Transient Intraocular Pressure Fluctuations After Intravitreal Bevacizumab Injection in Proliferative Diabetic Retinopathy Patients: A Prospective Study.

INTRODUCTION: The clinical use of intravitreal bevacizumab (IVB), a recombinant humanized monoclonal antibody that functions as an anti-vascular endothelial growth factor (anti-VEGF), has recently increased in patients with retinal ischemic diseases such as proliferative diabetic retinopathy (PDR). The short-term and long-term complications associated with this procedure have not been well established. We aimed to study the possible short-term complication of intraocular pressure (IOP) fluctuations shortly after IVB injection in patients with PDR. MATERIALS AND METHODS: A prospective case series of diabetic patients with PDR who underwent IVB injection was performed in the Department of Ophthalmology, Medical Teaching Institution, Khyber Teaching Hospital, Peshawar, Pakistan, from November 1, 2020, to May 1, 2021. The total number of PDR patients of both sexes included in the study was 101. A slit lamp examination was performed, and IOP readings were recorded before and 30 min after IVB injection using Goldmann applanation tonometry (GAT). IBM Statistical Package for the Social Sciences version 22 for Windows was used to analyze the data. Safety of the procedure, defined as IOP ≤20 mmHg 30 min after IVB injection, was determined and stratified according to sex, age, duration of diabetes, and baseline IOP. A post-stratification chi-square test was applied, and a p-value <0.05 was taken as statistically significant. RESULTS: In this study, 60.4% of the participants were male and 39.6% were female. The age of the patients ranged from 30 to 75 years, with a mean age of 55.66±6.37 years. The mean duration of diabetes among the participants was 7.73±2.94 years and the mean baseline IOP was 15.40±1.77 mmHg. Safety (IOP ≤20 mmHg 30 min after IVB injection) was observed in 90.1% of the patients. CONCLUSION: IVB injections are safe for use in patients with PDR in terms of immediate IOP changes. However, patients with higher baseline IOP (>15 mmHg) are more likely to develop increased IOP post-procedure and prophylaxis may be prudent in such cases.

Corneal thinning following bevacizumab intrastromal injection for the treatment of idiopathic lipid keratopathy.

Purpose: To describe the occurrence of corneal thinning in a patient following intrastromal injection of bevacizumab to treat lipid keratopathy. Observations: A 36-year-old female presented with decreased vision in her right eye with central posterior corneal haze and underwent a treatment regimen including artificial tears, cyclosporine 0.05% drops, prednisolone 1% and oral Valacyclovir 1g with no improvement. Neovascularization was noted at 18 months follow up and treated with intrastromal bevacizumab injections at 24 months. The feeder vessel was attenuated at 3- and 6-months post-injection, but tomography indicated sustained thinning and flattening of the cornea at the injection site contributing to the development of irregular astigmatism. Conclusions and Importance: Corneal thinning is an uncommon potential side effect of intrastromal bevacizumab injection that may affect postoperative visual acuity.

Incidence and management of acute endophthalmitis after intravitreal injection of bevacizumab.

PURPOSE: To report the incidence, management, and clinical outcomes of cases who developed acute endophthalmitis following the administering of the intravitreal bevacizumab (IVB) injection. METHODS: In this retrospective, non-comparative, single-center, cross-sectional study, the records of patients diagnosed with acute endophthalmitis following IVB injection between March 2013 and October 2019 were reviewed. Immediate injection of intravitreal antibiotics and early pars plana vitrectomy was performed for all cases after clinical diagnosis of acute post IVB endophthalmitis. RESULTS: A total of 28,085 IVB injections were performed during the study period. Nine eyes of nine patients developed acute post IVB endophthalmitis giving an overall incidence of 0.032% (95% CI, 0.01-0.06) (3.2 in 10,000 injections). Three cases (33%) were culture-positive (staphylococcus epidermidis). The mean time between IVB injection and presentation of endophthalmithis was 2.77 ± 1.25 days (Range, 1-6). The mean number of previously received IVB injections before developing of endophthalmitis was 4 ± 1.5 (range 2 to7). The mean best corrected visual acuity (BCVA) before IVB injection, at the presentation of endophthalmithis and three months after the treatment of endophthalmithis were 1.18 ± 0.62, 2.5 ± 0.42, and 1.94 ± 0.88 logMAR, respectively (P = 0.025). One eye developed phthisis bulbi. CONCLUSION: The incidence of acute endophthalmitis following Intravitreal injection of bevacizumab is very low. The time interval between injection and presentation is short. Prompt treatment with immediate intravitreal antibiotics and early pars plana vitrectomy are key in maximizing outcomes. The prognosis of post-IVB endophthalmitis is poor and may result in significantly visual impairment.

Reduction of Intraocular Pressure Spikes Due to Intravitreal Bevacizumab Injections by Scleral Indentation with Cotton Swab or Digital Ocular Massage: Innovative Techniques Compared.

PURPOSE: This study aims to evaluate the effectiveness of different decompressive injection techniques in reducing intraocular pressure (IOP) spikes, if compared to the injection without pressure applied on the eye, following the intravitreal injection of bevacizumab. PATIENTS AND METHODS: Two hundred patients with indication to intravitreal therapy were randomized into five arms: 40 received intravitreal injection without ocular decompression (arm A), 40 with pre-injection scleral indentation with cotton swab (arm B), 40 with pre-injection digital ocular massage (arm C), 40 with post-injection scleral indentation with cotton swab (arm D) and 40 with post-injection digital ocular massage (arm E). All patients underwent measurement of the IOP with Goldamm applanation tonometer 10 minutes before and 10 minutes after the injection. The primary endpoint of the study was variation of the post- injection IOP with the different techniques. RESULTS: An increase in post-injection IOP was observed in all the arms, if compared to pre-injection values. The greatest increase was observed in arm A with a mean IOP rise of 17.60 mmHg. All other techniques showed lower mean IOP increases: arm B 10.76 mmHg, arm C 9.35 mmHg, arm D 8.8 mmHg, arm E 3.4 mmHg. The post-injection IOP differences of innovative techniques compared to the technique without ocular decompression were all statistically significant (p-value <0.01). If compared to arm A (35%), a reduction in IOP spike ≥40 mmHg frequency was also observed. The status of phakia/pseudophakia, a previous diagnosis of glaucoma and the underlying pathology for which indication was given to inject bevacizumab did not significantly alter the post-injection IOP in any of the protocols. CONCLUSION: The introduction of new injection protocols, such as injections performed before or after decompressive treatments, could be a safe and effective approach to control post-injection IOP increase.

Macular Hole Formation in Eye After Cryotherapy and Intravitreal Bevacizumab Treatment for Vasoproliferative Tumor.

PURPOSE: To report a case of a full-thickness macular hole (MH) that developed after cryotherapy and intravitreal bevacizumab injection (IVB) to treat a retinal vasoproliferative tumor (VPT). METHODS: Case report of a man with a retinal VPT. RESULTS: A 64-year-old Japanese man complained of blurred vision in his right eye. At the initial examination, his best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/20 in the left eye. Ophthalmoscopy showed a VPT in the lower peripheral retina of the right eye. An exudative retinal detachment and hard exudates were seen around the tumor. Cryotherapy and intravitreal injections of bevacizumab (IVB) were performed. Although the exudative changes were reduced, a MH developed two months after the initial IVB treatment. He underwent 25-gauge pars plana vitrectomy, and the MH was closed. His postoperative BCVA was 20/32 and the VPT was inactive. The reduced BCVA was due to damage of the outer retinal layers. CONCLUSION: Our findings indicate that cryotherapy and IVB are effective treatments for VPT although the possibility of developing a MH should be considered.

Refractive outcome of intravitreal bevacizumab injection in comparison to spontaneous regression of retinopathy of prematurity (ROP).

Purpose: To assess refractive errors in preterm infants following intravitreal bevacizumab (IVB) injection for retinopathy of prematurity (ROP) and to compare it with premature babies with spontaneous regressed ROP.Materials and Methods: Eighty seven premature infants were included in this study, comprising group1: 38 infants who underwent IVB monotherapy, and group2: 49 infants with spontaneously regressed ROP. Cycloplegic refraction was performed for all infants at 1-year adjusted age and the refractive outcome was compared between the groups.Results: At 1- year adjusted age, the mean SEQ value was not significantly different between group 1 and 2 (p = .646). Four eyes (10.5%) in group1 and 4 eyes (8.2%) in group 2 were myopic. Also, refractive anisometropia was found in 9 infants (23.7%) from group1 and 5 infants (10.2%) in groups 2, which was not significantly different between groups (χ2 (1, n = 87) = 2.87, p = .081). At the time of follow up, none of our cases were strabismic. After making an adjustment for gestational age and birth weight in a logistic regression model, mean SEQ was not significantly different between two groups (p = .61)Conclusion: At adjusted 1 year of age, refractive outcomes were not significantly different between premature infants who underwent IVB injection and the infants with spontaneous regression of ROP. Further studies with longer duration are warranted to elucidate the effects of IVB on the emmetropization process. Biometry assessments would be helpful in this regard.

Effectiveness of prophylactic intravitreal bevacizumab injection to proliferative diabetic retinopathy patients with elevated preoperative intraocular VEGF in preventing complications after vitrectomy.

PURPOSE: This study aimed to elucidate the effects of intravitreal bevacizumab (IVB) injections for the prevention of post-vitrectomy complications in proliferative diabetic retinopathy (PDR) patients with elevated vitreous vascular endothelial growth factor (VEGF) concentration. DESIGN: Prospective case series. METHODS: Thirty-three patients (42 eyes) with PDR who underwent primary vitrectomy in the Department of Ophthalmology, Tokyo Medical University Hospital were studied. We measured VEGF concentrations in vitreous humor collected at the time of vitrectomy using ELISA. IVB injections were performed after vitrectomy in patients with vitreous VEGF levels exceeding 1,000 pg/mL. New bleeding occurring within 1 month of vitrectomy was defined as early vitreous hemorrhage (VH). MAIN OUTCOME MEASURE: The incidence of complications after vitrectomy including postoperative early VH. RESULTS: IVB injections were administered to 11 eyes (26%) with vitreous VEGF concentrations exceeding 1,000 pg/mL. None of the 11 eyes that received an IVB injection developed early VH. Among 31 eyes (74%) with vitreous VEGF concentrations lower than 1,000 pg/mL, two eyes (6%) developed early VH after vitrectomy. CONCLUSIONS: Prophylactic IVB injections administered to patients with elevated preoperative intraocular VEGF concentrations were effective in preventing post-vitrectomy early VH.

Preoperative Timing of Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy Patients.

OBJECTIVE: To evaluate the changes in aqueous concentrations of inflammatory cytokines and fibrosis-related factors, and to detect the expression of vascular endothelial growth factor (VEGF) and proliferating cells in fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR) after injection of intravitreal bevacizumab (IVB). METHODS: Forty-two eyes of 42 patients with PDR, including 28 eyes that received IVB (1.25 mg) 2, 5, and 14 days before pars plana vitrectomy (PPV), and 14 eyes without IVB, were enrolled, in addition to 10 eyes of 10 patients with nondiabetic ocular diseases. Aqueous concentrations of inflammatory cytokines and fibrosis-related factors were analyzed by a multiplex bead assay. Fluorescence immunostaining was performed to examine the expression of VEGF and proliferating cells in the excised epiretinal membranes. RESULTS: PDR eyes without IVB had the highest vitreous VEGF levels, and the level was statistically significant compared with that of PDR eyes that received IVB 2 days before surgery, PDR eyes that received IVB 5 days before surgery, and nondiabetic eyes (p = 0.011, p = 0.012, and p < 0.001, respectively). The expression of fibroblastic cells and connective tissue growth factor increased in epiretinal FVMs of the IVB group 21 days after treatment. CONCLUSIONS: IVB injection may lead to a decrease in the intraocular concentrations of VEGF after 2-5 days and induce the formation of proliferation after 21 days, which suggests that PPV in PDR patients should take place within 1 week of the administration of preoperative IVB.

[Treatment of macular hematoma complicating AMD by vitrectomy, subretinal r-TPA injection, intravitreal injection of bevacizumab combined with gas tamponade: Report of 4 cases]. / Traitement des hématomes maculaires compliquant la DMLA par vitrectomie, injection sous-rétinienne r-TPA, injection intravitréenne de bévacizumab associé à un tamponnement par gaz : à propos de 4 cas.

INTRODUCTION: The occurrence of a subretinal hematoma in age-related macular degeneration (AMD) is a serious complication that can impact the visual prognosis with a poor functional recovery. The management of this complication remains controversial. Several therapeutic methods have been described. We report the results of four patients treated with a protocol combining: vitrectomy, subretinal injection of r-TPA 0.025mg/0.3ml, intravitreal injection of 0.05ml of bevacizumab and retinal tamponade with 20% SF6 gas. PATIENTS AND METHODS: Our series consists of four patients with a submacular hematoma complicating AMD, included in succession between October 2013 and October 2014 and treated with the same treatment protocol and by the same surgeon. All patients underwent surgery within eight days after the onset of the macular hematoma. Patients with a consultation period longer than eight days did not undergo this treatment. Face down postoperative positioning was then carried out for seven days by the patients. RESULTS: We observed a shift in the macular hematoma in the four patients, which allowed the identification of secondary neovascularization responsible for the bleeding. The visual acuity improved in three patients from hand motion (HM) preoperatively to 2/10 at one month postoperatively. One patient maintained visual acuity 1/20 during the entire follow-up despite almost complete resorption of the subretinal hematoma. These visual acuities were stable at 6 months postoperatively. DISCUSSION: Macular subretinal hematoma can cause severe visual loss by several mechanisms. The blood accumulates between the neurosensory retina and the retinal pigment epithelium, which causes a toxic effect on the surrounding tissues, thus resulting in a loss of photoreceptors and cellular destruction in the pigment epithelium and choriocapillaris, evolving into a fibroglial scar. CONCLUSION: The therapeutic evaluation of this protocol in our series of four patients gives a favorable result. We observed an improvement in visual acuity in 3/4 of cases. This surgical technique appears to be effective in the treatment of this complication of AMD. However, a study on a larger scale is needed to confirm these results.

Serial Intravitreal Bevacizumab Injections Slow the Progression of Radiation Maculopathy Following Iodine-125 Plaque Radiotherapy.

BACKGROUND AND OBJECTIVE: To assess the outcomes of intravitreal bevacizumab injection in the management of radiation maculopathy secondary to plaque radiotherapy, and to identify optimal treatment strategies. STUDY DESIGN: A retrospective review of all choroidal melanoma patients at one referral center who were treated with plaque radiotherapy, subsequently developed radiation maculopathy, and received intravitreal bevacizumab. RESULTS: A total of 31 patients were identified. The mean visual acuity decreased three Snellen lines in the year leading up to the first bevacizumab injection. After initiating injection therapy, the mean visual acuity remained stable for 9 months. The change in visual acuity of patients who received injections within 90 days of previous injections was significantly better than the visual acuity of those who received injections more than 90 days apart (p=0.0003). Patients who demonstrated late-phase macular leakage on fluorescein angiography at the time of the first bevacizumab injection had better long-term visual acuity outcomes than patients who had no evidence of macular leakage (average of one line improvement of vision vs. ten line loss of vision, p=0.03). CONCLUSIONS: Intravitreal bevacizumab injection was effective in stabilizing visual acuity in patients with radiation maculopathy. Patients benefited most from injections administered every 90 days or sooner. Fluorescein angiography can help identify patients who will respond favorably to treatment.

Choroideremia associated with choroidal neovascularization treated with intravitreal bevacizumab.

PURPOSE: To report a rare case of central vision loss in a patient with choroideremia. PATIENTS AND METHODS: A retrospective, interventional case report. RESULTS: A 13-year-old male with history of choroideremia presented with subacute loss of central acuity in his left eye. Examination and diagnostic testing revealed subretinal fibrosis secondary to a choroidal neovascular membrane (CNVM). A trial of anti-vascular endothelial growth factor (VEGF) therapy with the injection of intravitreal bevacizumab was attempted. Mild improvements in acuity and anatomy were noted. CONCLUSION: Choroideremia is a rare hereditary choroidal dystrophy that predominantly affects males in the first and second decades of life. Visual acuity is usually spared until later in life. CNVM is a rare manifestation of choroideremia with only a handful of case reports presented in the literature. This case is unique in that it is the first reported case that received treatment with intravitreal anti-VEGF therapy.

Combined vitrectomy and intravitreal injection versus combined laser and injection for treatment of intractable diffuse diabetic macular edema.

BACKGROUND: The purpose of this study was to compare the safety and efficacy of combined vitrectomy, intravitreal triamcinolone acetonide (IVTA), and bevacizumab injection with that of IVTA and bevacizumab injection and subsequent macular grid laser photocoagulation for the treatment of intractable diffuse diabetic macular edema. METHODS: This randomized controlled clinical trial was performed at Benha University Hospital, Benha, Egypt, and included 34 eyes from 34 diabetic patients diagnosed with intractable diffuse diabetic macular edema without vitreomacular traction. The patients were divided into two groups. In group 1, pars plana vitrectomy with removal of the posterior hyaloid was performed, and at the end of the procedure, IVTA 0.1 mL (40 mg/mL) and bevacizumab 1.25 mg were injected. In group 2, macular grid laser photocoagulation was performed 2 weeks after the same intravitreal injection combination as used in group 1. The main outcome measures were best-corrected visual acuity (BCVA) and central foveal thickness, which were measured using optical coherence tomography at 3, 6, and 12 months. RESULTS: Changes in BCVA and central foveal thickness at 3, 6, and 12 months from baseline were highly statistically significant (P < 0.01). Mean BCVA was better in group 1 at 3 months, nearly equal at 6 months, and less at 12 months. Mean central foveal thickness was more improved in group 1 than in group 2 at 3 months, and was better in group 2 at subsequent measurement points. The major adverse events were development of cataract (more common in group 1) and elevation of intraocular pressure (more common in group 2). CONCLUSION: The combined therapy described here could represent a solution for the treatment of intractable diabetic macular edema, and could have a favorable long-term outcome. Combined treatment of IVTA and bevacizumab plus grid laser resulted in a more favorable reduction in central foveal thickness and improvement in BCVA at 12 months than vitrectomy combined with the same injections. This small study favors the safer, cheaper, and more available line of treatment.

Intravitreal bevacizumab for macular edema due to branch retinal vein occlusion: 12-month results.

PURPOSE: To present the functional and anatomic changes after intravitreal bevacizumab in eyes with macular edema (ME) due to branch retinal vein occlusion (BRVO). DESIGN: The study was a retrospective study. MATERIALS AND METHODS: The study included 31 patients with ME due to BRVO. We compared the examination findings of patients with ME before and after intravitreal bevacizumab therapy at 12 months. The study included patients who had macular edema secondary to BRVO treated with bevacizumab. The therapy was started in the first week after occlusion. The initial therapy was three intravitreal bevacizumab injections at monthly intervals with 1.25/0.05 mL bevacizumab. Patients with a baseline visual acuity less than 0.5 (logarithm of the minimum angle of resolution [logMAR] 0.30), central macular thickness (CMT) more than 290 µm, and no neovascularization were included. Patients with diabetes mellitus or a history of intravitreal triamcinolone or grid laser photocoagulation therapy or ischemic BRVO were excluded. The retreatment criteria were as follows: increased CMT more than 100 µm combined with a loss of visual acuity of five or more letters. The statistical analysis of this study was carried out by paired samples t-test (SPSS). A P value of less than 0.05 was considered to be statistically significant. RESULTS: This retrospective study included 33 eyes of 31 patients (20 women, 11 men; mean age was 55.30 ± 9.62 years (range 36-75 years). Patients received a mean of 5.3 injections during 12 months of follow-up. The best corrected visual acuity increased from 0.66 ± 0.20 (logMAR) at baseline to 0.22 ± 0.13 (logMAR) (t = 15.42; P < 0.001) at month 12. The CMT decreased from 494.15 ± 104.16 µm at baseline to 261.79 ± 45.36 µm at month 12 (- 232.36 ± 109.98 µm); P < 0.001). No bevacizumab-related systemic or ocular adverse effects following intravitreal drug injections were observed. The majority of patients required reinjection(s) treatment for ME (84.9%). CONCLUSION: Intravitreal therapy using bevacizumab appears to be an effective primary treatment option for ME due to BRVO. No serious ophthalmologic or systemic side effects were observed for intravitreal bevacizumab therapy. The main disadvantage of bevacizumab therapy is the requirement of multiple injections in order to maintain visual and anatomic improvements.

A case of intravitreal bevacizumab injection for the treatment of choroidal neovascularization in angioid streaks.

A 56-year-old Korean woman presented with decreased visual acuity of the right eye. She had a history of two photodynamic therapy treatments for choroidal neovascularization (CNV) due to angioid streaks in her left eye with central scarring and low visual acuity. She was diagnosed with subfoveal CNV due to angioid streaks in her right eye and treated with six intravitreal bevacizumab (1.25 mg / 0.05 mL) injections over one year. Best corrected visual acuity improved from 20 / 125 at baseline to 20 / 50 at the final visit. The area of CNV had changed into a fibrotic scar by the final visit, and fluorescein angiography and indocyanine green angiography revealed no evidence of leakage. Optical coherence tomography showed that central macular thickness decreased from 311 µm at baseline to 203 µm with complete resolution of subretinal and intraretinal fluid at the final visit. Intravitreal bevacizumab for CNV associated with angioid streaks prevented the progression of disease and resulted in the improvement of visual acuity after one year of follow-up in our patient.

Serous retinal detachment following combined photodynamic therapy and intravitreal bevacizumab injection.

We report a case of serous retinal detachment following combined photodynamic therapy (PDT) and intravitreal bevacizumab injection in subfoveal choroidal neovascularization (CNV). A 53-year-old woman was diagnosed with subfoveal CNV secondary to age-related macular degeneration (AMD) and treated with combined PDT and intravitreal bevacizumab injection. One day after treatment, the patient experienced a sudden decline of vision and optical coherence tomography (OCT) showed serous retinal detachment involving the macula. She was managed conservatively with an oral steroid beginning on the second day of the combined treatment and the subretinal fluid started to decrease one week following the initiation of steroids. This case suggests that combined PDT and intravitreal injection of bevacizumab can be associated with serous retinal detachment. Additional studies are needed to establish the safety and complications following this treatment regimen.

Intravitreal bevacizumab for treatment of diabetic macular edema.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on visual function and retinal thickness in patients with diabetic macular edema (DME). METHODS: Thirty eyes of twenty-eight patients (mean age, 57.9+/-13.8 years) with DME were included in this study. Complete ophthalmic examination, including determination of best-corrected visual acuity (BCVA), stereoscopic biomicroscopy, and retinal thickness measurement by optical coherence tomography (OCT), was done at baseline and at each follow-up visit. All patients were treated with a 0.05 mL intravitreal injection containing 1.25 mg of bevacizumab. RESULTS: All patients completed 3 months of follow-up with a mean follow-up period of 5.26+/-2.39 months. The mean BCVA at baseline was 0.73+/-0.36 logMAR, which significantly improved to 0.63+/-0.41 (p=0.02), 0.58+/-0.36 (p=0.003), and 0.61+/-0.40 logMAR (p=0.006) at 1 week, 1 month, and 3 months. Final BCVA analysis demonstrated that 15 eyes (50%) remained stable and 12 (40%) improved >or=2 lines on BCVA. The mean central retinal thickness was 498.96+/-123.99 microm at baseline and decreased to 359.06+/-105.97 (p<0.001), 334.40+/-121.76 (p<0.001), 421.40+/-192.76 microm (p=0.035) at 1 week, 1 month, and 3 months. No ocular toxicity or adverse effects were observed. CONCLUSIONS: Intravitreal bevacizumab injection resulted in significant improvement in BCVA and central retinal thickness as early as 1 week after injection in patients with DME, and this beneficial effect persisted for up to 3 months. However, the slight reduction in this improvement at 3 months suggests that repeated bevacizumab injections might be necessary. To evaluate the long-term safety and efficacy, further prospective randomized controlled clinical trials will be needed.