Iatrogenic Disease Research Articles

Herbal Nephropathy and Balkan Endemic Nephropathy: The Pathogenic Role of Aristolochic Acid

Aristolochic acid nephropathy is a worldwide iatrogenic disease affecting individuals consuming herbal remedies derived from Aristolochia and Asarum species. The disease is characterized by prominent renal atrophy and extensive interstitial fibrosis. A considerable proportion of patients, about 30-45 % develop also transitional cell carcinoma mainly of the upper urinary tract. A special attention to the disease was paid in early 90’s because of an epidemic of rapidly progressive interstitial nephropathy affecting young women consuming slimming pills, containing Chinese herbs, supplied from the same clinic in Brussels, Belgium. Detailed investigation of slimming pills showed that they inadvertently contained Aristolochic acid considered as the causative factor of the disease. Soon thereafter it was showed that another devastating chronic interstitial nephropathy accompanied also with increased incidence of upper urothelial cancer, known as Balkan Endemic Nephropathy, is the result of chronic intoxication of affected individuals with low doses of Aristolochic acid derived from the soil contamination from the plant Aristolochia clematitis. Although Aristolochic acid has already characterized as class I carcinogen for humans, Aristolochia species continues to be used as herbal remedies especially in Asia countries and China as well as in westernized communities. It is noteworthy that although Aristolochia species are used as herbal remedies since antiquity there are no references for nephrotoxicity and carcinogenicity until the Belgium epidemic. In this review article we attempt to elucidate the historical evolution of our knowledge upon the etiology of Aristolochic acid nephropathy as well as the underlying mechanisms of Aristolochic acid cytotoxicity.

A Review of Contact Lens-Induced Limbal Stem Cell Deficiency.

Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and destruction of stem cells, stem cell precursors and limbal cell niche in the corneal epithelium, leading to severe conjunctivalization of the cornea. Etiologies for LSCD span from congenital (aniridia), traumatic (chemical or thermal injuries), autoimmune (Stevens-Johnson syndrome) and iatrogenic disease to contact lens (CL) wear. Of these, CL wear is the least understood and is often a subclinical cause of LSCD. Even with recent advances in LSCD research, limitations persist in establishing the pathogenesis and treatment guidelines for CL-induced LSCD. A literature search was conducted to include original articles containing patients with CL-induced LSCD. This review will critically discuss the complex pathophysiology behind CL-induced LSCD, the underlying risk factors and epidemiology of the disease as well as methods to obtain a diagnosis. Various treatment options will be reviewed based on proposed treatment strategies.

Caesarean scar pregnancy – an ongoing therapeutic challenge. Case series and literature review

Introduction. Caesarean scar pregnancy (CSP) is a life-threatening and iatrogenic disease due to the rising number of caesarean sections (CS) in the last decades. The most practical and effective technique for the early diagnosis of CSP is transvaginal ultrasound (TVUS), complemented with color Doppler. The optimal approach is yet to be standardized. Method­ology. This is a monocentric, prospective, observational study performed in the one tertiary hospital – the prenatal unit of the County Emergency Clinical Hospital Craiova and Medgin/GinEcho Clinic Craiova. The study enrolled four patients, based on specific inclusion criteria: diagnosis of CSP using transvaginal ultrasound. We described the particularities of the conservative therapeutic approach in those cases correlated with the data from the literature. Results. Four CSP cases were identified during 2022-2023 at the standard dating scan. The treatment approaches involved conservative local methotrexate associated with various procedures – systemic methotrexate, embolization, Folley catheter compression and eventually aspiration, leading to a decrease of βHCG levels and to favorable ultrasound findings of pregnancy involution, indicating positive outcomes. Conclusions. Caesarean scar pregnancy is an increasing pathology worldwide. The management of CSP represents a challenge that should be individualized and sometimes assessed by a multidisciplinary team for the safest therapeutic option.

Evaluation of Dermatological Disorders Among Patients Admitted to the Intensive Care Units of a Tertiary Care Hospital in India

: Background: The management of critically-ill individuals in intensive care units (ICU) is complex. Immobility, pharmacological treatments, and reduced perfusion lead to compromised skin integrity, predisposing to complications like infections and allergies. The presence of dermatological disorders (DDs) may influence management strategies, the patient’s quality of life, duration of ventilation, length of hospitalization, and rate of mortality. Hence, it is critical to analyze the predictors of DDs among ICU inpatients. Objectives To determine the prevalence of DDs in ICUs, classify them, and analyze their associated parameters. Methods: Patients admitted to Medicine/Neonatal/Paediatric ICUs were enrolled in this hospital-based cross-sectional study conducted over two months at a tertiary care hospital. Patients with pre-existing DDs not leading to admission were excluded. The screening was initiated within 48 hours of admission, continued daily throughout the ICU stay, and terminated on discharge from the ICU, in the case of patient death or at the end of the data collection period. Requisite information was recorded using a predesigned proforma. Results: Out of 688 patients screened, 129 were found to have 136 skin lesions, with an overall prevalence of 18.9%; MICU had the highest prevalence (22.7%), followed by NICU (17.3%) and PICU (12%). Skin lesions were classified into seven major categories. A significant association was found between the type of dermatological disorder and age, the presence of comorbidity, and the route of admission (P-value < 0.05). Conclusions: This study identified modifiable predictors associated with DDs among ICU inpatients. Infectious disorders constituted the foremost category in children, and iatrogenic disorders were predominant in adults. More comprehensive prospective studies are needed to fully understand the impact of DDs on the prognosis and outcome of ICU patients.

Patient motivators to use opioids for acute pain after emergency care.

Patients are stakeholders in their own pain management. Factors motivating individuals to seek or use opioids therapeutically for treatment of acute pain are not well characterized but could be targeted to reduce incident iatrogenic opioid use disorder (OUD). Emergency departments (EDs) commonly encounter patients in acute pain for whom decisions regarding opioid therapy are required. Decision-making is necessarily challenged in episodic, unscheduled care settings given time pressure, limited information, and lack of pre-existing patient provider relationship. Patients may decline to take prescribed opioids or conversely seek opioids from other providers or non-medical sources. Using a framework analysis approach, we qualitatively analyzed transcripts from 29 patients after discharge from an ED visit for acute pain at a large, urban, academic hospital in the midwestern United States to describe motivating factors influencing patient decisions regarding opioid use for acute pain. A semi-structured interview guide framed participant discussion in either a focus group or interview transcribed and analyzed with conventional content analysis. Four major themes emerged from our analysis including a) pain management literacy, b) control preferences, c) risk tolerance, and d) cues to action. Our findings suggest targets for future intervention development and a framework to guide the engagement of patients as stakeholders in their own acute pain management.

Empty Nose Syndrome with Unilateral Ethmoidal Mucopyocoele – An Extremely Rare Presentation

Introduction Empty nose syndrome (ENS) is a poorly understood and rare iatrogenic disorder resulting from the destruction of normal nasal tissue. ENS is a recognized complication after turbinate excision. These patients suffer from endonasal crusting and dryness and a paradoxical sensation of nasal obstruction. These complications of ENS predispose these patients to recurrent sino-nasal infections. Case report Here we have reported the case of a 20-year-old female with right-sided nasal obstruction and headache. On diagnostic nasal endoscopy (DNE), the right nasal cavity was devoid of all anatomical landmarks. A hidden ethmoidal mucopyocoele was identified on radiological evaluation . This was drained surgically. Patient’s symptoms improved drastically postoperatively. Conclusion Despite the fact that occurrence of rhino-sinusitis is common in patients of ENS, a mucocoele or mucopyocoele has never been reported previously. To the best of our knowledge, this is the first ever reported case of ENS with ethmoidal mucopyocoele in a young, immuno-competent patient.

Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice.

Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare with naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced type 1 diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3- T cells, and a decrease in memory CD4+FoxP3- and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.

Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges

BackgroundLymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described.Case presentationA patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and “other iatrogenic immunodeficiency-associated lymphoproliferative disorder” (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD.ConclusionsThis is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.

What did COVID-19 really teach us about science, evidence and society?

What did COVID-19 really teach us about science, evidence and society?

Trastuzumab-deruxtecan in HER2-low metastatic/unresectable breast cancer: Real life data in two Parisian centers.

e13130 Background: Trastuzumab-deruxtecan (TDXT) is an antibody-drug conjugate which has been approved for HER2-positive metastatic breast cancer (BC) treatment. DESTINY-Breast04 phase III clinical trial published in July 2022, TDXD was also shown to increase progression-free and overall survival in patients with HER2-low score metastatic/unresectable BC previously treated by 1 or 2 lines of chemotherapy, regardless of their hormone-receptor (HR) status. TDXD therefore has become a new therapeutic option in this population and has received an early access authorization in November 2022 in France. We report here our first experiences with TDXD in HER2-low patients to discuss some real-life data in this population. Methods: This retrospective descriptive study reports efficacy and safety data of TDXD use in pre-treated metastatic/advanced HER2-low (IHC + or IHC ++/ISH-) BC. Data from the medical records of all HER-2 low BC patients treated with TDXD (5.4 mg/kg, one intravenous injection every 21 days) until December 31, 2022 at Tenon and Pitié-Salpêtrière Hospitals were collected and analyzed. Efficacy was evaluated with PET-scanner comparison. Toxicity was graded using CTCAE 5.0 classification. End-point date for follow-up was February 09th, 2023. Results: We included a total of 22 patients (only women). They had already received several chemotherapy regimens (median 4 range 1-10), 50% had received radiotherapy and 22.7% underwent surgery. 18 (81%) were HR+ whereas 4 had triple negative (TN) cancer. Most commons metastatic sites were bones (73%), lymph nodes (68%) and liver (50%). At TDXD start, median age was 57.9 years. 82% patients had a ECOG score 0-1 and 18% ECOG 2. Median time between initial diagnosis and TDXD start was 77 months (range: 21-240) and from first chemotherapy in metastatic situation and TDXD start was 31 months (range: 3-89). The median duration of TDXD treatment was 5.9 months in HR+ patients and 5.7 months in TN patients. At the 3-month evaluation, 61.1% HR+ patients had a treatment response (50% partial and 11.1% complete), 27.8% a stabilization and 11.1% a progression. The longest treatment follow-up was 12.6 months. Among the 4 TN patients, there were 2 cases of partial response, 1 case of stabilization and one progression at the 3-month evaluation. The longest treatment response was 15.8 months. A total of 7 cancer-related deaths have occurred (6 RH+ and 1 RH-). Out of 22 patients, 86% experienced ≥ 1 adverse effect (AE). They were mainly grade I or II asthenia (63% patients) and nausea (58%). 2 cases of grade III effects (anemia and hepatic cytolysis) were reported. Finally, 3 cases of iatrogenic interstitial lung disease have been observed, one of them being a grade V toxicity. Conclusions: First cases of TDXD use in HER2-low BC patients in 2 French hospitals show promising results with a 54.5% response rate at 3 months. TDXD is globally well tolerated with 13.6% of grade ≥ 3 AE reported.

1043 A Rare Case of Non-24-hour Sleep-Wake Rhythm Disorder in A Sighted Patient

Abstract Introduction Non-24-hour sleep-wake disorder is a circadian rhythm sleep disorder which causes failure of endogenous circadian rhythm cycles to synchronize to a 24-hour day. Despite an unknown prevalence in sighted people, it's thought to be rare. We present a case of a sighted patient with concurrent bipolar disorder who presented with excessive sleepiness since preadolescence, and was later found to have N24SWD. Report of case(s) A 29 year old woman with bipolar disorder presented with excessive daytime sleepiness and irregular sleep schedule since age 12. During her teenage years she often fell asleep at school, and she felt the sleepiness could be associated with psychotropic medication. As she grew up, despite her bipolar disorder was well-controlled, the daytime sleepiness persisted, which caused great challenge concentrating at work and difficulty holding a job. She denies cataplexy, hypnagogic hallucinations, sleep paralysis, or restless legs syndrome symptoms. She had no history of shift work or abnormal movements during sleep. Her bedtime advanced and cycled through a 24-hour period according to sleep diary. Her rise time maintains a consistent interval with her bedtime. Previously she had multiple sleep latency test and polysomnogram, after which she was diagnosed with idiopathic hypersomnia. She was treated with several stimulants without much improvement. She was offered CBT-I but hasn’t gone. She failed trial of a standardized schedule and found it stressful. She tried melatonin and light therapy for a short time without much of success, she was subsequently started on tasimelteon and the clinical response is to be followed. Conclusion N24SWD is reportedly rare in the sighted population, with a possible different mechanism from that of the blind population. Behavioral and environmental factors might contribute to the dysynchrony between a normal central circadian pacemaker and a non-24-hour sleep-wake behavioral pattern. Our patient's sleepiness persisted despite her psychiatric disorders were in remission. Altered circadian rhythms are not uncommon in patients with psychiatric disorders, and circadian rhythm dysfunction may be a trait marker of bipolar disease. Some antidepressant are also found to cause potential iatrogenic circadian rhythm sleep disorders. Psychosocial interventions that target stabilizing daily rhythms in patients with concurrent psychiatric illness can be helpful. Support (if any)

Iatrogenic Graves' disease - A case of severe Graves' disease and Graves' orbitopathy occuring after radioiodine therapy for toxic nodular goitre

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Premature ovarian insufficiency: an augmenting disorder in the growing female population

A primary ovarian abnormality such as absent menarche (primary amenorrhea) or early depletion of ovarian follicles/arrested folliculogenesis before the age of 40 is described as premature ovarian insufficiency (secondary amenorrhea). Itsprevalence is 1% and 0.1 % in women under 40 and 30 respectively. Common Symptoms include palpitations, excessive sweating, flushes, anxiety, depression, and fatigue. There could be a variety of causes, including chromosomal abnormalities, autoimmune diseases, infections, idiopathic diseases, iatrogenic diseases, and so on. Diagnosis is usually done based on the level of hormones like estradiol, Follicle Stimulating Harmone, and LuteinizingHarmone. Considering the complications of premature ovarian failure, it is necessary to educate the female population about this disorder. Hence, the Present review focuses on the etiology, symptoms, complications, diagnosis, and treatment of premature ovarian failure.

A Compendium on Perinatal Autopsy in Neonats.

Professionals who work in perinatal care must understand the advantages and disadvantages of perinatal autopsy since they are an essential tool for determining fetal and neonatal mortality. Perinatal is the period five months before one month after birth, while prenatal is before birth. The traditional prenatal autopsy is still the gold standard for establishing the cause of death and providing an accurate report, notwithstanding the development of new technology. The ideal locations for a prenatal autopsy are tertiary institutes that offer these procedures. It emphasizes the need for systematic histopathologic sampling, rigorous record-keeping, technological adaptation, and wise laboratory test use. When a laboratory does a microbiologic examination with a focus on the genital tract and neonatal problems, it is very beneficial. Karyotyping needs to be selective and works best when there are many aberrations if resources are to be saved. A perinatal autopsy is insufficient without examining the placenta, and severe lesions should be distinguished from deformities and abnormalities brought on by fetal death. In addition to providing epidemiology teams and auditing committees with high-quality data, the pathologist's role in perinatal medicine also includes participating in the multidisciplinary management of fetal abnormalities identified during pregnancy, monitoring the patterns of iatrogenic disease, and aiding the perinatal grief management process. Investigations into complicated multiple pregnancies, hydrops, bone dysplasias, and unexpected intrauterine fetal deaths provide unique obstacles and diagnostic difficulties. There hasn't been any research that contrasts postmortem computed tomography with postmortem x-rays in pregnant women, as far as we know. Histological analysis of many perinatal autopsies revealed healthy developing tissues. Only a tiny percentage of histological abnormalities can be expected in fetal anomaly terminations. On prenatal imaging, many organ abnormalities are commonly anticipated. A thorough database search was done in Pubmed, Medline, and Scopus using the phrases "fetal abnormalities," "karyotyping," "fetal abnormality," "postmortem," and "perinatal autopsy."

Corneal Sub-Basal Nerve Plexus in Non-Diabetic Small Fiber Polyneuropathies and the Diagnostic Role of In Vivo Corneal Confocal Microscopy.

In vivo corneal confocal microscopy (IVCM) allows the immediate analysis of the corneal nerve quantity and morphology. This method became, an indispensable tool for the tropism examination, as it evaluates the small fiber plexus in the cornea. The IVCM provides us with direct information on the health of the sub-basal nerve plexus and indirectly on the peripheral nerve status. It is an important tool used to investigate peripheral polyneuropathies. Small-fiber neuropathy (SFN) is a group of neurological disorders characterized by neuropathic pain symptoms and autonomic complaints due to the selective involvement of thinly myelinated Aδ-fibers and unmyelinated C-fibers. Accurate diagnosis of SFN is important as it provides a basis for etiological work-up and treatment decisions. The diagnosis of SFN is sometimes challenging as the clinical picture can be difficult to interpret and standard electromyography is normal. In cases of suspected SFN, measurement of intraepidermal nerve fiber density through a skin biopsy and/or analysis of quantitative sensory testing can enable diagnosis. The purpose of the present review is to summarize the current knowledge about corneal nerves in different SFN. Specifically, we explore the correlation between nerve density and morphology and type of SFN, disease duration, and follow-up. We will discuss the relationship between cataracts and refractive surgery and iatrogenic dry eye disease. Furthermore, these new paradigms in SFN present an opportunity for neurologists and clinical specialists in the diagnosis and monitoring the peripheral small fiber polyneuropathies.

Tardive dyskinesia

Tardive dyskinesia (TD) is a delayed, often irreversible iatrogenic movement disorder caused by long-term use of that dopamine receptors blocking drugs. Prevention of TD is paramount, and clinicians should follow best practice recommendations for prescribing antipsychotics, as well as reduction the using of dopamine receptor blocking drugs for non-psychiatric prescriptions. Replacement of antipsychotics with lower affinity for D2 receptors drugs, addition of VMAT2 (tetrabenazine), botulinum therapy, amantadine may be effective. In detection and incurable cases, the possibility of neuromodulation of brain structures should be considered. Most methods for testing TD currently have an insufficient level of evidence, although they include recommendations from professional communities. There is a great need for new clinical trials.

Drugs Causing Crystalline Retinopathy: Pathogenesis, Diagnosis, and Treatment (Tamoxifen, Canthaxanthin, Methoxyflurane, Nitrofurantoin, Talc)

Crystalline retinopathy is an umbrella term used to classify pathologies that result in refractile retinal deposits that are distributed in the macula, posterior pole, or all retinal areas. Crystalline retinopathies can be seen in a wide variety of genetic, toxic (drug-related), degenerative, iatrogenic, or idiopathic diseases. Toxic or drug-related etiologies are mostly bilateral. Taking a comprehensive medical history, questioning the drugs used, and determining the retinal location of the crystals through multimodal imaging methods can further narrow down the possible etiologies and enable us to confirm the diagnosis. Early diagnosis is important in terms of treatment opportunities and follow-up.

Iatrogenic immunodeficiency-associated lymphoproliferative disorders of the central nervous system: a treatment paradox.

Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens. With increasing prevalence of autoimmune disease and development of new immunosuppressants, a genetically distinct entity known as iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD) has emerged. Many of these cases arise following methotrexate use, challenging feasibility of standard HD-MTX regimens. The aim of this study was to further characterize this disorder and determine the optimal management strategy. We describe a case of a 76-year-old female with iatrogenic immunodeficiency-associated PCNSL successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency-associated LPD involving the CNS. We used a linear probability statistical model to determine correlations with outcome. Natalizumab was associated with EBV negative tumors (P=.023), and EBV positive tumors were associated with improved outcomes (P=.016). Surgical resection was associated with improved outcomes (P=.032), although limited by potential confounding effect. Antiviral treatment (P=.095), rituximab (P=.111), and stem cell transplant (SCT) (P=.198) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement. We propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency-associated LPD of the CNS. Further study through prospective cohort studies or randomized clinical trials is warranted.

Effectiveness evaluation of the interdisciplinary approach in the treatment of patients with iatrogenic functional disorders of the maxillofacial area associated with primary deep bite according to the dynamics of changes in electromyographic studies

The aim of our work is to improve the quality of comprehensive orthodontic treatment by searching for the most favorable conditions and terms necessary for the implementation of the adaptive capacity of the body at the stages of reconstructive manipulations in patients with occlusal disorders of the dentofacial system resulting from dental interventions.Material and methods. A prospective group clinical study was carried out. Groups were formed due to the total clinical sample of 105 patients, age range 18-45 years (mean age 29.9±6.1 years) with iatrogenic functional prosthetic disorders complicated with a primary deep bite. Three clinical groups were identified. The first included 37 patients with predominantly muscular symptoms, the second - 42 patients with dysfunction of the temporomandibular joints, and the third included 26 patients who, in addition to muscle and / or joint symptoms, had primary neurogenic disorders. In order to compare the effectiveness of treatment, each of the clinical groups was divided into 2 subgroups depending on the treatment algorithm used; namely, the first subgroup included patients who were treated according to the scheme developed by us, and the second subgroup included patients treated according to the generally accepted method.Results. There was a decrease in the amplitude of bioelectrical activity and a reduction in the time of the activity period, and, accordingly, the approximation of the activity coefficient to one in patients with vertical abnormalities, aggravated by crowding of the teeth, occurred already at the stage of splint therapy.Conclusions. Our studies allow us to predict both the duration of treatment and the amount of occlusal correction combined with the reconstruction of the position of the lower jaw and the improvement of the general somatic state of the patient's body.

Alternatives for corneal endothelial tissue engineering

AbstractCorneal endothelial diseases are common almost everywhere in the world and have 3 main origins: primary diseases, largely dominated by Fuchs' endothelial corneal dystrophy (FECD), iatrogenic diseases which mainly complicate lens surgery, whether cataract or clear lens, but also other surgeries. The frequency of these complications is very low but the number of these surgeries being gigantic (probably around 50 million cases/year/worlwide), the number of post‐surgical bullous keratopathy remains important. Post‐keratoplasty endothelial failure (early or late) is the 3rd cause.All these diseases “consume” 50% of corneal grafts in the world and a large part of the population does not have access to any graft. The number of corneal donors is absolutely insufficient to meet the world demand and corneal bioengineering appears to be a realistic solution to complete the offer. Because of its relative simplicity and the demonstrated effectiveness of endothelial keratoplasty, endothelial bioengineering is logically the first to be developed. The Japanese team of 2 Kyoto universities (Prof. S. Kinoshita, N. Koizumi and N. Okumura) is a pioneer in this field and has demonstrated the effectiveness of injection therapy, which consists of cultivating mature endothelial cells from a small number of corneas from young donors, then injecting them into the anterior chamber of patients. The industrialization of the process is underway in 2 different start‐ups, one in the United States, the other in Japan. In addition to injection therapy, the bioengineering of endothelial grafts (Tissue engineered endothelial keratoplasty, TEEK), which consists of cultivating endothelial cells on a “corneo‐compatible” carrier to exactly reproduce a DMEK or a DSAEK, has passed the preclinical stage. This presentation will detail these different processes, their current limitations and the short, medium and long term perspectives. These Advanced Therapy Medicinal products (ATMP) are clearly revolutionizing corneal transplantation. By offering a new treatment for endothelial diseases, they will make it possible to redirect donor corneas to other corneal diseases that have no therapeutic alternative. Finally, this paper will also discuss the prospects of medical and medico‐surgical treatments for FECD, which are at the frontier of endothelial bioengineering.