The Temporal Sequence of Combined Intravitreal Triamcinolone Acetonide and Photodynamic Therapy for Exudative Age-Related Macular Degeneration
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■ c l i n i c a l s c i e n c e ■
The Temporal Sequence of Combined
Intravitreal Triamcinolone Acetonide and
Photodynamic Therapy for Exudative
Age-Related Macular Degeneration
Daniel B. Roth, MD; Kaushal M. Kulkarni, MD; William J. Feuer, MS
n BACKGROUND AND OBJECTIVE: To com- .084), 6 to 12 weeks of follow-up (P = .085), or 1 year
pare visual acuity results in patients with exudative of follow-up (P = .093). When visual acuity outcomes
age-related macular degeneration treated with two dif- were adjusted for baseline visual acuity, spot size, le-
ferent temporal sequences of combination intravitreal sion type, age, and gender, there was no significant
triamcinolone acetonide and photodynamic therapy difference in visual acuity at 6 to 12 weeks (P = .44)
with verteporfin. or 1 year (P = .28).
n PATIENTS AND METHODS: A retrospective, n CONCLUSIONS: There appears to be no signifi-
comparative, interventional case series was used. Thir- cant difference in visual outcomes in eyes with exu-
ty-one eyes received intravitreal triamcinolone aceton- dative age-related macular degeneration treated with
ide 1 week prior to photodynamic therapy, and 30 eyes intravitreal triamcinolone acetonide 1 week prior to
received intravitreal triamcinolone acetonide followed photodynamic therapy or those treated with intravit-
by photodynamic therapy the same day. real triamcinolone acetonide on the same day as pho-
todynamic therapy.
n RESULTS: There was no significant difference
in visual acuity between the groups at baseline (P = [Ophthalmic Surg Lasers Imaging 2008;39:12-16.]
INTRODUCTION treatment for choroidal neovascularization secondary
to exudative age-related macular degeneration. How-
Since its approval in 1999, photodynamic thera- ever, most patients undergoing PDT with verteporfin
py (PDT) with verteporfin has become an important still experience a decrease in mean visual acuity and re-
quire a high number of retreatments. This is because
the anti-angiogenic effects of PDT are often short lived
From the Retina Vitreous Center (DBR, KMK), Department of Ophthal-
mology, Robert Wood Johnson Medical School, New Brunswick, New Jersey; owing to the reopening of the choroidal neovascular
and the Bascom Palmer Eye Institute (WJF), University of Miami Miller complex.1-3 Furthermore, photodynamic damage to
School of Medicine, Miami, Florida.
the surrounding normal choroidal vasculature and
Accepted for publication September 27, 2007. retinal pigment epithelium can lead to new blood ves-
Address correspondence to Daniel B. Roth, MD, Department of Oph-
sel formation, which feeds the neovascular complex.4
thalmology, University of Medicine & Dentistry of New Jersey, Robert Wood
Johnson Medical School, Clinical Academic Building, 4th Floor, 125 Paterson It has been hypothesized that inflammatory media-
Street, New Brunswick, NJ 08901-1977. tors also contribute to the development of choroidal
12 Ophthalmic Surgery, Lasers & Imaging · January/February 2007 · Vol 39, No 1neovascularization associated with age-related macular PATIENTS AND METHODS
degeneration5 and that PDT itself may induce a rapid
inflammatory tissue response.6 We conducted a retrospective chart review of 61
Corticosteroids are potent anti-angiogenic and eyes of 60 patients. All patients were treated by one of
anti-inflammatory agents that have the potential to eight retina specialists at a single vitreoretinal practice.
mediate the deleterious effects of PDT. They have The study protocol was approved by the Institutional
been widely used in a variety of ocular conditions to Review Board of the Robert Wood Johnson Medical
suppress intraocular inflammation and exudation and School.
have been used with modest success as monotherapy in Inclusion criteria were patients with choroidal neo-
the treatment of exudative age-related macular degen- vascularization secondary to age-related macular degen-
eration.4 The possible synergistic effect of intravitreal eration who were older than 55 years. No restriction
triamcinolone acetonide (IVTA) in combination with was made regarding lesion subtype. Exclusion criteria
PDT for choroidal neovascularization was first reported included lesion size greater than 6.4 mm greatest lin-
by Spaide et al.7,8 and has been supported by positive ear diameter, lesions with greater than 50% subretinal
results from several further reports.9-19 These studies blood, eyes with subretinal fibrosis, or eyes with cho-
have shown that combined IVTA and PDT results in roidal neovascularization from other etiologies.
the stabilization of vision with the possibility of slight At baseline and at each follow-up visit (1 week, 1
visual improvement. They have also shown a decrease month, 6 to 12 weeks, 6 months, and 1 year), patients un-
in the number of required retreatments with PDT. derwent visual acuity measurement with a Snellen chart,
The mechanism through which this is accomplished ophthalmologic examination including slit-lamp biomi-
is unclear and, as suggested by Spaide et al., the sequence croscopy, fundus examination, and intraocular pressure
and temporal interval of the combined treatments is like- measurement. All patients who required retreatment were
ly to affect the outcome.7 It has been suggested that the treated with IVTA and PDT according to their initial
injection of IVTA up to 1 month prior to PDT would treatment group (1 week prior or same day).
offer two theoretical advantages. First, the decreased The intravitreal injection was performed after pre-
capillary permeability, reduction of subretinal fluid, and paring the eye with antibiotic drops followed by 5% to
flattening of the retinal pigment epithelium at the time 10% povidone iodine solution. Anesthesia consisted of
of PDT treatment could hypothetically lead to more topical proparacaine followed by either subconjuncti-
effective closure of blood vessels within the lesion.19,20 val lidocaine 1% given through a 30-gauge needle or
Second, IVTA should decrease expression of vascular cotton swabs of lidocaine 4% applied to the injection
endothelial growth factor and other inflammatory me- site. A sterile wire lid speculum was inserted in the eye.
diators prior to the administration of PDT.21 However, Four milligrams of triamcinolone acetonide (Kenalog 1
these advantages are merely theoretical and steroids may cc, 40 mg/mL; Bristol-Myers Squibb, New York, NY)
simply suppress the deleterious inflammatory effect of was drawn from a new, sterile bottle without removal
PDT treatment in the surrounding retinal and choroidal of the supernatant and injected through the pars plana
tissues or suppress angiogenic growth factors that would of the inferotemporal quadrant with a 27-gauge nee-
promote continued choroidal neovascularization. These dle. Rarely, a paracentesis was performed as necessary.
latter mechanisms could be equally accomplished with PDT was performed according to the recommended
PDT followed by IVTA. standard procedure for approved forms of age-related
We report a retrospective, comparative, interven- macular degeneration.1,2
tional case series of two groups of eyes with choroidal The primary endpoints were visual acuity at 6 to
neovascularization secondary to exudative age-related 12 weeks and at 1 year. Proportions were compared be-
macular degeneration that were treated with combined tween the groups with the chi-square test or Fisher’s
IVTA and PDT. We sought to determine whether there exact test as appropriate. Means were compared with
was a difference in visual outcomes between eyes that the independent samples t test and comparison of the
received IVTA 1 week prior to PDT (1 week prior visual results between the two groups after adjusting
group) and eyes that received IVTA on the same day as for important covariates was performed using multiple
PDT (same day group). linear regression.
Intravitreal Triamcinolone Acetonide and Photodynamic Therapy · Roth et al. 13TABLE
Baseline Data and Visual Acuity Results for the Treatment Groups
Variable 1 Week Prior Group Same Day Group P
No. of eyes 31 30
No. of females (%) 15 (48%) 15 (50%) .90
Mean (SD) age (y) 82 (6.8) 80 (7.0) .25
Lesion type .086
Classic/predominantly classic 15 (48%) 9 (30%)
Minimally classic 5 (16%) 2 (7%)
Occult 11 (36%) 19 (63%)
Mean (SD) spot size 4.8 (1.4) 5.2 (1.2) .23
Mean (SD) retreatments (1 year) 1.19 (1.0) 1.2 (0.93) .87
Visual acuity*
Baseline 1.08 (0.45) 0.90 (0.38) .084
6 to 12 week 1.07 (0.47) 0.88 (0.42) .085
1 year 1.14 (0.43) 0.93 (0.48) .093
SD = standard deviation.
*Visual acuity data expressed as logarithm of the minimum angle of resolution (SD).
RESULTS DISCUSSION
Demographic information and visual acuity results It is known that combining IVTA and PDT re-
are listed in the table. There was no statistically sig- sults in the stabilization of visual acuity and a decreased
nificant difference between the two groups regarding need for retreatments with PDT. However, the optimal
age, gender, lesion type, or baseline visual acuity. In the temporal relationship between the administration of
1 week prior group, Snellen visual acuity was 20/240, steroids and treatment with PDT remains obscure and
20/234, and 20/276 at baseline, 6 to 12 weeks, and 1 we are not aware of any published studies that have in-
year, respectively. In the same day group, Snellen visual vestigated this relationship. In the current study, there
acuity was 20/158, 20/151, and 20/170 at baseline, 6 was no statistically significant difference in visual out-
to 12 weeks, and 1 year, respectively. Twenty-eight of comes between the 1 week prior group and the same
31 (90.3%) eyes in the 1 week prior group and 28 of day group. Although slightly better visual outcomes
30 (93.3%) eyes in the same day group completed the were observed in the same day group, this difference
1-year follow-up. was small and did not reach statistical significance; fur-
There was no statistically significant difference in thermore, the same day group began with slightly bet-
visual acuity between the groups at baseline, 6 to 12 ter baseline visual acuity.
weeks, or 1 year. When the visual acuity outcomes In their pilot study on the combination of IVTA
were adjusted for baseline visual acuity, spot size, le- and PDT for choroidal neovascularization, Spaide et
sion type, age, and gender, there was no statistical dif- al. suggested that the sequence and temporal inter-
ference in visual acuity between the groups at either 6 val of the combined treatments is likely to affect the
to 12 weeks (P = .44) or 1 year (P = .28). There was outcome.7 There have been reports of successful out-
no difference in the mean number of required repeat comes in non-randomized groups of patients who re-
treatments between the two groups, 1.19 for the 1 ceived IVTA from 4 days to 1 month prior to PDT for
week prior group and 1.2 for the same day group (P choroidal neovascularization secondary to age-related
= .87). macular degeneration.18,19 The overall results of the
14 Ophthalmic Surgery, Lasers & Imaging · January/February 2007 · Vol 39, No 1current study are comparable to these reports, as well of photodynamic therapy on expression of vascular en-
as to reports describing IVTA injection at the time of dothelial growth factor (VEGF), VEGF receptor 3, and
or shortly after PDT.7-17,22 However, there have been pigment epithelium-derived factor. Invest Ophthalmol
no randomized trials comparing the timing of IVTA Vis Sci. 2003;44:4473-4480.
administration in relation to PDT, and the optimal 5. Schmidt-Erfurth U, Michels S, Augustin A. Perspec-
timing and sequence of therapy remains unknown. tives on verteporfin therapy combined with intravitreal
The limitations of this study include its retrospec- corticosteroids. Arch Ophthalmol. 2006;124:561-563.
tive nature, the small number of patients, limited fol- 6. Gollnick SO, Evans SS, Baumann H, et al. Role of cyto-
low-up, and nonstandard visual acuities. In addition, kines in photodynamic therapy-induced local and sys-
other clinical measures, such as fluorescein angiographic temic inflammation. Br J Cancer. 2003;88:1772-1779.
leakage, were not assessed, and it is possible that a larger 7. Spaide RF, Sorenson J, Maranan L. Combined photo-
and more comprehensive study may detect a benefit of dynamic therapy with verteporfin and intravitreal tri-
one temporal sequence over another. Nevertheless, this amcinolone acetonide for choroidal neovascularization.
study adds valuable information to the growing body of Ophthalmology. 2003;110:1517-1525.
literature on combined IVTA and PDT for exudative 8. Spaide RF, Sorenson J, Maranan L. Photodynamic ther-
age-related macular degeneration and further investiga- apy with verteporfin combined with intravitreal injec-
tion into the optimal sequence of treatment is warranted. tion of triamcinolone acetonide for choroidal neovascu-
With the recent availability of effective anti-vascular en- larization. Ophthalmology. 2005;112:301-304.
dothelial growth factor therapy for exudative age-related 9. Rechtman E, Danis RP, Pratt LM, Harris A. Intravitreal
macular degeneration, the need to identify the efficacy, triamcinolone with photodynamic therapy for subfo-
safety, and optimal sequence of combined IVTA and veal choroidal neovascularisation in age related macular
PDT is still necessary because these results could yield degeneration. Br J Ophthalmol. 2004;88:344-347.
insight into future combination therapies for exudative 10. Spaide RF, Sorenson J, Maranan L. Combined photo-
age-related macular degeneration. dynamic therapy and intravitreal triamcinolone for non-
subfoveal choroidal neovascularization. Retina. 2005;
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Erratum
On page 505 of the article “In Vivo Evidence of Hypotrophic Ciliary Body in Ocular
Ischemic Syndrome by Ultrasound Biomicroscopy,” by Furino et al., which was published
in the November/December 2007 issue of Ophthalmic Surgery, Lasers & Imaging, the name
of the fifth author should be Nicola Cardascia, MD, instead of Cardascia Nicola, MD.
This has been corrected in the full-text PDF on the journal web site.
16 Ophthalmic Surgery, Lasers & Imaging · January/February 2007 · Vol 39, No 1You can also read
