The effect of blue-light filtering intraocular lenses on the development and progression of macular atrophy in eyes with nAMD.

PURPOSE: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective clinical cohort study. METHODS: nAMD patients with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All OCT scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. Using the Heidelberg software, the area of MA was manually evaluated and calculated (mm2) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event. RESULTS: Included were 373 eyes of 373 patients (mean age 78.6±6.7 years at surgery, 67.4% females). 206 eyes were implanted with BLF IOLs and 167 with non-BLF IOLs with comparable follow-up times (3164±1420 days vs. 3180±1403 days, respectively, P=0.908), and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine pre-existing and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P=0.598 and P=0.399, respectively). Both univariate Kaplan-Meier (P=0.366) and multivariate Cox regression analysis adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (HR 1.236, 95% CI 0.784-1.949, P=0.363). Final MA area at the last visit was 5.14±4.71mm2 for BLF IOLs and 8.56±9.17mm2 for non-BLF IOLs (P=0.028), with the mean annual MA area increase of 0.78±0.84mm2 and 1.26±1.32mm2, respectively (P=0.042). CONCLUSIONS: BLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of nAMD patients.

Efficacy comparison of combining cross-linking and refractive laser ablation in progressive keratoconus: systematic review and meta-analysis.

OBJECTIVE: This study assessed the effect of combining corneal collagen cross-linking (CXL) with refractive laser ablation techniques for the treatment of keratoconus, a progressive corneal disorder. METHODS: We performed a systematic review and meta-analysis to assess the effect of combined CXL and refractive techniques. We included all published clinical trials or observational studies published by September 1, 2023. We calculated and compared the standardized mean difference (SMD) between CXL alone and CXL plus laser ablation for uncorrected distance visual acuity, best-corrected distance visual acuity, spherical equivalent manifest refraction, sphere and cylinder, flat keratometry (K1), steep keratometry (K2), and central corneal thickness. RESULTS: We identified 13 studies that fulfilled our inclusion and exclusion criteria. The average follow-up was 21.3 ± 11.8 months. The CXL plus laser ablation group showed improvement in uncorrected distance visual acuity logMAR (SMD, -0.35; 95% CI, -0.67 to -0.04; p = 0.029), best-corrected distance visual acuity logMAR (SMD, -0.17; 95% CI, -0.30 to -0.03; p = 0.014), spherical equivalent manifest refraction (SMD, -0.28; 95% CI, 0.06-0.50; p = 0.013), and change in maximal corneal curvature (Kmax; SMD, -0.41; 95% CI, -0.69 to -0.13; p = 0.004) compared with CXL alone. However, central corneal thickness decreased further among patients who underwent CXL plus laser ablation (SMD, -0.37; 95% CI, -0.66 to -0.07; p = 0.016). No effect was observed in terms of sphere (p = 0.878), cylinder (p = 0.859), K1 (p = 0.907), or K2 (p = 0.169). Ectasia was not observed as an adverse effect resulting from the additional corneal ablation performed during the CXL treatments. CONCLUSIONS: This study showed that combining refractive laser ablation techniques with standard or accelerated CXL treatment improved visual and refractive outcomes and anterior corneal curvature values.

Ethnicity, Progressive Keratoconus, and Outcomes after Corneal Cross-Linking in Southern Israel.

PURPOSE: To assess clinical outcomes of corneal cross-linking (CXL) intervention in a population diagnosed with progressive keratoconus. METHODS: This single-center retrospective cohort study included consecutive patients who underwent standard CXL or accelerated CXL for progressive keratoconus at a major teaching hospital in southern Israel between January 2015 and December 2019. Patients' medical files were reviewed, and pre-operative and post-operative data regarding demographics and clinical and tomographic characteristics were extracted and analyzed. RESULTS: This study included 166 patients (representing 198 eyes), out of which 98 patients (123 eyes) were ethnically Bedouin, and 68 patients (75 eyes) were ethnically Jewish. Overall, 126 patients (144 eyes) had a follow-up of at least 12 months (16.84 ± 5.76). The mean patient age was 20.62 ± 7.1 years old. There were significant baseline differences between the two ethnic groups in best-corrected visual acuity (BCVA; p < 0.001), uncorrected visual acuity (UCVA; p < 0.001), mean keratometry (p = 0.028), and corneal thickness (p < 0.001). Significant changes in BCVA, UCVA, and pachymetry parameters within each group were found after 12 months. Negative binomial regression analysis showed a maximal keratometry below 55D (RR = 1.247, p < 0.001), and a standard CXL procedure (RR = 1.147, p = 0.041) are significantly related to the stability of KC after 12 months. However, the effect size of the origin of patients is negligible (RR = 1.047, p = 0.47). CONCLUSIONS: In this study, the Bedouin population suffered from more progressive keratoconus when compared to the Jewish population. CXL was significantly effective in improving BCVA and UCVA in both groups after 12 months of follow-up. The effect size of the origin of patients on the stability of KC was found to be negligible.

Accelerated high fluence photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study.

Introduction: Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) has garnered substantial interest among researchers and ophthalmologists due to its high promise as a potential treatment for infectious keratitis. The aim of this study is to evaluate the efficacy and safety of high fluence PACK-CXL, using 10.0 J/cm2 (30 mW/cm2, 5 min, and 33 s) at the slit lamp. Methods: This prospective interventional, nonrandomized cohort study included 20 eyes of 20 patients with bacterial, fungal, or mixed origin keratitis who underwent high fluence PACK-CXL treatment as an adjunct therapy to conventional antimicrobial therapy per American Academy of Ophthalmology treatment guidelines. The re-epithelization time was recorded, and corneal endothelial cell density was counted before and after treatment. Results: The average re-epithelization time was 8.2 ± 2.8 days (range 3-14 days). After PACK-CXL treatment, eight patients (40%) were directly discharged, while the remained patients stayed in the hospital for an average of 5.6 ± 3.5 days. No eyes required keratoplasty. Endothelial cell density counts before and after the PACK-CXL procedure were 2,562.1 ± 397.3, and 2,564.8 ± 404.5 cells/mm2, respectively (p = 0.96). Conclusion: although it was not a randomized control trial, we conclude that high fluence PACK-CXL as an adjuvant therapy is safe with no complications observed, and efficient as time to re-epithelization was less than 14 days for all patients and no patients underwent tectonic keratoplasties. Further research is needed to compare it to the current standard of care.

Risk factors for a phacodonesis surprise during cataract surgery in patients with pseudoexfoliation.

PURPOSE: To evaluate the association of different pre-operative parameters with surprise phacodonesis during cataract surgery among patients with pseudoexfoliation (PXF). MATERIALS AND METHODS: This is a retrospective charts review of all PXF patients who underwent cataract surgery between the years 2013 and 2018. Pre-operative parameters (demographics, biometry, intraocular pressure (IOP), endothelial cell count, pupil size, cataract density, glaucoma status, cup to disc ratio, number of glaucoma medications, prior intra-vitreous injections, risk for intraoperative floppy iris syndrome) were compared between patients with and without surprise phacodonesis. Binary logistic regression was used to calculate the predictive value of each parameter. RESULTS: Out of 396 surgical cases with computerized pre-operative assessment, we included 127 eyes of 120 PXF patients without evidence of phacodonesis preoperatively. The mean age was 77.8 ± 12.0 years, 63 (52.7%) were male, and 106 (84.2%) underwent phacoemulsification surgery. We identified 10 cases of surprise phacodonesis during surgery (8.2%). Compared to PXF cases without intraoperative phacodonesis, they had higher pre-operative IOP (23.0 ± 11.0 mmHg vs. 14.9 ± 3.8 mmHg, p < 0.001) and a higher rate of B scan use due to dense cataract obscuring posterior pole evaluation [4 (40%) vs. 15 (12.8%), p = 0.04]. Multivariant binary logistic regression confirmed that only baseline IOP contributed to the prediction of surprise phacodonesis (OR 1.22 CI 1.04-1.43, p = 0.014). CONCLUSIONS: Among patients with PXF undergoing cataract surgery, elevated IOP and poor posterior segment visibility requiring B scan use were associated with zonular instability putting these patients at risk for intra-operative complications.

Are Periocular and Systemic Allergy Conditions Risk Factors for Pterygium?

PURPOSE: To evaluate risk factors for pterygium and prevalence of periocular and systemic diseases among patients with pterygium. METHODS: A retrospective case-control study was conducted among members of Clalit Health Services (CHS) in Israel, from 2001 to 2022. A total of 13,944 patients diagnosed with pterygium were included. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Mixed models were used to assess differences in demographic characteristics, ocular and systemic diseases between the groups. Generalized estimating equation (GEE) logistic regression was used to estimate the odds ratios (OR) and adjust for confounders. RESULTS: The average age of pterygium patients was 49 ± 17 years; 51% were male. The results showed significant associations between pterygium and risk factors of vernal kerato-conjunctivitis (OR 2.52, 95% confidence interval [CI]: [1.96-3.24]), chronic allergic conjunctivitis (OR 1.98, 95% CI: [1.65-2.39]), blepharitis (OR 1.91, 95% CI: [1.78-2.04]), chalazion (OR 1.47, 95% CI: [1.30-1.67]) and unspecified systemic allergy (OR 1.21, 95% CI [1.09-1.34]), after adjusting for rural residency status. Glaucoma (OR 0.74, 95% CI [0.64-0.85]) and smoking (OR 0.70, 95% CI [0.66-0.75]) were protective factors against pterygium. CONCLUSION: Systemic and periocular inflammatory and allergic diseases are risk factors for pterygium.

Use of corneal cross-linking beyond keratoconus: a systemic literature review.

PURPOSE: The success of corneal collagen cross-linking in altering keratoconus' clinical course has driven a search for further uses of this procedure. This literature review aims to analyze the scientific evidence available for the benefit of cross-linking in the management of ophthalmic diseases other than progressive keratoconus or ectasia induced by corneal refractive procedures. METHODS: A systemic literature review. RESULTS: We reviewed 97 studies. We found that collagen cross-linking can limit the progression of several other corneal ectasias, thus reducing and limiting the need for keratoplasty. Collagen cross-linking also can reduce the refractive power of the cornea and can be considered for a moderate degree of bacterial keratitis or when the organism is unidentified, which is refractive to antibiotics alone. However, the comparative rarity of these procedures has limited the extent of evidence. In fungal, Acanthamoeba, and herpes virus keratitis, the evidence is inconclusive of the safety and efficacy of cross-linking. CONCLUSION: Current clinical data is limited, and laboratory data has not fully correlated with published clinical data.

The Integrity of the Blood-Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury.

A healthy blood-brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.

The Antibacterial Efficacy of High-Fluence PACK Cross-Linking Can Be Accelerated.

Purpose: To determine whether high-fluence photoactivated chromophore for keratitis cross-linking (PACK-CXL) can be accelerated. Methods: Solutions of Staphylococcus aureus and Pseudomonas aeruginosa with 0.1% riboflavin were prepared and exposed to 365 nm ultraviolet (UV)-A irradiation of intensities and fluences from 9 to 30 mW/cm2 and from 5.4 to 15.0 J/cm2, respectively, representing nine different accelerated PACK-CXL protocols. Irradiated solutions and unirradiated controls were diluted, plated, and inoculated on agar plates so that the bacterial killing ratios (BKR) could be calculated. Additionally, strains of Achromobacter xylosoxidans, Staphylococcus epidermidis, and Stenotrophomonas maltophilia were exposed to a single accelerated PACK-CXL protocol (intensity: 30 mW/cm2, total fluence: 15.0 J/cm2). Results: With total fluences of 5.4, 10.0, and 15.0 J/cm2, the range of mean BKR for S. aureus was 45.78% to 50.91%, 84.13% to 88.16%, and 97.50% to 99.90%, respectively; the mean BKR for P. aeruginosa was 69.09% to 70.86%, 75.37% to 77.93%, and 82.27% to 91.44%, respectively. The mean BKR was 41.97% for A. xylosoxidans, 65.38% for S. epidermidis, and 78.04% for S. maltophilia for the accelerated PACK-CXL protocol (30 mW/cm2, 15 J/cm2). Conclusions: The BKR of high-fluence PACK-CXL protocols can be accelerated while maintaining a high, but species-dependent, BKR. The Bunsen to Roscoe law is respected in fluences up to 10 J/cm2 in S. aureus and P. aeruginosa, whereas fluences above 10 J/cm2 show strain dependence. Translational Relevance: The high-fluence PACK-CXL protocols can be accelerated in clinical practice while maintaining high levels of BKR.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment.

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate's concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

Diagnostic Algorithm for Surgical Management of Limbal Stem Cell Deficiency.

BACKGROUND: Limbal stem cell deficiency (LCSD) presents several challenges. Currently, there is no clearly defined systematic approach to LSCD diagnosis that may guide surgical tactics. METHODS: The medical records of 34 patients with LSCD were analyzed. Diagnostic modalities included standard (visometry, tonometry, visual field testing, slit-lamp biomicroscopy with corneal fluorescein staining, Schirmer test 1, ultrasonography) and advanced ophthalmic examination methods such as anterior segment optical coherence tomography, in vivo confocal microscopy, impression cytology, and enzyme-linked immunoassay. RESULTS: Standard ophthalmological examination was sufficient to establish the diagnosis of LSCD in 20 (58.8%) cases, whereas advanced evaluation was needed in 14 (41.2%) cases. Depending on the results, patients with unilateral LSCD were scheduled to undergo glueless simple limbal epithelial transplantation (G-SLET) or simultaneous G-SLET and lamellar keratoplasty. Patients with bilateral LSCD with normal or increased corneal thickness were enrolled in the paralimbal oral mucosa epithelium transplantation (pLOMET) clinical trial. CONCLUSIONS: Based on the diagnostic and surgical data analyzed, the key points in LSCD diagnosis were identified, helping to guide the surgeon in selecting the appropriate surgical procedure. Finally, we proposed a novel step-by-step diagnostic algorithm and original surgical guidelines for the treatment of patients with LSCD.

Clinical comparison of manual and laser-cut corneal tunnel for intrastromal air injection in femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK).

PURPOSE: The most crucial step in deep anterior lamellar keratoplasty (DALK) is to achieve a bare Descemet's membrane. We aimed to assess a new femtosecond laser software that allows for a precise intrastromal tunnel creation for big bubble (BB) air injection using a real-time microscope-integrated optical coherence tomography. MATERIALS AND METHODS: A retrospective review of 61 eyes of 61 patients with keratoconus. Before introducing the new software update, DALK was performed using a partial-assisted femtosecond laser (partial-thickness circular cut followed by a lamellar cut) with manual intrastromal tunnel creation (partial FS-DALK group). After the software update, the femtosecond laser created the intrastromal tunnel (full FS-DALK group). RESULTS: In the full FS-DALK group, the BB's formation was significantly higher (64.3% vs. 36.4%, p = 0.04), and surgery time was shorter (21.8 ± 5.1 vs. 25.6 ± 6.8 min, p = 0.025) than in the partial FS-DALK. Penetrating keratoplasty conversion rate (7.1% vs. 15.1%, p = 0.432) was similar between the groups. Both groups showed statistically significant improvement in uncorrected and corrected distance visual acuity, central corneal thickness, surface asymmetry, and regularity indices. Endothelial cell density loss at 12 and 18 months was lower in the full compared with the partial FS-DALK group (12 months:10.0% vs. 16; 18 months: 10.7 vs. 16.5%, p < 0.001 for both comparisons). CONCLUSIONS: Creating the intrastromal guiding tunnel using FS laser for air injection resulted in a higher rate of BB formation, reduced long-term endothelial cell loss, and operating room time.

Three-year follow-up of accelerated versus standard corneal cross-linking in paediatric Keratoconus.

PURPOSE: Standard corneal collagen cross-linking (S-CXL) is an effective treatment to arrest Keratoconus (KC) progression in children. Less is known on the long-term efficacy of accelerated CXL (A-CXL) in paediatric populations. METHODS: A historical cohort analysis of paediatric patients (≤18 years) with KC who underwent S-CXL and A-CXL at two tertiary referral centres in Israel between 2010-2017. Preoperative and 3-year postoperative evaluation included changes in visual acuity (best spectacle corrected [BSCVA]) and uncorrected [UCVA]), refractive errors, and keratometric data. RESULTS: Ninety-three eyes of 93 patients were analysed (A-CXL: n = 39; S-CXL: n = 54). Baseline characteristics were similar between groups. Both groups showed a significant improvement in visual acuity compared to baseline (S-CXL: 0.810-0.602 LogMAR UCVA; A-CXL: 0.890-0.306 LogMAR UCVA, p < 0.05 for both). Improvement in BSCVA and UCVA following A-CXL was non-inferior to S-CXL (< ± 0.2 LogMAR). Kmax decreased by a mean of 0.98 ± 5.56 dioptres following S-CXL (p = 0.02) and by 1.48 ± 8.4 dioptres following A-CXL (p = 0.015). Thinnest pachymetry decreased following both treatments (S-CXL: by 26.8 ± 40.7 µm, p = 0.001, A-CXL: by 10.2 ± 13.4 µm, p = 0.028), the difference between groups was within the non-inferiority margin (< ± 10 µm). CONCLUSIONS: Paediatric patients followed for three years after A-CXL showed improved visual function, reduced corneal astigmatism and Kmax, and decreased thinnest corneal thickness. A-CXL was non-inferior to S-CXL at three years in terms of best-corrected and uncorrected visual acuity, thinnest pachymetry, and astigmatism. For Kmax, non-inferiority could not be concluded.

Association of Blue Light-Filtering Intraocular Lenses With All-Cause and Traffic Accident-Related Injuries Among Patients Undergoing Bilateral Cataract Surgery in Finland.

Importance: Blue light-filtering (BLF) intraocular lenses (IOLs) have been widely used in clinical practice for more than 20 years and have been implanted in millions of patients with cataracts worldwide. However, little evidence on the association of BLF IOLs with injuries is available. Objective: To assess the association of BLF IOLs with all-cause and traffic accident-related injuries and quality of vision while driving after bilateral cataract surgery. Design, Setting, and Participants: This retrospective registry-based cohort study included patients who underwent bilateral cataract surgery between September 3, 2007, and December 14, 2018, and were followed until December 14, 2021. Surgery was performed at the Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. The 4986 participants received non-BLF IOLs (n = 2609) or BLF IOLs (n = 2377) in both eyes. Patients undergoing bilateral surgery between 2015 to 2016 with non-BLF IOLs (n = 102) or BLF IOLs (n = 91) and currently driving a car were interviewed using a structured questionnaire for visual performance while driving. Exposures: Follow-up for a mean (SD) of 2166 (1110) days after second eye surgery. Main Outcomes and Measures: Kaplan-Meier and multivariable Cox proportional hazards regression analyses for the risk of all-cause and traffic accident-related injuries after surgery in the second eye obtained from the patient medical records were assessed. To improve follow-up precision, both death and the end of the follow-up were used as censoring events. Results: A total of 4986 patients were included in the analysis (1707 [34.2%] men and 3279 [65.8%] women; mean [SD] age, 73.2 [8.6] years at the first surgery and 74.3 [8.8] years at the second). Injury-free survival rates preceding the first eye surgery were comparable between the non-BLF and BLF IOL groups (hazard ratio adjusted for age and sex, 0.95 [95% CI, 0.81-1.13; P = .57]). In multivariable Cox proportional hazards regression analysis controlling for age and sex, the use of BLF IOLs showed no advantage in overall injuries compared with the use of non-BLF IOLs (hazard ratio, 0.99 [95% CI, 0.88-1.11]; P = .85) or in any injury subtype. Subjective visual performance parameters for driving were all comparable between the non-BLF and BLF IOL groups except for glare when driving in the dark (evening or night), which occurred among 9 of 80 patients with BLF IOLs compared with 0 of 83 non-BLF IOLs (P < .001). Conclusions and Relevance: The findings of this cohort study suggest that use of BLF IOLs was not associated with reduced risk of injuries, whereas glare during nighttime driving was significantly worse in the BLF IOL group with pseudophakia.

[CORNEAL TRANSPLANTATION DEVELOPMENTS].

INTRODUCTION: Cornea is the anterior transparent tissue of the eye. Loss of vision due to corneal disease is one of the leading causes of blindness. Some corneal conditions may be treated by replacing the cornea with a donor implant. The success rates for vision rehabilitation following corneal grafting are rather good generally, depending on the indication and the technique of the transplantation. Corneal transplantation surgery has been around for over 100 years, but in the last two decades there has been significant development in surgical methods, with the possibility of replacing only the damaged layer of the cornea. Along with donor corneal transplantation, various methods of artificial corneal transplantation have been developed. Extensive research continues in order to find artificial solutions for patients who need to undergo corneal transplantation.

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety.

Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats' depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.

PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial.

BACKGROUND: Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. METHODS: This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. RESULTS: Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups. CONCLUSIONS: PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871.

Intracameral r-tPA for the management of severe fibrinous reactions in TASS after cataract surgery.

BACKGROUND: To describe the use of intracameral recombinant tissue plasminogen activator (r-tPA) in the treatment of severe fibrinous reactions in toxic anterior segment syndrome (TASS) after cataract surgery. METHODS: A case series of 59 eyes of 59 patients with severe fibrinous anterior chamber reaction following cataract surgery who received intracameral r-tPA (25 µg/0.1 ml). The main outcome measures after intracameral r-tPA were the incidence of complete fibrinolysis, time of maximal effect, visual acuity, and complications. RESULTS: Severe fibrinous reactions appeared 11.5 ± 5.3 days after cataract surgery. Fibrinolysis was observed 2.33 ± 2.70 days after rtPA use and 36 eyes (61%) exhibited resolution of the fibrin by the end of the first day following injection (p < 0.001). Transient corneal edema observed at 1-day after injection was the only complication reported during the injection of r-tPA or at follow-up. Eight eyes (13.6%) required a second r-tPA injection. Best-corrected visual acuity improved from 0.88 ± 0.67 logMAR units before rtPA injection to 0.48 ± 0.49 logMAR units at 1-month (p < 0.001). CONCLUSIONS: The application of r-tPA was a quick and efficacious therapeutic approach for the management of severe fibrinous reactions in TASS after cataract surgery. In a clinical setting, intracameral r-tPA may be useful when rapid visual recovery is needed.

PACK Cross-Linking as Adjuvant Therapy Improves Clinical Outcomes in Culture-Confirmed Bacterial Keratitis.

PURPOSE: We recently showed the positive clinical effects of combining accelerated corneal cross-linking (PACK-CXL) with antibiotic treatment in patients with presumed bacterial keratitis. In this study, we compare the impacts of a combined PACK-CXL/standard antibiotic treatment (PACK-ABX group) with standard antibiotic treatment alone (ABX group) in patients with culture-confirmed bacterial keratitis. METHODS: We reviewed patients with moderate and severe bacterial keratitis and confirmed bacterial cultures. Clinical outcomes were compared for standard antibiotic treatment alone, before the initiation of PACK-CXL, and after adjuvant use of PACK-CXL. RESULTS: A total of 47 eyes of 47 patients were included: 26 eyes in the PACK-ABX group and 21 eyes in the ABX group. Pathogens, baseline demographics (besides age), and clinical parameters were similar between the 2 groups. The PACK-ABX patients had better final uncorrected visual acuity [mean difference 0.57 Logarithm of the Minimum Angle of Resolution, 95% Confidence Interval (CI): 0.16-0.99, P = 0.07] and best-corrected visual acuity (mean difference 0.70 Logarithm of the Minimum Angle of Resolution, 95% CI: 0.23-1.16, P = 0.04), shorter reepithelialization time (mean difference 9.63 days, 95% CI: 3.14-16.12, P = 0.004), and reduced number of clinic visits (mean difference 4.8 meetings, 95% CI: 1.4-8.2, P = 0.007) and need for tectonic grafts (0 vs. 33.3%, P = 0.002). A multivariate analysis controlling for age, sex, ulcer size, and Gram stain showed that PACK-ABX treatment remained significantly associated with reepithelialization time (ß = 14.5, P = 0.001). CONCLUSIONS: In our study, PACK-CXLs addition to the standard of care in cases of culture-proven bacterial keratitis had a positive effect on the final visual acuity and time to resolution, compared with the standard-of-care treatment.