Exome sequencing and genome-wide association analyses unveils the genetic predisposition in hydroxychloroquine retinopathy.

OBJECTIVES: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). METHODS: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. RESULTS: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). CONCLUSIONS: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.

Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells.

Introduction: Glaucoma is a vision-threatening disease associated with accelerated aging of trabecular meshwork (TM) which results in elevated intraocular pressure (IOP). Increased oxidative stress in TM plays an important role in cellular molecular damage which leads to senescence. Autophagy is an intracellular lysosomal degradation process which is activated when cells are under stressful condition, and emerging studies have demonstrated increased expression of modulators of apoptosis and expression of autophagic cascade in ex-vivo TM specimens or cultured TM cells under oxidative stress. Recently, studies have shown neuroprotective and IOP-lowering effects after transplanting mesenchymal stem cells (MSCs) or injecting condition medium (CM) of MSCs into ocular hypertension animal models. However, knowledge of the underlying mechanism accounting for these effects is limited. Using condition medium (CM) from human bone marrow-derived mesenchymal stem cells (BM-MSCs), we investigated the effects of the CM derived from BM-MSCs on TM autophagy and apoptosis. Methods: H2O2 was added to culture medium of human TM cells to mimic oxidative damage in glaucomatous eyes, and the autophagic and anti-apoptotic effects of BM-MSCs-derived CM was explored on the oxidatively damaged cells. Mitochondrial ROS production was examined by MitoSOX™, apoptosis was evaluated using terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) staining, and the expression of proteins involved in autophagy as well as extracellular matrix was investigated via Western blot. Results: There were no significant differences in TM cell viability when the cells were treated with different concentrations of CM in the absence of oxidative stress. Cell viability was significantly higher in oxidatively damaged TM cells treated with 1X or 5X CM compared to untreated TM cells under oxidative stress. The mitochondrial ROS level significantly increased with oxidative stress, which was mitigated in the CM treatment groups. DNA fragmentation significantly decreased in oxidatively stressed TM cells after treatment with CM. LCB3 II/LCB3 I was significantly elevated in the oxidative stress group compared to the control group and was significantly decreased in the CM treatment groups. Expression of fibronectin was not significantly different among the groups. Conclusion: The CM derived from human BM-MSCs has the capacity to rescue oxidatively damaged human TM cells associated with decreased autophagy and apoptosis. The BM-MSCs CM has potential for slowing down age- and disease-related degeneration of TM in patients with glaucoma, facilitating success in the control of IOP.

Risks of posterior segment ocular ischaemic events in patients with systemic lupus erythematosus: a population-based cohort study in Taiwan.

BACKGROUD/AIM: Ocular involvement in systemic lupus erythematosus (SLE) is often primarily recognised by ophthalmologists rather than internists. This study aims to investigate the incidence and risk factors for the occurrence of posterior ocular ischaemic events (OIE), including retinal vein occlusion (RVO), retinal artery occlusion (RAO) and ischaemic optic neuropathy (ION), in patients with SLE. METHODS: A national database in Taiwan was used to identify 24 472 patients newly diagnosed with SLE and 244 720 age-matched and sex-matched controls between 1997 and 2012. New occurrences of OIE and confounding factors were recorded. The Kaplan-Meier method was used to compare the risk of OIE between the two groups. Fixed effect models were applied to evaluate the risk factors for OIE. RESULTS: The mean age was 36.24±15.82 years and women accounted for 88.4%. Patients with SLE had significantly increased risk of overall OIE (HR 3.89, 95% CI 3.36 to 4.50, p<0.001) as well as each OIE subtype. End-stage renal disease (ESRD; HR 2.91, 95% CI 2.05 to 4.14, p<0.001), hypertension (HR 1.77, 95% CI 1.21 to 2.58, p=0.003) and congestive heart failure (HR 1.67, 95% CI 1.12 to 2.48, p=0.01) were associated with RVO development. Hypertension (HR 2.89, 95% CI 1.10 to 3.96, p=0.02) and ischaemic stroke (HR 3.58, 95% CI 1.97 to 6.48, p<0.001) had increased risk of RAO. ESRD was associated with ION (HR 3.03, 95% CI 1.41 to 6.51, p=0.004). Intravenous steroid was associated with RVO development (HR 2.54, 95% CI 1.67 to 3.84, p<0.001). CONCLUSIONS: SLE increases the risk of developing OIE. Systemic comorbidities and higher dosage of steroid in patients with SLE are associated with severe ocular ischaemic complications.

Bleb-related infection after primary trabeculectomy: medical chart reviews from 1993 to 2021.

BACKGROUND: To investigate the incidence of and risk factors for bleb-related infection (BRI) in patients who underwent mitomycin C-augmented primary trabeculectomy. METHODS: We reviewed the medical charts of consecutive patients who had received primary trabeculectomy in Taipei Veterans General Hospital. We recorded the demographic and clinical characteristics of patients before, during and after surgery. Furthermore, we recorded the time interval between surgery and infection onset, clinical manifestations and visual outcomes of patients with BRI. The cumulative incidence of BRI was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to explore factors associated with BRI. RESULTS: In total, 1663 eyes were postoperatively followed up for 94.57±65.23 months. The cumulative incidence of BRI was 1.86 per 1000 person-years during the 28-year follow-up period: 24 (1.44%) patients developed BRI and 6 (0.36%) patients additionally developed endophthalmitis. A multivariate analysis revealed a significant association of BRI with wound manipulation, high myopia and hyperlipidaemia. Patients younger than 60 years were more likely to receive wound manipulation than their elderly counterparts (<0.001). One year after BRI, the best corrected visual acuity of the eyes with blebitis did not change significantly, whereas that of the eyes with endophthalmitis worsened significantly. CONCLUSION: Risk factors for BRI after trabeculectomy include wound manipulation, high myopia and hyperlipidaemia. Considering myopia is highly prevalent throughout the world and is a risk factor for glaucoma, the lifelong risk of BRI after trabeculectomy in eyes with high myopia warrants the attention of ophthalmologists.

Development of topical chitosan/ ß-glycerophosphate-based hydrogel loaded with levofloxacin in the treatment of keratitis: An ex-vivo study.

Staphylococcus species are responsible for most cases of post-operative endophthalmitis. Topical ocular drug was applied for post-operative infection prevention, but the way of delivery encounters many challenges in terms of patient's compliance, drug efficacy, and drug penetration. We used the levofloxacin-loaded chitosan/gelatin/ß-glycerophosphate hydrogel sustained releasing system with good in vitro anti-bacterial efficacy and biocompatibility, which we had previously designed, for ex vivo keratitis model to test the preclinical drug efficacy and to determine drug level in the anterior chamber of the eye. The result showed that the ex-vivo corneal keratitis model with S. aureus infection revealed mild opacity over the central cornea with stromal infiltrate, but without obvious stromal infiltration post levofloxacin-loaded hydrogel treatment after 24 h of infection. Quantification of viable bacteria showed a significant anti-bacterial activity. The histological evidence also showed no visible S. aureus after levofloxacin-loaded hydrogel treatment, with a significant anti-inflammatory effect. We also examined the drug concentration in the aqueous humor 24 h after instilling one drop of the levofloxacin-loaded hydrogel. The concentration achieved to a desired drug level. These results suggested that by the ex-vivo model, levofloxacin-loaded hydrogel can be applied for treatment in post-operative endophthalmitis or keratitis after the ophthalmic surgery.

FACTORS RELATED TO UNFAVORABLE VISUAL OUTCOME AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY IN PATIENTS WITH GLAUCOMA.

PURPOSE: To evaluate the visual outcomes after idiopathic epiretinal membrane surgery in glaucomatous and nonglaucomatous eyes and factors related to unfavorable outcomes in glaucomatous eyes. METHODS: This was a retrospective cohort study including patients undergoing idiopathic epiretinal membrane surgery with ≥12-month follow-up. Final visual acuity at pseudophakic status was compared among groups of glaucoma, glaucoma suspect, and nonglaucoma and correlated with optical coherence tomography and visual field characteristics in patients with glaucoma. RESULTS: Of the 314 patients enrolled, 31 had glaucoma and 22 were glaucoma suspect. Baseline visual acuity and central foveal thickness were similar across the groups. Most patients had improved/stable visual acuity postoperatively, with a lower proportion of 83.9% with glaucoma than 96.9% and 100% without glaucoma and glaucoma suspect, respectively (P = 0.002). The mean visual acuity did not change in the glaucoma group (from 6/29 to 6/23), but it improved from 6/25 to 6/12 (a gain of 16.7 approxETDRS letters) in nonglaucoma and 6/26 to 6/14 in glaucoma suspect (a gain of 14.0 approxETDRS letters) (both P < 0.001). The change of visual acuity was correlated with preoperative visual field defects (P < 0.001, r2 = 0.554). Patients with glaucoma with more advanced, fixation-threatening defects or temporally located inner nuclear layer microcysts were more likely to have worsened visual acuity. CONCLUSION: Visual field testing is imperative for patients with glaucoma before idiopathic epiretinal membrane surgery for outcome assessment.

Epidemiology and risk of invasive fungal infections in systemic lupus erythematosus: a nationwide population-based cohort study.

INTRODUCTION: Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited. METHODS: Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan's National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs. RESULTS: A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 [95% confidence interval (CI): 9.8-12.6] relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9-86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30-36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes. CONCLUSION: Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE. PLAIN LANGUAGE SUMMARIES: Patients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections.Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens.Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.

Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/ thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study.

Post-operative endophthalmitis (POE) is one of the most dreadful complications after intraocular surgery. For cataract surgery patients, both commercially available topical 0.5% levofloxacin and 1% prednisolone acetate (PA) ophthalmic solution require at least 3 to 4 times application daily. In this study, we develop a dual drug delivery system composed of the thermosensitive chitosan/gelatin-based hydrogel containing PA and levofloxacin-loaded nanoparticles (LNPs). LNPs with negative surface charge show the monodisperse (polydispersity index ~0.045), nanosize (~154.7 nm) and sphere-like structure. The optimal concentration of LNPs and PA to corneal epithelial cells was 5 µg/mL and 50 µg/mL, respectively. The developed dual drug delivery system (PAgel-LNPs) could gel at 34 °C within 63 s. The osmolarity of PAgel-LNPs was 301.2 ± 1.5 mOsm/L. PAgel-LNPs showed a sustained-release profile for 7 days. Post-treatment of PAgel-LNPs in TNF-α-damaged corneal epithelial cells could decrease the inflammation (inflammatory genes (TNF-α, IL-6, MMP-3 andMMP-9) and IL-6 production) and cell death. In ex-vivo rabbit model of S. aureus keratitis, the anti-inflammation and anti-bacterial property have been demonstrated. These results suggest that thermosensitive PAgel-LNPs may have the potential to use for the prevention of POE.

XEN45 Gel Stent implantation in eyes with primary open angle glaucoma: A study from a single hospital in Taiwan.

BACKGROUND: To evaluate the effectiveness and safety of the XEN45 Gel Stent in East Asian patients with primary open angle glaucoma (POAG). METHODS: We retrospectively reviewed 37 medically uncontrolled POAG patients who received XEN45 Gel Stent. The primary outcomes were reduction in intraocular pressure (IOP) and in the number of glaucoma medications 12 months after surgery. The secondary outcomes were requirement for intervention and further glaucoma surgery. The adverse intraoperative and postoperative events were investigated. RESULTS: At the 12-month postoperative follow-up, the mean IOP was significantly reduced from the preoperative value of 21.7 ± 7.7 mmHg to 15.0 ± 2.0 mmHg (p = 0.001). The mean number of glaucoma medications decreased from 3.4 ± 0.9 to 1.3 ± 1.5 (p < 0.001). Seventeen patients (45.9%) required postoperative interventions. Four patients (10.8%) received additional glaucoma surgery. Postoperative IOP at month 1 was significantly associated with outcomes at the 12-month follow-up and the need for subsequent intervention and additional glaucoma surgery. CONCLUSION: The XEN45 Gel Stent effectively reduced the IOP values and number of glaucoma medications in East Asian patients with POAG. No major complications were observed, but almost half of the eyes in the study required intervention for wound healing modification. Postoperative IOP at month 1 was a predictor of surgical success at 12 months after surgery.

Dendrimer-mediated columnar mesophase of surfactants.

The columnar mesophase, in which the molecular or supramolecular building blocks with rod-like geometry pack into two-dimensional (2D) lattices, is an important class of mesomorphic structure having been found in various liquid crystalline materials for practical applications. The cylindrical micelles assembled by amphiphilic surfactants may also form columnar mesophases with the micelle packing symmetry being tunable by the molecular characteristics of the surfactants. In this study, we demonstrate that a positively charged tree-like polymer, poly(amidoamine) (PAMAM) G4 dendrimer, acted as an effective structure-directing agent for the columnar mesophase of a common anionic surfactant, sodium dodecyl sulfate (SDS), via their electrostatic interaction. By adjusting the dendrimer charge density and the nominal binding ratio (Xn) of SDS to dendrimer, the electrostatic complexes self-assembled to form a body-centered cubic (BCC) sphere phase, wherein the dendrimers were staggered between the interspaces of the SDS spherical micelles packed in the BCC lattice. Four types of 2D columnar mesophase composed of SDS cylindrical micelles and dendrimers were accommodated within the interstitial tunnels, including the hexagonal columnar phase (Colhex), simple rectangular columnar phase (Colsr), oblique columnar phase (Colob) and centered rectangular columnar phase (Colcr). A detailed analysis of the geometry of the dendrimer in the columnar mesophases revealed that the structural transition was governed by the interplay among the lateral and axial deformations of the dendrimer, and the deformation of the SDS micelle cross section for achieving effective charge matching and accommodation of the dendrimer. The present study demonstrated the power of the dendrimer in directing the long-range ordered packing of oppositely charged cylinders to yield a rich structural polymorphism of the columnar mesophase that may be exploited for the development of functional materials.

Fourier analysis of circumpapillary retinal nerve fiber layer thickness in optical coherence tomography for differentiating myopia and glaucoma.

Differentiating glaucoma from myopic eye is a challenge to ophthalmologists. We try to develop a new discrete Fourier transform (DFT) model for analyzing optical coherence tomography data for the circumpapillary retinal nerve fiber layer (cpRNFL), and investigate DFT as a new diagnostic tool for glaucomatous myopic eyes. The thicknesses of 12 equidistant cpRNFL points were transformed into 6 signals in the frequency domain, ranging from 1 to 6 Hz. In all 232 eyes, generalized linear model showed that 1 Hz, 2 Hz, and 4 Hz were associated with glaucoma, high myopia, and the interaction between glaucoma and high myopia. The 3 Hz signal was associated with glaucoma and high myopia exclusively. A receiver operating characteristic curve analysis of the 3 Hz signals showed areas under the curves of 0.93 (95% CI 0.90-0.96) and 0.93 (95% CI 0.88-0.98), for diagnosing glaucoma in all subjects and in the highly myopic group, respectively. The DFT model is useful to differentiate glaucoma from non-glaucomatous change and showed potential as a diagnostic tool for glaucomatous myopic eyes.

Deep learning assisted detection of glaucomatous optic neuropathy and potential designs for a generalizable model.

PURPOSE: To evaluate ways to improve the generalizability of a deep learning algorithm for identifying glaucomatous optic neuropathy (GON) using a limited number of fundus photographs, as well as the key features being used for classification. METHODS: A total of 944 fundus images from Taipei Veterans General Hospital (TVGH) were retrospectively collected. Clinical and demographic characteristics, including structural and functional measurements of the images with GON, were recorded. Transfer learning based on VGGNet was used to construct a convolutional neural network (CNN) to identify GON. To avoid missing cases with advanced GON, an ensemble model was adopted in which a support vector machine classifier would make final classification based on cup-to-disc ratio if the CNN classifier had low-confidence score. The CNN classifier was first established using TVGH dataset, and then fine-tuned by combining the training images of TVGH and Drishti-GS datasets. Class activation map (CAM) was used to identify key features used for CNN classification. Performance of each classifier was determined through area under receiver operating characteristic curve (AUC) and compared with the ensemble model by diagnostic accuracy. RESULTS: In 187 TVGH test images, the accuracy, sensitivity, and specificity of the CNN classifier were 95.0%, 95.7%, and 94.2%, respectively, and the AUC was 0.992 compared to the 92.8% accuracy rate of the ensemble model. For the Drishti-GS test images, the accuracy of the CNN, the fine-tuned CNN and ensemble model was 33.3%, 80.3%, and 80.3%, respectively. The CNN classifier did not misclassify images with moderate to severe diseases. Class-discriminative regions revealed by CAM co-localized with known characteristics of GON. CONCLUSIONS: The ensemble model or a fine-tuned CNN classifier may be potential designs to build a generalizable deep learning model for glaucoma detection when large image databases are not available.

Optic Disc and Macular Vessel Density Measured by Optical Coherence Tomography Angiography in Open-Angle and Angle-Closure Glaucoma.

There is distinct pathogenesis between primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Although elevated intraocular pressure (IOP) is the major risk factor for glaucoma, non-IOP risk factors such as vascular abnormalities and lower systolic/diastolic perfusion pressure may play a role in the pathogenic process. This study aimed to compare the vessel density (VD) in the optic disc and macula using optical coherence tomography angiography (OCTA) between POAG and PACG eyes. Thirty-two POAG eyes, 30 PACG eyes, and 39 control eyes were included. All the optic disc VD parameters except the inside disc VD were significantly lower in glaucomatous eyes than in control eyes. Compared with PACG eyes, only the inferior temporal peripapillary VD was significantly lower in POAG eyes. The parafoveal VD was significantly lower in each quadrant in glaucomatous eyes than in control eyes. The central macular and parafoveal VD did not differ between POAG and PACG eyes. In conclusion, the inferior temporal peripapillary VD was significantly reduced in POAG eyes compared with PACG eyes, while PACG eyes showed a more evenly distributed reduction in the peripapillary VD. The distinct patterns of VD change may be associated with the different pathogenesis between POAG and PACG.

Diagnostic utility of neuroretinal rim thickness, measured in clock-hour sectors with HD optical coherence tomography, in preperimetric glaucoma.

BACKGROUND: We evaluated the usefulness of neuroretinal rim (NRR) thicknesses, measured in clock-hour sectors with Cirrus HD optical coherence tomography, for diagnosing preperimetric glaucoma (PPG). METHODS: This prospective study included 39 eyes of 39 patients with PPG and 39 eyes of 39 controls that were matched to patients for age and refractive error. We measured the circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with optical coherence tomography. The clock-hour NRR thicknesses were derived from a 360° circumferential rim thickness curve. We analyzed the area under the receiver operating characteristics curve (AUROC), cutoff values, and sensitivities at specificities of 90% and 95%. RESULTS: The largest area under the receiver operating characteristics curves were observed for the NRR thickness at 6 o'clock (0.823), the inferior RNFL thickness (0.821), the average RNFL thickness (0.819), and the NRR thickness at 7 o'clock (0.818). The performance of the NRR thickness at 6 o'clock was comparable to the best performances of the cpRNFL, GCIPL, and ONH parameters (all p > 0.05). CONCLUSION: The ability of the clock-hour NRR thickness assessment to diagnose PPG was comparable to the diagnostic abilities of cpRNFL, GCIPL, and ONH parameters. The best indicator of PPG was the NRR thickness parameter that was at 6 o'clock. This finding could play a role in detecting early structural changes in PPG.

Glaucoma assessment in high myopic eyes using optical coherence tomography with long axial length normative database.

BACKGROUND: We investigated the performance of glaucoma assessment using RS-3000 spectral domain optical coherence tomography with a long axial length (AL) normative database versus Cirrus HD-OCT in eyes with high myopia. METHODS: This is a prospective case-control study. Eyes with AL ≥26 mm were enrolled, including 40 control eyes and 41 eyes with primary open-angle glaucoma. Each participant received OCT imaging with both devices at the same visit. We calculated the area under receiver operating characteristic curve (AUROC) for circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (GCC) parameters, and compared the false-positive and false-negative rates between the two devices. RESULTS: Both devices performed comparably well in glaucoma assessment regarding cpRNFL parameters, with the best parameter being the average cpRNFL for RS-3000 (AUROC: 0.899) and the clock-hour 7 cpRNFL for Cirrus HD (AUROC: 0.912). Regarding macular GCC parameters, although the nasal-inferior outer sector of the RS-3000 (AUROC 0.873) and the inferior-temporal sector of the Cirrus HD (AUROC 0.840) performed well in glaucoma assessment, generally speaking there was a higher false-positive rate using Cirrus HD when compared with that of RS-3000. CONCLUSION: For eyes with long AL, both OCT devices are comparable in the ability of discriminating glaucoma from non-glaucoma in terms of cpRNFL parameters, while the macular GCC parameters of RS-3000 were less likely to over-diagnose glaucoma in highly myopic eyes.

Sustained release of levofloxacin from thermosensitive chitosan-based hydrogel for the treatment of postoperative endophthalmitis.

In the field of ophthalmology, postoperative endophthalmitis (POE) is a serious surgical complication, which may lead to poor visual outcome even after the infection has been controlled. In the study, we develop a sustained drug releasing system loaded with levofloxacin which is expected to be effective against common pathogens responsible for POE for at least 7 days after single application at the end of surgery. The results of study showed that the sol-gel transition temperature of the levofloxacin-loaded chitosan-gelatin-based solution was ~34°C. The gelation time of the developed formulation was ~81 s at 34°C. The results showed that the osmolality of developed hydrogel was 304 mOsm/L. The in vitro drug release studies revealed that levofloxacin release from the developed hydrogel displayed a sustained-release profile. The long-term antibacterial property of the developed hydrogel has been demonstrated. The biocompatibility of the developed hydrogel was evaluated in vitro. These results suggest that the levofloxacin-containing hydrogel could be applied to ocular surface at the end of ophthalmic surgery, without the risks of intracameral injection of antibiotics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:8-13, 2020.

Macular ganglion cell-inner plexiform vs retinal nerve fiber layer measurement to detect early glaucoma with superior or inferior hemifield defects.

BACKGROUND: To compare the diagnostic ability of Cirrus high-definition spectral-domain optical coherence tomography measurements of the macular ganglion cell-inner plexiform layer (GCIPL) vs the circumferential retinal nerve fiber layer (cpRNFL) to detect early glaucoma with hemifield visual field (VF) defects. METHODS: This prospective study included 96 patients with primary open-angle glaucoma (48 with superior hemifield defects and 48 with inferior hemifield defects) and 48 normal control subjects. All glaucomatous eyes had a mean deviation of the VF defect ≥-6.0 dB confined to one hemifield. cpRNFL and GCIPL thicknesses were recorded. Area under the receiver operating characteristic curve (AUROC) was calculated for each parameter and compared. RESULTS: All GCIPL parameters and most cpRNFL parameters (except at the nasal quadrant, and 2-, 3-, and 4-o'clock sectors) were significantly lower in glaucomatous eyes vs those in normal controls. In the superior hemifield defect group, the best discriminating parameters were 7-o'clock-sector cpRNFL thickness (AUROC value, 0.963), inferior cpRNFL thickness (0.926), and inferotemporal GCIPL thickness (0.923). Performance was comparable between the best measures of GCIPL analysis (inferotemporal GCIPL thickness) and those of cpRNFL (7-o'clock-sector thickness, p = 0.28). In the inferior hemifield defect group, the best discriminating parameters were 11- and 10-o'clock-sector cpRNFL thickness (0.940 and 0.904, respectively), and average cpRNFL thickness (0.909). Performance was comparable between the best measures from each method (superotemporal GCIPL thickness vs. 11-o'clock-sector cpRNFL thickness [0.857 vs 0.940, p = 0.07]). CONCLUSION: Diagnostic abilities of GCIPL parameters and cpRNFL parameters for early glaucoma were comparable for eyes with either superior or inferior hemifield VF defects.

Diagnostic ability of macular ganglion cell asymmetry in Preperimetric Glaucoma.

BACKGROUND: To evaluate the diagnostic ability of macular ganglion cell asymmetry to diagnose preperimetric glaucoma (PPG), using Cirrus spectral domain optical coherence tomography (OCT). METHODS: This prospective study included 67 eyes of 67 patients with PPG and 67 eyes of 67 age- and refractive error-matched controls. We measured circumpapillary RNFL (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness and optic nerve head (ONH) parameters using OCT. Macular ganglion cell asymmetries were expressed as absolute difference and ratios between inferior hemisphere and superior hemisphere, inferotemporal (IT) and superotemporal (ST), IT and superonasal (SN), IT and inferonasal (IN), ST and IN as well as temporal and nasal. An asymmetry index was assigned by taking the absolute value of log10 of the ratio. The area under the receiver operating characteristics curve (AUROC), partial AUROC (pAUROC) ≥ specificities 90 and 95%, cutoff values and sensitivities at specificities 90 and 95% was analyzed. RESULTS: Parameters with largest AUROCs were IT GCIPL thickness (0.784), average RNFL thickness (0.767), and average C/D (0.746). For macular asymmetry parameters, log IT/SN index had the largest AUROC (0.734), followed by log IT/IN index (0.725), and absolute difference of IT-SN GCIPL thickness (0.715). Performance was comparable between the best measures of asymmetry analysis (log IT/SN index) and those of cpRNFL, GCIPL, and ONH parameters (all P > 0.05). The IT/SN asymmetry index not only had the largest pAUROC based on the pAUROCs ≥90 and 95% specificity (0.044 and 0.019) but also had the highest diagnostic sensitivity at 90 and 95% specificities (52.2 and 46.3%). CONCLUSIONS: GCIPL asymmetry measurements have diagnostic ability comparable to cpRNFL, GCIPL, and ONH analysis for PPG. The best macular ganglion cell asymmetry parameter was IT/SN asymmetry index, which could be a new parameter to detect early structural changes in PPG.

Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment.

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 µM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma.