Peripapillary Perfusion Analysis Using Optical Coherence Tomography Angiography in Patients with Normal Tension Glaucoma.

PURPOSE: This study aimed to assess the difference in the vascular parameters of perfusion in the optic nerve head in normal tension glaucoma (NTG) across disease stages using optical coherence tomography angiography and its correlation with peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: In this retrospective study, 83 eyes with varying stages of NTG (25 mild, 31 moderate, and 27 severe) and 90 healthy eyes were enrolled. The perfusion density (PD) and flux index (FI) of the optic nerve head divided into four sectors were determined. We compared the vascular, structural, and functional parameters between normal and glaucomatous eyes and performed a subgroup analysis among the NTG stages. Pearson correlation coefficient was used to assess the topographic correlation between vascular parameters and RNFL thickness. RESULTS: PD and FI were significantly decreased in the NTG group. Subgroup analysis revealed a significant decrease in vascular parameters in most regions in the NTG group, except for the nasal PD and temporal FI. Post hoc analysis showed a significant decrease in PD in the inferior region across all severity levels (mild vs. moderate, p = 0.012; moderate vs. severe, p = 0.012; mild vs. severe, p < 0.001). PD and FI were strongly correlated with RNFL thickness in all quadrants (all p < 0.001), with the strongest correlation observed in the inferior region. CONCLUSIONS: Vascular parameters were significantly decreased in glaucomatous eyes, and the degree of decrease in vascular parameters was proportional to glaucoma severity. Peripapillary perfusion analysis using optical coherence tomography angiography may complement other measurements used for glaucoma diagnosis.

Unusual Presentations of Low-Tension Glaucoma.

Low-tension glaucoma can sometimes be difficult to diagnose, particularly if patients do not have a classic presentation. This case series shows the value of Humphrey visual field (HVF) 10-2 tests to identify deficits in central vision. Case 1 describes a female in her mid-60s who presented complaining of a "blind spot" in her right eye. While a HVF 24-2 suggested her test was "within normal limits," an HVF 10-2 showed an unusually shaped scotoma in her right eye that matched her visual complaint. Case 2 describes a male in his mid-60s who was referred to the glaucoma service by a retina specialist. He complained of a "blind spot" in his left eye and was revealed to have a focal central scotoma on his HVF 10-2 test. Both patients presented with normal intraocular pressures, and both had been cleared by retina specialists and neuro-ophthalmologists. Both patients were then diagnosed with low-tension glaucoma, and treatment to date has been successful in slowing vision loss.

Analysis of the Optic Nerve Head Microcirculation Using Optical Coherence Tomography Angiography and the Upstream Macrocirculation Using Color Doppler Imaging in Low-Tension and High-Tension Glaucoma Patients.

INTRODUCTION: The aim of the study was to analyze the optic nerve head (ONH) microcirculation using optical coherence tomography angiography (OCT-A) and the upstream macrocirculation using color Doppler imaging (CDI) in low-tension and high-tension glaucoma (LTG and HTG, respectively). METHODS: This cross-sectional study included 67 eyes of 67 HTG patients, 55 eyes of 55 LTG patients, and 42 eyes of 42 healthy controls. We recorded the complete ophthalmological examination, visual fields, retinal nerve fiber layer (RNFL) thickness, ONH vessel density (VD) measured using OCT-A, peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) measured using CDI. SPSS software was used for data analysis. Data are presented as mean ± standard deviation or median (interquartile range) and compared using t test or Mann-Whitney U test, as appropriate. Pearson χ2 test or Fisher's exact test was used for comparisons, as appropriate. Pearson correlation analysis was used to evaluate the correlations between variables. p < 0.05 was considered statistically significant. RESULTS: The ONH VD and RNFL thickness were considerably lower in glaucomatous eyes than in healthy eyes (both p < 0.001). Compared with the HTG group, the LTG group had lower VD in the peripapillary region (p = 0.027). Compared with the healthy group, the HTG group had lower PSV (p = 0.029 and = 0.023, respectively), lower EDV (p = 0.023 and <0.001, respectively), and higher RI (p = 0.019 and = 0.006, respectively) of the internal carotid artery (ICA) and central retinal artery (CRA). The LTG group had lower PSV (p = 0.015 and <0.001, respectively) and EDV (p = 0.047 and = 0.001, respectively) of the ophthalmic artery (OA) and CRA. The LTG group had lower PSV of CRA than the HTG group (p = 0.034). In glaucomatous eyes, peripapillary VD had a significant association with the mean defect (p < 0.001) and RNFL thickness (p < 0.001), but not with the other CDI indices (all p > 0.05). CONCLUSION: The ONH microcirculation and upstream macrocirculation of the large arteries exhibited differences in the blood flow characteristics between the LTG and HTG groups. These differences may improve our understanding of glaucoma. There was no correlation between the characteristics of the ONH microcirculation and the upstream macrocirculation of large vessels in the LTG and HTG groups.

Individuals with and without normal tension glaucoma exhibit comparable performance on tests of cognitive function.

AIM: To evaluate aspects of cognition impacted by individuals with and without normal tension glaucoma. METHODS: Fifty normal tension glaucoma (NTG) and 50 control patients ≥50y of age were recruited from the UCSF Department of Ophthalmology. Demographic data and glaucoma parameters were extracted from electronic medical records for both groups. Tests of executive function [Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER)] and learning and memory [California Verbal Learning Test-Second Edition (CVLT-II)] were administered to both NTG and controls. Race, handedness, best-corrected visual acuity, maximum intraocular pressure, optic nerve cup-to-disc ratio, visual field and optic nerve optical coherence tomography parameters, and a measure of general health (Charlson Comorbidity Index) were compared between NTG and controls as well as within NTG subgroups. Multivariate linear regression was used to compare group performances on the EXAMINER battery and CVLT-II while controlling for age, sex, and years of education. RESULTS: NTG and controls were comparable with respect to age, sex, race, education, handedness, and the Charlson Comorbidity Index (P>0.05 for all). Performance on the EXAMINER composite score and the CVLT-II did not differ between NTG and controls (P>0.05 for both). CONCLUSION: This is the first prospective study in which the cognitive function of subject with NTG were evaluated using a comprehensive, computerized neurocognitive battery. Subjects with NTG do not perform worse than unaffected controls on tests of executive function, learning, and memory. Results do not support the hypothesis that individuals with NTG are at higher risk for cognitive dysfunction and/or dementia.

WDR36-Associated Neurodegeneration: A Case Report Highlights Possible Mechanisms of Normal Tension Glaucoma.

WDR36 is one of a number of genes implicated in the pathogenesis of adult-onset primary open angle glaucoma (POAG). Here we describe in detail the phenotype of a patient with pathogenic variation in WDR36 who presented with a protracted history of central vision loss. On exam visual acuities were at 20/100 level, had a tritan color defect and showed central arcuate visual field defects on visual field testing. Enlarged cup-to-disk ratios with normal intraocular pressures were associated with severe thinning of the ganglion cell layer (GCL) and retinal nerve fiber layer consistent with a clinical diagnosis of normal tension glaucoma. Full-field electroretinograms revealed a severe inner retinal dysfunction with reduced amplitudes and remarkably delayed timings of the b-wave, but preserved photoreceptor (a-wave) function. The pattern described herein recapitulates some of the findings of an animal model of WDR36-associated POAG and suggests a mechanism of disease that involves a retina-wide inner retinal dysfunction and neurodegeneration beyond the GCL. Further detailed structural and functional characterizations of patients with a pathogenic variant in the WDR36 gene are required to confirm these findings.

Clinical Evaluation of Unilateral Open-Angle Glaucoma: A Two-Year Follow-Up Study.

To evaluate the clinical characteristics of unilateral open-angle glaucoma, patients diagnosed with unilateral open-angle glaucoma from January 2017 to October 2018 were divided into primary open-angle glaucoma and normal-tension glaucoma groups according to the type of glaucoma diagnosed. The glaucoma and the contralateral eyes were compared, and the contralateral eye was analyzed for conversion to glaucoma and its risk factors were assessed during the 2-year follow-up period. Among 99 patients, 36 were diagnosed with primary open-angle glaucoma and 63 with normal-tension glaucoma. When comparing the glaucoma eye with the contralateral eye, the visual field mean deviation value (all p<0.001), peripapillary retinal nerve fiber layer thickness (all p<0.001), macular ganglion cell layer-inner plexiform layer thickness (p<0.001, p=0.003), and optic nerve cup-disc ratio (p=0.005, p<0.001) were significantly different in both the primary open-angle glaucoma and normal-tension glaucoma groups. In normal-tension glaucoma, peripapillary retinal nerve fiber layer thickness was significantly thinner in the glaucoma conversion group than in the glaucoma non-conversion group (p=0.008). It was significantly associated with glaucoma conversion (odds ratio=0.97, p=0.023). In conclusion, in patients with unilateral open-angle glaucoma, the contralateral eye may develop glaucoma. In particular, if the peripapillary retinal nerve fiber layer thickness is decreased in normal-tension glaucoma, the possibility of glaucoma conversion is high; hence, careful examination is required.

Comparing Healthcare Resource Utilization and Costs for Patients with Normal Tension Glaucoma Across Levels of Severity: A Retrospective Cohort Study.

PURPOSE: To estimate the healthcare resource utilization (HCRU) and costs for patients with normal tension glaucoma (NTG) as well as their payers across various levels of disease severity. PATIENTS AND METHODS: Our study was a retrospective cohort study of 6330 US NTG patients. Patients were enrolled if they were 40 years or older and had two or more qualifying NTG diagnoses within the enrollment period, October 1st, 2015 to December 31st, 2017. Our analysis was carried out for two cohorts - those with unilateral disease and those with bilateral disease. Baseline demographic and clinical characteristics were assessed for a 12-month pre-index period. The follow up period was 12-months post-index. We employed generalized linear models to model HCRU and costs. RESULTS: Patients with severe, bilateral disease, filled more than two additional prescriptions annually (2.5, p<0.001, 95% CI [2.0, 3.1]) when compared to their mild counterparts and accounted for 111 (p<0.001, 95% CI [83.5, 139.1]) extra days of supply of glaucoma medications. These patients face an adjusted $187 (p<0.001, 95% CI [145, 229]) more out-of-pocket (OOP), and payers an additional $598 (p<0.001, 95% CI [$370, $826]), than their counterparts with a mild diagnosis on an annual basis. Total annual payer costs, on average (SD) for those with severe bilateral NTG were $1175 ($2222). CONCLUSION: Our results suggest that patient and payer burden is significantly greater for those with severe disease compared to those with mild NTG. The excess burden is attributed to additional HCRU and the associated financial burden. Payers experienced a much larger financial burden from patients with severe disease compared to those with mild NTG. Approximately half of the cost differences can be attributed to additional prescription use.

Efficacy and safety of fixed-combination brimonidine tartrate/timolol maleate in primary open-angle glaucoma, including normal-tension glaucoma.

PURPOSE: To assess the 12-month efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol maleate 0.5% (FCBT) with or without bimatoprost 0.01% (BIM) in primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG). STUDY DESIGN: Prospective, multicenter, open-label study. METHODS: FCBT was self-administered twice daily after applicable washout (study eye). Intraocular pressure (IOP) was measured at baseline and months 1, 3, 6, 9, and 12. BIM could be added for IOP ≥ 21 mmHg, IOP reduction from baseline < 20%, or the investigator deemed it necessary. Primary endpoint: mean (11-a.m.) month-12 IOP change from baseline. Secondary endpoints included mean IOP changes from baseline at other visits, median time to achieving and patients (%) achieving target IOP reduction with FCBT, and visual field (VF) progression rate over 12 months. Safety was assessed at each visit. RESULTS: Of 118 eyes with POAG (NTG, n = 93), 87 used FCBT; 31 required FCBT + BIM. Mean IOP changes from baseline (16.8 and 15.3 mmHg) to month 12 were - 4.1 mmHg (FCBT, n = 62) and - 3.5 mmHg (FCBT + BIM, n = 15), respectively (both P < 0.0001). Patients who achieved target IOP reduction with FCBT did so in 1 month (median). VF progression rates were 0.17%/year (FCBT, P = 0.8367) and - 0.08%/year (FCBT + BIM, P = 0.9410). Ocular treatment-emergent adverse events occurred in 42.5% (FCBT) and 71.0% (FCBT + BIM) of patients; most were mild and included ocular hyperemia (9.2% and 41.9%, respectively). CONCLUSIONS: Despite low mean baseline IOP, ≥ 20% IOP reduction from baseline persisted over 12 months with FCBT and FCBT + BIM, without clinically significant VF progression. Tolerability was consistent with reported drug safety profiles.

Normal-tension Glaucoma Management: A Survey of Glaucoma Sub-specialists in Korea.

PURPOSE: To investigate the current management patterns of glaucoma subspecialists with regard to normal-tension glaucoma (NTG) in Korea and to determine the effect of the two largest NTG trials on their clinical practice. METHODS: A questionnaire survey was sent to glaucoma subspecialist members of the Korean Glaucoma Society. The questionnaire concerned regular practice with respect to NTG and the extent to which it has been influenced by the Collaborative Normal-tension Glaucoma Study and the Low-pressure Glaucoma Treatment Study (LoGTS). RESULTS: A total of 134 glaucoma subspecialists completed the survey, with a response rate of 56%. The survey reported that 88% and 78% of glaucoma subspecialists were familiar with the Collaborative Normal-tension Glaucoma Study and the LoGTS, respectively. With respect to mild or moderate NTG, most of the respondents (87%-91%) tended to treat their patients immediately without waiting for structural or functional progression. Among the respondents, 47 indicated that the LoGTS results-according to which, 20% of the respondents tended to use brimonidine more often-affected their management. The first-choice topical drugs for NTG were prostaglandin analogues (76%), brimonidine (9%), beta-blockers (8%), and topical carbonic anhydrase inhibitor (6%). CONCLUSIONS: Regarding mild-to-moderate NTG, Korean glaucoma subspecialists tended to initiate treatment without waiting for further progression. The impact of the LoGTS on NTG management was not dominant in clinical practice in Korea. Prostaglandin analogs are the most frequently selected first-choice drugs for the management of NTG in Korea.

Effective treatment of a normal-tension glaucoma patient with bilateral ab externo XEN Gel Stent implantation.

PURPOSE: To provide the first report of effective use of bilateral XEN Gel Stent implantation using an ab externo open-conjunctival approach designed to improve bleb function and meet the uniquely low intraocular pressure requirements of a Japanese patient with normal-tension glaucoma refractory to topical medical therapy. OBSERVATIONS: A 54-year-old phakic Japanese woman with severe normal-tension glaucoma on maximally tolerated medical therapy of four topical agents presented with above-goal intraocular pressures and new medication intolerances. She underwent bilateral ab externo open-conjunctival XEN Gel Stent implantation with tenectomy and sub-Tenon's injection of 40µg of mitomycin-C, which resulted in reduction of intraocular pressures by 41.2 and 28.6% to 10 and 10 mmHg in the right and left eyes, respectively at the most recent visit. Postoperatively, a diffuse filtering bleb with good morphology developed in both eyes. The procedure has so far allowed for complete cessation of all four topical medications for up to eight months following surgery without any serious complications. CONCLUSIONS: This case illustrates the potential of Xen Gel Stent implantation through an ab externo, open-conjunctival approach to be an effective, simple alternative to trabeculectomy to meet the unique low-pressure requirements of normal-tension glaucoma patients with practical and safety benefits of a micro-invasive approach.

Effect of Prostaglandin Analogues on Central Corneal Thickness: 3-Year Follow-up Results.

PURPOSE: To evaluate the effects of each subgroup of prostaglandin analogues (PGAs) on central corneal thickness (CCT) in patients with normal tension glaucoma (NTG). METHODS: We retrospectively reviewed 55 eyes of 55 patients with NTG who were receiving PGA therapy. Patients who were treated with 0.005% latanoprost (16 eyes), 0.0015% tafluprost (16 eyes), or 0.004% travoprost (23 eyes) monotherapy were included. CCT assessments were performed at baseline and 1, 2, and 3 years after initiation of treatment. RESULTS: In the NTG group, the mean CCT showed a decreasing trend, and there was a significant difference in mean CCT at 1, 2, and 3 years compared with baseline (baseline, 538.16 ± 32.14; 1 year, 526.55 ± 37.30 µm [p = 0.00]; 2 years, 521.67 ± 36.79 µm [p = 0.00]; 3 years, 520.43 ± 36.88 µm [p = 0.00]). The reduction of CCT was confirmed by subgroup analysis. In the 0.005% latanoprost group, mean CCT was decreased at 1 year (p = 0.11), 2 years (p = 0.00), and 3 years (p = 0.02). In the 0.0015% tafluprost group and the 0.004% travoprost group, mean CCT was also significantly decreased at all years (p = 0.00). No statistical difference was observed between the NTG subgroups (p = 0.06). CONCLUSIONS: Topical therapy with PGAs appeared to cause a significant decrease in CCT reduction in patients with NTG. A long-term follow-up study including more participants is needed.

Profiles and Clinical Characteristics of Newly Diagnosed Glaucoma in Urban Korea: A Multicenter Study.

PURPOSE: To explore the clinical characteristics and profiles of newly diagnosed glaucoma subtypes in urban Korea. METHODS: All newly diagnosed glaucoma patients enrolled in the participating ophthalmology outpatient clinics were included. A review of medical history including family history of glaucoma was conducted. The patients underwent complete ophthalmologic examinations including visual field test. The diagnosis of glaucoma was based on the International Society of Geographical and Epidemiological Ophthalmology criteria developed by glaucoma specialists. RESULTS: A total of 198,671 patients visited the participating ophthalmology outpatient clinics during the study period (from January 1, 2001 to June 30, 2016), of which 5,530 (2.8%) were diagnosed with glaucoma. The mean age of the newly diagnosed glaucoma patients was 52.0 ± 17.3 years (range, 6 to 89) and 2,830 patients were male (51.2%). The mean untreated intraocular pressure and vertical cup-to-disc ratio of the optic nerve head of newly diagnosed glaucoma eyes were 22.1 ± 10.6 mmHg and 0.66 ± 0.22, respectively. The most frequently observed subtypes of glaucoma were: normal tension glaucoma (33.0%) primary open-angle glaucoma (28.4%), ocular hypertension (11.1%), chronic angle-closure glaucoma (6.8%), neovascular glaucoma (5.2%), glaucoma associated with inflammation (3.8%), acute angle-closure glaucoma (3.3%), and glaucoma associated with aphakia or pseudophakia (2.2%). CONCLUSIONS: Normal tension glaucoma was the most frequently observed glaucoma subtype in urban ophthalmology outpatient clinics in Korea.

Clinical Predictors of the Region of First Structural Progression in Early Normal-tension Glaucoma.

PURPOSE: This study aimed to compare the clinical characteristics of patients who showed structural progression in the peripapillary retinal nerve fiber layer (RNFL) first against those who showed progression in the macular ganglion cell-inner plexiform layer (GCIPL) first and to investigate clinical parameters that help determine whether a patient exhibits RNFL or GCIPL damage first. METHODS: A retrospective review of medical records of patients diagnosed with early-stage normal-tension glaucoma was performed. All eyes underwent intraocular pressure measurement with Goldmann applanation tonometer, standard automated perimetry, and Cirrus optical coherence tomography at 6-month intervals. Structural progression was determined using the Guided Progression Analysis software. Blood pressure was measured at each visit. RESULTS: Forty-one eyes of 41 patients (mean age, 52.6 ± 16.7 years) were included in the study. In 21 eyes, structural progression was first detected in the RNFL at 54.2 ± 14.8 months, while structural progression was first observed at the macular GCIPL at 40.5 ± 11.0 months in 20 eyes. The mean intraocular pressure following treatment was 13.1 ± 1.8 mmHg for the RNFL progression first group and 13.4 ± 1.8 mmHg for the GCIPL progression first group (p = 0.514). The GCIPL progression first group was older (p = 0.008) and had thinner RNFL at baseline (p = 0.001). The logistic regression analyses indicated that both age and follow-up duration until first progression predicted the region of structural progression (odds ratio, 1.051; 95% confidence interval, 1.001-1.105; p = 0.046 for age; odds ratio, 0.912; 95% confidence interval, 0.840-0.991; p = 0.029 for time until progression). CONCLUSIONS: Age of glaucoma patients and time until progression are associated with the region of the first structural progression in normal-tension glaucoma. Further studies exploring the association between glaucomatous progression and the location of damage are needed.

Parafoveal vessel changes in primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography angiography.

PURPOSE: To evaluate parafoveal and peripapillary perfusion in healthy, glaucoma suspect, normal-tension glaucoma, and primary open-angle glaucoma subjects. PATIENTS AND METHODS: This was a retrospective cross-sectional study with optical coherence tomography angiography imaging with RTVue XR Avanti (Optovue, Inc., Fremont, CA) of 56 eyes (14 healthy, 14 glaucoma suspect, 16 normal-tension glaucoma, and 12 primary open-angle glaucoma) at a tertiary academic referral center. Parafoveal and peripapillary superficial vessel density and parafoveal superficial retinal thickness were the main parameters of interest. Area under receiver operating characteristic curves were calculated. RESULTS: There were significant decreases in parafoveal superficial vessel density in primary open-angle (40.06±4.54%, P<0.001) and normal-tension glaucoma (42.82±5.16%, P=0.010) but not suspect eyes (45.72±4.37%, P=0.916) compared to healthy eyes (48.10±2.82%). Similarly, decreases were observed in parafoveal inner retinal thickness in primary open-angle (83.19±14.29 µm, P<0.001) and normal-tension glaucoma eyes (94.97±12.44 µm, P=0.035), but not suspect eyes (99.93±9.00 µm, P=0.648), compared to healthy controls (107.00±9.55 µm). Only primary open-angle glaucoma eyes displayed significant changes in peripapillary vessel density (37.63±7.19%) compared to healthy controls (49.12±2.80%, P<0.001). Further statistical adjustment for sex and age revealed a significant decrease in parafoveal vessel density in suspects relative to controls (P=0.039). Diagnostic accuracy of parafoveal vessel density was high with an area under the curve of 0.833±0.073 for normal-tension glaucoma and 0.946±0.049 for primary open-angle glaucoma. CONCLUSION: Parafoveal vessel density was significantly reduced in glaucomatous eyes, with good diagnostic accuracy. These findings provide further evidence that these changes may be useful in the diagnosis and monitoring of disease in glaucoma patients.

Differentiating Leber Hereditary Optic Neuropathy from Normal-Tension Glaucoma.

Glaucoma is a neurodegenerative disorder characterized by thinning of neuroretinal rim, enlarged cup-to-disc ratio (CDR) and visual field damage. Although raised intraocular pressure is main risk factor for development of glaucoma, it can occur with consistently normal measurements in the intraocular pressure as normal tension glaucoma (NTG). Enlargement of CDR is a classical sign of glaucoma, but it can also result from non-glaucomatous optic neuropathies such as Leber hereditary optic neuropathy (LHON). We describe a case of LHON with increased CDR, discuss its differential diagnosis with NTG and highlight the reasons for misdiagnoses between these two entities.

Cognitive performance of primary open-angle glaucoma and normal-tension glaucoma patients / Desempenho cognitivo em pacientes com glaucoma primário de ângulo aberto e glaucoma de pressão normal

ABSTRACT Purpose: To assess cognitive performance differences among primary open-angle glaucoma (POAG) patients, normal-tension glaucoma (NTG) patients, and healthy control (C) subjects. Methods: A total of 60 participants (20 POAG, 20 NTG, and 20 C subjects) were included in this study. A detailed ophthalmologic examination was performed on all participants. A spectral domain-optical coherence tomography (SD-OCT) system was used to measure the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thicknesses. To assess the cognitive performance of all participants, detailed neurological examinations, including the mini-mental state examination (MMSE), were performed by the same neurologist. Results: There were no significant differences among the groups in terms of age (p =0.348) or gender (p =0.935). The mean RNFL thicknesses were significantly different among the groups (85.2 ± 14.7, 76.8 ± 10.3, and 91.4 ± 7.7 µm in the POAG, NTG, and C subjects, respectively; p <0.001). The mean GC-IPL thicknesses were 77.5 ± 9.7 µm in the POAG group, 73.4 ± 7.8 µm in the NTG group, and 78.8 ± 3.8 µm in the C group. Differences among the groups were not statistically significant (p =0.085). MMSE scores were 26.1 ± 1.4, 25.7 ± 2.3, and 28.8 ± 0.9 in the POAG, NTG, and C groups, respectively. There were significant differences among the three groups (p <0.001). Specifically, there were significant differences between the NTG and C groups (p <0.001), and between the POAG and C groups (p =0.001). There was no significant difference between the POAG and NTG groups (p =0.595). Conclusions: There appear to be similar risk factors in glaucoma and neurodegenerative disorders that cause deterioration in cognitive performance. Comparing the low MMSE scores of the POAG and NTG patients with the scores of healthy C participants supports our hypothesis. Consequently, it is recommended that a neurologist should also examine glaucoma patients.

RESUMO Objetivos: Avaliar as diferenças de desempenho cognitivo entre pacientes com glaucoma primário de ângulo aberto (POAG), glaucoma de pressão normal (NTG) e controle de indivíduos saudáveis (C). Métodos: Um total de 60 pessoas (20 POAG, 20 NTG e 20 indivíduos saudáveis) foram incluídos neste estudo. Um exame oftalmológico detalhado foi realizado em todos os participantes. Um sistema de tomografia de coerência óptica de domínio espectral (SD-OCT) foi utilizado para medir as espessuras da camada de células ganglionares plexiforme interna (GC-IPL) e da camada de fibras nervosas da retina (RNFL). Para avaliar o desempenho cognitivo de todos os participantes, foi realizado pelo mesmo neurologista um exame neurológico detalhado, incluindo mini-exame do estado mental (MMSE). Resultados: Não houve diferenças significativas entre os grupos em termos de idade (p=0,348) e sexo (p=0,935). Espessuras médias da RNFL foram significativamente diferentes, sendo 85,2 ± 14,7, 76,8 ± 10,3 e 91,4 ± 7,7 µm nos grupos POAG, NTG e controles, respectivamente (p<0,001). As espessuras médias da GC-IPL observadas foram 77.5 ± 9.7 μm no grupo POAG, 73,4 ± 7,8 µm no grupo NTG e 78,8 ± 3,8 µm nos controlos. As diferenças entre os grupos não foram estatisticamente significantes (p=0,085). Graduações do MMSE foram 26,1 ± 1,4, 25,7 ± 2,3 e 28,8 ± 0,9 nos grupos POAG, NTG e controles, respectivamente. Houve diferenças significativas entre os três grupos (p<0,001). Houve diferença significativa entre NTG e saudáveis (p<0,001). Houve diferença significativa entre POAG e saudáveis (p=0,001). Não houve diferença significativa entre o POAG e NTG (p=0,595). Conclusões: Parecem haver fatores de risco semelhantes no glaucoma e nos distúrbios neurodegenerativos que causam deterioração no desempenho cognitivo. Comparando a baixa graduação do MMSE de pacientes com POAG e NTG com controles saudáveis referenda nossa hipótese. Consequentemente recomenda-se que um neurologista também examine os pacientes de glaucoma.

Comparison of risk factors for initial central scotoma versus initial peripheral scotoma in normal-tension glaucoma.

PURPOSE: To investigate the risk factors for initial central scotoma (ICS) compared with initial peripheral scotoma (IPS) in normal-tension glaucoma (NTG). METHODS: Fifty-six NTG patients (56 eyes) with an ICS and 103 NTG patients (103 eyes) with an IPS were included. Retrospectively, the differences were assessed between the two groups for baseline characteristics, ocular factors, systemic factors, and lifestyle factors. Also, the mean deviation of visual field was compared between the two groups. RESULTS: Patients from both ICS and IPS groups were of similar age, gender, family history of glaucoma, and follow-up periods. Frequency of disc hemorrhage was significantly higher among patients with ICS than in patients with IPS. Moreover, systemic risk factors such as hypotension, migraine, Raynaud's phenomenon, and snoring were more prevalent in the ICS group than in the IPS group. There were no statistical differences in lifestyle risk factors such as smoking or body mass index. Pattern standard deviation was significantly greater in the ICS group than in the IPS group, but the mean deviation was similar between the two groups. CONCLUSIONS: NTG Patients with ICS and IPS have different profiles of risk factors and clinical characteristics. This suggests that the pattern of initial visual field loss may be useful to identify patients at higher risk of central field loss.

Detecting the progression of normal tension glaucoma: a comparison of perimetry, optic coherence tomography, and Heidelberg retinal tomography.

PURPOSE: We compared the abilities of Stratus optical coherence tomography (OCT), Heidelberg retinal tomography (HRT) and standard automated perimetry (SAP) to detect the progression of normal tension glaucoma (NTG) in patients whose eyes displayed localized retinal nerve fiber layer (RNFL) defect enlargements. METHODS: One hundred four NTG patients were selected who met the selection criteria: a localized RNFL defect visible on red-free fundus photography, a minimum of five years of follow-up, and a minimum of five reliable SAP, Stratus OCT and HRT tests. Tests which detected progression at any visit during the 5-year follow-up were identified, and patients were further classified according to the state of the glaucoma using the mean deviation (MD) of SAP. For each test, the overall rates of change were calculated for parameters that differed significantly between patients with and without NTG progression. RESULTS: Forty-seven (45%) out of 104 eyes displayed progression that could be detected by red-free fundus photography. Progression was detected in 27 (57%) eyes using SAP, 19 (40%) eyes using OCT, and 17 (36%) eyes using HRT. In early NTG, SAP detected progression in 44% of eyes, and this increased to 70% in advanced NTG. In contrast, OCT and HRT detected progression in 50 and 7% of eyes during early NTG, but only 30 and 0% of eyes in advanced NTG, respectively. Among several parameters, the rates of change that differed significantly between patients with and without progression were the MD of SAP (p = 0.013), and the inferior RNFL thickness (p = 0.041) and average RNFL thickness (p = 0.032) determined by OCT. CONCLUSIONS: SAP had a higher detection rate of NTG progression than other tests, especially in patients with advanced glaucoma, when we defined progression as the enlargement of a localized RNFL defect. The rates of change of the MD of SAP, inferior RNFL thickness, and average RNFL thickness differed between NTG patients with and without progression.

Comparison of the thickness of the lamina cribrosa and vascular factors in early normal-tension glaucoma with low and high intraocular pressures.

PURPOSE: To compare the thickness of the lamina cribrosa (LC) and vascular factors of early normal-tension glaucoma (NTG) patients with high and low intraocular pressure (IOP) that are expected to be associated with the development of glaucoma. METHODS: Seventy-one Korean NTG patients with low IOP (the highest IOP <15 mmHg, 40 patients) and high IOP (the lowest IOP >15 mmHg, 31 patients) were included in this study. The thickness of LC and vascular factors were compared. The thickness of the LC was measured using the enhanced depth imaging method with spectral domain optical coherence tomography (Heidelberg Spectralis). RESULTS: The mean thickness of the central LC was 190.0 ± 19.2 µm in the low IOP group and 197.8 ± 23.6 µm in the high IOP group, but there was no statistical significant difference between the two groups (p > 0.05). The prevalence of self-reported Raynaud phenomenon was significantly higher in the low IOP group (33.0%) than the high IOP group (10.3%, p = 0.04). CONCLUSIONS: The laminar thickness did not significantly differ between the high and low IOP groups. However, the prevalence of Raynaud phenomenon was higher in the low IOP groups. These results suggest that the development of glaucoma with low IOP patients may be more influenced by peripheral vasospasm, such as Raynaud phenomenon, rather than laminar thickness in NTG.

Patterns of subsequent progression of localized retinal nerve fiber layer defects on red-free fundus photographs in normal-tension glaucoma.

PURPOSE: To investigate patterns of subsequent progression of localized retinal nerve fiber layer (RNFL) defects and to quantify the extent of progression in normal-tension glaucoma (NTG) patients. METHODS: Thirty-three eyes of 33 consecutive NTG patients who had shown continuous progression of localized RNFL defect on serial red-free fundus photographs were selected for the study. Patterns of subsequent progression of localized RNFL defects were categorized, and extents of progression were quantified. Serial evaluations of disc stereophotographs and visual fields were also performed to detect progression. RESULTS: The most common pattern was continuous widening of the defect towards the macula (n = 11, 33.3%) followed by sharpening of the defect border after widening of the defect towards the macula (n = 5, 15.2%), continuous widening of the defect away from the macula (n = 2, 6.1%), and deepening of the defect after appearance of a new defect (n = 2, 6.1%). Four eyes (12.1%) simultaneously showed two patterns of subsequent progression. In 13 eyes that showed continuous widening of the defect, subsequent angular widening towards the macula and away from the macula were 9.2 ± 6.0° (range, 1.1° to 24.4°; n = 11) and 5.2 ± 4.9° (range, 0.3° to 11.3°; n = 2), respectively. Thirty-two eyes showed no progression of optic disc cupping. Out of the 21 eyes in which Humphrey central 30-2 threshold visual field tests were performed after progression of RNFL defects, 15 eyes showed no deterioration in the visual field. CONCLUSIONS: There were nine patterns of subsequent progression of localized RNFL defects. Among them, continuous RNFL loss proceeding temporally was the most common one. Initial progression of the defect proceeded temporally, especially in the defect located at the inferior fundus, might be at a risk of further RNFL loss temporally.