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Biomolecules Nov 2023: The global epidemic status of diabetic retinopathy (DR) and its burden presents an ongoing challenge to health-care systems. It is of great interest to investigate...
: The global epidemic status of diabetic retinopathy (DR) and its burden presents an ongoing challenge to health-care systems. It is of great interest to investigate potential prognostic biomarkers of DR. Such markers could aid in detecting early stages of DR, predicting DR progression and its response to therapeutics. Herein, we investigate the prognostic value of intravitreal concentrations of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in a DR cohort. : Vitreous sample acquisition was conducted at King Abdullah University Hospital (KAUH) between December 2020 and June 2022. Samples were obtained from any patient scheduled to undergo a pars plana vitrectomy (PPV) for any indication. Included patients were categorized into a DR group or a corresponding non-diabetic (ND) control group. Demographics, clinicopathological variables, standardized laboratory tests results, and optical coherence tomography (OCT) data were obtained for each included individual. Intravitreal concentrations of VEGF and PDGF were assessed using commercial enzyme-linked immunosorbent assay (ELISA). : A total of 80 eyes from 80 patients (DR group: = 42 and ND control group: = 38) were included in the analysis. The vitreous VEGF levels were significantly higher in the DR group compared to the ND control group (DR group 5744.06 ± 761.5 pg/mL versus ND control group 817.94 ± 403.1 pg/mL, = 0.0001). In addition, the vitreous PDGF levels were also significantly higher in the DR group than those in the ND control group (DR group 4031.51 ± 410.2 pg/mL versus ND control group 2691.46 ± 821.0 pg/mL, = 0.001). Bassline differences between test groups and clinical factors impacting VEGF and PDGF concentrations were investigated as well. Multiple regression analysis indicated PDGF as the sole independent risk factor affecting best-corrected visual acuity (BCVA) at the last follow-up visit: the higher the PDGF vitreous levels, the worst the BCVA. : Vitreous concentrations of VEGF and PDGF are correlated with DR severity and may exhibit a possible prognostic potential value in DR. Further clinical and experimental data are warranted to confirm the observed findings and to help incorporate them into daily practice.
Topics: Humans; Diabetes Mellitus; Diabetic Retinopathy; Platelet-Derived Growth Factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vitreous Body
PubMed: 38002312
DOI: 10.3390/biom13111630 -
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 -
BMC Ophthalmology Nov 2023Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton's tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain.
METHODS
A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies.
RESULTS
The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%).
CONCLUSION
The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects.
TRIAL REGISTRATION
CRD42023400305.
Topics: Humans; Methotrexate; Retinal Neoplasms; Prospective Studies; Vitreous Body; Central Nervous System Neoplasms; Lymphoma
PubMed: 37993841
DOI: 10.1186/s12886-023-03226-3 -
Indian Journal of Ophthalmology Dec 2023When primary angle-closure glaucoma occurs during an acute attack, routine phacoemulsification is challenging because of the high intra-ocular pressure (IOP) and shallow...
When primary angle-closure glaucoma occurs during an acute attack, routine phacoemulsification is challenging because of the high intra-ocular pressure (IOP) and shallow anterior chamber (AC). To reduce IOP and deepen the AC before phacoemulsification, a portion of the vitreous body is often removed. In this report, we introduce an extended trocar/cannula system with lateral micropores to drain the liquid vitreous before routine phacoemulsification to solve this problem. A modified trocar was used to drain the liquefied vitreous before routine phacoemulsification. We demonstrated that this novel trocar/cannula system is safe and effective for draining liquefied vitreous before routine phacoemulsification. It also facilitates the transition to smooth phacoemulsification.
Topics: Humans; Vitreous Body; Cannula; Glaucoma; Phacoemulsification; Drainage; Intraocular Pressure; Glaucoma, Angle-Closure
PubMed: 37991312
DOI: 10.4103/IJO.IJO_31_23 -
Investigative Ophthalmology & Visual... Nov 2023To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched...
PURPOSE
To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL).
METHODS
A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared.
RESULTS
The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples.
CONCLUSIONS
Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.
Topics: Humans; Vitreous Body; Retinal Neoplasms; Retrospective Studies; Interleukin-6; Interleukin-10; Myeloid Differentiation Factor 88; Biopsy; Lymphoma; Liquid Biopsy; High-Throughput Nucleotide Sequencing; Phenotype; Genotype
PubMed: 37975847
DOI: 10.1167/iovs.64.14.27 -
BMC Ophthalmology Nov 2023To explore the feasibility and safety of using a foldable capsular vitreous body (FCVB) in managing severe ocular trauma and silicone oil-dependent eyes.
OBJECTIVES
To explore the feasibility and safety of using a foldable capsular vitreous body (FCVB) in managing severe ocular trauma and silicone oil-dependent eyes.
METHODOLOGY
This is a retrospective study of 61 ocular trauma patients (61 eyes) who presented to the Department of Eye Emergency, Hebei Eye Hospital from May 1, 2018, to May 31, 2019, including 51 male patients (51 eyes) and 10 female patients (10 eyes) with an average age of 44.98 ± 14.60 years old. The oldest patient was 75 years old, and the youngest was 8 years old. These cases represented 51 eyes with severe eyeball rupture and 10 eyes with severe, complicated ocular trauma, which became silicone oil-dependent after the operation. These patients received FCVB implants, and data regarding their visual acuity, intraocular pressure, changes in eye axis, cornea, retina, and FCVB state were recorded after the operation.
RESULTS
In all patients, the FCVB was properly positioned and well supported with the retina. All 61 patients cleared a follow-up window of 1-36 months with no reports of important changes in their visual acuity. Among the patients, 91.8% reported normal intraocular pressure, the retinal reattachment rate reached 100%, and the eyeball atrophy control rate reached 100%. There was no report of rupture of the FCVB, allergies to silicone, intraocular infection, intraocular hemorrhage, silicone oil emulsification, or sympathetic ophthalmia.
CONCLUSIONS
Foldable capsular vitreous bodies (FCVBs) designed to mimic natural vitreous bodies are suitable as long-term ocular implants that can provide sustained support for the retina without the need for any special postoperative postures. Their barrier function may effectively prolong the retention time of the tamponade and prevent various complications caused by direct contact of the eye tissues with the tamponade.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Child; Vitreous Body; Vitrectomy; Silicone Oils; Retrospective Studies; Retinal Detachment; Eye Injuries; Rupture
PubMed: 37974090
DOI: 10.1186/s12886-023-03209-4 -
International Journal of Retina and... Nov 2023Age-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1)....
Correlations between subfoveal choroidal thickness, macular thickness, and visual outcome in neovascular age-related macular degeneration using swept source OCT: insights from intravitreal aflibercept treatment.
BACKGROUND
Age-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1). Currently, antiangiogenic therapy is the primary treatment approach for neovascular AMD (2). The choroid has gained significant attention in recent years due to its involvement in various ocular pathologies (7). The objective of this study was to evaluate visual acuity and correlate pre-treatment variables, such as foveal thickness and choroidal thickness, with post-treatment outcomes.
MATERIALS AND METHODS
This study was designed as a prospective interventional study to investigate the changes in choroidal and macular thickness in patients with neovascular AMD who received intravitreal aflibercept injections. The study utilized medical records and employed Swept Source Optical Coherence Tomography (OCT-SS) for evaluation. The data was collected from patients treated in Presidente Prudente, Brazil, during a three-month load dose period.
RESULTS
The best-corrected mean visual acuity significantly improved from 1.0 logarithm of the minimum resolution angle (logMAR) units to 0.55 logMAR after treatment with aflibercept (p < 0.001). Patients undergoing treatment exhibited a significant decrease in average macular thickness from 323 μm to 232 μm (p = 0.001), as well as a reduction in choroidal thickness from 206 μm to 172 μm (p = 0.031), while maintaining intraocular pressure within the normal range (p = 0.719) without significant variation. Statistically significant associations were found between the difference in pre- and post-treatment choroidal thickness and the pretreatment values of macular thickness (p = 0.005) and choroidal thickness (p = 0.013). There was also a statistically significant correlation between the difference in pre- and post-treatment macular thickness and the pretreatment macular thickness value (p < 0.001).
CONCLUSION
In this study, aflibercept exhibited remarkable effectiveness in reducing macular and choroidal thickness, as evaluated using OCT-SS, and significantly improved visual acuity in patients with neovascular AMD. The assessment of both choroidal and macular changes, as well as their correlations, can provide valuable insights for clinicians, enabling them to make well-informed therapeutic decisions and effectively monitor treatment outcomes. Notably, this study contributes to the existing body of literature as the first to establish a correlation between pretreatment foveal thickness, variation in choroidal thickness, and post-treatment choroidal thickness.
PubMed: 37968771
DOI: 10.1186/s40942-023-00506-4 -
Cureus Oct 2023Diabetes mellitus (DM) has become a worldwide problem, endangering the well-being of people. This issue is further aggravated by the increased fatty content in the diet... (Review)
Review
Diabetes mellitus (DM) has become a worldwide problem, endangering the well-being of people. This issue is further aggravated by the increased fatty content in the diet of most of the Indian population. It is a preeminent source of the genesis of morbidity in the citizens of any given continent, including both new-world countries and old ones too. A major stumbling block that diabetes creates in the healthy living of any of its sufferers is a complication called diabetic retinopathy (DR), which, in its most elementary and perspicuous form, refers to damage to the blood vessels in the retina of the human eye that occurs as a result of high serum glucose levels. DR can have many symptoms, including obscure and blurred vision, trouble observing and distinguishing various colors, and eye floaters. One of the most significant reasons for the manifestation of new cases of complete blindness may be attributed to DR. The appearance of lesions in the body's small blood vessels forms the basis of retinopathic detection. The currently accepted approach for the prevention and cure of this ailment targets deterring the microvascular complexities through medicinal agents that are placed directly into the vitreous space, photocoagulation through laser medium (visual perceptivity is balanced), and some other surgeries related to the vitreous chamber. Anti-vascular endothelial growth factor (anti-VEGF) therapy provided to the patient by intravitreal route is, at present, the most crucial process for curing the sufferer of the given illness, as it can result in optical advancement with decreased unfavorable effects.
PubMed: 37954772
DOI: 10.7759/cureus.46842 -
Ophthalmology and Therapy Jan 2024Personalized medicine and patient-tailored drug dosing have been substantiated through thousands of clinical studies, demonstrating their safety and efficacy. The...
INTRODUCTION
Personalized medicine and patient-tailored drug dosing have been substantiated through thousands of clinical studies, demonstrating their safety and efficacy. The principle: "as much as necessary, as little as possible" is widely spread. Quantities and doses are therefore adjusted individually. This is not the case for intravitreal injections in the context of retinal diseases. Intravitreal injections are not adjusted in relation to the vitreous volume. The vitreous body is described as "approx. 4 cm" in the literature.
METHODS
In this retrospective observational study, we included 72 eyes of patients who had undergone magnetic resonance imaging (MRI) of the orbit and biometry measurements of the anterior chamber depth (ACD) and axial length. After segmentation of the volume data, the vitreous volume was extracted by voxel integration, and a simple prediction model was derived to determine the vitreous volume from the axial length (AL) measurement with AL·π/6·(0.76 + 0.012·(AL-24). This is the volume of a sphere AL·π/6 and a correction term 0.76 + 0.012·(AL-24) to account for the portion of the vitreous in the entire globe and the proportional increase of the vitreous portion for long (myopic) eyes.
RESULTS
Emmetropic eyes with an axial length of 22.50-23.50 mm had a vitreous volume of around 4.5-5.5 cm. Myopic eyes with an axial length of 30.00 mm had a calculated vitreous volume of 9.0-10.0 cm. Hypermetropic eyes with an axial length of 20.00 mm showed a vitreous volume of 3.0-4.0 cm.
CONCLUSIONS
By implementing the new calculation formula on the IOLCON website, it will be easy to get the exact individual vitreous volume. The data could be used by retinal surgeons prior to surgery. The knowledge of anatomical dimensions and exact individual vitreous volume seems to be important for gas and silicone oil fillings. With the newly derived knowledge, multicentric studies can evaluate the impact of the dose in intravitreal therapies. Patient-tailored dosing could prevent side effects and improve effectiveness.
PubMed: 37938450
DOI: 10.1007/s40123-023-00838-2 -
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