Managing Chronic Canine Endotheliitis: Relapses, Long-Term Therapy and the Emerging Role of ROCK Inhibitors

Managing canine endotheliitis can quickly become frustrating for both veterinarians and pet owners. Initial improvement with topical anti-inflammatory therapy is often encouraging, but many dogs experience recurrence shortly after treatment reduction, highlighting the chronic nature of endothelial inflammation^1,2. 

Increasingly, clinical experience suggests that canine endotheliitis behaves less like an isolated episode of uveitis and more like a long-term inflammatory endothelial disorder requiring sustained management. 

Why Relapses Are Common 

A striking feature observed in affected dogs is recurrence of corneal edema following tapering or discontinuation of anti-inflammatory therapy^1,2. 

In one Chihuahua mix, corneal edema relapsed within a week of stopping diclofenac despite earlier improvement with corticosteroids. Another dog developed renewed conjunctival hyperemia, ocular discomfort, and diffuse edema shortly after transitioning away from neomycin-polymyxin B-dexamethasone therapy^1,2. 

Repeated inflammatory episodes appear capable of causing progressive endothelial compromise over time. In severe cases, dogs developed diffuse edema with only small areas of unaffected cornea remaining visible^1,2. Persistent inflammatory deposits on the endothelium were also noted months after apparent stabilization. 

These cases reinforce the importance of long-term monitoring, even in patients that initially respond well to treatment. 

Anti-Inflammatory Therapy Remains the Foundation 

Topical corticosteroids continue to play a central role in management. Prednisolone acetate, dexamethasone, and combination steroid preparations were repeatedly associated with improved corneal clarity and reduced discomfort^1,2. 

However, prolonged steroid use requires careful balancing of benefits and complications. Some dogs developed subtle crystalline stromal opacities compatible with steroid keratopathy during long-term treatment. Nevertheless, continuous low-frequency anti-inflammatory therapy appeared to preserve endothelial stability more effectively than repeated withdrawal and relapse ^1,2. 

In some patients, additional medications such as diclofenac, tacrolimus, oral carprofen, and hypertonic sodium chloride were incorporated to support long-term control.1 Tacrolimus may offer particular value in chronic cases because adequate intraocular penetration has previously been demonstrated in ophthalmic use³. 

Could ROCK Inhibitors Help Preserve the Endothelium? 

One of the more clinically interesting developments is the use of rho-associated coiled-coil kinase (ROCK) inhibitors such as netarsudil^1,2. 

ROCK inhibition has been associated with enhanced endothelial cell proliferation, migration, and reduced apoptosis in both experimental and clinical ophthalmology settings^4,5,6. This has generated growing interest in its potential role for canine endothelial disease. 

In one canine patient receiving topical netarsudil alongside dexamethasone, endothelial cell density increased substantially during follow-up, while another showed a reduction in the extent of corneal edema in the less severely affected eye^1,2. Although endothelial morphology remained variable, these findings suggest a possible regenerative or protective effect. 

While larger clinical investigations are still needed, ROCK inhibitors may eventually become an important adjunctive therapy in dogs with progressive endothelial dysfunction. 

The Possible Viral Connection 

Interestingly, two littermate Australian cattle dogs with recurrent endotheliitis had previous exposure to modified live canine adenovirus vaccination, and one later demonstrated positive titers against canine adenovirus-1 (CAV-1)^1,2. 

Corneal endothelial injury associated with CAV-1 may occur through direct viral replication or immune complex-mediated inflammation within the anterior chamber¹. Although a definitive causal relationship remains uncertain, these observations suggest infectious and immune-mediated mechanisms may both contribute to endothelial injury in some dogs. 

Clinical Takeaway 

Canine endotheliitis should be approached as a chronic inflammatory endothelial disease with potential for progressive endothelial loss and recurrent edema. Early recognition, long-term monitoring, and sustained anti-inflammatory control are essential to preserving corneal function. 

Most importantly, recurrence after tapering medication may indicate persistent endothelial inflammation rather than inadequate therapy alone. 

Reference 

1. Mayes MA, Casanova MI, Park S, Steele K, Linton L, Kim S, Good KL, Moore BA, Newbold GM, Leonard BC, Li JY. Canine endotheliitis: Clinical characteristics, advanced imaging features, and treatment. Veterinary ophthalmology. 2022 May;25:185-92. https://pmc.ncbi.nlm.nih.gov/articles/PMC9243184/pdf/nihms-1765869.pdf 

2. Thomasy SM, Cortes DE, Hoehn AL, Calderon AC, Li JY, Murphy CJ. In vivo imaging of corneal endothelial dystrophy in Boston terriers: a spontaneous, canine model for Fuchs' endothelial corneal dystrophy. Investigative ophthalmology & visual science. 2016 Jul 1;57(9):OCT495-503. https://iovs.arvojournals.org/arvo/content_public/journal/iovs/935468/i1552-5783-57-9-oct495.pdf 

3. Shoughy SS, Aljassar FM, Tabbara KF. Aqueous penetration of topical tacrolimus. American Journal of Ophthalmology Case Reports. 2020 Mar 1;17:100582. https://www.sciencedirect.com/science/article/pii/S2451993619301884 

4. Meekins LC, Rosado-Adames N, Maddala R, Zhao JJ, Rao PV, Afshari NA. Corneal endothelial cell migration and proliferation enhanced by rho kinase (ROCK) inhibitors in in vitro and in vivo models. Investigative ophthalmology & visual science. 2016 Dec 1;57(15):6731-8. https://iovs.arvojournals.org/arvo/content_public/journal/iovs/935913/i1552-5783-57-15-6731.pdf 

5. Okumura N, Kinoshita S, Koizumi N. Application of Rho kinase inhibitors for the treatment of corneal endothelial diseases. Journal of ophthalmology. 2017;2017(1):2646904. https://onlinelibrary.wiley.com/doi/pdf/10.1155/2017/2646904 

6. Miyagi H, Kim S, Li J, Murphy CJ, Thomasy SM. Topical rho-associated kinase inhibitor, Y27632, accelerates corneal endothelial regeneration in a canine cryoinjury model. Cornea. 2019 Mar 1;38(3):352-9. https://pmc.ncbi.nlm.nih.gov/articles/PMC6397656/pdf/nihms-1509791.pdf