Prevalence of Glaucoma and Its Systemic Risk Factors in a General Japanese Population: The Hisayama Study.

Purpose: To estimate the prevalence of glaucoma and its risk factors in a Japanese community. Methods: This study included 3405 Japanese community dwellers who were ≥40 years of age and enrolled in the Hisayama Study. This population-based, cross-sectional study was conducted from 2017 to 2018. A glaucoma screening test was performed using stereo fundus images and swept-source optical coherence tomography. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Results: The prevalence of glaucoma was 7.6% (95% confidence interval [CI], 6.7-8.6) overall. The prevalence of primary open-angle glaucoma (POAG) was 5.8% (95% CI, 5.0-6.6); that of primary angle-closure glaucoma (PACG) was 0.7% (95% CI, 0.5-1.1); and that of exfoliation glaucoma was 1.1% (95% CI, 0.7-1.4). In addition to aging, lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] = 1.15; 95% CI, 1.02-1.33), higher intraocular pressure (OR = 1.06; 95% CI, 1.01-1.12), longer axial length (OR = 1.44; 95% CI, 1.31-1.59), and thinner central corneal thickness (CCT) (OR = 1.09; 95% CI, 1.04-1.15) were significant risk factors for POAG. Diabetes (OR = 2.81; 95% CI, 1.19-6.62) was a significant risk factor for PACG, and diabetes (OR = 2.15; 95% CI, 1.03-4.47) and thinner CCT (OR = 1.14; 95% CI, 1.02-1.28) were significant risk factors for exfoliation glaucoma. Conclusions: The prevalence of glaucoma was approximately 8%, probably due to the increase in the Japanese aging population. Not only ocular factors but also lower eGFR for POAG and diabetes for PACG and exfoliation glaucoma were risk factors in a general Japanese population. Translational Relevance: Systemic factors such as eGFR and diabetes must also be considered when implementing preventive measures against glaucoma.

Clinical utility of antimicrobial susceptibility measurement plate covering formulated concentrations of various ophthalmic antimicrobial drugs.

PURPOSE: The purpose of this study was to evaluate the clinical utility of SG17, an ophthalmic antimicrobial susceptibility measurement plate. DESIGN: This was a multicenter, retrospective, observational study. PATIENTS AND METHODS: Using clinical isolates from patients with ocular infections, drug susceptibility testing using the Clinical Laboratory and Standards Institute standards was routinely conducted at five facilities. The minimum inhibitory concentrations of the isolated strains were determined using SG17 at the Research Foundation for Microbial Diseases of Osaka University. The records of antimicrobial drugs used and the therapeutic course were evaluated for all cases. The susceptibility results from SG17 and routine methods used at each facility were compared. RESULTS: A total of 112 bacterial strains were isolated from 92 patients. Of these cases, keratitis was the most common (52.2%), followed by conjunctivitis (21.7%) and others (26.1%). Principal signs and symptoms resolved in all patients, indicating that therapeutic effects had been achieved. With SG17, drug susceptibility was determined in 98.9% of isolates compared with 30.4% of isolates determined using conventional methods. By adapting the Clinical Laboratory and Standards Institute standards to SG17 results, we found that 91.3% of patients were susceptible and 7.6% were resistant. In five patients, drugs with a resistant evaluation were initially administered with no effect, and the patients were then switched to drugs with a susceptible evaluation with final resolution, indicating agreement of clinical results with SG17. CONCLUSION: SG17 can be used to determine drug susceptibility to antimicrobial agents currently used in ophthalmic practice. SG17 is useful for selecting antimicrobial drugs.

Properties of new diffusion filters for treatment of amblyopia with accurate occlusive effects.

PURPOSE: Our purpose is to present the characteristics of newly developed diffusion filters that can reduce the best-corrected visual acuity (BCVA) of the non-amblyopic eye to a specified value and that can be used to treat amblyopia. METHODS: Silica sol is a colorless and transparent colloidal gel of different particle sizes. The silica was added to an emulsion adhesive, thoroughly mixed, and coated evenly on polyethylene terephthalate films. Twelve filters with 12 different concentrations of silica were constructed. The density of the silica particles on the films was determined by scanning electron microscopy, and the haze values and light transmittance were measured with a goniophotometer. The reduction of the BCVA by the filters was determined in 16 healthy young women (mean age, 22.0 ± 2.3 years) by attaching the filters to spectacles. RESULTS: Scanning electron microscopy showed a monolayer of evenly spaced silica particles. The haze values of the 12 filters were related to the concentration of silica. The total light transmittance of the 12 filters was not significantly correlated to the concentration of silica. The BCVAs measured with the 12 filters were significantly and inversely correlated with the concentration of silica for both eyes (right eye, y = 0.174x - 0.197, R(2) = 0.951; left eye, y = 0.173x - 0.212, R(2) = 0.983). CONCLUSIONS: These findings indicate that these diffusion filters can reduce the BCVA with no reduction of light transmittance. We conclude that they can be used to degrade the image of the dominant eye by known amounts in patients with amblyopia without affecting the overall light levels to the eye, i.e., form deprivation without light deprivation.

Submicroscopic deletions at 13q32.1 cause congenital microcoria.

Congenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR.

[Questionnaire survey of ocular injuries due to fireworks in Japan].

PURPOSE: To report the results of a questionnaire survey of ocular injuries caused by fireworks in 2011. METHODS: A survey was performed by recovery of questionnaire postcards asking details of firework-related ocular injuries which were sent to 1,094 institutes recognized as training hospitals by the Japan Ophthalmological Society. RESULTS: The cards were recovered from 57.9% institutes, and showed that 23 eyes of 20 patients (17 men and 3 women) with firework-related ocular injuries were seen in 19 institutes. The patients' ages ranged from 1 to 45 (average 18.4) years old. Injuries were caused by either carelessness or accidents in 18 eyes of 15 patients, and by wrong usage of fireworks in 5 eyes of 5 young men (15-27 years old). These 5 eyes showed severe injuries involving the lens and/or retina, and required surgical treatment with finally measured visual acuities 0.4 or less. CONCLUSIONS: In Japan, hazardous use of fireworks seems to cause severe eye injuries from which at least 5 young adults suffered during one fireworks' season. Therefore, preventive measures should be taken including public education on the usage of fireworks.

Familial acorea, microphthalmia and cataract syndrome.

PURPOSE: To describe the clinical features of members of a family with acorea, microphthalmia and cataract syndrome. In addition, to perform linkage analysis on family members to determine possible candidate genes. METHODS: Comprehensive ophthalmic examinations were performed on five affected members of a family consisting of a paternal grandmother, father and three children. In addition, DNA was extracted from nine family members (the five affected and four normal members) and used for genome-wide single nucleotide polymorphism genotyping and linkage analysis. RESULTS: All of the affected patients had acorea or fibrous occlusion of the pupil, microphthalmia and cataracts in both eyes. They also had microcornea and iridocorneal dysgenesis. Examination of the crystalline lens was hindered by the abnormal iris surface, but cataracts were detected by ultrasound biomicroscopy. Surgical reconstruction of the pupil allowed a better view of the posterior pole of the eye, and ophthalmoscopy showed a normal retina and optic disc. No systemic abnormalities were observed. Linkage analysis did not reach significance but narrowed the location of possible candidate genes to chromosomes 1, 5, 8, 11 and 17. CONCLUSIONS: This acorea, microphthalmia and cataract syndrome has not previously been reported. Genetic analyses indicate that this syndrome is probably due to an autosomal dominant mutation.

The effects of a convex rear-view mirror on ocular accommodative responses.

Convex mirrors are universally used as rear-view mirrors in automobiles. However, the ocular accommodative responses during the use of these mirrors have not yet been examined. This study investigated the effects of a convex mirror on the ocular accommodative systems. Seven young adults with normal visual functions were ordered to binocularly watch an object in a convex or plane mirror. The accommodative responses were measured with an infrared optometer. The average of the accommodation of all subjects while viewing the object in the convex mirror were significantly nearer than in the plane mirror, although all subjects perceived the position of the object in the convex mirror as being farther away. Moreover, the fluctuations of accommodation were significantly larger for the convex mirror. The convex mirror caused the 'false recognition of distance', which induced the large accommodative fluctuations and blurred vision. Manufactures should consider the ocular accommodative responses as a new indicator for increasing automotive safety.

Reconstruction of a nonfunctional trabeculectomy bleb using an amniotic membrane-wrapped silicone sponge to treat refractory glaucoma.

BACKGROUND: This study was conducted to verify the usefulness of nonfunctional trabeculectomy bleb reconstruction using a silicone sponge wrapped with amniotic membrane. Its purpose was to allow aqueous humor to flow from the flap to the posterior orbital space. METHODS: Seven consecutive patients who had undergone two or more surgeries in one eye for refractory glaucoma followed by our operation were included in this study. Conjunctival adhesion to the sclera was detached with a limbus-based conjunctival incision, followed by reopening the former trabeculectomy flap. A 1.5 × 12 mm silicone sponge used for retinal detachment surgery was wrapped three to four times with amniotic membrane, placed longitudinally on the sclera, and fixed with 10-0 nylon sutures. The anterior end of the amniotic membrane was fixed underneath the scleral flap with sutures, and the conjunctival wound was closed. We periodically checked the intraocular pressure (IOP) and for complications. Follow-up periods ranged from 15 to 30 months (average 19.4 months). Surgical success was defined as a final IOP of ≤ 21 mmHg with or without additional treatment. We defined failure as an IOP of > 21 mmHg on the second of two consecutive visits after the first 4 weeks, or the need for additional glaucoma surgery. RESULTS: Surgery was successful in five of the seven eyes, although bleb needling was performed in two eyes and amniotic membrane patch covering for early aqueous leakage was needed in one eye. In four of the five successful eyes, IOP was well controlled for longer than the period between the previous and present surgeries. One of the unsuccessful eyes, with neovascular glaucoma, had high IOP with hyphema followed by phthisis of the eyeball. The other, with aqueous leakage via the conjunctival wound, required trabeculectomy in a different area. There were no other complications. CONCLUSIONS: Reconstruction of the nonfunctional trabeculectomy bleb using a silicone sponge wrapped with amniotic membrane can be a useful strategy for treating refractory glaucoma.

Genetic variants of FZD4 and LRP5 genes in patients with advanced retinopathy of prematurity.

PURPOSE: Retinopathy of prematurity (ROP) is a complex disease with a genetic predisposition, but little is known about its genetic background. It has a clinical resemblance to familial exudative vitreoretinopathy (FEVR), a hereditary disease characterized by defects in the development of retinal vessels. Several studies have suggested that mutations in the causative genes for FEVR may account for a proportion of advanced ROP, but conflicting data have also been reported for some variants. To address the possibility of genetic involvement of FEVR genes in ROP, we performed comprehensive sequence analyses of 53 Japanese patients with advanced ROP for the FEVR-causing genes. METHODS: Peripheral blood DNA was obtained from 53 patients referred to our hospitals for retinal surgery. Polymerase chain reaction followed by direct sequencing of the coding regions of the known FEVR-causing genes (FZD4, LRP5, TSPAN12, and NDP) and a noncoding exon of the NDP gene was performed. Possible pathogenicity of the sequence changes were analyzed by orthologous protein sequence alignment and by computational predictions. RESULTS: We identified six different nonsynonymous DNA variants in the coding region of either the FZD4 gene (p.H69Y, p.R127H, and p.Y211H) or the LRP5 gene (p.R1219H, p.H1383P, and p.T1540M) in seven patients. The corresponding codons of these changes were highly conserved among species, and these changes were predicted to be pathogenic by at least two of four computational prediction programs. No such changes were found in the TSPAN12 and NDP genes. CONCLUSIONS: Six possibly pathogenic variants of FZD4 or LRP5 were found in seven advanced ROP patients. Although these variants do not yet provide definitive evidence that they are causal, the results imply a role of the FZD4 and LRP5 genes in the development of advanced ROP.

A classic temporal optic disc pit showing progression in the corresponding optic nerve fiber and visual field defects.

PURPOSE: We report a rare case with a classic temporal optic disc pit (ODP) showing the progression of an associated nerve fiber layer defect (NFLD) with the corresponding visual field defect (VFD). METHODS: We describe the patient's medical records and review the pertinent literature. RESULTS: A 54-year-old woman had a temporal ODP, which was considered to be congenital, associated with both NFLD expanded to both the upper and lower sides of the horizontal line and corresponding VFD and a small ODP-like excavation at the 6.5 o'clock position on the disc edge with a narrow NFLD OD. During the 5-year follow-up period, both the NFLD and VFD associated with the temporal pit progressed without serous retinal detachment. The small ODP-like excavation located at the 6.5 o'clock position also showed progressive NFLD in the temporal lower quadrant with advanced VFD, which suggested that the excavation might be associated with glaucoma. CONCLUSION: Based on the observation that the VFD occupied the two temporal quadrants with no step, an NFLD with corresponding VFD associated with a classic temporal ODP, although not considered to be related to glaucoma, can progress.

Identification of causative pathogens in eyes with bacterial conjunctivitis by bacterial cell count and microbiota analysis.

PURPOSE: To determine the causative pathogens in eyes with bacterial conjunctivitis. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Thirteen eyes diagnosed clinically with bacterial conjunctivitis and 12 eyes with normal conjunctival sac were studied. METHODS: The bacterial cell numbers were counted in the samples stained by ethidium bromide (EtBr). The microbiota was determined by the clone library method using polymerase chain reaction (PCR) amplification of the 16S ribosomal RNA (rRNA) gene with universal primers. In addition, examinations of smears and cultures of samples were performed. MAIN OUTCOME MEASURES: Bacterial cell numbers determined by the EtBr staining method and microbiota analysis based on 16S rRNA gene of samples from eyes with bacterial conjunctivitis. RESULTS: The bacterial cell numbers in the eyes with bacterial conjunctivitis were significantly higher than those in the normal conjunctival sacs. Ten of 13 samples from the eyes with bacterial conjunctivitis had positive PCR results. The remaining 3 samples and all 12 samples from the normal conjunctiva had negative PCR results. In 5 of the 10 PCR-positive samples, the predominant species accounted for 84.5% or more of each clone library. In the remaining 5 samples, the predominant and the second dominant species accounted for 27.4% to 56.3% and 19.0% to 26.8%, respectively, of each clone library. The number of detected species in the clone libraries was between 8 and 20 (average ± standard deviation, 7.5 ± 5.8). Bacteria were detected in 8 of the 10 bacterial conjunctivitis samples and in 5 of the 12 normal samples in the cultures. The number of species detected by cultures was 1 in the eyes with bacterial conjunctivitis and between 1 and 3 (mean ± standard deviation, 1.6 ± 0.9) in the normal conjunctiva. CONCLUSIONS: These results showed that the bacterial cell number in a sample is a good method of determining bacterial conjunctivitis. The microbiota analysis detected a diverse group of microbiota in the eyes with bacterial conjunctivitis and showed that the causative pathogens could be determined based on percentages of bacterial species in the clone libraries. The combination of bacterial cell count and microbiota analysis is a good method for identifying the causative pathogens in cases of monomicrobial and polymicrobial conjunctivitis.

Novel compound heterozygous mutations in the MFRP gene in a Japanese patient with posterior microphthalmos.

PURPOSE: To report a case of posterior microphthalmos caused by novel compound heterozygous mutations in the membrane-type frizzled-related protein (MFRP) gene. METHODS: A 9-year-old girl with posterior microphthalmos underwent a standard ophthalmological examination and genetic screening by direct sequencing. RESULTS: The patient had a short axial length, high hyperopia, crowded optic discs, and dilation and tortuosity of the retinal vessels. No signs of retinitis pigmentosa were present. A diagnosis of posterior microphthalmos rather than nanophthalmos was made because the corneal diameter and anterior chamber depth were normal. Genetic analysis revealed two novel nonsense mutations in the MFRP gene, Q123X and W443X. Her parents were heterozygous carriers of one of the mutations. CONCLUSIONS: Posterior microphthalmos can be caused by nonsense compound heterozygous mutations in the MFRP gene.

Potential preventive effects of a new visual intervention for accommodative insufficiency and asthenopia due to sustained near task.

BACKGROUND: The objective of this study was to experimentally investigate whether a new visual intervention with optical and binocular vergence demands prevents accommodative insufficiency and asthenopia after sustained periods of visual task. METHODS: Fourteen female students were given the intervention with optical and binocular vergence demands for 1.5 min immediately after 20 min of a sustained task on a three-dimensional display. Before and after the trial, their ocular functions were measured and their symptoms assessed. A new type of intervention was developed that can vary optical and binocular vergence demands. For control, the subjects rested with eyes closed for 1.5 min after the task instead of the intervention. RESULTS: In the control group, accommodative contraction time (from far to near) and accommodative relaxation time (from near to far) was delayed from 1.13 to 1.68 s and from 1.36 to 1.60 s, respectively, and the symptom of asthenopia increased after rest. In the intervention group, however, changes in those functions were smaller than those in the control group. CONCLUSIONS: These results suggest that the new intervention with optical and binocular vergence demands is effective for the treatment of accommodative insufficiency that follows sustained periods of visual task, and consequently, the symptom of asthenopia induced by accommodative insufficiency may decrease.

IOP measured by dynamic contour tonometry correlates with IOP measured by Goldmann applanation tonometry and non-contact tonometry in Japanese individuals.

PURPOSE: The purpose of this study was threefold. We sought to compare the intraocular pressure (IOP) measured by dynamic contour tonometry (DCT) with that measured by Goldmann applanation tonometry (GAT) and noncontact tonometry (NCT). We also examined the influence of central corneal thickness (CCT) and corneal curvature radius (CCR) on the IOP measurements. Last, we investigated the factors that could affect the ocular pulse amplitude (OPA) measurements. METHODS: Seventy-four patients with no history of intraocular surgery were enrolled in this study. We measured IOP by DCT, GAT, and NCT, and the CCT, CCR, and axial length (AL) in the right eye of each patient. We also measured OPA by DCT. We subsequently analyzed the correlation of IOP measurements between GAT and DCT and between NCT and DCT. We also examined the influence of CCT, CCR, and AL on IOP readings by the 3 tonometers. In addition, we investigated the factors that could affect the OPA measurements. RESULTS: The mean IOP measured by DCT was 2.8 mm Hg higher than that by GAT and 3.2 mm Hg higher than that by NCT. This difference was greater with thinner CCT in the lower IOP group than in the higher IOP group. IOP measurements by both GAT and NCT significantly correlated with CCT; however, IOP measurement by DCT did not correlate with CCT. No significant correlations were shown between the IOP measured by each of the 3 tonometers and either CCR or AL. OPA measurements positively correlated with age, IOP measurement by DCT, and pulse pressure. CONCLUSIONS: IOP measured by DCT correlates with IOP measured by GAT or NCT with a roughly 3.0 mm Hg higher value, and these differences were greater in the patients with a thinner CCT. IOP measurements by both GAT and NCT significantly correlated with CCT; however, IOP measurement by DCT did not correlate with CCT. Our findings also indicate that OPA measured using DCT shows a positive correlation with patient age, IOP measurement by DCT, and pulse pressure.

Mutations in the TSPAN12 gene in Japanese patients with familial exudative vitreoretinopathy.

PURPOSE: To search for mutations in the TSPAN12 gene in 90 Japanese probands with familial exudative vitreoretinopathy (FEVR) and their family members and to determine the types and frequencies of the mutations. DESIGN: Laboratory investigation and clinical case analyses. METHODS: Direct sequencing after polymerase chain reaction of the coding exons of TSPAN12 was performed for 90 probands with FEVR and some of their family members. The clinical signs and symptoms that were characteristic of individuals with TSPAN12 mutations were determined. RESULTS: Three families were found to carry 2 mutations in TSPAN12. One of these mutations was a new missense change, L245P, and the other was an already reported nonsense mutation, L140X, in 2 families. Mutations in TSPAN12 accounted for 3% of Japanese FEVR patients and 8% of the FEVR families who did not have mutations in any of the known FEVR genes, FZD4, LRP5, and NDP. The clinical signs and symptoms varied among the patients, but the retinal findings with TSPAN12 mutations were not different from those with mutations in the known FEVR-causing genes. CONCLUSIONS: Mutant TSPAN12 is responsible for approximately 3% of FEVR patients in Japan. The results provide further evidence that mutations in TSPAN12 are FEVR causing and that the gene products most likely play a role in the development of retinal vessels.

Transcriptional regulation of activating transcription factor 4 under oxidative stress in retinal pigment epithelial ARPE-19/HPV-16 cells.

PURPOSE: Oxidative stress plays an important role in the pathogenesis of various ocular diseases such as retinopathy, glaucoma, and age-related macular degeneration. Activating transcription factor 4 (ATF4) is induced by various stressors, including endoplasmic reticulum (ER) and oxidative stress, and ATF4 expression is regulated translationally through the PERK pathway of eIF2α phosphorylation. Transcriptional regulation of the ATF4 gene under oxidative stress was investigated in human papillomavirus 16 (HPV-16)-transformed retinal pigment epithelial ARPE-19/HPV-16 cells. METHODS: Retinal pigment epithelial cells, trabecular meshwork cells, and corneal endothelial cells were treated with anoxia and thapsigargin (TG). Gene expression of ATF4 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and transcription factors was investigated by Western blot analysis, reporter assays, chromatin immunoprecipitation (ChIP) assays, and small interfering (si)RNA strategies. Cellular sensitivity to oxidative stress was determined. RESULTS: The expression of two transcriptional factors, ATF4 and Nrf2, was significantly induced by anoxia and TG. The Nrf2 regulator Keap1 was downregulated by anoxia. Downregulation of Nrf2 abolished ATF4 expression. On the other hand, downregulation of Keap1 enhanced the expression of both Nrf2 and ATF4. The promoter activity of ATF4 was transactivated by the co-transfection of Nrf2 expression plasmids and reduced by the transfection of Nrf2-specific siRNA. The ChIP assays demonstrated that Nrf2 bound to the promoter of the ATF4 gene. Nrf2 downregulation nearly abolished the ATF4 induction by anoxia and TG. Consistent with these findings, the promoter activity of ATF4 was augmented by treatment with TG, HCA, H(2)O(2), and anoxia. However, stress induction of ATF4 promoter activity was observed, even when a mutation was introduced into the antioxidant-responsive elements site. Furthermore, stress induction of the ATF4 promoter was completely abolished when the 5' untranslated region of the ATF4 gene was deleted. Downregulation of ATF4 rendered ARPE-19/HPV-16 cells sensitive to oxidative stress. CONCLUSIONS: These results suggest that the stress induction of ATF4 is significantly regulated transcriptionally through a Nrf2-dependent mechanism and may be a double-edged sword in the pathogenesis of various retinopathies.

Quercetin induces the expression of peroxiredoxins 3 and 5 via the Nrf2/NRF1 transcription pathway.

PURPOSE: The flavonoids have potent antioxidant and free-radical scavenging properties and are beneficial in the prevention and treatment of ocular diseases including glaucoma. The authors have previously reported that antiglaucoma agents could transcriptionally activate the antioxidant protein peroxiredoxin (PRDX)2. The purpose of this study was to investigate whether quercetin can activate transcription factors and induce the expression of the PRDX family. METHODS: To demonstrate whether quercetin can transcriptionally induce the expression of the PRDX family, trabecular meshwork cells were treated with quercetin, and PRDX expression and transcription factors were both investigated by Western blot analysis, reporter assays, and siRNA strategies. Subsequently, cellular sensitivity to oxidative stress was determined. RESULTS: Expression of the PRDX3 and PRDX5 genes was induced by quercetin in a time- and dose-dependent manner. NRF1 transactivates the promoter activity of both PRDX3 and PRDX5 but not PRDX2 and PRDX4. Quercetin can also induce the expression of Nrf2 and NRF1 but not of Ets1, Ets2, or Foxo3a. Knockdown of NRF1 expression significantly reduced the expression of both PRDX3 and PRDX5. Reporter assays showed that NRF1 transactivated the promoter activity of both PRDX3 and PRDX5 and that the downregulation of NRF1 with siRNA repressed the promoter activity of both PRDX3 and PRDX5. Furthermore, the downregulation of NRF1, PRDX3, and PRDX5 renders trabecular meshwork cells sensitive to hydrogen peroxide. Finally, NRF1 activation by quercetin was completely abolished by the knockdown of Nrf2. CONCLUSIONS: Quercetin upregulates the antioxidant peroxiredoxins through the activation of the Nrf2/NRF1 transcription pathway and protects against oxidative stress-induced ocular disease.

Angiographic changes in iris and iridocorneal angle neovascularization after intravitreal bevacizumab injection.

OBJECTIVE: To evaluate the effects of the intravitreal (IV) injection of bevacizumab on anterior segment neovascularization using anterior segment angiography. METHODS: We observed 1 eye with iris and iridocorneal angle neovascularization and 3 with neovascular glaucoma from 4 patients with diabetic retinopathy in 3 eyes and central retinal vein occlusion in 1 eye. Two healthy eyes from 2 other patients served as control eyes. Three eyes, including 1 normal eye, were examined by iris angiography; the other eyes underwent iridocorneal angle angiography with fluorescein (FA) and indocyanine green (IA) using a Heidelberg Retina Angiograph 2. After angiography, 4 eyes with neovascularization were treated with IV bevacizumab (1.25 mg per 0.05 mL) and underwent angiography once more 4 to 6 days after treatment. RESULTS: Iris angiography with indocyanine green revealed many iris vessels, but not dye leaking, in both normal and glaucomatous eyes, and the angiography with fluorescein showed intensive vessel leakage in the iris as well as iridocorneal angle neovascularization, but not in normal eyes. Angle angiography revealed vessel structures with indocyanine green and intensive leakage with fluorescein in the iris and showed iridocorneal angle neovascularization and neovascular glaucoma, whereas no vessel structures appeared with IA or FA in the normal eye. After IV bevacizumab injection in eyes with neovascularization, the vascular structure did not change with IA, but dye leakage remarkably decreased with FA in the iris and angle. However, newly formed vessels in the iris and iridocorneal angle seemed to disappear on slitlamp examination. CONCLUSION: Intravitreal injection of bevacizumab effectively reduces vascular permeability, whereas newly formed vessels are still present in the iris and iridocorneal angle.

Amniotic Membrane Transplantation for Repair of Leaking Glaucoma Filtering Blebs with Scleral Perforation.

Leaking glaucoma filtering blebs with scleral perforation were successfully repaired in two patients using amniotic membrane transplantation. The amniotic membrane was placed into the subconjunctival space to cover the perforated scleral area. The edge of the limbal conjunctiva was sutured to the peripheral cornea with conjunctival advancement over the amniotic membrane. The bleb leaks were successfully closed. In addition, good and functioning filtration was maintained during a follow-up period of 12 months in both cases. Amniotic membrane transplantation may be effective for the surgical management of high risk of leaking glaucoma blebs with scleral perforation.