm, p < 0.001). BMP2 gene expression was rapidly upregulated in eyes wearing the +10 D lens, being statistical significance after 2 h, as well as 48 h of treatment. With the 2 h treatment, the latter gene expression pattern persisted for 15 min into the recovery period, before decreasing to the same level as that of contralateral control eyes, with a short-lived rebound, i.e., upregulation, 24 h into the recovery period. With the longer, 48 h treatment, BMP2 gene expression decreased more gradually, from 739 ± 121% at the end of the treatment period, to 72 ± 14% after 48 h of recovery. Two and 48 h of both -10 D and FD treatments resulted in BMP2 gene expression downregulation, with the time taken for gene expression levels to fully recover varying with the duration of initial treatments. In both cases, BMP2 gene expression downregulation persisted for 15 min into the recovery period, but reversed to upregulation by 2 h. Similar gene expression patterns were also observed for BMP4, although the changes were smaller. CONCLUSIONS: The observed changes in BMP gene expression in chick RPE imply dynamic, albeit complex regulation, with the duration of exposure and recovery being critical variables for all three types of visual manipulations. This study provides further evidence for a role of the RPE as an important signal relay linking the retina to the choroid and sclera in eye growth regulation.


Assuntos
Galinhas , Regulação da Expressão Gênica , Epitélio Pigmentado da Retina , Animais , Epitélio Pigmentado da Retina/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Erros de Refração/genética , Erros de Refração/metabolismo , Corioide/metabolismo , Corioide/diagnóstico por imagem
4.
Sci Rep ; 14(1): 23940, 2024 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-39397115

RESUMO

Central serous chorioretinopathy (CSCR) is a retinal disease characterised by the accumulation of subretinal fluid, which often resolves spontaneously in acute cases. However, approximately one-third of patients experience recurrences that may cause severe and irreversible vision. This study aimed to identify parameters derived from optical coherence tomography (OCT) that are associated with CSCR recurrence. Our dataset included 5211 OCT scans from 344 eyes of 255 patients diagnosed with CSCR. 178 eyes were identified as recurrent, 109 as non-recurrent, and 57 were excluded. We extracted parameters using artificial intelligence algorithms based on U-Nets, convolutional kernels, and morphological operators. We applied inferential statistics to evaluate differences between the recurrent and non-recurrent groups, and we used a logistic regression predictive model, reporting the coefficients as a measure of biomarker importance. We identified nine predictive biomarkers for CSCR recurrence: age, intraretinal fluid, subretinal fluid, pigment epithelial detachments, choroidal vascularity index, integrity of photoreceptors and retinal pigment epithelium layer, choriocapillaris and choroidal stroma thickness, and thinning of the outer nuclear layer, and of the inner nuclear layer combined with the outer plexiform layer. These results could enable future developments in the automatic detection of CSCR recurrence, paving the way for translational medical applications.


Assuntos
Biomarcadores , Coriorretinopatia Serosa Central , Recidiva , Tomografia de Coerência Óptica , Humanos , Coriorretinopatia Serosa Central/diagnóstico por imagem , Coriorretinopatia Serosa Central/patologia , Coriorretinopatia Serosa Central/metabolismo , Coriorretinopatia Serosa Central/diagnóstico , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Líquido Sub-Retiniano/metabolismo , Corioide/patologia , Corioide/diagnóstico por imagem , Corioide/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/diagnóstico por imagem
5.
Transl Vis Sci Technol ; 13(10): 26, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39412767

RESUMO

Purpose: Choroidal dysfunction is implicated in various ocular pathologies. The parasympathetic pterygopalatine ganglion (PPG) innervates orbital vessels supplying the choroid. While PPG stimulation has been shown to dilate cerebral blood flow, its effects on the choroid, particularly in human subjects, require further elucidation. This study aimed to investigate the short-term influence of PPG stimulation via electroacupuncture on choroidal structure. Methods: In this crossover study, 22 healthy adults received PPG electrical stimulation and sham stimulation for one session each on two separate days in a randomized order. Measurements including choroidal thickness (ChT), choroidal vascularity index (ChVI), central subfield thickness, axial length, anterior chamber depth, and lens thickness were recorded before and at intervals (0, 15, 30, 45, and 60 minutes) postintervention. Results: The ChT on the side receiving PPG stimulation demonstrated a sustained increase, peaking at 15 minutes poststimulation (17.2 µm, P < 0.001) and persisting for up to 60 minutes. Conversely, the ChVI exhibited a more immediate response, with a peak increase immediately poststimulation (3.8%, P = 0.003), followed by a gradual return to baseline. ChT and ChVI in the contralateral eye showed a nonsignificant trend to decrease. Additionally, a notable reduction in ipsilateral axial length was observed at specific time points poststimulation. Conclusions: PPG activation via electroacupuncture elicited a short-term increase in ChT and ChVI in the ipsilateral eye compared to sham stimulation, with ChT increases trailing those of ChVI but displaying greater persistence. Translational Relevance: Electrical stimulation of the PPG can produce a short-term increase in ipsilateral ChT and ChVI.


Assuntos
Corioide , Estudos Cross-Over , Eletroacupuntura , Gânglios Parassimpáticos , Humanos , Masculino , Feminino , Eletroacupuntura/métodos , Adulto , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Adulto Jovem , Gânglios Parassimpáticos/fisiologia , Voluntários Saudáveis , Tomografia de Coerência Óptica , Fossa Pterigopalatina
6.
BMC Ophthalmol ; 24(1): 449, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39407170

RESUMO

BACKGROUND: We aimed to compare choroidal thickness (ChT) and retinal nerve fiber layer (RNFL) thickness in the affected and contralateral eyes of patients with Posner-Schlossman Syndrome (PSS) during acute, remission, and intermittent phases. METHODS: This prospective observational study included 18 patients(36 eyes) diagnosed with PSS. These patients underwent a comprehensive ophthalmologic evaluation including slit lamp examination, visual acuity testing, intraocular pressure (IOP) measurement, and funduscopic examination, and assessment of RNFL thickness, macular thickness, and macular ChT. Patient data collected included gender, age, number of keratic precipitates (KPs), and number of episodes. Optical coherence tomography (OCT) was used to measure RNFL thickness, macular thickness, and macular ChT in both eyes during the acute, remission, and intermittent phases. The affected eye was compared with the unaffected eye at each phase. RESULTS: In affected eyes, macular ChT was lower in the acute phase compared to the remission phase at N1500, N1000, N500, and subfoveal locations (allp < 0.05).The central macular recess ChT was also significantly thinner in the acute phase compared to the intermittent and remission phases. Age significantly correlated with ChT in the central recess (p = .024). Macular thickness was thinner during the acute phase in the affected eye (p = .048). The RNFL in the affected eye was thinner in the intermittent phase than in the acute phase at the inferior-temporal (p = .011) and global sectors (p = .044). During the acute phase, RNFL in the affected eye was thinner at the superior-nasal (p = .049), inferior-temporal (p = .003), and global (p = .041) sectors compared to the unaffected eye. In the intermittent phase, the affected eye's RNFL was thinner at the superior-nasal, inferior-temporal, inferior-nasal, and global sectors compared to the unaffected eye (allp < 0.05), while no difference was observed in both eyes at the nasal, superior-temporal, and temporal sectors. The number of episodes and age were significantly associated with RNFL thickness (p < .05). CONCLUSION: This study demonstrated that in eyes affected by PSS, RNFL, macular ChT, and macular thickness thinned during the acute phase. The number of episodes and age are significant factors in the development of PSS.


Assuntos
Corioide , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Masculino , Feminino , Estudos Prospectivos , Corioide/patologia , Corioide/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Acuidade Visual/fisiologia , Fibras Nervosas/patologia , Pressão Intraocular/fisiologia , Adulto Jovem , Retina/patologia , Retina/diagnóstico por imagem
7.
Int J Mol Sci ; 25(19)2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39408582

RESUMO

In the aging population, choroidal vessels grow through the Bruch's membrane, resulting in a loss of central vision due to choroidal neovascularization (CNV). During active neovascularization, CNV is associated with inappropriate levels of apoptosis in multiple cell types, including choroidal endothelial cells (ChECs). Bim is a pro-apoptotic member of the Bcl-2 family. It is essential for cell apoptosis due to exposure to drugs such as dexamethasone or decreased pro-survival factors, including vascular endothelial growth factor (VEGF). To better elucidate the cell autonomous contribution of Bim expression in the integrity and neovascularization of the choroidal vasculature, we isolated ChECs from wild-type and Bim-deficient (Bim-/-) mice. ChECs lacking Bim expression demonstrated increased expression of VEGF, osteopontin, and the inflammatory cytokines Rantes/Ccl5 and IL6. Bim-/- ChECs were more proliferative and demonstrated an increased capacity to undergo capillary morphogenesis. Anti-VEGF had a diminished capacity to disrupt capillary morphogenesis in Bim-/- ChECs. In vivo, utilizing the mouse laser photocoagulation model, anti-VEGF treatment mitigated CNV in wild-type but not Bim-/- mice. We also tested other modalities that are thought to not require the intrinsic death pathway for their function and showed that propranolol, anti-CTGF, and the TSP1-mimetic peptide ABT898 mitigated CNV in mice lacking Bim expression to varying degrees. Thus, in ChECs, Bim expression could impact the effectiveness of treatment modalities that require the intrinsic death pathway to mitigate CNV.


Assuntos
Proteína 11 Semelhante a Bcl-2 , Corioide , Neovascularização de Coroide , Células Endoteliais , Animais , Proteína 11 Semelhante a Bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Células Endoteliais/metabolismo , Camundongos , Corioide/metabolismo , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Camundongos Knockout , Apoptose , Camundongos Endogâmicos C57BL , Proliferação de Células , Propranolol/farmacologia
8.
Transl Vis Sci Technol ; 13(10): 29, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39432402

RESUMO

Purpose: To investigate the long-term effects of repeated low-level red light (RLRL) therapy on the axial length (AL), spherical equivalent (SE), and choroidal parameters. Methods: Two hundred eight myopic eyes were recruited. The RLRL group included 100 eyes, whereas the control group included 108 eyes. Throughout the one-year follow-up period, changes in AL and SE were recorded for both groups. The RLRL group underwent additional choroidal imaging, and changes in choroidal thickness (CT), choroidal vascularity (CV), and choriocapillaris luminal area (CLA) were assessed before and after RLRL therapy. Results: During the follow-up period, the changing trends in AL and SE differed significantly between the RLRL and control groups. In the RLRL group, AL decreased at three and six months (both P < 0.05) and returned to pretreatment values at 12 months (P = 0.453). In contrast, AL increased significantly throughout the follow-up period (three, six, and 12 months) in the control group (all P < 0.001). The SE increased significantly during the entire follow-up period in the RLRL group (all P < 0.001), whereas it decreased significantly in the control group (all P < 0.05). Regarding choroidal parameters, significant improvements were observed in CT, CV and CLA throughout the follow-up period (all P < 0.05), and changes in most choroidal parameters were significantly correlated with changes in AL and SE during the follow-up period (all P < 0.05). Furthermore, AL, SE, and most choroidal parameters showed significant correlations between changes at three and 12 months (all P < 0.05). Conclusions: RLRL therapy significantly improved choroidal blood perfusion and circulation, which may explain the observed slowing or reversal of myopia progression in the RLRL group. Thus RLRL therapy may be a novel and effective method for controlling myopia. Furthermore, the short-term effect of photobiomodulation therapy (i.e., changes at three months) can be used to predict the long-term effects (i.e., changes at 12 months). Translational Relevance: In this study, RLRL therapy showed a significant control effect on the development of axial length and spherical equivalent. RLRL therapy also promoted the choroidal blood perfusion and circulation. RLRL therapy could be a novel and effective method for myopia control.


Assuntos
Comprimento Axial do Olho , Corioide , Terapia com Luz de Baixa Intensidade , Miopia , Tomografia de Coerência Óptica , Humanos , Corioide/diagnóstico por imagem , Corioide/irrigação sanguínea , Corioide/patologia , Corioide/efeitos da radiação , Feminino , Masculino , Miopia/terapia , Miopia/fisiopatologia , Miopia/patologia , Adulto , Comprimento Axial do Olho/diagnóstico por imagem , Terapia com Luz de Baixa Intensidade/métodos , Adulto Jovem , Seguimentos , Refração Ocular/fisiologia , Resultado do Tratamento
9.
J Neuroinflammation ; 21(1): 247, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354493

RESUMO

'Wet' age-related macular degeneration (AMD) is characterized by pathologic choroidal neovascularization (CNV) that destroys central vision. Abundant evidence points to inflammation and immune cell dysfunction in the progression of CNV in AMD. Mast cells are resident immune cells that control the inflammatory response. Mast cells accumulate and degranulate in the choroid of patients with AMD, suggesting they play a role in CNV. Activated mast cells secrete various biologically active mediators, including inflammatory cytokines and proteolytic enzymes such as tryptase. We investigated the role of mast cells in AMD using a model of CNV. Conditioned media from activated mast cells exerts proangiogenic effects on choroidal endothelial cells and choroidal explants. Laser-induced CNV in vivo was markedly attenuated in mice genetically depleted of mast cells (KitW-sh/W-sh) and in wild-type mice treated with mast cell stabilizer, ketotifen fumarate. Tryptase was found to elicit pronounced choroidal endothelial cell sprouting, migration and tubulogenesis; while tryptase inhibition diminished CNV. Transcriptomic analysis of laser-treated RPE/choroid complex revealed collagen catabolism and extracellular matrix (ECM) reorganization as significant events correlated in clusters of mast cell activation. Consistent with these analyses, compared to wildtype mice choroids of laser-treated mast cell-deficient mice displayed less ECM remodelling evaluated using collagen hybridizing peptide tissue binding. Findings herein provide strong support for mast cells as key players in the progression of pathologic choroidal angiogenesis and as potential therapeutic targets to prevent pathological neovascularization in 'wet' AMD.


Assuntos
Neovascularização de Coroide , Modelos Animais de Doenças , Degeneração Macular , Mastócitos , Camundongos Endogâmicos C57BL , Animais , Mastócitos/metabolismo , Mastócitos/patologia , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Camundongos , Degeneração Macular/patologia , Degeneração Macular/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Corioide/patologia , Corioide/metabolismo , Triptases/metabolismo , Camundongos Transgênicos , Cetotifeno/farmacologia
10.
BMC Med Imaging ; 24(1): 281, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39425019

RESUMO

BACKGROUND: This study aimed to evaluate the effectiveness of DeepLabv3+with Squeeze-and-Excitation (DeepLabv3+SE) architectures for segmenting the choroid in optical coherence tomography (OCT) images of patients with diabetic retinopathy. METHODS: A total of 300 B-scans were selected from 21 patients with mild to moderate diabetic retinopathy. Six DeepLabv3+SE variants, each utilizing a different pre-trained convolutional neural network (CNN) for feature extraction, were compared. Segmentation performance was assessed using the Jaccard index, Dice score (DSC), precision, recall, and F1-score. Binarization and Bland-Altman analysis were employed to evaluate the agreement between automated and manual measurements of choroidal area, luminal area (LA), and Choroidal Vascularity Index (CVI). RESULTS: DeepLabv3+SE with EfficientNetB0 achieved the highest segmentation performance, with a Jaccard index of 95.47, DSC of 98.29, precision of 98.80, recall of 97.41, and F1-score of 98.10 on the validation set. Bland-Altman analysis indicated good agreement between automated and manual measurements of LA and CVI. CONCLUSIONS: DeepLabv3+SE with EfficientNetB0 demonstrates promise for accurate choroid segmentation in OCT images. This approach offers a potential solution for automated CVI calculation in diabetic retinopathy patients. Further evaluation of the proposed method on a larger and more diverse dataset can strengthen its generalizability and clinical applicability.


Assuntos
Corioide , Retinopatia Diabética , Redes Neurais de Computação , Tomografia de Coerência Óptica , Humanos , Retinopatia Diabética/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Corioide/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Aprendizado Profundo
11.
J Transl Med ; 22(1): 898, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367441

RESUMO

Retinal neurovascular unit (NVU) is a multi-cellular structure that consists of the functional coupling between neural tissue and vascular system. Disrupted NVU will result in the occurrence of retinal and choroidal vascular diseases, which are characterized by the development of neovascularization, increased vascular permeability, and inflammation. This pathological entity mainly includes neovascular age-related macular degeneration (neovascular-AMD), diabetic retinopathy (DR) retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Emerging evidences suggest that the angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) signaling pathway is essential for the development of retinal and choroidal vascular. Tie receptors and their downstream pathways play a key role in modulating the vascular development, vascular stability, remodeling and angiogenesis. Angiopoietin 1 (Ang1) is a natural agonist of Tie2 receptor, which can promote vascular stability. On the other hand, angiopoietin 2 (Ang2) is an antagonist of Tie2 receptor that causes vascular instability. Currently, agents targeting the Ang/Tie signaling pathway have been used to inhibit neovascularization and vascular leakage in neovascular-AMD and DR animal models. Particularly, the AKB-9778 and Faricimab have shown promising efficacy in improving visual acuity in patients with neovascular-AMD and DR. These experimental and clinical evidences suggest that activation of Ang/Tie signaling pathway can inhibit the vascular permeability, neovascularization, thereby maintaining the normal function and structure of NVU. This review seeks to introduce the versatile functions and elucidate the modulatory mechanisms of Ang/Tie signaling pathway. Recent pharmacologic therapies targeting this pathway are also elaborated and summarized. Further translation of these findings may afford a new therapeutic strategy from bench to bedside.


Assuntos
Transdução de Sinais , Humanos , Animais , Doenças Retinianas/metabolismo , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/patologia , Doenças Vasculares/metabolismo , Doenças Vasculares/tratamento farmacológico , Receptores de TIE/metabolismo , Corioide/patologia , Corioide/metabolismo
12.
Int Ophthalmol ; 44(1): 404, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373776

RESUMO

PURPOSE: To evaluate the peripapillary/parapapillary choroidal vascular parameters in the keratoconus (KC) and to determine the relationship between topography parameters and the peripapillary/parapapillary choroidal vascular parameters. METHOD: Ninety eyes of ninety patients with different stages of KC and 29 eyes of twenty-nine patients without KC were enrolled in the study. Patients with KC were divided into three groups according to the Amsler-Krumeich classification scale. The choroidal vasculature was assessed by choroidal vascular parameters [such as parapapillary choroidal microvascular density (pCMVd) and peripapillary choroidal vascularity index (pCVI)]. These parameters were also evaluated for correlation with other parameters. RESULT: The retinal nerve fibre layer thickness (RNFLT) of the superior-temporal area and the pCVI were decreased in group 3 compared to the control group (superiror-temporal RNFLT: 122.27 ± 21.43 vs 139.90 ± 21.7, p = 0.01 and pCVI: 67.04 ± 4.14 vs 69.99 ± 4.38, p = 0.04). The superior-temporal RNFLT was decreased in group 3 compared to group 2 (122.27 ± 21.43 vs 141.83 ± 25.58, p = 0.006). There was a negative correlation between pCVI and average simulated keratometry (mean sim K), but this association was weak (r = - 0.29 p = 0.001). CONCLUSION: This study demonstrated that there may be changes in pCVI in patients with grade 3 KC and that there may be an association between pCVI and mean sim K. As KC grade increases, pCVI may decrease. Furthermore, pCVI may have a negative correlation with mean sim K.


Assuntos
Corioide , Ceratocone , Disco Óptico , Tomografia de Coerência Óptica , Humanos , Ceratocone/diagnóstico , Ceratocone/fisiopatologia , Masculino , Feminino , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/patologia , Adulto , Tomografia de Coerência Óptica/métodos , Adulto Jovem , Disco Óptico/irrigação sanguínea , Disco Óptico/patologia , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Topografia da Córnea/métodos , Adolescente , Acuidade Visual
13.
BMJ Open Ophthalmol ; 9(1)2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39401953

RESUMO

OBJECTIVE: To investigate the change in choroidal components of patients with Graves' ophthalmopathy (GO) with different degrees of disease activity and severity by using the image binarisation method of optical coherence tomography (OCT). METHODS: This cross-sectional study included 151 eyes of 90 patients with GO. Patients were grouped according to the clinical activity score (CAS) and disease severity. Total choroidal area (TCA), luminal area, stromal area (SA) and choroidal vascularity index (CVI) were acquired by image binarisation of the OCT. Ocular parameters between groups were compared using generalised estimating equations, accounting for intereye correlation and adjusting for relevant factors. RESULTS: As for the included eyes, 104 eyes were inactive GO and 47 eyes were active GO. Local choroidal thicknesses were thicker in active GO than in inactive GO. TCA and SA were significantly larger in active GO than in inactive GO group (3.44±0.91 mm2 vs 3.14±0.88 mm2, p=0.046; 1.16 (1.03-1.50) mm2 vs 1.10 (0.96-1.27) mm2, p=0.002, respectively). CAS was positively correlated with TCA (r=0.171, p=0.036) and SA (r=0.172, p=0.035), and negatively associated with CVI (r=-0.174, p=0.032). In multiple regression models, age, diopter and intraocular pressure (IOP) exhibited significant correlations with the SA (ß=-0.006, p=0.010; ß=0.076, p<0.001; ß=0.015, p=0.010, respectively). CONCLUSIONS: Thickened choroid was observed in active GO compared with inactive GO. The proportional increase of SA was augmented as the disease activity progressed. Age, diopter and IOP were independent factors that affected choroidal area and components in patients with GO. Multicentre prospective cohort studies with a large sample size are still needed.


Assuntos
Corioide , Oftalmopatia de Graves , Tomografia de Coerência Óptica , Humanos , Estudos Transversais , Oftalmopatia de Graves/diagnóstico por imagem , Oftalmopatia de Graves/patologia , Corioide/diagnóstico por imagem , Corioide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Pressão Intraocular/fisiologia , Estudos Retrospectivos , Idoso , Índice de Gravidade de Doença
14.
BMC Ophthalmol ; 24(1): 441, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379869

RESUMO

BACKGROUND: This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. METHODS: Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. RESULTS: A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55 µm to 278.31 ± 157.34 µm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037). CONCLUSIONS: Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept.


Assuntos
Angiofluoresceinografia , Injeções Intravítreas , Pólipos , Proteínas Recombinantes de Fusão , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Acuidade Visual/fisiologia , Pólipos/tratamento farmacológico , Pólipos/diagnóstico , Pólipos/fisiopatologia , Idoso , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Corioide/irrigação sanguínea , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Doenças da Coroide/tratamento farmacológico , Doenças da Coroide/diagnóstico , Doenças da Coroide/fisiopatologia , Seguimentos , Resultado do Tratamento , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/fisiopatologia , Neovascularização de Coroide/diagnóstico , Fundo de Olho , Vasculopatia Polipoidal da Coroide
15.
Rom J Ophthalmol ; 68(3): 321-324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39464773

RESUMO

Introduction: Neovascularization of the lens is a rare entity linked to lens-induced inflammation due to many causes like trauma. We describe a case managed using suprachoroidal triamcinolone, an anti-VEGF injection, in conjunction with cataract surgery and IOL implantation. Patient and clinical findings: A male patient, 27, presented with a severe reduction in vision in his right eye (RE) accompanied by redness for one month. He also had a distant history of blunt trauma to the RE approximately eight years before. His vision in the RE was reduced to hand motion and 20/20 in the left eye. Examining the anterior segment in RE revealed lenticular neovascularization, irregular anterior capsular thickening, iris sphincter tear at the 12 o'clock position, and fine KPs, with iris pigment clumps on the anterior capsule. Diagnosis treatment and results: To reduce vascularization and inflammation, the patient was treated with intravitreal Anti-VEGF and suprachoroidal triamcinolone by an innovative technique, along with cataract surgery, following which visual acuity improved to 20/20. Conclusions and significance: In this exceptional case report, suprachoroidal TA has been used for the first time to treat ocular inflammation and vascularization in traumatic cataract with capsular neovascularization and lens-induced uveitis.


Assuntos
Corioide , Glucocorticoides , Acuidade Visual , Humanos , Masculino , Glucocorticoides/uso terapêutico , Adulto , Corioide/irrigação sanguínea , Cápsula do Cristalino , Neovascularização Patológica/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/uso terapêutico , Implante de Lente Intraocular/métodos , Injeções Intravítreas , Traumatismos Oculares/diagnóstico , Traumatismos Oculares/complicações
16.
Indian J Ophthalmol ; 72(Suppl 5): S887-S892, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39449532

RESUMO

PURPOSE: To compare choroidal structural features in eyes with central macular atrophy related to Stargardt disease (STGD) and non-exudative age-related macular degeneration (AMD). METHODS: Twenty-five eyes of 25 Stargardt cases and 25 eyes of 25 non-exudative AMD cases were included in this retrospective study. Region Finder software was used to measure atrophic areas on blue-light fundus autofluorescence images centered on the macula. The total choroidal area (TCA), luminal area (LA), and stromal area (SA) were calculated using the ImageJ program and Niblack autolocal thresholding method. The choroidal vascularity index (CVI) was assessed. RESULTS: The mean age was 59.4 ± 10.9 years in the STGD group and 68.1 ± 7.6 years in the non-exudative AMD group (P = 0.002). The mean macular atrophic area was 16.06 ± 10.61 mm2 in STGD and 11.73 ± 7.65 mm2 in non-exudative AMD (P = 0.171). The STGD group had significantly higher mean subfoveal choroidal thickness (184.0 ± 62.6 vs. 131.8 ± 62.4 µm), TCA (0.553 ± 0.201 vs. 0.406 ± 0.189 mm2), LA (0.344 ± 0.150 vs. 0.253 ± 0.124 mm2), and SA values (0.208 ± 0.062 vs. 0.153 ± 0.069 mm2) compared to the non-exudative AMD group (P = 0.004, P = 0.011, P = 0.023, and P = 0.004, respectively). However, CVI values did not differ significantly between the two groups (60.58 ± 7.4 vs. 61.93 ± 5.8%, P = 0.432). According to the results of the ANCOVA test, differences in mean SFCT, TCA, and SA persisted when the data were readjusted for age (P = 0.018, P = 0.035, and P = 0.017, respectively). CONCLUSION: In non-exudative AMD with geographic atrophy, the reductions in the choroidal compartments are more pronounced than those in STGD. However, similar CVI values may suggest that controversy still exists regarding the role of choroidal compartmental changes in the development of atrophy.


Assuntos
Corioide , Angiofluoresceinografia , Fundo de Olho , Doença de Stargardt , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Doença de Stargardt/diagnóstico , Masculino , Estudos Retrospectivos , Feminino , Tomografia de Coerência Óptica/métodos , Pessoa de Meia-Idade , Corioide/patologia , Corioide/diagnóstico por imagem , Angiofluoresceinografia/métodos , Idoso , Degeneração Macular/diagnóstico , Degeneração Macular/congênito , Macula Lutea/patologia , Seguimentos
17.
Indian J Ophthalmol ; 72(Suppl 5): S893-S901, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39449533

RESUMO

PURPOSE: To evaluate the effects of normal vaginal delivery (NVD) and cesarean section (CS) on the retina, optic disc, and choroid in healthy pregnant women by using optical coherence tomography (OCT). METHODS: This prospectively designed study included 60 healthy pregnant women, of whom 30 underwent NVD and 30 underwent CS. Ophthalmological examinations and OCT scans were performed on all pregnant women during the third trimester and the first postpartum week. The measurements were compared between the two visits within each group. Central retinal thickness, ganglion cell layer and inner plexiform layer (GCL + IPL) thickness, peripapillary retinal nerve fiber layer thickness, and optic disc morphology were determined using OCT scans. Central, nasal, and temporal choroidal thicknesses were manually measured using HD-line OCT. Choroidal vascular parameters were calculated from HD-line OCT scans by using a special image processing module. The ratio of the luminal choroidal area to the total choroidal area was determined as the choroidal vascular index (CVI). RESULTS: In the NVD group, the thinning in the mean and inferior pRNLF, the decrease in the rim area, and the increase in the mean cup/disc and cup volume at the first postpartum week were found to be statistically significant (P < 0.05). In the same group, the CVI was calculated as 0.69 ± 0.02 in the third trimester and 0.66 ± 0.03 in the first postpartum week (P = 0.001). In the CS group, except for the increase in the GCL + IPL thickness, no significant difference was detected in the measurements of the retina, optic disc, and choroid (P < 0.001 and P > 0.05). CONCLUSION: This is the first study to evaluate the effect of the delivery method on the retina, choroid, and optic disc. In NVD, changes in the choroidal vascular structure and optic disc morphology can be observed in the early postpartum period, which may be attributed to hormonal effects.


Assuntos
Cesárea , Corioide , Parto Obstétrico , Disco Óptico , Tomografia de Coerência Óptica , Humanos , Feminino , Tomografia de Coerência Óptica/métodos , Gravidez , Estudos Prospectivos , Adulto , Disco Óptico/diagnóstico por imagem , Corioide/diagnóstico por imagem , Parto Obstétrico/métodos , Segmento Posterior do Olho/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Fibras Nervosas/patologia , Seguimentos , Adulto Jovem , Retina/diagnóstico por imagem , Retina/patologia
18.
Medicina (Kaunas) ; 60(10)2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39459461

RESUMO

Background and Objectives: The aim of the present study is to analyze choroidal and choriocapillaris structural and functional changes in eyes affected by Central serous chorioretinopathy after Photodynamic Therapy (PDT) and Subthreshold Micropulse laser (SML) treatment. Materials and Methods: Forty-two eyes of forty-two patients were analyzed in this observational study. Twenty-four patients underwent SML treatment, whereas eighteen patients were treated with PDT. Examinations were performed at baseline and after 3 months of treatment. Main outcome measures were: Best corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), pigment epithelial detachment (PED) presence and maximum height (PEDMH), and choroidal vascularity index (CVI) measured by means of Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) Optical coherence tomography (OCT) and choriocapillaris flow voids (CCFV) measured on Optical Coherence Tomography Angiography (OCT-A) platform PLEX Elite 9000 device (Carl Zeiss Meditec Inc., Dublin, CA, USA). Results: Changes in BCVA were registered in both groups over time (p < 0.001). Structural changes in terms of reduced CMT and PED presence were noted in the two groups at follow-up (p < 0.001 and p = 0.001, respectively). Structural and functional choroidal changes were found in the two groups with reduced CCT and CVI over time (p = 0.004 and p = 0.007, respectively), with significant differences between the two groups for CVI parameter (p = 0.001). CCFV increased over time in the PDT group and decreased in the SML group. Conclusions: PDT and SML are effective approaches in CSC eyes and are able to improve structural and functional parameters over time. Choroidal and choriocapillaris parameters are promising biomarkers able to monitor disease course, showing greater impact of PDT on choroid-choriocapillaris complex over time.


Assuntos
Coriorretinopatia Serosa Central , Corioide , Fotoquimioterapia , Tomografia de Coerência Óptica , Humanos , Coriorretinopatia Serosa Central/cirurgia , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/fisiopatologia , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Masculino , Feminino , Fotoquimioterapia/métodos , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Adulto , Acuidade Visual , Resultado do Tratamento , Terapia a Laser/métodos
19.
BMC Res Notes ; 17(1): 317, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39444009

RESUMO

OBJECTIVE: To obtain physicians' "real-world" perspectives on early experiences with triamcinolone acetonide suprachoroidal injection (SCS-TA) for treatment of patients with uveitic macular edema (UME). RESULTS: Twelve retina/uveitis specialists in the United States were surveyed about SCS-TA injection procedure and patient outcomes. Survey participants administered ≥ 291 SCS-TA injections to 243 patients with UME with various disease characteristics (etiologies, chronicity, and anatomical subtypes). Commonly reported reasons for SCS-TA adoption included potential for lowering the risk of steroid-associated intraocular pressure elevations versus intravitreal injections or implants (100%), potential for longer duration of action versus intravitreal steroid injections or implants (92%), and desire to use a new delivery modality (83%). Nearly all participants (92%) found injection procedure relatively easy post-training, with most (75%) procedurally comfortable after completing 2-5 injections. 58% of participants indicated that their patients gained 2-3 lines of vision by first follow-up visit, and 92% reported having patients who experienced 100-150 µm or greater reduction in central subfield thickness. Overall, 92% of participants were satisfied with SCS-TA treatment outcomes. Findings from this survey of early adopters of SCS-TA indicate that the suprachoroidal injection technique was easy to learn and resulted in favorable patient outcomes consistent with clinical trial data.


Assuntos
Edema Macular , Triancinolona Acetonida , Uveíte , Humanos , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/uso terapêutico , Edema Macular/tratamento farmacológico , Masculino , Feminino , Uveíte/tratamento farmacológico , Uveíte/complicações , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto , Resultado do Tratamento , Corioide/efeitos dos fármacos , Corioide/diagnóstico por imagem , Injeções Intraoculares , Médicos , Idoso , Estados Unidos
20.
Retina ; 44(11): 1983-1991, 2024 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-39436303

RESUMO

PURPOSE: To distinguish between central serous chorioretinopathy (CSC) with and without thick choroid and to elucidate their characteristics of choroidal vasculature. METHODS: This prospective observational study enrolled 76 eyes with treatment-naive CSC and 76 normal eyes. Mean + 2 times SD of subfoveal choroidal thickness of healthy individuals was set as the upper limit of normal choroidal thickness to divide patients with CSC into two groups: the thick-choroid and non-thick-choroid groups. Their choroid blood flow was compared using widefield swept-source optical coherence tomography angiography. RESULTS: According to the discrimination value of subfoveal choroidal thickness as 326.8 µm, 76 eyes with CSC were divided into the thick-choroid (55, 72.4%) and non-thick-choroid (21, 27.6%) groups. Higher proportions of vortex vein anastomosis were found in the thick-choroid group (81.8% vs. 33.3%, P < 0.001). Choroid thickness, three-dimensional choroidal vascularity index, and mean choroidal stroma volume per 1 mm2 were higher in the thick-choroid group. In multivariate analysis, younger age, higher percentages of vortex vein anastomosis, and double layer sign were the independent predictors of choroid thickening in CSC. CONCLUSION: There are discrepancies in the degree of choroidal congestion and distribution of vortex veins in the CSC with different choroidal thicknesses.


Assuntos
Coriorretinopatia Serosa Central , Corioide , Angiofluoresceinografia , Tomografia de Coerência Óptica , Humanos , Coriorretinopatia Serosa Central/diagnóstico , Tomografia de Coerência Óptica/métodos , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Estudos Prospectivos , Masculino , Feminino , Angiofluoresceinografia/métodos , Pessoa de Meia-Idade , Adulto , Fundo de Olho , Acuidade Visual , Vasos Retinianos/patologia , Vasos Retinianos/diagnóstico por imagem
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