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   Table of Contents      
ORIGINAL ARTICLE
Year : 2006  |  Volume : 54  |  Issue : 4  |  Page : 247-250

Combination therapy of intravitreal triamcinolone and photodynamic therapy with verteporfin for subfoveal choroidal neovascularization


1 Smt Kanuri Santhamma Retina Vitreous Center, Hyderabad, India
2 ICARE, L. V. Prasad Eye Institute, Hyderabad, India

Correspondence Address:
Nazimul Hussain
Smt Kanuri Santhamma Retina Vitreous Center, L.V. Prasad Eye Institute, L. V. Prasad Marg, Banjara Hills, Hyderabad - 500 034
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0301-4738.27949

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  Abstract 

Aim: To evaluate the six months follow-up outcome of combined intravitreal triamcinolone acetonide (IVTA) and photodynamic therapy (PDT) for subfoveal choroidal neovascularization compared to PDT alone.
Study design: Prospective interventional pilot study.
Materials and Methods:
Patients with six months follow-up of IVTA following PDT (Group I, eight eyes) and PDT alone (Group II, eight eyes) were included. Four mg/ 0.1 ml of IVTA was injected 7-10 days following PDT. The patients were reevaluated every month for the first two months and every three months thereafter in both the groups.
Results:
Group I: The mean age was 65.811.8 years (range: 47-79 years). Five patients were male. The total treatment sessions in six months were 11 (mean: 1.36). At six months, one eye had 10 letters gain and three eyes had > 10 letters loss. Four eyes had stable vision. Two eyes (25%) developed increased intraocular pressure (>40 mmHg) during follow-up. Group II: The mean age was 58.711.7 years (range: 46-76 years). Five patients were male. The total treatment sessions in six months were 17 (mean: 2.13). At six months, six eyes had 10 letters gain and none had > 10 letters loss. Two eyes had stable vision.
Conclusion: The mean number of treatment sessions following combination therapy of IVTA (4 mg) and PDT appears relatively less (1.36 at six months) compared to PDT alone (mean: 2.13). ( P =0.02)

Keywords: Intravitreal triamcinolone, photodynamic therapy, subfoveal choroidal neovascularization


How to cite this article:
Hussain N, Das T, Rawal H, Kallukuri SB, Mohan Ram L S, Khanna R. Combination therapy of intravitreal triamcinolone and photodynamic therapy with verteporfin for subfoveal choroidal neovascularization. Indian J Ophthalmol 2006;54:247-50

How to cite this URL:
Hussain N, Das T, Rawal H, Kallukuri SB, Mohan Ram L S, Khanna R. Combination therapy of intravitreal triamcinolone and photodynamic therapy with verteporfin for subfoveal choroidal neovascularization. Indian J Ophthalmol [serial online] 2006 [cited 2018 May 26];54:247-50. Available from: http://www.ijo.in/text.asp?2006/54/4/247/27949

Table 1: Demographic, clinical characteristics and visual acuity


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Table 1: Demographic, clinical characteristics and visual acuity


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Recently, photodynamic therapy (PDT) with verteporfin has been proved beneficial for subfoveal choroidal neovascularization (CNV). [1],[2],[3],[4],[5]PDT with verteporfin causes a short-term but powerful anti-angiogenic effect on the CNV.[6] It has been shown that a week after PDT there is a remarkable decrease in perfusion of the neovascular complexes.[7],[8] Often local vascular endothelial growth factor (VEGF) increases after PDT along with associated increase in macular edema.[9] There is upregulation of VEGF and VEGF receptor 3 expression suggesting increased permeability and vascular proliferation. This is selectively localized at the damaged choroidal endothelium.

Histopathologic evidence also suggests that inflammatory process and choroidal neovascularization commonly accompany each other. This has also been found to be proportional to the amount of VEGF.[7],[8] Hence, shortly following the treatment, reperfusion and growth of neovascularization could occur. In such a situation, it is necessary to retreat to achieve complete occlusion of the neovascular process.

Corticosteroids have both antiinflammatory and antiangiogenic properties.[8] Intravitreal triamcinolone (IVTA) is reportedly useful in the management of exudative age-related macular degeneration (AMD).[10],[11] PDT with verteporfin not only induces marked temporary antiangiogenic effect but also induces VEGF and VEGF receptor 3 expression. This enables proliferation. Hence, with combination therapy of IVTA and PDT, it may be possible to tackle the additional effects that may occur following PDT.

In this communication we report the six months follow-up outcome of combination therapy of PDT and IVTA in subfoveal CNV in eyes of Indian origin.


  Materials and Methods Top


Patients who completed six months follow-up of IVTA following PDT with verteporfin (Group I, "case") and PDT alone (Group II, "control") were included in the study. The PDT alone group was selected from the prospective PDT-AMD treatment group in the hospital. The inclusion criteria were subfoveal CNV, visual acuity (VA) 20/200 and greatest linear diameter 5400 microns. Patients with prior laser therapy for any macular disease, any other vascular or nonvascular retinopathy that affects the macula, cataract that obscures macular evaluation and eyes with glaucoma were excluded.

Subfoveal CNV was defined as presence of entire CNV component lying within the foveolar avascular zone (FAZ) or part of the CNV extending beneath the geometric center of FAZ. Protocol of PDT with verteporfin in both the groups was similar to the TAP/VIP trial.[1],[3]

Nature of treatment was explained and informed consent was taken from every patient.

All patients underwent VA assessment with ETDRS chart at four meters in standard conditions. The clinical examination included slit lamp, gonioscopy, applanation tonometry and fundus examination with 90 D non contact lens and indirect ophthalmoscopy. A color fundus photograph and digital (Carl Zeiss, Zeiss Gmbh, Germany) or confocal scanning laser fundus fluorescein angiography (Heidelberg retinal angiograph, Heidelberg, Germany) was done to evaluate and measure the CNV lesion. Trained optometrists did the above examinations in every visit.

The greatest linear dimension (GLD) of the lesion was measured from the fluorescein angiogram. Any area of hypofluorescence due to overlying blood or serous detachment of the retinal pigment epithelium contiguous with CNV was considered in the GLD. One thousand micron was added to GLD to calculate the spot size. Verteporfin was infused intravenously over 10 min. Fifteen minutes later, a laser light (689 nm) was delivered at 50 J/cm[2] at an intensity of 600 mW/cm[2] for 83 seconds.

Four mg/ 0.1 ml of IVTA was injected between 7th-10th days following PDT. Several drops of topical proparacaine were instilled and then single drop of 5% betadine was instilled in the cul-de-sac. Intravitreal injection was given under sterile condition. Prior to the intravitreal injection, paracentesis was done with 30-gauge needle and then 0.1 ml of 4 mgm triamcinolone acetonide was injected in the inferonasal or inferotemoral quadrant 3.5 to 4.0 mm from the limbus using a 26-gauge needle. A single drop of 5% betadine was instilled in the cul-de-sac at the end of the procedure. The patients were reevaluated the first day (only for Group I), every month for the first two months and then every three months thereafter in both the groups.

Repeat PDT was performed in both the groups if there was any evidence of active leakage on follow-up angiogram as per the guidelines of the TAP/VIP study.[1],[3] Repeat IVTA was not given.

The primary outcome measure was the mean number treatments and the secondary outcome measure was the change in VA. Improvement of vision was defined as gain of 10 letters (two lines) and deterioration as 10 letters loss. Stable vision was defined as a loss or gain of upto 9 letters. Complications were noted during the follow-up. The PDT has been approved by the institutional review board (IRB) for the treatment of CNV and proliferative vasculopathy in 2001. Informed consent was taken for PDT and existing off-label use of intravitreal triamcinolone prior to institution of therapy.

Statistical analysis

To find out the difference in mean number of treatments and difference in posttreatment letter acuity in the two groups, nonparametric Mann Whitney test was done. A P value of < 0.05 was considered significant.


  Results Top


The demography and lesion characteristics in both groups were similar.

Group I [Figure - 1] and [Figure - 2]: The mean age of eight patients was 65.8 11.8 years (range: 47-79 years). Five patients were male. Left eye was affected in four eyes. All patients had subfoveal CNV. Seven of eight eyes had classic CNV. Choroidal neovascularization was secondary to AMD (six eyes), parafoveal telengiectasis (one eye) and myopia of > 6 D (one eye).

The initial GLD ranged from 860-4950 m (mean: 3240 1484.8 m). The total treatment sessions in six months were 11 (mean: 1.36). The initial VA was 20/40 in two eyes, 20/50 -20/100 in two eyes and 20/125 -20/200 in four eyes. Five eyes had VA of 20/50 -20/100 and three eyes had 20/125 -20/200 at six months follow-up. At six months, one eye had 10 letters gain and three eyes had > 10 letters loss. Thus, one eye had improvement, three eyes had deterioration and four eyes had stable vision [Table - 1].

Two eyes (25%) developed increased intraocular pressure (IOP) (>40 mmHg) during follow-up (second month) and were controlled with topical antiglaucoma medications (two topical drugs for two months).

Group II : The mean age of eight patients was 58.7 11.7 years (range: 46-76 years). Five patients were male. Right eye was affected in five eyes. All patients had subfoveal classic CNV and it was secondary to AMD in all eyes.

The initial GLD ranged from 1520-4200 m (mean: 2766 960.7 m). The total treatment sessions in six months were 17 (mean: 2.13). The initial VA was 20/40 in one eye and 20/50 -20/100 in seven eyes. Six eyes had VA of > 20/40 and two eyes had 20/125 -20/200 at six months follow-up. At six months, six eyes had 10 letters gain and none had > 10 letters loss. Thus six eyes had improvement and two eyes had stable vision [Table - 1].

The number of PDT treatments was significantly less in Group I patients compared to Group II in six months ( P =0.02). Six eyes had > 10 letters gain in Group II and one eye had vision improvement in Group I suggestive of significant difference in posttreatment letter acuity between the two groups ( P =0.03).


  Discussion Top


This interim six months prospective comparative study evaluated the outcome of combination therapy of PDT and IVTA compared to PDT alone. In both groups, the vision could be stabilized in at least half of the eyes (100% in Group II vs. 62.5% in Group I). The visual improvement was better in Group II (75%) compared to Group I (12.5%). The only significant advantage observed in the combination therapy (Group I) was the decrease in the mean number of treatments compared to PDT alone ( P =0.02).

Spaide et al.[7],[8] have reported six and 12 months follow-up outcome following combination therapy. In the newly treated group (13 eyes) the mean change in VA was 2.4 lines in Snellen's acuity at the end of six months and 2.5 lines at the end of 12 months. The mean number of treatments was 1.24 at 12 months. In contrast, Rechtman et al .[11] used combination treatment in each repeat treatment. Most of the eyes (56.5%) with any lesion had stable vision (+ 14 letters). This study did not show the statistical significance of combination therapy and the lesion type. Three patients received second session of combined treatment after six months (mean: 1.2).

The present and reported studies[7],[8],[11] suggest that the use of IVTA reduces the mean number of PDT treatments. We did not notice any significant improvement of vision with the combined therapy in this study.

We did not observe any eventful adverse effects. Two eyes (25%) in Group I had glaucoma after two months, which was controlled with antiglaucoma medication. Spaide et al .[8] reported increase in IOP beyond 24 mmHg in 10 of 26 (38.5%) eyes and Rechtman et al .[11] reported transient IOP elevation in 28.5% and cataract progression in 50% of the phakic eyes.

The timing of IVTA was different in the published studies which varied from same day injection up to within six weeks.[7],[8],[11] We injected between 7th and 10th day. The present study demonstrated that there was 12.5% improvement of vision and over 50% stabilization of vision at six months after combined PDT and IVTA compared to the 75% improvement of vision in the PDT alone group. All the same, we cannot comment on the vision due to small sample size. But it was evident that the number of retreatments reduces when intravitreal triamcinolone is combined with PDT.

In a developing country like India where the cost of the drug in repeat treatments affects the willingness of the patient, combination therapy of IVTA and PDT could reduce the recurring cost.

This study raises the following questions:

1. Is combination therapy necessary in retreatments?

2. Does the type of lesion (classic or occult) influence the visual outcome in the combined therapy?

3. Does the time of intervention with IVTA affect the outcome?

4. Does the use of IVTA affect the final VA?

A larger prospective study could address these above questions.


  Conclusion Top


The mean number of treatment sessions following combination therapy of IVTA (4 mg) and PDT appears relatively less (1.36 at six months) compared to PDT alone (mean: 2.13 at six months; P =0.02). This is unlikely to affect the visual outcome. We believe that combined therapy could prevent recurrence of CNV.



 
  References Top

1.
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. 1
    
2.
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. 2
    
3.
Verteporfin In Photodynamic Therapy Study Group. Verteporfin therapy of subfoveal choroidal neovascularisation in age related macular degeneration: Two-year results of a randomized clinical trial with occult no classic choroidal neovascularistion - verteporfin in photodynamic therapy report 2. Am J Ophthalmol 2001;131:541-60.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.
Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, et al . Verteporfin therapy of subfoveal choroidal neovascularisation in patients with age related macular degeneration. Additional information regarding baseline lesion compositions impact on visual outcome. TAP Report No. 3. Arch Ophthalmol 2002;120:1443-54.  Back to cited text no. 4
    
5.
Azab M, Boyer DS, Bressler NM, Bressler SB, Cihelkova I, Hao Y, et al . Verteporfin therapy of subfoveally minimally classic choroidal neovascularisation in age related macular degeneration. 2 - year results of a randomized clinical trial. Arch Ophthalmol 2005;123:448-57.   Back to cited text no. 5
    
6.
Schmidt - Erfurth U, Michels S, Barbazetto I, Laqua H. Photodynamic effects on choroidal neovascularisation and physiological choroids. Invest Ophthalmol Vis Sci 2002;43:830-41.  Back to cited text no. 6
    
7.
Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization. Ophthalmology 2003;110:1517-25.  Back to cited text no. 7
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8.
Spaide RF, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization. Ophthalmology 2005;112:301-4.  Back to cited text no. 8
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9.
Schmidt-Erfurth U, Schlotzer-schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3 and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 2003;44:4473-80.  Back to cited text no. 9
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10.
Challa JK, Gillies MC, Penfold PL, Gyory JF, Hunyor AB, Billson FA. Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up. Aust NZ J Ophthalmol 1998;26:277-81.  Back to cited text no. 10
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11.
Rechtman E, Danis RP, Pratt LM, Harris A. Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularisation in age related macular degeneration. Br J Ophthalmol 2004;88:344-7.   Back to cited text no. 11
[PUBMED]  [FULLTEXT]  


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