Topical treatment of Infectious Bovine Keratoconjunctivitis - case reportABSTRACT
Infectious Bovine Keratoconjunctivitis (IBK) is the most prevalent ocular disease in cattle herds worldwide. The primary etiological agent is Moraxella bovis, a bacterium that adheres to the corneal epithelial cells. Due to its high contagiousness, IBK has significant impacts on animal health and welfare, as well as economic losses. The present study reports the case of a Hereford calf presenting lesions in both eyes. Upon examination, clinical signs such as keratitis, corneal opacity, corneal ulceration, and melting were detected in the left eye. In the right eye, corneal perforation was observed. Additionally, the animal exhibited progressive weight loss, impaired vision, and difficulty in locomotion and feeding. The treatment was performed topically using ophthalmic solutions containing ciprofloxacin, acetylcysteine, and homologous serum. Corneal re-epithelialization of the left eye occurred within 30 days. Subsequently, antibiotic therapy was discontinued, and treatment continued with eye drops containing dexamethasone. At 45 days after the initiation of treatment, clinical resolution was achieved, with recovery of vision in the left eye. The topical treatment was successful, and the animal returned to normal behavior, locomotion, and feeding patterns.
Keywords:
bovine; cornea; eye drop; moraxella; ophthalmology
RESUMO
A ceratoconjuntivite infecciosa bovina (CIB) é a doença ocular de maior prevalência em rebanhos bovinos globalmente. O principal agente etiológico é a Moraxella bovis, bactéria que se adere às células do epitélio da córnea. Por ser altamente contagiosa, gera grandes impactos relacionadas à saúde e ao bem-estar animal, além de perdas econômicas. O presente estudo relata o caso de um bezerro da raça Hereford, o qual possuía lesões em ambos os olhos. Após o exame, foram detectados sinais como ceratite, opacidade, úlcera de córnea e melting no olho esquerdo. Já no olho direito, havia perfuração corneana. Além disso, o animal apresentava perda de peso progressiva, visão comprometida e dificuldade em se locomover e se alimentar. O tratamento foi realizado por via tópica, com soluções oftálmicas contendo ciprofloxacino, acetilcisteína e soro homólogo. A reepitelização da córnea do olho esquerdo ocorreu em um período de 30 dias. Posteriormente, a antibioticoterapia cessou, e o tratamento passou a ser realizado com colírio contento dexametasona. Aos 45 dias após o início do tratamento, houve a resolução do quadro clínico, com recuperação da visão do olho esquerdo. O tratamento por via tópica realizado foi bem-sucedido, e o animal retornou aos padrões normais de comportamento, locomoção e alimentação.
Palavras-chave:
bovino; colírio; córnea; Moraxella; oftalmologia
INTRODUCTION
Infectious Bovine Keratoconjunctivitis (IBK) is a globally occurring disease and is considered the most significant ocular condition in cattle (Angelos, 2015). This disease affects the superficial structures of the eyes in animals of all ages, with a higher prevalence in young cattle (Ferraz et al., 2008). It has a high morbidity rate due to its highly contagious nature, spreading rapidly through herds and potentially affecting up to 80% of animals within less than a month (Dima and Fikedu, 2021). Furthermore, IBK causes significant economic losses related to treatment costs, labor, weight loss, reduced reproductive performance, decreased milk production, and culling of animals (Ferraz et al., 2008).
The gram-negative polymorphic bacterium Moraxella bovis is the primary etiological agent of IBK (Irby and Angelos, 2018; Dima and Fikedu, 2021). Other species of this genus, such as M. bovoculi and M. ovis, have also been isolated from cattle diagnosed with IBK, though the latter is less frequently reported (Libardoni et al., 2012; Loy et al., 2021). Among the various virulence factors, fimbriae are common to pathogenic strains, enabling bacterial adhesion to corneal epithelial cells, particularly corneal dark cells, preventing their removal by mechanisms such as ocular secretion and the mechanical action of the eyelids (Postma et al., 2008). Subsequently, the bacteria produce RTX exotoxins that damage ocular tissues (Loy et al., 2021).
Transmission of IBK can occur through direct animal contact, via ocular and nasal discharge, through mechanical vectors such as flies (Musca autumnalis), or via fomites (Dima and Fikedu, 2021). Clinically, IBK presents with signs such as corneal edema, opacity, and ulceration, in addition to blepharospasm, photophobia, epiphora, and ocular discharge (Irby and Angelos, 2018; Kneipp, 2021). Pain, fever, reduced appetite, and weight loss are also common symptoms. Severe cases can progress to panophthalmitis, keratoconus, and corneal perforation, potentially leading to partial or permanent vision loss, impairing the animal's ability to move and feed (Ferraz et al., 2008; Angelos, 2015).
Several risk factors increase the likelihood of this disease, including ultraviolet radiation and mechanical irritation from dust, pastures, and insects (Maier et al., 2021). The disease is more common during warmer months due to increased solar radiation and fly proliferation. Taurine breeds, especially Hereford, Jersey, and Holstein, are more susceptible than Zebu breeds, and animals with minimal periocular pigmentation are at a higher risk of IBK (Irby and Angelos, 2018; Dima and Fikedu, 2021).
Early treatment is essential to ensure therapeutic success, preventing disease progression and the spread of Moraxella spp. throughout the herd. Antibiotic therapy is recommended to eliminate the pathogen and can be administered topically, subconjunctivally, or systemically (Ferraz et al., 2008; Cullen et al., 2016). While IBK can exhibit a self-limiting nature, with spontaneous recovery in some cases, treatment is advised due to the risks of severe outcomes, such as blindness, along with the pain and discomfort experienced by affected animals (O’Connor and Kneipp, 2021).
Prevention involves measures such as insecticide use for vector control, isolation of affected animals, and minimizing exposure to environmental risk factors (Irby and Angelos, 2018). Additionally, commercial vaccines containing M. bovis bacterins are available, although their efficacy is limited due to strain variability (Dima and Fikedu, 2021). Given the challenges of controlling IBK, it remains highly prevalent in cattle herds, necessitating continued treatment efforts. Topical therapy using ophthalmic solutions is uncommon in bovine practice, thus, the aim of the present study is to report a case of IBK and the successful topical treatment applied.
ETHICAL ASPECTS
This study was not submitted to the Ethics Committee on Animal Use, but the person responsible signed a free and informed consent form authorizing the publication of the data.
CASUISTRY
On November 23, 2023, a male Hereford bovine weighing approximately 200kg and around six months old was admitted to the Veterinary Clinics Hospital at the Federal University of Pelotas (Hospital de Clínicas Veterinária da Universidade Federal de Pelotas). The animal was brought from a rural property practicing extensive beef cattle farming. The owner's primary complaint was ocular lesions in both eyes of the animal. During the anamnesis, the owner reported that the animal was having trouble walking and feeding, accompanied by progressive weight loss.
During inspection, it was evident that the animal exhibited some degree of visual impairment, appearing disoriented, moving irregularly, and having difficulty navigating the environment, frequently colliding with obstacles such as fences and feeders. Additionally, the animal displayed altered behavior, appearing startled and irritable, especially when approached from the right flank. A general clinical examination revealed that vital signs were within the physiological parameters for the species (Dirksen et al., 1993). However, the animal appeared thin and slightly dehydrated, consistent with the owner’s report of reduced feed intake. A specific ophthalmic examination showed signs characteristic of infectious bovine keratoconjunctivitis (IBK), a diagnosis further supported by the epidemiological factors observed in this case.
The animal was placed in a dark environment to avoid ultraviolet radiation exposure, preventing further aggravation of its clinical condition. It was also housed in an individual stall to remain isolated from other animals due to the highly contagious nature of this disease. On the same day, subconjunctival applications of 100 mg/mL enrofloxacin (Floxiclin, Biofarm Química e Farmacêutica Ltda., São Paulo, Brazil) were administered in both eyes. However, after 24 hours, pronounced conjunctival swelling and necrotic areas were observed, prompting the discontinuation of the subconjunctival treatment.
A detailed ophthalmic evaluation was subsequently performed, including visual inspection, neuro-ophthalmic assessment (menace response and pupillary light reflex testing), Schirmer I tear test, slit-lamp biomicroscopy, fluorescein staining, indirect ophthalmoscopy, and ocular tonometry. This assessment revealed signs such as conjunctivitis, epiphora, blepharitis, and blepharospasm in both eyes (Fig. 1). Examination of the left cornea revealed approximately 80% opacity and corneal melting, vascularization, and curvature abnormalities. Ulcerative keratitis in the left eye was confirmed by fluorescein staining.
In the right eye, corneal perforation was noted. Following this evaluation, topical therapy was initiated.
Appearance of the left (A) and right (B) eyes of a Hereford bovine diagnosed with infectious bovine keratoconjunctivitis as of November 24, 2023. Notable signs include conjunctivitis, blepharitis, epiphora, and keratitis. In the left eye (A), corneal opacity due to melting and ulceration is observed (black arrow). In the right eye (B), visualization of the ocular globe is impaired due to atrophy caused by corneal perforation. Additionally, conjunctival swelling with areas of necrosis (blue arrow) is evident in both eyes, resulting from the subconjunctival enrofloxacin treatment.
The topical treatment lasted a total of 45 days, beginning on November 24, 2023, and concluding on January 8, 2024 (Fig. 2). Initially, the treatment involved the application of eye drops containing ciprofloxacin hydrochloride 3.5mg/mL (Maxiflox, Cristália Prod. Quím. Farm. Ltda., São Paulo, Brazil), with two drops instilled in each eye every two hours. Additionally, an ophthalmic solution containing atropine sulfate 1% (Allergan Produtos Farmacêuticos Ltda., São Paulo, Brazil) was administered, with two drops applied to each eye every eight hours. Homologous serum was also utilized, with two drops applied to each eye every two hours. The serum was obtained by collecting blood from the jugular vein of a healthy adult bovine into a tube without anticoagulant, followed by centrifugation at 3000 rpm for 10 minutes and subsequent refrigeration for storage.
The atropine eye drop treatment was discontinued due to the onset of ruminal tympany, which was managed with an oral dose of acetyl-butylene (Blo-trol, Zoetis, São Paulo, Brazil). After three days, the frequency of treatments was adjusted to two drops every hour from 8:00 AM to 6:00 PM, due to challenges in providing overnight nursing care. On November 27, 2023, the homologous serum application was discontinued and replaced with a solution of acetylcysteine (5% in a lubricating eye drop formulation with dextran and hydroxypropyl methylcellulose - Lácrima Plus®), with two drops applied to each eye at the same frequency as the other treatments. After complete recovery of the corneal epithelium in the left eye on December 22, 2023, antibiotic therapy was discontinued, and treatment was switched to an eye drop containing dexamethasone 1mg/mL (Maxidex, Novartis Biociências S.A., São Paulo, Brazil).
Timeline of the topical therapy administered to a Hereford bovine diagnosed with infectious bovine keratoconjunctivitis. The figure illustrates the chronological progression of treatments applied, including the initiation, adjustment, and discontinuation of various topical therapies, spanning from November 24, 2023, to January 8, 2024.
The clinical progression of the left eye is presented in Fig. 3. After three weeks of treatment, the animal showed significant improvement, with no conjunctival swelling and the absence of corneal melting. The corneal epithelium of the left eye achieved complete recovery 30 days after the initiation of treatment. The animal regained vision in the left eye, leading to the normalization of its behavior, movement, and feeding. Due to the advanced severity of the lesion in the right eye, characterized by stromal malacia, corneal perforation, and the occurrence of phthisis bulbi, enucleation of the right eye was recommended to the owner.
Clinical progression of the left eye of a bovine diagnosed with infectious bovine keratoconjunctivitis during topical treatment. The figure shows the recovery of the conjunctiva and cornea, culminating in the restoration of vision.
DISCUSSION
The treated animal exhibited minimal pigmentation around the eyes, a characteristic that increases the risk of bovine infectious keratoconjunctivitis (IBK) due to heightened susceptibility to irritation, inflammation, and greater sensitivity to solar radiation (Ferraz et al., 2008). Furthermore, the low melanin presence in these areas contributes to increased vulnerability to infections, as this pigment possesses antimicrobial properties (Dima and Fikedu, 2021). The treatment was conducted at the end of November, a period close to the beginning of summer, characterized by high solar radiation exposure, which promotes the proliferation of dark epithelial cells of the cornea, preferentially targeted by M. bovis (Loy et al., 2021).
After the adhesion of M. bovis to the corneal epithelium, toxins are released, destroying epithelial cells and causing disorganization of the collagen fibers in the corneal stroma (Silva, 2017). During the inflammatory process, there is cellular infiltration, melanosis, and vascularization. Additionally, water from the pre-corneal tear film may infiltrate the stroma through the ulcerated epithelial area. Damage to the endothelium affects ion pumping by endothelial cells, impairing water removal from the aqueous humor (Maggs, 2008). Together, these changes can compromise corneal transparency, resulting in opacity, as observed in the animal’s left eye in this case report, thereby reducing light refraction through the cornea and impairing vision (Loy et al., 2021).
Corneal re-epithelialization in the animal occurred in approximately 30 days, a duration longer than that reported in the literature, which ranges from a few days to three weeks (Ferraz et al., 2008). However, the advanced degree of corneal injury in this case may explain the prolonged epithelial healing time. After treatment completion, a small scarred leukoma was observed in the left eye. This results from granulation tissue and replacement of the lost stromal collagen with irregular collagen fibers, contributing to the loss of corneal transparency. In contrast, the right eye exhibited phthisis bulbi due to the damage caused to the ocular globe by severe ulcerative keratitis (Maggs, 2008; Silva, 2017).
Antibiotic therapy is the treatment of choice for IBK, with commonly used antibiotics including penicillin, ampicillin, gentamicin, neomycin, ceftiofur, enrofloxacin, and oxytetracycline (Ferraz et al., 2008). Recent studies have demonstrated that certain Moraxella spp. strains exhibit varying degrees of sensitivity or resistance to different antibiotic classes (Cullen et al., 2016). Maboni et al. (2015) reported resistance of M. bovis and M. ovis strains to oxytetracycline. Conversely, a study conducted in the United States found that M. bovoculi strains were sensitive to ciprofloxacin, the active ingredient used in this case report (Angelos, 2015). This antibacterial agent belongs to the fluoroquinolone class, which is effective against bacteria of the Moraxella genus (Pimenov et al., 2024).
The use of atropine aimed to minimize ciliary spasm, facilitating the application of topical drugs, especially in animals exhibiting blepharospasm (Ferraz et al., 2008). However, its parasympatholytic effect can reduce gastrointestinal peristalsis by relaxing smooth muscle (Huang et al., 2023). A study conducted in sheep found that ophthalmic atropine 1% solution reduced ruminal and intestinal motility by 46% and 58%, respectively, within the first 30 minutes after application (Ribeiro et al., 2014). Another study, using accelerometers located in the bovine reticulum, reported reduced ruminal motility following atropine administration (Choi et al., 2020). The bloating observed in the animal may have been caused by ruminal hypomotility resulting from atropine’s effects. Consequently, atropine treatment was discontinued, and acetyl-butylenol, an anti-foaming agent, was administered (Ferreira et al., 2020).
Acetylcysteine possesses protease and collagenase inhibitory properties, enzymes that delay corneal healing. It chelates free calcium, required for enzyme activation, thereby facilitating corneal re-epithelialization and accelerating the healing of the ulcerated region (Eghtedari et al., 2022). Numerous studies have demonstrated the potential of topical serum application for ophthalmic diseases in humans and animals (von Hofsten et al., 2016). The presence of growth factors, such as epidermal growth factor, and antiproteinase activity aids corneal healing (Quinto et al., 2008). Its use is indicated for cases of corneal melting, which may occur due to elevated proteolytic activity, leading to stromal liquefaction (Tsvetanova et al., 2021). In this way, its protease-inhibitory activity controls stromal destruction, aiding in the healing process (Ollivier, 2005).
Corticosteroids can be used to treat ocular diseases, as they help control inflammation and reduce corneal opacity by decreasing vascularization, melanosis, and fibroplasia (Maggs, 2008; O’Connor and Kneipp, 2021). However, steroidal anti-inflammatories can delay corneal epithelial regeneration by increasing collagenase activity, which degrades collagen fibers and heightens the risk of corneal perforation (Ferraz et al., 2008). Thus, dexamethasone treatment for the left eye was initiated only after complete corneal epithelial recovery was confirmed.
Although ointments are commonly used for IBK treatment in countries like Australia, topical treatment is uncommon in Brazilian cattle farming due to the need for frequent ophthalmic solution applications to maintain adequate therapeutic levels on the cornea (McConnel et al., 2007; Ferraz et al., 2008; Silva, 2017; Dima and Fikedu, 2021). However, this therapeutic strategy ensures high drug concentrations at the infection site, which may not be achieved with systemic treatment (O’Connor and Kneipp, 2021). Additionally, administering topical eye drops is simpler than subconjunctival injection, which carries a risk of ocular tissue damage (Ferraz et al., 2008). Given the labor-intensive nature of topical treatment, this method is suited for breeding operations focused on producing high-genetic-merit bulls and dams. Such operations typically have veterinary presence, a skilled professional team, periodic handling routines, and ease of animal restraint.
CONCLUSIONS
The present study reported a topical treatment performed on a Hereford steer affected by IBK. The therapy successfully reversed an advanced clinical case of IBK, as complete re-epithelialization of the left eye cornea was achieved, allowing the animal to resume normal locomotion and feeding. Thus, despite the management demands, the therapeutic strategy via the topical route can be effectively utilized in cattle for the treatment of IBK.
ACKNOWLEDGMENTS
The present study was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES, Brasilia, Brazil) and the Brazilian National Council for Scientific and Technological Development (CNPq, Brasilia, Brazil).
REFERENCES
- ANGELOS, J.A. Infectious bovine keratoconjunctivitis (pinkeye). Vet. Clin. Food Anim., v.31, p.61-79, 2015.
- CHOI, W.; RO, Y.; HONG, L. et al. Evaluation of ruminal motility using an indwelling 3-axis accelerometer in the reticulum in cattle. J. Vet. Med. Sci., v.82, p.1750-1756, 2020.
- CULLEN, J.N.; YUAN, C.; TOTTON, S. et al. A systematic review and meta-analysis of the antibiotic treatment for infectious bovine keratoconjunctivitis: an update. Anim. Health Res. Rev., v.17, p.60-75, 2016.
- DIMA, F.G.; FIKEDU, T. Review on infectious bovine keratoconjunctivitis, J. Bacteriol. Infect. Dis., v.4, p.1-6, 2021.
- DIRKSEN, G.; GRUNDER, H.D.; STOBER, M. Rosenberger - exame clínico dos bovinos. 3.ed. , Rio de Janeiro: Guanabara Koogan, 1993.
- EGHTEDARI, Y.; LAURENCE, J.O.; GIROLAMO, N.D.; WATSON, S.L. The role of topical N-acetylcysteine in ocular therapeutics. Surv. Ophthalmol., v.67, p.608-622, 2022.
- FERRAZ, H.T.; MORINI, R.M.; VIU, M.A.O. et al. Etiologia, fisiopatologia e clínica da ceratoconjuntivite infecciosa bovina. Pubvet, v.2, p.1-10, 2008.
- FERREIRA, J.P.A.; SANTOS, A.S.; FONSECA, B.C.O. et al. Guia farmacoterapêutico do hospital veterinário da Universidade Federal de Goiás. Guia farmacoterapêutico HV/UFG. Curitiba: Brazil Publishing, 2020.
- HUANG, H.; YANG, Q.; LIU, C. et al. Application of atropine injection in the treatment of ruminant diseases. Anim. Vet. Sci., v.11, p.27-29, 2023.
- IRBY, N.L.; ANGELOS, J.A. Ocular diseases. In: PEEK, S.F.; DIVERS, T.J. Rebhun’s diseases of dairy cattle. 3.ed. [Philadelphia]: Elsevier, 2018. p.668-712.
- KNEIPP, M. Defining and diagnosing infectious bovine keratoconjunctivitis. Vet. Clin. Food Anim., v.37, p237-252, 2021.
- LIBARDONI, F.; SCHERER, C.F.C.; FARIAS, L. et al. Moraxella bovoculi em casos de ceratoconjuntivite infecciosa bovina no Rio Grande do Sul. Pesqui. Vet. Bras., v.32, p.743-746, 2012.
- LOY, J.D.; HILLE, M.; MAIER, G.; CLAWSON, M.L. Component causes of Infectious Bovine Keratoconjunctivitis - the role of moraxella species in the epidemiology of infectious bovine keratoconjunctivitis. Vet. Clin. Food Anim., v.37, p.279-293, 2021.
- MABONI, G.; GRESSLER, L.T.; ESPINDOLA, J.P. et al. Differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis. Braz. J. Microbiol., v.46, p.545-549, 2015.
- MAGGS, D.J. Cornea and sclera. Slatter’s fundamentals of veterinary ophthalmology. 4.ed. Missouri: Saunders Elsevier, , 2008, p.175-202.
- MAIER, G.; DOAN, B.; O’CONNOR, A.M. The role of environmental factors in the epidemiology of infectious bovine keratoconjunctivitis. Vet. Clin. Food Anim., v.37, p.309-320, 2021.
- MCCONNEL, C.S.; SHUM, L.; HOUSE, J.K. Infectious bovine keratoconjunctivitis antimicrobial therapy. Aust. Vet. J., v.85, p.65-69, 2007.
- O’CONNOR, A.M.; KNEIPP, M. Evidence base for treatment of infectious bovine keratoconjunctivitis. Vet. Clin. Food Anim., v.37, p.329-339, 2021.
- OLLIVIER, F.J. Medical and surgical management of melting corneal ulcers exhibiting hyperproteinase activity in the horse. Clin. Tech. Equine Pract., v.4, p.50-71, 2005.
- PIMENOV, N.; AIGININ, A.; EVTEEV, N. et al. Drift of antimicrobial resistance of bacterial pathogens of the Moraxella group. BIO Web Conferences, v.121, 2024.
- POSTMA, G.C.; CARFAGNINI, J.C.; MINATEL, L. Moraxella bovis pathogenicity: An update. Comp. Immunol. Microbiol. Infect. Dis., v.31, p.449-458, 2008.
- QUINTO, G.G.; CAMPOS, M.; BEHRENS, A. Autologous serum for ocular surface diseases. Arq. Bras. Oftalmol., v.71, p.47-54, 2008.
- RIBEIRO, A.P.; CRIVELARO, R.M.; TEIXEIRA, P.P.M. et al. Effects of different mydriatics on intraocular pressure, pupil diameter, and ruminal and intestinal motility in healthy sheep. Vet. Ophthalmol., v.17, p.397-402, 2014.
- SILVA, A.C.E. Oftalmologia veterinária. Londrina: Editora e Distribuidora Educacional S.A, 2017.
- TSVETANOVA, A.; POWELL, R.M.; TSVETANOV, K.A. et al. Melting corneal ulcers (keratomalacia) in dogs: A 5-year clinical and microbiological study (2014-2018). Vet. Ophthalmol., v.24, p.265-278, 2021.
- VON HOFSTEN, J.; EGARDT, M.; ZETTERBERG, M. The use of autologous serum for the treatment of ocular surface disease at a swedish tertiary referral center. Int. Med. Case Rep. J., v.9, p.47-54, 2016.
Data-in-article - the research data are available within the article itself.
