Normal Tension Glaucoma

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Continuing Education Activity

Normal-tension glaucoma is a characteristic glaucomatous optic neuropathy with intraocular pressures in the normal range. It is a common condition and can lead to bilateral blindness. Monitoring and treatment can reduce the risk of visual morbidity in most patients. This activity reviews the evaluation and management of normal-tension glaucoma and highlights the interprofessional team in evaluating and treating patients with this condition.

Objectives:

  • Summarize the risk factors for developing normal-tension glaucoma.
  • Explain the physical exam findings associated with normal-tension glaucoma.
  • Outline management considerations for patients with normal-tension glaucoma.
  • Describe how to counsel a patient with normal-tension glaucoma.

Introduction

Glaucoma is characteristic progressive optic neuropathy, featuring optic disc cupping and visual field loss, associated with raised intraocular pressure (IOP). Normal-tension glaucoma (NTG), also known as normal or low-pressure glaucoma, is defined as open-angle glaucoma with a presenting IOP in the normal range.[1] The pathogenesis remains poorly understood, and there is controversy over whether it is a spectrum of primary open-angle glaucoma (POAG) or represents heterogeneous diseases.

The impact of NTG can range from non-progressive, asymptomatic disease to bilateral blindness. An impaired visual field leading to loss of a driving license can have a major impact on quality of life. Adverse effects and costs of medical and surgical treatments should be weighed against the risk of visual loss. NTG can masquerade as other optic neuropathies, and care should be taken to adequately investigate other causes when indicated.

Etiology

A variety of mechanisms have been proposed to explain the pathogenesis of NTG. Whereas IOP is the main driver of progressive visual loss in most patients with POAG, NTG likely represents a heterogeneous or multifactorial group of etiologies, with a common final pathway of retinal ganglion cell loss. Despite IOP in the statistically normal range, there is evidence that an IOP-dependent mechanism plays a role in the etiology in many eyes with NTG.[2][3]

Proposed IOP-independent mechanisms include vascular insufficiency at the optic nerve head, metabolic and neurodegenerative disorders, oxidative stress, and abnormal biomechanics of the lamina cribrosa.[4] Genetics is known to play a role because of the strong association with family history and variation in prevalence in different ethnicities that persists after migration. Three Mendelian genes have been associated with NTG but are rare even among patients with NTG and are more likely in those with an early onset and strong family history of NTG.[5] 

Genes associated with NTG

  • Optineurin (OPTN)
  • TANK binding kinase (TBK1)
  • Myocilin (MYOC)

Risk factors for NTG[3][6][7][8]

  • Age
  • Family history
  • Female gender
  • Above-average IOP
  • Thin central corneal thickness
  • Systemic hypertension
  • Nocturnal hypotension
  • Migraine
  • Raynaud phenomenon
  • Fronto-temporal and Alzheimer dementia
  • Obstructive sleep apnea

Epidemiology

The prevalence of NTG varies significantly by ethnicity. The population prevalence of POAG in East Asian countries is reportedly between 1 and 4%. However, NTG comprises up to 95% of these cases.[9][10] The prevalence of POAG is among white European populations is approximately 2%, but only around one third are NTG,[11][12] with higher prevalences (3 to 8%) and proportions (around 50%) of NTG in sub-Saharan African populations.[13][14] With increasing life expectancy, the burden of disease from both POAG and NTG is expected to increase.

IOP normal ranges are defined by population IOP studies in healthy subjects, with an interval of 2 standard deviations from the mean. Approximately 95% of normal subjects will have an IOP between 11 and 21mmHg.[15] Therefore, a cut-off of 21mmHg is often applied to define NTG.

Pathophysiology

The histopathological changes in NTG are the same as those found in POAG, namely loss of retinal ganglion cell axons (retinal nerve fiber layer - RNFL) and glial tissue at the optic nerve head, leading to optic disc excavation and cupping.[16] Typically, RNFL loss is more common in the supero- and inferotemporal neuroretinal bundles, leading to notches, but loss may also be global and concentric. Some changes are more common in NTG compared with POAG. These include Drance hemorrhages and temporal RNFL defects, with localized, deep paracentral scotomas, more often in the superior hemifield.[17][18]

History and Physical

Patients are usually asymptomatic at presentation, with suspicion of glaucoma raised by an optometrist on routine eye testing or an incidental finding with an ophthalmologist.[19] Even with moderately advanced disease, patients may be unaware of field defects because of unilateral disease, negative scotoma, and gradual onset. Because the IOP is normal, suspicion will usually be roused by optic disc appearance or a visual field defect on automated perimetry. If the presentation is advanced, patients may have symptoms of reduced vision, difficulty with low contrast situations, and awareness of visual field defects. They may experience glare and difficulty adjusting to extreme lighting conditions.

A family history of glaucoma and blindness should be obtained. Past medical history should include assessing risk factors for glaucoma, such as the history of steroid use, ocular trauma or surgery, and contraindications to treatments, including allergies. Medication usage should be reviewed.

A relative afferent pupillary defect is typical, though it may not be present in the early or symmetrical disease. Colour vision is usually preserved, except in advanced disease. By definition, the IOP will be in the normal range.[20]

Slit-lamp examination and gonioscopy are essential to determine an open iridocorneal angle status and to exclude secondary causes of glaucoma. In particular, evidence of angle-closure, uveitis, pigment dispersion, and pseudoexfoliation syndrome should be sought, as these are common causes of glaucoma presenting with an IOP in the normal range.

Dilated fundus examination reveals glaucomatous optic disc changes. There is a progressive loss of ganglion cell neurons, leading to enlargement of the cup-to-disc ratio. This may be a focal (notch, retinal nerve fiber layer (RNFL) defect) or concentric defect (excavation, senile sclerotic disc). Disc pallor occurs in advanced disease. Measurement of the optic disc size can help identify hypoplasia, physiological disc cupping, and disc asymmetry. Optic disc hemorrhages are more common in NTG than POAG.[6] So-called Drance hemorrhages are typically small flame hemorrhages at the disc margin in superior or inferior quadrants. Peripapillary atrophy may be seen but is non-specific. Glaucomatous disc abnormalities typically precede visual field defects in early (preperimetric) disease.[21]

Evaluation

Automated perimetry, particularly the Humphrey 24-2 visual field, is the most common algorithm for monitoring glaucoma, including NTG. Alternatively, 10-2 fields (especially in advanced disease) and wide-field exams (30-2 and Estermann) can be employed.[22] SITA fast and faster algorithms shorten test duration, achieving similar accuracies.[23]

Stereoscopic fundus photos of the optic nerve head at presentation provide a baseline comparison for future fundus examination. Photos can be repeated to document change.

OCT technology has revolutionized the monitoring of glaucoma. A variety of methods are in common use but have variations between imaging platforms. All compare measurements of ganglion cell neuron layers against a normative database calibrated for the device. OCT helps determine a healthy optic nerve structure or to document structural progression on serial scans.[24][25]

Corneal pachymetry is used to measure the central corneal thickness (CCT). Reduced CCT is associated with progression risk. Thinner corneas are associated with the underestimation of intraocular pressure using applanation tonometry.[26] However, other factors such as corneal hysteresis also contribute to measurement error in applanation tonometry.[27] 

Larger than normal diurnal variations in IOP are seen in POAG and NTG, with the highest pressures typically in the early morning.[28] IOP phasing is repeated IOP measurements, measured throughout the day during office hours or at home over 24 hours with a home rebound tonometry device. IOP phasing can help demonstrate an IOP mechanism in patients with rapidly progressive disease, with apparently controlled IOP measured in the office. An alternative method to simulate labile IOP in the office is the water-drinking test.[29]

Treatment / Management

Not all eyes with NTG will progress to clinically significant vision loss. In the Collaborative Normal-Tension Glaucoma Study (CNTGS), 65% of eyes without treatment showed no progression over five years.[30] Monitoring a patient without treatment is a suitable initial management strategy in many cases but requires discussion with the patient.

IOP lowering treatment should be instituted if there are confirmed progressive changes of the optic disc or visual field, and such progression is likely to lead to visual morbidity in their lifetime. Optic disc hemorrhages are also often interpreted as a marker of disease progression.[31][32]

Treatment at diagnosis may also be recommended in eyes with moderate or advanced disease, paracentral visual field defects that threaten fixation, and those with multiple risk factors for blindness. Once progression has been demonstrated, CNTGS showed aggressive IOP lowering of 30%, which led to a slower rate of visual field loss. However, 12% of the treated group still progressed despite aggressive treatment.[30] The presumed benefit of escalating treatment should always be weighed against each patient's risks and side effects.

IOP lowering is the only known modifiable risk factor that can alter disease progression in POAG and NTG. Strategies include topical IOP lowering medications, laser treatments such as selective laser trabeculoplasty (SLT) or cyclodiode laser, and drainage surgery. The role of micro-invasive glaucoma surgeries (MIGS) remains controversial. Prostaglandin analogs are a common first-line therapy. A comparison of topical brimonidine and timolol showed similar IOP lowering but less progression with brimonidine.[33]

It is hypothesized that brimonidine may have an additional neuroprotective effect. Studies have shown SLT can still have a pressure-lowering effect in the normal range. In eyes with continued progression, or very low pressure (less than 12mmHg) requiring treatment, surgical management with augmented trabeculectomy is likely required to achieve optimal IOP lowering. In the latter case, postoperative IOP below 10mmHg has been shown to eliminate VF progression.[34][35][34]

No IOP independent treatments have been proven to alter disease progression; however, non-IOP risk factors are being investigated to understand better their role in the pathogenesis of NTG and feasibility as interventions. In patients with these risk factors or progressive disease despite IOP treatment, treatment could be considered. These risk factors include:

  • Nocturnal hypotension – It is hypothesized that this causes reduced perfusion pressure at the optic nerve head. A 24-hour blood pressure analysis and avoiding nighttime dosing of systemic anti-hypertensives can be considered.[36]
  • Diet and nutritional supplementation – Nicotinamide (vitamin B3) and ginkgo biloba are under investigation.[37][38]
  • Obstructive sleep apnoea – This is hypothesized to alter optic nerve perfusion pressure. Screening questions for this disease can be asked to identify patients at risk.[39]
  • Exercise – Regular exercise is associated with lower IOP afterward, but a positive or negative effect on the pathogenesis of NTG is unknown.[40][41] Exercise is beneficial for many other aspects of health and should not be discouraged. Even in those with severe sight loss, supporting safe exercise will likely help the person holistically. However, yoga positions held for extended periods that position the eye below the rest of the body (such as headstands or downward dog) can significantly raise intraocular pressure, and case studies have shown rapidly progressive disease.[42]
  • Meditation – A randomized-controlled trial showed mindfulness meditation could lower IOP, reduce IOP fluctuation, and positively affect neuroprotective markers.[43][44][43]
  • Cannabinoids – These have been shown to reduce IOP, but not in a clinically meaningful way.[45] Cannabinoids are not currently recommended as a treatment for glaucoma.
  • Smoking – Smoking may be associated with both raised IOP and glaucoma.[46]

Differential Diagnosis

Alternate subtypes of glaucomas are the most common considerations in the differential diagnosis and may present with normal IOP. These include:

  • Angle-closure glaucoma
  • Hypertensive uveitis
  • Pigmentary glaucoma
  • Pseudoexfoliative glaucoma
  • POAG with thin central corneas, underestimating the true IOP.

Previous episodes of raised IOP, including a history of ocular trauma, hyphema, steroid use, or vitrectomy.

Previous vascular insults or compromise can cause a non-progressive picture similar to NTG. These include retinal vascular occlusions, arteritic or non-arteritic anterior ischaemic optic neuropathy, and severe systemic hypotension (e.g., after surgery, trauma, or sepsis).

Non-progressive disc abnormalities that may be misdiagnosed as NTG include physiological disc cupping, tilted discs, myopic fundus, disc drusen, optic disc pit, or congenital anomalies such as optic disc coloboma or superior segmental optic nerve hypoplasia.

Other optic neuropathies may be considered, including optic neuritis and hereditary, toxic, traumatic, and inflammatory optic neuropathies.

Intraorbital or intracranial tumors, including pituitary adenomas, are an important differential. Red flags include young age without a family history, rapid progression, unilateral disease, proptosis, associated neurological symptoms or signs, atypical disc findings, such as disc pallor without cupping, or field defects that respect the vertical midline. In the presence of these red flags, contrast-enhanced MRI of the anterior visual pathway is indicated to exclude compressive lesions.

Prognosis

NTG can progress to bilateral blindness in the worst cases, sometimes despite treatment. However, not all patients progress to visual morbidity. On average, progression is slower in NTG than POAG. Those at higher risk of visual field progression are females and those with a history of migraines, presence of optic disc hemorrhages, greater variation in diurnal IOP.[30][47][7] Patients who present with advanced disease or rapidly progressing visual field loss are most likely to be blinded by the condition, and these so-called ‘rapid progressors’ should be identified and treated more aggressively.[48]

Complications

Morbidity from vision loss in NTG can be significant and can lead to difficulty with activities of daily living (ADL). Tasks that involve visual searching are commonly affected, and fall risk increases.[49][50][51][52] On the other hand, asymmetric disease may preserve the ability to perform ADLs, even with a severe loss in one eye. As paracentral defects are more common in NTG, there is a higher risk of developing a central defect on binocular visual field testing.[53] In many countries, licensing rules would exclude them from driving.[54][55] However, professional drivers or pilots may lose their license with only relatively mild disease in one eye.

Conjunctival hyperemia and ocular surface symptoms are the most common side effects seen with all classes of topical IOP lowering medications. Side effects of prostaglandin analogs include hypertrichosis and changes in iris pigmentation. Prostaglandin-associated periorbitopathy is an important complication of long-term prostaglandin analog use. This includes orbital fat atrophy, ptosis, chronic inflammation of the eyelids, and skin discoloration. It is seen most commonly with bimatoprost.[56][57] In addition, filtration surgery may have lower success rates in these patients. Topical beta-blockers are relatively contraindicated in patients with asthma and COPD. Additional systemic side effects include cardiovascular effects, vivid dreams, erectile dysfunction, and mood changes. Carbonic anhydrase inhibitors should be used with caution in those with a history of sulfonamide allergy. Alpha-agonists are contraindicated in young children. 

Complications from SLT are rare but may include intraocular inflammation or an IOP spike after treatment.

Glaucoma surgery complications include failure, hypotony, cataract, blebitis, tube erosion, endophthalmitis, and corneal decompensation.

Consultations

The psychological burden of having an incurable, potentially blinding condition should not be underestimated.[58] Even asymptomatic patients who are only being monitored for a suspicious optic disc appearance can experience a negative impact on their general wellbeing. In addition, quality of life can be impaired by the side effects of treatment. For some patients and their families, the cost of treatment or attending the clinic can be challenging.

Tailored treatment strategies should be weighed against an individual risk assessment of patients experiencing visual morbidity in their lifetime. Opportunities for patients to comfortably raise concerns and discuss their desired treatment goals should routinely be created by the interprofessional team. A personalized approach to treatment and monitoring can thereby be delivered.

Deterrence and Patient Education

Glaucoma is the second most common cause of irreversible blindness worldwide and is a public health concern in both the developed and developing world.[59] Early detection is challenging due to the lack of symptoms. Various public health measures, including population screening, have been considered to try and reduce the burden of patients presenting with advanced disease. Educating the public on the importance of regular eye exams will facilitate the detection of NTG and other eye diseases.[19]

Patients who are diagnosed with glaucoma should be instructed to advise first-degree relatives to have regular eye exams to enable early detection.[60]

Enhancing Healthcare Team Outcomes

As individuals live longer, there is an increased burden of age-associated eye disease on society. This includes glaucoma, where many countries have a shortage of specialists, necessitating innovative methods to meet the needs of patients. This includes refined referral pathways, virtual clinics, artificial intelligence, community-based clinics, and training of allied health professionals in delivering patient care independently or as part of a consultant-led team.

Glaucoma is a chronic condition, and utilizing the communication skills of nursing and allied health staff in educating and training patients can improve patient understanding and treatment concordance. For those with glaucoma-related vision loss, low vision clinics can maximize remaining vision and help patients adapt to their disability. Local and national societies can provide patients with peer support, as well as opportunities for collaboration between healthcare providers and patient groups. Health professionals should be advocates for their patients to enable access to the treatments and services needed in their area.


Article Details

Article Author

Daniel Gosling

Article Editor:

Jay J. Meyer

Updated:

11/21/2022 8:37:44 PM

References

[1]

Lee BL,Bathija R,Weinreb RN, The definition of normal-tension glaucoma. Journal of glaucoma. 1998 Dec;     [PubMed PMID: 9871857]

[2]

The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. American journal of ophthalmology. 1998 Oct;     [PubMed PMID: 9780094]

[3]

Heijl A,Leske MC,Bengtsson B,Hyman L,Bengtsson B,Hussein M,Early Manifest Glaucoma Trial Group., Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Archives of ophthalmology (Chicago, Ill. : 1960). 2002 Oct;     [PubMed PMID: 12365904]

[4]

Adeghate J,Rahmatnejad K,Waisbourd M,Katz LJ, Intraocular pressure-independent management of normal tension glaucoma. Survey of ophthalmology. 2019 Jan - Feb;     [PubMed PMID: 30300625]

[5]

Wiggs JL,Pasquale LR, Genetics of glaucoma. Human molecular genetics. 2017 Aug 1;     [PubMed PMID: 28505344]

[6]

Killer HE,Pircher A, Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis. Eye (London, England). 2018 May;     [PubMed PMID: 29456252]

[7]

Drance S,Anderson DR,Schulzer M,Collaborative Normal-Tension Glaucoma Study Group., Risk factors for progression of visual field abnormalities in normal-tension glaucoma. American journal of ophthalmology. 2001 Jun;     [PubMed PMID: 11384564]

[8]

Chen YY,Lai YJ,Yen YF,Shen YC,Wang CY,Liang CY,Lin KH,Fan LW, Association between normal tension glaucoma and the risk of Alzheimer's disease: a nationwide population-based cohort study in Taiwan. BMJ open. 2018 Nov 5;     [PubMed PMID: 30397009]

[9]

Chen MJ, Normal tension glaucoma in Asia: Epidemiology, pathogenesis, diagnosis, and management. Taiwan journal of ophthalmology. 2020 Oct-Dec;     [PubMed PMID: 33437596]

[10]

Shiose Y,Kitazawa Y,Tsukahara S,Akamatsu T,Mizokami K,Futa R,Katsushima H,Kosaki H, Epidemiology of glaucoma in Japan--a nationwide glaucoma survey. Japanese journal of ophthalmology. 1991;     [PubMed PMID: 1779484]

[11]

Klein BE,Klein R,Sponsel WE,Franke T,Cantor LB,Martone J,Menage MJ, Prevalence of glaucoma. The Beaver Dam Eye Study. Ophthalmology. 1992 Oct;     [PubMed PMID: 1454314]

[12]

Dielemans I,Vingerling JR,Wolfs RC,Hofman A,Grobbee DE,de Jong PT, The prevalence of primary open-angle glaucoma in a population-based study in The Netherlands. The Rotterdam Study. Ophthalmology. 1994 Nov;     [PubMed PMID: 7800368]

[13]

Rotchford AP,Johnson GJ, Glaucoma in Zulus: a population-based cross-sectional survey in a rural district in South Africa. Archives of ophthalmology (Chicago, Ill. : 1960). 2002 Apr;     [PubMed PMID: 11934321]

[14]

Mason RP,Kosoko O,Wilson MR,Martone JF,Cowan CL Jr,Gear JC,Ross-Degnan D, National survey of the prevalence and risk factors of glaucoma in St. Lucia, West Indies. Part I. Prevalence findings. Ophthalmology. 1989 Sep;     [PubMed PMID: 2789357]

[15]

Colton T,Ederer F, The distribution of intraocular pressures in the general population. Survey of ophthalmology. 1980 Nov-Dec;     [PubMed PMID: 7466591]

[16]

Tomita G, The optic nerve head in normal-tension glaucoma. Current opinion in ophthalmology. 2000 Apr;     [PubMed PMID: 10848217]

[17]

Kosior-Jarecka E,Wróbel-Dudzińska D,Łukasik U,Żarnowski T, Ocular and Systemic Risk Factors of Different Morphologies of Scotoma in Patients with Normal-Tension Glaucoma. Journal of ophthalmology. 2017;     [PubMed PMID: 28815087]

[18]

Kottler MS,Drance SM, Studies of hemorrhage on the optic disc. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie. 1976 Apr;     [PubMed PMID: 1078325]

[19]

Quigley HA, Glaucoma. Lancet (London, England). 2011 Apr 16;     [PubMed PMID: 21453963]

[20]

Lawlor M,Quartilho A,Bunce C,Nathwani N,Dowse E,Kamal D,Gazzard G, Patients With Normal Tension Glaucoma Have Relative Sparing of the Relative Afferent Pupillary Defect Compared to Those With Open Angle Glaucoma and Elevated Intraocular Pressure. Investigative ophthalmology     [PubMed PMID: 29049724]

[21]

Spaeth GL,Henderer J,Liu C,Kesen M,Altangerel U,Bayer A,Katz LJ,Myers J,Rhee D,Steinmann W, The disc damage likelihood scale: reproducibility of a new method of estimating the amount of optic nerve damage caused by glaucoma. Transactions of the American Ophthalmological Society. 2002;     [PubMed PMID: 12545692]

[22]

Weinreb RN,Khaw PT, Primary open-angle glaucoma. Lancet (London, England). 2004 May 22;     [PubMed PMID: 15158634]

[23]

Jampel HD,Singh K,Lin SC,Chen TC,Francis BA,Hodapp E,Samples JR,Smith SD, Assessment of visual function in glaucoma: a report by the American Academy of Ophthalmology. Ophthalmology. 2011 May;     [PubMed PMID: 21539982]

[24]

Garway-Heath DF,Zhu H,Cheng Q,Morgan K,Frost C,Crabb DP,Ho TA,Agiomyrgiannakis Y, Combining optical coherence tomography with visual field data to rapidly detect disease progression in glaucoma: a diagnostic accuracy study. Health technology assessment (Winchester, England). 2018 Jan;     [PubMed PMID: 29384083]

[25]

Bussel II,Wollstein G,Schuman JS, OCT for glaucoma diagnosis, screening and detection of glaucoma progression. The British journal of ophthalmology. 2014 Jul;     [PubMed PMID: 24357497]

[26]

Ventura AC,Böhnke M,Mojon DS, Central corneal thickness measurements in patients with normal tension glaucoma, primary open angle glaucoma, pseudoexfoliation glaucoma, or ocular hypertension. The British journal of ophthalmology. 2001 Jul;     [PubMed PMID: 11423450]

[27]

Deol M,Taylor DA,Radcliffe NM, Corneal hysteresis and its relevance to glaucoma. Current opinion in ophthalmology. 2015 Mar;     [PubMed PMID: 25611166]

[28]

Bhartiya S,Gangwani M,Kalra RB,Aggarwal A,Gagrani M,Sirish KN, 24-hour Intraocular pressure monitoring: the way ahead. Romanian journal of ophthalmology. 2019 Oct-Dec;     [PubMed PMID: 31915728]

[29]

Sakata R,Aihara M,Murata H,Saito H,Iwase A,Yasuda N,Araie M, Intraocular pressure change over a habitual 24-hour period after changing posture or drinking water and related factors in normal tension glaucoma. Investigative ophthalmology     [PubMed PMID: 23821194]

[30]

Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. American journal of ophthalmology. 1998 Oct;     [PubMed PMID: 9780093]

[31]

Higashide T,Ohkubo S,Udagawa S,Sugiyama K,Tanihara H,Araie M,Tomita G,Matsumoto C,Fukuchi T,Tomidokoro A,Hangai M,Kawata H,Inai M,Tanaka Y,SVF Prospector Study Group., Spatial and Temporal Relationship between Structural Progression and Disc Hemorrhage in Glaucoma in a 3-Year Prospective Study. Ophthalmology. Glaucoma. 2020 Aug 21;     [PubMed PMID: 32835837]

[32]

Jeoung JW,Park KH,Kim JM,Kang SH,Kang JH,Kim TW,Kim DM, Optic disc hemorrhage may be associated with retinal nerve fiber loss in otherwise normal eyes. Ophthalmology. 2008 Dec;     [PubMed PMID: 19041474]

[33]

Krupin T,Liebmann JM,Greenfield DS,Ritch R,Gardiner S,Low-Pressure Glaucoma Study Group., A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. American journal of ophthalmology. 2011 Apr;     [PubMed PMID: 21257146]

[34]

Mataki N,Murata H,Sawada A,Yamamoto T,Shigeeda T,Araie M, Visual Field Progressive Rate in Normal Tension Glaucoma Before and After Trabeculectomy: A Subfield-Based Analysis. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2014 Sep-Oct;     [PubMed PMID: 26107911]

[35]

Iverson SM,Schultz SK,Shi W,Feuer WJ,Greenfield DS, Effectiveness of Single-Digit IOP Targets on Decreasing Global and Localized Visual Field Progression After Filtration Surgery in Eyes With Progressive Normal-Tension Glaucoma. Journal of glaucoma. 2016 May;     [PubMed PMID: 25719235]

[36]

Graham SL,Drance SM, Nocturnal hypotension: role in glaucoma progression. Survey of ophthalmology. 1999 Jun;     [PubMed PMID: 10416743]

[37]

Cimaglia G,Votruba M,Morgan JE,André H,Williams PA, Potential Therapeutic Benefit of NAD{sup} {/sup} Supplementation for Glaucoma and Age-Related Macular Degeneration. Nutrients. 2020 Sep 19;     [PubMed PMID: 32961812]

[38]

Labkovich M,Jacobs EB,Bhargava S,Pasquale LR,Ritch R, Ginkgo Biloba Extract in Ophthalmic and Systemic Disease, With a Focus on Normal-Tension Glaucoma. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2020 May-Jun;     [PubMed PMID: 32282348]

[39]

Cesareo M,Giannini C,Martucci A,Di Marino M,Pocobelli G,Aiello F,Mancino R,Nucci C, Links between obstructive sleep apnea and glaucoma neurodegeneration. Progress in brain research. 2020;     [PubMed PMID: 32988471]

[40]

Hecht I,Achiron A,Man V,Burgansky-Eliash Z, Modifiable factors in the management of glaucoma: a systematic review of current evidence. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2017 Apr;     [PubMed PMID: 27743157]

[41]

Tseng VL,Yu F,Coleman AL, Association between Exercise Intensity and Glaucoma in the National Health and Nutrition Examination Survey. Ophthalmology. Glaucoma. 2020 Sep - Oct;     [PubMed PMID: 32741639]

[42]

Cramer H,Krucoff C,Dobos G, Adverse events associated with yoga: a systematic review of published case reports and case series. PloS one. 2013;     [PubMed PMID: 24146758]

[43]

Dada T,Mittal D,Mohanty K,Faiq MA,Bhat MA,Yadav RK,Sihota R,Sidhu T,Velpandian T,Kalaivani M,Pandey RM,Gao Y,Sabel BA,Dada R, Mindfulness Meditation Reduces Intraocular Pressure, Lowers Stress Biomarkers and Modulates Gene Expression in Glaucoma: A Randomized Controlled Trial. Journal of glaucoma. 2018 Dec;     [PubMed PMID: 30256277]

[44]

Dada T,Bhai N,Midha N,Shakrawal J,Kumar M,Chaurasia P,Gupta S,Angmo D,Yadav R,Dada R,Sihota R, Effect of Mindfulness Meditation on Intraocular Pressure and Trabecular Meshwork Gene Expression: A Randomized Controlled Trial. American journal of ophthalmology. 2021 Mar;     [PubMed PMID: 33393484]

[45]

Wang MTM,Danesh-Meyer HV, Cannabinoids and the eye. Survey of ophthalmology. 2021 Mar-Apr;     [PubMed PMID: 32763339]

[46]

Law SM,Lu X,Yu F,Tseng V,Law SK,Coleman AL, Cigarette smoking and glaucoma in the United States population. Eye (London, England). 2018 Apr;     [PubMed PMID: 29303150]

[47]

Baek SU,Ha A,Kim DW,Jeoung JW,Park KH,Kim YK, Risk factors for disease progression in low-teens normal-tension glaucoma. The British journal of ophthalmology. 2020 Jan;     [PubMed PMID: 31055450]

[48]

Prata TS,De Moraes CG,Teng CC,Tello C,Ritch R,Liebmann JM, Factors affecting rates of visual field progression in glaucoma patients with optic disc hemorrhage. Ophthalmology. 2010 Jan;     [PubMed PMID: 19896197]

[49]

Lee SS,Wood JM,Black AA, Impact of glaucoma on executive function and visual search. Ophthalmic     [PubMed PMID: 32189400]

[50]

Azoulay-Sebban L,Zhao Z,Zenouda A,Lombardi M,Gutman E,Brasnu E,Hamard P,Sahel JA,Baudouin C,Labbé A, Correlations Between Subjective Evaluation of Quality of Life, Visual Field Loss, and Performance in Simulated Activities of Daily Living in Glaucoma Patients. Journal of glaucoma. 2020 Oct;     [PubMed PMID: 32649451]

[51]

Montana CL,Bhorade AM, Glaucoma and quality of life: fall and driving risk. Current opinion in ophthalmology. 2018 Mar;     [PubMed PMID: 29266021]

[52]

Ramulu PY,Mihailovic A,West SK,Gitlin LN,Friedman DS, Predictors of Falls per Step and Falls per Year At and Away From Home in Glaucoma. American journal of ophthalmology. 2019 Apr;     [PubMed PMID: 30639366]

[53]

Chow-Wing-Bom H,Dekker TM,Jones PR, The worse eye revisited: Evaluating the impact of asymmetric peripheral vision loss on everyday function. Vision research. 2020 Apr;     [PubMed PMID: 32179339]

[54]

Bhorade AM,Yom VH,Barco P,Wilson B,Gordon M,Carr D, On-road Driving Performance of Patients With Bilateral Moderate and Advanced Glaucoma. American journal of ophthalmology. 2016 Jun;     [PubMed PMID: 26949136]

[55]

Bro T,Andersson J, The effects of visual field loss from glaucoma on performance in a driving simulator. Acta ophthalmologica. 2021 Feb 2;     [PubMed PMID: 33529454]

[56]

Kucukevcilioglu M,Bayer A,Uysal Y,Altinsoy HI, Prostaglandin associated periorbitopathy in patients using bimatoprost, latanoprost and travoprost. Clinical     [PubMed PMID: 23844550]

[57]

Sakata R,Shirato S,Miyata K,Aihara M, Recovery from deepening of the upper eyelid sulcus after switching from bimatoprost to latanoprost. Japanese journal of ophthalmology. 2013 Mar;     [PubMed PMID: 23233196]

[58]

Quaranta L,Riva I,Gerardi C,Oddone F,Floriani I,Konstas AG, Quality of Life in Glaucoma: A Review of the Literature. Advances in therapy. 2016 Jun;     [PubMed PMID: 27138604]

[59]

GBD 2019 Blindness and Vision Impairment Collaborators.,Vision Loss Expert Group of the Global Burden of Disease Study., Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. The Lancet. Global health. 2021 Feb;     [PubMed PMID: 33275949]

[60]

Stein JD,Khawaja AP,Weizer JS, Glaucoma in Adults-Screening, Diagnosis, and Management: A Review. JAMA. 2021 Jan 12;     [PubMed PMID: 33433580]