Rapid and Reliable HLA-B*59:01 Genotyping to Prevent Carbonic Anhydrase Inhibitor-Induced Severe Cutaneous Adverse Reactions.

OBJECTIVE: Carbonic anhydrase inhibitors (CAIs) are intraocular pressure-reducing medications used in ophthalmology. Human leukocyte antigen-B*59:01 (HLA-B*59:01) is strongly associated with CAI-induced severe cutaneous adverse reactions (SCARs). This study aimed to develop and validate a rapid and economical screening method for HLA-B*59:01 to prevent carbonic anhydrase inhibitor-induced SCARs. METHODS: Duplex allele-specific polymerase chain reaction (PCR) with an internal control was performed for HLA-B*59:01 genotyping. The accuracy of duplex allele-specific PCR for HLA-B*59:01 genotyping was evaluated in 200 blood samples, using sequence-based typing (SBT) as the reference method. RESULTS: In total, 50 HLA-B*59:01-positive and 150 HLA-B*59:01-negative results obtained using duplex allele-specific PCR were in complete agreement with the SBT results. CONCLUSION: Duplex allele-specific PCR is a rapid, reliable, and economical assay for screening the HLA-B*59:01 allele.

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study.

Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called 'normal-tension glaucoma [NTG]') is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and 1,104 controls) cohorts were further investigated by targeted genotyping. SNP rs116121322 in LRRC27 showed nominally significant association with POAG in the discovery cohort (OR = 29.85, P = 2E-06). This SNP was validated in the Korean replication cohort but only in the NTG subgroups (OR = 9.86, P = 0.007). Japanese replication cohort did not show significant association with POAG (P .00.44). However, the meta-analysis in the entire cohort revealed significant association of rs116121322 with POAG (ORcombined = 10.28, Pcombined = 1.4E-07). The LRRC27 protein expression was confirmed from human trabecular meshwork cells. For gene-based testing, METTL20 showed a significant association in POAG (Pcombined = 0.002) and in the subgroup of NTG (Pcombined = 0.02), whereas ZNF677 were significantly associated with only in the subgroup of high-tension glaucoma (Pcombined = 1.5E-06). Our findings may provide further genetic backgrounds into the pathogenesis of POAG, especially for the patients who have lower baseline intraocular pressures.

Comparison of glaucoma patients referred by glaucoma screening versus referral from primary eye clinic.

PURPOSE: To investigate whether mass glaucoma screening relative to opportunistic case finding at a primary eye clinic is helpful for early detection of glaucoma. METHODS: Subjects referred by glaucoma screening (by non-contact tonometry and non-mydriatic fundus photography; group A, n = 220) and from a primary eye clinic (group B, n = 327) were retrospectively recruited. The positive predictive value (PPV) for glaucoma and the rate of glaucoma awareness were compared. Also, for the newly diagnosed glaucoma ('definite glaucoma') patients, the demographics and structural and functional severities of glaucoma were compared. RESULTS: The PPV for definite glaucoma was 25.5% for group A and 52.4% for group B. The rate of false-positive for 'glaucoma referral to tertiary hospital' was significantly higher for group A than for group B (38.6 vs. 18.3%, P < 0.001). Among the definite-glaucoma patients (group A: n = 56; group B: n = 182), the proportion of glaucoma awareness was significantly higher in group B (69.2%) than in group A (8.9%, P < 0.001). The mean deviation (MD) of visual field (VF) was significantly higher in group A than in group B (-3.08 ± 3.99 vs. -6.70 ± 7.29 dB, Padjusted = 0.040), and the inferior and inferotemporal ganglion cell-inner plexiform layer (GCIPL) thicknesses tended to be greater in group A than in group B, with marginal significance (Padjusted < 0.10). CONCLUSIONS: Glaucoma screening can be helpful for early detection of glaucoma. However, improvement of the screening strategy is needed in order to enhance its specificity for glaucoma.

Case series: Use of stromal lenticule as patch graft.

PURPOSE: To introduce cases of the use, as patch grafts, of stromal lenticules obtained by small incision lenticule extraction (SMILE) surgery. OBSERVATIONS: Case 1 was a 79-year-old man who presented with Ahmed-valve-tube exposure in his left eye. His uncorrected visual acuity (UCVA) was 20/40, best-corrected visual acuity (BCVA) 20/32, and intraocular pressure (IOP) 11 mmHg. He was treated with stromal lenticule patch that had been extracted by SMILE surgery. The patch was positioned underneath of the conjunctiva and sutured to it. At postoperative 8 months, the graft site was well maintained without Ahmed valve-tube exposure, the UCVA was 20/32, BCVA 20/20, and IOP 12 mmHg.Case 2 was a 60-year-old man who presented with Ahmed-valve-tube exposure in his right eye. His UCVA was finger-count (FC) 30 cm, his BCVA 20/125, and his IOP 14 mmHg. He was treated with stromal lenticule patch by the same method as employed in case 1. At postoperative 10 days, tube re-exposure and displacement of the Ahmed valve external plate toward the limbus area occurred due to loosening of the anchoring suture. So, we removed the Ahmed valve device, which had been implanted in the supero-temporal area, and performed new Ahmed valve implantation, with a stromal lenticule flap instead of a partial scleral flap, in the supero-nasal area. As of 6 months post-reoperation, the patient was stable, with UCVA 20/200, BCVA 20/40 and IOP 13 mmHg.Case 3 was a 74-year-old man who presented with bullous keratopathy in his right eye, which was blind. Due to severe adhesions, his conjunctiva could not cover the entire cornea. Therefore, we performed a stromal lenticule patch graft with conjunctival advance flap. At postoperative 3 months, the patient's right eye was stable, without displacement or melting of the lenticule graft. CONCLUSIONS & IMPORTANCE: It is suggested that the stromal lenticule, with its biocompatibility, sufficient strength, ease of handling and low cost, is a useful patch graft for various therapeutic purposes in the ophthalmic field.

Impending extrusion of Ex-PRESS shunt treated by shunt-position adjustment: a case report.

BACKGROUND: To report a case of impending extrusion of Ex-PRESS shunt treated by shunt-position adjustment. CASE PRESENTATION: A 56-year-old Asian woman presented with impending extrusion and malposition of Ex-PRESS shunt in her left eye. The bleb of the left eye was shallow and diffuse. In the past, the patient was treated by Ex-PRESS shunt implantation under the scleral flap in both eyes. There had been no Ex-PRESS shunt-related complication in her right eye, and she reported no history of left-eye trauma. Based on these findings, we hypothesized that the source of the left-eye problem was a loosely fixed Ex-PRESS shunt spur. It was thought, furthermore, that this inadequate scleral resistance during the Ex-PRESS shunt implantation was due to the low scleral rigidity resulting from high myopia and insufficient maintenance of the anterior chamber. We proceeded to make an incision in the area adjacent to the Ex-PRESS shunt using a super sharp blade. The shunt was then pushed into the anterior chamber with forceps, and the spur was fixed firmly. Pushing the shunt to the anterior chamber was found to have been sufficient to fix it firmly. In fact, when the sclera was palpated with a sponge, aqueous outflow was observed with no shunt displacement. Postoperative intraocular pressure (IOP) was managed well, and the bleb had formed with diffuse, prominent shapes. The Ex-PRESS shunt was well sustained with good positioning. CONCLUSIONS: When an Ex-PRESS shunt operation is performed on a patient who shows a tendency for low scleral rigidity, shunt implantation should be accomplished carefully and with force adequate for firm spur fixation.

Assessment of peripapillary choroidal thickness in primary open-angle glaucoma patients with choroidal vascular prominence.

PURPOSE: To investigate the relationship between peripapillary choroidal thickness (PCT) and choroidal vascular prominence (CVP) colocalized with retinal nerve fiber layer (RNFL) defect in primary open-angle glaucoma (POAG) eyes and to evaluate the relationship between PCT and POAG severity. METHODS: In this cross-sectional comparative study, 29 POAG patients with CVP on RNFL imaging (Group A), 70 POAG patients without CVP (Group B) and 63 healthy controls (Group C) were examined. Various factors including age, intraocular pressure (IOP), spherical equivalent (SE), axial length (AXL), central corneal thickness (CCT), peripapillary RNFL thickness, visual-field mean deviation (MD) and pattern standard deviation (PSD) were investigated. Also, PCT (average, clock-hour) was measured by swept-source optical coherence tomography. The differences in each of the factors were analyzed among the groups. RESULTS: There was no significant difference in age, IOP, SE, AXL or CCT among the three groups (P > 0.05). MD, PSD and RNFL thickness (RNFLT) in Groups A and B were lower than in Group C, but there was no difference between Groups A and B. There was a significant difference in adjusted PCT between Groups A and B (79.39 ± 6.56 vs. 115.87 ± 4.25, P < 0.001). Every adjusted clock-hour PCT in Group A was significantly thinner than in Group B. CONCLUSIONS: CVP in red-free RNFL images indicated severe thinning of PCT. Although PCT thinning was not related to glaucoma severity, CVP in red-free RNFL images should be observed as an indicator of PCT thinning, associated with POAG.

Valsalva Maneuver-induced Changes in Anterior Lamina Cribrosa Surface DEPTH: A Comparison Between Normal and Glaucomatous Eyes.

PURPOSE: The purpose of this study is to investigate the influence of the Valsalva maneuver (VM) on anterior lamina cribrosa surface depth (ALCSD), and to compare normal with treated glaucomatous eyes in terms of this effect. METHODS: Thirty-two patients (32 eyes) with early-to-moderate glaucoma under treatment and 30 normal healthy participants (30 eyes) were prospectively enrolled. Study subjects performed the VM by blowing through a mouthpiece attached to a handheld manometer; expiratory pressure during the maneuver ranged from 35 to 40 mm Hg. Swept-source optical coherence tomography B-scans were performed during phase 2 of the VM (from 10 to 15 s). RESULTS: The ALCSD was significantly different in the normal eyes only, decreasing by 31.90±14.81 µm (-8.79%; 394.85±53.63 µm at baseline vs. 362.95±44.23 µm during the VM; P<0.001). In the glaucomatous eyes, the ALCSD decreased by only 3.57±4.91 µm (-0.75%; 473.85±64.35 µm at baseline vs. 470.28±68.18 µm during the VM; P=0.092). In multivariate regression analysis, the mean ALCSD change was greater when the central corneal thickness was thinner in glaucomatous eyes (standardized ß value=0.21; P=0.02), whereas that was greater in normal eye when baseline IOP was lower (standardized ß value=0.37; P<0.001). CONCLUSIONS: During the VM, the ALCSD was decreased in normal eyes, but was not significantly changed in eyes with treated glaucoma. These results suggest that the physiology of LC displacement in response to IOP and cerebrospinal fluid pressure dynamics might differ between normal and glaucomatous eyes.

Development of visual field defect after first-detected optic disc hemorrhage in preperimetric open-angle glaucoma.

PURPOSE: To evaluate functional progression in preperimetric glaucoma (PPG) with disc hemorrhage (DH) and to determine the time interval between the first-detected DH and development of glaucomatous visual field (VF) defect. METHODS: A total of 87 patients who had been first diagnosed with PPG were enrolled. The medical records of PPG patients without DH (Group 1) and with DH (Group 2) were reviewed. When glaucomatous VF defect appeared, the time interval from the diagnosis of PPG to the development of VF defect was calculated and compared between the two groups. In group 2, the time intervals from the first-detected DH to VF defect of the single- and recurrent-DH were compared. RESULTS: Of the enrolled patients, 45 had DH in the preperimetric stage. The median time interval from the diagnosis of PPG to the development of VF defect was 73.3 months in Group 1, versus 45.4 months in Group 2 (P = 0.042). The cumulative probability of development of VF defect after diagnosis of PPG was significantly greater in Group 2 than in Group 1. The median time interval from first-detected DH to the development of VF defect was 37.8 months. The median time interval from DH to VF defect and cumulative probability of VF defect after DH did not show a statistical difference between single and recurrent-DH patients. CONCLUSIONS: The median time interval between the diagnosis of PPG and the development of VF defect was significantly shorter in PPG with DH. The VF defect appeared 37.8 months after the first-detected DH in PPG.

Assessment of Open-Angle Glaucoma Peripapillary and Macular Choroidal Thickness Using Swept-Source Optical Coherence Tomography (SS-OCT).

OBJECTIVE: To compare peripapillary and macular choroidal thickness (PCT and MCT) between open-angle glaucoma (OAG) and normal controls using swept-source optical coherence tomography (SS-OCT), and to evaluate global and localized relationships between choroidal thickness and various factors in OAG, also using SS-OCT. METHODS: In this cross-sectional comparative study, 134 OAG patients and 73 normal controls were examined. PCT (global, 12 clock-hour sectors), MCT (global, six sectors) were measured by SS-OCT. The difference in choroidal thickness between the OAG patients and the normal controls was analyzed. The relationships between choroidal thickness and various factors including age, sex, spherical equivalent (SE), axial length (AXL), central corneal thickness (CCT), intraocular pressure (IOP), peripapillary retinal nerve fiber layer thickness (pRNFLT), visual field mean deviation (MD), ganglion cell-inner plexiform layer thickness (GCIPLT), and disc area were analyzed by univariate and multivariate linear regression. Global and regional analyses were performed in 12 segments of the peripapillary circle and in six sectors of the macula. RESULTS: There were significant differences in global PCT and MCT between the OAG patients and the normal controls (115.22±41.17 vs. 138.89±44.70, P<0.001), (184.36±57.15 vs. 209.25±61.11, P = 0.004). The difference in global PCT remained, both after adjusting for age, AXL (117.08±3.45 vs. 135.47±4.70, P = 0.002) and also after adjusting for age, AXL, disc area (117.46±3.46 vs. 135.67±4.67, P = 0.002). But the difference in global MCT did not remain after adjusting for age, AXL, SE (188.18±4.46 vs. 202.25±6.08, P = 0.066). PCT showed significant differences between the groups in all of the 12 clock-hour sectors. These differences remained after adjusting for age, AXL and for age, AXL, disc area, with the exception of the 10 o'clock (o/c) sector. MCT in six sectors showed differences between the two groups, but they did not remain after adjusting for age, AXL, SE. In a multivariate regression analysis of the OAG patients, global PCT showed correlations with age (ß = -1.18, P = 0.001), AXL (ß = -14.01, P<0.001), and disc area (ß = -16.67, P = 0.026). Global MCT, meanwhile, showed a significant correlation with age (ß = -1.92, P<0.001), AXL. (ß = -21.97, P<0.001). Choroidal thickness did not show any global or localized relationship with glaucoma severity in the OAG patients. CONCLUSIONS: The global and all 12 clock-hour PCT, with the exception of the 10 o/c sector, were thinner in OAG; however, they did not show any correlation with glaucoma severity. Possible roles of PCT in glaucoma pathogenesis should be investigated further.