Increased Incidence of Pseudotumor Cerebri Syndrome Among Users of Tetracycline Antibiotics.

BACKGROUND: To determine whether the use of a tetracycline-class antibiotic is associated with an increased risk of developing pseudotumor cerebri syndrome (PTCS). METHODS: We identified patients in the University of Utah Health system who were prescribed a tetracycline-class antibiotic and determined what percentage of those individuals were subsequently diagnosed with PTCS secondary to tetracycline use. We compared this calculation to the number of patients with PTCS unrelated to tetracycline use. RESULTS: Between 2007 and 2014, a total of 960 patients in the University system between the ages of 12 and 50 were prescribed a tetracycline antibiotic. Among those, 45 were diagnosed with tetracycline-induced PTCS. We estimate the incidence of tetracycline-induced PTCS to be 63.9 per 100,000 person-years. By comparison, the incidence of idiopathic intracranial hypertension (IIH) is estimated to be less than one per 100,000 person-years (Calculated Risk Ratio = 178). CONCLUSIONS: Although a causative link between tetracycline use and pseudotumor cerebri has yet to be firmly established, our study suggests that the incidence of pseudotumor cerebri among tetracycline users is significantly higher than the incidence of IIH in the general population.

Refractive Outcomes Using Intraoperative Aberrometry for Highly Myopic, Highly Hyperopic, and Post-refractive Eyes.

PURPOSE: To evaluate whether intraoperative aberrometry improves the accuracy of refractive outcomes after cataract surgery in highly myopic, highly hyperopic, and post-refractive eyes. METHODS: This single-center, retrospective review compared the spherical equivalent of postoperative refraction to that predicted by the Barrett Universal II formula versus Optiwave Refractive Analysis (ORA) (Alcon Laboratories, Inc) for highly myopic and hyperopic eyes and to the Barrett True K formula versus ORA for post-refractive eyes. The number and magnitude of lens changes were analyzed and used to determine in how many cases refractive surprises were affected by ORA, with additional subanalysis of outcomes based on average keratometry values. RESULTS: ORA led to a change in the lens power implanted in 48% (96 of 198) of eyes, and prevented hyperopic surprise in 27% (15 of 55) and excess myopia in 46% (19 of 41). Steeper keratometry values correlated with more frequent changes on ORA-recommended implanted intraocular lens (P = .0031). ORA led to a similar percentage of eyes falling within ±0.50, ±0.75, and ±1.00 diopters compared to the Barrett Universal II and Barrett True K formulas. In post-refractive eyes, ORA led to a similar mean absolute error when compared to the Barrett True K formula (P = .62). For highly myopic eyes with an axial length of greater than 27 mm, ORA demonstrated a trend toward lower mean absolute error when compared to the Barrett Universal II formula (P = .076). CONCLUSIONS: ORA demonstrated similar refractive results to the Barrett True K formula in post-refractive eyes and to the Barrett Universal II formula in highly myopic and hyper-opic eyes and may provide additional benefit for eyes with steeper corneas or an axial length of greater than 27 mm. [J Refract Surg. 2021;37(9):609-615.].

Optical Quality and Tear Film Analysis Before and After Intranasal Stimulation in Patients with Dry Eye Syndrome.

PURPOSE: To evaluate the optical quality and tear film quality in patients with dry eye syndrome (DES) before and after using an intranasal neurostimulation device to stimulate tear production. METHODS: Cross-sectional review of 33 eyes in 21 patients with DES who underwent optical quality and tear film analysis as part of their routine dry eye evaluation pre- and post-neurostimulation trial in office. Optical quality was assessed by measuring the objective scattering index (OSI) and modulation transfer function (MTF). The time to blink and mean tear film OSI were used to analyze the tear film. RESULTS: Optical quality after the use of the intranasal neurostimulator improved with an average decrease (improvement) in OSI of 0.30±0.68 (P=0.015) and an average increase (improvement) in MTF of 2.12±9.2 (P=0.15). Pre-intranasal neurostimulation OSI had a positive correlation with age (Spearman's rho 0.60, p < 0.001), while MTF had a negative correlation (Spearman's rho -0.38, p = 0.03). Pre-intranasal neurostimulation OSI had a negative correlation with MTF (Spearman's rho -0.85, p < 0.001) and a positive correlation with tear film mean OSI (Spearman's rho 0.85, p <0.001). CONCLUSION: The optical quality of patients with DES is improved with the use of intranasal neurostimulation for tear production, and there was a trend towards improved MTF though not statistically significant. Future studies are needed to follow patients longitudinally.

Clinical Outcomes of Lifitegrast 5% Ophthalmic Solution in the Treatment of Dry Eye Disease.

PURPOSE: To evaluate the clinical characteristics, outcomes, and adverse reactions after the use of lifitegrast 5% ophthalmic solution for the treatment of patients with dry eye disease (DED). METHODS: Retrospective chart review was performed in 121 patients seen at the Duke Eye Center with DED who were prescribed lifitegrast 5% and seen for follow-up after treatment initiation. Charts were reviewed for meibomian gland dysfunction (MGD) grading, conjunctival and corneal staining scores, and tear breakup time (TBUT), as well as matrix metalloproteinase-9 (MMP-9) levels. Ocular Surface Disease Index (OSDI) questionnaire scores and self-reported adverse reactions were also assessed. RESULTS: The average patient age was 60.5 years (range, 22-88 years); 87.6% were female, and 20.7% had a previous autoimmune disease diagnosis. Of the 54 eyes with an initial positive MMP-9, 21 eyes (38.9%) normalized after treatment. The ocular symptoms OSDI subscore demonstrated an improvement of -2.43±6.85 (P=0.011) after treatment. Corneal staining scores showed an average change of -0.15 (P=0.007). The average change in TBUT was 1.9 sec (P<0.001). Self-reported adverse reactions were noted in 31.4% of patients. There was no statistically significant change in MGD grading. Patients with moderate-severe DED showed statistically significant improvements in conjunctival and corneal staining scores and TBUT (-0.17±0.66, P=0.0442; -0.54±0.65, P<0.001; +2.02±2.63, P=0.004, respectively). CONCLUSION: Lifitegrast 5% is a useful therapeutic option for DED with a moderate proportion of self-reported adverse reactions, all of which were related to ocular discomfort. Treatment with lifitegrast was associated with statistically significant improvements in MMP-9 levels, ocular symptoms, corneal staining, and TBUT.

Comparison of agreement and efficiency of a swept source-optical coherence tomography device and an optical low-coherence reflectometry device for biometry measurements during cataract evaluation.

PURPOSE: To compare the agreement and efficiency of a swept source-optical coherence tomography biometer, IOLMaster 700 (IOLM700), and a low-coherence optical reflectometry biometer, LENSTAR LS 900 (LS900), when acquiring biometry measurements during cataract evaluation. METHODS: A retrospective chart review of biometry measurements that were performed in 64 eyes of 32 patients on the same day using the LS900 and the IOLM700. The total image acquisition time per subject was compared between the two machines using a Wilcoxon rank-sum test. Bland-Altman plots showing the mean difference and 95% limits of agreement were graphed. Intraclass correlation coefficients (ICCs) were calculated for the mean axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and two keratometry mean values (K1 and K2) that were output from each device. RESULTS: The average time to complete biometry measurements in both eyes was significantly shorter for the IOLM700 compared with the LS900 (44.5±12.4 vs 168.8±67.2 seconds, P<0.001). The Bland-Altman analysis and ICCs showed high degrees of agreement for the mean biometry values (ICC: AL 0.9999, ACD 0.9993, LT 0.9571, K1 0.9922, K2 0.9926) generated by the two devices. CONCLUSION: There was a high level of agreement between the mean biometry output measures for IOLM700 and LS900. However, it took ~73% less time on average to acquire the images when using the IOLM700 compared with the LS900. In a busy clinic setting, use of the IOLM700 for biometry measures may save time and prove more efficient.

AAV2 delivery of Flt23k intraceptors inhibits murine choroidal neovascularization.

Long-term inhibition of extracellular vascular endothelial growth factor (VEGF) in the treatment of age-related macular degeneration (AMD) may induce retinal neuronal toxicity and risk other side effects. We developed a novel strategy which inhibits retinal pigment epithelium (RPE)-derived VEGF, sparing other highly sensitive retinal tissues. Flt23k, an intraceptor inhibitor of VEGF, was able to inhibit VEGF in vitro. Adeno-associated virus type 2 (AAV2)-mediated expression of Flt23k was maintained for up to 6 months postsubretinal injection in mice. Flt23k was able to effectively inhibit laser-induced murine choroidal neovascularization (CNV). VEGF levels in the RPE/choroid complex decreased significantly in AAV2.Flt23k treated eyes. Neither retinal structure detected by Heidelberg Spectralis nor function measured by electroretinography (ERG) was adversely affected by treatment with AAV2.Flt23k. Hence AAV2.Flt23k can effectively maintain long-term expression and inhibit laser-induced CNV in mice through downregulation of VEGF while maintaining a sound retinal safety profile. These findings suggest a promising novel approach for the treatment of CNV.

Artificial tears potpourri: a literature review.

Numerous brands and types of artificial tears are available on the market for the treatment of dysfunctional tear syndrome. Past literature has focused on comparing the components of these products on patient's clinical improvement. The wide array of products on the market presents challenges to both clinicians and patients when trying to choose between available tear replacement therapies. Different formulations affect patients based on etiology and severity of disease. In order to provide an unbiased comparison between available tear replacement therapies, we conducted a literature review of existing studies and National Institutes of Health clinical trials on commercially available, brand name artificial tears. Outcomes evaluated in each study, as well as the percent of patients showing clinical and symptomatic improvement, were analyzed. Fifty-one studies evaluating different brands of artificial tears, and their efficacy were identified. Out of the 51 studies, 18 were comparison studies testing brand name artificial tears directly against each other. Nearly all formulations of artificial tears provided significant benefit to patients with dysfunctional tear syndrome, but some proved superior to others. From the study data, a recommended treatment flowchart was derived.

Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice.

Cerebral cavernous malformations (CCMs) are a common type of vascular malformation in the brain that are a major cause of hemorrhagic stroke. This condition has been independently linked to 3 separate genes: Krev1 interaction trapped (KRIT1), Cerebral cavernous malformation 2 (CCM2), and Programmed cell death 10 (PDCD10). Despite the commonality in disease pathology caused by mutations in these 3 genes, we found that the loss of Pdcd10 results in significantly different developmental, cell biological, and signaling phenotypes from those seen in the absence of Ccm2 and Krit1. PDCD10 bound to germinal center kinase III (GCKIII) family members, a subset of serine-threonine kinases, and facilitated lumen formation by endothelial cells both in vivo and in vitro. These findings suggest that CCM may be a common tissue manifestation of distinct mechanistic pathways. Nevertheless, loss of heterozygosity (LOH) for either Pdcd10 or Ccm2 resulted in CCMs in mice. The murine phenotype induced by loss of either protein reproduced all of the key clinical features observed in human patients with CCM, as determined by direct comparison with genotype-specific human surgical specimens. These results suggest that CCM may be more effectively treated by directing therapies based on the underlying genetic mutation rather than treating the condition as a single clinical entity.

Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza.

The innate immune system provides a first line of defense against invading pathogens by releasing multiple inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, which directly combat the infectious agent and recruit additional immune responses. This exuberant cytokine release paradoxically injures the host by triggering leakage from capillaries, tissue edema, organ failure, and shock. Current medical therapies target individual pathogens with antimicrobial agents or directly either blunt or boost the host's immune system. We explored a third approach: activating with the soluble ligand Slit an endothelium-specific, Robo4-dependent signaling pathway that strengthens the vascular barrier, diminishing deleterious aspects of the host's response to the pathogen-induced cytokine storm. This approach reduced vascular permeability in the lung and other organs and increased survival in animal models of bacterial endotoxin exposure, polymicrobial sepsis, and H5N1 influenza. Thus, enhancing the resilience of the host vascular system to the host's innate immune response may provide a therapeutic strategy for treating multiple infectious agents.