Intravitreal Injections In Patients Research Articles

Incidence of elevated intraocular pressure after intravitreal injection in Japanese patients with age-related macular degeneration

The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.

PHARMACOKINETIC STUDY OF INTRAVITREAL AFLIBERCEPT IN HUMANS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To investigate the half-life of aflibercept in aqueous humor after a single intravitreal injection in patients with neovascular age-related macular degeneration. Prospective, noncomparative, interventional case series of five eyes with neovascular age-related macular degeneration naive to anti-vascular endothelial growth factor therapy were enrolled and treated with intravitreal aflibercept. At baseline, best-corrected visual acuity, optical coherence tomography imaging, and aqueous humor (treatment eye) and blood/plasma samples were taken. Patients underwent best-corrected visual acuity, optical coherence tomography imaging, and sampling of aqueous humor from the eye and blood/plasma at six additional post-treatment time points of 4 hours and Days 1, 3, 7, 14, and 28. Concentrations of aflibercept were quantified using an enzyme-linked immunosorbent assay. Median peak concentration (Cmax) of free aflibercept in the aqueous was 122 mg/L. The median half-life of free aflibercept was 11 days in the eye. In plasma, the concentrations of free aflibercept were low and transient, reaching undetectable levels during the first week after injection, and undetectable in all patients at time points beyond 7 days. The pharmacokinetic profile in the aqueous humor described here together with the previously reported affinity of aflibercept for vascular endothelial growth factor is consistent with and adds to our understanding for the duration of its clinical efficacy.

Effect of Topical Antibiotic Prophylaxis on Conjunctival Flora and Antibiotic Resistance Following Intravitreal Injections in Patients with Type 2 Diabetes.

PurposeWe sought to determine changes in the conjunctival bacterial flora and antibiotic resistance after topical antibiotic drops for infection prophylaxis were administered following intravitreal injections in patients with type 2 diabetes.MethodsThis prospective and nonrandomized cohort study included 116 eyes of 116 treatment-naive patients with type 2 diabetes who received six serial intravitreal anti-vascular endothelial growth factor injections for macular edema. Three conjunctival cultures were obtained from each eye over the course of the study (Culture 1, baseline; Culture 2, 1 month after the third injection; and Culture 3, 1 month after the sixth injection). The study subjects were given topical moxifloxacin hydrochloride for 4 days after each monthly intravitreal injection. The growth patterns of conjunctival bacterial flora and the antibiotic resistance to several commonly used antibiotics were examined.ResultsThe rate of culture positivity increased significantly during the observation period (Culture 1, n = 47, 40.5%; Culture 2, n = 58, 50%; Culture 3, n = 76, 65.5%, p < 0.001). The bacterium with the highest baseline culture positivity was Staphylococcus epidermidis (n = 45, 38.8%), which increased significantly during the observation period (p < 0.001). No significant increase was noted in the culture positivity of the other bacteria with baseline culture positivity (p > 0.05). Regarding antibiotic susceptibility, significant increases in resistance to the fluoroquinolone group of drugs were noted (p < 0.001). No significant changes in sensitivity were detected in the other 11 investigated antibiotics that are commonly used in clinical practice (p > 0.05).ConclusionsThe use of topical moxifloxacin after each intravitreal injection significantly increases the fluoroquinolone resistance of the ocular surface flora and the culture-positivity rate of S. epidermidis in patients with type 2 diabetes.

Real-World Results of Switching Treatment from Ranibizumab to Aflibercept in Macular Oedema Secondary to Branch Retinal Vein Occlusion.

IntroductionTo investigate treatment outcomes after switching from ranibizumab to aflibercept intravitreal injections in patients with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO).MethodsEligible patients with refractory MO secondary to BRVO, post treatment with a minimum of three intravitreal injections of ranibizumab at 4-weekly intervals were recruited. Suboptimal or non-responders were defined as patients who had persistent intraretinal fluid (< 75% decrease from baseline) despite a minimum of three consecutive injections. These patients were switched to aflibercept injections on an as-needed basis. The primary study outcomes assessed trends in best-corrected distance visual acuity (BCVA) and central retinal thickness (CRT). To compare means of BCVA and CRT, a paired t test two-tailed with a level of significance set at 0.05 was used. Pearson correlation coefficient was also applied to demonstrate correlation. Participants were followed up for a period of 24 weeks after switching.ResultsThirty-eight eyes of 38 patients were included in the study. Patients had an average of 8.37 ranibizumab intravitreal injections over a mean period of 12 months presenting suboptimal or no response. A significant decrease of mean CRT from 388.63 ± 93.4 μm to 290.29 ± 93.5 μm (p < 0.001) and an improvement in mean BCVA from logMAR 0.66 ± 0.38 to logMAR 0.57 ± 0.27 (p = 0.025) was achieved after an average of 2.27 aflibercept injections.ConclusionsGiven the spectrum of therapies available to date for the management of MO secondary to BRVO, aflibercept appears to be an effective treatment option in cases refractory to ranibizumab. This study based on a small cohort of patients indicates that satisfactory results on retinal anatomy and visual outcomes can be accomplished with a smaller number of injections. Larger-scale studies are needed to extrapolate these promising results.

Corrigendum to “Two-Year Outcome of Aflibercept in Patients with Pigment Epithelial Detachment due to Neovascular Age-Related Macular Degeneration (nAMD) Refractory to Ranibizumab”

[This corrects the article DOI: 10.1155/2017/8984313.].

Early changes in macular optical coherence tomography parameters after Ranibizumab intravitreal injection in patients with exsudative age-related macular degeneration

BackgroundEvaluation of the impact of different macular optical coherence parameters on visual acuity as early as 1 day after injection of ranibizumab in patients with subfoveal exsudative age-related macular degeneration.MethodsThis was an interventional, non randomized, open label prospective study, where we evaluated 20 eyes of 20 patients affected by exudative age-related macular degeneration. These patients were treated with injections of ranibizumab between February 2013 and January 2015. The primary endpoint of this study was to evaluate the early changes in optical coherence tomography parameters (retinal thickness, central and total retinal volume) and impact on best-corrected visual acuity (BCVA) obtained by logarithm of minimum resolution using ETDRS protocol in patients treated with a single dose intravitreal injection of ranibizumab (0.5 mg/0.05 mL) during the first month of follow. The patients were evaluated on the first day, them at 7 and 30 days after the treatment. The National Eye Institute Visual Functioning Questionnaire was applied during the study period to assess early perception of ranibizumab injection effectiveness. The adverse events were monitored throughout the study.ResultsCentral retinal thickness values at 1 (464.0 ± 97.8 µm), 7 (379.9 ± 107.8 µm) and 30 days (365.5 ± 95.1 µm) after ranibizumab injection showed a statically significant reduction when compared with baseline results (P = 0.01, P = 0.001, P = 0.001, respectively). Similar alterations were observed in central and total retinal volume, which were detected early on the first day of evaluation, after the measurement at baseline (central: 0.36 ± 0.07 vs. 0.40 ± 0.10 mm3, P = 0.01; total: 9.62 ± 1.10 vs. 9.99 ± 2.56 mm3, P = 0.002) and remained steady at 7 (P = 0.001, P = 0.002, respectively) and 30 days (P = 0.001, P = 0.004, respectively) with slight variations without losing their gains in these parameters. The best-corrected logarithm of minimum angle of resolution (logMAR) showed a statistically significant difference when compared to the baseline. (0.81 ± 0.16 vs. 0.67 ± 0.24, P = 0.005). The NEI-VFQ-25 questionnaire demonstrate statically significant results after treatment. When patients were asked about the subjective improvement in visual quality, over 80% reported early improvement. Throughout the period of follow-up visits, no serious adverse events were reported.ConclusionIntravitreal injection of ranibizumab can produce early changes in optical coherence tomography parameters and an improvement in perceived visual quality of patients with subfoveal exsudative age-related macular degeneration.

Long – Term Intraocular Pressure Changes after Intravitreal Injections

Abstract Introduction. Direct drug delivery by intravitreal injection is an essential tool in the treatment of retinal diseases and the studies have demonstrated that patients undergoing treatment with intravitreal anti-VEGF agents may experience sustained and delayed elevation of intraocular pressure. According to literature, the incidence of sustained elevation of intraocular pressure varied from 3.45% - 11.6%. Aim of the Study.To research the changes of intraocular pressure after intravitreal injections in patients with a diagnosis of agerelated macular degeneration, diabetic maculopathy, and retinal vein occlusions. Material and Methods. A prospective study was done in Pauls Stradins Clinical University Hospital, Riga, Latvia from November 2015 - January 2016. In this study were interviewed and examined 31 patients who had had intravitreal injections. For data analysis, SPSS 23 was used. Results. From 31 patient there were 20 (65.5%) females and 11 (35.5%) males. They were divided into three groups depending on the diagnosis. There were 26 (83.9%) patients with age-related macular degeneration, 3 (9.7%) with diabetic retinopathy and 2 (6.5%) with retinal vein thrombosis. From 31 patient the IOP after intravitreal injections were increased in 21 (67.7%) patient - 13 (41.9%) in the right eye and 10 (32.2%) in the left eye. In both eyes the pressure was increased from 14 to 17 mmHg (14.08 to 17.08 mmHg in the right eye and 14.1 to 17.3 in the left eye). From 6 (19.3%) patients who had glaucoma before intravitreal injections, in 4 (66%) intraocular pressure had increased from 14.7 to 18.5 mmHg in the right eye and from 12.5 to 17 mmHg in the left eye. Conclusions. Patients with previously diagnosed glaucoma had a greater rise in intraocular pressure compared to patients with no glaucoma diagnosis. Further studies with a greater number of patients and identical intraocular pressure measuring method before and after injections are needed to better evaluate the effects of intravitreal injections on intraocular pressure.

Paracentesis following intravitreal drug injections in maintaining physiologic ocular perfusion pressure.

A retrospective analysis was performed of patients who received a paracentesis immediately following an intravitreal injection of bevacizumab or triamcinolone acetonide. These patients were previously diagnosed as having glaucoma, ocular hypertension, or had responded previously with sustained elevated intraocular pressure. Of 1661 procedures were performed. Totally 219 (13%) of the injections were on phakic patients. A median (SD) of 210 µL (40 µL) of aqueous was removed during each paracentesis. There were no reported incidences of any complications. We propose performing a paracentesis immediately following intravitreal injections for patients at risk for ocular hypertension, glaucoma, and retinal vein or artery occlusion.

Outcomes of switching treatment to aflibercept in patients with macular oedema secondary to central retinal vein occlusion refractory to ranibizumab.

To assess the treatment outcome of switching from ranibizumab to aflibercept intravitreal injections in patients with macular oedema secondary to central retinal vein occlusion (CRVO). A prospective interventional study was conducted in a tertiary retina service in Leicester Royal Infirmary, UK, where patients with CRVO and associated macular oedema were recruited. First-line treatment involved three monthly ranibizumab injections. Non-responders were defined as patients who despite a minimum of three consecutive injections had persistent intraretinal fluid one month after the last injection. In these cases, a treatment change to aflibercept injections on a per-needed basis was decided. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and after switching of treatment. Follow-up period lasted for a minimum of 24weeks after switching. Twenty-nine eyes of 29 patients with refractory macular oedema secondary to CRVO were included. All eyes had an average of 4.5 ranibizumab intravitreal injections in a mean period of 6months without reduction in intraretinal fluid and/or no visual acuity gain. A significant decrease in mean CRT from 633.67±242.42 to 234.62±78.28μm and improvement in mean BCVA from 1.34±0.66 log MAR to 0.91±0.73 log MAR were noticed after switching treatment to aflibercept. The average number of aflibercept injections needed for oedema resolution was 2.19. Aflibercept is an effective alternative treatment for macular oedema secondary to CRVO refractory to ranibizumab. Good anatomical and functional result can be achieved with few injections. The maintenance of these results after 6months is yet to be investigated.

SYSTEMIC BETA-BLOCKERS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To evaluate whether oral beta-blockers (BBs) are associated with a decreased number of intravitreal injections in patients with incident neovascular age-related macular degeneration. A retrospective cohort study of subjects with a new diagnosis of neovascular age-related macular degeneration was conducted using a medical claims database from a large national US insurer. Two cohorts were created for comparison consisting of patients with regular use of BBs or calcium channel blockers. The main outcome measured was the difference in the mean number of intravitreal injections administered between the two cohorts. After inclusion and exclusion criteria, 239 BB and 155 calcium channel blocker subjects remained for analysis. Univariate analysis revealed that the mean number of injections in the BB cohort was 6.43 (95% confidence interval [CI] 5.90-6.95) versus 6.55 (95% CI 5.85-7.25) in the calcium channel blocker cohort (P = 0.78). After multivariate adjustment, the mean number of injections in the BB group was 6.32 (95% CI 5.77-6.87) versus 6.71 (95% CI 6.02-7.40) in the calcium channel blocker group. The overall difference between the 2 groups was -0.39 (95% CI difference -1.29 to 0.51; P = 0.40). The use of oral BBs is not associated with a decreased number of intravitreal injections in incident neovascular age-related macular degeneration patients.

Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections.

PurposeThe aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy.MethodsThis study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders.ResultsTwelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation.ConclusionIn patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA.

Two-Year Outcome of Aflibercept in Patients with Pigment Epithelial Detachment due to Neovascular Age-Related Macular Degeneration (nAMD) Refractory to Ranibizumab.

Purpose To evaluate the response of intravitreal aflibercept injection (IAI) in eyes with detachment of retinal pigment epithelium (DEP) secondary to nAMD refractory to monthly ranibizumab. Patients and Methods This is a retrospective, multicenter study. All patients received 3 IAI then treated as needed every 4 weeks for 12 months. During the second year, the eyes were treated with a treat- and-extend regimen. Results Forty-four eyes were included. Best-corrected visual acuity improved significantly after the loading phase (3.1 ± 6.4 letters) and at 6 months (2.8 ± 6.4 letters), but change was not significant at 1 year and 2 years. The height of the DEP was significantly decreased at 3 months and 6 months, but the difference did not reach statistical difference at 1 and 2 years. Rate of eyes with complete resolution of exudation was 59% after the loading phase and 34.3% at 2 years. Mean interval of anti-VEGF injection was extended from 31 ± 2.6 days to 61 ± 5 days after conversion. Conclusions Aflibercept intravitreal injection in patients with fibrovascular DEP due to nAMD who respond poorly to monthly ranibizumab led to short-term functional and anatomical improvement. Reduction of intravitreal injection frequency was obtained until 2 years of follow-up.

Treatment outcome of switching from ranibizumab to aflibercept in patients with central retinal vein occlusion

PurposeTo describe the outcome of switching from ranibizumab to aflibercept intravitreal injections in patients with macular oedema secondary to central retinal vein occlusion (CRVO).MethodsA prospective observational study was conducted in a tertiary retina service in East Midlands, UK. Twenty one patients with CRVO and associated macular oedema were reviewed. All patients had a detailed systemic and ocular history obtained and a thorough ocular examination including visual acuity assessment, intraocular pressure measurement and dilated fundus examination. Best‐corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at the initial and all following visits. Non‐responders were defined as patients who despite a minimum of 3 consecutive ranibizumab injections at 4–6 weeks intervals had persistent intraretinal fluid 1 month after the last injection. These patients were switched to aflibercept. BCVA and CRT were measured before and after switching.ResultsTwenty‐two eyes of 21 patients with refractory macular oedema secondary to CRVO were included. All eyes had a mean 4.5 ranibizumab intravitreal injections after a mean period of 6 months without reduction of intraretinal fluid and/or no visual acuity gain. In these cases, a treatment change to aflibercept injections on a per‐needed basis was decided. A significant decrease of mean CRT from 631 to 285 μm and improvement in mean BCVA from 1.3 logMAR to 1.0 logMAR was noticed. The mean number of aflibercept injections needed for oedema resolution was 2.ConclusionsAflibercept is an efficient alternative treatment for macular oedema secondary to CRVO refractory to ranibizumab. Good anatomic and functional result can be achieved with few injections. The maintenance of these results after 6 months is yet to be investigated.

Long-term effect of anti-vascular endothelial growth factor injections on intraocular pressure.

Objective:There is a substantial debate in the ophthalmology community about whether anti-vascular endothelial growth factor (VEGF) injections result in a long-term increase in intraocular pressure (IOP).Design:We performed a retrospective study to investigate how the number and timing of intravitreal injections in patients with age-related macular degeneration (AMD) and diabetic macular edema (DME) affect IOP over time.Methods:We collected long-term IOP data on patients receiving anti-VEGF injections at our institution. Patients over the age of 40 years who received injections for AMD (n = 76) or DME (n = 55) were included. Patients were grouped according to indication as well as number of injections received (1–3, 4–6, 7–9, or 10+ injections). IOP measurements were then placed into time points (0–6, 6–12, 12–18, 18–24, or 24+ months) and compared to the preinjection average IOP.Results:For patients with DME, average preinjection IOP was 15.7 mmHg. At 24+ months after injection, the average IOP was 15.2 (P = 0.68) for patients receiving 1–3 injections, 16.8 (P = 0.23) for 4–6 injections, and 14.4 (P = 0.66) for 7–9 injections. For patients with AMD, average initial IOP was 15.6 mmHg. At 24+ months after injection, the average IOP was 12.6 (P = 0.97) for 1–3 injections, 14.9 (P = 0.96) for 4–6 injections, 14.8 (P = 0.84) for 7–9 injections, and 15.7 (P = 0.56) for 10+ injections.Conclusions:There was no increase in IOP over time for AMD or DME patients, regardless of how many injections they received. For patients receiving unilateral injections, there was no increase in IOP in the injected eye when compared to the noninjected eye.

Safety of Intravitreal Ocriplasmin for Focal Vitreomacular Adhesion in Patients with Exudative Age-Related Macular Degeneration

The evaluation of the safety and preliminary efficacy of 125 μg ocriplasmin intravitreal injection in patients with focal vitreomacular adhesion (VMA) and exudative age-related macular degeneration (AMD). Randomized, sham-injection controlled, double-masked, multicenter, phase II trial. A total of 100 patients with VMA and wet AMD were randomized 3:1 to receive 125 μg ocriplasmin intravitreal injection or sham injection. Study treatment was administered in the mid-vitreous cavity by injection. Post-treatment safety and efficacy assessments were made at baseline and on days 7, 14, and 28 and months 3, 6, and 12 after injection. Secondary efficacy end points were exploratory in nature. The safety and tolerability of ocriplasmin were evaluated. The primary efficacy end point was the proportion of patients with VMA release at day 28 after injection. Secondary end points reported included VMA release over time, total posterior vitreous detachment (PVD), change in visual acuity from baseline, and number of anti-vascular endothelial growth factor (VEGF) injections. The safety of ocriplasmin in patients with VMA and wet AMD was shown to be comparable to the known safety profile, with the majority of adverse events in the study eye occurring in the first 7 days after study treatment. A greater proportion of patients achieved VMA resolution and total PVD at month 12 with ocriplasmin compared with sham treatment. There was a decrease in the number of anti-VEGF injections with ocriplasmin at month 12 compared with the sham group, although no differences in visual acuity were observed. Ocriplasmin treatment in this population seems to be generally safe and well tolerated and resulted in more patients achieving VMA resolution and PVD with less anti-VEGF use compared with sham treatment.

Intraocular pressure changes after repeated intravitreal antivascular endothelial growth factor injections in patients with neovascular age-related macular degeneration with or without glaucoma

PurposeTo investigate the long-term effects of multiple intravitreal injections on intraocular pressure (IOP) in patients with exudative age-related macular degeneration, and to determine whether this is related to a pre-existing diagnosis of glaucoma. MethodsA retrospective study was carried out on 209 eyes in 173 patients with neovascular age-related macular degeneration who received at least three intravitreal injections of bevacizumab or ranibizumab, or both, from January 2006 to December 2012 at Shin Kong Wu Ho-Su Memorial Hospital. Sequential changes in IOP following the intravitreal injections were documented and the incidence and characteristics of the patients diagnosed with glaucoma were recorded and analyzed. ResultsTwo hundred and nine eyes in 173 patients were included in this study. The mean number of injections was 10.1 (range 3–23). No significant change was found in IOP (p = 0.41, paired t test) and none of the patients experienced delayed ocular hypertension during the treatment course. No correlation was found between differences in IOP and the number of injections (correlation coefficient −0.086) and no significant change in IOP was found in patients with or without glaucoma (p = 0.42 and 0.37, respectively, paired t test). In addition, the use of drugs to lower IOP did not increase with repeated intravitreal injections in patients with glaucoma [single drug, 24 (63.2%) patients; two drugs 14 (36.8%) patients]. ConclusionRepeated intravitreal antivascular endothelial growth factor injections of bevacizumab or ranibizumab, or both, did not increase the risk of increasing IOP in patients with exudative age-related macular degeneration, with or without glaucoma.

Fixation stability measurements in patients with neovascular age-related macular degeneration treated with ranibizumab

ObjectiveTo evaluate which of 2 measuring units (bivariate contour ellipse area [BCEA] vs Fujii) yields more accurate measurements of fixation stability, obtained using the MP-1 device, in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab, during a 12-month follow-up period. DesignSmall retrospective, noncomparative, interventional case series. ParticipantsA total of 25 eyes in 25 patients (13 males, 12 females; mean age 71.72 ± 7.98 years). MethodsAll participants were older than 50 years, diagnosed with active subfoveal choroidal neovascularization, had best corrected visual acuity (BCVA) values above 20/100, and all lesion types were included. All patients underwent a loading phase with 3 consecutive intravitreal injections of 0.05 mg ranibizumab at monthly intervals. Patients were retreated after the third injection if they exhibited a 100-μm increase in macular thickness or evidence of intraretinal and/or subretinal fluid and new subretinal hemorrhage, observed with spectral-domain optical coherence tomography and fluorescein angiography. The data collected included BCVA and mean macular sensitivities, BCEA, and fixation patterns, performed at baseline and at months 4 and 12, using the MP-1 device. ResultsThe mean total injection number was 5.92 ± 1.18 (minimum 3, maximum 8). Mean BCVA at baseline was 0.55 ± 0.28 logMAR and increased significantly to 0.50 ± 0.33 logMAR. Mean macular sensitivity at baseline was 7.06 ± 4.59 dB and increased significantly to 8.40 ± 4.82. Mean BCEA was 2.19 ± 1.38 deg2 and decreased significantly to 1.68 ± 1.43 deg2. Fixation stability patterns, according to the protocol set out by Fujii, did not change significantly during follow-up. ConclusionsCompared with Fujii fixation stability patterns, BCEA correlated better with variations in macular sensitivity and BCVA. BCEA can be added to the traditional parameters used to evaluate the efficacy of intravitreal injections in patients with nAMD.

Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study

BackgroundThe purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.ResultsAt month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug.ConclusionLocal administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.

Vascular endothelial growth factor plasma levels before and after treatment of neovascular age‐related macular degeneration with bevacizumab or ranibizumab

To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age-related macular degeneration (AMD). Forty-three patients with exudative AMD and 19 age- and sex-matched control patients without chorioretinal diseases were studied. Nineteen patients were treated with intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood samples were collected just before the first injection, and 28 days after three initial consecutive injections performed in 4-weekly intervals (loading dose). Concentration of VEGF in the plasma was measured by ELISA. At baseline, the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma concentrations in patients with wet AMD were comparable to controls (p = 0.225). Twenty-eight days after the third injection, a significant reduction of 42% in the median VEGF plasma levels was found in bevacizumab-treated patients (109.97 pg/ml; p = 0.0002) but not in ranibizumab-treated patients (189.97 pg/ml; p = 0.198) where a reduction of 0.7% in the median value was found. Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days after intravitreal injection in patients with exudative AMD. Ranibizumab did not achieve a significant plasma VEGF reduction at the same time-point. These findings alert to the potential systemic safety differences between the two drugs after intravitreal administration.

Systemic Adverse Drug Reactions Secondary to Anti-VEGF Intravitreal Injection in Patients with Neovascular Age-Related Macular Degeneration

The wet form of age related macular degeneration (AMD), known also as exudative or neovascular, is characterized by the formation of a pathological choroidal neovascular membrane (CNV) responsible for most cases of severe blindness. Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein acting as a growth factor selective for endothelial cells; it regulates angiogenesis and enhances vascular permeability and plays a leading role in this disorder. The consistent association between CNV and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular AMD. The importance of VEGF for the development of AMD-related CNV has led to the development of a strategy able to block its pathologic effects. The rationale is that a blockade of VEGF actions could be effective in arresting choroidal angiogenesis and also reducing the vascular permeability, which is frequently the main cause of visual acuity deterioration. However, VEGF has also important functions in vascular physiology. The effects of anti-VEGF therapy may inhibit these functions. Herein we report the systemic adverse events secondary to intravitreal administration of these compounds i.e. the main cardiovascular effects (thrombosis, hemorrhage, hypertension, proteinuria), as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thrombophlebitis.