|Year : 2019 | Volume
| Issue : 2 | Page : 55-60
Clinical profile and burden of primary glaucoma in rural camp patients attending a tertiary care center in India
Rekha R Khandelwal1, Dhananjay Raje2, Rachit R Khandelwal1
1 Department of Ophthalmology, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
2 Data Analytics Group, MDS Bioanalytics, Nagpur, Maharashtra, India
|Date of Submission||02-Oct-2018|
|Date of Acceptance||18-Dec-2018|
|Date of Web Publication||21-Aug-2019|
Rekha R Khandelwal
Department of Ophthalmology, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur - 440 019, Maharashtra
Source of Support: None, Conflict of Interest: None
Purpose: To study clinical profile and burden of primary glaucoma in rural camp patients attending a tertiary care center. Materials and Methods: A cross-sectional study was conducted in a tertiary care hospital of a single academic institute after ethical approval. Primary glaucoma patients aged ≥40 years, referred from the outreach camps, were included for a period of 12 months (2016–2017). A detailed history was recorded. Ocular examination included visual acuity, slit-lamp examination, disc evaluation, gonioscopy, intraocular pressure (IOP), and visual fields. Glaucoma was defined according to the International Society Geographical and Epidemiological Ophthalmology. Results: Out of 4204 referred cases from community program, 115 cases had primary glaucoma. Open-angle group had 63 (54.78%) cases whereas narrow-angle group had 52 (45.22%). The hospital-based prevalence for open-angle glaucoma was 1.11% (95% confidence interval [CI]: 0.8, 1.44) and for narrow-angle glaucoma was 1.07% (95% CI: 0.76, 1.38). The mean IOP was higher in narrow-angle group (P < 0.0001). The proportion of unilateral blindness was significantly high in narrow-angle category (P = 0.0203). Conclusions: The ratio of open-angle glaucoma to narrow-angle glaucoma was 1.2:1. Associated risk factors were age, gender, high IOP, refractive errors, and systemic illness. Narrow-angle glaucoma was more blinding as compared to open-angle glaucoma. Majority of the primary glaucoma found in camp patients was undiagnosed.
Keywords: Blindness, narrow-angle glaucoma, open-angle glaucoma, undiagnosed glaucoma, visual morbidity
|How to cite this article:|
Khandelwal RR, Raje D, Khandelwal RR. Clinical profile and burden of primary glaucoma in rural camp patients attending a tertiary care center in India. J Clin Ophthalmol Res 2019;7:55-60
|How to cite this URL:|
Khandelwal RR, Raje D, Khandelwal RR. Clinical profile and burden of primary glaucoma in rural camp patients attending a tertiary care center in India. J Clin Ophthalmol Res [serial online] 2019 [cited 2022 Jul 1];7:55-60. Available from: https://www.jcor.in/text.asp?2019/7/2/55/264898
Glaucoma is the second leading cause of world blindness after cataract. Worldwide, the prevalence of glaucoma is increasing and is expected to affect 111.8 million people by 2040. The prevalence of open-angle glaucoma is reported to be highest in Africa and that of narrow-angle in Asia. In a systematic meta-analysis, the global prevalence of glaucoma was found to be 3.54%. Asians represent 47% of those with glaucoma and 87% of those with angle closure glaucoma (ACG). Prevalence of primary ACG (PACG) in Southeast Asian countries is more than the rest of the world. India accounts for a minimum of 12.9% of primary open angle glaucoma (POAG) blindness and 12.7% of PACG (PACG) blindness in the world. The prevalence and risk factors of glaucoma have been studied by many population-based studies and in many hospitals in India. The Central India Eye and Medical Study, Chennai Glaucoma Study (CGS) for rural and urban population for PACG and POAG groups, Vellore Eye Study (VES), Andhra Pradesh Eye Disease Study (APEDS), and Aravind Comprehensive Eye Survey (ACES) have shown that increasing age, high intraocular pressure (IOP) systemic hypertension, diabetes, and myopia are some of the risk factors for the glaucoma.,,,,,,,
The purpose of this article was to study clinical profile and burden of primary glaucoma in camp patients attending a tertiary care center.
| Materials and Methods|| |
A cross-sectional study was conducted in a tertiary care hospital of a single academic institute. Institutional Ethics Committee approval was taken. Patients with primary glaucoma aged ≥40 years, who were referred from the peripheral outreach camps, were included for a period of 12 months (2016–2017). A written informed consent was obtained from all. All patients who were referred for either cataract surgery or for the diagnosis and management of other ocular diseases such as glaucoma, diabetic retinopathy, age-related macular degeneration, pterygium, and secondary glaucoma underwent complete ocular examination to detect cases of primary glaucoma. Patients with congenital or juvenile glaucoma or secondary glaucoma (lens induced, pseudoexfoliation, neovascular, and uveitic) were excluded. The demographic data, socioeconomic information, medical and ophthalmic history were recorded. All camp cases underwent preliminary ophthalmic examination (senior ophthalmologist) which included recording of the best corrected visual acuity (BCVA) using Snellen's chart at 6 m, slit-lamp biomicroscopy (Topcon, Oakland, NJ, USA), assessment of peripheral anterior chamber depth (ACD) using Van Herick technique, fundus examination using indirect ophthalmoscopy, the stereoscopic optic disc evaluation using +78D lens (×16 magnification), and IOP measurement with a Goldmann applanation tonometer. After above examination, suspected glaucoma cases were referred for further glaucoma-related workup such as gonioscopy, disc evaluation, and visual field testing in glaucoma clinic (glaucoma consultant). Gonioscopy was performed using four-mirror Sussman gonioscope (Ocular Instruments, Inc., Bellevue, WA), and the angle was graded by modified Shaffer's classification. The vertical cup-disc ratio (VCDR) was measured, and morphological features of glaucomatous optic neuropathy were noted. The visual field test was done if IOP was ≥18 mmHg, or VCDR ≥0.7 in either eye. If the difference in VCDR was >0.2 between the two eyes with presence of glaucomatous disc, even then visual field test was performed to rule out primary glaucoma. Visual field examination using a Humphrey Field Analyzer (SITA 24–2; Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc., Oberkochen, Germany) was attempted whenever possible.
The patients were categorized on the basis of International Society Geographical and Epidemiological Ophthalmology (ISGEO) classification.
Category 1 (structural and functional evidence): VCDR (>0.7)/VCDR asymmetry (>0.2), i.e., ≥97.5th percentile of the normal population, or a neuroretinal rim width reduced to ≤0.1 VCDR, between 11 and 1 o'clock or 5 and 7 o'clock with corresponding visual field defect. Category 2 (advanced structural damage with unproved field loss): If the patient could not satisfactorily complete visual field testing but had a VCDR (>0.8) or VCDR asymmetry (s0.3), i.e., ≥99.5th percentile for the normal population, glaucoma was diagnosed solely on the structural evidence. Category 3 (optic disc not seen, visual field (VF) not possible): If one of the following was encountered, that is, (a) the corrected visual acuity <3/60 and the IOP (≥25 mmHg) >99.5th percentile or (b) the visual acuity <3/60 and the eye shows evidence of glaucoma filtering surgery or medical records were available confirming glaucomatous visual morbidity.
The glaucomatous visual field defect was considered to be present if (1) Glaucoma Hemifield Test was outside normal limit and (2) a cluster of three or more nonedge, contiguous points, not crossing the horizontal meridian with a probability of <5%, was found on pattern deviation plot on two separate tests.
(1) Primary angle closure suspect (PACS): When ≥180° of iridotrabecular contact was seen (occludable angles) in the primary position on four-mirror gonioscopy with normal IOP, optic disc, and visual fields. (2) Primary angle closure (PAC): When ≥180° of iridotrabecular contact was present with raised IOP and/or peripheral anterior synechiae, iris whorling, “glaukomflecken” but with normal optic disc and visual fields, and (3) PACG: PAC with evidence of glaucoma (optic disc and visual field changes). Disc suspects – those who met category 1 (but not category 2) disc criteria but were not proved to have definite field defects. Field suspects – those with definite field defects but not meeting category 1 disc criteria.
Other variables: systolic and diastolic blood pressure (BP) were recorded using an automated sphygmomanometer. Random blood samples were drawn to determine the levels of serum glucose. A participant was labeled hypertensive if the systolic BP >140 mmHg or diastolic BP >90 mmHg or self-reported history of hypertension. Diabetes was diagnosed if random blood sugar was >200 mg/dl or if the patient was using diabetic medication or had a physician diagnosis of diabetes. Other systemic illness was recorded as reported by the physician or patient. BCVA of <3/60 or constriction of the visual field <10° from fixation was considered as a “blind eye.”
The data of primary glaucoma patients attending the hospital were analyzed, and descriptive statistics such as mean, standard deviation, and percentage were obtained for the study variables considering the measurement scale. These analyses were performed according to diagnostic categories, i.e., open angle and narrow angle. The variables on nominal scale were compared using Pearson's Chi-square test, while those on continuous scale were compared using t-test for independent samples. The statistical significance was tested at 5% level, and the entire analysis was performed using SPSS version 20.0 (IBM corp., Armonk, USA).
| Results|| |
Out of 4204 adult patients, aged 40+ years who were referred from peripheral camps, 115 were diagnosed with primary glaucoma (ISGEO). The distribution of patients according to the age, gender, type of glaucoma is shown in [Table 1]. The mean IOP was 17.52 ± 5.03 mmHg in open-angle group and 25.79 ± 11.46 mmHg in narrow-angle group. The risk factors associated with primary glaucoma are shown in [Table 2]. The proportion of patients with one or more systemic illness was insignificantly different in two groups (P = 0.2199). However, the proportion of patients with hypertension in open-angle category was significantly higher (74.29%) than that of narrow angle (50%) as indicated by P = 0.0359. As regards refractive errors, proportion of myopia cases was significantly higher in open-angle group (55.56%) as compared to narrow angle (7.69%) with P < 0.0001 while proportion of hypermetropia in open-angle group (6.35%) was significantly smaller than narrow-angle group (61.54%) with P < 0.0001. The correlation between IOP and VCDR was 0.1329 in open-angle group, which was statistically insignificant (P = 0.3071). In narrow-angle category, the correlation was 0.34, which was statistically significant with P = 0.0159. Scatter plot showing the correlation of IOP and VCDR in the two glaucoma types is shown in [Figure 1].
|Figure 1: Scatter plot showing relationship between intraocular pressure and vertical cup-disc ratio in two diagnostic groups|
Click here to view
Visual status of eyes was obtained in two glaucoma categories as shown in [Table 3]. Out of 230 eyes of 115 patients, 126 eyes had POAG while 104 had narrow angle. In open-angle category, 96 eyes (76.19%) had normal/near normal vision while in narrow angle, 62 eyes (59.61%) had normal vision. Visual impairment (BCVA <6/18) was seen in 15.08% (19/126) eyes in open angle as compared to 22.12% (23/104) eyes in narrow-angle category. Unilateral blindness (BCVA <3/60) was found in 8.73% (11/126) eyes in open-angle category and 18.27% (19/104) eyes in narrow-angle group. There were six cases (5.21%) with bilateral blind eyes due to primary glaucoma (open and narrow angle). There were two cases (3.17%) with bilaterally blind eyes (BCVA <3/60) in open-angle group and four cases (7.69%) in narrow angle. The proportion of eyes with visual impairment in the two groups was studied for statistical significance of difference using Pearson's Chi-square test of homogeneity, which resulted into P = 0.0203 indicating significant difference.
| Discussion|| |
The prevalence of glaucoma varies by region and race. In a systematic meta-analysis in 2014, the global prevalence of glaucoma was found to be 3.54%. There is necessity of actively looking at the disease because 1 in 8 people above the age of 40 years in India is either suffering from glaucoma or is at risk of the disease.
It is difficult to compare the data from different epidemiological studies due to differences in the diagnostic criteria used in them. The more recent studies have used the ISGEO definitions so that there is uniformity in reporting glaucoma prevalence and comparison is rational. We have used ISGEO system in this study to define open-angle and narrow-angle glaucoma.
In this hospital-based cross-sectional study on patients referred from rural health camps, the prevalence of open-angle glaucoma was 1.11% (95% confidence interval [CI]: 0.8, 1.44) and for PACG/PAC was 1.07% (95% CI: 0.76, 1.38). The distribution of open-angle to narrow-angle glaucoma in our study was 1.2:1.
For Indian population, the prevalence of glaucoma has been previously reported by the VES, APEDS, ACES, CGS, and the West Bengal Glaucoma Study.,,,,, These studies were carried out in urban or semiurban population, and rural cases were few.
The prevalence of POAG and PACG reported by a population-based study for rural patients in Central India for adults aged 30+ years was 1.93% and 0.24%, respectively. The ratio of open-angle to narrow-angle glaucoma in this study was 8:1. The high proportion of POAG in this study as compared to our study could be due to difference in inclusion criteria, study design, and its remote location.
The prevalence of PACG (1.07%) in our study is comparable to studies done in Southern India which ranges from 0.5% to 4.3%. The CGS by Vijaya et al. reported a prevalence of PACG and POAG in South Indian population (aged 40+ years) to be 0.88% (95% CI: 0.60, 1.16) and 3.51% (95% CI: 3.04, 4.0), respectively., The ACES (aged 40+ years) reported a prevalence of 2.6% (95% CI: 2.2, 3.0), and the ratio of open-angle to narrow-angle glaucoma was 1.7% to 0.5% (3.4:1).
The distribution of open-angle and narrow-angle cases in our study was comparable to a study done in North India by Agarwal et al. A study done from East India reported that the prevalence of glaucoma was >4% in adults ≥70 years of age.
A population-based study by Garudadri et al. reported that the prevalence for POAG and PACG was greater in urban than rural population. This study reported the prevalence of open and suspected open-angle glaucoma to narrow-angle glaucoma to be 2.41% to 0.71% (3.4:1). The age-standardized prevalence of POAG and PACG by urban Indian population study done at Singapore reported it to be 1.25% (95% CI: 0.89, 1.73) and 0.12% (95% CI: 0.04, 0.33), respectively. Overall prevalence of open-angle glaucoma was more than narrow-angle glaucoma in almost all reported studies.
In our study, maximum patients were in the age range of 40–70 years. Studies in the literature suggest that aging is a risk factor for POAG.,, Increasing age is a risk factor for PACG too, but it does not appear to follow the exponential curve described for POAG. We did not find the significant correlation with increasing age.
As regard gender, overall male predominance was noted in primary glaucoma. We also found male preponderance in open-angle glaucoma which is comparable to the Barbados Eye Study.
Consistent with other studies, we found female predominance in narrow-angle glaucoma suggesting more risk of PACG in the female population. This is related to biometric differences between genders since women have shorter eyes and more shallow ACD than men. In a cross-sectional population-based survey, a similar correlation of gender with PACG was found in Nepalese population.
In our study, we used ISGEO definitions to categorize glaucoma cases and found that our results were comparable to other population-based studies. However, it is reported that with ISGEO, there is a possibility of overdiagnosis in eyes with abnormally large discs and underdiagnosis in abnormally small discs., There was only one case who had glaucoma surgery POAG (category 3), and no patients in POAG were using antiglaucoma medications. In narrow-angle group, the laser PI was not found in any case although three cases had a history of intermittent closure in the past and were advised laser. They were using antiglaucoma medications. Most of the patients in both the groups had undiagnosed advanced glaucoma.
Most population-based studies reported that elevated IOP is one of the modifiable risk factors for glaucoma. We found higher IOP in PACG as compared to POAG in accordance with other studies.,, There was a significant correlation of VCDR and IOP in PACG which suggests that a VCDR of >0.6 is suspicious of glaucoma.
Related to systemic illness, we found a high proportion hypertension and diabetes in open-angle cases, similar to the Los Angeles Latino Eye Study. In a study done by Salim and Shields, systemic hypertension was found to be associated with glaucoma in 73% of the total population.
Association of refractive errors with type of glaucoma was also studied. Myopia was more prevalent in open-angle group and hypermetropia in narrow-angle group. These findings were comparable to earlier published studies.,,
The prevalence of unilateral and bilateral blindness was correlated in all glaucoma patients. We found statistically significant unilateral blindness in narrow-angle glaucoma as compared to open-angle glaucoma. Bilateral blindness was more in narrow-angle group as compared to open-angle group. Narrow angle also presented with more visual morbidity, as compared to open angle similar to other published studies on the Indian population.,,,, However, there are few studies reporting POAG to be more blinding than PACG.,
Association of glaucoma with low-income group and lower socioeconomic setting similar to our rural community was reported by a large UK cohort.
The limitations of our study are as follows. This is a cross-sectional study of the referred cases from the on-going community program run for the neighboring villages (radius of 40–60 Km). As it is not a population-based study, it may not represent the true prevalence of primary glaucoma in rural population.
We were unable to perform visual field assessments in all cases due to illiteracy in rural patients and difficulty in understanding the test. We could not find association of family history in our study due to lack of awareness about glaucoma. The risk of glaucoma increases significantly with a positive family history.,
We have not studied other risk factors such as body mass index, anemia, thinner corneas, and longer axial length. The Barbados Eye study and the Rotterdam study reported thinner CCT in POAG patients., However, there are very few Indian studies who have reported CCT in glaucoma and found no significant difference than the normal population.
The proportion of undiagnosed glaucoma found in this study may be the tip of the iceberg. Most of our primary glaucoma patients had advanced glaucoma in one or both eyes and had irreversible blindness at the time of presentation. All cases of established POAG (75%) and PACG (86.53%) were then treated with either antiglaucoma medications or surgical line of management. Suspected cases were advised close follow-up.
There is a need to increase awareness about glaucoma through peripheral outreach activities to prevent irreversible loss of vision.
In summary, the distribution of open-angle and narrow-angle glaucoma in our study was 1.2:1. Narrow-angle glaucoma (PACG) was more blinding than open-angle glaucoma in our study patients. The associated risk factors for primary glaucoma were age, gender, high IOP, refractive errors, and systemic illness.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY, et al.
Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology 2014;121:2081-90.
Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol 2002;86:238-42.
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006;90:262-7.
Nangia V, Jonas JB, Matin A, Bhojwani K, Sinha A, Kulkarni M, et al.
Prevalence and associated factors of glaucoma in rural central India. The central India eye and medical study. PLoS One 2013;8:e76434.
Vijaya L, George R, Arvind H, Baskaran M, Ve Ramesh S, Raju P, et al.
Prevalence of primary angle-closure disease in an urban South Indian population and comparison with a rural population. The Chennai Glaucoma Study. Ophthalmology 2008;115:655-60.
Vijaya L, George R, Baskaran M, Arvind H, Raju P, Ramesh SV, et al.
Prevalence of primary open-angle glaucoma in an urban South Indian population and comparison with a rural population. The Chennai Glaucoma Study. Ophthalmology 2008;115:648-54.
Jacob A, Thomas R, Koshi SP, Braganza A, Muliyil J. Prevalence of primary glaucoma in an urban South Indian population. Indian J Ophthalmol 1998;46:81-6.
] [Full text]
Dandona L, Dandona R, Mandal P, Srinivas M, John RK, McCarty CA, et al.
Angle-closure glaucoma in an urban population in Southern India. The Andhra Pradesh eye disease study. Ophthalmology 2000;107:1710-6.
Dandona L, Dandona R, Srinivas M, Mandal P, John RK, McCarty CA, et al.
Open-angle glaucoma in an urban population in Southern India: The Andhra Pradesh eye disease study. Ophthalmology 2000;107:1702-9.
Ramakrishnan R, Nirmalan PK, Krishnadas R, Thulasiraj RD, Tielsch JM, Katz J, et al.
Glaucoma in a rural population of Southern India: The Aravind Comprehensive Eye Survey. Ophthalmology 2003;110:1484-90.
Ronnie G, Ve RS, Velumuri L, Asokan R, Vijaya L. Importance of population-based studies in clinical practice. Indian J Ophthalmol 2011;59, Suppl S1:S11-8.
Vijaya L, George R, Paul PG, Baskaran M, Arvind H, Raju P, et al.
Prevalence of open-angle glaucoma in a rural South Indian population. Invest Ophthalmol Vis Sci 2005;46:4461-7.
Raychaudhuri A, Lahiri SK, Bandyopadhyay M, Foster PJ, Reeves BC, Johnson GJ, et al.
Apopulation based survey of the prevalence and types of glaucoma in rural West Bengal: The West Bengal glaucoma study. Br J Ophthalmol 2005;89:1559-64.
Agarwal S, Shamshad MA, Goel D, Ansari M. Distribution of glaucoma in the major religious communities of a North Indian town: A hospital survey. J Clin Diagn Res 2013;7:499-502.
Paul C, Sengupta S, Choudhury S, Banerjee S, Sleath BL. Prevalence of glaucoma in Eastern India: The Hooghly River Glaucoma Study. Indian J Ophthalmol 2016;64:578-83.
] [Full text]
Garudadri C, Senthil S, Khanna RC, Sannapaneni K, Rao HB. Prevalence and risk factors for primary glaucomas in adult urban and rural populations in the Andhra Pradesh eye disease study. Ophthalmology 2010;117:1352-9.
Narayanaswamy A, Baskaran M, Zheng Y, Lavanya R, Wu R, Wong WL, et al.
The prevalence and types of glaucoma in an urban Indian population: The Singapore Indian Eye Study. Invest Ophthalmol Vis Sci 2013;54:4621-7.
Leske MC, Connell AM, Schachat AP, Hyman L. The Barbados Eye Study. Prevalence of open angle glaucoma. Arch Ophthalmol 1994;112:821-9.
George R, Paul PG, Baskaran M, Ramesh SV, Raju P, Arvind H, et al.
Ocular biometry in occludable angles and angle closure glaucoma: A population based survey. Br J Ophthalmol 2003;87:399-402.
Thapa SS, Paudyal I, Khanal S, Twyana SN, Paudyal G, Gurung R, et al.
Apopulation-based survey of the prevalence and types of glaucoma in Nepal: The Bhaktapur glaucoma study. Ophthalmology 2012;119:759-64.
Jonas JB, Zäch FM, Gusek GC, Naumann GO. Pseudoglaucomatous physiologic large cups. Am J Ophthalmol 1989;107:137-44.
Chopra V, Varma R, Francis BA, Wu J, Torres M, Azen SP, et al.
Type 2 diabetes mellitus and the risk of open-angle glaucoma the Los Angeles Latino Eye Study. Ophthalmology 2008;115:227-320.
Salim S, Shields MB. Glaucoma and systemic diseases. Surv Ophthalmol 2010;55:64-77.
Xu L, Wang Y, Wang S, Wang Y, Jonas JB. High myopia and glaucoma susceptibility the Beijing eye study. Ophthalmology 2007;114:216-20.
Sun J, Zhou X, Kang Y, Yan L, Sun X, Sui H, et al.
Prevalence and risk factors for primary open-angle glaucoma in a rural Northeast China population: A population-based survey in Bin county, Harbin. Eye (Lond) 2012;26:283-91.
Rossetti L, Digiuni M, Montesano G, Centofanti M, Fea AM, Iester M, et al.
Blindness and glaucoma: A multicenter data review from 7 academic eye clinics. PLoS One 2015;10:e0136632.
Kyari F, Entekume G, Rabiu M, Spry P, Wormald R, Nolan W, et al.
Apopulation-based survey of the prevalence and types of glaucoma in Nigeria: Results from the Nigeria national blindness and visual impairment survey. BMC Ophthalmol 2015;15:176.
Shweikh Y, Ko F, Chan MP, Patel PJ, Muthy Z, Khaw PT, et al.
Measures of socioeconomic status and self-reported glaucoma in the U.K. Biobank cohort. Eye (Lond) 2015;29:1360-7.
Dielemans I, Vingerling JR, Wolfs RC, Hofman A, Grobbee DE, de Jong PT, et al.
The prevalence of primary open-angle glaucoma in a population-based study in the Netherlands. The Rotterdam study. Ophthalmology 1994;101:1851-5.
Vijaya L, George R, Arvind H, Ve Ramesh S, Baskaran M, Raju P, et al.
Central corneal thickness in adult South Indians: The Chennai Glaucoma Study. Ophthalmology 2010;117:700-4.
[Table 1], [Table 2], [Table 3]