Intravitreal Bevacizumab Group Research Articles

Comparison of efficacy of combination therapy of an Intravitreal injection of bevacizumab and photocoagulation versus Pan Retinal Photocoagulation alone in High risk Proliferative Diabetic Retinopathy.

Objective:To compare efficacy of intravitreal bevacizumab augmented with Panretinal photocoagulation versus Panretinal photocoagulation alone in high risk proliferative diabetic retinopathy.Methods:This is Randomized clinical control trial study conducted at ISRA University Hospital, Hyderabad from July 2018 to December 2018. A total of 76 eyes were randomized into two groups, 38 eyes undergone PRP plus intravitreal bevacizumab, while 38 eyes had PRP alone. Status of neovessels was assessed before and after treatment with the help of fundus fluorescein angiography. Neovessels at disc (NVD’s) and neovessels elsewhere (NVE’s) were assessed with the disc surface diameter.Results:Seventy-six eyes were enrolled in this randomized clinical trial into two groups consecutively, that all completed the six months follow-up. In the PRP group mean BCVA (logMAR) worsened significantly from mean 0.30±0.07 to mean 0.40±0.04 at a 30th day and mean 0.40±0.04 at day 90. While BCVA become improved from 0.30±0.05 to 0.1±0.03 at week four and 0.1±0.02 at week 12 in PRP-Plus group. There was significant change in regression of NVES in PRP only group at week 4 is 2.25±0.75 (p=0.00004) and at 12 weeks 2.00±0.50 (p=0.00002), while in PRP + intravitreal bevacizumab group at 4th week was 1±0.5 (p =0.0001) and at 12th week was 0.75±0.25 (p=0.0001).Conclusion:Intravitreal Bevacizumab augmented with PRP is more effective in early regression of neovessels in high risk PDR patients.

Neurodevelopmental Outcomes after Bevacizumab Treatment for Retinopathy of Prematurity: A Meta-analysis

To evaluate neurodevelopmental outcomes after intravitreal bevacizumab (IVB) therapy in retinopathy of prematurity (ROP) infants compared with those not exposed to IVB. The primary concern regarding IVB treatment of ROP is the potential systemic side effects, especially the risk of causing severe neurodevelopmental impairment (sNDI). Results regarding neurodevelopmental outcomes after IVB therapy are conflicting. We conducted a meta-analysis and searched PubMed, Embase, and Web of Science for related publications from inception through March 12, 2020. The eligibility criteria were as follows: comparative studies of ROP patients that (1) included IVB as a treatment arm, (2) included a control group without bevacizumab treatment, and (3) reported on at least 1 neurodevelopmental outcome, such as sNDI, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), composition scores, or cerebral palsy (CP). The primary outcome was sNDI, with the odds ratio (OR) calculated. Secondary outcomes were mean differences (MDs) for cognitive, language, and motor scores (Bayley III) and OR for CP. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation approach. Eight studies, 6 including laser-controlled ROP infants and 2 including ROP infants not requiring treatment, were included. The weighted OR for sNDI in the IVB group was 1.39 (95% confidence interval [CI], 0.98-1.97). The weighted MDs were -1.92 (95% CI, -4.73 to 0.88), -1.32 (95% CI, -4.65 to 1.99), and -3.66 (95% CI, -6.79 to -0.54) for cognitive, language, and motor scores in Bayley III, respectively. The OR for CP was 1.20 (95% CI, 0.56-2.55). No differences were observed between the preset subgroups comprising laser-controlled ROP infants and ROP infants not requiring treatment. The current quality of evidence was rated as low (sNDI and all Bayley III scores) to very low (CP). Risk of sNDI was not increased in ROP patients after IVB treatment. Bayley III scores were similar in the IVB and control groups, except for a minor difference in motor performance. These findings suggest that the risk of additional sNDI after IVB treatment is low. Randomized trials are warranted to provide a higher quality of evidence.

Comparison of Safety and Efficacy of Intravitreal Ziv-Aflibercept Vs Bevacizumab for the Treatment of Macular Edema

Purpose: To study the safety and efficacy of intravitreal Ziv-Aflibercept vs. Bevacizumab for the management of edema caused by different retinal pathologies.
 Study Design: Comparative interventional study.
 Place and Duration of Study: Lahore General Hospital, Lahore, from July 2018 to June 2019.
 Material and Methods: Patients with resistant, center involving macular edema due to diabetes, retinal vein occlusion and age related macular degeneration were recruited. Complete ocular examination was performed. All the patients were randomly grouped into two i.e. IVZ (intravitreal Ziv-Aflibercept) and IVB (intravitreal bevacizumab). Each eye underwent intravitreal injection of 0.05 ml of fresh filtered ziv-aflibercept (1.25 mg) or 0.05 ml of fresh filtered Bevacizumab. Outcome was measured in terms of variation in central macular thickness (CMT) and also best corrected visual acuity (BCVA) at 3 months.
 Results: Total of 156 eyes of 136 patients completed whole duration of study and were included in the results. The mean baseline CMT was 510 μm (± 94 μm) in the IVB group and 493μm (±102 μm) in the IVZ group (P = 0.94). The mean baseline BCVA (log MAR) was 0.78 (Snellen's equivalent 6/36) in the IVZ and 0.70 (Snellen's equivalent 6/30) in the IVB group (P = 0.78). Central macular thickness was significantly reduced at 1st, 2nd and 3rd month in the IVZ group and IVB group (P < 0.001).
 Conclusion: Intravitreal Ziv-Aflibercept is safe and more effective than Bevacizumab for the treatment of edema caused by diabetes mellitus, retinal vein occlusion and wet age related macular degeneration.

ASSESSMENT OF HYPERREFLECTIVE FOCI AFTER BEVACIZUMAB OR DEXAMETHASONE TREATMENT ACCORDING TO DURATION OF MACULAR EDEMA IN PATIENTS WITH BRANCH RETINAL VEIN OCCLUSION

To evaluate the association between hyperreflective foci (HRF) on spectral domain optical coherence tomography and therapeutic effect of intravitreal bevacizumab (IVB) or intravitreal dexamethasone implants (IVD) according to macular edema (ME) duration in branch retinal vein occlusion. Consecutive treatment-naive patients received IVB or IVD for at least 6 months. Each group was subdivided according to ME duration (<3 months vs. ≥3 months). Hyperreflective foci and best-corrected visual acuity were compared. Of 139 eyes (139 patients), 69 received IVB and 70 received IVD. At baseline, eyes with ME ≥ 3 months had more outer and total retinal HRF than eyes with ME < 3 months (P < 0.001 and P = 0.001). At 6 months, the IVD group exhibited a greater reduction in outer retinal HRF than the IVB group in both ME duration subgroups (P = 0.015 and P < 0.001). In the ME ≥ 3 months group, IVD resulted in greater best-corrected visual acuity improvement than IVB (P = 0.017). Increased outer retinal HRF at baseline in eyes with ME ≥ 3 months together with a greater reduction in HRF at 6 months and better visual outcomes after IVD suggests that the inflammatory aspect of disease should be considered in the treatment of ME. Thus, IVD injection could be more appropriate for patients with a longer ME duration after branch retinal vein occlusion.

Comparison of outcomes of four different treatment modalities for diabetic vitreous haemorrhage

We compared outcomes of four different management modalities for diabetic VH. Patients with diabetic VH were identified in this retrospective study undertaken at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. Eyes were grouped based on the treatment received: control (observation only), intravitreal bevacizumab (IVB) injection(s), pars plana vitrectomy (PPV), and preoperative single IVB injection before PPV. Best-corrected visual acuity (BCVA) and status of VH were noted at baseline and the last follow up (Minimum: 6 months, maximum: 29 months). The proportion of eyes with Snellen BCVA improvement by two lines or more and VH clearance at the last follow up were compared between groups. The four groups – Control, IVB, PPV, and IVB-before-PPV had 23, 29, 17, and 20 eyes, respectively. The proportion of eyes gaining ≥2 lines was substantially higher in the IVB-before-PPV and PPV groups (90% and 77%, respectively) compared with IVB and observation groups (41% and 22%, respectively). Surgical treatment was associated with a 2.38 times higher likelihood of gaining ≥2 lines than the non-surgical one (incidence ratio: 2.38, 95% CI 1.19, 4.78 P = 0.015) after adjusting for age, hyperglycemia and BCVA at presentation. Less invasive treatment such as IVB injections did not result in the same amount of improvement in vision as did PPV. Prospective randomized studies are needed to better define the role of IVB injections in the management of diabetic VH.

RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY.

To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy. In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan. A total of 176 infants (340 eyes) were included in this study. The mean follow-up was 197.3 ± 110 weeks. All of the baseline demographic and ROP characteristics among the laser, IVB, and IVR groups were similar. The overall recurrence rate after treatment was 44 of 340 eyes (12.9%). The IVB group had a recurrence rate of 10.0%, followed by the laser group (18.0%) and the IVR group (20.8%); however, these rates were not significantly different (P = 0.0528). Compared with the laser group, the IVB and IVR groups exhibited recurrence at later ages (43.4 ± 3.5 weeks for the IVB group, 42.3 ± 2.0 weeks for the IVR group, and 39.5 ± 2.8 weeks for the laser group; P = 0.0058). The mean interval of recurrence from initial treatment in the laser group was 3.6 ± 1.4 weeks compared with 8.8 ± 3.9 weeks and 8.3 ± 1.6 weeks in the IVB and IVR groups, respectively (P = 0.0001). Overall, the independent risk factors of recurrence included an early postmenstrual age at initial treatment (P = 0.0160), Zone I (P = 0.0007), low Apgar score (P = 0.0297), and multiple births (P = 0.0285). There was no significant difference in progression to retinal detachment among the three groups (laser: 3/61, 4.9%; IVB: 2/231, 0.9%;and IVR: 1/48, 2.1%; P = 0.2701). Laser, IVR, and IVB are effective for Type 1 ROP. Retinopathy of prematurity recurrence requiring re-treatment was encountered as late as 50 weeks of postmenstrual age after IVB or IVR but earlier after laser. Longer follow-up for infants treated with anti-vascular endothelial growth factor is needed, especially in patients with significant risk factors such as an early postmenstrual age at initial treatment, Zone I ROP, low Apgar score, and multiple births.

PHACOEMULSIFICATION CATARACT SURGERY WITH PROPHYLACTIC INTRAVITREAL BEVACIZUMAB FOR PATIENTS WITH COEXISTING DIABETIC RETINOPATHY: A Meta-Analysis.

To evaluate the clinical effectiveness of intravitreal bevacizumab (IVB) injection combined with cataract surgery in the treatment of patients with cataract and coexisting diabetic retinopathy (DR). Pertinent comparative studies were identified through systemic searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register up to March 1, 2016. Outcome measures included corrected distance vision acuity, central macular thickness, and progression of DR and maculopathy. A meta-analysis was performed using RevMan (Cochrane Collaboration, Oxford, United Kingdom). Six studies describing a total of 283 eyes were identified. The meta-analysis results showed that corrected distance vision acuity measured at 1 month and 3 months after cataract surgery was significantly better in the IVB groups than in the control groups (P < 0.00001 and P = 0.01), whereas the corrected distance vision acuity at 6 months did not vary significantly between the 2 groups (P = 0.24). Similarly, the central macular thickness at 1, 3, and 6 months after surgery was significantly thinner in the IVB groups than in the control groups (P = 0.01, P = 0.0004, and P = 0.01, respectively). At 6 months, the progression of postoperative DR and maculopathy occurred more frequently in the control group than in the IVB group (P = 0.0001 and P < 0.0001, respectively). Our meta-analysis indicates that cataract surgery combined with IVB seems to be an effective treatment in patients with coexisting DR in the short term (up to 6 months). More randomized, prospective, and large-sample-sized trials are needed to evaluate the long-term effects of IVB at the time of cataract surgery in patients with DR.

Long-term outcomes of intravitreous bevacizumab or tissue plasminogen activator or vitrectomy for macular edema due to branch retinal vein occlusion.

PurposeThe purpose of this study was to determine the long-term outcomes of intravitreal bevacizumab (IVB) or intravitreal tissue plasminogen activator (tPA) or vitrectomy for macular edema associated with a branch retinal vein occlusion (BRVO).MethodsThis was a retrospective, interventional case series. Forty-one patients received a single 1.25 mg of IVB injection and followed by pro re nata protocol, 71 patients received a single intravitreal tPA, and 116 patients underwent phacovitrectomy with intraocular lens implantation.ResultsThe baseline characteristics and follow-up periods were not significantly different among the three groups. The mean follow-up period was 55.5 months with a range of 12–160 months. Sixteen patients (39.0%) in the IVB group, 24 patients (33.8%) in the tPA group, and two patients (1.7%) in the vitrectomy group underwent additional surgeries during the follow-up period. The best-corrected visual acuity (BCVA) significantly improved in all groups at 1 year after the initial treatment (all, P<0.0001) and at the final visit (all, P<0.0001). The differences in the BCVA between the three groups were not significant at all times after the initial treatment.ConclusionThe three groups led to similar long-term good visual outcomes. However, additional surgeries were performed in more than 30% of patients in the IVB and tPA groups.

A real-world study of effectiveness of intravitreal bevacizumab and ranibizumab injection for treating retinal diseases in Thailand

BackgroundTo evaluate the effectiveness of intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) in actual practice for treating patients with retinal diseases in Thailand.MethodsA prospective, multi-centre, observational study was conducted among eight hospitals in their ophthalmology outpatient departments. Participants consisted of patients who had previously not received any IVB or IVR treatment between 2013 and 2014. The primary outcome measurement was the change in best-corrected visual acuity (BCVA) at the end of the follow-up period compared to baseline.ResultsThere were 1629 treatment-naïve patients for the pro re nata (PRN) treatment pattern and 226 treatment-naive patients for the three-injections (3Inj) treatment pattern. BCVA improvements were found in 35% of the PRN group and 47% of the 3Inj group; however, it was not clinically meaningful between the IVB and IVR groups (P-value = 0.568 for PRN, P-value = 0.103 for 3Inj). A multivariable logistic regression (using the propensity score) showed that positive factors associated with vision improvement for the PRN pattern were the number of drug injections, having retinal vein occlusion, and under 60 years of age, while good BCVA at baseline was a negative predictive factor. For the 3Inj pattern, under 60 years of age and baseline BCVA were statistically significant predictors. Nonetheless, diabetes mellitus (DM) without other comorbidities was a statistically significant predictor of low response to vision improvement compared to DM with other comorbidities.ConclusionsThis study was the first observational, prospective study to evaluate the real-life effectiveness of IVB and IVR in Thailand. The majority of participants who used IVB or IVR showed improvements in BCVA after treatment. Further evaluation such as long-term follow-ups and subsequent comparison of effectiveness between IVB and IVR should be investigated due to the limited sample of IVR patients.Trial registrationThai Clinical Trial Registry TCTR20141002001. Registered 02 October 2014 (retrospectively registered).

Comparison of intravitreal bevacizumab and ranibizumab used for myopic choroidal neovascularization: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

Background:To evaluate the effect of intravitreal bevacizumab (IVB) and ranibizumab (IVR) for the treatment of choroidal neovascularization (CNV) secondary to pathologic myopia (PM) by meta-analysis.Methods:Pertinent publications of randomized controlled trials (RCTs) were identified through systemic searches of PubMed, EMBASE, Web of science, Cochrane Library, clinicaltrials.gov, CNKI, CQVIP, and Wanfang database. All comparative studies of IVB or IVR as treatment for CNV secondary to pathologic myopia were included. Meta-analysis of these RCTs was performed using Review Manager 5.3 software. The χ2 test and I2 values were used to analyze heterogeneity. Measurements included best-corrected visual acuity (BCVA) and central foveal thickness (CFT).Results:A total of 3 randomized controlled clinical trials involving 158 eyes were included, 81 eyes in IVB group and 77 eyes in IVR group. Compared with baseline, at 1, 3, 6, and 12 months after IVB or IVR treatment, BCVA was significantly increased. Change of BCVA at 1, 3, 6, and 12 months did not vary significantly between IVB and IVR group (1 month: Z = 0.30, 95% CI = −0.08 to 0.11, P = .76; 3 months: Z = 0.36, 95% CI = −0.10 to 0.15, P = .72; 6 months: Z = 0.17, 95% CI = −0.10 to 0.12, P = .86; 12 months: Z = 0.64, 95% CI = −0.15 to 0.08, P = .52).Conclusion:Both IVR and IVB can significantly improve BCVA of eyes with mCNV, but there was no significant difference between the 2 therapies on the treatment of mCNV.

LEVELS OF HYPOXIA INDUCIBLE FACTOR-1α (HIF-1α) AND INTERCELLULAR ADHESION MOLECULE-1 (ICAM-1) AFTER INTRAVITREAL BEVACIZUMAB IN PROLIFERATIVE DIABETIC RETINOPATHY

Purpose: to assess the levels of Hypoxia-inducible factor-1α (HIF-1α) and intercellular adhesion molecule-1 (ICAM-1) in vitreous of proliferative diabetic retinopathy patients which were given intravitreal bevacizumab (IVB), as well as its relation to the central macular thickness (CMT) measured prior to vitrectomy.&#x0D; Methods: thirty-two eyes were randomized into two groups, one that received an IVB injection at 1-2 weeks previtrectomy and the control group which did not receive any injection. Measurement of HIF-1α and ICAM-1 was conducted using enzyme-linked immunosorbent assay (ELISA). The CMT were measured at the initial visit, prior to vitrectomy, and at follow up time (2, 4, and 12 weeks postoperatively) using Stratus OCT.&#x0D; Results: The mean levels of HIF-1α vitreous (ng/mg protein) in the control group and IVB respectively 0.020 (0.006; 0.077) and 0.029 (0.016; 0.21). Vitreous levels of ICAM-1 (ng /mL) in control group and IVB group were 20.10 (3.41; 40.16) and 23.33 (0.63; 68.5). The mean levels of HIF-1α and ICAM-1 vitreous obtained did not differ significantly between the two groups.&#x0D; Conclusion: The levels of HIF-1α and ICAM-1 in PDR patients do not decrease after one injection of intravitreal Bevacizumab 1-2 weeks prior to vitrectomy. The concentration of vitreous HIF-1α and ICAM-1 are not directly related to the CMT.

Early-scatter laser photocoagulation promotes the formation of collateral vessels in branch retinal vein occlusion.

To investigate the effect of early-scatter laser photocoagulation on the formation of collateral vessels in branch retinal vein occlusion. The medical records of 40 cases (40 patients) of branch retinal vein occlusion with macular edema were retrospectively reviewed. Of them, 23 patients were treated with intravitreal bevacizumab injection and 17 patients underwent intravitreal bevacizumab injection with additional laser treatment. Early-scatter laser photocoagulation was applied for capillary non-perfusion areas, regardless of retinal neovascularization. Collateral vessel presence, recurrence rate of macular edema, and number of intravitreal bevacizumab injections were compared between the groups. During the follow-up period, collateral vessel formation was noted in 10/23 eyes (43.5%) in the intravitreal bevacizumab injection group and 15/17 eyes (88.2%) in the laser combined treatment group (p = 0.004). The recurrence rate of macular edema was lower in the laser combined treatment group (29.4%) than in the intravitreal bevacizumab injection group (65.2%); this difference was statistically significant (p = 0.025). The average numbers of intravitreal bevacizumab injections were 3.57 ± 3.23 in the intravitreal bevacizumab group and 2.14 ± 2.26 in the laser combined treatment group (p = 0.044). Early-scatter laser photocoagulation promotes collateral vessel formation; the presence of collateral vessels seemed to affect the course of macular edema in branch retinal vein occlusion. Combined early-scatter laser photocoagulation treatment after intravitreal bevacizumab injection lowered the recurrence rate of macular edema and number of intravitreal bevacizumab injections in the cases of branch retinal vein occlusion.

Fluorescein Angiography in Retinopathy of Prematurity: Comparison of Infants Treated with Bevacizumab to Those with Spontaneous Regression

Medium- and long-term sequelae of intravitreal bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) are uncertain. Our aim was to describe the fluorescein angiography (FA) findings in patients who received IVB as primary treatment for type 1 ROP and compare them to findings in patients with ROP that spontaneously regressed. Retrospective cohort. Twenty-eight patients with a history of ROP who underwent fluorescein angiography between December 1, 2013, and July 31, 2018. Patients were divided into 2 groups based on whether they had received IVB or had ROP that spontaneously regressed. We reviewed the angiograms in the 2 groups for neovascularization (NV) and other abnormal vascular patterns in both the periphery and the posterior pole. Fluorescein angiography findings, including NV, peripheral, and macular vascular abnormalities. Forty eyes of 20 infants were included in the IVB group and 16 eyes of 8 infants in the untreated group. Median gestational age at birth was similar in the 2 groups (24.5 and 24.7 weeks, respectively; P= 0.44), as was the median birth weight (648.5 and 560.0 g, respectively; P= 0.26). Median postmenstrual age at the time of FA was 65.1 and 83.9 weeks, respectively (P= 0.0002). Review of angiograms demonstrated NV in 30.0% and 37.5% in the IVB and untreated cohorts, respectively (P= 0.75). Abnormal vascular patterns in the periphery were similar in both groups (100.0%), whereas posterior pole findings of vessels encroaching onto the fovea were more prevalent in the IVB cohort (65.0% vs. 25.0%; P= 0.009). Fluorescein angiography after bevacizumab for ROP reveals abnormal vascular patterns in all eyes and NV in approximately one-third. Similar abnormal vascular patterns on FA are seen at a similar prevalence after spontaneous regression of ROP. These findings suggest that the abnormal vascular patterns identified by FA in patients with ROP result from the disease process itself rather than as a result of exposure to anti-vascular endothelial growth factor medications.

The Effect of Panretinal Photocoagulation (PRP) versus Intravitreal Bevacizumab (IVB) Plus PRP on Peripapillary Retinal Nerve Fiber Layer (RNFL) Thickness Analyzed by Optical Coherence Tomography in Patients with Proliferative Diabetic Retinopathy.

Purpose:The current study aimed to evaluate changes in peripapillary retinal nerve fiber layer (RNFL) thickness in diabetic patients with bilateral proliferative diabetic retinopathy (PDR) after receiving panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB) with PRP.Methods:Ocular examination and peripapillary optical coherent tomography (OCT) were performed for each patient at baseline, 1, 3, 6, and 10 months after treatment. Both eyes of each patient were randomized into either PRP or PRP + IVB group.Results:Sixty-four eyes (32 patients) were enrolled in this randomized clinical trial. In the PRP group, global RNFL thickness initially increased and reached statistical significance in the third month (from 105.9 ± 21.4μm at baseline to 119 ± 41.6μm at 3 months, P = 0.03). Subsequent decline was observed with no significant difference from baseline at 10 months (106 ± 19.3μm, P = 0.914). There were no statistically significant changes in the PRP + IVB group (from 101.7 ± 22.2μm at baseline to 109.3 ± 26.9μm at 3 months, P = 0.996 and 101.9 ± 16.5μm at 10 months, P = 0.999). In the latter group, slight increase in RNFL thickness was observed in the first month (107.7 ± 21.1μm). RNFL thickness was similar to baseline in the two groups at month 10, with the exception of significant increase in superior-temporal sector in the PRP group (145.3 ± 13.4μm vs. 127.2 ± 17.3μm, P = 0.045).Conclusion:Compared to eyes treated with PRP, eyes treated with adjunctive IVB showed less significant post-treatment changes in RNFL thickness.

Effects of subthreshold diode micropulse laser photocoagulation on treating patients with refractory diabetic macular edema

PurposeTo evaluate the effects of subthreshold diode micropulse laser photocoagulation on treating patients with refractory diabetic macular edema (DME). MethodsThis randomized clinical trial recruited patients with DME in both eyes that were resistant to treatment with intravitreal bevacizumab (IVB). The eyes were randomly divided into two groups who received laser therapy and IVB, or IVB alone. Subthreshold diode micropulse laser photocoagulation and IVB injection were administered in one eye, and an IVB injection was administered in the second eye. IVB injections were repeated in both eyes within one month and two months after the first injection. Best corrected visual acuity (BCVA) logarithm of the minimum angle of resolution (logMAR) and central macular thickness (CMT) were measured before, within a month, and three months after start of intervention. ResultsIn this study, 42 eyes of 21 patients were evaluated. The mean age of patients was 60.86 ± 8.57 years. Ten patients (47.6%) were male. Within-group analysis showed a significant decreased in BCVA logMAR in the laser + IVB group reflecting improvement in visual acuity (VA) (P < 0.001); it increased in the control group during study reflecting more vision loss (P = 0.01). In the laser + IVB group, a significant decrease in mean ± standard deviation (SD) CMT at 3 months compared to baseline was observed (baseline: 513 ± 126.29 vs. three months: 408.1 ± 95.28; P < 0.001). The mean ± SD CMT was significantly lower in the laser + IVB group of eyes than in the control group three months after intervention (P = 0.02). ConclusionUsing subthreshold diode micropulse laser photocoagulation in combination with IVB can significantly reduce CMT and improve BCVA in patients with refractory DME.

Intravitreal injection of a Rho-kinase inhibitor (fasudil) combined with bevacizumab versus bevacizumab monotherapy for diabetic macular oedema: a pilot randomised clinical trial

Click here to listen to the PodcastBackground/aimsTo compare the efficacy of combined intravitreal injection of bevacizumab and a Rho-kinase inhibitor, fasudil (intravitreal bevacizumab (IVB)/intravitreal fasudil (IVF)), with IVB alone for...

Sustained and targeted episcleral delivery of celecoxib in a rabbit model of retinal and choroidal neovascularization

BackgroundTo evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).MethodsNine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group). The bFGF was mixed with matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal bevacizumab groups were treated within 03 days from matrigel injection. Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days, 2, 4 and 8 weeks after matrigel injection. Persistence or regression of three clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and retinal fibrotic spots) was independently evaluated in each study group at all follow-up periods. Statistical analysis using Fisher’s exact test was performed to compare the frequency of findings at each time point between treated groups and control.ResultsIn all study eyes, matrigel induced the appearance of subretinal blebs and the development of retinal and subretinal neovascularization characterized by progressive and late hyperfluorescence on FA. Persistence of subretinal hyperfluorescence was higher in non-treated (control) animals compared to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of ERG recordings did not reveal statistically significant differences between the study groups. Control animals retained in average 40% (± 7%) of the pre-treatment recorded b-wave amplitude, compared to 53% (± 29%) after bevacizumab and 53% (± 17%) after celecoxib treatment.ConclusionIn this rabbit model of retinal and subretinal neovascularization, episcleral celecoxib delivery was demonstrated to significantly inhibit neovascularization. It was also noticed, although not statistically significant, an apparent effect of episcleral celecoxib on preventing tractional retinal detachment secondary to epiretinal fibrovascular proliferation. The transscleral delivery of celecoxib combined with sustained-release strategy may have impact in the treatment of retinal and choroidal proliferative diseases.

Real-World Safety of Intravitreal Bevacizumab and Ranibizumab Treatments for Retinal Diseases in Thailand: A Prospective Observational Study.

BackgroundThere is very limited evidence examining serious systemic adverse events (SSAEs) and post-injection endophthalmitis of intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) treatments in Thailand and low- and middle-income countries. Moreover, findings from the existing trials might have limited generalizability to certain populations and rare SSAEs.ObjectivesThis prospective observational study aimed to assess and compare the safety profiles of IVB and IVR in patients with retinal diseases in Thailand.MethodsBetween 2013 and 2015, 6354 patients eligible for IVB or IVR were recruited from eight hospitals. Main outcomes measures were prevalence and risk of SSAEs, mortality, and endophthalmitis during the 6-month follow-up period.ResultsIn the IVB and IVR groups, 94 and 6% of patients participated, respectively. The rates of outcomes in the IVB group were slightly greater than in the IVR group. All-cause mortality rates in the IVB and IVR groups were 1.10 and 0.53%, respectively. Prevalence rates of endophthalmitis and non-fatal strokes in the IVB group were 0.04% of 16,421 injections and 0.27% of 5975 patients, respectively, whereas none of these events were identified in the IVR group. There were no differences between the two groups in the risks of mortality, arteriothrombotic events (ATE), and non-fatal heart failure (HF). Adjustment for potential confounding factors and selection bias using multivariable models for time-to-event outcomes and propensity scores did not alter the results.ConclusionsThe rates of SAEs in both groups were low. The IVB and IVR treatments were not associated with significant risks of mortality, ATE, and non-fatal HF.Trial RegistrationThai Clinical Trial Registry identifier TCTR20141002001.Electronic supplementary materialThe online version of this article (10.1007/s40261-018-0678-5) contains supplementary material, which is available to authorized users.

Findings in Persistent Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVE:To determine whether retinopathy of prematurity (ROP) that persists beyond a postmenstrual age (PMA) of 45 weeks has abnormalities that can be documented by fundus photography or fluorescein angiography (FA).PATIENTS AND METHODS:Fundus photographs and FAs were reviewed for all premature infants who underwent FA for persistent ROP after 45 weeks PMA.RESULTS:Of the 487 infants who were screened for ROP, 16 (3.3%) demonstrated ROP beyond 45 weeks. Seven (43.8%) infants received prior treatment with intravitreal bevacizumab (IVB) for Type 1 ROP. FAs were obtained in eight cases; four subjects were previously treated with IVB. Leakage at the vascular-avascular border was demonstrated in seven subjects (87.5%). Shunt vessels, posterior retinal nonperfusion, and absence of the foveal avascular zone was limited to the IVB group.CONCLUSIONS:There are persistent vascular abnormalities among infants with ROP beyond 45 weeks. Findings that may be missed by RetCam fundus photographs were highlighted with FA.

Comparison of Bevacizumab and Ranibizumab in the Treatment of Type 1 Retinopathy of Prematurity Affecting Zone 1

Purpose: To investigate the effects of bevacizumab and ranibizumab in the treatment of type 1 retinopathy of prematurity (ROP) affecting zone 1. Methods: Files of the patients who received intravitreal bevacizumab (IVB) or ranibizumab (IVR) treatment for ROP affecting zone 1 were evaluated retrospectively. Spherical equivalent (SE) and axial length (AXL) measurements were performed at 1 year of adjusted age. Results: Sixty-eight eyes of 37 patients were included in the study. All patients had initial disease regression but 6 patients (4 in the IVB, 2 in the IVR group) showed reactivation (p = 0.679). The number of eyes with incomplete vascularization were 15 and 12 in the IVB and IVR groups, respectively (p = 0.725). Mean AXL was 20.50 ± 0.99 mm in the IVB group and 19.30 ± 0.48 mm in the IVR group (p < 0.001). Mean SE was –1.49 ± 2.38 dpt in the IVB group and 0.98 ± 2.18 dpt in the IVR group (p < 0.001). Conclusion: Bevacizumab and ranibizumab showed similar effectiveness in the treatment of type 1 ROP affecting zone 1. The AXL was longer and SE was more myopic in eyes treated with IVB. This difference might be caused by the longer intravitreal half-life of bevacizumab than ranibizumab.