Topical bevacizumab for the treatment of corneal vascularization in dogs: A case series.

OBJECTIVE: To evaluate the effect and safety of topical anti-human vascular endothelial growth factor bevacizumab in dogs with persistent corneal vascularization. ANIMALS STUDIED: Prospective case series of 15 adult dogs (20 eyes). PROCEDURES: Dogs received 0.25% bevacizumab eye drops BID for 28 days. Follow-ups were scheduled 28 days and 6-7 months after treatment start. Macroscopic findings were scored for conjunctival hyperemia, chemosis, ocular discharge, corneal edema, vascularization, and pigmentation. Vascularized area was assessed by analyzing photographs using an imaging software. RESULTS: The treatment response was variable. Some cases showed a marked reduction in vascularized area and edema, while other eyes had subtle signs of improvement. Vascularization score decreased from 1.5 to 1.1 and vascularized area was reduced by 48.8% after 28 days. A thinning of vessels, consolidation of areal bleedings into fine vascular networks, decrease in distal vessel branching, and a change from blurry vascularized beds into demarcated thin vessels were observed. One dog developed a SCCED 6 months after the last bevacizumab administration. Two dogs died 4 and 4.5 months after the last bevacizumab administration, aged 16 and 12 years, respectively. In all events, a causal relationship is unlikely but cannot be ruled out with certainty. CONCLUSIONS: Our findings suggest that topical 0.25% bevacizumab may be an effective treatment option for corneal vascularization in dogs. Further long-term placebo-controlled studies with larger patient cohorts are recommended to provide scientific evidence of efficacy and to investigate dosage, safety, possible use as a single treatment, and routes of administration.

Intracorneal hemorrhage in 19 dogs (22 eyes) from 2000 to 2010: a retrospective study.

OBJECTIVE: The aim of this retrospective study is to review clinical data on patients that suffered intracorneal hemorrhage (ICH), and the veterinary and human literature available for this condition. ANIMAL STUDIED: A search for ICH was performed within the clinical database of the Animal Health Trust. Nineteen cases were identified (22 eyes). PROCEDURES: The patient's age, breed, and gender were reviewed, together with etiology, location, treatment, and follow-up. The relevant data were compared with the Animal Health Trust (AHT) ophthalmology referral population for the same period of time (n=5555). RESULTS: Twenty-two eyes were affected. No breed or sex predisposition could be identified. Patients aged 10 years and above were more frequently affected when compared with the AHT ophthalmology referral population. ICH was recorded in all corneal quadrants, with the mid-peripheral cornea more often affected. Areas of corneas affected by the ICH showed long-term loss of transparency. Ocular diseases as a source of neovascularization varied from ocular surface to intraocular disease. Systemic diseases were investigated in some patients, and no concomitant disease could be linked to the development of ICH. CONCLUSIONS: Intracorneal hemorrhage is a rare condition associated with corneal neovasculature. As in the human ophthalmology literature, ICH could not be linked to a specific ocular or systemic disease. Severe complications described in humans with this condition, such as pupillary block or corneal perforation, were not seen in any of these canine patients. Canine ICH seem to reabsorb with time, with or without medical treatment. Surgical treatment was not required in any of our patients.

Effects of topical 0.2 percent Cyclosporine A on corneal neovascularization induced by xenologous amniotic membrane implantation into a corneal stroma micropocket of rats / Efeitos do uso tópico da Ciclosporina A (CsA) 0,2 por cento na neovascularização corneal induzida pelo implante de membrana amniótica xenógena em microbolsa no estroma da córnea de ratos

The objective of the study was to evaluate the topical effects of 0.2 percent Cyclosporine A (CsA) on corneal neovascularization of rats following surgical implantation of equine amniotic membrane into a corneal stroma micropocket. The implantation of xenologous amniotic membrane was performed bilaterally in 90 rats. In the same day of the surgery each right eye started receiving topical CsA twice a day. The left eye received no medication and served as a control. The evaluation of corneal neovascularization was performed by computerized image analysis and histopathological evaluation at 1, 3, 7, 15, 30 and 60 days postoperatively. For the image analysis 10 animals were used per time period, and for the histopathological examination, five animals were used per time period. Image analysis found that corneal neovascularization began on the 3rd postoperative day, reached its peak on the 7th day, and then progressively and rapidly decreased. Statistic analysis indicated that neovascularization of the CsA treated eye on the 7th day was significantly higher than that observed in untreated eyes. On the 30th day, however, this pattern was reversed with the neovascularization observed in the CsA treated eyes declining to the low levels observed on the 3rd day. The degree of neovascularization in the untreated eyes on the 30th day declined to the baseline levels found on day 3 at the 60th day. Histopathological analysis indicated that deposition of collagen in the implanted tissue was completed by the 15th day. Therefore, we concluded that (1) equine amniotic membrane in rat corneal stroma produced an intense neovascularization until the 15th day postoperatively and then regressed, (2) deposition of collagen of the implanted tissue was completed on the 15th day postoperatively, and (3) use of CsA was associated with increase in the corneal neovascularization initially, followed by a quick and intense regression.

Este estudo teve como objetivo a avaliação dos efeitos tópicos da Ciclosporina a 0,2 por cento (CsA) sobre a neovascularização corneana de ratos após implante cirúrgico de membrana amniótica eqüina em microbolsa do estroma corneana. O implante da membrana foi feito bilateralmente em 90 ratos. O tratamento com CsA iniciou-se no mesmo dia da cirurgia, nos olhos direitos dos animais, duas vezes ao dia. Os olhos esquerdos não receberam nenhum tratamento e serviram de controle. A avaliação da neovascularização corneana foi feita por análise de imagem computadorizada e por exame histopatológico aos dias 1, 3, 7, 15, 30 e 60 de pós-cirúrgico. Para a análise de imagem foram utilizados 10 animais por período, e para o exame histopatológico, 5 por período. A análise de imagem demonstrou que a neovascularização iniciou-se no 3º dia pós-cirúrgico, alcançou seu pico no 7º dia e então regrediu rápida e progressivamente até o 60º dia. A análise estatística indicou que a neovascularização no 7º dia nos olhos tratados com CsA foi significantemente mais acentuada do que aquela observada nos olhos não tratados. Entretanto, no 30º dia este fato se reverteu, e a neovascularização observada nos olhos tratados com CsA diminuíra a níveis baixos comparáveis àquela do 3º dia. Já nos olhos não tratados, o grau de neovascularização somente pôde ser comparado àquele nível básico encontrado no 3º dia aos 60 dias de pós-operatório. A análise histopatológica demonstrou que a deposição de colágeno no tecido implantado se completou no 15º dia. Desta maneira, foi possível concluir que (1) a membrana amniótica em estroma corneano de ratos produz intensa neovascularização até o 15º dia de pós-operatório com posterior regressão, (2) a deposição de colágeno do tecido implantado foi completa ao 15º dia de pós-operatório, e que (3) o uso de CsA esteve associado com aumento inicial da neovascularização corneana, seguido de rápida e intensa regressão.

Corneal stromal sequestration in a dog.

A case of corneal sequestrum in a 9-year-old Shih Tzu is reported. On the ophthalmic examination a brown-pigmented ulcer with mild edema and corneal vascularization was present. The brownish plaque was facing an inferior palpebral tumor. A superficial keratectomy followed by a grid keratotomy and removal of the palpebral mass were performed. Histological findings revealed an inflammatory cell infiltration underneath the acellular stromal layers. No melanin granules were observed. No vascular infiltration was present within the necrotic stroma. The surgical area healed and no recurrence has been reported by the owners at the time of writing. To the authors' knowledge, this is the first report of a corneal sequestrum in a dog.

Corneal vascularization in the Florida manatee (Trichechus manatus latirostris) and three-dimensional reconstruction of vessels.

The cornea of the Florida manatee is unique and unusual in its anatomy in that blood vessels have been found throughout. In all other animal species, this is considered a pathological condition impeding vision, and is usually caused by injury or trauma. The purpose of this study was to more clearly describe corneal vascularization by examining the architecture through three-dimensional reconstruction in order to find possible patterns in size, distribution, and location of blood vessels relative to gender, age, location, and season. Twenty-six eyes from 22 individuals were prepared for histologic examination and subsequent three-dimensional reconstruction. Every specimen examined had blood vessels in the cornea, comprising an average of 0.3% of total surface density (volume) of the cornea. No differences were found between individuals based on gender, age, and season. Environmental influences were not a significant factor either, which was not originally anticipated. The presence of vessels at the level of the anterior epithelium was surprising and it appeared that the vascularization was directed more anteriorly than was originally thought. The presence of blood vessels in a prenatal eye was also found. In all the eyes examined, no signs of injury or trauma could be observed. The presence of blood vessels appears to minimally impair vision based on their low density, size, and location. The association of vessels with the anterior epithelium and development of vessels within the fetus point to an evolutionary adaptation possibly due to the manatee's unique ability to move between water bodies.

Repair of a full thickness corneoscleral defect in a German shepherd dog using porcine small intestinal submucosa.

Porcine small intestinal submucosa (SIS) was used, in conjunction with a conjunctival graft, to repair a full thickness corneoscleral defect resulting from the excision of a limbal melanoma in a German shepherd dog. The SIS was found to provide adequate mechanical support and to act as a suitable physical barrier in place of the excised cornea and sclera. Corneal vascularisation was present distant to the graft by two weeks postoperatively but this was effectively controlled with topical cyclosporin. By six weeks postoperatively, the graft had become incorporated into the cornea and sclera, and the associated corneal neovascularisation had resolved. From this initial case, porcine SIS would appear to be a suitable material for the repair of corneoscleral defects in dogs.

Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis.

BACKGROUND: We have previously shown that basic fibroblast growth factor (FGF-2) enhances corneal epithelial healing in different experimental models in vivo. In order to study the healing effect of this growth factor in pathological conditions of the cornea, we investigated whether topical application of FGF-2 could affect herpes keratitis in rabbits. Since HSV-1 infection is prevented in vitro by incubation with heparin, we also topically applied heparin and suramin, considering the similar interaction of herpes simplex virus and FGF-2 with cell membrane-anchored heparan sulfate. METHODS: After virus inoculation with a human BEY.2 strain, rabbits were treated with either FGF-2 (200 ng to 2 micrograms/application), heparin (250 micrograms/application) or suramin (250 micrograms/application) 4 times daily until day 14. Acyclovir and placebo administrations served as controls (n = 48 rabbits). Computerized ulcer surface analysis, clinical observations and virus recovery assays were performed. RESULTS: Topical FGF-2, heparin and suramin treatment revealed a significant reduction in peak ulcer sizes, and complete epithelial healing was achieved earlier than in placebo-treated corneas. However, no significant antiviral effect of FGF-2, heparin and suramin was detectable in plaque assays from conjunctival swabs. CONCLUSIONS: These experiments demonstrate that FGF-2 is effective in promoting herpetic epithelial ulcer healing, either due to its proliferative effects on epithelial cells or indirectly by occupying the sites on cell surface heparan sulfate necessary for the attachment of the virion. The latter mechanism of action is presumably the reason for the similar effect of heparin and suramin.