Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US ...Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Lutein is a carotenoid with reported anti-inflammatory properties. A large body of evidence shows that lutein has several beneficial effects, especially on eye health. In particular, lutein is known ...to improve or even prevent age-related macular disease which is the leading cause of blindness and vision impairment. Furthermore, many studies have reported that lutein may also have positive effects in different clinical conditions, thus ameliorating cognitive function, decreasing the risk of cancer, and improving measures of cardiovascular health. At present, the available data have been obtained from both observational studies investigating lutein intake with food, and a few intervention trials assessing the efficacy of lutein supplementation. In general, sustained lutein consumption, either through diet or supplementation, may contribute to reducing the burden of several chronic diseases. However, there are also conflicting data concerning lutein efficacy in inducing favorable effects on human health and there are no univocal data concerning the most appropriate dosage for daily lutein supplementation. Therefore, based on the most recent findings, this review will focus on lutein properties, dietary sources, usual intake, efficacy in human health, and toxicity.
Abstract Post-traumatic endophthalmitis is an uncommon yet devastating complication of an open globe injury. Risk factors include presence of an intraocular foreign body (IOFB), lens rupture, delayed ...primary globe repair, rural trauma, and trauma with contaminated objects. Visual prognosis in post-traumatic endophthalmitis is affected by the virulence of the microbe, the presence of a retinal break or detachment, the timing of treatment, the presence or absence of an IOFB, and the extent of initial injury. Treatment should be started emergently with systemic and intravitreal antibiotics. In the setting of penetrating ocular trauma, antibiotic prophylaxis of endophthalmitis should be considered. The best treatment regimen has not been determined. The most frequent prophylactic regimens are: treatment with oral antibiotics, a short course of intravenous antibiotics followed by oral antibiotics, or intravitreal antibiotics plus oral antibiotics.
The Acanthamoeba–Fungal Keratitis Study Raghavan, Anita; Baidwal, Shaffie; Venkatapathy, Narendran ...
American journal of ophthalmology,
20/May , Letnik:
201
Journal Article
Recenzirano
To ascertain the incidence of Acanthamoeba keratitis and the coexistence of Acanthamoeba and fungi in microbial keratitis.
Prospective cross-sectional study.
Patients presenting with stromal ...keratitis were additionally tested for Acanthamoeba irrespective of the clinical diagnosis. Culture positivity was the gold standard.
Of the 401 cases included in the study, 40 were positive for Acanthamoeba (10%); of these 40, 16 were positive for both Acanthamoeba and fungi (4.5% of the study group was Acanthamoeba and fungal keratitis positive); 5 were positive for Acanthamoeba and bacteria; and 2 had triple infection with Acanthamoeba, fungi, and bacteria. Ring infiltrates and stromal edema are frequently associated with Acanthamoeba keratitis, as well as in Acanthamoeba coinfections. Ring infiltrates in particular were more frequently seen in the Acanthamoeba and fungal keratitis group (8/16) and they were often yellowish with hyphate edges (vs ring infiltrates only, which are seen in the patients with Acanthamoeba alone). Only 2 patients were contact lens wearers: however, they presented with history of trauma.
Acanthamoeba coinfections are much more frequent and are not restricted to contact lens users. Anticipating coinfections is necessary for establishing a diagnosis as well as for appropriate and timely therapeutic interventions.
•This is the first definitive study establishing the incidence of Acanthamoeba coinfections.•The study makes specific reference to coexistent Acanthamoeba and fungal keratitis.
Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has ...been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.
Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know ...little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears.
To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches.
This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy.
We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text.
We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias.
OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.
Overall, approximately one‐quarter of patients with genetic eye diseases will receive a molecular diagnosis. Patients with developmental eye disorders face a number of diagnostic challenges including ...phenotypic heterogeneity with significant asymmetry, coexisting ocular and systemic disease, limited understanding of human eye development and the associated genetic repertoire, and lack of access to next generation sequencing as regarded not to impact on patient outcomes/management with cost implications. Herein, we report our real world experience from a pediatric ocular genetics service over a 12 month period with 72 consecutive patients from 62 families, and that from a cohort of 322 patients undergoing whole genome sequencing (WGS) through the Genomics England 100,000 Genomes Project; encompassing microphthalmia, anophthalmia, ocular coloboma (MAC), anterior segment dysgenesis anomalies (ASDA), primary congenital glaucoma, congenital cataract, infantile nystagmus, and albinism. Overall molecular diagnostic rates reached 24.9% for those recruited to the 100,000 Genomes Project (73/293 families were solved), but up to 33.9% in the clinic setting (20/59 families). WGS was able to improve genetic diagnosis for MAC patients (15.7%), but not for ASDA (15.0%) and congenital cataracts (44.7%). Increased sample sizes and accurate human phenotype ontology (HPO) terms are required to improve diagnostic accuracy. The significant mixed complex ocular phenotypes distort these rates and lead to missed variants if the correct gene panel is not applied. Increased molecular diagnoses will help to explain the genotype–phenotype relationships of these developmental eye disorders. In turn, this will lead to improved integrated care pathways, understanding of disease, and future therapeutic development.
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In this thesis the term eye amputation (EA) covers the removing of an eye by: evisceration, enucleation and exenteration. Amputation of an eye is most frequently the end‐stage in a complicated ...disease, or the primary treatment in trauma and neoplasm. In 2010 the literature is extensive due to knowledge about types of surgery, implants and surgical technique. However, not much is known about the time past surgery.
The purpose of the PhD thesis was: To indentify the number of EA, the causative diagnosis and the indication for surgical removal of the eye, the chosen surgical technique and to evaluate a possible change in surgical technique in Denmark from 1996 until 2003 (paper I); To describe the phantom eye syndrome and its prevalence of visual hallucinations, phantom pain and phantom sensations (paper II); To characterise the quality of phantom eye pain, including its intensity and frequency among EA patients. We attempted to identify patients with increased risk of developing pain after EA and investigated if preoperative pain is a risk factor for a later development of phantom pain (paper III); In addition we wanted to investigate the health related quality of life, perceived stress, self rated health, job separation due to illness or disability and socio‐economic position of the EA in comparison with the general Danish population (paper IV).
The studies were based on: Records on 431 EA patients, clinical ophthalmological examination and an interview study of 173 EA patients and a questionnaire answered by 120 EA patients.
Conclusions: The most frequent indications for EA in Denmark were painful blind eye (37%) and neoplasm (34%). During the study period 1996–2003, the annual number of eye amputations was stable, but an increase in bulbar eviscerations was noticed. Orbital implants were used with an increasing tendency until 2003. The Phantom eye syndrome is frequent among EA patients. Visual hallucinations were described by 42% of the patients. The content were mainly elementary visual hallucinations, with white or colored light as a continuous sharp light or as moving dots. The most frequent triggers were darkness, closing of the eyes, fatigue and psychological stress. Fifty‐four percent of the patients had visual hallucinations more than once a week. Ten patients were so visually disturbed that it interfered with their daily life.
Approximately 23% of all EA experience phantom pain for several years after the surgery. Phantom pain was reported to be of three different qualities: (i) cutting, penetrating, gnawing or oppressive (n = 19); (ii) radiating, zapping or shooting (n = 8); (iii) superficial burning or stinging (n = 5); or a mixture of these different pain qualities (n = 7). The median intensity on a visual analogue scale, ranging from 0 to 100, was 36 range: 1–89. One‐third of the patients experienced phantom pain every day. Chilliness, windy weather and psychological stress/fatigue were the most commonly reported triggers for pain. Factors associated with phantom pain were: ophthalmic pain before EA, the presence of implant and a patient reported high degree of conjunctival secretion. A common reason for EA is the presence of a painful blind eye. However, one third of these patients continue to have pain after the EA. Phantom sensations were present in 2% of the patients.
The impact of an eye amputation is considerable. EA patients have poorer health related quality of life, poorer self‐rated health and more perceived stress than does the general population. The largest differences in health related quality of life between the EA patients and the general population were related to role limitations due to emotional problems and mental health. Patients with the indication painful blind eye are having lower scores in all aspects of health related quality of life and perceived stress than patients with the indication neoplasm and trauma. The percentage of eye amputated which is divorced or separated was twice as high as in the general population. Furthermore, 25% retired or changed to part‐time jobs due to eye disease and 39.5% stopped participating in leisure activities due to their EAs.
Red eye is the cardinal sign of ocular inflammation. The condition is usually benign and can be managed by primary care physicians. Conjunctivitis is the most common cause of red eye. Other common ...causes include blepharitis, corneal abrasion, foreign body, subconjunctival hemorrhage, keratitis, iritis, glaucoma, chemical burn, and scleritis. Signs and symptoms of red eye include eye discharge, redness, pain, photophobia, itching, and visual changes. Generally, viral and bacterial conjunctivitis are self-limiting conditions, and serious complications are rare. Because there is no specific diagnostic test to differentiate viral from bacterial conjunctivitis, most cases are treated using broad-spectrum antibiotics. Allergies or irritants also may cause conjunctivitis. The cause of red eye can be diagnosed through a detailed patient history and careful eye examination, and treatment is based on the underlying etiology. Recognizing the need for emergent referral to an ophthalmologist is key in the primary care management of red eye. Referral is necessary when severe pain is not relieved with topical anesthetics; topical steroids are needed; or the patient has vision loss, copious purulent discharge, corneal involvement, traumatic eye injury, recent ocular surgery, distorted pupil, herpes infection, or recurrent infections.
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