Intravitreal triamcinolone in recurrence of choroidal neovascularisation

In a previous BJO editorial Mori¹ discussed the limitations of photocoagulation and photodynamic therapy, pointing to the need for pharmacological therapies that prevent the development of choroidal neovascularisation (CNV). In the May issue of the BJO Ranson et al report the findings of a 14 patient uncontrolled consecutive case series in which the inclusion criteria and visual acuity data are compared with the Macular Photocoagulation Study (MPS).² The article is the latest in a series of independent studies to employ intravitreal triamcinolone acetonide (IVTA) in the treatment of exudative retinopathy and represents a further indication for the procedure.

The visual acuity of the study group at 1 year is similar to laser photocoagulated subfoveal recurrences and better than the MPS observation group. The baseline visual acuity of patients receiving IVTA in the Ranson study was, however, marginally worse than the MPS treatment group. The authors are appropriately circumspect about the significance of their study and suggest that IVTA may be an acceptable treatment of subfoveal recurrent neovascularisation while avoiding early persistent vision loss from laser retreatment. In the discussion it is remarked that IVTA may be useful as an adjunct to other therapies, including photodynamic therapy.

The study provides an additional impression of the potential side effects of intravitreal triamcinolone administration—for example, three of 14 eyes required topical suppressants for mild elevation of intraocular pressure, consistent with clinical expectation.³ Studies involving IVTA, published to date, have reported no significant incidence of endophthalmitis, vitreous haemorrhage, retinal detachment or visual field loss, although, an increased incidence of lens opacities has been described.^4–6 In the article by Ranson et al, in contrast with previous studies, no clinically significant effect on cataract progression was evident despite the use of an identical regimen and dose (4 mg Kenalog). It is tempting to speculate why this may be so. One possibility is that recurrent neovascularisation is associated with modulation of cytokine profiles within the vitreous which may influence cataractogenesis. Alternatively, in a setting where extensive neovascularisation has occurred, increased expression of glucocorticoid receptors by choroidal new vessels may reduce the bioavailability of the steroid to receptors in the anterior segment and lens.

A number of clinical pilot studies have previously examined the therapeutic potential of IVTA for the treatment of exudative age related macular degeneration (AMD).^4–6 IVTA has also been reported to be potentially efficacious for the treatment of diabetic retinopathy,⁷ cystoid macular oedema (CMO) associated with uveitis,^8,9 and birdshot retinochoroidopathy.¹⁰ Martidis et al¹⁰ observe that the intravitreal route of administration alleviates the pharmacological issues of penetration and bioavailability. In a randomised trial comprising 27 patients with exudative macular degeneration, including occult and classic lesions, Danis et al⁶ reported short term improvement in visual acuity using IVTA. The study additionally reported favourable fundus findings, which reflect the statement “angiographic images are similar to baseline” in the present study (Fig 1B).

The mode of action of triamcinolone on human choroidal endothelial cells remains to be completely defined

The rationale for the use of glucocorticoids for the treatment of exudative macular degeneration has been derived from observations of both animal models^11–14 and pathological specimens.¹⁵ Evidence relating leucocytes and cytokines to the aetiology of choroidal new vessels and the role of retinal microglia in AMD has been reviewed previously.¹⁶ In vitro studies indicate that triamcinolone has the capacity to modulate epithelial cell resistance and ICAM-1 expression. The findings are consistent with clinical observations indicating that reduction of the permeability of the outer blood-retinal barrier, resorption of exudation, and downregulation of inflammatory stimuli are the principal effects of intravitreal triamcinolone in vivo.¹⁵ While CNV is most commonly found in AMD, its occurrence in younger patients with posterior uveitis and other inflammatory conditions suggests that chorioretinal inflammation may be a principal aetiological factor in the development of CNV.¹⁷ Glucocorticoids are known to display differential capacities to mediate antiangiogenic, anti-inflammatory and permeability effects, although the mode of action of triamcinolone on human choroidal endothelial cells remains to be completely defined.

Clinical Evidence—Call for contributors.

Clinical Evidence is a regularly updated evidence based journal available world wide both as a paper version and on the internet. Clinical Evidence urgently needs to recruit a number of new contributors. Contributors are health care professionals or epidemiologists with experience in evidence based medicine and the ability to write in a concise and structured way.

We are presently interested in finding contributors with an interest in the following clinical areas:

• Acute bronchitis

• Acute sinusitis

• CataractHIV

• Genital warts

• Hepatitis B

• Hepatitis C

Being a contributor involves:

• Appraising the results of literature searches (performed by our Information Specialists) to identify high quality evidence for inclusion in the journal.

• Writing to a highly structured template (about 1500–3000 words), using evidence from selected studies, within 6–8 weeks of receiving the literature search results.

• Working with Clinical Evidence Editors to ensure that the text meets rigorous epidemiological and style standards.

• Updating the text every eight months to incorporate new evidence.

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If you would like to become a contributor for Clinical Evidence or require more information about what this involves please send your contact details and a copy of your CV, clearly stating the clinical area you are interested in, to Polly Brown (pbrown@bmjgroup.com).