Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma.

Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by retinal ganglion cell (RGC) death leading to cupping of the optic nerve head and visual field loss at normal intraocular pressure (IOP). The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the methyltransferase-like 23 (METTL23) gene identified in 3 generations of a Japanese family with NTG. This mutation caused METTL23 mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-knock-in (Mettl23+/G and Mettl23G/G) and -knockout (Mettl23+/- and Mettl23-/-) mice developed a glaucoma phenotype without elevated IOP. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23G/G mice, which recapitulated both clinical and biological phenotypes. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina and was required for the transcription of pS2, an estrogen receptor α target gene that was critical for RGC homeostasis through the negative regulation of NF-κB-mediated TNF-α and IL-1ß feedback. These findings suggest an etiologic role of METTL23 in NTG with tissue-specific pathology.

Effects of optic nerve head-related parameters on retinal vessel calibers measurement results on fundus photographs.

BACKGROUND: Although relationship between the retinal vessel caliber (RVC) and glaucoma is well known, there has been a paucity of information on the effects of glaucoma-related optic nerve head (ONH) structural factors on the RVC. Information on this relationship should be useful in studying possible roles of ocular circulation in the development and progression of glaucoma. METHOD: Subjects were from Kumejima Study participants aged 40 years and older in Kumejima, Japan. Normal subjects and eyes were defined according to standardized systemic and ocular examinations. The central retinal artery and vein equivalents (CRAE and CRVE) were determined on fundus photographs by correcting the magnification using the refractive error, corneal curvature, and axial length (AL) of an individual eye and paraxial ray tracing; the ONH structural parameters were determined by planimetry. RESULTS: In a total of 558 right eyes (558 normal subjects), aged 49.0 ± 7.1 (standard deviation) years with gradable photographs and planimetric results, CRAE averaged 136.1 ± 12.3 µm and CRVE 216.9 ± 17.4 µm. After adjustment for the effects of confounding factors in multivariate analysis, the AL (P < 0.001), rim area (P = 0.019), disc area (P = 0.042), and smoking (P = 0.035-0.043) correlated positively, and the mean blood pressure (P < 0.001) negatively with CRAE; the AL (P < 0.001), rim area (P = 0.001), disc area (P = 0.005), smoking (P < 0.001), and male sex (P = 0.013) correlated positively, and the ß-peripapillary atrophy (ß-PPA) area (P = 0.044), vertical Cup/Disc ratio (v-C/D) (P = 0.035), and age (P < 0.001) negatively with CRVE. CONCLUSION: The current study showed significant effects of rim area, v-C/D or ß-PPA area determined on the photographs on the RVC measurement results. Further, it showed a necessity to incorporate the glaucoma-related ONH structural parameters as co-variables to correctly estimate the effects of various factors on the RVC.

Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation.

To characterize laser speckle flowgraphy (LSFG) pulse waveform parameters for ocular circulation evaluation, a multicenter, prospective, cross-sectional study was conducted in 111 eyes of 86 healthy Japanese individuals. Optic nerve head (ONH) tissue-area, vessel-area mean blur rate (MT and MV, respectively), and MT and MV pulse waveform parameters were obtained using LSFG and ONH structural parameters using planimetry. Multivariate linear mixed-effects modeled regression analysis identified factors contributing to MT- or MV-waveforms using age, gender, smoking history, body mass index, systolic and diastolic blood pressure, heart rate, intraocular pressure, axial length, disc, rim, and ß-peripapillary atrophy areas, MT or MV, central retinal artery, and vein equivalents (CRAE and CRVE) as explanatory variables. MT- and MV-waveforms significantly correlated with one or more systemic factors, consistent with previous studies. Following confounding factor adjustment, MT-Skew significantly negatively correlated with ß-PPA area (P = 0.026); MT- and MV-flow acceleration index positively correlated with CRAE, MT, and MV (P = 0.041-< 0.001), compatible with these parameters' observed correlations to systemic factors. Significantly negative correlations of the blowout score and acceleration time index to CRAE partly conflicted with their correlations to systemic factors, and other waveform parameters showed little correlation to ocular factors. Thus, Skew and flow acceleration index assisted the in vivo ocular circulation characterization.

Ocular and Systemic Factors Affecting Laser Speckle Flowgraphy Measurements in the Optic Nerve Head.

Purpose: To investigate the ocular and systemic factors related to glaucoma and to be adjusted for interindividual comparison of ocular blood flow measurement results by laser speckle flowgraphy (LSFG) obtained from the optic nerve head (ONH) in normal Japanese individuals. Methods: A multicenter, prospective cross-sectional study was conducted. The ONH tissue-area and vessel-area mean blur rate (MT and MV) were evaluated using LSFG and ONH structural parameters using planimetric methods. Multivariate linear mixed-effects modeled regression analysis was used to identify the contributing factors to the MT and MV. The explanatory variables were age; gender; smoking history; body mass index; mean arterial pressure (MAP); heart rate; intraocular pressure; axial length (AL); disc, rim, cup, and ß-peripapillary atrophy (ß-PPA) areas; and central retinal artery and vein equivalents. Results: In total, 195 eyes of 126 healthy individuals with an average age of 48.1 years were included. Multivariate analysis showed that MAP and disc area had a negative (P < 0.001) correlation, whereas ß-PPA area had a positive correlation with MT (P = 0.010). Age and AL had a negative correlation (P = 0.001 and P = 0.011, respectively), whereas cup area had a positive correlation (P = 0.012) with MV. Conclusions: Interindividual comparison of MT or MV must be adjusted for both systemic factors (blood pressure or age) and local ocular factors (AL and disc, cup, or ß-PPA area). Translational Relevance: Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.

Frequency of hypotonic maculopathy observed by spectral domain optical coherence tomography in post glaucoma filtration surgery eyes.

PURPOSE: To report the frequency of post glaucoma filtration surgery hypotonic maculopathy determined by spectral domain optical coherence tomography (SD-OCT). METHODS: A cross-sectional retrospective observational study. Post glaucoma filtration surgery patients whose intraocular pressures (IOP) achieved 30% reduction from baseline or was controlled to IOP <14 mm Hg and had SD-OCT images and fundus photographs were enrolled. Hypotonic maculopathy was diagnosed independently on SD-OCT images and on fundus photographs. RESULTS: 112 eyes of 88 patients were included in this study. 17 eyes of 14 patients were diagnosed with hypotonic maculopathy on SD-OCT images (17/112, 15.2%). Among these eyes, only 3 eyes were also diagnosed with hypotony maculopathy on fundus photography. Hypotonic maculopathy on SD-OCT was found only in eyes with IOP ≤10 mm Hg. (17.4% in eyes with IOPs between 7 and 10 mm Hg, and 22.7% in eyes with IOP ≤ 6 mm Hg). Associations with age, sex, central corneal thickness, refractive error, IOP reduction rate and interval between surgery and OCT acquisition were not significant (P > 0.05). CONCLUSION: In most cases, hypotonic maculopathy detected by SD-OCT were not recognizable on fundus photographs. Hypotonic maculopathy was detected not only in eyes with conventional ocular hypotony (IOP < 6 mm Hg) but also in eyes with IOP between 7 and 10 mm Hg.

Pseudoexfoliation syndrome and relating factors in a rural Japanese population: the Kumejima Study.

PURPOSE: To report the prevalence of pseudoexfoliation (PEX) syndrome and glaucoma associated with PEX (PEX-G) and their relating factors of them in a south-western island of Japan. METHODS: A population-based survey of all residents aged ≥ 40 years was conducted in Kumejima, Okinawa, Japan, and 3762 subjects (participation rate, 81.2%) underwent detailed ophthalmic examinations. Presence of PEX material on the lens capsule, iris surface and/or pupillary margin was determined by slit-lamp biomicroscopy. Glaucoma was diagnosed according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology. RESULTS: In subjects aged ≥ 40 years, prevalence rates of PEX syndrome, PEX without glaucoma and PEX-G in at least one eye were 1.5% (95% confidence interval [CI]: 1.0-1.9%), 1.3% (95% CI: 0.9-1.7%) and 0.1% (95% CI: 0.0-0.2%), respectively, excluding eyes after cataract surgery; and 2.8% (95% CI: 2.3-3.3%), 2.2% (95% CI: 1.8-2.6 %) and 0.4% (95% CI: 0.2-0.6%), respectively, including eyes after cataract surgery. Cataract surgery had been performed in 61% of subjects with PEX in at least one eye; presence of PEX showed no significant effects on the intraocular pressure (IOP). A multivariate analysis showed that PEX was associated with older age (p < 0.0001, odds ratio: 1.10 [95% CI: 1.07-1.13]) and working outdoors (p = 0.0395, odds ratio: 2.18 [95% CI: 0.99-4.82]). CONCLUSIONS: The prevalence rates of PEX syndrome and PEX-G in a south-western island of Japan were reported. PEX showed no significant effect on IOP, and age and working outdoors were significantly related with PEX.

Diurnal and 24-h Intraocular Pressures in Glaucoma: Monitoring Strategies and Impact on Prognosis and Treatment.

The present review casts a critical eye on intraocular pressure (IOP) monitoring and its value in current and future glaucoma care. Crucially, IOP is not fixed, but varies considerably during the 24-h cycle and between one visit and another. Consequently, a single IOP measurement during so-called office hours is insufficient to characterize the real IOP pathology of a patient with glaucoma. To date IOP remains the principal and only modifiable risk factor for the development and progression of glaucoma. Only by evaluating IOP characteristics (mean, peak and fluctuation of IOP) at diagnosis and after IOP-lowering interventions can we appreciate the true efficacy of therapy. Unfortunately, a major limiting factor in glaucoma management is lack of robust IOP data collection. Treatment decisions, advancement of therapy and even surgery are often reached on the basis of limited IOP evidence. Clearly, there is much room to enhance our decision-making and to develop new algorithms for everyday practice. The precise way in which daytime IOP readings can be used as predictors of night-time or 24-h IOP characteristics remains to be determined. In practice it is important to identify those at-risk glaucoma patients for whom a complete 24-h curve is necessary and to distinguish them from those for whom a daytime curve consisting of three IOP measurements (at 10:00, 14:00 and 18:00) would suffice. By employing a staged approach in determining the amount of IOP evidence needed and the rigour required for our monitoring approach for the individual patient, our decisions will be based on more comprehensive data, while at the same time this will optimize use of resources. The patient's clinical picture should be the main factor that determines which method of IOP monitoring is most appropriate. A diurnal or ideally a 24-h IOP curve will positively impact the management of glaucoma patients who show functional/anatomical progression, despite an apparently acceptable IOP in the clinic. The potential impact of nocturnal IOP elevation remains poorly investigated. The ideal solution in the future is the development of non-invasive methods for obtaining continuous, Goldmann equivalent IOP data on all patients prior to key treatment decisions. Moreover, an important area of future research is to establish the precise relationship between 24-h IOP characteristics and glaucoma progression.

Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

Prevalence and factors associated with age-related macular degeneration in a southwestern island population of Japan: the Kumejima Study.

AIMS: To evaluate the prevalence of and factors associated with age-related macular degeneration (AMD) in a rural population of southwestern Japan. METHODS: This population-based cross-sectional study of all residents aged 40 years or older was conducted on the island of Kumejima, Okinawa, Japan. Of 4632 eligible residents, 3762 completed a comprehensive questionnaire and underwent ocular examination (participant rate, 81.2%). A non-mydriatic fundus photograph was used to grade AMD lesions according to the Wisconsin protocol. Prevalence of AMD was calculated and factors associated with AMD were identified by logistic regression. RESULTS: Of 3068 subjects with gradable photographs, 469 had early AMD and 4 had late AMD. Age-adjusted prevalence was 13.4% for any AMD, 13.3% for early AMD and 0.09% for late AMD. In multivariate analysis, any AMD was positively associated with age (OR 1.04 per year, 95% CI 1.03 to 1.05), male sex (OR 1.42, 95% CI 1.14 to 1.75) and history of cataract surgery (OR 1.35, 95% CI 1.00 to 1.82) and was negatively associated with longer axial length (OR 0.85 per millimetre, 95% CI 0.74 to 0.96). Early AMD similarly showed significant associations with these same factors. CONCLUSIONS: Prevalence of early or late AMD in a southwestern island population of Japan was 13.4% or 0.09%. Our data suggest relatively high prevalence for early AMD and low prevalence for late AMD in this sample of rural Japanese population. Significant factors associated with any or early AMD were mostly similar to that of previous studies.

Genetic analysis of Japanese primary open-angle glaucoma patients and clinical characterization of risk alleles near CDKN2B-AS1, SIX6 and GAS7.

PURPOSE: To test the genetic association between Japanese patients with primary open-angle glaucoma (POAG) and the previously reported POAG susceptibility loci and to perform genotype-phenotype analysis. METHODS: Genetic associations for 27 SNPs from 16 loci previously linked to POAG were assessed using genome-wide SNP data of the primary cohort (565 Japanese POAG patients and 1,104 controls). Reproducibility of the assessment was tested in 607 POAG cases and 455 controls (second cohort) with a targeted genotyping approach. For POAG-associated variants, a genotype-phenotype correlation study (additive, dominant, recessive model) was performed using the objective clinical data derived from 598 eyes of 598 POAG patients. RESULTS: Among 27 SNPs from 16 loci previously linked to POAG, genotypes for total of 20 SNPs in 13 loci were available for targeted association study. Among 8 SNPs in 3 loci that showed at least nominal association (P < 5.00E-02) in the primary cohort, a representative SNP for each loci (rs2157719 for CDKN2B-AS1, rs33912345 for SIX6, and rs9913911 for GAS7) were selected. For these SNPs the association was found significant in both the second cohort analysis and meta-analysis. The genotype-phenotype analysis revealed significant correlations between CDKN2B-AS1 (rs2157719) and decreased intraocular pressure (ß = -6.89 mmHg, P = 1.70E-04; dominant model) after multiple corrections. In addition, nominal correlation was observed between CDKN2B-AS1 (rs2157719) and optic nerve head blood flow (ß = -0.54 and -0.67 arbitrary units (AU), P = 2.00E-02 and 1.39E-02), between SIX6 (rs33912345) and decreased total peripapillary retinal nerve fiber layer thickness (ß = -2.16 and -2.82 µm, P = 4.68E-02 and 2.40E-02, additive and recessive model, respectively) and increased optic nerve head blood flow (ß = 0.44 AU, P = 2.20E-02; additive model) and between GAS7 (rs9913911) and increased cup volume (ß = 0.03 mm3, P = 4.60E-02) and mean cup depth (ß = 0.03 mm3, P = 4.11E-02; additive model) and decreased pattern standard deviation (ß = -0.87 dB, P = 2.44E-02; dominant model). CONCLUSION: The association between SNPs near GAS7 and POAG was found in Japanese patients for the first time. Clinical characterization of the risk variants is an important step toward understanding the pathology of the disease and optimizing treatment of patients with POAG.

Laser speckle and hydrogen gas clearance measurements of optic nerve circulation in albino and pigmented rabbits with or without optic disc atrophy.

PURPOSE: The purpose of this study was to evaluate the correlation between laser speckle flowgraphy measurements of mean blur rate (MBR) and hydrogen gas clearance measurements of capillary blood flow (CBF) in the optic nerve head (ONH) of albino and pigmented rabbits, with or without chronic ischemia-induced ONH atrophy. METHODS: The ONH MBR and ONH CBF were measured at baseline, 30 and 60 minutes after the intravenous administration of endothelin-1 (ET-1) (10(-10) mol/kg) in six albino and six pigmented rabbit eyes. The ONH MBR and ONH CBF were also measured in nine pigmented rabbit eyes that underwent the intravitreal administration of ET-1 (20 pmol) twice per week for 4 weeks to provoke chronic ischemia-induced ONH atrophy. RESULTS: In the group that received intravenous ET-1, average measurements of ONH MBR and ONH CBF at all time points were correlated in both the albino (r = 0.88, P < 0.001, n = 18) and pigmented rabbits (r = 0.85, P < 0.001, n = 18), with no intrarabbit correlations (P = 0.524). The ONH MBR and ONH CBF were also correlated in the model of chronic ischemia-induced ONH atrophy (r = 0.78, P = 0.013, n = 9). Pooled ONH MBR and ONH CBF measurements in both the intravenous and intravitreal groups were also highly correlated (r = 0.87, P < 0.001, n = 45), with no significant intergroup differences in the relationship between ONH MBR and ONH CBF (P = 0.138). CONCLUSIONS: Regardless of the presence of fundus pigmentation or ONH atrophy, ONH MBR and ONH CBF were highly correlated, suggesting that MBR in the ONH tissue is usable for interindividual and intergroup comparisons.

The 5-year incidence of bleb-related infection and its risk factors after filtering surgeries with adjunctive mitomycin C: collaborative bleb-related infection incidence and treatment study 2.

PURPOSE: To report the 5-year incidence of bleb-related infection after mitomycin C-augmented glaucoma filtering surgery and to investigate the risk factors for infections. DESIGN: Prospective, observational cohort study. PARTICIPANTS: A total of 1098 eyes of 1098 glaucoma patients who had undergone mitomycin C-augmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation performed at 34 clinical centers. METHODS: Patients were followed up at 6-month intervals for 5 years, with special attention given to bleb-related infections. The follow-up data were analyzed via Kaplan-Meier survival analysis and the Cox proportional hazards model. MAIN OUTCOME MEASURES: Incidence of bleb-related infection over 5 years and risk factors for infections. RESULTS: Of the 1098 eyes, a bleb-related infection developed in 21 eyes. Kaplan-Meier survival analysis revealed that the incidence of bleb-related infection was 2.2±0.5% (cumulative incidence ± standard error) at the 5-year follow-up for all cases, whereas it was 7.9±3.1% and 1.7±0.4% for cases with and without a history of bleb leakage, respectively (P = 0.000, log-rank test). When only eyes with a well-functioning bleb were counted, it was 3.9±1.0%. No differences were found between the trabeculectomy cases and the combined surgery cases (P = 0.398, log-rank test) or between cases with a fornix-based flap and those with a limbal-based flap (P = 0.651, log-rank test). The Cox model revealed that a history of bleb leakage and younger age were risk factors for infections. CONCLUSIONS: The 5-year cumulative incidence of bleb-related infection was 2.2±0.5% in eyes treated with mitomycin C-augmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation in our prospective, multicenter study. Bleb leakage and younger age were the main risk factors for infections.

Factors related to future peripheral anterior synechiae formation on ultrasound biomicroscopy: 7-year follow-up in eyes with shallow peripheral anterior chambers.

PURPOSE: To study factors associated with future peripheral anterior synechiae (PAS) formation on ultrasound biomicroscopy (UBM) in eyes with a shallow peripheral anterior chamber. PATIENTS AND METHODS: Fifteen subjects with a shallow peripheral anterior chamber but no PAS in both eyes, in 2001, that had no medical or surgical intervention until 2008 were included in this study. The same examiners performed gonioscopy and UBM at the 3, 6, 9, and 12 o'clock limbal positions under dark and light conditions in 2001 and 2008. A masked examiner performed a quantitative evaluation of the angle configurations in the UBM images. The presence or absence of PAS was determined by compression gonioscopy. The UBM parameters and the number of appositional closures per eye were compared between PAS-positive eyes and PAS-negative eyes. RESULTS: One eye from 15 subjects were randomly selected and included in the analyses. The gonioscopic gradings and UBM parameters did not change significantly (P>0.1) between 2001 and 2008. Seven (47%; 95% confidence interval, 25-70) of 15 eyes developed PAS. In 2001, under dark conditions, the appositional angle closure in 3 to 4 quadrants was found more often (P=0.026) in 7 eyes where PAS developed during the following 7 years than in other 8 eyes. CONCLUSIONS: In eyes with a shallow peripheral anterior chamber but no PAS, PAS developed in 47% of eyes followed without intervention for 7 years. PAS was significantly more likely to develop in eyes with the appositional angle closure found in 3 to 4 quadrants under dark conditions.

Comparison of CCD-equipped laser speckle flowgraphy with hydrogen gas clearance method in the measurement of optic nerve head microcirculation in rabbits.

The aim of this study was to verify the correlation between mean blur rate (MBR) obtained with CCD-equipped laser speckle flowgraphy (LSFG) and capillary blood flow (CBF) obtained by the hydrogen gas clearance method in rabbit optic nerve head (ONH). Using Japanese white rabbits under systemic anesthesia, a hydrogen electrode was inserted an area of the ONH free from superficial capillaries. MBR was measured with LSFG near the hydrogen electrode. CBF and MBR were measured in the range of 32.4-83.5 mL/min/100 g and 3.5-6.0, respectively. MBR and CBF were significantly correlated (r = 0.73, P < 0.01, n = 14). After inhalation of carbon dioxide (CO(2)) or intravenous administration of endothelin-1 (ET-1), MBR and CBF were changed in the relative range of 0.74-1.27 and 0.76-1.35, respectively. The relative changes in MBR and CBF induced by CO(2) and ET-1 were also significantly correlated (r = 0.67, P < 0.01). The current results suggest that MBR may correlate with CBF and also change with CBF, as an index of blood flow in the ONH, linearly.

An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation.

We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [(11)C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [(11)C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [(11)C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma.

Effect of trabeculectomy on ocular and corneal higher order aberrations.

PURPOSE: To examine the effect of trabeculectomy on ocular and corneal higher order wavefront aberrations. METHODS: Trabeculectomy with a limbal-based conjunctival flap was performed in 13 patients (13 eyes). Ocular and corneal higher order aberrations were measured using a wavefront analyzer before and after surgery. The higher order aberrations for a 4-mm pupil diameter were expanded into Zernike's polynomials. Coma aberration, spherical aberration, and total higher order aberrations were evaluated as root mean square values. RESULTS: Mean intraocular pressure was significantly reduced from 15.5 ± 3.1 mmHg preoperatively to 7.5 ± 3.5 and 7.2 ± 4.4 mmHg at 1 and 3 months after surgery, respectively. The mean spherical equivalent refractive error was not changed by the surgery. Mean vector powers for surgically induced refractive changes at 1 and 3 months postoperatively were 1.29 ± 0.69 and 1.30 ± 0.89 diopters, respectively. Corneal coma-like, spherical-like, and total higher order aberrations were not significantly changed by surgery. Trabeculectomy significantly increased ocular coma-like (P = 0.0021) and total (P = 0.0019) higher-order aberrations at 1 month, but not at 3 months postoperatively. CONCLUSION: Ocular coma-like and total aberrations were significantly increased at 1 month after trabeculectomy with a limbal-based conjunctival flap, but they had returned to normal levels by 3 months.

Identification of Schlemm's canal and its surrounding tissues by anterior segment fourier domain optical coherence tomography.

PURPOSE: To identify Schlemm's canal (SC) and trabecular meshwork (TM) by anterior segment Fourier-domain optical coherence tomography (AS-FD-OCT) with histologic confirmation in enucleated human eyes and to quantitatively evaluate SC and TM in living human eyes. METHODS: In enucleated human eyes, the imaging of the anterior chamber angle by AS-FD-OCT was performed before and after surgical expansion of SC with an injection of a viscoelastic material, followed by histologic examination. In 60 living human eyes, the agreement of identification of SC between examiners was evaluated with the Cohen's κ values, and the lengths of SC and TM and the area of TM were measured on temporal and nasal sections of the AS-FD-OCT images. RESULTS: In enucleated human eyes, SC was observed to be a thin, linear, lucent space in the AS-FD-OCT image obtained with the high-definition raster scan protocol, but not in those obtained with the bi-angle radial scan protocol. This space was enlarged after the SC expansion. In the histologic study, the SC was confirmed to be in the same position as in the AS-FD-OCT images. The κ values of observable SC in living human subjects were 0.92 or higher. The axial length of the SC averaged 347.2 ± 42.3 µm, TM length 466.9 ± 60.7 µm, and TM area 0.0671 ± 0.0058 mm². These measurements showed sufficient repeatability and reproducibility. CONCLUSIONS: Using the high-definition images of the AS-FD-OCT, SC and its surrounding tissues were successfully observed in most of the living eyes and were quantitatively evaluated in a noninvasive manner.