Phacoemulsification combined with goniosynechialysis versus phacoemulsification alone for patients with primary angle­closure disease: A meta-analysis.

This meta-analysis aims to systematically compare the efficacy between phacoemulsification (PE) combined with goniosynechialysis (GSL) and PE alone for primary angle-closure disease (PACD) patients. All the data were searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was used to evaluate the quality of the included studies. Additionally, this meta-analysis was performed by using the Revman 5.4 software. Nine randomized controlled trials (RCTs) were included in this study. Compared with PE alone group, PE+GSL could result significant reduction in the IOP (MD, 1.81; p = 0.002). In the instrumental subgroup, also more reduction of IOP was shown in the PE+GSL group (MD, 2.11; p = 0.02). In the viscogonioplasty (VGP) subgroup, there was not no statistical difference between PE alone group and PE+GSL group (MD, 1.53; p = 0.11). Also, more reduction of peripheral anterior synechiae (PAS) was shown in the PE+GSL group (MD,59.15; p<0.00001). For the change in angle open distance (AOD)500, AOD 750, trabecular-iris space (TISA)500, number of glaucoma medications and best corrected visual acuity (BCVA), there was no difference between two groups (p = 0.25, 0.35, 0.17, 0.56, 0.08). For TISA 750, more improvement was shown in the PE+GSL group (p<0.00001). Instrumental separation had better effect on lowering IOP when it combined with PE. Both instrumental separation and VGP could reduce postoperative PAS. The operation of GSL has no obvious effect on postoperative vision.

Myopic Versus Glaucomatous Parapapillary Beta Zone in Myopic Eyes Versus Eyes With Secondary Angle-Closure Glaucoma.

Purpose: To search for histologic differences in the beta zone between myopic eyes versus eyes with secondary angle-closure glaucoma. Methods: The histomorphometric study consisted of human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. Results: The study included 100 eyes (age: 62.1 ± 15.1 years; axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic glaucomatous eyes compared with non-highly myopic nonglaucomatous eyes, the parapapillary alpha zone was longer (223 ± 168 µm vs. 125 ± 128 µm; P = 0.03), beta zone prevalence (15/20 vs. 6/41; P < 0.001) and length (277 ± 245 µm vs. 44 ± 150 µm; P = 0.001) were higher, and RPE cell density in the alpha zone and alpha zone border was lower (all P < 0.05). In highly myopic nonglaucomatous eyes compared with non-highly myopic glaucomatous eyes, parapapillary RPE drusen prevalence (2/19 vs. 10/10; P = 0.01) and alpha zone prevalence (2/19 vs. 16/20; P < 0.001) and length (23 ± 68 µm vs. 223 ± 168 µm; P < 0.001) were lower. In non-highly myopic glaucomatous eyes, Bruch's membrane (BM) thickness decreased (P < 0.001) from the beta zone (6.0 ± 3.1 µm) to the alpha zone (5.1 ± 4.3 µm) and peripheral to it (3.0 ± 0.9 µm). In highly myopic nonglaucomatous eyes, BM thickness did not differ (P > 0.10) between all three regions. In the total study population, RPE cell density in the alpha zone (24.5 ± 9.3 cells/240 µm) was higher than at the alpha zone border (19.2 ± 4.8 cells/240 µm; P < 0.001) or peripheral to it (19.0 ± 3.6 cells/240 µm; P < 0.001). Conclusions: The glaucomatous beta zone in eyes with chronic angle-closure glaucoma (with the alpha zone, parapapillary RPE drusen, thickened BM, and higher RPE cell count in the adjacent alpha zone) differs histologically from the myopic beta zone (characterized by the absence of the alpha zone and parapapillary RPE drusen, unremarkable BM thickness, and unremarkable parapapillary RPE). The differences suggest different etiologies of the glaucomatous versus myopic beta zone.

The inflammatory cytokine profiles and ocular biometric characteristics of primary angle-closure glaucoma.

OBJECTIVE: To investigate the pathogenesis of primary angle-closure disease (PACG) by measuring the anatomical structures of the anterior and posterior segments of the eye and inflammatory markers in the peripheral blood. METHODS: This case-control study enrolled patients diagnosed with acute PACG (APACG) and chronic PACG (CPACG). It also enrolled control subjects without PACG. The anterior and posterior anatomical features were measured in all study participants. The levels of interleukin (IL)-6, tumour necrosis factor-α and the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood were measured. RESULTS: This study analysed a total of 99 eyes: 34 eyes from 34 patients with APACG, 28 eyes from 28 patients with CPACG and 37 eyes from 37 control patients with senile cataract. The axis length, corneal diameter, anterior chamber depth and anterior chamber volume were significantly smaller in the APACG and CPACG groups compared with the controls. The level of IL-6 in the peripheral blood of patients with PACG was significantly lower than that of the controls. The NLR in the peripheral blood of patients with PACG was significantly greater than that of the controls. CONCLUSIONS: Changes in the ocular anatomy and some inflammatory markers might be involved in the pathogenesis of PACG.

[Phacoemulsification combined with goniosynechialysis under a gonioscope in the treatment of angle-closure glaucoma: the effect of reopening the synechial anterior chamber angle].

A total of 170 consecutive patients (181 eyes) who were diagnosed with primary angle-closure glaucoma (PACG) and underwent phacoemulsification and intraocular lens implantation (PEI) combined with goniosynechialysis (GSL) with an instrument under a gonioscope in the Eye Hospital, Wenzhou Medical University from January 1, 2017 to December 31, 2019 were observed. Anterior chamber angle synechiae of 0 (0, 2) clock hour were released after PEI, while after combined goniosynechialysis, synechiae of 6 (3, 8) clock hours were further released. No matter in chronic PACG and acute PACG with cornea edema, the extent of anterior chamber angle synechiae was different before surgery and after PEI, and so was it in post-PEI and PEI-GSL prospectively (all P<0.01). Phacoemulsification alone can reopen the synechial anterior chamber angle in both chronic PACG and acute PACG in part, but not sufficiently. Combined goniosynechialysis under a gonioscope with an instrument is essential and effective.

Biallelic variants in CPAMD8 are associated with primary open-angle glaucoma and primary angle-closure glaucoma.

BACKGROUND/AIMS: This study aims to assess the contribution of biallelic CPAMD8 variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on a systematic analysis of exome sequencing (ES). METHODS: Potentially pathogenic CPAMD8 variants were selected from the ES data of 5307 subjects with various eye conditions through multiple bioinformatics analyses. Of the 5307 subjects, 1221 probands had different forms of primary glaucoma. The genotype-phenotype correlation was assessed by a systematic review of biallelic CPAMD8 variants that including our data and data from the literature. The expression profile of CPAMD8 in human tissues was determined at the mRNA and protein levels. RESULTS: Biallelic CPAMD8 variants, including one frameshift and six missense variants, were exclusively present and significantly enriched in patients with glaucoma (one with juvenile open-angle glaucoma (JOAG), two with POAG and two with PACG) compared with none of the 4086 probands with other eye conditions in this cohort (p=4.1E-07). The effect of variants in these patients is relatively mild compared with that reported in patients with anterior segment dysgenesis or primary congenital glaucoma. CPAMD8 mRNA was highly expressed in the optic nerve, ciliary body, retina and iris, whereas the CPAMD8 protein was mainly detected in the nonpigmented epithelium of the iris and ciliary process, determined by immunohistochemistry. CONCLUSIONS: The data from this study not only provide further evidence to support the association of biallelic CPAMD8 variants with JOAG but also suggest that biallelic CPAMD8 variants might be associated with POAG and PACG.

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris.

PURPOSE: To characterize the proteome of the iris in primary angle closure glaucoma (PACG). EXPERIMENTAL DESIGN: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log2 two-fold difference in expression in iris between PACG and controls. RESULTS: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.

Association of High-Mobility Group Box-1 with Inflammationrelated Cytokines in the Aqueous Humor with Acute Primary Angle-Closure Eyes.

AIM: The aim of this study was to measure the levels of High-mobility group box-1 (HMGB1) and inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure glaucoma (APAG) and age-related cataract eyes (ARC). METHODS: Aqueous humor samples were obtained from 59 eyes of 59 Chinese subjects (APAG, 32 eyes; and ARC, 27eyes). The multiplex bead immunoassay technique was used to measure the levels of HMGB1 and IL-8, IL-6, G-CSF, MCP-3, VEGF, sVEGFR- 1, sVEFGR-2, TNF-α, PDGF, and IL-10 in aqueous. The data of Patients' demographics and preoperative intraocular pressure (IOP) were also collected for detailed analysis. RESULTS: The APAG group showed significantly elevated concentrations of HMGB1, IL- 8, IL-6, G-CSF, VEGF, sVEGFR-1, and TNF-α than those in the ARC group. Aqueous HMGB1 level correlated significantly with IOP, IL-8, IL-6, G-CSF and sVEGFR-1 levels but not with age, TNF-α, or VEGF levels. CONCLUSION: The aqueous level of HMGB1 is elevated in APAG and associated with aqueous level of inflammation-related cytokines, suggesting an association between elevated levels of HMGB1, APAC and certain inflammatory modulators which, of course, should lead to further investigations in order to demonstrate the cause and effect.

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.

Retinal Pigment Epithelium Cell Density and Bruch's Membrane Thickness in Secondary versus Primary High Myopia and Emmetropia.

To assess differences between secondary high myopia (SHM) due to congenital glaucoma and primary high myopia (PHM) and non-highly myopic eyes (NHM) in the relationships between axial length and Bruch's membrane (BM) thickness and retinal pigment epithelium (RPE) density. The histomorphometric study included human globes enucleated for reasons such as malignant uveal melanoma, end-stage painful secondary angle-closure glaucoma and congenital glaucoma. BM thickness and RPE cell density were measured upon light microscopy. The investigation included 122 eyes (mean axial length: 26.7 ± 3.7 mm; range: 20.0-37.0 mm): 7 eyes with SHM (axial length: 33.7 ± 2.1 mm; range: 31.0-37.0 mm), 56 eyes with PHM (mean axial length: 29.1 ± 2.4 mm; range: 26.0-36.0 mm) and 59 eyes in the NHM-group (axial length: 23.5 ± 1.3 mm; range: 20.0-25.5 mm). In the SHM group, longer axial length was associated with lower RPE cell density at the posterior pole (standardized regression coefficient beta: 0.92; non- standardized regression coefficient B: -2.76; 95% confidence interval (CI): -4.41, -1.10;P = 0.01), at the midpoint posterior pole/equator (beta: -0.87; B: -3.60; 95% CI: -6.48, -0.73;P = 0.03), and at the equator (beta: -0.88; B: -0.95; 95% CI: -1.68, -0.23; P = 0.02), but not at the ora serrata (P = 0.88). In the PHM-group and NHM group, RPE cell density at the posterior pole (P = 0.08) and ora serrata (P = 0.88) was statistically independent of axial length, while at the midpoint posterior pole/equator (P = 0.01) and equator (P < 0.001), RPE cell density decreased with longer axis. BM thickness in the SHM group decreased with longer axial length at the posterior pole (beta: -0.93;B: -0.29; 95% CI: -0.39, -0.14; P = 0.003), midpoint posterior pole/equator (beta: -0.79; B: -0.22; 95% CI: -0.42, -0.02; P = 0.035) and equator (beta: -0.84; B: -0.21; 95% CI: -0.37, -0.06; P = 0.017), while in the PHM-group and NHM-group, BM thickness at any ocular region was not statistically significantly correlated with axial length (all P > 0.05). In the SHM-group, but not in the PHM-group or NHM-group (P = 0.98), lower BM thickness was associated with lower RPE cell density (beta: 0.93; B: 0.09; 95% CI: 0.04, 0.14; P = 0.007), while in the eyes without congenital glaucoma the relationship was not statistically significant. In SHM in contrast to PHM, BM thickness and RPE cell density decrease in a parallel manner with longer axial length. The findings fit with the notion of BM being a primary driver in the process of axial elongation in PHM as compared to SHM.

Characteristic Manifestations regarding Ultrasound Biomicroscopy Morphological Data in the Diagnosis of Acute Angle Closure Secondary to Lens Subluxation.

PURPOSE: To investigate the mechanisms underlying the occurrence of acute angle closure (AAC) and to further explore the sensitive indicators for clinical diagnosis of acute angle closure secondary to lens subluxation (AACSLS) through qualitative and quantitative analysis of ultrasound biomicroscopy (UBM) imaging features of eyes with AAC to provide a theoretical basis for the selection of treatment schemes. METHODS: A retrospective analysis was conducted from 2013 to 2018 on 160 eyes (160 patients) with uniocular acute angle closure crisis (AACC) complicated by cataract. The case group consisted of 29 eyes (29 patients) with lens subluxation and the control group consisted of 131 eyes (131 patients) without lens subluxation. Before the operation, computer optometry, best corrected visual acuity, intraocular pressure, slit lamp, gonioscopy, preset lens, A-mode ultrasonography, and UBM were performed. All the enrolled subjects underwent cataract surgery with or without other operations. The pupil was fully dilated, and the position of the lens was recorded before the operation. The zonular rupture and lens subluxation were further confirmed during operation. SPSS version 20.0 was used to analyze UBM imaging data from the lens subluxation group and non-lens subluxation group. RESULTS: The iris span (IS) value in the whole quadrant of the lens subluxation group was significantly higher than that of the non-lens subluxation group (P=0.033, 95%CI 0.01 to 0.31). The iris lens angle (ILA) in the lens subluxation group was significantly lower than that in the non-lens subluxation group in the upper, lower, nasal, temporal, and whole quadrants (P<0.001, 95%CI -8.79 to -2.78; P=0.001, 95%CI -8.36 to -2.27; P<0.001, 95%CI -9.85 to -4.98; P=0.015, 95%CI -6.67 to -0.72; P<0.001, 95%CI -8.74 to -5.83, respectively). However, the ILA of the maximum difference among the four quadrants in the lens subluxation group was significantly higher than that in the non-lens subluxation group (P<0.001, 95%CI 4.74 to 9.86). The ILA and iris lens contact distance (ILCD) showed significant negative correlations in both the lens subluxation group and non-lens subluxation group (Y=20.984-7.251X, R=0.520, and P<0.001; Y=19.923-3.491X, R=0.256, and P<0.001, respectively). The risk ratio of lens subluxation in exposed eyes with ILA=0 in one quadrant at least was significantly higher than that in nonexposed eyes without ILA=0 in all quadrants (X 2 =87.859, P<0.001, and odds ratio (OR)=79.200, 95% CI 23.063 to 271.983). The risk ratio of zonular rupture in exposed quadrants with ILA=0 was significantly lower than that in nonexposed eyes without ILA=0 (X 2 =33.884, P<0.001, OR=0.122, and 95% CI 0.053 to 0.278). The risk ratio of zonular rupture in exposed quadrants with nonforward convexity of iris was significantly lower than that in nonexposed quadrants with forward convexity of iris (X 2 =6.413, P=0.011, and OR=0.381; 95% CI 0.176 to 0.825). CONCLUSIONS: ILA=0 and nonforward convexity of iris as UBM sensitive and characteristic indicators for screening lens subluxation and zonular rupture can provide new ideas and hints for clinical diagnosis of acute angle closure secondary to lens subluxation.

Anterior Segment Features in Nanophthalmos With Secondary Chronic Angle Closure Glaucoma: An Ultrasound Biomicroscopy Study.

Purpose: We compare anterior segment parameters and the risk of malignant glaucoma between nanophthalmos with secondary chronic angle closure glaucoma (NSCACG) and chronic primary angle-closure glaucoma (CPACG). Methods: This retrospective case-control study included 32 NSCACG (32 eyes) and 36 CPACG (36 eyes) patients. Anterior segment parameters, including anterior chamber depth (ACD) and width (ACW), pupil diameter (PD), lens vault (LV), ciliary process-ciliary process distance (CCD), angle opening distance500 (AOD500), trabecular-iris angle (TIA), trabecular-ciliary processes distance (TCPD), ciliary body max thickness (CBMT), iris convexity (IC), peripheral iris thickness (PIT), iris-zonule distance (IZD), trabecular ciliary process angle (TCPA), and anterior vault (AV), were measured by ultrasound biomicroscopy. A-scan ultrasonography measurements, including lens thickness (LT) and axial length (AL), also were reviewed. Results: ACD, ACW, CCD, TCPD, and AL were smaller, whereas the LV, LT/AL, LV/LT, LV/ACD, LT/ACD, LV/AV, and AV/AL were larger in NSCACG compared to CPACG eyes (all Bonferroni-corrected P < 0.05). Eyes with NSCACG had a higher risk of malignant glaucoma postoperatively than eyes with CPACG (P = 0.018). Conclusions: Characterized by narrower anterior segment, forward movement of larger lens, more anteriorly rotated ciliary bodies, and smaller CCD, NSCACG eyes have a higher risk of malignant glaucoma than CPACG eyes.

Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma.

PRéCIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma. PURPOSE: Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease IOP by reducing aqueous production. Anecdotal experience in angle-closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma. PATIENTS AND METHODS: A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted. RESULTS: In 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up, the 22 eyes with chronic angle-closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open-angle glaucoma at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14). CONCLUSIONS: Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.

A new rhodopsin R135W mutation induces endoplasmic reticulum stress and apoptosis in retinal pigment epithelial cells.

Rhodopsin mutations are associated with the autosomal-dominant form of retinitis pigmentosa (RP). Here we report simultaneous occurrence of RP associated with bilateral nanophthalmos and acute angle-closure glaucoma in patient with a new mutation in rhodopsin (R135W). ARPE-19 cells were transfected with myc-tagged wild-type (WT) and R135W rhodopsin constructs. The half-life of WT and R135W rhodopsin was analyzed via cycloheximide chase analysis. We found that R135W rhodopsin was accumulated in the endoplasmic reticulum (ER) and induced unfolded protein response (UPR) and apoptosis. Moreover, chaperone HSP70 alleviated ER stress and prevented apoptosis induced by R135W rhodopsin by attenuating UPR signaling. These findings reveal the novel pathogenic mechanism of RP and suggest that chaperone HSP70 has potential therapeutic significance for RP.

Inflammatory cytokine profiles in eyes with primary angle-closure glaucoma.

Acute primary angle-closure (APAC) eyes show an early 'acute inflammatory' condition, while the inflammation condition has not been fully elucidated in the development of primary angle-closure glaucoma (PACG). To evaluate the roles of inflammatory cytokines in the pathogenesis of PACG, this cross-sectional study involved 40 eyes of 32 PACG patients who required trabeculectomy and 24 eyes of 24 patients who required cataract surgery. The aqueous humor samples were collected at the time of surgery. Fifteen inflammatory cytokines were detected using the multiplex bead immunoassay technique, and the clinical information was recorded for the correlation analysis. Eight of the 15 cytokines were all detectable in both groups, including granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, MCP-3, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1ß, and vascular endothelial growth factor (VEGF). When compared with the cataract patients, the MCP-3, MDC, and VEGF levels were elevated in the PACG patients, while the MCP-1 and MIP-1ß levels were decreased. However, the G-CSF, IL-6, and IL-8 levels were similar between the two groups. The MCP-1 concentration was elevated accordingly as the disease progressed in the PACG patients. Our results suggest the PACG eyes retained a 'mild inflammation' condition in the aqueous humor, and MCP-1 may play an important role in the progression of this disease.

The treatment of refractory angle-closure glaucoma in a patient with X-linked juvenile retinoschisis.

X-Linked Retinoschisis (XLRS) is a common genetically determined form of macular degeneration affecting young males. XLRS is due to mutations in the RS1 gene located on chromosome Xp22 which codes for retinoschisin and is estimated to affect between 1:5000 to 1:20000 individuals worldwide. We report a case of refractory angle-closure glaucoma in a thirty-nine-year-old Caucasian man with atypical XLRS. The patient presented with a two-day history of left eye pain, acutely reduced vision and a nine-month history of hemicranial pain. Examination identified left intraocular pressure (IOP) of 52mmHg. Gonioscopy confirmed complete angle closure. Following failure of medical management and persistently raised left IOP (43-46mmHg), the patient underwent left phacoemulsification and intraocular lens insertion without complication. After surgery, his IOP reduced to 10-14mmHg on all follow up examinations without the need for glaucoma drops. His iridocorneal angle remained open and vision improved to 20/100. Our case demonstrates the additional role of lens surgery in the treatment of secondary angle-closure glaucoma in the presence of an inherited retinal dystrophy. All patients with inherited retinopathy presenting with a headache or eye pain should undergo gonioscopic examination to exclude angle-closure glaucoma.

Matricellular Protein Levels in Aqueous Humor and Surgical Outcomes of Trabeculectomy.

Purpose: The purpose of this study was to quantify levels of three matricellular proteins in the aqueous humor in patients with previous acute primary angle closure (APAC) and investigate their correlation with bleb morphology and surgical outcomes of trabeculectomy. Methods: In this prospective study, aqueous humor samples were collected from 40 previous APAC eyes. Concentrations of three matricellular proteins-secreted protein acidic and rich in cysteine (SPARC), thrombospondin-2, and osteopontin-were measured using multiplexed immunoassays kits. Intraocular pressure was measured using Goldmann application tonometry. Bleb morphology was assessed using anterior segment optical coherence tomography, and bleb score was calculated according to bleb size and reflectivity. Results: When previous APAC eyes were divided according to surgical outcome 18 months after trabeculectomy, SPARC protein was significantly higher in aqueous humor in the failure group (P = 0.009). When previous APAC eyes were divided according to SPARC level, eyes with low SPARC levels had significantly higher overall success rate compared with eyes with high SPARC levels (P = 0.005 for complete success and P = 0.018 for qualified success). Multiple logistic regression analyses showed that eyes with higher levels of SPARC were more likely to have a failed filtration surgery than were eyes with lower levels of SPARC. For complete success, P = 0.006 and odds ratio (OR) = 6.458; for qualified success, P = 0.033 and OR = 2.608. The level of SPARC was found to have a positive correlation with bleb score (P < 0.001, R2 = 0.471). Conclusions: In previous APAC patients, the SPARC level in aqueous humor is a prognostic factor for surgical results of trabeculectomy. Modulation of SPARC expression may have potential clinical applications after filtration surgery.

Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology.

Feasibility of laser trabeculoplasty in angle closure glaucoma: a review of favourable histopathological findings in narrow angles.

Selective laser trabeculoplasty (SLT) has been indicated as a safe and efficient treatment for primary open-angle glaucoma; however, recent studies have also shown positive results with the use of SLT in some clinical conditions related to primary angle-closure glaucoma (PACG). Despite the potential benefits of SLT in selected cases of PACG, the mechanisms underlying the modifications in the trabecular meshwork tissue of patients with PACG are poorly understood. This narrative review approached both the current, limited knowledge about the histological changes observed in different forms of PACG and the clinical results of SLT treatment for PACG. Favourable outcomes of SLT in patients with PACG, specifically in areas of non-occluded angle, need further substantiation through large controlled clinical trials. A deeper understanding of the biomolecular changes of those areas is essential to improve both laser technical details and the clinical efficacy of SLT therapy.

High intensity focused ultrasound as first line treatment in patients with chronic angle closure glaucoma at risk for malignant glaucoma.

PURPOSE: Evaluation of high intensity focused ultrasound (HIFU) transscleral cyclocoagulation as an alternative to trabeculectomy in the treatment of refractory chronic angle closure glaucoma (CACG). METHODS: This prospective one armed single center pilot study was conducted on patients with medically uncontrolled CACG who underwent high intensity focused ultrasound (HIFU) cyclocoagulation as first line surgical treatment, using the Eye-OP1 HIFU device (Eyetechcare-Rillieux-la-Pape, France) driven by ultrasound biomicroscopic (UBM) ciliary body localization. All patients had documented progression of their glaucoma despite conventional medical and laser therapy. The primary efficacy outcome was intraocular pressure (IOP) reduction; secondary outcomes included changes in number of glaucoma medications and complications after cyclocoagulation. RESULTS: The study involved 8 eyes of 7 patients between May 2013 and September 2014. The average follow-up was 5.6±2.1 months. The mean IOP was reduced from 18.4±3.5mmHg preoperatively to 14.8±4.1mmHg 6 months postoperatively. The average number of glaucoma medications decreased from 3.4±1.1 at baseline to 3.3±0.7 after 6 months. Visual acuity remained stable (median 0.17 log MAR preoperatively and 0.19 log MAR at last follow-up visit). No significant side effect occurred during the 6 months follow-up period. CONCLUSIONS: HIFU cyclocoagulation appears to be a safe and reliable alternative to filtering surgery in the management of chronic angle closure glaucoma among patients with a high risk of malignant glaucoma.

Flat Anterior Chamber after Trabeculectomy in Secondary Angle-Closure Glaucoma with BEST1 Gene Mutation: Case Series.

PURPOSE: Trabeculectomy has been regarded as a mainstay of initial treatment in eyes of angle closure glaucoma (ACG) with peripheral anterior synechia > 180° in the Chinese population while its efficacy in secondary ACG with BEST1 gene mutation remains unclear. We set out to investigate the treatment outcome of trabeculectomy for secondary ACG in a group of patients with autosomal recessive bestrophinopathy (ARB). METHODS: In this retrospective case series study, 8 secondary ACG patients with ARB and their 4 recruited family members underwent a thorough ophthalmic examination including best-corrected visual acuity, Goldmann applanation tonometry, gonioscopy, and fundus examinations. Ultrasound biomicroscopy, optical coherence tomography (OCT), ultrasound A-scan, B-scan, electro-oculography (EOG), Humphrey perimetry, fundus photography, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were also performed. Blood samples were obtained in the patients and their available family members to analyze the variants of the BEST1 gene. Trabeculectomy was performed in the 8 patients (15 eyes). RESULTS: The age of onset varied from 13 to 38 years. The average axial length (AL) of the affected eyes was 21.82 ± 0.92 mm and the average anterior chamber depth (ACD) was 2.19 ± 0.29 mm. There was marked axial shallowing of the anterior chamber in all 15 eyes after trabeculectomy, and was not improved with potent mydriatics. The IOP was elevated in 3 eyes. Variable degree of yellowish subretinal deposits was observed in the posterior retina. The FFA showed punctuate or patched hyperfluorescence suggesting retinal pigment epithelium impairment. The ICGA demonstrated dilatation of choroidal vessels. The OCT revealed diffused neuroretinal detachment in the posterior and midperipheral retina, with intraretinal fluid collections, and hyperreflective subretinal accumulations. The average subfoveal choroidal thickness of the patients was 382.36 ± 80.09 µm. All the patients and enrolled family members carried mutation in BEST1 gene. CONCLUSIONS: ARB is a rare condition with fundus manifestations mimicking various diseases. Careful discrimination should be taken to exclude any secondary causes for ACG before treatment. Concerning the high incidence of postoperative shallow anterior chamber, selection of filtering surgery should be very careful in these patients.