Aim Norfloxacin (NFX) has low ocular bioavailability. The current work aimed to develop NFX-loaded nanoparticle (NP)-laden hydrogels to improve the ocular potential of NFX, minimize the need for frequent instillations and lower undesirable side effects. Methods NFX-loaded NPs were developed via the double-emulsion/solvent evaporation technique, according to 2 1 .4 1 full factorial design, using two types of polylactic-co-glycolic acid (PLGA) polymer and four (drug: polymer) ratios. NPs were evaluated for particle size (PS), polydispersity index (PDI), zeta potential (ZP), drug entrapment efficiency percentage (EE%), drug percentage released after 30 min (Q 30min ) and 12 hours (Q 12h ), drug percentage permeated through goat corneas after 30 min (P 30min ) and 12 hours (P 12h ) and morphology. Two formulae were statistically selected and incorporated into hydroxypropyl methylcellulose (HPMC)-based hydrogels; G1 – G4. The latter systems were evaluated for appearance, clarity, pH, spreadability, rheology, drug percentages released, drug percentages permeated, antimicrobial activity against Pseudomonas aeruginosa , and histopathological changes. Results The selected NPs (NP2 and NP6) were spherical in shape and possessed suitable PS (392.02 nm and 190.51 nm) and PDI (0.17 and 0.18), high magnitude of ZP (−30.43 mV and −33.62 mV), high EE% (79.24% and 91.72%), low Q 30min (10.96% and 16.65%) and P 30min (17.39% and 21.05%) and promising Q 12h (58.23% and 71.20%) and P 12h (53.31% and 65.01%), respectively. Clear, spreadable, tolerable, pseudoplastic, and thixotropic HPMC-based hydrogels were developed. They showed more prolonged drug release and drug permeation profiles. NP2- and NP6-laden hydrogels (G3 and G4 systems, respectively) had promising antibacterial activity, and reasonable histopathological safety. Conclusion G3 and G4 are potential ocular delivery systems for NFX.

Purpose: To evaluate corneal biomechanical parameters with an ocular response analyzer (ORA) in patients with psoriasis and compare these parameters with age-matched control subjects. Study Design: This was a cross-sectional observational case-control study. Methods: Thirty eyes of 15 psoriasis patients were included in the study and compared with 30 eyes of 15 control subjects. Corneal biomechanical properties were calculated by ORA. Central corneal thickness (CCT) was measured by anterior-segment optical coherence tomography. The main outcome measures were corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), and Goldmann-correlated IOP (IOPg). For dry-eye evaluation, Schirmer's test was used. Results: Mean CH in the psoriasis group was 10.20±1.55 mmHg and in the control group 10.66±1.36 mmHg (p=0.215). Mean CRF in the psoriasis group was 9.76±1.60 mmHg and in the control group 10.97±1.42 mmHg (p=0.003). Mean IOPcc in the psoriasis group was 14.84±3.43 mmHg and in the control group 16.67±3.17 mmHg (p=0.035). Mean IOPg in the psoriasis group was 13.92±3.35 mmHg and in the control group 16.62±3.10 mmHg (p=0.002). Mean CCT in the psoriasis group was 543.90±37.27 µm and in the control group 551.23±28.63 µm (p=0.392). Schirmer's test results in the psoriasis group were 11.4 ±1.57 mm/5 min and in the control group 17.5±1.52 mm/5 min (p<0.001). Conclusion: Psoriasis affects corneal biomechanical properties with statistically significantly lower corneal biomechanics than normal. CH correlates negatively with disease activity. These corneal biomechanical changes should be considered when determining IOP values and during corneal evaluation for keratoconus-suspected patients.

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Introduction: TLRs are fundamental elements in the orchestration of innate immune system. These receptors seem to be responsible for the inflammation and fibrosis in chronic dacryocystitis. The aim of the present study was to investigate the role of toll-Like receptors (TLR2 and TLR4) signaling pathway and its downstream effector chemokine genes in the pathogenesis of chronic dacryocystitis. Method: This study was conducted on 20 patients diagnosed with chronic dacryocystitis and underwent external dacryocystorhinostomy. Estimation of gene expression of TLR2, TLR4, CCL2, CCL4, CXCL3, CXCR4 and c-FOS genes in the lacrimal sac tissues was performed together with assessment of the inflammatory markers TNFα, IL-1β, IFN-γ and IL-22. Histopathological examination of the lacrimal sac walls using hematoxylin and eosin (H&E) stain, in addition to immunohistochemical staining of the CD68 and CD163 macrophage markers were also performed. Results: Our results showed that TLR2, TLR4 and c-FOS gene expressions were significantly increased in chronic dacryocystitis group with subsequent increase in their downstream effector chemokine genes CCL2, CCL4 and CXCL3. This up-regulation of genes was accompanied by macrophage shift of polarization toward the M1 pro-inflammatory phenotype (increased CD68 and decreased CD163 expression), leading to increased levels of the pro-inflammatory cytokines (TNF-α, IL-1β and IFN-γ) and decreased anti-inflammatory marker IL-22 with chronic dacryocystitis. Conclusion: It is essential to fine tune TLR activation through emerging therapeutic approaches. Targeting of TLR signaling at the level of receptors or downstream adaptor molecules represents a new challenge for treatment of chronic dacryocystitis.