Reactive macular edema and acute visual loss after photodynamic therapy on the same day of fluorescein angiography.

Reactive macular edema can occur following photodynamic therapy (PDT) in patients who have undergone fluorescein angiography (FA) on the same day. It might be better not to perform PDT on the same day of FA to avoid side effects. The safety interval between FA and PDT should be at least 24 hours, considering fluorescein retention in the body.

Introduction

Verteporfin is the first light-activated drug that has been shown in large, randomized clinical trials to reduce the risk of visual loss compared with no treatment in choroidal neovascularization (CNV). The 2005 update in guidelines for using verteporfin in photodynamic therapy (PDT) for CNV due to age-related macular degeneration (AMD) only indicates that the therapy should be initiated ideally within 1 week of the initial fluorescein angiography (FA). No mention has been made about the shortest safe interval between FA and PDT. We report a 65-year-old male patient of reactive macular edema which occurred following PDT performed on the same day of FA.

Case Report

A 65-year-old male complained of blurred vision OS. Best-corrected visual acuity (BCVA) was 1.0 OD and 0.5 OS. FA revealed predominantly classic CNV due to AMD OS. Optical coherent tomography (OCT) showed macular edema and intraretinal fluid OS.

After seven intravitreal bevacizumab injections and one ranibizumab injection, BCVA remained 0.5, but CNV persisted. OCT showed retinal pigment epithelium (RPE) detachment and intraretinal fluid [Figure 1]. Repeat FA was performed. Verteporfin (6 mg/m2 of body surface area) was administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm2 at an intensity of 600 mW/cm2 (total 127 mW) over 83 seconds, using a spot size with a diameter of 5000 mm. Intravitreal 1.25 mg bevacizumab injection was also administered on the same day after 1 hour of PDT as per the patient's request.

Figure 1

Optical coherent tomography showing retinal pigment epithelium detachment and intraretinal fluid before photodynamic therapy

The whole procedure went on smoothly; however, blurred vision and central scotoma were noted soon after PDT. Vision dropped from 0.5 to hand movement. OCT showed profound macular edema [Figure 2]. Posterior subtenon triamcinolone was given. BCVA improved to 0.05 one day later. After 1 week, BCVA improved to 0.1. Indocyanine green angiography (ICGA) revealed focal hypofluorescence compatible with the irradiated area [Figure 3]. Acetylsalicylic acid (100 mg) one tablet daily was prescribed. After 1 month, BCVA recovered to 0.7. After 2 months, BCVA remained 0.7 and FA showed no CNV. OCT revealed no more macular edema [Figure 4].

Figure 2

One day after photodynamic therapy, optical coherent tomography showed profound macular edema

Figure 3

After 1 week, Indocyanine green angiography revealed focal hypofluorescence compatible with the irradiated area

Figure 4

After 2 months, Optical coherent tomography revealed no more macular edema

Discussion

Verteporfin is the first light-activated drug that has been shown in large, randomized clinical trials to reduce the risk of losing ≥3 lines of visual acuity or losing ≥6 lines of visual acuity compared with no treatment in patients with CNV. Laser irradiation is performed with laser light at 689 nm using a Coherent Opal Photoactivator.

Sodium fluorescein is a hydrocarbon that responds to light energy between 465 and 490 nm and fluoresces at a wavelength of 520–530 nm. The excitation wavelength is blue; the resultant fluorescence is green-yellow. The peak emission is at 520–530 nm, but the wavelength can be up to 700 nm. Fluorescein is eliminated by the liver and kidneys within 24 hours, although traces may be found in the body for up to a week after injection.

The 2005 update in guidelines for using verteporfin in PDT for CNV due to AMD and other causes only indicates that the therapy should be initiated ideally within 1 week of the initial FA on which the clinical decision to treat is based.[1] The shortest safe interval between FA and PDT has not been mentioned.

In our case, reactive macular edema developed soon after PDT given on the same day of FA. Vision deteriorated from 0.5 to hand movement. ICGA revealed focal non-perfusion compatible with the irradiated area. Fortunately, BCVA recovered to 0.7 under conservative treatment after 1 month.

Transient choroidal ischemia after PDT with verteporfin in AMD has been observed previously in human and animal studies.[2-4] Acute visual decreases after PDT for AMD have been documented; choroidal hypoperfusion was one of the reasons.[34] However, visual recovery in some patients was observed.[4] Choroidal infarction following PDT with verteporfin has been reported.[56] There were nine patients with age ranging from 75 to 93 years. Five of the nine patients were treated with combination PDT and intravitreal triamcinolone. Our patient is relatively younger (65 years) and was treated with combination PDT and intravitreal bevacizumab. It is unknown whether therapy combining PDT with intravitreal triamcinolone or older age alters the response of the choroid because there have been no pathological studies of such eyes. All nine patients had poor visual outcomes. Conversely, our patient's vision improved after 1 month.

Schmidt-Erfurth et al. found that there was no apparent correlation between FA findings and final visual acuity. Because the incidence of hypofluorescence in eyes that did not have a post-treatment visual acuity decrease was not documented, it was not possible to establish a relationship between the hypofluorescence and unfavorable vision outcomes.[7] They also proposed that hypoperfusion might actually help to reduce recanalization of CNV and permit neuronal recovery by decreasing exposure to oxygen and oxidative radicals. Just like our case, though focal non-perfusion was well demonstrated by ICGA, his vision recovered to 0.7 after 1 month.

Reactive macular edema soon after PDT on the same day of FA has not reported in the literature. The possible mechanism is not well understood. We propose there might be drug interaction between sodium fluorescein and verteporfin, which reduced the selectivity of verteporfin and caused higher photosensitization to 689 nm laser light. Adjacent structures such as photoreceptors, RPE and choroid were more damaged in the course of PDT. Compromised RPE pumping function, damaged photoreceptors and choroidal non-perfusion resulted in profuse macular edema and acute visual loss.

According to our experience, reactive macular edema can occur following PDT in patients who have undergone FA on the same day. It might be better not to perform PDT on the same day as that of FA to avoid unwanted immediate side effects such as reactive macular edema and acute visual loss. The safety interval between FA and PDT should be at least 24 hours to 1 week, considering the possible fluorescein retention in the body. Further studies are necessary to clarify this issue.