Ocular Adverse Events Research Articles

INNV-13. OPHTHALMOLOGICAL COMPLICATIONS IN NF-1 PATIENTS RECEIVING MEK INHIBITORS: MD ANDERSON CANCER CENTER EXPERIENCE

Abstract BACKGROUND MEK inhibitors (MEKi) are a novel therapy for plexiform neurofibromas and optic gliomas in Neurofibromatosis type 1 (NF1). Potential ophthalmic complications are MEKi-induced retinopathy (MEKAR) requiring regular ophthalmologic assessments. We assess the importance of screening and ocular adverse events (OAE) in pediatric NF1 patients receiving MEKi. METHODS We reviewed 45 NF1 patients with baseline and follow-up examinations before and post MEKi treatment initiation. Evaluations included comprehensive eye examination, visual acuity, dilated fundoscopic examination, optical coherence tomography (OCT) of the macula and nerve fiber layer, and Humphrey visual field testing. RESULTS Twenty-six (62% male) of 45 patients were included. Median age at treatment was 15 (range 2-23) years. Plexiform neurofibromas were the most common indication for MEKi (n=22). Selumetinib was the most common MEKi (n=19, 77%), then trametinib (n=6, 23%), and mirdametinib (n=1, 4%). Only two patients had to switch to different MEKi. Patients were followed for a mean of 413-days after treatment initiation (range 103-1122 days) for an average of 3.85 ophthalmology exams per patient. No retinopathy was observed at each of the 3–6 month follow-ups. Around 15% of patients experienced dry eye symptoms with none requiring artificial tears for management. Seven patients had pre-existing optic neuropathy. No dose adjustments were needed due to OAEs. One patient’s visual acuity decreased temporarily but returned to baseline and the patient remains on MEKi. CONCLUSIONS Regular ophthalmologic assessments are crucial for NF1 patients undergoing MEKi treatment. Consensus guidelines on frequency of ophthalmologic screening during MEKi treatment are not well reported. In our cohort no patients had MEKAR at regular 3–6 month follow ups. In addition to baseline screening, future larger cohort studies are needed to confirm if decreasing the frequency of retinal exams is safe while on MEKi to inform future clinical screening guidelines for NF1 patients on MEKi.

Ocular adverse events associated with GLP-1 receptor agonists: a real-world study based on the FAERS database and network pharmacology

ABSTRACT Objective This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods. Methods FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms. Results Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs. Conclusion The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

ONS-5010 (bevacizumab-vikg) Safety and Efficacy in Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration.

This was a prospective multicenter, randomized, double-masked, active-controlled study, the aim of which was to demonstrate the efficacy and safety of intravitreal ONS-5010 (bevacizumab-vikg) in eyes with neovascular age-related macular degeneration (nAMD). This was a phase III trial on ONS-5010 (NORSE TWO). Treatment-naïve nAMD patients aged 50 years and older with a best-corrected distance visual acuity (BCVA) of 25 to 67 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and evidence of disease activity were included. Subjects randomized to ONS-5010 received monthly intravitreal doses of 1.25 mg of ONS-5010, bevacizumab-vikg (Outlook Therapeutics) for 12 months. Subjects randomized to ranibizumab received 0.50 mg of ranibizumab on days 0, 30, 60, 150, and 240 based on the PIER study dosing regimen. The primary end point was the proportion of subjects who gained ≥ 15 letters from baseline in BCVA at 11 months, and evaluating the safety and tolerability of intravitreal injections of ONS-5010 administered monthly from baseline to 12 months. One hundred thirteen subjects were included in the ONS-5010 group and 115 subjects were included in the ranibizumab group. Respectively, 41.7% and 23.1% of patients gained ≥ 15 letters (3 lines) of visual acuity, with a risk difference of 0.1859 [95% CI = 0.0442, 0.3086]; P = 0.0052. The change in BCVA from baseline to 11 months was found to be 11.2 ± 12.19 and 5.8 ± 14.80 ETDRS letters, respectively. The number of subjects gaining ≥ 5 and ≥ 10 letters and subjects losing < 15 letters was significantly higher in the ONS-5010 group. Similarly, subjects with a Snellen visual acuity equivalent of 20/200 (35 ETDRS letters) or worse at 11 months were significantly fewer in the ONS-5010 group. Only one subject in the ONS-5010 group had a study-related serious ocular adverse event (SAE), namely, elevated intraocular pressure. The most common adverse event in the ONS-5010 group was conjunctival hemorrhage (8.8%), and reduced visual acuity in the ranibizumab group (12.2%). In the prescribed treatment plan, ONS-5010 exhibited strong effectiveness in improving or stabilizing visual acuity and was also well tolerated. Bevacizumab and ranibizumab displayed a comparable safety profile. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Efficacy of intracameral mydriatics in pediatric lens surgery.

Introduction To evaluate the efficacy of intracameral administration of Mydrane® in children undergoing lens surgery. Methods We set up a single center prospective cohort trial including 40 consecutive patients between 8 weeks and 17 years old who were planned for lens surgery, including cataract, persistent fetal vasculature (PFV) or lens subluxation. We injected 0,1 ml of intracameral Mydrane at the beginning of surgery, no preoperative mydriatic eye drops were used. The aim of the study was to measure pupil size, and to monitor the evolution of the pupil size during surgery and the need for additional pupil expanding techniques. Results In 30 patients (75% (95%CI: 59 - 87%)), we did not need additional manipulations to obtain sufficient pupillary dilatation to perform the surgery and to implant an intraocular lens (IOL) following the bag-in-the-lens (BIL) technique. In the remaining 10 patients (25%), we saw an initiation of dilatation, but not to the required pupil diameter to continue the surgery without additional surgical maneuvers. The duration of surgery was significantly longer in the partial response group, reflecting the need for additional surgical steps. A significant relation between increase of pupillary diameter and age (P = 0.003), gender (P = 0.032) and horizontal corneal diameter (P < 0.001) could be shown. Even at baseline there is a larger pupil diameter in eyes with larger horizontal corneal diameters (p=0.039). No adverse events were observed during this study. Conclusion Intracameral administration of Mydrane resulted in some degree of dilatation in all eyes in this series, 75% of eyes did not need additional techniques to proceed with the surgery. Smaller pupils at baseline, younger age, male sex and small horizontal corneal diameter were related to a poorer response to Mydrane. The mydriasis persisted for the entire duration of the surgery, no ocular adverse events were observed during this study. This leads us to conclude that intracameral Mydrane is an effective and safe way to dilate the pupil in pediatric lens surgery.

Unraveling the Spectrum of Ocular Toxicity with Oxaliplatin: Clinical Feature Analysis of Cases and Pharmacovigilance Assessment of the US Food and Drug Administration Adverse Event Reporting System Database

Ocular adverse events (oAEs) are a class of adverse events associated with oxaliplatin that are realistically observed in real-world settings. Herein, we aim to describe the clinical characteristics of oAEs associated with oxaliplatin through a systematic review of case reports and to assess a potential safety signal. PubMed, Embase, and Cochrane Library databases were used to retrieve case reports. The global disproportionality study was performed leveraging the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2023. Bayesian information component (IC) and reporting odds ratio (ROR) were applied to identify and evaluate potential oAEs associated oxaliplatin. A total of 20 cases from the systematic case review (of 13 screened articles) were reported on oAEs associated with oxaliplatin, with ages between 26 and 76 years. Therein, 16 (84.2%) cases described loss of vision, and the remaining cases presented with bilateral blepharoptosis, papilledema, and optic disc swelling. Insights from the US Food and Drug Administration Adverse Event Reporting System database showed that oAEs accounted for 4.28% (n = 1194) of the overall oxaliplatin-related adverse event reports, of which 1140 (95.48%) had a serious outcome. The median (interquartile range) onset time of oAEs with oxaliplatin was day 1 (0-25; n = 649). Disproportionality analysis revealed that ocular injuries NEC (n = 28, ROR, 22.72; lower limit of the 95% 2-sided CI for IC, 3.12) was the most significant signals detected. Additionally, unexpected significant oAEs, including eyelid ptosis, eyelid edema, eye movement disorder, blepharospasm, periorbital edema, swelling of eyelid, ophthalmoplegia, retinal vein thrombosis, cataract nuclear, blindness cortical, cataract subcapsular, and lacrimation disorder, were also reported disproportionality. Our study systematically described the characteristics and outcomes of oxaliplatin-related ocular toxicity and also uncovered potential oAEs that were not disclosed in the package insert. Further prospective epidemiologic studies to validate these findings are warranted.

Ocular Adverse Events Following COVID-19 Infection: A Self-controlled Case Series Study from the Entire Korean Population

Ocular Adverse Events Following COVID-19 Infection: A Self-controlled Case Series Study from the Entire Korean Population

Efficacy and Safety of an Indian Bevacizumab BIOSimilar (BEVATAS) for Retinal Vein Occlusion (BIOS-RVO Study).

To evaluate the efficacy and safety of Bevatas®, an Indian bevacizumab biosimilar, in the management of both Central Retinal Vein Occlusion (CRVO) and Branch Retinal Vein Occlusion (BRVO) (BIOS-RVO). The BIOS-RVO study was a retrospective interventional study conducted at a single tertiary eye care facility in India. 154 treatment-naïve eyes with RVO (CRVO: 62 eyes; BRVO: 92 eyes) received intravitreal bevacizumab biosimilar (IVBb) therapy. Data on best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were collected at baseline and at 3, 6, and 12 months post-therapy. The average age of participants was approximately 55.99 (+12.56) years, with a nearly equal gender distribution (M:F = 49.4:50.6). Age differences between BRVO and CRVO groups were not significant (P=0.501), but gender distribution varied significantly (P=0.035), with more males in the CRVO group. Significant improvements in BCVA were observed in both CRVO and BRVO groups at 3 months, 6 months, and 1 year compared to baseline (P<0.001). Both groups showed significant reductions in CMT throughout the follow-up period (P<0.001). The mean number of injections was higher in the CRVO group (5.27[±1.45]) compared to the BRVO group (4.27 [±1.28]) (P<0.001). Significant IOP increases were observed at 1 month (P<0.001) and 6 months (P<0.001) in both BRVO and CRVO groups, although not clinically significant. Safety analysis revealed no additional ocular or systemic adverse events during the study period. The BIOS-RVO study demonstrates that Bevatas is an effective and safe treatment option for both CRVO and BRVO. These findings support the use of Bevatas as a cost-effective alternative to branded anti-VEGF agents, particularly in resource-limited settings.

Immune-mediated meibomian gland dysfunction and dry eye disease related to trastuzumab emtansine chemotherapy in HER2 breast cancer: A case report

One of the most commonly administered drugs for human epidermal growth factor receptor 2 (HER2) breast cancer is trastuzumab emtansine (TDM-1). Unfortunately, this drug causes ocular surface disease as an adverse effect. This case report describes the diagnosis and management of meibomian gland dysfunction (MGD) and dry eye related to TDM-1 in HER2 a breast cancer patient. Our patient was a 43-year-old female diagnosed with HER2 breast cancer with metastasis to the peritoneum and liver. After a cycle of TDM-1 chemotherapy, she complained of recurrent hordeolum, ocular discomfort, and blurry vision. We initially prescribed topical and oral medications and gradually combined them with hordeolum incision and drainage, in-office meibomian gland expression, and intense pulse light therapy to improve symptoms. Ocular adverse effects due to anticancer agents are not preventable. Ophthalmologists must be aware of them and instigate needed therapy to ensure patients’ compliance with cancer treatment and improve quality of life.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema

ObjectiveTo investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME).MethodsForty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 μm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity.ResultsOne-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed.ConclusionThe SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME.Clinical Trial Number (CAAE)22969019.4.0000.5440.

Preliminary antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery in primary open-angle glaucoma.

To investigate the antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery (MIGS). Human trabecular meshwork (TM) cells were treated with different concentrations of adrenaline (0%, 0.0005%, 0.01%), and we measured the effects on contractility, cell viability and the expression of key cell cycle and fibrosis genes. Adrenaline 0.05% was also injected intracamerally in five primary open-angle glaucoma patients undergoing iStent inject or MINIject surgery combined with phacoemulsification. All patients were assessed for ocular and systemic adverse reactions, including the effects on intraoperative pupil size, preoperative and postoperative visual acuity, intraocular pressure, and anterior segment OCT results. Adrenaline significantly reduced the contractility of TM cells in a dose-dependent manner (87.8%, 80.6%, 7.9% matrix contraction with adrenaline 0%, 0.0005%, 0.01%, respectively). Adrenaline did not exhibit any significant cytotoxicity even at high concentrations (P > 0.05). Adrenaline 0.01% significantly downregulated the expression of key cell cycle genes in the G2 and M phases, and also decreased the expression of MRTFB and ACTA2 genes (P < 0.05). Intracameral injections of adrenaline 0.05% in the five MIGS patients did not result in any ocular or systemic adverse effects. We recommend intracameral injections of adrenaline 0.05% as a cheap and safe drug to be used before MIGS insertion. Adrenaline decreases the risk of bleeding from the trabecular meshwork and also exhibits antifibrotic effects by arresting the cell cycle, thereby increasing the postoperative success rates in MIGS. What is known Fibrosis is the main cause of surgical failure in minimally invasive glaucoma surgery (MIGS). Mitomycin-C and 5-fluorouracil are too toxic to be used inside the eye. What is new Adrenaline reduced the contractility of trabecular meshwork cells and inhibited the expression of key cell cycle genes and fibrosis genes, without significant cytotoxicity. Intracameral injection of adrenaline 0.05% did not result in any ocular or systemic adverse reactions in MIGS patients.

Ocular and Periocular Tattoo Adverse Effects: A Review.

Ocular and periocular tattoos, involving ink application to the eyeball or surrounding skin, have gained popularity as forms of self-expression. However, this trend raises significant concerns about potential complications that can adversely affect ocular health and esthetics. Awareness of these risks is crucial for both patients and practitioners. A comprehensive literature review was conducted, focusing on studies discussing complications related to ocular and periocular tattooing. Relevant studies were identified through the MEDLINE, PubMed, and Ovid databases. The reviewed papers were evaluated based on study design, including blinding, sample size, control use, randomization, and objective endpoints, and classified according to the Oxford Center for Evidence-Based Medicine evidence hierarchy. The review identified a wide range of complications, including immediate issues like bleeding, infections (conjunctivitis, endophthalmitis), and allergic reactions. Delayed reactions included granuloma formation, often requiring further treatment. The most serious risk identified was potential visual impairment due to improper technique or ink placement. With the growing trend in ocular and periocular tattooing, there is an urgent need for increased awareness of associated risks. It is crucial to ensure that only qualified professionals perform these procedures, emphasizing the importance of understanding ocular anatomy. Developing strict regulatory guidelines and prioritizing research on the long-term effects of these tattoos are essential for patient safety. A collaborative approach among healthcare providers, regulatory bodies, and educational institutions is needed to mitigate risks and promote best practices in cosmetic tattooing.

Exposure–response relationships of mirvetuximab soravtansine in patients with folate receptor‐α‐positive ovarian cancer: Justification of therapeutic dose regimen

AimsThis study aimed to investigate exposure–response (ER) relationships in efficacy and safety for mirvetuximab soravtansine (MIRV) which is a first‐in‐class antibody–drug conjugate approved for the treatment of folate receptor‐α‐positive platinum‐resistant ovarian cancer.MethodsMIRV was characterized in 4 clinical studies. Exposure metrics for MIRV, its payload and a metabolite were derived from a population pharmacokinetic model. Efficacy was analysed in MIRV‐treated patients (n = 215) in a recent confirmatory, randomized, chemotherapy‐controlled MIRASOL trial and safety was evaluated in patients pooled across all 4 clinical studies (n = 757).ResultsIn the MIRASOL trial (NCT04209855), MIRV demonstrated significant benefit over chemotherapy in progression‐free survival (PFS), objective response rate (ORR) and overall survival (OS). The most common adverse events (AEs) included ocular disorders, peripheral neuropathy and pneumonitis. For PFS, ORR and OS, the trough concentration of MIRV was the predictor consistently found in ER models for efficacy. In contrast, for ocular AEs (as well as the time to onset of ocular AEs) and peripheral neuropathy, the area under the concentration–time curve (AUC) of MIRV was identified as the exposure metric in ER models for safety. No exposure parameters were found to correlate with pneumonitis. Covariates in all models did not show clinically meaningful impact on efficacy or safety. Logistic regression models for ORR and ocular AEs based on AUC of MIRV were used to justify the clinical dose regimen approved for MIRV.ConclusionThe trough concentration of MIRV correlated with efficacy whereas the AUC of MIRV was associated with major AEs. The ER relationships supported the selected therapeutic dose regimen.

Assessing the awareness and knowledge of the adverse ocular side effects associated with oral contraceptives among women between the ages of 16 and 40 in Benin-city, Edo state, Nigeria

PurposeOral contraceptives are routinely used by women, because they are effective birth control methods, but few women are aware of their adverse ocular side effects. This study was carried out to determine the level of awareness and knowledge of the adverse ocular side effects associated with oral contraceptive use among women in Benin-City, Edo State, Nigeria. MethodThis was a cross-sectional study conducted over an eight-month period from February 2023 to September 2023, including 402 women (n = 402). The study employed both self-administered online and printed questionnaires. ResultsThe mean age of the participants was 27.76 ± 7.03. A total of 196 had tertiary education, 131 had secondary education and 75 had no educational background. Two-hundred thirty-seven participants were users of oral contraceptives, while 165 had never used them. Of the participants that were users of oral contraceptives, 44 had previously experienced visual problems as a side. The study results reveal that 289 participants (71.9%) were not aware of the potential adverse effects of oral contraceptives, while only 82 participants (20.4%) were aware. ConclusionThe results of this study show that there is poor awareness of the side effects of oral contraceptives, more specifically, the adverse effects on the eyes. It is recommended that more public health awareness campaigns be initiated, with the goal of accurately educating women about the ocular pathologic risks associated with oral contraceptives. Furthermore, healthcare workers should effectively communicate the risks associated with oral contraceptives to their patients. This can help women looking for contraception options make informed decisions about using oral contraceptives.

Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration.

Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT®PBM treatment device in patients with dAMD. The EYE-LIGHT® device employs two wavelengths, 590nm (yellow) and 630nm (red), in both continuous and pulsed modes. Patients over 50years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month. This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013). These preliminary results indicate that PBM treatment using the EYE-LIGHT® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment's short-term efficacy. ClinicalTrials.gov identifier NCT06046118.

Two-year efficacy and safety of different anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: a network meta-analysis of randomized controlled trials.

To compare the 2-year efficacy and safety of various anti-vascular endothelial growth factor (VEGF) regimens for neovascular age-related macular degeneration (nAMD). A comprehensive search was performed on multiple electronic databases up to April 2023 and updated in June 2024, to identify relevant randomized controlled trials (RCTs). Key outcomes included the proportion of patients achieving a vision gain of ≥15 letters and maintaining stable vision (loss of <15 letters) in best-corrected visual acuity (BCVA), changes in mean BCVA from baseline, serious ocular adverse events (SAEs), adverse events leading to treatment discontinuation and any cause of death at 2 years. Nineteen trials with 12,654 patients and 25 treatment regimens were analyzed in the study. All anti-VEGF regimens showed superior efficacy compared to sham therapy. Specifically, faricimab 6 mg (4+up to Q16W) and ranibizumab 0.5 mg (2-week T&E) displayed top-level effect in vision gain. Bevacizumab 1.25 mg (2-week T&E) and aflibercept 2 mg (2-week T&E) demonstrated the most stable vision outcomes. Bevacizumab 1.25 mg (2-week T&E) and ranibizumab 0.5 mg (2-week T&E) exhibited the most pronounced mean BCVA improvement. Compared to sham therapy, the risk of SAEs was significantly higher for brolucizumab 6 mg (3 + Q12W/ Q8W) (RR = 6.04, 95% CI: 1.30-28.02) and PDS 100 mg/ml (Q24W) (RR = 10.95, 95% CI: 2.14-56.02), but not for other anti-VEGF regimens. Ranibizumab 0.5 mg (2-week T&E) emerges as a potentially optimal regimen for nAMD over a 2-year period. Future studies need to consider the impact of baseline characteristics on treatment outcomes.

Bedside bilateral sequential intravitreal anti-VEGF injections for retinopathy of prematurity.

To evaluate the outcome and ocular adverse events of bedside bilateral sequential intravitreal anti-vascular endothelial growth factor injections for retinopathy of prematurity (ROP) (BBSIR). This retrospective interventional study included infants who received BBSIR with a follow-up of at least 1 month. Clinical history, intravitreal injection details, indications, intraoperative and postoperative ocular adverse events, and outcomes were analyzed. The study cohort included 192 babies (384 eyes) spread over 9 years. The mean gestational age was 30.2 ± 2.6 weeks (28.8-34.1), and the birth weight was 1098.11 ± 271.65 g (650-2000). The indications for BBSIR were as follows: 73.4% (n = 141 infants) were too sick to transfer to an ophthalmic unit, 10.9% (n = 21 infants) due to the parents' inconvenience of traveling to the ophthalmic center, and 15. 6% (n = 30 infants) due to both reasons. The injections were given by an ROP specialist/ROP-trained ophthalmologist after due parental consent, considering each eye as a fresh eye with separate scrubbing and draping. Light from the head-worn indirect ophthalmoscope served as the source of illumination. The retinopathy was regressing/regressed in 92.4% of babies until the last follow-up. The major ocular complication was cataract in 2 eyes (0.5%). There was no incidence of endophthalmitis till last follow-up (median 5.7 months). As per this study, BBSIR was observed to be effective and safe if given by those fully trained in the management of ROP. Though the rate of complications like cataract is small, they can pose management challenges and impact vision in a growing child.

Brolucizumab in patients with neovascular age-related macular degeneration: Real-life outcomes from a tertiary care eye hospital.

To report real-world clinical evidence of brolucizumab in treating neovascular age-related macular degeneration (nAMD). This study included 37 eyes with nAMD treated with intravitreal injections of brolucizumab. The main outcomes were best corrected visual acuity (BCVA) changes, central retinal thickness (CRT), and serious ocular adverse events. Intraretinal fluid (IRF) and subretinal fluid (SRF), subretinal hyperreflective material (SHRM), pigment epithelial detachments (PEDs), hyperreflective foci, macular atrophy, and retinal pigment epithelial tears were evaluated. The mean BCVA of all patients showed a post-treatment value of 0.47 ± 0.33 log of minimum angle of resolution (LogMAR), compared to a baseline measure of 0.50 ± 0.28 LogMAR (P = 0.372). For treatment-naïve patients, a non-statistically significant improvement in BCVA was observed (P = 0.116). Both treatment-naive patients and the entire patient cohort exhibited a statistically significant improvement in the mean CRT after injections. Majority of patients exhibited improvements in optical coherence tomography findings, specifically in the resolution of IRF, SRF, SHRM, and PEDs. Four eyes experienced ocular adverse events in the form of intraocular inflammation. Brolucizumab did not yield a substantial improvement in BCVA, but it exhibited efficacy in reducing CRT in the entire study population and treatment-naive patients with nAMD. Our study identified intraocular inflammation as a significant adverse event with brolucizumab. Thus, precise patient selection, education, and vigilant inflammation monitoring are crucial for patients undergoing this treatment.

Bio-spectroscopic investigation linking changes of retinal structure with short-term administration of Amiodarone and revealing the ameliorative effect of vitamin E supplementation

Long term use of Amiodarone (AMIO) is associated with the development of ocular adverse effects. This study investigates the short term effects, and the ameliorative consequence of vitamin E on retinal changes that were associated with administration of AMIO. This is accomplished by investigating both retinal structural and conformational characteristics using Fourier transform infrared spectroscopy (FTIR) and Fundus examination. Three groups of healthy rabbits of both sexes were used; the first group served as control. The second group was orally treated with AMIO (160 mg /kg body weight) in a daily basis for two weeks. The last group orally received AMIO as the second group for two weeks then, oral administration of vitamin E (100 mg/kg body weight) for another two weeks as well. FTIR results revealed significant structural and conformational changes in retinal tissue constituents that include lipids and proteins due to AMIO administration. AMIO treatment was associated with fluctuated changes (increased/decreased) in the band position and bandwidth of NH, OH, and CH bonds. This was concomitant with changes in the percentage of retinal protein constituents in particularly α-helix and Turns. AMIO facilitates the formation of intra-molecular hydrogen bonding and turned retinal lipids to be more disordered structure. In conclusion, the obtained FTIR data together with principal component analysis provide evidence that administration of vitamin E following the treatment with AMIO can ameliorate these retinal changes and, these biophysical changes are too early to be detected by Fundus examination.

Ocular Adverse Events After Influenza Vaccination in Older Adults: Self-Controlled Case Series Using a Large Database in Japan

ABSTRACT Background To clarify the risk of adverse ocular events following influenza vaccination. Methods This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0–56 days after vaccination) compared to the control period. Results A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis. Conclusions This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events. Abbreviation HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series

Effects of High Temperature and High Humidity on the Degree of Ocular Damage Caused by 60 GHz Millimeter Wave Exposure.

Millimeter waves (MMW) are pervasive in society; however, studies on the biological effects of MMW exposure are usually performed in laboratory settings not reflecting global environmental diversity. We investigated the effects of a 6-min exposure to 60 GHz MMW (wavelength, 5.0 mm) at incident power densities of 200 and 300 mW cm-2 in eyes (exposed right eyes vs. unexposed left eyes) under various ambient temperature/relative humidity environments (24 °C/50%, 45 °C/20%, and 45 °C/80%) using an in vivo rabbit model. Correlations were examined with adverse ocular events, including corneal epithelial damage (assessed using fluorescein staining), corneal opacity (evaluated by slit-lamp microscopy), and corneal thickness (measured via optical coherence tomography). Our findings indicate that higher temperatures and humidity tend to exacerbate MMW-induced ocular damage, albeit not significantly in the present study. Further research with a larger sample size is warranted. Incident power density emerged as a factor that was directly linked to the ocular damage threshold. High ambient temperature and humidity tended to exacerbate ocular damage from MMW exposure, although the effect was secondary. Ocular damage in a high-temperature (45 °C), high-humidity (80%) environment was increased to the same extent as that by incident power density increased by approximately 100 mW cm-2 in an ocular damage model in a standard environment (24 °C, 50%). In a high-humidity environment, the internal ocular tissue temperature increased at a high ambient temperature of 45 °C, suggesting that the eyeball may respond differently compared to other tissues.