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.

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.

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.

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.

Angle-closure glaucoma in Asians: comparison of biometric and anterior segment parameters between Japanese and Chinese subjects.

PURPOSE: To compare anterior segment parameters in Chinese and Japanese subjects with angle closure using anterior segment optical coherence tomography (ASOCT). METHODS: One hundred and forty-two Japanese and one hundred and ninety-two Chinese subjects with primary angle closure (PAC) or primary angle-closure glaucoma (PACG) were recruited. All participants underwent A-scan biometry and ASOCT imaging (Visante, Carl Zeiss Meditec, Dublin, CA, USA). Customized software was used to measure ASOCT parameters in horizontal ASOCT scans. The parameters were compared, and multivariate analysis was performed to determine predictors of angle opening distance at 750 µm from the scleral spur (AOD750). RESULTS: Ethnic difference evaluated by multiple linear regression adjusted for age, gender, spherical equivalent, pupil diameter, and axial length showed that Japanese angle-closure subjects had significantly shallower anterior chamber depth (ACD;ß = -0.3, p < 0.001), smaller anterior chamber area (ACA; ß = -0.21, p = 0.02) and volume (ACV; ß = -0.19, p = 0.01), greater lens vault (LV, ß = 0.3, p < 0.001), lens thickness (LT; ß = 0.48, p < 0.001), greater iris area (IArea; ß = 0.19, p = 0.01), and more curved iris (ICurv; ß = 0.16, p = 0.04). The significant determinants of AOD750 were iris thickness (IT; ß = -0.21, p = 0.04), ICurv (ß = -0.17, p = 0.04), pupil diameter (PD; ß = -0.34, p = 0.001) and ACV (ß = 0.32, p < 0.001) in Japanese; and IT (ß = -0.25, p = 0.001), ACV (ß = 0.37, p < 0.001), PD (ß = -0.26, p = 0.001), and LV (ß = -0.18, p = 0.03) in Chinese. CONCLUSIONS: Compared to Chinese, Japanese angle-closure eyes have smaller and more crowded anterior segment with thicker lenses. ACV, IT, and PD are important factors for angle width in both races. These results suggest possible ethnic differences in angle-closure mechanism(s).

A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Prospective, noncomparative, nonrandomized case study of short-term outcomes of 360° suture trabeculotomy ab interno in patients with open-angle glaucoma.

BACKGROUND: In this paper, we describe 360° suture trabeculotomy (360°LOT) ab interno and the short-term course in patients who underwent this procedure. METHODS: We prospectively studied 12 patients (12 eyes) with open-angle glaucoma who underwent 360°LOT ab interno at the Sato Eye Clinic between February and July 2014. The surgical procedure involved making a 1.7 mm temporal corneal incision, exposing an approximately 15° opening in the inner wall of Schlemm's canal (nasal side) using a Trabectome with a gonioscope, and inserting a 5-0 nylon suture rounded at the tip into Schlemm's canal opened via the anterior chamber. The suture was then threaded around Schlemm's canal, and the tip of the suture that emerged on the other side was then advanced through the opening to make a circumferential incision. Intraocular pressure (IOP), number of anti-glaucoma medications used, complications, and the surgery completion rate were prospectively studied. RESULTS: Mean IOP, which was 19.4 mmHg at baseline, showed a significant decrease at each of the monthly observation points, reaching 13.8 mmHg at 6 months after surgery (P=0.0004, paired t-test). The mean number of anti-glaucoma medications decreased from 3.2 at baseline to 1.1 at 6 months after surgery. IOP spikes ≥30 mmHg were seen in 25% of patients, but there were no other serious complications and the surgery completion rate was 92%. CONCLUSION: The 360°LOT ab interno procedure preserves the conjunctiva and sclera, and has a high surgery completion rate when using the anterior chamber approach, and could therefore be an effective short-term treatment of open-angle glaucoma.

Outcomes of 360° suture trabeculotomy with deep sclerectomy combined with cataract surgery for primary open angle glaucoma and coexisting cataract.

BACKGROUND: The purpose of this study was to investigate treatment outcomes in 360° suture trabeculotomy with deep sclerectomy combined with phacoemulsification and aspiration and intraocular lens implantation (360P-LOT + DS). METHODS: Thirty-two eyes in 32 consecutive patients treated by 360P-LOT + DS for primary open angle glaucoma with coexisting cataracts at Sato Eye Clinic from March 2011 to April 2013 were retrospectively compared with 23 eyes in 23 consecutive patients treated by cataract surgery and 120° trabeculotomy with deep sclerectomy (120P-LOT + DS) at the same clinic from January 2010 to February 2011. The parameters investigated during the 15 months after surgery were the course of intraocular pressure, number of antiglaucoma medications, best-corrected visual acuity, and complications. RESULTS: Both groups showed a significant decrease in intraocular pressure starting at one month after surgery when compared with values before surgery. At 3, 6, 9, and 15 months after surgery, the intraocular pressure was significantly lower and the survival rate was significantly higher in the 360P-LOT + DS group compared with the 120P-LOT + DS group. The number of antiglaucoma medications, best-corrected visual acuity value, and complications did not differ significantly between the groups. CONCLUSION: Although the complications are similar to those seen in 120P-LOT + DS, treatment of primary open angle glaucoma and coexisting cataracts using 360P-LOT + DS may yield better outcomes.

Intracorneal hematoma with descemet membrane detachment after viscocanalostomy.

PURPOSE: To describe a case of intracorneal hematoma with Descemet membrane detachment after viscocanalostomy. DESIGN: Interventional case report. METHODS: A 63-year-old with uncontrolled primary open-angle glaucoma underwent viscocanalostomy. During the introduction of hyaluronate 2.3% under the superficial flap, a limited lysis of Descemet membrane was observed. RESULT: Slit-lamp biomicroscopy showed an intracorneal hematoma with Descemet membrane detachment 1 day after viscocanalostomy. The creation of an intentional break of Descemet membrane and descemetopexy using sulfur hexafluoride gas were performed. The cornea regained transparency after surgery. CONCLUSIONS: Intracorneal hematoma with Descemet membrane detachment is a possible complication of viscocanalostomy.