Verteporfin and other Cytotoxics for the Eye

Cytotoxic drugs have a role in sub-specialist ophthalmology units in the treatment of a few conditions, examples of which are outlined below. As with other conditions requiring these drugs, therapy is initiated and monitored by specialists.

Age-Related macular degeneration: verteporfin

• Action - this is a light-activated compound which selectively exerts its cytotoxic effects on the subretinal neovascular membrane found in wet age-related macular degeneration.
• Administration - photodynamic therapy (PDT) is offered to those patients with a visual acuity of 6/60 or above. It is carried out in an outpatient setting: verteporfin is infused intravenously over 10 minutes and then 5 minutes later, a laser diode is applied to the target area on the retina. The treatment can be repeated at 3 monthly intervals.¹
• Ocular side-effects - visual disturbances, sub-retinal and vitreous haemorrhage are possible problems.
• Systemic side-effects - photosensitivity: patients are advised to avoid bright light during treatment and for 48 hours thereafter. Hypersensitivity reactions, nausea, pruritis, fever, back pain, hypercholesterolaemia and reactions at the site of injection.

Glaucoma: 5-fluorouracil

• Action - it prevents normal cellular division by irreversible combination with cellular enzymes.
• Administration - subconjunctival injection during or soon after a trabeculectomy procedure to suppress episcleral fibrosis of the drainage bleb.²
• Ocular side-effects - there may be local irritation and failure of action.
• Systemic side-effects - not seen with topical injection but should the drug inadvertently enter the circulation, they include: oral mucositis, hyperuricaemia, nausea and vomiting, bone marrow suppression, alopecia and disruption of reproductive function. The quantities used (stat 5mg dose) are unlikely to cause these effects.

Other conditions

• PDT can be used for other conditions presenting with formation of a neovascular membrane, such as in the presence of retinal angioid streaks, ocular histoplasmosis syndrome and in Best's disease² but verteporfin is not yet licensed for this in the UK.
• Von Hippel-Lindau Syndrome, which gives rise to retinal capillary hemangiomata, can also be treated with photodynamic therapy.³
• Certain patients with severe or chronic uveitis associated with non-infectious, multi-system disease such as Behçet's disease and Vogt-Koyanagi-Harada Syndrome show poor response to conventional steroids and eventually necessitate cyclosporin, azathioprine or chlorambucil.^{3 4 5}

• Tumours can arise within the globe (retina, choroids, iris), the optic nerve and the surrounding tissues (eyelid, conjunctiva, orbit) but can also be exogenous (chronic lymphocytic leukaemia), intraocular lymphoma.⁶
• Treatment of these lesions tends to revolve around radiotherapy, thermotherapy and surgery but chemotherapy finds a place in the treatment of metastatic disease, particularly in debulking large tumours, such as in the case of retinoblastoma.⁴
• Topically applied chemotherapy can be used in more superficial lesions such as conjunctival melanomas and squamous cell carcinomas,^{7 8} especially where there is poor definition of lesion margins. Otherwise, surgical excision is the mainstay of therapy.⁴