Intravitreal Triamcinolone for the Treatment of Ischemic Macular Edema Associated With Branch Retinal Vein Occlusion

Intravitreal Triamcinolone for the Treatment of Ischemic Macular Edema Associated With Branch Retinal Vein Occlusion SIMON D. M. CHEN, FRCOPHTH, VENKI SUNDARAM, BM, BCH, JONATHAN LOCHHEAD, FRCOPHTH, AND C. K. PATEL, FRCOPHTH

● PURPOSE:

To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) for ischemic macular edema associated with branch retinal vein occlusion (BRVO) and foveal ischemia. ● DESIGN: Prospective interventional case series. ● METHODS: SETTING: Clinical practice. STUDY POPULATION: Eighteen eyes of 18 patients with macular edema associated with BRVO and foveal ischemia. INTERVENTION: Four mg IVTA. MAIN OUTCOME MEASURES: Visual acuity (VA), optical coherence tomography, macular thickness measurements, and treatment-related complications. ● RESULTS: The mean duration of BRVO before treatment was 14 months. All patients were followed for a minimum of nine months, and 12 patients completed 12 months follow-up. The mean logarithm of the minimum angle of resolution (logMAR) VA improved significantly from 0.81 ⴞ 0.36 at baseline to 0.65 ⴞ 0.30 at one month (P ⴝ .03) but did not vary significantly from baseline at three, six, nine, and 12 months. Macular thickness improved significantly in all eyes from a mean of 400 ⴞ 134 ␮m preinjection, to 228 ⴞ 58 ␮m at one month (P < .01) and 256 ⴞ 121 ␮m at three months (P < .01) but did not vary significantly from baseline at six, nine, and 12 months. Eight eyes developed posterior subcapsular cataract, intraocular pressure (IOP) exceeded 21 mm Hg in four eyes, and two eyes developed vitreomacular traction during follow-up. ● CONCLUSIONS: IVTA is effective in reducing ischemic macular edema associated with BRVO and foveal capillary nonperfusion. This reduction is often associated with a temporary improvement in VA. Raised IOP and development of posterior subcapsular cataract are disadvantages of this treatment. (Am J Ophthalmol 2006; Accepted for publication Dec 8, 2005. From the Oxford Eye Hospital, Oxford, United Kingdom (S.D.M.C., V.S., C.K.P.), and St Mary’s Hospital, Newport, Isle of Wight, United Kingdom (J.L.). Inquiries to C. K. Patel, FRCOphth, Oxford Eye Hospital, Woodstock Road, Oxford OX2 6HE, United Kingdom; e-mail: [email protected]

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141:876 – 883. © 2006 by Elsevier Inc. All rights reserved.)

B

RANCH RETINAL VEIN OCCLUSION (BRVO) IS A COM-

mon retinal vascular disorder occurring in approximately 1% of adults over the age of 48, the natural history of which has been well documented.1,2 The most common cause of poor visual acuity (VA) associated with BRVO is macular edema, which has been reported in 60% of patients following BRVO.3 In eyes without foveal ischemia, argon laser grid photocoagulation is of proven benefit for the treatment of macular edema associated with BRVO and VA of 20/40 or worse.2 However, laser treatment is ineffective in eyes with foveal capillary nonperfusion demonstrable on fundus fluorescein angiography (FFA).4 There is currently no proven treatment for eyes with visual loss due to ischemic macular edema (defined as macular edema and BRVO associated with foveal capillary nonperfusion). A high proportion of such patients go on to develop chronic and irreversible retinal changes (such as a lamellar hole) with permanently impaired vision. Intravitreal injection of the corticosteroid suspension triamcinolone acetonide has been shown to be relatively safe and effective when used for the treatment of macular edema as a result of a variety of retinal conditions, including uveitis,5–7 exudative diabetic macular edema,8 –10 pseudophakic cystoid macular edema,11–13 central retinal vein occlusion,14,15 and BRVO.16 –18 We evaluated the safety and efficacy of this modality in treating ischemic macular edema associated with BRVO and foveal ischemia in a prospective case series of 18 eyes.

METHODS THIS WAS A PROSPECTIVE, NONRANDOMIZED, CONSECU-

tive, interventional case series of 18 eyes of 18 patients undergoing a single intravitreal triamcinolone acetonide injection (IVTA) for the treatment of macular edema associated with BRVO and foveal ischemia. Informed

ELSEVIER INC. ALL

RIGHTS RESERVED.

0002-9394/06/$32.00 doi:10.1016/j.ajo.2005.12.011

FIGURE 1. Fundus fluorescein angiograms demonstrating branch retinal vein occlusions associated with foveal capillary nonperfusion and macular edema. (Left) Case 13. (Middle) Case 14. (Right) Case 1.

consent was obtained from all patients. Ethics Committee approval was not required for this study. Inclusion criteria included the ability and willingness to understand the informed consent, a diagnosis of ischemic macular edema associated with BRVO and foveal capillary nonperfusion, and VA of 6/9 (20/30) or worse. All patients were capable of determining the onset of symptoms caused by the BRVO. Patients with ocular hypertension, glaucoma, or retinal disease other than BRVO were excluded. The diagnosis of BRVO was made in the presence of flame-shaped retinal hemorrhages along a dilated and tortuous retinal tributary vein, which angiographically showed delayed dye filling and late dye leakage peripheral to the causative arteriovenous crossing site. The presence of macular edema was confirmed if perifoveal dye leakage was visible on FFA and optical coherence tomography (OCT) demonstrated hyporeflective intraretinal cavities on radial scans centered on the fovea. Foveal capillary nonperfusion was considered to be present if the transit phase of the FFA demonstrated a broken perifoveal capillary ring at the border of the foveal avascular zone associated with a distinct area of capillary nonperfusion within 1 disk diameter of the foveal center. (Specific case examples are shown in Figure 1.) Evaluation and treatment took place at the Oxford Eye Hospital, Oxford, England, by one of three authors (S.D.C., J.L., C.K.P.) in the period from November 2002 to November 2003. Baseline assessment included VA using a pinhole and a Snellen chart with the following levels: 6/6 (20/20), 6/7.4 (20/25), 6/9 (20/30), 6/12 (20/40), 6/18 (20/60), 6/24 (20/80), 6/36 (20/120), 6/60 (20/200), 3/60 (10/200), and counting fingers at 2 m; dilated slit-lamp fundus biomicroscopy; assessment of lenticular status; intraocular pressure (IOP) measurement; FFA; and macular thickness measurement using OCT (Stratus OCT version 3.0, Carl-Zeiss, Oberkochen, Germany). All OCT scanning was performed with pupillary dilation by the same experienced operator using the Stratus OCT fast macular thickness VOL. 141, NO. 5

protocol with six 6-mm scans oriented radially, 30 degrees from one another, and intersecting at the foveal center. The central foveal thickness was automatically calculated using the Stratus OCT fast macular thickness map software. After obtaining informed consent, topical 0.5% proxymetacaine and then 10% povidone-iodine solution was instilled in the eye. A lid speculum was placed. Four milligrams of triamcinolone acetonide (Kenalog, BristolMyers Squibb, Middlesex, England) in 0.1 ml was injected into the vitreous cavity using a 27-gauge needle in the inferotemporal quadrant 3.5 or 4.0 mm posterior to the limbus in pseudophakic and phakic eyes, respectively. An anterior chamber paracentesis using a 27-gauge needle to remove 0.1 ml of aqueous humor was performed after the injection of intravitreal triamcinolone. Perfusion of the optic disk was confirmed using slit-lamp biomicroscopy. Topical chloramphenicol 0.5%, four times daily for five days, was prescribed for all patients. Patients were reviewed within two weeks and at one month, three months, and three-month intervals thereafter. The response to treatment was monitored functionally by VA assessment and anatomically by OCT macular thickness measurement. The VA and OCT macular thickness measurements at one, three, six, nine, and 12 months were the principal outcome measures. Potential injection-related and corticosteroid-induced complications were also observed. If the IOP exceeded 21 mmHg at any time point, treatment was started with topical timolol 0.5% twice daily. If the first-line therapy was not effective at keeping the pressure below 21 mmHg, additional medications were added to effect control. All patients completing a minimum of nine months follow-up were analyzed. The data analyzed were extracted from the patients’ records. Snellen VA was converted to the logarithm of the minimum angle of resolution (logMAR) and averaged for

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2). Mean VA also improved, but not significantly, at three months (0.64 ⫾ 0.30, P ⫽ .07), six months (0.62 ⫾ 0.27, P ⫽ .06), nine months (0.65 ⫾ 0.35, P ⫽ .05), and 12 months (0.71 ⫾ 0.45, P ⫽ .32). Measured in Snellen lines, mean VA improved by 0.76, 1.36, 0.57, 1.25, and 0.83 lines at the one-, three-, six-, nine-, and 12-month follow-up intervals, respectively. Of the 17 eyes evaluated at one month, 8 eyes (47%) showed improvement ranging from 1 to 3 lines, 7 eyes showed no change, and two eyes lost vision. Of the 14 eyes evaluated at three months, 7 eyes (50%) showed improvement ranging from 1 to 6 lines, 5 eyes showed no change, and two eyes lost vision. Of the 14 eyes evaluated at six months, 7 eyes (50%) showed improvement ranging from 1 to 2 lines, 5 eyes showed no change, and two eyes lost vision. Of the 12 eyes evaluated at nine months, 6 eyes (50%) showed improvement ranging from 1 to 5 lines, 5 eyes showed no change, and one eye lost vision. Of the 12 eyes evaluated at 12 months, 6 eyes (50%) showed improvement ranging from 1 to 6 lines, 4 eyes showed no change, and one eye lost vision. A significant correlation was found between baseline VA and VA at one month (Spearman ␳ ⫽ 0.75, P ⬍ .01) and six months (Spearman ␳ ⫽ 0.79, P ⬍ .01). A significant correlation was also found between age and VA at six months (Spearman ␳ ⫽ 0.72, P ⬍ .01) and nine months (Spearman ␳ ⫽ 0.78, P ⬍ .01). The mean VA in the subgroup of eight patients with a duration of symptoms before treatment of 12 months or more was worse than that in the subgroup of 10 patients with a duration of symptoms of less than 12 months before treatment, at each of the time points. This was significant at one month (P ⫽ .03) and six months (P ⫽ .02). Baseline central foveal thickness for the 18 treated eyes averaged 400 ⫾ 134 ␮m. All eyes demonstrated an improvement in macular thickness following IVTA injection. Seventeen eyes evaluated at one month showed a significant reduction in mean macular thickness of 41%, from 389 ⫾ 131 ␮m to 228 ⫾ 58 ␮m (P ⬍ .01). Thirteen eyes evaluated at three months showed a significant reduction in mean macular thickness of 33%, from 380 ⫾ 140 ␮m to 256 ⫾ 121 ␮m (P ⬍ .01). The difference in mean macular thickness from preinjection values at six, nine, and 12 months did not reach statistical significance (P ⫽ .51, .18, and .21, respectively). Fourteen eyes evaluated at six months showed a reduction in mean macular thickness of 14%, from 407 ⫾ 151 ␮m to 352 ⫾ 171 ␮m (P ⫽ .51). Eleven eyes evaluated at nine months showed a reduction in mean macular thickness of 17%, from 389 ⫾ 148 ␮m to 321 ⫾ 141 ␮m (P ⫽ .18). Eleven eyes evaluated at 12 months showed a reduction in mean macular thickness of 21%, from 382 ⫾ 133 ␮m to 300 ⫾ 104 ␮m (P ⫽ .21). Recurrence of macular edema with macular thickness measurements reaching baseline values or greater occurred in nine patients (50%) during follow-up. There were no significant correlations between macular thickness at any time point and patient age, duration of BRVO, presenting

TABLE 1. Pretreatment Characteristics of Patients With Branch Retinal Vein Occlusion (BRVO) Associated With Ischemic Macular Edema

Case

Gender

Age (y)

Duration of BRVO (mo)

Hypertension

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Male Male Female Male Female Female Male Female Male Female Male Male Female Male Male Male Female Female

38 67 70 55 59 64 62 87 68 83 67 65 76 73 68 68 57 65

6 10 7 15 4.5 54 8 17 28 13.5 36 7 5 12 5 24 4.5 4

No No Yes Yes Yes No Yes No Yes Yes Yes No Yes No Yes Yes Yes Yes

the purpose of statistical analysis. A VA of counting fingers at 2 m was given a logMAR value of 1.5 according to a standard conversion protocol.19 Statistical analysis was performed using commercial statistical software (SPSS for Windows, version 10.0.1; SPSS Inc, Chicago, Illinois, USA). VA outcomes and OCT retinal thickness measurements were analyzed with respect to variables, including age, gender, hypertension, VA at first presentation, VA immediately before treatment, and duration of BRVO before treatment. Wilcoxon rank test, Fisher’s exact test, Mann-Whitney test, and Spearman correlation analysis were used to compare data where appropriate. A P value of less than .05 was considered significant.

RESULTS EIGHTEEN EYES OF 18 PATIENTS WERE TREATED. PRETREAT-

ment characteristics are summarized in Table 1. The mean age of the patients was 66 years (range 38 to 87 years). The mean duration of symptoms before treatment was 14 months (range 4 to 54 months), with eight patients having a duration of symptoms of 12 months or more, before treatment. Seventeen eyes were phakic, and one eye was pseudophakic (case 18). All 18 patients completed a minimum of nine months of follow-up, and 12 of these completed follow-up of 12 months or more. No patient received repeated treatment with IVTA. The results of treatment with IVTA are presented in Table 2. The mean VA improved significantly from 0.81 ⫾ 0.36 at baseline to 0.65 ⫾ 0.31 at one month (P ⫽ .03) (Figure 878

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VOL. 141, NO. 5 TABLE 2. Results of Intravitreal Triamcinolone Injection for Ischemic Macular Edema Due to Branch Retinal Vein Occlusion

ISCHEMIC MACULAR EDEMA ASSOCIATED WITH BRVO

Visual Acuity Case

Initial

1m

3m

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

CF 20/200 20/200 20/200 20/30 20/120 20/30 20/200 20/80 20/120 20/120 20/200 20/60 CF 20/120 20/80 20/120 20/60

20/120 20/200 20/80 20/200 20/30 20/80 20/20 20/200 20/120 20/120 20/80

20/80 20/200 20/80 20/200

20/60 20/200 20/120 20/120 20/40 20/40

CF ⫽ counting fingers.

20/120

20/120 20/120 20/120 20/40 20/80 20/40 20/120 20/20 20/60

6m

Macular Thickness (␮m) 9m

20/60 20/120

20/200

20/25 20/120 20/30 20/200 20/60 20/120 20/80

20/20 20/80 20/200 20/200 20/200

20/80 20/200 20/60 20/120 20/60 20/60

20/120 20/120 20/80 20/30 20/40

12 m

Initial

1m

20/40 20/200 20/120 20/200 20/20 20/120 20/20 CF 20/60 20/200 20/80 20/200

337 333 394 435 574 205 362 233 556 451 537 236 500 435 481 326 625 171

195 232 324 287 233 298 179 201 230 151 229 252 346 173 189 204 146

3m

6m

203 406 198 363 171

151 229 228 222 199 576 222 166

Intraocular Pressure (mm Hg) 9m

390 374 182 381 200 168 203 261 295 630 697 516 365 454 196

206 150 403

12 m

Initial

1m

142 325 480 439 360 273 328 224 158

14 14 16 14 16 16 14 19 16 18 18 16 20 14 13 19 16 14

20 13 16 16 14 18 18 17 18 19 32

199 247 417 635 259 392 228

291 278

28 15 14 26 16 20

3m

6m

20 16 16 20 23

24 22 12 20

12 m

18

16 20 17 15 17 18

16 12 20 14 16 18 20 20 16 30 15 17

17 16

9m

18

10 18 14 18

14

20 17 12 14 18 16 10

20 18

Follow-up (mo)

12 12 12 12 12 12 12 12 12 12 12 12 9 9 9 9 9 9

879

FIGURE 2. Scattergram demonstrating visual acuities of patients before and three months after treatment with intravitreal triamcinolone for branch retinal vein occlusion with ischemic macular edema.

VA, preinjection VA, or VA at any postinjection time point. The mean IOP rose significantly by 18% (P ⬍ .01) and 17% (P ⫽ .02) from baseline at the one- and three-month follow-up intervals, respectively, but did not differ significantly from baseline at any subsequent time point. For the 17 eyes evaluated at one month, the mean IOP rose from 16 mmHg to 19 mmHg; 3 of 17 eyes (18%) had an IOP exceeding 21 mmHg. For the 11 eyes evaluated at three months, the mean IOP rose from 16 mmHg to 19 mmHg; 3 of 11 eyes (27%) had an IOP exceeding 21 mmHg. For the 12 eyes evaluated at six months, the mean IOP rose from 17 mmHg to 18 mmHg; one eye sustained an IOP exceeding 21 mmHg. No eye evaluated at nine or 12 months had an IOP above 21 mmHg. In the 4 eyes (22%) that developed an IOP exceeding 21 mmHg during followup, topical timolol 0.5% twice daily achieved IOP control in three patients (cases 8, 11, and 16). One additional patient (case 12) had a persistently raised IOP of 30 mmHg at the most recent follow-up despite the use of timolol and dorzolamide. The lens status was not graded in this study by a formalized method such as the Lens Opacities Classification System version II (LOCS II); however, eight eyes (44%) exhibited development of posterior subcapsular cataract during follow-up. One of these was noted at the six-month follow-up, one at the nine-month follow-up, and six at the 12-month follow-up. No eye underwent cataract extraction during the follow-up period. Two eyes developed vitreomacular traction confirmed by OCT and associated with a marked increase in macular thickness (Figure 3). One of these (case 14) was noted at six months postinjection and was associated with a reduction in VA from 6/24 (20/80) to 6/60 (20/200). The patient declined vitrectomy surgery. The second (case 16) was noted at three months postinjection and was associ880

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FIGURE 3. Optical coherence tomography (OCT) scans performed after intravitreal triamcinolone acetonide (IVTA) treatment for branch retinal vein occlusion with ischemic macular edema. (Top) This patient (case 14) developed vitreomacular traction associated with a reduction in visual acuity from 6/24 (20/80) to 6/60 (20/200) six months following IVTA injection. (Bottom) This patient (case 16) reported metamorphopsia occurring three months following IVTA injection. OCT demonstrated vitreomacular traction in association with an epiretinal membrane. Vitrectomy with epiretinal membrane peeling was performed four months postinjection.

ated with metamorphopsia and an epiretinal membrane. Vitrectomy with epiretinal membrane peeling was performed four months postinjection and resulted in improvement of the metamorphopsia and VA and reduction in macular thickness. In one patient (case 16), accumulation of hard exudates at the macula after resolution of macular edema was felt to be responsible for a reduction in VA from 6/24 (20/80) preinjection to 6/36 (20/120) at one month postinjection. This patient subsequently developed vitreomacular traction as previously described. The development of retinal neovasculization was not seen in any eye. No patient developed endophthalmitis, pseudoendophthalmitis, vitreous hemorrhage, or retinal detachment at any time point.

DISCUSSION THIS SINGLE-CENTER PROSPECTIVE CONSECUTIVE CASE SE-

ries found potential short-term benefit in the use of IVTA for the treatment of ischemic macular edema associated OF

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with BRVO and foveal capillary nonperfusion. In particular, a statistically significant improvement in VA and macular thickness measurements was found at the onemonth postinjection visit. In addition, macular thickness was significantly reduced at three months postinjection. Improvements in these parameters were also seen at the six-, nine-, and 12-month postinjection visits but did not reach statistical significance. Macular edema due to BRVO carries a variable visual prognosis, with only 37% of eyes gaining two or more lines of VA. In eyes with intact foveal capillary perfusion, the Branch Vein Occlusion Study Group demonstrated a significant benefit of argon laser grid photocoagulation for the treatment of BRVO and macular edema reducing VA to 20/40 or worse. However, 12% of eyes treated with laser will still have VA 20/200 or worse after three years.2 Laser treatment has been shown to be of no benefit in eyes with foveal capillary nonperfusion.4 Eyes with BRVO and a broken foveal capillary ring have a poorer prognosis for visual outcome. In one study, none of 22 patients with foveal ischemia showed an improvement in VA after two years of follow-up.4 Finkelstein20 reported that 21 of 23 eyes with BRVO associated with foveal capillary nonperfusion spontaneously improved in VA and suggested that ischemic macular edema is a transient phenomenon, with visual improvement occurring as the edema resolves. However, in the majority of cases with a good visual outcome, patients presented with a VA of 20/100 or better. Poor presenting VA is correlated with a poor visual prognosis.21 The lack of any proven effective treatment for eyes with foveal capillary nonperfusion has prompted interest in other treatment methods, including surgical treatment with vitrectomy and internal limiting membrane peel, arteriovenous sheathotomy, or both.22 These treatments have not been subjected to randomized clinical trials, and their efficacy remains uncertain. Intravitreal injection of the corticosteroid triamcinolone acetonide has been shown experimentally to reduce breakdown of the blood-retinal barrier.23 Stabilization of the blood-retinal barrier provides a rationale for corticosteroid treatment of macular edema associated with BRVO. In keeping with other studies evaluating the use of IVTA for the treatment of macular edema associated with different conditions, such as pseudophakic cystoid macular edema,11–13 uveitis,5–7 exudative age-related macular degeneration,24 –26 exudative diabetic macular edema,8 –10 and central retinal vein occlusion,14,15 this study demonstrates the efficacy of IVTA in reducing macular edema. Recent reports have demonstrated an improvement in VA and macular edema following IVTA for the treatment of BRVO.16 –18 In a prospective comparative nonrandomized study, Jonas and associates18 treated 10 eyes with 20 mg to 25 mg IVTA for macular edema associated with BRVO. They reported significant improvement in mean VA from baseline at one month postinjection but not at VOL. 141, NO. 5

subsequent time points. In contrast to previous studies on central retinal vein occlusion and exudative age-related macular degeneration, which have demonstrated an initial increase in VA in the first few months after IVTA injection followed by a subsequent decline in VA approximately three to five months postinjection,14,15,24,25 Jonas and associates did not show a clear tendency of a decrease in VA toward the end of the study. This led them to suggest that in eyes with BRVO, IVTA may be associated with a longer-lasting increase in VA compared with eyes with central retinal vein occlusion and age-related macular degeneration. The two patients in their study classified as having ischemic BRVO did not experience any significant improvement in VA. It might be expected that any potential improvement in VA associated with resolution of macular edema would be greatly reduced by the presence of macular ischemia. However, Chen and associates17 recently reported a favorable response to IVTA in a patient with ischemic macular edema associated with BRVO (the patient represented as case 1 in the current study). In the current series, 8 (47%) of 17 eyes reviewed one month following IVTA injection gained in VA; five (29%) of these gained in VA by at least 2 Snellen lines, thus providing further confirmation that resolution of macular edema may be associated with an improvement in VA despite the presence of foveal capillary ischemia. The results must be interpreted in light of the characteristics of the study population. All eyes had macular edema with thickening of the foveal center associated with a broken perifoveal capillary ring and exhibited cystoid changes on OCT. The variable degree of ischemia, wide range in duration of BRVO, and consequent variation in the extent of permanent macular atrophy associated with chronic BRVO would limit VA improvement in some eyes. Additionally, the development of posterior subcapsular cataract in eight patients would be expected to negate some of the visual improvement associated with reduction in macular edema. It is probable that patients with an initial improvement, then subsequent decline, in VA after IVTA may benefit from repeated treatment with IVTA; however, this was not evaluated in the present study. IVTA has also been reported to have antiangiogenic effects and has consequently been used for the treatment of neovascular glaucoma,27 neovascular age-related macular degeneration,24 and proliferative diabetic retinopathy.28 This raises the possibility that IVTA may be of benefit in reducing the risk of subsequent retinal neovascularization and associated vitreous hemorrhage in patients with ischemic BRVO. No patients in this series developed retinal neovascularization during follow-up; however, the number of cases is too small to draw meaningful conclusions regarding this hypothesis. The safety of IVTA has been supported by animal studies and human trials.29,30 Potential complications include retinal detachment, vitreous hemorrhage,

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pseudoendophthalmitis,31 and endophthalmitis in 0.87%.32 No such complications were experienced in the current study. The major ocular side effects attributed to corticosteroids include raised IOP and cataract. In the current series, IVTA injection was well tolerated, and the most common adverse effects were a transient rise in IOP, with 4 patients (22%) requiring topical ocular hypotensive treatment for a rise in IOP to above 21 mmHg, and the development of posterior subcapsular cataract in 8 patients (44%) during the first 12 months of follow-up; additional cases would be expected with longer follow-up. Although no patient underwent cataract surgery in this series, cataract progression is a particular concern in this group of patients because the need for subsequent cataract surgery may be associated with a risk of aggravating the macular edema. Other adverse ocular events observed included the development of vitreomacular traction in two patients at three and six months postinjection, respectively. It is unclear whether the IVTA was a contributory factor to the development of these events or coincidental. Following the resolution of macular edema within one month after IVTA injection, one patient developed accumulation of macular hard exudates, which may have contributed to a reduction in VA. This study has several weaknesses that limit the generalizability of the findings, including a relatively small sample size and the lack of control patients. Thus it is possible that the improvement in anatomic and functional parameters found was simply a reflection of the natural history of the condition; however, this is unlikely in view of the characteristic time course of initial improvement followed by subsequent deterioration seen. VA was measured on a Snellen chart, as opposed to the more standardized and accepted Early Treatment Diabetic Retinopathy Study chart. This makes comparisons less meaningful and does not allow for the determination of moderate visual loss or gain. Best-corrected VA was not ascertained, but all eyes were tested with the same correction throughout the follow-up period. In addition, there was no formal grading of lens opacity changes using a standardized grading system. The range of foveal and peripheral retinal nonperfusion was wide and may influence the results of this study. Therefore, findings from this study should not be used as justification to treat patients in an uncontrolled fashion. Anatomic data are presented in a highly objective, quantitative fashion using OCT. The duration of follow-up is also relatively short, but the studied intervention appears to have a rapid onset of effect. Positive statistically significant anatomic and visual responses were apparent at the 1-month posttreatment interval. The findings from the present case series suggest that IVTA offers the possibility of a reduction in macular edema and improvement of VA at least in the short term. However, these potential benefits must be balanced against the risks of endophthalmitis and raised 882

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IOP, as well as the longer-term risk of cataract progression. The prospective randomized controlled Standard Care vs Corticosteroid for Retinal Vein Occlusion Study is currently under way and should clarify matters raised by the present study.

REFERENCES 1. Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia: The Blue Mountains Eye Study. Arch Ophthalmol 1996;114:1243–1247. 2. The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol 1984;98:271–282. 3. Greer DV, Constable IJ, Cooper RL. Macular oedema and retinal branch vein occlusion. Aust J Ophthalmol 1980;8: 207–209. 4. Shilling JS, Jones CA. Retinal branch vein occlusion: a study of argon laser photocoagulation in the treatment of macular oedema. Br J Ophthalmol 1984;68:196 –198. 5. Young S, Larkin G, Branley M, et al. Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis. Clin Experiment Ophthalmol 2001;29:2– 6. 6. Antcliff RJ, Spalton DJ, Stanford MR, et al. Intravitreal triamcinolone for uveitic cystoid macular oedema: an optical coherence tomography study. Ophthalmology 2001;108: 765–772. 7. Degenring RF, Jonas JB. Intravitreal injection of triamcinolone acetonide as treatment of chronic uveitis. Br J Ophthalmol 2003;87:361. 8. Jonas JB, Sofker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular oedema. Am J Ophthalmol 2001;132:425– 427. 9. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920 –927. 10. Jonas JB, Kreissig I, Sofker A, et al. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 2003;121:57– 61. 11. Conway MD, Canakis C, Livir-Rallatos C, et al. Intravitreal triamcinolone acetonide for refractory chronic pseudophakic cystoid macular edema. J Cataract Refract Surg 2003;29:27–33. 12. Benhamou N, Massin P, Haouchine B, et al. Intravitreal triamcinolone for refractory pseudophakic macular oedema. Am J Ophthalmol 2003;135:246 –249. 13. Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide for pseudophakic cystoid macular oedema. Am J Ophthalmol 2003;136:384 –386. 14. Greenberg PB, Martidis A, Rogers AH, et al. Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion. Br J Ophthalmol 2002;86:247–248. 15. Park CH, Jaffe GJ, Fekrat S. Intravitreal triamcinolone acetonide in eyes with cystoid macular edema associated with central retinal vein occlusion. Am J Ophthalmol 2003;136: 419 – 425. 16. Degenring RF, Kamppeter B, Kreissig I, et al. Morphological and functional changes after intravitreal triamcinolone acetonide for retinal vein occlusion. Acta Ophthalmol Scand 2003;81:548 –550. OF

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17. Chen SDM, Lochhead J, Patel CK, et al. Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by branch retinal vein occlusion. Br J Ophthalmol 2004;88:154 –155. 18. Jonas JB, Akkoyun I, Kamppeter B, et al. Branch retinal vein occlusion treated by intravitreal triamcinolone acetonide. Eye 2005;19:65–71. 19. Holladay JT. Visual acuity measurements. J Cataract Refract Surg 2004;30:287–290. 20. Finkelstein D. Ischemic macular edema. Recognition and favorable natural history in branch vein occlusion. Arch Ophthalmol 1992;110:1427–1434. 21. Glacet-Bernard A, Coscas G, Chabanel A, et al. Prognostic factors for retinal vein occlusion: prospective study of 175 cases. Ophthalmology 1996;103:551–560. 22. Mason J III, Feist R, White M Jr, et al. Sheathotomy to decompress branch retinal vein occlusion: A Matched Controlled Study. Ophthalmology 2004;111:540 –555. 23. Wilson CA, Berkowitz BA, Sato Y, et al. Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation. Arch Ophthalmol 1992; 110:1155–1159. 24. Gillies MC, Simpson JM, Luo W, et al. A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age related macular degeneration: one-year results. Arch Ophthalmol 2003;121:667– 673.

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25. Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization. Ophthalmology 2003; 110:1517–1525. 26. Jonas JB, Akkoyun I, Budde WM, et al. Intravitreal reinjection of triamcinolone for exudative age-related macular degeneration. Arch Ophthalmol 2004;122:218 –222. 27. Jonas JB, Hayler JK, Sofker A, Panda-Jonas S. Regression of neovascular iris vessels by intravitreal injection of crystalline cortisone. J Glaucoma 2001;10:284 –287. 28. Jonas JB, Hayler JK, Sofker A, Panda-Jonas S. Intravitreal injection of crystalline cortisone as adjunctive treatment of proliferative diabetic retinopathy. Am J Ophthalmol 2001; 131:468 – 471. 29. McCuen BW II, Bessler M, Tano Y, et al. The lack of toxicity of intravitreally administered triamcinolone acetonide. Am J Ophthalmol 1981;91:785–788. 30. Gillies MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial. Arch Ophthalmol 2004;122: 336 –340. 31. Roth DB, Chieh J, Spirn MJ, et al. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol 2003;121:1279 –1282. 32. Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2003;136:791–796.

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Biosketch Simon D. M. Chen, FRCOphth, completed Ophthalmology Training at Addenbrooke’s Hospital, Cambridge, Massachusetts and at the Oxford Eye Hospital, Oxford, United Kingdom. He undertook surgical and medical retina fellowships at the Oxford Eye Hospital, the Royal Perth Hospital, and the Lions Eye Institute, Australia. As a Consultant Ophthalmologist at the University of Auckland, New Zealand, his clinical and research interests are in the areas of vitreoretinal surgery and medical retinal disease, particularly in the use of intravitreal triamcinolone.

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