A comprehensive review of intravitreal immunosuppressants and biologicals used in ophthalmology

Abstract

Systemic immunosuppressants and biologicals have been a valuable tool in the treatment of inflammatory diseases and malignancies. The safety profile of these drugs has been debatable, especially in localized systems, such as the eye. This has led to the search for fairly local approaches, such as intravitreal, subconjunctival, and topical route of administration. Immunosuppressants have been used as a second-line drug in patients intolerable to corticosteroids or those who develop multiple recurrences on weaning corticosteroids. Similarly, biologicals have also been used as the next line of therapy, when adequate control of inflammation could not be attained or immunosuppressants were contraindicated to patients. Intravitreal immunosuppressants, such as methotrexate and sirolimus, have been extensively studied in noninfectious posterior uveitis, whereas limited studies have established the efficacy of intravitreal biologicals, such as infliximab and adalimumab. Most of these drugs have shown good safety profile and tolerability in animal studies alone and have not been studied further in human subjects. However, most of the studies in literature are single-case reports or case series which limits the level of evidence. In this comprehensive review, we discuss the mechanism of action, pharmacodynamics, pharmacokinetics, indications, efficacy, and side effects of different intravitreal immunosuppressants and biologicals that have been studied in literature.

Case report: Intravitreal methotrexate in intraocular acute lymphoblastic leukemia

“…Intravitreal rituximab has been employed against intraocular lymphomas, and it would be reasonable to use it in ocular infiltration from CD20-positive leukemia ( 12 , 13 ).…”

“…MTX is also employed against intraocular lymphomas ( 13 ). MTX treatment for primary leukemic invasion was first reported by Ong and White, who described a case of biopsy-proven intraocular localization of lymphocytic leukemia refractory to intravitreal triamcinolone and intrathecal MTX.…”

Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

“…Infliximab (Remicade®, Janssen Biotech, Inc. Horsham, PA, USA), a murine-human chimeric monoclonal antibody, was approved by the FDA in 1998 for the treatment of Crohn's disease, and was later used in the treatment of rheumatoid arthritis (RA) and ankylosing spondylitis (AS), among others [43],…”

“…Thousand Oaks, CA, USA) is a soluble recombinant TNF receptor fusion protein, mainly composed of TNF-α receptor and IgG1 Fc [51], which was approved by the FDA in 1998 for the treatment of RA, AS, psoriatic arthritis(PsA) and so on. The main mechanism of action of this drug is to act as an anti-inflammatory by combining with TNF1 and TNF2 receptors thereby preventing the binding to TNF-α and thus providing an anti-inflammatory effect [43]. The current recommended dose is 25 mg twice a week.…”

Research Progress of Bioinspired Nanostructured Systems for the Treatment of Ocular Disorders

“…Although IVI can achieve therapeutic drug concentrations, it may result in infection, hemorrhage, cataracts, and retinal detachment [ 3 ]. Due to its rapid elimination, the drugs are usually administered as multiple injections, which has been shown to further increase the risk of side-effects [ 4 ]. To address these problems of traditional ocular dosage forms, there is an urgent need to develop new and more effective ocular drug delivery systems.…”