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48IRSTI 76.29.56 UDC 617.711-004.4
ETIOPATOGENETIC ASPECTS OF THE TREATMENT OF PTERYGIUM
E. Nurlybekova, T. Teleuova, M. Suleymenov, Z. Utelbaeva, M. Rakhimova
Department of Ophthalmology, Kazakh National Medical University named after S.D. Asfendiyarov, Kazakhstan, 050000 , Almaty, Tole bi, 94
Yerkezhan Nurlybekova - PhD candidate department of Ophthalmology, Kazakh National Medical University named after S.D. Asfendiyarov, Almaty, Kazakhstan. E-mail: yerke-zhan@mail.ru ORCID: 0000-0002-0195-1516.
Tynyskul Teleuova - professor at department of Ophthalmology, Kazakh National Medical University named after S.D. Asfendiyarov, Almaty, Kazakhstan. E-mail: ttelеuova@mail.ru. ORCID: 0000-0002-8238-265X.
Marat Suleymenov - professor at department of Ophthalmology, Kazakh National Medical University named after S.D. Asfendiyarov, Almaty, Kazakhstan. E-mail: maratsuleymenov.71@mail.ru. ORCID: 0000-0001-6038-8009.
Zauresh Utelbayeva - professor at department of Ophthalmology, Kazakh National Medical University named after S.D. Asfendiyarov, Almaty, Kazakhstan. E-mail:utelbayeva_zaure@mail.ru ORCID: 0000-0003-4312-9093.
Meruert Rakhimova - student of Kazakh National Medical University named after S.D. Asfendiyarov, Almaty, Kazakhstan. ORCID 0000-0002-5089-9144.
Pterygium is a common disease of the ocular surface associated with the growth of fibrovascular tissue from the conjunctiva through the limbal zone to the cornea, which in the advanced stage is not only a cosmetic defect, but also reduces visual acuity. The main problem of successful surgical treatment of pterygium is the high risk of recurrence. In modern pterygium surgery, the method of choice is the use of the so-called barrier method of treatment, with the replacement of the defect of the bulbar conjunctiva above the bed of the removed pterygium with various biocompatible tissues. These operations are performed selectively or in combination with adjuvant therapy. The search for an adequate method of treating pterygium, which combines ease of implementation, minimal risk of recurrence and complications, and optimal cosmetic effect, remains an urgent problem in modern ophthalmology.
Key words: pterygium, conjunctival autograft, amniotic membrane, adjuvant therapy.
ЭТИОПАТОГЕНЕТИЧЕСКИЕ АСПЕКТЫ ЛЕЧЕНИЯ ПТЕРИГИУМА Е.Н. Нурлыбекова, Т.С. Телеуова, М.С. Сулейменов, З.Т. Утелбаева, М.Д. Рахимова
Казахский национальный медицинский университет имени С.Д. Асфендиярова, кафедра офтальмологии, Казахстан, 050000, г. Алматы, ул. Толе би, 64
Нурлыбекова Еркежан Нурлыбеккызы - докторант кафедры офтальмологии Казахского Национального медицинского университета им. С.Д. Асфендиярова, Алматы, Казахстан. Электронная почта: yerke-zhan@mail.ru . ORCID: 0000-0002-0195-1516.
Телеуова Тыныскуль Сулейменовна - профессор кафедры офтальмологии Казахского Национального медицинского университета им. С.Д. Асфендиярова, Алматы, Казахстан. Электронная почта: ttelеuova@mail.гu ORCID: 0000-0002-8238-265X.
Сулейменов Марат Смагулович - профессор кафедры офтальмологии Казахского Национального медицинского университета им. С.Д. Асфендиярова, Алматы, Казахстан. Электронная почта: maratsuleymenov.71@mail.ru. ORCID : 0000-0001-6038-8009.
Утелбаева Зауреш Турсуновна - профессор кафедры офтальмологии Казахского национального медицинского университета им. С.Д. Асфендиярова, Алматы, Казахстан. Электронная почта: utelbaeva zaure@mail.ru. ORCID: 0000-0003-4312-9093.
Рахимова Меруерт Данияркызы - студентка Казахского национального медицинского университета им. С.Д. Асфендиярова, Алматы, Казахстан. ORCID : 0000-0002-5089-9144.
Птеригиум - распространенное заболевание глазной поверхности, связанное с нарастанием фиброваскулярной ткани со стороны конъюнктивы через лимбальную зону на роговицу, которое в развитой стадии не только является косметическим дефектом, но и снижает остроту зрения. Основной проблемой успешного хирургического лечения птеригиума является высокий риск рецидивов. В современной хирургии птеригиума методом выбора считается использование так называемого барьерного способа лечения, с замещением дефекта бульбарной конъюнктивы над ложем удаленного птеригиума различными биосовместимыми тканями. Данные операции проводятся селективно или в комбинации с антирецидивной адьювантной терапией. Поиск адекватного метода лечения птеригиума, сочетающего простоту выполнения,
минимальный риск рецидивов и осложнений, оптимальный косметический эффект, остается актуальной проблемой в современной офтальмологии.
Ключевые слова: птеригиум, аутотрансплантат конъюнктивы,амниотическая мембрана, адъювантная терапия.
ПТЕРИГИУМДЫ ЕМДЕУДЩ ЭТИОПАТОГЕНЕТИКАЛЬЩ АСПЕКТ1ЛЕР1
Нурлыбекова Е.Н., Телеуова Т.С., Сулейменов М.С., Утелбаева З.Т., Рахимова
М.Д.
С.Д. Асфендияров атындагы Казак улгтык медицина университет^ офтальмология кафедрасы, офтальмология кафедрасы, Казакстан, 050000, Алматы, Теле би кешеа, 64
Нурлыбекова Еркежан Нурлыбеккызы - С.Д. Асфендияров атындагы Казак улттык медицина университетшщ офтальмология кафедрасыньщ докторанты. Алматы, Казакстан. E-mail: yerke-zhan@mail.ru ORCID: 0000-0002-0195-1516.
Телеуова Тыныскул Сулейменкызы - С.Д. Асфендияров атындагы Казак улттык медицина университет офтальмология кафедрасыныц профессоры. Алматы, Казакстан. E-mail: ttelеuova@mail.ru. ORCID: 0000-0002-8238-265X.
Сулейменов Марат Смагулулы - С.Д. Асфендияров атындагы Казак улттык медицина университет офтальмология кафедрасыныц профессоры. Алматы, Казакстан. E-mail: maratsuleymenov.71@mail.ru. ORCID: 0000-0001-6038-8009.
Утелбаева Зэуреш Турсынкызы - С.Д. Асфендияров атындагы Казак улттык медицина университет! офтальмология кафедрасыныц профессоры. Алматы, Казакстан. E-mail:utelbayeva_zaure@mail.ru ORCID: 00000003-4312-9093.
Рахимова Меруерт Дамяркызы - С.Д. Асфендияров атындагы Казак улттык медицина университетшщ студенп. Алматы, Казакстан. ORCID 0000-0002-5089-9144.
Птеригиум - кез бетшщ жиi кездесетiн ауруынын бipi, фиброваскулярлы тшнщ конъюнктивадан лимбальды аймак аркылы касаи кабыкка дешн есучмем байланысты. Ол аскынган кезенде косметикалык акау гана емес, сонымен катар керу еткiрлiгiн темендетедi. Птеригумнын сэти хирургиялык емдеудщ негiзгi мэселе« - кайталану каупi жогары. Заманауи птеригиум хирургиясында тацдалган эдк емдеудщ тоскауылдык эдiсi деп аталатын. Жойылган птеригиум тесегшщ Yстiндегi бульбар конъюнктивасыныц акауын эртYPлi биоYЙлесiмдi тiндермен алмастыру болып табылады. Бул оталар селективи тYPде немесе рецидивке карсы кемеким терапиямен бiрiктiрiлiп орындалады. 1ске асырудыц карапайымдылыгын, кайталану мен аскынулардыц минималды каупiн жэне оцтайлы косметикалык эсердi бiрiктiретiн птеригиумды емдеудщ адекватты эдкш iздеу казiргi замангы офтальмологияньщ езеки мэселео болып кала бередi.
ТYЙiн сездер: птеригиум, конъюнктивалык аутотрансплантат, амнион мембранасы, адъювантты терапия.
Corresponding author: Yerkezhan Nurlybekova - PhD candidate department of Ophthalmology, Kazakh National Medical University named after S.D. Asfendiyarov, Almaty, Kazakhstan. E-mail: yerke-zhan@mail.ru ORCID: 0000-0002-0195-1516.
Received: 13.03.2022
Accepted: 17.03.2022
Bibliographic reference: Etiopatogenetic aspects of the treatment of pterygium/E. Nurlybekova, T. Teleuova, M. Suleymenov et al. //Астана медициналык журналы. - 2022. - № 1 (111). - С. 14-20
Introduction
In Kazakhstan and the republics of Central Asia, pterygium is one of the dominant diseases in the ophthalmopathology of the local population [1]. At the same time, the pterygoid hymen most often affects people of 30-60 age group and is characterized by frequent and multiple relapses after treatment [2].According to various authors, the incidence of pterygium ranges from 1.1 to 53.0% [3]. In addition, less frequently it also found among agricultural workers living in hot climates and exposed to excessive insolation.The presence of many etiopathogenetic mechanisms for the formation of the pterygoid hymen requires the search for new ways to solve this problem.Various surgical methods are available for the treatment of pterygium. Removal of the pterygoid hymen is one of the most common ophthalmic surgeries. However, a significant number of surgical techniques indicate the absence of a truly universal operation. With a variety of surgical treatment
methods, the number of relapses remains high. Furthermore, the treatment of recurrent pteryugium is particularly difficult. Despite the use of modern combined surgical techniques in combination with cytostatics or radiation treatment, the number of pterygium recurrences remains high. These reasons are due to the dissatisfaction of ophthalmic surgeons with the results of pterygium treatment and the constant development of new methods of surgical treatment of pterygium.
Materials and methods
This study aimed to analyze the literature review on the prevalence, etiology, treatment of pterygium.This review provides an analysis of the literature related to the prevalence, etiology, treatment of pterygium. Full-text publications in written in English and Russian languages devoted to pterygium were studied. Pubmed, Web of science, Cyberleninka, Google Scholar search engines were used for literature search. Thus, applying the keywords "pterygium", "pterygoid hymen", "surgical treatment", 5345 publications were found. Of these, 253 publications corresponded to the purpose of our review. The inclusion criteria were limited to publications with evidence level A and B: meta-analyses, systematic reviews, cohort and cross-sectional studies. On the other hand, brief reports, newspaper articles and personal.
Results
Epidemiology
Pterygoid hymen is common in countries that are closer to the equator due to higher levels of ultraviolet (UV) exposure [4]. Pterygium is a common ophthalmic disease in regions of the so-called "pterygial belt" located between 40°N and 40°S from the equator [5]. Farhad Rezvan and colleagues examined 3255 articles from which 68 articles were selected with a total of 415,911 contributors from 24 countries. The authors determined the prevalence of pterygium in the general population to be 12% (95% confidence interval, CI, 11-14%). The lowest and highest prevalence rates were 3% (95% CI 0-9%) in the 10-20 age group and 19.5% (95% CI 14.3-24.8%) in the age group above 80 years old, respectively. The prevalence was 13% (95% CI 11-15%) in men and 12% (95% CI 913%) in women. The lowest prevalence of pterygium was reported in a clinical study in Saudi Arabia (0.07%) and the highest in China (53%) [6]. A multivariate regression analysis conducted in Korea analyzed data from 9193 participants. The study showed that the overall prevalence of pterygium at the age of 40 years and older was 8.8% [7]. According to a systematic review conducted in Iran among 10,838 people from 2004 to 2015, the overall prevalence was 11%, with 18% among women and 13% among men (95% CI 3 - 18%) [8]. In the southwestern region of Brazil, the incidence of pterygium was 8.12% between 2000 and 2003 [9]. In the epidemiological part, we sought to compare the prevalence of pterygium in Kazakhstan and throughout the world. The average prevalence of pterygium in Kazakhstan is 33%, and in the world, according to a recent metaanalysis, the average level is 12% [9]. Therefore, we can say that pterygium occupies one of the first places in ophthalmopathology in terms of frequency of occurrence in Kazakhstan.
Etiology
There are many theories trying to explain the pathogenesis of pterygium. However, its etiology has not yet been established. It is believed that the disease is multifactorial. In this part, we will consider several theories. Older age, male gender, outdoor work, and rural living are the leading demographic risk factors for pterygium occurrence [11,12]. According to recent studies, UV radiation is the main risk factor leading to pterygium [13,14].
According to a study by Notara et al, prolonged exposure to UV radiation causes genetic changes in limbal stem cells [15]. Ultimately, this can lead to inflammation, remodeling of the extracellular matrix, and dehydration of the Bowman's membrane. Complications are caused by damage to DNA, proteins and lipids, (both direct and induced by active forms of oxygen), viral infections (in the extrinsic virus of proctogo, cytomegaoviru papillvecamy). According to Kadayifcilar et al, exposure to UV can also change the composition of the tear film in pterygium [16]. Thus, the main cause of the pathogenesis is the disfunction of tear secretion, or by non-specific effects of lactic acid secreted by the sweat glands. Based on this, it can be said that there is an association between pterygium and manifestations of dry eye, such as decrease in tear film rupture time [17]. Malozhen pterygium is a manifestation of a generalized dysfunction of the corneal
surface, including chronic inflammatory reaction [18]. According to a study by Suarez et.al, pterygium develops because of inflammation due to the products of DNA damage which can lead to neoplastic transformation. This was justified by the reduced levels of C10orf90, RARRES1, DMBT1 and SCGB3A1 in patients with pterygium. Acker and co-workers noted that during pterygium molecular and genetic changes such as point mutations in proto-oncogenes (like K-ras, and impaired expression of p53 or p63 tumor suppressor genes) and activation of growth factors (such as bFGF or VEGF) could happen [20]. Yet another theorized cause of pterygium is heredity. This theory was proposed in as early as in 1893 by Gutierrez-Ponce who described the heredity of pterygium. In his study five pterygium-affected males were identified in three generations. However, according to Hecht and co-workers, pterygium results from genetic-environmental interactions. Thus, it can be said that genetic factors determine the predisposition to pterygium.
Treatment
Despite the huge number of works devoted to the study of the treatment of pterygium, the problem of predicting the risk of developing and treating this complex multifactorial disease remains practically unresolved. The main method of treatment for this pathology is through surgery. There are many types of operations. Based on the pathogenetic mechanisms of pterygium growth, today preference is given to the use of the so-called barrier method with the replacement of the pterygium bulbar conjunctiva defect with various biocompatible tissues that create a barrier that prevents its re-growth. Various tissues are used as barrier transplants for the sclera: autotransplantation of the conjunctiva, lip mucosa, allotransplantation of biological materials (donor cornea, dura mater, amniotic membrane, etc.) [22]. Autotransplantation of the conjunctiva was first described in 1985 by Kenen. This method involves obtaining a free autograft from the nearby conjunctiva, which is then applied to the exposed scleral bed after performing pterygium excision. One of the most effective ones is the "pterygium extended removal followed by extended conjunctival transplantation" ("PERFECT") technique. The recurrence rate for this treatment is 1.6% [23]. The combination of autoconjunctival palsy with intraoperative administration of 0.02% mitomycin C (MMC) can reduce the recurrence rate to 3%. [24]. The current stage of application of the amniotic membrane in ophthalmic surgery was discovered by Tseng et al. in 1997. The amniotic membrane is successfully used for the treatment of burns and corneal ulcers, bullous keratopathy, persistent corneal erosions, Stevens-Johnson syndrome, pemphigoid, recurrent pterygium, symblepharon, as well as for formation of the conjunctival cavity in anophthalmic syndrome [25]. The main goals of using the amniotic membrane in clinical practice are to accelerate epithelialization, reduce pain, and reduce inflammation. These goals are achieved using various surgical techniques for amniotic membrane transplantation, such as Inlay technique (transplantation), Onlay technique ("covering"), and Inlay-Onlay technique ("sandwich" method) [26]. The recurrence rate for amniotic membrane transplantation ranges from 3.8 to 40.9%. Also, adjuvant therapy is often used in addition to surgery to reduce the likelihood of recurrence. Such methods in the surgical treatment of pterygium include beta-irradiation, thiotepa, MMC, 5-fluorouracil (5-FU), B-irradiation, anti-VEGF therapy, cyclosporine. [27]. From adjuvant therapy, the use of MMC has become more widespread. The number of relapses during the use of MMC varies from 2.3 to 12.5% [28-30]. The use of the anti-VEGF and bevacizumab in the form of instillations or subconjunctival injections has shown its effectiveness in reducing the recurrence of pterygium to about 3.7% [31]. Despite the use of modern combined surgical techniques, the number of pterygium relapses remains high, and recurrence usually happens with more severe complications than primary pterygium.
Conclusion
To date, there is no optimal way to treat and prevent the progression of pterygium. Thus, the analysis of literature shows that the study of the pathogenesis and the emergence of new methods of surgical treatment of pterygium has come a long way from the simplest methods to modern, more complex combined methods of surgeries. Nevertheless, the search for effective methods continues. As of now, the main issues of pterygium treatment are not limited to only excision of the pterygium itself but extends to the prevention of its recurrence.
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