CC BY
39
УДК 617.7-007.681(574)
DOI 10.53065/kaznmu.2022.19.44.083
L. Tashtitova1, M. Kulmaganbetov23, N. Aldasheva2, A. Auyezova1
1Higher School of Public Health, Kazakhstan Medical University, Almaty, Kazakhstan 2Glaucoma Department, Kazakh Eye Research Institute, Almaty, Kazakhstan 3School of Optometry and Vision sciences, Cardiff University, Cardiff, UK
PREVALENCE OF NORMAL-TENSION GLAUCOMA IN KAZAKHSTAN: RESULTS OF STATE
SCREENING PROGRAM
Resume: To assess the prevalence of normal-tension glaucoma in Kazakhstan using the results of the State Screening program. Materials and methods. 1 806 876 participants aged 40-70 years underwent screening examinations for the detection of glaucoma. Also, the measurement of intraocular pressure (IOP) using applanation tonometry employing a Maklakov tonometer under topical anaesthesia was carried out with the other ophthalmologic examinations: visometry, autorefractometry, computerized examination of the visual field, slit-lamp observation of the anterior and posterior eye segments and evaluation of the optic disc using direct ophthalmoscopy.
Results. The prevalence of various types of glaucoma, including primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG) and normal-tension glaucoma (NTG) were investigated, with the particularfocus on the latter. NTG was detected in 10 711 respondents, which is 0.6% of all participants with normal or lower IOP.
Conclusion. The study of NTG prevalence was demonstrated in this paper and more than 10 thousand people were diagnosed with normal or low tension glaucoma according to the outcomes of the State Screening program. Keywords: glaucoma, intraocular pressure, screening, tonometry, Kazakhstan
Л. Б. Таштитова 1-2, М. Кульмаганбетов 2,3, Н.А. Алдашева 2, А.М. Ауезова 1
1 «Казахстанский медицинский университет «ВШОЗ», Алматы, Казахстан 2 ТОО "Казахский ордена "Знак Почета" научно-исследовательский институт глазных болезней", Алматы, Казахстан 3School of Optometry and Vision sciences, Cardiff University, Cardiff, UK
РАСПРОСТРАНЕННОСТЬ ГЛАУКОМЫ НОРМАЛЬНОГО НАПРЯЖЕНИЯ В КАЗАХСТАНЕ: РЕЗУЛЬТАТЫ ГОСУДАРСТВЕННОЙ ПРОГРАММЫ СКРИНИНГА
Резюме: Оценить распространенность глаукомы нормального напряжения в Казахстане с использованием результатов Государственной программы скрининга.
Материалы и методы. 1 806 876участников в возрасте 40-70 лет прошли скрининговые обследования на предмет выявления глаукомы. Кроме того, измерение внутриглазного давления (ВГД) с помощью аппланационной тонометрии с использованием тонометра Маклакова под местной анестезией проводилось вместе с другими офтальмологическими исследованиями: визометрией, авторефрактометрией, компьютерным исследованием поля зрения, наблюдением переднего и заднего сегментов глаза при щелевой лампе и оценкой диска зрительного нерва с помощью прямой офтальмоскопии.
Результаты. Была исследована распространенность различных типов глаукомы, включая первичную открытоугольную глаукому (POUG), первичную закрытоугольную глаукому (PACG) и глаукому нормального напряжения (NTG), с особым акцентом на последнем. НТГ был обнаружен у 10 711 респондентов, что составляет 0,6% от всех участников с нормальным или более низким ВГД.
Выводы. В этой статье было продемонстрировано исследование распространенности НТГ, и более чем у 10 тысяч человек была диагностирована глаукома нормального или низкого напряжения в соответствии с результатами Государственной программы скрининга.
Ключевые слова: глаукома, внутриглазное давление, скрининг, тонометрия, Казахстан
Л.Б. Таштитова 1-2, М. Кульмаганбетов 2'3, Н. А. Алдашева 2, А.М.Ауезова
1КДСМ «Казакстандык медицина университетi», Алматы, Казакстан 2"Курмет Белгс" opdeHdi Казак, квз аурулары гылыми-зерттеу институты"ЖШС, Алматы, Казахстан 3School of Optometry and Vision sciences, Cardiff University, Cardiff, UK
КДЗАКСТАНДА КДЛЫПТЫ КЕРНЕУ ГЛАУКОМАСЫНЫН, ТАРАЛУЫ: МЕМЛЕКЕТТ1К СКРИНИНГ БАFДАРЛАМАСЫНЫН НЭТИЖЕЛЕР1
Тушн: мемлекеттШ скрининг багдарламасыныц нэтижелерт пайдалана отырып, Казакстанда калыпты кернеу глаукомасыныц таралуын багалау.
Материалдармен adicmep. 40-70 жас аралыгындагы 1 806 876 катысушылар глаукоманы аныктау ушт скринингтк тексеруден вттг Сонымен катар, жергiлiктi анестезиямен Маклаков тонометрт колдана отырып, аппланациялык тонометрия квмегiмен квзшшк кысымды влшеу баска офтальмологиялык зерттеулермен бiрге жyргiзiлдi: визометрия, авторефрактометрия, квру врiсiн компьютерлк зерттеу, сацылаулы шаммен квздщ алдыцгы жэне арткы сегменттерт байкау жэне ткелей офтальмоскопия аркылы оптикалык нерв дисюст багалау.
Нэтижелерь Глаукоманыц apmypAi турлертщ таралуы зерттелд1 оныц штде бастапцы ашыц бурышты глаукома (POUG), бастапцы жабыц бурышты глаукома (PACG) жэне цалыпты кернеулi глаукома (NTG), соцгысына ерекше назар аударылды. 10 711 респонденттен аныцталды, бул цалыпты немесе темен децгейде барлыц цатысушылардыц 0,6% цурайды.
Цорытынды. Бул мацалада глаукома таралуын зерттеу керсетiлдi жэне 10 мыцнан астам адамга мемлекеттк скринингтШбагдарламаныц нэтижелерте сэйкес цалыпты немесе темен кернеулiглаукома диагнозы цойылгандыгын керсетедь
Tyurndi свздер: глаукома, кезшшк цысым, скрининг, тонометрия, Цазацстан
Introduction
Glaucoma is the leading cause of irreversible blindness, which affects 70 million people worldwide [1, 2]. Due to the asymptomatic nature of the disease, there is an assumption that the real prevalence of glaucoma is much greater than the reported values [3]. Normal-tension glaucoma (NTG) is a disease with progressive optic neuropathy and is characterised by a normal range of intraocular pressure (IOP) equalling the IOP of a healthy human (<22 mmHg) [4]. The incidence rate of NTG varies from region to region, majorly depending on the population's geographical area [5]. Multiple factors can cause NTG, and the pathogenesis of the disease remains unclear. Treatment options also vary, but similar procedures of therapy of open-angle glaucoma can be used. However, due to the normal/low IOP of patients with NTG, it is difficult to reach the values of eye pressure, which is not progressing the disease pathogenesis. While the primary management strategy includes the monitoring and prevention of systemic risk factors, the secondary interventions of the standard treatment of NTG are to decrease IOP and improvement of ocular perfusion [4]. Measurement of IOP has been the general method of screening for glaucoma. The sensitivity and specificity of this technique, however, is low, and there is a demand for more extensive detection methods [6]. The Glaucoma State Screening program was one of the main achievements in the organisation of the fight against glaucoma in the Republic of Kazakhstan. The program began in 2011 and was aimed at early detection of glaucoma. 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 cabinets. These specialised glaucoma cabinets with state-of-art glaucoma diagnostic machines were opened as part of the state program "Salamatty Kazakhstan" for health care system development in the Republic of Kazakhstan between 2011-2015. Availability of the retinal tomography and computer perimeters in the regional glaucoma cabinets, therefore, upgraded the quality of disease management and follow-up strategy. 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 prevalence of NTG in Kazakhstan to date. It is thus unclear whether these state programs enhance NTG detection in the country and identify the vulnerable population groups. To address this knowledge gap, we aimed to investigate the prevalence of normal-tension glaucoma in Kazakhstan using the results of the State Screening program. Materials and methods Population and Geographic area
The study aimed to investigate the data obtained from the State Screening program [7], where the glaucoma epidemiology of the whole population of Kazakhstan over 40 years of age was investigated. The proportion of this cohort constitutes around 40% of the entire population of
the country. Assuming the 2% prevalence of glaucoma according to the outcomes of the State Screening program [7] and a margin of the standard error of 1.5-2%, it has been calculated the number of people with overall glaucoma in 2011 and the participants with the normal IOP, but glaucoma manifestation, or else the number of patients with NTG.
The country population who is aged over 40 years to be enrolled on the study was selected on the basis of data provided by the State Statistics Dataset [8] and our recent study [9] as they contained the data of all participants who underwent the screening programs. Each selected participant was invited by the glaucoma cabinet specialists - Ophthalmologists/Optometrists following the simple random sampling. All participants were informed of the study purposes and procedures, signed an informed consent form. Procedures
The study was conducted in all fourteen regions and two major cities of Kazakhstan, in specially equipped screening centres, so-called glaucoma cabinets. The ophthalmic examinations were performed by trained and tested medical practitioners, who underwent periodical to quality control by the specialists of Kazakh Eye Research Institute. It was important to use the same instruments and devices throughout the entire screening period to be consistent in data collection and avoid deviations in the scanning of the retinal topography, measurement of IOP and visual field. All data obtained from patients were recorded on the record cards - History of Disease. 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) prior to 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. Screening examination
Apart from the medical history survey there was conducted an ophthalmologic examination, which included visometry, 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 tonometer under topical anaesthesia. Glaucoma classification
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 the damage of the visual field and ONH, with no characteristic symptoms of secondary glaucoma and closure of anterior chamber angle. POAG is characterised by ocular hypertension, glaucomatous ONH and visual field
abnormalities. However, the chamber angle is not occluded, whereas the sing of partly or totally closed anterior chamber angle is closed in PACG. Moreover, PACG is also manifested by the above-mentioned glaucoma signs. The main difference of 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.
Statistical analysis
The dataset was analysed using the MATLAB application
package version R2017b (MathWorks, USA).
Results
An upward trend in the number of patients diagnosed with glaucoma was noted in the detection of the disease in different age groups according to the screening results in the framework of the State Program of the Development of Healthcare (Figure 1). More than 50% of older age groups starting from 64 years of age were identified, reaching 80% in 69-70 years old participants.
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 depicts the epidemiology of open-angle glaucoma in Kazakhstan by region. It can be noted that the screening covered 94.83% of adults from 40 to 70 years. Latter is the indicator of the successful accomplishment of
the first mission of the state screening - to maximize the diagnostic coverage throughout the country. On the other hand, not all regions reached the highest degree of screening. For instance, only 67.57% of people attended the screening in the Mangystau region.
Table 1 - Results of the screening examinations of men and women aged 40-70 years for the detection of glaucoma (POAG and PACG)
Regions Subject to screening Underwent screening Detected patients
Number Proportion, % Number Proportion, %
Akmola region 95 183 88 329 92.8 166 0.19
Aktobe region 88 275 88 275 100 51 0.06
Almaty region 264 410 225 643 85.34 640 0.28
Atyrau region 55 135 51 086 92.66 59 0.12
West-Kazakhstan region 68 871 66 427 96.45 151 0.23
Zhambyl region 124 558 124 591 100 112 0.09
Karagandy region 199 976 190 632 95.33 491 0.26
Kostanai region 122 424 113 369 92.6 71 0.06
Kyzylorda region 131227 47 752 36.39 128 0.27
Mangystau region 31 969 21 603 67.57 40 0.19
South-Kazakhstan region 264 484 231201 87.42 1 501 0.65
Pavlodar region 71 376 61 573 86.27 46 0.07
North-Kazakhstan region 85 784 84 925 99 112 0.13
East-Kazakhstan region 185 173 177213 95.7 317 0.18
Astana city 30 457 47 797 156.9 228 0.48
Almaty city 86 165 186 460 216.4 356 0.19
Total 1 905 467 1 806 876 94.83 4 469 0.247
All in all, for the screening period of 2011-2015, 1,8 million people underwent the glaucoma screening from recommended 1,9 million potential risk group. Of these, 1,8 million respondents underwent the screening, and only 4 469 participants have been diagnosed with glaucoma, which is 0.25% of overall respondents. From Table 2, it can be concluded that IOP was measured in 1 806 876 patients, 98.8% of them had normal eye
pressure. Although 21 478 participants (or 1.19%) have either OH, POAG or PACG, the details of each glaucoma type proportion were beyond the scope of this paper. So, the aim was to investigate the presence of glaucomatous abnormalities of ONH and visual field among 1 785 282 respondents with normal IOP, hence the prevalence of NTG.
Table 2 - Results of the screening examinations of men and women aged 40-70 years for the detection of IOP
Regions Underwent screening Intraocular pressure (IOP)
Normal IOP Increased IOP
Absolute value Proportion, % Absolute value Proportion, %
Akmola region 88 329 87 540 99.1 789 0.9
Aktobe region 88 275 87 704 99.4 571 0.6
Almaty region 225 643 221886 98.3 3 757 1.7
Atyrau region 51 086 50 555 98.9 531 1.1
West-Kazakhstan region 66 427 65 960 99.3 467 0.7
Zhambyl region 124 591 122 816 98.6 1 775 1.4
Karagandy region 190 632 188234 98.7 2 398 1.3
Kostanai region 113 369 112 476 99.2 893 0.8
Kyzylorda region 47 752 47 083 98.6 667 1.4
Mangystau region 21 603 21 461 99.3 142 0.7
South-Kazakhstan region 231201 225626 97.6 5 461 2.4
Pavlodar region 61 573 61 355 99.7 218 0.3
North-Kazakhstan region 84 925 84 440 99.4 485 0.6
East-Kazakhstan region 177213 175 541 99.1 1 672 0.9
Astana city 47 797 47 364 99.1 433 0.9
Almaty city 186 460 185 241 99.3 1 219 0.7
Total 1 806 876 1 785 282 98.8 21 478 1.19
Of these 1,78 million participants, 0.6% (or 10 711) had one or more manifestations of NTG: IOP < 22 mmHg with the damage of the visual field and optic disc, no signs of
secondary glaucoma and closure of the angle of the anterior chamber (Figure 2).
Figure 2 - Glaucoma screening results. Here: POAG - primary open-angle glaucoma; OH - ocular hypertension; PACG -primary angle-closure glaucoma; NTG - normal-tension glaucoma
Discussion
Normal-tension glaucoma in Kazakhstan amounts to 0.6% of all population aged 40-70 years, which corresponds to the literature data. For instance, in the study of Bonomi et al., the prevalence of NTG was similar and the proportion of NTG was 0.6%, whereas OH was 2.1%, POAG - 1.4% and PACG - 0.6% [10].
However, it should be noted that in Asia, the prevalence of NTG varies depending on the geographical area and methodology of screening [5, 10, 11]. For example, Japan (3.5%) and Singapore (4.3%) are the countries with the highest incidence of NTG not only in Asia but in the world [12, 13], while the proportion of NTG is lower in the western world. The epidemiological studies in the Netherlands (0.3%) and Italy (0.6%) were elegantly conducted by Klein et al. [14] and Bonomi et al. [10], respectively.
Among other limitations, the screening methods of NTG should be updated and focused on the detection of early subtle retinal signs [15], which can be achieved using highresolution optical coherence tomography. This may help to detect the neurodegeneration of the retinal ganglion cell body and dendrites before the clinical manifestations of glaucoma and irreversible vision loss. For future investigations, detailed epidemiological studies of NTG and its aetiopathogenesis are needed to construct the strategy of prevention and management of NTG in Kazakhstan.
Although Kazakhstan is recognised as an Asian country, the prevalence of NTG in the country is close to European statistical ranges. Nonetheless, there is a huge concern about the ignorance of NTG as a socially significant eye condition. Hence, further monitoring of NTG is required in terms of the early treatment and preventive measurements of glaucoma.
Recently, in our study, we illustrated the possibilities of early detection of ocular neurodegeneration of retinal diseases in the example of artificial phantoms of the retina [15]. Application of the techniques of machine learning in the interpretation of the outcomes of the optical coherence tomography will place a role in the detection of early signs
of retinal ganglion cell apoptosis. This study is the first attempt to calculate the number of normal-tension glaucoma in Kazakhstan, a more hidden and dangerous type of this disease.
All in all, our study and literature data conclude the complexity of the detection of normal-tension glaucoma. The prevalence of NTG in Kazakhstan amounts to more than 10 thousand according to the outcomes of the State Screening program and can be increased if not diagnosed earlier. This disease is a hidden and more dangerous type of POAG, where the signs and symptoms can be detected only in the late stage of the disease. In this situation, irreversible vision loss is inevitable and cannot be treated medically and surgically.
Disclosures: There is no conflict of interest for all authors. Acknowledgements: We thank all patients for their participation in this study. We also acknowledge all our colleagues for their patience, consultation and support. Funding: None.
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Сведения об авторах:
Таштитова Ляйла Болатовна - заведующая дневным стационаром ТОО "Казахский ордена "Знак Почета" научно-исследовательский институт глазных болезней", PhD докторант «Казахстанский медицинский университет «ВШОЗ», г. Алматы, Казахстан» Email: [email protected] ORCID: https://orcid.org/0000-0002-2670-4554
Алдашева Найля Ахметовна 2, д.м.н., и.о. генерального директора
ТОО " Казахский ордена "Знак Почета" научно-исследовательский институт глазных болезней", ORCID: https://orcid.org/0000-0002-2096-9738
Ауезова Ардак Мухамеджановна1, Казахстанский Медицинский Университет «ВШОЗ», кафедра Управления здравоохранением, PhD ORCID: https://orcid.org/0000-0001-5620-1651
