Joinpoint regression analysis of recent trends in desmoplastic malignant melanoma incidence and mortality: 15-year multicentre retrospective study.

BACKGROUND: Recent data reveal a marked rise in the detection and mortality rates of Desmoplastic Malignant Melanoma (DMM). This trend underscores the imperative for an in-depth analysis of DMM's epidemiology, which is crucial for the formulation of precise medical and public health strategies. This investigation seeks to elucidate the variations in the incidence and mortality of DMM over a 15-year period (2005-2019). METHODS: Data on DMM patients was sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Both incidence and incidence-based mortality rates (IBM) were directly extracted from the SEER database. Joinpoint regression was used to analyze and calculate the average annual percent change (AAPC) and its 95% confidence interval (CI). RESULTS: Between 2005 and 2019, 3,384 DMM cases were identified, boasting an age-adjusted incidence rate of 36.3 cases per 1000,000 person-years (95% CI 3.51-3.76) and an IBM of 1.65cases per 1000,000 person-years (95% CI 1.57-1.74). Of these, 2,353 were males (69.53%) and 1,031 were females (30.47%). There were 1894 patients (55.97%) who were over 70 years old. Predominantly, DMM lesions manifested in exposed areas: Limbs (955, 28.22%), Face (906, 26.77%), and Scalp and Neck (865, 25.56%). The incidence of DMM increased significantly at a rate of APC = 0.9% during 2005-2019, while the incidence-based mortality showed a significant upward trend (APC = 7%) during 2005-2012, and slowly increasing trend (APC = 0.6%) during 2012-2019. In contrast to the modest upward trajectory in female incidence and mortality, male incidence initially surged, later declining, while male mortality peaked and stabilized post-2012. The primary sites for incidence and mortality were chronically sun-exposed areas: Face, Scalp and Neck, and Limbs. CONCLUSIONS: In recent years, the incidence and incidence-based mortality of DMM have significantly increased. Each subgroup analysis has different trends, and these trends can provide better support for our exploration of DMM.

Robot-assisted retractor in spine surgery: Preliminary evaluation of its feasibility and two operation mode in beagles.

OBJECTIVE: To assess the feasibility of the robot-assisted retractor. To compare the muscle injury of the two operation modes, intermittent retraction mode and continuous retraction mode in the robot-assisted retractor to find a better robot operation mode. METHODS: A new robot-assisted retractor experimental platform was developed. Three incisions were made on the backs of three beagles. The robot-assisted retractor was used to retract the muscle on both sides of the incisions in intermittent retraction mode and continuous retraction mode, and the operation of the robot system was observed. The muscle samples were stained with hematoxylin-eosin (HE) to observe the muscle injury. The difference between the muscle injuries of the two groups was statistically compared using paired t test. RESULTS: The robot-assisted retractor can precisely retract to the specified position without malfunction or dangerous actions. Histologic evaluation showed that fewer muscle injury was found in the intermittent retraction mode group of the robot-assisted retractor compared to the continuous retraction mode group. CONCLUSION: The robot-assisted retractor offers a certain degree of feasibility and safety. The robot-assisted retractor is able to effectively reduce muscle injury with the intermittent retraction mode.

Iris volume change with physiologic mydriasis to identify development of angle closure: the Zhongshan Angle Closure Prevention Trial.

AIMS: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects. METHODS: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression. RESULTS: A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement). CONCLUSION: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease. TRIAL REGISTRATION NUMBER: ISRCTN45213099.

Role of Static and Dynamic Ocular Biometrics Measured in the Dark and Light as Risk Factors for Angle Closure Progression.

PURPOSE: To assess the role of static and dynamic ocular biometric parameters measured in the dark and light for predicting progression of primary angle closure suspect (PACS) to primary angle closure (PAC). DESIGN: Retrospective cohort study using prospective randomized controlled trial data from untreated, control eyes. METHODS: Zhongshan Angle Closure Prevention Trial subjects underwent anterior segment optical coherence tomography (AS-OCT) imaging in the dark and light. Static biometric parameters were measured, consisting of angle, iris, lens, and anterior chamber parameters. Dynamic change parameters were calculated by subtracting light measurements from dark measurements. Cox proportional hazards regression models were developed to assess risk factors for PACD progression. RESULTS: A total of 861 eyes of 861 participants were analyzed (36 progressors). On univariable analysis, TISA500 measurements in the light and dark were associated with progression (P < .001), whereas dynamic change parameters were not (P ≥ .08). In the primary multivariable model, older age (hazard ratio [HR] = 1.09 per year), higher intraocular pressure (IOP) (HR = 1.13 per mm Hg), and smaller TISA500 in the light (HR = 1.28 per 0.01 mm2) were significantly associated with greater risk of progression (P ≤ .04). Dark TISA500 had similar significance (HR = 1.28, P = .002) when replacing light TISA500. Risk of progression was more predictive among eyes in the lowest quartile of light TISA500 measurements (HR = 4.56, P < .001) compared to dark measurements (HR = 2.89, P = .003). CONCLUSION: Static parameters measured in the light are as predictive, and possibly more so, of angle closure progression as those measured in the dark. Ocular biometrics measured under light and dark conditions may provide additional information for risk-stratifying patients for angle closure progression.

A prognostic nomogram for the cancer-specific survival of white patients with invasive melanoma at BANS sites based on the Surveillance, Epidemiology, and End Results database.

Objective: The purpose of this study was to develop a comprehensive nomogram for the cancer-specific survival (CSS) of white patients with invasive melanoma at back, posterior arm, posterior neck, and posterior scalp (BANS) sites and to determine the validity of the nomogram by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system. Methods: This study analyzed the patients with invasive melanoma in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divide the patients into training and validation cohorts at a ratio of 7:3. Multivariable Cox regression was used to identify predictive variables. The new survival nomogram was compared with the AJCC prognosis model using the concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), calibration plotting, and decision-curve analysis (DCA). Results: A novel nomogram was established to determine the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma. According to the nomogram, the Age at Diagnosis had the greatest influence on CSS in invasive melanoma, followed by Bone Metastasis, AJCC, Stage, Liver Metastasis, Histologic Subtype, Brain Metastasis, Ulceration, and Primary Site. The nomogram had a higher C-index than the AJCC staging system in both the training (0.850 versus 0.799) and validation (0.829 versus 0.783) cohorts. Calibration plotting demonstrated that the model had good calibration ability. The nomogram outperformed the AJCC staging system in terms of AUC, NRI, IDI, and DCA. Conclusion: This was the first study to develop and evaluate a comprehensive nomogram for the CSS of white patients with invasive melanoma at BANS sites using the SEER database. The novel nomogram can assist clinical staff in predicting the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma more accurately than can the AJCC staging system.

Biometric Risk Factors for Angle Closure Progression After Laser Peripheral Iridotomy.

Importance: Laser peripheral iridotomy (LPI) is the most common primary treatment for primary angle closure disease (PACD). However, there are sparse data guiding the longitudinal care of PAC suspect (PACS) eyes after LPI. Objective: To elucidate the anatomic effects of LPI that are associated with a protective outcome against progression from PACS to PAC and acute angle closure (AAC) and to identify biometric factors that predict progression after LPI. Design, Setting, and Participants: This was a retrospective analysis of data from the Zhongshan Angle Closure Prevention (ZAP) trial, a study of mainland Chinese people aged 50 to 70 years with bilateral PACS who received LPI in 1 randomly selected eye. Gonioscopy and anterior-segment optical coherence tomography (AS-OCT) imaging were performed 2 weeks after LPI. Progression was defined as the development of PAC or an acute angle closure (AAC) attack. Cohort A included a random mix of treated and untreated eyes, and cohort B included only eyes treated with LPI. Univariable and multivariable Cox regression models were developed to assess biometric risk factors for progression in cohorts A and B. Data were analyzed from January 4 to December 22, 2022. Main Outcome and Measure: Six-year progression to PAC or AAC. Results: Cohort A included 878 eyes from 878 participants (mean [SD] age, 58.9 [5.0] years; 726 female [82.7%]) of whom 44 experienced progressive disease. In a multivariable analysis, treatment (hazard ratio [HR], 0.67; 95% CI, 0.34-1.33; P = .25) was no longer associated with progression after adjusting for age and trabecular iris space area at 500 µm (TISA at 500 µm) at the 2-week visit. Cohort B included 869 treated eyes from 869 participants (mean [SD] age, 58.9 [5.0] years; 717 female [82.5%]) of whom 19 experienced progressive disease. In multivariable analysis, TISA at 500 µm (HR, 1.33 per 0.01 mm2 smaller; 95% CI, 1.12-1.56; P = .001) and cumulative gonioscopy score (HR, 1.25 per grade smaller; 95% CI, 1.03-1.52; P = .02) at the 2-week visit were associated with progression. Persistent angle narrowing on AS-OCT (TISA at 500 µm ≤0.05 mm2; HR, 9.41; 95% CI, 3.39-26.08; P <.001) or gonioscopy (cumulative score ≤6; HR, 2.80; 95% CI, 1.13-6.93; P =.04) conferred higher risk of progression. Conclusions and Relevance: Study results suggest that persistent angle narrowing detected by AS-OCT or cumulative gonioscopy score was predictive of disease progression in PACS eyes after LPI. These findings suggest that AS-OCT and gonioscopy may be performed to identify patients at high risk of developing angle closure who may benefit from closer monitoring despite patent LPI.

Cataract progression after Nd:YAG laser iridotomy in primary angle-closure suspect eyes.

BACKGROUND/AIMS: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS. METHODS: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery. RESULTS: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59±5 years, 83% female). At 72 months, treated eyes had slightly higher average nuclear grades (p<0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2% in LPI vs 19.4% in control, p=0.401) or cataract surgery (1% for both). While LPI-treated eyes had a 10% higher risk of progression over 6 years (HR=1.10 (95% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43). CONCLUSION: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time. TRIAL REGISTRATION NUMBER: ISRCTN45213099.

Automatically measuring the Cobb angle and screening for scoliosis on chest radiograph with a novel artificial intelligence method.

OBJECTIVES: To establish an automatic approach for the measurement of the Cobb angle and the diagnosis of scoliosis on chest radiograph. METHODS: We developed an artificial intelligence (AI) automatic program which contained a supervised learning module and an inference module. After the filtering and pre-processing process, 96 images from the Shenzhen chest X-ray set were used for training with the supervised learning module, and 491 test images were separately gauged by the AI and the corresponding manual methods. The results of the two methods were further compared through statistical analyses. RESULTS: Among the test images, 6068 (99.49%) vertebral bodies were identified within the deviation of one vertebral segment. The value difference between the Cobb angle obtained by the AI program and that measured by specialists was 0.4020±0.8703. The intraclass correlation coefficient of 0.915 indicated the strong agreement. AI scoliosis diagnosis achieved an accuracy of 98.37%, with a specificity of 98.73%, a sensitivity of 88.24% and a kappa coefficient of 0.781. And the area under the receiver operating characteristic curve of 0.979 confirmed the consistency of the two methods in diagnosis. CONCLUSIONS: We developed a novel automatic AI method with the abilities to measure the Cobb angle, and to identify the approximate vertebral segment and diagnosis of scoliosis on chest radiograph. The results suggest that this method might be a promising alternative strategy for scoliosis screening on chest radiograph and worth further investigation.

Effectiveness and postoperative rehabilitation of one-stage combined anterior-posterior surgery for severe thoracolumbar fractures with spinal cord injury.

BACKGROUND: Thoracolumbar fractures are generally combined with spinal cord injury to varying degrees, which may cause deterioration of the patients' condition and increase the difficulty of clinical treatment. At present, anterior or combined anterior-posterior surgery is preferred for severe thoracolumbar fractures. AIM: To investigate the effectiveness and postoperative rehabilitation of one-stage combined anterior-posterior surgery for severe thoracolumbar fractures with spinal cord injury. METHODS: One-hundred-and-twenty patients who received surgery for severe thoracolumbar fractures with spinal cord injury at our hospital from February 2018 to February 2020 were randomly enrolled. They were randomly divided into group 1 (one-stage combined anterior-posterior surgery, n = 60) and group 2 (one-stage anterior-approach surgery, n = 60). Treatment efficacy was compared between the two groups. RESULTS: Blood loss was greater and the operation time was longer in group 1 than in group 2, and the differences were statistically significant (P < 0.05). Incision length, intraoperative X-rays, and length of hospital stay were not significantly different between the two groups (P > 0.05). Preoperative function of the affected vertebrae was not significantly different between the two groups (P > 0.05). In each group, the patients showed significant improvement after surgery. The anterior vertebral height ratio and the posterior vertebral height ratio in group 1 after surgery were significantly higher than those in group 2. The Cobb angle after surgery was significantly lower in group 1 than in group 2 (P < 0.05). The canal-occupying ratio of the affected vertebrae was not significantly different between the two groups (P > 0.05). Before surgery, there was no significant difference in the quality of life scores between the two groups (P > 0.05). The above indicators were significantly improved after surgery compared with before surgery in each group. In addition, these indicators were markedly better in group 1 than in group 2 after surgery (P < 0.05 for each). CONCLUSION: One-stage combined anterior-posterior surgery effectively improves the function of the affected vertebrae and the life quality of patients with severe thoracolumbar fractures and spinal cord injury. This surgical approach is worthy of popularization in clinical use.

Outcomes of cervical degenerative disc disease treated by anterior cervical discectomy and fusion with self-locking fusion cage.

BACKGROUND: Cervical degenerative disc (CDD) disease is a common type of spondylosis. Although anterior cervical discectomy and fusion (ACDF) is the preferred treatment for CDD disease, internal fixation with a titanium plate may cause various complications. The invention of the ACDF with a self-locking fusion cage (ROI-C) has effectively decreased the incidence of postoperative complications. AIM: To observe the outcomes of CDD disease treated by ACDF with a ROI-C. METHODS: Ninety patients with CDD disease treated at our hospital from March 2019 to March 2021 were included. They were divided into two groups (control group and observation group, n = 45 in each) using a random number table. Patients in the control group received ACDF plus internal fixation with a titanium plate. Those in the observation group received ACDF + ROI-C placement. The two groups of patients were compared in terms of surgical parameters, pain, cervical spine function, range of motion, and complications. RESULTS: The two groups of patients showed no significant differences in surgical time, blood loss, drainage volume, and length of hospital stay (P > 0.05). No significant differences in the visual analogue scale (VAS), Japanese Orthopedic Association (JOA), and neck disability index (NDI) scores were observed between the two groups before surgery (P > 0.05). The VAS and NDI scores in the observation group were considerably lower than those in the control group after surgery; however, the JOA scores in the observation group were significantly higher than those in the control group (P < 0.05). No significant differences were observed in cervical disc height and the range of motion of the superior or inferior adjacent vertebrae between the two groups before surgery (P > 0.05). The disc height in the observation group was larger than that in the control group after surgery. The range of motion of both the superior and inferior adjacent vertebrae was significantly smaller in the observation group than in the control group (P < 0.05). The incidence of complications was only 2.22% in the observation group compared to 15.56% in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Cervical spine function restoration was better with ROI-C with internal fixation in ACDF than with conventional titanium plates in ACDF for CDD disease.

Acute Angle-Closure Attacks Are Uncommon in Primary Angle-Closure Suspects after Pharmacologic Mydriasis: The Zhongshan Angle-Closure Prevention Trial.

PURPOSE: Angle-closure glaucoma is a major cause of blindness worldwide that carries an excessive risk of severe, bilateral visual impairment. A common concern among clinicians is the precipitation of acute angle-closure (AAC) attacks because of mydriasis. We evaluated the risk of AAC after pharmacologic dilation in Chinese individuals classified as having bilateral primary angle-closure suspects (PACSs). DESIGN: Randomized, interventional, controlled trial. PARTICIPANTS: A total of 889 patients with bilateral PACSs, aged between 50 and 70 years, were identified through community screening in Guangzhou, China, and enrolled in the study. METHODS: In the Zhongshan Angle-Closure Prevention Trial, bilateral PACSs were treated with laser peripheral iridotomy (LPI) in 1 randomly selected eye, with the fellow eye serving as an untreated control. Over 72 months of follow-up, the participants had their pupils pharmacologically dilated 6 times with 5% phenylephrine and 0.5% tropicamide. MAIN OUTCOME MEASURES: Incidence and risk of post-mydriasis AAC in LPI-treated and untreated, control eyes classified as PACSs. RESULTS: One bilateral AAC attack occurred after mydriasis at the 2-week post-LPI visit. No other AAC events occurred in the LPI-treated eyes. In the untreated eyes, 4 additional attacks occurred: 2 occurred after dilation (1 at 54 months and 1 at 72 months of follow-up) and 2 occurred spontaneously. The risk of post-mydriasis AAC in the untreated eyes was 1 attack in 1587 dilations. The risk of spontaneous AAC in the untreated eyes was 0.44 per 1000 eye-years (95% confidence interval, 0.11-1.77 per 1000 eye-years). CONCLUSIONS: The risk of incident AAC attacks in PACSs was extremely low, even in a higher-risk group that underwent repeated pharmacologic pupillary dilation over 6 years of follow-up. Prophylactic LPI reduced this small but real risk. This trial was registered at ISRCTN.com as ISRCTN45213099.

Ocular Biometric Risk Factors for Progression of Primary Angle Closure Disease: The Zhongshan Angle Closure Prevention Trial.

PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective, observational study. PARTICIPANTS: Six hundred forty-three mainland Chinese with untreated PACS. METHODS: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Six-year progression from PACS to PAC or AAC. RESULTS: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 µm from the scleral spur (AOD500; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72). CONCLUSIONS: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.

Laser in Glaucoma and Ocular Hypertension Trial (LIGHT) in China - A Randomized Controlled Trial: Design and Baseline Characteristics.

PURPOSE: To describe the baseline characteristics of a trial to evaluate whether selective laser trabeculoplasty (SLT), as a first-line treatment, provides superior economic and health-related quality of life outcomes to medical treatment in China. DESIGN: The LiGHT China trial is an unmasked, single-center, pragmatic, randomized controlled trial. METHODS: A total of 771 previously undiagnosed patients with primary open angle glaucoma (POAG, 622 patients) or ocular hypertension (OHT, 149 patients) at Zhongshan Ophthalmic Center were recruited from March 2015 to January 2019. Subjects were randomized to SLT-1st (followed by medication then surgery when required) or Medicine-1st (medication followed by surgery when required). The primary outcome was health-related quality of life (HRQL). The secondary outcomes were clinical outcomes, cost, cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, visual function, and safety. RESULTS: The mean age of POAG patients was 49.8 years and 38.8 years for OHT. The median intraocular pressure was 20 mm Hg for the 1,105 POAG eyes and 24 mm Hg for the 271 OHT eyes. POAG eyes had thinner central cornea thickness (CCT, 536 µm) than OHT eyes (545 µm). Median mean deviation of the visual field in POAG eyes was -4.2 dB. Median refractive error was -1.5 D for OHT eyes and -1.25 D for POAG eyes. There was no difference between POAG and OHT patients on baseline scores of GUI, GSS and VF-14. The difference between OHT and POAG on the EQ-5D-5L was 0.024. CONCLUSIONS: Compared with participants in the LiGHT UK trial, participants in this trial were younger, more myopic and had more severe visual field defects.

Anatomic Changes and Predictors of Angle Widening after Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial.

PURPOSE: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy. DESIGN: Prospective observational study. PARTICIPANTS: Primary angle-closure suspects (PACSs) 50 to 70 years of age. METHODS: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 µm from the scleral spur (AOD750); poor angle widening, defined as the lowest quintile of change in mean AOD750; and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomic changes and predictors of angle widening and opening after LPI. RESULTS: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD750 (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD750 (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening. CONCLUSIONS: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI.

Long-term effect of YAG laser iridotomy on corneal endothelium in primary angle closure suspects: a 72-month randomised controlled study.

PURPOSES: To evaluate the effect of YAG laser peripheral iridotomy (LPI) on corneal endothelial cell density (ECD) and morphology in primary angle closure suspects (PACS) over 72 months. METHODS: The Zhongshan Angle Closure Prevention Trial is a single-centre randomised controlled trial. Subjects with bilateral PACS received YAG LPI prophylactic treatment in one eye randomly, while the fellow eye served as control. Central corneal ECD and morphology were assessed using non-contact specular microscopy (SP-2000P, Topcon) at baseline, 6, 18, 36, 54 and 72 months postoperatively. Mixed model analysis was conducted to compare the difference between treated and fellow eyes. RESULTS: A total of 875 participants were included, with a mean age of 59.3±5.0 years and 83.5% female. The ECD declined significantly (p<0.001) over time in both treated and fellow eyes, but the treated eyes showed more progressive cell loss with increasing time (p<0.001). The difference in ECD loss between LPI-treated and fellow eyes was not significant at each follow-up until 72 months (4.9% in LPI eyes vs 4.2% in non-LPI eyes, p=0.003). Mean cell areas increased significantly over time in both treated and fellow eyes (p<0.001), but no longitudinal change was observed for hexagonality. In LPI-treated eyes, no significant correlation was found between age, gender, ocular biometrics, intraocular pressure and laser settings with endothelium change, except for time effect (p<0.01). CONCLUSION: ECD decreases over time primarily due to ageing effect. YAG LPI does not appear to cause clinically significant corneal endothelial damage over 72 months after treatment. TRIAL REGISTRATION NUMBER: ISRCTN45213099.

Mutations in SPATA13/ASEF2 cause primary angle closure glaucoma.

Current estimates suggest 50% of glaucoma blindness worldwide is caused by primary angle-closure glaucoma (PACG) but the causative gene is not known. We used genetic linkage and whole genome sequencing to identify Spermatogenesis Associated Protein 13, SPATA13 (NM_001166271; NP_001159743, SPATA13 isoform I), also known as ASEF2 (Adenomatous polyposis coli-stimulated guanine nucleotide exchange factor 2), as the causal gene for PACG in a large seven-generation white British family showing variable expression and incomplete penetrance. The 9 bp deletion, c.1432_1440del; p.478_480del was present in all affected individuals with angle-closure disease. We show ubiquitous expression of this transcript in cell lines derived from human tissues and in iris, retina, retinal pigment and ciliary epithelia, cornea and lens. We also identified eight additional mutations in SPATA13 in a cohort of 189 unrelated PACS/PAC/PACG samples. This gene encodes a 1277 residue protein which localises to the nucleus with partial co-localisation with nuclear speckles. In cells undergoing mitosis SPATA13 isoform I becomes part of the kinetochore complex co-localising with two kinetochore markers, polo like kinase 1 (PLK-1) and centrosome-associated protein E (CENP-E). The 9 bp deletion reported in this study increases the RAC1-dependent guanine nucleotide exchange factors (GEF) activity. The increase in GEF activity was also observed in three other variants identified in this study. Taken together, our data suggest that SPATA13 is involved in the regulation of mitosis and the mutations dysregulate GEF activity affecting homeostasis in tissues where it is highly expressed, influencing PACG pathogenesis.

Effect of a complex intervention to improve post-vision screening referral compliance among pre-school children in China: A cluster randomized clinical trial.

BACKGROUND: We investigated whether specific appointments for quality-assured care could increase referral uptake, often low in China, in children's vision screening. METHODS: We randomized children aged 4-7 years in Yudu, Jiangxi, China, by school to Control (free school-based eye screening, parents of children failing screening recommended for further examination [usual practice]) or Intervention (identical examinations, with parents additionally provided with specific appointments for further examinations by quality-assured doctors at a designated local hospital). Both groups could select any hospital for referral exams, which were not free. Six months after screening, parents were interviewed on referral compliance at any hospital (primary outcome) and potential determinants. This trial is registered at the ClinicalTrials.gov, number NCT03251456. FINDINGS: Among 9936 children at 63 schools randomized to Intervention (32 schools, 5053 [50·9%] children) or Control (31 schools, 4883 [49·1%] children), 1114 children (11·2%) failed screening. Among 513 referred Intervention children (46·1%, 32 schools, mean age 5·36 years, 53·0% boys) and 601 referred Control children (53·9%, 31 schools, mean age 5·30 years, 57·7% boys), 104 (20·3%) and 135 (22·5%) were lost to follow-up respectively. Under Intention to Treat analysis, assuming children lost to follow-up were non-compliant, Intervention children had significantly higher compliance than Controls (308/513 = 60·0% vs. 225/601 = 37·4%, P < 0·001). In regression models, Intervention group membership (Relative risk [RR] 1·53, 95% confidence interval, 1·36-1·72), travel time to hospital (RR: 0·97, 0·95-0·999), baseline glasses wear (RR: 1·37, 1·17-1·60), strabismus (RR: 1·17, 1·01-1·36) and worse uncorrected vision (RR: 1·41, 1·03-1·92) were associated with compliance. INTERPRETATION: Providing specific appointments for quality-assured eye care improved referral compliance in this setting.