|Year : 2022 | Volume
| Issue : 2 | Page : 175-181
Exposure keratopathy and its associated risk factors in patients undergoing general anesthesia in nonocular surgeries
Nazanin Amini1, Korosh Rezaei2, Hesameddin Modir3, Rezvan Kazemi Majd1, Neda Graminejad1, Fatemeh Rafiei4, Reza Rezaei5, Zohreh Davoodabady2, Akram Bayati2
1 Department of Paramedicine, Arak University of Medical Sciences, Arak, Iran
2 Department of Nursing, School of Nursing and Midwifery, Arak University of Medical Sciences, Arak, Iran
3 Department of Anesthesiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
4 Department of Biostatistics and Epidemiology, Scientific Research Center, School of Health, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Ophtalmology, Medical School, Arak University of Medical Sciences, Arak, Iran
|Date of Submission||14-Mar-2021|
|Date of Decision||01-Sep-2021|
|Date of Acceptance||29-Nov-2021|
|Date of Web Publication||29-Jun-2022|
Dr. Hesameddin Modir
Department of Anesthesiology, Faculty of Medicine, Arak University of Medical Sciences, Arak
Source of Support: None, Conflict of Interest: None
| Abstract|| |
INTRODUCTION: The most common eye injury during and after general anesthesia is corneal abrasion which can occur at any time after anesthesia and even up to 24 h after it. The aim of this study was to investigate the incidence and factors associated with corneal injury in patients undergoing nonocular surgery.
METHODS: This was a descriptive cross-sectional study. A total of 170 patients, who were admitted to the operating room and met the inclusion criteria, were selected through simple nonprobability sampling. Data collection forms were used in order to assess the incidence of corneal injury and its related risk factors. The National Eye Institute scale with fluorescein paper and cobalt blue light by slit lamp were utilized to examine exposure keratopathy.
RESULTS: Overall, the results showed that the incidence of keratopathy immediately after eye care removal was found to be 64.7% in the operating room, 65.9% in the recovery room, and 41.2% in 24 h after the surgery. Smokers' patients and drug abusers under general anesthesia underwent endotracheal intubation, received more opioids preoperatively, and had more perioperative bleeding and fluid intake. Moreover, in patients who had received more oxygen flow in the recovery room; the rate of keratopathy was higher.
CONCLUSION: Smoking, drug usage, and receiving endotracheal intubation are the risk factors of keratopathy. Therefore, for high-risk patients and procedures, it is indispensable to both obtain preoperative information and take intraoperative precautions in order to prevent eye injuries. Future studies are needed to demonstrate these finding.
Keywords: Eye injury, general anesthesia, incidence, keratopathy, risk factors
|How to cite this article:|
Amini N, Rezaei K, Modir H, Majd RK, Graminejad N, Rafiei F, Rezaei R, Davoodabady Z, Bayati A. Exposure keratopathy and its associated risk factors in patients undergoing general anesthesia in nonocular surgeries. Oman J Ophthalmol 2022;15:175-81
|How to cite this URL:|
Amini N, Rezaei K, Modir H, Majd RK, Graminejad N, Rafiei F, Rezaei R, Davoodabady Z, Bayati A. Exposure keratopathy and its associated risk factors in patients undergoing general anesthesia in nonocular surgeries. Oman J Ophthalmol [serial online] 2022 [cited 2022 Aug 15];15:175-81. Available from: https://www.ojoonline.org/text.asp?2022/15/2/175/349004
| Introduction|| |
Naturally, there are various mechanisms for eye protection; in fact, in a healthy eye, blinking, and tear flow help flush out microorganisms and foreign particles. The corneal epithelium is an effective barrier against the entry of microorganisms. The conjunctiva also has lymphoid tissue that provides an immediate immune response. If any of these protective mechanisms are disrupted, the eye will be damaged.
One of the conditions that can destroy the protective mechanisms is general anesthesia. In general anesthesia, tonic contractions of the orbicularis oculi muscle are reduced due to the use of sedatives and muscle relaxants, resulting in lagophthalmos so that, in 59% of patients, the eyelids do not close completely. Furthermore, general anesthesia leads to reduced tear production, resulting in dryness of the corneal epithelium and reduced liposomal protection., During general anesthesia, the incidence of corneal injury lies between 44% and 60%, and in case they remain closed, the incidence rate is between 0.1% and 0.5%.,,
According to the American Society of Anesthesiologists' (ASA) report in 1992, 35% of medical complaints about corneal injuries were related to general anesthesia. In 2004, however, only 2% of patient complaints against the anesthesia team were due to eye injuries. One of the most common eye injuries during and after general anesthesia is corneal abrasion which can occur at any time during anesthesia and even up to the subsequent 24 h. The most common causes of corneal abrasions during general anesthesia include exposure keratopathy, chemical damage, and direct eye trauma. The majority of corneal abrasions occur during general anesthesia following dry eyes and keratopathy. Ocular surface diseases usually begin with dry eye and eventually lead to exposure keratopathy, corneal abrasions, and even loss of vision.
Exposure keratopathy refers to dryness of the cornea along with the rupture of corneal epithelium, the most important risk factor of which is lagophthalmos (incomplete closure of the eyelids). Other possible causes of corneal abrasions during anesthesia include direct impact to the eyes, face masks, laryngoscope, anesthesia circuits, surgical instruments, and drapes.
Corneal abrasions in the recovery room also occur following injury caused by the patient's finger hitting the eye, pulse oximetry, pillow, and oxygen mask. Whenever the cornea is not well moistened and covered by eyelids, corneal abrasions occur and, if left untreated, can lead to ulcers in corneal epithelium tissue, the spread of infection, corneal perforation, and even vision loss.
There are several risk factors associated with corneal abrasions during and after anesthesia, of which old age and duration of anesthesia, especially more than 90 min, are among the most important risk factors., There is also a significant relationship between corneal abrasion and surgical position so that more corneal injuries have been observed in patients with prone position. In addition, research shows that head-and-neck surgery, drop in preoperative hemoglobin, intraoperative hypotension, poor physical status based on the classification of ASA, and the use of talc powdered gloves by anesthesia team are among the other factors that increase corneal abrasions.,,
To date, no study has been conducted on the incidence of eye injuries and its related risk factors during general anesthesia at the national level. As such, the current research was undertaken to shed light on the incidence of exposure keratopathy and its associated risk factors in patients undergoing general anesthesia in nonophthalmic surgeries in the operating room of hospitals affiliated to Arak University of Medical Sciences in Arak, Iran.
| Methods|| |
This is a descriptive cross-sectional study carried out in 2018 with the aim of determining the incidence of corneal abrasions and its related risk factors in patients under general anesthesia in nonocular surgeries. The study population included patients who had referred to hospitals affiliated to Arak University of Medical Sciences for nonocular surgery. Inclusion criteria were patients over 18 years of age, nonocular surgery under general anesthesia, absence of clear facial and eye injuries, absence of any damage to the eye before surgery according to the patients' remarks, absence of eye conditions (i.e., keratitis, keratopathy, glaucoma, and other eye conditions), and no allergy to fluorescein. Exclusion criteria included the admission of patients from critical wards, having artificial airways on the way to the operating room, patients with tear production or tear film stability, and the need for continuing mechanical ventilation in the recovery room.
A total of 170 patients, who were admitted to the operating room and met the inclusion criteria, were selected through simple nonprobability sampling. Data collection forms were used in order to assess the incidence of corneal injury and its related risk factors. At the beginning of surgery, all patients were examined for symptoms of corneal injury and included in the study in case there was no specific corneal injury. Therefore, the baseline examination based on the patients' declaration and absent of any signs conducted for all eligible subjects, and they entered to study when the complete eye health is assessed. Examination of both eyes for assessing corneal injury was performed by an experienced trained person under the supervision of an ophthalmologist. In order to examine exposure keratopathy (Grade 1, 2, and 3), the National Eye Institute scale applied, and the fluorescein paper and cobalt blue light by slit lamp was utilized to examine the cornea for exposure keratopathy in the operation room, in the recovery room, and after 24 h., The grading scale of corneal changes is divided into six steps based on the severity of the injury: (1) punctate damage to the surface layer of the cornea in the lower third of the cornea; (2) punctate damage to the surface layer of the cornea involving more than one lower third of the cornea; (3) macroepithelial damage; (4) epithelial damage with clear stroma; (5) stromal scar; and (6) bacterial keratitis. In the case of Grade 3 keratopathy (macroepithelial damage), the study came to an end, and the patients were referred for specialized treatment.
Data collection form included items about age, gender, body mass index, ASA physical status classification, history of tobacco smoking and drug abuse, history of diabetes and hypertension, type of surgery (emergency or elective), surgical position, type of surgical operation, airway management method (endotracheal intubation or other methods), eye care method (adhesive tapes alone, ointment alone, adhesive tapes, and ointment or other methods), use of talc powdered gloves, intraoperative blood loss, volume and type of fluid intake, duration of anesthesia, pre- and post-operative blood pressure, and information about the recovery room such as oxygen use, oxygen transfer method, duration of oxygen use, maximum oxygen flow, and duration of patient's stay in the recovery room. This questionnaire was completed by the principal investigator. The questionnaire also included symptoms of eye injuries such as eye pain, foreign body sensation, itching, burning, photophobia, blurred vision, and red eye, which was completed by the patient 24 h after general anesthesia.
After removal of the artificial airway and eye care, examination of both eyes was performed by a trained and experienced person under the supervision of an ophthalmologist. At first, a fluorescein paper was gently placed on the conjunctiva for staining; then, a cobalt blue light filter was flashed on the cornea, and the cornea was examined for exposure keratopathy. The eye examination was performed again in the same way upon leaving the recovery room. After that, in case keratopathy appeared, it was recorded in the patient information form.
The collected data were analyzed using frequency, percentage, mean and standard deviation, and odds ratio analysis.
This study was registered under the ethical code number of (IR.ARAKMU.REC.1396.231) in the Research Council and the Ethics Committee of Arak University of Medical Sciences. The patients were assured that all data would only be used for research purposes and remain confidential. The objectives and method of the study were explained to the patients before general anesthesia, and written consent was obtained from them. They were told that they could withdraw from the study at any time after regaining consciousness without any alteration in their treatment. In all stages of the research, the researchers followed the ethical principles as proclaimed by the ministry of health, treatment, and medical Education.
| Results|| |
This cross-sectional descriptive study was conducted from September 22, 2018, to June 22, 2019, in the operating room of teaching hospitals in Arak. A total of 170 patients, who were admitted to the operating room and met the inclusion criteria, were selected through simple nonprobability sampling. All in all, the results showed that the majority of patients in this study were male (96 patients or 56.2%), with a mean age and standard deviation of 41.78 ± 15.96 and body mass index of 25.68 ± 4.18. In addition, 141 patients (82.9%) were of ASA Class I and 29 patients (17.1%) were of ASA Class II physical status. Forty-three patients (25.3%) were smokers and drug abusers. Nine patients (5.3%) had diabetes, and 20 patients (11.8%) had hypertension. The results revealed that the incidence of total keratopathy (keratopathy Grade 1, 2, and 3) was found to be 64.7% immediately after removal of eye care in the operating room, 65.9% in the recovery room, and 41.2% in 24 h after surgery [Table 1]. Moreover, a significant relationship was found to exist between smoking, drug abuse, endotracheal intubation, volume of perioperative opioid intake, intraoperative bleeding, and volume of intraoperative fluid intake on the one hand, and the incidence of keratopathy immediately after general anesthesia and withdrawal of eye care on the other hand. However, there was no significant relationship between the incidence of keratopathy and age, body mass index, gender, ASA physical status, history of diabetes and hypertension, preoperative mean arterial pressure, type of surgery, surgical position, type of eye care, duration of anesthesia, and postoperative mean arterial pressure [Table 2]. The results pertaining to the recovery room also showed that there was a significant relationship between oxygen flow and the incidence of keratopathy so that patients receiving more oxygen flow had more keratopathy. However, no significant relationship was found between the incidence of keratopathy in the recovery room and the duration of oxygen intake and stay in the recovery room [Table 3]. In addition, based on a 24-h follow-up after surgery, a statistically significant relationship was found to exist between red eye, itching and burning, and keratopathy [Table 4]. After coding, data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). With regard to descriptive statistics, mean and standard deviation were utilized for quantitative variables and frequency and percentage for qualitative variables. Furthermore, odds ratio analysis was used to determine the risk factors of corneal injury.
|Table 1: Determining the frequency of exposure keratopathy immediately after the end of surgery and eye care removal, on leaving the recovery room and 24 h after general anesthesia|
Click here to view
|Table 2: Determining the risk factors associated with exposure keratopathy immediately after the end of surgery and eye care removal|
Click here to view
|Table 3: Determining the risk factors associated with exposure keratopathy on leaving the recovery room|
Click here to view
| Discussion|| |
Patients undergoing general anesthesia are susceptible to eye injuries, especially keratopathy, for a variety of reasons. The results of the current study showed that the incidence of total keratopathy (keratopathy Grade 1, 2, and 3) in the operating room immediately after removal of eye care was found to be 64.7%, 65.9% in the recovery room and 41.2% 24 h after the surgery.
In 2006, Contractor and Hardman reported that about 2% of all surgeries under general anesthesia resulted in eye injuries. Due to the fact that, in most studies, corneal abrasions have been studied instead of exposure keratopathy, its incidence has been underreported compared to the current study. Based on the findings of the current study, the first stage of eye injury after corneal dryness is exposure keratopathy, eventually leading to corneal abrasion. Moreover, the discrepancies in the findings can be accounted for by different study designs, retrospective nature of most studies, and lack of complete review and extraction of information from patient records, different examination tools, and the type of eye injury. On the other hand, previous studies have only examined eye injuries in the operating room, while the incidence of eye injuries in the recovery room and 24 h after general anesthesia has not been studied. In the present study, the incidence of keratopathy was higher in smokers and drug abusers. In 2017, Kim et al. showed that chronic nicotine use accelerates angiogenesis and corneal fibrosis following alkaline damage. In addition, healing of corneal epithelium in smokers with corneal abrasions and keratitis is delayed compared to nonsmokers.
In the current study, the patients who had more perioperative blood loss and fluid intake were exposed to keratopathy. In a study by Segal et al., it was found that patients with corneal abrasions had more perioperative blood loss (191 ml compared with 90 ml).
In 2016, Gandhi et al. reported that more perioperative blood loss was as a noticeable risk factor in terms of statistical significance. The study by Gkegkes et al. revealed that patients who had perioperative fluid intake of more than 1500 ml were at higher risk of corneal abrasions, which was in tandem with the results of the current study. However, Yu et al. found no association between perioperative bleeding and blood transfusion and the incidence of eye injuries. In the current study, patients undergoing endotracheal intubation were more likely to develop keratopathy. The results of the study by Wiseman et al., carried out in 2015, were in line with those of the current study. In addition, Yu et al. showed that endotracheal intubation puts patients at greater risk for eye injuries than mask ventilation. Eye damage can occur following direct trauma during laryngoscopy. In the current study, there was no significant relationship between age, gender, and body mass index and the incidence of keratopathy. Similarly, Yu et al. found no relationship between the variables of age, gender, and body weight and eye injuries.
Contrary to the results of the current study, Gkegkes et al. found that patients with a body mass index of more than 25 had more corneal abrasions. In their research in 2017, Carniciu et al. found that corneal abrasions were not associated with gender. In the current study, no relationship was found to exist between a history of diabetes, hypertension, and the incidence of keratopathy in the operating room. The study by Carniciu et al. also showed that corneal abrasions were not associated with a history of diabetes.
Contrary to the results of the present study, Cousen et al. revealed that diabetics are susceptible to corneal abrasions and eye injuries, possibly due to reduced tear production. In the current study, no association was found between the type of eye care (using eye tape or eye ointment) and keratopathy. Moreover, Contractor and Hardman showed that ocular complications when the eyes were just closed were not different from those in which the eyes were protected with paraffin-containing ointment.
In the current study, although the incidence of keratopathy was higher in patients with longer surgical duration, no significant association was found to exist between them. Several studies have concluded that the duration of anesthesia, particularly more than 90 min, is one of the risk factors for corneal abrasions., Along the same lines, Lichter et al. maintained that patients with an average surgical duration of 207.93 min were at higher risk for corneal abrasions. In a study by Nair et al., it was also shown that, if the duration of anesthesia lasted more than 90 min, the rate of eye damage would be higher. Segal also reports the longer surgical duration as a risk factor. Furthermore, Carniciu et al. demonstrated surgical durations of longer than 3 h increased the rate of corneal abrasions in patients.
Several studies have shown that patients who are in a prone position during surgery are at higher risk for corneal injury.,, In another study, Gkegkes et al. found that patients in Ttrendelenburg positions, especially in laparoscopic surgery, showed a higher incidence of corneal abrasions. No correlation was found between preoperative and postoperative mean arterial pressure and the incidence of keratopathy in our study. Contrary to the results of the present study, a number of studies have reported intraoperative hypotension as a risk factor for corneal injury.,, Yu et al. have identified deliberate perioperative hypotension as a risk factor for corneal injury. In the current study, the mean blood pressure of patients undergoing surgery was higher than 90 mmHg, which might account for the absence of any correlation. The current study found no significant relationship between the patient's physical status and the incidence of keratopathy. In some studies, unlike the results of the current study, patients' poor physical status, according to the ASA, has been reported as a risk factor for corneal injury.,, It might be explained by the fact patients in the current study were neither in poor physical status nor above ASA II classification.
In the present study, patients who received more oxygen flow in the recovery room had more keratopathy. However, no significant relationship was found between duration of oxygen intake and patients' stay in the recovery room and keratopathy. In line with the present study, Segal found that patients who received supplemental oxygen in the recovery room had more corneal abrasions, but no correlation was found between the duration of oxygen intake and corneal abrasions. However, White and Crosse reported that inadequate oxygen supply to the cornea predisposes the person to corneal abrasions.
In the present study, follow-up 24 h after surgery revealed that there exists a statistically significant relationship between red eye, itching and burning, and keratopathy. Corneal abrasions can result in eye pain in response to bright light or inflammation, sores, and infections. Although corneal abrasions may improve with conservative treatment for 2–3 days, proper eye protection is required to prevent it. In 2014, Segal et al. reported that if patients left the recovery room without ophthalmological consultation, the most common symptom to appear would be eye pain requiring consultation in the next 24 h. Along the same lines, Ting Wan reported that, in 6 of the 30 eyes protected by the adhesive tapes, eye discomfort occurred immediately after surgery with symptoms such as pain, foreign body sensation, photophobia, tears, and dry eyes, but the symptoms disappeared in the next 24 h.
Our study could show the risk factors of exposure keratopathy in patients undergoing general anesthesia in nonocular surgeries. Nevertheless, the sample size of this study was limited, and this one was a limitation for this study.
| Conclusion|| |
The results of this study reveal that most eye injuries occur in intubated smokers or drug abusers under general anesthesia, patients with a higher volume of perioperative opioid intake, higher volume of perioperative fluid intake and blood loss, and more oxygen flow intake in the recovery room. Should similar results be obtained in future studies with larger sample sizes and conditions almost similar to the present one, they can be used for designing an eye care protocol in the operating room.
The authors, hereby, wish to express their gratitude to clinical research council in Vali Asr Hospital as well as the vice chancellor for research of Arak University of Medical Sciences for their financial and moral support. They also wish to extend their thanks to all the staff of Vali Asr Hospital who contributed to this research project.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ramírez F, Ibarra S, Varon J, Tang R. The neglected eye: Ophthalmological issues in the intensive care unit. Crit Care Shock 2008;11:72-82.
Augustin DK, Heimer SR, Tam C, Li WY, Le Due JM, Evans DJ, et al.
Role of defensins in corneal epithelial barrier function against Pseudomonas aeruginosa
traversal. Infect Immun 2011;79:595-605.
Kocatürk Ö, Kocatürk T, Kaan N, Dayanır V. The Comparison of Four Different Methods of Perioperative Eye Protection under General Anesthesia in Prone Position. J Clin Anal Med 2012;3:163-5.
Contractor S, Hardman JG. Injury during anaesthesia. Contin Educ Anaesth Crit Care Pain 2006;6:67-70.
McHugh J, Alexander P, Kalhoro A, Ionides A. Screening for ocular surface disease in the intensive care unit. Eye (Lond) 2008;22:1465-8.
Martin DP, Weingarten TN, Gunn PW, Lee K, Mahr MA, Schroeder DR, et al.
Performance improvement system and postoperative corneal injuries: Incidence and risk factors. Anesthesiology 2009;111:320-6.
Nair PN, White E. Care of the eye during anaesthesia and intensive care. Anaesth Intensive Care Med 2014;15:40-3.
Lee SJ, Chung JK, Koh EH, Cho A, Cho HB, Han YM. Comparison of eye protection methods for corneal abrasion during general anesthesia. Anesth Pain Med 2016;11:99-103.
Lichter JR, Marr LB, Schilling DE, Hudson ME, Boretsky RH, Barad RF, et al.
A department-of-anesthesiology-based management protocol for perioperative corneal abrasions. Clin Ophthalmol (Auckland, NZ) 2015;9:1689.
Davoodabady Z, Rezaei K, Rezaei R. The impact of normal saline on the incidence of exposure keratopathy in patients hospitalized in intensive care units. Iran J Nurs Midwifery Res 2018;23:57-60.
Kocaçal Güler E, Eşer İ, Eğrilmez S. Nurses can play an active role in the early diagnosis of exposure keratopathy in intensive care patients. Jpn J Nurs Sci 2018;15:31-8.
So HM, Lee CC, Leung AK, Lim JM, Chan CS, Yan WW. Comparing the effectiveness of polyethylene covers (Gladwrap™) with lanolin (Duratears®) eye ointment to prevent corneal abrasions in critically ill patients: A randomized controlled study. Int J Nurs Stud 2008;45:1565-71.
Grover V, Jangra K. Perioperative vision loss: A complication to watch out. J Anaesthesiol Clin Pharmacol 2012;28:11-6.
] [Full text]
Kwee MM, Ho YH, Rozen WM. The prone position during surgery and its complications: A systematic review and evidence-based guidelines. Int Surg 2015;100:292-303.
Kim K, Kim H, No J, Kim TW, Kim YB, Suh C. Increased risk for post-operative corneal injuries in patients who undergo laparoscopic gynecologic surgery. Acta Anaesthesiol Scand 2012;56:504-6.
Yu HD, Chou AH, Yang MW, Chang CJ. An analysis of perioperative eye injuries after nonocular surgery. Acta Anaesthesiol Taiwan 2010;48:122-9.
Moos DD, Lind DM. Detection and treatment of perioperative corneal abrasions. J Perianesth Nurs 2006;21:332-8.
Batra YK, Bali IM. Corneal abrasions during general anesthesia. Anesth Analg 1977;56:363-5.
Kim JW, Lim CW, Kim B. Effects of nicotine on corneal wound healing following acute alkali burn. PLoS One 2017;12:e0179982.
Segal KL, Fleischut PM, Kim C, Levine B, Faggiani SL, Banerjee S, et al.
Evaluation and treatment of perioperative corneal abrasions. J Ophthalmol 2014;2014:901901.
Gandhi S, Zavala A, Williams U, Van Meter A, Hsu P. A retrospective review of corneal abrasions after oncologic surgery in a tertiary cancer center. Int J Anesthetic Anesthesiol 2016;3:046. doi: 10.23937/2377-4630/3/2/1046.
Gkegkes ID, Karydis A, Tyritzis SI, Iavazzo C. Ocular complications in robotic surgery. Int J Med Robot 2015;11:269-74.
Wiesmann T, Kranke P, Eberhart L. Postoperative nausea and vomiting –
A narrative review of pathophysiology, pharmacotherapy and clinical management strategies. Expert Opin Pharmacother 2015;16:1069-77.
Carniciu AL, Fazzari MJ, Tabibian P, Batta P, Gentile RC, Grendell JH, et al.
Corneal abrasion following anaesthesia for non-ocular surgical procedures: A case-controlled study. J Perioper Pract 2017;27:247-53.
Cousen P, Cackett P, Bennett H, Swa K, Dhillon B. Tear production and corneal sensitivity in diabetes. J Diabetes Complications 2007;21:371-3.
Marcucci C, Kirsch JR. Avoiding Common Anesthesia Error. Philadelphia: Lippincott Williams & Wilkins; 2019.
White E, Crosse M. The aetiology and prevention of peri-operative corneal abrasions. Anaesthesia 1998;53:157-61.
Wan T, Wang Y, Jin XM. Corneal injury and its protection using hydro-gel patch during general anesthesia. Int J Ophthalmol 2014;7:964-7.
[Table 1], [Table 2], [Table 3], [Table 4]