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Purpose To investigate the retinal vessel density (VD) in healthy and normal-tension glaucoma (NTG) eyes through optical coherence tomography angiography (OCTA) and to determine the correlation between VD and the retinal nerve fiber layer (RNFL) thickness and functional visual field (VF) defects for different locations. Methods A total of 74 NTG eyes and 24 healthy eyes were included. OCTA VD at 4.5 × 4.5 mm peripapillary region and 3.0 × 3.0 mm macula area, RNFL thickness, and VF pattern deviation results were individually analyzed on the basis of the Garway-Heath sectorization. Correlations between VD and VF/RNFL and VF were compared. Results In the NTG group, peripapillary VD, superficial macula VD, RNFL thickness, and ganglion cell complex thickness were significantly lower. In the whole peripapillary area and inferotemporal sector, anatomic correlations between VD and VF pattern deviation values were significantly higher than those between the RNFL thickness and VF values. In the subgroup analysis, VD was anatomically correlated with VF in early-, moderate-, and severe-stage NTG eyes, whereas the RNFL thickness was correlated with VF in moderate- and severe-stage NTG eyes. Conclusions We observed VD reduction in the peripapillary retina and superficial macula area in NTG eyes. The microvascular dropout of VD in the peripapillary retina, especially in the inferotemporal sector, provided a more accurate anatomic correlation with functional VF defects than that of the RNFL thickness, especially in early-stage NTG eyes. Translational relevance In patients who cannot comply VF exam, VD is a good tool for disease detection.

Purpose Anti-vascular endothelial growth factor (VEGF) injections, while used to effectively treat numerous retinal vascular conditions, can be associated with transient and prolonged ocular hypertension. There is minimal literature detailing the development of normal-tension glaucoma (NTG) following intravitreal anti-VEGF injections. Observations A 38-year-old Caucasian male with no medical or ocular history was diagnosed with an inferior HRVO with macular edema in the left eye. The patient received a total of eleven monthly intravitreal aflibercept injections over one year, with maintenance of stable vision and intraocular pressure (IOP) throughout the treatment period and during follow-up. Nine months after the last aflibercept injection, cup-to-disc asymmetry, inferior thinning of retinal nerve fiber layer (RNFL), and reduced superior visual field was evident in the left eye. Clinically, the patient was consistent with normal tension glaucoma and thus, the patient was started on daily timolol drops; however, the role of the glaucomatous findings being secondary to repeated injection-related IOP elevations is possible. Conclusions and Importance While the clinical features based on visual fields and RNFL thinning with unmedicated normotensive IOP may suggest NTG in a patient, this clinical presentation may be a masquerader of NTG with the etiology of the glaucoma optic neuropathy caused by cumulative impact of transient IOP elevations secondary to intravitreal injections.

Background and Objective: Glaucoma is a progressive optic neuropathy in which the optic nerve is damaged. The optic nerve is exposed not only to intraocular pressure (IOP) in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Here, we analyse ICP differences between patients with glaucoma and healthy subjects (HSs). Materials and Methods: Ninety-five patients with normal-tension glaucoma (NTG), 60 patients with high-tension glaucoma (HTG), and 62 HSs were included in the prospective clinical study, and ICP was measured non-invasively by two-depth transcranial Doppler (TCD). Results: The mean ICP of NTG patients (9.42 &plusmn, 2.83 mmHg) was significantly lower than that of HSs (10.73 &plusmn, 2.16 mmHg) (p = 0.007). The mean ICP of HTG patients (8.11 &plusmn, 2.68 mmHg) was significantly lower than that of NTG patients (9.42 &plusmn, 2.83 mmHg) (p = 0.008) and significantly lower than that of HSs (10.73 &plusmn, 2.16 mmHg) (p &lt, 0.001). Conclusions: An abnormal ICP value could be one of the many influential factors in the optic nerve degeneration of NTG patients and should be considered as such instead of just being regarded as a &ldquo, low ICP&rdquo

Yoko Ikeda,1,2,* Kazuhiko Mori,1,* Kaori Tada,3 Morio Ueno,1 Shigeru Kinoshita,4 Chie Sotozono1 1Department of Ophthalmology, Kyoto Prefectural University of Medicine, 2Oike-Ganka Ikeda Clinic, 3Department of Ophthalmology, Japanese Red Cross Society Kyoto Daini Hospital, 4Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan *These authors contributed equally to this work Purpose: To evaluate and compare the intraocular pressure (IOP) reduction efficacy and safety between the ophthalmic solutions 0.005% latanoprost (Lat) and 0.0015% tafluprost (Taf) in Japanese patients with normal-tension glaucoma (NTG).Methods: In this randomized nonmasked study, we prospectively enrolled 30 Japanese NTG patients who had used Lat monotherapy for more than 4 weeks, and randomly divided them into the following two groups: 1) Lat-to-Taf group (LT group) and 2) Taf-to-Lat group (TL group). At the beginning of the study, both groups were switched from initial Lat to Lat or Taf for 12 weeks, and then switched over to the other drug (crossover) for 12 additional weeks. At0,4, 12, 16, and 24 weeks, we evaluated each patient’s IOP, conjunctival injection, and corneal epitheliopathy score, and at 0, 12, and 24 weeks, we evaluated their eyelash changes and pigmentation of the eyelids and irises.Results: The mean IOP of the LT group (15 eyes) was 10.5, 10.6, and 11.1 mmHg, at 0, 12, and 24 weeks, respectively, whereas that of the TL group (15 eyes) was 11.7, 11.1, and 10.5 mmHg at 0, 12, and 24 weeks, respectively. No significant differences were found between the two groups and in the intragroup comparisons. Moreover, no significant differences were found between Lat and Taf in regard to the conjunctival injection score and corneal epitheliopathy score. Eyelash changes and eyelid and iris pigmentation were similar in both groups.Conclusion: The findings of this study show that Lat and Taf have equivalent efficacy and safety in Japanese patients with NTG. Keywords: latanoprost, tafluprost, normal-tension glaucoma, crossover

Glaucomatous optic neuropathy is the most commonly acquired optic neuropathy encountered in clinical practice. It is the second leading cause of blindness globally, after cataracts, but it presents a greater public health challenge than cataracts, because the blindness it causes is irreversible. It has pathogenesis still largely unknown and no established cure. Alterations in serum antibody profiles, upregulation, and downregulation have been described, but it still remains elusive if the autoantibodies seen in glaucoma are an epiphenomenon or causative. Hypertension, diabetes, and hearing disorders also are associated. This review is a glaucoma update with focus about the recent advances in the last 15 years.

As ocular hypertension refers to a condition in which the intraocular pressure is consistently elevated but without development of glaucoma, study of it may provide important clues to factors that may play a protective role in glaucoma. β-amyloid, one of the key histopathological findings in Alzheimer's disease, has been reported to increase by chronic elevation of intraocular pressure in animals with experimentally induced ocular hypertension and to cause retinal ganglion cell death, pointing to similarities in molecular cell death mechanisms between glaucoma and Alzheimer's disease. On the other hand, recent studies have reported that intracranial pressure is higher in patients with ocular hypertension compared with controls, giving rise to the idea that elevated intracranial pressure may provide a protective effect for the optic nerve by decreasing the trans-lamina cribrosa pressure difference. The speculation that the higher intracranial pressure reported in ocular hypertension patients may protect against glaucoma mainly through a lower trans-lamina cribrosa pressure difference remains at least questionable. Here, we present an alternative viewpoint, according to which the protective effect of higher intracranial pressure could be due, at least in part, to a pressure-independent mechanism, namely faster cerebrospinal fluid production leading to increased cerebrospinal fluid turnover with enhanced removal of potentially neurotoxic waste products that accumulate in the optic nerve. This suggests a new hypothesis for glaucoma, which, just like Alzheimer's disease, may be considered then as an imbalance between production and clearance of neurotoxins, including β-amyloid. If confirmed, then strategies to improve cerebrospinal fluid flow are reasonable and could provide a new therapeutic approach for stopping the neurotoxic β-amyloid pathway in glaucoma.

As ocular hypertension refers to a condition in which the intraocular pressure is consistently elevated but without development of glaucoma, study of it may provide important clues to factors thatmay play a protective role in glaucoma. beta-amyloid, one of the key histopathological findings in Alzheimer's disease, has been reported to increase by chronic elevation of intraocular pressure in animals with experimentally induced ocular hypertension and to cause retinal ganglion cell death, pointing to similarities in molecular cell death mechanisms between glaucoma and Alzheimer's disease. On the other hand, recent studies have reported that intracranial pressure is higher in patients with ocular hypertension compared with controls, giving rise to the idea that elevated intracranial pressure may provide a protective effect for the optic nerve by decreasing the trans-lamina cribrosa pressure difference. The speculation that the higher intracranial pressure reported in ocular hypertension patients may protect against glaucomamainly through a lower trans-lamina cribrosa pressure difference remains at least questionable. Here, we present an alternative viewpoint, according to which the protective effect of higher intracranial pressure could be due, at least in part, to a pressure-independent mechanism, namely faster cerebrospinal fluid production leading to increased cerebrospinal fluid turnover with enhanced removal of potentially neurotoxic waste products that accumulate in the optic nerve. This suggests a new hypothesis for glaucoma, which, just like Alzheimer's disease, may be considered then as an imbalance between production and clearance of neurotoxins, including beta-amyloid. If confirmed, then strategies to improve cerebrospinal fluid flow are reasonable and could provide a new therapeutic approach for stopping the neurotoxic beta-amyloid pathway in glaucoma.

Purpose To characterize differences in the lamina cribrosa (LC) morphology between healthy, ocular hypertension (OHT), and naive normal-tension glaucoma (NTG) eyes. Methods Each group consisted of 80 eyes of 80 participants who were matched for age, sex, and axial length. The participants underwent enhanced-depth-imaging volume scanning of the optic nerve head using spectral-domain optical coherence tomography. The lamina cribrosa curvature index (LCCI) and lamina cribrosa thickness (LCT) were measured in horizontal B-scan images spaced equidistantly across the vertical diameter of the optic disc. Results The LCCIs in all seven planes were smaller in both OHT and healthy eyes than in NTG eyes (all P < 0.001), and did not differ significantly between the OHT and healthy eyes. The LCTs in all three planes were greatest in OHT eyes followed by healthy and then NTG eyes (all P < 0.001). Overall, the larger LCCI was associated with smaller LCT (P < 0.001). Conclusions The LC was thin and steeply curved in NTG eyes than in healthy and OHT eyes. In OHT eyes, the LC was thick, and its curvature was comparable to healthy eyes. Longitudinal studies are required to examine whether the straight and thickened LCs in OHT eyes precede the onset of OHT or are a protective response to elevated intraocular pressure.

Structural differences have been reported between primary open angle glaucoma (POAG) and normal tension glaucoma (NTG), and biomechanical differences between POAG and NTG may account for why NTG patients are more vulnerable to lower intraocular pressure (IOP). This study compared the biomechanical properties of POAG and NTG patients using the Corvis scheimpflug technology (ST) non-contact Scheimpflug-based tonometer, and determined the factors associated with these properties. In this retrospective cross-sectional study, 46 eyes with POAG, 54 eyes with NTG, and 61 control eyes were included. A non-contact Scheimpflug-based tonometer was used to examine and compare the corneal biomechanical responses in the POAG, NTG, and normal groups. We used univariate and multivariate regression analyses to determine the factors associated with the deformation amplitude in each group. Baseline characteristics, including age, IOP, spherical equivalent, keratometry, axial length, and central corneal thickness, were similar among the 3 groups. Severity of glaucoma, as measured by mean deviation, was similar between POAG and NTG groups. Applanation 1 velocity and deformation amplitude were significantly smaller in POAG (0.13 ± 0.02 and 1.06 ± 0.14, respectively) than NTG (0.14 ± 0.01 and 1.13 ± 0.11, respectively) and normal groups (0.14 ± 0.02 and 1.13 ± 0.10, respectively). Radius of curvature was significantly larger in the POAG group compared to the normal group. In normal controls, IOP and keratometry were significant factors related to deformation amplitude. In POAG eyes, IOP was a statistically significant predictor of deformation amplitude. In NTG eyes, however, IOP , keratometry, and axial length were statistically significant predictors of deformation amplitude. POAG eyes showed less deformable corneas compared to NTG and normal controls. IOP was significantly correlated with deformation amplitude in all groups. However, axial length was positively correlated with deformation amplitude only in NTG eyes. Characterization of the differences in biomechanical properties between POAG and NTG may contribute to a better understanding of the underlying pathophysiologies associated with these diseases.

Glaucoma is one of the leading causes of irreversible blindness in the world. It is characterized by the progressive loss of retinal ganglion cells (RGCs), mainly through the process of apoptosis. Glaucoma patients often come to clinical attention when irreversible loss of visual function has been already established; therefore, early recognition of RGC apoptosis is inordinately important in disease prevention. The novel technology called Detection of Apoptosing Retinal Cells (DARC) allows real-time in vivo quantification of apoptosing cells through the use of a fluorescent biomarker and a confocal scanning ophthalmoscope. A recent Phase I clinical trial has evaluated the safety of DARC and its ability to detect retinal apoptosis in glaucoma patients and healthy volunteers. Results suggest that DARC may have potential in the early detection of glaucoma, which could help alleviate the medical, social, and economic burden associated with this blinding condition.

Background: Glaucoma is the leading cause of irreversible blindness worldwide. Several techniques exist for the diagnosis and follow-up of patients. Optical coherence tomography (OCT) angiography (OCTA) is a recently developed technique that provides a quantitative assessment of the microcirculation of the retina and choroid in a fast, noninvasive way. Despite it being a novel technique, several publications have already been done in the glaucoma field. However, a summary of findings is currently lacking. Aims: To perform a literature review to assess the role of OCTA in glaucoma diagnosis and follow-up. Methods: A database search was carried out using MEDLINE, Embase, and Web of Science, including all original works registered until July 23, 2017. Results: OCTA (1) has a high repeatability and reproducibility, (2) has good discriminatory power to differentiate normal eyes from glaucoma eyes, (3) is more strongly correlated with visual function than conventional OCT, (4) has good discriminatory power to differentiate early-glaucoma eyes from normal eyes (i.e., at least equal to that of OCT), (5) reaches a floor effect at a more advanced disease stage than OCT, and (6) is able to detect progression in glaucoma eyes. Conclusion: OCTA shows potential to become a part of everyday glaucoma management.

Glaucoma is thought to be the main cause of severe visual impairment or permanent loss of vision. Current therapeutic strategies are not sufficient to protect against glaucoma. Thus, new therapies and potential novel therapeutic targets must be developed to achieve progress in the treatment of this insidious disease. This study was undertaken to verify whether the time of administration of an extract from predegenerated rat sciatic nerves as well as exposure time of this extract onto retinal ganglion cells (RGCs) influences the survival of RGCs in a rat glaucoma model. We have demonstrated that extract obtained from the predegenerated sciatic nerves protects RGCs in a rat glaucoma model. The neuroprotective effect depends mostly on the time of administration of the extract and less clearly on the time of exposure to the extract and is associated with stimulation of endogenous BDNF expression both in RGCs and glial cells. The 14th day following glaucoma induction represents a therapeutic window for effective treatment in a glaucoma model. Mass Spectrometry analysis demonstrated that metallothionein 2 (MT2) may be a key molecule responsible for neuroprotective effects on RGC survival.

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

Glaucoma (GL) and atrial fibrillation (AF) are diseases of significant social importance. Cardiovascular disorders such as systemic hypertension, hypotension, increased blood viscosity, vasospasm, and diabetes are potential risk factors of GL, especially when intraocular pressure is not elevated. Only a few studies have reported a possible connection between cardiac arrhythmias and GL. The purpose of this study was to evaluate the risk of GL in patients with AF. A total of 117 patients were included in the study, 79 with AF (AF group) and 38 with sinus rhythm (Control group), matched for age and sex. The mean ± standard deviation age was 73.6 ± 7.2 and 71.6 ± 4.7 years for the AF and control groups, respectively. There were no statistically significant differences in the percentage of systemic hypertension, congestive heart failure, diabetes mellitus type 2, or vascular disease between the groups. Patients were examined for the presence of normal-tension glaucoma (NTG) by an ophthalmologist. NTG was confirmed in 40 patients (34.2%) in the entire group, with 35 (44.3%) in the AF group and 5 (13.15%) in the Control group. The incidence of NTG was significantly higher in the AF group (P = .0221). Women represented 60% of GL patients in the AF group and 80% in the control group. There were no significant differences in intraocular pressure between the groups (mean ± standard deviation, 14.3 ± 2.3 vs. 14.2 ± 2.8 mmHg, P = .4202). Approximately three-fourths of patients with AF and NTG had early visual field damage based on the Hodapp classification. AF, independent of other known cardiovascular risk factors, increases the risk of developing NTG. Many AF patients do not have conspicuous symptoms of GL, so understanding the possible risk of its development is critical because early detection might help to prevent later visual impairment and even irreversible blindness.

Purpose A common question of patients to their physician is what they can do themselves against glaucoma, except taking their daily medication. However, for ophthalmologists, it is often hard to give their patients an advice on their dietary intake. To help ophthalmologists in answering this question, an overview of the current scientific literature on the association of nutrients with glaucoma is presented. Methods A comprehensive systematic review was conducted in which articles published up to September 2017 were identified in PubMed and reference lists. Nutrients were categorized into minerals and trace elements, nutrition with antioxidative properties and omega-fatty acids. Results The literature search revealed a total of 407 articles of which a total of 46 met the inclusion criteria. Most of these articles studied the effect of nutrients on open-angle glaucoma. Many trace elements have been investigated in the literature, but the most interesting are selenium and iron (both may increase the risk of glaucoma). Investigated nutrients with antioxidative properties and omega-fatty acids included glutathione, nitric oxide, carotenoids, flavonoids, and omega-3 and omega-6 fatty acids. Of these, glutathione, nitric oxide, and flavonoids had a significant protective effect on glaucoma. Conclusion Intake of selenium and iron may increase the risk of glaucoma, though, only few studies have been done on this topic. Nitric oxide present in other dark green leafy vegetables seems to have a beneficial effect on glaucoma. However, the evidence for an association of dietary intake with glaucoma is still not strong. More (longitudinal and randomized clinical trials) studies are required to make the presented findings clinically applicable.

Author(s): Rao, Harsha L; Pradhan, Zia S; Weinreb, Robert N; Riyazuddin, Mohammed; Dasari, Srilakshmi; Venugopal, Jayasree P; Puttaiah, Narendra K; Rao, Dhanaraj AS; Devi, Sathi; Mansouri, Kaweh; Webers, Carroll AB | Abstract: PurposeTo compare the diagnostic abilities of vessel density measurements of the optic nerve head (ONH), peripapillary and macular regions on optical coherence tomography (OCT) angiography in eyes with primary open angle glaucoma (POAG) with that of the ONH rim area, peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (GCC) thickness measurements.MethodsIn a cross sectional study, 78 eyes of 50 control subjects and 117 eyes of 67 POAG patients underwent vessel density and structural measurements with spectral domain OCT. POAG was diagnosed based on the masked evaluation of optic disc stereo photographs. Area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities of vessel densities in ONH, peripapillary and macular regions were compared with rim area, RNFL and GCC thickness.ResultsThe AUC (sensitivity at 95% specificity) of average vessel densities within the ONH, peripapillary and macular region were 0.77 (31%), 0.85 (56%) and 0.70 (18%) respectively. The same of ONH rim area, average RNFL and GCC thickness were 0.94 (83%), 0.95 (72%) and 0.93 (62%) respectively. AUCs of vessel densities were significantly lower (pl0.05) than that of the corresponding structural measurements. Pre-treatment IOP (coefficient: 0.08) affected (pl0.05) the AUC of ONH vessel density but not of any other vessel density or structural measurements.ConclusionsDiagnostic abilities of ONH, peripapillary and the macular vessel densities in POAG were significantly lower than ONH rim area, peripapillary RNFL and macular GCC measurements respectively. At fixed levels of glaucoma severity, the diagnostic ability of the ONH vessel density was significantly greater in eyes with higher pre-treatment IOP.

EDITOR: We read with great interest the paper recently published in Clinical and Experimental Optometry by McMonnies.2016 We are grateful to the author for sharing his valuable review article with ...

The pathophysiology of primary open-angle glaucoma is still largely unknown, although a joint contribution of vascular, biomechanical, and biochemical factors is widely acknowledged. Since glaucoma is a leading cause of irreversible blindness worldwide, exploring its underlying pathophysiological mechanisms is extremely important and challenging. Evidence from recent studies appears supportive of the hypothesis that a "glymphatic system" exists in the eye and optic nerve, analogous to the described "glymphatic system" in the brain. As discussed in the present paper, elucidation of a glymphatic clearance pathway in the eye could provide a new unifying hypothesis of glaucoma that can incorporate many aspects of the vascular, biomechanical, and biochemical theories of the disease. It should be stressed, however, that the few research data currently available cannot be considered as proof of the existence of an "ocular glymphatic system" and that much more studies are needed to validate this possibility. Even though nothing conclusive can yet be said, the recent reports suggesting a paravascular transport system in the eye and optic nerve are encouraging and, if confirmed, may offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder.

The pathophysiology of primary open-angle glaucoma is still largely unknown, although a joint contribution of vascular, biomechanical, and biochemical factors is widely acknowledged. Since glaucoma is a leading cause of irreversible blindness worldwide, exploring its underlying pathophysiological mechanisms is extremely important and challenging. Evidence from recent studies appears supportive of the hypothesis that a “glymphatic system” exists in the eye and optic nerve, analogous to the described “glymphatic system” in the brain. As discussed in the present paper, elucidation of a glymphatic clearance pathway in the eye could provide a new unifying hypothesis of glaucoma that can incorporate many aspects of the vascular, biomechanical, and biochemical theories of the disease. It should be stressed, however, that the few research data currently available cannot be considered as proof of the existence of an “ocular glymphatic system” and that much more studies are needed to validate this possibility. Even though nothing conclusive can yet be said, the recent reports suggesting a paravascular transport system in the eye and optic nerve are encouraging and, if confirmed, may offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder.

Toyoaki Tsumura,1 Keiji Yoshikawa,2 Tairo Kimura,3 Hirotaka Suzumura,4 Miwako Kawashima,5 Mami Nanno,6 Kiyotaka Ishijima,7 Ryuji Takeda81Fussa Hospital, Tokyo, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Ueno Eye Clinic, Tokyo, Japan; 4Suzumura Eye Clinic, Tokyo, Japan; 5Nakano General Hospital, Tokyo, Japan; 6Kagurazaka Minamino Eye Clinic, Tokyo, Japan; 7Irumagawa Hospital, Saitama, Japan; 8Department of Biological Chemistry, Faculty of Agriculture, Kinki University, Nara, JapanBackground: To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG) patients.Methods: Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP) of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation.Results: Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years) completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, P

Purpose To report on the optic canal cross-sectional area (OCA) in Caucasian patients with normal-tension glaucoma (NTG) compared with Caucasian control subjects without known optic nerve (ON) diseases. Methods Retrospective analysis of computed tomographic images of the cranium and orbits in 56 NTG patients (30 females and 26 males; 99 of 112 eyes; mean age 67.7 ± 11.1 years). Fifty-six age- and gender-matched subjects (mean age: 68.0 ± 11.2 years) without known ON diseases served as controls. The OCA at the orbital opening was measured in square millimeters by using the tool “freehand.” Statistical analysis was performed by using the independent two-tailed t-test. Results The mean orbital opening OCA in NTGs measured 14.5 ± 3.5 mm2 (right OCA: 14.4 ± 3.6 mm2, left OCA: 14.5 ± 3.4 mm2) and in controls measured 18.3 ± 2.6 mm2 (right OCA: 18.5 ± 2.7 mm2, left OCA: 18.1 ± 2.5 mm2). The difference between NTG and controls was statistically significant (p

Primary open angle glaucoma (POAG) is a complex progressive optic nerve neuropathy triggered by both environmental and genetic risk factors. Several ocular tissues, including the ciliary body, trabecular meshwork and optic nerve head, and perhaps even brain tissues, are involved in a chain of pathological events leading to POAG.Genetic risk evidence for POAG came from family linkage-studies implicating a small number of disease genes (MYOC, OPEN, WDR36). Recent Genome Wide Association Studies (GWAS) identified a large number of new POAG loci and disease genes, such as CAV1, CDKN2B and GAS7. In the current study, we reviewed over 120 family and GWA studies. We selected in total 65 (candidate) POAG disease genes and proceeded to assess their function, mRNA expression in POAG relevant eye tissues and possible changes in disease state. We found that the proteins corresponding to these 65 (candidate) POAG disease genes take part in as few as four common functional molecular networks. Functions attributed to these 4 networks were developmental (dys)function, lipid metabolism, and inflammatory processes. For the 65 POAG disease genes, we reviewed the available (transgenic) mouse models of POAG, which may be useful for future functional studies. Finally, we showed that the 65 (candidate) POAG genes substantially increased the specificity and sensitivity of a discriminative POAG risk test. This suggests that personal risk assessment and personalized medicine for POAG are on the horizon. Taken together, the data presented are essential to comprehend the role of genetic variation in POAG, and may provide leads to understand the pathophysiology of POAG as well as other neurodegenerative disorders, such as Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.

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

In randomized, controlled trials of open-angle glaucoma (OAG) or ocular hypertension (OHT), bimatoprost 0.01 % improved tolerability while retaining the intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.03 %. Given geographic/racial differences in glaucoma presentation, the APPEAL study assessed the occurrence and severity of hyperemia produced by bimatoprost 0.01 %, and its efficacy, in the Taiwanese clinical setting. In this multicenter, open-label, observational study, treatment-naive and previously treated patients with OHT or OAG received once-daily bimatoprost 0.01 % for 12 weeks. Hyperemia (primary endpoint) was graded at baseline, week 6, and week 12 using a photonumeric scale (0, +0.5, +1, +2, +3), grouped (≤ +1, none to mild; ≥ +2, moderate to severe), and reported as unchanged from baseline, improved, or worsened. IOP assessments followed the same schedule. Supplemental efficacy analyses were conducted based on previous therapies. The intent-to-treat population (N = 312) included treatment-naive (13.5 %) and previously treated (86.5 %) patients; mean age was 53.3 years. At baseline, 46.3 % of previously treated patients were receiving prostaglandin analog (PGA) monotherapy. At week 12, 91.2 %, 5.9 %, and 2.9 % of treatment-naive patients exhibited unchanged, worsened, and improved hyperemia from baseline, respectively; 77.9 %, 12.9 %, and 9.2 % of previously treated patients showed no change, worsening, and improvement, respectively. There were no statistically significant shifts in hyperemia severity in either group, or in subgroups based on previous use of any PGA, any non-PGA, latanoprost, or travoprost monotherapies. In treatment-naive patients, mean IOP reduction from baseline (18.0 ± 3.8 mm Hg) was 3.6 mm Hg at week 12 (P

An 80-year-old woman with normal-tension glaucoma was transferred to our clinic 9 years ago. She exhibited progressive visual field defect despite intraocular pressure in both eyes remaining stable in the low teens after treatment with prostaglandin-derivative eye drops. Increased short-term fluctuation in optic nerve head (ONH) blood flow was detected using laser speckle flowgraphy. After the patient was administered kallidinogenase tablets, the fluctuation was reduced and her visual field defect was ameliorated. However, the fluctuation increased and the visual field defect deteriorated after the patient discontinued the medication. The increased short-term fluctuation in ONH blood flow seemed to be associated with the development of glaucomatous visual field defect in this case.

There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.

Tomoko Naito,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Mami Nanno,4 Tairo Kimura,5 Hirotaka Suzumura,6 Yuzo Umeda,7 Fumio Shiraga1 1Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 4Kagurazaka Minamino Eye Clinic, 5Ueno Eye Clinic, 6Suzumura Eye Clinic, Tokyo, Japan; 7Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan Purpose: To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma.Patients and methods: In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction.Results: A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran–Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03–1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94–0.99) had a significant association with MD slope deterioration.Conclusion: In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.Keywords: primary open-angle glaucoma, normal-tension glaucoma, myopia, refraction, visual field progression, MD slope, intraocular pressure reduction rate

Background To investigate the incidence and risk factors of glaucoma in normal-tension glaucoma (NTG) suspect patients who had been lost-to-follow-up for at least 24 months. Methods Seventy-two eyes of 72 NTG suspect patients who returned to the hospital after at least 24 months of follow-up loss were enrolled in this study between January 2009 and June 2013. The data were collected retrospectively. The incidence of glaucoma was investigated using a comprehensive glaucoma evaluation in lost-to-follow-up NTG suspect patients. The patients were classified into the glaucoma group, who developed glaucoma during the study period, and the glaucoma suspect group, who did not, to analyse the risk factors for glaucoma. Results The number of patients who developed glaucoma was 7 (9.7 %) out of the 72 NTG suspect patients who had been mean lost-to-follow-up for 44 months. The rate of progression from suspected to glaucoma was 2.6 %/year. In the glaucoma group, the baseline intraocular pressure (IOP) was 18.43 ± 2.44 mmHg, and the average retinal nerve fiber layer (RNFL) thickness was 78.14 ± 7.60 μm; in the glaucoma suspect group, the baseline IOP was 14.95 ± 2.47 mmHg, and the average RNFL thickness was 92.55 ± 7.65 μm. The study results showed that the glaucoma group had higher baseline IOP and a thinner average RNFL (p = 0.003; p

International audience; PURPOSE. To investigate the characteristics of the prelamina and lamina cribrosa (LC) of both eyes in glaucoma patients with unilateral visual field (VF) defect.METHODS. Forty-one subjects diagnosed with primary open-angle glaucoma with unilateral VF loss and 41 age-matched healthy control subjects were scanned by swept-source optical coherence tomography (SS-OCT). All eyes were divided into three groups: VF-affected glaucomatous eyes (group A, n = 41), perimetrically unaffected fellow eyes (group B, n = 41), and healthy control eyes (group C, n = 41). The anterior prelaminar depth (APLD) and LC depth (LCD) were measured at the center of the reference line (the Bruch's membrane opening plane). The prelaminar tissue thickness (PTT) was obtained by subtracting the APLD from the LCD. The APLD, LCD, and PTT were compared among these groups.RESULTS. The APLD and LCD were significantly greater in group A than in the other groups (group B, P < 0.001; group C, P < 0.001). The prelaminar tissue was significantly thinner in group A than in the other groups (group B, P = 0.007; group C, P < 0.001). Also, the prelaminar tissue was significantly thinner in group B than in group C (P = 0.003). Multivariate analysis demonstrated a significant association between PTT and initial IOP among the overall study population (P < 0.05).CONCLUSIONS. In the fellow eyes with unilateral glaucoma patients, APLD was significantly greater, and the prelaminar tissue was significantly thinner, than in the healthy control eyes. Our findings suggest that subclinical or preperimetric changes of the LC and/or prelaminar tissue are already present in the fellow eyes with unilateral glaucoma.