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Acta Medica Portuguesa Oct 2023A 17-year-old male was taken to the emergency department for decreased left visual acuity and floaters beginning that same day. There was a history of exposure to...
A 17-year-old male was taken to the emergency department for decreased left visual acuity and floaters beginning that same day. There was a history of exposure to pulmonary tuberculosis five years before (mother as index case) followed by a four-month period of isoniazid prophylaxis. The ophthalmic examination showed posterior and intermediate uveitis in the left eye. Laboratory tests were normal; IgG for herpes simplex 1 was positive and both the varicella-zoster virus and remaining serologic tests were negative. Chest radiography was normal. Two weeks later, an epiretinal membrane with risk of tractional retinal detachment was observed. The Mantoux tuberculin skin test showed an induration of 15 mm and the IGRA test was positive. Sputum and vitreous humor samples were collected. Quadruple therapy and prednisolone were started. Ten days later, a posterior vitreous detachment with underlying vitreous hematoma was observed. Posterior vitrectomy and peripheral endolaser were performed without complications. One month later, the microbiological results became available, with the identification of Mycobacterium tuberculosis. Corticosteroids were weaned progressively. Antituberculous drugs were maintained for six months. The patient made a full recovery.
Topics: Male; Humans; Child; Adolescent; Tuberculosis, Ocular; Vitreous Body; Vitrectomy; Eye Diseases; Mycobacterium tuberculosis
PubMed: 37080196
DOI: 10.20344/amp.19245 -
Experimental Eye Research Oct 2023Although mouse models are widely used in retinal drug development, pharmacokinetics in mouse eye is poorly understood. In this study, we applied non-invasive in vivo...
Although mouse models are widely used in retinal drug development, pharmacokinetics in mouse eye is poorly understood. In this study, we applied non-invasive in vivo fluorophotometry to study pharmacokinetics of intravitreal fluorescein sodium (molecular weight 0.38 kDa) and fluorescein isothiocyanate-dextran (FD-150; molecular weight 150 kDa) in mice. Intravitreal half-lives of fluorescein and FD-150 in mouse eyes were 0.53 ± 0.06 h and 2.61 ± 0.86 h, respectively. These values are 8-230 times shorter than the elimination half-lives of similar compounds in the human vitreous. The apparent volumes of distribution in the mouse vitreous were close to the anatomical volume of the mouse vitreous (FD-150, 5.1 μl; fluorescein, 9.6 μl). Dose scaling factors were calculated from mouse to rat, rabbit, monkey and human translation. Based on pharmacokinetic modelling and compound concentrations in the vitreous and anterior chamber, fluorescein is mainly eliminated posteriorly across blood-retina barrier, but FD-150 is cleared via aqueous humour outflow. The results of this study improve the knowledge of intravitreal pharmacokinetics in mouse and facilitate inter-species scaling in ocular drug development.
Topics: Mice; Rats; Humans; Animals; Rabbits; Vitreous Body; Retina; Blood-Retinal Barrier; Fluorescein; Anterior Chamber; Intravitreal Injections
PubMed: 37657528
DOI: 10.1016/j.exer.2023.109638 -
Investigative Ophthalmology & Visual... Apr 2024The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration...
PURPOSE
The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration (AMD) at the 10q26 locus, age, sex, AMD status, and/or AMD disease severity, and, therefore, to determine the contribution of systemic and ocular HtrA1 to the AMD disease process.
METHODS
A custom-made sandwich ELISA assay (SCTM ELISA) for detection of the HtrA1 protein was designed and compared with three commercial assays (R&D Systems, MyBiosource 1 and MyBiosource 2) using 65 serum samples. Concentrations of HtrA1 were thereafter determined in serum and vitreous samples collected from 248 individuals and 145 human donor eyes, respectively.
RESULTS
The SCTM ELISA demonstrated high specificity, good recovery, and parallelism within its linear detection range and performed comparably to the R&D Systems assay. In contrast, we were unable to demonstrate the specificity of the two assays from MyBioSource using either recombinant or native HtrA1. Analyses of concentrations obtained using the validated SCTM assay revealed that genetic risk at the 10q26 locus, age, sex, or AMD status are not significantly associated with altered levels of the HtrA1 protein in serum or in vitreous humor (P > 0.05).
CONCLUSIONS
HtrA1 levels in serum and vitreous do not reflect the risk for AMD associated with the 10q26 locus or disease status. Localized alteration in HTRA1 expression in the retinal pigment epithelium, rather than systemic changes in HtrA1, is the most likely driver of elevated risk for developing AMD among individuals with risk variants at the 10q26 locus.
Topics: Aged; Female; Humans; Male; Chromosomes, Human, Pair 10; Enzyme-Linked Immunosorbent Assay; Genetic Predisposition to Disease; High-Temperature Requirement A Serine Peptidase 1; Macular Degeneration; Risk Factors; Sensitivity and Specificity; Serine Endopeptidases; Vitreous Body
PubMed: 38648039
DOI: 10.1167/iovs.65.4.34 -
Scientific Reports Aug 2023To investigate the clinical and computer tomography (CT) features and visual prognostic factors of pars plana vitrectomy (PPV) for management of retained posterior...
To investigate the clinical and computer tomography (CT) features and visual prognostic factors of pars plana vitrectomy (PPV) for management of retained posterior segment intraocular foreign body (IOFB). Medical records of 96 patients with IOFB removed by PPV between July 2017 and June 2021 were retrieved. The medical records, including demographic data, initial and final best corrected visual acuity (BCVA) using standard Snellen chart, characteristics of IOFB, CT findings, and surgical details, were reviewed. Outcome was evaluated according to the final BCVA and prognostic factors were obtained. The mean age was 42.31 ± 12.05 years (range 13-71 years) with 94 males (97.9%) and two females (2.1%). CT was sensitive of IOFB in 93.75% (90 eyes) and the locations were consistent with that found during PPV: 20 foreign bodies were located in vitreous, 6 near ciliary body, and 70 on or in retina. Mean diameter of IOFB removed by PPV is 3.52 mm ± 3.01 mm (range 1-22; median 3), and mean area is 6.29 ± 6.48 mm (range 0.5-40; median 3), which was statistically associated with the initial VA < 0.1 and endophthalmitis. Endophthalmitis was found in 24 (25.0%) eyes and large wound together with scleral entry site might be related to the endophthalmitis. Visual outcome < 0.1 was associated with relative afferent pupillary defect, initial VA < 0.1, and presence of endophthalmitis. Initial VA ≥ 0.1 was independent predictive factor for a better final BCVA. Relative afferent pupillary defect, initial BCVA < 0.1, and presence of endophthalmitis are poor visual prognostic factors.
Topics: Female; Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Vitrectomy; Prognosis; Eye Foreign Bodies; Endophthalmitis; Ciliary Body; Pupil Disorders
PubMed: 37644096
DOI: 10.1038/s41598-023-41105-5 -
Genes Dec 2023Due to the scarcity of literature data on the DNA content of different human tissues, this study aimed to isolate DNA from different tissues and fluids of the human body...
Due to the scarcity of literature data on the DNA content of different human tissues, this study aimed to isolate DNA from different tissues and fluids of the human body together with the determination of its content in the samples studied. Material was collected and tests were performed between 1990 and 2010, during autopsies performed for prosecutor's offices in the Department of Forensic Medicine. Goiter and thyroid cancer tissues were obtained from the Department of General Surgery, Gastroenterology and Endocrinology of Wroclaw Medical University. Isolated samples were measured spectrophotometrically, yielding an R 260/280 nm between 1.5 and 1.6. In some cases (when a sufficiently pure preparation could not be obtained), isolation was continued using the silica-based commercial QIAquick PCR Purification Kit (Qiagen). If the sampling tissues showed signs of decomposition such as bad odour or colour, the results were calibrated by Real-Time PCR, using the Quantifiler DNA assay (Thermo Fisher Scientific, Applied Biosystems). The results have shown that the maximum amount of genetic material was obtained from hair roots, adrenal glands, gonads and lymph nodes. The lowest DNA content per gram or milliliter of tissue or body fluid was found in adipose tissue, blood, saliva, bile, sweat, tears and the vitreous body of the eye. The presented findings indicate the best sources of high-quality DNA from the human body: gonads, kidneys, muscle (including heart), blood and bones (after decalcification).
Topics: Humans; Human Body; Body Fluids; DNA; Saliva; Real-Time Polymerase Chain Reaction
PubMed: 38275599
DOI: 10.3390/genes15010017 -
Journal of Pharmaceutical Sciences Aug 2023Many biotherapeutics such as monoclonal antibodies (mAbs) consist of various glycoforms, which can have different PK properties upon administration to animals and human....
Many biotherapeutics such as monoclonal antibodies (mAbs) consist of various glycoforms, which can have different PK properties upon administration to animals and human. As a result, it is necessary to monitor the abundance of glycoforms and limit lot-to-lot variability during the manufacturing process. However, limited information is known about the clearance of mAb glycoforms from ocular space upon intravitreal injection. We present here an assessment of glycoform clearance of a biotherapeutic mAb (IgG1) from rabbit vitreous humor, aqueous humor and retina tissue using LC/MS. The results show that G0, G0F and G1F have similar T1/2, while mannose-5 has a longer T1/2 and is cleared slower in rabbit ocular space, which contradicted with what has been reported in the literature in which Mann5 was cleared faster systematically.
Topics: Animals; Rabbits; Humans; Retina; Antibodies, Monoclonal; Chromatography, Liquid; Kinetics; Mass Spectrometry
PubMed: 37062414
DOI: 10.1016/j.xphs.2023.04.008 -
Epidemiologia (Basel, Switzerland) Jan 2024Theories of myopia etiology based on near work and lack of outdoor exposure have had inconsistent support and have not prevented the rising prevalence of global myopia....
Theories of myopia etiology based on near work and lack of outdoor exposure have had inconsistent support and have not prevented the rising prevalence of global myopia. New scientific theories in the cause and prevention of myopia are needed. Myopia prevalence is low in native people consuming traditional diets lacking in sodium chloride, and nutritional epidemiological evidence supports the association of rising myopia prevalence with dietary sodium intake. East Asian populations have among the highest rates of myopia associated with high dietary sodium. Similar associations of sodium and rising myopia prevalence were observed in the United States in the late 20th century. The present perspective synthesizes nutritional epidemiology evidence with pathophysiological concepts and proposes that axial myopia occurs from increased fluid retention in the vitreous of the eye, induced by dietary sodium chloride intake. Salt disturbs ionic permeability of retinal membranes, increases the osmotic gradient flow of fluid into the vitreous, and stretches ocular tissue during axial elongation. Based on the present nutritional epidemiology evidence, experimental research should investigate the effect of sodium chloride as the cause of myopia, and clinical research should test a very low-salt diet in myopia correction and prevention.
PubMed: 38390916
DOI: 10.3390/epidemiologia5010003 -
Case Reports in Ophthalmological... 2024The aim of this report is to present the onset of bilateral endophthalmitis negative to culture testing and vitreous tapping in a postpartum immunocompetent patient.
PURPOSE
The aim of this report is to present the onset of bilateral endophthalmitis negative to culture testing and vitreous tapping in a postpartum immunocompetent patient.
METHODS
A 33-year-old patient developed floaters and severe blurry vision in both eyes 3 weeks after childbirth. With no previous surgery, no comorbidities in her clinical history, and negative diagnostic reports, endogenous endophthalmitis was suspected. Two days later, a pars plana vitrectomy was performed in both eyes one week apart, and intravitreal antibiotics and antifungals were administered during the surgery. No infectious source was identified since the cultures from the aqueous and vitreous humor returned negative in both cases.
RESULTS
Residual fibrosis around the fovea in the right eye and on the optic disc in the left eye was described. Nevertheless, the best corrected visual acuity of the patient was 20/20 in both eyes 4 months after the onset of the presumed endogenous endophthalmitis.
CONCLUSION
This is the first report presenting a bilateral case of postpartum endophthalmitis negative to culture testing and vitreous tapping in a healthy patient with no previous surgeries nor long-term treatment. Early pars plana vitrectomy was fundamental for the correct management of this condition.
PubMed: 38694847
DOI: 10.1155/2024/8746755 -
Ophthalmology. Retina Apr 2024To investigate the clinical features, risk factors, and prognosis of the intraocular recurrence in primary vitreoretinal lymphoma (PVRL).
PURPOSE
To investigate the clinical features, risk factors, and prognosis of the intraocular recurrence in primary vitreoretinal lymphoma (PVRL).
DESIGN
Retrospective case-control study.
PARTICIPANTS
Ninety-seven eyes of 51 patients diagnosed with PVRL between December 2011 and January 2021 were enrolled in this study. Fourteen patients among them had experienced intraocular recurrence.
METHODS
Data on demographic and ophthalmic characteristics, results of diagnostic tests, treatments, and prognosis of intraocular recurrence and nonrecurrence for PVRL patients were collected and compared. Multivariate logistic regression was used to identify independent risk factors. Receiver operating characteristic curves were used to determine the cutoff values.
MAIN OUTCOME MEASURES
Clinical features and risk factors.
RESULTS
Fourteen (19 eyes) of 51 PVRL patients had intraocular recurrences, resulting in a recurrence rate of 27.5% over a mean follow-up period of 42.5 months. No difference was observed in central nervous system lymphoma (CNSL) relapse rate (54.3% vs. 64.3%, P = 0.52) or median time to CNSL (36.5 months; 95% confidence interval [CI], 24.6-48.3 vs. 37.3 months; 95% CI, 24.8-49.8; P = 0.78) between intraocular nonrecurrence and intraocular recurrence groups. Furthermore, there were no statistically significant differences in the survival outcomes, such as mortality (28.6% vs. 29.7%, P = 1.00) and median overall survival (70.8 months; 95% CI, 54.0-87.7 vs. 59.2 months; 95% CI, 44.8-73.6; P = 0.30), between these 2 groups. Younger onset age (odds ratio [OR] 0.90; 95% CI, 0.84-0.98; P = 0.010), isolated PVRL (OR, 35.3; 95% CI, 2.08-600.0; P = 0.014), and no history of intravitreal chemotherapy (OR, 7.72; 95% CI, 1.37-43.6; P = 0.021) were identified as independent risk factors for intraocular recurrences. Of the patients with intraocular recurrence, 23.6% were asymptomatic and were diagnosed during routine follow-up. The rate of interleukin-10 (IL-10)/interleukin-6 > 1 was significantly lower than that at diagnosis (43.8% vs. 92.3%, P = 0.008). However, the rate of IL-10 ≥ 50 pg/mL was high (81.3%) and not significantly different from that at diagnosis (92.3%, P = 0.61).
CONCLUSIONS
This study did not identify an impact of intraocular recurrence on CNS manifestations or survival outcomes in patients with PVRL. Younger patients have a higher risk of intraocular recurrence, and combined systemic and intravitreal chemotherapy may reduce intraocular recurrence. Regular ophthalmic follow-up and IL-10 testing are recommended to detect intraocular recurrence.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Retinal Neoplasms; Interleukin-10; Retrospective Studies; Case-Control Studies; Vitreous Body; Neoplasm Recurrence, Local; Prognosis; Lymphoma; Risk Factors
PubMed: 37918656
DOI: 10.1016/j.oret.2023.10.021 -
Antioxidants (Basel, Switzerland) Oct 2023Mitochondrial autophagy plays a contributary role in the pathogenesis of retina degeneration (RD). ZYAN1 is a novel proline hydroxylase domain (PHD) inhibitor that can...
Mitochondrial autophagy plays a contributary role in the pathogenesis of retina degeneration (RD). ZYAN1 is a novel proline hydroxylase domain (PHD) inhibitor that can enhance the expression of hypoxia-inducible factor 1-alpha (HIF-1α). This study investigated whether ZYAN1 could alleviate progressive photoreceptor loss and oxidative damage in a pharmacologically induced RD model via the modulation of mitophagy. ZYAN1 was injected into the vitreous body of the RD model, and the retinal autophagy level was analyzed. The therapeutic effects of ZYAN1 were evaluated via a function examination, a morphological assay, in situ reactive oxygen species (ROS) detection, and an immunofluorescence assay. It was shown that the thickness of the outer nuclear layer (ONL) increased significantly, and visual function was efficiently preserved via ZYAN1 treatment. The mitochondria structure of photoreceptors was more complete in the ZYAN1-treated mice, and the number of autophagosomes also increased significantly. Membrane disc shedding and ROS overproduction were alleviated after ZYAN1 treatment, and the axonal cilia were more structurally intact. A Western blot analysis showed that the expression levels of the autophagy-related proteins LC3-B, Beclin-1, and ATG5 increased significantly after ZYAN1 treatment, while the expression of P62 was down-regulated. Moreover, the expression levels of HIF-1α and BNIP3 were up-regulated after ZYAN1 treatment. Therefore, an intravitreal injection of ZYAN1 can act as part of the pharmacologic strategy to modulate mitophagy and alleviate oxidative stress in RD. These findings enrich our knowledge of RD pathology and provide insights for the discovery of a therapeutic molecule.
PubMed: 38001767
DOI: 10.3390/antiox12111914