The Effect of Bevacizumab versus Ranibizumab in the Treatment of Corneal Neovascularization: A Preliminary Study

Purpose

To compare the short term effects of bevacizumab and ranibizumab injections on the regression of corneal neovascularization (NV).

Methods

Sixteen eyes of 16 patients with corneal NV were randomly assigned for an injection with 2.5 mg of bevacizumab (group 1, n = 8) or 1 mg of ranibizumab (group 2, n = 8) through subconjunctival and intrastromal routes. The patients were prospectively followed-up for one month after the injections. Corneal NV areas, as shown on corneal slit-lamp photographs stored in JPEG format, were calculated using Image J software before the injection, one week after the injection, and one month after the injection. The corneal NV areas were compared before and after the injections.

Results

Seven women and nine men, with an average age of 51 years, presented with corneal NV secondary to herpetic keratitis (7 cases), graft rejection (6), chemical burn (1), pemphigoid (1), and recurrent ulcer (1). In group I, the preoperative corneal NV area (8.75 ± 4.33%) was significantly decreased to 5.62 ± 3.86% one week after the injection and to 6.35 ± 3.02% one month after the injection (p = 0.012, 0.012, respectively). The corneal NV area in group 2 also exhibited a significant change, from 7.37 ± 4.33% to 6.72 ± 4.16% one week after the injection (p = 0.012). However, no significant change was observed one month after the injection. The mean decrease in corneal NV area one month after injection in group 1 (28.4 ± 9.01%) was significantly higher than in group 2 (4.51 ± 11.64%, p = 0.001).

Conclusions

Bevacizumab injection resulted in a more effective and stable regression of corneal NV compared to the ranibizumab injection. The potency and dose of these two drugs for the regression of corneal NV require further investigation.     

Corneal endothelial safety following subconjunctival and intrastromal injection of bevacizumab for corneal neovascularization

The purpose of this study is to determine the effect on endothelial cell density and morphology of combined subconjunctival and intracorneal injection of bevacizumab for the treatment of corneal neovascularization (NV). The charts and specular microscopy images of ten consecutive patients with corneal NV, who received combined subconjunctival+intracorneal injections of bevacizumab were reviewed. Patients received three injections of bevacizumab 25 mg/mL (1.25 mg/0.05 mL subconjunctival and 1.25 mg/0.05 mL intrastromal) 4–6 weeks apart. Endothelial cell counts (ECCs) and morphological changes were assessed by non-contact specular microscopy performed at baseline, 1 month after each injection and at 3 and 6 months after the last injection. There were no significant changes in ECCs (p = 0.663), coefficient of variation (p = 0.076), percentage of hexagonal cells (p = 0.931) or mean corneal thickness (p = 0.462) from pre-injection values to the 6-month follow-up values. There were no intraoperative or postoperative complications. In our series, the use of combined subconjunctival and intracorneal bevacizumab did not cause any decrease in ECCs or morphological alterations up to 6 months after the last of three injections. Further studies are required to confirm long-term safety in a larger sample population with longer follow-up, as well as the ideal dose, route of administration and frequency of bevacizumab administration.     

Subconjunctival bevacizumab for corneal neovascularization

Objective To report the efficacy of subconjunctival bevacizumab injection in patients with corneal neovascularization (NV). Methods This retrospective interventional case study included two eyes of two patients with corneal NV due to aqueous-deficient dry eye with filamentary keratitis in the first case, and corneal graft failure in the second case. Patients received a subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphologic changes were investigated by slit-lamp biomicroscopy and corneal photography. Results Corneal NV was dramatically regressed a week after injection in the first case. In the second case, minor vessels were regressed while the major one did not. No infection or inflammation was observed. No relapse was seen within the follow-up of two to three months. Conclusion Subconjunctival injection of bevacizumab may offer an additional strategy for the treatment of corneal NV.     

Inhibition of experimental corneal neovascularization by using subconjunctival injection of bevacizumab (Avastin)

PURPOSE: To evaluate the effect of subconjunctival bevacizumab (Avastin) administration on corneal neovascularization (NV) in rabbits. METHODS: NV was induced by placing a suture at the corneal periphery of the right eye of 20 rabbits. Immediately after suturing and again 1 week later, rabbits were divided into 2 groups and administered a subconjunctival injection of normal saline (control) or bevacizumab (Avastin; 5 mg/0.2 mL), respectively. On day 14, digital photographs of the cornea were taken and analyzed to determine the area of the cornea covered by NV. In addition, immunohistochemical analysis was used to determine CD31 and vascular endothelial growth factor (VEGF) expression in corneal tissue. RESULTS: Analysis of digital photographs showed that there was less corneal NV in bevacizumab-treated eyes than in controls (P < 0.001, Mann-Whitney U test). In addition, there was less staining for VEGF and CD31 in corneas from bevacizumab-treated eyes than in control eyes. Subconjunctival bevacizumab injections were not associated with any complications during observation. CONCLUSIONS: Subconjunctival bevacizumab administration decreased suture-induced corneal neovascularization in rabbits.     

Combined scraping,coagulation, and subconjunctival bevacizumab in corneal transplantation for bullous keratopathy with corneal neovascularization

PurposeThis study investigated clinical outcomes of the combined method of scraping, coagulation, and subconjunctival bevacizumab for the treatment of corneal neovascularization (NV) in penetrating keratoplasty (PKP).MethodsThis study included patients undergoing PKP who were diagnosed with bullous keratopathy with dense subepithelial scarring that was not suitable for Descemet’s stripping automated endothelial keratoplasty. Corneal NV was treated by scraping the corneal epithelium and lightly coagulating the superficial corneal stromal NV combined with subconjunctival bevacizumab injection at the end of surgery. Patients without corneal NV were used as the control group.ResultsThere were six patients with vascularized corneas in the study group and three patients without vascularized corneas in the control group. The original corneal NV in the study group disappeared in all patients after surgery. Three of the six (50%) study patients experienced recurrent corneal NV. One of the three (33%) control patients developed corneal NV. These patients had no corneal NV recurrences over the next 6 months after repeat treatment. In both groups, no graft failure or chronic epithelial defects occurred.ConclusionThe combination of scraping the corneal epithelium, coagulating the superficial corneal stromal NV and the feeding vessels in the sclera after peritomy, and subconjunctival bevacizumab injection is an effective method to treat corneal NV in corneal transplantation for bullous keratopathy.     

Comparison of subconjunctivally injected bevacizumab, ranibizumab, and pegaptanib for inhibition of corneal neovascularization in a rat model

AIM:To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model. METHODS:Sixteen corneas of 16 rats were chemically cauterized and randomized into four groups:bevacizumab group that treated with 0.05mL/1.25mg bevacizumab, ranibizumab group that treated with 0.05mL/0.5mg ranibizumab, pegaptanib group that treated with 0.05mL/0.15mg pegaptanib sodium, and control group that treated with 0.05mL saline solution. Digital photographs of the corneas were taken and analyzed using an image analysis software program. All corneas were excised and examined histologically on the 15^th day. RESULTS: Each treatment group had significantly less neovascularized corneal areas and fewer blood vessels than the control group (all P<0.05). In addition, bevacizumab group had significantly less neovascularized corneal areas and fewer blood vessels than ranibizumab and pegaptanib groups (both P<0.05). However, there was no significant difference between the ranibizumab and pegaptanib groups regarding percentage of neovascularized corneal areas and number of blood vessels (both P>0.05). CONCLUSION:Subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium were effective with no corneal epitheliopathy for inhibiting corneal neovascularization after corneal burn in rats. Bevacizumab was more effective than ranibizumab and pegaptanib sodium.     

结膜下注射贝伐单抗对兔角膜新生血管的抑制作用

目的 观察碱烧伤后不同时间结膜下注射贝伐单抗（Bevacizumab）角膜新生血管（CNV）的形成与转归.方法 新西兰白兔54只,制成单眼碱烧伤模型,随机分为3组,每组18只眼,A组碱烧伤后结膜下立即注射贝伐单抗2.5 mg（0.1 ml）,B组碱烧伤后3d结膜下注射贝伐单抗2.5 mg（0.1 ml）,C组结膜下注射生理盐水0.1ml,为对照组.共观察28 d.裂隙灯显微镜下观察角膜新生血管生长情况,行眼前段照相并计算其面积,伤后7、14、28 d各组随机取6例角膜行共焦显微镜检查,观察角膜组织炎性细胞浸润情况及角膜新生血管形态学变化.结果 A、B及C组角膜新生血管开始出现的时间分别为（5.9＋0.8）d、（3.5＋0.6）d及（3.4＋1.1）d,其中A组明显较C组延长（P＜0.05）,B组与C组差异无统计学意义（P =0.068）.伤后各时间点A、B组角膜新生血管的生长面积均明显较C组减少（P＜0.05）,A组与B组角膜新生血管面积比较,差异有统计学意义（P＜0.05）.共焦显微镜检查可见C组烧伤区大量炎性细胞浸润及新生血管形成,而A组角膜炎性细胞较少,烧伤区无新生血管形成,B组见少量新生血管侵入烧伤区.3组基质层均可见纤维及瘢痕组织增生,其中治疗组纤维增生程度与瘢痕组织均较对照组轻.结论 结膜下注射贝伐单抗可抑制角膜炎性细胞形成,改善损伤角膜基质,促进角膜愈合,从而减少碱烧伤引起的角膜新生血管的生长,在早期注射能取得更好的疗效.     

Avastin use in high risk corneal transplantation

Background

Corneal neovascularization is a major risk factor for graft failure after corneal transplantation. The purpose of this study was to investigate the effect of subconjunctival, perilimbal, and/or intrastromal bevacizumab (Avastin®) on corneal neovascularization in patients with penetrating keratoplasty (PKP).

Methods

Fourteen eyes of 14 patients with high risk corneal transplantation and corneal neovascularization after PKP (nine men and five women with a mean age of 63 years) were included in this non-comparative interventional case series. Indications for PKP were: vascularized leucomas after herpetic keratitis and chemical burn, advanced pseudophakic bullous keratopathy with superficial and deep corneal vascularization, keratoconus, severe infection in hereditary corneal dystrophy, and failed corneal grafts. Subconjunctival, perilimbal, and/or intrastromal bevacizumab of dose of 2.5 mg/ 0.1 ml/ per affected quadrant was injected at the site of neovascularization in each patient at the end of surgery and/or at follow up visits. One or two injections were applied. At each visit a full eye examination with photo documentation was performed. Follow-up period was 2 to 8 months (mean 7.1 months).

Results

Decrease of corneal neovascularization was observed in eleven patients (78.6%). Regression of neovascularization with fading of small vessels was demonstrated. Despite high- risk patient pool, twelve grafts (85.7%) remained transparent for the period of observation, and patients maintained good visual acuity. In two patients with initial graft rejection and vascularization, subconjunctival and perilimbal application of bevacizumab was beneficial in overcoming the corneal inflammation and initial rejection. No adverse reactions have been detected to date in patients with subconjunctival, perilimbal, and/or intrastromal injection of bevacizumab.

Conclusions

Bevacizumab is an efficient and safe additional treatment option for improvement of prognosis in high-risk corneal transplantation with pre- and postoperative corneal neovascularization.

     

Comparison of the effects of bevacizumab and ranibizumab injection on corneal angiogenesis in an alkali burn induced model

AIM: To investigate the effects of bevacizumab and ranibizumab on corneal neovascularization in an alkali burn-induced model of corneal angiogenesis. METHODS: Fifteen Wistar albino rats were divided randomly into 3 groups after chemical cauterization of the cornea. The first group received a single dose of 0.1mL saline solution as a control group whereas second and third groups received a single dose of 2.5mg bevacizumab or 1mg ranibizumab by subconjunctival injection, respectively. After three weeks, the rat corneas were evaluated by biomicroscopy and corneal photographs were taken. The percentage of neovascularization area, length of the longest new vessel, corneal edema and corneal opacity scores were assessed. RESULTS: The analysis of digital photographs showed that the percentage of neovascularization area to the total corneal area, the length of the longest new vessel, corneal edema and opacity scores were significantly lower in both study groups compared to the control group (P<0.05). Additionally, the percentage of corneal neovascularization area, the length of the longest new vessel and corneal opacity score were less with bevacizumab than ranibizumab. CONCLUSION: Subconjunctival bevacizumab and ranibizumab treatments may be effective methods in reducing corneal neovascularization. Furthermore, bevacizumab is more effective than ranibizumab in the inhibition of corneal neovascularization.     

Subconjunctival bevacizumab injection for corneal neovascularization in recurrent pterygium

PURPOSE: We report on the use of subconjunctival bevacizumab on corneal vessel density in recurrent pterygia. METHODS: The charts of 5 patients with recurrent pterygium, who received subconjunctival injections of bevacizumab (2.5 mg/0.1 ml) were retrospectively reviewed. Ophthalmic evaluation included Snellen visual acuity (VA), tonometry and complete examination before the injection and at 1 week and 1 and 3 months thereafter. Digital photographs of the eyes were analyzed by image analysis software to determine the area of cornea covered by new vessels as a percentage of the total corneal area. RESULTS: No ocular or systemic adverse events were observed. No change in visual acuity was noted in any patient following the injection. The mean change in corneal vascularization after one bevacizumab injection was 0.03%+/-0.45, while after two injections the change was 0.025%+/-0.19 (both not statistically different than zero, t-test). CONCLUSIONS: Short-term results suggest that subconjunctival bevacizumab is well tolerated but does not cause regression of corneal vessels in recurrent pterygium.     

Subconjunctival bevacizumab injection for corneal neovascularization

PURPOSE: To report on the clinical use of subconjunctival bevacizumab in patients with corneal neovascularization. METHODS: The charts of 10 consecutive patients with corneal neovascularization who received subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) were reviewed. Digital photographs of the cornea were graded by 2 masked observers for density, extent, and centricity of corneal vascularization. Image analysis was used to determine the area of cornea covered by neovascularization as a percentage of the total corneal area. RESULTS: No significant ocular or systemic adverse events were observed during 3.5 +/- 1.1 months of follow-up. Seven patients showed partial regression of vessels. The extent decreased from 6.0 +/- 1.2 (SD) clock hours before the injection to 4.6 +/- 1.0 clock hours after bevacizumab injection (P = 0.008). Density decreased from 2.7 +/- 0.2 to 1.9 +/- 0.3, respectively. (P = 0.007). No change was noticed in the centricity of corneal vessels. Corneal neovascularization covered, on average, 14.8% +/- 2.5% (SD) of the corneal surface before the injections, compared with 10.5% +/- 2.8% (P = 0.36, t test) after bevacizumab injection. Therefore, bevacizumab decreased corneal neovascularization by 29%. CONCLUSIONS: Short-term results suggest that subconjunctival bevacizumab is well tolerated and associated with a partial regression of corneal neovascularization.     

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment*

Objective: To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Design: Retrospective, consecutive, interventional case series. Participants: Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Methods: Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Results: Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455?µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p?p?=?0.029). In patients with PED, there was a mean 27.9% reduction in height (p?=?0.046) at eight weeks’ follow-up. Conclusions: Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.     

Anti-VEGF-refractory Exudative Age-related Macular Degeneration: Differential Response According to Features on Optical Coherence Tomography

Purpose

To describe optical coherence tomography (OCT) characteristics of neovascular age-related macular degeneration (AMD) patients refractory to intravitreal anti-vascular endothelial growth factor (VEGF) injections (ranibizumab, bevacizumab) and their responses to alternative anti-VEGF agents or photodynamic therapy (PDT).

Methods

A retrospective review of 267 neovascular AMD patients treated with intravitreal anti-VEGF injections.

Results

Twenty patients (7.5%) were refractory to anti-VEGF injections (stationary or increased retinal exudation despite three or more monthly injections). They were grouped into either the extensive intraretinal fluid group (IRF group, 9 patients) or the subretinal fluid only group (SRF group, 11 patients) according to OCT findings. In the IRF group, response rates to subsequent treatment were 0% (0 / 7) for bevacizumab, 50% (3 / 6) for ranibizumab and 50% (3 / 6) for PDT ± anti-VEGF. Three out of four bevacizumab-refractory patients showed response to ranibizumab as a secondary treatment. In the SRF group, response rates were lower with 0% (0 / 7) for bevacizumab, 22.2% (2 / 9) for ranibizumab and 28.6% (2 / 7) for PDT ± anti-VEGF. One out of four bevacizumab-refractory patients responded to ranibizumab. The visual outcome was worse in the IRF group (median 20 / 1,000) than in the SRF group (median 20 / 100).

Conclusions

In anti-VEGF-refractory neovascular AMD, patients with extensive IRF refractory to bevacizumab can be responsive to ranibizumab while patients with SRF may be refractory to both, suggesting a different pathophysiology and intraocular pharmacokinetics.     

Bevacizumab and ranibizumab for neovascular age-related macular degeneration: a treatment approach based on individual patient needs

ObjectiveTo compare the efficacy of intravitreal bevacizumab and ranibizumab for the treatment of neovascular age-related macular degeneration using an as-needed treatment regimen.DesignRetrospective chart review.ParticipantsOne hundred and ninety two eyes of 184 patients.MethodsPatients received an initial treatment of 3 monthly intravitreal injections of ranibizumab or bevacizumab and retreatment is individually considered for each patient on the basis of optical coherence tomography, angiography, and clinical examination.ResultsFifty eyes treated with ranibizumab and 142 eyes treated with bevacizumab were included. The average age of the patients at baseline was 76.9 ± 8 years and 76.4 ± 8 years in the ranibizumab and bevacizumab group respectively. Mean visual acuity improved from 0.69 to 0.55 logMAR at 12 months in the ranibizumab group and from 0.70 to 0.67 logMAR in the bevacizumab group. At 12 months, 92% of eyes treated with ranibizumab had lost fewer than 0.3 logMAR, as compared with 83% in the bevacizumab group. The ranibizumab group received a mean of 4.92 injections, compared to 4.75 injections in the bevacizumab group over 12 months. After the first 3 injections, 20% of patients in the ranibizumab group and 26% in the bevacizumab group never needed another injection.ConclusionsAn approach based on clinical onset and choroidal neovascularization progression at angiography may provide benefit by reducing the number of intravitreal injections required.     

Effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in guinea pigs

PURPOSE: To evaluate the effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in guinea pigs. METHODS: Forty eyes of 40 guinea pigs were chemically cauterized with 75% silver nitrate and 25% potassium nitrate sticks. Fifteen eyes (group 1) received 2 subconjunctival injections of bevacizumab (0.1 mL, 1.25 mg) simultaneously with cauterization and 3 days later. Fifteen eyes (group 2) received 2 subconjunctival injections of bevacizumab (0.1 mL, 1.25 mg) 3 and 5 days after cauterization. Ten eyes (group 3, control group) received 2 subconjunctival injections of 0.1 mL of balanced salt solution 3 and 5 days after cauterization. After we determined the burn and neovascularization scores for all groups, the animals were killed on the 10th day. The percentages of neovascularization on the surface of the cornea were measured in terms of pixels on digital photographs. The average number of vessels at maximally vascularized areas was determined for each specimen. RESULTS: Neovascularization score was 1.1 +/- 0.3 in group 1, 2.46 +/- 1.3 in group 2, and 3.5 +/- 0.5 in the control group. The difference was statistically significant (P < 0.001). The area of neovascularization at the cornea surface was 15.6% +/- 10.1% in group 1, 19.74% +/- 11.2% in group 2, and 23.5% +/- 7.4% in the control group (P = 0.194). The average number of neovascular vessels at group 1 was significantly reduced in comparison with group 2 and the control group (P < 0.001). CONCLUSIONS: Subconjunctival injection of bevacizumab decreases the extent of chemically induced corneal neovascularization in guinea pigs. The antineovascular effect of bevacizumab is higher if the injection is performed simultaneously with the chemical cauterization.     

The effect of different doses of subconjunctival bevacizumab injection on corneal neovascularization

To evaluate the effects of various doses of subconjunctival bevacizumab injections in the treatment of patients with corneal neovascularization. During the 6-month-follow-up, no significant ocular or systemic adverse events were observed related to the subconjunctival bevacizumab injection. In Group 1, the total area of corneal neovascularization before injection was 14.8 ± 3.2 % of the corneal surface and 10.2 ± 2.8 % 6 months after injection (p < 0.01). The mean decrease in Group 1 was 32.0 ± 3.0 %. In Group 2, the total area of corneal neovascularization before and 6 months after the injection was 14.2 ± 2.5 and 9.8 ± 2.3 %, respectively (p < 0.01). The mean decrease in Group 2 was 31.0 ± 2.3 %. The difference between the two groups was not statistically significant (p > 0.05). Twenty-four eyes of 24 patients with corneal neovascularization who were treated with a subconjunctival injection of bevacizumab were included in this retrospective study. Fourteen eyes were treated with 2.5 mg/0.1 ml (Group 1), and 10 eyes were treated with 5.0 mg/0.2 ml (Group 2) of subconjunctival bevacizumab. Digital photographs of the cornea were used to determine the area of corneal neovascularization before injection and at 1 month, 3 months, and 6 months after treatment. Subconjunctival injection of bevacizumab is well tolerated and associated with a partial regression of corneal neovascularization. The efficacy of this treatment is not correlated to the injection dose.     

Regression of Iris Neovascularization after Subconjunctival Injection of Bevacizumab

To describe three cases of neovascular glaucoma (NVG) where iris or angle neovascularization regressed remarkably after subconjunctival bevacizumab injections used as the initial treatment before pan retinal photocoagulation (PRP) and/or filtering surgery. Three consecutive NVG patients whose intraocular pressure (IOP) was not controlled with maximal medication were offered an off-label subconjunctival injection of bevacizumab (2.5-3.75 mg/0.1-0.15 mL, Avastin). Bevacizumab was injected into the subconjunctival space close to the corneal limbus in two or three quadrants using a 26-gauge needle. Serial anterior segment photographs were taken before and after the injection. Following subconjunctival injection of bevacizumab, iris or angle neovascularization regressed rapidly within several days. Such regression was accompanied by lowering of IOP in all three cases. The patients underwent subsequent PRP and/or filtering surgery, and the IOP was further stabilized. Our cases demonstrate that subconjunctival bevacizumab injection can be potentially useful as an initial treatment in NVG patients before laser or surgical treatment.     

Bilateral same-session intravitreal injections of anti-vascular endothelial growth factors

AIM: To document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.METHODS:A retrospective case series study. Consecutive records of seventy four patients receiving simultaneous bilateral intravitreal injections of either ranibizumab or bevacizumab, between September 2010 and September 2013, were reviewed and the outcomes were assessed. Data collected included number of injections, indications for injections, pre-injection and post-injection visual acuity (VA), pre-injection and post-injection intraocular pressure and ocular and systemic complications/complaints after each injection.RESULTS: A total of 342 injections were administered to 74 patients, with a mean of 4.62 injections per patient. Seventy-three patients received bevacizumab (Avastin; Genentech Inc., South San Francisco, California, USA) alone, and only one patient received both bevacizumab and ranibizumab (Lucentis; Genentech Inc.) distributed between the injections. Pre- and post-injection VA follow-up measurements were available for 65 patients. Mean follow up period was 22mo. The indications for initiating therapy were choroidal neovascular membrane from age-related macular degeneration (3 patients) and diabetic macular edema (71 patients). The mean Snellen VA before each injection was 6/22. The next post-injection follow-up mean Snellen VA was 6/20. One patient had a painful, culture-positive endophthalmitis in one eye 3d after bilateral bevacizumab. Another patient had a painless subconjunctival hemorrhage in one eye. No other ocular or systemic adverse side effects/complaints have been registered in this study group.CONCLUSION:Bilateral same-session intravitreal injections using a separate povidone-iodine preparation, speculum, needle, and syringe for each eye are well-tolerated. None of the subjects in this study requested to switch to alternating unilateral injections. Proper patient counseling as to the risk of complications with this procedure is necessary.     

Complications of intravitreal injections--own experience

PURPOSE: Authors present complications associated with intravitreal injection perfomed in Ophthalmic Clinic CMKP MATERIAL AND METHODS: retrospective study, between January 2006 and July 2009 we performed intravitreal injections with triamcinolone acetonide (Kenalog, 4 mg), ranibizumab (Lucentis, 0.5 mg), bevacizumab (Avastin, 1.25 mg) and pegaptanib (Macugen, 0.3 mg). We treated eyes with age-related macular degeneration, diabetic macular edema, after retinal venous occlusion, with uveitis, Irvine-Gass syndrome, idiopathic juxtafoveolar teleangiectasia and central serous retinopathy. RESULTS: 943 eyes received intravitreal injections. The most common ocular complication was subconjunctival hemorrhage which was seen in 36% cases. Temporary elevated intraocular pressure above 21 mmHg was noticed in 18 eyes (5%) after anti-VEGF agents injections and in 30 eyes (23.4%) after Kenalog injection. Anterior uveitis developed in sixteen cases (1.7%) from the Avastin (5 eyes) and Lucentis (3 eyes) group. Anterior-posterior inflammation occurred in 8 eyes (0.8%), including four eyes (0.4%) with sterile endophthalmitis (3 following bevacizumab and 1 following ranibizumab injection), one eye (0.1%) with pseudoendophthalmitis (after triamcinolone). There were three cases of suspected endophthalmitis (2 following bevacizumab and 1 following triamcinolone injection). The infectious endophthalmitis after triamcinolone injection was culture-proven and revealed Staphylococcus epidermidis. Cataract formation or progression was noted in 34 eyes totally. In Kenalog group progression of cataract was seen in 23.4% of eyes (30 cases) during 2-years of follow-up and in anti-VEGF agents group--in two cases (0.6%) and 2 cases of iatrogenic cataract. Three diabetic patients suffered systemic adverse events: one patient developed renal insufficiency, one patient developed cerebrovascular accidents and one suffered a myocardial infarction resulting in death. Conclusions: Intravitreal injections are associated with a low incidence of serious adverse events. The most common ocular complication was subconjunctival hemorrhage. There was one case of serious complication--the culture-proven infectious endophthalmitis after Kenalog injection. Cataract formation and increase of intraocular pressure were more often observed following intravitreal triamcinolone injection.     

Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep

AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.