Purpose: The purpose of this study was to investigate the contribution of mast cells to early neutrophil recruitment during ocular inflammation. Methods: In a murine model of corneal injury, the epithelium and anterior stroma were removed using a handheld motor brush. Cromolyn sodium (2% in PBS) eye drops were administered topically for mast cell inhibition. In vitro, bone marrow-derived mast cells were cultured alone or with corneal tissue. The frequencies of CD45+ inflammatory cells, CD11b+Ly6G+ neutrophils, and ckit+FcεR1+ mast cells in the cornea were assessed by flow cytometry. mRNA expression of CXCL2 was evaluated by real-time PCR and protein expression by ELISA. β-Hexosaminidase assays were performed to gauge mast cell activation. Results: Neutrophil infiltration of the cornea was observed within 1 hour of injury, with neutrophil frequencies increasing over subsequent hours. Concurrent expansion of mast cell frequencies at the cornea were observed, with mast cell activation (assessed by β-hexosaminidase levels) peaking at 6 hours after injury. Evaluation of CXCL2 mRNA and protein expression levels demonstrated augmented expression by injured corneal tissue relative to naïve corneal tissue. Mast cells were observed to constitutively express CXCL2, with significantly higher expression of CXCL2 protein compared with naïve corneal tissue. Culture with harvested injured corneas further amplified CXCL2 expression by mast cells. In vivo, mast cell inhibition was observed to decrease CXCL2 expression, limit early neutrophil infiltration, and reduce inflammatory cytokine expression by the cornea. Conclusions: Our data suggest that mast cell activation after corneal injury amplifies their secretion of CXCL2 and promotes the initiation of early neutrophil recruitment.

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

PURPOSE: To investigate the feasibility of remote assessment and follow-up of dry eye symptoms using electronic versions of two validated questionnaires. METHODS: We conducted a prospective study of consecutive patients with dry eye disease (DED). Patients were enrolled during a clinical visit and were explained how to respond electronic versions of the Ocular surface Disease Index (OSDI) and the Symptom Assessment in Dry Eye (SANDE) questionnaires using a computer in the presence of investigators. A secure link to both questionnaires was sent to each patient every 2 weeks in order to respond and submit their symptoms over a 3-month period. We analyzed the number of patients who responded to both questionnaires, the recurrence, and the symptoms scores reported. RESULTS: A total of 1121 questionnaires were collected; 103 patients (85%) reported their symptoms at least once during the 3-month study duration. The majority of participants who completed the study (71.6%) responded remotely at least once per month during the 3-month duration of the study. The mean OSDI and SANDE scores from the total of remote evaluations were 34.9 ± 21.9 (range 0-97.5) and 50.3 ± 24.9 (range 0-100), respectively. There was a statistically significant correlation between the total scores collected with the two questionnaires (R = 0.67, P < 0.001). CONCLUSIONS: Patients are motivated to report DED symptoms while away from the clinic. Distance-based evaluation of DED symptoms is both feasible and convenient, and can be implemented to follow symptoms in large populations with chronic dry eye.

The ocular surface is a unique mucosal immune compartment in which anatomical, physiological, and immunological features act in concert to foster a particularly tolerant microenvironment. These mechanisms are vital to the functional competence of the eye, a fact underscored by the devastating toll of excessive inflammation at the cornea - blindness. Recent data have elucidated the contributions of specific anatomical components, immune cells, and soluble immunoregulatory factors in promoting homeostasis at the ocular surface. We highlight research trends at this distinctive mucosal barrier and identify crucial gaps in our current knowledge.

PURPOSE: To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. DESIGN: Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). PARTICIPANTS: Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. METHODS: Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. MAIN OUTCOME MEASURES: The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. RESULTS: Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non-adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. CONCLUSIONS: A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non-adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.

We report a unique case of optic nerve lymphoma after completion of chemotherapy for non-Hodgkin's lymphoma. The uncommon nature of presentation, our therapeutic dilemma and the further course of treatment are reported. In cases with extremely poor prognosis, unnecessary treatment puts additional strain both financially and psychologically on the patients and their family. Therapeutic focus should be on hospice care and family counselling. The decision to not treat is a crucial component of cancer management; however, the ethics of this decision are yet to be suitably addressed by the literature.

PURPOSE: To compare the response of dry eye disease (DED) to treatment with topical steroid in patients with and without graft-vs-host disease (GVHD). DESIGN: Post hoc analysis of a double-masked, randomized clinical trial. METHODS: This single-center study included 42 patients with moderate-to-severe DED associated with (n = 21) or without (n = 21) chronic GVHD. In each group, patients received either loteprednol etabonate 0.5% ophthalmic suspension or artificial tears twice daily for 4 weeks. Clinical data, including Ocular Surface Disease Index (OSDI) questionnaire, corneal fluorescein staining (CFS), conjunctival lissamine green staining, tear break-up time (TBUT), and Schirmer test, were evaluated before and after treatment. RESULTS: There were no significant differences in signs and symptoms of DED between the groups at baseline. In non-GVHD patients receiving loteprednol treatment, the average OSDI score decreased by 34% from 49.5 ± 5.9 to 32.6 ± 4.8 (mean ± standard error of the mean, P = .001) and the average CFS score decreased by 41% from 5.6 ± 0.6 to 3.3 ± 0.9 (P = .02). On the other hand, loteprednol treatment in GVHD patients resulted in minimal change in OSDI (59.2 ± 6.7 to 61.1 ± 7.1, 3% increase, P = .66) and CFS (5.5 ± 0.5 to 5.3 ± 1.1, 4% decrease, P = .85) scores. Treatment with artificial tears resulted in 22% decrease of OSDI (P = .10) and 32% decrease of CFS (P = .02) scores in non-GVHD patients, and had minimal effect in patients with GVHD. CONCLUSIONS: DED patients with ocular GVHD have a less favorable response to a low-dose topical steroid regimen compared with those without ocular GVHD even with similar baseline disease severity.

Oncoming headlight glare (HLG) reduces the visibility of objects on the road and may affect the safety of nighttime driving. With cataracts, the impact of oncoming HLG is expected to be more severe. We used our custom HLG simulator in a driving simulator to measure the impact of HLG on pedestrian detection by normal vision subjects with simulated mild cataracts and by patients with real cataracts.Five normal vision subjects drove nighttime scenarios under two HLG conditions (with and without HLG: HLGY and HLGN, respectively), and three vision conditions (with plano lens, simulated mild cataract, and optically blurred clip-on). Mild cataract was simulated by applying a 0.8 Bangerter diffusion foil to clip-on plano lenses. The visual acuity with the optically blurred lenses was individually chosen to match the visual acuity with the simulated cataract clip-ons under HLGN. Each nighttime driving scenario contains 24 pedestrian encounters, encompassing four pedestrian types; walking along the left side of the road, walking along the right side of the road, crossing the road from left to right, and crossing the road from right to left. Pedestrian detection performances of five patients with mild real cataracts were measured using the same setup. The cataract patients were tested only in HLGY and HLGN conditions. Participants' visual acuity and contrast sensitivity were also measured in the simulator with and without stationary HLG.For normal vision subjects, both the presence of oncoming HLG and wearing the simulated cataract clip-on reduced pedestrian detection performance. The subjects performed worst in events where the pedestrian crossed from the left, followed by events where the pedestrian crossed from the right. Significant interactions between HLG condition and other factors were also found: (1) the impact of oncoming HLG with the simulated cataract clip-on was larger than with the plano lens clip-on, (2) the impact of oncoming HLG was larger with the optically blurred clip-on than with the plano lens clip-on, but smaller than with the simulated cataract clip-on, and (3) the impact was larger for the pedestrians that crossed from the left than those that crossed from the right, and for the pedestrians walking along the left side of the road than walking along the right side of the road, suggesting that the pedestrian proximity to the glare source contributed to the performance reduction. Under HLGN, almost no pedestrians were missed with the plano lens or the simulated cataract clip-on (0 and 0.5%, respectively), but under HLGY, the rate of pedestrian misses increased to 0.5 and 6%, respectively. With the optically blurred clip-on, the percent of missed pedestrians under HLGN and HLGY did not change much (5% and 6%, respectively). Untimely response rate increased under HLGY with the plano lens and simulated cataract clip-ons, but the increase with the simulated cataract clip-on was significantly larger than with the plano lens clip-on. The contrast sensitivity with the simulated cataract clip-on was significantly degraded under HLGY. The visual acuity with the plano lens clip-on was significantly improved under HLGY, possibly due to pupil myosis. The impact of HLG measured for real cataract patients was similar to the impact on performance of normal vision subjects with simulated cataract clip-ons.Even with mild (simulated or real) cataracts, a substantial negative effect of oncoming HLG was measurable in the detection of crossing and walking-along pedestrians. The lowered pedestrian detection rates and longer response times with HLGY demonstrate a possible risk that oncoming HLG poses to patients driving with cataracts.

PURPOSE: The purpose of this study was to examine the effect of corneal biomechanical properties on intraocular pressure (IOP) measurements obtained using a rebound self-tonometer (Icare HOME) compared with Goldmann applanation tonometry (GAT). METHODS: An observational study of 100 patients with glaucoma or ocular hypertension. All had a comprehensive ophthalmic examination and standard automated perimetry. IOP was assessed by GAT, Icare HOME and Ocular Response Analyzer, which was also used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Central corneal thickness (CCT) was recorded. RESULTS: Mean (±SD) IOP measurements were 14.3±3.9 and 11.7±4.7 mm Hg using GAT and Icare HOME, respectively. Average CCT, CRF, and CH were 534.5±37.3 μm, 9.0±1.7 mm Hg, and 9.4±1.5 mm Hg, respectively. The mean difference between Icare HOME and GAT was -2.66±3.13 mm Hg, with 95% limits of agreement of -8.80 to 3.48 mm Hg, however, there was evidence of proportional bias. There was negative correlation between IOP and CH [5.17 mm Hg higher Icare HOME IOP (P=0.041, R=0.029) and 7.23 mm Hg higher GAT IOP (P=0.008, R=0.080) for each 10 mm Hg lower CH], whereas thinner CCT was significantly associated with lower IOP (P0.001, R=0.14 for Icare HOME and P0.001, R=0.08 for GAT). In multivariable analysis, although CRF and CH remained associated with IOP measured using either GAT or Icare HOME, CCT was no longer significant. CONCLUSION: IOP measurements obtained using a self-tonometer, similar to GAT, were more influenced by overall corneal biomechanics than CCT.

We report a case of myeloid sarcoma with multifocal skeletal involvement, including the greater wing of the sphenoid bone. A 23-month-old boy presented with left-sided proptosis and fevers, and was found to have an infiltrative mass involving the left sphenoid bone on orbital imaging. Full body imaging further demonstrated multiple bony lesions in the pelvis, thoracic and lumbar vertebrae, bilateral femura, and left humerus, and biopsies of the humerus were consistent with myeloid sarcoma. The patient was started on a standard chemotherapy regimen and is responding well. Myeloid sarcoma presenting with proptosis due to sphenoid bone involvement with simultaneous multifocal skeletal involvement is very uncommon and highlights the importance of biopsy for establishing a definitive diagnosis.