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.

Neuroprotection in Glaucoma: Basic Aspects and Clinical Relevance.

Glaucoma is a neurodegenerative disease that affects primarily the retinal ganglion cells (RGCs). Increased intraocular pressure (IOP) is one of the major risk factors for glaucoma. The mainstay of current glaucoma therapy is limited to lowering IOP; however, controlling IOP in certain patients can be futile in slowing disease progression. The understanding of potential biomolecular processes that occur in glaucomatous degeneration allows for the development of glaucoma treatments that modulate the death of RGCs. Neuroprotection is the modification of RGCs and the microenvironment of neurons to promote neuron survival and function. Numerous studies have revealed effective neuroprotection modalities in animal models of glaucoma; nevertheless, clinical translation remains a major challenge. In this review, we select the most clinically relevant treatment strategies, summarize preclinical and clinical data as well as recent therapeutic advances in IOP-independent neuroprotection research, and discuss the feasibility and hurdles of each therapeutic approach based on possible pathogenic mechanisms. We also summarize the potential therapeutic mechanisms of various agents in neuroprotection related to glutamate excitotoxicity.

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.

Widen the Applicability of a Convolutional Neural-Network-Assisted Glaucoma Detection Algorithm of Limited Training Images across Different Datasets.

Automated glaucoma detection using deep learning may increase the diagnostic rate of glaucoma to prevent blindness, but generalizable models are currently unavailable despite the use of huge training datasets. This study aims to evaluate the performance of a convolutional neural network (CNN) classifier trained with a limited number of high-quality fundus images in detecting glaucoma and methods to improve its performance across different datasets. A CNN classifier was constructed using EfficientNet B3 and 944 images collected from one medical center (core model) and externally validated using three datasets. The performance of the core model was compared with (1) the integrated model constructed by using all training images from the four datasets and (2) the dataset-specific model built by fine-tuning the core model with training images from the external datasets. The diagnostic accuracy of the core model was 95.62% but dropped to ranges of 52.5-80.0% on the external datasets. Dataset-specific models exhibited superior diagnostic performance on the external datasets compared to other models, with a diagnostic accuracy of 87.50-92.5%. The findings suggest that dataset-specific tuning of the core CNN classifier effectively improves its applicability across different datasets when increasing training images fails to achieve generalization.

Traumatic aniridia with extensive episcleral pigmentation: a case report.

BACKGROUND: Traumatic aniridia has been documented in eyes with a history of cataract extraction through a clear corneal wound. The proposed hypothesis is that the iris tissue was squeezed out from the corneal wound as it is a relative weak point. However, traumatic aniridia with extensive pigmentation of the episclera has never been reported. CASE PRESENTATION: A patient, who has surgical histories of trabeculectomy and cataract surgery many years ago, presented with refractory high intraocular pressure (IOP), almost complete loss of the iris, and diffuse pigmentation of the episclera after he had suffered from a contusion injury. In addition to numerous pigment particles and cells in the anterior chamber and a well-centered intraocular lens, protruding uvea tissue with overlying conjunctiva adjacent to the site of trabeculectomy was noted. Gonioscopy showed absence of the iris with clear view of the ciliary body. CONCLUSIONS: The distinct presentation of this case indicates that the torn iris was displaced to the trapdoor instead of the clear cornea incision and was confined to the subconjunctival space. The scleral fistula serves as a less resistant point for releasing pressure compared to a healed corneal wound when the eye encounters a contusion injury. Further treatment options to lower IOP include repeated trabeculectomy, implantation of glaucoma drainage device, and endoscopic cyclophotocoagulation. Transscleral cyclophotocoagulation may be considered only after episcleral pigmentation has become less so as to avoid the risk of surface burn.

Outcomes and risk factors for failure after trabeculectomy in Taiwanese patients: medical chart reviews from 2006 to 2017.

AIMS: To determine long-term outcomes and risk factors for failure after mitomycin C (MMC)-augmented initial trabeculectomy (IT) in Taiwanese patients. METHODS: We reviewed medical records of patients with glaucoma undergoing IT during December 2006-December 2016. We defined complete success as an intraocular pressure (IOP) of >5 or ≤21 mm Hg or IOP reduction of ≥20% from baseline without supplemental medications and qualified success as the aforementioned IOP levels with or without supplemental medications. Kaplan-Meier survival and Cox proportional analyses evaluated success rates and risk factors for failure, respectively. RESULTS: We enrolled 190 patients (237 eyes; mean age: 54.0±15.3 years; mean postoperative follow-up period: 68.4±35.1 months). Mean IOP and glaucoma medications decreased from 22.2±10.8 to 14.4±5.2 mm Hg (p<0.001) and 3.0±0.7 to 1.8±1.2 (p=0.015), respectively, at the last visit. Cumulative qualified success rates were 93.9%, 93.0%, 86.5% and 67.1% at the 1, 2, 5 and 10 years follow-up, respectively; however, only 7.7% of the eyes reached complete success at the last visit. Eyes with poor preoperative visual acuity were associated with low qualified success rates (HR=1.689, p=0.027); patients aged >70 years had higher complete success rates than did those aged ≤70 years. Five cases (2.11%) exhibited bleb-associated complications. CONCLUSION: Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.

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.

Comparison of clinical outcomes of LASIK, Trans-PRK, and SMILE for correction of myopia.

Transepithelial photorefractive keratectomy (Trans-PRK), laser-assisted in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE) are three mainstay refractive surgeries worldwide. The applicability, efficacy, safety, and predictability of these different techniques are quite similar. Trans-PRK has the strongest biostability, earliest return to normal corneal sensitivity but the longest recovery time, most uncomfortable postoperative experience, and possibility of corneal haze. LASIK possesses the fastest visual rehabilitation but the slowest corneal nerve reinnervation, and flap displacement is possibly lifelong. SMILE incurs no flap-related complications and has intermediate vision recovery time and biomechanics compared with Trans-PRK and LASIK. However, it lacks the cyclotorsion-compensation system, eye-tracking system, and customized treatment profile for high astigmatism or irregular corneal surface. This review aims to introduce the mechanisms, pros, and cons of these three types of refractive surgery. With full understanding, practitioners could advise patients on the most suitable treatment of choice.

Optical coherence tomography-guided early postoperative management of XEN Gel implant.

This interventional case series demonstrates the usefulness of anterior segment optical coherence tomography (AS-OCT) in guiding early postoperative management following XEN45 Gel Stent implantation, in conjunction with intraocular pressure (IOP) readings and slit lamp findings. Three primary open-angle glaucoma patients undergoing XEN45 Gel Stent implantation were included. Two patients received early postoperative needling because the IOP was not low enough and AS-OCT revealed that the XEN stent orifice was trapped by the Tenon's capsule. Immediately after needling, the distal tip of the XEN stent was freed and connected to a cystic space with significant IOP reduction. The third patient suffered from abrupt bleb flattening on the 5th postoperative day following XEN stent implantation. AS-OCT revealed internal occlusion of the XEN stent with exudative material, which resolved spontaneously after intensifying topical steroids with improved bleb functioning 2 days later. AS-OCT provides in-depth microscopic evaluation of the XEN stent and its relationship with surrounding tissue. This information is helpful in identifying causes of impaired outflow, determining the timing, and effect of needling intervention in eyes with inadequate bleb functioning or IOP control, especially during the early postoperative period.

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.

Comparison of the iCare, Tono-Pen, non-contact airpuff, and Goldmann applanation tonometers in eyes with corneal edema after penetrating keratoplasty.

BACKGROUND: To compare the utility of the iCare, Tono-Pen, and non-contact airpuff (NCT) tonometers with the Goldmann applanation tonometer (GAT) for measuring intraocular pressure (IOP) in patients with corneal edema after penetrating keratoplasty (PKP) and to assess the effects of central corneal thickness (CCT) and corneal curvature (CC) on IOP measurements. METHODS: Thirty-two eyes of 27 patients with corneal edema after PKP due to corneal abnormalities and 43 control eyes of 30 patients with normal corneas were recruited. Before IOP measurements, all patients underwent a baseline examination, including auto-refraction, keratometry, slit lamp biomicroscopy, and CCT measurement. IOP was measured using the devices in the same order: first the NCT, followed by the iCare, Tono-Pen, and GAT. The differences between the iCare, Tono-Pen, NCT, and GAT were calculated with repeated-measures analysis of variance. The Bland-Altman method was used to assess the agreement between the iCare, Tono-Pen, and NCT versus the GAT. The influences of CCT and CC on IOP measurement were evaluated by correlation analysis using Pearson's correlation coefficient. RESULTS: Mean IOP measurements were significantly higher with the NCT and Tono-Pen than with the GAT in the PKP and control groups. When compared with GAT, iCare showed significantly higher IOP readings in the control group, but the IOP readings did not differ between the iCare and GAT in the PKP group. Poor agreement was noted between the NCT and GAT in both groups. The Tono-Pen showed clinically acceptable agreement with GAT in control eyes and poor agreement in PKP eyes. The agreement between the iCare and GAT appeared to be clinically acceptable in both groups. Correlation analysis of the results from control eyes showed that the IOP measurements with the GAT and NCT were weakly related to CCT and moderately correlated with CC. The iCare IOP readings were weakly correlated with CCT and CC. CONCLUSION: In the PKP group, the NCT and Tono-Pen significantly overestimated IOP, whereas the iCare IOP readings were similar to those obtained using the GAT. Poor agreement was noted between the NCT and GAT as well as between the Tono-Pen and GAT, but the iCare showed clinically acceptable agreement with GAT. In normal corneas, the GAT, NCT, and iCare were affected by CCT and CC. The iCare tonometer was less affected by corneal edema than were the NCT and the Tono-Pen. The iCare appears to be a useful device for IOP measurement in eyes with corneal edema after PKP.

Determinants of post-mydriatic intraocular pressure in phakic eyes with prevalent angle closure diseases.

PURPOSE: This study aimed to identify acute angle closure (AAC) risk following pharmacologic mydriasis and the factors affecting post-mydriatic intraocular pressure (IOP) in a population with a high prevalence of angle closure disease. METHODS: In total, 460 individuals aged ≥ 72 years were enrolled in this cross-sectional community-based screening program. IOP was measured at baseline and 1 hour after mydriasis. Individuals with post-mydriatic IOP spike > 6 mmHg received indentation gonioscopy and IOP-lowering medication. Linear regression analysis was used to identify ocular parameters associated with post-mydriatic IOP elevation. RESULTS: The mean age of participants was 77.8 ± 4.1 years, and 65.4% of them were men. In total, 21 eyes of 16 participants (3.48%) had post-mydriatic IOP spikes (range: 6-13.7 mmHg); among them, 15 eyes had an IOP of > 21 mmHg. None of the participants developed AAC. All eyes with IOP spikes were phakic, except for one with pseudophakic angle closure. Analysis of 381 participants with at least one phakic eye revealed that higher post-mydriatic IOP and IOP changes were associated with narrower angle grading, more extensive peripheral anterior synechiae, shallower central anterior chamber, and thicker lens. According to multiple linear regression analysis, post-mydriatic IOP was independently associated with baseline IOP and factors suggestive of crowded anterior chamber based on gonioscopic findings and central or peripheral anterior chamber depth evaluation in conjunction with lens thickness. CONCLUSION: Post-mydriatic IOP should be measured in phakic eyes with a crowded anterior chamber. Post-mydriatic IOP spikes can be effectively blunted with intervention to prevent AAC.

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.

Prevalence of glaucoma in the elderly population in Taiwan: The Shihpai Eye Study.

BACKGROUND: This study aimed to evaluate the prevalence, characteristics, and the awareness status of glaucoma in an elderly Chinese population. METHODS: A total of 460 individuals aged ≥72 years were enrolled in this cross-sectional community-based eye disease screening program. Glaucoma was diagnosed according to the diagnostic criteria proposed by the International Society of Geographical and Epidemiological Ophthalmology. Characteristics of subjects with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) were described and compared between groups using Mann-Whitney U and Fisher's exact tests. RESULTS: Forty subjects were diagnosed with glaucoma, including 17 subjects with POAG, 22 with PACG, and one with secondary glaucoma. The estimated prevalence of glaucoma, POAG, and PACG was 8.7%, 3.7%, and 4.8%, respectively. In total, 71% of the subjects with PACG and 77% of POAG subjects presented with a normal intraocular pressure (IOP) of <19 mmHg. The demographic and ocular characteristics were similar between the two groups; however, subjects with POAG had a longer axial length and smaller vertical disc diameter than those with PACG. Further, 95% of the glaucoma subjects ever visited the eye clinic, but only 32.5% of them were aware of the disease. CONCLUSION: Glaucoma is prevalent in the elderly population in Taiwan, but the diagnostic rate and disease awareness are low. Since most subjects with glaucoma presented with normal IOPs, optic disc evaluation is critical for diagnosing glaucoma in the elderly in Taiwan.

The influence of topical non-steroidal anti-inflammatory drugs on the intraocular pressure lowering effect of topical prostaglandin analogues-A systemic review and meta-analysis.

PURPOSE: This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in glaucoma patients who were treated with prostaglandin analogues (PGs). METHOD: The presenting study was designed as a meta-analysis of previous research. Databases include PubMed, Web of science, Cochrane library, and Embase were searched with keywords of "intraocular pressure, prostaglandin analogues, NSAIDs, latanoprost, travoprost, bimatoprost, tafluprost, unoprostone, latanoprostene bunod, ketorolac, diclofenac, nepafenac, bromfenac, flurbiprofen". Inclusion criteria were: 1. Study population were glaucoma patients; 2. Comparison between PGs monotherapy and PGs in combination with topical NSAIDs; 3. Changes of IOP as final outcomes. Studies with non-randomized design, treatments combining other anti-glaucomatous drugs, or unavailable absolute IOP were excluded from the analysis. Estimated difference in IOP were calculated using STATA 14.0. RESULT: Seven studies were retrieved for this meta-analysis. Since there is a significant heterogeneity (I2 = 94%) in these studies, random-effect model was used to calculate pooled standardized mean differences (SMD). Our results showed a significantly favorable IOP lowering effect in glaucoma patients treated with combination of topical NSAIDs and PGEs (SMD: 1.3 and -0.03, 95% CI: 0.29 to 2.38 and -0.32 to 0.26, Z = 2.50 and 0.23, p = 0.013 and 0.820, respectively). CONCLUSION: Results of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients.

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.

Change of Eyelid Parameters in Patients With Marin-Amat Syndrome.

PURPOSE: Marin-Amat syndrome is an acquired facial synkinesis manifesting as involuntary eyelid closure on jaw movement. The authors investigate the clinical features, especially the quantitative changes in eyelid parameters of patients with Marin-Amat syndrome. METHODS: Patients with Marin-Amat syndrome between 2015 and 2017 in a medical center were collected. Clinical features and the change of eyelid parameters, including margin reflex distance 1 (MRD-1), margin reflex distance 2 (MRD-2), and palpebral fissure height, were evaluated. RESULTS: There were 5 men and 3 women with a mean age of 76 years. All had a history of facial palsy. The mean time to onset of Marin-Amat syndrome was 4.4 years after facial palsy. Seven patients (87.5%) developed subsequent ipsilateral facial spasm after facial palsy. Most patient complaints were ptosis (62.5%) and ptosis on eating (37.5%). The mean palpebral fissure height of involved eyes decreased from 5.88 to 2 mm on jaw opening (p = 0.011), which resulted from decrease in MRD-1 (from 2.06 to 0.06 mm, p = 0.012) and MRD-2 (from 3.81 to 1.94 mm; p = 0.012). Botulinum toxin A (Botox) injection into the periorbital orbicularis muscle in 6 patients significantly relieved the change of palpebral fissure height on jaw opening compared with that before injection (9.9% vs. 68.6 %, p = 0.027). CONCLUSIONS: Most patients with Marin-Amat syndrome present with ptosis and might be overlooked or underestimated. The reduction in palpebral fissure height in our patients with Marin-Amat syndrome was due to involuntary orbicularis oculi muscle contraction, resulting in decrease of both the MRD-1 and MRD-2 on jaw opening.

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.

Selective laser trabeculoplasty versus medication for open-angle glaucoma: systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: The only widely accepted, effective treatment for open-angle glaucoma (OAG) is to reduce the intraocular pressure (IOP), with medical therapy being the typical first-line therapy. Notably, an alternative therapy is selective laser trabeculoplasty (SLT), which is safe and effective in lowering the IOP. Nonetheless, whether SLT could replace medication as the first-line therapy for OAG is still under debate. METHODS: Studies involving randomised controlled trials conducted before August 2019 that compared the efficacy of SLT-related and medication-only treatments for OAG were selected from PubMed, Embase, Cochrane Library and Web of Science. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology was employed to rate the quality of the body of evidence. RESULTS: 1229 patients in eight trials were included. The overall results revealed no significant differences between SLT-related and medication-only treatments regarding the IOP reduction (mean difference (MD): 0.18, 95% CI -0.72 to 1.07, p=0.70, I2=73%) and the success rate of IOP control (risk ratio: 1.02, 95% CI 0.99 to 1.04, p=0.74, I2=0%). The SLT-related therapy group required significantly fewer medications compared with the medication-only group (MD: -1.06, 95% CI -1.16 to -0.96, p<0.0000, I2=5%). A quantitative analysis was not performed concerning adverse events and quality of life because of the limited data available. CONCLUSION: SLT is safe and has a lower incidence of ocular side effects. SLT can be the choice of first-line therapy for OAG. However, clinicians should consider the cost-effectiveness, as well as the patient's characteristics, before deciding on the therapeutic option.