Sir,

Randomized clinical trials have shown that photodynamic therapy (PDT) with verteporfin is associated with few ocular or systemic adverse events.1, 2, 3, 4 However, severe visual loss within 7 days after treatment has been reported in 4.4% from the Verteporfin in Photodynamic Therapy Study Group (VIP).2, 5 A few cases were reported from an Asian patient. We report one case of marked visual acuity deterioration within a few days after PDT.

Case report

A 51-year-old Thai female patient presented with blurred vision in the left eye for 1 year. Her visual acuity was 20/20 in the right eye and 20/200 in the left. The fundus examination showed central subretinal fluid, haemorrhage, and exudates in the left eye. Fluorescein angiography demonstrated a juxtafoveal occult CNV. The diagnosis was presumed to be idiopathic choroidal neovascularization because there was no definite sign of age-related macular degeneration in either eye. The patient underwent argon-laser photocoagulation at the lesion and visual acuity improved to 20/25. At 10 months after laser photocoagulation, we found the recurrent lesion from the previous laser scar had extended into the foveolar area (subfoveal occult CNV) and her left visual acuity had deteriorated to 20/40. The patient was considered to be a candidate for treatment by PDT with verteporfin.

Method

The patient underwent PDT with verteporfin (visudyneâ„¢ Novartis, Ophthalmics) according to the standard protocol.1 At 2 days after PDT, she noted severe visual deterioration in the left eye. The best-corrected visual acuity was 20/100 and the fundus examination demonstrated exudative retinal detachment around the treated area (Figure 1). Nevertheless, the vision and subretinal fluid slowly improved and the visual acuity returned to 20/50 after 2 weeks. Fluorescein angiography revealed improvement of CNV leakage and showed intact retinal circulation (Figure 2). At 6 weeks after PDT, there was complete resorption of subretinal fluid and the best-corrected visual acuity was 20/50. The condition continued improving, and at month 3 after PDT, the visual acuity was 20/40. Fluorescein angiography demonstrated no leakage from the subfoveal CNV, so retreatment by PDT was deferred.

Figure 1
figure 1

The fundus photograph demonstrated exudative retinal detachment after PDT: (top) before PDT; (bottom) 2 days after treatment.

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Figure 2
figure 2

A fluorescein angiogram (FFA) at 2 weeks after PDT demonstrated intact retinal circulation: (top) FFA at 44 s; (bottom) FFA at late phase (10 min).

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Discussion

The Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) and VIP Study Group reported severe visual loss (at least 20 letters of visual acuity compared with pretreatment acuity) within 7 days following treatment, with incidences of 0.7 and 4.4%, respectively.5 From the VIP study group , 10 in 225 participants exhibited this degree of visual reduction, and two cases were associated with the development of extensive subretinal fluid.2 A recent report from TAP and VIP study (TAP and VIP report No. 3)5 demonstrated that most acute severe visual loss events occurring in patients with baseline visual acuity letters score better than approximately 20/50, regardless of lesion compositions.

Holz et al6 reported two cases of marked central subretinal fluid accumulation associated with visual loss within 2 days following PDT with verteporfin. Both cases were diagnosed with age-related macular degeneration (AMD) associated with occult subfoveal CNV. Fluorescein angiography demonstrated intact retinal circulation and indocyanine green angiography showed diffuse hyperfluorescence in the late phase throughout the treated areas in both. The cases were observed and subretinal fluid resolved slowly over the following 2–3 months, with return of vision to near pretreatment levels. Rogers et al7 and Costa et al8 also reported the optical coherence tomography (OCT) and indocyanine green angiography (ICGA) findings of subretinal fluid accumulation following PDT. They suggested that acute inflammatory response was the main event within 7 days after the treatment.

In this report, the patient complained of visual acuity deterioration 2 days after PDT, similar to the report from Holz et al.6 At 2 weeks after PDT, fluorescein angiography revealed intact retinal circulation and could not identify the origin of subretinal fluid. Therefore, we agree with the previous report6, 7, 8 that sudden fluid accumulation after PDT might occur as a result of pumping impairment of retinal pigment epithelium (RPE) and/or abnormal permeability of the choroid from acute inflammatory response. This hypothesis is also supported in studies of animals that demonstrated RPE and choriocapillaris damage after PDT with verteporfin.9 That study also demonstrated that verteporfin-targeted LDL receptors within RPE cells, after which, reactive oxygen species could be generated by PDT and result in cell damage with consequential impairment of fluid transport.

At the last follow-up in our case, the subretinal fluid had spontaneously resolved accompanied by the return of vision to near-pretreatment levels within 3 months. With respect to lesion composition, this report and others2, 5, 6 have reported that most cases of subretinal fluid accumulation after PDT occur in the patients with occult lesions. Nevertheless, they suggest a severe visual loss event occurring in patients with good baseline visual acuity, regardless of lesion components.

In summary, although PDT has very few vision-threatening complications, the clinician should be aware of the possibility of sudden vision loss caused by a marked exudative response, particularly when dealing with relatively good baseline visual acuity and/or occult lesions.