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Original Article

Role of Photodynamic Therapy in Polypoidal Choroidal Vasculopathy

Hussain, Nazimul MS, DNB; Hussain, Anjli MS; Natarajan, Sundaram DO

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Indian Journal of Ophthalmology: Apr–Jun 2005 - Volume 53 - Issue 2 - p 101-104
doi: 10.4103/0301-4738.16172
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Abstract

Polypoidal choroidal vasculopathy (PCV) has been recognised for nearly two decades as a distinct exudative disorder of the macula. It is characterised by a network of vessels with two distinct components: 1. Complex of branching vessels and; 2. Multiple, terminal, reddish orange, aneurysmal or polypoidal lesions. PCV is presumed to be a variant of choroidal vascularisation or Polypoidal CNV. This is best imaged with Indocyanine green angiography (ICGA) as it can penetrate the RPE as well the associated exudation with enhanced sensitivity and specificity.

PCV was described as an entity predominantly seen in black females and usually in the peripapillary region.12345 But the current expansion of its clinical entity recognizes PCV as prevalent also at the macula in elderly people irrespective of race and gender.6789 PCV can involve both the macular area and peripheral retina. Laser photocoagulation is advised for PCV. Though the lesion could respond to thermal laser, occurrence of subretinal haemorrhage is not uncommon. However, thermal laser photocoagulation is not justified when PCV involves the fovea.

Photodynamic therapy (PDT) with verteporfin has been proven beneficial for patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD).101112 Verteporfin therapy has also been found beneficial in CNV secondary to myopia, however data for histoplasmosis, angioid streaks and idiopathic CNV are limited and only suggest possible benefit.1314 Hence, PDT with verteporfin for PCV involving the fovea appears to be a viable option. This article is a retrospective evaluation of PDT using Verteporfin (Visudyne) in PCV involving the fovea in Indian eyes.

Materials and Methods

This analysis consists of 9 eyes of 9 consecutive patients diagnosed with PCV and subfoveal involvement during the period September 2001 to October 2002.

The diagnosis of PCV was based on clinical examination and Indocyanine Green Angiography (ICGA), clinically seen either as multiple areas of Pigment Epithelial Detachment (PED) with, haemorrhage serosanguinous serous detachment of the macula with subretinal hard exudation or retinal thickening associated with visible subretinal yellowish orange nodules. On ICG angiography, it is seen as network of branching vessels and polypoidal lesions in the macular area or as a brightly fluorescing polypoidal lesion in the area of PED.

Ophthalmic examination included snellen′s visual acuity, Amsler grid, slitlamp biomicroscopy and indirect ophthalmoscopy. Fundus photographs, Fundus Fluorescein Angiography (FFA) and primarily Indocyanine Green Angiography (ICGA) was done initially in all patients and subsequently at each visit. Follow-up was done every month for 3 months, followed by every 2 months for the next 6 months, and at 12 months with basic ophthalmic examination and angiograms. All patients completed 12 months′ follow-up. ICGA was done using Confocal scanning laser ophthalmoscope (Heidelberg Retinal Angiograph, Heidelberg Engineering Inc, Heidelberg, Germany).

The treatment area was primarily based on the findings on ICGA and the associated leakages seen on FFA. This was used to calculate the greatest linear dimensions (GLD). Any area of hypofluorescence due to overlying thick blood or associated retinal pigment epithelial detachment (RPED) was included in GLD. Lesions temporal to the disk and at least 200 microns from the optic disc were treated. Only the area within 5400 microns was treated.

A diode laser of 689 nm Zeiss laser slitlamp delivery system (Visulas 690sTM Carl Zeiss, GmbH, Germany) was used. The system was tuned to deliver 50 mJ/ cm2 of energy at an intensity of 600 mW/cm2 over 83 seconds. Before starting the treatment the physician confirmed the parameters on the laser machine. Following TAP protocol,101112 the dose of verteporfin was calculated and diluted with 5% dextrose in water prepared up to 30 ml. The drug was infused at the rate of 3 ml per minute over a period of 10 minutes and 5 minutes later, laser light was applied and over the lesion area for 83 seconds. Patients were instructed to avoid direct bright light for 48 hours and wear sunglasses with low transmittance for 7 days.

Retreatment on follow-up visits was done after evaluation on ICGA. The criteria for retreatment were: the persistent polypoidal lesions that had potential to cause further exudations in the macula on ICGA and or associated presence of increased exudations as seen on clinical examination. When resolution of PCV was seen on ICG with sustained findings on two consecutive visits associated with clinical resolution after 6 months, ICG was not repeated.

The outcome parameters were: Improvement in VA defined as two Snellen line acuity increase on the Snellen Chart, stabilisation as ± one line and deterioration as more than two line Snellen acuity loss. The clinical outcome was measured as decrease in the exudation and retinal thickening, resolution of serous detachment and RPED. The angiographic outcome was based on ICGA. Success was defined as thinning or disappearance of the vascular network with resolution of the polypoids with minimal leakage. Informed consent was taken prior to PDT and the disease process was explained to every patient and the yet unproven value of treatment.

Results

Of 11 eyes of 10 patients, 9 eyes (81.8%) underwent PDT. 70% of the patients were females [Table 1]. Their ages ranged from 38 to 82 years (mean: 67.2 ± 12.98 years). The follow-up ranged from 12 months to 16 months (mean: 14.5 ± 0.7 months). The GLD varied from 3420-5400 microns (Mean: 4906 ± 613.3 microns). Repeat treatment was performed in one eye (11.1%).

Table 1
Table 1:
Demographic and treatment outcome

Seven of 9 eyes (77.8%) of the patients in this study had extensive exudation with areas of PED involving the macular area. After treatment these patients showed resolution with diffuse subretinal fibrosis [Figure 1]. Two eyes (22.2%) had PED with areas of subretinal and sub-RPE haemorrhage surrounding and partially sparing the fovea but involving the macula [Figure 2]. These eyes resolved completely with improvement in VA. All the eyes had foveal involvement. One eye which had also a few large extrafoveal large polyps was not included in the treatment area.

Figure 1
Figure 1:
Top left: Colour fundus photograph showing peripapillary PCV with foveal involvement. Top right: ICG angiogram showing large extrafoveal polyp along the inferotemporal vessel and multiple small polypoids in the foveal area. Middle left: Colour fundus photograph showing resolution 2 months following PDT. Middle Right: Corresponding ICGA shows resolved status of the polypoids and vascular patterns. Bottom left: Fundus appearance 6 months following treatment. Note the subretinal scarring (arrowhead). Bottom right: Fundus picture one-year following treatment
Figure 2
Figure 2:
Top left: Colour fundus photograph showing sub RPE haemorrhage with PED. Components of subretinal haemorrhage is also seen. Top right: Corresponding ICGA shows large area of hypofluorescences due to PED and subRPE / subretinal haemorrhage. Multiple polypoidal lesions are seen in the foveal area. Bottom left: Colour fundus picture 3 months following PDT. Note the resolution of PED and haemorrhage. Bottom right: Corresponding FA and ICGA (Inset) showing resolution of PCV 3 months following treatment

Initial VA ranged from 6/360 to 6/12 while final VA varied from 6/360 to 6/9 at the end of follow-up [Table 1]. VA improved by one line in 4/9 eyes (44.4%), which was less than the improvement outcome parameter. It remained unchanged in 5/9 eyes (55.6%). Considering the VA criteria, all the treated eyes had stable vision at the end of 12 months. None of the patients had decreased in vision from the baseline. A significant decrease in retinal thickness exudation and RPED or subretinal haemorrhage was observed in all the patients. However, most of our patients had large PED with subretinal exudates and thickening, hence the poor initial VA.

Post treatment, it was observed that more patients with subretinal exudations and serous sanguineous neurosensory or PED resolved with fibrosis (77.8%; Figure 1) than patients associated with haemorrhagic or serous RPED (22.2%; Figure 2). However, all the patients had stable VA at the end of follow-up. No adverse effects or events were observed during or after treatment with verteporfin.

ICGA was not done at the end of the 12th month follow-up, as the status was resolved on ICGA on previous two visits with clinical resolution.

Discussion

PCV has expanded over the past years, and the diagnosis is no longer restricted to specific demographic attributes or specific retinal locations. PCV has been reported in 85% (72.5%: haemorrhagic PED and 27.5%: exudative PED) of patients with RPED, subretinal haemorrhages and exudation in the macular area on ICGA in patients with haemorrhagic AMD.8 ICGA, clinical characteristics and demographic pattern often differentiate a PCV from occult CNV. The natural history of PCV involving the macular area suggests that 42.9% of the eyes will have visual loss and or stabilise vision within a mean follow-up of 39.9 months.15

We also know the favourable natural history of PCV, a chronic long-term persistent disease with some repeated recurrences and spontaneous resolutions of leakage or haemorrhage at the macula. Almost 50% of patients have favourable course.15 However, good visual acuity at the initial examination is the predictor of favourable outcome. But, again rest of the patients may have poor visual prognosis. Observation to allow favourable history to occur is a question when the fovea is involved. This is because, during the process of resolution associated damage by RPE alteration and subretinal scarring can occur in haemorrhagic and or sero sanguineous PCV to cause further decrease in visual outcome.

Treatment by photocoagulation in PCV associated with foveal involvement is not possible. Surgical treatment of the lesion is a practical impossibility. However, submacular surgery to remove the thick subretinal blood and exudation is a valid possibility. Shiraga et al16 reported the visual outcome of surgical treatment of submacular haemorrhage associated with idiopathic polypoidal choroidal vasculopathy. In all 5 eyes that underwent removal of submacular haemorrhage, most of the blood was removed at the end of the study. The remaining 3 eyes underwent pneumatic displacement with most of the subretinal blood displaced from the fovea and became much thinner. Later, laser treatment was performed in 4 eyes. Postoperatively, 3 eyes developed a retinal pigment epithelial tear without involving the fovea, one eye had retinal detachment and one eye developed subfoveal choroidal neovascularisation 8 months after surgery. Other surgical options are a possibility but the chances of altering the milieu of PED and the associated risk of complications with vitrectomy still exist.

Transpupillary Thermotherapy may have a value in the treatment of subfoveal lesions but the safety and efficacy is yet to be determined in PCV. Encouraging results have been shown in the treatment of CNV secondary to Myopia and AMD and other expanding indications with Verteporfin therapy.1011121314 The minimal risk of complications with improved safety and efficacy is the advantage of PDT in comparison to surgery.

The present study shows that 44.4% of eyes had one line improvement at the end of follow-up. In the remaining eyes VA was unchanged. Hence all the eyes had stable vision at the end of follow-up. All our patients were associated with either RPED, subretinal haemorrhage and exudation. Moreover, baselines VA of the study patients were poor but improvement in the clinical picture has been associated with either minimal improvement or unchanged vision. The baseline clinical characteristics of the sample probably are associated with mild to moderate subretinal fibrosis after resolution at the end of the follow-up. This is also the confounding factor in the visual improvement. However, if the case selection had included PCV without subretinal exudation or sero-sanguineous changes, subjective visual improvement may have been observed.

Photodynamic therapy for PCV has shown encouraging results and without any complications by Spaide et al.17 Sixteen consecutive patients underwent PDT for PCV. VA improved in 9 (56.3%), remained the same in 5 (31.3%) and decreased in 2 (12.5%). The mean change in VA of the group was an improvement of 2.38 lines (P = 0.004). The final VA was positively correlated with initial visual acuity (r = -0.83, P < 0.001) and negatively correlated with increasing age (r = -0.67, P = 0.005). However there was no correlation with size and number of treatments. In comparison, the visual outcome in the present study is not significant, primarily due to initial poor VA but the overall outcome appears beneficial. Recently, Lee et al18 have shown similar results.

Our results suggest that there is no adverse risk of PDT for PCV with subfoveal involvement. However, we do not know as yet if the conventional PDT treatment protocol is logical enough to prove its long-term efficacy. Results do suggest a possible beneficial effect of PDT in PCV with foveal involvement in this ethnic population. The relative rarity of the disease, poor initial VA and small sample size are limitations of the study. This pilot report suggests the potential benefit and requirement for further long-term treatment outcome with variety of presentation of PCV with foveal involvement.

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Keywords:

Photodynamic therapy; Verteporfin; sub retinal pigment epithelial haemorrhage; pigment epithelial detachment

© 2005 Indian Journal of Ophthalmology | Published by Wolters Kluwer – Medknow