Exploratory Search for Characteristic Symptoms to Distinguish Meibomian Gland Dysfunction from Dry Eye in a Population-Based Study in Japan.

Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson's correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation.

Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome.

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Relation of Dietary Fatty Acids and Vitamin D to the Prevalence of Meibomian Gland Dysfunction in Japanese Adults: The Hirado-Takushima Study.

Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16-0.97) for total fat, 0.40 (0.17-0.97) for saturated FAs, 0.40 (0.17-0.97) for oleic acid, 0.52 (0.23-1.18) for n-3 PUFAs, 0.63 (0.27-1.49) for n-6 PUFAs, 1.32 (0.59-2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17-0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.

Multicenter Study of Intense Pulsed Light for Patients with Refractory Aqueous-Deficient Dry Eye Accompanied by Mild Meibomian Gland Dysfunction.

Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer's test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer's test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE.

Meibomian Gland Dysfunction and Dry Eye Are Similar but Different Based on a Population-Based Study: The Hirado-Takushima Study in Japan.

PURPOSE: To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. DESIGN: A population-based cross-sectional study. METHODS: Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. RESULTS: A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, -0.017). CONCLUSIONS: MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.

360-degree suture trabeculotomy ab interno with phacoemulsification in open-angle glaucoma and coexisting cataract: a pilot study.

OBJECTIVE: We performed a pilot trial to evaluate the 24-month safety and efficacy of 360-degree suture trabeculotomy ab interno with phacoemulsification used to treat mild to moderate open-angle glaucoma coexisting with cataract. METHODS AND ANALYSIS: We randomly assigned 18 eyes with open-angle glaucoma and coexisting cataract to undergo 360-degree suture trabeculotomy ab interno with phacoemulsification (combined) or phacoemulsification alone (control) (1:1 ratio) and followed up patients for 24 months. Main outcome measures were mean postoperative intraocular pressure (IOP) and success probabilities based on Kaplan-Meier life table analyses. Surgical success was defined as follows: criterion A: IOP value ≥6 mm Hg and ≤15 mm Hg, with ≥20 % reduction without medication; criterion B: IOP value ≥6 mm Hg and ≤12 mm Hg, with ≥30% reduction without medication. Secondary outcome measures included the number of medications, complications and best-corrected visual acuity. RESULTS: Mean IOP values (number of medications), which were 18.4 mm Hg (0.9) and 17.1 mm Hg (1.3) at baseline, showed significant reductions to 11.8 mm Hg (1.0) and 14.6 mm Hg (1.5) at 24 months postoperatively in the combined and control groups, respectively (p=0.0003 and 0.0192, respectively). Success rates for criterion A in the combined and control groups were 77.8% and 11.1%, respectively (p=0.0110) and those for criterion B in the combined and control groups were 46.7% and 0%, respectively (p=0.0036). Both groups had a similar overall occurrence of postoperative complications. CONCLUSION: Using 360-degree suture trabeculotomy ab interno with phacoemulsification appeared to be a more beneficial option for mild to moderate open-angle glaucoma with coexisting cataract than phacoemulsification alone. TRIAL REGISTRATION NUMBER: UMIN000021170, date of registration: 2016/03/01.

Multicenter Study of Intense Pulsed Light Therapy for Patients With Refractory Meibomian Gland Dysfunction.

PURPOSE: To evaluate the efficacy of intense pulsed light (IPL) therapy combined with meibomian gland expression (MGX) for refractory meibomian gland dysfunction (MGD) in a prospective study conducted at 3 sites in Japan. METHODS: Patients with refractory obstructive MGD were enrolled and underwent 4 to 8 IPL-MGX treatment sessions at 3-week intervals. Clinical assessment included the Standard Patient Evaluation of Eye Dryness questionnaire; noninvasive breakup time of the tear film and interferometric fringe pattern as determined by tear interferometry; lid margin abnormalities, fluorescein breakup time of the tear film, corneal and conjunctival fluorescein staining (CFS), and meibum grade as evaluated with a slit-lamp microscope; meibomian gland morphology (meiboscore); and tear production as measured by the Schirmer test without anesthesia. RESULTS: Sixty-two eyes of 31 patients (17 women, 14 men; mean age ± SD, 47.6 ± 16.8 years) were enrolled. The Standard Patient Evaluation of Eye Dryness score (P < 0.001), noninvasive breakup time (P < 0.001), and interferometric fringe pattern (P < 0.001) were significantly improved after therapy, with 74% of eyes showing a change in the interferometric fringe pattern from 1 characteristic of lipid deficiency to the normal condition. Meibum grade, lid margin abnormality scores, fluorescein breakup time, and CFS were also significantly improved (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively) after treatment, whereas the meiboscore and Schirmer test value remained unchanged. CONCLUSIONS: IPL-MGX ameliorated symptoms and improved the condition of the tear film in patients with refractory MGD and is therefore a promising treatment option for this disorder.

360-degree suture trabeculotomy ab interno to treat open-angle glaucoma: 2-year outcomes.

PURPOSE: The purpose of this study was to evaluate the efficacy of 360-degree suture trabeculotomy (360S-LOT) ab interno for treating open-angle glaucoma (OAG). Risk factors of surgical failure were examined. PATIENTS AND METHODS: 360S-LOT ab interno alone was performed for patients with uncontrolled OAG, and combined 360S-LOT ab interno/phacoemulsification was performed for patients with controlled OAG with a visually significant cataract between March 2014 and September 2015 at a single center. The patients were prospectively followed for 2 years. The main outcome measures included 2-year intraocular pressure (IOP), number of anti-glaucoma medications used, postoperative complications, and predictive factors of surgical failure. Kaplan-Meier analysis was performed, with surgical success (with or without medication use) defined as postoperative IOP ≤15 mmHg and IOP reduction ≥20% (criterion A) or IOP ≤12 mmHg and IOP reduction ≥30% (criterion B). Predictive factors were evaluated using Cox proportional hazard ratios. RESULTS: A total of 64 eyes of 64 patients were included, and 50 (78%) eyes of 64 eyes underwent a phacoemulsification combination procedure. Surgery significantly reduced IOP from 18.4 ± 2.9 mmHg before surgery to 13.4 ± 3.0 mmHg after surgery (P < 0.001). Patients used an average of 1.8 ± 1.5 medications before surgery and 1.3 ± 1.5 medications after surgery (P = 0.101). No serious postoperative complications were observed. The probability of surgical success was 49.2% and 16.0% using criteria A and B, respectively. No risk factors of surgical failure were identified. CONCLUSION: The 360S-LOT ab interno procedure is a favorable option for treating eyes with mild or moderate OAG.

Efficacy of 0.05% epinastine and 0.1% olopatadine for allergic conjunctivitis as seasonal and preseasonal treatment.

PURPOSE: To evaluate the efficacy and safety of 0.05% epinastine and 0.1% olopatadine eye drop preparations as seasonal and preseasonal treatments in patients with seasonal allergic conjunctivitis (SAC). SUBJECTS AND METHODS: This was a prospective, randomized, case-control study involving two institutions. The subjects were patients diagnosed with SAC at two institutions between February and March in 2014. To examine the clinical effects of seasonal treatment, 0.05% epinastine and 0.1% olopatadine were administered, and their effects were investigated every 2 weeks (Stage 1). To evaluate the clinical effects of preseasonal therapy, in January 2015, the same eye drop preparations as adopted in Stage 1 were administered to patients who had participated in Stage 1 and provided consent to participate in this study, and their effects were investigated every month (Stage 2). RESULTS: In Stage 1, the 0.05% epinastine group consisted of 43 patients, and the 0.1% olopatadine group consisted of 42 patients. There were significant improvements in the total symptom and objective finding scores at each time point after administration in comparison with those before its baseline, but there were no significant differences between the two groups. In Stage 2, the 0.05% epinastine group consisted of 15 patients, and the 0.1% olopatadine group consisted of 14 patients. The rate of change in the total symptom score in comparison with that at the baseline of preseasonal treatment was significantly higher in the 0.1% olopatadine group 1 month after the start of treatment, suggesting symptom deterioration (P=0.025). There was no significant difference in the rate of change in the total objective finding score between the two groups. CONCLUSION: Seasonal treatment with 0.05% epinastine or 0.1% olopatadine was equally effective for patients with allergic conjunctivitis. However, for preseasonal therapy, 0.05% epinastine was more effective than 0.1% olopatadine.

Morphology and Function of Meibomian Glands and Other Tear Film Parameters in Junior High School Students.

PURPOSE: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. METHODS: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0-14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0-4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0-9), meiboscore as determined by noncontact meibography (0-6), Schirmer test value, and meibum grade (0-3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). RESULTS: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = -0.220, P = 0.021), and LLT (ρ = -0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = -0.338, P < 0.001), and fluorescein staining score (ρ = -0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = -0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. CONCLUSIONS: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1.

Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Changes in Japanese eyes after laser peripheral iridotomy: an anterior segment optical coherence tomography study.

BACKGROUND: The aim was to investigate the changes in anterior segment parameters, as assessed by anterior segment optical coherence tomography in Japanese subjects after laser peripheral iridotomy (LPI). DESIGN: This was a prospective observational study. PARTICIPANTS: The participants include 72 subjects with angle closure including primary angle closure suspect (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG). METHODS: Anterior segment optical coherence tomography parameters was measured by customized software. Complete data of 51 subjects were available for final analysis. MAIN OUTCOME MEASURES: These were the following parameters: angle opening distance, trabecular-iris space area, anterior chamber depth, width, area and volume (iris thickness, curvature, and area, and lens vault (LV). RESULTS: A total of 25 PACS, 17 PAC and 9 PACG were included. Mean age was 74.7 ± 6.7 years, and majority were women (80.4%). Following LPI, there was a significant increase in mean gonioscopic angle width (1.16 vs. 1.93, P < 0.001) and a corresponding increase in angle opening distance, trabecular-iris space area, and angle recess area (all P < 0.001). The anterior chamber area (P < 0.001), anterior chamber volume (P < 0.001) and anterior chamber depth (P = 0.003) increased significantly; and iris curvature (P < 0.001) was significantly reduced. There were no significant changes in anterior chamber width, LV, iris thickness and area. Age-adjusted and gender-adjusted analysis for predictors of percentage change in angle opening distance 750 showed significant association with greater baseline LV (ß = 0.32, P = 0.03). No significant differences were noted in the mean percentage change in parameters between the PACS and PAC-PACG. CONCLUSIONS: An increase in anterior chamber dimensions, angle widening and iris flattening; with a constant LV, iris thickness and iris area after LPI was demonstrated in Japanese eyes with angle closure.

Clinical results of Trabectome surgery for open-angle glaucoma.

BACKGROUND: The purpose of this study was to determine outcomes when using Trabectome surgery and to evaluate factors associated with its effects in primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). METHODS: This was a prospective, non-randomized, observational, comparative cohort study in which Trabectome surgery was used alone in patients with POAG or EXG. Trabectome surgery was considered to have failed when at least one of the following three criteria was fulfilled: intraocular pressure (IOP) ≥21 mmHg and a <20% reduction below the baseline IOP on two consecutive follow-up visits 3 months or more after surgery; need for additional glaucoma surgery; and an increase in number of medications compared with baseline. RESULTS: The subjects were 32 males (34 eyes) and 46 females (48 eyes). POAG was observed in 43 eyes and EXG in 39 eyes. IOP after Trabectome surgery decreased significantly from 22.3±6.8 mmHg at baseline to 14.0±3.9 mmHg (23.0% reduction) at month 24 in all cases (P<0.0000). The success rate at 2 years was 51.2% for all cases (POAG, 50.9%; EXG, 49.2%). There was no significant difference in success rate between POAG and EXG (P=0.91). Preoperative IOP (P=0.033) and number of medications (P=0.041) were significant factors for surgical success/failure in multivariate logistic regression. No serious complications were observed. CONCLUSION: Trabectome surgery achieved favorable IOP control and was equally effective in patients with POAG and those with EXG. Its effects were influenced by preoperative IOP and number of preoperative medications.

Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus.

Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (∼40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis.

Plateau iris in Japanese patients with primary angle closure and primary angle closure glaucoma.

PURPOSE: To determine the prevalence of plateau iris in Japanese patients with primary angle closure (PAC) and primary angle closure glaucoma (PACG) and analyze the biometric parameters in patients with plateau iris using ultrasound biomicroscopy (UBM). METHODS: In this cross-sectional observational study, subjects aged >50 years with PAC and PACG who had previously undergone a patent laser peripheral iridotomy underwent UBM in one eye. UBM images were qualitatively analyzed using standardized criteria. Plateau iris in a quadrant was defined by anteriorly directed ciliary body, absent ciliary sulcus, steep iris root from its point of insertion followed by a downward angulation, flat iris plane, and irido-angle contact. At least two quadrants had to fulfill these UBM criteria for an eye to be classified as having plateau iris. A-scan biometry was used to measure anterior segment parameters. RESULTS: Ninety-one subjects with PAC (58 subjects) or PACG (33 subjects) and 68 normal controls were recruited. The mean (standard deviation) ages of PAC and PACG patients and normal controls were 73.5 (6.2) and 72.6 (7.3), respectively. Based on UBM criteria, plateau iris was found in 16 eyes (17.6%) of 91 eyes. In these 16 eyes, quadrant-wise analysis showed ten eyes (62.5%) had plateau iris in two quadrants; four eyes (25%) had plateau iris in three quadrants; and two eyes (12.5%) had plateau iris in four quadrants. Anterior chamber depth, lens thickness, axial length, lens position, and relative lens position were not statistically significant between the group having plateau iris and that not having plateau iris, respectively. CONCLUSION: Approximately 20% of Japanese subjects with PAC and PACG with a patent laser peripheral iridotomy were found to have plateau iris on UBM. No morphological difference was noted in the anterior segment of the eye between those with or without plateau iris.