Ocular Adverse Events Research Articles

Aflibercept monotherapy versus aflibercept with targeted retinal laser to peripheral retinal ischemia for diabetic macular oedema (LADAMO)

ObjectiveWe tested the hypothesis that targeted retinal laser photocoagulation (TPRP) to peripheral retinal ischaemia reduces the overall burden of aflibercept injections when treating diabetic macular oedema (DMO) over a 24-month period.MethodsProspective, double-masked, multicentre, randomised controlled trial in Australia comparing aflibercept monotherapy, following a treat-and-extend protocol, or combination therapy of aflibercept and TPRP for DMO. The aflibercept monotherapy group received placebo laser. The primary outcome measure was the mean number of intravitreal aflibercept injections for each group at 24 months. Secondary outcome included: mean change in central macular thickness (CMT) and vision at trial completion, the proportion of eyes whose DMO resolved and the mean injection treatment interval. Ocular and systemic adverse events were recorded.ResultsWe enrolled 48 eyes of 47 patients; 27 eyes were randomised to combination therapy (aflibercept and TPRP) and 21 to aflibercept monotherapy. Thirty-two eyes (67%) completed the 2-year study. The number of intravitreal treatments given were similar for combination therapy (10.5 (SD 5.8) and monotherapy (11.8 (SD5.6)) (P = 0.44). The mean visual improvement (+4.0 (−1.8, 9.8) and +7.8 (2.6, 12.9) letters, P = 0.32), mean decrease in CMT (−154 (−222,−87) µm and −152 (−218,−86) µm, P = 0.96), proportion of eyes with CMT < 300 µm (48% and 67%; P = 0.50) and safety outcomes were similar in both the combination and monotherapy treatment groups (respectively).ConclusionsLaser to areas of ischaemic peripheral retina does not reduce the burden of intravitreal aflibercept injections when treating diabetic macular oedema.

Abstract LB118: Evidence of tumor response in orbital lesions treated with tebentafusp in metastatic uveal melanoma patients

Abstract Background: Tebentafusp, a bispecific (gp100 x CD3) ImmTAC that can redirect T cells to target gp100+ melanoma cells, has shown a superior overall survival (OS) benefit compared to investigator choice for HLA-A*02:01+ patients (pts) with untreated metastatic uveal melanoma (mUM). Although local control rates for primary UM are high, a minority of patients with mUM have recurrent or untreated orbital disease. Here we present safety and efficacy from tebentafusp treated mUM pts with orbital lesions including intraocular lesions. Methods: Tumor response according to RECIST v1.1 and ocular Adverse Events (AEs) were assessed in a pooled analysis of mUM pts with orbital lesions from 3 tebentafusp trials: IMCgp100-01 (Phase (Ph) 1/2, 19 2L+ mUM pts), IMCgp100-102 (Ph 1/2 2L+ mUM, 146 pts) and IMCgp100-202 (Ph3 1L mUM, 245 tebentafusp pts). Pre-treatment biopsies, taken prior to the IMCgp100-202 trial, were analyzed by immunohistochemistry for gp100 and CD3+ or CD8+ T cell infiltration prior to tebentafusp treatment. Results: In the 3 clinical trials, 12 mUM pts with radiologically detectable orbital lesions received tebentafusp, the majority of which were intra-ocular. All lesions were stable or had achieved shrinkage. 5/12 pts had orbital target lesions (TL), of which 4/5 had achieved tumor shrinkage (best % change -3 to -40) and 1/5 had no change in tumor size. All non-target orbital lesions were stable or achieved a complete response. 9 eye disorder AEs occurred in 5 pts, the majority of which were G1. The most common (7/9) AEs were extra-ocular local edema. One G3 eye pain AE, in a post eviscerated eye, did not resolve and occurred in the setting of disease progression resulting in treatment discontinuation. All other eye disorder AEs recovered and none led to tebentafusp discontinuation. 37 primary UM and 195 liver metastasis baseline biopsies were evaluated. Expression of gp100 in primary UM and mUM was high (95% and 80%, respectively). CD3+ and CD8+ T cell numbers were generally lower in primary UM compared to liver metastasis (median CD3: 231 and 504 cells/mm2, p=0.035; CD8: 121 and 238 cells/mm2, p=0.53, respectively). Conclusions: Following tebentafusp treatment, tumor reduction or stabilization of all orbital lesions including intra-ocular lesions were observed. Most AEs were extra-ocular mild local edema. Primary UM showed a high level of gp100 expression and also T cell infiltration. These preliminary signals of tebentafusp activity in orbital disease, including intra-ocular lesions, suggest a role for tebentafusp as a neoadjuvant therapy in UM and warrant further investigation. Citation Format: Marcus O. Butler, Takami Sato, Friedegund Meier, Ramakrishna Edukulla, Sarah Stanhope, Fraser S. Peck, Jessica C. Hassel. Evidence of tumor response in orbital lesions treated with tebentafusp in metastatic uveal melanoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB118.

Management of macular oedema due to retinal vein occlusion: An evidence-based systematic review and meta-analysis.

Central retinal vein occlusion and branch retinal vein occlusion are common causes of visual loss due to associated macular oedema. The aim of this review was to assess the effectiveness of interventions improving vision and treating macular oedema in central retinal vein occlusion and branch retinal vein occlusion. Medical search engines and clinical trial registries were systematically searched. Randomised clinical trials with ≥90 eyes and real-world outcome studies with ≥100 eyes each with ≥6 months follow-up were included. There were 11 randomised controlled trials evaluating treatments for central retinal vein occlusion which met the inclusion criteria and 10 for branch retinal vein occlusion. There were 10 real world outcome studies of central retinal vein occlusion and 5 real world outcome studies of branch retinal vein occlusion. Meta-analysis was performed on studies that met the defined inclusion criteria. Main outcomes were change in visual acuity at 6-, 12-, 24- and 36 months by treatment. Intravitreal anti-vascular endothelial derived growth factor is recommended as first line treatment over intravitreal corticosteroid due to its effectiveness and lower rate of ocular adverse events. Best outcomes are achieved when intravitreal treatment is started early. Macular laser may have an adjunctive role in branch retina vein occlusion but not central retinal vein occlusion.

Real-Life Experience and Predictors of Visual Outcomes with Intravitreal Brolucizumab Switch for Treatment of Neovascular Age-Related Macular Degeneration

Introduction: To analyze visual and anatomical outcomes after switch to intravitreal brolucizumab therapy in eyes affected by neovascular age-related macular degeneration (nAMD) previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: Retrospective study of eyes with nAMD that underwent intravitreal brolucizumab at San Raffaele Hospital (Milan, Italy) or San Rocco Clinical Institute (Ome, Italy) between January 2021 and July 2022. All study eyes had persistent residual retinal fluid after receiving at least 3 intravitreal injections of other anti-VEGF agents prior to switch to brolucizumab. Results: Among 66 eyes from 60 patients (35 males; mean age 76.5 ± 7.4 years) with nAMD, 43 (65.2%) eyes received a complete loading dose of 3 brolucizumab injections, while 15 (22.7%) and 8 (12.1%) eyes were treated with 2 or 1 brolucizumab injections, respectively. The average number of brolucizumab injections was 2.5 during 4.0 ± 2.0 months (mean interval between two injections of 51.2 days). Lower letter gains (<5 letter improvement from baseline) were found in eyes that did not complete a loading dose, after a greater number of previous anti-VEGF injections, after a longer duration of disease, and in eyes with a greater rate of macular atrophy at baseline. No serious ocular or systemic adverse events were found after switch to brolucizumab. Conclusion: nAMD eyes with persistent residual retinal fluid despite frequent anti-VEGF treatment can still gain functional and anatomical improvements after switch to brolucizumab therapy. Despite a relevant heterogeneity in patients’ response to brolucizumab, we identified potential biomarkers for functional and anatomical improvement.

Comparisons of efficacy and safety between preserved and preservative-free brimonidine tartrate in glaucoma and ocular hypertension: a parallel-grouped, randomized trial

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.

Paracentral acute middle maculopathy progressing to central retinal artery occlusion following coronavirus disease vaccination: a multimodal imaging report

Background: Coronavirus disease (COVID-19) vaccines can cause adverse ocular effects, including vascular insults, acute macular neuroretinopathy, paracentral acute middle maculopathy (PAMM), ophthalmic vein thrombosis, Graves’ disease, arteritic anterior ischemic optic neuropathy (A-AION), and nonarteritic AION. Here, we report a case of unilateral PAMM progressing to central retinal artery occlusion (CRAO) after COVID-19 vaccination, identified using multimodal imaging.&#x0D; Case Presentation: A 24-year-old healthy man presented with unilateral progressive blurring of vision in the right eye. He had a recent history of fever without rashes 2 weeks after coronavirus disease vaccination. He was diagnosed with PAMM in the right eye at a local hospital and treated with a tapering dose of oral steroids. At presentation, he showed progressive blurring of vision in the right eye and the best-corrected distance visual acuity (BCDVA) was 20/60. The anterior segment was normal. Fundus examination revealed a pale optic disc with arteriolar attenuation and barrage laser scarring at the inferotemporal periphery. CRAO was diagnosed based on the right eye findings. The patient underwent multimodal imaging, including wide-field fundus photography using Optos® (Optos Carfornia®, Optos Inc., Dunfermline, United Kingdom), multicolor imaging with Spectralis™ (Heidelberg Retinal Angiograph; Heidelberg Engineering, Inc., Dossenheim, Germany), fundus fluorescence angiography (Heidelberg Retinal Angiograph; Heidelberg Engineering, Inc., Dossenheim, Germany), and optical coherence tomography angiography (ANGIOVUE, OPTOVUE, Inc., Fremont, CA, USA) using the split-spectrum amplitude-decorrelation angiography algorithm. The condition progressed from PAMM to CRAO during the oral steroid treatment course. At the 2-month follow-up, the right eye BCDVA had improved to 20/50, with fundus findings remaining the same as at the previous visit.&#x0D; Conclusions: This was the first report of a young patient with PAMM presenting with focal vascular occlusion that evolved to global occlusion in the form of CRAO in the absence of systemic vascular risk factors and with a normal coagulation profile. This case suggests that arterial occlusion may exert a temporary effect secondary to COVISHIELD™ vaccination. Randomized controlled trials and case – control studies on the role of vaccination in precipitating thromboembolic events in healthy individuals would provide insight into the causation.

PD11-03 THE USE OF PHOSPHODIESTERASE 5 INHIBITORS IS NOT ASSOCIATED WITH OCULAR ADVERSE EVENTS

You have accessJournal of UrologyCME1 Apr 2023PD11-03 THE USE OF PHOSPHODIESTERASE 5 INHIBITORS IS NOT ASSOCIATED WITH OCULAR ADVERSE EVENTS Federico Belladelli, Shufeng Li, Chiyuan A. Zhang, Francesco Del Giudice, Frank Glover, Wade Muncey, Nicolas Serranio, Satvir Basran, Francesco Montorsi, Andrea Salonia, and Michael Eisenberg Federico BelladelliFederico Belladelli More articles by this author , Shufeng LiShufeng Li More articles by this author , Chiyuan A. ZhangChiyuan A. Zhang More articles by this author , Francesco Del GiudiceFrancesco Del Giudice More articles by this author , Frank GloverFrank Glover More articles by this author , Wade MunceyWade Muncey More articles by this author , Nicolas SerranioNicolas Serranio More articles by this author , Satvir BasranSatvir Basran More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , and Michael EisenbergMichael Eisenberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003251.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Phosphodiesterase-5 inhibitors (PDE5i) are the first-line line treatment for men with ED. The use of PDE5I has recenty been linked to several ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). However, the risk factors for major ocular events and ED overlap suggesting that the association may not be causative. The current study investigated the risk for SRD, RVO, and ION in patients using PDE5Is. METHODS: We utilized the IBM® MarketScan® (2007 to 2016) Commercial and Medicare Supplemental Databases (v 2.0, DOI: 10.57761/ray7-1g16). Cox proportional hazard models were applied to calculate the risk of ocular events after the diagnosis and or treatment of ED (i.e. PDE5i, penile injection/urethral suppositories, penile prosthesis placement) while adjusing for relevant comorbidities. As a further analysis, the use of PDE5i in men with BPH was also examined. RESULTS: In total, 1,565,006 men with an ED diagnosis were identified. Among them, 525,624 (33.6%) were treated with a PDE5i. In total, 1,806,803 men with a BPH diagnosis were observed during the study period with 141,607 (7.8%) treated with a PDE5i. On adjusted analysis, PDE5i use was not consistently associated with SRD, ION, and any ocular event when compared to ED diagnosis and other ED treatments. However, men who received a penile prosthesis had a higher risk of ocular events RVO (HR: 2.36; 95% CI: 1.81–3.09). In addition, PDE5i use was associated with SRD, RVO, and ION in the BPH cohort. In fact, BPH patients using 5a reductase/alpha blocker or prostatectomy had the highest risk of ocular events. CONCLUSIONS: In the current report, no consistent association with PDE5i use and adverse ocular events (i.e. SRD, RVO, and ION) was identified. For erectile dysfunction, men requiring more invasive treatment of ED (i.e. men with more severe ED who required more invasive treatments) carried the highest risk of adverse ocular events. The link between PDE5i use and ocular events is consistent with biases related to common risk factors suggesting patient counseling about this association is unnecessary. Source of Funding: Data for this project were accessed using the Stanford Center for Population Health Sciences Data Core. The PHS Data Core is supported by a National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1TR003142) and from Internal Stanford funding. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e333 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Federico Belladelli More articles by this author Shufeng Li More articles by this author Chiyuan A. Zhang More articles by this author Francesco Del Giudice More articles by this author Frank Glover More articles by this author Wade Muncey More articles by this author Nicolas Serranio More articles by this author Satvir Basran More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Michael Eisenberg More articles by this author Expand All Advertisement PDF downloadLoading ...

Effectiveness of the Use of Three-Dose Intravitreal Ziv-Aflibercept in the Management of Diabetic Macular Edema in a Real-Life Setting.

It has been reported that intravitreal Ziv-aflibercept is a safe and effective drug for the treatment of diabetes macular edema (DME). The objective of this study was to evaluate in a real-life setting, the efficacy of intravitreal Ziv-aflibercept in the treatment of DME after the administration of three consecutive monthly doses. A single arm, prospective cohort study. We included patients with DME who received three doses of intravitreal Ziv-aflibercept. Data such as best corrected visual acuity (BCVA) and tomographic biomarkers before treatment and a month after the third dose were collected. DME was staged using the Panozzo classification. Thirty-eight patients participated for a total of 53 eyes. The mean age was 59 ± 8.1 years. We observed significant changes after the third dose in the parameters studied (BCVA in LogMAR pre-treatment (0.6 ± 0.33) and post-treatment (0.4 ± 0.29) [p<0.001], macular thickness pre-treatment (501 ± 167 µm) and post-treatment (324 ± 114 µm) [p<0.001], macular volume pre-treatment 10.8 (7.5-17.8) mm3 and post-treatment 9.3 (0-13.6) mm3 [p<0.005]). And 73.6% of the patients presented an advanced severe stage during their pre-treatment evaluation and after post-treatment, 64.2% of the patients no longer presented edema. No systemic or ocular adverse events occurred. The use of three consecutive monthly doses of intravitreal Ziv-aflibercept in a real-life setting is effective and safe in the management of diabetic macular edema.

Off-label use of intravitreal brolucizumab injection for fibrinous central serous chorioretinopathy

The authors describe the first case report of management of central serous chorioretinopathy (CSCR) associated with subretinal fibrin deposition by intravitreal injection (IVI) of brolucizumab in a 45-year-old male. At 3 months, his best-corrected visual acuity (BCVA) improved from 20/200 to 20/80. On fundus evaluation, there was complete resolution of the subretinal fluid (SRF) and fibrin, which was confirmed on spectral-domain optical coherence tomography (SD-OCT). There were no reports of ocular or systemic adverse effects. Increased flux and permeability of the retinal pigment epithelium secondary to anti-vascular endothelial factor (anti-VEGF) injection agent can explain the migration of the fibrin toward the choroid and its resolution. Further molecular and clinical studies are warranted to better understand the role of brolucizumab in the management of fibrinous CSCR.

Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial

Background/ObjectivesTo assess the safety and efficacy of avacincaptad pegol (ACP), a C5 inhibitor, for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) over an 18-month treatment course.Subjects/MethodsThis study was an international, prospective, randomized, double-masked, sham-controlled, phase 2/3 clinical trial that consisted of 2 parts. In part 1, 77 participants were randomized 1:1:1 to receive monthly intravitreal injections of ACP 1 mg, ACP 2 mg, or sham. In part 2, 209 participants were randomized 1:2:2 to receive monthly ACP 2 mg, ACP 4 mg, or sham. The mean rate of change of GA over 18 months was measured by fundus autofluorescence.ResultsCompared with their respective sham cohorts, monthly ACP treatment reduced the mean GA growth (square root transformation) over 18 months by 28.1% (0.168 mm, 95% CI [0.066, 0.271]) for the 2 mg cohort and 30.0% (0.167 mm, 95% CI [0.062, 0.273]) for the 4 mg cohort. ACP treatment was generally well tolerated over 18 months, with most ocular adverse events (AEs) related to the injection procedure. Macular neovascularization (MNV) was more frequent in both 2 mg (11.9%) and 4 mg (15.7%) cohorts than their respective sham control groups (2.7% and 2.4%).ConclusionsOver this 18-month study, ACP 2 mg and 4 mg showed continued reductions in the progression of GA growth compared to sham and continued to be generally well tolerated. A pivotal phase 3 GATHER2 trial is currently underway to support the efficacy and safety of ACP as a potential treatment for GA.

NOV03 for Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction: The Randomized Phase 3 MOJAVE Study

To evaluate the efficacy and safety of NOV03 (perfluorohexyloctane) ophthalmic drop for the treatment of signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). Randomized, double-masked, controlled trial. Patients ≥18 years of age with a history of DED and signs of MGD were randomly assigned 1:1 to treatment with NOV03 or hypotonic saline (0.6%) 4 times daily for 8 weeks. The primary sign and symptom endpoints were change from baseline to week 8 in total corneal fluorescein staining (tCFS; National Eye Institute scale) and eye dryness score (0-100 visual analog scale), respectively. A total of 620 patients (NOV03, n = 311; saline, n = 309) were randomized and treated. Least-squares (LS) mean change from baseline to week 8 was statistically significantly greater for NOV03 compared with saline for both tCFS (-2.3 vs -1.1; LS mean treatment difference, -1.2 [95% confidence interval -1.7 to -0.8]; P < .001) and visual analog scale dryness score (-29.4 vs -19.2; LS mean treatment difference, -10.2 [95% CI -14.4 to -6.1]; P < .001), with statistically significant between-group differences observed as early as week 2. The incidence of ocular adverse events was similar for NOV03 (12.9%) and saline (12.3%). There were no serious adverse events and no adverse events leading to treatment discontinuation. In this randomized controlled trial of patients with DED associated with MGD, NOV03 significantly reduced both signs and symptoms of DED compared with hypotonic saline control. NOV03 was well tolerated, with an adverse event profile similar to that of saline.

Visual outcome in patients of branch retinal vein occlusion (BRVO) with macular edema after one injection of intravitreal biosimilar ranibizumab

: This study aims to determine the effects of intravitreal biosimilar ranibizumab injection on best corrected visual acuity (BCVA) and central macular thickness (CMT) in patients of branch retinal vein occlusion (BRVO) with macular edema. : A retrospective, unmasked, and data-based study was conducted on 50 patients of BRVO with macular edema, who presented to our OPD over a period of 2 years. Cases in our study received one intravitreal injection of biosimilar Ranibizumab (0.5 mg/0.05 ml) at presentation and were followed up one month after injection. The data was collected from patients and available records. The data regarding BCVA and CMT (by Optical Coherence Tomography) before and 1 month after treatment was recorded and analyzed statistically.: In this study, we included fifty eyes of fifty patients. The mean patients’ age (in years) was 53.08 ± 9.58. There were 24 (48%) male and 26 (52%) female patients. The baseline mean BCVA ± SD (logMAR) was 0.79 ± 0.16 and mean CMT ± SD (in µm) was 688.14 ± 98.41 before treatment. Mean BCVA (logMAR) and mean CMT (in µm) after one biosimilar ranibizumab injection, at 1-month follow-up, were 0.33 ± 0.13 and 307.18 ± 34.97 respectively. We used paired t-test to compare mean BCVA and mean CMT before and after injection, and we found a statistically significant difference (p-value of &amp;#60;0.001) for both. None of the patients experienced any significant ocular and systemic adverse effects on post-op day 1, and at 1 month.: Intravitreal biosimilar ranibizumab is an effective and safe therapy for patients of BRVO with macular edema and results in improvement of BCVA and decrease in CMT. Biosimilar injection has also reduced the cost of treatment leading to an increase in patients’ compliance.

Topical Ocular TRPV1 Antagonist SAF312 (Libvatrep) for Postoperative Pain After Photorefractive Keratectomy.

Evaluation of safety and efficacy of topical ocular SAF312 (Libvatrep) in post-photorefractive keratectomy (PRK) pain. In this placebo (vehicle)-controlled, participant- and investigator-masked study, 40 participants were randomized (1:1) to two treatment sequences in a bilateral PRK crossover design (SAF312 2.5% followed by vehicle [or vice versa], one eye drop, four times daily for 72hours after PRK). Primary endpoints were visual analog scale (VAS) pain scores at 6hours after first drop of study drug and average VAS scores over 0 to 12hours postoperatively. Secondary endpoints included postoperative oral rescue medication (ORM) use and adverse events (AEs). All 40 participants completed the study. Both primary endpoints were met; mean difference in VAS pain scores between SAF312- and vehicle-treated eyes was -11.13 (P = 0.005, -25%) at 6hours postoperatively and -8.56 (P = 0.017, -22%) over 0 to 12hours. Mean VAS pain scores with SAF312 were consistently lower than with vehicle from 1hour postoperatively up to 30hours (P ≤ 0.10 observed in 8/11 time points). Less ORM was taken with SAF312 up to 0 to 72hours postoperatively, with a trend of fewer participants taking ORM at 0 to 24hours postoperatively with SAF312 versus vehicle. No serious AEs were reported. All ocular AEs were mild and transient, and none were drug related. SAF312-treated eyes showed no delay in wound healing and had a lower grade 4 conjunctival hyperemia 24hours postoperatively versus vehicle-treated eyes. SAF312 was well tolerated and effective in reducing ocular pain post-PRK. Topical SAF312 presents a new therapeutic option for patients undergoing PRK.

Ocular Toxicities of MEK Inhibitors in Patients With Cancer: A Systematic Review and Meta-analysis.

Mitogen-activated protein kinase (MEK) inhibitors, which integrate the important signaling chain of the RAS-RAF-MEK-ERK1/2 pathway, regulate cell functions such as division and proliferation for patients with solid tumors. However, various ocular adverse effects (AEs) affect patients during clinical treatment. This systematic review aimed to assess the occurrence of AEs during treatment with MEK inhibitors plus targeted therapy or chemotherapy. A scientific literature search was conducted in PubMed, the Cochrane Library, Embase, and several Chinese databases to identify randomized controlled trials. Overall, ocular AEs were assessed as the primary end point; blurred vision, chorioretinopathy, and retinal detachment were assessed as secondary end points. Seventeen randomized controlled trials were included. Overall, the use of MEK inhibitors combined with other targeted inhibitors or chemotherapy was significantly associated with a nearly 7.3% increased risk of overall ocular toxicities vs therapy without MEK inhibitors (risk ratio [RR], 2.88; 95% CI, 1.42-5.85, P < .05). An increased risk of blurred vision (RR, 4.10; 95% CI, 2.55- 6.58; P < .05), chorioretinopathy (RR, 8.36; 95% CI, 3.42-20.47; P < .05), and retinal detachment (RR, 8.98; 95% CI, 3.92-20.57; P < .05) was demonstrated. Treatment with MEK inhibitors combined with targeted drugs or chemotherapy seems to increase overall ocular AEs. A more practical algorithm for the screening of ocular AEs was suggested to be conducted whenever new or worsening ocular toxicities occur.

Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results

To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD). Phase 3, randomized, multicenter, open-label, active-comparator trial. Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy. Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years). Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters). PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 60/64 and 88/92 of +0.4 (95% confidence interval [CI], -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3). Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events (AEs) of special interest were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. Most common AE of special interest reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab. PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. AEs were generally manageable, with learnings continually implemented to minimize PDS-related AEs.

Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis.

Intravitreal injections of antiangiogenic agents are pivotal in treating neovascular age-related macular degeneration (nAMD). The comparative efficacy and safety of treat-and-extend (T&E) versus bimonthly, monthly, and pro re nata (PRN) dosing remains unclear. A systematic review and meta-analysis of English-language RCTs reporting on efficacy and/or safety outcomes of dosing regimens of anti-VEGF agents in nAMD was performed. Best-corrected visual acuity (BCVA, ETDRS letters) at last follow-up represented the primary endpoint, while central subfield thickness (CSFT, μm), injection burden, and ocular adverse events were secondary endpoints. A random effects meta-analysis was performed, and 95% confidence intervals were calculated. Across six RCTs, 781 T&E-, 663 monthly-, 130 PRN-, and 123 bimonthly treated eyes were included. Mean changes in BCVA and CSFT at last follow-up were similar between T&E versus monthly (WMD, -0.62 letters; 95% CI, -2.12 to 0.87; P = 0.41; WMD, 5.30 microns; 95% CI, -10.67 to 21.26; P = 0.52, respectively), bimonthly (WMD, 1.68 letters; 95% CI, -3.55 to 6.91; P = 0.53; WMD, -18.91 microns; 95% CI, -46.41 to 8.60; P = 0.18, respectively), and PRN (BCVA WMD, 1.08 letters; 95% CI, -2.95 to 5.11; P = 0.60) regimens. T&E was associated with a reduced injection burden versus monthly (WMD, -4.52 injections; 95% CI, -6.66 to 2.39; P < 0.001) but higher injection burden versus PRN (WMD, 1.81 injections; 95% CI, 1.12 to 2.51; P < 0.001) dosing. There was no significant difference in safety outcomes amongst comparators. There was no significant difference in efficacy and safety between T&E, bimonthly, monthly, and PRN dosing. T&E resulted in fewer injections versus monthly and fewer clinic visits versus PRN.

Tisotumab Vedotin Safety and Tolerability in Clinical Practice: Managing Adverse Events

Tisotumab vedotin-tftv, an antibody-drug conjugate indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, demonstrated clinically meaningful and durable responses with a manageable safety profile in the pivotal phase II innovaTV 204 clinical trial. Based on the proposed mechanism of action of tisotumab vedotin, experience from clinical trials, and the US prescribing information, certain adverse events (AEs) including ocular AEs, peripheral neuropathy, and bleeding have been identified as AEs of interest. This article highlights practical considerations and provides recommendations to support the management of selected AEs associated with tisotumab vedotin. Central to monitoring of patients on tisotumab vedotin is a comprehensive care team comprised of oncologists, advanced practice providers (including nurse practitioners, physician assistants, and pharmacists), and other specialists such as ophthalmologists. As ocular AEs may be less familiar to gynecologic oncology practitioners, adherence to the "Premedication and Required Eye Care" section outlined in the US prescribing information, as well as the incorporation of ophthalmologists into the oncology care team, can help provide timely and appropriate eye care for patients receiving tisotumab vedotin.

Safety and Tolerability of Bilastine 0.6% Ophthalmic Solution: An 8-Weeks Phase III Study.

The objective of this study was to assess the safety and tolerability of preservative-free bilastine 0.6% ophthalmic solution after 8 weeks of once-daily administration in patients with allergic conjunctivitis (AC). Multi-center, international, randomized, double blind, placebo-controlled, parallel-group, phase III study of adult patients with seasonal or perennial AC. The study was conducted in 26 centers of 5 European countries. Duration of daily treatment with bilastine 0.6% ophthalmic solution or placebo was 8 weeks. Safety was evaluated by analyzing incidence of ocular treatment-emergent adverse events (TEAEs); additionally, and as secondary parameters, ocular tolerability was assessed, in addition efficacy was also assessed by the average daily total eye symptoms score (TESS). A total of 333 randomized patients with AC were included (bilastine, N=218; placebo, N=115). Mean (SD) age of the patients was 39.9 (13.7) and were 63.7% female. Overall, the percentage of ocular related TEAEs was low, and the percentage of patients with ocular related TEAEs was lower in the bilastine ophthalmic solution group (2.8%) than in the placebo group (4.3%). No severe TEAEs were reported. The ocular symptoms and TESS improved during the trial in both treatment groups. Statistically significant treatment differences were observed at Week 8 for the TESS and all individual ocular symptoms, being significantly better in the bilastine ophthalmic solution group than in placebo group. Bilastine 0.6% ophthalmic solution revealed no safety concerns in patients with AC after 8 weeks of once-daily administration. Bilastine was effective in reducing ocular symptoms associated with AC in response to both seasonal and perennial allergens.

Adverse Ocular Effects of Systemic Medications.

While ocular complications of systemic medications are uncommon, it is important to recognize that vision-threatening toxicities can occur. This review details the vision-threatening adverse effects of a select group of commonly prescribed systemic medications and describes the recommended screening guidelines for those that are particularly high risk.

Oral ibuprofen is associated with reduced likelihood of early bleb failure following trabeculectomy in high-risk glaucoma patients.

Individuals prescribed ibuprofen post-trabeculectomy have a better post-operative intraocular pressure control and higher chance of bleb survival despite being at a higher risk of scarring. To investigate the effects of early adjunctive oral ibuprofen treatment on intraocular pressure (IOP) and bleb failure in eyes at high risk of scarring. In these retrospective analyses, 288 eyes of 273 patients (mean±SD age: 68.56±10.47y; 32.60% females) with primary glaucoma who underwent trabeculectomy/phacotrabeculectomy at the Singapore National Eye Centre between April 2020 to April 2021 with a follow-up duration ≥1 year were included. Of these, 77 (26.7%) eyes deemed to be at high risk of scarring were administered oral ibuprofen ≥3 months post-operatively (mean±SD ibuprofen administration duration: 4.08±2.28wk). Participants' IOPs at baseline and at post-operative weeks 1, 2-3; and months 1, 2, 3, 6, and 12 were recorded. Bleb failure was defined as two consecutive IOP readings of >21, >18 and >15mmHg, and/or requiring remedial post-operative laser or surgery. The ibuprofen group experienced significantly greater post-operative IOP reductions at week 1 (mean difference [95% confidence interval]: -2.89 [-5.22, -0.56] mmHg) and month 1 (-2.29 [-4.53, -0.05] mmHg); and substantially lower odds of bleb failure at the >18mmHg (odds ratio [95% confidence interval]: 0.39 [0.20-0.79]) and >15mmHg (0.52 [0.29-0.94]) thresholds, compared to the non-ibuprofen group. No differences in adverse ocular hypotony events were observed. Early adjunctive oral ibuprofen administered to individuals at high risk of post-trabeculectomy scarring is associated with greater IOP reductions and reduced likelihood of bleb failure. Our results suggest that oral NSAIDs may be a safe way of improving trabeculectomy survival in high risk eyes.