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Primary angle-closure glaucoma affects 20 million people worldwide. People classified as primary angle closure suspects have a higher but poorly quantified risk of developing glaucoma. We aimed to assess efficacy and safety of laser peripheral iridotomy prophylaxis against primary angle-closure glaucoma in Chinese people classified as primary angle closure suspects. In this randomised controlled trial, bilateral primary angle closure suspects aged 50–70 years were enrolled at the Zhongshan Ophthalmic Center, a tertiary specialised hospital in Guangzhou, China. Eligible patients received laser peripheral iridotomy in one randomly selected eye, with the other remaining untreated. The primary outcome was incident primary angle closure disease as a composite endpoint of elevation of intraocular pressure, peripheral anterior synechiae, or acute angle-closure during 72 months of follow-up in an intention-to-treat analysis between treated eyes and contralateral controls. This trial is registered with the ISRCTN registry, number ISRCTN45213099. Of 11 991 screened individuals, 889 individuals were randomly assigned from June 19, 2008 (889 treated and 889 untreated eyes). Incidence of the primary outcome was 4·19 per 1000 eye-years in treated eyes compared with 7·97 per 1000 eye-years in untreated eyes (hazard ratio 0·53; 95% CI 0·30–0·92; p=0·024). A primary outcome event occurred in 19 treated eyes and 36 untreated eyes with a statistically significant difference using pair-wise analysis (p=0·0041). No serious adverse events were observed during follow-up. Incidence of angle-closure disease was very low among individuals classified as primary angle closure suspects identified through community-based screening. Laser peripheral iridotomy had a modest, albeit significant, prophylactic effect. In view of the low incidence rate of outcomes that have no immediate threat to vision, the benefit of prophylactic laser peripheral iridotomy is limited; therefore, widespread prophylactic laser peripheral iridotomy for primary angle-closure suspects is not recommended. Fight for Sight, the Sun Yat-Sen University 5010 Project Fund, Moorfields Eye Charity, and the National Natural Science Foundation of China.

Background/aimsTo assess baseline ocular parameters in the prediction of long-term intraocular pressure (IOP) control after clear lens extraction (CLE) or laser peripheral iridotomy (LPI) in patients with primary angle closure (PAC) disease using data from the Effectiveness of Early Lens Extraction for the treatment of primary angle-closure glaucoma (EAGLE) tria.MethodsThis study is a secondary analysis of EAGLE data where we define the primary outcome of ‘good responders’ as those with IOP<21 mm Hg without requiring additional surgery and ‘optimal responders’ as those who in addition were medication free, at 36-month follow-up. Primary analysis was conducted using a multivariate logistic regression model to assess how randomised interventions and ocular parameters predict treatment response.ResultsA total of 369 patients (182 in CLE arm and 187 in LPI arm) completed the 36-month follow-up examination. After CLE, 90% met our predefined ‘good response’ criterion compared with 67% in the LPI arm, and 66% met ‘optimal response’ criterion compared with 18% in the LPI arm, with significantly longer drops/surgery-free survival time (p<0.05 for all). Patients randomised to CLE (OR=10.1 (6.1 to 16.8)), Chinese (OR=2.3 (1.3 to 3.9)), and those who had not previously used glaucoma drops (OR=2.8 (1.6 to 4.8)) were more likely to maintain long-term optimal IOP response over 36 months.ConclusionPatients with primary angle closure glaucoma/PAC are 10 times more likely to maintain drop-free good IOP control with initial CLE surgery than LPI. Non-Chinese ethnicity, higher baseline IOP and using glaucoma drops prior to randomisation are predictors of worse long-term IOP response.

To examine recent nationwide trends in cataract surgeries and laser peripheral iridotomy (LPI) in Korea, and to assess their temporal association and patient-level characteristics influencing procedure patterns. This retrospective cohort study used data from the Korean National Health Information Database. Individuals aged 65 years and older who underwent cataract surgery or LPI between 2016 and 2021 were analyzed. Primary outcomes included the annual volumes of cataract surgeries and LPIs, their temporal association, patient demographics, the proportion of LPI patients subsequently undergoing cataract surgery, and the interval to surgery. Cataract surgeries increased annually until 2019, declined in 2020, and rose again in 2021, whereas LPI procedures steadily decreased after 2017. A negative correlation was observed between annual cataract surgeries and LPIs (r = -0.657, P = 0.156), although not statistically significant. Among patients aged 65-74 years, the correlation was significant (r = -0.943, P = 0.005). Among those who underwent LPI, 92.1% subsequently received cataract surgery, with a median interval of 121 days between procedures. This nationwide study demonstrated a temporal association and demographic characteristics underlying the recent increase in cataract surgeries and the concurrent decline in LPI procedures in Korea. Notably, most patients who underwent LPI subsequently received cataract surgery within a relatively short interval, suggesting a possible clinical shift toward earlier lens extraction in the management of angle closure.

IntroductionPrimary angle-closure glaucoma (PACG) is a major subtype of glaucoma that accounts for most bilateral glaucoma-related blindness globally. Filtering surgery is a conventional strategy for PACG, yet it has a long learning curve and undesirable disastrous complications. Minimally invasive glaucoma surgery (MIGS) plays an increasing role in the management of glaucoma due to its safer and faster recovery profile; cataract surgery-based MIGS is the most commonly performed such procedure in PACG. However, for patients with a transparent lens or no indications for cataract extraction, incorporation of MIGS into PACG treatment has not yet been reported. Therefore, this multicentre, non-inferiority, randomised controlled clinical trial aims to compare the efficacy and safety of trabeculectomy versus peripheral iridectomy plus an ab interno goniotomy in advanced PACG with no or mild cataracts.Methods and analysisThis non-inferiority, multicentre, randomised controlled trial will be conducted at seven ophthalmic departments and institutes across China. Eighty-eight patients with no or mild cataracts and advanced PACG will be enrolled and randomised to undergo trabeculectomy or peripheral iridectomy plus ab interno goniotomy. Enrolled patients will undergo comprehensive ophthalmic examinations before and after surgery. The primary outcome is intraocular pressure (IOP) at 12 months postoperatively. The secondary outcomes are cumulative success rate of surgery, surgery-related complications and number of IOP-lowering medications. Participants will be followed up for 36 months postoperatively.Ethics and disseminationThe study protocol was approved by the ethical committees of the Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ191) and of all subcentres. All participants will be required to provide written informed consent. The results will be published in peer-reviewed journals and disseminated in international academic meetings.Trial registration numberNCT05163951.

Background China has the largest burden of primary angle-closure glaucoma (PACG) worldwide. The mechanism of the angle closure is complex and includes pupillary block and non-pupillary block. Currently, opinion is that laser peripheral iridotomy (LPI) alone is not sufficient to prevent disease progression. Laser peripheral iridoplasty (LPIP) is an alternative and effective way of widening the angle recess in eyes that are affected by primary angle closure (PAC). However, it is not known if greater benefit would be achieved using LPI plus LPIP for PAC with multiple mechanisms (MAC). Thus, the aim of this study is to demonstrate if LPI plus LPIP would be more effective than single LPI in controlling the progression of PAC with multiple mechanisms, based on ultrasound biomicroscopy (UBM) classification. A secondary aim is to determine whether or not this would result in the use of less medication and/or prolong the time to antiglaucoma surgery. Methods This multiple-mechanism angle-closure study will comprise a 3-year, multicenter, randomized, parallel-group, open-label, superiority trial, the aim of which will be to evaluate the safety and efficacy of LPI plus LPIP versus LPI for PAC. It is anticipated that 240 adults, diagnosed with PAC (the mechanism of angle closure will be assessed by UBM and it will be determined whether or not it involves multiple mechanisms) will be recruited from ten ophthalmic centers in China. Participants will be randomly allocated to receive either single LPI or LPI plus LPIP. Participant assessment will be designed to test the rate of disease progression and who will be followed up for 3 years. The primary outcome will be the disease progression rate and a comparison will be made between the LPI and LPI plus LPIP groups using Pearson’s χ 2 test. Logistic regression analysis will be performed to account for the central effect. Discussion If the LPI plus LPIP is found to significantly decrease the rate of PAC progression, this intervention could potentially be a standard therapy to be used to treat PAC when multiple mechanisms are involved in angle closure. Subsequently, this would have the potential to delay the rate of PAC progression to PACG and delay the time to the administration of antiglaucoma medication or trabeculectomy surgery. Trial registration ClinicalTrials.gov, NCT02613013 . Registered on 24 November 2015. In fact, the study was due to start in late October 2015, however, there were no patients recruited in October, and when we registered at ClinicalTrials.gov on 5 November 2015, we received suggestions on the English translation of our protocol from the PRS Team at Clinicaltrial.gov, so the final successful registration date was on 24 November 2015.

PurposeTo describe the results of darkroom prone provocative testing (DRPPT) in primary angle closure suspects (PACS) and to compare the findings to controls with open angles.Methods889 subjects with PACS in the Zhongshan Angle Closure Prevention Trial (a randomised controlled trial to compare prophylactic laser iridotomy to no treatment in PACS) and 89 with open angles in the 5-year follow-up of Liwan Eye Study were placed in a darkroom face down for 15 min. Intraocular pressure (IOP) was measured immediately before and after DRPPT.ResultsPACS participants were of similar age than controls (59.3 vs 60.5), more often female (82.9% vs 58.4%) and had lower IOP (14.3 vs 15.2 mm Hg). The average IOP increases after DRPPT was 4.3±3 mm Hg in PACS and 5.2±2.8 in controls (p<0.05). 20.5% of controls and 13.9 % of those with PACS developed an IOP spike ≥8 mm Hg after DRPPT (p<0.05). Among PACS, 15.8 % of those with all four quadrants closed had an IOP elevation of ≥ 8 mm Hg as opposed to 10.0%–12.4 % with two or three closed quadrants (p<0.05). DRPPT failed to predict who would reach a clinical trial endpoint over 6-year follow-up of those with PACS.ConclusionsA modified DRPPT failed to separate PACS from those with open angle. Although the test resulted in greater IOP elevation among those PACS participants with all four quadrants closed than in those with two or three closed quadrants, it did not offer any insight into the risk of developing acute or chronic angle closure disease over 6-year follow-up.

Background/AimsProphylactic 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.MethodsIn 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.ResultsIn 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).ConclusionAlthough 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.

Background To explore the efficacy and safety of laser peripheral iridoplasty (LPIp) with different energy levels and locations in the treatment of primary angle closure disease (PACD) assessed by swept-source anterior segment optical coherence tomography (AS-OCT). Methods We enrolled patients with PACD following best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber gonioscopy, ultrasound biomicroscopy(UBM), optic disc OCT, and visual field examinations. After Pentacam and AS-OCT measurements, the patients were randomly divided into four treatment groups for LPIp with two different energy levels (high vs. low energy) and two locations (far from the periphery vs. near the periphery) and combined with laser peripheral iridotomy. BCVA, IOP, pupil diameter, central anterior chamber depth, anterior chamber volume, anterior opening distance (AOD)500, AOD750, trabecular iris angle (TIA)500, and TIA750 in four quadrants before and after laser treatment were compared. Results We followed up 32 patients (64 eyes; average age, 61.80 ± 9.79 years; 8 patients/16 eyes per group) for up to 2 years. The IOP of all enrolled patients was decreased after surgery compared to that before (t = 3.297, P  = 0.002), the volume of the anterior chamber was increased (t=-2.047, P  = 0.047), and AOD500, AOD750, TIA500, and TIA750 were increased (all P  < 0.05). Within-group comparisons showed that BCVA in the low-energy/far-periphery group was improved after surgery ( P  < 0.05). After surgery, the IOP was decreased in the two high-energy groups, whereas the volume of the anterior chamber, AOD500, AOD750, TIA500, and TIA750 were increased in all groups (all P  < 0.05). However, when comparing every two groups, the high-energy/far-periphery group showed a stronger effect on pupil dilation than the low-energy/near-periphery group ( P  = 0.045). The anterior chamber volume in the high-energy/near-periphery group was larger than that in the high-energy/far-periphery group ( P  = 0.038). The change in TIA500 was for 6 points smaller in the low-energy/near-periphery group than in the low-energy/far-periphery group ( P  = 0.038). Other parameters showed no significant group differences. Conclusion LPIp combined with iridotomy can effectively reduce IOP, increase anterior chamber volume, increase chamber angle opening distance, and widen the trabecular iris angle. Intraoperatively, high-energy laser spots positioned one spot diameter from the scleral spur can obtain the best effect and safety. Swept-source AS-OCT can safely and effectively quantify the anterior chamber angle.

Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.

PurposesTo 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.MethodsThe 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.ResultsA 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).ConclusionECD 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.