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   Table of Contents      
ORIGINAL ARTICLE
Year : 2007  |  Volume : 55  |  Issue : 4  |  Page : 277-281

A pilot trial for comparison of photodynamic therapy and transpupillary thermotherapy for the management of classic subfoveal choroidal neovascularization secondary to age-related macular degeneration


1 Centre for Sight, B-5/24, Safdarjang Enclave, New Delhi, India
2 Vitreo-Retina Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi - 110 029, India

Date of Submission21-Aug-2005
Date of Acceptance08-Feb-2007

Correspondence Address:
Raj V Azad
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0301-4738.33040

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  Abstract 

Aim: The aim of the study was to compare the visual outcomes of photodynamic therapy (PDT) with verteporfin and transpupillary thermotherapy (TTT) for classic subfoveal choroidal neovascularization (CNVM) secondary to age-related macular degeneration (ARMD).
Settings and Design: Patients with subfoveal classic CNVM caused by ARMD attending vitreo-retinal services at a tertiary care setup were included in this nonrandomized, open label, prospective, clinical, comparative pilot trial.
Materials and Methods: Standardized refraction, visual acuity testing, evaluation of fundus and serial color photography and fundus fluorescein angiography were carried out to evaluate the effects of treatment in 32 eyes each undergoing either PDT or TTT. Follow-up was carried out at four weeks, 12 weeks and six months. Retreatment if indicated was carried out three months post treatment.
Results:
Stabilization or improvement occurred in 69% of patients undergoing PDT and 50% patients undergoing TTT at six months of follow-up. Among patients with a pretreatment visual acuity greater than or equal to 20/63, only one out of six patients who underwent PDT had a drop of visual acuity > 2 lines as compared to four patients (100%) who underwent TTT. ( P =0.0476, two-tailed Fisher's exact test).
Conclusion:
For short-term preservation of vision in patients of classic CNVM due to ARMD, PDT seems to be better than TTT if the pre-laser best corrected visual acuity is > 20/63 but both are equally effective if pre-laser best corrected visual acuity is < 20/63.

Keywords: Classic choroidal neovascularization, photodynamic therapy, transpupillary therapy


How to cite this article:
Tewari HK, Prakash G, Azad RV, Talwar D, Kai S. A pilot trial for comparison of photodynamic therapy and transpupillary thermotherapy for the management of classic subfoveal choroidal neovascularization secondary to age-related macular degeneration. Indian J Ophthalmol 2007;55:277-81

How to cite this URL:
Tewari HK, Prakash G, Azad RV, Talwar D, Kai S. A pilot trial for comparison of photodynamic therapy and transpupillary thermotherapy for the management of classic subfoveal choroidal neovascularization secondary to age-related macular degeneration. Indian J Ophthalmol [serial online] 2007 [cited 2020 Jun 1];55:277-81. Available from: http://www.ijo.in/text.asp?2007/55/4/277/33040

Table 6: Complications of the two laser modalities seen during the treatment period

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Table 6: Complications of the two laser modalities seen during the treatment period

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Table 5: Change in best corrected visual acuity after laser treatment of patients with prelaser visual acuity less than 20/63 (or ETDRS letter score 60)

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Table 5: Change in best corrected visual acuity after laser treatment of patients with prelaser visual acuity less than 20/63 (or ETDRS letter score 60)

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Table 4: Change in best corrected visual acuity after laser treatment of patients with prelaser visual acuity equal to or more than 20/63 (or ETDRS letter score 60)

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Table 4: Change in best corrected visual acuity after laser treatment of patients with prelaser visual acuity equal to or more than 20/63 (or ETDRS letter score 60)

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Table 3: Comparison of percentage of eyes with improvement or stabilization and deterioration in vision

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Table 3: Comparison of percentage of eyes with improvement or stabilization and deterioration in vision

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Table 2: Change in visual acuity (in letter scores from ETDRS chart) of patients undergoing photodynamic therapy and transpupillary thermotherapy

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Table 2: Change in visual acuity (in letter scores from ETDRS chart) of patients undergoing photodynamic therapy and transpupillary thermotherapy

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Table 1: Baseline parameters of patients undergoing photodynamic therapy and transpupillary thermotherapy

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Table 1: Baseline parameters of patients undergoing photodynamic therapy and transpupillary thermotherapy

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Age-related macular degeneration (ARMD) is today the commonest cause of visual loss in patients over the age of 65 years in the western world. [1] Ninety per cent of the visual loss due to ARMD is because of the exudative form of the disease. While treatment of extrafoveal choroidal neovascular membrane (CNVM) due to ARMD can be easily managed by direct laser photocoagulation of the lesion, the treatment of subfoveal CNVM by this technique results in ≥ 6 lines loss in 20% patients in three months. [2] Management of subfoveal CNVM, especially those with good visual acuity, therefore poses a formidable challenge. In recent times, two important laser treatments have emerged for the treatment of subfoveal CNVM, i.e. photodynamic therapy (PDT) and transpupillary thermotherapy (TTT). The utility of PDT with verteporfin for subfoveal classic CNVM secondary to ARMD has been definitively confirmed by the TAP trial. [3],[4] Anecdotal reports of treatment of classic subfoveal CNVM due to ARMD by TTT are available in the literature, some of which have reported the results in a large number of patients. [5],[6],[7],[8] However, there is no prospective comparative study of TTT with PDT in a homologous group available in the literature. The aim of the study was to carry out a prospective comparative trial of PDT versus TTT in patients with classic subfoveal CNVM.


  Materials and Methods Top


The subjects of this pilot study were 32 eyes of 30 patients of subfoveal classic or predominantly classic CNVM secondary to ARMD, who were willing to participate in the trial. The recruitment for the study was done from 2002 September to 2003 December. All patients who agreed to participate in the study were given a choice of PDT and TTT after explaining the costs, benefits and risks of each treatment. This approach provided a measure of randomization, though true randomization was not possible in this trial due to substantial differences in the cost of the two treatments . The two groups in the study comprised 16 eyes of 16 patients who underwent PDT and 16 eyes of 14 patients who underwent TTT. The principal inclusion criteria for patients participating in the trial were age > 50 years, fluorescein angiographic evidence of subfoveal classic CNVM due to ARMD, greatest linear dimension (GLD) of entire lesion of 5400 microns or less with the nasal side of the CNV being located more than 500 microns from the temporal border of the optic nerve head. As the treatment protocol in Indian eyes was evolving at the time of initiation of the study and results in Indian eyes were yet to be seen, it was considered to stay further away from causing damage to the papillomacular bundle and optic nerve head. All the patients included in the study had to have a best corrected visual acuity (BCVA) ≥20/400 and ≤20/32 with ocular media clear enough to perform all examinations, investigations and treatment by PDT and TTT.

Only patients who were willing and able to come for follow-up for at least six months were included in the study. The principal exclusion criteria were patients with CNVM due to other causes, previous history of central serous retinopathy, concurrent ocular pathology, history of prior laser photocoagulation and substantial hepatic, renal or neurological disease or uncontrolled hypertension. Other illnesses that could independently affect visual acuity such as diabetic retinopathy, hypertensive retinopathy, collagen vascular diseases and retinovascular diseases were excluded from the study. Patients with active hepatitis or clinically significant liver disease were also excluded from the study.

Standardized refraction, visual acuity testing with early treatment of diabetic retinopathy study (ETDRS) charts, ophthalmic examination of the anterior segment by slit-lamp biomicroscopy and of posterior segment by direct and indirect ophthalmoscopy and slit-lamp biomicroscopy using a 90D lens were carried out in all patients. Color photography and fundus fluorescein angiography (FFA) were carried out with a Zeiss FF-450 IR digital imaging system. Color photography was carried out by using a Sony 950 DXC video camera while fluorescein angiography was carried out by Kodak 1.6 Mega pixel camera with a megaplus lens. Follow-up was carried out at four weeks, 12 weeks and six months following the treatment. All the tests were carried out at each follow-up.

Transpupillary thermotherapy was carried out using a dedicated slit-lamp with infrared diode laser (810 nm) (OcuLight SLx Infrared, Iridex Corporation, CA, USA), mounted and modified to provide a spot size of up to 3 mm. It was done under topical anesthesia with continuous observation through the slit-lamp. The spot size corroborated with the angiographic size of the lesion. Due to deeply pigmented fundi in the Indian population, the power setting had to be calibrated in each patient individually and no blanket protocol could be followed in TTT. Test spots were given in the inferonasal quadrant (and thus disturbing the superior field, normally covered by the eyelid) with progressive reduction in power till a just visible reaction occurred. It took 3 to 5 test spots on an average to come to this value. A 10% reduction in thus obtained power was used to do TTT. If the lesion was > 3 mm, multiple almost confluent spots, centering the first 3 mm spot on the entire foveal avascular zone was applied. End point was no visible reaction at the end of treatment. Time of initial spot was kept as 60 seconds. Test spots in the inferior quadrant of the eye were used to titrate the final power to be used for treatment.

The standard therapeutic regimen for PDT carried out in our patients has already been described in the treatment of ARMD with PDT (TAP) trials. [3],[4] Photosensitizing dye Visudyne® (Novartis AG, Basel, Switzerland) was injected intravenously at a dose of 6 mg/m 2 body surface area.The dry form of the drug was reconstructed by adding 7 ml of sterile water for injection to reach a final concentration of 2 mg/ml. The required amount of drug was diluted in 5% dextrose to reach a final volume of 30 ml. The drug was injected over a period of 10 min using an infusion pump. Following which a diode laser irradiation at 690 nm was carried out with slit-lamp delivery system (Zeiss Visulas 690s laser and Visulink PDT/U adapter, Carl Ziess Inc. Thornwood, NY). It delivered 50J/cm 2 at an intensity of 600 mw/cm 2 , over 83 seconds to a spot size that was 1000 microns greater than GLD of the lesion (so as to have a margin of additional treatment area to compensate for any slight eye movement during treatment).

Although both treatments work on different principles, the final end result could be clinically quantified with FFA. Transpupillary thermotherapy retreatment wasn't well defined in the literature at the time of the initiation of study; the retreatment criteria were considered as similar for both groups. Retreatment was considered if FFA performed 12 weeks after the initial therapy showed evidence of dye leakage.

Stabilization of visual acuity was defined as a visual acuity decrease of less than five letters on ETDRS chart. Visual acuity change was the primary treatment outcome measured and stabilization or an improvement in visual acuity was considered a positive outcome.

Statistical analysis used

Wilcoxon Rank sum test was used to analyze changes in mean visual acuity as well as demographic data and two-tailed Fischer's exact test was used to analyze quantitative difference in outcomes wherever required.


  Results Top


The demographic data of the patients included in the present study in both the groups is given in [Table - 1]. There was no statistically significant difference seen in variables in both the groups.

The changes in mean visual acuity in the ETDRS chart following treatment by PDT and TTT are shown in [Table - 2].

Scatter analysis of the prelaser and postlaser BCVA for both groups shows similar change in visual acuity at six months [Graph 1].

At the end of six months, 11 of the 16 patients treated by PDT had less than one line loss of visual acuity or had improved from baseline, as compared to eight of the 16 patients managed by TTT [Table - 2]. Visual acuity loss of ≤ 15 letters of the ETDRS chart was seen in 13 out of 16 treated by PDT and 14 out of 16 treated by TTT. The difference between these two groups was not statistically significant ( P =0.47 and P =1.0 respectively, Fischer's two-tailed test) [Table - 2].

In patients with initial visual acuity ≥ 20/63 there was fall of ≥ 2 lines at six months in all four of the patients who underwent TTT. Only one of the six patients undergoing PDT with similar pretreatment visual acuity had a similar drop in vision ( P =0.048, Fischer's two-tailed test). There was no statistically significant difference between the GLD and the initial visual acuity between patients undergoing PDT and TTT with a vision of <20/63 ( P value = 0.74 and 0.2 respectively, Rank sum test) [Table - 4].

In patients with initial visual acuity < 20/63 there was fall of ≥ 2 lines in one out of 12 patients of TTT and two out of 10 patients of PDT ( P =0.57, Fischer's two-tailed test). There was no statistically significant difference between the GLD and the pretreatment visual acuity between patients undergoing PDT and TTT with a vision of < 20/63 ( P value =0.57 and 0.84 respectively, Rank sum test) [Table - 5].

A few complications of PDT and TTT occurred in the study patients [Table - 6]. All of them have been described in the literature previously.

Representative FFA of patients undergoing PDT and TTT have been shown in [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4].


  Discussion Top


There has been a large long-term randomized double-blind trial for the efficacy of PDT with verteporfin in the form of the TAP trial. [3],[4] This trial has shown that patients treated by PDT behave significantly better as compared to placebo in terms of visual outcome. At six months, patients treated by PDT had a mean change on ETDRS Charts of -8.5 letters compared to a change of -16 letters in patients receiving placebo. Patients included in the present study who were treated by PDT showed better results than the TAP trial at six months with a change of mean -0.62 letters on the ETDRS chart. The Japanese ARMD trial [9] for treatment of classic CNVM by PDT with verteporfin showed a change from baseline of +6.5 letters at 12 months. While it is too early to make any definitive comment, the possibility of differences in the rate of response of the Caucasian and Asian population to PDT needs to be investigated further.

Verma et al . have evaluated 50 consecutive patients of CNVM of which 14 patients had classic CNVM. [5] Their patients had a mean pretreatment letter score of 39.52. They found a mean change of - 4.24 letters at the end of follow-up. Our patients undergoing TTT had a pretreatment mean score of 50.73, which is 11.21 letters higher. We observed a mean change of -1.58 at the six months follow-up after TTT. Agarwal et al . did a retrospective analysis of 28 patients (seven of them were classic, seven mixed and 14 occult). [8] They showed a change of - 12.85 letters from a mean initial vision of 55 letters (converted to Snellens' equivalent). The efficacy of TTT in the present study was at least as high as previous reports in the literature.

The present study is the first prospective comparative trial of PDT and TTT for treatment of classic subfoveal CNVM using standardized protocol for evaluation of the patients.

Both the treatment groups in the study were matched in terms of age, GLD and initial visual acuity. The study showed that there was no significant difference in the mean visual acuity at the end of follow-up between the two groups at six months. However, subgroup analysis showed a significant difference between the two groups in patients with good initial visual acuity (≥ 20/63). Patients with good visual acuity treated with PDT showed significantly better visual outcome at six months compared to those treated by TTT. Not only was there a difference between mean letter score of the two groups but also in the mean change in letter score between the two groups at six months follow-up. Therefore the difference in the outcome was reflected not only into the groups per se but also in the individual visual outcomes. This difference was not explained by difference in the GLD or the initial visual acuity of the two groups. This difference was not seen in patients with vision poorer than 20/63. In patients with poor initial visual acuity it may be hypothesized that the damage to the photoreceptors by the disease process had already reached increased levels where the use of a selective laser like PDT may not make a significant difference to the overall outcome compared to a thermal laser like TTT. The differences therefore do not get reflected in overall visual outcome. This finding if substantiated by a large, randomized trial could have significant influence on the pattern of healthcare management, especially in developing countries where economic constraints may play a big role in the selection of the modality of treatment.

Based on the result of the present study we recommend that patients of subfoveal classic CNVM secondary to ARMD with good vision (≥ 20/63) should be treated with PDT in view of the significantly better visual outcome at six months.

While preliminary results suggest that the use of TTT seems to an acceptable option when the initial visual acuity is <20/63, the validity of this statement needs to be confirmed with a larger prospective study of PDT and TTT in patients with subfoveal classic CNVM due to ARMD.

 
  References Top

1.
Neely K, Bressler NM, Bressler SB. Epidemiology, clinical characteristics and natural history of age-related macular degeneration. In : Ophthalmology Clinics of North America: Macular Diseases. editors, Grossniklaus, HE, Kincaid, MC. WB Saunders Company: 1993.   Back to cited text no. 1
    
2.
Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Macular Photocoagulation Study Group. Arch Ophthalmol 1991;109:1242-57.   Back to cited text no. 2
    
3.
Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Arch Ophthalmol 1999;117:1329-45.  Back to cited text no. 3
    
4.
Bressler NM; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: Two-year results of 2 randomized clinical trials-tap report 2. Arch Ophthalmol 2001;119:198-207.  Back to cited text no. 4
    
5.
Verma L, Tewari HK, Nainiwal S, Ravindranathan J. Transpupillary thermotherapy in subfoveal choroidal neovascular membrane secondary to age-related macular degeneration. Indian J Ophthalmol 2004;52:35-40.   Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.
Nagpal M, Nagpal K, Sharma S, Puri J, Nagpal PN. Transpupillary thermotherapy for treatment of choroidal neovascularization secondary to age-related macular degeneration in Indian eyes. Indian J Ophthalmol 2003;51:243-50.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.
Newsom RS, McAlister JC, Saeed M, McHugh JD. Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularisation. Br J Ophthalmol 2001;85:173-8.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.
Agarwal M, Shanmugam MP, Gopal L, Shetty N, Bhende M, Gopal L, et al . Transpupillary thermotherapy for choroidal neovascular membrane in age related macular degeneration. Indian J Ophthalmol 2004;52:45-9.   Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.
Japanese Age-Related Macular Degeneration Trial (JAT) Study Group. Japanese age-related macular degeneration trial: 1-year results of photodynamic therapy with verteporfin in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2003;136:1049-61.  Back to cited text no. 9
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]



 

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