Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of choroidal neovascularisation secondary to pathological myopia: a pilot study

Short abstract

Intravitreous triamcinolone associated with PDT should preferably be used among elderly patients who usually show lower visual acuity and a poorer response to PDT, or among patients with recurrent or greater CNVs

High myopia is a major cause of legal blindness in many developed countries, affecting 2% of the general population. Myopic maculopathy, mainly in the form of subfoveal choroidal neovascularisation (CNV), is the most common cause of vision loss in patients with high myopia. The appearance of lacquer cracks and the presence of high levels of vascular endothelial growth factor and pigment epithelium‐derived factor¹ are probably involved in the development of myopic CNV. These findings have given way to new theories and approaches to the treatment of myopic CNV.

Different therapeutic approaches have been tried for this condition. Photocoagulation² and surgical removal of subfoveal or juxtafoveal myopic CNV³ are no longer performed because of poor final visual acuity. During the past few years, the two main approaches to subfoveal myopic CNV have been macular translocation⁴ and photodynamic therapy (PDT). PDT has been a major advance in the management of this condition after the good results achieved by the Verteporfin in Photodynamic 1 Study.⁵,⁶ The response of myopic CNV to PDT is considerably better than that of age‐related macular degeneration (AMD), requiring less PDT sessions and resulting in better final visual acuity.⁷ This is probably related to the aetiopathogenic mechanism of myopic CNV, with less inflammation and a more reduced activity of the choriocapillaris. It has also been shown that age plays a role in the outcome of myopic CNV treated by PDT showing a better prognosis among younger patients.⁷

However, the need to re‐treat and the progressive decrease in visual acuity until complete closure of CNV is achieved have prompted the association of other drugs with PDT, as previously seen in CNV associated with AMD treated with steroids (triamcinolone acetonide, dexamethasone and fluocinolone acetonide) and antiangiogenic drugs (Macugen, Eyetech Pharmaceuticals, New York, USA; Avastin, Genetech Inc, San Francisco, USA, and Lucentis, Norvatis Pharmaceuticals, New York, USA).

The local induction of the vascular endothelial growth factor by PDT with a photosensitising agent (Photophrin, Axcan Pharma, Birmingham, AL, USA) was first described in 2000 by Ferrario et al⁸, who showed that PDT‐mediated hypoxia and oxidative stress could be involved in the overexpression of vascular endothelial growth factor and other hypoxia‐induced factors. These findings were later confirmed for Visudyne (Novartis AG, Switzerland) by Schmidt–Erfurth et al⁹ and associated with the deleterious effect of PDT on the fragile retinal pigment epithelium of myopic¹⁰ and non‐myopic eyes,¹¹ suggesting a need to reduce the number of PDT sessions in order to preserve macular function.

New considerations have also arisen regarding the efficacy of the treatment. Not only the subtype of CNV but also the size of the lesion¹² and the initial visual acuity¹³ seem to be predictors of the final visual outcome in AMD. Younger patients and those with better initial visual acuity seem to have a better visual outcome after PDT in myopic CNV.¹⁴,¹⁵

The availability of new therapeutic options and a deeper knowledge of the mechanism of apparition of CNV have led to the development of new strategies associated or not associated with PDT, for the management of CNV. For instance, intravitreous Avastin not associated with PDT has shown positive results, as has been recently reported.¹⁶,¹⁷ Nevertheless, there is also growing confusion regarding which treatment may be the best. Furthermore, we must be aware of the potential risks of using antiangiogenic drugs in young patients, especially among fertile women.

The use of intravitreous triamcinolone associated with PDT to treat CNV was first proposed by Spaide et al¹⁸ in a short series of eyes with AMD and was later followed by different authors for varied indications such as retinal angiomatous proliferation,¹⁹ inflammatory and idiopathic CNV.²⁰,²¹ Presently there is no consensus on the dosage (1–24 mg), timing (before or after PDT) and procedure for concentration (filtration, decantation, or centrifugation of commercially available triamcinolone), or on the removal of benzyl alcohol from commercial triamcinolone for any of these indications. Neither is there a consensus on the need or frequency of re‐injections, or on whether they should be performed always in association with new PDT sessions, in cases of CNV reactivation or before intraocular surgery. Most of the authors agree on the potential risks of this adjuvant treatment: cataract formation (21–50% during the first year),¹³,²²,²³ which may be of greater consequence among young patients, as is the case for myopic or inflammatory CNV; apparition of transitory high intraocular pressure (20–83% during the first year),²²,²⁴,²⁵ which may occasionally need surgical treatment or may disappear during the first or the second year depending on the amount of drug injected; less frequently and highly on the injecting technique, cataracts, retinal detachment, vitreous haemorrhages and infectious or sterile endophthalmitis.²⁶,²⁷ However, the trend for associating intravitreous triamcinolone with PDT has been on the rise.²⁸,²⁹

PDT associated with intravitreous triamcinolone for myopic CNV has been reported previously.²⁴,³⁰,³¹ However, the use of adjuvant triamcinolone to treat myopic CNV may show several disadvantages. Firstly, the apparition of cataracts after triamcinolone injection in a group of young patients implies a need to perform surgery with cessation of the accommodation capability and a higher risk of retinal detachment. Secondly, myopic eyes are known to be more sensitive to damage caused by high intraocular pressure, and glaucomatous damage is more difficult to be monitored. Thirdly, the zonule is known to be more fragile in myopic than in normal eyes, and the risk of having an anterior transit of triamcinolone should therefore be higher.³² We should also consider a higher risk of retinal detachment associated with the injection procedure, owing to the more frequent presence of degenerative lesions and peripheral vitreoretinal adhesions.

In this issue, Chan et al³³(see page 174) report their results after treating myopic CNV by PDT associated with intravitreal triamcinolone. In their experience, the subgroup of patients with greater diameter of CNV and worse initial visual acuity is the one that shows more benefit from the association of PDT with intravitreous triamcinolone. A combined treatment seems to offer similar results to PDT alone in the whole group of patients, or among those with better initial visual acuity and smaller CNVs.

Myopic and inflammatory CNVs are among the cases with better response to PDT. The use of intravitreous triamcinolone as an adjuvant treatment to PDT in myopic CNV should be carefully individualised. We must be aware of the potential hazards of this treatment among young patients, and limit its use to those cases which do not show an adequate response to PDT alone. Intravitreous triamcinolone associated with PDT should preferably be used among elderly patients who usually show lower visual acuity and a poorer response to PDT, or among patients with recurrent or greater CNVs.