Early versus Delayed Timing of Primary Repair after Open-Globe Injury: A Systematic Review and Meta-analysis.

TOPIC: The timing of primary repair of open-globe injury is variable in major trauma centers worldwide, and consensus on optimal timing is lacking. CLINICAL RELEVANCE: Surgery is the mainstay of open-globe injury management, and appropriate timing of surgical repair may minimize the risk of potentially blinding complications such as endophthalmitis, thereby optimizing visual outcomes. METHODS: A systematic literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (International Prospective Register of Systematic Reviews identifier, CRD42023442972). The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and ISRCTN registries and ClinicalTrials.gov were searched from inception through October 29, 2023. Prospective and retrospective nonrandomized studies of patients with open-globe injury with a minimum of 1 month of follow-up after primary repair were included. Primary outcomes included visual acuity at last follow-up and the proportion of patients with endophthalmitis. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: Fifteen studies met inclusion criteria, reporting a total of 8497 eyes. The most common injury types were penetrating and intraocular foreign body (IOFB). Meta-analysis found that primary repair less than 24 hours after open-globe injury was associated with 0.30 odds of endophthalmitis compared with primary repair conducted more than 24 hours after trauma (odds ratio, 0.39; 95% confidence interval [CI], 0.19-0.79; I2 = 95%; P = 0.01). No significant difference was found in reported visual outcomes between patients whose open-globe injuries were repaired more than, compared with less than, 24 hours after trauma (odds ratio, 0.89; 95% CI, 0.61-1.29; I2 = 70%; P = 0.52). All included studies were retrospective and nonrandomized, demonstrating an overall low certainty of evidence on GRADE assessment. DISCUSSION: Only retrospective data exist around the effect of timing of open-globe repair, resulting in low certainty of the available evidence. However, this review of current evidence, predominantly including penetrating and IOFB injuries, suggests that primary repair performed less than 24 hours after open-globe injury is associated with a reduced endophthalmitis rate compared with longer delays, consistent with delay to primary repair increasing endophthalmitis risk. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies: A Meta-analysis.

TOPIC: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial. CLINICAL RELEVANCE: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat. METHODS: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR). RESULTS: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%-0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%-0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%-0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal; 95% CI, -0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data. DISCUSSION: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A time-series analysis of blood-based biomarkers within a 25-year longitudinal dolphin cohort.

Causal interactions and correlations between clinically-relevant biomarkers are important to understand, both for informing potential medical interventions as well as predicting the likely health trajectory of any individual as they age. These interactions and correlations can be hard to establish in humans, due to the difficulties of routine sampling and controlling for individual differences (e.g., diet, socio-economic status, medication). Because bottlenose dolphins are long-lived mammals that exhibit several age-related phenomena similar to humans, we analyzed data from a well controlled 25-year longitudinal cohort of 144 dolphins. The data from this study has been reported on earlier, and consists of 44 clinically relevant biomarkers. This time-series data exhibits three starkly different influences: (A) directed interactions between biomarkers, (B) sources of biological variation that can either correlate or decorrelate different biomarkers, and (C) random observation-noise which combines measurement error and very rapid fluctuations in the dolphin's biomarkers. Importantly, the sources of biological variation (type-B) are large in magnitude, often comparable to the observation errors (type-C) and larger than the effect of the directed interactions (type-A). Attempting to recover the type-A interactions without accounting for the type-B and type-C variation can result in an abundance of false-positives and false-negatives. Using a generalized regression which fits the longitudinal data with a linear model accounting for all three influences, we demonstrate that the dolphins exhibit many significant directed interactions (type-A), as well as strong correlated variation (type-B), between several pairs of biomarkers. Moreover, many of these interactions are associated with advanced age, suggesting that these interactions can be monitored and/or targeted to predict and potentially affect aging.

Pulsed corneal crosslinking in the treatment of Keratoconus: a systematic review and meta-analysis.

PURPOSE: Corneal crosslinking (CXL) procedures are the treatment of choice in halting progressive corneal ectasia and preserving visual acuity due to keratoconus. Pulsed crosslinking (P-CXL) was developed using intermittent pulsing ultraviolet (UV) light to mitigate the depletion of oxygen levels that occurs with continuous UV exposure in standard crosslinking protocols (C-CXL). This study aimed to explore the use of P-CXL in the treatment of keratoconus and determine whether the availability of oxygen in P-CXL carries superior efficacy outcomes as an alternative to C-CXL modalities. METHODS: This review was undertaken in accordance with PRISMA guidelines. A search of several databases conducted with two separate reviewers resulted in 29 papers meeting inclusion criteria for the review, 14 selected for meta-analysis. Primary outcomes assessed by the included papers included maximum keratometry (Kmax), corrected and uncorrected distance visual acuity (CDVA, UDVA), and secondary outcomes included central corneal thickness (CCT), endothelial cell count and demarcation line. Statistical analyses were carried out on Review Manager 5.4 and the meta-analysis employed a random-effects model, which estimated the weighted effect size of raw means using inverse variance weights. RESULTS: At 12 months P-CXL showed statistically significant reductions in Kmax (-0.75 D; p < 0.001) and improvement in CDVA (-0.10 logMAR; p < 0.001) compared to baseline. The meta-analysis of comparative studies determined that mean differences in Kmax, CDVA, UDVA, Kmean and CCT after 12 months were not statistically significant between pulsed and continuous crosslinking groups. CONCLUSIONS: Overall, P-CXL is effective in improving visual acuity and keratometry outcomes in keratoconus. The meta-analysis did not show a statistically significant difference in Kmax and CDVA between P-CXL and C-CXL, indicating a non-inferiority of P-CXL. However, findings of the meta-analysis are limited by the fact that different energy levels and exposure times were used for P-CXL in comparison to C-CXL in some studies, making it unsuitable to determine whether the efficacy of CXL is improved by the use of pulsed light. KEY MESSAGES: What is Known • Pulsed crosslinking (P-CXL) uses intermittent UV light to prevent oxygen depletion when using higher energy protocols, unlike continuous UV exposure in standard continuous crosslinking (C-CXL). • This should theoretically enhance the efficacy of the treatment by maintaining higher oxygen levels that are crucial to the cross-linking process. • There are no systematic reviews or meta-analyses directly comparing the efficacy or safety of P-CXL to C-CXL. What is New • Meta-analysis revealed differences in keratometry between P-CXL and C-CXL groups with equivalent fluence (7.2 J/cm2) at 12 months were not statistically significant (Kmax -0.04 dioptres; p = 0.84). • Meta-analysis revealed differences in visual acuity between P-CXL and C-CXL groups with equivalent fluence (7.2 J/cm2) at 12 months were not statistically significant (CDVA -0.01 logMAR letters; p = 0.57). • The use of intermittent pulsing in higher energy CXL protocols renders statistically similar outcomes as continuous light exposure at equivalent fluence (7.2 J/cm2).

Antimicrobial resistance in ocular infection: A review.

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.

Epithelium-on versus epithelium-off corneal collagen crosslinking for keratoconus: a systematic review and meta-analysis.

PURPOSE: Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to compare the efficacy and safety of epithelium-on versus epithelium-off CXL to treat keratoconus. METHODS: We searched PubMed, Medline, Embase, Web of Science, and Scopus databases. We included studies that compared standard epithelium-off with epithelium-on CXL. The primary outcome measures were changes in corrected distance visual acuity (CDVA) and maximum keratometry (Kmax), and the secondary outcomes were uncorrected distance visual acuity (UDVA), central corneal thickness (CCT), and adverse events. A meta-analysis was performed on the primary and secondary outcomes based on the weighted mean differences between baseline to 12-month follow-up. RESULTS: The search retrieved 887 publications with 27 included in the systematic review. A total of 1622 eyes (1399 patients; age 25.51 ± 4.02 years) were included in comparisons of epithelium-off to epithelium-on CXL in keratoconus. Epithelium-off CXL treated 800 eyes and epithelium-on CXL for 822 eyes. At 12-month follow-up, CDVA and Kmax showed no significant difference between the epithelium-off and epithelium-on CXL. The secondary outcomes showed that UDVA was better in epithelium-off CXL (- 0.11D, 95% CI - 0.12, - 0.1; p < 0.001) and there was more thinning in CCT in epithelium-off CXL (- 3.23 µm, 95% CI - 4.64, - 1.81; p <0.001). CONCLUSION: Epithelium-off and epithelium-on CXL were both effective to treat progressive keratoconus. Further research is needed to compare the long-term outcomes and safety of both CXL protocols for adaptation into clinical practice.

Badminton-related eye injuries: a systematic review.

OBJECTIVES: To report the nature of badminton-related eye injuries in the published literature. METHODS: A review of the literature with key word and MeSH terms: 'Eye injury', 'Ocular trauma', 'Badminton' 'Shuttlecock' using CENTRAL, MEDLINE, EMBASE and Informit Health Collection databases. Papers were reviewed to assess the circumstances of the injury, patient demographics and clinical data. RESULTS: 19 studies from 1974 to 2020 from 12 countries reported 378 monocular badminton-related eye injuries from 378 patients with a male-to-female ratio of 2.5:1. A closed globe injury was sustained in 97% of eyes and a shuttlecock responsible for 85% of injuries. Doubles play, the shuttlecock and a lack of eye protection were associated with eye injury. CONCLUSION: Vision impairment was associated with the majority of badminton-related eye injuries, and doubles play, the shuttlecock and a lack of eye protection were risk factors.

A 25-y longitudinal dolphin cohort supports that long-lived individuals in same environment exhibit variation in aging rates.

While it is believed that humans age at different rates, a lack of robust longitudinal human studies using consensus biomarkers meant to capture aging rates has hindered an understanding of the degree to which individuals vary in their rates of aging. Because bottlenose dolphins are long-lived mammals that develop comorbidities of aging similar to humans, we analyzed data from a well-controlled, 25-y longitudinal cohort of 144 US Navy dolphins housed in the same oceanic environment. Our analysis focused on 44 clinically relevant hematologic and clinical chemistry measures recorded during routine blood draws throughout the dolphins' lifetimes. Using stepwise regression and general linear models that accommodate correlations between measures obtained on individual dolphins, we demonstrate that, in a manner similar to humans, dolphins exhibit independent and linear age-related declines in four of these measures: hemoglobin, alkaline phosphatase, platelets, and lymphocytes. Using linear regressions and analyses of covariance with post hoc Tukey-Kramer tests to compare slopes (i.e., linear age-related rates) of our four aging rate biomarkers among 34 individual dolphins aging from 10 y to up to 40 y old, we could identify slow and accelerated agers and differentiate subgroups that were more or less likely to develop anemia and lymphopenia. This study successfully documents aging rate differences over the lifetime of long-lived individuals in a controlled environment. Our study suggests that nonenvironmental factors influencing aging rate biomarkers, including declining hemoglobin and anemia, may be targeted to delay the effects of aging in a compelling model of human biology.

Five-year corneal cross-linking outcomes: A Save Sight Keratoconus Registry Study.

BACKGROUND: We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients. METHODS: An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes. RESULTS: There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p < 0.001) in year 1, and 6.9 (p < 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p < 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years. CONCLUSIONS: Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

Mucous membrane grafting for cicatricial entropion repair: review of surgical techniques and outcomes.

Mucous membrane graft (MMG) is used for moderate-to-severe cicatricial entropion repair either in primary or recurrent cases. We conducted a review to comprehensively summarize the various surgical techniques, outcomes, and complications of using MMG for cicatricial entropion. Though the comparison between different techniques is limited by multiple factors like small numbers of cicatricial entgropion patients, variable severity and success criteria across studies, and different underlying cicatricial entropion etiologies, the author has brought forth the nuances of the use of MMG for cicatricial entropion repair along with its outcomes and complications. MMG use in moderate-to-severe cicatricial entropion gives favourable outcomes. The shortened tarsoconjunctiva is lengthened using MMG, which is used either with terminal tarsal rotation or anterior lamellar recession (ALR) or tarsotomy alone. Non-trachomatous entropion has poor outcomes compared to trachomatous entropion. The most common source of MMG is labial or buccal mucosa and the exact size of MMG harvested is variable according to the defect, and very few prefer oversizing the graft by 10-30%. The outcomes of ALR+MMG appear similar to tarsal rotation and MMG for severe cicatricial entropion. The recurrences of trichiasis or entropion can occur for up to one year after surgery, irrespective of the technique used. Factors affecting the outcomes of cicatricial entropion repair are not well known. There is a non-uniformity in data reporting across literature; hence, future studies with details on severity of entropion, ocular surface changes, forniceal depth and ocular surface inflammation, and the degree of dry eye disease would be informative.

Efficacy of treatments for neurotrophic keratopathy: a systematic review and meta-analysis.

PURPOSE: Management of NK can be difficult, involving a range of treatments with variable efficacy. We conducted a systematic review and meta-analysis to evaluate the efficacy of medical and surgical treatments for neurotrophic keratitis (NK). METHOD: PubMed, Cochrane Library, Embase, ClinicalTrial.gov, and ScienceDirect were searched for studies assessing efficacy of NK treatments. We computed random-effect meta-analyses on corneal healing, time to complete healing, and visual acuity changes between baselines and after treatment, stratified on treatment classes. We followed the PRISMA guidelines (registration number CRD42021225721). RESULTS: We included 20 studies: 571 patients and 5 treatment classes (2 surgical and 3 non-surgical). The percentage of patients with complete corneal healing did not differ between specific treatments (nerve growth factor eyedrops (NGF), 75%, 95CI 46 to 104%; autologous serum (AS), 92%, 86 to 98%; neurotization, 99%, 95 to 103%; amniotic membrane transplantation (AMT), 86%, 78 to 94%). All specific treatments had better percentage of complete healing (p < 0.001) than non-specific treatment groups, i.e., mainly lubricants (23%, 14 to 32). Time to complete healing was 24.2 days (5.4 to 43.1) with NGF, 27.6 days (15.2 to 40.0) with AS, 117 days (28.8 to 205.2) with neurotization, and 16.4 days (11.1 to 21.7) with AMT. Only NGF and AMT improved visual acuity. Efficacy outcomes were not affected by sociodemographic (age, sex) nor severity of disease (Mackie stages). CONCLUSION: We confirmed the efficacy of specific treatments in NK. Further comparative trials are needed to investigate the medical and economic benefits of innovative therapies.

Eye injuries from fireworks used during celebrations and associated vision loss: the international globe and adnexal trauma epidemiology study (IGATES).

PURPOSE: To report on the factors associated with severe vision loss from fireworks-related ocular trauma during celebrations, including festivals. METHODS: Tertiary eye care hospitals in 5 countries and private ophthalmology practices in the Netherlands. Patients included received treatment for fireworks-related ocular trauma during celebrations. Demographic and clinical data for patients affected were analyzed and associations with severe vision loss reported. RESULTS: Of 388 patients, 71 (18.3 %) had severe vision loss (worse than 6/60) at 4-week follow-up due to fireworks-related ocular trauma. Mean age overall was 20.6 years (range 2 to 83 years), and there was a male predominance of 4:1. Clinical factors associated with severe vision loss included penetrating injury (OR 4.874 [95% CI 1.298-18.304; p = 0.02]) and lens injury (OR 7.023 [95% CI 2.378-20.736; p = 0.0004]). More patients with closed-globe injuries (CGIs) had improved vision after 4 weeks (OR 3.667, 1.096-12.27) compared to those with open-globe injuries (OGI) (p = 0.035). Eye protection use was reported by 7 patients, and 39.4% patients < 18 years were unsupervised by an adult at the time of injury. CONCLUSIONS: Severe vision loss from fireworks-related ocular trauma occurred during celebrations in a variety of countries and was associated with penetrating and/or lens injury and poor presenting vision. New initiatives are needed to prevent severe vision loss associated with these injuries.

The application of clinical registries in ophthalmic trauma-the International Globe and Adnexal Trauma Epidemiology Study (IGATES).

Ophthalmic trauma is a leading cause of preventable monocular blindness worldwide. The prevalence of ophthalmic trauma varies considerably based on geographic location, socio-economic status, age groups, occupation, and cultural practices such as firework celebrations. Clinical registries are known to be valuable in guiding the diagnosis, management, and prognostication of complex diseases. However, there is currently a lack of a centralized international data repository for ophthalmic trauma. We draw lessons from past and existing clinical registries related to ophthalmology and propose a new suitable international multicenter clinical registry for ophthalmic trauma: the International Globe and Adnexal Trauma Epidemiology Study (IGATES). IGATES is hosted on a secure web-based platform which exhibits user-friendly smart features, an integrated Ocular Trauma Score (OTS) prognosis calculator, efficient data collection points, and schematic graphical software. IGATES currently has 37 participating centers globally. The data collected through IGATES will be primarily used to develop a more robust and improved ophthalmic trauma prognostic classification system, the Ocular Trauma Score-2 (OTS-2), which builds on previous systems such as the Birmingham Eye Trauma Terminology System (BETTS) and Ocular Trauma Score (OTS). Furthermore, IGATES will act as a springboard for further research into the epidemiology, diagnosis, and management of ophthalmic trauma. Ultimately, IGATES serves to advance the field of ophthalmic trauma and improve the care that patients with ophthalmic trauma receive.

Infectious keratitis: A review.

Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.

Quality of life impact of eye diseases: a Save Sight Registries study.

BACKGROUND: The objectives of this study were to evaluate the quality-of-life (QoL) impact of eye diseases (keratoconus; neovascular age-related macular degeneration, AMD; retinal vein occlusion, RVO; and diabetic macular edema, DME) using the Impact of Vision Impairment (IVI) questionnaire, and to determine the relationship between the IVI scores and visual acuity. METHODS: This cross-sectional, multicentre, real-world study utilised the prospective, web-based Save Sight Registries. The IVI was completed by 1557 patients: 307 with keratoconus, 1049 with AMD, 148 with RVO and 53 with DME. Statistical analysis included Rasch analysis, Welch t-test, one-way ANOVA, Tukey's test, Pearson correlation, and multiple regression. RESULTS: The IVI scales (Overall; Visual Function, VF; Emotional, EM) had robust psychometric properties. The keratoconus patients had the worst Overall (adjusted mean: 48.2 vs. DME 58.8, RVO 64.6, AMD 67.6 units), VF (47.7 vs. DME 59.4, RVO 65.9, AMD 68.9 units) and EM (50.8 vs. DME 63.1, RVO 69.2, AMD 71.8 units) scores (all p < 0.05). The IVI scales scores weakly correlated with better and worse eye visual acuity (Pearson's r 0.24-0.39, all p < 0.05). The correlations were similar in the better eye (Overall 0.35, VF 0.39, EM 0.24) and the worse eye (Overall 0.31, VF 0.33, EM 0.25) visual acuity. Correlations with visual acuity were stronger for VF than for the EM scores. CONCLUSIONS: The IVI was a psychometrically robust QoL questionnaire. Keratoconus patients had worse IVI scores than patients with retinal diseases. The low strength of correlations between visual acuity and QoL scores, although statistically significant, suggested that a complex relationship exists.

The Management of Ocular Surface Squamous Neoplasia (OSSN).

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.

Dietary effects on urinary physicochemistry in Navy bottlenose dolphins (Tursiops truncatus) for the prevention of ammonium urate kidney stones.

Bottlenose dolphins are susceptible to developing ammonium urate (NH4U) kidney stones. The current study was designed to test the hypothesis that diet influences the urinary physicochemistry risk factors associated with nephrolithiasis in dolphins. A comprehensive nutrient analysis was performed revealing that the baseline diet (BD) commonly fed to dolphins under professional care had a greater purine content and a more negative dietary cation-anion difference (DCAD) when compared with a model diet consumed by free-ranging dolphins. A modified diet (MD) was formulated to include free-ranging diet fish species and achieve a more positive DCAD. The BD had a more negative DCAD (-52 mEq/Mcal metabolizable energy) when compared with the MD (+51 mEq/Mcal ME), which more closely approximated the DCAD of the free-ranging model diet (+152 mEq/Mcal ME). Six dolphins (with stones) were fed the BD followed by the MD for a minimum of 4 wk. At the end of each feeding trial, a 6-h continuous urine collection was performed to compare urine parameters of dolphins fed the BD versus MD. Dolphins consuming the MD demonstrated a significant decrease in urinary ammonium, net acid excretion, saturation index of ammonium urate, and phosphorous, and a significant increase in urinary citrate and net gastrointestinal (GI) alkali absorption, as compared with urine parameters assessed when fed the BD. Increasing the proportion of free-ranging diet fish species and optimizing the DCAD positively influenced some of the risk factors believed to be associated with NH4U kidney stone development in bottlenose dolphins under professional care.

Low-dose Btk inhibitors selectively block platelet activation by CLEC-2.

Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinemia (XLA) caused by a deficiency or absence of Btk. In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved. A similar set of results is seen with the second-generation inhibitor, acalabrutinib. The differential effect of Btk inhibition in CLEC-2 relative to GPVI signalling is explained by the positive feedback role involving Btk itself, as well as ADP and thromboxane A2 mediated activation of P2Y12 and TP receptors, respectively. This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. Nevertheless, thrombosis was absent in 8 out of 13 mice treated with ibrutinib. These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at 'low dose' in patients to target CLEC-2 in thrombo-inflammatory disease.

Application of unsupervised machine learning to identify areas of blood product wastage in transfusion medicine.

BACKGROUND: Wastage of blood products can be a significant cost to blood banks. However, the cause of wastage is often complex and makes it difficult to determine wastage-associated factors. Machine learning techniques may be useful tools to investigate these complex associations. We investigated whether unsupervised machine learning can identify patterns associated with wastage in our blood bank. MATERIALS AND METHODS: Data on red blood cells, platelets and frozen products were obtained from the laboratory information system of the Central Zone Blood Transfusion Services at Nova Scotia Health Authority. A total of 879 532 transactions were analysed by association rule mining, a type of machine learning algorithm. Associations with lift scores greater than 25 and with clinical relevance were flagged for further examination. RESULTS: Association rule mining returned a total of 3355 associations related to wastage. Several notable associations were identified. For example, certain wards were associated with wastage due to thawing unused frozen products. Other examples included association between smaller blood banks and evening work shifts with product wastage due to excess time outside the laboratory or returning products with high temperatures. CONCLUSION: This paper demonstrates the effective use of unsupervised machine learning for the purpose of investigating wastage in a large blood bank. The use of association rule mining was able to identify wastage factors, which can help guide quality improvement initiatives. This technique can be automated to provide rapid analysis of complex associations contributing to wastage and could be utilized in modern blood banks.

Pregnancy and the eye.

PURPOSE OF REVIEW: The aim of this study was to summarize common eye changes that may occur during pregnancy, and how pregnancy may affect preexisting eye conditions such as glaucoma and diabetic retinopathy. Challenges and complexities surrounding the treatment of these eye conditions during pregnancy are also highlighted. RECENT FINDINGS: Refractive changes are common and may persist in the postpartum in patients with keratoconus. Although new medical and surgical glaucoma treatments are available, their safety in pregnancy is unknown. Limited use of topical and systemic glaucoma therapies is recommended, with a preference for selective laser trabeculoplasty as first line treatment in appropriate cases. The impact of pregnancy on diabetic retinopathy remains unclear. Although anti-vascular endothelial growth factor agents are first-line treatment for sight-threatening diabetic retinopathy, their effect on the developing foetus remains unknown and are therefore best avoided in the first and second trimesters. Noninfectious uveitis tends to become less active during pregnancy, allowing the potential tapering of systemic therapy and the use of local topical or injected corticosteroid treatment for active disease as required. SUMMARY: Significant changes can occur to the eye during pregnancy, wherein the optimal treatment for many ocular conditions remains uncertain, highlighting the need for further research to develop clear recommendations that best balance the need to preserve the mother's sight, and the health of the developing foetus. The need for preconception planning, and collaborative multidisciplinary care between the obstetrician, physician, ophthalmologist and paediatrician is paramount.