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Investigative Ophthalmology & Visual... Sep 2022To characterize and pharmacologically influence subconjunctival lymphatics in rabbit and mouse eyes.
PURPOSE
To characterize and pharmacologically influence subconjunctival lymphatics in rabbit and mouse eyes.
METHODS
Rabbits received subconjunctival injections of trypan blue or fixable fluorescent dextrans. Bleb-related outflow pathways were quantified. Immunofluorescence for vessel-specific markers (lymphatics [podoplanin and LYVE-1] and blood vessels [CD31]) were performed in native rabbit conjunctiva and after fixable fluorescent dextran injection. Vascular endothelial cell growth factor-C (VEGFC) was injected subconjunctivally in rabbits. mRNA and protein were assessed for the above markers using RT-PCR and Western blot. Alternatively, mouse studies used Prox1-tdTomato transgenic reporter mice. Subconjunctival injection conditions included: no injection, balanced salt solution (BSS), VEGFC, 5-fluorouracil (5FU) and two concentrations of mitomycin-C (MMC). Two mouse injection protocols (short and long) with different follow-up times and number of injections were performed. Mouse eyes were enucleated, flat mounts created, and subconjunctival branching and length assessed.
RESULTS
Rabbit eyes demonstrated clear bleb-related subconjunctival outflow pathways that were distinct from blood vessels and were without nasal/temporal predilection. Immunofluorescence against vessel-specific markers showed lymphatics and blood vessels in rabbit conjunctiva, and these lymphatics overlapped with bleb-related subconjunctival outflow pathways. Subconjunctival VEGFC increased lymphatic (P = 0.004-0.04) but not blood vessel (P = 0.77-0.84) mRNA or protein in rabbits. Prox1-tdTomato transgenic reporter mice demonstrated natively fluorescent lymphatics. Subconjunctival VEGFC increased murine lymphatic branching and length (P ≤ 0.001-0.004) while antimetabolites (P ≤ 0.001-0.043) did the opposite for the long protocol.
DISCUSSION
Subconjunctival lymphatics are pharmacologically responsive to both VEGFC and antimetabolites in two animal models studied using different methodologies. These results may be important for bleb-forming glaucoma surgeries or ocular drug delivery.
Topics: Animals; Mice; Rabbits; Antimetabolites; Conjunctiva; Dextrans; Fluorouracil; Glaucoma; Intraocular Pressure; Mitomycin; RNA, Messenger; Trypan Blue
PubMed: 36166215
DOI: 10.1167/iovs.63.10.16 -
Indian Journal of Ophthalmology Oct 2021To study the clinical presentation, radiological features, diagnosis, and treatment response in subconjunctival and atypical orbital myocysticercosis.
PURPOSE
To study the clinical presentation, radiological features, diagnosis, and treatment response in subconjunctival and atypical orbital myocysticercosis.
METHODS
Retrospective analysis of diagnosed subconjunctival and atypical (strabismus, diplopia, and blepharoptosis) orbital myocysticercosis was performed. A diagnostic criterion (2 of the 3) among clinical features, radiological findings, and treatment response was used in our study. A minimum of "post-treatment" follow-up of 12 months was observed.
RESULTS
Thirty-five patients were included with a mean age of 16 years having male predominance (n = 22, 62.8%). All had a unilateral presentation, with 24 (68.6%) patients having subconjunctival cysticercosis, of which 22 were located in close proximity of the rectus muscle insertion. At presentation, 10 patients had diplopia, 7 had strabismus, and 6 had face turn. Pseudo Duane's and pseudo-Brown's syndrome were noted in 5 and 4 patients, respectively. Radiologically, single muscle myositis without scolex was seen in 12 (34.3%) cases. All patients first received medical treatment, and surgical intervention (cyst removal) was attempted after treatment failure. Complete resolution of symptoms was noted in 22 (after medical treatment only) and in 8 (after surgery).
CONCLUSION
In the majority, the subconjunctival cysticercosis is found in proximity to the rectus muscle insertion, as a part of orbital myocysticercosis. In atypical scenarios, a satisfactory response to medical treatment can be considered as diagnostic of cysticercosis.
Topics: Adolescent; Cysticercosis; Eye Infections, Parasitic; Humans; Male; Oculomotor Muscles; Orbital Diseases; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 34571635
DOI: 10.4103/ijo.IJO_568_21 -
Journal of Current Glaucoma Practice 2015Subconjunctival and subscleral fibrosis are the major causes of failure of filtering surgery. Antiproliferative agents have been successfully used to improve the... (Review)
Review
Subconjunctival and subscleral fibrosis are the major causes of failure of filtering surgery. Antiproliferative agents have been successfully used to improve the long-term success of this surgery. Recent advancement in the field of glaucoma surgery has been the use of bioengineered, biodegradable, porous collagen-glycosaminoglycan matrix implant in the subconjunctival and/or subscleral space to modify the wound-healing process and reduce scar formation, hence improving the surgical success without the need for anti-fibrotic agents. Biodegradable, collagen implants have shown favorable results when used with deep sclerectomy. There have been variable results regarding the success of trabeculectomy when combined with these implants. These implants also decrease the dose of mitomycin C required with trabeculectomy and hence, decrease the side effect associated with these drugs. The use of the biodegradable implants in glaucoma surgery is still evolving and further studies are needed to find the appropriate surgical technique, the ideal size and site of placement and determine their long-term impact on trabeculectomy outcomes and complications. How to cite this article: Ichhpujani P, Dada T, Bhartiya S. Biodegradable Collagen Implants in Trabeculectomy. J Curr Glaucoma Pract 2015;9(1):24-27.
PubMed: 26997829
DOI: 10.5005/jp-journals-10008-1179 -
The British Journal of Ophthalmology Mar 1985We report two cases of bacterial keratitis caused by Capnocytophaga, a genus of capnophilic Gram negative bacilli. Both responded to topical and subconjunctival...
We report two cases of bacterial keratitis caused by Capnocytophaga, a genus of capnophilic Gram negative bacilli. Both responded to topical and subconjunctival clindamycin.
Topics: Adult; Bacterial Infections; Capnocytophaga; Clindamycin; Cytophagaceae; Female; Humans; Keratitis; Male
PubMed: 3978064
DOI: 10.1136/bjo.69.3.187 -
Oman Journal of Ophthalmology 2024
PubMed: 38524340
DOI: 10.4103/ojo.ojo_130_23 -
Annals of Medicine Dec 2024To evaluate the role of M2 macrophages in subconjunctival fibrosis after silicone implantation (SI) and investigate the underlying mechanisms.
PURPOSE
To evaluate the role of M2 macrophages in subconjunctival fibrosis after silicone implantation (SI) and investigate the underlying mechanisms.
MATERIALS AND METHODS
A model of subconjunctival fibrosis was established by SI surgery in rabbit eyes. M2 distribution and collagen deposition were evaluated by histopathology. The effects of M2 cells on the migration (using wound-scratch assay) and activation (by immunofluorescence and western blotting) of human Tenon's fibroblasts (HTFs) were investigated.
RESULTS
There were more M2 macrophages (CD68+/CD206+ cells) occurring in tissue samples around silicone implant at 2 weeks postoperatively. Dense collagen deposition was observed at 8 weeks after SI. experiment showed M2 expressed high level of CD206 and transforming growth factor-β1 (TGF-β1). The M2-conditioned medium promoted HTFs migration and the synthesis of collagen I and fibronectin. Meanwhile, M2-conditioned medium increased the protein levels of TGF-β1, TGF-βR II, p-Smad2/3, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ). Verteporfin, a YAP inhibitor, suppressedTGF-β1/Smad2/3-YAP/TAZ pathway and attenuated M2-induced extracellular matrix deposition by HTFs.
CONCLUSIONS
TGF-β1/Smad2/3-YAP/TAZ signalling may be involved in M2-induced fibrotic activities in HTFs. M2 plays a key role in promoting subconjunctival fibrosis and can serve as an attractive target for anti-fibrotic therapeutics.
Topics: Animals; Humans; Rabbits; Collagen; Culture Media, Conditioned; Fibrosis; Macrophages; Silicones; Transforming Growth Factor beta1; YAP-Signaling Proteins; Transcriptional Coactivator with PDZ-Binding Motif Proteins
PubMed: 38335557
DOI: 10.1080/07853890.2024.2313680 -
Journal of Current Glaucoma Practice 2016Preoperative preparation should improve the likelihood of successful trabeculectomy surgery. The team can reconsider the appropriateness of the proposed surgery, and... (Review)
Review
Preoperative preparation should improve the likelihood of successful trabeculectomy surgery. The team can reconsider the appropriateness of the proposed surgery, and steps can be taken to maximize the chance of a good outcome. For example, adjustments to anti-hypertensive or anti-coagulant medications may be made, and topical ocular medications adjusted. Choice of anesthesia technique is of particular relevance to the trabeculectomy patient. Some anesthesia techniques are more likely to have serious complications, and glaucoma patients may be at higher risk of some sight-threatening complications, because the optic nerve is already damaged and vulnerable. Posterior placement of local anesthesia (retrobulbar, peribulbar, posterior sub-Tenon's techniques) could potentially damage the optic nerve, and thereby cause "wipe-out" of vision. Anesthesia technique may influence the likelihood of vitreous bulge and surgical difficulty. Regarding long-term control of intraocular pressure, there is no good evidence to indicate that any particular anesthesia technique is better than another. There is little high-quality evidence on this topic. The author's preferred technique for trabeculectomy is subconjunctival-intracameral anesthesia without sedation. How to cite this article: Eke T. Preoperative Preparation and Anesthesia for Trabeculectomy. J Curr Glaucoma Pract 2016; 10(1):21-35.
PubMed: 27231416
DOI: 10.5005/jp-journals-10008-1198 -
Human & Experimental Toxicology 2022To investigate the effects of subconjunctival bevacizumab, ranibizumab, and aflibercept in an experimental corneal neovascularization model.
PURPOSE
To investigate the effects of subconjunctival bevacizumab, ranibizumab, and aflibercept in an experimental corneal neovascularization model.
MATERIALS AND METHODS
The eyes of 24 rats were chemically cauterized and randomly divided into four groups: bevacizumab group (0.05 mL/1.25 mg bevacizumab), ranibizumab group (0.05 mL/0.5 mg ranibizumab), aflibercept group (0.05 mL/1.25 mg aflibercept), and control group (0.05 mL saline solution). Plasma vascular endothelial growth factor (VEGF) levels were among the major measurement outcomes to assess corneal neovascularization. The collected plasmas were analyzed using the SIGMA RAB0511 Rat VEGF Elisa kit. The PCR technique and VEGF amplification procedures were used for molecular analysis. Each cornea was removed and histologically examined on day 21. Corneal images were evaluated by image analyzer software.
RESULTS
In the post-injection period, the number of major corneal arteries decreased significantly in the injection groups when compared to the control group ( = 0.037), but no statistically significant differences were noted among the injection groups ( > 0.05). The aflibercept group had the lowest area of neovascularization. Immunohistochemical staining revealed substantially lower VEGF percentages in neovascularized arteries of the injection groups than the control group ( = 0.015). In TUNEL staining, the mean TUNEL value (number/1hpf) was substantially greater in the control group than in the injection groups, but the mean TUNEL values were similar between the injection groups ( = 0.019, > 0.05, respectively). No statistically significant differences were observed between the groups in terms of corneal surface area with increased cellularity, edema, and inflammation ( = 0.263). The mean plasma VEGF concentration in the control group was statistically greater than those in the injection groups ( = 0.001).
CONCLUSION
Subconjunctival bevacizumab, ranibizumab, and aflibercept crossed the blood and seemed to be effective in inhibiting corneal neovascularization without causing epitheliopathy in an experimental rat model compared to the controls. However, no significant results were noted between these three anti-VEGF molecules.
Topics: Angiogenesis Inhibitors; Animals; Bevacizumab; Corneal Neovascularization; Disease Models, Animal; Ranibizumab; Rats; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A
PubMed: 35465742
DOI: 10.1177/09603271221084674 -
Bioengineering (Basel, Switzerland) Jan 2022Ocular drug delivery remains the focus of much modern research. Primary routes of administration include the surface, the intravitreal space, the subretinal space, and... (Review)
Review
Ocular drug delivery remains the focus of much modern research. Primary routes of administration include the surface, the intravitreal space, the subretinal space, and the subconjunctival space, each with its own series of unique challenges, limitations, and advantages. Each of these approaches requires careful consideration of the local anatomy, physical barriers, and key cells as well as the interface between the anatomy and the drug or drug system being delivered. While least invasive, the topical route poses a challenge with the many physical barriers that prevent drug penetration into the eye; while injection into the intravitreal, subretinal, and subconjunctival spaces are direct and targeted but limited due to the many internal clearance mechanisms and potential for damage to the eye. Polymeric-based, sustained-release drug delivery systems have been identified as a potential solution to many of these challenges; however, the design and successful implementation of a sustained-release system that is well-tolerated, bioactive, biocompatible, and degradable remains, in many cases, only in the early stages. The drugs and biomaterials in question also require special attention as small chemical changes could result in vastly different outcomes. This paper explores the anatomy and key cells of these four primary drug delivery routes as well as the interface between drug and drug delivery systems and the anatomy, reviewing the recent developments and current state of research in each area. Finally, this paper also examines the frequently used drugs and biomaterials found in ocular drug delivery and summarizes the primary interactions observed.
PubMed: 35049750
DOI: 10.3390/bioengineering9010041