시신경유두출혈을 보이는 녹내장 환자의 전신적인 자율신경계 상태와 사상판 소견에 대한 연구 = Features of the Lamina Cribrosa and the Autonomic Nervous System in Glaucoma Patients with Disc Hemorrhages

다국어 초록 (Multilingual Abstract)

Purpose: To assess the effects of structural changes in the lamina cribrosa (LC) and the status of the autonomic nervous system on disc hemorrhages (DHs).
Methods: A retrospective study was performed on 68 eyes of 68 patients with primary open-angle glaucoma and optic DHs. We divided the patients into two groups using optical coherence tomography according to the presence of LC defects, and then compared both groups. We also analyzed autonomic nervous system function using the heart rate variability test, and compared the two groups.
Results: Eyes with LC defects had significantly longer axial lengths than those without defects (p = 0.029), and the DH was located more proximally (p < 0.001). A significantly larger proportion of eyes without LC defects had configurational optic disc changes such as optic disc rim notching, focal rim thinning, or generalized thinning (p = 0.001). On heart rate variability testing, the group without LC defects had a significantly higher “low frequency/high frequency ratio” than the group with defects (p = 0.008).
Conclusions: There was a difference in the clinical features of DH between eyes with and without LC defects. Eyes with LC defects were more myopic and the proximal part of the DH tended to be on the disc cup or characterized by peripapillary atrophy. These results suggest that the DH developed due to a mechanical cause in eyes with LC defects. Patients without LC defects had a more dysregulated autonomic nervous system. The DH location was related to disc rim notching and neural rim losses, which implies ischemia as the pathogenic mechanism involved in the development of DH in eyes without LC defects. Therefore, more careful observations of the LC would facilitate a better understanding of the specific pathogenic mechanisms underlying DH.

국문 초록 (Abstract)

목적: 사상판의 구조적 변화 및 자율신경계 상태가 시신경유두출혈의 임상 양상에 어떤 영향을 미치는지 알아보았다.
대상과 방법: 시신경유두출혈 소견이 보이는 개방각 녹내장 환자의 총 68안을 대상으로 빛간섭단층촬영(optical coherence tomography)을 이용하여 사상판에 결손이 있는 환자군(사상판 결손군)과 사상판 결손이 없는 군으로 나누어 각 군에서 나타나는 시신경유두출혈의 양상에 어떤 차이가 있는지 분석하였다. 또한 심박변이도검사를 통해 두 군 간의 자율신경계 기능에 어떤 차이가 있는지 알아보았다.
결과: 사상판 결손군에서 사상판 결손이 없는 군에 비해 유의하게 안축 길이가 길었으며(p=0.029) 시신경유두출혈이 더 근위부에 발생하였다(p <0.001). 사상판 결손군에 비해 사상판 결손이 없는 군에서 시신경유두테의 패임(notching), 국소적 유두테의 얇아짐, 전반적 유두테의 얇아짐 등의 시신경의 형태학적 변화가 더 빈번하게 관찰되었다(p=0.001). 심박변이도 검사에서는 사상판 결손이 없는 군에서 사상판 결손군보다 저주파수/고주파수 비가 유의하게 높은 것으로 확인되었다(p=0.008).
결론: 시신경유두출혈이 있는 개방각 녹내장 환자에서 사상판의 결손이 관찰되는 군과 관찰되지 않는 군은 서로 다른 임상 특징을 보였다. 사상판 결손이 관찰되는 군의 경우 더 근시였고, 사상판 결손이 관찰되지 않는 군의 경우 자율신경계 불균형 소견이 있고, 시신경유두출혈의 발생 위치가 시신경유두테의 패임이나 유두테 소실과 관련이 있어 허혈성 발생 원인이 관여할 가능성을 시사하였다. 따라서 시신경유두출혈 환자에서 사상판을 관찰하는 것은 환자의 시신경유두출혈 원인을 유추하는 데 도움이 될 수 있겠다.

참고문헌 (Reference)

• 1 Park HY, "Visual field characteristics in normal-tension glaucoma patients with autonomic dysfunction and abnormal peripheral microcirculation" 154 : 466-475, 2012
• 2 Delaney Y, "Vasospasm in glaucoma: clinical and laboratory aspects" 83 : 406-414, 2006
• 3 Nicolela MT, "Various glaucomatous optic nerve appearances: clinical correlations" 103 : 640-649, 1996
• 4 Morrison JC, "Ultrastructural location of extracellular matrix components in the optic nerve head" 107 : 123-129, 1989
• 5 Grieshaber MC, "The pathogenesis of optic disc splinter haemorrhages: a new hypothesis" 84 : 62-68, 2006
• 6 Flammer J, "The impact of ocular blood flow in glaucoma" 21 : 359-393, 2002
• 7 Sugiyama K, "The associations of optic disc hemorrhage with retinal nerve fiber layer defect and peripapillary atrophy in normal-tension glaucoma" 104 : 1926-1933, 1997
• 8 Clark CV, "Systemic autonomic neuropathy in open-angle glaucoma" 64 : 179-185, 1986
• 9 Morrison JC, "Structural proteins of the neonatal and adult lamina cribrosa" 107 : 1220-1224, 1989
• 10 Drance S, "Risk factors for progression of visual field abnormalities in normal-tension glaucoma" 131 : 699-708, 2001
• 11 Usui T, "Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese" 75 : 224-226, 1991
• 12 Pagani M, "Power spectral density of heart rate variability as an index of sympatho-vagal interaction in normal and hypertensive subjects" 2 : S383-S385, 1984
• 13 Pagani M, "Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho- vagal interaction in man and conscious dog" 59 : 178-193, 1986
• 14 Quigley HA, "Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage" 99 : 635-649, 1981
• 15 Park HY, "Optic disc hemorrhage is related to various hemodynamic findings by disc angiography" 2015
• 16 Park HY, "Ocular characteristics associated with the location of focal lamina cribrosa defects in open-angle glaucoma patients" 31 : 578-587, 2017
• 17 Ahn JK, "Morphometric change analysis of the optic nerve head in unilateral disk hemorrhage cases" 134 : 920-922, 2002
• 18 Jonas JB, "Morphologic predictive factors for development of optic disc hemorrhages in glaucoma" 43 : 2956-2961, 2002
• 19 Kiumehr S, "In vivo evaluation of focal lamina cribrosa defects in glaucoma" 130 : 552-559, 2012
• 20 Brown CM, "Impaired cardiovascular responses to baroreflex stimulation in open-angle and normal-pressure glaucoma" 102 : 623-630, 2002
• 21 Choi BM, "Heart rate variability" 8 : 45-86, 2004
• 22 You JY, "Focal lamina cribrosa defects associated with glaucomatous rim thinning and acquired pits" 131 : 314-320, 2013
• 23 Park SC, "Factors associated with focal lamina cribrosa defects in glaucoma" 54 : 8401-8407, 2013
• 24 Nitta K, "Does the enlargement of retinal nerve fiber layer defects relate to disc hemorrhage or progressive visual field loss in normal-tension glaucoma?" 20 : 189-195, 2011
• 25 Drance SM, "Disc hemorrhages in the glaucomas" 33 : 331-337, 1989
• 26 Bengtsson B, "Disc hemorrhages and treatment in the early manifest glaucoma trial" 115 : 2044-2048, 2008
• 27 Sonnsjo B, "Disc haemorrhages, precursors of open angle glaucoma" 21 : 35-56, 2002
• 28 Budenz DL, "Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study" 113 : 2137-2143, 2006
• 29 Tatham AJ, "Defects of the lamina cribrosa in eyes with localized retinal nerve fiber layer loss" 121 : 110-118, 2014
• 30 Sugiyama T, "Comparative study of cerebral blood flow in patients with normal-tension glaucoma and control subjects" 141 : 394-396, 2006
• 31 Kashiwagi K, "Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography" 9 : 239-246, 2000
• 32 Choi J, "Circadian fluctuation of mean ocular perfusion pressure is a consistent risk factor for normal-tension glaucoma" 48 : 104-111, 2007
• 33 Malliani A, "Cardiovascular neural regulation explored in the frequency domain" 84 : 482-492, 1991
• 34 Grassi G, "Assessment of sympathetic cardiovascular drive in human hypertension: achievements and perspectives" 54 : 690-697, 2009
• 35 Burgoyne CF, "A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma" 93 : 120-132, 2011