Effective injection

Subconjunctival bevacizumab injection is effective in the management of paediatric corneal neovascularisation and fine needle diathermy can enhance its results, particularly with mature vessels, reported Mohamed Elalfy MD at the XXXIV Congress of the ESCRS in Copenhagen, Denmark. A review of 20 eyes of 16 paediatric patients receiving subconjunctival injections of the anti-vascular endothelial growth factor (anti-VEGF) agent for corneal neovascularisation with or without fine needle diathermy showed that 16 eyes had regression of the neovessels, and visual acuity improved in 14 eyes. However, four eyes that received only bevacizumab injections had no response, noted Dr Elalfy, Queen Victoria Hospital, East Grinstead, UK. The patients included seven males and nine females with a mean age of 7.9 years, with a range from 2.83 to 16 years. All were treated over a five-year period and had an average follow-up of 19 months with a range of six to 60 months. Their indications included corneal neovascularisation from stem cell failure in two eyes, inflammation following penetrating keratoplasty in six eyes, ocular surface inflammation in 11 eyes, and herpes simplex keratitis in one eye. All eyes received subconjunctival bevacizumab at a dosage of 1.25mg/0.05ml injected subconjunctivally 1mm from the limbus at the root of the new vessels. Twelve eyes with mature vessels, according to Dua’s classification for corneal vascularisation, received adjunctive fine needle diathermy. Injections were repeated as needed. All procedures were performed under general anaesthesia by Dr Samer Hamada at Great Ormond Street Hospital, London, and Queen Victoria Hospital, East Grinstead, UK. “We started to treat paediatric patients as a means of preventing amblyopia during the critical early phase of visual development,” Dr Elalfy explained. Eleven eyes required two injections, four eyes required three injections, and one eye required four injections. Eyes with chronic inflammatory corneal conditions required multiple subconjunctival bevacizumab injections in addition to local and/or systemic treatment to control the inflammatory process. No eye required more than one session of fine-needle diathermy.

The cornea usually remains avascular due to the delicate balance between angiogenic and anti-angiogenic factors

DELICATE BALANCE Dr Elalfy noted that the cornea usually remains avascular due to the delicate balance between angiogenic and anti-angiogenic factors. The most frequent cause of vascularisation is hypoxia and inflammation. Angiogenic factors are released in the cornea by epithelial and endothelial cells, keratocytes, and by the new corneal vessels themselves. That in turn leads to enzymatic degradation of basement membrane of perilimbal vessels, which causes vascular endothelial cells to migrate and proliferate to form new vessels. He added that corneal vascularisation can arise from the limbus, the conjunctiva and the iris, and always travels through preformed planes where they exist. They preferentially travel along planes created by corneal incisions and principally follow the depth of the inciting pathology. The network of corneal vessels is always best established at the site of the inciting pathology, where they tend to persist as a vascular complex, fed by one or more pairs of efferent and afferent vessels. Dua’s classification system describes five separate stages of corneal vascularisation: active young, active old, partially regressed, mature, and regressed. In active young vessels, there are freshly formed bright red vessels with minimal fibrous tissue sheathing. There is also a well-defined arborising network of fine capillaries, with leakage and oedema evident in the surrounding stroma. In active old neovascularisation, progression has ceased but consolidation continues, although the vessels appear less bright. Partially regressed vessels have slow circulation and are less gorged with blood. Mature vessels are relatively large, with minimal arborisation, regressed or absent capillary networks, and persist in scar tissue or stroma after the pathology has healed. Regressed cases have ghost vessels in the stroma, and no corneal oedema. Dr Elalfy noted that their study indicated that, in common with adult patients, paediatric eyes with early disease have the best response to anti-VEGF injections, while those with chronic inflammation are less responsive because of the ongoing pathology. In mature neovascularisations, the pathology is less affected by injection of anti-VEGF and best results are achieved with adjunctive fine needle diathermy occlusion. “Larger sample sizes with longer follow-up are needed to determine the long-term safety and efficacy of these agents in paediatric patients, the best dosing frequency intervals and the best route of administration,” he added. Mohamed Elalfy: m.s.elalfy@gmail.com