Maria H. Berrocal

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 (p = 0.002). Conclusions: TRD may occur or progress shortly following administration of intravitreal bevacizumab in patients with severe PDR.

Variations in the clinical course of submacular hemorrhage

PURPOSE To assess variations in the clinical course of submacular hemorrhages. METHODS We reviewed fundus photography charts taken of patients during a 27-month period. Thirty-one eyes of 31 patients with submacular hemorrhages under the foveal avascular zone were reviewed. RESULTS In 20 of the eyes, the underlying etiology was age-related macular degeneration (ARMD). The other 11 eyes had various underlying conditions, including macroaneurysms (two), presumed ocular histoplasmosis syndrome (two), trauma (one), Valsalvas retinopathy (one), idiopathic central serous choroidopathy (one), diabetic retinopathy (two), central retinal vein occlusion (one), and choroidal rupture (one). Of the eyes with ARMD (mean follow-up, 29 months), eight (40%) of 20 showed an improvement in visual acuity (> or = 2 Snellen lines), six (30%) of 20 had a final visual acuity of 20/80 or better, and three (15%) had a final visual acuity of 20/40 or better (range, 20/25 to 20/80). Of the eyes without ARMD (mean follow-up, 29 months), five (45) of 11 had an improvement in visual acuity and five (45%) of 11 attained a final visual acuity of 20/40 or better (range, 20/20 to 20/40). The best predictive factor for poor final visual acuity was the presence of a subretinal neovascular membrane. CONCLUSIONS Patients with submacular hemorrhage may have spontaneous improvement in visual acuity without surgery. Patients without subretinal neovascular membranes had a better visual improvement rate.

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.

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

OBJECTIVE To 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. DESIGN Interventional, retrospective, multicenter study. PARTICIPANTS Thirty-six eyes of 31 patients with refractory CME after cataract surgery and with a mean age of 68.2 years (range, 67-87 years). METHODS Patients were treated with at least 1 IVT injection of 1.25 or 2.5 mg bevacizumab. Patients were followed up for 12 months. MAIN OUTCOME MEASURES Best-corrected visual acuity (BCVA) and central macular thickness (CMT) by optical coherence tomography (OCT). RESULTS Twenty-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. CONCLUSIONS Short-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.

Perfluorocarbon liquid in the management of retinal detachment with proliferative vitreoretinopathy.

PURPOSE To describe the techniques and results of perfluoro-N-octane used during vitrectomy for managing retinal detachment with severe proliferative vitreoretinopathy (PVR). METHODS The authors retrospectively studied 223 consecutive patients who underwent vitreoretinal surgery for severe PVR (93% D1-D3). Patients underwent an average of 1.72 prior vitreoretinal surgeries. Perfluoro-N-octane was used intraoperatively to flatten the retina, avoiding posterior drainage retinotomy, to identify areas of residual retinal traction and periretinal membranes, to stabilize the peripheral retina during dissection of anterior PVR, and to help determine the extent and location of relaxing retinotomies. Extended-term gas tamponade was used in 91% of eyes. All patients were followed for a minimum of 6 months. RESULTS Seventy-eight percent of the retinas were reattached posterior to the scleral buckle after a single vitreoretinal surgery and 96% were reattached after multiple surgeries. An average of 1.24 vitrectomy surgeries were required. The final visual acuity was 20/400 or better in 74% of eyes and 20/80 or better in 30% (P = 0.004). Preoperative hypotony (intraocular pressure < or = 5 mmHg) and multiple prior vitreoretinal surgeries were associated with a poor final visual acuity (P = 0.01 and 0.02, respectively). Preoperative hypotony (intraocular pressure < or = 5 mmHg) was associated with a greater frequency of relaxing retinotomies (P = 0.02). Retained perfluoro-N-octane was observed postoperatively in the vitreous cavity in 1.3% and subretinal perfluoro-N-octane in 0.9%. CONCLUSION Experience with perfluoro-N-octane has demonstrated its usefulness both diagnostically and therapeutically as an intraoperative tool and improved the anatomic and visual outcome for retinal detachment complicated by severe PVR.

Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

PURPOSE To assess the role of bevacizumab in inflammatory ocular neovascularization. DESIGN Retrospective, multicenter, consecutive case series of inflammatory ocular neovascularization. METHODS Patients with inflammatory ocular neovascularization of varying causes for whom standard therapy failed were treated with intravitreal injection of bevacizumab. Main outcome measures included improvement of best-corrected visual acuity (BCVA) expressed in logarithm of minimum angle of resolution units, response of inflammatory ocular neovascularization by funduscopy and angiography, and decrease in central foveal thickness as measured by optical coherence tomography at the three-month follow-up. RESULTS At the three-month follow-up, 84 eyes of 79 patients had been treated with a mean of 1.3 injections (range, one to three). Thirty-four eyes showed juxtafoveal choroidal neovascularization (CNV), 34 eyes showed subfoveal CNV, eight eyes showed peripapillary CNV, and 11 eyes showed neovascularization of the disc (NVD) or neovascularization elsewhere (NVE). BCVA improved 2.4 lines from 0.68 (6/28 or 20/94) to 0.44 (6/17 or 20/55) (P < .001). BCVA improved by one to three lines in 34.5% of the eyes, by four to six lines in 16.7% of the eyes, and by more than six lines in 14.2% of the eyes. Function was unchanged in 23.8% of the eyes. BCVA worsened in 10.7% (zero to three lines in 7.1%, more than four lines in 3.6%). Central foveal thickness decreased from baseline 346 to 252 microm (P < .001). For CNV, 32 eyes (43.2%) had complete regression after the injection, 27 (36.5%) had partial regression, five (6.8%) had no response, and 10 eyes (13.5%) were not evaluated by the contributors. For NVD or NVE, seven eyes (63.6%) had complete regression of new vessels and four eyes (36.4%) had partial regression after the injection. CONCLUSIONS Intravitreal bevacizumab led to short-term significant visual improvement and regression of inflammatory ocular neovascularization in a wide variety of inflammatory ocular diseases.

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.

Endophthalmitis after pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group.

Purpose: To determine the incidence of endophthalmitis after 20-, 23-, and 25-gauge pars plana vitrectomies (PPVs). Methods: Retrospective comparative case series of consecutive patients who underwent 20-, 23-, or 25-gauge PPV at 11 centers from Latin America between 2005 to 2009. Pars plana vitrectomy cases were identified through a search of the billing records of each institution. Cases of PPV performed in the management of trauma, endophthalmitis, and combined PPV phacoemulsification cases were excluded. Endophthalmitis was diagnosed by clinical criteria regardless of the microbiologic results. The incidence of post-PPV endophthalmitis was compared between 20-, 23-, and 25-gauge PPVs. Results: A total of 35,427 cases of PPV were identified during the study period (n = 19,865 for 20 gauge, n = 10,845 for 23 gauge, and n = 4,717 for 25 gauge). The 5-year post-PPV endophthalmitis incidence rates were 0.020% (4 of 19,865), 0.028% (3 of 10,845), and 0.021% (1 of 4,717) for 20 gauge, 23 gauge, and 25 gauge, respectively (P = 0.9685). Conclusion: Small-gauge transconjunctival PPV does not appear to increase the rates of post-PPV endophthalmitis.