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Cornea Evaluation of Corneal Vessels Deepa R Anijeet, 1 Adrian Tey, 2 Yalin Zheng, 3 Henri Sueke, 4 Sajjad Ahmed 5 and Stephen B Kaye 6 1. Consultant in Ophthalmology, Greater Glasgow and Clyde NHS Trust, UK; 2. Consultant in Ophthalmology, St Paul’s Eye Unit, Liverpool, UK; 3. Lecturer, Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, UK; 4. Academic Clinical Fellow, St Paul’s Eye Unit, Liverpool, UK; 5. Senior Lecturer and Consultant in Ophthalmology, St Paul’s Eye Unit and Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, UK; 6. Consultant and Honorary Professor in Ophthalmology, St Paul’s Eye Unit and Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, UK Abstract Corneal new vessels can result in significant loss of vision as well as reduce graft survival. Recently, newer treatment modalities have been introduced. However, attempts to meet the challenge of evaluating corneal vessels by quantification are evolving. In vivo evalua- tions range from computer-aided analysis of colour images to determination of area, diameter and tortuousity of blood vessels on indo- cyanine green angiography images. Attempts at developing a fully automated process of evaluation and quantification are hampered by the anatomical variations of limbus, random nature of blood vessels and multiple levels of involvement of the corneal stroma. Currently, semi-automated methods require manually fixing the limbus prior to quantification of vessels. Using indocyanine green angiography, the full extent of corneal vessels even in the presence of scarring can be determined. With the evolution of new techniques, it is hoped that a robust corneal vessel quantifying tool will be described in the near future that will aid the effectiveness of treatment strategies. Keywords Corneal neovascularisation, contourlet imaging, fluorescein angiography, indocyanine green angiography, semi-automated imaging Disclosure: The authors have no conflicts of interest to declare. Received: 14 June 2013 Accepted: 1 July 2013 Citation: European Ophthalmic Review, 2013;7(2):70–3 Correspondence: Deepa Anijeet, Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow G12 0YN, UK. E: danijeet@hotmail.com Avascularity of the cornea optimises its optical performance and also helps confer it immunological privilege. 1 Loss of this immune privilege leads to poor survival of corneal grafts. 2 Corneal new vessels (NVs) can also lead to oedema, lipid deposition, inflammation and scarring leading to reduced vision. 3 Maintenance of corneal avascularity is an active process dependent on the interplay between angiogenic and antiangiogenic factors in the tissue. 4 Pathological environments such as hypoxia, inflammation, degeneration, limbal stem cell deficiency, etc. can destabilise this balance and lead to corneal lymph and blood vessel formation, sprouting from the adjacent limbal vasculature. Our understanding of angiogenesis and lymphogenesis come from the early description in 1974 of a corneal angiogenesis model by Gimbrone et al. 5 and much later of an animal model of lymphangiogenesis dissociated from angiogenesis. 6 Although the presence of blood vessels in the cornea has been well recognised, the role of lymph vessels has only more recently been defined by the work of Collin et al. who used an animal model using radioactive iodine labelled albumin. 7 These studies have shown that lymphangiogenesis occurs earlier in the stage of corneal new vessel formation. It is estimated that the incidence of corneal NVs in the US is 1.4 million. 8 Until recently the mainstay of treatment has been using topical steroids, the long-term use of which is restricted by glaucoma and cataract formation. 9 Other immunomodulators such as cyclosporine or methotrexate, 10,11 laser photocoagulation, 12 fine needle diathermy 13 and photodynamic therapy (PDT) 14 have been described in the treatment of corneal NVs. These treatments, however, have had variable or inconsistent 70 success in addition to the side effects. As the molecular mechanisms of angiogenesis are being better understood and with the advent of anti- angiogenic treatments for exudative age-related macular degeneration, the prospect for corneal new vessel management looks brighter. Vascular endothelial growth factor (VEGF) inhibitors, by targeting the angiogenic process at a molecular level can limit or cause regression of corneal NVs with minimal side effects. A recent meta-analysis found that both topical and subconjunctival bevacizumab achieved significant reduction in the area of corneal NVs. 15 With the introduction of new treatment modalities comes the challenge of evaluation of effectiveness. Accurate comparison requires adequate quantification of corneal blood vessels. In Vitro Corneal New Vessel Imaging Several animal studies have described different in vitro methods of quantification that have been insufficiently validated. Proia et al. used India ink enhancement of blood vessels on histological samples. 16 Later, immunofluorescent staining of vascular endothelial cells was utilised to quantify corneal NVs on animal models. 17,18 While these experimental in vitro animal models have broadened our understanding of the pathology, they are of little assistance in the day-to-day management of a patient with corneal NVs. In Vivo Corneal New Vessel Imaging The simplest method of documenting corneal NVs is colour-coded drawings. The reproducibility of this method is limited, especially if different assessors are involved. The traditional method of imaging corneal NVs for documentation purposes is colour photography (see © Touc h ME d ic a l ME d ia 2013