Laser Photocoagulation and Intravitreal Injection of Triamcinolone for Retinal Vein OcclusionsTREATMENT FOR RETINAL VEIN OCCLUSIONS

Commentary

Retinal vein occlusion, following diabetic retinopathy, is the second most common retinal vascular disease to cause visual impairment.^{1 - 2} The occlusion can occur as the central retinal vein exits through the optic nerve head or at the common crossing point, typically with the retinal artery compressing the branch of the vein. The disease is characterized by the presence of retinal hemorrhages, tortuous and dilated veins throughout the retina in central retinal vein occlusion (CRVO), and in the distribution of the branch retinal vein occlusion (BRVO) that is affected.

Macular edema is the most frequent cause of vision loss in eyes with retinal vein occlusions in both CRVO and BRVO. Previous reports of randomized controlled trials of grid laser photocoagulation established the standard of care for macular edema associated with retinal vein occlusions.^{1 ,3} Laser treatment was found to be beneficial for BRVO but not for CRVO.

The pathogenesis of retinal vein occlusion is not well understood, whereas previous studies have demonstrated elevated levels of vascular endothelial growth factor (VEGF) in the vitreous⁴ and inflammation has been implicated.⁵ During the past decade, a number of therapies have been investigated for the treatment of retinal vein occlusions, including surgical procedures, intravitreal injection of tissue plasminogen activator, and intravitreal injection of aptamers or antibodies targeted at VEGF. Corticosteroids also have inhibitory effects on VEGF activity and the inflammatory process and may have additional neuroprotective effects. A few case series reported the use of intravitreal injections of corticosteroids for the treatment of vein occlusions. Subsequently, this off-label treatment has been used routinely in clinical practice with limited data from randomized controlled trials on the benefits and safety of intravitreal treatment with corticosteroids. The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) CRVO trial⁶ and the SCORE BRVO trial⁷ (sponsored by the National Eye Institute and the National Institutes of Health) were conducted to test the use of intravitreal corticosteroids. The important findings from the SCORE trials were recently reported in the September issue of the Archives of Ophthalmology.^{6 - 7}

The SCORE trials assessed 2 intravitreal doses (1-mg and 4-mg preservative-free formulations of triamcinolone) given every 4 months. This preservative-free formulation was chosen to decrease the potential risk of intraocular inflammation associated with commercially available steroids. The study design compared the 2 doses with the standard care of grid laser photocoagulation for BRVO and with the standard care of observation for CRVO. The main outcome was the proportion of participants with clinically meaningful visual gain of 3 or more lines of vision at 12 months. Follow-up at 36 months was required to monitor the adverse effects of intravitreal triamcinolone, including elevation of intraocular pressure and development of cataract and procedure-related complications of endophthalmitis and retinal detachment. Additional outcomes include the reduction of retinal thickness as measured by optical coherence tomography.

The data from the SCORE CRVO trial⁶ demonstrated a 5-fold increase in the rates of visual acuity gain among participants treated with 1 mg of triamcinolone or 4 mg of triamcinolone (odds ratio, 5.0; 95% confidence interval, 1.8 to ~ 14) compared with observation at 1 year. Approximately 7% of participants in the 1 mg of triamcinolone group, 27% of the 4 mg of triamcinolone group, and 26% of the observation group gained 3 lines or more vision at 1 year. Despite the differences in visual outcome, the median reduction in retinal thickness as measured by optical coherence tomography was similar in all 3 treatment groups. In the triamcinolone-treated groups, 20% of the 1-mg group and 35% of the 4-mg group required intraocular pressure–lowering medications (P = .02) and lens progression occurred in 26% and 33% in the 1-mg and 4-mg groups, respectively. Three eyes in the 1-mg group and 21 eyes in the 4-mg group required cataract surgeries by 24 months (P = .001). None of the participants had the serious procedure-related adverse effects of endophthalmitis or retinal detachment. The treatment of choice for macular edema associated with CRVO is 1 mg of intravitreal triamcinolone given the visual acuity improvement and its safety profile compared with 4 mg of intravitreal triamcinolone.

The results of the SCORE BRVO trial showed that all 3 treatment groups experienced vision gains of 3 lines or more in approximately 25% to 29% of patients (not statistically significant). The need for intraocular pressure–lowering medications in the first year was 3% for patients in the laser photocoagulation group, 8% for the 1 mg of triamcinolone group, and 41% for the 4 mg of triamcinolone group. One participant assigned to the 4-mg group required surgical intervention for elevated intraocular pressure secondary to corticosteroid treatment. Cataract progression was detected clinically in 13% of patients in the laser photocoagulation group, 25% of the 1 mg of triamcinolone group, and 35% of the 4 mg of triamcinolone group. One participant in the 4-mg group developed infectious endophthalmitis. Given the similar results in vision gain and the less favorable safety profile of intravitreal triamcinolone compared with laser photocoagulation in this population, laser photocoagulation remains the standard of care for persons affected with BRVO. There may, however, be occasions when the use of intravitreal triamcinolone would be appropriate.

The SCORE CRVO trial has proven that 1 mg of intravitreal triamcinolone is beneficial for the treatment of vision loss from macular edema associated with CRVO. This is the first successful treatment that offers hope for those patients affected with this condition. Laser photocoagulation for BRVO has withstood the test of time and remains the standard care against which other experimental treatments are compared.

Individuals affected with CRVO or BRVO appear to have similar risk profiles. Are they simply a spectrum of a common disease, with BRVO affecting a smaller proportion of the retina compared with the involvement of the entire retina in CRVO? Why does laser photocoagulation only work in BRVO and not CRVO? The same question may be posed for the use of intravitreal corticosteroids for CRVO and not BRVO. These questions are intriguing and the answers may only be speculative.

Similarly, laser photocoagulation has proven to be effective for diabetic macular edema in a trial conducted to compare laser photocoagulation with intravitreal injections of triamcinolone.⁸ Triamcinolone did not offer added advantage to the current standard of laser photocoagulation for diabetic retinopathy. Like diabetic retinopathy, there is interest in administering intravitreal injections of antibodies against VEGF for the therapy of retinal vein occlusions.⁹ Trials are under way to evaluate these agents.

In the SCORE trials, approximately 75% of participants had hypertension, 25% had diabetes, and 20% had coronary disease, which are similar percentages to a previous report in which hyperlipidemia also was a risk factor.¹⁰ The importance of medical management of these patients needs to be emphasized because approximately 15% of those affected will have bilateral involvement.

The results of the SCORE trials have resulted in important recommendations for treatment of the macular edema associated with CRVO and BRVO. However, there is room for improvement because up to 25% of those treated lost 3 or more lines of vision during this study.^{6 - 7} Further research is required for therapies that will result in greater visual acuity gains in a larger proportion of those affected. There also is a need to emphasize the role of preventive therapy to treat common chronic diseases such as hypertension, hyperlipidemia, cardiovascular disease, and diabetes, which are all known risk factors associated with the development of retinal vein occlusions.