The Relationship between Low Ocular Perfusion Pressure with Acute Non-Arterial Anterior Ischemic Optic Neuropathy

Objective: To investigate the relationship between low ocular perfusion pressure (OPP) with acute non-arterial anterior ischemic optic neuropathy (ANAION). Methods: Forty- six patients (46 eyes) with ANAION from July 2010 to December 2016 were retrospectively analyzed. The 24-h intraocualr pressure (IOP) in sitting position was measured by non-contact tonometer. The brachial artery systolic blood pressure (SBP) and diastolic blood pressure (DBP) were simultaneously measured by electrocardiogram monitor. The 24-h OPP was calculated according to the measured blood pressure and intraocular pressure: OPP= 45% DBP-IOP. OPP< 10mmHg was dened as low OPP. Sudden visual acuity declining or visual eld defect was recorded as the attack of ANAION. 24h was divided into four periods: period A (1-6 A.M), period B (6-12 A.M), period C (12-18 P.M) and period D (18-24 P.M). The correlation between low OPP and ANAION was analyzed. Statistical method was used by Person correlation analysis. Results: There was a statistical difference in the low OPP in the four periods (P< 0.05). The most common period of low OPP was period A (1-6 A.M), with the incidence of low OPP as high as 58.3%. There was a statistical difference in the incidence of ANAION in the four periods (P< 0.05). Most common time period of ANAION was also period A (1-6 A.M), with the incidence rate as high as 46.3%. Person correlation analysis showed that the period of low OPP was associated with the period of ANAION onset (r=0.934, P < 0.05). Conclusion: There was a signicant clinical correlation between low OPP and ANAION. Period A (1-6 A.M) was the high-risk period for low OPP and ANAION. The occurrence of ANAION can be reduced by elevating the OPP to improve the blood perfusion of the anterior optic nerve.


Introduction
Acute non-arteritic anterior ischemic optic neuropathy (ANAION) is the most common acute optic nerve disease in patients over 50 years old. The onset time of ANAION is often in the morning, with the clinical manifestations includng sharp declining of visual acuity, edema of optic nerve head, and quadrant or upper and lower (mostly horizontal) visual eld defects associated with physiological blind spots [1,2,3].
Currently, the pathogenesis of ANAION is still not clear. Insu cient blood supply of the short posterior ciliary artery (SPCA) may be the main cause of ANAION. Acute non-perfusion or hypoperfusion is the hemodynamic basis for ANAION [4,5]. However, the clinical correlation between OPP and ANAION is still controversial. Therefore, we retrospectively analyzed the 24-h OPP of 46 patients with ANAION to investigate the clinical correlation between low OPP and the attack of ANAION.

Patients And Methods
Patients Forty-six patients with ANAION admitted to our hospital from July 2010 to December 2016 were collected. ANAION was diagnosed by analysing the peri-disc nerve ber thickness, visual eld, visual electrophysiology, and fundus uorescein angiography: 1) sudden vision acuity loss or visual eld damage, no eye pain, 2) relative afferent pupillary re ex disorder (+), 3) paleness and unclear boundary in the localized or the overall optic disc, 4) thickening of nerve ber layer around optic disc, 5) quadrantal visual eld defect associated with physiological blind spot, 6) low uorescence in localized optic disc before and during the early arterial period. Inclusion criteria included diagnosed ANAION, detailed onset time of ANAION, and blood pressure and intraocular pressure monitored for 24 hours.
Exclusion criteria were included as follow. First, patients with POAG, optic neuritis, optic disc vasculitis, Leber hereditary optic neuropathy and drug-induced optic neuropathy were excluded. Second, patients with intracranial and intraorbital lesions causing vision acuity loss or visual eld damage by CT and MRI scanning were excluded. Third, patients with macular lesions, high myopia, refractive interstitial opacity, optic disc burial vitreous membrane warts, and hypertension were excluded.
Blood pressure, intraocular pressure (IOP) and OPP 24-h IOP in the sitting position were measured by non-contact tonometer (nidek-2000, Japan). IOP was measured for 3 consecutive times and the average value of IOP was calculated. Goldmann tonometer was used to correct the results of two tonometers. The values measured by the two tonometers were normal. At the same time, the brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the sitting position were measured by electrocardiogram monitor (Mindry-AQ, shenzhen). Blood pressure and IOP were measured hourly for 24 hours.
The patient was placed in a relatively xed ward during blood pressure and IOP measuring. Before measuring, we routinely conducted propaganda and education to the patients and obtained their cooperation. In the daytime, stay in bed during the day or engage in daily activities in the ward, avoiding activities that increase blood pressure or heart rate (e.g. climbing stairs). Stay in bed from 9 p.m. to 7 a.m. in the next day. Alcohol, strong tea, coffee and other high-calorie diet were not recommended. Drugs affecting IOP and blood pressure were banned in 3 days before measurement. The measurements were made by the same trained nurse with standard operation. The accuracy of tonometer and electrocardiogram monitor were regularly corrected.
Blood pressure and IOP of ANAION patients were recorded for 24 h. According to IOP and blood pressure, OPP was calculated: OPP = 45% DBP-IOP [6,7] (Table 1). 10 mmHg of Hayreh was the OPP risk value of anterior optic ischemia [8]. The OPP value ≤ 10 mmHg is determined as low OPP. Patients with low OPP at ≥ 2 points were con rmed as having low OPP. The onset time of ANAION patients was the time of visual acuity loss and/or visual eld defect.  The time points of low OPP was 8, and onset of ANAION was 7Am. OPP-ocular perfusion pressure, Rright, L-left.

Statistical analysis
The Person correlation was used to analyze the correlation between low OPP and ANAION. SPSS22.0 was used for statistical analysis, and P < 0.05 was statistically signi cant.

Results
The 46 patients with ANAION included 26 males (26 eyes) and 20 females (20 eyes). The age ranged from 38 to 73 years old, with an average age of (60.5 ± 2.3) years old. There were 8 cases with diabetes mellitus, 11 cases with myocardial ischemia, and 11 cases with cerebral infarction. The onset time of ANAION ranged from one week to 3week. In 29 cases (63%, 29/46), OPP was low and the hypoperfusion point was at least 2. The occurrence of low OPP was higher in period A (17 cases, 58.3%), followed by period C (5 cases, 16.5%). Twenty-one (46.3%) cases had ANAION attack in the morning and six (14%) cases after siesta.
The number of cases with ANAION and low OPP over time.
Low OPP and onset of ANAION mostly occurred in the period from sleep at night to early morning.
Onset of ANAION was associated with low OPP in the time period.
There was a statistical difference in the incidence of low OPP in the four time periods (P < 0.05). The most common period of low OPP was period A (1-6 A.M), with the incidence of low OPP as high as 58.3%. There was a statistical difference in the incidence of ANAION in the four periods (P < 0.05). Most common time period of ANAION was also period A (1-6 A.M), with the incidence rate as high as 46.3%. Person correlation analysis showed that the period of low OPP was associated with the period of ANAION onset (r = 0.934, P < 0.05). The Person correlation analysis found that the low OPP period was correlated with the onset period of ANAION (r = 0.934, P = 0.046).

Discussion
Low OPP is an important risk factor for ANAION. OPP is driving force of blood supply to the anterior optic nerve. Hayreh found that vessels in the papilla of optic nerve and choroidal membrane were not lled with blood when OPP was less than 10 mmHg by fundus uorescein angiography [8]. Studies showed that ANAION was caused by multiple local and systemic risk factors such as small optic disc and super cial optic cup, insu cient blood supply of anterior optic nerve, and vascular self-regulation disorder. Most of all, low OPP plays a major or important role in its pathogenesis [5,10,11]. Although there is a lack of large scale prospective studies on the correlation between OPP and ANAION, low OPP is one of the risk factors for ANAION, which has been accepted by most scholars. In our study, there was a signi cant correlation between low OPP and onset of ANAION in the time period (r = 0.934, P < 0.05), which was consistent with relevant previous studies.
Period A (1-6 am) is the high-risk period for the incidence of low OPP and ANAION.
In 1994, Hayrech proposed that the incidence of ANAION was related to the low diastolic blood pressure at night and the sharp decrease in anterior optic nerve perfusion caused by poor blood circulation in the posterior ciliary artery [12]. Wang runsheng studied the blood pressure in 50 patients with ANAION and 50 healthy subjects and found that DBP in ANAION at night was lower than the control group [13]. Our study found that DBP in patients with ANAION signi cantly decreased compared with the control group (P < 0.05), particularly in the whole period A. DBP could be reduced to 60 mmHg or lower. This was consistent with the research results by Hayrech and wang runsheng. IOP at night was signi cantly higher than during the daytime, and reached its highest level from deep sleep to wakefulness [14,15]. IOP increased signi cantly when the position changed from sitting to supine position or lateral position [16,17,18]. IOP in the lateral position was higher than supine position [16,17,18]. Postural changing that caused IOP may be also an important risk factor for the onset of ANAION [19]. Therefore, low DBP at night, high IOP and the low OPP are the main reasons for the occurrence of ANAION in the period from falling asleep at night to getting up in the morning. OPP physiological circadian rhythm loss caused by ascular autonomic nerve regulation disordermay be also a part of the pathogenesis of ANAION [20,21,22,23].
Closely monitoring blood pressure and IOP in high-risk period for reducing the incidence of low OPP.
When OPP excessively reduces, the time of DBP of the short posterior ciliary artery at the critical level exceeds its own compensation limit and tolerance. If the patients themselves have anatomic bases such as small optic disc and shallow optic cup, the small vessels in the narrow environment in front of the optic disc sieve plate are limited and not easy to self-regulate. At this time, ANAION is more likely to occur after prolonged hypoperfusion, which leads to optic nerve ischemia behind the optic nerve papilla and sieve plate. Therefore, for patients with small optic disc and super cial optic cup, night blood pressure, IOP and OPP should be closely monitored. If necessary, the OPP should be improved to increase the blood ow of anterior optic nerve [24,25] and reduce the occurrence of ANAION (especially iatrogenic ANAION). The e cacy of this method could be evaluated by FFA, visual eld, vision acuity and OCT.

Conclusion
Low OPP was signi cantly associated with the incidence of ANAION. Period A (1 Am ~ 6Am) is the highrisk period for the occurrence of low OPP and ANAION.