Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa

AimsTo report the safety and efficacy of intravitreal aflibercept (Eylea) (ivA) for retinitis pigmentosa-associated cystoid macular oedema (RP-CMO) at 12 months via mean central macular thickness (CMT) and reported adverse events.MethodsA prospective, exploratory, phase II, non-randomised, single-centre, open-label, 1-arm clinical trial involving 30 eyes of 30 patients. Serial ivA was given via loading dose (three injections) followed by treat and extend protocol over 12 months.ResultsTwenty-nine out of 30 (96.7%) patients completed 12 months of follow-up. A total of four to 11 injections per patient were given over the 12 month study. No statistically significant reduction of CMT or visual acuity (VA) improvement was demonstrated in the group overall. Eleven out of 29 (37.9%) participants were considered as ‘responders’, demonstrating at least an 11% reduction of CMT at 12 months on spectral domain optical coherence tomography compared with baseline. A reduction of CMT by mean (SD) 28.1% (12.9 %) was observed in responders at 12 months, however, no statistically significant corresponding improvement in best corrected VA was seen. Baseline characteristics were similar between responder and non-responder groups. No clinically significant adverse events were deemed secondary to ivA.ConclusionThis first prospective exploratory study demonstrates both the safety and acceptability of serial ivA in patients with RP-CMO, effective at reducing CMT in 37.9% of patients. All patients demonstrating anatomical response did so after their first injection. Longer duration of CMO did not negatively affect response to anti-VEGF. Further study in a larger cohort of patients with shorter CMO duration would be valuable to better establish the utility of VEGF blockade in RP-CMO.Trial registration numbersEudraCT (2015-003723-65); ClinicalTrials.gov (NCT02661711).

Download Full-text

Treatment of Retinitis Pigmentosa-Associated Cystoid Macular Oedema Using Intravitreal Aflibercept (Eylea) despite Minimal Response to Ranibizumab (Lucentis): A Case Report

Case Reports in Ophthalmology ◽

10.1159/000448427 ◽

2016 ◽

Vol 7 (2) ◽

pp. 389-397 ◽

Cited By ~ 4

Author(s):

Stacey A. Strong ◽

Avinash Gurbaxani ◽

Michel Michaelides

Keyword(s):

Case Report ◽

Retinitis Pigmentosa ◽

Macular Oedema ◽

Macular Thickness ◽

Cystoid Macular Oedema ◽

Inadequate Response ◽

Central Macular Thickness ◽

Intravitreal Ranibizumab ◽

Intravitreal Aflibercept ◽

Minimal Reduction

Background: We present an interesting case of bilateral retinitis pigmentosa (RP)-associated cystoid macular oedema that responded on two separate occasions to intravitreal injections of aflibercept, despite previously demonstrating only minimal response to intravitreal ranibizumab. This unique case would support a trial of intravitreal aflibercept for the treatment of RP-associated cystoid macular oedema. Case Presentation: A 38-year-old man from Dubai, United Arab Emirates, presented to the UK with a 3-year history of bilateral RP-associated cystoid macular oedema. Previous treatment with topical dorzolamide, oral acetazolamide, and intravitreal ranibizumab had demonstrated only minimal reduction of cystoid macular oedema. Following re-confirmation of the diagnosis by clinical examination and optical coherence tomography imaging, bilateral loading doses of intravitreal aflibercept were given. Central macular thickness reduced and the patient returned to Dubai. After 6 months, the patient was treated with intravitreal ranibizumab due to re-accumulation of fluid and the unavailability of aflibercept in Dubai. Only minimal reduction of central macular thickness was observed. Once available in Dubai, intravitreal aflibercept was administered bilaterally with further reduction of central macular thickness observed. Visual acuity remained stable throughout. Conclusions: This is the first case report to demonstrate a reduction of RP-associated CMO following intravitreal aflibercept, despite inadequate response to ranibizumab on two separate occasions. Aflibercept may provide superior action to other anti-VEGF medications due to its intermediate size (115 kDa) and higher binding affinity. This is worthy of further investigation in a large prospective cohort over an extended time to determine the safety and efficacy of intravitreal aflibercept for use in this condition.

Download Full-text

Endolaserless Vitrectomy With Intravitreal Aflibercept Injection for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage (LASER LESS TRIAL)

Journal of VitreoRetinal Diseases ◽

10.1177/2474126418764972 ◽

2018 ◽

Vol 2 (3) ◽

pp. 127-137

Author(s):

Dennis M. Marcus ◽

Harinderjit Singh ◽

Davis C. Starnes ◽

Harveen Walia ◽

Amina Farooq ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Proliferative Diabetic Retinopathy ◽

Vitreous Hemorrhage ◽

Panretinal Photocoagulation ◽

Short Term ◽

Safety And Efficacy ◽

Intravitreal Aflibercept ◽

Central Subfield Thickness ◽

Endothelial Growth Factor

Purpose: For proliferative diabetic retinopathy (PDR) eyes not requiring vitrectomy, Diabetic Retinopathy Clinical Research Protocol S and the CLARITY trial demonstrated better visual function and anatomical outcomes with less proliferative and diabetic macular edema consequences in the antivascular endothelial growth factor groups compared to the panretinal photocoagulation groups. Intravitreal aflibercept injection (IAI) may represent a useful therapy with vitrectomy for PDR-related vitreous hemorrhage (VH) as a viable alternative to intraoperative endolaser during vitrectomy. We will determine the safety and efficacy when aflibercept is used for PDR-related VH with endolaserless vitrectomy. Methods: Evaluation of endolaserless vitrectomy and 2 mg IAI for PDR-related VH. Eyes receive 1 preoperative and intraoperative IAI followed by randomization to a q8week group receiving 4 postoperative q4week IAI followed by q8week IAI or q16week group receiving 2 postoperative q4week IAI followed by q16week IAI. Main Outcome Measures: Herein, we present pooled safety and efficacy outcomes through 4 months. Results: Twenty-one of 24 eyes were randomized. Preoperative average visual acuity (VA) was 36 letters (20/200). At 4-month follow-up, 18 of 21 randomized eyes showed an average VA of 72 letters (20/40) with an average visual gain of 38 (range, 0-84 gain) letters. Average optical coherence tomography (OCT) central subfield thickness (CST) at 1-month postoperative follow-up was 311 µm. Average OCT CST at 4-month follow-up was 272 µm (average thinning of 38 µm). No significant short-term ocular or systemic adverse events were observed through 4 months. Conclusions: Endolaserless vitrectomy with IAI for PDR-related VH demonstrates short-term safety with significant VA improvement.

Download Full-text

Efficacy of additional topical betamethasone in persistent cystoid macular oedema after carbonic anhydrase inhibitor treatments in retinitis pigmentosa

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2017-000107 ◽

2018 ◽

Vol 3 (1) ◽

pp. e000107

Author(s):

Shohei Kitahata ◽

Yasuhiko Hirami ◽

Seiji Takagi ◽

Cody Kime ◽

Masashi Fujihara ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Retinitis Pigmentosa ◽

Macular Oedema ◽

Medical Records ◽

Cystoid Macular Oedema ◽

Topical Steroids ◽

Foveal Thickness ◽

Central Foveal Thickness ◽

Corrected Visual Acuity ◽

Iop Elevation

ObjectiveWe investigated the efficacy of additional topical betamethasone in persistent cystoid macular oedema (CMO) after carbonic anhydrase inhibitors (CAIs) therapy.Methods and analysisThis retrospective cohort study included 16 eyes of 10 patients with retinitis pigmentosa (RP). All patients were previously administered CAI for at least 3 months to treat CMO secondary to RP and lacking an effective reduction (≥11%) of central foveal thickness (CFT). We administered topical 0.1% betamethasone daily in each affected eye following a preceding course of the CAI medication as a first treatment. CMO was diagnosed using spectral-domain optical coherence tomography. CFT was regarded as the average of vertical and horizontal foveal thickness. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained from patient medical records. We compared the CFT and BCVA between baseline and the average of 1–3, 5–7, 10–14 and 16–20 months period.ResultsIn treatments with brinzolamide in 14 eyes, dorzolamide in 2 eyes and bromfenac in 2 eyes, CFT effectively decreased in 12 of 16 eyes (81%). CFT decreased significantly in 1–3 months (326±102 µm; n=16; P=0.029) and 5–7 months (297±102 µm; n=12; P=0.022) compared with baseline but not within 10–14 months (271±96 µm; n=9; P=0.485) or 16–20 months (281±134 µm; n=9; P=0.289). There were no significant intergroup differences in BCVA throughout the study. Betamethasone treatment was stopped in three patients because of IOP elevation.ConclusionOur data suggested that additional betamethasone might improve treatments for persistent CMO. Topical steroids could be an alternative option for managing persistent CMO in RP.

Download Full-text

Treatment of cystoid macular oedema secondary to pentosan polysulfate maculopathy using anti-VEGF and intravitreal steroid injections

European Journal of Ophthalmology ◽

10.1177/11206721211066387 ◽

2021 ◽

pp. 112067212110663

Author(s):

Samantha Roshani De Silva ◽

Isuru De Silva ◽

Bishwanath Pal

Keyword(s):

Treatment Outcomes ◽

Macular Oedema ◽

Therapeutic Options ◽

Cystoid Macular Oedema ◽

Pentosan Polysulfate ◽

Steroid Injections ◽

Anti Vegf ◽

Drug Cessation

Background Pentosan polysulfate-related maculopathy is a recently described clinical entity, related to dose and long term use of this medication, and may progress despite drug cessation. Cystoid macular oedema (CMO) has been reported in some cases, but there are few reports of treatment outcomes in the literature. Aims We present the case of a 55 year old female, with CMO secondary to pentosan polysulfate maculopathy, that was responsive to treatment with both intravitreal anti-VEGF and steroid injections, stabilising vision over a four year follow up period. Conclusions This is the first report, to our knowledge, of CMO related to pentosan polysulfate maculopathy responding to intravitreal steroid injections, broadening the therapeutic options for preserving vision in these patients.

Download Full-text

Cystoid macular oedema after descemet membrane endothelial keratoplasty

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319455 ◽

2021 ◽

pp. bjophthalmol-2021-319455

Author(s):

Damien Guindolet ◽

Odile Huynh ◽

Gilles C Martin ◽

Hugo Disegni ◽

Georges Azar ◽

...

Keyword(s):

Macular Oedema ◽

Univariate Analysis ◽

Cystoid Macular Oedema ◽

Bullous Keratopathy ◽

Endothelial Keratoplasty ◽

Descemet Membrane Endothelial Keratoplasty ◽

Descemet Membrane ◽

Spectral Domain Oct ◽

History Of ◽

Clinically Significant

AimsTo determine the incidence and risk factors of cystoid macular oedema (CMO) following descemet membrane endothelial keratoplasty (DMEK) with or without combined cataract surgery (triple-DMEK).MethodsWe reviewed the records of patients who underwent DMEK surgery alone or triple-DMEK performed at the Rothschild Foundation Hospital (Paris, France) between January 2019 and March 2020. Patients with pre-existing CMO observed on the preoperative macular optical coherence tomography (OCT) were excluded. Spectral-domain OCT was performed in patients with postoperative visual impairment. Data regarding comorbidities, intraoperative characteristics and postoperative treatments or complications were collected and analysed. Univariate and multivariate analyses were performed.ResultsTwenty three of 246 eyes (9.36%) developed clinically significant (cs)-CMO after DMEK. Triple-DMEK was not associated with a higher risk to develop CMO (12.2% in DMEK alone and 6.1% in triple-DMEK). Pseudophakic bullous keratopathy (PBK ; 39.1% vs 9%; OR=3.5 (1.0 to 11.8), p=0.045) and epiretinal membrane (ERM; 39.1% vs 7.7%; OR=10.5 (3.4 to 32.3), p<0.001) were more frequently observed in patients who developed CMO. The occurrence of hyphaema during surgery was statistically associated with postoperative CMO (13% vs 1.3%; OR=7.1 (1.0 to 48.8) p=0.045). Peroperative epithelial debridement was statistically associated with postoperative CMO (65.2% vs 33.2%, p=0.005), but only in univariate analysis.ConclusionsWe identified a clinically significant CMO incidence of 9.35% after DMEK. Patients with a history of ERM, PBK and intraoperative hyphaema may be at risk of developing CMO after DMEK surgery and should be monitored.

Download Full-text

Safety and Outcomes of Linezolid Use for Nocardiosis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa090 ◽

2020 ◽

Vol 7 (4) ◽

Cited By ~ 2

Author(s):

Natalie Davidson ◽

Matthew J Grigg ◽

Sarah L Mcguinness ◽

Robert J Baird ◽

Nicholas M Anstey

Keyword(s):

Adverse Events ◽

Hospital Setting ◽

Drug Susceptibility ◽

Therapeutic Drug ◽

Primary Analysis ◽

Safety And Efficacy ◽

Treatment Regimens ◽

Linezolid Therapy ◽

Tropical Australia ◽

Clinically Significant

Abstract Background Tropical Australia has a high incidence of nocardiosis, with high rates of intrinsic antimicrobial resistance. Linezolid, the only antimicrobial to which all local Nocardia species are susceptible, has been recommended in empirical combination treatment regimens for moderate–severe Nocardia infections at Royal Darwin Hospital (RDH) since 2014. We report the safety and efficacy of linezolid use for nocardiosis in this setting. Methods We identified cases through a retrospective review of all RDH Nocardia isolates from December 2014 to August 2018 and included 5 linezolid-treated cases from a previous cohort. Laboratory, demographic, and clinical data were included in the primary analysis of safety and treatment outcomes. Results Between 2014 and 2018, Nocardia was isolated from 35 individuals; 28 (80%) had clinically significant infection and 23 (82%) received treatment. All isolates were linezolid-susceptible. Safety and efficacy were assessed for 20 patients receiving linezolid-containing regimens and 8 receiving nonlinezolid regimens. Median linezolid induction therapy duration was 28 days. Common adverse effects in those receiving linezolid were thrombocytopenia (45%) and anemia (40%). Adverse events prompted discontinuation of trimethoprim-sulfamethoxazole more often than linezolid (40% vs 20%). Linezolid therapeutic drug monitoring was used in 1 patient, with successful dose reduction and outcome. There was no difference in 30-day survival between those treated with linezolid (90%) vs no linezolid (87%). One Nocardia-attributed death occurred during linezolid therapy. Conclusions Linezolid is safe and efficacious in empirical treatment for moderate to severe nocardiosis in a monitored hospital setting, with 100% drug susceptibility and no difference in adverse events or outcomes compared with nonlinezolid regimens.

Download Full-text

DOP60 Vedolizumab treatment persistence and safety in an extended access program (XAP)

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.099 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S099-S100

Author(s):

S Danese ◽

K Subramanian ◽

J Van Zyl ◽

S Adsul ◽

D Lindner ◽

...

Keyword(s):

Data Analysis ◽

Adverse Events ◽

Dose Escalation ◽

Open Label ◽

Dose Escalation Study ◽

Extended Access ◽

Dosing Frequency ◽

Access Program

Abstract Background Vedolizumab, a gut-selective, α 4β 7 integrin antagonist, has been established as an effective and safe treatment for patients with UC or CD in the GEMINI phase 3 program and long-term safety (LTS) study. An extended access program (XAP) was initiated to provide continued access to patients who were benefiting from vedolizumab in GEMINI LTS and to monitor safety. We now report persistence and safety results from a 2-year data analysis. Methods Vedolizumab XAP (NCT02743806) is a phase 3b/4 prospective, open-label, multinational interventional study. A rollover from GEMINI LTS (NCT00790933) to the XAP, patients reduced dosing frequency from vedolizumab 300 mg IV every 4 weeks (Q4W) to every 8 weeks (Q8W) or remained on vedolizumab 300 mg IV Q4W if medically indicated. This 2-year data analysis assessed persistence on Q8W dosing after dosing frequency reduction, need for escalation to Q4W dosing, incidence of relapse (defined as dose escalation, study withdrawal due to adverse event, loss of adequate benefit from vedolizumab, or increased corticosteroid [CS] or immunomodulator dose), and safety 2 years after rollover from GEMINI LTS. Results A total of 311 patients (142 UC, 169 CD) from GEMINI LTS enrolled in the XAP. Median (range) duration of exposure to vedolizumab prior to the XAP was 8.0 years (5.2–10.0) for patients with UC and 7.5 years (5.4–9.9) for patients with CD. Of patients with UC and CD, 93.0% and 84.6%, respectively, reduced dosing frequency to Q8W at XAP start, and 87.3% and 77.5%, respectively, remained on Q8W after 2 years. At baseline, 93.0% of all patients with UC and 88.2% of all patients with CD were in CS-free remission; patients who maintained Q4W dosing at baseline had lower CS-free remission rates (62.5% in UC and 69.2% in CD). Of patients who initiated Q8W dosing at enrolment in the XAP, 95% had no relapse for ≥6 months (97.0% UC, 93.7% CD; Table 1). Only 7.3% of patients required dose escalation to Q4W, and 11.6% experienced relapse during the 2-year follow-up. Times to dose escalation and relapse were similar in patients with UC and CD (Figures 1 and 2). At 2 years, 4 of 8 patients with UC and 4 of 12 patients with CD who required dose escalation to Q4W discontinued vedolizumab early due to loss of benefit or adverse events. Adverse events related to vedolizumab were infrequent; no new or serious events attributed to vedolizumab were reported. Conclusion High patient persistence on Q8W vedolizumab was observed in the first 2 years after reduction of dosing frequency in the XAP. Overall, there were low rates of Q4W dose escalation and CD or UC disease relapse. The safety profile was consistent with previous reports with no new signals observed.

Download Full-text

Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000144 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000144 ◽

Cited By ~ 6

Author(s):

Sarah Abou Alaiwi ◽

Wanling Xie ◽

Amin H Nassar ◽

Shaan Dudani ◽

Dylan Martini ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Median Time ◽

Immune Checkpoint ◽

Renal Cell ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Safety And Efficacy ◽

Clinically Significant

BackgroundImmune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.MethodsThis multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had >1 week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.ResultsOf 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2–31.6). After retreatment, 50% (n=18/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3–13.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95% CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.ConclusionsDespite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.

Download Full-text

Safety of 6000 intravitreal dexamethasone implants

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-313991 ◽

2019 ◽

Vol 104 (1) ◽

pp. 39-46 ◽

Cited By ~ 13

Author(s):

Bindu Rajesh ◽

Javier Zarranz-Ventura ◽

Adrian T Fung ◽

Catharina Busch ◽

Niroj Kumar Sahoo ◽

...

Keyword(s):

Intraocular Pressure ◽

Retinal Detachment ◽

Macular Oedema ◽

Real Life ◽

Cystoid Macular Oedema ◽

Dexamethasone Implant ◽

Intravitreal Dexamethasone Implant ◽

Intravitreal Dexamethasone ◽

Phakic Eyes

PurposeTo evaluate the real-life safety profile of intravitreal dexamethasone implant injection for various retinal conditions.MethodsRetrospective multicenter analysis of intravitreal dexamethasone implant injections (700 µg) due to various retinal conditions including central retinal venous occlusion (1861 injections), diabetic macular oedema (3104 injections), post-surgical cystoid macular oedema (305 injections) and uveitis (381 injections). The eyes were evaluated mainly for the occurrence of adverse events such as glaucoma, cataract, retinal detachment and endophthalmitis along during the follow-up period.ResultsA total of 6015 injections in 2736 eyes of 1441 patients (mean age of 65.7±12.9 years) were in total analysed over an average period of 18 months (range 6 months to 102 months). A total of 576 eyes (32.5% of the phakic eyes) developed cataract requiring surgical intervention. However, visually insignificant cataract progression was observed in another 259 phakic eyes (14.6%) which did not require surgical removal. A total of 727 eyes (26.5%) experienced an intraocular pressure (IOP) rise of >25 mm Hg, with 155 eyes (5.67%) having a prior history of glaucoma and 572 eyes (20.9%) having new onset IOP rise. Overall, more than 90% of eyes with IOP rise were managed medically, and 0.5% eyes required filtering surgery. Endophthalmitis (0.07%), retinal detachment (0.03%) and vitreous haemorrhage (0.03%) were rare. There was no significant change in visual acuity (p=0.87) and central macular thickness (p=0.12) at the last follow-up.ConclusionThis is the largest real-life study assessing the safety of intravitreal dexamethasone implant injections in various retinal conditions. Cataract progression and intraocular pressure rise are the most common side effects, but are often rather easily manageable.

Download Full-text