Population-based screening leads to improved glaucoma diagnosis in Kazakhstan

Abstract

To analyse the effect of the state screening program for glaucoma, funded by the Kazakhstan State programs for the health care system “Salamatty Kazakhstan” (2011–2015) and “Densaulyk” (2016–2019), on glaucoma diagnosis. This study involved 1,620,658 men and women 40–70 years of age. State screening for glaucoma includes measures of intraocular pressure (IOP) and corneal thickness. Data for glaucoma incidence were retrieved from the state statistics dataset. Studies of vulnerable age groups and ophthalmologists’ availabilities were assessed, and correlations with glaucoma detection were determined. For the statistical analysis, MATLAB application package version R2017b (MathWorks, USA) was used. The number of registered glaucoma patients was 43,337 in 2010. In 2016, following the screening program, this figure increased to 68,195. A 49% increase in newly identified glaucoma cases from 70.8 (in 2010) to 124 (in 2016) per 100,000 population was determined. Thus, the sufficiency and effectiveness of the screening program were confirmed by the increase in the number of patients diagnosed with glaucoma, which also depended on age. A correlation between suspected glaucoma and age groups was exposed with the observation of a high number of cases in the older population. The state screening programs for glaucoma in the Republic of Kazakhstan constitute initial steps in the prevention of irreversible blindness and disability due to glaucoma. Such screening seems to allow timely and adequate diagnosis of the disease in people>40 years of age.

Key Messages

• The implementation of the Kazakhstan State programs for the health care system “Salamatty Kazakhstan” (2011–2015) and “Densaulyk” (2016–2019) enabled the detection of glaucoma cases in Kazakhstan of the population aged over 40 years.

• Education of the population about the prevention and treatment of glaucoma has a vital role in lowering the cases of this socially significant pathology.

• Increasing the number of eye care specialists and implementing high-tech diagnostic tools will be the main steps in the strategy for early detection of glaucoma.

Keywords:

• Glaucoma
• screening
• Kazakhstan
• population
• diagnosis

1. Introduction

Glaucoma is a group of diseases caused by multiple factors and manifested by visual field deterioration and progressive optic neuropathy (Jonas et al., 2017; Quigley & Broman, 2006). The main and common pathogenetic symptom is optic nerve degeneration, usually accompanied by increased intraocular pressure (IOP) (Armaly, 1969; Foster et al., 2002; Sommer et al., 1991). At the cellular level, apoptosis of retinal ganglion cells leads to the loss of retinal ganglion cell dendrites and thinning of the retinal nerve fibre layer (Garcia‐valenzulela et al., 1994; Jonas et al., 2017).

Glaucoma is a major cause of blindness (Coleman, 1999), especially in developing countries (Cedrone et al., 2008), and is the most frequent cause of irreversible vision loss in Kazakhstan (Islamova, 2009). According to data collected by Islamova (Islamova, 2009), the incidence of glaucoma in the Republic of Kazakhstan has increased by 25% over the past 10 years. This might be the result of the influence of lifestyle, environmental and genetic factors (Pasquale & Kang, 2009; Renard et al., 2013), and the growth of the average life expectancy in the country (undefined). For the same decade, the number of disabilities due to glaucoma grew 3.7-fold, and its position among the causes of disabilities in the country rose from fifth to second place (Islamova, 2009).

Now, and as of 2014, glaucoma can be attributed to the cause of blindness in around a third of people in Kazakhstan (Buribayeva et al., 2016). Every fifth visually disabled person (21.6%) is a person of working age (Buribayeva et al., 2016). Considering the increase in the number of people with blindness and the age demography, glaucoma constitutes an urgent social and economic issue (Gramer & Gramer, 2018). Hence, early detection and treatment of glaucoma might be a huge contribution to the prevention of glaucoma-related blindness.

According to Sommer (Sommer, 1990), the average age of presentation with glaucoma was 57.83 years in 2012. However, this data portrays glaucoma that has already progressed and early detection of the disease from 40 years of age is needed.

Measurement of IOP has been the general method of screening for glaucoma. The sensitivity and specificity of this technique, however, are low, and there is a demand for more extensive detection methods (Sommer, 1990). The main achievement in the organisation of the fight against glaucoma in the Republic of Kazakhstan has been the state screening program, which began in 2011 and was aimed at early detection of the disease (Aizhan & Saipinov, 2014). The mission of the Kazakhstan State screening program was to identify cases of increased IOP among persons over 40 years of age, followed by an examination for glaucoma in specialised glaucoma offices. These glaucoma offices were opened as part of the state programs “Salamatty Kazakhstan” (Aizhan & Saipinov, 2014) and “Densaulyk” (undefined) for health care system development in the Republic of Kazakhstan between 2011–2015 and 2016–2019, respectively, and elevated the quality of disease management due to the availability of retinal tomography and computer perimeters. The innovative development of diagnostic ophthalmic equipment has led to improved standards of diagnosis and monitoring of glaucoma. Despite this great implementation, there have been no systematic comparative studies of the epidemiology and screening methods of glaucoma in Kazakhstan to date. It is thus unclear whether these state programs enhance glaucoma detection in the country and identify vulnerable population groups. To address this knowledge gap, we aimed to investigate the effect of the state screening programs on the incidence of glaucoma diagnosis in Kazakhstan and determine whether the state programs can identify glaucoma from as early as 40 years.

2. Materials and methods

This population-based study involved 1,620,658 men and women in the age range of 40–70 years (Table S1, Supplementary material). Each selected participant was invited by the glaucoma cabinet specialists—Ophthalmologists/Optometrists following the simple random sampling by generating random numbers using the random number function (RAND) in MS Excel. The glaucoma examination involved tonometry (to assess the intraocular pressure) and pachymetry (to assess the corneal thickness) methods. The first state screening program, “Salamatty Kazakhstan”, aimed to identify those with increased IOP; however, cases of glaucoma with low IOP and underestimation of IOP indices with thin central cornea thickness go unnoticed by ophthalmologists. In this regard, the indications for examination of glaucoma with systemic hypertension were expanded during screening in the second program, “Densaulyk”, and measurement of corneal thickness with endothelial tissue investigation was included in the protocols for the diagnosis and treatment of glaucoma as a mandatory research method. Moreover, additional training was provided for ophthalmologists to raise awareness of this issue. It should be noted that glaucoma is one of the main socially significant diseases included in these programs among other pathologies.

Apart from the medical history survey there was conducted an ophthalmologic examination, which included viscometry, autorefractometry, computerized examination of the visual field (not available in all regions), slit-lamp observation of the anterior and posterior eye segments, evaluation of the optic disc using direct ophthalmoscopy and applanation (contact) tonometry utilizing a Maklakov applanation tonometer (MAT) under topical anaesthesia (Tables S2 and S3, Supplementary material). Although among the IOP measurement methods, the Goldmann applanation tonometry (GAT) is considered the gold standard (Goldmann & Schmidt, 1957), we were limited to using MAT in this study. This is a historically determined issue when Kazakhstan’s current healthcare system was constructed by the USSR’s standards.

To classify the screening outcomes, the following diagnostic criteria were adopted: ocular hypertension (OH); primary open-angle glaucoma (POAG); primary angle-closure glaucoma (PACG) and normal-tension glaucoma (NTG).

Ocular hypertension manifests with the IOP≥22 mmHg without damage of the visual field and ONH, with no characteristic symptoms of secondary glaucoma and closure of the anterior chamber angle. POAG is characterised by ocular hypertension, glaucomatous ONH and visual field abnormalities. However, the chamber angle is not occluded, whereas the sign of a partly or totally closed anterior chamber angle is closed in PACG. Moreover, PACG is also manifested by the above-mentioned glaucoma signs. Assessment of the anterior chamber angle was performed using the Van-Herick grading technique (Van Herick et al., 1969). The main difference between NTG from OH, POAG and PACG is the normal eye pressure (IOP<22 mmHg) with other pathognomic symptoms: the damage of the visual field and ONH.

The study was conducted in different parts of the country, and the diagnosis of glaucoma was standardized across areas using the above-mentioned diagnostic procedures and glaucoma classification. All procedures performed in studies involving human participants were reviewed and approved by the Institutional Review Board of the Local ethics committee of the Kazakh Eye Research Institute (Almaty, Kazakhstan) before the initiation of the study and were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All participants gave their written informed consent before their inclusion in the study.

Data were retrieved from official statistics from Medinform LLP (undefined), which prepares and publishes analytical data on the state of public health. The data were analysed using the MATLAB application package version R2017b (MathWorks, USA). Comparative studies of vulnerable age groups and the influence of the availability of ophthalmological personnel on the incidence of glaucoma were conducted. For the latter, linear regression analysis was performed with the calculation of the R-square value.

3. Results

3.1. Glaucoma epidemiology in Kazakhstan

We first aimed to study the effectiveness of the state glaucoma screening programs. Despite the risks of underdiagnosing the disease during screening due to the risk of normal-tension glaucoma, we saw an upward trend in the number of patients diagnosed with glaucoma. This trend depended on age (Figure 1 and Table 1), whereby an increase in the percentage of detectable glaucoma was observed in older age groups. 0.6% (or 10 711) had one or more manifestations of NTG: IOP<22 mmHg with damage of the visual field and optic disc, no signs of secondary glaucoma and closure of the angle of the anterior chamber. These initial findings suggest that the screening program is effective at identifying cases of glaucoma in the population.

Figure 1. Glaucoma detection in different age groups according to the screening results in the framework of the State Program of the Development of Healthcare.

Table 1. Results of preventive medical examinations performed between 01/01/2016–31/12/2016 to detect glaucoma in men and women aged 40–70 years

Age	The total number of people examined	Patients with suspected glaucoma*	Patients with confirmed glaucoma	Global incidence data in % with confidence intervals (Kapetanakis et al., 2016)
40–49	634857	882 (0.14%)	781 (0.12%)	0.4 (0.2–0.5)
50–59	609427	1730 (0.28%)	1566 (0.26%)	0.7 (0.5–1.0)
60–69	344364	1784 (0.52%)	1660 (0.48%)	1.4 (1.0–1.9)
70	32010	257 (0.80%)	246 (0.77%)	2.7 (2.1–3.7)
Total	1620658	4653	4253

 * if any of the following symptoms was detected: family history of glaucoma, increased IOP (≥21 mmHg), increased cup-to-disc ratio, thinning or/and defect of RNFL.

According to the data from Medinform LLP (undefined), the number of registered glaucoma patients when screening began in 2011 was 43,337. By contrast, after the program was completed at the end of 2016, this number had increased to 68,195.

The total number of newly diagnosed glaucoma cases during screening increased by an average of 49%, meaning that from 2012 an average of 4,000 new glaucoma cases were detected every year (Figure 2). We thus infer that the effectiveness of screening to detect new cases of the disease is 49%. These findings were confirmed by the Medinform LLP data on the primary incidence of glaucoma: 70.8 per 100,000 population in 2011 against 124 per 100,000 population in 2016.

Figure 2. The total number of patients with newly diagnosed glaucoma (Medinform LLP) [15].

3.2. Regional variation of glaucoma in Kazakhstan

We also collated data on glaucoma incidence across regions of Kazakhstan and saw a higher than average prevalence in the southern territories of the country (Figure 3). In particular, this growth was noted in Kyzylorda and South Kazakhstan oblasts. More than 136 glaucoma cases per 1,000 population were observed in Pavlodar and Atyrau oblasts, and between 83 and 117 cases per 1,000 were detected in Zhambyl, West, North and East Kazakhstan oblasts. The number of confirmed glaucoma cases was lower in the rest of the country. These observations may help to focus on specific endemic regions of Kazakhstan in the future in terms of prevention of the disease, allocation of funds and understanding the causes of glaucoma in vulnerable groups of the population.

Figure 3. Cartogram showing glaucoma incidence in different regions of the Republic of Kazakhstan per 100,000 population. WKO – West Kazakhstan oblast, NKO – North Kazakhstan oblast, EKO – East Kazakhstan oblast, SKO – South Kazakhstan oblast.

3.3. Influence of the availability of ophthalmologists on glaucoma incidence

To understand the reason behind this variability in prevalence according to geographical region, we sought to determine whether there might be a correlation between glaucoma incidence and the availability of ophthalmological personnel (Table 2 and Figure 4). Indeed, upon analysing the dependence of glaucoma incidence rates on the availability of ophthalmologists, we revealed high correlations in various regions of the republic.

Figure 4. Dependence of the incidence of glaucoma on the availability of ophthalmic personnel.

Table 2. The number of patients with glaucoma and ophthalmologists in Kazakhstan and its regions. WKO – West Kazakhstan oblast, SKO – South Kazakhstan oblast, NKO – North Kazakhstan oblast, EKO – East Kazakhstan oblast

	Glaucoma patients per 100,000 people	Ophthalmologists per 100,000 people
Kazakhstan	113.9	0.8
Akmola oblast	69.1	0.6
Aktobe oblast	68.1	1.2
Almaty oblast	48.9	0.2
Atyrau oblast	150.9	0.7
WKO	62.4	0.7
Zhambyl oblast	66.0	0.4
Karaganda oblast	63.5	0.8
Kostanay oblast	88.1	0.5
Kyzylorda oblast	144.8	0.3
Mangystau oblast	49.5	0.5
SKO	194.8	0.5
Pavlodar oblast	120.5	0.7
NKO	117.7	0.7
EKO	73.4	0.9
Astana	142.3	1.9
Almaty	228.0	2.4

4. Discussion

In this study, we confirmed the strength of the state screening programs on the high accuracy of glaucoma detection in Kazakhstan. Overall, the number of registered glaucoma patients increased from 43,337 to 68,195 during the screening programs, amounting to around 4,000 glaucoma cases yearly due to the access of all potentially vulnerable populations to the glaucoma cabinets with the essential diagnostic tools, financial support from the screening programs and involvement of specialists from Almaty and Astana to the operation of screening bases in the rural regions. Consistent with the epidemiology of glaucoma worldwide (Allison et al., 2020; Kolko et al., 2015; Kreft et al., 2021; Ooba et al., 2020), we noted an increase in glaucoma incidence with age (Quigley & Broman, 2006).

We were interested to find a high incidence of the previously undetected disease in remote regions of the country, especially in Atyrau, Pavlodar, Kyzylorda, and South Kazakhstan oblasts, which correlated with the lack of specialists in these regions. These data have helped uncover the existing situation of undetected cases of glaucoma in these oblasts due to the screening program helping to identify otherwise undetected cases of glaucoma in regions that are typically poor in terms of ophthalmologic personnel. The causes of this high-level incidence are unexplained; thus, our findings highlight a requirement to further investigate the local variations in high-risk oblasts.

Based on our findings, the estimated number of officially registered cases of glaucoma should have exceeded 113,000 by the end of 2016. However, according to Medinform LLP, the estimated number is only 68,195. The database showing the total number of registered patients with a particular disease is compiled based on at least one annual visit to outpatient clinics. Therefore, we might assume that approximately 25% of patients with an established glaucoma diagnosis do not undergo follow-up and clinical examination for the disease. The most likely reasons for this drop-off in glaucoma follow-up are the lack of a glaucomatous patient register and an insufficient level of information and guidance given to affected patients about the consequences of the disease. Potential dropouts and missing cases are the topics of further investigation of the glaucoma screening programs.

Many developing countries suffer from a lack of eye care specialists and diagnostic machines. In our study, we saw how reduced numbers of ophthalmologists impacts glaucoma detection, as evidenced by the high dependencies of the incidence of glaucoma on the availability of ophthalmic personnel (R² = 0.8865). These data confirm the need for further funding in rural communities of developing countries, such as the distant areas of the Kazakhstan republic.

Overall, the two screening programs employed in Kazakhstan were successful in expanding the detection of glaucoma cases. However, the increased screening and newly provided diagnostic equipment were not enough for the prevention and early detection of glaucoma. Consequently, it is necessary to raise the level of public awareness and improve the knowledge of ophthalmologists. These solutions are possible within the framework of the implemented state program of health development “Densaulyk” adopted in the Republic of Kazakhstan between 2016–2019 (undefined).

The delegation of authority concerning follow-up observation of glaucoma patients can be lengthy due to the use of high-tech diagnostic equipment in monitoring the disease, which incurs financial costs. In countries of the Organisation for Economic Co-operation and Development (OECD), hospital funding amounts to 34%, and a huge share of the Ministry of Health budget (61%) is spent on primary health care. In Kazakhstan, 62% of the Ministry of Health budget goes to the inpatient sector, while only 34% is allocated to the primary health care service (undefined). As such, the strategy for the reduction of glaucoma incidence should be focused on the increased funding of the outpatient health sector.

Among the limitations of the study, it should be noted that the age range was limited between 40 and 70. Thus, with the growing risk of glaucoma in younger age groups (Marx-Gross et al., 2017; Park et al., 2017), studies of the younger population were not conducted. This might be put into practice in Kazakhstan and countries with similar demographics. Moreover, we have shown that the screening programs have identified people with glaucoma but not the follow-up of these patients. It would help to assess the effectiveness of the screening in terms of the prevention of blindness and vision-related disability.

In summary, the implementation of the state programs “Salamatty Kazakhstan” (Aizhan & Saipinov, 2014) and “Densaulyk” (undefined) has played a crucial role in the detection of glaucoma cases in Kazakhstan. We conclude that this structured approach to identifying those suffering from this socially significant ophthalmic pathology is essential and should be available to the population aged over 40 years to aid the early detection of glaucoma. It is also important to educate the population about glaucoma prevention, effective methods of treatment, and the opportunities provided by domestic medicine, including a list of services within the guaranteed volume of free medical care. Going forwards, we hope to investigate further the prevalence of glaucoma in the country and prepare a strategy for early detection of the disease before the onset of the clinical manifestations by increasing the number of eye care specialists and implementing high-tech diagnostic tools, such as optical coherence tomography with the analysis of the retinal texture (Kulmaganbetov et al., 2022). Although the understanding of the reasons for regional variations was beyond the scope of this study, further observations are needed to perform the targeted treatment and prophylactic activities.

Author contributions

Conception and design: LBT, NAA. MK; Analysis and interpretation of the data: LBT, MK; Drafting of the paper, revising it critically for intellectual content: MK, AMA; Final approval of the version to be published: NAA. All authors agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.

Statements

1. All methods were carried out in accordance with relevant guidelines and regulations.

2. All patients provided written informed consent before participation in this study.

Acknowledgments

The authors would like to thank all patients and their families for their participation in this study. The authors would also like to thank the Government of the Republic of Kazakhstan for the implementation of the state programs “Salamatty Kazakhstan” (2011–2015) and “Densaulyk” (2016–2019). MK acknowledges the InnoHK initiative and the Hong Kong Special Administrative Region Government.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The authors confirm the terms of the share upon reasonable request data policy and have deposited on the location: https://drive.google.com/drive/u/0/my-drive.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Lyaylya Bolatovna Tashtitova

Lyaylya Bolatovna Tashtitova is the Head of the outpatient department and ophthalmic surgeon at the Kazakh Eye Research Institute, and the doctor of the highest category. Her research interests include the treatment of glaucoma, cataract and glaucoma surgeries, and the epidemiology of ophthalmic diseases.

Neilya Akhmetovna Aldasheva

Neilya Akhmetovna Aldasheva is a doctor of medical sciences, General Director and ophthalmic surgeon at the Kazakh Eye Research Institute, and the doctor of the highest category. Her research interests include glaucoma surgery, epidemiology of ophthalmic diseases, and management of the eye health care system.

Ardak M. Auyezova

Ardak M. Auyezova is the Rector of the Higher School of Public Health of Kazakhstan Medical University and an ophthalmologist. Her research interests include vascular pathology of the eye, organization of medical activities, and public health.

Mukhit Kulmaganbetov

Mukhit Kulmaganbetov is a Postdoctoral Fellow in the Quantum Optics Lab at the Centre for Eye and Vision Research (CEVR), a research collaboration between The Hong Kong Polytechnic University and the University of Waterloo in Canada under the InnoHK initiative of the HKSAR Government. His research interests include retinal neuronal degeneration (including glaucoma, age-related macular degeneration, and Alzheimer’s disease), machine learning tools for image processing and classification, optical coherence tomography, and quantum optics.