This study aimed to investigate the impact of ocular demodicosis on dry eye disease (DED) and meibomian gland dysfunction (MGD) across different age populations: young (20 to < 40), middle-aged (40 to < 60), and elderly (≥ 60), based on the retrospective medical chart review. In each age subgroup, Demodex infestation and its count were correlated with clinical parameters of DED and MGD. Among the total of 351 subjects, 52.7% had ocular demodicosis, with a mean of 2.31 ± 1.39 mites per four eyelashes (0.58 per lash) in a unilateral eye. In the age subgroup 1 (age < 40; N = 44), subjects with Demodex had significantly higher meibum quality grades. In subgroup 2 (40 ≤ age < 60; N = 122), subjects with Demodex had higher ocular surface disease index scores and higher MG expressibility grades. However, in subgroup 3 (age ≥ 60; N = 185), demographics and all parameters did not differ according to Demodex infestation. Moreover, the number of mites did not correlate with MGD severity in any of the subgroups. In conclusion, age may act as a significant confounding factor in the relationship between ocular Demodex infestation and clinical features of DED and MGD, despite older patients aged 60 years and above being at a higher risk of Demodex infestation and experiencing more severe MGD.

This study aimed to propose a neural network (NN)-based method to evaluate thyroid-associated orbitopathy (TAO) patient activity using orbital computed tomography (CT). Orbital CT scans were obtained from 144 active and 288 inactive TAO patients. These CT scans were preprocessed by selecting eleven slices from axial, coronal, and sagittal planes and segmenting the region of interest. We devised an NN employing information extracted from 13 pipelines to assess these slices and clinical patient age and sex data for TAO activity evaluation. The proposed NN’s performance in evaluating active and inactive TAO patients achieved a 0.871 area under the receiver operating curve (AUROC), 0.786 sensitivity, and 0.779 specificity values. In contrast, the comparison models CSPDenseNet and ConvNeXt were significantly inferior to the proposed model, with 0.819 ( p = 0.029) and 0.774 ( p = 0.04) AUROC values, respectively. Ablation studies based on the Sequential Forward Selection algorithm identified vital information for optimal performance and evidenced that NNs performed best with three to five active pipelines. This study establishes a promising TAO activity diagnosing tool with further validation.

Précis: Although Omidenepag isopropyl drops elicited stable intraocular pressure reductions in NTG patients, transient changes in refraction and corneal endothelial cells, significant increase of central corneal thickness, and corneal erosion should be considered. Purpose: To analyze the efficacy and safety of 0.002% omidenepag Isopropyl (OMDI) eye drops in patients with normal tension glaucoma (NTG). Methods: Medical records for 62 eyes treated with OMDI for ≥6 months were analyzed. Intraocular pressure (IOP), refraction, keratometry, central corneal thickness (CCT), endothelial cell count, coefficient of variation of endothelial cell area (CV), corneal erosion, and central retinal thickness were compared at baseline and 1, 3, and 6 months. Results: IOP significantly decreased from 13.4±3.8 to 11.9±3.0, 11.7±2.9, and 12.2±3.3 mm Hg at each follow-up (P<0.001). Endothelial cell count did not change, but CV transiently increased from 12.6 to 17.0 at 1 month, CCT increased from 531.5 to 538.4 μm, myopia changed from −1.5 to −1.9 D, and keratometry changed from 44.5 to 44.7 D. CV, myopia, and keratometry recovered to baseline at 6 months; however, CCT remained high. Significant corneal erosion was observed at 6 months. Central retinal thickness changes were not observed. There were improvements in prostaglandin-associated skin pigmentation (86.7%), eyelash elongation (40.0%), and deepening of the upper eyelid sulcus and ptosis (~30%) at 3 months after exchange to OMDI. Adverse reactions were corneal erosion (27.4%), corneal thickening (21.0%), conjunctival hyperemia (11.3%), photophobia (5.7%), blurred vision (5.7%), and anterior chamber cells (4.8%). Conclusions: OMDI eye drops elicited significant and stable IOP reductions after 6 months in NTG patients with low IOP. However, transient myopic and corneal endothelial cell changes, development of corneal thickening, and corneal erosion should be considered when using OMDI.

Purpose: To evaluate the effect of the intense pulsed light (IPL) and meibomian gland (MG) expression (MGX) combination therapy according to the total numbers of sessions in the meibomian gland dysfunction (MGD).Methods: Ninety patients with MGD were included. Patients had maximal five sessions of IPL (Aqua Cel, Jeisys Medical) and MGX combination therapy at 2-week intervals. The ocular surface disease index (OSDI) questionnaire score, MG profile grades, tear matrix metalloproteinase-9 (MMP-9), tear break-up time (BUT), tear osmolarity, tear secretion, and corneal erosions were evaluated.Results: The number of patients who had a total of one to five sessions (1S to 5S) was 10, 25, 17, 20, and 18, respectively. The time-serial decrease of OSDI scores was significant in patients who had three or more sessions (3S, p = 0.002; 4S, p < 0.001; 5S, p < 0.001). The MG expressibility grade decreased with two or more sessions (2S–5S, p < 0.001), but the meibum quality significantly improved with all sessions (1S, p = 0.012; 2S, p = 0.024; 3S, p = 0.015; 4S, p < 0.001; 5S, p < 0.001). Although tear BUT increased even in patients with one session (1S, p = 0.040; 3S, p = 0.005; 4S, p = 0.006; 5S, p = 0.021), tear MMP-9, osmolarity, Schirmer I, and corneal erosions were not improved in every number of sessions. The female sex was the sole contributor to the final symptomatic improvement (p = 0.042), and the MGD stages were not related to the final OSDI decrease.Conclusions: The OSDI score, MGD grades, and BUT were improved after the IPL and MGX combination therapy in MGD patients. Unlike MGD grades and tear film instability might be improved just after a few sessions, the overall subjective relief was accomplished in three or more sessions.

Purpose: To report a case with bilateral circumscribed posterior keratoconus with different results of refractive error between eyes after cataract surgery. Case summary: A 57-year-old man was referred for decreased vision and suspected keratoconus in both eyes. The corrected visual acuity was 0.04 in the right eye and 0.2 in the left eye. On slit-lamp microscopy and anterior-segment optical coherence tomography (AS-OCT) examination, the excavation of the posterior corneal surface was observed in the central area of the right eye and in the mid-to-inferior area of the left eye. Considering the posterior corneal refractive power measured within the 8-mm zone on AS-OCT, we expected the postoperative hyperopic shift in the refractive error of 2.61 diopters (D) in the right eye and 2.17 D in the left eye. Accordingly, the adjusted predicted refractive error was determined as -0.68 D in the right eye and -1.06 D in the left eye, based on the Barrett Universal II formula. The postoperative values of the spherical equivalent by manifest refraction was -1.0 D in the right eye and -3.0 D in the left eye at 1 month, which was close to the predicted target in the right eye, but myopic by approximately 2.0 D in the left eye, compared to the predicted values. Conclusions: In patients with bilateral circumscribed posterior keratoconus, the location, depth, and area of the excavation of the posterior corneal surface should be considered independently in both eyes to calculate the intraocular lens power more accurately. J Korean Ophthalmol Soc 2021;62(6):855-861

We evaluated the reliability and validity of the 5-scale grading system to interpret the point-of-care immunoassay for tear matrix metalloproteinase (MMP)-9. Six observers graded red bands of photographs of the readout window in MMP-9 immunoassay kit (InflammaDry) two times with 2-week interval based on the 5-scale grading system (i.e. grade 0–4). Interobserver and intraobserver reliability were evaluated using intraclass correlation coefficients. The interobserver agreements were analyzed according to the severity of tear MMP-9 expression. To validate the system, a concentration calibration curve was made using MMP-9 solutions with reference concentrations, then the distribution of MMP-9 concentrations was analyzed according to the 5-scale grading system. Both intraobserver and interobserver reliability was excellent. The readout grades were significantly correlated with the quantified colorimetric densities. The interobserver variance of readout grades had no correlation with the severity of the measured densities. The band density continued to increase up to a maximal concentration (i.e. 5000 ng/mL) according to the calibration curve. The difference of grades reflected the change of MMP-9 concentrations sensitively, especially between grade 2 and 4. Together, our data indicate that the subjective 5-scale grading system in the point-of-care MMP-9 immunoassay is an easy and reliable method with acceptable accuracy.

Purpose: We investigated the contributing factors affecting the ocular discomfort on instillation and compliance of 0.1% cyclo-sporin A (CsA) cationic nanoemulsion eye drops. Methods: We enrolled patients who were prescribed 0.1% CsA eye drops (Ikervis (R)) and who filled out an eye drop satisfaction questionnaire to assess ocular discomfort on instillation (questions Q1-Q4) and compliance of eye drops (Q5-Q7). First, to identify the contributing factors affecting the early ocular discomfort of 0.1% CsA instillation and compliance, Q1-Q7 scores were correlated with respect to age, sex, instillation period duration, meibomian gland dysfunction, tear secretion, corneal sensitivity, corneal erosions, Sjogren's International Collaborative Clinical Alliance ocular staining score (OSS), tear matrix metalloproteinase 9 (MMP-9), and ocular surface disease index in patients who completed the first questionnaire within the first 3 months of instillation of 0.1% CsA (referred to as Cohort 1). Second, to evaluate the change in ocular discomfort on instillation and compliance, along with the prolonged instillation of 0.1% CsA, the changes in individual scores for questions Q1-Q7 were analyzed in patients who completed at least two or more serial questionnaires (corresponding to Cohort 2). Results: In Cohort 1 (74 eyes in 39 patients), the scores for ocular discomfort on instillation (Q1-Q4) were higher in females and correlated negatively with the instillation period duration and age and positively with tear secretion, corneal erosions, OSS, and tear MMP-9 grades. The higher the grade of tear MMP-9, the lower the compliance score of Q5. In Cohort 2 (34 patients), the scores for ocular discomfort on instillation tended to decrease as the cumulative instillation period lengthened. Conclusions: The results of this study may aid clinicians in explaining to patients the ocular discomfort on instillation of 0.1% CsA, so as to improve treatment compliance.

ABSTRACT Purpose: To investigate the efficacy and safety of a new cyclosporine A (CsA) delivery system using contact lenses (CLs) for the treatment of experimental dry eye (EDE). Methods: CsA-laden porous carriers and CsA-eluting CLs were fabricated using the supercritical fluid technique. The release of CsA from carriers and CLs was investigated using high-performance liquid chromatography. The CsA concentrations in the cornea, conjunctiva, and crystalline lens of rabbits were measured. Dry eye was induced using 0.1% benzalkonium chloride in rabbits, which were subdivided into the normal, EDE, balanced salt solution (BSS), 0.05% CsA, hydrogel CL, or CsA-CL groups. Tear volume, tear film break-up time (TBUT), and corneal staining scores were measured at 1 and 2 weeks after treatment. Periodic acid-Schiff staining for the evaluation of conjunctival goblet cell density was performed at 2 weeks. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and interferon-γ levels in the conjunctiva were measured using enzyme-linked immune-sorbent assay. Results: The porous carrier showed the release of drug. CsA-eluting CLs showed initial burst and sustained release of CsA until 48 h. The concentration of CsA elevated in the cornea, conjunctiva, and lens until 48 h after application of CsA-CLs. The CsA-CL group showed significantly higher tear volume, TBUT, and lower corneal staining scores compared to the other groups (p < 0.05). Goblet cell density was significantly higher in the CsA-CL group compared to the other groups. The CsA-CLs group showed a lower level of IL-1β than the BSS and soft CL groups (p < 0.01), and a lower level of IFN-γ than the other groups (all p < 0.01). Conclusions: The newly designed CsA-eluting CLs released drug continuously and showed good penetration in the eye. In addition, the use of CsA-eluting CLs improved clinical parameters and conjunctival goblet cell density and decreased inflammatory cytokines.

OBJECTIVES:Solid dispersion formulations have attracted attention to improve solubility and bioavailability of water-insoluble drugs. In this study, the variation of solubility and bioavailability by different preparation methods were studied using itraconazole (ITZ) solid dispersions.METHODS:Itraconazole solid dispersions were prepared by a solvent-controlled precipitation method (SCPM) using HPMCAS-LF, HCl antisolvent or a spray-drying method (SDM) for comparison. Dissolution tests by pH transition and pharmacokinetic study using male Sprague Dawley rats were conducted.KEY FINDINGS:Itraconazole solid dispersion dissolution tests by pH transition exhibited better dissolution compared to naive ITZ, limited dissolution in acidic conditions and a burst release at neutral pH. The ITZ solid dispersions by SCPM indicated a smaller-sized particle dispersion, limited dissolution at acidic pH and a higher release at neutral pH compared to those by SDM, suggesting that the increased protonation of anionic polymers and HPMCAS-LF by acidic antisolvent could form a tighter hydrophobic aggregation with ITZ in solid dispersions. ITZ solid dispersion prepared by SCPM also showed improved ITZ absorption in male Sprague Dawley rats compared to SDM and naïve ITZ.CONCLUSIONS:This study suggests that the SCPM method can be widely used for solid dispersion preparations due to improved dissolution and PK profile.

Nanoemulsions (NE) are advantageous nanosized delivery agents for ophthalmic medications because of their ability to penetrate into the ocular structure, as well as their sustained effects. We prepared a NE system composed of isopropyl myristate, triacetin, Tween 80, and ethyl alcohol to increase the solubility and permeability of lutein, an effective medication in macular degeneration. The pseudo-ternary phase diagram was constructed to identify the self-emulsifying region. Eight formulations were selected to characterize each formulation. We examined physical characteristics including particle size, drug solubility, formulation stability, and turbidity. We selected the optimized formulations NE 5 (NE-5) and NE-8, both of which are transparent. The particle size of NE was ca. 10-12 nm with a narrow size distribution. Neither separation nor change in the particle size was observed for 7 days. The lutein loading NEs demonstrated a significant increase in lutein release and sustained release. In contrast, lutein prepared with oil and starch had. limited drug release profiles under 5%. The prepared lutein NE formulation is a potential alternative for lutein delivery systems. (C) 2016 Elsevier B.V. All rights reserved.

Nanotechnology has been applied to the oral drug delivery for enhancing bioavailability after oral administration. Numerous forms of reported nanomedicines are classified as lipid based nanomedicine (LBNM), polymer based nanomedicine (PBNM), and nanosuspension. LBNM includes self nano-emulsifying drug delivery systems, liposomes and solid lipid nanoparticle (SLN). PBNM includes polymeric nanoparticles and polymeric micelles. Unlike intravenous administration, oral administration has more complicated barriers that are hard to overcome. The various nanoplatforms described above are used to surmount physical and bio-chemical barriers due to advantageous characteristics of nanoplatforms. The characteristics of nanoplatforms including particle size, stimuli-sensitivity, preventing drug efflux, solubility and permeation of the drug induce the enhanced absorption and high bioavailability. Regardless of passionate researches, some limitations still exist, for instance economic problems, toxicity issue, and development of biopharmaceutic oral nanomedicine. In this review, physiological barriers in oral administration, advantages of nanomedicines, classification of oral nanomedicines, and their challenges are described concisely.