Limitations and advances in new treatments and future perspectives of corneal blindness / Limitações e avanços em novos tratamentos e perspectivas futuras na cegueira corneal

ABSTRACT This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.(AU)

RESUMO O presente trabalho traz uma revisão das abordagens terapêuticas para a cegueira da córnea. O estudo detalha as etapas e os elementos envolvidos na cicatrização da córnea. Ele mostra as limitações das estratégias cirúrgicas e farmacológicas usadas para restaurar e manter a transparência da córnea em termos de sobrevida a longo prazo e alcance geográfico. As perspectivas dos agentes anabólicos, incluindo vitamina A, hormônios, fatores de crescimento e novos moduladores pró-mitóticos e anti-inflamatórios para auxiliar a cicatrização da ferida na córnea, são revisadas criticamente. Aqui, apresentamos estudos envolvendo nanotecnologia, terapia gênica e reengenharia de tecidos como possíveis estratégias futuras para atuar de maneira isolada ou combinada com a cirurgia da córnea para prevenir ou reverter a cegueira corneana.(AU)

Limitations and advances in new treatments and future perspectives of corneal blindness.

This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.

Corneal blindness in Plato's cave: the acting forces to prevent and revert corneal opacity. Part I: epidemiology and new physiopathological concepts.

The burden of corneal blindness and visual deficiency can be felt worldwide. Its association with several endemic diseases such as childhood blindness, trauma, infectious keratitis (including variants caused by herpes, hanseniasis, and fungi), vitamin A deficiency, diabetes mellitus, and other dry eye syndromes reflects its poorly understood underlying mechanisms and suggests that the actual frequency of the disease is underestimated. The low effectiveness of preventive and therapeutic strategies against corneal scarring or deformity predicts a high frequency of patients with corneal blindness in the future. Corneal blindness is associated with environmental factors and socioeconomic limitations that restrain health assistance and maintain a modest efficiency of the current therapeutic strategies for resolving corneal diseases in large-scale programs. We present here a critical review of the concepts associated with corneal blindness that need to be considered when planning strategies to prevent and treat corneal blindness worldwide (to be able to leave Plato's cave, where corneal blindness is encaged.

Prevention of Corneal Neovascularization by Adenovirus Encoding Human Vascular Endothelial Growth Factor Soluble Receptor (s-VEGFR1) in Lacrimal Gland.

Purpose: The aims of this study were (1) to determine the efficacy of adenovirus vector serotype 5 (Ad) encoding human soluble VEGF receptor 1 (s-VEGFR1) gene transfer to the lacrimal gland (LG); (2) to investigate whether expression of s-VEGFR1 prevents corneal neovascularization (CNV) induced by alkali burns; and (3) to evaluate the safety of the procedure. Methods: AdVEGFR1 vectors (25 µL, 1 × 1010 pfu/mL) were injected in the right LGs of rats and were compared with AdNull vector (25 µL, 1 × 1010 pfu/mL) or 25 µL of saline (Control) before cornea alkali burns with 1 M NaOH. After 7 days, CNV was documented at the slit lamp. Tear secretion was measured with phenol red threads. The animals were tested for s-VEGFR1 mRNA and protein in the LG by quantitative (q)PCR and immunohistochemistry staining, respectively. qPCR was used to compare the mRNA levels of IL-1ß, IL-6, and TNF-α in the LG and ipsilateral trigeminal ganglion (TG). Results: Ad-VEGFR1 transfected 83% (10/12) of the rats. VEGFR1 was present in LG acinar cells. CNV was prevented in 9 of 12 animals in the Ad-VEGFR1 group, compared with the Ad-Null (3:10) and Control groups (1:10) (P = 0.0317). The tear secretion and cytokine mRNA levels in the LG and TG were similar in all three groups (P > 0.05). Conclusions: Adenoviral vector gene transfer was safe for LG structure and function. The LG as the target tissue showed local expression of human s-VEGFR1, and CNV was prevented in most of the eyes exposed to alkali burns.

Hormones and dry eye syndrome: an update on what we do and don't know.

PURPOSE OF REVIEW: Dry eye syndrome (DES) prevalence is large and its relationship with hormonal diseases is becoming clearer, although more complex. This review provides insight to this association as well as clarifying what remains unanswered about how to interpret and treat findings common to both DES and hormonal diseases. RECENT FINDINGS: Several sex hormone-related diseases are associated with DES. Hormone replacement therapy to correct such conditions has conflicting outcomes based on epidemiologic studies and clinical trials. Thyroid-associated diseases are frequently involved in DES and must be investigated in cases where the cause of the ocular disease is undetermined. Diabetes mellitus is one of the major causes of DES, whereas correcting the metabolic imbalance minimizes its ocular symptomology. Gene therapy to treat DES-related hormonal diseases is a promising option based on animal studies. SUMMARY: Diagnosis and management of hormonal diseases can minimize the ocular surface damage and severity of DES. Clinical care of DES includes patient evaluation of hormonal status. Future research requires clarification of the underlying disease mechanisms and identifying novel strategies to reprogram the endocrine system rather than chronic medication usage.

Correlation between NT-pro BNP levels and early mitral annulus velocity (E') in patients with non-ST-segment elevation acute coronary syndrome.

UNLABELLED: Acute coronary syndromes in the absence of ST-segment elevation (NSTE-ACS) are a heterogeneous entity in which early risk stratification is essential. Diastolic dysfunction is precocious and associated with poor prognosis. BNP has been recognized as a biochemical marker of ventricular dysfunction and ischemia. OBJECTIVE: To investigate if there is correlation of NT pro-BNP levels with diastolic dysfunction in patients with NSTE-ACS. METHODS: Fifty-two patients with NSTE-ACS admitted to the coronary unit were included. NT-pro brain natriuretic hormone (BNP) levels and a Doppler echocardiogram were obtained in all and systolic and diastolic functions were analyzed. Their Doppler indexes were compared with those of 53 age- and sex-matched controls, without heart failure symptoms and with normal ejection fraction (EF) and normal NT-pro BNP levels. RESULTS: Twenty-four patients (46%) with unstable angina and 28 patients (54%) with acute myocardial infarction (AMI) were included. Mean EF was 55.9 +/- 10.7% and mean NT-pro BNP level was 835 +/- 989 pg/ml. No mitral or pulmonary venous flow parameters of diastolic function correlated with NT-pro BNP levels. E'/A' correlated with NT-pro BNP level in univariate analysis but, in a multivariate analysis, only the EF and the E' showed negative correlation with the peptide level (r =-0.33, P = 0.024 and r =-0.29, P = 0.045, respectively). Thirteen patients presented with stage II diastolic dysfunction but the NT-pro BNP level in these patients did not differ from the level in stage I patients. CONCLUSION: NT-pro BNP levels are elevated in acute coronary syndromes, even in the absence of significant necrosis. Of all echocardiographic parameters investigated, only E' and the EF correlated with the levels of NT-pro BNP in this group of patients.