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Important Studies in Vitreoretinal Surgery
Published in Pradeep Venkatesh, Handbook of Vitreoretinal Surgery, 2023
Drug delivery for diseases of the posterior segment has always been challenging because of restricted availability of drugs administered systemically owing to the blood–ocular barrier, the chronicity of many of these conditions, and the risk of systemic complications from prolonged drug administration [e.g., corticosteroids]. To bypass these challenges, local delivery using intravitreal implants has been extensively explored, but only a few have received FDA approval. Twin challenges while using drug implants include risks related to the procedure such as endophthalmitis, vitreous haemorrhage, retinal detachment, extrusion, and dislocation and those related to the drug itself, like elevated IOP and progression of cataract. Some of the diseases that have been managed using intravitreal drug implants include cytomegalovirus retinitis [Vitrasert]; chronic, non-infectious uveitis [Retisert, Iluvien, Posurdex]; diabetic macular edema [Retisert, Iluvien, Posurdex]; and exudative age-related macular degeneration [port delivery system, Susmivo]. An entirely different route to deliver drugs into the posterior segment that is under active exploration is suprachoroidal delivery using microinjectors.
Antiangiogenic gene therapy: prospects for human application
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
Mori Keisuke, Gehlbach Peter L
A number of ocular diseases are amenable to gene therapy approaches, and the eye has characteristics that are potentially advantageous to these strategies. In brief, the eye is a small compartment and is relatively isolated by virtue of its ocular coat and the blood–ocular barrier. Therefore, intraocular injection of a small amount of vector results in the transduction of a relatively large proportion of susceptible ocular cells and relatively little entry into cells outside of the eye. This makes it possible to minimize systemic side-effects.
Bacteriology of Ophthalmic Infections
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
Arumugam Priya, Shunmugiah Karutha Pandian
In endogenous endophthalmitis, the organisms from the bloodstream enter the ocular surface either through retina or uvea and invades the tissue after transecting through the blood ocular barrier. With subsequent establishment, the pathogens reside in the aqueous or vitreous humor. Bacterial load and the infiltration of inflammatory cells will initiate destruction of the tissue and physiological imbalance resulting in the loss of function in the anterior segment. If the pathogen enters via retinal artery, the dissemination of bacteria along the retinal vessels will cause irreversible tissue damage due to toxins produced by the pathogens and by the activity of inflammatory cells (Greenwald et al., 1986).
Disease progression pathways of wet AMD: opportunities for new target discovery
Published in Expert Opinion on Therapeutic Targets, 2022
Amber T. Wolf, Alon Harris, Francesco Oddone, Brent Siesky, Alice Verticchio Vercellin, Thomas A. Ciulla
In addition to sustained delivery treatments, gene therapy with viral vectors has the potential to provide the ultimate long-term continuous expression of anti-angiogenic proteins, such as pigment epithelium-derived factor, fms-like tyrosine kinase-1, ranibizumab, aflibercept, angiostatin, and endostatin [24]. Adeno-associated virus (AAV) vectors, are especially suitable for treating ocular diseases as they only have two genes, making them straightforward to work with and show low inflammatory potential, as well as nonintegrating nature with a favorable safety record [25]. The eye is a strong candidate for gene therapy because it is easily accessible, has a tight blood-ocular barrier, and can be monitored for functional and structural outcomes non-invasively [26]. Furthermore, the ocular relative immune-privilege reduces the immune response to the genetic material that is inserted. Once the appropriate vector has been chosen and delivered via a subretinal injection, it may enter RPE cells or photoreceptors. These cells then transcribe and translate the genetic material into therapeutic protein. IVT injections have also been tested; however, the penetration of viral vector to the targeted tissue is thought to be inferior to subretinal delivery [24]. A 3-year follow-up of Phase 1 and 2a rAAV.sFLT-1 subretinal gene therapy (Avalanche Biotechnology) trial for nAMD was unable to determine the biologic efficacy of the therapy given the small sample size, but was able to confirm that it was well tolerated among the elderly [27].
Combination of Intravenous Methotrexate and Methylprednisolone Therapy in the Treatment of Severe Ocular Inflammatory Diseases
Published in Ocular Immunology and Inflammation, 2021
Arash Maleki, Jordan A. Ueberroth, Marisa Walsh, Frances Foster, Peter Y. Chang, Stephen D. Anesi, Charles Stephen Foster
IV-MTX has been employed in different types of cancer, eosinophilic granuloma, and in resistant rheumatoid arthritis.7–9,13,16 Few significant adverse effects have been reported with high doses of IV-MTX (more than 100 mg) in patients with rheumatoid arthritis and eosinophilic granuloma, such as gastrointestinal symptoms, stomatitis, and hair loss.7–9 The concentration of MTX after intravenous MTX infusion in patients with recurrent intraocular lymphoma was measured by Smet et al. and it was demonstrated that in contrast to cerebrospinal fluid, the concentration of MTX was at a toxic level for lymphocytes in the anterior chamber of the eye.17 This is an interesting finding as the blood-ocular barrier disruption in cases with uveitis and possibly scleritis will allow a sufficient concentration of medication in inflamed ocular tissues.
The Effect of Latanaprost on Intraocular Inflammation and Macular Edema
Published in Ocular Immunology and Inflammation, 2019
In most reports on the Latanoprost and ME, Latanoprost has been used with other anti-glaucoma medications which means the IOP has been high and multiple medications have been necessary to control IOP.52,55,58,72 In a study on macular thickness measurement by OCT in patients that underwent cataract surgery, the mean change in foveal thickness was higher in the primary open angle glaucoma group than in the pseudoexfoliative glaucoma (a condition with impaired blood-ocular barrier) and the control groups. The only determinant that was associated with increased fluorescein leakage of the optic disc was higher IOP levels in patients with primary open angle glaucoma compared with control group.73 Therefore, the blood-ocular barrier damage may not be the only mechanism for ME development.