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International Journal of Molecular... May 2024To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography...
To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography (AS-OCT). Forty-two candidate patients for MP-TLT were consecutively enrolled and underwent AS-OCT at baseline and after six months. MP-TLT success was defined as an intraocular pressure (IOP) reduction by one-third. The main outcome measures were the mean superior (S-), inferior (I-), and total (T-) intra-scleral hypo-reflective space area (MISHA: mm) and scleral reflectivity (S-SR, I-SR, T-SR; arbitrary scale) as in vivo biomarkers of uveoscleral aqueous humor (AH) outflow. The IOP was the secondary outcome. The relations between the baseline-to-six months differences (D) of DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, DT-SR, and DIOP, were investigated. At 6 months, the median IOP reduction was 21% in the failures and 38% in the successes. The baseline S-MISHA, I-MISHA, and T-MISHA did not differ between the groups, while S-SR and T-SR were higher in the successes ( < 0.05). At six months, successful and failed MP-TLTs showed a 50% increase in S-MISHA ( < 0.001; = 0.037), whereas I-SR and T-SR reduced only in the successes ( = 0.002; = 0.001). When comparing DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, and DT-SR, there were no significant differences between the groups. In the successful procedures, DIOP was positively correlated with DT-MISHA and DI-MISHA (ρ = 0.438 and ρ = 0.490; < 0.05). MP-TLT produced potentially advantageous modifications of the sclera in refractory glaucoma. Given the partial correlation between these modifications and post-treatment IOP reduction, our study confirmed that the activation of the uveoscleral AH outflow route could significantly contribute to the IOP lowering after MP-TLT.
Topics: Humans; Tomography, Optical Coherence; Sclera; Male; Female; Glaucoma; Middle Aged; Intraocular Pressure; Laser Therapy; Aged; Aqueous Humor; Uvea; Adult; Treatment Outcome
PubMed: 38892100
DOI: 10.3390/ijms25115913 -
The American Journal of Pathology Jun 2024Retinoblastoma (RB) is an intraocular malignancy initiated by loss of RB1 function and/or dysregulation of MYCN oncogene. RB is primarily treated with chemotherapy;...
Retinoblastoma (RB) is an intraocular malignancy initiated by loss of RB1 function and/or dysregulation of MYCN oncogene. RB is primarily treated with chemotherapy; however, systemic toxicity and long-term adverse effects remain a significant challenge necessitating the identification of specific molecular targets. Aurora kinase A (AURKA), a critical cell cycle regulator, contributes to cancer pathogenesis, especially in RB1-deficient and MYCN-dysregulated tumors. Our immunohistochemistry study in patient specimens (n = 67) discovered that AURKA is overexpressed in RB, and elevated expression correlates with one or more histopathologic high-risk factors, such as tumor involvement of the optic nerve, choroid, sclera, and/or anterior segment. More specifically, AURKA is ubiquitously expressed in most advanced-stage RB tumors that show a suboptimal response to chemotherapy. shRNA-mediated depletion/pharmacologic inhibition studies in cell lines, patient-derived cells, in vivo xenografts, and enucleated patient specimens confirm that RB cells are highly sensitive to a lack of functional AURKA. In addition, we deciphered that AURKA and MYCN associate with each other to regulate their levels in RB cells. Overall, our results demonstrate a previously unknown up-regulation of AURKA in RB, facilitated by its crosstalk with MYCN, and elevated levels of this kinase may indicate unfavorable prognosis in tumors refractory to chemotherapy. This study provides a rationale and confirms that therapeutic targeting of elevated AURKA in RB could be a potential treatment approach.
PubMed: 38879085
DOI: 10.1016/j.ajpath.2024.05.006 -
Science China. Life Sciences Jun 2024High myopia (HM) is the primary cause of blindness, with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a...
High myopia (HM) is the primary cause of blindness, with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues. In a previously reported myopic linkage region, MYP5 (17q21-22), a potential candidate gene, LRRC46 (c.C235T, p.Q79X), was identified in a large Han Chinese pedigree. LRRC46 is expressed in various eye tissues in humans and mice, including the retina, cornea, and sclera. In subsequent cell experiments, the mutation (c.C235T) decreased the expression of LRRC46 protein in human corneal epithelial cells (HCE-T). Further investigation revealed that Lrrc46 mice (KO) exhibited a classical myopia phenotype. The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age, the activity of limbal stem cells decreased, and microstructural changes were observed in the fibroblasts of the sclera and cornea. We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type (WT) mice, which indicated a significant downregulation of the collagen synthesis-related pathway (extracellular matrix, ECM) in KO mice. Subsequent in vitro studies further indicated that LRRC46, a member of the important LRR protein family, primarily affected the formation of collagens. This study suggested that LRRC46 is a novel candidate gene for HM, influencing collagen protein VIII (Col8a1) formation in the eye and gradually altering the biomechanical structure of the cornea and sclera, thereby promoting the occurrence and development of HM.
PubMed: 38874710
DOI: 10.1007/s11427-024-2583-6 -
Scientific Reports Jun 2024This study aims to correlate adaptive optics-transscleral flood illumination (AO-TFI) images of the retinal pigment epithelium (RPE) in central serous chorioretinopathy...
This study aims to correlate adaptive optics-transscleral flood illumination (AO-TFI) images of the retinal pigment epithelium (RPE) in central serous chorioretinopathy (CSCR) with standard clinical images and compare cell morphological features with those of healthy eyes. After stitching 125 AO-TFI images acquired in CSCR eyes (including 6 active CSCR, 15 resolved CSCR, and 3 from healthy contralateral), 24 montages were correlated with blue-autofluorescence, infrared and optical coherence tomography images. All 68 AO-TFI images acquired in pathological areas exhibited significant RPE contrast changes. Among the 52 healthy areas in clinical images, AO-TFI revealed a normal RPE mosaic in 62% of the images and an altered RPE pattern in 38% of the images. Morphological features of the RPE cells were quantified in 54 AO-TFI images depicting clinically normal areas (from 12 CSCR eyes). Comparison with data from 149 AO-TFI images acquired in 33 healthy eyes revealed significantly increased morphological heterogeneity. In CSCR, AO-TFI not only enabled high-resolution imaging of outer retinal alterations, but also revealed RPE abnormalities undetectable by all other imaging modalities. Further studies are required to estimate the prognosis value of these abnormalities. Imaging of the RPE using AO-TFI holds great promise for improving our understanding of the CSCR pathogenesis.
Topics: Humans; Retinal Pigment Epithelium; Central Serous Chorioretinopathy; Male; Female; Middle Aged; Tomography, Optical Coherence; Adult; Fluorescein Angiography; Optical Imaging; Sclera
PubMed: 38871803
DOI: 10.1038/s41598-024-64524-4 -
Clinical features of primary and compound forms of wide macular posterior staphyloma in high myopia.BMC Ophthalmology Jun 2024To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity.
BACKGROUND
To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity.
METHODS
In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS.
RESULTS
A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P < 0.001) than those with primary WMPS. Compared to primary WMPS, compound WMPS had a higher grade of myopic macular degeneration (P < 0.001) and a higher frequency of lamellar or full-thickness macular hole associated with myopic traction (21.5% vs. 10.4%; P = 0.028) and active or scarred myopic choroidal neovascularization (33.8% vs. 20.1%; P = 0.030). On swept-source optical coherence tomography, eyes with compound WMPS had significantly thinner choroid and sclera.
CONCLUSIONS
The compound form of WMPS had more severe myopic macular changes and worse visual prognosis compared to the primary form of WMPS, and these were associated with more structural deformation in the posterior eyeball. Compound WMPS should be considered as an advanced form of staphyloma.
Topics: Humans; Female; Male; Cross-Sectional Studies; Myopia, Degenerative; Middle Aged; Visual Acuity; Tomography, Optical Coherence; Aged; Sclera; Retrospective Studies; Adult; Choroid; Scleral Diseases; Macula Lutea; Dilatation, Pathologic
PubMed: 38862935
DOI: 10.1186/s12886-024-03519-1 -
Current Eye Research Jun 2024This study describes a prototype developed for aphakia without capsular support (AWCS) and its proof of concept.
PURPOSE
This study describes a prototype developed for aphakia without capsular support (AWCS) and its proof of concept.
METHODS
This descriptive study used a 3D software to create and analyze virtual prototypes before manufacturing. A nylon-6/nylon-6.6 copolymer filament and a 3D printer were used for prototyping. A device implantation technique was developed using a 23-gauge hypodermic needle. Two opposing markings, 2 mm posterior to the limbus, were made to determine the location of the scleral punctures and the final position of the device. After adequate centralization and positioning of the device, its haptics were cut and cauterized to generate thermal modeling of the extremity and allow the thickening of the tips (flange), serving as an anchoring mechanism to the sclera. The efficacy and adequacy of the technique and device were then evaluated.
RESULTS
Vitreous tissue extrusion was not observed during the sclerotomy. The device was well fixed to the sclera; however, adequate IOL stability and centralization still needed to be achieved. The surgeon evaluated the adequacy of all the other devices' characteristics.
CONCLUSIONS
The development of a technology prototype for correcting AWCS was possible. Although the proposed prototype met most of the established concept guidelines, the stability of the IOL position remains challenging.
PubMed: 38856046
DOI: 10.1080/02713683.2024.2362839 -
Biomedical Optics Express May 2024The sclera plays an important role in the structural integrity of the eye. However, as myopia progresses, the elongation of the eyeball exerts stretching forces on the...
The sclera plays an important role in the structural integrity of the eye. However, as myopia progresses, the elongation of the eyeball exerts stretching forces on the posterior sclera, which typically happens in conjunction with scleral remodeling that causes rigidity loss. These biomechanical alterations can cause localized eyeball deformation and vision impairment. Therefore, monitoring scleral rigidity is clinically important for the management and risk assessment of myopia. In this study, we propose fundus pulsation optical coherence elastography (FP-OCE) to characterize posterior scleral rigidity in living humans. This methodology is based on a choroidal pulsation model, where the scleral rigidity is inversely associated with the choroidal max strain obtained through phase-sensitive optical coherence tomography (PhS-OCT) measurement of choroidal deformation and thickness. Using FP-OCE, we conducted a pilot clinical study to explore the relationship between choroidal strain and myopia severity. The results revealed a significant increase in choroidal max strain in pathologic myopia, indicating a critical threshold beyond which scleral rigidity decreases significantly. Our findings offer a potential new method for monitoring myopia progression and evaluating therapies that alter scleral mechanical properties.
PubMed: 38855699
DOI: 10.1364/BOE.523835 -
Clinical Case Reports Jun 2024The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the...
The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the jaw and atypical femoral fractures have gained significant recognition, the ocular adverse effects, particularly scleritis, are not yet fully comprehended. Here, we present the case of a 75-year-old female patient with osteoporosis who developed bilateral redness and intense eye pain 48 h after receiving a 5 mg intravenous dose of zoledronic acid. Clinical presentation suggested bilateral conjunctivitis, but treatment with levofloxacin eye drops and acyclovir ophthalmic gel exacerbated the symptoms over 2 days, predominantly affecting the left eye. Ocular ultrasonography revealed thickening of the left eyeball wall with a "T" sign, while an orbital CT scan showed increased thickness of the left sclera. Treatment with methylprednisolone 80 mg intravenous infusion twice daily led to gradual symptom improvement and eventual resolution of inflammation. This report, based on a review of relevant literature, investigates the treatment and outcomes of zoledronic acid-induced scleritis, emphasizing the importance for clinicians to promptly identify and manage this rare and serious ocular adverse reaction.
PubMed: 38855089
DOI: 10.1002/ccr3.9068 -
Frontiers in Oncology 2024Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied...
BACKGROUND
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma.
CASE PRESENTATION
A 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor.
CONCLUSION
It is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.
PubMed: 38846973
DOI: 10.3389/fonc.2024.1385214 -
Annals of Medicine and Surgery (2012) Jun 2024It is common for the liver to be supplied blood by a hepatic artery branching off the coeliac trunk. Occasionally, a replaced common hepatic artery (RCHA), emerges from...
INTRODUCTION
It is common for the liver to be supplied blood by a hepatic artery branching off the coeliac trunk. Occasionally, a replaced common hepatic artery (RCHA), emerges from the superior mesenteric artery (SMA), can supply the liver in 1.5-4.0% of cases. Computed tomography (CT) angiography is a highly accurate method for identifying arterial anomalies, which may remain undetected until the time of surgery, leading to unexpected complications.
CASE PRESENTATION
A 53-year-old male exhibiting symptoms of decreased appetite, weight loss, vomiting, and altered sclera, urine, and stool colour, underwent a contrast-enhanced CT scan revealing biliary tract dilatation and pancreatic abnormalities, leading to a pancreaticoduodenectomy. During the surgery, an uncommon arterial finding-CHA from SMA-was noted. Pancreatic cancer was confirmed. The patient was discharged a week post-surgery without issues, emphasizing perioperative care progress.
DISCUSSION
The authors' study focused on the detection conditions of the same hepatic artery anomaly in eight cases reported between 2017 and 2023. In two of them the anomaly was discovered in cadaver by routine autopsy. In three cases, this variation was identified before the surgery, but in three other cases it wasn't detected until the surgical procedure. In the authors' case, due to multiple reasons, the anomaly remained undetectable until the surgery.
CONCLUSION
This study underscores the importance of thorough preoperative evaluation to grasp vascular variations for better patient care. Also, a noteworthy observation in our case is that the surgeon identified an expanded hepatic vessel, prompting further investigation into this anomaly.
PubMed: 38846897
DOI: 10.1097/MS9.0000000000002102