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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.

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.HThere 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.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.

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.

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. 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. 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. 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.

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.

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.

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.

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.

To evaluate the visual outcomes after idiopathic epiretinal membrane surgery in glaucomatous and nonglaucomatous eyes and factors related to unfavorable outcomes in glaucomatous eyes.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.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 P0.001). The change of visual acuity was correlated with preoperative visual field defects (P0.001, 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.Visual field testing is imperative for patients with glaucoma before idiopathic epiretinal membrane surgery for outcome assessment.

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.

BackgroundTo investigate the incidence of and risk factors for bleb-related infection (BRI) in patients who underwent mitomycin C-augmented primary trabeculectomy.MethodsWe 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.ResultsIn 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 (ConclusionRisk 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.

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.

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.

Cytomegalovirus (CMV) retinitis comorbid with diabetic retinopathy is uncommon. We report a case of bilateral CMV retinitis and diabetic retinopathy in a patient who underwent pancreas transplantation and share the experience of the treatment outcome. An 18-year-old male diagnosed with type-1 diabetes mellitus received pancreas transplantation and immunosuppressive therapy suffered from progressively blurred vision in both eyes for several days. His visual acuity was 20/100 in the right eye and 20/50 in the left eye. Ophthalmic examination revealed bilateral diabetic macular edema (DME) without intraocular inflammatory signs in either eye. The DME subsided after 2 monthly intravitreal injections of aflibercept. However, bilateral panuveitis with CMV retinitis was observed after antivascular endothelial growth factor therapy. The retinitis subsided gradually but completely after systemic and intravitreal antiviral therapy. However, bilateral DME recurred and persisted despite repeated injections of aflibercept during the resting follow-up period. Our case suggests that CMV retinitis can coexist with other retinal diseases, including diabetic retinopathy. Treatment is difficult in such cases.

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/β-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., Levofloxacin; Chitosan/β-glycerophosphate-based Hydrogel; ex-vivo corneal keratitis model.

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.

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.

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.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 spike6 mmHg received indentation gonioscopy and IOP-lowering medication. Linear regression analysis was used to identify ocular parameters associated with post-mydriatic IOP elevation.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 of21 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.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.

PurposeThis 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).MethodThe 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.ResultSeven 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).ConclusionResults of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients.

Although current studies suggested that conjunctivitis is not a common presentation of coronavirus disease 2019 (COVID-19), several studies have reported the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ocular secretions. Coronavirus had not yet been successfully cultured from tears or conjunctival swabs in humans, neither SARS-CoV-2 nor SARS-CoV. However, live feline coronavirus has been isolated from conjunctival swabs. In addition, infection of COVID-19 through unprotected eye exposure had been suspected in several articles. Reports of ophthalmologists and otolaryngologists died of COVID-19 also raised concern on ocular transmission. As a result, we strongly suggest that personal protective equipment (PPE) should cover the mouth, nose, and eyes of ophthalmologists, especially when conjunctivitis caused by SARS-CoV-2 is clinically indistinguishable from other viral follicular conjunctivitis.

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.

Purpose. To compare the clinical characteristics and treatment outcome between benign and malignant lacrimal sac tumors. Methods. We retrospectively reviewed the medical records of all patients with pathologically confirmed lacrimal sac lesions from 1995 to 2018 in a tertiary medical center. Results. Among 65 eligible cases, 46 (70.8%) were benign lacrimal sac tumors and 19 (29.2%) were malignant lacrimal sac tumors. Secondary malignancy from nasal or paranasal cancer accounted for 47% of malignant lacrimal sac tumors. The patient’s mean age at the time of diagnosis was 60 years in the benign group and 48 years in the malignant group (p=0.03). The most common presenting symptoms were a palpable lump/mass and epiphora in both groups. Palpable mass extending above the medial canthal tendon was noted in 9% of the benign group and in 74% of the malignant group, respectively (p<0.001). Bloody tears were noted in 5% of the benign group and in 20% of the malignant group (p=0.21). In the malignant group, 10 (52.6%) were primary tumors and 9 (47.4%) were secondary tumors. The primary sites of the metastatic tumor to the lacrimal sac area were mostly from neighboring paranasal sinuses and nasal cavity. The recurrence rate was higher in patients with malignant tumors, as compared to the benign tumors (42% and 6%, respectively, p=0.001). The metastatic rate was 47% and the mortality rate was 53% in malignant lacrimal sac tumors. Conclusion. Although benign and malignant lacrimal sac tumors may present similar initial symptoms, timely diagnosis and intervention for malignant lacrimal sac lesions are important because they tend to be infiltrating tumors with a poor outcome.

Hsin-Yu Yang,1 Yu-Fan Chang,1,2 Chih-Chien Hsu,1,2 Yu-Chieh Ko,1–3 Catherine Jui-Ling Liu,1,3 Mei-Ju Chen1,3 1Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 3School of Medicine, National Yang-Ming University, Taipei, Taiwan Purpose: We evaluated macular ganglion cell asymmetry as a tool for diagnosing paracentral scotoma (PCS) in early glaucoma.Patients and methods: This prospective study compared 58 patients with early glaucoma and PCS to 58 age-matched control individuals. All glaucomatous eyes had scotoma within the central 12 degrees of fixation and confined to one hemifield. We measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with Cirrus spectral domain optical coherence tomography. Macular ganglion cell asymmetry was expressed as the absolute differences and the ratios between the inferior and superior hemispheres, inferotemporal (IT) and superotemporal (ST) areas, IT and superonasal (SN) areas, IT and inferonasal (IN) areas, and ST and IN areas. The asymmetry index was the absolute log10 of the ratio. The area under the receiver operating characteristics curve (AUROC) and partial AUROC (pAUROC, specificities ≥90%) were analyzed for each parameter.Results: All GCIPL parameters and most cpRNFL parameters were significantly lower in early glaucoma than in controls. The best discriminating parameters were inferior RNFL thickness, average RNFL thickness, and minimum GCIPL thickness. The macular ganglion cell asymmetry parameters with the largest AUROCs were the log IT/ST index, the absolute difference in IT-ST GCIPL thicknesses, and the log IT/SN index. Performance was comparable between the log IT/ST index and the cpRNFL (inferior RNFL thickness, P=0.129), GCIPL (minimum GCIPL thickness, P=0.358), and ONH parameters (vertical cup-to-disc ratio, P=0.475).Conclusion: The IT/ST asymmetry index may be useful as a new parameter for detecting structural changes in glaucoma patients with PCS.Keywords: macular ganglion cell, paracentral scotoma, glaucoma, optical coherence tomography

A 64-year-old male presented with progressive proptosis of the left eye for 3 months. Orbital computed tomography (CT) demonstrated a 3.9 cm infiltrative mass over the superotemporal quadrant of the left orbit. Pathology of biopsy revealed a ductal adenocarcinoma of lacrimal gland with positive immunohistochemical staining for androgen receptor (AR), cytokeratin-7 (CK7), and gross cystic disease fluid protein 15 (GCDFP-15). The patient received orbital exenteration and adjuvant chemoradiotherapy. No recurrence or metastasis was noted 27 months after treatment. Another case was a 64-year-old male who came for proptosis of the right eye and diplopia for 3 weeks. Orbital CT revealed a 5 cm infiltrated right superotemporal orbital mass with destruction of the lateral and inferior orbital walls. Biopsy showed primary ductal adenocarcinoma of lacrimal gland with positive immunohistochemical staining for CK7, AR, and epidermal growth factor receptor. The patient underwent exenteration and concomitant chemoradiotherapy. However, lung and neck metastasis was noted 21 months after surgery. Collectively, 26 cases in the literature were reviewed. The mean age was 57 years old and male was prevalent (73%). Most immunohistological staining showed positive for AR (46%), CK7 (46%), Ki-67 (38%), and GCDFP-15 (35%). More than half of the patients developed metastasis and one-third of the patients died of disease. Early diagnosis, treatment, and long-term follow-up are required for this aggressive tumor.

Immune checkpoint blockade therapy is relatively a new treatment for cancer which has shown promising results. However, immune-related side effects including uveitis have occasionally been reported during this therapy. Herein, we report the case of a 65-year-old male who suffered bilateral anterior uveitis after immune checkpoint blockade therapy with pembrolizumab and ipilimumab for malignant melanoma. His symptoms and signs improved after topical treatment with corticosteroids. Clinicians should be aware that uveitis can be an immune-related adverse event of immunotherapy.

BackgroundThe 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.MethodsStudies 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.Results1229 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, p2=5%). A quantitative analysis was not performed concerning adverse events and quality of life because of the limited data available.ConclusionSLT 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.

The cold pressor test (CPT) induces a cardiovascular response, which may affect ocular blood flow and neuronal function. This study assessed whether optical coherence tomography angiography (OCT-A) can be used to evaluate CPT-induced changes in healthy eyes and in eyes with primary open-angle glaucoma (POAG). Twenty-two healthy subjects and 23 subjects with POAG and retinal fibre layer defects in only one hemifield were included in this study. The CPT was performed by submerging a subject’s hand in cold water (0–4 °C) for 1 minute. The results showed that baseline peripapillary and macular vessel density (VD) measurements were significantly lower in subjects with POAG than in controls (all P

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.

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. Electronic supplementary material The online version of this article (10.1186/s12886-018-1019-4) contains supplementary material, which is available to authorized users.

Background The aim of this study was to verify the accuracy of a formula predicting postoperative intraocular pressure (IOP) after phacoemulsification and intraocular lens implantation (PHCE-IOL) in primary angle-closure glaucoma (PACG). In a retrospective chart review of patients with PACG who underwent PHCE-IOL between 2011 and 2014, we collected preoperative IOP, axial length, anterior chamber depth (ACD), number of pre-PHCE glaucoma medications, and IOP and glaucoma medications at 1 month and 3 months post-PHCE. Methods Post-PHCE IOP values at 1 month and 3 months were compared with those predicted using the formula: postoperative IOP = 6.354 + 0.186 pre-PHCE IOP × pre-PHCE ACD. Agreements between measured and predicted IOP values were analyzed using correlation coefficients and Bland–Altman plots. Results Of the 62 eyes included, the average pre-PHCE IOP was 19.47 ± 5.84 mm Hg. Post-PHCE IOP values were 14.94 ± 4.03 mm Hg at 1 month and 14.21 ± 3.51 mm Hg at 3 months. Patients using more preoperative medications tended to show greater postoperative declines in medication usage. Predicted IOP significantly correlated with post-PHCE IOP measured at 1 month ( R = 0.314, p = 0.013) and 3 months ( R = 0.325, p = 0.01). Bland–Altman plots of difference against average of measured and estimated IOP revealed two cases falling outside±1.96 standard deviation at 1 month, and five cases at 3 months, indicating good consistency between measurement and prediction. Conclusion This formula was useful for predicting IOP at 1 month and 3 months after PHCE-IOL in PACG. It aids clinicians in preoperative assessment of whether PHCE-IOL alone is likely to achieve acceptable postoperative IOP control.

Background: High myopia is associated with multiple ocular morbidities that may lead to irreversible blindness. Because high myopia in an adult is thought to be related to onset of myopia in very early childhood, detecting myopia early and working to improve modifiable risk factors may help reduce the development of high myopia. In this study, we tried to evaluate the prevalence of myopia and associated risk factors in second-grade primary school children in Taipei, Taiwan. Methods: A questionnaire was distributed to the participants’ parents, and their written informed consent was obtained before performing eye examinations that included visual acuity testing and cycloplegic autorefraction. Multiple logistic regression models were applied to assess possible risk factors associated with myopia. Myopia was defined as spherical equivalent of −0.50 D or less in either eye. Results: The prevalence of myopia in the second graders was 36.4%. After adjustment for other characteristics, the following variables were significantly associated with a higher risk of myopia: male sex [odds ratio (OR)=1.24, p