A New Contact Lens Sensor System for Continuous Intraocular Pressure Monitoring: Evaluation of Safety and Tolerability.

PURPOSE: To assess the safety and tolerability of a new contact lens sensor (CLS) system for continuous 3- and 24-hr intraocular pressure (IOP) monitoring in human eyes. METHODS: Twenty-five subjects were recruited for 3-hr IOP measurement by CLS. Corneal fluorescein staining (CFS) scores were evaluated before and after measurement. Then, 30 participants (10 normal subjects and 20 glaucoma patients) were recruited for 24-hr IOP monitoring. Ocular surface disease index (OSDI) was assessed before and one day after measurement. Contact lens dry eye questionnaire-8 was assessed immediately after measurement. Visual analog scale of discomfort was measured before, immediately after, and one day after measurement. Best-corrected visual acuity (BCVA), tear break-up time (TBUT), and CFS were assessed before, immediately after, and 1 day after measurement. RESULTS: All participants completed 3- or 24-hr IOP measurement by CLS. Corneal fluorescein staining increased from 0.6±0.7 to 2.4±1.5 after 3-hr IOP measurement ( P <0.001). For participants undergoing 24-hr IOP monitoring, OSDI increased from 9.1±9.7 to 18.0±12.4 ( P =0.001). CLDEQ-8 score was 11.6±5.8. Visual analog scale increased from 11.1±14.2 to 35.2±21.8 after measurement ( P <0.001) and decreased to 26.7±18.4 one day later ( P <0.001 compared with baseline). BCVA decreased from 1.0±0.01 to 0.8±0.1 ( P <0.001) and returned to 0.9±0.1 after one day ( P <0.001 compared with baseline). TBUT decreased from 5.1±3.9 to 2.6±1.5 s ( P =0.001) and returned to 4.8±2.5 s ( P =0.465 compared with baseline). Corneal fluorescein staining increased from 0.7±0.9 to 4.3±0.8 ( P <0.001) and dropped to 0.8±0.7 ( P =0.599 compared with baseline). No significant difference was found for all variations of indicators between normal subjects and glaucoma patients ( P >0.1 for all comparisons). CONCLUSIONS: The CLS shows a great potential for a safe and tolerable 24-hr IOP monitoring in normal subjects and glaucoma patients. Clinical attention to the worsening signs and symptoms after measurement is required.

Factors impacting cumulative dissipated energy levels and postoperative visual acuity outcome in cataract surgery.

PURPOSE: To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification. DESIGN: Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China. SUBJECTS: Patients who underwent cataract surgery at UCSF 03/2014-03/2019 and at ZOC 10/2018-05/2019. METHODS: Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month. OUTCOME MEASURES: CDE, postoperative BCVA. RESULTS: In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20-0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12-0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34-0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13-0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL). CONCLUSIONS: Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.

AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodelling in ET-1-induced POAG.

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of ß-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.

Evaluation of integrated modular teaching in Chinese ophthalmology trainee courses.

BACKGROUND: Before attending ophthalmology trainee courses in Zhongshan Ophthalmic Centre, the medical students from Sun Yat-sen University had finished two years of premedical education after the six-year medical courses including basic medical courses, clinical medical courses, clerkship, and research training in medical college. Integrated modular teaching using different problem-based teaching methods in ophthalmology was designed by the teaching steering committee of Zhongshan Ophthalmic Centre. This study aimed to evaluate the effectiveness and satisfaction scales of the integrated modular teaching among the trainee students. METHODS: A total of 100 medical students attending ophthalmology trainee courses in Zhongshan Ophthalmic Centre were enrolled and randomly allocated into 4 groups according to the teaching arrangement. The trainee courses consisted of several sessions delivered in multiple methods, such as "flipped classroom" session and team-based learning session. The pre- and post-class tests were delivered to evaluate the effectiveness of the integrated modular teaching. The satisfaction survey questionnaire was collected from all participants to investigate the degree of satisfaction. RESULTS: Compared with the first-day-test score, the total last-day-test score was significantly improved by a paired t-test (t = 3.288, P = 0.001). Nineteen students obtained a significant improvement in ranking increased by more than 10 in the last-day-test, whereas they failed to obtain a higher average score for daily performance than other students (t = 0.469, P = 0.654). According to the participant satisfaction questionnaires, these innovative teaching methods were considered as effective and satisfactory. CONCLUSIONS: Integrated modular teaching in ophthalmology trainee courses is effective and appreciated by the medical college students.

Preparation and evaluation of HPMC-based pirfenidone solution in vivo.

CONTEXT: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability. OBJECTIVE: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops. MATERIALS AND METHODS: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution. RESULTS: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration. CONCLUSIONS: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.

[A prospective randomized study of selective laser trabeculoplasty (SLT) as a replacement for medical therapy in primary open-angle glaucoma].

OBJECTIVE: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) as a replacement for medical therapy in primary open-angle glaucoma (POAG). METHODS: A prospective, randomized, controlled study.SLT treatment with SOLO SLT Nd: YAG laser was provided to 45 participants with advanced POAG (67 eyes, IOP ≤ 21 mmHg, 1 mmHg = 0.133 kPa) under anti-glaucomatous medications control). A table of random numbers was created by simple randomization method. Participants were randomly divided into two groups: the standard-energy group (34 eyes), which received a 270° standard-energy SLT treatment and the sub-threshold energy group (33 eyes), which received a 360° sub-threshold energy treatment. The intraocular pressure (IOP) before and after SLT, daytime IOP curve, dosage of anti-glaucoma drugs and treatment complications were observed, which were be followed up for 6-9 months (average 6.4 months). Two-tailed t-test or paired t test was used when the continuous variables were normal distribution, such as the basic data, daily fluctuations of IOP, laser energy. Non-parametric Mann-Whitney U test or Wilcoxon rank test was used when data was not distributed normally, such as drug category. Chi-square or Fisher's exact test was used when count variables such as success rate and complications were analyzed. RESULTS: The number of anti-glaucomatous drugs used in the standard-energy group and the sub-threshold energy group before SLT was (2.3 ± 0.5) and (2.1 ± 0.4), respectively; whereas, after the last treatment, it reduced to (1.3 ± 0.5) and (1.1 ± 0.3), respectively (Z = -5.477, -5.396; P < 0.05). The success rate of the standard-energy group and the sub-threshold energy group was 91.1%, and 87.9%, respectively, which was not significant different (P = 0.70). Laser treatment was found to reduce the IOP fluctuation during the daytime.IOP fluctuation decreased from (3.6 ± 1.0) mmHg to (2.3 ± 1.0) mmHg in the standard-energy group, and decreased from (3.9 ± 1.4) mmHg to (2.4 ± 0.9) mmHg in the sub-threshold energy group, which was significant different (t = 4.911, 4.679; P < 0.05). The total laser energy of the standard-energy group (47.8 ± 6.0) mJ was higher than the sub-threshold energy group (43.2 ± 5.1) mJ (t = 12.006, 3.233; P < 0.05). However, there was no significant difference in the daily IOP fluctuations, success rate, reduction of medication categories, preoperative and postoperative IOP, and adverse reactions between the two groups. CONCLUSIONS: SLT is a safe and effective replacement for medical therapy in primary open-angle glaucoma treatment. SLT could reduce the applications of anti-glaucoma drugs. There was no significant difference between therapeutic effects of which eyes received 360° sub-threshold energy and 270° standard-energy.

Early impairment of magnocellular visual pathways mediated by isolated-check visual evoked potentials in primary open-angle glaucoma: a cross-sectional study.

OBJECTIVE: To explore different performances in the magnocellular (MC) and parvocellular (PC) visual pathways in patients with primary open-angle glaucoma (POAG) and to objectively assess impairment in early stage of POAG. METHODS AND ANALYSIS: This is a cross-sectional study. MC and PC visual pathways were assessed using isolated-check visual evoked potential (ic-VEP). Visual acuity, intraocular pressure, fundus examination, optical coherence tomography and visual field were measured. Signal-to-noise ratios (SNRs), mediated by ic-VEP were recorded. The Spearman's correlation analysis was used to estimate the relationships between visual functions and structures. Receiver-operating-characteristic (ROC) curves were used to estimate the accuracy in detection of early POAG. RESULTS: 60 participants (30 early POAG eyes and 30 age-matched control subjects) were recruited. MC visual pathway showed a non-linear response function, while PC visual pathway was a linear response function as contrast increased. Early POAG eyes exhibited significantly weaker initial contrast gains and lower maximum responses in the MC visual pathway (p=0.001, p=0.004, respectively). The SNRs at 8% and 32% depths of modulation (DOM) were significantly correlated with temporal-side retinal nerve fibre layer (RNFL) thickness in early POAG in MC-biased stimulation (p=0.017, p=0.020, respectively). The areas under ROC of 16% DOM were 0.780 (sensitivity 80.0%, specificity 63.3%) with the cut-off SNR of 2.07. CONCLUSIONS: The MC visual pathway was damaged in the early stage of POAG. The SNRs at 8% and 32% DOM of MC-biased stimulation were significantly correlated with temporal-side RNFL thickness in early POAG, which helped in understanding the mechanisms of visual impairment in the early stage of POAG.

Development and Validation of an Internet-Based Remote Perimeter (Perimouse).

Purpose: We sought to validate the feasibility of Perimouse, an internet-based remote perimeter that allows for natural fixation and can be performed on most computers via a web page. Methods: In this cross-sectional study, Perimouse evaluated the visual field of 45 healthy people and 27 patients with primary open-angle glaucoma on a laptop. Participants used a mouse cursor to locate new dots on the screen that were determined by preset saccade vectors. A "click and confirm" strategy was used to eliminate the unwanted visual search. Dot brightness was either fixed at 12 dB in the suprathreshold program (screening program) or variable in the threshold program. We compared Perimouse outcomes with the Humphrey Field Analyzer (HFA) 24-2 Swedish Interactive Testing Algorithm standard program. Results: In the screening program, Perimouse showed moderate to high concordance with HFA. The intraclass coefficient ranged from 0.58 to 0.86 in different areas of Garway-Heath mapping. In the threshold program, normal subjects had threshold ranging from 19 to 16 dB, presenting sensitivity changes according to the "hill of vision". The test-retest difference was 0.09 dB. Habitual spectacle correction and environmental luminance (2-337 lux) had little impact on the central or peripheral threshold (P > 0.05). The correlation between Perimouse and HFA threshold sensitivity was strong (R = 0.950), although Perimouse mean defect was 4.40 dB higher than the HFA mean defect. Conclusions: Perimouse is a reliable visual field test that correlates strongly with HFA. It shows potential for population screening and monitoring visual field defects. Translational Relevance: Perimouse assesses the visual field using saccade vectors without eye trackers, enhancing its accessibility via a web page.

Deep Learning Classification of Angle Closure based on Anterior Segment OCT.

PURPOSE: To assess the performance and generalizability of a convolutional neural network (CNN) model for objective and high-throughput identification of primary angle-closure disease (PACD) as well as PACD stage differentiation on anterior segment swept-source OCT (AS-OCT). DESIGN: Cross-sectional. PARTICIPANTS: Patients from 3 different eye centers across China and Singapore were recruited for this study. Eight hundred forty-one eyes from the 2 Chinese centers were divided into 170 control eyes, 488 PACS, and 183 PAC + PACG eyes. An additional 300 eyes were recruited from Singapore National Eye Center as a testing data set, divided into 100 control eyes, 100 PACS, and 100 PAC + PACG eyes. METHODS: Each participant underwent standardized ophthalmic examination and was classified by the presiding physician as either control, primary angle-closure suspect (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG). Deep Learning model was used to train 3 different CNN classifiers: classifier 1 aimed to separate control versus PACS versus PAC + PACG; classifier 2 aimed to separate control versus PACD; and classifier 3 aimed to separate PACS versus PAC + PACG. All classifiers were evaluated on independent validation sets from the same region, China and further tested using data from a different country, Singapore. MAIN OUTCOME MEASURES: Area under receiver operator characteristic curve (AUC), precision, and recall. RESULTS: Classifier 1 achieved an AUC of 0.96 on validation set from the same region, but dropped to an AUC of 0.84 on test set from a different country. Classifier 2 achieved the most generalizable performance with an AUC of 0.96 on validation set and AUC of 0.95 on test set. Classifier 3 showed the poorest performance, with an AUC of 0.83 and 0.64 on test and validation data sets, respectively. CONCLUSIONS: Convolutional neural network classifiers can effectively distinguish PACD from controls on AS-OCT with good generalizability across different patient cohorts. However, their performance is moderate when trying to distinguish PACS versus PAC + PACG. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system.

AIMS: To investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm Hg) continuously. METHODS: Fifty-nine eyes of 59 normal Chinese adults completed 24-hour IOP monitoring using the novel CLS. A descriptive analysis was conducted on the 24-hour IOP mean, peak and acrophase, trough and bathyphase, fluctuation, and mean amplitude of intraocular pressure excursion (MAPE). The continuous data were analysed at several periods (diurnal period, 08:00-20:00 hours; nocturnal period, 22:00-06:00 hours; sleep time, 0:00-06:00 hours), and compared between right and left eyes, males and females, and different age ranges (<30, and ≥30), respectively. RESULTS: Normal adults had a lower peak, higher trough, smaller fluctuation and smaller MAPE (p<0.05 for all comparisons) but non-significantly different mean (p=0.695) in the nocturnal period or sleep time compared with the diurnal period. The 24-hour IOP peak and trough showed the frequency of occurrence ranging from 1.69% to 15.25% at an interval of 2 hours. No IOP parameter showed significant difference between right and left eyes (p>0.1 for all comparisons). The male group had larger 24-hour and diurnal IOP fluctuation and MAPE (p<0.05 for all comparisons). Subjects aged 30 or over had higher 24-hour and diurnal mean, higher peak, and larger MAPE (p<0.05 for all comparisons). CONCLUSION: Continuous 24-hour IOP output from the CLS in normal Chinese was stable with a comparable mean level between day and night, as well as scattered acrophase and bathyphase. The 24-hour IOP mean increased with age, and IOP variations were positively correlated to age and male sex.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Pirfenidone inhibits migration, differentiation, and proliferation of human retinal pigment epithelial cells in vitro.

PURPOSE: To investigate the effects of pirfenidone (PFD) on the migration, differentiation, and proliferation of retinal pigment epithelial (RPE) cells and demonstrate whether the drug induces cytotoxicity. METHODS: Human RPE cells (line D407) were treated with various concentrations of PFD. Cell migration was measured with scratch assay. The protein levels of fibronectin (FN), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), transforming growth factor beta (TGFßS), and Smads were assessed with western blot analyses. Levels of mRNA of TGFßS, FN, and Snail1 were analyzed using reverse transcriptase-polymerase chain reaction. Cell apoptosis was detected with flow cytometry using the Annexin V/PI apoptosis kit, and the percentages of cells labeled in different apoptotic stage were compared. A Trypan Blue assay was used to assess cell viability. RESULTS: PFD inhibited RPE cell migration. Western blot analyses showed that PFD inhibited the expression of FN, α-SMA, CTGF, TGFß1, TGFß2, Smad2/3, and Smad4. Similarly, PFD also downregulated mRNA levels of Snail1, FN, TGFß1, and TGFß2. No significant differences in cell apoptosis or viability were observed between the control and PFD-treated groups. CONCLUSIONS: PFD inhibited RPE cell migration, differentiation, and proliferation in vitro and caused no significant cytotoxicity.

Inhibition of TGF-ß2-Induced Trabecular Meshwork Fibrosis by Pirfenidone.

Purpose: Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. This study investigated the inhibitory effect of PFD on TM fibrosis and evaluated its efficacy in lowering intraocular pressure (IOP). Methods: Human TM cells were isolated, cultured, and characterized. Cell Counting Kit-8 was used to evaluate the proliferation and toxicity of different concentrations of PFD on normal or fibrotic TM cells. TM cells were treated with transforming growth factor beta-2 (TGF-ß2) in the absence or presence of PFD. Western blotting and immunofluorescence analyses were used to analyze changes in the TM cell cytoskeleton and extracellular matrix (ECM) proteins, including alpha-smooth muscle actin (α-SMA), F-actin, collagen IV (COL IV), and fibronectin (FN). An ocular hypertension (OHT) mouse model was induced with Ad-TGF-ß2C226/228S and then treated with PFD or latanoprost (LT) eye drops to confirm the efficacy of PFD in lowering IOP. Results: PFD inhibited the proliferation of fibrotic TM cells in a dose-dependent manner and inhibited TGF-ß2-induced overexpression of α-SMA, COL IV, and FN in TM cells. PFD stabilized F-actin. In vivo, PFD eye drops reduced the IOP of the OHT models and showed no significant difference compared with LT eye drops. Conclusions: PFD inhibited TGF-ß2-induced TM cell fibrosis by rearranging the disordered cytoskeleton and decreasing ECM deposition, thereby enhancing the aqueous outflow from the TM outflow pathway and lowering IOP, which provides a potential new approach to treating glaucoma. Translational Relevance: Our work with pirfenidone provides a new approach to treat glaucoma.

Intraocular pressure and diurnal fluctuation of open-angle glaucoma and ocular hypertension: a baseline report from the LiGHT China trial cohort.

AIMS: To report the baseline intraocular pressure (IOP) characteristics and its diurnal fluctuation in the Laser in Glaucoma and Ocular Hypertension China cohort. METHODS: 622 primary open-angle glaucoma (POAG) patients and 149 ocular hypertension (OHT) patients were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. Standardised ocular examinations were performed including IOP measurement using the Goldmann applanation tonometer. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30, 17:00 hour. RESULTS: The mean baseline IOP was 20.2 mm Hg for POAG patients and 24.4 mm Hg for OHT. Multiple regression analysis revealed that thicker central corneal thickness (CCT) was correlated with higher IOP in both POAG and OHT. Male gender and younger age were correlated with higher IOP only for POAG. As for diurnal IOP fluctuation, mean IOP fluctuation was 3.4 mm Hg in POAG eyes and 4.4 mm Hg in OHT. The peak and trough IOP occurred at 8:00 and 14:30 hour in both POAG and OHT eyes. CONCLUSIONS: Younger age, male gender and thicker CCT are correlated to higher IOP in POAG patients while only thicker CCT is related to higher IOP in OHT patients. Peak IOP appears mostly at early morning or late afternoon and trough value occurs mostly at early afternoon.

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

Wide Corneal Epithelial Thickness Mapping in Eyes With Topical Antiglaucoma Therapy Using Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the corneal epithelial thickness (CET) of the 9-mm diameter zone in patients treated using topical antiglaucoma medications and to evaluate the factors associated with CET changes. Methods: Seventy-five patients treated using topical antiglaucoma medications and 65 healthy subjects were included in this cross-sectional study. Each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent examinations including the Schirmer I test, tear breakup time (TBUT), and fluorescein staining. CET mapping of the 9-mm diameter zone was performed using RTVue XR. The CET of the different analyzed zones was compared between groups. The relationship between CET and confounding factors was investigated. Results: The patient group had a significantly shorter TBUT, shorter Schirmer I test, and greater fluorescein staining than those of the control group (all P < 0.05). The mean CET of patients with glaucoma was significantly lower than that of controls in the central, paracentral, mid-peripheral, and peripheral zones (all P < 0.001). Age affected the CET in the paracentral, mid-peripheral, and peripheral zones (all P < 0.01). The number of medications affected the CET in the central, paracentral, and mid-peripheral zones (all P < 0.05). The duration of treatment affected the CET in the central and peripheral zones (all P < 0.05). Conclusions: Use of topical IOP-lowering medications leads to epithelial thinning in the 9-mm diameter zone in glaucomatous eyes. Epithelial protection should be considered in older patients and patients treated with multiple medications from the early stages of long-term topical antiglaucoma therapy. Translational Relevance: The 9-mm diameter CET mapping by using widefield optical coherence tomography (OCT) can be a valuable and convenient method to assess the ocular surface damage in patients with topical antiglaucoma therapy.

Anterior Segment OCT in Primary Angle Closure Disease Compared With Normal Subjects With Similar Shallow Anterior Chamber.

PRCIS: Compared with normal subjects with similar shallow anterior chamber depth (ACD), patients with primary angle closure disease (PACD) had narrower angle structures measured by swept-source optical coherence tomography (SS-OCT) at 250 µm from scleral spur (very root of iris), especially along oblique and vertical axis. PURPOSE: To examine anterior segment structures in normal subjects whose ACD was shallow on slit-lamp examination but did not meet the diagnostic criteria of PACD, and to compare them with PACD patients with similar ACD. MATERIALS AND METHODS: Patients were recruited from glaucoma clinic at Zhongshan Ophthalmic Center. A total of 40 eyes from 29 PACD patients and 40 eyes from 34 normal subjects received full ophthalmic examination and CASIA SS-1000 OCT tests. PACD eyes and control eyes were 1:1 matched for ACD at 0 degree of scan. Generalized linear model that accounted for inter-eye correlation was used to compare differences between the 2 groups for intraocular pressure and SS-OCT parameters. P-values were adjusted for multiple comparisons using the Bonferroni method. RESULTS: The PACD and control groups had similar age, but the PACD group had a significantly higher intraocular pressure (18.4 vs. 14.0 mm Hg, P=0.005). Angle parameters, representative of angle area, such as angle recess area and trabecular iris space area measured at 250 µm along axes of 90, 135, 225, and 315 degrees were significantly smaller in PACD group than those of control group (adjusted P<0.05), while most of angle parameters at 500 and 750 µm, volume parameters, and anterior chamber parameters, were similar (adjusted P>0.05). CONCLUSIONS: In PACD patients compared with normal subjects with similar anterior chamber shallowing, OCT findings measured at the iris root 250 µm from the scleral spur, especially in the oblique and vertical axes, including angle recess area and trabecular iris space area, may match gonioscopic findings more closely and provide further insight into mechanisms of PACD.

The risk of glaucoma associated with phacomatosis cesioflammea and phacomatosis cesioflammeo-marmorata

Background: The ocular features of phacomatosis pigmentovascularis (PPV) have rarely been reported, and glaucoma is the leading cause of blindness in patients with this condition. To protect vision in these patients, it is important to identify glaucoma as early as possible. Objectives: To systematically report the systemic and ocular manifestations of phacomatosis cesioflammea and phacomatosis cesioflammeo-marmorata, and to investigate a glaucoma risk scoring system. Materials & Methods: In this prospective study, patients with PPV from 2014 to 2021 were included. Clinical information was collected, and associations with glaucoma were evaluated. The suitability of the scoring system was assessed. A systematic literature review and analysis of reported cases of PPV was performed. Results: A total of 28 participants with PPV were included. Their ocular findings were similar, ranging from episcleral hyperpigmentation (78.5%), glaucoma (75%), choroid haemangioma (38%), and retinal vascular abnormalities (48%), to hyperpigmentation of the cornea, iris, lens and fundus. Glaucoma was associated with multiple factors, especially a thick choroid (odds ratio: 2.61; p = 0.008) and a diffuse mass-type of episcleral hyperpigmentation (odds ratio: 41.3; p = 0.027). The risk scoring system was characterized by high sensitivity (84%) and specificity (80%; AUC = 0.91) in predicting glaucoma. Conclusion: In addition to involving the systemic system, phacomatosis cesioflammea and phacomatosis cesioflammeo-marmorata also represent a specific spectrum of ophthalmic vascular malformations and hyperpigmentation. Early and periodic detailed ocular examination are recommended. The novel scoring system will help to tailor follow-up for visual protection.

Medication Adherence and Common Barriers for Caregivers of Preschool Children with Pediatric Glaucoma.

Purpose: To investigate the medication adherence among caregivers of preschool children with pediatric glaucoma and to elucidate common barriers leading to poor adherence. Methods: A cross-sectional study. Caregivers of preschool children with pediatric glaucoma completed a questionnaire on demographic information of caregivers, demographic and disease characteristics of children, caregivers-reported medication adherence (by an adapted Morisky Adherence Scale), and possible 13 barriers. Results: Overall 132 questionnaires were considered valid. Thirty-six percent of all reported poor medication adherence. Caregivers' age and self-evaluated knowledge about pediatric glaucoma showed a significant difference between the adherent and nonadherent groups (P < 0.05). Nineteen percent of all reported only one barrier as important, 65% cited multiple barriers, and 16% cited no barriers. Anxiety and depression were cited as important by most caregivers in both groups. Univariate logistic regression analysis demonstrated that difficulty with the acquisition of medications (OR, 2.5; 95% CI, 1.1-5.7; P=0.025), difficulty with medication schedule (OR, 2.3; 95% CI, 1.0-5.0; P=0.043), and high expenses for medications (OR, 4.8; 95% CI, 1.4-15.9; P=0.011) were significantly associated with higher odds of poor adherence. Conclusions: Over one-third of caregivers of preschool children with pediatric glaucoma were in poor medication adherence. Nearly two-thirds of caregivers cited multiple barriers simultaneously as important hindrances to medication usage. Anxiety and depression, difficulty with the acquisition of medications, difficulty with the medication schedule, and high expenses for medications were prominent barriers. Individualized solutions should be provided according to reported barriers by each caregiver and the other most common barriers.