Abstract
Corneal disease, including traumatic injuries, are commonly observed in marine and zoo animals under human care and in the wild.1 These injuries can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Since cetaceans have a prolonged elimination time with oral nonsteroidal anti-inflammatory drugs,2 the use of natural modalities for pain support should be considered.
A multi-drug and holistic approach was used in a multiparous, 42-year-old female, Atlantic bottlenose dolphin (Tursiops truncatus) with pre-existing chronic bilateral medial keratopathy that developed traumatic secondary corneal ulcers and abscesses infected with Pseudomonas spp. The suspected traumatic injury occurred while she was pregnant resulting in a perforated cornea OS with resulting phthisis bulbi; and OD corneal ulcer resolved with diffuse fibrosis and inactive vascularization. Her ocular regimen involved chronic use of oral antimicrobials including amoxicillin with and without clavulanic acid, ciprofloxacin, and ceftriaxone; topical antimicrobials including neomycin-polymyxin-gramicidin, tobramycin, ofloxacin, gentamicin, amikacin, 0.1% doxycycline, and 1% voriconazole; oral pain medication including tramadol, and topical nonsteroidal anti-inflammatory medications including ketorolac and Nevanac®, or nepafenac.
As traditional medical pain and inflammation control options were exhausted, the decision was made to utilize laser therapy and nutraceutical supplements for discomfort and to support the immune system. Some ingredients included a potent blend of mushrooms, turmeric, white willow bark, boswellia, methylsulfonylmethane, and bromelain.3-6 The K laser is a class IV, high power therapy used as an alternative modality, applied to the eyelids and not the cornea, to help increase vascularization and oxygen supply to the area and to promote healing.
Though the study subject responded positively to the laser therapy, it became clear that additional, alternative approaches were necessary to enhance the body’s normal repair of connective tissue and to support a normal inflammatory response. As such, a crystalline hemp extract isolate with 0% THC was administered orally using a precautionary approach regarding third party testing to ensure consistency with the farm bill along with associated federal and state regulations. This hemp supplement uses a proprietary microemulsion technology called Liquid Structure that in human clinical trials, completed at the Hadassah Medical Center, Jerusalem, Israel, had been shown to enhance bioavailability or entry into the bloodstream. Hemp is a variant of the cannabis plant that lacks psychoactive properties.7 Recent studies in humans and animals, regarding the use of hemp-derived CBD (i.e., the aerial parts of the plant), have shown that it may have calming properties, help with discomfort, and maintain a normal inflammatory response.8-10 To the authors’ knowledge, this is the first report of crystalline hemp extract administered to an Atlantic bottlenose dolphin for discomfort from a chronic ocular condition. The positive outcome supports research documenting that activation of the ocular endocannabinoid system (e.g., receptors CB1R and/or CB2R) in some species has proven effective in the mitigation of corneal pain and inflammation.10 Though preliminary, this warrants formal research studies, pending IACUC approval.
Acknowledgments
The authors would like to acknowledge Dolphins Plus and Dolphins Plus Marine Mammal Responder for their help to support novel alternative modalities.
*Presenting author
Literature Cited
1. Colitz CM, Walsh MT, McCulloch SD. 2016. Characterization of anterior segment ophthalmologic lesions identified in free-ranging dolphins and those under human care. J Zoo Wildl Med 47:56–75.
2. Simeone CA, Nollens HH, Meegan JM, Schmitt TL, Jensen ED, Papich MG, Smith CR. 2013. Pharmacokinetics of single-dose oral meloxicam in bottlenose dolphins (Tursiops truncatus). IAAAM 44th Annual Conference Proceedings, Sausalito, CA; P. 36.
3. Brein S, Lewith G, Walker A, Hicks SM, Middleton D. 2004. Bromelain as a treatment for osteoarthritis: a review of clinical studies. Evid-Based Compl Alt 1:251–257.
4. Hewlings SJ, Kalman DS. 2017. Curcumin: a review of its effects on human health. Foods 6:92.
5. Maroon JC, Bost JW, Maroon A. 2010. Natural anti-inflammatory agents for pain relief. Surg Neurol Int 1:80.
6. Butawan M, Benjamin RL, Bloomer RJ. 2017. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients 9:290.
7. Mead A. 2019. Legal and regulatory issues governing cannabis and cannabis-derived products in the United States. Front Plant Sci 10: 697.
8. Gamble LJ, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown H, Berthelsen ES, Wakshlang JJ. 2018. Pharmacokinetics, safety, and clinical efficacy of cannabidiol treatment in osteoarthritic dogs. Front Vet Sci 5:165.
9. McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL. 2019. Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. J Am Vet Med Assoc 254:1301–1308.
10. Thapa D, Cairns EA, Szczesniak AM, Toguri JT, Caldwell MD, Kelly ME. 2018. The cannabinoids Δ⁸THC, CBD, and HU-308 act via distinct receptors to reduce corneal pain and inflammation. Cannabis Cannabinoid Res 3:11–20.