|Year : 2016 | Volume
| Issue : 2 | Page : 204-208
Update on normal tension glaucoma
Jyotiranjan Mallick MS 1, Lily Devi MD 2, Pradeep K Malik MD 3, Jogamaya Mallick MBBS 4
1 Department of Ophthalmology, AIIMS, Bhubaneswar, Odisha, India
2 Department of General Medicine, MKCG Medical College, Brahmapur, Odisha, India
3 Department of Pediatrics, MKCG Medical College, Brahmapur, Odisha, India
4 Department of General Medicine, SCB Medical College, Cuttack, Odisha, India
|Date of Submission||23-Jun-2015|
|Date of Acceptance||15-Jul-2015|
|Date of Web Publication||13-Jun-2016|
Flat 001, Plot 1173, Sai Arati Homes, Lane 2, Aerodrome Area, Bhubaneswar - 751 020, Odisha
Source of Support: None, Conflict of Interest: None
Normal tension glaucoma (NTG) is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP) constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases), systemic calcium channel blockers (such as nifedipine) and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.
Keywords: Normal Tension Glaucoma; Ocular Hypoperfusion; Vasospasm
|How to cite this article:|
Mallick J, Devi L, Malik PK, Mallick J. Update on normal tension glaucoma. J Ophthalmic Vis Res 2016;11:204-8
| Introduction|| |
Normal tension glaucoma (NTG) is an optic neuropathy associated with glaucomatous optic nerve head damage, progressive retinal nerve fiber layer thinning, characteristic visual field defects, open anterior chamber angles on gonioscopy and maximum intraocular pressure (IOP) below 21 mmHg.
Glaucoma is a major optic neuropathy characterized by significant death of retinal ganglion cells. According to global surveys, the second leading cause of blindness after cataracts is glaucoma. Glaucoma affects more than 66 million people and is the second leading cause of visual loss worldwide., NTG accounted for 92% of primary open-angle glaucoma (POAG) in a Japanese population.
| Risk Factors|| |
- Patients with NTG tend to be older than those with primary open angle glaucoma (POAG)
- Female subjects have a higher prevalence of the disease than male counterparts
- NTG is more frequent among Japanese people 
- The most important risk factor for glaucoma is elevated IOP. It has been established that high IOP is a part of the pathogenic process of NTG; however, the pressure theory cannot sufficiently explain how NTG causes loss of vision. Multicenter clinical trials have confirmed the value of reducing IOP both in POAG , and NTG., There is yet to be a consensus regarding the specific relationship between IOP and NTG. However, in many cases the progression of GON has been observed even after lowering IOP. Patients with NTG have wider diurnal fluctuations of IOP as compared to the healthy population. IOP spikes may occur at night, and thus IOPs measured during office hours may miss nocturnal spikes in many patients. Associated changes in nocturnal orbital blood pressure and IOP may affect optic nerve head blood perfusion differently in glaucomatous eyes as compared to healthy eyes, and this issue may also influence the susceptibility of the optic nerve to damage
- Central corneal thickness (CCT) in patients with NTG is lower than POAG subjects 
- Vascular dysfunction and ischemia have been considered as important factors in the progression of NTG.,,, However, the ischemia in glaucoma is not simply insufficiency of blood flow, but also due to improper vascular autoregulation,,, and hypothetically episodes of transient ischemia and re-perfusion injury occur 
- Cold hands and feet, as an over-reaction to cold or stress, are suggestive of defective vasoregulation. Abnormal vasoregulation such as Raynaud's phenomenon and migraine are more associated with NTG than POAG. A study of peripheral vascular endothelial function in patients with NTG found impaired acetylcholine-induced peripheral endothelium-mediated vasodilation in comparison to healthy age- and sex-matched control subjects, and polymorphisms of the endothelin receptor type A gene have been associated with NTG 
- Patients with NTG have an increased frequency of headaches with or without migraine features 
- Non-IOP-related cardiovascular dysregulation factors, such as systemic hypertension, systemic hypotension, nocturnal hypotension, and cardiac arrhythmia are implicated in NTG
- There are reports suggesting that signs of glaucoma in certain eyes may be related to an acute ischemic episode (shock-induced neuropathy), or chronic obstructive arterial disease,, which may be non-progressive
- Mojon et al suggested that patients with sleep apnea syndrome are at high risk for glaucoma. The prevalence of obstructive sleep apnea syndrome (OSAS) was higher in patients with NTG. OSAS may cause optic nerve head hypoperfusion and glaucomatous optic neuropathy by creating transient hypoxemia and increasing vascular resistance
- Abnormally low diastolic double product (dDP = diastolic blood pressure × heart rate) may represent a state of cardiovascular autonomic dysregulation, resulting in low ocular perfusion in certain NTG patients 
- NTG patients with lower heart-rate variability, which reflects autonomic dysfunction with sympathetic predominance, manifested a faster rate of central visual field progression as compared to patients with higher heart-rate variability 
- Glaucoma patients have a decrease in central retinal vein (CRV) blood velocities. Spontaneous venous pulsation is less prevalent in glaucoma patients than in healthy individuals. This is particularly important in NTG patients 
- Duplication of the TANK-binding kinase 1 (TBK1) gene can be a rare cause of NTG 
- Lifestyle factors such as smoking and high body mass index can cause progression of glaucomatous visual field defect. In the Blue Mountain Eye Study, smokers were found to have higher IOP than non-smoker counterparts 
- Out of the metabolic syndrome components, hypertension and impaired glucose tolerance (IGT) may contribute to an increased risk of NTG.
| Diagnosis|| |
History has to be taken regarding migraine, Raynaud's phenomenon, episodes of shock, head injury, headache and other neurological symptoms. Use of medications including systemic steroids and antihypertensive agents such as beta blockers should also be taken into account.
Goldmann applanation tonometry, gonioscopy, stereoscopic biomicroscopy of the optic nerve head, optical coherence tomography and Humphrey field analyser are the main tools of investigation for diagnosis of NTG. IOP is usually in the higher teens but may rarely be in low teens.
Increased cup to disc ratio or asymmetry of cupping between the two eyes (difference more than 0.2) is significant [Figure 1]. A region of absent retinal pigment epithelium (RPE) is more often seen as a crescent or halo at the disc border in NTG. The cupping is often worse in the region of absent RPE, with field loss more marked in the corresponding region.,, Occasionally, there is a notch due to thin or absent neuro-retinal rim, referred as a “focal ischemic” type of cupping. This is associated with a highly localized dense arcuate field defect or even a dense hemifield defect. Other discs have diffuse shallow cupping and pallor, leading to the designation “senile sclerotic” disc.
Patients with high myopia may be particularly susceptible to NTG. With a frequent temporal crescent, scotomas tend to be closer to fixation than the paracentral scotomas of non-myope cases. Still other discs have cupping resembling ordinary glaucoma with mildly elevated IOP. Splinter hemorrhages are seen more commonly in NTG, but may also be found in POAG. Hemorrhages may simply indicate poor control. Although the optic nerve head may be larger in NTG than in POAG, glaucomatous cupping is comparable. Normal-tension glaucoma eyes can have greater optic nerve head (ONH) torsion as compared to POAG eyes with matched axial length. The direction of the ONH tilt and torsion can be related to the location of the visual field defect only in NTG eyes. As compared to normal subjects, peripapillary choroidal thickness was significantly thinner in NTG patients, at least in some locations.
Visual field defects in NTG are essentially comparable to POAG. In general, patients with NTG appear to have deeper, more localized scotomas. One study found a significantly greater rate of progressive visual field loss in NTG. Another revealed a difference in the progression pattern as compared to POAG patients; in POAG eyes, field defects initially increased in area and later in depth, whereas in patients with NTG, the increases in area and depth remained in constant proportion.
Other investigations include 24-hour blood pressure monitoring to exclude nocturnal systemic hypotension; blood tests to rule out other causes of glaucomatous optic neuropathy such as vitamin B12 and folate levels, ESR/CRP and serum ACE. Cranial MRI may be necessary to rule out intracranial space occupying lesions (SOLs); and nail fold capillaroscopy with cold provocation may detect blood flow abnormalities.
| Differential Diagnosis|| |
A number of congenital disorders may be confused with NTG; these include optic nerve anomalies including coloboma, pits, oblique insertion of the optic nerve, in addition to autosomal dominant optic atrophy (Kjer type). Acquired disorders which need to be considered in the differential diagnosis of NTG include history of steroid use by any route which may have led to prior elevated IOP, prior trauma or surgery which may have caused elevated IOP, hemodynamic crisis, methyl alcohol poisoning, optic neuritis, ischemic optic neuropathy (both arteritic and non-arteritic), compressive lesions of the optic nerve and tract (e.g., meningioma, vascular lesion); and wide diurnal fluctuation in IOP.
| Treatment|| |
The main goal of glaucoma treatment is IOP reduction. The Early Manifest Glaucoma Trial showed that glaucoma progression was decreased by 10% with reduction of each mmHg of IOP. According to the Collaborative Normal Tension Glaucoma Study Group, an IOP reduction of 30% slowed the progression of normal-tension glaucoma.
Choices for medical treatment in progressive cases include betaxolol eye drops which have a beneficial effect on optic nerve blood flow in addition to IOP reduction. Other beta blockers and adrenergic drugs (such as dipivefrine) should better be avoided because of the probability of nocturnal systemic hypotension and optic nerve hypoperfusion. Prostaglandin derivatives tend to have greater IOP lowering effect which may be of overriding consideration. Dorzolamide-timolol fixed combination (DTFC) is a safe and effective IOP-lowering agent in patients with NTG. Brimonidine significantly improved retinal vascular autoregulation in NTG patients; however, short-term alterations in visual function could not be demonstrated.
In the collaborative normal tension glaucoma study (CNTGS), 57% of the patients achieved 30% IOP reduction with topical medications, laser trabeculoplasty or both. The remaining 43% required filtering surgery which may prevent progressive damage.,,, A single session of selective laser trabeculoplasty (SLT) for NTG achieved IOP reduction of 20% from pre-study IOP and 30% reduction from baseline IOP at 6 months. Surgery is considered if progression occurs despite medications and IOP reduction. Deep sclerectomy seems to be effective and safe in reducing IOP in patients with NTG. Intraoperative use of MMC results in lower postoperative IOP after 12 months without an increased rate of complications.
An additional part of managing NTG is treatment of any cardiovascular abnormality such as anemia, hypotension, congestive heart failure (CHF), transient ischemic attacks and cardiac arrhythmias to increase optic nerve head perfusion. If significant nocturnal dips in blood pressure are detected, it may be necessary to reduce the antihypertensive medication especially at bedtime.
Finally treatment is aimed at neuroprotection to improve the retinal ganglion cell or optic nerve head function. Nilvadipine, a calcium channel blocker, increases blood flow to the optic nerve head and fovea. There was a significant reduction in the rate of disc and field damage in NTG patients who received calcium channel blockers.,,
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
| References|| |
Werner EB. Normal-tension glaucoma. In: Ritch R, Shields MB, Krupin T, editors. The Glaucomas. 2nd
ed. St. Louis: Mosby-Year Book; 1996. p. 769-797.
Quigley HA. Glaucoma. Lancet
Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, et al.
Global data on visual impairment in the year 2002. Bull World Health Organ
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol
Berenson K, Kymes S, Walt JG, Siegartel LR. The relationship of mean deviation scores and resource utilization among patients with glaucoma: A retrospective United States and European chart review analysis. J Glaucoma
Iwase A, Suzuki Y, Araie M, Yamamoto T, Abe H, Shirato S, et al.
The prevalence of primary open-angle glaucoma in Japanese: The Tajimi study. Ophthalmology
Kanski JJ, Bowling B, Nischal K, Pearson R. Clinical Ophthalmology: A Systematic Approach. 7th
ed. Edinburgh: Elsevier Saunders; 2011. p. 346-348.
Flammer J, Mozaffarieh M. What is the present pathogenetic concept of glaucomatous optic neuropathy? Surv Ophthalmol
2007;52 Suppl 2:S162-S173.
The advanced glaucoma intervention study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol
Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, et al.
Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology
The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol
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. Arch Ophthalmol
Gramer E, Leydhecker W. Glaucoma without ocular hypertension. A clinical study. Klin Monbl Augenheilkd
Shields MB. Normal-tension glaucoma: Is it different from primary open-angle glaucoma? Curr Opin Ophthalmol
Shetgar AC, Mulimani MB. The central corneal thickness in normal tension glaucoma, primary open angle glaucoma and ocular hypertension. J Clin Diagn Res
Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol
Flammer J, Orgül S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, et al.
The impact of ocular blood flow in glaucoma. Prog Retin Eye Res
Demailly P, Cambien F, Plouin PF, Baron P, Chevallier B. Do patients with low tension glaucoma have particular cardiovascular characteristics? Ophthalmologica
Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol
Anderson DR. Glaucoma, capillaries and pericytes 1. Blood flow regulation. Ophthalmologica
Mozaffarieh M, Flammer J. Pocket reference to ocular blood flow and glaucomatous optic atrophy. Ch. 5. London: Current Medical Group; 2008.
Mozaffarieh M, Flammer J. Pocket reference to ocular blood flow and glaucomatous optic atrophy. Ch. 7. London: Current Medical Group; 2008.
Drance SM. Some factors in the production of low tension glaucoma. Br J Ophthalmol
Henry E, Newby DE, Webb DJ, O'Brien C. Peripheral endothelial dysfunction in normal pressure glaucoma. Invest Ophthalmol Vis Sci
Kim SH, Kim JY, Kim DM, Ko HS, Kim SY, Yoo T, et al.
Investigations on the association between normal tension glaucoma and single nucleotide polymorphisms of the endothelin-1 and endothelin receptor genes. Mol Vis
Phelps CD, Corbett JJ. Migraine and low-tension glaucoma. A case-control study. Invest Ophthalmol Vis Sci
Schulzer M, Drance SM, Carter CJ, Brooks DE, Douglas GR, Lau W. Biostatistical evidence for two distinct chronic open angle glaucoma populations. Br J Ophthalmol
Leung DY, Tham CC, Li FC, Kwong YY, Chi SC, Lam DS. Silent cerebral infarct and visual field progression in newly diagnosed normal-tension glaucoma: A cohort study. Ophthalmology
Mojon DS, Hess CW, Goldblum D, Fleischhauer J, Koerner F, Bassetti C, et al.
High prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology
Bilgin G. Normal-tension glaucoma and obstructive sleep apnea syndrome: A prospective study. BMC Ophthalmol
Nesher R, Kohen R, Shulman S, Siesky B, Nahum Y, Harris A. Diastolic double-product: A new entity to consider in normal-tension glaucoma patients. Isr Med Assoc J
Park HY, Park SH, Park CK. Central visual field progression in normal-tension glaucoma patients with autonomic dysfunction. Invest Ophthalmol Vis Sci
Abegão Pinto L, Vandewalle E, De Clerck E, Marques-Neves C, Stalmans I. Lack of spontaneous venous pulsation: Possible risk indicator in normal tension glaucoma? Acta Ophthalmol
Ritch R, Darbro B, Menon G, Khanna CL, Solivan-Timpe F, Roos BR, et al.
TBK1 gene duplication and normal-tension glaucoma. JAMA Ophthalmol
Lee AJ, Rochtchina E, Wang JJ, Healey PR, Mitchell P. Does smoking affect intraocular pressure? Findings from the Blue Mountains Eye Study. J Glaucoma
Kim M, Jeoung JW, Park KH, Oh WH, Choi HJ, Kim DM. Metabolic syndrome as a risk factor in normal-tension glaucoma. Acta Ophthalmol
Anderson DR. Correlation of the peripapillary anatomy with the disc damage and field abnormalities in glaucoma. Doc Ophthalmol Proc Ser
Buus DR, Anderson DR. Peripapillary crescents and halos in normal-tension glaucoma and ocular hypertension. Ophthalmology
Heijl A, Samander C. Peripapillary atrophy and glaucomatous visual field defects. Doc Ophthalmol Proc Ser
Javitt JC, Spaeth GL, Katz LJ, Poryzees E, Addiego R. Acquired pits of the optic nerve. Increased prevalence in patients with low-tension glaucoma. Ophthalmology
Park HY, Lee KI, Lee K, Shin HY, Park CK. Torsion of the optic nerve head is a prominent feature of normal-tension glaucoma. Invest Ophthalmol Vis Sci
Hirooka K, Tenkumo K, Fujiwara A, Baba T, Sato S, Shiraga F. Evaluation of peripapillary choroidal thickness in patients with normal-tension glaucoma. BMC Ophthalmol
Gramer E, Althaus G, Leydhecker W. Site and depth of glaucomatous visual field defects in relation to the size of the neuroretinal edge zone of the optic disk in glaucoma without hypertension, simple glaucoma, pigmentary glaucoma. A clinical study with the octopus perimeter 201 and the optic nerve head analyzer. Klin Monbl Augenheilkd
Gliklich RE, Steinmann WC, Spaeth GL. Visual field change in low-tension glaucoma over a five-year follow-up. Ophthalmology
Gramer E, Althaus G. Quantification and progression of the visual field defect in glaucoma without hypertension, glaucoma simplex and pigmentary glaucoma. A clinical study with the delta program of the 201 octopus perimeter. Klin Monbl Augenheilkd
Allingham RR, Damji KF, Freedman SF, Moroi SE, Rhee DJ, Shields MB. Shields' Textbook of Glaucoma. 6th
ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2010. p. 180.
Kim TW, Kim M, Lee EJ, Jeoung JW, Park KH. Intraocular pressure-lowering efficacy of dorzolamide/timolol fixed combination in normal-tension glaucoma. J Glaucoma
Feke GT, Bex PJ, Taylor CP, Rhee DJ, Turalba AV, Chen TC, et al.
Effect of brimonidine on retinal vascular autoregulation and short-term visual function in normal tension glaucoma. Am J Ophthalmol
Schulzer M. Intraocular pressure reduction in normal-tension glaucoma patients. The Normal Tension Glaucoma Study Group. Ophthalmology
Bloomfield S. The results of surgery for low-tension glaucoma. Am J Ophthalmol
Sugar HS. Low tension glaucoma: A practical approach. Ann Ophthalmol
Abedin S, Simmons RJ, Grant WM. Progressive low-tension glaucoma: Treatment to stop glaucomatous cupping and field loss when these progress despite normal intraocular pressure. Ophthalmology
Lee JW, Gangwani RA, Chan JC, Lai JS. Prospective study on the efficacy of treating normal tension glaucoma with a single session of selective laser trabeculoplasty. J Glaucoma
Suominen S, Harju M, Kurvinen L, Vesti E. Deep sclerectomy in normal-tension glaucoma with and without mitomycin-c. Acta Ophthalmol
Chumbley LC, Brubaker RF. Low-tension glaucoma. Am J Ophthalmol
Sawada A, Kitazawa Y, Yamamoto T, Okabe I, Ichien K. Prevention of visual field defect progression with brovincamine in eyes with normal-tension glaucoma. Ophthalmology
Koseki N, Araie M, Tomidokoro A, Nagahara M, Hasegawa T, Tamaki Y, et al.
A placebo-controlled 3-year study of a calcium blocker on visual field and ocular circulation in glaucoma with low-normal pressure. Ophthalmology
Netland PA, Chaturvedi N, Dreyer EB. Calcium channel blockers in the management of low-tension and open-angle glaucoma. Am J Ophthalmol
|This article has been cited by|
||Prevalence of normal tension glaucoma in the Chinese population: A systematic review and meta-analysis
| ||Jing Zhao,Marisse Masis Solano,Catherine E. Oldenburg,Tianshu Liu,Yaxing Wang,Ningli Wang,Shan C. Lin |
| ||American Journal of Ophthalmology. 2018; |
|[Pubmed] | [DOI]|
||The coma in glaucoma: Retinal ganglion cell dysfunction and recovery
| ||Lewis E. Fry,Eamonn Fahy,Vicki Chrysostomou,Flora Hui,Jessica Tang,Peter van Wijngaarden,Steven Petrou,Jonathan G. Crowston |
| ||Progress in Retinal and Eye Research. 2018; |
|[Pubmed] | [DOI]|
||iDrugs and iDevices Discovery Research: Preclinical Assays, Techniques, and Animal Model Studies for Ocular Hypotensives and Neuroprotectants
| ||Najam A. Sharif |
| ||Journal of Ocular Pharmacology and Therapeutics. 2018; |
|[Pubmed] | [DOI]|
||Discovery, characterization and clinical utility of prostaglandin agonists for the treatment of glaucoma
| ||Peter G Klimko,Najam A Sharif |
| ||British Journal of Pharmacology. 2018; |
|[Pubmed] | [DOI]|
||Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis
| ||HE Killer,A Pircher |
| ||Eye. 2018; |
|[Pubmed] | [DOI]|
||The diagnostic use of choroidal thickness analysis and its correlation with visual field indices in glaucoma using spectral domain optical coherence tomography
| ||Zhongjing Lin,Shouyue Huang,Ping Huang,Lei Guo,Xi Shen,Yisheng Zhong,James Fielding Hejtmancik |
| ||PLOS ONE. 2017; 12(12): e0189376 |
|[Pubmed] | [DOI]|
||Characterizing the “POAGome”: A bioinformatics-driven approach to primary open-angle glaucoma
| ||Ian D. Danford,Lana D. Verkuil,Daniel J. Choi,David W. Collins,Harini V. Gudiseva,Katherine E. Uyhazi,Marisa K. Lau,Levi N. Kanu,Gregory R. Grant,Venkata R.M. Chavali,Joan M. OæBrien |
| ||Progress in Retinal and Eye Research. 2017; |
|[Pubmed] | [DOI]|
||Diffuse brain damage in normal tension glaucoma
| ||Antonio Giorgio,Jian Zhang,Francesco Costantino,Nicola De Stefano,Paolo Frezzotti |
| ||Human Brain Mapping. 2017; |
|[Pubmed] | [DOI]|
||Aquaporins: Novel Targets for Age-Related Ocular Disorders
| ||Rajkumar Patil,Haishan Wang,Najam A. Sharif,Alok Mitra |
| ||Journal of Ocular Pharmacology and Therapeutics. 2017; |
|[Pubmed] | [DOI]|
||Is atrial fibrillation a risk factor for normal-tension glaucoma?
| ||Anna Zaleska-Zmijewska,Maciej Janiszewski,Zbigniew M. Wawrzyniak,Marek Kuch,Jerzy Szaflik,Jacek P. Szaflik |
| ||Medicine. 2017; 96(43): e8347 |
|[Pubmed] | [DOI]|