Lihteh Wu

Twelve-month safety of intravitreal injections of bevacizumab (Avastin®): results of the Pan-American Collaborative Retina Study Group (PACORES)

BackgroundVascular endothelial growth factor (VEGF) plays an important role in many diseases of the posterior pole that are characterized by macular edema and/or intraocular neovascularization. Recently anti-VEGF agents such as ranibizumab and pegaptanib sodium have been shown to be beneficial in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). However in most parts of the world, both pegaptanib sodium and ranibizumab are not readily available. Bevacizumab, a humanized recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been proposed as an alternative treatment option.MethodsA total of 1,265 consecutive patients were injected with bevacizumab for diseases such as proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusions, and CNV of several etiologies including ARMD at eight Latin American institutions from 1 September 2005 to 31 January 2006. Of these 1,265, 92 were excluded because they were injected once and lost to follow-up. The remaining 1,173 patients constitute the subjects of this retrospective, multicenter, open label, uncontrolled interventional case series that reports the cumulative systemic and ocular adverse events following intravitreal bevacizumab during 12xa0months of follow-up. Patients were examined at baseline and then monthly. If the patients were unable to attend the 12-month visit, a telephone interview was conducted to assess for possible systemic complications.ResultsA total of 4,303 intravitreal injections of bevacizumab on 1,310 eyes was reported. All 1,173 patients were accounted for at the 12-month visit. Systemic adverse events were reported in 18 (1.5%) patients. These included seven (0.59%) cases of an acute elevation of systemic blood pressure, six (0.5%) cerebrovascular accidents, five (0.4%) myocardial infarctions, two (0.17%) iliac artery aneurysms, two (0.17%) toe amputations and five (0.4%) deaths. Ocular complications included seven (0.16%) bacterial endophthalmitis, seven (0.16%) tractional retinal detachments, four (0.09%) uveitis, and a case (0.02%) each of rhegmatogenous retinal detachment and vitreous hemorrhage.ConclusionDespite the limited follow-up, repeated intravitreal injections of either 1.25xa0mg or 2.5xa0mg of bevacizumab appears to be safe and well tolerated during the 1st year.

Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy

Aims: The aim of this study was to report the development or progression of tractional retinal detachment (TRD) after the injection of intravitreal bevacizumab (Avastin) used as an adjuvant to vitrectomy for the management of severe proliferative diabetic retinopathy (PDR). Methods: The clinical charts of patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 mg bevacizumab before vitrectomy for the management of PDR were reviewed. Results: Eleven eyes (patients) out of 211 intravitreal injections (5.2%) that developed or had progression of TRD were identified. All eyes had PDR refractory to panretinal photocoagulation (PRP). Nine patients had type 1 diabetes mellitus (DM), and two patients had type 2 DM. Patients had a mean age of 39.5 years (range 22–62 years). In the current study, all patients used insulin administration and had poor glycaemic control (mean HbA1c 10.6%). Time from injection to TRD was a mean of 13 days (range 3–31 days). Mean best correct visual acuity (BCVA) at TRD development or progression was logarithm of the minimal angle of resolution (LogMAR) 2.2 (range 1.0–2.6) (mean Snellen equivalent hand motions; range 20/200 to light perception), a statistically significant worsening compared with baseline BCVA (p<0.0001). Eight eyes underwent vitrectomy and three patients refused or were unable to undergo surgery. The final mean BCVA after surgery was LogMAR 0.9 (range 0.2–2.0) (mean Snellen equivalent 20/160; range 20/32 to counting fingers), a statistically significant improvement compared with TRD BCVA (pu200a=u200a0.002). Conclusions: TRD may occur or progress shortly following administration of intravitreal bevacizumab in patients with severe PDR.

Primary intravitreal bevacizumab for diffuse diabetic macular edema: the Pan-American Collaborative Retina Study Group at 24 months.

PURPOSEnTo report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin; Genentech, Inc., San Francisco, CA; 1.25 or 2.5 mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of the 2 different doses of intravitreal bevacizumab (IVB) used is presented.nnnDESIGNnRetrospective, multicenter, interventional, comparative case series.nnnPARTICIPANTSnThe clinical records of 115 consecutive patients (139 eyes) with DDME at 11 centers from 8 countries were reviewed.nnnMETHODSnPatients were treated with at least 1 intravitreal injection of 1.25 or 2.5 mg of bevacizumab. All patients were followed up for 24 months. Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at the baseline, 1-, 3-, 6-, 12-, and 24-month visits.nnnMAIN OUTCOME MEASURESnChanges in BCVA and OCT results.nnnRESULTSnThe mean age of the patients was 59.4+/-11.1 years. The mean number of IVB injections per eye was 5.8 (range, 1-15 injections). In the 1.25-mg group at 1 month, BCVA improved from 20/150 (0.88 logarithm of the minimum angle of resolution [logMAR] units) to 20/107, 0.76 logMAR units (P<0.0001). The mean BCVA at 24 months was 20/75 (0.57 logMAR units; P<0.0001). Similar BCVA changes were observed in the 2.5-mg group: at 1 month, BCVA improved from 20/168 (0.92 logMAR units) to 20/118 (0.78 logMAR units; P = 0.02). The mean BCVA at 24 months was 20/114 (0.76 logMAR units; P<0.0001). In the 1.25-mg group, the mean central macular thickness (CMT) decreased from 466.5+/-145.2 microm at baseline to 332.2+/-129.6 microm at 1 month and 286.6+/-81.5 microm at 24 months (P<0.0001). Similar results were obtained in the 2.5-mg group.nnnCONCLUSIONSnPrimary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT, and FA in DDME at 24 months. The results show no evident difference between IVB at doses of 1.25 or 2.5 mg.

Comparison of two doses of intravitreal bevacizumab (Avastin) for treatment of macular edema secondary to branch retinal vein occlusion: results from the Pan-American Collaborative Retina Study Group at 6 months of follow-up.

Purpose: To report the 6-month anatomical and visual outcomes after injecting two different doses of intravitreal bevacizumab in patients with macular edema secondary to branch retinal vein occlusion (BRVO). Methods: An interventional, retrospective multicenter study of 45 eyes that were treated with at least one intravitreal injection (24 eyes, 1.25 mg; 21 eyes, 2.5 mg) of bevacizumab is reported. The main outcome measures were the central 1-mm macular thickness (CMT) and the change in ETDRS lines of best-corrected visual acuity (BCVA) at 6 months. Results: Forty-five eyes were injected on average 26.1 months (range, 3–86 months) after the diagnosis. The average follow-up was 35.2 weeks (range, 24–52 weeks). All patients completed at least 6 months of follow-up. In the 1.25-mg dose group, at 1 month, there was an average gain of 4.5 lines of BCVA; at 3 months, 5.1 lines of BCVA; and at 6 months, 5.1 lines of BCVA (P < 0.005). In the 2.5-mg dose group, at 1 month, there was an average gain of 2.3 lines of BCVA; at 3 months, 3.8 lines of BCVA; and at 6 months, 4.8 lines of BCVA (P = 0.05). In the 1.25-mg dose group, the mean CMT ± SD decreased from 461 ± 211 &mgr;m at baseline to 321 ± 152 &mgr;m at 1 month, 273 ± 99 &mgr;m at 3 months, and 277 ± 114 &mgr;m at 6 months (P = 0.0002). In the 2.5-mg group, the mean CMT ± SD decreased from 385 ± 168 &mgr;m at baseline to 279 ± 111 &mgr;m at 1 month, 249 ± 97 &mgr;m at 3 months, and 240 ± 93 &mgr;m at 6 months (P = 0.011). Conclusion: There were no statistically significant differences between the two dose groups with regard to the number of injections and anatomical and functional outcomes. Intravitreal injection of bevacizumab at doses up to 2.5 mg appears to be effective in improving BCVA and reducing CMT in BRVO in the short term. Multiple injections are needed in a large number of eyes for continued control of macular edema and preservation of visual acuity in the short term. Longer studies are needed to determine what role if any intravitreal injection of bevacizumab may play in the long-term treatment of this condition.

Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up

BackgroundTo report the 12-month anatomic and ETDRS best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin®) (1.25xa0mg or 2.5xa0mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of the two different doses of intravitreal bevacizumab (IVB) utilized was made.MethodsWe reviewed the clinical records of 82 consecutive patients (101 eyes) with DDME in this interventional retrospective multicenter study. All patients with a minimum follow-up of 12xa0months (mean 57.6u2009±u20098.4xa0weeks) were included in this analysis. Patients underwent ETDRS best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and follow-up visits.ResultsThe mean age of our patients was 59.7u2009±u20099.3xa0years. The mean number of IVB injections per eye was three (range: one to six injections) at a mean interval of 14.1u2009±u200910.5xa0weeks. In the 1.25xa0mg group at 1xa0month BCVA improved from 20/190, logMARu2009=u20090.97 to 20/85, logMAR 0.62, a difference that was statistically significant (pu2009=u20090.0001). This improvement was maintained throughout the 3-, 6-, and 12-month follow-up. The mean final BCVA at 12xa0months was 20/76, logMARu2009=u20090.58 (pu2009<u20090.001), a statistically significant difference from baseline BCVA. Similar BCVA changes were observed in the 2.5xa0mg group. In the 1.25xa0mg group, the mean central macular thickness (CMT) decreased from 419.1u2009±u2009201.1xa0µm at baseline to 295.11u2009±u200991.5xa0µm at 1xa0month, 302.1u2009±u2009124.2xa0µm at 3xa0months, 313.4.1u2009±u200996.3xa0µm at 6xa0months, and 268.2u2009±u200995.5xa0µm at 12xa0months (pu2009<u20090.0001). Similar CMT changes were observed in the 2.5xa0mg group. Adverse events included transient high blood pressure in one patient (1.2%), transient increased intraocular pressure in one eye (1%), and tractional retinal detachment in one eye (1%).ConclusionsPrimary IVB at doses of 1.25 to 2.5xa0mg seem to provide stability or improvement in BCVA, OCT, and FA in DDME at 12xa0months. There seems to be no difference in our results between intravitreal bevacizumab at doses of 1.25xa0mg or 2.5xa0mg. In addition, our results suggest the need for at least three injections a year to maintain the BCVA results.

Intravitreal Bevacizumab for Refractory Pseudophakic Cystoid Macular Edema The Pan-American Collaborative Retina Study Group Results

OBJECTIVEnTo determine the feasibility, safety, and clinical effect of intravitreal (IVT) bevacizumab (Avastin; Genentech, Inc., San Francisco, CA) in patients with refractory cystoid macular edema (CME) after cataract surgery.nnnDESIGNnInterventional, retrospective, multicenter study.nnnPARTICIPANTSnThirty-six eyes of 31 patients with refractory CME after cataract surgery and with a mean age of 68.2 years (range, 67-87 years).nnnMETHODSnPatients were treated with at least 1 IVT injection of 1.25 or 2.5 mg bevacizumab. Patients were followed up for 12 months.nnnMAIN OUTCOME MEASURESnBest-corrected visual acuity (BCVA) and central macular thickness (CMT) by optical coherence tomography (OCT).nnnRESULTSnTwenty-six eyes (72.2%) demonstrated improvement of BCVA (> or =2 Early Treatment Diabetic Retinopathy Study [ETDRS] lines), and no eye experienced worsening of visual acuity (> or =2 ETDRS lines). Mean baseline BCVA was 20/200 (0.96 logarithm of the minimum angle of resolution [logMAR] units), and the mean 12-month BCVA was 20/80 (0.62 logMAR units; P<0.0001). Optical coherence tomography demonstrated that mean CMT at baseline was 499.9 microm (range, 298-784 microm) and decreased to a mean of 286.1 microm (range, 168-499 microm) at 12 months (P<0.0001). Four (11%) eyes received 2 injections, 10 (27.8%) eyes received 3 injections, 10 (27.8%) eyes received 4 injections, 1 (2.8%) eye received 5 injections, and 1 (2.8%) eye received 6 injections. The mean number of injections was 2.7 (range, 1-6), and the mean interval between injections was 15.1 weeks (range, 4-45 weeks). No ocular or systemic adverse events were observed.nnnCONCLUSIONSnShort-term results suggest that IVT bevacizumab is well tolerated in patients with refractory pseudophakic CME. Treated eyes had a significant improvement in BCVA and decrease in macular thickness by OCT at 12 months.

Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degeneration: results of the Pan-American Collaborative Retina Study Group at 12 months follow-up.

Purpose: To report the 12-month anatomic and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin™, Genentech Inc., San Francisco, CA) (1.25 mg or 2.5 mg) in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Methods: Sixty-three eyes of 63 consecutive patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration, a mean age of 73.7 ± 7.5 years and a minimum of 12 months (mean 55.5 ± 6.2 weeks) of follow-up participated in this interventional retrospective multicenter case series in 7 centers from 6 countries. Patients were treated with at least 1 intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab. Patients underwent Early Treatment Diabetic Retinopathy Study BCVA testing, ophthalmoscopic examination, optical coherence tomography, and fluorescein angiography at baseline and follow-up visits. Repeated measures analysis of variance was used to compare mean values. Results: The mean number of intravitreal bevacizumab injections per eye was 3.5 (range, 1–8). Mean baseline BCVA was 20/320, logarithm of the minimum angle of resolution = 1.2, and mean final BCVA was 20/200, logarithm of the minimum angle of resolution = 1.0 (P < 0.001). Central macular thickness at baseline by optical coherence tomography had a mean of 389.2 ± 149.6 &mgr;m which was significantly reduced to a mean of 281.0 ± 96.1 &mgr;m, 268.2 ± 82.6 &mgr;m, 262.6 ± 92.3 &mgr;m, and 241.3 ± 76.7 &mgr;m at 1, 3, 6, and 12 months after initial treatment, respectively (P < 0.0001). Ocular adverse events included transient increased intraocular pressure in 2 (3.1%) eyes, endophthalmitis in 2 (3.1%) eyes, and transient hypotony in 1 eye (1.1%). No systemic adverse events were observed. Conclusion: Primary intravitreal bevacizumab at doses of 1.25 mg or 2.5 mg seems to provide stability or improvement in BCVA, optical coherence tomography, and fluorescein angiography in subfoveal choroidal neovascularization secondary to age-related macular degeneration at 12 months.

Comparison of two doses of intravitreal bevacizumab as primary treatment for macular edema secondary to branch retinal vein occlusions: results of the Pan American Collaborative Retina Study Group at 24 months.

Purpose: The purpose of this study was to compare the injection burden, central macular thickness (CMT), and change in best-corrected visual acuity (BCVA) after injecting 1.25 mg or 2.5 mg of bevacizumab as needed in patients with primary macular edema secondary to branch retinal vein occlusion. Methods: An interventional, retrospective, comparative multicenter study was conducted of 63 eyes with macular edema secondary to branch retinal vein occlusion that were treated primarily with intravitreal bevacizumab (38 eyes, 1.25 mg; 25 eyes, 2.5 mg). The main outcome measures were the CMT and the change of BCVA at 24 months. Results: All patients completed at least 24 months of follow-up. The mean number of injections per eye was 3.6 in the 1.25-mg group and 4.3 in the 2.5-mg group (P = 0.4770). At 24 months, in the 1.25-mg group, the logarithm of the minimum angle of resolution BCVA improved from baseline 0.38 ± 0.63 (P < 0.0001) units to 0.64 ± 0.6 units for the 2.5-mg group (P < 0.0001). In the 1.25-mg group, 26 (68%) eyes gained ≥3 of Early Treatment of Diabetic Retinopathy Study visual acuity and 2 (5%) eyes lost ≥3 lines of Early Treatment of Diabetic Retinopathy Study visual acuity. In the 2.5-mg group, 18 (72%) eyes improved ≥3 of Early Treatment of Diabetic Retinopathy Study visual acuity, and none of the eyes lost ≥3 lines of Early Treatment of Diabetic Retinopathy Study visual acuity. The CMT in the 1.25-mg group improved from 453 ± 140 &mgr;m to 244 ± 125 &mgr;m (P < 0.0001) versus 444 ± 175 &mgr;m to 234 ± 80 &mgr;m in the 2.5-mg group (P < 0.0001). There were no cases of endophthalmitis. No systemic adverse events were reported. Conclusion: Intravitreal bevacizumab at doses up to 2.5 mg seems to be effective in improving BCVA and reducing CMT in macular edema secondary to branch retinal vein occlusion. No statistically significant differences were found between the two dose groups with regard to the number of injections, CMT, and change in BCVA.

Primary intravitreal bevacizumab for the management of pseudophakic cystoid macular edema Pilot study of the Pan-American Collaborative Retina Study Group

PURPOSE: To determine the feasibility, safety, and clinical effect of primary intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME) after cataract surgery. SETTING: Five institutions in Venezuela, Costa Rica, Puerto Rico, Peru, and Brazil. METHODS: Twenty‐eight eyes of 25 patients treated with at least 1 intravitreal injection of 1.25 mg or 2.50 mg of Avastin participated in this interventional retrospective multicenter study at 5 institutions from 5 countries. Baseline and follow‐up visits included Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination. RESULTS: The mean follow‐up was 32 weeks (range 24 to 52 weeks). Twenty eyes (71.4%) had improved best corrected visual acuity (BCVA) (≥2 ETDRS lines), and no eye had worse visual acuity (≥2 ETDRS lines). The BCVA remained stable in 8 eyes (28.6%). The mean baseline BCVA was 20/160 (logMAR = 0.92) and the mean final BCVA, 20/63 (logMAR = 0.50); the difference was statistically significant (P<.0001). The mean central macular thickness at baseline (466.3 μm; range 208 to 784 μm) decreased significantly (264.5 μm; range 176 to 513 μm) by the end of follow‐up (P<.0001). Eight eyes (28.6%) required a second injection and 4 (14.3%), a third injection. The mean interval between injections was 13 weeks (range 5 to 26 weeks). No ocular or systemic adverse events were observed. CONCLUSIONS: Short‐term results suggest that primary intravitreal Avastin is well tolerated in patients with pseudophakic CME. Treated eyes had a significant improvement in BCVA and decrease in macular thickness by OCT.

Radial optic neurotomy for central retinal vein occlusion: Results of the pan-american collaborative retina study group (pacores)

Objective: To evaluate the complications after radial optic neurotomy (RON) for central retinal vein occlusion (CRVO). Methods: Seventy-three consecutive patients (73 eyes) with CRVO who were treated with RON participated in a retrospective, uncontrolled, interventional, multicenter case series at 7 institutions from 6 countries. Results: In the ischemic CRVO group (n = 53), 32% of eyes had an improvement in best-corrected visual acuity (BCVA) (mean, 5.5 lines), 35.8% had worse BCVA (mean, 6.4 lines), and 32% had BCVA that remained the same after RON. In the nonischemic CRVO group (n = 20), 50% of eyes had an improvement in BCVA (mean, 6.5 lines), 15% had worse BCVA (mean, 4.3 lines), and 35% had BCVA that remained the same after RON. Complications occurred in 71.2% of cases, including cataract in 17 eyes (23.2%), vitreous hemorrhage in 16 eyes (20.5%), persistent macular edema in 15 eyes (20.5%), neovascular glaucoma in 7 eyes (9.5%), anterior segment neovascularization in 5 eyes (6.8%), retinal detachment in 3 eyes (4.1%), and phthisis bulbi, choroidovitreal neovascularization, central retinal artery perforation, and optic nerve atrophy in 1 eye (1.3%) each. Conclusions: RON may improve visual acuity in some eyes with CRVO, but complications are common. In our series, surgery by itself did not seem to improve the outcome of CRVO when compared with its natural history.