Comprehensive management of post-LASIK ectasia: From prevention to treatment.

Post-laser in situ keratomileusis (post-LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high-fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross-linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long-term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide.

The anti-scarring role of Lycium barbarum polysaccharide on cornea epithelial-stromal injury.

PURPOSE: Cornea epithelial-stromal scarring is related to the differentiation of fibroblasts into opaque myofibroblasts. Our study aims to assess the effectiveness of Lycium barbarum polysaccharide (LBP) solution as a pre-treatment in minimizing corneal scarring. METHODS: Human corneal fibroblasts were cultured in a three-dimensional collagen type I-based hydrogel in an eye-on-a-chip model. Fibroblasts were pre-treated with 2 mg/mL LBP for 24 h, followed by another 24-h incubation with 10 ng/mL transforming growth factor-beta 1 (TGF-ß1) to induce relevant physiological events after stromal injury. Intracellular pro-fibrotic proteins, extracellular matrix proteins, and pro-inflammatory cytokines that involved in fibrosis, were assessed using immunocytochemistry and enzyme-linked immunosorbent assays. RESULTS: Compared to the positive control TGF-ß1 group, LBP pre-treated cells had a significantly lower expression of alpha-smooth muscle actin, marker of myofibroblasts, vimentin (p < 0.05), and also extracellular matrix proteins both collagen type II and type III (p < 0.05) that can be found in scar tissues. Moreover, LBP pre-treated cells had a significantly lower secretion of pro-inflammatory cytokines interleukin-6 and interleukin-8 (p < 0.05). The cell-laden hydrogel contraction and stiffness showed no significant difference between LBP pre-treatment and control groups. Fibroblasts pretreated with LBP as well had reduced angiogenic factors expression and suppression of undesired proliferation (p < 0.05). CONCLUSION: Our results showed that LBP reduced both pro-fibrotic proteins and pro-inflammatory cytokines on corneal injury in vitro. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option prior to corneal refractive surgeries with an improved prognosis.

Dexamethasone-Eluting Contact Lens for the Prevention of Postphotorefractive Keratectomy Scar in a New Zealand White Rabbit Model.

PURPOSE: To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. METHODS: Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. RESULTS: The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. CONCLUSIONS: In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1% dexamethasone drops applied 4 times a day for 4 weeks.

Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study.

Aim: Cisplatin is a widely used and highly effective anti-cancer agent and one of the limiting side effects of cisplatin is ocular toxicity. Achillea millefolium, also known as yarrow, is a plant that has been used for many years to treat various health problems including chemotherapy-related toxicities. Methods: The present investigation was designed to evaluate the biochemical, molecular and histopathological effects of Achillea Millefolium on cisplatin-induced oxidative and inflammatory ocular damage in rats. Twenty-four adult male rats were assigned randomly to four groups (n = 6) as (1) control, (2) cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Achillea millefolium (200 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Levels of total antioxidant capacity and total oxidant status, SOD, MDA, IL-1ß, and IL-10 were measured in ocular tissue. The mRNA expressions of TNF-α, nuclear factor kappa B and Caspase-3 were evaluated. Also, ocular sections were evaluated histopathologically.Results: Achillea Millefolium upregulated ocular antioxidant enzymes and downregulated inflammation. The SOD activity and total antioxidant capacity increased whereas total oxidant status and MDA levels decreased significantly at high dose group. High dose Achillea millefolium treatment reduced the IL-1ß concentrations, whereas IL-10 levels increased significantly in that group. Moreover, we observed that Achillea millefolium restored ocular histopathological structure and significantly suppressed apoptosis by reducing the expression of Caspase-3.Conclusion: Collectively, our results suggest that Achillea millefolium have protective effects against cisplatin-induced ocular toxicity and is a promising adjuvant therapy with the potential to prevent cisplatin related ocular toxicity.

Long-term Outcomes of Boston Type I Keratoprosthesis, and Efficacy of Amphotericin B and Povidone-Iodine in Infection Prophylaxis.

PURPOSE: To evaluate the long-term outcomes, anatomic retention, and complications of Boston type I keratoprosthesis (KPro). DESIGN: Retrospective, interventional case series METHODS: A retrospective chart review of implantations performed January 2008-December 2017 was conducted. Risk factors for anatomical retention and functional success were analyzed. The incidences of infections with and without antimicrobial medications were compared. RESULTS: Twenty-seven eyes of 26 patients were recruited. The most common indication for KPro surgery was failed penetrating keratoplasties (22 eyes, 81.5%). All patients had preoperative best-corrected visual acuity (BCVA) worse than 3/60. Over the mean follow-up of 83.4 ± 28.4 months, 15 eyes (55.6%) demonstrated improved BCVA. The anatomical retention rate was 88.9%, and the functional success rate was 44.4% (retained KPro with BCVA ≥ 3/60). Eyes with ocular surface disease (OSD) had significantly more complications than those without OSD. The most common complications were retroprosthetic membrane formation (15 eyes, 55.6%) and infection (13 eyes, 48.1%). Infectious keratitis was primarily caused by gram-positive bacteria, whereas endophthalmitis was chiefly caused by fungal infection. The infection incidence was significantly lower in eyes using topical 0.1% amphotericin B and 5% povidone iodine (P = .008 and .021, respectively). CONCLUSIONS: With its good retention rate and visual outcomes, Boston type I KPro could be an alternative treatment for patients with conventional penetrating keratoplasty failure, especially with appropriate patient selection and complication prevention. Standard prophylactic antibiotics with the addition of topical 0.1% amphotericin B and 5% povidone iodine might be optional effective regimens for infection prevention, especially in tropical countries.

Priming human adipose-derived mesenchymal stem cells for corneal surface regeneration.

Limbal stem cells (LSC) maintain the transparency of the corneal epithelium. Chemical burns lead the loss of LSC inducing an up-regulation of pro-inflammatory and pro-angiogenic factors, triggering corneal neovascularization and blindness. Adipose tissue-derived mesenchymal stem cells (AT-MSC) have shown promise in animal models to treat LSC deficiency (LSCD), but there are not studies showing their efficacy when primed with different media before transplantation. We cultured AT-MSC with standard medium and media used to culture LSC for clinical application. We demonstrated that different media changed the AT-MSC paracrine secretion showing different paracrine effector functions in an in vivo model of chemical burn and in response to a novel in vitro model of corneal inflammation by alkali induction. Treatment of LSCD with AT-MSC changed the angiogenic and inflammatory cytokine profile of mice corneas. AT-MSC cultured with the medium that improved their cytokine secretion, enhanced the anti-angiogenic and anti-inflammatory profile of the treated corneas. Those corneas also presented better outcome in terms of corneal transparency, neovascularization and histologic reconstruction. Priming human AT-MSC with LSC specific medium can potentiate their ability to improve corneal wound healing, decrease neovascularization and inflammation modulating paracrine effector functions in an in vivo optimized rat model of LSCD.

Modulating Ocular Surface Pain Through Neurokinin-1 Receptor Blockade.

Purpose: The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain. Methods: Eight-week-old C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. 5 M NaCl was topically applied on the cornea, followed by topical fosaprepitant 2, 10, and 50 mg/mL; 4 mg/mL oxybuprocaine chloride, or 0.1% diclofenac. Th eye wiping test was used to quantify ocular surface pain. SP content was quantified in the tear fluid and trigeminal ganglia (TG), and TAC1 mRNA was assessed in the cornea. Corneas were immunostained for ß3-tubulin and NK1R, or CD45, to quantify leukocyte infiltration. Results: TAC1-KO mice displayed a significant reduction of ocular pain (P < 0.001). Similarly, a single dose of 10 or 50 mg/mL fosaprepitant applied topically to WT mice reduced ocular pain as compared to vehicle (P < 0.001). Fosaprepitant 2 mg/mL, instead, induced corneal analgesia only when it was administered for 10 days, 6 times/day (P < 0.05). Diclofenac or oxybuprocaine reduced corneal nociception when compared to vehicle or fosaprepitant (P < 0.05). Fosaprepitant or oxybuprocaine groups showed lower SP content in tear secretions and TG (P < 0.05), and reduction in TAC1 mRNA (P < 0.05), and leukocyte infiltration (P < 0.05) in the cornea. Colocalization of NK1R and ß3-tubulin was detected in mouse corneas. Conclusions: Topical administration of the NK1R antagonist fosaprepitant effectively reduces ocular surface nociception by decreasing SP release in the tear fluid and TG, and corneal leukocyte infiltration. Fosaprepitant repurposing shows promise for the treatment of ocular pain.

Evaluation of corneal safety in systemic lupus erythematosus patients undergoing long-term hydroxychloroquine treatment.

PURPOSE: The aim of this study was to examine the effects of long-term use of hydroxychloroquine (HQ) on the pachymetric, aberrometric, and densitometric values of the cornea and corneal endothelium in lupus patients. METHOD: Twenty-two eyes (study group) of 22 patients using HQ for treatment of lupus and 25 eyes (control group) of 25 healthy individuals were included in this prospective study. A specular microscopy was used to measure corneal endothelial cell density (ECD), percentage of hexagonal cells (HEX%), coefficient of variation of the cell size (CV). Then, a Pentacam® HR corneal tomography system was used to measure central corneal thickness (CCT), corneal aberrometry values in 6-mm pupil diameters and corneal densitometry values in 6-mm corneal zones (0-2 mm and 2-6 mm). RESULTS: While ECD was significantly lower in the study group than in the control group (p = 0.034), CCT was significantly higher in the study group (p = 0.032). The higher-order aberrations values and the anterior corneal densitometry values in the 0-2 mm and 2-6 mm corneal zones in the study group were found to be significantly higher than the control group (p = 0.021, p = 0.007 and p = 0.013). CONCLUSION: Prolonged use of HQ may cause some changes in the cornea. In the follow-up of these cases, detailed examination of the cornea as well as the macula may be important for the protection of corneal health.

Iatrogenic corneal diseases or conditions.

Any prescribed or self-administered therapy carries inherent risks of secondary adverse events. While the volume of treatments being administered through healthcare systems has been increasing, scientific advancements in our understanding of the mechanisms of pharmaceutical side effects and complications from procedures now allow us to reduce the risk of non-intentional damage to ocular health. This review summarizes the most common and leading causes of iatrogenic visual impairment, corneal diseases, and conditions that present in a general ophthalmologic practice, including a comprehensive analysis of their pathophysiology and recommendations for management and prophylaxis.Iatrogenic corneal diseases and conditions can arise from topical drugs, contact lens use, eye surgeries and procedures, systemic drugs, non-ophthalmological events, and cosmetic procedures. Topical and systemic drugs may disturb tear film homeostasis or result in ocular surface deposits. The use of ill-fitted contact lenses can trigger eye discomfort and poor hygiene conditions that can predispose to severe infections. Procedures to the eye may result in a variety of anatomical and functional complications that ophthalmologists should be aware of how to avoid or at least be prepared to manage if they occur. Even non-ophthalmological events such as non-invasive ventilation, radiation therapies and, immune-based conditions, or cosmetic procedures such as eyelash growth and fillers, can result in unwanted damage to the ocular surface.

Análise do perfil epidemiológico dos pacientes submetidos a transplante de córnea no Espírito Santo / Analysis of the epidemiological profile of patients submitted to corneal transplantation in the Espirito Santo

Resumo Objetivo: Descrever o perfil epidemiológico dos pacientes submetidos a transplante de córnea no estado do Espírito Santo. Métodos: Estudo transversal e descritivo realizado entre o período de janeiro de 2017 a janeiro de 2018, com o total de 1310 cadastrados na Central de Notificação, Captação e Distribuição de Órgãos do Espírito Santo (CNCDO/ES) por meio do Sistema Nacional de Transplantes (SNT) e que foram submetidos a transplante de córnea. Os dados foram apresentados em estatística descritiva como frequências e mediana e a análise dos dados foi realizada com o software SPSS versão 23. Resultados: em relação à frequência, obteve-se 54,3% do gênero feminino, 57,33% (751) provenientes da Região Metropolitana de Vitória. Os pacientes do Espírito Santo correspondem a 86% da frequência na fila, seguidos por Rio de Janeiro, Minas Gerais e Bahia, que juntos correspondem a 6,3%. O principal diagnóstico na indicação de transplante foi a Ceratopatia Bolhosa (25,9%), seguido por Ceratocone (16,5%) e Ceratite Intersticial (15,5%). A média de tempo de espera foi de 195 dias, sendo no máximo 1345 dias. Verificou-se que 1310 pacientes foram transplantados de córnea, a faixa etária dos transplantados é de 57 anos, sendo a maioria destes da Região Metropolitana de Vitória. Conclusão: Os diagnósticos mais prevalentes nos pacientes transplantados no Espírito Santo foram Ceratopatia Bolhosa e Ceratocone, em pacientes majoritariamente do sexo feminino, 57 anos em média, da região metropolitana da grande Vitória e provenientes do próprio estado. O estudo permite traçar estratégias de prevenção, cuidado e ações sociais de conscientização de doação de córnea.

Abstract Objective: To describe the epidemiological profile of patients submitted to corneal transplantation in state of Espirito Santo, Brazil. Methods: Transversal and descriptive study, with 1301 patients, in the period of January 2017 until to January 2018, the patients were registered in the Central Notification, Captation and Distribution of Organs of Espirito Santo (CNCDO/ES) through the National Transplant System (SNT) and submitted to corneal transplantation. The data were shown as descriptive statistics (frequencies and medians) and analysis of the data was performed using SPSS software, 23 version. Results: In relation to frequency, it was obtained 54.5% female, 57.33% from the metropolitan area of Vitória. Eighty-six percent were patients from Espirito Santo and the others 6.3% were from Rio de Janeiro, Minas Gerais and Bahia. The main indications for corneal transplantation were Bullous Keratopathy (25.9%), Keratoconus (16.5%) and interstitial keratitis (15.5%). The average of waiting time was 195 days and the longest was 1345 days. It was found that 1301 patients underwent corneal transplantation, they are in the 57-year age group, and the biggest part of them are from the metropolitan area of Vitória. Conclusion: The most prevalent diagnoses in patients submitted to corneal transplantation in state of Espirito Santo were Bullous Keratopathy and Keratoconus, in patients mostly female, 57 years old on average, from the metropolitan region of greater Vitória and from the state itself. The study allows to outline prevention strategies, care and social actions to raise awareness of corneal donation.

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.

Eye care in the intensive care unit during the COVID-19 pandemic.

Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.

Trehalose for Ocular Surface Health.

Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s.

Orbicularis Oculi Muscle Reinnervation Confers Corneal Protective Advantages over Static Interventions Alone in the Subacute Facial Palsy Patient.

BACKGROUND: Corneal protection is a priority in flaccid facial palsy patients. Denervation of the orbicularis oculi muscle results in weak palpebral closure and predisposes patients to severe corneal sequelae. While periorbital static procedures enhance corneal coverage in repose, voluntary closure is only regained through dynamic reinnervation of the muscle. This study aims to elucidate the added effect of dynamic reinnervation of the orbicularis oculi muscle on long-term corneal integrity as well as on dynamic closure of the palpebral aperture. METHODS: Retrospective review was performed on two groups of complete palsy patients: those who received solely periorbital static procedures and those who underwent concomitant orbicularis oculi muscle reinnervation and static lid procedures. Only patients with complete ophthalmic examinations were included. Corneal punctate epithelial erosions in addition to static and dynamic palpebral measurements were serially assessed preoperatively and postoperatively. RESULTS: Of 272 facial palsy patients, 26 fit the inclusion criteria. Eleven patients underwent combined muscle reinnervation involving facial-to-masseteric nerve coaptation in addition to static eye procedures, and 15 patients underwent solely static interventions. Analysis revealed a 65.3 percent lower mean punctate epithelial erosion score in reinnervation patients as compared with static patients when evaluated at more than 9 months postoperatively (p < 0.01). Reinnervation patients were also found to have 25.3 percent greater palpebral aperture closure (p < 0.05) and 32.8 percent higher closure velocity (p < 0.01) compared with static patients. CONCLUSION: In patients with subacute facial palsy, dynamic reanimation of the orbicularis oculi muscle with concomitant static interventions provides lasting corneal protection not seen in patients who receive solely static interventions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Keratopigmentation combined with strabismus surgery to restore cosmesis in eyes with disabling corneal scarring and squint.

BACKGROUND: Therapeutic corneal pigmentation has modernly evolved into different sophisticated techniques to camouflage cosmetically disabling corneal opacities and scars with good reported outcomes. Blind eyes frequently suffer from strabismus which further deteriorates the cosmesis of the patient. Combined keratopigmentation (KTPG) with strabismus surgery may be an option for these patients. METHODS: A total of 72 consecutive patients were retrospectively reviewed in this investigation. Main outcome measures were postoperative residual squint, and cosmesis evaluated by an independent observer, patient satisfaction, reoperation rates for KTPG and squint, and complications. RESULTS: A total of 72 consecutive patients and 73 eyes that underwent KTPG and strabismus surgery were included in this study. Mean follow-up time was 2.5±3 years. Patient age ranged from 5 to 83 years, with 93% having visual acuity worse than 0.1. 14 eyes (24.5%) underwent repeated KTPG, 24 (42.1%) had repeated strabismus surgery. 14 patients (19.4%) had a repeat muscle surgery, although 55 (76.4%) of the 72 patients achieved orthotropia or had deviations within 10 prism dioptres at the end of the follow-up period. Corneal microperforation was encountered in two (2.8%) patients and conjunctival staining in 10 eyes. Cosmesis was good for all patients. Patients who required repeat KTPG or strabismus surgery, or those in whom orthotropia was not totally restored, considered their cosmetic appearance sufficiently improved. CONCLUSION: Corneal KTPG combined with strabismus surgery provides good cosmesis for patients with corneal scarring and strabismus with minimal complications. Reoperation rates are relatively high in the short term to accomplish an optimal cosmetic result.

Literature review and suggested protocol for prevention and treatment of corneal graft rejection.

Effective prophylaxis and treatment of corneal graft rejection are essential to improve outcomes in corneal transplantation. To date, there has been no standardized protocol published that outlines the optimal prophylactic and therapeutic approaches and, furthermore, the published controlled trials on this subject are limited. Likewise, no study has addressed how the level of antigen exposure varies between different types of keratoplasties. The aim of this paper is to provide a simple evidence-based protocol for the prevention and treatment of corneal graft rejection.