Therapeutic Effects of Lactoferrin in Ocular Diseases: From Dry Eye Disease to Infections

Lactoferrin is a naturally occurring iron-binding glycoprotein, produced and secreted by mucosal epithelial cells and neutrophils in various mammalian species, including humans. It is typically found in fluids like saliva, milk and tears, where it reaches the maximum concentration. Thanks to its unique anti-inflammatory, antioxidant and antimicrobial activities, topical application of lactoferrin plays a crucial role in the maintenance of a healthy ocular surface system. The present review aims to provide a comprehensive evaluation of the clinical applications of lactoferrin in ocular diseases. Besides the well-known antibacterial effect, novel interest has been rising towards its potential application in the field of dry eye and viral infections. A growing body of evidence supports the antimicrobial efficacy of lactoferrin, which is not limited to its iron-chelating properties but also depends on its capability to directly interact with pathogen particles while playing immunomodulatory effects. Nowadays, lactoferrin antiviral activity is of special interest, since lactoferrin-based eye drops could be adopted to treat/prevent the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which has conjunctivitis among its possible clinical manifestations. In the future, further data from randomized controlled studies are desirable to confirm the efficacy of lactoferrin in the wide range of ocular conditions where it can be used

Motor skills in children affected by strabismus

Objectives: To compare motor skills in patients with infantile strabismus and age and sex-matched control subjects aged 5–11 years. Methods: Motor performances were assessed by the Italian version of Developmental Coordination Disorder Questionnaire 2007 (DCDQ) in children with infantile strabismus and age and sex-matched control subjects. Patients affected by specific neurological, cognitive and behavioural disorders were excluded from the study. Results: There were 43 patients included in the study, 23 in the strabismus group (14 males, 9 females, mean age 7.5 ± 2.0 years) and 24 in the control group (14 males and 10 females, mean age 7.2 ± 1.7 years. The overall DCDQ score was significantly lower in children with strabismus compared with control subjects (58.7 ± 11.3 vs. 74.2 ± 1.5; P < 0.001). Children with strabismus and no stereopsis showed a lower DCDQ score compared with those with normal stereopsis (50.8 ± 9.5 vs. 67.3 ± 4.8; P < 0.001). Conclusion: Motor skills are reduced in children with strabismus compared with control subjects. Strabismus and lack of binocular vision are factors potentially contributing to developmental coordination disorder

Minimally invasive strabismus surgery (MISS) for inferior obliquus recession

PURPOSE: To present a novel, minimally invasive strabismus surgery (MISS) technique for inferior obliquus recessions. METHODS: Graded MISS inferior obliquus recessions were performed in 20 eyes of 15 patients by applying two small conjunctival cuts, one at the insertion of inferior obliquus and another where the scleral anchoring of the muscle occurred. RESULTS: The amount of recession was 12.2 +/- 2.3 mm (range 6 to 14 mm). The vertical deviation, which was measured in 25 degrees of adduction, decreased from preoperatively 12.8 degrees +/- 5.6 degrees to 2.7 degrees +/- 2.2 degrees (p 0.1). In one eye (2.5%) the two cuts had to be joined because of excessive bleeding. Binocular vision improved in eight patients, remained unchanged in six patients, and decreased from 30 to 60 arcsec in one patient (p > 0.1). Conjunctival and lid swelling were hardly visible on the first postoperative day in primary gaze position in 10/20 (50%) of eyes. Five of the eyes (25%) had mild and five (25%) moderate visibility of surgery. One patient out of 15 (7%) needed repeat surgery because of insufficient reduction of the sursoadduction within the first 6 months. The dose-effect relationship 6 months postoperatively for an accommodative near target at 25 degrees adduction was 0.83 degrees +/- 0.43 degrees per mm of recession. CONCLUSIONS: This study demonstrates that small-incision, minimal dissection inferior obliquus graded recessions are feasible and effective to improve ocular alignment in patients with strabismus sursoadductorius

Resuscitation of Severe Uncontrolled Hemorrhage 7.5% Sodium Chloride/6% Dextran 70 vs 0.9% Sodium Chloride

Objectives: Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Methods: Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. Results: One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 ± 20 mL/kg) and group III (31 ± 13 mL/kg) as compared with group I (5 ± 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. Conclusion: In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73625/1/j.1553-2712.2000.tb02060.x.pd

Biodegradable collagen matrix implant vs mitomycin-C as an adjuvant in trabeculectomy: a 24-month, randomized clinical trial

AIM: To verify the safety and efficacy of Ologen (OLO) implant as adjuvant compared with low-dosage mitomycin-C (MMC) in trabeculectomy. METHODS: This was a prospective randomized clinical trial with a 24-month follow-up. Forty glaucoma patients (40 eyes) were assigned to trabeculectomy with MMC or OLO. Primary outcome includes target IOP at ≤21, ≤17, and ≤15 mm Hg; complete (target IOP without medications), and qualified success (target IOP regardless of medications). Secondary outcomes include bleb evaluation, according to Moorfields Bleb Grading System (MBGS); spectral domain optical coherence tomography (SD-OCT) examination; number of glaucoma medications; and frequency of postoperative adjunctive procedures and complications. RESULTS: The mean preoperative IOP was 26.5 (±5.2) in MMC and 27.3 (±6.0) in OLO eyes, without statistical significance. One-day postoperatively, the IOP dropped to 5.2 (±3.5) and 9.2 (±5.5) mm Hg, respectively (P=0.009). The IOP reduction was significant at end point in all groups (P=0.01), with a mean IOP of 16.0 (±2.9) and 16.5 (±2.1) mm Hg in MMC and OLO, respectively. The rates and Kaplan-Meier curves did not differ for both complete and qualified success at any target IOP. The bleb height in OLO group was higher than MMC one (P<0.05). SD-OCT analysis of successful/unsuccessful bleb in patients with or without complete success at IOP ≤17  mm Hg indicated a sensitivity of 83% and 73% and a specificity of 75% and 67%, respectively, for MMC and OLO groups. No adverse reaction to OLO was noted. CONCLUSIONS: Our results suggest that OLO implant could be a new, safe, and effective alternative to MMC, with similar long-term success rate

A case of serendipity*

An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of “trigger” events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed

More frequent, more costly? Health economic modelling aspects of monitoring glaucoma patients in England

BACKGROUND: Chronic open angle glaucoma (COAG) is an age-related eye disease causing irreversible loss of visual field (VF). Health service delivery for COAG is challenging given the large number of diagnosed patients requiring lifelong periodic monitoring by hospital eye services. Yet frequent examination better determines disease worsening and speed of VF loss under treatment. We examine the cost-effectiveness of increasing frequency of VF examinations during follow-up using a health economic model. METHODS: Two different VF monitoring schemes defined as current practice (annual VF testing) and proposed practice (three VF tests per year in the first 2 years after diagnosis) were examined. A purpose written health economic Markov model is used to test the hypothesis that cost effectiveness improves by implementing proposed practice on groups of patients stratified by age and severity of COAG. Further, a new component of the model, estimating costs of visual impairment, was added. Results were derived from a simulated cohort of 10000 patients with quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) used as main outcome measures. RESULTS: An ICER of £21,392 per QALY was derived for proposed practice improving to a value of £11,382 once savings for prevented visual impairment was added to the model. Proposed practice was more cost-effective in younger patients. Proposed practice for patients with advanced disease at diagnosis generated ICERs > £60,000 per QALY; these cases would likely be on the most intensive treatment pathway making clinical information on speed of VF loss redundant. Sensitivity analysis indicated results to be robust in relation to hypothetical willingness to pay threshold identified by national guidelines, although greatest uncertainty was allied to estimates of implementation and visual impairment costs. CONCLUSION: Increasing VF monitoring at the earliest stages of follow-up for COAG appears to be cost-effective depending on reasonable assumptions about implementation costs. Our health economic model highlights benefits of stratifying patients to more or less monitoring based on age and stage of disease at diagnosis; a prospective study is needed to prove these findings. Further, this works highlights gaps in knowledge about long term costs of visual impairment

A 6-Month Study Comparing Efficacy, Safety, and Tolerability of the Preservative-free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% versus Each of Its Individual Preservative-Free Components

The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015\% and timolol 0.5\% (once daily) were compared to those of the individual components (PF tafluprost 0.0015\% once daily and PF timolol 0.5\% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6\ua0months.A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n\ua0=\ua095) or timolol 0.5\% (TIM; n\ua0=\ua094). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n\ua0=\ua0188) or tafluprost 0.0015\% (TAF; n\ua0=\ua0187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of\ua0 6522\ua0mmHg when on timolol (TIM) or of\ua0 6520\ua0mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6\ua0weeks, 3 and 6\ua0months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m.In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was -8.55\ua0mmHg (32\%) for FC and -7.35\ua0mmHg (28\%) for TIM. The model-based treatment difference (FC-TIM) was -0.885\ua0mmHg [95\% confidence interval (CI) -1.745 to -0.024; p\ua0=\ua00.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was -8.61\ua0mmHg (33\%) for FC and -7.23\ua0mmHg (28\%) for TAF. The model-based treatment difference (FC-TAF) was -1.516\ua0mmHg (95\% CI -2.044 to -0.988; p\ua0<\ua00.001) demonstrating the superiority of FC over TAF. In the TS, related ocular adverse events (AEs) were more frequent for patients treated with FC compared to TIM (16.8\% versus 6.4\%), whereas related non-ocular AEs were more frequent with TIM compared to FC (2.1\% versus 0.0\%). In the PS, AEs were similarly distributed between FC and TAF. The frequency of conjunctival hyperemia of FC was low (6.4\%).The preservative-free fixed combination of tafluprost and timolol provided a substantial and significant IOP reduction in both strata. The IOP reduction was superior to both tafluprost 0.0015\% and timolol 0.5\% when given as monotherapies. Overall, the study treatments were safe and well tolerated.Santen Oy, Tampere, Finland