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Diabetologia Jan 2021Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were...
AIMS/HYPOTHESIS
Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR.
METHODS
We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration.
RESULTS
We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024).
CONCLUSIONS/INTERPRETATION
These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.
Topics: Adult; Aged; Aged, 80 and over; Amino Acids; Animals; Chromatography, High Pressure Liquid; Creatine; Diabetic Retinopathy; Female; Humans; Male; Mass Spectrometry; Metabolomics; Mice; Mice, Inbred C57BL; Middle Aged; Retinal Neovascularization; Vitreous Body
PubMed: 33099660
DOI: 10.1007/s00125-020-05309-y -
Science Advances Nov 2023Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment...
Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.
Topics: Animals; Mice; Vitreous Body; Vitrectomy; Hydrogels; Neoplasm Recurrence, Local; Melanoma; Choroid Neoplasms; Melphalan; Immunotherapy
PubMed: 37910617
DOI: 10.1126/sciadv.adh1582 -
Translational Vision Science &... Apr 2022A growing body of evidence suggests complement dysregulation is present in the vitreous of patients with diabetic eye disease. Further translational study could be...
PURPOSE
A growing body of evidence suggests complement dysregulation is present in the vitreous of patients with diabetic eye disease. Further translational study could be simplified if aqueous-as opposed to vitreous-were used to sample the intraocular complement environment. Here, we analyze aqueous samples and assess whether a correlation exists between aqueous and vitreous complement levels.
METHODS
We collected aqueous, vitreous, and plasma samples from patients with and without proliferative diabetic retinopathy (PDR) undergoing vitrectomy. We assessed correlation between complement levels in aqueous and vitreous samples after using a normalizing ratio to correct for vascular leakage. Spearman correlation coefficients were used to assess the correlation between complement levels in the aqueous and vitreous.
RESULTS
Aqueous samples were obtained from 17 cases with PDR and 28 controls. In all patients, aqueous Ba, C3a, and albumin levels were strongly correlated with vitreous levels (Spearman correlation coefficient of 0.8 for Ba and C3a and 0.7 for albumin; all P values < 0.0001). In PDR eyes only, aqueous and vitreous C3a levels were significantly correlated (Spearman correlation coefficient 0.7; P = 0.002), whereas in control eyes, both Ba and C3a (Spearman correlation coefficients of 0.7; P < 0.0001) were significantly correlated.
CONCLUSIONS
A strong correlation exists between aqueous and vitreous complement levels in diabetic eye disease.
TRANSLATIONAL RELEVANCE
The results establish that accurate sampling of the intraocular complement can be done by analyzing aqueous specimens, allowing for the rapid and safe measurement of experimental complement targets and treatment response.
Topics: Albumins; Aqueous Humor; Complement Activation; Complement System Proteins; Diabetes Mellitus; Diabetic Retinopathy; Humans; Vitreous Body
PubMed: 35420644
DOI: 10.1167/tvst.11.4.13 -
Molecules (Basel, Switzerland) Jun 2020Ethanol (ethylic alcohol) represents the most commonly used drug worldwide and is often involved in clinical and forensic toxicology. Based on several reports, excessive...
Ethanol (ethylic alcohol) represents the most commonly used drug worldwide and is often involved in clinical and forensic toxicology. Based on several reports, excessive alcohol consumption is the main contributing factor in traffic accidents, drownings, suicides, and other crimes. For these reasons, it becomes essential to analyze the alcohol concentration during autopsy. Although blood is usually used for alcohol analysis in cases, it could suffer alterations, putrefaction, and microbial contaminations. As an alternative to whole blood, vitreous humor has been successfully used in medico-legal studies. In this work, specimens were analyzed for ethanol determination. The analysis of blood and vitreous humor were carried-out using gas chromatography-flame ionized detector (GC-FID) with a total run time of 6 min. The method was validated in terms of limit of detection, limit of quantification, dynamic range, sensibility, recovery, precision and trueness. A linear regression analysis indicated a coefficient of determination (R) of 0.9981. The study confirmed no statistically differences between alcohol concentration in blood and vitreous humor, leading vitreous humor as an excellent matrix that could be used as an alternative to whole blood in toxicological analysis in cases where blood is not available.
Topics: Autopsy; Body Fluids; Chromatography, Gas; Ethanol; Forensic Toxicology; Humans; Postmortem Changes; Vitreous Body
PubMed: 32545471
DOI: 10.3390/molecules25122724 -
Indian Journal of Ophthalmology Feb 2022Scleral buckling is considered an art, which has a long learning curve compared to other surgical retina techniques. Unfortunately, this beautiful surgical technique is...
BACKGROUND
Scleral buckling is considered an art, which has a long learning curve compared to other surgical retina techniques. Unfortunately, this beautiful surgical technique is getting less attention as new retina surgeons don't get much exposure to this age-old surgical technique, reason being less interest shown by young retina surgeons and tremendous advancement in micro-incision vitrectomy system.This video is a modification of the present technique of placement of band buckle, which uses science rather than art.The most important aspect in band buckle is getting the optimal buckle height which needs a lot of experience before one can achieve it. Most of the surgeons tend to tighten it more than needed that can lead to complications. This new technique is easy to learn and will give controlled reproducible buckle height and can be done safely by the trainees.
PURPOSE
The aim of this video is to simplify the technique of scleral buckling which can produce controlled and reproducible buckle height and will reduce the complications associated with a tight band buckle.
SYNOPSIS
A 360-degree peritomy is made. Four recti muscles are identified and separated and traction sutures are passed under their insertions. A partial thickness scleral tunnel is made in all four quadrants. A silicone band (style#41 used in this video) is passed through the scleral tunnel and under the insertion of all four recti.The two ends of the silicone band are trimmed so that they are opposed to each other. Then a 12-mm strip is cut off from one end, and the two remaining ends are tied with a 5-0 nonabsorbable suture. This technique ensures a 2-mm optimal buckle height.
HIGHLIGHTS
We present an elegant technique of placing the band buckle in retinal detachment surgery.
VIDEO LINK
https://youtu.be/9_dh6qsd-7A.
Topics: Humans; Retina; Retinal Detachment; Scleral Buckling; Vitrectomy; Vitreous Body
PubMed: 35086296
DOI: 10.4103/ijo.IJO_156_22 -
Molecular Pharmaceutics Jul 2020Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supranormal concentrations suppress preretinal...
Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supranormal concentrations suppress preretinal neovascularization. Herein we investigated the pharmacokinetics of opticin following intravitreal injection in rabbits. To measure simultaneously concentrations of human and rabbit opticin, a selected reaction monitoring mass spectrometry assay was developed. The mean concentration of endogenous rabbit opticin in 7 uninjected eyes was measured and found to be 19.2 nM or 0.62 μg/mL. When the vitreous was separated by centrifugation into a supernatant and collagen-containing pellet, 94% of the rabbit opticin was in the supernatant. Intravitreal injection of human opticin (40 μg) into both eyes of rabbits was followed by enucleation at 5, 24, and 72 h and 7, 14, and 28 days postinjection ( = 6 at each time point) and measurement of vitreous human and rabbit opticin concentrations in the supernatant and collagen-containing pellet following centrifugation. The volume of distribution of human opticin was calculated to be 3.31 mL, and the vitreous half-life was 4.2 days. Assuming that rabbit and human opticin are cleared from rabbit vitreous at the same rate, opticin is secreted into the vitreous at a rate of 0.14 μg/day. We conclude that intravitreally injected opticin has a vitreous half-life that is similar to currently available antiangiogenic therapeutics. While opticin was first identified bound to vitreous collagen fibrils, here we demonstrate that >90% of endogenous opticin is not bound to collagen. Endogenous opticin is secreted by the nonpigmented ciliary epithelium into the rabbit vitreous at a remarkably high rate, and the turnover in vitreous is approximately 15% per day.
Topics: Angiogenesis Inhibitors; Animals; Collagen; Extracellular Matrix Proteins; Half-Life; Humans; Intravitreal Injections; Male; Mass Spectrometry; Neovascularization, Physiologic; Proteoglycans; Rabbits; Retina; Vitreous Body
PubMed: 32437164
DOI: 10.1021/acs.molpharmaceut.0c00151 -
Hematological Oncology Dec 2022Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are...
Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p < 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs.
Topics: Humans; Aged; Transplantation, Autologous; Hematopoietic Stem Cell Transplantation; Retinal Neoplasms; Retrospective Studies; Vitreous Body; Lymphoma
PubMed: 35789106
DOI: 10.1002/hon.3044 -
Molecular Vision 2021Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age,...
PURPOSE
Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age, resulting in the separation of the posterior hyaloid membrane (PHM) from the retina in what is called complete posterior vitreous detachment (PVD). Incomplete separation of the posterior hyaloid or tight adherence or both can lead to retinal detachment, vitreomacular traction syndrome, or epiretinal membrane formation, which requires surgical intervention. Pharmacological vitrectomy has the potential of avoiding surgical vitrectomy; it is also useful as an adjunct during retinal surgery to induce PVD. Previously studied enzymatic reagents, such as collagenase derived from are nonspecific and potentially toxic. We studied a novel collagenase from (VMC) which remains active (VMA), even after deletion of 51 C-terminal amino acids. To limit the activity of VMA to the vitreous cavity, a fusion construct (inhibitor of hyaluronic acid-VMA [iHA-VMA]) was made in which a 12-mer peptide (iHA, which binds to HA) was fused to the N-terminus of VMA. The construct was evaluated in the context of PVD.
METHODS
VMA and iHA-VMA were expressed in purified, and characterized with gelatin zymography, collagen degradation assay, fluorescamine-based assay, and cell-based assays. Two sets of experiments were performed in New Zealand albino rabbits. Group A (n = 10) received iHA-VMA, while group B (n = 5) received the equivalent dose of VMA. In both groups, saline was injected as a control in the contralateral eyes. Animals were monitored with indirect ophthalmoscopy, optical coherence tomography (OCT), and B-scan ultrasonography. Retinal toxicity was assessed with hematoxylin and eosin (H&E) staining of retinal tissue.
RESULTS
The activity of iHA-VMA and VMA was comparable and 65-fold lower than that of collagenase Type IV. In the iHA-VMA group, all the rabbits (n = 10) developed PVD, with complete PVD seen in six animals. No statistically significant histomorphological changes were seen. In the VMA group, four of the five rabbits developed complete PVD; however, retinal morphological changes were seen in two animals.
CONCLUSIONS
iHA-VMA displays targeted action confined to the vitreous and shows potential for safe pharmacologic vitreolysis.
Topics: Animals; Cell Survival; Collagenases; Electrophoresis, Polyacrylamide Gel; Flow Cytometry; Goats; Hyaluronic Acid; Intravitreal Injections; Microscopy, Electron, Scanning; Ophthalmoscopy; Rabbits; Recombinant Fusion Proteins; Retina; Vibrio mimicus; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 33907368
DOI: No ID Found -
Pharmacological Research Sep 2021Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the...
Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.
Topics: Animals; Cell Line; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Docosahexaenoic Acids; Endothelial Cells; Female; Humans; Macular Edema; Male; Mice, Inbred C57BL; Retina; Symporters; Vitreous Body; Wound Healing; Mice
PubMed: 34229049
DOI: 10.1016/j.phrs.2021.105755 -
Ophthalmology. Retina Jan 2024Vitreoretinal lymphoma is a malignancy with high mortality. Incidence is rare, and there is a lack of medical evidence to direct management. This work describes... (Observational Study)
Observational Study
PURPOSE
Vitreoretinal lymphoma is a malignancy with high mortality. Incidence is rare, and there is a lack of medical evidence to direct management. This work describes presentation, diagnostic testing, and first treatment approaches in a recently diagnosed and treated patient cohort.
DESIGN
Clinical registry-based observational study.
SUBJECTS
Forty-eight women and 32 men (age range, 32-91 years; median age, 64 years) diagnosed with vitreoretinal lymphoma.
METHODS
An international network of ophthalmologists reported clinical features and management of patients presenting with vitreoretinal lymphoma between January 1, 2020 and December 31, 2022 via an electronic platform.
MAIN OUTCOME MEASURES
Visual acuity at presentation (logarithm of the minimum angle of resolution [logMAR]); basis for diagnosis; first treatment.
RESULTS
Vitreoretinal lymphoma was bilateral at presentation in 65% of patients (n = 52) and an initial site of lymphoma in 78% (n = 62). Of 127 eyes with lymphoma at presentation, vitreous was involved in 89% (n = 113) and was the only involved eye tissue in 40% (n = 51), and retina was involved in 46% (n = 59) and was the only involved eye tissue in 9% (n = 11). Median logMAR visual acuity of the worse-seeing eye was 0.50. The lymphoma was diagnosed from ocular specimens in 80% of patients (64/80), usually vitreous (57/64 patients [89%]), and on other clinical information in 20% of patients (16/80). Cellular studies were performed on ocular specimens from 59 of 64 patients (92%), most often cytology. Tumor gene analysis was used in 21 of 64 patients (33%), and cytokine assays were used in 13 of 64 patients (20%). For 76 patients (95%), treatment was initiated within 6 months of diagnosis and included ocular (38/76 [48%]), extraocular (17/76 [21%]), and ocular plus extraocular (21/76 [26%]) approaches. Intravitreal methotrexate was the most common ocular treatment (83/87 eyes [95%]).
CONCLUSIONS
Using data collected from 80 patients diagnosed with vitreoretinal lymphoma since 2020, we show that visual impairment is common, and that management often involves diagnosis by cellular tests and treatment with intravitreal chemotherapy.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Male; Humans; Female; Middle Aged; Adult; Aged; Aged, 80 and over; Retinal Neoplasms; Vitreous Body; Eye Neoplasms; Lymphoma; Diagnostic Techniques and Procedures
PubMed: 37648063
DOI: 10.1016/j.oret.2023.08.012