Opioids and Ocular Surface Pathology: A Literature Review of New Treatments Horizons

Abstract

This review discusses the role of opioids in the corneal surface and the different pathways and therapeutic methods of management. A literature review was performed using PubMed database. For the database search, the main searching words “opioid” and “topical opioid treatment” were used with the descriptors “cornea”, “ocular surface”, “neuropathic corneal pain”, “corneal sensitivity” and “naltrexone”; original scientific articles and reviews were included to achieve the purpose of the review. The endogenous opioid system has relevant functions in the organism, and in daily use, opioids are used as painkillers. However, these drugs may be employed for other indications as opioid pathways have a wide spectrum. The corneal surface for topical treatment is easily accessible, hence sparing the side effects of systemic opioids. Instillation of opioid antagonist substances, such as naltrexone, increases corneal healing rates and stimulates the division of corneal epithelium cells without deleterious effects. The natural modulation of endogenous opioids controls different forms of pain, including inflammatory and neuropathic pain, both in the ocular surface and in the central nervous system. There are diverse methods in controlling pain using opioids, especially in refractory forms. This review attempts to collect the literature about corneal surface and opioid pathways to provide an overview image and a possible direction of the news treatments.

Corneal neuropathic pain: a review to inform clinical practice

“…As well as antagonising opoid receptors, naltrexone acts on non-opioid receptors such as the Toll-like receptor on macrophages and microglia and has roles in modulating pain. Topical naltrexone may increase corneal healing rates and promote corneal epithelial cell division [76]. In a small phase 1 study topical naltrexone was found to be tolerable in escalating doses in normal volunteers [77].…”

“…Low-dose naltrexone can be compounded as an eyedrop but is a high-risk product due to issues with sterility [66] and there is a lack of clinical evidence on its efficacy and safety in CNP. Topical enkephalin modulators may have a therapeutic role via their actions as a neuropeptide inhibitor to modulate pain [66,76]. Libvatrep (transient receptor potential vanilloid 1 antagonist) a topical TRPV1 antagonist SAF312 (libvetrep) has been investigated for post-surgical pain in a clinical trial including patients following photorefractive keratectomy [78]; it may have a role in CNP.…”

Granulomatosis with Polyangiitis (Wegener’s Granulomatosis) Manifesting with Cranial Nerve Palsies and Pachymeningitis: A Case Report.

“…Tramadol is an analgesic used for prevention and treatment of multiple pain conditions, such as postoperative pain, renal colic, dental pain, neuropathic pain, and pain from cancer (Abdel-Zaher et al, 2011; Elkhateeb et al, 2015). Tramadol, a member of the opioid family, acts as a weak mu opioid receptor agonist and a reuptake inhibitor of serotonin and noradrenaline (Close, 2005;García-López et al, 2022). This dual mechanism contributes to its analgesic properties.…”

Ocular Surface Microbiome: Influences of Physiological, Environmental, and Lifestyle Factors

“…This microbiome varies between individuals and is influenced by host factors such as age, diet, hygiene, and geographic location [11, 12]. Recent studies have indicated that changes in the ocular surface microbiome can be associated with various ocular diseases, including conjunctivitis, dry eye, keratoconus and microbial keratitis [13,14,15,16,17,18]. The Ocular Microbiome Project, initiated in 2010, aimed to investigate the relationship between the ocular microbiome and ocular diseases [19].…”