Treatment of progressive myopia with 0.01% Atropine in children and adolescents: an Italian 4-year follow-up study.

Purpose: To assess the effectiveness of atropine 0.01% in slowing the progression of myopia in young patients. Methods: 2,387 patients with progressive myopia (more than -0.50 spherical diopters increased in the last year) were enrolled. They received, every evening, one drop of atropine 0.01% in each eye. Refraction was then measured at baseline (T0) and once a year (T1, T2, T3, T4) for a 4-years follow-up period, and compared with a non-treated control group. Results: A reduction in the myopic progression was observed in the treated group respect to the control one. The average spherical refraction after 4 years increased by 27.06% in the treated group versus 241% of the control one. The difference in spherical increase between the two groups respect to time 0 was appreciable already at the first control, (T1 -T0, -0.21D vs. -1D) and continued to increase for all the 4-years follow-up period (T2-T0, -0.38D vs. -1.91D;T3-T0, -0.52D vs. -2.74D; T4-T0, -0.73D vs. -3.63D, respectively). It was always significant (P<0.01). Compared to the previous year, the average spherical increase was quite stable in the two groups (0.17 vs. 0.87, respectively). No significant tachyphylaxis or adverse effects were observed throughout the examination period. Conclusions: 0.01% atropine was effective in slowing the progression of myopia in the treated group vs. control one. The clinical effect was noticeable already from the first control, and continued for all the observation period. The results of this study agree with those already reported in literature, and confirm the validity of this treatment.

Retinal Function in Young Adults Following Topical Application of Levodopa to the Eye.

Purpose: Levodopa has been investigated as a therapeutic solution for ocular disorders involving dysregulation of the dopaminergic system, especially in the context of myopia. However, given the critical role dopamine plays in normal vision, this phase I trial examined whether levodopa/carbidopa eye drops induce any regional changes in retinal structure and function. Methods: Twenty-nine healthy male subjects 18 to 30 years of age were randomly assigned to receive either a low (1.4/0.34 µmoles/day, n = 14) or high (2.7/0.68 µmoles/day, n = 15) dose of levodopa/carbidopa eye drops in 1 eye for 28 consecutive days. A placebo solution was applied to all fellow eyes. Measures included visual acuity, regional frequency doubling perimetry, regional multifocal electroretinogram (mfERG) and optical coherence tomography (retinal thickness). Outcome measures were undertaken at baseline, end-of-treatment (4 weeks), and at a follow-up (4 months post-treatment). Results: For low dose treated eyes, regional analysis showed a small, statistically significant change in mfERG recordings (increase in ring 5 amplitude in low dose treated eyes, P < 0.05) and the retinal thickness map (localized retinal thinning in low dose treated eyes, P < 0.05). These changes were not clinically significant. No significant changes were observed in high dose treated eyes. Pharmacokinetic analysis (rabbits) demonstrated that levodopa was not detectable within blood and peaked within the eye at 15 to 30 minutes (and eliminated within 4 hours). Conclusions: No clinically significant effects of levodopa/carbidopa eye drops were found with regard to normal retinal structure and function following short-term use. Translational Relevance: This study further demonstrates the safety of topical levodopa, which may support its use in the treatment of ocular disorders in which the dopamine system is dysregulated.

Comparison of the effectiveness of 0.5% and 0.25% proparacaine hydrochloride eye drops as topical anesthetics in routine ocular investigations and procedures.

Aim: To compare the effectiveness of 0.5% and 0.25% proparacaine eye drops in providing topical anesthesia for routine ocular procedures. Methodology: 137 patients (274 eyes) were included in this study. They were categorized into two groups. Group A patients received 0.5% and Group B received 0.25% proparacaine drops. A single surgeon performed all the procedures. Intraprocedural and postprocedural pain scores, surgeon comfort, supplemental anesthesia, and vital parameters, were noted. Results: The mean age of the participants was 69.42 years (±12.05). An equal number of procedures were performed (n = 30) for applanation tonometry, lacrimal sac syringing, and A-scan biometry. The other procedures performed were removal of the conjunctiva (n = 5) and corneal foreign bodies (n = 16 per group), corneal scraping (n = 8 per group), and corneal suture removal (n = 18 per group).The mean visual analog pain score during the procedure was 6.9663 in Group A and 8.0803 in Group B (P = 0.66). The mean postprocedural pain score was not significant (P = 0.21). None of the patients required any additional anesthesia during or after the procedure. The average surgeon's experience was 0.152±0.507 in Group A and 0.111±0.402 in Group B (P = 0.07).In Group A, 133 of 137 patients (97.08%), and in Group B, 132 out of 137 patients (96.35%) preferred to use the same anesthetic for future procedures. None of the patients experienced a vasovagal attack or any change in vital parameters. Discussion: The present study aimed to establish equivalence between two concentrations of proparacaine hydrochloride in which false positive and false negative errors were expected. This is the inherent challenge in the equivalence and inferiority trials. To mitigate these risks, the present study was carefully designed with specific statistical methods, sample size calculation, and rigorous methodology. Nevertheless, it is crucial to recognize that the risk of false positive errors remains, and the results should be interpreted with this in mind. Conclusion: These findings indicated that 0.25% proparacaine is a viable alternative to the standard 0.5% concentration in routine ophthalmic procedures, with the potential for improved patient comfort.

The effects of topical latanoprost 0.005% treatment on microvascular changes in the optic nerve head and macula.

PURPOSE: This prospective study aimed to assess the impact of topical latanoprost 0.005% treatment on the microvasculature of the macula and optic nerve head (ONH) in primary open-angle glaucoma (POAG). METHODS: Fifty-seven eyes of 31 subjects were enrolled. ONH whole-image (wiVD), peripapillary (ppVD), and macular vascular density (VD) parameters were measured using optical coherence tomography angiography before treatment, at the 1st month, and at the 3rd month of treatment. RESULTS: There was a significant reduction in IOP post treatment, with a decrease of 17.0 ± 2.3 mmHg in the 1st month and 16.3 ± 2.5 mmHg in the 3rd month (P < 0.001 for both). ONH wiVD and ppVD significantly increased at the post-treatment 1st month (P = 0.001 for both) but decreased by the 3rd month, returning to baseline levels (P < 0.001 for both), indicating a return to pre-treatment levels (P > 0.05 for both). Similarly, macular wiVD and perifoveolar VD (pefVD) increased significantly at the 1st month (P = 0.013 and P < 0.001, respectively) but returned to baseline by the 3rd month (P < 0.001 for both). No significant difference was observed between before-treatment and post-treatment 3rd month regarding the macular wiVD and pefVD (P > 0.05 for both). Deep capillary plexus and foveal avascular zone parameters did not change during follow-up (P > 0.05 for both). CONCLUSION: The initial increase in ONH and peripapillary VD, as well as macular VD, is attributed to the acute reduction in IOP from topical latanoprost 0.005%. However, the diminishment of sustained differences by the 3rd month indicates adaptation of the ONH and retinal microvasculature to decreased IOP through compensatory mechanisms.

Tolerability of Diquas LX on tear film and meibomian glands findings in a real clinical scenario.

Long-acting diquafosol ophthalmic solution (DQS-LX) has significant advantages regarding patient adherence owing to the reduced frequency of required eye drops; however, some patients prefer conventional diquafosol ophthalmic solution (DQS) over DQS-LX. Herein, to clarify the characteristics of patients according to their preference for ophthalmic solutions, dry eye (DE) and meibomian gland (MG) findings were retrospectively investigated. This study enrolled 341 patients with DE (mean age, 62.1 ± 11.7 years) treated at the Itoh Clinic between November 8, 2022, and July 31, 2023, who switched from DQS to DQS-LX. Patients were divided into two groups: those who continued DQS-LX administration (DQS-LX group) and those who wished to revert to conventional DQS (DQS group). Data regarding subjective symptoms assessed using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear film breakup time (BUT), tear meniscus height (TMH), corneal and conjunctival fluorescein staining (CFS), conjunctival hyperemia/papilla, meiboscore, plugging, vascularity, meibum grade, and Schirmer's score at the time of DQS-LX switch were evaluated. Of the 341 patients, 31 (9.1%) wished to revert to conventional DQS. In total, 16 eyes of 16 patients in the DQS group and 32 eyes of 32 patients in the DQS-LX group-for whom complete data were available-were included in the analysis. The DQS-LX group had higher SPEED scores, lower TMHs (P < 0.001, respectively), shorter FBUTs, greater CFS findings, larger meibum grades, lower Schirmer scores, and more pluggings compared with the DQS group (P = 0.005, 0.001, 0.001, 0.046, 0.003, respectively). Meiboscores and vascularity did not differ significantly between the two groups (P = 0.73 and 0.39, respectively). In conclusion, patients with low tear film volume and DE complicated by moderate or severe meibomian gland dysfunction (MGD) preferred DQS-LX, while those with allergic findings preferred conventional DQS.

Development of a Temperature and pH Dual-Sensitive In-Situ Gel for Treating Allergic Conjunctivitis.

The purpose of this study was to improve the efficacy of olopatadine hydrochloride (OT) in treating allergic conjunctivitis (AC). To achieve this goal, we developed an eye formulation without antimicrobial agents using a temperature-pH dual-sensitive in situ gel technology combined with heat sterilization. Various types of carbomers were evaluated and their optimal doses determined. The prescription containing poloxamer 407 (P407) and poloxamer 188 (P188) was optimized using central composite design for response surface methodology (CCD-RSM). The final optimized dual-sensitive in situ gel (TP-gel) consisted of 0.1% olopatadine hydrochloride, 18.80% P407, 0.40% P188, 0.30% Pemulen™TR-1(TR-1), 4.0% mannitol, and 0.08% Tri(hydroxymethyl)aminomethane(Tris).Sterilization was performed at a temperature of 121℃ for a duration of 20 min. Experimental results showed that TP-gel had good safety profile and remained on the ocular surface for approximately (65.83 ± 8.79) minutes, which is four times longer than eye drops. The expression levels of IL-13, IL-17, and OVA-IgE in mouse ocular tissues with allergic conjunctivitis treated with TP-gel were significantly reduced. This suggests that TP-gel has the potential to be an effective treatment method for allergic conjunctivitis.

Elucidating acceptance and clinical indications to support the rational design of drug-eluting contact lenses.

The advent of drug-eluting contact lenses (DECLs) has opened up new avenues for the treatment of eye diseases. DECLs is expected to partially overcome the shortcomings of eye drops due to single-dose packaging, accurate dosing, prolonged drug elution behavior, and simplified dosing procedures. Currently, a significant proportion of the DECLs design effort has been directed towards enhancing the compatibility of contact lenses with drugs. The appropriate elution time for the drug remains unclear. Additionally, it is ambiguous for which ophthalmic diseases DECLs offers the greatest therapeutic advantage. To rationally design DECLs in practice, it is necessary to understand the acceptance of DECLs by patients and practitioners and to clarify the indications for DECLs. This review will first focus on the acceptance of DECLs by different patients and practitioners and discuss the factors that influence its acceptance. Secondly, this review presents an overview of the current effectiveness of DECLs treatments in animals and in the clinical phase, with a particular focus on the suitability of DECLs for the treatment of ophthalmic diseases. Overall, patients and practitioners expressed positive attitudes towards DECLs. However, this is related to factors such as DECLs' treatment cycle, safety, and price. In addition, DECLs has good application prospects for ocular wound healing, postoperative management, and treatment of contact lenses-related complications. Furthermore, chronic diseases such as glaucoma that necessitate long-term medication and intraocular diseases that require implants or injections represent additional potential applications for DECLs. It is hoped that this review will facilitate a deeper understanding of DECLs acceptance and indications, thereby supporting the rational design of DECLs. At the same time, this review provides a reference for the design of other drug-device combination products.

Lubratex eye ointment with polyethylene cover significantly reduces corneal abrasion in ICU patients: a randomized controlled trial.

Corneal abrasion is a frequent complication in critically ill, intubated patients, potentially leading to visual impairment. This study compares the efficacy of three ocular care methods in preventing corneal abrasion among this vulnerable population. We conducted a randomized controlled trial involving 156 intubated adult patients admitted to the ICU. Participants were randomly allocated to one of three intervention groups (n = 52 per group): (1) polyethylene cover only, (2) polyethylene cover with artificial tear drops, and (3) polyethylene cover with Lubratex eye ointment. One eye per patient was randomly assigned as the control, receiving standard ICU eye care. Daily assessments over five days included a standardized dryness and corneal abrasion checklist, graded strip evaluation of eye dryness, and documentation of corneal abrasion incidence. Data were analyzed using descriptive and inferential statistics (SPSS-18). The incidence of corneal abrasion was significantly lower in the group receiving polyethylene cover with Lubratex eye ointment (4%) compared to the polyethylene cover with artificial tears group (36%, p < 0.001) and the polyethylene cover only group (60%, p < 0.001). The combined application of a polyethylene cover with Lubratex eye ointment effectively prevents corneal abrasion in intubated ICU patients. This method demonstrates superior efficacy compared to polyethylene covers used alone or with artificial tears. We recommend its implementation as standard practice for corneal abrasion prophylaxis in this high-risk population.Trial Registration. This study is registered with the Iranian Registry of Clinical Trials (IRCT201506294736N8) and can be accessed at www.IRCT.ir .

[Effectiveness of the Eye Care Protocol in the Intensive Care Unit Patients: A Randomized Controlled Trial].

PURPOSE: This study investigated the effects of an eye care protocol (ECP) on patients in the intensive care unit (ICU). METHODS: This study utilized a randomized controlled design. Participants were patients who met the inclusion criteria and were admitted to the ICU (36 in the experimental group and 38 in the control group). The experimental group received an ECP, while the control group received standard eye care, starting the day after admission, for a duration of 10 days. The ECP classifies the degree of eyelid obstruction into three stages based on the degree of exposure to the lower eyelid conjunctiva and cornea. The protocol included cleansing with normal saline gauze, administering eye drops, applying silicone and polyurethane films, and recommending consultation with an ophthalmologist if necessary. The effectiveness of ECP was assessed by analyzing tear volume, hyperemia, chemosis, and eye discharge. Data analysis was conducted using SPSS 27.0, employing the Mann-Whitney U-test and generalized estimating equations. RESULTS: On day 5, the experimental group demonstrated a significant increase in tear volume in both eyes compared with the control group. However, no statistically significant differences were observed in the incidence of hyperemia, chemosis, and eye discharge on days 5 and 10 of the intervention. CONCLUSION: The application of the ECP in this study increased tear volume in ICU patients, thereby reducing discomfort caused by dry eyes. It has the potential to prevent complications such as damage to the surface of the eyeball resulting from decreased tear volume.

Preventative Effect of Topical Rebamipide Against Corneal Epithelium Disorders Caused by Diclofenac Sodium.

Purpose: This study aimed to investigate the relationship between diclofenac sodium ophthalmic solution (DFNa) and corneal epithelial cell damage and to evaluate the preventive effect of rebamipide (RBM) on it. Methods: DFNa, DFNa/preservative-free (PF), or 0.5% chlorobutanol (CB) solution was instilled into the conjunctival sac of a normal rabbit eye, and corneal resistance measurement (using a corneal resistance device [CRD]) was performed 120 min after the end of instillation. Then, fluorescent staining (FL), corneal tissue staining (hematoxylin and eosin [H&E]), and immunostaining (zona occlusion-1) were performed (RBM-untreated group). However, RBM was instilled into the eyes of another group of normal rabbits, followed by each of the solutions; 120 min after the end of instillation, all evaluations were performed for this group (RBM treatment group). Results: Using the CRD method, in the RBM-untreated group, corneal resistance (CR; %) was found to be significantly reduced in DFNa (79.9 ± 19.4%), DFNa/PF (89.1 ± 17.3%), and 0.5% CB (83.8 ± 10.6%). In addition, DFNa and 0.5% CB solutions showed positive staining in the FL staining method. In the H&E staining method, some clear voids were observed in the outermost layer of the cornea using DFNa and 0.5% CB solutions. However, corneal epithelial damage was suppressed in the RBM treatment group. ZO-1 immunostaining in DFNa and 0.5% CB solutions revealed discontinuous localization of ZO-1 at the cell periphery. Conclusions: RBM eye drops were effective in preventing corneal epithelial damage caused by DFNa eye drops, and CB was considered to be the main causative agent of this damage.

Comparison of the effects of 0.05% topical cyclosporine A versus 0.1% topical cyclosporine A on recurrence and clinical parameters following pterygium surgery.

Background/aim: To compare the efficacy of topical 0.05% cyclosporine A (CsA) and 0.1% topical cyclosporine A (CsA) over a 6-month period following pterygium surgery, specifically evaluating their effects on postoperative recurrence and clinical parameters. Material and methods: This clinical study enrolled 245 patients with pterygium who underwent surgery using the conjunctival autograft technique with mitomycin C (MMC) were enrolled. Participants were divided into three groups: Group 1 (0.05% CsA) (n = 80), Group 2 (0.1% CsA) (n = 80), and a control group (n = 85). They were examined at postoperative first day, first week, first month and sixth month. The examination included best corrected visual acuity (BCVA), intraocular pressure (IOP), presence of inflammation, and ptergium recurrence, all of which were compared across the groups. Results: The mean age of the patients was 63.22 ± 9.39 years, with 53.3% male and 46.7% female. The three groups were similar in terms of demographic characteristics and pterygium size. Inflammation in surgical area significantly regressed in all groups at 6 months postoperatively (p < 0.05). Inflammation in the first and sixth months was not different between the groups (p = 0.118, p = 0.580, and p = 0.435, respectively). The recurrence rate was not different between groups (p = 0.890). There was no statistically significant difference between groups regarding IOP (p = 0.818). A significant increase in BCVA after surgery was observed in three groups compared to preoperative levels (p < 0.05). Conclusion: This study showed that there was no difference between the efficacy of 6 month topical 0.05% CsA and 0.1% CsA application after pterygium surgery with the conjunctival autograft technique with MMC on postoperative outcomes. Including postoperative recurrence, IOP changes, BCVA changes and surgical area inflammation.

Pain perception during intravitreal injections is related to the timing of instilling anesthetic eyedrops.

PURPOSE: To evaluate the correlation between the timing of instilling anesthetic eyedrops prior to intravitreal injection and the patient's perception of pain associated with the injection. METHODS: A prospective observational study which included 192 eyes of 192 patients. Time interval between instillation of Oxybuprocaine-0.4% and Tetracaine-0.5% eyedrops upon checking-in and injection was measured and pain level was evaluated by the 101-point-Numeric Rating Scale. RESULTS: We found significant correlation between time interval from the first eyedrops to injection and injection related pain. The lowest pain score (11 ± 18) was found in the 11-15 min group, while the highest was found in the 0-6 min (26 ± 25) and in the > 35 min (31 ± 28) groups. The highest percentage of patients without pain was found in the 11-15 min (64%), followed by the 7-10 min (56%) and 16-20 min (47%) groups. 10% or 17% of the 0-6 min or > 35 min. groups, respectively, reported no pain. No patients in 11-15 min group reported severe pain versus 10% in the 0-6 min and 17% in the > 35 min groups. The highest percentage of patients with 'absent-to-mild' pain was in the 11-15 min (89%) and the 7-10 min (87%) compared to all other groups. CONCLUSIONS: Administration of first dose of anesthetic eyedrops within 11-15 min before intravitreal injection yields the lowest levels of injection-related pain, with 7-10 min being second best. Administration of eyedrops outside of this time-window results in higher pain levels avoidable with more attention to the timing issue.

Mathematical Models of Ocular Drug Delivery.

Drug delivery is an important factor for the success of ocular drug treatment. However, several physical, biochemical, and flow-related barriers limit drug exposure of anterior and posterior ocular target tissues during drug treatment via topical, subconjunctival, intravitreal, or systemic routes. Mathematical models encompass various barriers so that their joint influence on pharmacokinetics (PKs) can be simulated in an integrated fashion. The models are useful in predicting PKs and even pharmacodynamics (PDs) of administered drugs thereby fostering development of new drug molecules and drug delivery systems. Furthermore, the models are potentially useful in interspecies translation and probing of disease effects on PKs. In this review article, we introduce current modeling methods (noncompartmental analyses, compartmental and physiologically based PK models, and finite element models) in ocular PKs and related drug delivery. The roles of top-down models and bottom-up simulations are discussed. Furthermore, we present some future challenges, such as modeling of intra-tissue distribution, prediction of drug responses, quantitative systems pharmacology, and possibilities of artificial intelligence.

Effectiveness of cyclosporine nanoemulsion eye drops in patients with mild-to-moderate dry eyes: objective and subjective evaluation.

BACKGROUND: To compare and evaluate objective and subjective clinical parameters between 0.05% cyclosporine nanoemulsion (CsN) and 0.15% hyaluronic acid (HA) administration in patients with mild-to-moderate dry eyes. METHODS: In this prospective, randomized, double-masked, single-center, and placebo-controlled parallel study, patients with mild-to-moderate dry eyes were randomly allocated to be treated with 0.05% CsN or 0.15% HA twice daily. Patients were followed-up at 4, 8, and 12 weeks. Objective and subjective parameters were evaluated during each visit. RESULTS: A total of 35 patients were enrolled in this study. Compared with baseline, tear film break-up time and fluorescein staining scores at 4, 8, and 12 weeks significantly improved in the CsN group. However, the Schirmer I test showed no statistically significant change until week 12. Using the Symptom Assessment in Dry Eye (SANDE) score, both groups gradually showed significant improvement compared with baseline values. However, the Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) showed no statistically significant change during the treatment period. CONCLUSIONS: Both 0.05% CsN and 0.15% HA administration twice a day effectively improved the objective signs and subjective symptoms of patients with mild-to-moderate dry eyes. However, patients treated with 0.05% CsN experienced greater and faster improvement.

Safety and Tolerability of Anti-microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study.

PURPOSE: microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children. METHODS: This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability. FINDINGS: There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as "unrelated to study drug." IMPLICATIONS: SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. CLINICALTRIALS: gov identifier: NCT04928144.

Long-Term Safety and Efficacy Evaluation of Travoprost Intracameral Implant Based on Pooled Analyses from Two Phase III Trials.

AIM: The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: Subjects with OAG or OHT, on 0-3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12. RESULTS: A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study (p <  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study (p <  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased. CONCLUSION: The travoprost intracameral implant demonstrated robust IOP-lowering efficacy that was sustained and statistically non-inferior to timolol over the entire 12 months, resulting in a significant reduction in topical IOP-lowering medication use, with the majority of SE implant eyes remaining completely free of all topical IOP-lowering medications. In addition, the implant demonstrated a favorable safety and tolerability profile based on this pooled 12-month analysis of two pivotal trials. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03519386 (registered May 09, 2018) and NCT03868124 (registered March 08, 2019).

Safety and tolerability of pooled human immune globulins after topical ophthalmic administration in New Zealand White rabbits.

PURPOSE: To evaluate the safety and tolerability of pooled human immune globulins, Flebogamma® 5% DIF and Flebogamma® 10% DIF, administered by topical ophthalmic instillation to New Zealand White (NZW) rabbits. METHODS: Male NZW rabbits were used in this study. In the acute single dose tolerability study, rabbits (n = 12) received a single topical dose of Flebogamma® 5% DIF. In the two-week repeated-dose tolerability study, rabbits (n = 5 for each group) were administered either Flebogamma® 5% DIF or Flebogamma® 10% DIF by topical bilateral administration four times daily (q.i.d.) between 8 am and 6 pm for a period of two weeks. Full ophthalmic examinations were conducted to evaluate ocular tolerability at baseline, Day 7, and Day 14. RESULTS: In the acute single dose study, mild hyperaemia was observed in 1 out of 4 eyes at each 4 h and 24 h post-instillation of Flebogamma® 5% DIF. In the repeated dose study, no ocular signs were detected after q.i.d. topical instillation of Flebogamma® 5% DIF, while Flebogamma® 10% DIF resulted in mild hyperaemia in 8 out of 10 eyes on Day 7, and 5 out of 10 eyes on Day 14. No positive corneal fluorescein staining was detected. Schirmer tear test results were unremarkable. No other ocular signs were observed. Administration of immune globulins had no effect on intraocular pressure. CONCLUSIONS: Flebogamma® 5% DIF and Flebogamma® 10% DIF were well-tolerated by NZW rabbits following single and repeat dose topical ophthalmic administration, supporting the future development of topical pooled human immune globulins for the treatment of ocular surface disease.

Prefilled Ophthalmic syringes - New Possibilities in Terminal Sterilization.

In a joint study carried out by Gerresheimer, Sterigenics and Früh, it could be shown that also NO2 is well suited to terminally sterilize prefilled ophthalmic syringes. In detail 5 topics were addressed: (1) Compare EtO vs. NO2 penetration into the filled syringe; (2) Analyze gas ingress though 4 different plunger stoppers including silicone oil free and standard rubber plungers; (3) Scrutinize gas ingress through 2 different cap designs based on different elastomer properties; (4) Investigate gas permeation through COP plastic barrels compared to glass; (5) Check if the Tyvek®-layer has an influence on either sterilization.Depending on the needs a suitable sterilization method, packaging and syringe type can be suggested to customers.

Small Molecule Topical Ophthalmic Formulation Development-Data Driven Trends & Perspectives from Commercially Available Products in the US.

Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems.

Effects of combined intense pulsed light and cyclosporine 0.05% eyedrops in ocular surface matrix metalloproteinase-9 levels in patients with moderate-to-severe MGD.

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02 s to 3.12 ± 1.08 s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.