Chinese expert consensus on the diagnosis and treatment of normal tension glaucoma (2025)

BackgroundTo investigate the association between estimated trans-lamina cribrosa pressure difference (TLCPD) and prevalence of normal tension glaucoma (NTG) with low-teen and high-teen intraocular pressure (IOP) using a population-based study design.MethodsA total of 12,743 adults (≥ 40 years of age) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Using a previously developed formula, cerebrospinal fluid pressure (CSFP) in mmHg was estimated as 0.55 × body mass index (kg/m2) + 0.16 × diastolic blood pressure (mmHg)—0.18 × age (years)—1.91. TLCPD was calculated as IOP–CSFP. The NTG subjects were divided into two groups according to IOP level: low-teen NTG (IOP ≤ 15 mmHg) and high-teen NTG (15 mmHg < IOP ≤ 21 mmHg) groups. The association between TLCPD and the prevalence of NTG was assessed in the low- and high-teen IOP groups.ResultsIn the normal population (n = 12,069), the weighted mean estimated CSFP was 11.69 ± 0.04 mmHg and the weighted mean TLCPD 2.31 ± 0.06 mmHg. Significantly higher TLCPD (p < 0.001; 6.48 ± 0.27 mmHg) was found in the high-teen NTG compared with the normal group. On the other hand, there was no significant difference in TLCPD between normal and low-teen NTG subjects (p = 0.395; 2.31 ± 0.06 vs. 2.11 ± 0.24 mmHg). Multivariate logistic regression analysis revealed that TLCPD was significantly associated with the prevalence of NTG in the high-teen IOP group (p = 0.006; OR: 1.09; 95% CI: 1.02, 1.15), but not the low-teen IOP group (p = 0.636). Instead, the presence of hypertension was significantly associated with the prevalence of NTG in the low-teen IOP group (p < 0.001; OR: 1.65; 95% CI: 1.26, 2.16).ConclusionsTLCPD was significantly associated with the prevalence of NTG in high-teen IOP subjects, but not low-teen IOP subjects, in whom hypertension may be more closely associated. This study suggests that the underlying mechanisms may differ between low-teen and high-teen NTG patients.

The "not quite" natural history of normal-tension glaucoma.

Aim The aim of this study is to clinically investigate the challenges and pitfalls of normal-tension glaucoma (NTG) diagnostic methods by ophthalmic clinical and investigative examinations. Setting This study was conducted at Al-Agouza Police Authority Hospital and Badr University Hospital. Methods A cross-sectional comparative study between the diagnosis of normal nonglaucoma patients and NTG. It included 40 normal nonglaucoma patients’ eyes as controls and 40 NTG patients’ eyes who met inclusion criteria. They were assessed by a complete ophthalmic exam., visual field (VF), and optical coherence tomography (OCT) variables between January 2022 and September 2022. Results The median age of the control group was 38 years old, while that of glaucomatous patients was 41 years old. The mean intraocular pressure (IOP) for the normal group was 15.53 mmHg (±1.935), while that for the glaucomatous group was 16.85 mmHg (±1.703). The intraocular pressure was considerably higher in the NTG group compared with the control (P = 0.0017). The mean deviation (MD) in dB of VF loss was considerably higher in the NTG group compared with the control (P = 0.0001). Also, the mean standard deviation (MSD) was considerably varied between the two groups (P &lt; 0.0001). The average Retinal Nerve Fiber Layer (RNFL) in the NTG group, with a mean of 72.3 JOURNAL/jeos/04.03/01735167-202316030-00002/inline-graphic1/v/2023-09-27T140929Z/r/image-jpeg (±10.239) was significantly lower than in the control group with a mean of 102.025 JOURNAL/jeos/04.03/01735167-202316030-00002/inline-graphic2/v/2023-09-27T140929Z/r/image-jpeg (±7.454), P = 0.0001. Optic Disc Parameters: The Cup Area (mm2) was significantly wider in the NTG group with a mean of 1.62 (±0.476) than in the control with a mean of 1.297 (±0.44), P = 0.0024. Also, the Rim Area was significantly smaller in the NTG group with a mean of 0.614 (±0.342) than in the control with a mean of 1.135 (±0.319), P = 0.0024. The Cup/disc ratio was significantly larger in the NTG group than in the control group (P &lt; 0.0001). The average Ganglion cell complex (GCC) was considerably thinner in the NTG patients in comparison to the controls (P = 0.0001). Conclusion The effects of NTG on VF and optic nerve seems to be more intensive. More focal notches and disc hemorrhage were noted in NTG. In the NTG group, the Cup Area was potentially wider, the rim area was significantly thinner, and the Cup/disc ratio was significantly larger.

Prevalence of Normal-Tension Glaucoma in Patients With Primary Aldosteronism

Aim: Prevalence of Open angle glaucoma with normal intraocular pressure in Peshawar Methodology: It is a cross sectional study. It is done at Physiology Department, Khyber Medical College, Peshawar in collaboration with Ophthalmology deptt. Khyber Teaching Hospital, Peshawar Study period: six months Sample size: 394 cases attended the department of Ophthalmology, Khyber Teaching Hospital Peshawar. Out of 394 patients, 100 patients were included in this study. Results: There were 33(33%) males and 67(67%) females in the study. There were 27(27%) patients lying in the age range of 35-45 years, 46(46%) were in 46-55 years and 27 (27%) patients of 56-65 years. The mean age of patients was 51.21±8.12. All patients were with normal tension glaucoma. There were 29(29%) cases who had a positive family history of glaucoma. The “mean IOP” of the eye on the right side was 17.15±1.78mmHg and the “mean IOP” of the eye on the left side was 17.30±1.94mmHg. Conclusion: Prevalence of normal tension glaucoma (NTG) was 25.4% in Peshawar and its surroundings. Most of the patients were elderly females and 29 (29%) cases had a positive family history of glaucoma. Keywords: Open angle glaucoma, normal tension glaucoma, prevalence

The high prevalence of normal tension glaucoma (NTG) in the Japanese requires special screening tests other than measurements of only the intraocular pressure (IOP). This study was carried out to determine whether there is a significant association between the axial length of the eye and the presence of NTG. We reviewed the medical records of all patients who were scheduled to undergo cataract surgery alone or combined with glaucoma surgery at the same time. There were 87 patients with NTG, 137 with POAG, and 978 non-glaucomatous control cases. The axial length, IOP, curvature of the anterior corneal surface, age, and gender were determined at the time of the operation. If both eyes had surgery, data from only the right eyes were analyzed. An association of these parameters with NTG and POAG was analyzed by logistic regression analysis. The three groups were analyzed for differences in the axial length using the Kruskal-Wallis test followed by the Mann-Whitney U test. The axial length was significantly associated with NTG (odds = 1.24, P = 0.002) and POAG (odds = 1.28, P = 0.001). The incidence of either POAG or NTG was significantly higher in patients with axial lengths >or=25.0 mm (odds = 2.29, P < 0.001, Fisher's exact test). The age at the time of cataract surgery was weakly but significantly correlated negatively with the axial length (r = -0.24, P < 0.001, Pearson's correlation coefficient test). Men had significantly longer axial lengths than women. Long axial lengths can be considered a risk factor for NTG and POAG, and patients with long axial lengths need to be carefully examined for glaucoma.

To explore the prevalence of normal tension glaucoma (NTG) among patients with obstructive sleep apnea syndrome (OSAS) and to examine OSAS as a risk factor of NTG. Fifty-one consecutive white patients with OSAS were compared with 40 healthy subjects. All the study subjects underwent blood gas analysis, polysomnography, oxyhemoglobin saturation, and an ophthalmologic examination including visual field, visually evoked potential (VEP), and pattern electroretinography (PERG) and disc analysis with the Heidelberg Retina Tomograph II. Three of 51 OSAS patients (5.9%) had NTG. No patient in the control group had OSAS or NTG. The severity of OSAS correlated with intraocular pressure, the mean deviation of the visual field, the cup/disk ratio and the mean of the retinal nerve fiber layer thickness (P<0.01 to 0.001). Apnea hypopnea index and intraocular pressure were significantly greater in OSAS patients with abnormal VEP and PERG, compared to those with normal PERG and VEP. The present study suggests that the prevalence of NTG in our OSAS patients is higher than expected in a white population of the same age and that OSAS may be an important risk factor for NTG. Our data underline the importance of taking an accurate sleep history from patients with NTG and referring patients with sleep disturbance for polysomnography.

To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet), Denmark from 1980 to 2001. The rate of a subsequent diagnosis of dementia as recorded in nationwide health care registers from 1980 to 2005 was estimated and compared with the rate for the general population [standard mortality rate (SMR) = observed number of cases of dementia/expected number of cases of dementia]. The 69 patients had a median age of 64 years (quartiles 57 and 73) at the time of the diagnosis, and the average follow-up period was 12.7 years. The SMR(dementia) was 0.20 (95% CI 0.01-1.11). No patient developed AD. Normal tension glaucoma was not associated with an increased risk of developing dementia/AD.

Purpose. To determine the presence and type of glaucoma in a cohort of adult Chinese subjects with systemic hypertension. Methods. This prospective cohort study included 200 hypertensive Chinese adults aged >40 years old who underwent screening via frequency doubling technology (FDT) perimetry and intraocular pressure (IOP) measurement by noncontact tonometry (NCT) in a general outpatient clinic. Those with IOP > 21 mmHg and/or visual field (VF) defects on FDT were referred for complete ophthalmological examination. The diagnosis of glaucoma was based on an abnormal VF on Humphrey Field Analyzer (HFA) by Hodapp-Parrish-Anderson's criteria and an increased vertical cup-disc ratio (VCDR). Results. The mean age of the subjects was 64.66 ± 9.47 years, and the male:female ratio was 92 : 108. All patients were hypertensive with a mean blood pressure (BP) of 131.1 ± 15.1/76.6 ± 11.1 mmHg whilst on systemic antihypertensive medication. Of the 111 patients that had an abnormal initial screening, 14 (7.9%) were confirmed to have glaucoma with the highest prevalence of normal tension glaucoma (NTG) (6.2%), followed by primary angle closure glaucoma (PACG) (1.1%) and primary open angle glaucoma (POAG) (0.5%). The positive predictive value of FDT perimetry was 71%. Conclusion. Nearly 8% of the adults with systemic hypertension had glaucoma, and NTG was the most prevalent type.

Glaucoma is an optic neuropathy and the second major cause of blindness worldwide next to cataracts. The protection from retinal ganglion cell (RGC) loss, one of the main characteristics of glaucoma, would be a straightforward treatment for this disorder. However, the clinical application of neuroprotection has not, so far, been successful. Here, we report that apolipoprotein E-containing lipoproteins (E-LPs) protect primary cultured RGCs from Ca(2+)-dependent, and mitochondrion-mediated, apoptosis induced by glutamate. Binding of E-LPs to the low density lipoprotein receptor-related protein 1 recruited the N-methyl-d-aspartate receptor, blocked intracellular Ca(2+) elevation, and inactivated glycogen synthase kinase 3β, thereby inhibiting apoptosis. When compared with contralateral eyes treated with phosphate-buffered saline, intravitreal administration of E-LPs protected against RGC loss in glutamate aspartate transporter-deficient mice, a model of normal tension glaucoma that causes glaucomatous optic neuropathy without elevation of intraocular pressure. Although the presence of α2-macroglobulin, another ligand of the low density lipoprotein receptor-related protein 1, interfered with the neuroprotective effect of E-LPs against glutamate-induced neurotoxicity, the addition of E-LPs overcame the inhibitory effect of α2-macroglobulin. These findings may provide a potential therapeutic strategy for normal tension glaucoma by an LRP1-mediated pathway.

Introduction: Normal Tension Glaucoma (NTG) is a form of glaucoma in which there are distinct demographic characteristics and associated factors to its development. Identifying these characteristics helps early diagnosis and prevention of blindness. Aim of the study is to identify the various demographic characteristics and associated factors with the diagnosis of NTG in patients presenting to the glaucoma clinic of a tertiary hospital. Methods: All consecutive newly diagnosed glaucoma patients attending the eye clinic of EKSUTH, Ado Ekiti, from January 2012 to December 2014 were selected for the study. They all had thorough ocular and systemic examination. The patients with diagnosis of normal tension glaucoma had a protocol prepared for the study administered on them. Demographic data, family history of glaucoma, history of migraine, hypertension, and use of antihypertensive drugs at night were obtained from them. Data were analysed using SPSS version 18 and presented as tables, and figures, in frequencies, and percentage. Result: A total of 1265 patients were newly diagnosed to have glaucoma, of these, 864(68.3%) were POAG, 336(26.6%) were secondary glaucomas, 48(3.8%) normal tension glaucoma, 12(0.9%) angle closure glaucoma and 5(0.4%) were developmental glaucoma. Among the NTG patients, 30(62.5%) were females and 18(37.5%) males, (M:F =1.7:1) Age range was between 30years to 68years, median age of 59.3years. The identifiable associated factors in NTG patients include; family history of glaucoma 33(68.8%), hypertension and use of antihypertensive at night before sleep 24(50%), history suggestive of sleep apnea 6(12.5%), migraine headaches 10(20.8%) and thyroid disease 2(4.2%). No statistically significant association of these factors with severity of visual field defect in the subjects studied. Conclusion: This study suggests that age and positive family history of glaucoma are important demographic characteristics for consideration in diagnosis of NTG.

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.

To determine the prevalence of normal tension glaucoma (NTG) in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) and further investigate whether the severity of OSAHS would increase the risk of glaucoma. Two hundred fifty-six participants were consecutively admitted for polysomnographic exam to diagnose OSAHS. All participants, then underwent a complete ophthalmologic evaluation, including best-corrected visual acuity, intraocular pressure, slit lamp biomicroscopy, gonioscopy, fundoscopy, automated visual field (VF), and retinal nerve fiber layer (RNFL) evaluation. A total of 247 participants were enrolled in the study. Two hundred nine patients were OSAHS and 38 participants were classified as the normal group. Among the OSAHS patients, NTG was found in 12 patients with a prevalence of 5.7%, which was higher than that in the normal group (P=0.003). In the NTG patients, 1 was in the mild, 3 were in the moderate, and 8 were in the severe OSAHS group. There was no glaucoma patient in the normal group. The prevalence of NTG in moderate/severe OSAHS patients was 7.1%, significantly higher (P=0.033) than that in normal/mild OSAHS patients. The mean saturation of oxygen and lowest saturation of oxygen correlated with the average thickness of RNFL in the OSAHS patients. Patients with OSAHS had a high prevalence of NTG, especially in patients with moderate and severe OSAHS. The severity of OSAHS inversely correlated with retinal nerve fiber layer thickness. Clinicians need to consider the possibility of glaucoma in patients with moderate and severe OSAHS.

PURPOSE:To measure lamina cribrosa thickness (LCT) and lamina cribrosa depth (LCD), optic nerve subarachnoid space width (ONSASW) in patients with normal tension glaucoma and in healthy individuals and to compare these data with the results of our own pilot study.&#x0D; MATERIALS AND METHODS:The 1st group included 13 patients (22 eyes) with normal tension glaucoma aged 39 to 88 years (59.8 10.9 years). The 2nd (control) group included 10 healthy people (20 eyes) aged 40 to 59 years (47.9 5.5 years). All subjects underwent structural and functional assessment of the optic nerve head using optical coherent tomograph (OCT) RTVue-100 (Optovue, USA), Humphrey perimeter (HFA II 745i, Germany-USA), and our own modification of Frequency Doubling Technology perimetry. LCT and LCD were measured by OCT RS-3000 Advance (Nidek, Japan). To measure ONSASW we used a cross-sectional image of the optic nerve taken with Magnetic Resonance Imaging (GE Optima MR450w MRI, USA).&#x0D; RESULTS:Differences in the 1st and 2nd groups between the mean values of LCT (234.14 27.73 and 336.25 21.0 m, respectively;p= 0.0000), LCD (461.8 101.7 and 361.65 58.2 m, respectively;p= 0.0004) and ONSASW (1.371 0.035 and 1.52 0.133 mm, respectively;p= 0.011) were statistically significant.&#x0D; CONCLUSION:Patients with normal tension glaucoma had significantly higher LCD value with significantly lower LCT and ONSASW values compared to healthy individuals, which is comparable with the results of our pilot study, and confirms the importance of these morphometric criteria in normal tension glaucoma diagnosis verification.

Medical Treatment of Normal Tension Glaucoma