Flare levels after intravitreal injection of brolucizumab for diabetic macular edema.

PURPOSE: This study aimed to evaluate anterior flare intensity (AFI) after intravitreal injection of brolucizumab (IVBr) in patients with diabetic macular edema (DME), and to identify the factors associated with the change of AFI after IVBr. METHODS: This prospective multicenter study was conducted at five sites in Japan for patients with DME who underwent a single IVBr. AFI and central retinal thickness (CRT) were measured using a laser flare meter and spectral-domain optical coherence tomography, respectively, at weeks 0 and 6. RESULTS: Sixty-five patients (phakia, 37 eyes; pseudophakia, 28 eyes) were enrolled. Six weeks after IVBr, CRT and best-corrected visual acuity significantly improved (p < 0.0001). AFI (p = 0.0003) and age (p = 0.0054) were significantly higher in patients with pseudophakic eyes than those with phakic eyes. The AFI of the phakic eyes decreased after IVBr (p = 0.043). As the AFI before injection is higher (p = 0.0363) and the age is lower (p = 0.0016), the AFI decreases after IVBr. There was a significant positive correlation between the rates of change in CRT and AFI (p = 0.024). CONCLUSION: After IVBr, AFI decreases in phakic eyes but not in pseudophakic eyes. The age, AFI and CRT before injection and changes of CRT are involved in the change in AFI after IVBr.

Intermitochondrial signaling regulates the uniform distribution of stationary mitochondria in axons.

In the central nervous system (CNS), many neurons develop axonal arbors that are crucial for information processing. Previous studies have demonstrated that premature axons contain motile and stationary mitochondria, and their balance is important for axonal arborization. However, the mechanisms by which neurons determine the positions of stationary mitochondria as well as their turnover remain to be elucidated. We observed that the distribution of stationary mitochondrial spots along the unmyelinated and nonsynaptic axons is not random but rather relatively uniform both in primary cultured neurons and in tissues. Intriguingly, whereas the positions of each mitochondrial spot changed over time, the overall distribution remained uniform. In addition, local inactivation of mitochondria by KillerRed mediated chromophore-assisted light inactivation (CALI) inhibited the translocation of mitochondrial spots in adjacent axonal regions, suggesting that functional mitochondria enhance the motility of other mitochondria in the vicinity. Signals of ATP:ADP sensor, PercevalHR indicated that the ATP:ADP ratio was relatively high around mitochondria, and treating axons with phosphocreatine (PCr), which supplies ATP, reduced the immobile mitochondria induced by the local mitochondrial inactivation. In a mathematical model, we found that the ATP gradient generated by mitochondria, and ATP dependent regulation of mitochondrial motility could establish uniform mitochondrial distribution. These observations suggest that axons in the CNS possess the system that distributes mitochondria uniformly, and intermitochondrial signaling contribute to the regulation. In addition, our results suggest the possibility that ATP might be one of the molecules mediating the signaling.

Optic Nerve Injury Enhanced Mitochondrial Fission and Increased Mitochondrial Density without Altering the Uniform Mitochondrial Distribution in the Unmyelinated Axons of Retinal Ganglion Cells in a Mouse Model.

Glaucomatous optic neuropathy (GON), a major cause of blindness, is characterized by the loss of retinal ganglion cells (RGCs) and the degeneration of their axons. Mitochondria are deeply involved in maintaining the health of RGCs and their axons. Therefore, lots of attempts have been made to develop diagnostic tools and therapies targeting mitochondria. Recently, we reported that mitochondria are uniformly distributed in the unmyelinated axons of RGCs, possibly owing to the ATP gradient. Thus, using transgenic mice expressing yellow fluorescent protein targeting mitochondria exclusively in RGCs within the retina, we assessed the alteration of mitochondrial distributions induced by optic nerve crush (ONC) via in vitro flat-mount retinal sections and in vivo fundus images captured with a confocal scanning ophthalmoscope. We observed that the mitochondrial distribution in the unmyelinated axons of survived RGCs after ONC remained uniform, although their density increased. Furthermore, via in vitro analysis, we discovered that the mitochondrial size is attenuated following ONC. These results suggest that ONC induces mitochondrial fission without disrupting the uniform mitochondrial distribution, possibly preventing axonal degeneration and apoptosis. The in vivo visualization system of axonal mitochondria in RGCs may be applicable in the detection of the progression of GON in animal studies and potentially in humans.

Role of Microaneurysms in the Pathogenesis and Therapy of Diabetic Macular Edema: A Descriptive Review.

Background and Objectives: This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. Materials and Methods: We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. Results: MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. Conclusions: MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.

Posture-Induced Intraocular Pressure Changes after iStent Inject W Combined with Phacoemulsification in Open Angle Glaucoma Patients.

Background and Objectives: The purpose of this study was to evaluate the posture-induced intraocular pressure (IOP) changes after iStent inject W combined with phacoemulsification procedure in Japanese patients with open-angle glaucoma. Materials and Methods: We prospectively evaluated the posture-induced IOP changes after surgery. The primary outcome was the posture-induced IOP changes postoperatively. Secondary outcome measures included postoperative complications, visual acuity, visual field, and corneal endothelial cell density. Results: This study completed the prospective observation for 15 eyes (15 patients). The mean preoperative IOP with the Goldmann applanation tonometer was 16.0 ± 2.6 mm Hg with a mean glaucoma medication usage of 2.5 ± 1.2, which decreased to 14.4 ± 2.4 mm Hg (p = 0.14) and 0.5 ± 0.9 medications (p < 0.01), respectively, 12 months postoperatively. The mean baseline IOP with the ICare was 12.0 ± 2.7 mmHg in the sitting position, which significantly increased to 15.2 ± 3.8 mmHg in the lateral decubitus position (p < 0.01). This postural IOP difference was 3.2 ± 2.2 mmHg and 3.2 ± 2.4 mmHg at baseline and 12 months postoperatively, respectively, with no significant changes (p > 0.99). Conclusions: iStent inject W combined with cataract surgery reduced the IOP and the number of glaucoma medications during short-term follow-ups with high safety. However, iStent inject W did not affect the degree of posture-induced IOP changes.

Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome.

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

Regional Variety of Reduction in Retinal Thickness of Diabetic Macular Edema after Anti-VEGF Treatment.

Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis.

Comparison of 5-year outcomes between trabeculectomy combined with phacoemulsification and trabeculectomy followed by phacoemulsification: a retrospective cohort study.

BACKGROUND: We aimed to compare the outcomes of trabeculectomy combined with phacoemulsification and those of trabeculectomy followed by phacoemulsification. METHODS: A total of 141 patients with primary open-angle glaucoma, exfoliation glaucoma, and glaucoma secondary to uveitis glaucoma who underwent trabeculectomy followed by (n = 48) or combined with (n = 93) phacoemulsification were included. We analyzed data collected from the Collaborative Bleb-Related Infection Incidence and Treatment Study, a prospective cohort study conducted in 34 clinical centers that included 1249 eyes. The main outcome was the cumulative probability of success based on intraocular pressure (IOP) within 5 years. Surgical failure was defined as a case in which additional glaucoma surgery is required or one of the following criteria are met: preoperative IOP > 21 (A), > 18 (B), or > 15 mmHg (C). The secondary outcomes were cumulative probability of success, risk factors of surgical failure, and Δ visual acuity. However, the data on phacoemulsification during the 5-year follow-up were censored. RESULTS: No significant difference was found in the cumulative probability of success as the main outcome. When the data on phacoemulsification during the 5-year follow-up were censored, the probabilities of success of trabeculectomy followed by phacoemulsification were significantly higher for criteria A (p = 0.02), B (p <  0.01), and C (p <  0.01). Lower preoperative IOP, younger age, and trabeculectomy combined with phacoemulsification were associated with poorer outcome. Trabeculectomy followed by phacoemulsification had significantly worse Δ logMAR visual acuity at 6 and 12 months (p <  0.01). CONCLUSION: The cumulative probability of success after trabeculectomy combined with or followed by phacoemulsification remained unchanged. Combining phacoemulsification with trabeculectomy adversely affected the cumulative probability of success after trabeculectomy. The visual acuity improvements observed in the early postoperative period after combining phacoemulsification with trabeculectomy disappeared within 5 years.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

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 × 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 × 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.

Characteristic distribution of microaneurysms and capillary dropouts in diabetic macular edema.

PURPOSE: To investigate the distribution pattern of microaneurysms (MAs) and capillary dropouts (CDOs) related to retinal thickness in patients with diabetic macular edema (DME). METHODS: We designed a cross-sectional observational study in which we manually merged fluorescein angiography and optical coherence tomography (OCT) map and located MAs and CDOs areas. The density of MAs, the width and the length of circumference of CDOs, and the number of MAs adjacent to CDOs were compared between highly thickened (white area (WA) in OCT map) and border areas (red area (RA)). RESULTS: We examined 115 eyes of 115 patients with DME. The density of MAs in RA (1.086 ± 0.616) was significantly higher than that in WA (0.8601 ± 1.086) (p = 0.002). The MA rates adjacent to CDOs in WA and RA were 79.1% and 80.7%, respectively. In the RA, the size of CDO adjacent to MAs was smaller (p = 0.013), but its circumference was longer (p = 0.018), and the number of MAs adjacent to CDOs was larger than those in WA (p = 0.002). The total length of circumference of CDOs was significantly correlated with the number of MAs adjacent to CDOs in WA (p = 0.011, R2 = 0.68) and RA (p = 0.008, R2 = 0.81). CONCLUSION: Smaller but more CDOs with longer circumference adjacent to MAs contribute to the higher density of MAs in the surrounding areas of DME.

Conjunctival structure of glaucomatous eyes treated with anti-glaucoma eye drops: a cross-sectional study using anterior segment optical coherence tomography.

BACKGROUND: To determine the effect of various factors to the preservation rate of the conjunctival layer borderlines of glaucomatous eyes treated with anti-glaucoma eye drops. METHODS: Anterior segment optical coherence tomography (AS-OCT) images of the bulbar conjunctiva of 328 eyes were analyzed with and without anti-glaucoma eye drops to quantify the preservation rates of the conjunctival layer borderlines. RESULTS: More anti-glaucoma eye drops and a longer duration of administration were associated with lower preservation rates of the borderlines between both the conjunctival stroma/Tenon's capsule (P < 0.001 and P < 0.001, respectively) and Tenon's capsule/sclera (P < 0.001 and P < 0.001, respectively). Prostaglandin analogs and fixed combinations of ß-blockers/prostaglandin analogs were prognostic factors for lower preservation rates of the borderlines between both the conjunctival stroma/Tenon's capsule (P < 0.001 and P = 0.009, respectively) and Tenon's capsule/sclera (P < 0.001 and P = 0.008, respectively). CONCLUSIONS: Numerous anti-glaucoma eye drops and their long-term administration are associated with the disruption of the bulbar conjunctival borderlines detected by AS-OCT.

Prospective cohort study of risk factors for choroidal detachment after trabeculectomy.

PURPOSE: To investigate risk factors for choroidal detachment after trabeculectomy. METHODS: We prospectively evaluated 97 patients with open-angle glaucoma who underwent primary trabeculectomy to investigate risk factors for choroidal detachment after trabeculectomy. The primary outcome measure was risk factors for the occurrence and severity of choroidal detachment after trabeculectomy. Choroidal detachment severity was quantified as the number of fundus quadrants with choroidal detachment. RESULTS: Sixteen patients (16.5%) had choroidal detachment. Mean period between surgery and occurrence of choroidal detachment was 7.9 ± 5.7 days. Mean intraocular pressure (IOP) on the first day of choroidal detachment was 6.1 ± 3.0 mm Hg. Multivariable analyses revealed that the exfoliation glaucoma, greater ΔIOP between preoperative and lowest postoperative IOPs, and thicker cornea were associated with choroidal detachment (P = 0.022, P = 0.002, and P = 0.013, respectively). These factors were also associated with the severity of choroidal detachment (exfoliation glaucoma; P = 0.013, greater ΔIOP; P < 0.001, and thicker cornea; P = 0.006). CONCLUSIONS: Exfoliation glaucoma, more IOP reduction, and thicker cornea are associated with the occurrence and severity of choroidal detachment after trabeculectomy.

Flare levels after intravitreal injection of ranibizumab, aflibercept, or triamcinolone acetonide for diabetic macular edema.

PURPOSE: To evaluate anterior flare intensity (AFI) and central retinal thickness (CRT) values after intravitreal injection of aflibercept (IVA), ranibizumab (IVR), or triamcinolone acetonide (IVTA) in patients with diabetic macular edema (DME). METHODS: This research was conducted as a prospective study for patients with DME. Patients with phakia received either IVA or IVR, whereas patients with pseudophakia received IVA, IVR, or IVTA. AFI and CRT were measured using a laser flare meter and spectral domain optical coherence tomography, respectively, at days 0, 1, 7, 30, and 90. RESULTS: Forty patients with phakia and 60 patients with pseudophakia were enrolled this study. In the IVTA group, AFI of pseudophakic eyes was significantly decreased at days 1 (p = 0.0487), 7 (p = 0.0201), and 30 (p = 0.0211). In the IVA group, AFI of phakic eyes was transiently increased at day 1 (p = 0.0078) and returned to baseline at day 7, whereas no significant change was observed in AFI of pseudophakic eyes. In the IVR group, there was no significant change in AFI regardless of phakic condition. All groups showed significant reduction in CRT at day 7 and later. CONCLUSION: DME improved after treatment by IVTA, IVR, or IVA, whereas AFI was reduced only in eyes treated with IVTA. The temporal profiles of AFI are likely related to differences in the pharmacological properties of the drugs.

In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS.

The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23-25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.

Circumpapillary retinal nerve fiber layer thickness, anterior lamina cribrosa depth, and lamina cribrosa thickness in neovascular glaucoma secondary to proliferative diabetic retinopathy: a cross-sectional study.

BACKGROUND: To compare the lamina cribrosa between eyes with and without neovascular glaucoma (NVG) using enhanced depth imaging spectral-domain optical coherence tomography. METHODS: Forty-six patients with proliferative diabetic retinopathy were enrolled in this cross-sectional study. The patients were divided into two groups based on the absence or presence of NVG (the non-NVG group and the NVG group, respectively). The intraocular pressure (IOP), circumpapillary retinal nerve fiber layer (cpRNFL) thickness, anterior lamina cribrosa depth (ALD), and laminar thickness (LT) were compared between the groups. RESULTS: In the non-NVG group, the mean age was 66.2 ± 2.4 (mean ± standard error) years, mean maximum IOP was 18.8 ± 1.8 mmHg, mean cpRNFL thickness was 91.2 ± 3.9 µm, mean ALD was 407.0 ± 22.9 µm, and mean LT was 155.0 ± 4.7 µm. In the NVG group, the mean age was 61.4 ± 2.1 years, mean maximum IOP was 33.1 ± 1.6 mmHg, mean cpRNFL thickness was 73.6 ± 3.4 µm, mean ALD was 403.9 ± 20.1 µm, and mean LT was 156.9 ± 4.2 µm. The IOP was significantly higher and the cpRNFL was significantly thinner in the NVG group (P < 0.001 and P = 0.002, respectively). However, the age, ALD, and LT were not statistically different between the groups (P = 0.151, 0.919, and 0.757, respectively). CONCLUSIONS: Although the cpRNFL was thinner, the structure of the lamina cribrosa was unchanged in the NVG eyes. Axonal loss of the retinal ganglion cells in NVG patients was prior to lamina cribrosa deformation.

The effect of triamcinolone acetonide or bevacizumab on the levels of proinflammatory cytokines after retinal laser photocoagulation in pigmented rabbits.

Although laser photocoagulation is a gold standard for the treatment of retinal ischemic diseases, thermal burn induces the inflammation and the progression of macular edema. To prevent this complication, combination therapy using anti-vascular endothelial growth factor (VEGF) drugs or steroids is clinically utilized, however the mechanisms are still unclear. In this study, we aimed to evaluate the changes in inflammatory and angiogenic cytokine levels in aqueous humor and vitreous body after intravitreal injection of bevacizumab (IVB) or triamcinolone (IVTA), as well as sub-Tenon injection of triamcinolone (STTA) after retinal laser photocoagulation in rabbits. Pigmented rabbits were treated with retinal laser photocoagulation and divided into 4 groups, namely Control (no additional treatment), IVB, IVTA or STTA accordingly. Samples of vitreous and aqueous humor were collected on post-treatment days 0, 1, 7 and 14. The levels of intraocular VEGF, interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) were measured using an immunoassay. The levels of VEGF, IL-6, ICAM-1 and MCP-1 were significantly elevated 1 day after laser treatment. IVTA and STTA significantly reduced the increase in the levels of VEGF, IL-6, ICAM-1 and MCP-1, while IVB reduced that of VEGF only in aqueous humor and vitreous body. The protein amount in the aqueous humor transiently increased 1 day after laser, and was significantly prevented by IVTA or STTA but not IVB. Data showed that bevacizumab only reduced intraocular VEGF after laser, while triamcinolone suppressed both the expression of VEGF and proinflammatory cytokines. We propose that these cytokine profiles may play an important role in the pathogenesis of inflammation after photocoagulation and the underlying mechanism of treatment with anti-VEGF drug and steroids.

The relationship between self-reported habitual exercise and visual field defect progression: a retrospective cohort study.

BACKGROUND: Exercise reduces intraocular pressure (IOP) in the short term. However, it is not known whether exercise contributes to slower glaucomatous visual field defect progression. METHODS: Twenty-four primary open-angle glaucoma or exfoliation glaucoma patients who were evaluated by the Humphrey Field Analyzer (HFA) 24-2 program ≥ four times in 3 years were enrolled. Patients with a history of intraocular surgery in past 3 years or other eye diseases threatening visual fields were excluded. Patients were classified into two groups whether they had exercise habits or not. RESULTS: Eleven patients had exercise habits. The mean ± standard error of IOP and MD slope were 14.8 ± 0.9 mmHg and +0.20 ± 0.20 dB/year in the exercise group and 13.3 ± 0.8 mmHg and -0.53 ± 0.18 dB/year in the non-exercise group (P = 0.24 and P = 0.01, respectively). Higher IOP [odds ratio (OR) = 0.44/1 mmHg increase; P = 0.02] and habitual exercise (OR = 0.04; P = 0.02) reduced the visual field defect progression risk in logistic regression analyses. CONCLUSIONS: Patients with self-reported exercise habits had slower glaucoma progression.

Haemangiopericytoma of the lacrimal sac.

Haemangiopericytomas (HPCs) are rare tumours which infrequently occur in the lacrimal sac. Only 8 cases of lacrimal sac HPC have previously been reported. The authors report 2 additional cases presenting clinically with epiphora and a mass. One case recurred 3 times during an 18-year period. The other case did not recur during 51 months of follow-up. The tumours showed immunohistochemical features consistent with a diagnosis of HPC. The authors recommend wide excision for these tumours and careful long-term follow-up to detect recurrence which is not uncommon.

Current Status of Glaucoma-related Data Management and Efforts toward Data Standardization.

Purpose: ï¼·e conducted a survey to evaluate the current status of glaucoma-related medical data management and standardization, aiming to improve the development of glaucoma care and research in Japan. Materials and methods: The survey was performed as a paper-based questionnaire of 14 universities that both participate in the glaucoma-related data standardization committee, established by the Japan Glaucoma Society in 2014, and actively perform glaucoma care. Results: All enrolled university hospitals installed an electronic hospital information system and used any of three ophthalmology-limited electronic chart systems. However, only 30.8% of the hospitals established a data extraction system from an electronic medical chart system, and only 14.3% could practically apply medical data for secondary research purposes. In all, 35.7% of the hospitals operate a medical cooperation system with local medical institutions and 42.9% electronically managed medical data inside their departments. Conclusion: This survey clarified the current state of medical data management and standardization.

Determinants of anterior chamber angle narrowing after mydriasis in the patients with cataract.

PURPOSE: To identify the determinants of anterior chamber angle narrowing after mydriasis by quantitative assessment of the anterior chamber components using anterior segment optical coherence tomography (AS-OCT). METHODS: In this intervention study, anterior chamber angle analysis was performed using AS-OCT in patients with cataract before pharmacological pupillary dilation and 30 min afterwards. Angle narrowing was quantified by the change of angle opening distance 500 after mydriasis (ΔAOD500). Multivariate linear regression and stepwise selection regression were used to identify which parameters in AS-OCT significantly determined ΔAOD500. RESULTS: One hundred and two Japanese patients (age, mean ± standard deviation, 71.9 ± 11.2 years) were enrolled. Multivariate analysis indicated that smaller ΔAOD500 were significantly associated with larger lens vault (LV; P < 0.001), larger iris area (IA; P = 0.003), and posterior corneal arch distance (PCAL; P = 0.01). Stepwise linear regression analysis revealed that smaller ΔAOD500 was independently associated with larger LV (partial R (2) = 0.232, P < 0.001), larger IA (partial R (2) = 0.080, P = 0.001), and smaller PCAL (partial R (2) = 0.066, P = 0.002) before mydriasis. These three factors explained 37.7 % of the decrease in ΔAOD500. CONCLUSION: Larger LV, larger IA, and smaller PCAL contribute considerably to anterior chamber angle narrowing after mydriasis in patients with cataract.