An Update on the Management of Vitreoretinal Diseases

.: PREFACE
PREFACE
ÖN SÖZ
Prof. Dr. Tongalp H. TEZEL
Columbia University, Vagelos College of Physicians and Surgeons, Department of Ophthalmology, Edward S. Harkness Eye institute, New York, NY, USA
Article Language: EN
''Change is the only constant in life.'' What the philosopher Heraclitus of Ephesus said almost 2,500 years ago summarizes the times we live in now best. The rapid development of technology, especially the internet, resulted in the exponential growth of human knowledge. In the 1900s, it required 100 years to double human knowledge, which decreased to 25 years in 1945 and now to 12 hours. Medical knowledge has taken its share from this rapid growth of new information. When my father graduated from medical school in 1952, it required 50 years to double his medical knowledge. When I graduated from Hacettepe University Medical School in 1984, the doubling time decreased to 7 years. Unfortunately, when my daughter graduates in 2024, half of what she learned in medical school will be outdated in 2 months. Although educational tools and systems have adapted to the rapid phase of knowledge expansion, the human brain is not built to grasp exponential changes. The human brain is rather accustomed to natural changes, which usually happen linearly, like the aging of living beings or timely changes in seasons. This disparity naturally creates an adaptation problem. To keep up with the evolving medical field's pace, utmost attention must be paid to infusing the habit of reading current literature to the trainees. Through post-graduate medical education programs, current practitioners must also continuously be trained in new fields such as genomics, robotics, and artificial intelligence. Physicians who don't educate themselves about evolving technologies and knowledge are destined to be outdated and fail to adhere to the principles of modern clinical practice. Thus, the greater physician is no longer the one who has the greatest experience but the one who also enriches this experience with a continuous search for knowledge through reading and learning.

In this book of the Türkiye Klinikleri, we hope to serve this purpose by presenting recent advances and evolving technologies in the clinical and surgical management of vitreoretinal diseases. Drs. Şermet and Yanık summarized the current and developing clinical imaging modalities, such as Quantitative Autofluorescence Imaging, Fluorescence Lifetime Imaging Ophthalmoscopy, and the use of Adaptive Optics technology in retinal imaging. Drs. Silverman and Urs have taken us out of the boundaries of A- and B-scan of ultrasonography and introduced linear arrays to perform ultrafast plane-wave imaging and display choroid blood flow. Dr. Akar Doğan gave us a summary of completed Diabetic Retinopathy Clinical Research Network (DRCR Network) studies which has become the main source of our clinical knowledge in managing diabetic retinopathy. Artificial intelligence is a rapidly evolving field. Over more than 400 publications appeared within the last five years about artificial intelligence applications in ophthalmology. Drs. Koenigstein and Tezel described the use of advanced machine learning and deep learning with convo lutional networks in diabetic retinopathy screening. Despite time and effort spent, age-related macular degeneration remains the leading cause of irreversible vision in the elderly population. After the initial hype, long-term experience with anti-VEGF agents revealed that almost 20% of the patients still lose sight, and almost half of them end up with visual acuities less than 20/40. This resulted in development of longer-acting drugs, ocular depot systems, and different targets. Drs. Saatci and Kartı will briefly summarize the recent advances in pharmacotherapy for agerelated macular degeneration. Although the rate of introducing new drugs into the market lags the pace of medical knowledge growth, approximately 20 to 30 new drugs have been added to pharmacists' shelves per year within the last 30 years. Introducing new drugs has resulted in new reports about the ocular side effects of some new agents, such as Pentosan Polysulphate, Vemurafenib, and Immune Checkpoint Inhibitors. Drs. Ustaoğlu and Wang summarized the clinical presentations of the ocular side effects of these drugs. Inherited retinal diseases are a heterogeneous group of visually debilitating diseases affecting more than 2 million people worldwide. 50-70% of these degenerations have been attributed to pathogenic variants of more than 300 genes. Gene discovery and advances in gene treatment strategies have led to the approval of several clinical trials of gene treatment. The recent approval of voretigene neparvovec-rzyl (Luxturna), for treating biallelic RPE65 mutation-associated Leber's Congenital Amaurosis, created an important tranche in the evolution of ocular gene therapy. Dr. Tsang and his colleagues gave us a comprehensive review of the ocular gene therapy with ongoing clinical trials. Considering that more than 60 genes are involved in retinitis pigmentosa, the development of gene-specific treatment for each of these mutations will not be possible in the near future. Drs. Kaplan and Piri took a gene-independent approach that can be used for all outer retinal degenerations. He describes the rationale and the method of reactivating dormant cones in his chapter. Although the dislocation of an intraocular lens is not a common complication, alternatives to fix this problem may sometimes be puzzling. Drs. Avcı and Yıldız gave us a synopsis of different techniques to manage dislocated intraocular lenses in our surgery section. Surgical management of lamellar holes has always been challenging. In this book, Drs. Chang and Chang describe their experience, shed light on the timing, and employed surgical techniques for treating lamellar macular holes. Epiretinal human amniotic membrane grafting for complex macular pathologies, such as large failed macular holes or complications of degenerative myopia, is a technique, we have been employing at our clinic for the last four years. This technique differs from stuffing the amniotic or internal limiting membrane into the hole or underneath the retina. In this book, my colleagues and I briefly describe our rationale, preclinical research, and clinical experience. Finally, Drs. Yeager and Marr update us on the treatment of choroidal malignant melanomas.

I would like to thank the contributing authors for sharing their experiences and insights with us. Also, I would like to extend my sincere gratitude to the editor-in-chief of Türkiye Klinikleri, Prof. Dr. Hikmet Akgül, Ms. Ayfer Koç, and all members of the publication team who created this platform for the distribution of knowledge and wisdom among colleagues. Through such noble efforts, medical education and patient care can excel.

Prof. Dr. Tongalp H. TEZEL
Editor
''Değişmeyen tek şey değişimin kendisidir. ''Efesli Heraklitos'un yaklaşık 2.500 yıl önceki sözü, günümüzü de en iyi şekilde özetliyor. Teknolojinin, özellikle internetin hızlı gelişimi, insanlığın bilgisinin de katlanarak artmasını sağladı. 1900'lü yıllarda, insanlığın bilgisinin ikiye katlanması için 100 yıl gerekti, 1945'te 25 yıla düşen bu süre, şu an ise 12 saat. Tıp bilgisi de bu yeni bilgi birikiminden nasibini aldı. Babam 1952'de tıp fakültesinden mezun olduğunda, tıbbi bilgisini ikiye katlaması 50 yılını aldı. Ben 1984'te Hacettepe Üniversitesi Tıp Fakültesi'nden mezun olduğumda, bu süre 7 yıla düştü. Kızım ise 2024'te mezun oluyor ancak tıp fakültesinde öğrendiklerinin yarısı 2 ay içerisinde eskimiş olacak. Eğitim araçları ve sistemleri, bu hızlı bilgi artışına adapte olmuş olsa bile, insan beyni katlanarak çoğalan değişiklikleri kavramak için yaratılmamıştır. İnsan beyni daha çok canlıların yaşlanması, zamanla mevsimlerin değişmesi gibi doğrusal olarak gerçekleşen doğal değişimlere alışmıştır. Bu eşitsizlik de doğal olarak bir uyum sorunu yaratır. Gelişen tıp alanının hızına yetişebilmek için, öğrencilere güncel literatürleri okuma alışkanlığı kazandırılmasına azami özen gösterilmelidir. Mezuniyet sonrası tıbbi eğitim programları aracılığıyla, mevcut pratisyenlerin de genomik, robotik ve yapay zekâ gibi yeni alanlarda devamlı olarak eğitilmeleri gerekir. Gelişen teknoloji ve bilgi konusunda kendini eğitmeyen hekimlerin kaderi modern klinik uygulama ilkelerinden uzaklaşmak ve nihayetinde çağ dışı kalmaktır. Bu yüzden, daha iyi hekim artık daha çok tecrübesi olan hekim değil, bu tecrübesini okuyarak ve öğrenerek sürekli bilgi arayışıyla zenginleştiren hekimdir.

Türkiye Klinikleri'nin bu kitabında, vitreoretinal hastalıkların klinik ve cerrahi yönetimindeki son gelişmeleri ve gelişen teknolojileri sunarak biz de bu amaca hizmet etmeyi umuyoruz. Dr. Şermet ve Yanık, retinal görüntülemede Kantitatif Otofloresans Görüntüleme, Floresans Ömür Boyu Görüntüleme Oftalmoskopi gibi güncel ve gelişen klinik görüntüleme yöntemlerini ve Adaptif Optik teknolojisinin kullanımını özetlemişlerdir. Dr. Silverman ve Urs, bizi ultrasonografi A- ve B-taramalarının sınırlarının ötesine taşımışlardır ve ultra hızlı düzlem dalga görüntüleme gerçekleştirmek ve koroid kan akışını görüntülemek için linear array teknolojisini tanıtmışlardır. Dr. Akar ve Doğan, bize diyabetik retinopati yönetimindeki klinik bilgilerimizin ana kaynağına dönüşen, tamamlanmış Diyabetik Retinopati Klinik Araştırma Ağı [Diabetic Retinopathy Clinical Research Network (DRCR Network)] çalışmalarının özetini sunmuştur. Yapay zekâ hızla gelişen bir alandır. Son 5 yılda oftalmolojide yapay zekâ kullanımı ile ilgili 400'den fazla yayın literatüre girmiştir. Dr. Koenigstein ve Tezel, diyabetik retinopati görüntülemede gelişmiş makine öğreniminin ve evrişimsel ağların derin öğreniminin kullanımını tanımlamıştır. Harcanan zaman ve emeğe rağmen yaşa bağlı makula dejenerasyonu, yaşlı popülasyonda geri dönüşü olmayan görme kaybının en baştaki nedenlerinden olmaya devam etmektedir. İlk enjeksiyondan sonra, anti-VEGF ajanlarla uzun süreli deneyim, hastaların yaklaşık %20'sinin hâlâ görme kaybı yaşadıklarını ve neredeyse yarısının görme keskinliğinin 20/40'tan düşük olduğunu ortaya çıkardı. Bu da, daha uzun etkili ilaçların, oküler depo sistemlerinin ve farklı hedeflerin gelişmesiyle sonuçlandı. Dr. Saatci ve Kartı, yaşa bağlı makula dejenerasyonu için farmakoterapide son gelişmeleri kısaca özetlemişlerdir. Piyasaya yeni ilaç sunma hızı tıbbi bilginin büyüme hızının gerisinde kalsa da, son 30 yıl içinde eczacıların raflarına yılda yaklaşık 20-30 yeni ilaç eklenmiştir. Yeni ilaçların eklenmesi; Pentosan Polysulphate, Vemurafenib ve Bağışıklık Kontrol Noktası İnhibitörleri gibi bazı yeni ajanların oküler yan etkileri hakkında yeni bilgilerin ortaya çıkmasını sağlamıştır. Dr. Ustaoğlu ve Wang bu ilaçların oküler yan etkilerinin klinik sunumlarını özetlemişlerdir. Kalıtsal retinal hastalıklar, dünya çapında 2 milyondan fazla insanı etkileyen, görmeyi zayıflatan heterojen bir hastalık grubudur. Bu dejenerasyonların %50-70'i, 300'den fazla genin patojenik varyantlarına dayandırılır. Genlerin keşfi ve gen tedavisi stratejilerinin gelişmesi, gen tedavisine yönelik birkaç klinik denemenin kabul edilmesini sağlamıştır. Bialelik RPE65 mutasyonuna bağlı Leber konjenital amorozisi tedavisinde kullanılan Voretigene neparvovec-rzyl (Luxturna)'nın güncel kabulü, oküler gen terapisi evriminde önemli bir dilim yaratmıştır. Dr. Tsang ve meslektaşları, devam eden klinik denemelerle, oküler gen terapisinin kapsamlı bir incelemesini sunmuşlardır. Retinitis pigmentosada 60'tan fazla genin rol oynadığı göz önünde bulundurulursa, bu mutasyonların her birinin gen spesifik tedavisi yakın bir gelecekte de mümkün olmayacaktır. Dr. Kaplan ve Piri, tüm dış retinal dejenerasyonlar için kullanılabilecek genlerden bağımsız bir yaklaşım ele almıştır. Aktif olmayan konileri yeniden aktifleştirmenin mantığını ve yöntemini kendi bölümünde açıklamıştır. İntraoküler lensin yerinden çıkması yaygın bir komplikasyon olmasa da, bu sorunu çözme alternatifleri bazen anlaşılmaz olabilir. Dr. Avcı ve Yıldız, cerrahi bölümümüzde yerinden çıkmış intraoküler lensleri tedavi etmenin farklı tekniklerinin bir özetini sunmuştur. Lamellar deliklerin cerrahi tedavisi her zaman zorlayıcı olmuştur. Bu kitapta, Dr. Chang ve Chang, lamellar makula deliklerinin tedavisi konusunda deneyimlerini paylaşmış, zamanlamaya ışık tutmuş ve cerrahi teknikler kullanmıştır. Geniş makula delikleri ya da dejeneratif miyopinin makulada yarattığı komplikasyonlar gibi tedavisi zor karmaşık makula hastalıkları için epiretinal insan amniotik membranı nakli, kliniğimizde son 4 yıldır kullandığımız bir tekniktir. Bu teknik, amniyotik veya iç sınırlayan zarın deliğe ya da retinanın altına doldurulmasından farklıdır. Bu kitapta, meslektaşlarım ve ben, mantığımızı, ön klinik araştırmalarımızı ve klinik tecrübemizi kısaca paylaşıyoruz. Son olarak, Dr. Yeager ve Marr, koroid malign melanoma tedavisi hakkında bizi son gelişmelerden haberdar ediyor.

Katkıda bulunan yazarlara deneyimlerini ve görüşlerini bizimle paylaştıkları için teşekkür ediyorum. Ayrıca meslektaşlarımız arasında bilgi ve birikimlerimizi yayma amaçlı bu platformu kuran Türkiye Klinikleri baş editörü Prof. Dr. Hikmet Akgül, Ayfer Koç ve yayın ekibinin tüm üyelerine en içten teşekkürlerimi sunmak istiyorum. Böyle asil emekler sayesinde, tıp eğitimi ve hasta bakımı en üst seviyeye çıkabilir.

Prof. Dr. Tongalp H. TEZEL
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