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Intravitreal Versus Retrobulbar Injections of Triamcinolone for Macular Edema Associated With Branch Retinal Vein Occlusion
Intravitreal Versus Retrobulbar Injections of Triamcinolone for Macular Edema Associated With Branch Retinal Vein Occlusion KEN HAYASHI, MD, AND HIDEYUKI HAYASHI, MD
● PURPOSE:
To compare the short-term effect of intravitreal versus retrobulbar injection of triamcinolone acetonide for the treatment of macular edema caused by branch retinal vein occlusion. ● DESIGN: Randomized clinical trial. ● METHODS: Sixty eyes of 60 patients who had macular edema associated with branch retinal vein occlusion were randomly assigned to receive a single intravitreal injection (4 mg) or repeated retrobulbar injections (40 mg, three times) of triamcinolone. These injections (first injection in the retrobulbar group) were given approximately 1 week after focal laser photocoagulation. Using optical coherence tomography, the central retinal (foveal) thickness and total macular volume were measured before and at 1 and 3 months after injection. Visual acuity, intraocular pressure, and the incidence of reinjection were also examined. Fifty-two patients (86.7%) completed the 3-month follow-up. ● RESULTS: The mean foveal thickness and total macular volume decreased significantly after either intravitreal or repeated retrobulbar triamcinolone injections. Foveal thickness and macular volume were significantly less after intravitreal injection than after repeated retrobulbar injections, although there had been no significant differences at baseline. The percent reductions in foveal thickness and macular volume were also greater after intravitreal injection than after retrobulbar injections. Improvement in visual acuity was significantly better after intravitreal injection than after the retrobulbar injections. The incidence of intraocular pressure rise (to >20 mm Hg) was greater in the intravitreal group than in the retrobulbar group, but this was readily controlled by the use of antiglaucoma medications. After completion of the 3-month follow-up, 24 patients (46.2%) underwent reinjection. The need for reinjections was signifiAccepted for publication Dec 28, 2004. From the Hayashi Eye Hospital (K.H.) and the Department of Ophthalmology, School of Medicine, Fukuoka University (H.H.), Fukuoka, Japan. Inquiries to Ken Hayashi, MD, Hayashi Eye Hospital, 4-7-13 Hakataekimae, Hakata-ku, Fukuoka 812-0011, Japan; fax: 81-92-441-5303; e-mail: [email protected]
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cantly greater in the retrobulbar group than in the intravitreal group (P ⴝ .0001). ● CONCLUSIONS: A single intravitreal injection of triamcinolone is significantly more effective than are repeated retrobulbar injections in reducing macular edema associated with branch retinal vein occlusion, and leads to greater improvement in visual acuity. (Am J Ophthalmol 2005;139:972–982. © 2005 by Elsevier Inc. All rights reserved.)
I
NTRAVITREAL INJECTION OF TRIAMCINOLONE ACE-
tonide has been performed recently for macular edema associated with various retinal diseases, including diabetic retinopathy,1–5 uveitis,6 pseudophakic cystoid macular edema,7–9 exudative age-related macular degeneration,10 –14 and central retinal vein occlusion.15–18 Most studies showed that intravitreal triamcinolone was effective in reducing edema and in improving visual acuity. However, such injections have been reported to cause a high incidence of marked rise in intraocular pressure (IOP).19,20 Moreover, this procedure is known to confer a potential risk for cataract formation, endophthalmitis, and retinal detachment.21–24 Since the 1950s, subtenon’s and retrobulbar injections of long-acting corticosteroids have been used for the treatment of uveitis and for pseudophakic and diabetic cystoid macular edema.25–29 It has been demonstrated that corticosteroids injected periocularly penetrate the sclera and decrease the intraocular inflammation.30,31 Furthermore, even when several injections are given, the risk of intraocular complications such as cataract formation, endophthalmitis, and retinal detachment is less likely after periocular injection than after intravitreal injection. Branch retinal vein occlusion may cause persistent macular edema, which, in turn, can lead to visual impairment. Accordingly, various modalities have been used to lessen the macular edema caused by branch retinal vein occlusion. Traditionally, focal grid laser photocoagulation is performed in the edematous region.32–36 In addition, vitrectomy has been shown to be beneficial in reducing macular edema.37– 42 More recently, Chen and associates43 reported a case in which intravitreal triamcinolone de-
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0002-9394/05/$30.00 doi:10.1016/j.ajo.2004.12.087
creased substantially the macular edema caused by branch retinal vein occlusion. Based on these reports, we recently began to perform either intravitreal or retrobulbar injection of triamcinolone for macular edema associated with branch retinal vein occlusion. The purpose of the study described herein was to compare the short-term effect of intravitreal vs retrobulbar injections of triamcinolone in reducing edema. Our preliminary study using Stratus optical coherence tomography (OCT; Carl Zeiss Ophthalmic Systems, Dublin, California, USA) had shown that a single retrobulbar injection of 40 mg of triamcinolone had little effect on the foveal thickness in eyes with branch retinal vein occlusion. Accordingly, three retrobulbar injections, given once every 2 weeks. were used in the present study.
PATIENTS AND METHODS THIS STUDY WAS DESIGNED AS A RANDOMIZED CLINICAL
trial. ● PATIENTS:
The study protocol was approved by the institutional review board. All consecutive patients who were seen in our outpatient clinic between August 2003 and April 2004 because of visual impairment due to branch retinal vein occlusion were screened for inclusion in this study. When both eyes had branch retinal vein occlusion, only the eye that was more recently affected was included. One of the authors (K.H.) verified the presence of macular edema associated with branch retinal vein occlusion using slit-lamp biomicroscopy with a ⫹90-diopter lens, Stratus OCT, and fluorescein angiography. When the total macular volume was greater than 2.60 mm3 on OCT and when leakage from the vessels around the macula was present on fluorescein angiography, the eye was considered to have macular edema. The patient was then further screened for eligibility. Inclusion criteria were (1) being seen at our clinic within 12 months after the approximate onset of symptoms, (2) foveal ischemia of less than 180 degrees, (3) no other pathology of the macula or optic nerve, (4) no remarkable media opacities involving cornea, lens, or vitreous body, (5) availability of a clear OCT image, and (6) availability of the patients for 3-month follow-up. The occurrence of branch retinal vein occlusion was determined by the approximate date on which the patient first noted symptoms. The degree of foveal ischemia was determined on fluorescein angiography by the nonperfusion area around the fovea. Intravitreal or retrobulbar injection of triamcinolone was offered to treat the macular edema caused by branch retinal vein occlusion, and informed consent was obtained from each patient. Patient screening was continued until 60 eyes of 60 patients were recruited.
● RANDOMIZATION:
A clinical research coordinator randomized all patients on the day of enrollment into one of
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two groups: intravitreal injection or repeated retrobulbar injections. A randomization code with equal numbers was generated by the use of random number tables. To mask the ophthalmic technicians who performed the OCT and visual acuity examinations, and physicians who measured the IOP, the coordinator who made the randomization code kept concealed the assignment schedule until all data were collected. One of the authors (K.H.), who performed all laser photocoagulations and intravitreal triamcinolone injections, is also a data analyst, and was not informed of the assignment schedule. Ophthalmic technicians who performed the OCT and visual acuity examinations and physicians who measured the IOP were not informed of the purpose of this study or of assignment schedule. ● PREINJECTION TREATMENTS: Before injection, one of the authors (K.H.) performed grid laser photocoagulation in the region of edema outside the macula according to the recommendation of the Branch Retinal Vein Occlusion Study Group.32 A yellow or yellow-green laser was applied in the edematous region usually with 100- spot size, 0.2-second exposure, and power sufficient to create a light gray burn, with a range of 38 to 103 shots. The burn was created in a random grid pattern with spacing of about one burn-width, outside the macula and as peripheral as the retinal vascular arcade. Sectorial laser photocoagulation to the ischemic area outside the major vascular arcade was not performed before injection, except for three eyes in which laser photocoagulation had already been performed at another facility. The only medication used in the 60 patients was oral aspirin (81 mg) once a day in 9 patients (15%) and kallidinogenase (500 mg) three times a day in 8 (13.3%). ● INJECTION PROCEDURES: Approximately 1 week after focal laser photocoagulation, all patients underwent either intravitreal or retrobulbar injection of triamcinolone acetonide (Bristol Pharmaceuticals, Tokyo, Japan). The intravitreal triamcinolone injection was done under sterile conditions in the operating room. Eyes receiving the intravitreal injection were anesthetized by topical instillation of 0.4% oxybuprocaine and a retrobulbar injection of 1.5 ml of 2% xylocaine. In this study, to perform intravitreal injection safely, retrobulbar anesthesia was added. However, it may be possible to use only topical anesthesia, if the surgeon is experienced in performing the procedure. Under the operating microscope, 0.1 ml of triamcinolone acetonide (4 mg) was injected slowly via a 30-gauge needle through the pars plana, 3.0 mm posterior to the limbus in pseudopakic eyes, and 4.0 mm posterior to the limbus in phakic eyes. In the present study, the retrobulbar injection of triamcinolone was performed three times, once every 2 weeks, because a single retrobulbar injection was found in our preliminary study to inadequately reduce the macular
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edema. Retrobulbar injections were performed in the outpatient clinic. After topical instillation of 0.4% oxybuprocaine, 1.0 ml of triamcinolone (40 mg) mixed with 0.1 ml of 2% xylocaine was injected via a 25-gauge needle through the inferior lid margin and into the retrobulbar space.
TABLE 1. Patient Characteristics in the Intravitreal and Retrobulbar Triamcinolone Injection Groups Characteristic
No. of eyes Age Gender (male/ female) Left/right Interval†
● MAIN OUTCOME MEASURES:
Main outcomes evaluated were the central retinal (foveal) thickness and total macular volume measured using the OCT, visual acuity, and IOP. All patients underwent these examinations before injection and at 1 and 3 months after injection. During the OCT procedure, each eye underwent six radial scans centered on the fovea. Each radial scan line consisted of 100 samples of 5.92 mm in length, yielding a total of 600 samples from the six radial scans. Macular volume was calculated as follows. A central macular thickness map measuring 3.45 mm in diameter was generated. The circular map was subdivided into nine quadrants. The middle and inner circle diameters were 2.22 mm and 1.00 mm, respectively. The mean retinal thickness was calculated for each of the nine quadrants from the previously obtained radial scans. Multiplying the mean retinal thickness by the area of the quadrant generated the volume for each of the nine quadrants. The total macular volume was thus determined as the sum of the nine quadrant volumes. Best-corrected visual acuity on decimal charts was examined at each visit and was converted to the logarithm of minimal angle of resolution (logMAR) scale for statistical analysis. The IOP was measured using Goldmann applanation tonometry, and the number of glaucoma medications used was also recorded. When an additional injection was performed after the 3-month follow-up, the incidence of reinjection, reasons for reinjection, and foveal thickness and macular volume at the time of reinjection were also recorded. The OCT and visual acuity examinations were carried out by experienced ophthalmic technicians; IOPs were measured by physicians in our clinic.
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27 65.2 ⫾ 11.3 10/17
25 64.6 ⫾ 10.4 10/14
14/13 2.8 ⫾ 3.1
15/9 2.8 ⫾ 2.5
P Value
— .6536* ⬎.9999* .4130* .7347*
*No statistically significant difference. Interval between presumed occurrence and injection (months). †
RESULTS A TOTAL OF 76 EYES DIAGNOSED AS HAVING MACULAR
edema associated with branch retinal vein occlusion were screened. Before enrollment, 9 eyes were excluded because the onset of symptoms was more than 12 months previously, 2 because of foveal ischemia greater than 180 degrees, 1 because of pathology of the optic nerve, 2 because of extensive media opacity due to cataract or vitreous hemorrhage, and 2 because of anticipated difficulty in follow-up. Therefore, 60 eyes of 60 patients were recruited and randomized. After injection, 3 eyes in the intravitreal injection group and 5 in the retrobulbar injection group were lost to follow-up because of scheduling conflict or because of patients’ refusal. Accordingly, of the 60 patients, 52 eyes of 52 patients (86.7%) completed the 3-month follow-up and were available for analysis. The mean age of the patients (⫾SD) was 64.9 ⫾ 10.8 years, with a range of 38 to 83 years. There were 20 men and 31 women. The mean duration from the approximate onset of branch retinal vein occlusion to injection was 2.8 ⫾ 2.8 months. Patient demographics are shown in Table 1. No statistically significant differences were found between groups regarding age, gender, the ratio of left to right eyes, or the interval between onset of symptoms and injection. Comparisons of mean central retinal (foveal) thickness and total macular volume in the intravitreal and retrobulbar injection groups are shown in Figures 1 and 2, respectively. Temporal changes in total macular volume are depicted in Figure 3. When comparing the two groups, no significant differences were found in mean foveal thickness or macular volume before injection. After injection, however, both foveal thickness and macular volume decreased significantly in the intravitreal group (P ⬍ .0001). In the retrobulbar group, the macular volume also decreased significantly (P ⫽ .0391), but the reduction in foveal thickness was not significant (P ⫽ .2139). At both 1 and 3 months, the mean foveal thickness and macular volume in the intravitreal injection group were significantly less than those in the retrobulbar injection group.
● STATISTICAL ANALYSIS: For the continuous variables, normality of data distribution was first tested using the Kolmogorov-Smirnov test. Temporal changes in central retinal thickness and total macular volume, logMAR visual acuity, and IOP were compared using the KruskalWallis test. When there was a significant difference, the difference between each group was further compared using the Mann-Whitney U test with the Bonferroni adjustment. The differences between groups in foveal thickness and macular volume, logMAR visual acuity, IOP, and other continuous variables were compared using the Mann-Whitney U test. Categorical variables were compared using the Fisher’s exact test or the 2 test for independence. The survival curves of the need for reinjections were compared using the Mantel-Cox log rank test. Any differences showing a P value of less than .05 were considered to be statistically significant.
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FIGURE 1. Comparison of mean (ⴞSD) [median] values of central retinal (foveal) thickness between the intravitreal injection and retrobulbar injection groups as measured by optical coherence tomography. No significant difference between the groups was observed in mean foveal thickness before injection. At 1 and 3 months after injection, foveal thickness in the intravitreal injection group was significantly less than that in the retrobulbar injection group.
FIGURE 2. Comparison of mean (ⴞSD) [median] values of total macular volume between the intravitreal injection and retrobulbar injection groups as measured by optical coherence tomography. No significant difference between the groups was found in the mean total macular volume before injection. At 1 and 3 months after injection, the total macular volume in the intravitreal injection group was significantly less than that in the retrobulbar injection group.
Percentage reductions in foveal thickness and macular volume (Figure 4) in the intravitreal group were also greater than those in the retrobulbar group. The mean logMAR visual acuity in the intravitreal injection group improved significantly (P ⫽ .0065), whereas that in the retrobulbar group did not show a VOL. 139, NO. 6
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significant change (P ⫽ .6290). When comparing groups, there was no significant difference in mean visual acuity before injection or at 1 or 3 months after injection (Table 2). However, improvement in visual acuity in the intravitreal injection group was significantly greater than that in the retrobulbar injection group.
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FIGURE 3. Temporal changes in the mean total macular volume (ⴞSD) in the intravitreal injection and retrobulbar injection groups. In the intravitreal injection group, the mean total macular volume decreased significantly up to 1 month after injection (P < .0001). In the retrobulbar injection group, the volume did not decrease up to 1 month after injection, but the reduction of the volume became significant by 3 months after injection.
FIGURE 4. Comparison of mean (ⴞSD) percentage reduction in central retinal thickness and total macular volume in the intravitreal injection and retrobulbar injection groups. Percentage reductions in both foveal thickness and total macular volume in the intravitreal injection group were significantly greater than those in the retrobulbar injection group at 1 and 3 months after injection.
Regarding postinjection complications, serious problems such as cataract formation, endophthalmitis, and retinal detachment did not occur in this series, and the mean IOP did not increase significantly in either group (P ⫽ .1315 in the intravitreal group and P ⫽ .2504 in the retrobulbar group). Comparisons of the mean IOP and percentage increase in the IOP in the intravitreal 976
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and retrobulbar injection groups are shown in Table 3. No significant difference was found in the mean IOP at baseline or at 3 months after injection, but IOP in the intravitreal group was higher than that in the retrobulbar group at 1 month after injection. There was also no significant difference in the percentage increase in IOP between the two groups throughout the follow-up peOF
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TABLE 2. Comparison Between Intravitreal and Retrobulbar Injection Groups of Mean (⫾SD) and Median logMAR Visual Acuity and Improvement in logMAR Visual Acuity Intravitreal Group Mean (median)
Parameter
Visual acuity Preoperative 1 month postoperatively 3 months postoperatively Improvement in visual acuity 1 month postoperatively 3 month postoperatively
0.598 ⫾ 0.375 (0.398) 0.373 ⫾ 0.308 (0.398) 0.312 ⫾ 0.315 (0.155) ⫺0.224 ⫾ 0.218 (⫺0.176) ⫺0.285 ⫾ 0.269 (⫺0.204)
Retrobulbar Group Mean (median)
P Value
0.433 ⫾ 0.285 (0.301) 0.409 ⫾ 0.259 (0.301) 0.341 ⫾ 0.186 (0.301)
.0835* .4235* .1585*
⫺0.024 ⫾ 0.170 (0) ⫺0.092 ⫾ 0.225 (0)
.0002† .0078†
logMAR ⫽ logarithm of minimal angle of resolution. *No statistically significant difference. † Statistically significant difference.
TABLE 3. Comparison Between Intravitreal and Retrobulbar Injection Groups of Mean (⫾SD) and Median Intraocular Pressure (IOP) and Percentage Increase in IOP Intravitreal Group Mean (median)
Parameter
IOP (mm Hg) Preoperative 1 month postoperatively 3 months postoperatively Percentage increase in IOP (%) 1 month postoperatively 3 months postoperatively
Retrobulbar Group Mean (median)
P Value
14.1 ⫾ 3.5 (14) 16.1 ⫾ 4.3 (16) 16.6 ⫾ 5.9 (16)
12.9 ⫾ 3.5 (12) 13.9 ⫾ 3.8 (13) 13.8 ⫾ 2.9 (13)
.1479* .0307† .0617*
18.5 ⫾ 37.0 (11.8) 24.8 ⫾ 61.8 (13.3)
9.7 ⫾ 19.9 (0) 12.1 ⫾ 29.4 (7.1)
.3843* .8047*
*No statistically significant difference. † Statistically significant difference.
riod. However, an increase in IOP to 20 mm Hg or greater occurred in nine eyes (33.3%) in the intravitreal group and in two eyes (7.4%) in the retrobulbar group, which represented a significantly higher incidence in the intravitreal group (P ⫽ .0404). Furthermore, the mean number of antiglaucoma medications used in the intravitreal group was greater than that in the retrobulbar group (2.7 in the intravitreal group vs 1.0 in the retrobulbar group; P ⫽ .0339). Of the 52 patients, reinjection of triamcinolone was performed in 24 patients (46.2%) after the conclusion of the 3-month follow-up. Of the 27 patients who received an intravitreal injection, 6 (22.2%) required reinjection; of the 25 patients who received retrobulbar injections, 18 (72.0%) received an intravitreal reinjection and 1 (4.0%) an additional retrobulbar injection. Kaplan-Meier survival analysis showed that the need for additional injections was significantly greater in the retrobulbar group than in the intravitreal group (P ⫽ .0001, Figure 5). Table 4 shows the reasons for reinjections as well as foveal thickness and macular volume at the time of reinjections. The reasons for reinjection in VOL. 139, NO. 6
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the intravitreal injection group were the recurrence of edema in five patients (18.5%) and inadequate effect in one (3.7%), whereas in the retrobulbar group the reason was inadequate effect in all 18 (72.0%); the reasons were significantly different (P ⬍ .0001). Furthermore, in both groups, the foveal thickness and macular volume in eyes that required reinjection were greater at the time of reinjection than in eyes that did not require reinjection. As a consequence of reinjections, however, no significant differences were found in foveal thickness, macular volume, or visual acuity between groups at 6 months after the first injection (Figure 6). Figure 7 illustrates changes in the OCTimages of a representative patient in the intravitreal injection group and of a patient in the retrobulbar injection group. In the eye that underwent intravitreal injection, macular edema decreased substantially and showed a virtually normal configuration at 1 and 3 months after injection. In the eye that had repeated retrobulbar injections, the macular edema decreased slightly over time, but severe edema persisted for up to 3 months, even after the last planned injection.
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TABLE 4. Reasons for Reinjection, and Foveal Thickness and Total Macular Volume at the Time of Reinjection, in Intravitreal and Retrobulber Injection Groups After Completion of the 3-month Follow-up
Parameter
Reasons for reinjection Inadequate effect Recurrence of edema Foveal thickness () Reinjection group‡ No reinjection group§ P value Total macular volume (mm3) Reinjection group‡ No reinjection group§ P value
FIGURE 5. Kaplan-Meier survival plots of the two groups for eyes requiring reinjection of triamcinolone after the planned follow-up. The survival curve in the intravitreal injection group was significantly better than that in the retrobulbar group (P ⴝ .0001).
DISCUSSION intravitreal injection or repeated retrobulbar injections of triamcinolone has a beneficial effect in reducing the macular edema associated with branch retinal vein occlusion. The single intravitreal injection decreased significantly the foveal thickness and macular volume at 1 month, whereas the reduction in foveal thickness and in macular volume at 1 month after retrobulbar injection was not statistically significant. These results suggest that repeated injections might be necessary to induce a significant effect when utilizing the periocular injection route, whereas a single intravitreal injection has an immediate effect. When comparing injections, the foveal thickness and macular volume after intravitreal injection were less than those after repeated retrobulbar injections at both 1 and 3 months. Furthermore, the percentage reductions in foveal thickness and in macular volume after intravitreal injection were significantly greater than those after three retrobulbar injections. These results indicate that a single intravitreal injection is more effective in reducing macular edema than are repeated retrobulbar injections. Visual acuity also improved significantly after intravitreal injection, whereas improvement in visual acuity after retrobulbar injections was not significant. The insignificant improvement in visual acuity despite a slight reduction in macular edema after retrobulbar injections suggests that almost complete resolution of macular edema may be necessary for significant improvement in visual acuity. When comparing the two groups, however, no significant differences were found AMERICAN JOURNAL
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1 (3.7%) 5 (18.5%)
18 (72.0%) 0
415 ⫾ 222 220 ⫾ 102
362 ⫾ 159 265 ⫾ 158
.0442*
.1549†
3.57 ⫾ 0.92 2.64 ⫾ 0.35
3.41 ⫾ 0.69 2.68 ⫾ 0.19
.0132*
.0142*
P Value
⬍.0001*
— —
— —
*Statistically significant difference. † No significant difference. ‡ Patients who were scheduled for reinjection. § Patients who did not receive reinjection.
OUR STUDY HAS DEMONSTRATED THAT EITHER A SINGLE
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in mean visual acuity at either 1 or 3 months after injection. This is probably because visual acuity at baseline tended to be worse in the intravitreal injection group than in the retrobulbar injection group. In fact, improvement in visual acuity after intravitreal injection was significantly greater than improvement after repeated retrobulbar injections. These results indicate that intravitreal injection is more effective in improving visual acuity than are retrobulbar injections. Approximately 46% of all patients required an additional injection of triamcinolone after completion of the planned follow-up. Specifically, 72% of patients in the retrobulbar injection group received a supplemental intravitreal reinjection and 4% received an extra retrobulbar injection, whereas 22% of patients in the intravitreal group underwent a second intravitreal injection. These additional injections were needed primarily because of an inadequate response in terms of reduced edema after retrobulbar injection and a recurrence of edema after intravitreal injection. Thus, although intravitreal injection of triamcinolone has a strong effect on the macular edema, the most important problem may be recurrence. However, as a consequence of additional intravitreal injections, there were no significant differences in foveal thickness, macular volume, or visual acuity at 6 months after the first injection. For treatment of macular edema associated with branch retinal vein occlusion, grid laser photocoagulaOF
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FIGURE 6. Comparison of mean (ⴞSD) [median] foveal thickness and total macular volume at 6 months after the first injection. No significant differences were found in foveal thickness or macular volume between the intravitreal injection and retrobulbar injection groups at 6 months after the first injection.
tion in the region of the edema has been recommended,32–36 but this is known to be ineffective in many cases.44 It has been shown that vitrectomy with arteriovenous sheathotomy improves retinal vein circulation.37– 42 However, the surgical technique of vitrectomy with arteriovenous sheathotomy is difficult and the complication rate is not low. Chen and associates43 recently reported intravitreal injection of triamcinolone to be a safe and effective treatment for macular edema associated with branch retinal vein occlusion. Our results agree with those of Chen and associates. However, several other studies on the use of triamcinolone for retinal vascular diseases other than branch retinal vein occlusion reported that its effect in reducing macular edema was transient and that recurrence of edema occurred in many instances.4,5,12,13 In our study, approximately 22% of the patients who had undergone intravitreal injection of triamcinolone experienced a recurrence of edema and required a second injection at approximately 4 months after the first injection. It has been shown that 4 mg of triamcinolone injected into the vitreous cavity lasts for approximately 3 months after injection,45 so it is entirely possible that recurrence of macular edema occurs when the intravitreal triamcinolone is absorbed. Furthermore, intravitreal injection of triamcinolone is accompanied by the risk of cataract progression, intractable rise in IOP, infectious or noninfectious endophthalmitis, and retinal detachment.19 –24 Conversely, periocular injection of triamcinolone has been widely used for the treatment of uveitis and pseudophakic or diabetic macular edema.25–29 It has been demonVOL. 139, NO. 6
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strated that triamcinolone injected into the periocular space gradually penetrates the sclera30,31 and thereby decreases the intraocular inflammation.25–28 Periocular injection of triamcinolone is thought to be much safer than intravitreal injection. However, as shown by the present study, the effect of retrobulbar injection in reducing macular edema is not nearly as strong as is that of intravitreal injection. This suggests that periocular triamcinolone injection might best be used as an adjunctive treatment for slight edema or as prophylaxis for a recurrence. In the study described herein, the mean IOP at 1 month after intravitreal injection was higher than that after retrobulbar injection, although no significant difference was found at baseline. The incidence of marked rise in IOP was also greater after intravitreal injection than after retrobulbar injection. In addition, the number of topical antiglaucomatous medications required after intravitreal injection was greater than that after retrobulbar injection. Subsequently, however, the mean IOP at 3 months was not different between the two groups, suggesting that the IOP after intravitreal injection can be normalized by topical medications. It is well known that the a rise in IOP can occur after periocular injection of triamcinolone, as well as after intravitreal injection,19,25,26 but a case of secondary refractory glaucoma after intravitreal triamcinolone injection has been reported, and surgical removal of triamcinolone depot and trabeculectomy were necessary for IOP control in that patient.21 In the present study, an increase in IOP was noted in 33% of the patients after intravitreal injection and in 8% after retrobulbar injection. Thus, the
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FIGURE 7. Changes in the OCT images of a representative patient in the intravitreal and retrobulbar injection groups. In an eye that underwent intravitreal injection, the marked macular edema (A) decreased substantially and the eye showed virtually normal macular configuration at 1 month (B) and at 3 months (C) after injection. In an eye that underwent repeated retrobulbar injections, the severe macular edema (D) decreased slightly with time, but marked edema persisted at 1 month (E) and 3 months (F) after injection.
all patients in both groups had undergone laser photocoagulation according to the same protocol by the same surgeon. Because there was a significant difference in treatment effect between the groups, this difference must not be due to laser treatment but, rather, to type of injection used. In conclusion, a single intravitreal injection of triamcinolone has a strong effect on the reduction of macular edema caused by branch retinal vein occlusion and on the improvement of visual acuity. Although repeated retrobulbar injections also had a beneficial effect, the effect was weaker than that of intravitreal injection. However, macular edema recurred in approximately one-fifth of the patients, even after intravitreal injection, and there was a high incidence of a marked rise in IOP. Further study is obviously called for to examine for a longer time the effects and complication rates of triamcinolone injection for macular edema secondary to branch retinal vein occlusion.
incidence of IOP rise was not low and was similar to that noted in previous studies, although surgical intervention was not necessary. Accordingly, careful consideration must be given to the use of either intravitreal or periocular injection of triamcinolone in patients with or at high risk for glaucoma. Admittedly, several limitations exist in the present study. The first limitation is that follow-up was for only 3 months, and macular edema tends to recur after a greater length of time. However, the goal of this study was to compare the treatment effect on macular edema of a single intravitreal injection of triamcinolone vs repeated retrobulbar injections. Our results have clarified the difference in short-term effect of a single intravitreal injection and multiple retrobulbar injections. Furthermore, the differences in the incidence of reinjections and reasons for reinjections were clearly demonstrated. The second limitation is that laser photocoagulation was performed before injection. However, 980
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REFERENCES 1. Jonas JB, Sofker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Am J Ophthalmol 2001;132:425– 427. 2. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920 –927. 3. Jonas JB, Kreissig I, Sofker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 2003;121:57– 61. 4. Jonas JB, Degenring RF, Kamppeter BA, Kreissg I, Akkoyun I. Duration of the effect of intravitreal triamcinolone acetonide as treatment for diffuse diabetic macular edema. Am J Ophthalmol 2004;138:158 –160. 5. Massin P, Audren F, Haouchine B, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology 2004; 111:218 –224; discussion 224 –225. 6. Antcliff RJ, Spalton DJ, Stanford MR, Graham EM, ffytche TJ, Marshall J. Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study. Ophthalmology 2001;108:765–772. 7. Conway MD, Canakis C, Livir-Rallatos C, Peyman GA. Intravitreal trimamcinolone acetonide for refractory chronic pseudophakic cystoid macular edema. J Cataract Refract Surg 2003;28:27–33. 8. Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide for pseudophakic cystoid macular edema. Am J Ophthalmol 2003;136:384 –389. 9. Benhamau N, Massin P, Haouchine B, Audren F, Tadayoni R, Gaudric A. Intravitreal triamcinolone for refractory pseudophakic macular edema. Am J Ophthalmol 2003;135:246 – 249. 10. Penfold LP, Gyory JF, Hunyor AB, Bilson FA. Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Aust N Z J Ophthalmol 1995;23:293–298. 11. Danis RP, Ciulla TA, Pratt LM, Anliker W. Intravitreal triamcinolone acetonide in exudative age-related macular degeneration. Retina 2000;20:244 –250. 12. Jonas JB, Kreissig I, Hugger P, Sauder G, Panda-Jonas S, Degenring R. Intravitreal triamcinolone acetonide for exudative age related macular degeneration. Br J Ophthalmol 2003;87:462– 468. 13. 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. 14. Jonas JB, Akkoyun I, Budde WM, Kreissig I, Degenring RF. Intravitreal reinjection of triamcinolone for exudative agerelated macular degeneration. Arch Ophthalmol 2004;122: 218 –222. 15. Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2002; 240:782–783. 16. 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.
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17. Ip MS, Gottlieb JL, Kahana A, et al. Intravitreal triamcinolone for the treatment of macular edema associated with central retinal vein occlusion. Arch Ophthalmol 2004;122: 1131–1136. 18. Bashshur ZF, Ma’luf RN, Allam S, Jurdi FA, Haddad RS, Noureddin BN. Intravitreal triamcinolone for the management of macular edema due to nonischemic central retinal vein occlusion. Arch Ophthalmol 2004;122:1137–1140. 19. Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87:24 –27. 20. Kaushik S, Gupta V, Gupta A, Dogra MR, Singh R. Intractable glaucoma following intravitreal triamcinolone in central retinal vein occlusion. Am J Ophthalmol 2004;137: 758 –760. 21. Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2003;136:791–796. 22. Benz MS, Murray TG, Dubovy SR, Katz RS, Eifrig CWG. Endophthalmitis caused by Mycobacterium chelonae abscessus after intravitreal injection of triamcinolone. Arch Ophthalmol 2003;121:271–273. 23. Nelson ML, Tennant MTS, Sivalingam A, Regillo CD, Belmont JB, Martidis A. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina 2003;23:686 – 691. 24. Roth DB, Chieh J, Spian MJ, Green SN, Yarian DL, Chaudhry NA. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol 2003;121:1279 –1282. 25. Melberg NS, Olk RJ. Coticosteroid-induced ocular hypertension in the treatment of aphakic or pseudophakic cystoid macular edema. Ophthalmology 1993;100:164 –167. 26. Helm CJ, Holland GN. The effects of posterior subtenon injection of triamcinolone acetonide in patients with intermediate uveitis. Am J Ophthalmol 1995;120:55– 64. 27. Tanner V, Kanski JJ, Frith PA. Posterior sub-Tenon’s triamcinolone injections in the treatment of uveitis. Eye 1998;12: 679 – 685. 28. Okada AA, Wakabayashi T, Morimura Y, et al. TransTenon’s retrobulbar triamcinolone infusion for the treatment of uveitis. Br J Ophthalmol 2003;87:968 –971. 29. Ohguro N, Okada AA, Tano Y. Trans-Tenon’s retrobulbar triamcinolone infusion for diffuse diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2004;242:444 – 445. 30. McCartney HJ, Drysdale IO, Gornall AG, Basu PK. An autoradiographic study of the penetration of subconjunctivally injected hydrocortisone into the normal and inflamed rabbit eye. Invest Ophthalmol 1965;4:297–302. 31. Freeman WR, Green RL, Smith RE. Echographic localization of corticosteroids after periocular injection. Am J Ophthalmol 1987;103:281–288. 32. Branch Retinal Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch retinal vein occlusion. Am J Ophthalmol 1984;98:271–282. 33. Parodi MB, Saviano S, Ravalico G. Grid laser treatment in macular branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 1999;237:1024 –1027. 34. Arnarsson A, Stefansson E. Laser treatment and the mechanism of edema reduction in branch retinal vein occlusion. Invest Ophthalmol Vis Sci 2000;41:877– 879.
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41. Yamaji H, Shiraga F, Tsuchida Y, Yamamoto Y, Ohtsuki H. Evaluation of arteriovenous crossing sheathotomy for branch retinal vein occlusion by fluorescein videoangiography and image analysis. Am J Ophthalmol 2004;137:834 – 841. 42. Mason J 3rd, Feist R, White W Jr, Swanner J, McGwin G Jr, Emond T. Sheathotomy to decompress branch retinal vein occlusion: a matched control study. Ophthalmology 2004; 111:540 –545. 43. Chen SDM, Lochhead J, Patel CK, Frith P. Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by branch retinal vein occlusion. Br J Ophthalmol 2004;88:154 –155. 44. 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. 45. Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB 3rd, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology 2003;110:681– 686.
35. Maar N, Luksch A, Graebe A, et al. Effect of laser photocoagulation on the retinal vessel diameter in branch and macular vein occlusion. Arch Ophthalmol 2004;122:987–991. 36. Zaidi FH, Gair EJ, Gregory-Evans K. Criteria for improving visual acuity in ischaemic branch retinal vein occlusion using argon laser. Eye 2004;18:316 –318. 37. Opremcak EM, Bruce RA. Surgical decompression of branch retinal vein occlusion via arteriovenous crossing sheathotomy: a prospective review of 15 cases. Retina 1999;19:1–5. 38. Shah GK, Sharma S, Fineman MS, Federman J, Brown MM, Brown GC. Arteriovenous adventitial sheathotomy for the treatment of macular edema associated with branch retinal vein occlusion. Am J Ophthalmol 2000;129:104 –106. 39. Mester U, Dillinger P. Vitrectomy with arteriovenous decompression and internal limiting membrane dissection in branch retinal vein occlusion. Retina 2002;22:740 –746. 40. Cahill MT, Kaiser PK, Sears JE, Fekrat S. The effect of arteriovenous sheathotomy on cytoid macular oedema secondary to branch retinal vein occlusion. Br J Ophthalmol 2003;87:1329 –1332.
REPORTING VISUAL ACUITIES The AJO encourages authors to report the visual acuity in the manuscript using the same nomenclature that was used in gathering the data provided they were recorded in one of the methods listed here. This table of equivalent visual acuities is provided to the readers as an aid to interpret visual acuity findings in familiar units.
Table of Equivalent Visual Acuity Measurements Snellen Visual Acuities 4 Meters
6 Meters
20 Feet
Decimal Fraction
LogMAR
4/40 4/32 4/25 4/20 4/16 4/12.6 4/10 4/8 4/6.3 4/5 4/4 4/3.2 4/2.5 4/2
6/60 6/48 6/38 6/30 6/24 6/20 6/15 6/12 6/10 6/7.5 6/6 6/5 6/3.75 6/3
20/200 20/160 20/125 20/100 20/80 20/63 20/50 20/40 20/32 20/25 20/20 20/16 20/12.5 20/10
0.10 0.125 0.16 0.20 0.25 0.32 0.40 0.50 0.63 0.80 1.00 1.25 1.60 2.00
⫹1.0 ⫹0.9 ⫹0.8 ⫹0.7 ⫹0.6 ⫹0.5 ⫹0.4 ⫹0.3 ⫹0.2 ⫹0.1 0.0 ⫺0.1 ⫺0.2 ⫺0.3
From Ferris FL III, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol 1982;94:91–96.
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Biosketch Ken Hayashi, MD, is the director of the Hayashi Eye Hospital in Fukuoka, Japan. He graduated with a degree in medicine from Kyushu University in 1982 and completed postgraduate training in 1989. His main research interests are anterior segment diseases, particularly as they relate to cataract surgery, keratoplasty, and glaucoma surgery. He has published more than 60 peer-reviewed articles in internationally acclaimed journals. He currently serves as editor of the Japanese Journal of Cataract and Refractive Surgery.
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Biosketch Hideyuki Hayashi, MD, is a professor of ophthalmology at Fukuoka University, Fukuoka Japan. He graduated from Fukuoka University at 1978 and trained in Fukuoka University Hospital, Beth Israel Hospital at Boston, and Wilmer Eye Institute, Baltimore. His main interests are vitreo-retinal surgery, diagnostic ocular imaging, pediatric retinal diseases and ocular angiogenesis. He has published more than 60 international peer-reviewed articles.
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● PURPOSE:
To compare the short-term effect of intravitreal versus retrobulbar injection of triamcinolone acetonide for the treatment of macular edema caused by branch retinal vein occlusion. ● DESIGN: Randomized clinical trial. ● METHODS: Sixty eyes of 60 patients who had macular edema associated with branch retinal vein occlusion were randomly assigned to receive a single intravitreal injection (4 mg) or repeated retrobulbar injections (40 mg, three times) of triamcinolone. These injections (first injection in the retrobulbar group) were given approximately 1 week after focal laser photocoagulation. Using optical coherence tomography, the central retinal (foveal) thickness and total macular volume were measured before and at 1 and 3 months after injection. Visual acuity, intraocular pressure, and the incidence of reinjection were also examined. Fifty-two patients (86.7%) completed the 3-month follow-up. ● RESULTS: The mean foveal thickness and total macular volume decreased significantly after either intravitreal or repeated retrobulbar triamcinolone injections. Foveal thickness and macular volume were significantly less after intravitreal injection than after repeated retrobulbar injections, although there had been no significant differences at baseline. The percent reductions in foveal thickness and macular volume were also greater after intravitreal injection than after retrobulbar injections. Improvement in visual acuity was significantly better after intravitreal injection than after the retrobulbar injections. The incidence of intraocular pressure rise (to >20 mm Hg) was greater in the intravitreal group than in the retrobulbar group, but this was readily controlled by the use of antiglaucoma medications. After completion of the 3-month follow-up, 24 patients (46.2%) underwent reinjection. The need for reinjections was signifiAccepted for publication Dec 28, 2004. From the Hayashi Eye Hospital (K.H.) and the Department of Ophthalmology, School of Medicine, Fukuoka University (H.H.), Fukuoka, Japan. Inquiries to Ken Hayashi, MD, Hayashi Eye Hospital, 4-7-13 Hakataekimae, Hakata-ku, Fukuoka 812-0011, Japan; fax: 81-92-441-5303; e-mail: [email protected]
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cantly greater in the retrobulbar group than in the intravitreal group (P ⴝ .0001). ● CONCLUSIONS: A single intravitreal injection of triamcinolone is significantly more effective than are repeated retrobulbar injections in reducing macular edema associated with branch retinal vein occlusion, and leads to greater improvement in visual acuity. (Am J Ophthalmol 2005;139:972–982. © 2005 by Elsevier Inc. All rights reserved.)
I
NTRAVITREAL INJECTION OF TRIAMCINOLONE ACE-
tonide has been performed recently for macular edema associated with various retinal diseases, including diabetic retinopathy,1–5 uveitis,6 pseudophakic cystoid macular edema,7–9 exudative age-related macular degeneration,10 –14 and central retinal vein occlusion.15–18 Most studies showed that intravitreal triamcinolone was effective in reducing edema and in improving visual acuity. However, such injections have been reported to cause a high incidence of marked rise in intraocular pressure (IOP).19,20 Moreover, this procedure is known to confer a potential risk for cataract formation, endophthalmitis, and retinal detachment.21–24 Since the 1950s, subtenon’s and retrobulbar injections of long-acting corticosteroids have been used for the treatment of uveitis and for pseudophakic and diabetic cystoid macular edema.25–29 It has been demonstrated that corticosteroids injected periocularly penetrate the sclera and decrease the intraocular inflammation.30,31 Furthermore, even when several injections are given, the risk of intraocular complications such as cataract formation, endophthalmitis, and retinal detachment is less likely after periocular injection than after intravitreal injection. Branch retinal vein occlusion may cause persistent macular edema, which, in turn, can lead to visual impairment. Accordingly, various modalities have been used to lessen the macular edema caused by branch retinal vein occlusion. Traditionally, focal grid laser photocoagulation is performed in the edematous region.32–36 In addition, vitrectomy has been shown to be beneficial in reducing macular edema.37– 42 More recently, Chen and associates43 reported a case in which intravitreal triamcinolone de-
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/05/$30.00 doi:10.1016/j.ajo.2004.12.087
creased substantially the macular edema caused by branch retinal vein occlusion. Based on these reports, we recently began to perform either intravitreal or retrobulbar injection of triamcinolone for macular edema associated with branch retinal vein occlusion. The purpose of the study described herein was to compare the short-term effect of intravitreal vs retrobulbar injections of triamcinolone in reducing edema. Our preliminary study using Stratus optical coherence tomography (OCT; Carl Zeiss Ophthalmic Systems, Dublin, California, USA) had shown that a single retrobulbar injection of 40 mg of triamcinolone had little effect on the foveal thickness in eyes with branch retinal vein occlusion. Accordingly, three retrobulbar injections, given once every 2 weeks. were used in the present study.
PATIENTS AND METHODS THIS STUDY WAS DESIGNED AS A RANDOMIZED CLINICAL
trial. ● PATIENTS:
The study protocol was approved by the institutional review board. All consecutive patients who were seen in our outpatient clinic between August 2003 and April 2004 because of visual impairment due to branch retinal vein occlusion were screened for inclusion in this study. When both eyes had branch retinal vein occlusion, only the eye that was more recently affected was included. One of the authors (K.H.) verified the presence of macular edema associated with branch retinal vein occlusion using slit-lamp biomicroscopy with a ⫹90-diopter lens, Stratus OCT, and fluorescein angiography. When the total macular volume was greater than 2.60 mm3 on OCT and when leakage from the vessels around the macula was present on fluorescein angiography, the eye was considered to have macular edema. The patient was then further screened for eligibility. Inclusion criteria were (1) being seen at our clinic within 12 months after the approximate onset of symptoms, (2) foveal ischemia of less than 180 degrees, (3) no other pathology of the macula or optic nerve, (4) no remarkable media opacities involving cornea, lens, or vitreous body, (5) availability of a clear OCT image, and (6) availability of the patients for 3-month follow-up. The occurrence of branch retinal vein occlusion was determined by the approximate date on which the patient first noted symptoms. The degree of foveal ischemia was determined on fluorescein angiography by the nonperfusion area around the fovea. Intravitreal or retrobulbar injection of triamcinolone was offered to treat the macular edema caused by branch retinal vein occlusion, and informed consent was obtained from each patient. Patient screening was continued until 60 eyes of 60 patients were recruited.
● RANDOMIZATION:
A clinical research coordinator randomized all patients on the day of enrollment into one of
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two groups: intravitreal injection or repeated retrobulbar injections. A randomization code with equal numbers was generated by the use of random number tables. To mask the ophthalmic technicians who performed the OCT and visual acuity examinations, and physicians who measured the IOP, the coordinator who made the randomization code kept concealed the assignment schedule until all data were collected. One of the authors (K.H.), who performed all laser photocoagulations and intravitreal triamcinolone injections, is also a data analyst, and was not informed of the assignment schedule. Ophthalmic technicians who performed the OCT and visual acuity examinations and physicians who measured the IOP were not informed of the purpose of this study or of assignment schedule. ● PREINJECTION TREATMENTS: Before injection, one of the authors (K.H.) performed grid laser photocoagulation in the region of edema outside the macula according to the recommendation of the Branch Retinal Vein Occlusion Study Group.32 A yellow or yellow-green laser was applied in the edematous region usually with 100- spot size, 0.2-second exposure, and power sufficient to create a light gray burn, with a range of 38 to 103 shots. The burn was created in a random grid pattern with spacing of about one burn-width, outside the macula and as peripheral as the retinal vascular arcade. Sectorial laser photocoagulation to the ischemic area outside the major vascular arcade was not performed before injection, except for three eyes in which laser photocoagulation had already been performed at another facility. The only medication used in the 60 patients was oral aspirin (81 mg) once a day in 9 patients (15%) and kallidinogenase (500 mg) three times a day in 8 (13.3%). ● INJECTION PROCEDURES: Approximately 1 week after focal laser photocoagulation, all patients underwent either intravitreal or retrobulbar injection of triamcinolone acetonide (Bristol Pharmaceuticals, Tokyo, Japan). The intravitreal triamcinolone injection was done under sterile conditions in the operating room. Eyes receiving the intravitreal injection were anesthetized by topical instillation of 0.4% oxybuprocaine and a retrobulbar injection of 1.5 ml of 2% xylocaine. In this study, to perform intravitreal injection safely, retrobulbar anesthesia was added. However, it may be possible to use only topical anesthesia, if the surgeon is experienced in performing the procedure. Under the operating microscope, 0.1 ml of triamcinolone acetonide (4 mg) was injected slowly via a 30-gauge needle through the pars plana, 3.0 mm posterior to the limbus in pseudopakic eyes, and 4.0 mm posterior to the limbus in phakic eyes. In the present study, the retrobulbar injection of triamcinolone was performed three times, once every 2 weeks, because a single retrobulbar injection was found in our preliminary study to inadequately reduce the macular
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edema. Retrobulbar injections were performed in the outpatient clinic. After topical instillation of 0.4% oxybuprocaine, 1.0 ml of triamcinolone (40 mg) mixed with 0.1 ml of 2% xylocaine was injected via a 25-gauge needle through the inferior lid margin and into the retrobulbar space.
TABLE 1. Patient Characteristics in the Intravitreal and Retrobulbar Triamcinolone Injection Groups Characteristic
No. of eyes Age Gender (male/ female) Left/right Interval†
● MAIN OUTCOME MEASURES:
Main outcomes evaluated were the central retinal (foveal) thickness and total macular volume measured using the OCT, visual acuity, and IOP. All patients underwent these examinations before injection and at 1 and 3 months after injection. During the OCT procedure, each eye underwent six radial scans centered on the fovea. Each radial scan line consisted of 100 samples of 5.92 mm in length, yielding a total of 600 samples from the six radial scans. Macular volume was calculated as follows. A central macular thickness map measuring 3.45 mm in diameter was generated. The circular map was subdivided into nine quadrants. The middle and inner circle diameters were 2.22 mm and 1.00 mm, respectively. The mean retinal thickness was calculated for each of the nine quadrants from the previously obtained radial scans. Multiplying the mean retinal thickness by the area of the quadrant generated the volume for each of the nine quadrants. The total macular volume was thus determined as the sum of the nine quadrant volumes. Best-corrected visual acuity on decimal charts was examined at each visit and was converted to the logarithm of minimal angle of resolution (logMAR) scale for statistical analysis. The IOP was measured using Goldmann applanation tonometry, and the number of glaucoma medications used was also recorded. When an additional injection was performed after the 3-month follow-up, the incidence of reinjection, reasons for reinjection, and foveal thickness and macular volume at the time of reinjection were also recorded. The OCT and visual acuity examinations were carried out by experienced ophthalmic technicians; IOPs were measured by physicians in our clinic.
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Retrobulbar Group
27 65.2 ⫾ 11.3 10/17
25 64.6 ⫾ 10.4 10/14
14/13 2.8 ⫾ 3.1
15/9 2.8 ⫾ 2.5
P Value
— .6536* ⬎.9999* .4130* .7347*
*No statistically significant difference. Interval between presumed occurrence and injection (months). †
RESULTS A TOTAL OF 76 EYES DIAGNOSED AS HAVING MACULAR
edema associated with branch retinal vein occlusion were screened. Before enrollment, 9 eyes were excluded because the onset of symptoms was more than 12 months previously, 2 because of foveal ischemia greater than 180 degrees, 1 because of pathology of the optic nerve, 2 because of extensive media opacity due to cataract or vitreous hemorrhage, and 2 because of anticipated difficulty in follow-up. Therefore, 60 eyes of 60 patients were recruited and randomized. After injection, 3 eyes in the intravitreal injection group and 5 in the retrobulbar injection group were lost to follow-up because of scheduling conflict or because of patients’ refusal. Accordingly, of the 60 patients, 52 eyes of 52 patients (86.7%) completed the 3-month follow-up and were available for analysis. The mean age of the patients (⫾SD) was 64.9 ⫾ 10.8 years, with a range of 38 to 83 years. There were 20 men and 31 women. The mean duration from the approximate onset of branch retinal vein occlusion to injection was 2.8 ⫾ 2.8 months. Patient demographics are shown in Table 1. No statistically significant differences were found between groups regarding age, gender, the ratio of left to right eyes, or the interval between onset of symptoms and injection. Comparisons of mean central retinal (foveal) thickness and total macular volume in the intravitreal and retrobulbar injection groups are shown in Figures 1 and 2, respectively. Temporal changes in total macular volume are depicted in Figure 3. When comparing the two groups, no significant differences were found in mean foveal thickness or macular volume before injection. After injection, however, both foveal thickness and macular volume decreased significantly in the intravitreal group (P ⬍ .0001). In the retrobulbar group, the macular volume also decreased significantly (P ⫽ .0391), but the reduction in foveal thickness was not significant (P ⫽ .2139). At both 1 and 3 months, the mean foveal thickness and macular volume in the intravitreal injection group were significantly less than those in the retrobulbar injection group.
● STATISTICAL ANALYSIS: For the continuous variables, normality of data distribution was first tested using the Kolmogorov-Smirnov test. Temporal changes in central retinal thickness and total macular volume, logMAR visual acuity, and IOP were compared using the KruskalWallis test. When there was a significant difference, the difference between each group was further compared using the Mann-Whitney U test with the Bonferroni adjustment. The differences between groups in foveal thickness and macular volume, logMAR visual acuity, IOP, and other continuous variables were compared using the Mann-Whitney U test. Categorical variables were compared using the Fisher’s exact test or the 2 test for independence. The survival curves of the need for reinjections were compared using the Mantel-Cox log rank test. Any differences showing a P value of less than .05 were considered to be statistically significant.
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FIGURE 1. Comparison of mean (ⴞSD) [median] values of central retinal (foveal) thickness between the intravitreal injection and retrobulbar injection groups as measured by optical coherence tomography. No significant difference between the groups was observed in mean foveal thickness before injection. At 1 and 3 months after injection, foveal thickness in the intravitreal injection group was significantly less than that in the retrobulbar injection group.
FIGURE 2. Comparison of mean (ⴞSD) [median] values of total macular volume between the intravitreal injection and retrobulbar injection groups as measured by optical coherence tomography. No significant difference between the groups was found in the mean total macular volume before injection. At 1 and 3 months after injection, the total macular volume in the intravitreal injection group was significantly less than that in the retrobulbar injection group.
Percentage reductions in foveal thickness and macular volume (Figure 4) in the intravitreal group were also greater than those in the retrobulbar group. The mean logMAR visual acuity in the intravitreal injection group improved significantly (P ⫽ .0065), whereas that in the retrobulbar group did not show a VOL. 139, NO. 6
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significant change (P ⫽ .6290). When comparing groups, there was no significant difference in mean visual acuity before injection or at 1 or 3 months after injection (Table 2). However, improvement in visual acuity in the intravitreal injection group was significantly greater than that in the retrobulbar injection group.
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FIGURE 3. Temporal changes in the mean total macular volume (ⴞSD) in the intravitreal injection and retrobulbar injection groups. In the intravitreal injection group, the mean total macular volume decreased significantly up to 1 month after injection (P < .0001). In the retrobulbar injection group, the volume did not decrease up to 1 month after injection, but the reduction of the volume became significant by 3 months after injection.
FIGURE 4. Comparison of mean (ⴞSD) percentage reduction in central retinal thickness and total macular volume in the intravitreal injection and retrobulbar injection groups. Percentage reductions in both foveal thickness and total macular volume in the intravitreal injection group were significantly greater than those in the retrobulbar injection group at 1 and 3 months after injection.
Regarding postinjection complications, serious problems such as cataract formation, endophthalmitis, and retinal detachment did not occur in this series, and the mean IOP did not increase significantly in either group (P ⫽ .1315 in the intravitreal group and P ⫽ .2504 in the retrobulbar group). Comparisons of the mean IOP and percentage increase in the IOP in the intravitreal 976
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and retrobulbar injection groups are shown in Table 3. No significant difference was found in the mean IOP at baseline or at 3 months after injection, but IOP in the intravitreal group was higher than that in the retrobulbar group at 1 month after injection. There was also no significant difference in the percentage increase in IOP between the two groups throughout the follow-up peOF
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TABLE 2. Comparison Between Intravitreal and Retrobulbar Injection Groups of Mean (⫾SD) and Median logMAR Visual Acuity and Improvement in logMAR Visual Acuity Intravitreal Group Mean (median)
Parameter
Visual acuity Preoperative 1 month postoperatively 3 months postoperatively Improvement in visual acuity 1 month postoperatively 3 month postoperatively
0.598 ⫾ 0.375 (0.398) 0.373 ⫾ 0.308 (0.398) 0.312 ⫾ 0.315 (0.155) ⫺0.224 ⫾ 0.218 (⫺0.176) ⫺0.285 ⫾ 0.269 (⫺0.204)
Retrobulbar Group Mean (median)
P Value
0.433 ⫾ 0.285 (0.301) 0.409 ⫾ 0.259 (0.301) 0.341 ⫾ 0.186 (0.301)
.0835* .4235* .1585*
⫺0.024 ⫾ 0.170 (0) ⫺0.092 ⫾ 0.225 (0)
.0002† .0078†
logMAR ⫽ logarithm of minimal angle of resolution. *No statistically significant difference. † Statistically significant difference.
TABLE 3. Comparison Between Intravitreal and Retrobulbar Injection Groups of Mean (⫾SD) and Median Intraocular Pressure (IOP) and Percentage Increase in IOP Intravitreal Group Mean (median)
Parameter
IOP (mm Hg) Preoperative 1 month postoperatively 3 months postoperatively Percentage increase in IOP (%) 1 month postoperatively 3 months postoperatively
Retrobulbar Group Mean (median)
P Value
14.1 ⫾ 3.5 (14) 16.1 ⫾ 4.3 (16) 16.6 ⫾ 5.9 (16)
12.9 ⫾ 3.5 (12) 13.9 ⫾ 3.8 (13) 13.8 ⫾ 2.9 (13)
.1479* .0307† .0617*
18.5 ⫾ 37.0 (11.8) 24.8 ⫾ 61.8 (13.3)
9.7 ⫾ 19.9 (0) 12.1 ⫾ 29.4 (7.1)
.3843* .8047*
*No statistically significant difference. † Statistically significant difference.
riod. However, an increase in IOP to 20 mm Hg or greater occurred in nine eyes (33.3%) in the intravitreal group and in two eyes (7.4%) in the retrobulbar group, which represented a significantly higher incidence in the intravitreal group (P ⫽ .0404). Furthermore, the mean number of antiglaucoma medications used in the intravitreal group was greater than that in the retrobulbar group (2.7 in the intravitreal group vs 1.0 in the retrobulbar group; P ⫽ .0339). Of the 52 patients, reinjection of triamcinolone was performed in 24 patients (46.2%) after the conclusion of the 3-month follow-up. Of the 27 patients who received an intravitreal injection, 6 (22.2%) required reinjection; of the 25 patients who received retrobulbar injections, 18 (72.0%) received an intravitreal reinjection and 1 (4.0%) an additional retrobulbar injection. Kaplan-Meier survival analysis showed that the need for additional injections was significantly greater in the retrobulbar group than in the intravitreal group (P ⫽ .0001, Figure 5). Table 4 shows the reasons for reinjections as well as foveal thickness and macular volume at the time of reinjections. The reasons for reinjection in VOL. 139, NO. 6
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the intravitreal injection group were the recurrence of edema in five patients (18.5%) and inadequate effect in one (3.7%), whereas in the retrobulbar group the reason was inadequate effect in all 18 (72.0%); the reasons were significantly different (P ⬍ .0001). Furthermore, in both groups, the foveal thickness and macular volume in eyes that required reinjection were greater at the time of reinjection than in eyes that did not require reinjection. As a consequence of reinjections, however, no significant differences were found in foveal thickness, macular volume, or visual acuity between groups at 6 months after the first injection (Figure 6). Figure 7 illustrates changes in the OCTimages of a representative patient in the intravitreal injection group and of a patient in the retrobulbar injection group. In the eye that underwent intravitreal injection, macular edema decreased substantially and showed a virtually normal configuration at 1 and 3 months after injection. In the eye that had repeated retrobulbar injections, the macular edema decreased slightly over time, but severe edema persisted for up to 3 months, even after the last planned injection.
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TABLE 4. Reasons for Reinjection, and Foveal Thickness and Total Macular Volume at the Time of Reinjection, in Intravitreal and Retrobulber Injection Groups After Completion of the 3-month Follow-up
Parameter
Reasons for reinjection Inadequate effect Recurrence of edema Foveal thickness () Reinjection group‡ No reinjection group§ P value Total macular volume (mm3) Reinjection group‡ No reinjection group§ P value
FIGURE 5. Kaplan-Meier survival plots of the two groups for eyes requiring reinjection of triamcinolone after the planned follow-up. The survival curve in the intravitreal injection group was significantly better than that in the retrobulbar group (P ⴝ .0001).
DISCUSSION intravitreal injection or repeated retrobulbar injections of triamcinolone has a beneficial effect in reducing the macular edema associated with branch retinal vein occlusion. The single intravitreal injection decreased significantly the foveal thickness and macular volume at 1 month, whereas the reduction in foveal thickness and in macular volume at 1 month after retrobulbar injection was not statistically significant. These results suggest that repeated injections might be necessary to induce a significant effect when utilizing the periocular injection route, whereas a single intravitreal injection has an immediate effect. When comparing injections, the foveal thickness and macular volume after intravitreal injection were less than those after repeated retrobulbar injections at both 1 and 3 months. Furthermore, the percentage reductions in foveal thickness and in macular volume after intravitreal injection were significantly greater than those after three retrobulbar injections. These results indicate that a single intravitreal injection is more effective in reducing macular edema than are repeated retrobulbar injections. Visual acuity also improved significantly after intravitreal injection, whereas improvement in visual acuity after retrobulbar injections was not significant. The insignificant improvement in visual acuity despite a slight reduction in macular edema after retrobulbar injections suggests that almost complete resolution of macular edema may be necessary for significant improvement in visual acuity. When comparing the two groups, however, no significant differences were found AMERICAN JOURNAL
Retrobulbar Group
1 (3.7%) 5 (18.5%)
18 (72.0%) 0
415 ⫾ 222 220 ⫾ 102
362 ⫾ 159 265 ⫾ 158
.0442*
.1549†
3.57 ⫾ 0.92 2.64 ⫾ 0.35
3.41 ⫾ 0.69 2.68 ⫾ 0.19
.0132*
.0142*
P Value
⬍.0001*
— —
— —
*Statistically significant difference. † No significant difference. ‡ Patients who were scheduled for reinjection. § Patients who did not receive reinjection.
OUR STUDY HAS DEMONSTRATED THAT EITHER A SINGLE
978
Intravitreal Group
in mean visual acuity at either 1 or 3 months after injection. This is probably because visual acuity at baseline tended to be worse in the intravitreal injection group than in the retrobulbar injection group. In fact, improvement in visual acuity after intravitreal injection was significantly greater than improvement after repeated retrobulbar injections. These results indicate that intravitreal injection is more effective in improving visual acuity than are retrobulbar injections. Approximately 46% of all patients required an additional injection of triamcinolone after completion of the planned follow-up. Specifically, 72% of patients in the retrobulbar injection group received a supplemental intravitreal reinjection and 4% received an extra retrobulbar injection, whereas 22% of patients in the intravitreal group underwent a second intravitreal injection. These additional injections were needed primarily because of an inadequate response in terms of reduced edema after retrobulbar injection and a recurrence of edema after intravitreal injection. Thus, although intravitreal injection of triamcinolone has a strong effect on the macular edema, the most important problem may be recurrence. However, as a consequence of additional intravitreal injections, there were no significant differences in foveal thickness, macular volume, or visual acuity at 6 months after the first injection. For treatment of macular edema associated with branch retinal vein occlusion, grid laser photocoagulaOF
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FIGURE 6. Comparison of mean (ⴞSD) [median] foveal thickness and total macular volume at 6 months after the first injection. No significant differences were found in foveal thickness or macular volume between the intravitreal injection and retrobulbar injection groups at 6 months after the first injection.
tion in the region of the edema has been recommended,32–36 but this is known to be ineffective in many cases.44 It has been shown that vitrectomy with arteriovenous sheathotomy improves retinal vein circulation.37– 42 However, the surgical technique of vitrectomy with arteriovenous sheathotomy is difficult and the complication rate is not low. Chen and associates43 recently reported intravitreal injection of triamcinolone to be a safe and effective treatment for macular edema associated with branch retinal vein occlusion. Our results agree with those of Chen and associates. However, several other studies on the use of triamcinolone for retinal vascular diseases other than branch retinal vein occlusion reported that its effect in reducing macular edema was transient and that recurrence of edema occurred in many instances.4,5,12,13 In our study, approximately 22% of the patients who had undergone intravitreal injection of triamcinolone experienced a recurrence of edema and required a second injection at approximately 4 months after the first injection. It has been shown that 4 mg of triamcinolone injected into the vitreous cavity lasts for approximately 3 months after injection,45 so it is entirely possible that recurrence of macular edema occurs when the intravitreal triamcinolone is absorbed. Furthermore, intravitreal injection of triamcinolone is accompanied by the risk of cataract progression, intractable rise in IOP, infectious or noninfectious endophthalmitis, and retinal detachment.19 –24 Conversely, periocular injection of triamcinolone has been widely used for the treatment of uveitis and pseudophakic or diabetic macular edema.25–29 It has been demonVOL. 139, NO. 6
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strated that triamcinolone injected into the periocular space gradually penetrates the sclera30,31 and thereby decreases the intraocular inflammation.25–28 Periocular injection of triamcinolone is thought to be much safer than intravitreal injection. However, as shown by the present study, the effect of retrobulbar injection in reducing macular edema is not nearly as strong as is that of intravitreal injection. This suggests that periocular triamcinolone injection might best be used as an adjunctive treatment for slight edema or as prophylaxis for a recurrence. In the study described herein, the mean IOP at 1 month after intravitreal injection was higher than that after retrobulbar injection, although no significant difference was found at baseline. The incidence of marked rise in IOP was also greater after intravitreal injection than after retrobulbar injection. In addition, the number of topical antiglaucomatous medications required after intravitreal injection was greater than that after retrobulbar injection. Subsequently, however, the mean IOP at 3 months was not different between the two groups, suggesting that the IOP after intravitreal injection can be normalized by topical medications. It is well known that the a rise in IOP can occur after periocular injection of triamcinolone, as well as after intravitreal injection,19,25,26 but a case of secondary refractory glaucoma after intravitreal triamcinolone injection has been reported, and surgical removal of triamcinolone depot and trabeculectomy were necessary for IOP control in that patient.21 In the present study, an increase in IOP was noted in 33% of the patients after intravitreal injection and in 8% after retrobulbar injection. Thus, the
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FIGURE 7. Changes in the OCT images of a representative patient in the intravitreal and retrobulbar injection groups. In an eye that underwent intravitreal injection, the marked macular edema (A) decreased substantially and the eye showed virtually normal macular configuration at 1 month (B) and at 3 months (C) after injection. In an eye that underwent repeated retrobulbar injections, the severe macular edema (D) decreased slightly with time, but marked edema persisted at 1 month (E) and 3 months (F) after injection.
all patients in both groups had undergone laser photocoagulation according to the same protocol by the same surgeon. Because there was a significant difference in treatment effect between the groups, this difference must not be due to laser treatment but, rather, to type of injection used. In conclusion, a single intravitreal injection of triamcinolone has a strong effect on the reduction of macular edema caused by branch retinal vein occlusion and on the improvement of visual acuity. Although repeated retrobulbar injections also had a beneficial effect, the effect was weaker than that of intravitreal injection. However, macular edema recurred in approximately one-fifth of the patients, even after intravitreal injection, and there was a high incidence of a marked rise in IOP. Further study is obviously called for to examine for a longer time the effects and complication rates of triamcinolone injection for macular edema secondary to branch retinal vein occlusion.
incidence of IOP rise was not low and was similar to that noted in previous studies, although surgical intervention was not necessary. Accordingly, careful consideration must be given to the use of either intravitreal or periocular injection of triamcinolone in patients with or at high risk for glaucoma. Admittedly, several limitations exist in the present study. The first limitation is that follow-up was for only 3 months, and macular edema tends to recur after a greater length of time. However, the goal of this study was to compare the treatment effect on macular edema of a single intravitreal injection of triamcinolone vs repeated retrobulbar injections. Our results have clarified the difference in short-term effect of a single intravitreal injection and multiple retrobulbar injections. Furthermore, the differences in the incidence of reinjections and reasons for reinjections were clearly demonstrated. The second limitation is that laser photocoagulation was performed before injection. However, 980
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REFERENCES 1. Jonas JB, Sofker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Am J Ophthalmol 2001;132:425– 427. 2. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920 –927. 3. Jonas JB, Kreissig I, Sofker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 2003;121:57– 61. 4. Jonas JB, Degenring RF, Kamppeter BA, Kreissg I, Akkoyun I. Duration of the effect of intravitreal triamcinolone acetonide as treatment for diffuse diabetic macular edema. Am J Ophthalmol 2004;138:158 –160. 5. Massin P, Audren F, Haouchine B, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology 2004; 111:218 –224; discussion 224 –225. 6. Antcliff RJ, Spalton DJ, Stanford MR, Graham EM, ffytche TJ, Marshall J. Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study. Ophthalmology 2001;108:765–772. 7. Conway MD, Canakis C, Livir-Rallatos C, Peyman GA. Intravitreal trimamcinolone acetonide for refractory chronic pseudophakic cystoid macular edema. J Cataract Refract Surg 2003;28:27–33. 8. Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide for pseudophakic cystoid macular edema. Am J Ophthalmol 2003;136:384 –389. 9. Benhamau N, Massin P, Haouchine B, Audren F, Tadayoni R, Gaudric A. Intravitreal triamcinolone for refractory pseudophakic macular edema. Am J Ophthalmol 2003;135:246 – 249. 10. Penfold LP, Gyory JF, Hunyor AB, Bilson FA. Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Aust N Z J Ophthalmol 1995;23:293–298. 11. Danis RP, Ciulla TA, Pratt LM, Anliker W. Intravitreal triamcinolone acetonide in exudative age-related macular degeneration. Retina 2000;20:244 –250. 12. Jonas JB, Kreissig I, Hugger P, Sauder G, Panda-Jonas S, Degenring R. Intravitreal triamcinolone acetonide for exudative age related macular degeneration. Br J Ophthalmol 2003;87:462– 468. 13. 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. 14. Jonas JB, Akkoyun I, Budde WM, Kreissig I, Degenring RF. Intravitreal reinjection of triamcinolone for exudative agerelated macular degeneration. Arch Ophthalmol 2004;122: 218 –222. 15. Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2002; 240:782–783. 16. 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.
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17. Ip MS, Gottlieb JL, Kahana A, et al. Intravitreal triamcinolone for the treatment of macular edema associated with central retinal vein occlusion. Arch Ophthalmol 2004;122: 1131–1136. 18. Bashshur ZF, Ma’luf RN, Allam S, Jurdi FA, Haddad RS, Noureddin BN. Intravitreal triamcinolone for the management of macular edema due to nonischemic central retinal vein occlusion. Arch Ophthalmol 2004;122:1137–1140. 19. Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87:24 –27. 20. Kaushik S, Gupta V, Gupta A, Dogra MR, Singh R. Intractable glaucoma following intravitreal triamcinolone in central retinal vein occlusion. Am J Ophthalmol 2004;137: 758 –760. 21. Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2003;136:791–796. 22. Benz MS, Murray TG, Dubovy SR, Katz RS, Eifrig CWG. Endophthalmitis caused by Mycobacterium chelonae abscessus after intravitreal injection of triamcinolone. Arch Ophthalmol 2003;121:271–273. 23. Nelson ML, Tennant MTS, Sivalingam A, Regillo CD, Belmont JB, Martidis A. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina 2003;23:686 – 691. 24. Roth DB, Chieh J, Spian MJ, Green SN, Yarian DL, Chaudhry NA. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol 2003;121:1279 –1282. 25. Melberg NS, Olk RJ. Coticosteroid-induced ocular hypertension in the treatment of aphakic or pseudophakic cystoid macular edema. Ophthalmology 1993;100:164 –167. 26. Helm CJ, Holland GN. The effects of posterior subtenon injection of triamcinolone acetonide in patients with intermediate uveitis. Am J Ophthalmol 1995;120:55– 64. 27. Tanner V, Kanski JJ, Frith PA. Posterior sub-Tenon’s triamcinolone injections in the treatment of uveitis. Eye 1998;12: 679 – 685. 28. Okada AA, Wakabayashi T, Morimura Y, et al. TransTenon’s retrobulbar triamcinolone infusion for the treatment of uveitis. Br J Ophthalmol 2003;87:968 –971. 29. Ohguro N, Okada AA, Tano Y. Trans-Tenon’s retrobulbar triamcinolone infusion for diffuse diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2004;242:444 – 445. 30. McCartney HJ, Drysdale IO, Gornall AG, Basu PK. An autoradiographic study of the penetration of subconjunctivally injected hydrocortisone into the normal and inflamed rabbit eye. Invest Ophthalmol 1965;4:297–302. 31. Freeman WR, Green RL, Smith RE. Echographic localization of corticosteroids after periocular injection. Am J Ophthalmol 1987;103:281–288. 32. Branch Retinal Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch retinal vein occlusion. Am J Ophthalmol 1984;98:271–282. 33. Parodi MB, Saviano S, Ravalico G. Grid laser treatment in macular branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 1999;237:1024 –1027. 34. Arnarsson A, Stefansson E. Laser treatment and the mechanism of edema reduction in branch retinal vein occlusion. Invest Ophthalmol Vis Sci 2000;41:877– 879.
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41. Yamaji H, Shiraga F, Tsuchida Y, Yamamoto Y, Ohtsuki H. Evaluation of arteriovenous crossing sheathotomy for branch retinal vein occlusion by fluorescein videoangiography and image analysis. Am J Ophthalmol 2004;137:834 – 841. 42. Mason J 3rd, Feist R, White W Jr, Swanner J, McGwin G Jr, Emond T. Sheathotomy to decompress branch retinal vein occlusion: a matched control study. Ophthalmology 2004; 111:540 –545. 43. Chen SDM, Lochhead J, Patel CK, Frith P. Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by branch retinal vein occlusion. Br J Ophthalmol 2004;88:154 –155. 44. 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. 45. Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB 3rd, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology 2003;110:681– 686.
35. Maar N, Luksch A, Graebe A, et al. Effect of laser photocoagulation on the retinal vessel diameter in branch and macular vein occlusion. Arch Ophthalmol 2004;122:987–991. 36. Zaidi FH, Gair EJ, Gregory-Evans K. Criteria for improving visual acuity in ischaemic branch retinal vein occlusion using argon laser. Eye 2004;18:316 –318. 37. Opremcak EM, Bruce RA. Surgical decompression of branch retinal vein occlusion via arteriovenous crossing sheathotomy: a prospective review of 15 cases. Retina 1999;19:1–5. 38. Shah GK, Sharma S, Fineman MS, Federman J, Brown MM, Brown GC. Arteriovenous adventitial sheathotomy for the treatment of macular edema associated with branch retinal vein occlusion. Am J Ophthalmol 2000;129:104 –106. 39. Mester U, Dillinger P. Vitrectomy with arteriovenous decompression and internal limiting membrane dissection in branch retinal vein occlusion. Retina 2002;22:740 –746. 40. Cahill MT, Kaiser PK, Sears JE, Fekrat S. The effect of arteriovenous sheathotomy on cytoid macular oedema secondary to branch retinal vein occlusion. Br J Ophthalmol 2003;87:1329 –1332.
REPORTING VISUAL ACUITIES The AJO encourages authors to report the visual acuity in the manuscript using the same nomenclature that was used in gathering the data provided they were recorded in one of the methods listed here. This table of equivalent visual acuities is provided to the readers as an aid to interpret visual acuity findings in familiar units.
Table of Equivalent Visual Acuity Measurements Snellen Visual Acuities 4 Meters
6 Meters
20 Feet
Decimal Fraction
LogMAR
4/40 4/32 4/25 4/20 4/16 4/12.6 4/10 4/8 4/6.3 4/5 4/4 4/3.2 4/2.5 4/2
6/60 6/48 6/38 6/30 6/24 6/20 6/15 6/12 6/10 6/7.5 6/6 6/5 6/3.75 6/3
20/200 20/160 20/125 20/100 20/80 20/63 20/50 20/40 20/32 20/25 20/20 20/16 20/12.5 20/10
0.10 0.125 0.16 0.20 0.25 0.32 0.40 0.50 0.63 0.80 1.00 1.25 1.60 2.00
⫹1.0 ⫹0.9 ⫹0.8 ⫹0.7 ⫹0.6 ⫹0.5 ⫹0.4 ⫹0.3 ⫹0.2 ⫹0.1 0.0 ⫺0.1 ⫺0.2 ⫺0.3
From Ferris FL III, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol 1982;94:91–96.
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Biosketch Ken Hayashi, MD, is the director of the Hayashi Eye Hospital in Fukuoka, Japan. He graduated with a degree in medicine from Kyushu University in 1982 and completed postgraduate training in 1989. His main research interests are anterior segment diseases, particularly as they relate to cataract surgery, keratoplasty, and glaucoma surgery. He has published more than 60 peer-reviewed articles in internationally acclaimed journals. He currently serves as editor of the Japanese Journal of Cataract and Refractive Surgery.
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Biosketch Hideyuki Hayashi, MD, is a professor of ophthalmology at Fukuoka University, Fukuoka Japan. He graduated from Fukuoka University at 1978 and trained in Fukuoka University Hospital, Beth Israel Hospital at Boston, and Wilmer Eye Institute, Baltimore. His main interests are vitreo-retinal surgery, diagnostic ocular imaging, pediatric retinal diseases and ocular angiogenesis. He has published more than 60 international peer-reviewed articles.
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