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Verteporfin and other cytotoxics for the eye

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

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What are cytotoxics? (Background)

Cytotoxic drugs have a role in 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.

Ocular disease (non-oncological)

Age-related macular degeneration: verteporfin (Visudyne®)

  • 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. It is preferentially taken up by rapidly dividing endothelial cells of the developing vessels; laser light is then applied. Its energy is taken up by the photosensitive verteporfin causing damage to the vascular endothelial cells and thrombotic occlusion of the blood vessels with the neovascular membrane.

  • 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.

  • Ocular side-effects - transient visual disturbances occur in up to 38% of patients, but resolve spontaneously with time in the vast majority of people.1

  • Systemic side-effects - photosensitivity: patients are advised to avoid bright light during treatment and for 48 hours thereafter. Hypersensitivity reactions, nausea, pruritus, fever, back pain, hypercholesterolaemia and reactions at the site of injection.

  • Note that verteporfin photodynamic therapy has largely been replaced as a first-line therapy for late AMD, in favour of anti-vascular endothelial growth factor drugs. The National Institute for Health and Care Excellence (NICE) recommends that it is only used as an adjunct to these drugs as a second-line treatment in a randomised controlled trial.2

  • The Royal College of Ophthalmologists recommend photodynamic therapy as an option for patients with polypoidal choroidal vasculopathy who are not responding to anti-VEGF.3

  • A global shortage of verteporfin occurred in 2021, with ongoing shortages occurring in the years following.4

Age-related macular degeneration: anti-vascular endothelial growth factor treatment

  • Action - these are agents that interfere with angiogenesis by binding to vascular endothelial growth factors (VEGFs) to prevent endothelial cell proliferation. Ranibizumab (Lucentis®), aflibercept (Eylea®), and brolucizumab (Beovu®) are all licensed for the treatment of AMD in the UK.2 5 Bevacizumab (Avastin®) is not licensed for AMD, but is considered to be of equivalent effectiveness and safety to ranibizumab and aflibercept,2 and is considerably cheaper than those drugs. 6 Pegaptanib (Macugen®) is also licensed for AMD, but NICE deemed it to be less effective than ranibizumab, and not cost-effective to use.7

  • Administration - NICE guidelines give a list of criteria for the use of anti-VEGF agents in wet AMD.2 Anti-VEGF agents are administered directly into the vitreous of the eye under sterile conditions. Three doses are given at four-weekly intervals in the first instance and the patient's response is monitored according to strict protocols before further treatment is given; many units found the bi-monthly follow-up required for aflibercept easier to meet than the monthly follow-up required with ranibizumab.3

  • Ocular side-effects - these may be related to the procedure, which is invasive, or to the drug itself. Complications are uncommon but may include endophthalmitis, traumatic lens injury, retinal detachment, uveitis and periocular infections.8

  • Systemic side-effects - hypersensitivity reaction, thrombo-embolic phenomena.8

Glaucoma: 5-fluorouracil, mitomycin C9

  • Action - 5-fluorouracil prevents normal cellular division by irreversible combination with cellular enzymes. Mitomycin C's alkylating properties inhibit DNA replication.

  • Administration - subconjunctival injection during or soon after a trabeculectomy procedure to suppress episcleral fibrosis of the drainage bleb.

  • Ocular side-effects - there may be local irritation and failure of action. Mitomycin C may increase the risk of cataract formation in the long-term.10

  • 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 very small quantities used are unlikely to cause these effects.

Other conditions

  • PDT is also sometimes used, off-label, to treat chronic central serous retinopathy,11 , ocular haemangiomas, choroidal melanomas, and retinal angiomatous proliferations.4

  • PDT has been used in the treatment of choroidal neovascularisation associated with high myopia, although, again, anti-VEGF treatments have largely taken over.4

  • 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 ciclosporin, azathioprine or chlorambucil. 12 13

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Cytotoxic drugs in ophthalmic oncology

  • Tumours can arise within the globe (retina, choroids, iris), the optic nerve and the surrounding tissues (eyelid, conjunctiva, orbit) but can also be exogenous (metastatic deposits from primary carcinomas elsewhere).14

  • 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.15 Intravitreal chemotherapy has been successfully used to avoid enucleation in some cases.16

  • Topically applied chemotherapy has been used in more superficial lesions such as conjunctival melanomas and squamous cell carcinomas,17 18 especially where there is poor definition of lesion margins. Otherwise, surgical excision is the mainstay of therapy.

Further reading and references

  1. van Dijk EHC, van Rijssen TJ, Subhi Y, et al; Photodynamic Therapy for Chorioretinal Diseases: A Practical Approach. Ophthalmol Ther. 2020 Jun;9(2):329-342. doi: 10.1007/s40123-020-00250-0. Epub 2020 Apr 11.
  2. Age-related macular degeneration; NICE Guideline (Jan 2018)
  3. Commissioning Guidance: Age Related Macular Degeneration Services, Royal College of Ophthalmologists, June 2021.
  4. Sirks MJ, van Dijk EHC, Rosenberg N, et al; Clinical impact of the worldwide shortage of verteporfin (Visudyne(R)) on ophthalmic care. Acta Ophthalmol. 2022 Nov;100(7):e1522-e1532. doi: 10.1111/aos.15148. Epub 2022 Apr 6.
  5. Brolucizumab for treating wet age-related macular degeneration; NICE technology appraisal guidance, February 2021.
  6. Dyer C; Offering Avastin for wet AMD is legal, says appeal court. BMJ. 2020 Mar 27;368:m1273. doi: 10.1136/bmj.m1273.
  7. Pegaptanib and ranibizumab for the treatment of age-related macular degeneration; NICE Technology appraisal guidance, May 2012
  8. Falavarjani KG, Nguyen QD; Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye (Lond). 2013 Jul;27(7):787-94. doi: 10.1038/eye.2013.107. Epub 2013 May 31.
  9. Cabourne E, Clarke JC, Schlottmann PG, et al; Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery. Cochrane Database Syst Rev. 2015 Nov 6;2015(11):CD006259. doi: 10.1002/14651858.CD006259.pub2.
  10. Wilkins M, Indar A, Wormald R; Intra-operative mitomycin C for glaucoma surgery. Cochrane Database Syst Rev. 2005 Oct 19;2005(4):CD002897. doi: 10.1002/14651858.CD002897.pub2.
  11. Iacono P, Da Pozzo S, Varano M, et al; Photodynamic Therapy with Verteporfin for Chronic Central Serous Chorioretinopathy: A Review of Data and Efficacy. Pharmaceuticals (Basel). 2020 Oct 29;13(11):349. doi: 10.3390/ph13110349.
  12. O'Keefe GA, Rao NA; Vogt-Koyanagi-Harada disease. Surv Ophthalmol. 2017 Jan-Feb;62(1):1-25. doi: 10.1016/j.survophthal.2016.05.002. Epub 2016 May 27.
  13. Schwartzman S; Advancements in the management of uveitis. Best Pract Res Clin Rheumatol. 2016 Apr;30(2):304-315. doi: 10.1016/j.berh.2016.07.005. Epub 2016 Oct 31.
  14. Eagle RC Jr; The pathology of ocular cancer. Eye (Lond). 2013 Feb;27(2):128-36. doi: 10.1038/eye.2012.237. Epub 2012 Nov 16.
  15. Dimaras H, Kimani K, Dimba EA, et al; Retinoblastoma. Lancet. 2012 Apr 14;379(9824):1436-46. doi: 10.1016/S0140-6736(11)61137-9. Epub 2012 Mar 12.
  16. Abramson DH, Ji X, Francis JH, et al; Intravitreal chemotherapy in retinoblastoma: expanded use beyond intravitreal seeds. Br J Ophthalmol. 2019 Apr;103(4):488-493. doi: 10.1136/bjophthalmol-2018-312037. Epub 2018 Jun 6.
  17. Finger PT, Czechonska G, Liarikos S; Topical mitomycin C chemotherapy for conjunctival melanoma and PAM with atypia. BJO 1998; 82: 476-479.
  18. Midena E, Angeli CD, Valenti M et al.; Treatment of conjunctival squamous cell carcinoma with topical 5-fluorouracil. BJO 2000;84:268-272.

Article History

The information on this page is written and peer reviewed by qualified clinicians.

  • Next review due: 17 Aug 2033
  • 4 Oct 2023 | Latest version

    Last updated by

    Dr Doug McKechnie, MRCGP

    Peer reviewed by

    Dr Surangi Mendis
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