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Intravitreal Triamcinolone for the Management of Macular Edema Due to Nonischemic Central Retinal Vein Occlusion
Ziad F. Bashshur, MD;
Riad N. Ma'luf, MD;
Souha Allam, MD;
Fadi A. Jurdi, MD;
Randa S. Haddad, MD;
Baha' N. Noureddin, MD
Arch Ophthalmol. 2004;122:1137-1140.
ABSTRACT
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Objective To evaluate the efficacy of intravitreal triamcinolone acetonide in the management of persistent macular edema secondary to nonischemic central retinal vein occlusion (CRVO).
Methods Twenty consecutive patients were selected with a 3- to 4-month history of nonischemic CRVO and persistent macular edema. These patients received a single intravitreal injection of 4 mg of triamcinolone acetonide (40 mg/mL). The follow-up period ranged from 10 to 12 months. The amount of macular edema was assessed by the amount of retinal thickening on clinical examination using the Goldmann contact lens and by the area and intensity of staining on fluorescein angiography. Treated patients were compared with a retrospectively matched group of patients who were managed with observation only.
Main Outcome Measures Changes in visual acuity and amount of macular edema were assessed in the treated patients and compared with the observation group.
Results The mean baseline visual acuity in the treatment group was 20/132 vs 20/123 for the observation group (P = .57). After 1 week, the treated group had a mean visual acuity of 20/51. At final follow-up, the treated group had a mean visual acuity of 20/37 while the observation group had a mean visual acuity of 20/110 (P = .001). Sixty percent of treated patients had a final visual acuity of 20/40 or better vs only 20% in the observation group (P = .01). Forty percent of the untreated patients had a final visual acuity worse than 20/200 while none of the treated patients did (P<.001). At final follow-up, 75% of treated patients had complete resolution of macular edema on clinical examination vs only 20% of the untreated patients (P<.001). Two of the treated patients had recurrence of macular edema at 6 months, and 3 had elevated intraocular pressure.
Conclusion This study shows a treatment benefit from intravitreal triamcinolone in terms of visual acuity and macular edema for nonischemic CRVO.
INTRODUCTION
Central retinal vein occlusion (CRVO) is one of the most common retinal vascular diseases and can be associated with significant visual morbidity. Decrease in visual acuity (VA) due to CRVO may be secondary to retinal hemorrhages over the fovea, ischemia, or macular edema.1 The standard of care currently remains limited to the management of the neovascular sequelae with panretinal photocoagulation. The Central Vein Occlusion Study showed that grid-pattern photocoagulation significantly reduced angiographic macular edema but did not result in visual improvement.2
Recent reports have suggested various treatment options to improve the circulation status of the retina after CRVO. Some of these include intravitreal tissue plasminogen activator, radial optic neurotomy, surgical recanalization of the retinal vein, and laser-induced chorioretinal anastomosis.3-6 Such reports, although encouraging, are pilot studies, and larger well-controlled studies are needed to establish the efficacy of these procedures.
Corticosteroids have been proposed for the management of macular edema due to various retinal vascular disorders. Intravitreal triamcinolone acetonide was investigated for persistent macular edema in diabetic retinopathy, chronic uveitis, and postsurgical cystoid macular edema.7-10 Recently, Ip and Kumar11 described 2 patients (2 eyes) and Greenberg et al12 described 1 patient (2 eyes) in whom macular edema due to CRVO was managed with intravitreal triamcinolone. The eyes with nonischemic CRVO had both reduction in macular edema and improvement in VA.
The purpose of this study is to evaluate the efficacy of intravitreal corticosteroids in the management of persistent macular edema secondary to nonischemic CRVO.
METHODS
Between September 2001 and March 2002, patients with CRVO of 3 to 4 months' duration were considered for enrollment in the study. All patients received an eye examination that included best-corrected VA using the Snellen acuity chart, slitlamp inspection of the anterior segment, and dilated fundus examination with indirect ophthalmoscopy and Goldmann 3-mirror contact lens. All patients had fluorescein angiography to the affected eye. Those with nonischemic CRVO and persistent macular edema were considered for admission into the study. A patient was considered to have a nonischemic CRVO if there was no afferent pupillary defect greater than 0.3 log unit, no rubeosis iridis, and capillary nonperfusion on fluorescein angiography less than 10 disc areas. Table 1 summarizes the inclusion and exclusion criteria. The first 20 consecutive patients who met the inclusion requirements were assigned to the treatment group.
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Table 1. Inclusion and Exclusion Criteria
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The procedure was explained to the patients who then signed a consent form. A peribulbar injection of 1% lidocaine hydrochloride was given in the affected eye, which was then prepared with 5% Betadine Solution (Purdue Frederick, Stamford, Conn). An intravitreal injection of 4 mg in 0.1 mL of triamcinolone acetonide was given with a 30-gauge needle 3.5 mm posterior to the limbus. The intraocular pressure was examined immediately, and an anterior chamber paracentesis was performed if the pressure was greater than 25 mm Hg. Patients in the treatment group were seen 24 hours after the procedure, 1 week later, and monthly thereafter. At each follow-up visit, a complete eye examination was carried out including best-corrected VA, slitlamp examination of the anterior segment, dilated fundus examination, and fluorescein angiography. The follow-up period ranged from 10 to 12 months. Retinal examination was done by the same ophthalmologist (Z.F.B.) using the Goldmann 3-mirror contact lens. Macular edema was assessed by the amount of retinal thickening on clinical examination and by the area and intensity of staining on angiography.
The observation group was selected from our databases of CRVO patients seen over the previous 2 years. We selected 20 consecutive patients who, during their initial follow-up visits, met the inclusion criteria for the study. Their records were reviewed and all the pertinent data were tabulated. Patients who did not have adequate follow-up were excluded.
The main outcome measures in this study were VA and the amount of macular edema. A decrease in macular edema was considered if there was a decrease in retinal thickness on clinical examination accompanied by a decrease in the area or intensity of fluorescein staining. Complete resolution occurred if no retinal thickening could be identified on dilated fundus examination with the contact lens and if there was no leakage on angiography.
Because Snellen charts were used to measure vision for both groups, the acuities were converted to logMAR units to perform the appropriate statistical manipulation. The statistical tests used for data analysis were the  2 and t tests. The level of statistical significance was fixed at P<.05 with a 95% confidence interval.
RESULTS
In general, both groups were well matched. The average age was 64.3 years and 64.7 years in the treatment and observation groups, respectively (P = .94). Similarly, there was no statistically significant difference with respect to baseline VA, sex, and all other major baseline characteristics. Table 2 summarizes the baseline criteria for patients in both treatment and observation groups.
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Table 2. Baseline Characteristics for Treated and Untreated Patients
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All patients in the treatment group tolerated the intravitreal injection well with no immediate complications. A paracentesis was performed on 18 patients to decrease the intraocular pressure immediately after the injection. Throughout the entire follow-up period, no untoward effects were noted except for elevated intraocular pressure in 3 patients at the 1-month follow-up. The pressure was not greater than 25 mm Hg and responded well to topical 0.5% timolol maleate, treatment with which was discontinued at the 3-month follow-up.
The mean baseline best-corrected VA in the treatment group was 20/132 vs 20/123 for the observation group (P = .57). At 1 week from entry into the study, the treated group had a mean VA of 20/51; however, it was not possible to compare this with that of the observation group because this data was lacking for most patients. At 1 month, the treated patients improved to a mean VA of 20/36 while there was no change in the observation group (P<.001). The treated patients continued to show a stable mean VAof 20/36 at 3 months, and the observation group had a mean VA of 20/96 (P = .001). At the final follow-up, the treated group had a mean VA of 20/37 while the observation group had a mean VA of 20/110 (P = .001). Table 3 shows the average VA for both groups at various follow-ups. At the conclusion of the study, 12 (60%) of the 20 treated patients had a VA of 20/40 or better while only 4 (20%) of the 20 patients in the observation group had a final VA of 20/40 or better (P = .01). Eight (40%) of the untreated patients had a final VA worse than 20/200 while none of the treated patients did (P<.001). Table 4 summarizes the differences in final VA between the 2 groups.
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Table 3. Average Visual Acuity for Treated and Untreated Patients at Baseline, 1 Week, 1 Month, 3 Months, and at Final Follow-up Visit
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Table 4. Distribution of Final Visual Acuities for Treated and Untreated Patients
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Macular edema was noted to decrease within 1 week of treatment. By 1 month of follow-up, macular edema completely resolved in 16 (80%) of the treated patients (Figure 1). At the 6-month follow-up, 2 patients in the treatment group showed recurrence of macular edema both angiographically and clinically. One had a drop in VA from 20/20 to 20/30, and we elected not to re-treat (Figure 2). This patient remained stable as such until the end of the study. The second patient had a drop in VA from 20/20 to 20/50. He was re-treated, and his VA improved to 20/30 within 1 week along with complete resolution of the macular edema. He maintained that VA until the conclusion of the study. By the final follow-up, 15 (75%) of the treated patients had complete resolution of macular edema vs only 4 (20%) of the untreated patients (P<.001). Sixteen (80%) of the untreated patients had persistent macular edema at final follow-up vs only 5 (25%) in the treated group.
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Figure 1. A, Pretreatment angiogram (at 3 minutes 36 seconds) shows cystoid macular edema with a visual acuity of 20/100. B, One week after intravitreal injection of triamcinolone acetonide, visual acuity is 20/20 and there is a significant decrease in macular leakage on angiography (at 3 minutes 38 seconds). C, Six months after treatment, fluorescein angiogram (at 3 minutes 46 seconds) continues to show no leakage. There is, also, no evidence of macular edema clinically and the visual acuity remains 20/20.
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Figure 2. A, Pretreatment angiogram (at 3 minutes 55 seconds) shows diffuse leakage around the macula (visual acuity is 20/200). B, One week after intravitreal injection of triamcinolone acetonide, visual acuity is 20/50 and there is a significant decrease in leakage on angiography (at 3 minutes 43 seconds). The visual acuity continues to improve over the next month to 20/20. C, Six months after treatment, there is minimal leakage around the macula on the fluorescein angiogram (at 3 minutes 46 seconds). This is associated with mild retinal thickening, but the visual acuity is 20/30.
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Retinal hemorrhages and vascular retinal changes did not improve more rapidly in the treatment group. However, none of the treated patients developed iris neovessels while 2 of the untreated patients needed panretinal photocoagulation for rubeosis iridis. Statistical analysis was not possible owing to the limited sample size.
COMMENT
The mechanism of action of corticosteroids for macular edema in CRVO is unclear. Triamcinolone has been shown experimentally to reduce the breakdown of the blood-retina barrier.13 It may act by inhibiting such factors as prostaglandins and interleukins, which are inflammatory mediators implicated in the pathogenesis of cystoid macular edema.14-15 Elevated levels of vascular endothelial growth factor (VEGF) have been reported in CRVO.16 Vascular endothelial growth factor is known to play a role in retinal neovascularization and the breakdown of the blood-retina barrier.17-18 In vitro studies have shown that corticosteroids significantly reduce the expression of VEGF.19-20 Therefore, intravitreal triamcinolone may block the expression of VEGF induced by CRVO and prevent the breakdown of the blood-retina barrier. Another possible mechanism is that triamcinolone can interfere directly with protein kinase C, which has been associated with increased retinal vascular permeability.21
This study presents the anatomic and visual outcome of 20 patients with nonischemic CRVO treated with intravitreal triamcinolone. This data was compared with a retrospectively matched group of patients who were managed by observation alone. The data show a treatment benefit in terms of VA and macular edema (clinically and angiographically). Improvement was noted by the first week after treatment and usually remained stable for the rest of the follow-up. With the exception of elevated intraocular pressure in 3 patients, the procedure was well tolerated and without adverse effects. However, potential complications of intravitreal corticosteroid injection include retinal detachment, vitreous hemorrhage, bacterial endophthalmitis, sterile endophthalmitis, and cataract formation.8-9,22-23 The procedure can be further simplified by using topical anesthesia instead of peribulbar anesthesia and by avoiding a paracentesis to control the intraocular pressure which may normalize spontaneously within a few minutes. For the purpose of the study, we wanted aggressive intraocular pressure control because these patients had a compromised retinal circulation, and we feared that even a brief elevation of intraocular pressure could worsen retinal ischemia and confound our results.
Patients with ischemic CRVO were excluded from this study because benefit from the treatment was thought to be unlikely. Severe ischemia may have already caused irreversible damage to the inner retina, and this may prevent improvement in vision even if the macular edema resolved. However, intravitreal corticosteroids may have a role in preventing the neovascular sequelae in ischemic CRVO. We did not observe any neovascularization in the treated eyes while it occurred in 2 of the control eyes, but the sample size was too small for any statistical analysis. By blocking the expression of VEGF, intravitreal corticosteroids can potentially reduce the likelihood of neovascular proliferation on the retina and iris.
In conclusion, intravitreal triamcinolone may be a safe treatment for macular edema in nonischemic CRVO and can lead to rapid improvement in VA with resolution of macular edema. Triamcinolone is readily available, inexpensive, and well tolerated in the vitreous. The main shortcoming of this study is that the control group was not selected in a randomized prospective manner. However, both groups were well matched with respect to major criteria, especially baseline VA, age, and sex. Larger randomized prospective studies are necessary to better ascertain the benefit of intravitreal corticosteroids in the management of CRVO.
AUTHOR INFORMATION
Correspondence: Ziad F. Bashshur, MD, Department of Ophthalmology, American University of Beirut–Medical Center, PO Box 113-6044, Beirut, Lebanon (zb00{at}aub.edu.lb).
Submitted for publication March 25, 2003; final revision received January 6, 2004; accepted January 6, 2004.
From the Departments of Ophthalmology, American University of Beirut–Medical Center, Beirut (Drs Bashshur, Ma'luf, Allam, Haddad, and Noureddin), and the Ain Wa Zein Hospital, Shouf (Dr Jurdi), Lebanon. The authors have no relevant financial interest in this article.
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