Bevacizumab vs. Triamcinolone

The use of intravitreal corticosteroids in the management of macular oedema has recently gained widespread acceptance. New long-acting steroid preparations and methods of delivery have facilitated the use of these new modalities. This review describes the various types of macular oedema for which this therapeutic option is used and the results.

Cataract Surgery in Uveitis

Objective: To assess difference in visual outcome, macular thickness and need for laser treatment in patients receiving intravitreal triamcinolone acetonide or bevacizumab for macular oedema secondary to retinal vein occlusion. Design: Open labeled prospective randomised controlled trial, evaluating 38 retinal vein occlusion patients. 19 patients each were assigned, to Intravitreal Triamcinolone Acetonide (IVTA) and Bevacizumab (IVB) group. Methodology: Baseline ocular parameters like best corrected visual acuity (BCVA), intraocular pressure (IOP) by Applanation tonometry, fundus examination using indirect ophthalmoscope, slit lamp biomicroscopy, Ocular Coherence Tomography of the macula and Fundus Flourescein Angiography performed. Under aseptic conditions, Injection of 4 mg (0.1 ml) Triamcinolone Acetonide (Kenacort) or 1.25 mg (0.05 ml) Bevacizumab (Avastin) was injected into the vitreous. Patients were given re-injections or laser treatment according to requirement. BCVA and IOP at 15 days, 1, 3 and 6 months post injection was recorded. OCT and FFA were repeated at 3 and 6 month. Outcome: At 6 months, patients with BRVO receiving IVTA, there was significant improvement in visual acuity (p = 0.014), as well as decrease in macular edema (p ≈ 0.000), whereas patients of BRVO in the IVB group did not show significant improvement in visual acuity (p= 0.375). Visual acuity of CRVO patients in the IVTA (p = 0.178) and IVB (p = 0.109) group did not show any significant improvement. Though there was significant decrease in macular edema in both IVTA (p ≈ 0.000) and IVB (p =0.042) groups. No significant increase in IOP was noted in either IVTA (p= 0.089) or IVB (p = o.637).Results and Conclusion: The results show a favourable influence of IVTA on BCVA at 6 months.Positive effect in decreasing central macular thickness (CMT) was observed in patients receiving IVTA and IVB.FFA guided laser photocoagulation helps in stabilizing the visual acuity and prevents vision threatening complications. Changes in OCT can be used to monitor patient response to treatments for CRVO related macular oedema. Summary: IVTA injection when combined with FFA guided laser in BRVO eyes showed most favourable outcome in terms of both visual improvement and CMT during follow up period of 6 months.

Comparison Between Intravitreal and Orbital Floor Triamcinolone Acetonide After Phacoemulsification in Patients With Endogenous Uveitis

To compare the effects of intravitreal injection of bevacizumab (IVB) with intravitreal triamcinolone acetonide (IVTA) on the treatment of cystoid macular edema (CME) secondary to retinal vein occlusion (RVO). A literature search was conducted using PubMed, the Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Database. The comparison was divided into two groups, group 1 conducted comparison in branch RVO (BRVO) or central RVO (CRVO), group 2 conducted comparison in ischemic-RVO or nonischemic-RVO. Pooled mean differences (MDs) for changes in visual acuity (VA), central macular thickness (CMT) and intraocular pressure (IOP) were calculated in groups at 4, 12 and 24wk after treatment respectively. Eight studies comparing the efficacy of IVB with IVTA were included in the Meta-analysis. In group 1, in BRVO, significant difference was shown on the comparison of CMT at 24wk (MD, -45.66; 95% CI, -76.03 to -15.28; P=0.003), IVB was effective on BRVO for at least 24wk; no significant differences were found in the comparison of VA at each time points (P>0.05 respectively). In CRVO, no significant differences were found in the comparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). In group 2, in ischemic-RVO, significant differences were shown in the comparison of VA (MD, -0.28; 95% CI, -0.42 to -0.14; P<0.0001) and CMT (MD, -86.50; 95% CI, -151.18 to -22.43; P=0.008) at 24wk; In nonischemic-RVO, no significant differences were demonstrated in the comparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). The occurrence of high IOP was much lower in IVB group. This Meta-analysis suggested that IVB was effective in decreasing CMT in BRVO for at least 24wk, IVB is more effective on improving VA and reducing CMT in ischemic-RVO. IVB is more promising on RVO than IVTA.

To determine whether pretreatment with intravitreal triamcinolone acetonide (IVTA) before laser photocoagulation is effective in eyes with diabetic macular edema (DME). The study was a prospective, double-masked, placebo-controlled, clinical trial of eyes with DME and impaired vision (<or=20/40) randomized to IVTA 4 mg versus placebo 6 weeks before laser treatment. The main outcome measure was the proportion of eyes with improvement of best-corrected logarithm of minimum angle of resolution (logMAR) visual acuity of >or=5 letters after 6 months. Secondary outcomes were necessity of further treatment, change in central macular thickness, and incidence of adverse events. Eighty-four eyes of 54 participants were entered into the study, with 6-month data available for 81 (96%) of 84 eyes. Improvement of >or=5 logMAR letters was similar in eyes treated with IVTA before laser as placebo (18/42 [43%] IVTA vs. 16/34 [38%] laser alone; P = 0.807), as were retreatment rates at 6 months (22 [56%] IVTA vs. 21 [53%] laser alone; P = 0.727). Mean central macular thickness decreased by 50 microm (95% confidence interval, 10-96 microm) more in the IVTA treatment group than in the laser-alone group after 6 months (P = 0.016). Glaucoma therapy was necessary more frequently in IVTA-treated eyes than in those treated with laser alone (19/42 [45%] vs. 7/42 [17%]; P = 0.005). Visual results and the need for further laser treatment at 6 months were no better in the IVTA group than in the laser-alone group, despite a better anatomic outcome reflected by reduction in mean central macular thickness. This study found no evidence of a synergistic effect of IVTA and laser photocoagulation for DME. (ClinicalTrials.gov number, NCT00148265).

To evaluate the efficacy of intravitreal injection of bevacizumab (IVB) followed by modified grid laser photocoagulation (MGP) versus each alone as a primary treatment of diffuse diabetic macular edema. A randomized 3-arm clinical trial in which 62 eyes of 48 patients with diffuse diabetic macular edema were enrolled. Eyes were randomly distributed to 1 of 3 study groups: 19 eyes underwent MGP (MGP group), 21 eyes received 1.25 mg of IVB (IVB group), and 22 eyes received IVB followed by MGP (combined group). All eyes underwent a complete ophthalmic examination including fluorescein angiography and optical coherence tomography at baseline and at 1, 3, and 6 months, after treatment. Fluorescein angiography was performed at the 3 and 6 months follow up visits. The outcome measures were the change compared with baseline in central macular thickness (CMT), changes in best-corrected visual acuity (BCVA), changes in fluorescein angiography leakage, and any reported complication. A P value less than 0.05 was considered statistically significant. One month after treatment, the reduction in the mean CMT versus baseline was 49.88 μm (10.45%) in MGP group, 150.92 μm (31.30%) in IVB group, and 110.30 μm (23.77%) in the combined group, with a corresponding improvement in the mean BCVA. At 1 month, the improvement in CMT was better than baseline in all groups, yet only significant in the IVB group (P < 0.05) and the combined group (P < 0.05). The improvement in mean BCVA was significant in the IVB (P < 0.05) and the combined groups at 1 month (P < 0.05). At 3 months, the mean CMT was still better than baseline in all groups but this improvement was significant only in the combined group (P < 0.05). The improvement in the mean BCVA was significant only in the IVB and the combined groups (P < 0.05). Six months after treatment, the reduction in the mean CMT was significant in the combined group only (P < 0.05) and there was no significant improvement in the mean BCVA in all groups (P > 0.05). The BCVA did not deteriorate below baseline in all eyes included in the study, except three eyes in the MGP group. No complication related to the intravitreal injection was reported in the injected eyes. Combined therapy with IVB and sequential MGP 3 weeks later appeared to be superior to MGP or IVB alone in reducing macular thickening and improving visual acuity. However, no significant improvement in BCVA occurs 6 months after treatment. A combination of IVB and sequential MGP could be used as an initial treatment of diffuse diabetic macular edema.

Background: Both intravitreal bevacizumab and triamcinolone have been shown to be effective in treating macular edema secondary to VEGF-mediated disease. The purpose of this study is to describe the variable effects of intravitreal bevacizumab (IVB) and triamcinolone acetonide (IVTA) in the treatment of macular edema secondary to radiation retinopathy. Methods: Retrospective, nonrandomized, interventional case series. Charts of five patients with macular edema due to radiation retinopathy who received IVB with subsequent IVTA were reviewed. Clinical examination, Snellen visual acuity (VA), and central macular thickness (CMT) on optical coherence tomography (OCT) were examined. Main outcome measures included VA and CMT. Results: Of the five patients reviewed, patient 1 demonstrated complete resolution of macular edema both clinically and by OCT with IVB after the first two injections with a decrease in CMT to 243 and 284 µm from a baseline CMT of 340 µm. However, response diminished following successive injections and the patient was switched to IVTA with a complete response. Mean CMT was 249 µm following four injections of IVTA and vision improved 3 lines. Patients 2 and 3 demonstrated a partial response to IVB with a mean CMT of 362 and 451 µm from 436 and 596 µm, respectively. They similarly had a partial response to IVTA with a mean CMT of 363 and 433 µm from 460 and 429 µm. There was no improvement in vision. Patient 2 was then switched to a combination of IVB and IVTA with complete resolution of macular edema with a CMT of 299 and 289 µm following two treatments. Patients 4 and 5 failed to respond to IVB with a mean increase in CMT of 64.5 and 6 µm. Both responded well to IVTA with complete resolution of macular edema. Mean decrease in CMT was 146 and 183 µm with a mean CMT of 254 and 281 µm. Final vision was stable in patient 4 and improved 3 lines from 20/100 to 20/50 in patient 5. Conclusion: IVB and IVTA have variable effects on the reduction of macular edema due to radiation retinopathy. IVB appears to have an initial effect in reducing macular edema in some patients but after multiple injections there can be resistance to its effects. IVTA was effective in three of five patients with complete resolution of macular edema. The combination of IVB and IVTA completely resolved macular edema in one patient resistant to IVB or IVTA alone. The reason for this may be due to their different therapeutic mechanisms of action and consideration should therefore be given to their use in combination.

Editor, Cystoid macular oedema (CME) is the most significant cause of visual loss associated with uveitis (Rothova et al. 1996). Intravitreal triamcinolone (IVTA) has been used successfully as a primary treatment, particularly in unilateral disease, but a single injection lasts only approximately 3 months, and 15–30% of patients develop cataract and 25–45% of patients develop elevated intraocular pressure (IOP) (Kok et al. 2005; van Kooij et al. 2006). Studies investigating repeat IVTA injections in other conditions such as diabetic macular oedema have suggested that they become less effective with time and generate increasing problems with IOP (Chan et al. 2006; Gillies et al. 2007), but there is little evidence regarding the outcome of repeat injections in uveitis. This study was designed to address these issues and to determine whether repeated IVTA injections are a viable treatment option for recurrent uveitic CME. We report a retrospective, consecutive case series of 41 eyes of 35 patients with uveitis recruited from two tertiary referral uveitis clinics. Included eyes had CME proven on optical coherence tomography or fluorescein angiography, were given at least two IVTA injections and were followed up for at least 3 months following their last injection. All injections were given as 4 mg/0.1 ml triamcinolone acetonide (Kenalog), taken straight from the vial. Repeat injections were given in responsive patients if CME recurred, but were not repeated in patients with a marked steroid response. The study was approved by the Research Governance Committee of Moorfields Eye Hospital (LIGS1021) and the Institutional Review Board of Sydney Eye Hospital. Following the first IVTA injection, CME resolved in 36 of 41 eyes (88%) in a mean of 5 weeks (range 1–14 weeks), but recurred in all eyes at a mean of 7 months (range 2–23 months). After the second injection, CME improved in 31 of 41 eyes (76%), but recurred in 25 eyes at a mean of 5 months (range 1–13 months). Twenty patients had a third IVTA injection, and 10 patients had more than three injections. There was a statistically significant improvement in visual acuity after each injection (p < 0.01), with no evidence of reducing efficacy (Fig. 1A). Response to repeat intravitreal injections of triamcinolone acetonide. In (A) mean ± SEM improvement in logMAR visual acuity is shown, indicating no reduction in effect with repeat injections. In (B), the number of patients with IOP which increased to >21 and ≥30 mmHg is indicated. Note that patients with a marked steroid response were not offered further injections, so the number of patients with a steroid response declines over time. Nineteen of 41 eyes (46%) had an IOP increase of 10 mmHg or more from baseline, and 10 eyes (25%) developed an IOP >30 mmHg. However, no eyes required IOP-lowering surgery, and the magnitude of IOP changes did not increase with repeat injections, although patients with a marked steroid response were not offered further injections (Fig. 1B). As expected, repeat IVTA injections were associated with cataract (p < 0.01), and by the time of the fifth IVTA injection, all phakic patients had undergone cataract surgery (Fig. 2). IVTA injection otherwise had a good safety profile: from a total of 118 IVTA injections, only one eye developed IVTA-induced sterile endophthalmitis, and there were no other severe adverse events. Cataract surgery following repeat intravitreal triamcinolone (IVTA) acetonide injections. Kaplan–Meier survival to cataract surgery is shown, indicating that all phakic patients developed visually significant cataract requiring surgery by the fifth IVTA injection. Nineteen patients were being treated with systemic therapy at the start of the study. The mean dose of systemic prednisolone required to control the disease decreased significantly over the course of the study to <7.5 mg/day (Fig. 3), and 11 patients were able to reduce significantly or stop their second-line agents. Systemic immunosuppression. Doses of systemic corticosteroids are indicated (mean ± SEM) and indicate a significant reduction over time to long-term sustainable levels of ≤7.5 mg prednisolone per day. This study demonstrates the effects of repeated intravitreal triamcinolone injections in patients with uveitic CME: best corrected visual acuity (BCVA) improves, with no evidence of tachyphylaxis, and systemic immunosuppressive therapy can be withdrawn in some patients. However, all patients eventually develop cataract, and IOP-lowering medication is needed in nearly 50% of eyes. In summary, repeat IVTA treatment in patients with recurrent uveitic CME is associated with a repeatable improvement in visual acuity and is thus a viable treatment option for recurrent disease.

Intraocular Methotrexate in the Treatment of Uveitis and Uveitic Cystoid Macular Edema

To investigate the efficacy and safety of primary intravitreal triamcinolone acetonide (IVTA) in eyes affected by diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) therapy. Retrospective observational study METHODS: The medical records of patients who attended our clinic from March 2013 to September 2018 with refractory macular were reviewed. We included the patients who were injected at least one IVTA and completed 6 months of observation. Best-corrected Snellen visual acuity (VA), central macular thickness (CMT), intraocular pressure (IOP), and adverse events (AEs) were examined at baseline and at 1 month, 2 months, 3 months, and 6 months. Sixty-four eyes of 54 subjects were included. The mean VA was improved significantly at all time points compared to pre-treatment (P < 0.0001), with the greatest mean improvement at 1 month (0.3 logMAR). The reduction in mean CMT was also significant at all follow-up examinations compared to baseline (P < 0.0001), with the greatest decrease at 1 month (113.68 ± 53.78 μm). A poorer VA before injection was a factor that influenced visual gain 1 month post treatment (0.247 logMAR units/unit increase in baseline VA, P = 0.006). The most common AE associated with IVTA treatment was elevated IOP (11 eyes), observed significantly more often after IVTA injections containing a preservative (25.8%) than after those that were preservative-free (9.1%) (P = 0.033). IVTA injection can be an alternative steroid treatment for DME refractory to anti-VEGF therapy.

Purpose To assess the efficacy and safety of preoperative intravitreal triamcinolone acetonide (IVTA) combined with internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (IMEM). Methods This was a retrospective study. Thirty-six phakic eyes of 35 patients were included in this study. IVTA was administered to 18 patients (18 eyes, Group IVTA) 7 days before vitrectomy, while the other 17 patients (18 eyes, Group no-IVTA) only underwent vitrectomy and ILM peeling. Patients were followed up for at least 6 months. Data on best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), inner retinal thickness (IRT), vascular parameters (measured by optical coherence tomography angiography, OCTA), mean macular sensitivity (MMS), 63% bivariate contour ellipse area (BCEA) and P1 (measured by macular integrity assessment, MAIA) were collected. Results There were significant differences in BCVA and IRT between the IVTA group and the no-IVTA group at 6 months after surgery (p = .000 and p = .010). The CMT and MMS of the two groups significantly changed from the preoperative values; however, there were no differences between the 2 groups during the entire study period (p = .242 and p = .849). The changes in vascular parameters, including foveal avascular zone (FAZ) area and vessel densities of superficial and deep capillary plexus (SCP VD and DCP VD), in the two groups were not statistically significant. There were no statistically significant differences in 63% BCEA and P1 either. Conclusion Macular morphology and macular integrity improved after vitrectomy combined with ILM peeling surgery. Compared with the no-IVTA group, preoperative intravitreal triamcinolone acetonide can improve best corrected visual acuity and accelerate the absorption of intraretinal fluid in terms of a significant reduction in IRT.

Background: Diabetic macular edema is the commonest cause of visual impairment in diabetic patients. The aim of the study is to evaluate the effectiveness of repeated intravitreal bevacizumab injections alone versus injection with sequential macular grid laser photocoagulation in patients with diabetic macular edema. Methods: This study included 128 eyes of 64 patients with bilateral diabetic macular edema, randomly assigned into two groups. First group was treated with monthly intravitreal bevacizumab injections (IVB group). Second group was treated with 3 monthly IVB injections, followed by macular grid photocoagulation (MGP) 4 weeks later (combined group). All patients received a complete ophthalmic examination including measurement of best corrected visual acuity (BCVA) and measurement of central macular thickness (CMT) by optical coherence tomography at baseline and 3 weeks after each injection. Results: At the end of the follow-up period there was a statistically significant difference between the mean BCVA and the CMT compared to baseline in both groups. In the IVB group at the end of study, the mean BCVA was 0.46±0.11 LogMAR compared to 0.79±0.16 LogMAR preoperatively, and the mean CMT was 248.49±13.40µm compared to 497.25±27.97µm preoperatively. In the combined group the mean BCVA was 0.41±0.12 LogMAR compared to 0.89±0.12 LogMAR preoperatively, and the mean CMT was 239.47±13.53µm compared to 510.86±37.64µm preoperatively. The mean number of injections was significantly lower in combined group. Conclusion: Intravitreal injection of bevacizumab is effective in controlling DME. Performing MGP 4 weeks after the third injection decreased the number of IVB injections needed during the study duration.

Predicting 1-month response of macular edema to intravitreal bevacizumab from 1-hour response

신생혈관성 나이관련황반변성에서 베바시주맙 주입과광역학요법을 병합한 일차치료 효과명곡 안연구소 1 , 건양대학교 의과대학 안과학교실 2 목적: 나이관련황반변성에 의한 맥락막신생혈관에서 bevacizumab 단독치료와 광역학요법과의 병합치료 효과를 알아보고자 하였다.대상과 방법: 72명 72안을 대상으로 27안에서는 bevacizumab만을 주사하였고 45안에서는 광역학요법을 병행하여 6개월 뒤에 최대교 정시력, 중심황반두께와 재 치료 여부를 비교하였다.결과: 단독치료군의 경우 평균시력(LogMAR) 0.62±0.34에서0.56±0.33(p=0.03)으로,병합치료군은 0.61±0.33에서0.48±0.21(p=0.001)로 유의한 향상을 보였으며, 치료 6개월 뒤 병합치료군에서 더 시력이 향상되었다(p=0.049).중심황반두께는 모두 시술 전에