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Drugs Feb 2022Corneal injuries can occur secondary to traumatic, chemical, inflammatory, metabolic, autoimmune, and iatrogenic causes. Ocular infection may frequently occur concurrent... (Review)
Review
Corneal injuries can occur secondary to traumatic, chemical, inflammatory, metabolic, autoimmune, and iatrogenic causes. Ocular infection may frequently occur concurrent to corneal injury; however, antimicrobial agents are excluded from this present review. While practitioners may primarily rely on clinical examination techniques to assess these injuries, several pharmacological agents, such as fluorescein, lissamine green, and rose bengal, can be used to formulate a diagnosis and develop effective treatment strategies. Practitioners may choose from several analgesic medications to help with patient comfort without risking further injury or delaying ocular healing. Atropine, cyclopentolate, scopolamine, and homatropine are among the most frequently used medications for this purpose. Additional topical analgesic agents may be used judiciously to augment patient comfort to facilitate diagnosis. Steroidal anti-inflammatory agents are frequently used as part of the therapeutic regimen. A variety of commonly used agents, including prednisolone acetate, loteprednol, difluprednate, dexamethasone, fluorometholone, and methylprednisolone are discussed. While these medications are effective for controlling ocular inflammation, side effects, such as elevated intraocular pressure and cataract formation, must be monitored by clinicians. Non-steroidal medications, such as ketorolac, bromfenac, nepafenac, and diclofenac, are additionally used for their efficacy in controlling ocular inflammation without incurring side effects seen with steroids. However, these agents have their own respective side effects, warranting close monitoring by clinicians. Additionally, ophthalmologists routinely employ several agents in an off-label manner for supplementary control of inflammation and treatment of corneal injuries. Patients with corneal injuries not infrequently have significant ocular surface disease, either as a concurrent pathology or as an exacerbation of previously existing disease. Several agents used in the management of ocular surface disease have also been found to be useful as part of the therapeutic armamentarium for treatment of corneal injuries. For example, several antibiotics, such as doxycycline and macrolides, have been used for their anti-inflammatory effects on specific cytokines that are upregulated during acute injuries. There has been a recent wave of interest in amniotic membrane therapies (AMTs), including topical, cryopreserved and dehydrated variants. AMT is particularly effective in ocular injuries with violation of corneal surface integrity due to its ability to promote re-epithelialization of the corneal epithelium. Blood-based therapies, including autologous serum tears, plasma-enriched growth factor eyedrops and autologous blood drops, have additionally been explored in small case series for effectiveness in challenging and recalcitrant cases. Protection of the ocular surface is also a vital component in the treatment of corneal injuries. Temporary protective methods, such as bandage contact lenses and mechanical closure of the eyelids (tarsorrhaphy) can be particularly helpful in selective cases. Glue therapies, including biologic and non-biologic variants, can also be used in cases of severe injury and risk of corneal perforation. Finally, there are a variety of recently introduced and in-development agents that may be used as adjuvant therapies in challenging patient populations. Neurotrophic corneal disease may occur as a result of severe or chronic injury. In such cases, recombinant human nerve growth factor (cenegermin), topical insulin, and several other novel agents may be an alternate and effective option for clinicians to consider.
Topics: Adhesives; Adrenal Cortex Hormones; Amnion; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cornea; Corneal Injuries; Fluorescent Dyes; Humans; Mydriatics; Patient Acuity
PubMed: 35025078
DOI: 10.1007/s40265-021-01660-5 -
Translational Vision Science &... May 2023Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their...
PURPOSE
Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted.
METHODS
Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells.
RESULTS
The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations.
CONCLUSIONS
Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration.
TRANSLATIONAL RELEVANCE
When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.
Topics: Humans; Adrenal Cortex Hormones; Anti-Bacterial Agents; Bacteria; Eye Infections, Bacterial; Drug Interactions; Epithelium, Corneal; Cell Line; Drug Therapy, Combination; Corneal Diseases
PubMed: 37184498
DOI: 10.1167/tvst.12.5.16 -
Journal of Clinical Medicine Jul 2022This study sought to evaluate the efficacy of the isolated use of fluorometholone compared with the combined use of azelastine and fluorometholone for the treatment of...
This study sought to evaluate the efficacy of the isolated use of fluorometholone compared with the combined use of azelastine and fluorometholone for the treatment of severe allergic conjunctival disease (ACD). One hundred and eleven patients with severe ACD were randomized into two groups: one treated with topical 0.1% fluorometholone combined with 0.05% azelastine and the other with 0.1% fluorometholone alone. The Ocular Surface Disease Index (OSDI) and the signs of keratopathy, palpebral conjunctiva papillae and conjunctival congestion were scored before and at one, two and six weeks after treatment and compared between the groups. The intra-ocular pressure (IOP) was also monitored. There were no significant differences between the groups in the baseline mean scores of signs and OSDI scores, which gradually improved at all visits after therapy in both groups. Although the time effect was significant for all the parameters (all p < 0.001), the reduction in corneal involvement scores from week 2 to week 6 was insignificant in both groups (p = 0.460 for the steroids group and p = 0.074 for the combination group). All signs and symptoms were significantly more improved in the combination group than in the isolated group at each control visit. IOP remained stable at all visits (all p < 0.001), except one patient in each group had elevated IOP over 21 mmHg. While both the isolated use of fluorometholone and combined use of azelastine and fluorometholone are effective in alleviating the signs and symptoms of severe ACD, optimal response can be achieved with adjunctive treatment including azelastine.
PubMed: 35807160
DOI: 10.3390/jcm11133877 -
The Cochrane Database of Systematic... Mar 2022Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75%... (Review)
Review
BACKGROUND
Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care.
OBJECTIVES
To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021.
SELECTION CRITERIA
We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty.
AUTHORS' CONCLUSIONS
The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Conjunctivitis; Conjunctivitis, Viral; Cyclosporine; Dexamethasone; Female; Fluorometholone; Ganciclovir; Humans; Keratoconjunctivitis; Levofloxacin; Lubricant Eye Drops; Male; Middle Aged; Povidone-Iodine; Tacrolimus; Trifluridine; Young Adult
PubMed: 35238405
DOI: 10.1002/14651858.CD013520.pub2 -
Beyoglu Eye Journal 2020The aim of this study was to assess the effects of topical 0.1% nepafenac and 0.1% fluorometholone on macular thickness (MT) after a neodymium: yttrium-aluminum-garnet...
OBJECTIVES
The aim of this study was to assess the effects of topical 0.1% nepafenac and 0.1% fluorometholone on macular thickness (MT) after a neodymium: yttrium-aluminum-garnet (Nd: YAG) laser posterior capsulotomy and to compare the findings with those of untreated patients.
METHODS
This prospective study included 75 eyes of 75 patients with posterior capsule opacification. The patients were divided into 3 groups according to the medications administered after a capsulotomy procedure. Group 1 comprised 25 patients who were prescribed 0.1% nepafenac for a week, Group 2 consisted of 25 patients who were prescribed 0.1% fluorometholone for a week, and Group 3 consisted of 25 patients who were not prescribed any medication. A circular-shaped capsulotomy was performed in all cases. MT was measured before the capsulotomy and at the first day, first week, and first month after the procedure using spectral domain-optical coherence tomography and the change values were compared within and between groups.
RESULTS
In Group 1, the superior and nasal parafoveal MT, temporal, and nasal perifoveal MT values at the first month were statistically significantly greater than those observed in the first week (p<0.05 for all values). In Group 2, the superior and nasal parafoveal MT and inferior perifoveal MT measurements in the first month were greater than those recorded the first week (p<0.05 for all values). In Group 3, there was a gradual increase seen in the first day, first week, and first month in the superior and temporal parafoveal MT value (p<0.05 for all). The change value in the parafoveal temporal quadrant was significant between groups, indicating a greater increase in the untreated group compared with the nepafenac and fluorometholone groups (p=0.04).
CONCLUSION
An increase in MT can occur after an Nd: YAG laser posterior capsulotomy. Both topical 0.1% nepafenac and 0.1% fluorometholone can prevent this increase. The 2 drugs were comparable; neither demonstrated apparent superiority to the other.
PubMed: 35098066
DOI: 10.14744/bej.2020.96158 -
Indian Journal of Ophthalmology Jun 2021: To characterize the sequelae of microsporidia keratoconjunctivitis (MKC) and outline its management.
PURPOSE
: To characterize the sequelae of microsporidia keratoconjunctivitis (MKC) and outline its management.
METHODS
Retrospective analysis of microbiologically proven MKC returned with persistent disease between January 2015 and December 2019 was done. Demographics, clinical features, management, and outcome were analyzed.
RESULTS
Sixteen patients (21 eyes) of 332 treated for MKC returned with the persisting disease. The mean age of 11 males (68.7%), and 5 females was 35.1 ± 12.2 years. Three-quarter of them did not have a known predisposing risk factor and one-quarter of them were referred for chronic conjunctivitis. Past medications included topical antivirals (n = 8) and topical corticosteroid (n = 6). Three predominant presentations were persistent (>3 weeks) superficial punctate keratitis (SPKs, n = 7), sub-epithelial infiltrates (SEIs, n = 13), and uveitis (n = 2). The lesions recurred in eight eyes (SPK and SEI 4 each) after a disease-free interval of 60.4 ± 40.6 days; there were 13 episodes of recurrence. Topical low potent corticosteroids (loteprednol/fluorometholone), and tacrolimus ointment 0.03% were used in 17 (80.9%) and 8 (38%) eyes, respectively, for a mean duration of 44.8 ± 31.6 and 226.8 ± 180.5 days, respectively. At follow-up, 172.3 ± 183.6 days, visual recovery was statistically significant in persistent eyes (BCVA 0.07 ± 0.07 logMAR; P < 0.00001) but, not in recurrent eyes (BCVA 0.16 ± 0.08 logMAR; P = 0.07). Five of 21 eyes were left with residual significant scar.
CONCLUSION
The sequelae of microsporidial keratoconjunctivitis are not uncommon. Topical 0.03% tacrolimus ointment appeared to be an effective corticosteroid-sparing agent for the treatment of SEIs and prevention of recurrence.
Topics: Adult; Conjunctivitis; Female; Humans; Keratoconjunctivitis; Male; Middle Aged; Recurrence; Retrospective Studies; Tacrolimus; Young Adult
PubMed: 34011737
DOI: 10.4103/ijo.IJO_1971_20 -
Journal of Current Ophthalmology Jun 2018The aim of this study was to compare the ocular hypertensive effect of the commercially available Betamethasone, Fluorometholone in Iran and Loteprednol Etabonate in...
PURPOSE
The aim of this study was to compare the ocular hypertensive effect of the commercially available Betamethasone, Fluorometholone in Iran and Loteprednol Etabonate in patients undergoing keratorefractive surgery.
METHODS
In this prospective randomized clinical trial, 300 eyes of 150 patients were included, and patients were randomly assigned to 3 groups and used one of the 3 steroid drops (Betamethasone 0.1%, Fluorometholone 0.1%, and Loteprednol Etabonate 0.5%) after myopic photorefractive keratectomy (PRK). Intraocular pressure (IOP) was measured 2, 4, and 6 weeks post-surgery. Twenty-two mmHg was set as the threshold IOP for starting anti-glaucoma medication and tapering steroid drops.
RESULTS
Of 300 eyes from 150 patients over the first 6 postoperative weeks, 2 eyes in Fluorometholone group (2%), 12 eyes in Betamethasone group (12%), and 16 eyes in Loteprednol group (16%) had IOP equal or more than 22 mmHg. Analysis of variance (ANOVA) test showed that the rise in IOP was significantly different between groups in the 2nd and 4th ( ≤ 0.001) postoperative weeks but not at 6th week ( = 0.230). An IOP rise equal or more than 10 mmHg was detected in 13 and 15 eyes in Betamethasone and Loteprednol groups, respectively. None of the eyes in Fluorometholone group had such an IOP rise.
CONCLUSIONS
Loteprednol and Fluorometholone were associated with the most and least increase in IOP, respectively. The highest pressures were detected 4 weeks after surgery in the Betamethasone and Loteprednol groups and 6 weeks after surgery in the Fluorometholone group. Fluorometholone was the safest among the three examined steroid drops in terms of IOP rise.
PubMed: 29988925
DOI: 10.1016/j.joco.2017.11.008 -
Saudi Journal of Ophthalmology :... 2022This study aimed to assess the efficacy and safety of sodium cromoglycate with fluorometholone in patients with allergic conjunctivitis.
PURPOSE
This study aimed to assess the efficacy and safety of sodium cromoglycate with fluorometholone in patients with allergic conjunctivitis.
METHODS
We conducted a single-arm phase IV open-label trial where fifty patients who received the eye drops were followed for 4 weeks. Treatment efficacy was assessed using the ocular itching score, conjunctival assessment score, total symptom and sign (TSS) score, and Visual Analog Scale (VAS).
RESULTS
Patients who received sodium cromoglycate-fluorometholone eye drops experienced significant improvements in their ocular itching score (mean difference [MD]: 1.14, < 0.001) and conjunctival redness score (MD: 1.18, < 0.001). Statistically significant improvements in TSS and VAS were achieved in 78% of the patients reporting no conjunctivitis by the end of the study. The overall therapeutic response to the drug was as follows: 16% improved and 84% much improved. No serious adverse events were reported.
CONCLUSION
Sodium cromoglycate with fluorometholone eye drops achieved 100% therapeutic response among patients with allergic conjunctivitis. The eye drops improve the ocular itching, and conjunctival irritation without serious adverse events. This combination appears effective and tolerable for treatment of allergic conjunctivitis.
PubMed: 35971498
DOI: 10.4103/sjopt.sjopt_208_21 -
The Ocular Surface Jan 2018It was hypothesized that tear protein biomarkers could predict the effects of topical steroid treatment and desiccating stress in patients with dry eye disease (DED). To... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
It was hypothesized that tear protein biomarkers could predict the effects of topical steroid treatment and desiccating stress in patients with dry eye disease (DED). To test this concept, a randomized, double-masked, controlled clinical trial with 41 patients was conducted.
METHODS
The patients were treated topically with either 0.1% fluorometholone (FML) or polyvinyl alcohol (PA). Tear samples were collected using 1 μl glass capillaries at recruitment into the study and after a 3-week treatment period, both before and after 2 h exposure to desiccating stress, in a controlled environment chamber. Relative quantification of tear proteins was conducted by NanoLC-MSTOF using sequential window acquisition of all theoretical mass spectra (SWATH). Ocular surface integrity (corneal and conjunctival staining and conjunctival hyperemia) was selected as the key DED-related sign and analyzed with proteomic data. Analysis of covariance (ANCOVA) and linear models were used to analyze the data with R.
RESULTS
758 proteins were identified and relatively quantified from each tear sample. Analysis revealed 9 differentially expressed proteins between FML and PA treatments after 3 weeks and 7 after desiccating stress (P < 0.05). We also identified several differentially expressed proteins at the initial collection, which could be used to predict changes of conjunctival and corneal staining and conjunctival hyperemia after FML treatment and after desiccating stress. These proteins include complement C3 (C3) and calmodulin like 5 (CALML5), which could also differentiate the severity of DED at baseline.
CONCLUSIONS
The identified proteins could be further used as biomarkers to identify patients most benefiting from FML treatment.
Topics: Administration, Ophthalmic; Aged; Biomarkers; Calcium-Binding Proteins; Complement C3; Conjunctival Diseases; Double-Blind Method; Dry Eye Syndromes; Eye Proteins; Female; Fluorometholone; Glucocorticoids; Humans; Hyperemia; Male; Middle Aged; Proteomics; Stress Disorders, Traumatic, Acute; Tears
PubMed: 28918083
DOI: 10.1016/j.jtos.2017.09.003