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Introduction Neovascular glaucoma is characterized by neovascularization of the iris and the anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may improve intraocular pressure (IOP) and neovascularization. Methods The VEGA trial assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma in a 13-week, randomized, double-masked, sham-controlled, phase 3 study performed at multiple sites in Japan that enrolled patients with anterior segment neovascularization and IOP > 25 mmHg. Patients received background therapy plus IVT-AFL (2 mg) or sham injection at baseline. Patients were re-treated if presenting with IOP > 21 mmHg and incomplete regression of iris neovascularization, receiving additional sham or IVT-AFL injections at week 1 and IVT-AFL injections at weeks 5 and/or 9. Double-masking was maintained throughout. The primary endpoint was change in IOP from baseline to week 1. Results Fifty-four patients were randomly assigned (full analysis set); the per-protocol set comprised 52 patients. At week 1, the least squares mean change in IOP was −9.9 mmHg for IVT-AFL versus −5.0 mmHg for sham [full analysis set: difference −4.9 mmHg (95% confidence interval −10.2 to 0.3; P = 0.06); per-protocol set: −5.5 mmHg (95% CI −10.8 to −0.2; P = 0.04)]. At week 1, a greater proportion of patients administered IVT-AFL versus sham achieved IOP ≤ 21 mmHg and had improved neovascularization grades. Patients in the sham group who met re-treatment criteria and received IVT-AFL at week 1 [n = 22 (81.5%)] had an additional mean IOP decrease of 9.2 mmHg by week 2, and the proportion with improvement in neovascularization grades increased from 11.5% to 69.2%. Increases in the proportion of patients with improved neovascularization grades and the proportion who achieved IOP control (≤ 21 mmHg) were also observed by week 2 in this group. Overall, 77.8% and 74.1% of patients treated with IVT-AFL and sham/IVT-AFL, respectively, received a single IVT-AFL injection. The most common ocular treatment-emergent adverse event was punctate keratitis (9.3%: 7.4% and 11.1% in the IVT-AFL and sham/IVT-AFL groups, respectively). Conclusions IVT-AFL was associated with clinically meaningful improvements in IOP control, indicating that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. Trial Registration Clinicaltrials.gov identifier, NCT02396316. Electronic supplementary material The online version of this article (10.1007/s12325-020-01579-5) contains supplementary material, which is available to authorized users.

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.Retrospective case study.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.Two-sided Fisher exact test with an alpha level0.05 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.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.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]; P0.001). 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]; P0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P0.001). 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%], P0.001).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.

To investigate the association between asymmetry of visual field (VF) defects and optic nerve head (ONH) blood flow in patients with glaucoma using laser speckle flowgraphy.In total, 170 eyes of 85 patients with primary open-angle glaucoma were included. Intraocular pressure, VF (Humphrey 24-2, SITA program), mean blur rate in the tissue area (MBR-T) of the ONH measured by laser speckle flowgraphy, axial length, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), disc area, cup/disc area ratio, and parapapillary atrophy (PPA) area was measured in each eye. The paired eyes were divided into better and worse eyes according to the mean deviation (MD) of VF, and intereye differences of various parameters (better MD eye minus worse MD eye) were examined. Factors associated with MD difference, MBR-T difference, or cpRNFLT difference were investigated.MD of the VF in better and worse eyes were -10.2±7.3 dB and -16.8±7.4 dB, respectively. In stepwise multiple regression analysis, MBR-T differences, cpRNFLT differences and sex (male) were significantly correlated with MD differences (β, 0.26, 0.21, 0.20; P=0.01, 0.04, 0.047, respectively). MD differences were significantly associated with MBR-T differences (β, 0.28; P=0.01). For cpRNFLT differences, differences in β-PPA area and MD differences were identified as significant factors (β, -0.26, 0.22; P=0.02, 0.04, respectively).Asymmetry of ONH blood flow is significantly associated with asymmetry of visual field defects in patients with glaucoma independently of cpRNFLT.

PURPOSE To investigate factors associated with decreased corneal endothelial cell density (ECD) after trabeculectomy with mitomycin C (MMC). METHODS Retrospective review of consecutive glaucoma cases who underwent trabeculectomy with MMC. The types of glaucoma included were primary open-angle glaucoma, exfoliation glaucoma (XFG), neovascular glaucoma, and uveitic glaucoma (UG). The postoperative ECD changes compared with the preoperative ECD and risk factors for ECD decrease were analyzed using mixed-effects models. RESULTS In total, 162 eyes of 136 patients were included in this study. Postoperative ECD measurements were performed 3.7±1.8 times (mean±SD) during a median follow-up period of 34 months. The mean intraocular pressure decreased from 25.3±9.6 to 9.2±2.3 mm Hg postoperatively. The marginal mean (SE) ECD decrease at 24 months was 9.3% (1.3%) in all cases. The marginal mean ECD decrease at 24 months was 18.2% (3.1%) and 20.6% (4.7%) in eyes with XFG and UG, respectively, which was significantly greater than 4.8% (1.8%) in eyes with primary open-angle glaucoma (P

Introduction Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma. Methods This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1. Results Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, −8.3 mmHg [95% confidence interval; CI −12.2 to −4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8–70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%). Conclusions IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. Trial Registration Clinicaltrials.gov identifier NCT03639675. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-020-01580-y.

For research on circadian intraocular pressure (IOP), rebound tonometers are widely used with or without general anesthesia as a non-invasive approach to obtain IOP values. However, whether general anesthesia such as inhalation anesthesia with isoflurane affects the circadian rhythm of IOP and in turn IOP measurements is currently unclear. As such, data reporting IOP values obtained under general anesthesia should be interpreted with caution. The purpose of this study was to evaluate how general anesthesia with isoflurane inhalation affects the circadian rhythm of IOP.C57Bl/6J strain mice maintained using a 12h:12h light/dark cycle (lights on and off at ZT0 and ZT12, respectively) were used. IOPs were measured using a rebound tonometer (Icare TonoLab) before and 3, 5, 10, 15, and 30 min after initiating anesthesia in both light and dark phases (ZT 2-6 and ZT 14-18, respectively). Awake IOPs and IOPs at 3 and 5 min after anesthesia initiation were also obtained at ZT5, 8, 11, 14, 17, and 20 to assess IOP diurnal curves under gas anesthesia.IOP values gradually decreased after anesthesia initiation in both light and dark phases (P 0.001) and there was no interaction between light/dark phase and anesthesia time (P = 0.88). There was a slight, but not significant, reduction in IOP 3 min after initiating anesthesia (P = 0.23), and significant decreases in IOP occurred at subsequent timepoints (P ≤ 0.001). Both awake and anesthetized mice showed a robust IOP rhythm that reached a peak and trough in the dark and light phase, respectively. Awake IOP levels did not significantly differ from those for anesthetized mice at 3 min after anesthesia initiation at all time points (P ≥ 0.07).Both awake and anesthetized mice demonstrated a robust circadian rhythm for IOP. Murine IOP showed similar gradual decreases under inhalation anesthesia with isoflurane in both the light and dark phases. IOPs measured using a rebound tonometer within 3 min of initiating isoflurane anesthesia were comparable to awake IOPs, and thus may be useful to monitor the circadian rhythm of IOP in mice.

To investigate the spatial and temporal relationship between disc hemorrhage (DH) and structural progression in patients with primary open-angle glaucoma (POAG) in a 3-year prospective study.Prospective cohort study.Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs.Fundus photographs were taken at baseline and every 3 months for 3 years. Disc hemorrhage and structural progression were detected independently by flicker chronoscopy. If present, clock-hour disc locations in the right eye format and colocalization were determined. Statistical comparisons were based on mixed-effects models accounting for the correlation between different disc sites within the same eye and between fellow eyes in the same patient.Relationship between DH and structural progression at the same site.Among 195 eyes of 115 patients, DH appeared in 85 sites in 65 eyes (33.3%) and was most frequently at the 7 o'clock disc location (29.4%, P0.0001). Structural progression occurred at 63 sites of 52 eyes (26.7%) comparably in both superior and inferior hemidiscs, which was mostly detected as widening of the retinal nerve fiber layer defects (RNFLDs). Temporal RNFLD widening was common, whereas nasal widening occurred exclusively in the vertical quadrants (P = 0.035). Of 41 progression sites in eyes with DH, 28 sites (68.2%) had both DH and progression. Progression sites with DH were less common in the superior quadrant than in the inferior and temporal quadrants (P = 0.011). Eyes with DH had a significantly higher risk of progression than eyes without DH (hazard ratio, 3.72; P0.0001). For 63 progression sites, DH recurrence and more visits with DH at the progression site were significantly associated with shorter time to progression from baseline (P = 0.021, P = 0.017, respectively), whereas colocalization of DH and progression were not.In a 3-year prospective study with a Japanese POAG cohort, the relationship between DH and RNFLD and the pattern of RNFLD progression differed by disc location. The association between more frequent DH at the progression site and shorter time to progression indicates that DH may reflect vulnerability to same-site structural deterioration.

Purpose To report the occurrence probability of disc haemorrhage (DH) and risk factors for it in otherwise healthy Japanese normal-tension glaucoma (NTG) patients who had lower normal intraocular pressure (IOP) and were followed without treatment for 5 years. Methods A prospective observational study. Normal-tension glaucoma (NTG) patients with IOP consistently ≤15 mmHg without treatment were enrolled. The presence or absence of DH was checked semi-annually on the fundus photographs by three independent observers, while patients were followed without treatment. Cox proportional hazards model taking inter-eye correlation into consideration was adopted to identify risk factors for DH occurrence. The main outcomes were DH occurrence probability during 5-year period and its risk factors. Results One hundred seventeen eyes of 90 patients with mean age of 54.1 years, mean deviation value of -3.6 decibels and mean IOP during follow-up of 12.4 mmHg were included. Disc haemorrhage (DH) was observed at least once in 34 eyes and more than twice in 15 eyes during the follow-up. The DH occurrence probability at 5 years was 31% (95% confidence interval: 21-40%), and lower myopic refraction (HR = 1.18; p = 0.018), higher IOP during follow-up (HR = 1.35; p = 0.047) and presence of DH at baseline (HR = 4.19; p = 0.002) were its risk factors. Conclusion Disc haemorrhage (DH) occurrence probability of Japanese healthy NTG patients with mean IOP of 12.4 mmHg and no systemic and/or topical treatment was 31% at 5 years. Lower myopic refraction, higher IOP and its existence at baseline were its risk factors.

BACKGROUND/OBJECTIVES: To identify risk factors for glaucoma-related central visual field (VF) deterioration after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). SUBJECTS/METHODS: A prospective cohort study consisting of cases with or without glaucoma (33 eyes of 33 patients in each group) who underwent vitrectomy with ILM peeling for ERM. Humphrey 10–2 VFs and ganglion cell complex (GCC) thickness were measured at baseline and about 3, 6, and 12 months postoperatively. Longitudinal changes in VF indices and factors associated with their postoperative changes were investigated using mixed-effects models, as was sectorwise total deviation (TD) analysis using six sectors consisting of outer/inner arcuate and cecocentral sectors in each hemifield. RESULTS: VF mean deviation significantly deteriorated postoperatively only in the glaucoma group (P

Purpose To elucidate glaucoma-related fundus abnormalities in patients with primary aldosteronism (PA). Methods The study compared 272 eyes from 137 PA patients and 352 eyes from 177 control subjects selected randomly from 1173 participants of a public glaucoma screening. The presence of glaucomatous optic disc appearance (rim thinning and cup enlargement) and retinal nerve fiber layer defects (RNFLDs) was determined independently from fundus photographs. The results were compared between the PA and control groups. Results There were 9 patients (6.6%) with glaucomatous optic disc abnormalities in the PA group and 10 cases (5.6%) identified in the control group (p = 0.92). RNFLDs were detected more frequently in the PA group (55 eyes, 20.2%) than in the control group (26 eyes, 7.4%; p Conclusion Although the prevalence of glaucomatous optic disc appearance did not differ between the two groups, RNFLDs were more frequent in PA patients than in the control group. Moreover, RNFLDs with their central ends located around retinal vessels were characteristic of PA patients.

PURPOSE To evaluate the use of a 24-hr ocular dimensional profile recorded with a contact lens sensor (CLS) combined with a single tonometric intraocular pressure (IOP) reading to indicate the potential for exceeding the diagnostic threshold for normal tension glaucoma (NTG) in Japanese patients. METHODS Intraocular pressure (IOP) of untreated Japanese NTG patients was measured with tonometry every 3 hr from 9:00 to 24:00. The subsequent day a 24-hr CLS (SENSIMED Triggerfish, Sensimed AG, Lausanne, Switzerland) profile was recorded on the same eye. Patients initially diagnosed as NTG were reclassified as NTG when the measured IOP values were consistently

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 x 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 x 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. National Research Foundation of SingaporeNational Research Foundation, Singapore [NRF-NRFI2018-01]; US National Eye Institute of the National Institutes of Health [R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, EY015473]; Glaucoma Research Foundation of Canada [X052, CIRG17may053]; National Medical Research Council of SingaporeNational Medical Research Council, Singapore The study was funded by grant NRF-NRFI2018-01 from the National Research Foundation of Singapore. Additional support was provided by grants R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, and EY015473 from the US National Eye Institute of the National Institutes of Health, funding from the Glaucoma Research Foundation of Canada, and grants X052 and CIRG17may053 from the National Medical Research Council of Singapore.

To evaluate the effect of topically administrated ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head (ONH) of normal rats. Ripasudil (0.4%) or placebo was administered in the right eye of normal Brown Norway rats in a double-blind manner. Laser speckle flowgraphy was measured in the ONH of the right eye 20 or 40 min after a single instillation and before and after 7 or 14 days of twice daily instillation. Mean blur rate was evaluated in the total area (MA), the vessel region (MV), and the tissue region (MT). Intraocular pressure (IOP), blood pressure, ocular perfusion pressure (OPP), and heart rate were also recorded at each time point. After a single instillation, MV was significantly larger at 40 min than 20 min in the ripasudil group (P = 0.044) and was significantly lower in the placebo group (P = 0.023). MA and MV 40 min after instillation were significantly larger in the ripasudil group than in the placebo group (P = 0.022 and P = 0.006, respectively). After continuous instillation, MA and MV in the ripasudil group significantly increased from baseline after 7 and 14 days of treatment (both P

To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment.Prospective 5-year study.Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline.Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment.Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression.We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], -2.8 decibels [dB]). The MD slope averaged -0.33 dB/year (median, -0.23; 95% confidence interval [CI], -0.44 to -0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55-78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37-60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38-71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3.In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was -0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression.

Daisuke Takemoto, Tomomi Higashide, Yoshiaki Saito, Shinji Ohkubo, Sachiko Udagawa, Hisashi Takeda, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: We conducted a prospective study in patients with normal-tension glaucoma (NTG) who received either isopropyl unoprostone or latanoprost. We compared the drugs in terms of their effects on intraocular pressure (IOP) and visual field loss progression over a 3-year period. Study design: Prospective, randomized controlled study. Methods: We enrolled 48 patients with newly diagnosed NTG at Kanazawa University Hospital. Eligible patients were randomly allocated (1:1) to receive either unoprostone or latanoprost ophthalmic solutions. The primary outcomes were IOP changes and visual field deterioration within 36 months. Visual field changes were analyzed: the cumulative survival rates were calculated in terms of mean deviation, pattern standard deviation, and total deviation of the upper or lower hemi-visual field, each visual field sector, and guided progression analysis. In addition, we evaluated the progression of glaucomatous optic disc changes using fundus photography and confocal scanning laser ophthalmoscopy. Results: The mean pretreatment IOP was 15.0±2.4 mmHg in the Unoprostone group and 15.2±1.9 mmHg in the Latanoprost group. The mean IOP during the treatment period was 13.7±2.3 mmHg in the Unoprostone group and 13.0±1.8 mmHg in the Latanoprost group. In both groups, the IOP decreased significantly (p

PURPOSE To investigate postoperative changes and prognostic factors of visual impairment after vitrectomy for unilateral epiretinal membrane. METHODS A prospective observational study on 45 eyes from 45 patients with unilateral idiopathic epiretinal membrane who underwent vitrectomy. Visual parameters (best-corrected visual acuity, metamorphopsia using M-CHARTS, and aniseikonia using the New Aniseikonia Test) and spectral domain optical coherence tomography parameters (macular retinal layer thickness and microstructure of the outer retina) were measured preoperatively and 6 and 12 months postoperatively. Statistical analyses included linear mixed-effects models for the longitudinal changes and prognostic factors of visual parameters. RESULTS Best-corrected visual acuity and horizontal metamorphopsia improved significantly from 6 months after surgery (P < 0.001), whereas aniseikonia decreased significantly only at 12 months (P = 0.015). Vertical metamorphopsia remained unchanged. Preoperative inner nuclear layer thickness was significantly correlated with preoperative metamorphopsia. Besides baseline values, best-corrected visual acuity had no significant prognostic factors, but preoperative ellipsoid zone disruption had a negative direction of association with postoperative metamorphopsia (coefficients: -0.37 and -0.62, P = 0.015 and 0.006 for horizontal and vertical metamorphopsia, respectively), and preoperative horizontal metamorphopsia had a positive direction of association with postoperative aniseikonia (coefficient: 1.77, P = 0.002). CONCLUSION After vitrectomy, postoperative changes and prognostic factors for unilateral epiretinal membrane differed for best-corrected visual acuity, metamorphopsia, and aniseikonia.

To evaluate the correlation between metamorphopsia and outer retinal morphologic changes after successful vitrectomy for rhegmatogenous retinal detachment (RRD).Forty eyes from 40 patients with macula-off (26 eyes) or macula-on (14 eyes) RRDs that underwent pars plana vitrectomy were included. Metamorphopsia was quantified with M-CHARTS. The relationship between the integrity of the outer retinal layers examined by spectral domain optical coherence tomography and metamorphopsia at 6 and 12 months postoperatively was evaluated.Metamorphopsia was significantly more frequent in eyes with macula-off RRD (88%) than in eyes with macula-on RRD (21%) at 6 months postoperatively (P0.001) and became significantly less frequent in macula-off RRD eyes from 6 months to 12 months (64%) postoperatively (P = 0.041). Horizontal metamorphopsia scores in eyes with continuous interdigitation zone and ellipsoid zone bands were significantly smaller than in eyes with a disrupted interdigitation zone band and a continuous ellipsoid zone band or in eyes with disrupted ellipsoid zone and interdigitation zone bands (P = 0.003 and P0.001, respectively), which was consistent with the results of vertical metamorphopsia scores.Restoration of both the ellipsoid zone and interdigitation zone bands seems to be an important factor for the reduction of metamorphopsia after successful vitrectomy for macula-off RRD.

Purpose This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops. Methods Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy. Results There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group. Conclusions Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface.

Purpose To investigate visual field changes after vitrectomy for macular diseases in glaucomatous eyes. Methods A retrospective review of 54 eyes from 54 patients with glaucoma, who underwent vitrectomy for epiretinal membrane (ERM; 42 eyes) or macular hole (MH; 12 eyes). Standard automated perimetry (Humphrey visual field 24-2 program) was performed and analyzed preoperatively and twice postoperatively (1st and 2nd sessions; 4.7 ± 2.5, 10.3 ± 3.7 months after surgery, respectively). Postoperative visual field sensitivity at each test point was compared with the preoperative value. Longitudinal changes in mean visual field sensitivity (MVFS) of the 12 test points within 10° eccentricity (center) and the remaining test points (periphery), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and ganglion cell complex (GCC) thickness, and the association of factors with changes in central or peripheral MVFS over time were analyzed using linear mixed-effects models. In addition, 45 eyes from 45 patients without glaucoma who underwent vitrectomy for epiretinal membrane (ERM; 34 eyes) or macular hole (MH; 11 eyes) were similarly examined and statistically analyzed (control group). Results In glaucomatous eyes, visual field test points changed significantly and reproducibly; two points deteriorated only at the center and twelve points improved only at the periphery. Central MVFS decreased (p = 0.03), whereas peripheral MVFS increased postoperatively (p = 0.010). In the control group, no visual field test points showed deterioration, and central MVFS did not change significantly after vitrectomy. BCVA improved, GCC thickness decreased, and IOP did not change postoperatively in both groups. The linear mixed-effects models identified older age, systemic hypertension, longer axial length, and preoperative medication scores of ≥2 as risk factors for central MVFS deterioration in glaucomatous eyes. Conclusions Visual field sensitivity within 10° eccentricity may deteriorate after vitrectomy for ERM or MH in glaucomatous eyes.

Purpose To investigate the effect of trabeculectomy on the waveform changes of laser speckle flowgraphy (LSFG) in the optic nerve head (ONH) in patients with glaucoma. Methods Forty-eight eyes of 48 patients with open angle glaucoma were included in this prospective study. LSFG was performed before and 1, 3, and 6 months after trabeculectomy. Longitudinal changes in average mean blur rate (MBR), blow out score (BOS), resistivity index (RI), falling rate, skew, acceleration time index, and blow out time in the tissue area of the ONH were analyzed by using mixed-effects models. Results Intraocular pressure (IOP) decreased and ocular perfusion pressure increased significantly at each postoperative time point (P < 0.001, each). BOS increased (P < 0.001, each) and RI decreased (P < 0.001, each) significantly at each postoperative time point, although average MBR and other waveform parameters did not change significantly. Multivariate analyses revealed that younger age (coefficients = -0.13 and 0.0014, P = 0.006 and 0.03 for BOS change and RI change, respectively), worse baseline mean deviation of visual fields (coefficients = -0.18 and 0.0026, P = 0.009 and 0.005), larger IOP reduction (coefficients = -0.29 and 0.0037, P < 0.001, each), and larger pulse rate increase (coefficients = 0.17 and -0.0024, P < 0.001, each) are significantly associated with postoperative BOS increase and RI decrease. Conclusions Given that postoperative BOS increased and RI decreased with the average MBR remaining unchanged, IOP reduction by trabeculectomy may contribute to stable blood flow throughout the duration of the heartbeat in the tissue area of the ONH.

To investigate structural measurements of the macular area in preperimetric glaucoma (PG) patients using spectral domain optical coherence tomography with two functional measurements [10-2 Humphrey visual field (HFA) and 10-2 Microperimeter-1 (MP-1)] and by macular symmetry testing. Fifteen eyes of 15 PG subjects with a retinal nerve fiber layer defect in the inferior hemisphere and 15 eyes of 15 normal control subjects were enrolled. Macular symmetry testing was performed between the superior and inferior zones by comparing zone thickness in each hemisphere. Perimetric sensitivity asymmetry was calculated with two functional measurements. Structure–function relationships between macular symmetry testing and the mean retinal sensitivity of the corresponding hemifield or perimetric sensitivity asymmetry were calculated using Spearman’s rank correlation and linear regression. Macular zone thickness in the abnormal hemispheres was significantly less than that in normal hemispheres in PG eyes and the corresponding hemispheres in control eyes (P

Purpose: To differentiate superior segmental optic hypoplasia (SSOH) from normal-tension glaucoma (NTG) with inferior visual field defects only. Methods: Eighteen eyes with SSOH (SSOH group) and 19 eyes with NTG (NTG group) were examined by optical coherence tomography (OCT), Heidelberg retina tomography (Heidelberg Retinal Tomograph II, HRT II) and standard automated perimetry. Results: Retinal nerve fiber layer thickness (RNFLT) based on OCT measurements was significantly reduced (thinner) in the superior to superonasal sectors and significantly greater (thicker) in the inferotemporal sector in the SSOH group than in the NTG group. The cup was significantly smaller and the rim significantly larger in the superotemporal and temporal sectors in the SSOH group than in the NTG group based on HRT II measurements. The greatest area under the receiver operating characteristic curve for discrimination of SSOH from NTG by OCT and HRT II was for the RNFLT ratio of 1 + 2 o'clock/10 + 11 o'clock (0.985) and for the ratio of the superonasal to superotemporal sector of rim to disc area ratio and cup to disc area ratio (0.955), respectively. The frequent location of the inferior visual field defects corresponded to the difference in structural changes in both groups. Conclusions: Comparison of the superonasal to superotemporal sectors by OCT and HRT II were useful in differentiating SSOH from NTG with only inferior visual field defects. © 2012 Japanese Ophthalmological Society.

Purpose To report the morphologic changes of the subfoveal choroidal thickness using spectral-domain optical coherence tomography following segmental scleral buckling. Design Retrospective, observational case series. Methods The study included 21 eyes of 20 patients who underwent segmental scleral buckling for the treatment of rhegmatogenous retinal detachment. All patients underwent the measurements of the subfoveal choroidal thickness preoperatively and 1 week, 1 month, and 3 months after the surgery. The changes in choroidal thickness, 4 mm from the fovea, before and 1 week after surgery were analyzed in the buckled and unbuckled side. Results The preoperative mean subfoveal choroidal thickness of operated eyes was 239.2 ± 91.0 μm. The postoperative mean subfoveal choroidal thicknesses of operated eyes at 1 week, 1 month, and 3 months were 267.6 ± 96.8 μm, 250.6 ± 95.8 μm, and 239.4 ± 95.6 μm, respectively. There were significant differences between preoperative subfoveal choroidal thickness and 1-week-postoperative and 1-month-postoperative subfoveal choroidal thicknesses ( P P = .03, ANOVA), and there was no significant difference between subfoveal choroidal thicknesses preoperatively and 3 months postoperatively ( P > .99, ANOVA). The changes in choroidal thickness of the buckled and unbuckled side preoperatively and 1 week postoperatively were not significantly different (n = 8, P = .589, 2-way ANOVA). Conclusion The subfoveal choroidal thickness may change temporarily following segmental scleral buckling surgery. This may be the result of reversible subclinical microcirculatory dysfunction of the choroid.

It has been hypothesized that dysfunction of the solute carrier family 1, member1 gene (SLC1A1), which encodes the glutamate aspartate transporter, may play a role in normal tension glaucoma. In this study we investigate whether SLC1A1 is associated with normal tension glaucoma in Japanese patients.A total of 292 Japanese patients with normal tension glaucoma and 500 healthy control subjects were recruited. We genotyped 12 single-nucleotide polymorphisms in SLC1A1. We also performed an imputation analysis to evaluate the potential association of un-genotyped SLC1A1 single-nucleotide polymorphisms, and 165 single-nucleotide polymorphisms were imputed.We observed an increased frequency of the G allele of rs10739062 in patients compared to controls (p = 0.043, OR = 1.25). The rs10739062 polymorphism exhibited a dominant effect: individuals with genotype GG and GC showed a 1.91-fold increase in risk compared to genotype CC (p = 0.0082). However, the statistical significance disappeared after Bonferroni correction for multiple testing (pc 0.05). We did not find any significant association between any of the remaining 176 single-nucleotide polymorphisms and disease risk.Our study showed a lack of association between SLC1A1 variants and normal tension glaucoma in Japanese patients, suggesting that the SLC1A1 gene does not play a critical role in the development of the disorder in this patient population. However, further genetic studies with larger sample sizes are needed to clarify whether SLC1A1 may make some contribution that affects the risk of developing normal tension glaucoma.

Avascularity of the bleb is regarded as a risk of bleb infection, which is the most serious complication after filtration surgery with mitomycin C (MMC). There is no perfect way to prevent avascular bleb formation. We hypothesized that keeping the conjunctiva away from direct exposure to aqueous filtration may suppress avascular bleb formation after filtration surgery with MMC. In order to prove our hypothesis, we investigated whether a thin biodegradable, honeycomb-patterned film (HPF) can reduce bleb avascularity in a rabbit model of filtration surgery with mitomycin C (MMC).A fornix-based full-thickness filtration surgery was performed in one eye of each of five rabbits (control group). The same surgery with intraoperative MMC treatment was done in both eyes of six rabbits, with one eye receiving a 14-μm-thick HPF made from poly(L-lactide-co-ε-caprolactone), which was placed subconjunctivally over the filtration site with the honeycomb surface facing up. Intraocular pressure (IOP) measurements, bleb evaluations using ultrasound biomicroscopy (UBM), and in vivo confocal microscopy (IVCM) were performed periodically for 4 weeks postoperatively followed by histological examination.The postoperative IOP decrease and bleb survival were significantly greater in MMC-treated eyes than in control eyes, and were similar between MMC-only and MMC + HPF eyes. The avascular area in the bleb persisted for 4 weeks in MMC-only eyes. Postoperative IVCM showed morphological changes of the conjunctival epithelial cells (i.e., enlarged and variable in size and shape) and epithelial defects in MMC-only eyes, and significantly lower density of connective tissue and vascularity in the subepithelial space in MMC-only eyes compared to the control eyes. These IVCM findings agreed with those by UBM and histology. Bleb avascularity shown by clinical bleb appearance, IVCM and histology, conjunctival epithelial damage shown by IVCM and histology, and loose subepithelial connective tissue shown by UBM, IVCM, and histology were all reduced in MMC + HPF eyes compared to MMC-only eyes.IVCM successfully showed the characteristic conjunctival damage in MMC-treated blebs. The concomitant use of a thin biodegradable HPF reduced avascularity and conjunctival damage in blebs, without compromising filtration in rabbits following filtration surgery with MMC.

To compare the drug efficacy of four prostaglandin analogues (PGAs) by bilateral treatment in normal subjects. Three consecutive studies comparing latanoprost to three other PGAs (travoprost, tafluprost and bimatoprost) were performed in 24 healthy subjects. Each study was separated by a washout period of over 6 weeks. In each study, two drugs were randomly assigned to one eye of each subject. Study subjects instilled the assigned medication at 9:00 p.m. every day for 2 weeks. The same masked investigator measured intraocular pressure (IOP) at 9:00 a.m., 1:00 p.m. and 5:00 p.m. at baseline and repeated measurements on days 7 and 14. The differences in IOP reduction were compared between the drugs. Mean diurnal IOP reduction with latanoprost on days 7 and 14 was similar to that with travoprost and tafluprost, but was significantly lower than that with bimatoprost. The association of the mean diurnal IOP reduction between latanoprost and bimatoprost on day 14 (r 2 = 0.25) was weak, in remarkable contrast to the strong association between latanoprost and travoprost (r 2 = 0.81) and between latanoprost and tafluprost (0.82). The short-term bilateral treatment revealed a different IOP-lowering efficacy of bimatoprost compared to other PGAs in healthy subjects.

A 60-year-old man with neovascular glaucoma due to diabetic retinopathy received an intravitreal injection of 1.25 mg bevacizumab (IVB) followed by extensive panretinal photocoagulation in the right eye. The anterior segment neovascularization regressed within 10 days after IVB. One and a half months later, the patient underwent gastrectomy for stage IIIb gastric cancer. Two months later, he was started on S-1 orally (100 mg/day for 48, 26, and 32 consecutive days in the first, second, and third treatment cycle, respectively). The interval between the first and second treatment cycle was 20 days and between the second and third cycle it was 24 days. The patient developed anemia and diarrhea. At the end of the second S-1 cycle, cystoid macular edema developed in the right eye, although diabetic retinopathy and neovascular glaucoma were stable. Macular edema persisted for 5 months despite another IVB, and disappeared 3 months after termination of S-1 therapy. The time course of the magnitude of macular edema correlated well with the severity of anemia. The macular edema was possibly associated with anemia, which is a major side effect of S-1. Further studies are warranted to investigate the relationship between anemia and macular edema in patients with diabetic retinopathy.

Purpose Mucogenic glaucoma is an unusual form of secondary open-angle glaucoma caused by intracameral ectopic mucus-producing epithelium. To date, only 3 cases have been described in detail. Numerous goblet cells in the specimens indicated a possible conjunctival origin. We immunohistochemically characterized the implanted epithelium from an iris cyst responsible for mucogenic glaucoma. Methods A series of immunostaining analyses were performed on a sector-iridectomy specimen derived from an eye with mucogenic glaucoma and a history of limbal penetrating injury. An iris cyst was present in the inferonasal quadrant of the right eye of a 58-year-old man. The anterior chamber was filled with hazy, translucent material, and the chamber angle was gonioscopically open. The cyst was resected due to medically uncontrollable high intraocular pressure. Results The ectopic epithelium was mostly positive for CK19, a corneal and conjunctival epithelial marker. Negative staining for MUC5AC, a secretory mucin, and positive staining for MUC1, a membrane-bound mucin, corroborated the absence of goblet cells. Ectopic epithelial cells were abundantly positive for CK15, a limbal basal cell marker, but there was patchy immunostaining of CK13, a conjunctival epithelial marker, and sparse labeling with CK12, a corneal epithelial marker. Immunostaining patterns of CK15, CK13, and CK12 were nearly mutually exclusive. Conclusions The ectopic epithelium of an iris cyst causing mucogenic glaucoma was most likely to originate from limbal basal cells, which showed dual direction of differentiation toward both the conjunctival and corneal epithelia. The membrane-bound mucin may have caused mucogenic glaucoma in the absence of goblet cells.

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been reported to cause rapid regression of anterior segment neovascularization in eyes with neovascular glaucoma when administered intraocularly. Several studies have reported the safety profile of intravitreal injections of bevacizumab in patients with various retinal pathologies. We investigated the occurrence of adverse events associated with intraocular bevacizumab injections in patients with neovascular glaucoma. We retrospectively reviewed the charts of 84 eyes of 70 patients with neovascular glaucoma that received intraocular bevacizumab injections to treat anterior segment neovascularization for the first time at Kanazawa University Hospital. The mean age of the patients was 63.5 ± 13.3 years (± standard deviation; range, 31–85 years). The underlying retinal diseases were proliferative diabetic retinopathy in 58 eyes (69%), central retinal vein occlusion in 17 eyes (20%), ocular ischemic syndrome in four eyes (5%), central retinal artery occlusion in three eyes (4%), branch retinal vein occlusion in one eye (1%), and radiation retinopathy in one eye (1%). The total number of intraocular injections of bevacizumab was 116 (1.4 ± 0.8 injections/eye, range, one to five injections/eye). Most were intravitreal injections (1.25 mg/0.05 ml; 115 injections, 99%). No cases had marked inflammation, lens injuries, marked vitreous hemorrhage, retinal detachment, or endophthalmitis. However, two eyes (2%) of two cases (3%) developed central retinal artery occlusion 3 or 4 days after bevacizumab injection. Both were among four eyes (i.e., 50%) with ocular ischemic syndrome. One of them had received an intracameral injection of bevacizumab (0.75 mg/0.03 ml) before the adverse event. No cases experienced systemic side-effects including myocardial infarction and cerebrovascular accidents within 3 months after bevacizumab injection. Central retinal artery occlusion may be a relatively common complication following intraocular injection of anti-VEGF agents in patients with neovascular glaucoma, particularly when it was associated with ocular ischemic syndrome. Since visual prognosis of central retinal artery occlusions is usually poor, intraocular injection of anti-VEGF agents should be performed with thoughtful consideration of the risks and benefits of the treatment, and with a strict follow-up examination, especially in high-risk patients.

PURPOSE We investigated the difference in clinical characteristics between cases with enlarged retinal nerve fiber layer defects (RNFLD) and stable RNFLDs in normal-tension glaucoma (NTG). PATIENTS AND METHODS We retrospectively reviewed NTG patients that were diagnosed and followed up for at least 3 years at 1-month to 2-month intervals by the same examiner, and selected eyes with distinct RNFLD borders. Using fundus photographs, for which we extracted only a blue ingredient and processed it into black and white, we measured RNFLD angles and divided NTG cases into 2 groups, enlarged RNFLD and stable RNFLD, and compared the clinical characteristics between both groups. RESULTS Ninety-three eyes from 93 patients (mean follow-up, 8.2 y) were selected and enlargement of RNFLD was detected in 55 eyes. Disc hemorrhage (DH) was found in 35 of 55 eyes (63.6%) in the enlarged group and in 6 of 38 eyes (15.8%) in the stable group (P

金沢大学附属病院眼科, Purpose: To describe fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (SD-OCT) findings of leopard spots in nanophthalmic uveal effusion syndrome. Methods: A 34-year-old man with retinal detachment associated with nanophthalmic uveal effusion syndrome in the right eye underwent sclerotomy three times. After the final surgery, the subretinal fluid resolved gradually. Then, SD-OCT examination, FAF photography, fluorescein angiography (FA), and indocyanine green angiography (ICGA) were performed simultaneously with the spectralis Heidelberg retina angiograph + OCT system. Results: SD-OCT revealed focal thickening of the retinal pigment epithelium (RPE) layer at the same locations as leopard spots, which appeared hypofluorescent on FA and ICGA. These spots showed hyperautofluorescence on FAF imaging. Six months later, focal thickening of the RPE layer became smaller on OCT and hyperautofluorescence was attenuated on FAF imaging. Conclusions: Simultaneous imaging of the fundus with multiple modalities including OCT, FAF, FA, and ICGA indicates that leopard spots in the fundus of uveal effusion syndrome may show hyperautofluorescence and correspond to focal thickening of the RPE layer by SD-OCT. This imaging method may help elucidate the pathology of various fundus lesions in vivo. © 2010 Springer-Verlag.

This study aimed to investigate the effects of preoperative intravitreal bevacizumab (IVB) on outcomes in trabeculectomy for neovascular glaucoma (NVG).Charts for 52 NVG eyes of 52 consecutive patients who received primary trabeculectomy with mitomycin C (MMC) were reviewed. Postoperative follow-up periods for all patients wereor = 4 months. Thirty-two consecutive eyes were treated without IVB (control group) and 20 consecutive eyes received IVB (1.25 mg) 10 +/- 11 days before trabeculectomy (IVB group). The main outcome measures were postoperative intraocular pressure (IOP) and incidence of postoperative complications. Surgical success was defined as IOP21 mmHg with or without medication (qualified or complete success, respectively). Failure was defined as IOP exceeding these criteria, phthisis bulbi, loss of light perception or additional glaucoma surgeries. Kaplan-Meier survival analysis with the log-rank test was performed to compare surgical success rates between the two groups.Complete and qualified success rates at 6 months were 95% versus 50% and 95% versus 75% in the IVB and control groups, respectively. The IVB group achieved significantly better surgical success rates than the control group (complete success, p0.001; qualified success, p = 0.026). Postoperative hyphaema on day 1 or hyphaema with a duration of1 week occurred significantly less frequently in the IVB group than in the control group (p = 0.009, p = 0.014, respectively). The incidence of serious complications such as endophthalmitis, phthisis bulbi and a marked decrease in visual acuity did not increase in the IVB group.This retrospective study showed that preoperative IVB decreased postoperative hyphaema and increased surgical success rates, and thus may be an effective adjunct to trabeculectomy in NVG.

Kayo Nakamura1*, Masao Ota2*, Akira Meguro1, et al1Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan; 2Departmentof Legal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, JapanBackground: To investigate whether the GPDS1 locus, a potential causative locus of pigment-dispersion syndrome, is associated with normal-tension glaucoma (NTG) in Japanese patients. Materials and methods: We used polymerase chain reaction amplification with sequencespecific primers to analyze 20 polymorphic microsatellite markers in and around the GPDS1 locus with an automated DNA analyzer and automated fragment detection by fluorescent-based technology. The DNA samples used for these analyses were obtained from ethnicity- and gendermatched patients, including 141 Japanese patients with NTG and 101 healthy controls. Patients exhibiting a comparatively early onset were selected as this suggests that genetic factors may show stronger involvement.Results: One allele of D7S2462 exhibited a frequency that was significantly decreased in NTG cases compared to controls (P = 0.0013, Pc = 0.019, OR = 0.48, 95% CI = 0.30–0.75). Alleles at another six microsatellite loci were positively or negatively associated with NTG, but these associations did not retain statistical significance after Bonferroni correction (P< 0.05, Pc> 0.05).Conclusion: Our study showed a significant association between the GPDS1 locus and NTG, suggesting that there may be some genetic risk factor(s) in the development of NTG.Keywords: microsatellite, normal tension glaucoma, glaucoma-related pigment dispersion syndrome, GPDS1, DPP6

Purpose: To report clinical findings of three patients with unilateral peculiar choroidal excavation in the macula detected by spectral-domain (SD) optical coherence tomography (OCT). Methods: Three cases with unilateral choroidal excavation in the macula detected by SD OCT. Fluorescein angiography (FA), indocyanine green angiography (IA), ultrasonography, visual field tests and multifocal electroretinography (mfERG) were performed. Results: Although all three patients complained of metamorphopsia, visual acuity and central visual field were normal in the affected eyes. SD OCT demonstrated choroidal excavation in the macula despite a normal foveal contour along the inner retinal surface. The excavation involved the outer retinal layers up to the external limiting membrane in cases 1 and 2, while only the retinal pigment epithelium was involved in case 3. The excavation corresponded to foveal pigment mottling in cases 1 and 2 and to a parafoveal yellowish fusiform lesion in case 3. The lesions appeared hypoautofluorescent and unremarkable in FA except for circumferential hyperfluorescence in case 3 and hypofluorescent in IA. B-scan ultrasonography was unremarkable. MfERG in cases 1 and 2 was normal. Conclusions: SD OCT demonstrated two types of choroidal excavation in the macula. More case accumulation and a longer follow-up will elucidate the pathogenesis and prognosis of the lesions.

金沢大学附属病院眼科, PURPOSE: To evaluate the effectiveness and safety of a thin honeycomb-patterned biodegradable film for glaucoma filtration surgery in rabbits. METHODS: A 7 microm-thick film made from poly(L-lactide-co-epsilon-caprolactone) was placed in the subconjunctival space in one eye of rabbits, with or without full thickness filtration surgery. The film had a honeycomb-patterned surface that faced the subconjunctival Tenon tissue and the other side was smooth. Filtration surgery was also performed in the fellow eye, which received either no adjunctive treatment or 0.4 mg/mL mitomycin C (MMC; n=6 each). Intraocular pressure (IOP) measurements and bleb evaluations using ultrasound biomicroscopy were performed periodically for 28 days after surgery followed by histologic observation. RESULTS: Postoperative IOPs of the film-treated eyes were significantly lower than that of control eyes from day 10 to day 28 (P

To assess the efficacy and practical usefulness of the Heidelberg Retina Tomograph II (HRT II) compared with nonmydriatic stereoscopic photography in a public glaucoma screening.We examined 1173 local residents, aged 40 years or older, who visited a community health screening in Komatsu City. Initial glaucoma screening consisted of noncontact pneumotonometry, nonmydriatic stereoscopic fundus photography, and HRT II. When glaucoma was suspected, the subjects were referred for a definitive examination, in which slit-lamp biomicroscopic examination, Goldmann applanation tonometry, Humphrey 30-2 test, gonioscopy, and optic nerve head evaluation were performed.A total of 97.2% (2279/2345) of the nonmydriatic stereoscopic optic disc photographs could be interpreted and 93.4% (2189/2345) were good images. HRT II measurements were successful in 99.0% (2322/2345) of eyes, and acceptable images were obtained in 91.9% (2154/2345) of eyes. On the basis of clinical diagnoses, 94 eyes of 60 participants were diagnosed with glaucoma. The sensitivity of nonmydriatic stereoscopic photographs for personal-level analysis and eye-level analysis was 95.8% and 95.5%, respectively. Using Moorfield's regression analysis, HRT sensitivity and specificity were 72.3% to 91.5% and 84.0% to 93.1%, respectively, for personal-level analysis, and 60.3% to 72.6% and 89.7% to 95.6%, respectively, for eye-level analysis.Although HRT II did not detect glaucoma as well as optic nerve stereophotographs in this Japanese population, it may play a role in community health screening.

To describe the closure of a macular hole over residual subretinal fluid in patients with macular hole retinal detachment in high myopia who had been treated using an inverted internal limiting membrane flap technique.Three patients with macular hole retinal detachment in high myopia underwent pars plana vitrectomy using the inverted internal limiting membrane flap technique. One patient received a silicone oil injection, and the other two patients received a long-acting gas injection at the end of the surgery. After surgery, spectral domain ocular coherence tomography examination was performed.In the patient with the silicone oil injection, spectral domain optical coherence tomography revealed that the macular hole was sealed with an inverted internal limiting membrane flap in the presence of subretinal fluid 1 day after surgery. The inner retinal layers gradually regained a more physiologic configuration over the residual subretinal fluid. In all patients, macular holes were completely closed over the subretinal fluid, which was gradually absorbed.Using the inverted internal limiting membrane flap technique, macular holes were closed over residual subretinal fluid in patients with macular hole retinal detachment. The results indicate that reattachment of the retina may not be necessary for closure of macular holes.

Purpose To evaluate long-term outcomes and identify prognostic factors of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma. Methods Sixty-one eyes of 54 patients with neovascular glaucoma treated by trabeculectomy following intraocular bevacizumab injection were consecutively enrolled. Surgical success criteria were sufficient intraocular pressure (IOP) reduction (IOP ≤21 mmHg, ≥20% IOP reduction, no additional medications or glaucoma surgeries) without devastating complications (loss of light perception, phthisis bulbi, and endophthalmitis) or significant hypotony (IOP ≤5 mmHg continued ≥6 months and until the last follow-up visit or hypotony requiring intervention). Kaplan-Meier survival curves and Cox regression analysis were used to examine success rates and risk factors for surgical outcomes. Results The follow-up period after trabeculectomy was 45.0 ± 22.2 months (mean ± standard deviation). Surgical success rate was 86.9 ± 4.3% (± standard error), 74.0 ± 6.1%, and 51.3 ± 8.6% at 1, 3, and 5 years. Multivariate Cox regression analysis identified two risk factors; lower preoperative IOP (≤30 mmHg) for surgical failure and hypotony [hazard ratio (HR), 2.92, 6.64; 95% confidence interval (CI), 1.22 to 7.03, 1.47 to 30.0; P = 0.018, 0.014, respectively], and vitrectomy after trabeculectomy for surgical failure with or without hypotony criteria (HR, 2.32, 4.06; 95% CI, 1.02 to 5.28, 1.30 to 12.7; P = 0.045, 0.016, respectively). Conclusions The long-term outcomes of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma were favorable. Lower baseline IOP was associated with development of significant hypotony, while additional vitrectomy was related to insufficient IOP reduction.

To evaluate the efficacy and safety of trabeculectomy for patients with glaucoma who were enrolled in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS).Multicenter, prospective, cohort study.A total of 829 eyes in 829 patients with glaucoma who had undergone trabeculectomy alone or trabeculectomy combined with phacoemulsification at 34 clinical centers were examined in this study.Intraocular pressures (IOPs, in millimeters of mercury), risk factors for surgical failure, and surgical complications.The enrollment period was 2 years, and follow-up was conducted every 6 months for up to 5 years. Outcomes were measured at 6-month intervals. Four levels of success were defined by achievement of the following IOP: (A) 4IOP22, (B) 4IOP19, (C) 4IOP16, and (D) 4IOP13. The primary outcome was the qualified success rate according to the defined criteria. The secondary outcomes included IOP, risk factors for surgical failure, and surgical complications.Mean IOP and preoperative antiglaucoma medications were significantly decreased from 24.9±9.0 to 12.6±5.2 mmHg (P0.0001) and from 2.8±1.0 to 1.2±1.3 mmHg (P0.0001), respectively, 5 years after surgery. For criteria A, B, C, and D, the qualified success rates were 90.1%, 88.9%, 77.6%, and 57.7% at 1 year, respectively, and 71.9%, 66.7%, 50.1%, and 29.9% at 5 years, respectively. The third or subsequent trabeculectomy was less effective than the first and second trabeculectomies. Preoperative lens status and preoperative higher IOP were risk factors for trabeculectomy failure. The needling procedure and cataract surgery were associated with the risk of failure. The rates of postoperative hyphema, shallow anterior chamber, bleb leak, and choroidal detachment were 2.7%, 3.1%, 1.9%, and 7.2%, respectively, in our series.Trabeculectomy with mitomycin C is an effective and safe procedure for reducing IOP in the CBIITS. The number of previous glaucoma surgeries, preoperative lens status and IOP, the needling procedure, and cataract surgery after trabeculectomy influenced the success rate, as determined by the target IOP.

Leakage from a conjunctival break created during trabeculectomy may cause serious complications such as shallow anterior chamber, hypotony, and a flat bleb in the early postoperative period. Therefore, careful handling of the conjunctiva with a nontoothed forceps is essential. However, thin conjunctiva is susceptible to mechanical injury and is difficult to repair with suturing, especially when the point of leakage is close to the scleral flap. In 3 consecutive cases in which a small break in the thin conjunctiva adjacent to the scleral flap was created during trabeculectomy, sodium hyaluronate 2.3% (Healon5) was intraoperatively injected into the bleb. The break was successfully closed with an intraoperative injection of Healon5 into the bleb. This procedure appears to be a simple, safe, and effective method for closure of a small conjunctival break.

To examine whether intraocular pressure (IOP) reduction by latanoprost correlates with single nucleotide polymorphisms (SNPs) of the prostaglandin F2α (FP) receptor gene in patients with glaucoma and ocular hypertension (OH).The genotype of nine SNPs in the FP receptor gene was determined by direct DNA sequencing, or other techniques, in 82 patients with glaucoma or OH who were treated with latanoprost monotherapy in one eye. The IOP reduction was evaluated by the percent IOP reduction (%ΔIOP), estimated by subtracting IOP fluctuations in the untreated fellow eye. Subjects were classified by %ΔIOP into low responders (%ΔIOP10%) and others (%ΔIOP ≥10%). The correlation between %ΔIOP and SNPs in the FP receptor gene was analysed.Multiple regression analysis demonstrated that the rs12093097 was the only significant factor that correlated with %ΔIOP (p=0.039). Among estimated haplotypes, one haplotype that contained the minor allele only in rs3753380, was significantly correlated with low responders even after correction for multiple test (permutation test, p=0.037).An association was found between SNPs of the FP receptor gene and the response to latanoprost in patients with glaucoma or OH. The FP receptor genetic polymorphism may influence the degree of IOP reduction by latanoprost in these patients.

Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.

PURPOSE To examine the effect of cataract on signal strength index (SSI) and thickness measurements of the ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) with the RTVue-100 Fourier-domain optical coherence tomography device. METHOD GCC and pRNFL measurements were obtained preoperatively in 53 eyes of 53 patients, including 13 glaucoma patients and measurements were repeated postoperatively. Cataract degree was graded by the Lens Opacities Classification System III. Factors associated with segmentation error and with changes in SSI or average thickness of GCC and pRNFL were determined. RESULTS The prevalence and proportion of segmentation error were higher in GCC measurements compared with pRNFL measurements (prevalence: 28.3% vs. 5.6%, P

Pharmacogenomics is an evolving research discipline within ophthalmology, but genetic data are not currently used to guide daily clinical decisions. Ophthalmic pharmacogenomic research has thus far focused on open-angle glaucoma (OAG) and age-related macular degeneration (AMD), two common and worldwide causes of visual loss. In the treatment of OAG and allied disorders, there are reported associations between various polymorphisms in adrenergic receptor genes and topical β-antagonists as well as between the prostaglandin receptor gene and a topical prostaglandin analogue. In the treatment of exudative AMD, there are reported associations between AMD-associated genes, such as complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), and the efficacy of different treatment modalities including photodynamic therapy and intravitreal vascular endothelial growth factor (VEGF) antagonists. The steroid response associated with ophthalmic corticosteroids has been investigated, but no definite genetic associations have been reported. As additional pharmacogenomic trials are reported, the precise relationship between genotype and treatment response may become clearer.

Purpose To investigate longitudinal changes in mean blur rate (MBR) measured by laser speckle flowgraphy (LSFG) in the rat optic nerve head (ONH), and the reproducibility of MBR. Methods Rats were dilated under general anesthesia. Intraocular pressure (IOP), blood pressure, ocular perfusion pressure (OPP), heart rate, and LSFG were measured 30 minutes later. Mean blur rate in the ONH was determined using LSFG-Micro and was subdivided into MBR of the total area (MA), vessel region (MV), and tissue region (MT). Mean blur rate measurements were repeated at 10, 11, 13, 19, and 20 weeks, then every 5 weeks until 60 weeks of age. Intrasession repeatability, intrasession reproducibility, and intersession reproducibility were evaluated. Results Coefficient of variation of MBR was 0.3 to 6.2%, 1.3 to 5.2%, and 5.8 to 30.4% for intrasession repeatability, intrasession reproducibility, and intersession reproducibility, respectively. Mean blur rate of the total area, MV, and MT increased similarly until 19 weeks of age, but stabilized thereafter until 60 weeks. Mean blur rate of the total area in the inferior quadrant was significantly higher than in the temporal quadrant from 19 to 55 weeks. These changes exceeded a range of corresponding coefficient of reproducibility. There were no significant changes in IOP, blood pressure, or OPP during the experimental period. Conclusions Mean blur rate in the rat ONH changed over time, increased from 10 to 19 weeks of age, then stabilized until 60 weeks. Mean blur rate of the total area exhibited regional differences: higher in the inferior quadrant than in the temporal quadrant. Laser speckle flowgraphy-Micro may provide reliable information for evaluating longitudinal changes of rat ONH blood flow.

Purpose To report traumatic, hemorrhagic detachment of the retinal pigment epithelium that was detected by optical coherence tomography. Design Observational case report. Methods A 17-year-old boy with hemorrhagic fundus lesions caused by blunt ocular trauma was examined by optical coherence tomography and angiography. Results Initially, two dark red, mounded lesions were seen, with one in the macula and the other adjacent to the optic disk. The lesions blocked the fluorescence on fluorescein and indocyanine green angiography. Optical coherence tomography demonstrated dome-shaped elevations of the retinal pigment epithelium at each lesion. Four months later, the retinal pigment epithelium detachments disappeared in the tomography images, and no scarring was evident ophthalmoscopically. Small choroidal ruptures were detected in each lesion by angiography. Conclusions Optical coherence tomography was useful in evaluating the site of the hemorrhage in the chorioretinal layers caused by blunt ocular trauma.

To investigate the relationship between optic disc ovality and horizontal disc tilt.The ovality index (the ratio of minimum to maximum disc diameter), horizontal and vertical optic disc tilt, and optic disc torsion were measured on the Heidelberg Retina Tomograph 3 printout in 381 right eyes of 381 normal young subjects. Stereophotographically obvious horizontal tilt and the relationship between the ovality index and horizontal tilt were determined in non-torted discs with an absolute value of disc torsion ≤15°.The median values of the ovality index, horizontal and vertical tilt, and disc torsion in all subjects were 0.92, 9.0°, 0.0°, and 0.0°, respectively. In the non-torted discs (205 eyes, 53.8 %), a horizontal tilt of ≥20° was stereoscopically obvious. The ovality index was significantly correlated with horizontal tilt (r = -0.276, P0.001). The area under the receiver operation curve for the ovality index to discriminate a disc with a horizontal tilt of ≥20° was 0.861. The horizontal disc tilt was significantly correlated with spherical equivalent (r = -0.369, P0.001) and axial length (r = 0.277, P0.001), but the ovality index was not.Although the ovality index may be an indicator of stereoscopically obvious horizontal disc tilt, horizontal tilt is more closely related with myopia.

To evaluate the usefulness of automated fundus-oriented small-target perimetry in detecting glaucomatous visual field abnormalities.One eye from each of 60 normal, 37 pre-perimetric glaucoma (PPG) and 29 early stage of primary open-angle glaucoma (POAG) persons were included. The new perimeter had two monitors, one for a campimeter and the other for the examiner's operation. A test area within the central 15° was set in the fundus image. The target size was 2.9 min in diameter, and the distance between the two adjacent targets was 60 min. The rate of negative response (RNR) among the age-matched controls, PPG and POAG were compared. The relationship between the RNR and age of the normal or standard automated perimetry (SAP) global indices in PPG and POAG was examined. The areas under the receiver-operating characteristic curve (AROC) to discriminate PPG or POAG versus normal were determined.The RNR increased significantly with age in normal and differed significantly (P0.001) among control (1.8 ± 1.3 %), PPG (9.2 ± 10.4 %) and POAG (21.2 ± 14.3 %). Significant correlation was found between the RNR and SAP global indices. The AROC was 0.89 for PPG and 0.95 for POAG.Fundus-oriented small-target perimetry is useful in detecting visual field abnormalities in PPG.