The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1.

PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Immunosenescence and Skin: A State of Art of Its Etiopathogenetic Role and Crucial Watershed for Systemic Implications.

Immunosenescence is a complex multifactorial phenomenon consisting of wide-ranging remodeling of the immune system during the life span, resulting in an age-related qualitative-quantitative decline of immune cells and cytokines. A growing body of evidence in the international literature is highlighting the etiopathogenetic role of skin immunosenescence in the onset of various dermatologic conditions. Skin immunosenescence also serves as an interesting watershed for the onset of system-wide conditions in the context of allergic inflammation. Moreover, in recent years, an increasingly emerging and fascinating etiopathogenetic parallelism has been observed between some mechanisms of immunosenescence, both at cutaneous and systemic sites. This would help to explain the occurrence of apparently unconnected comorbidities. Throughout our review, we aim to shed light on emerging immunosenescent mechanisms shared between dermatologic disorders and other organ-specific diseases in the context of a more extensive discussion on the etiopathogenetic role of skin immunosenescence. A promising future perspective would be to focus on better understanding the mutual influence between skin and host immunity, as well as the influence of high inter-individual variability on immunosenescence/inflammaging. This can lead to a more comprehensive "immunobiographic" definition of each individual.

Alarmins in cutaneous malignant melanoma: An updated overview of emerging evidence on their pathogenetic, diagnostic, prognostic, and therapeutic role.

Malignant cutaneous melanoma is the leading cause of death for skin cancer to date, with globally increasing incidence rates. In this epidemiological scenario, international scientific research is exerting efforts to identify new clinical strategies aimed at the prognostic amelioration of the disease. Very promising and groundbreaking in this context is the scientific interest related to alarmins and their pioneering utility in the setting of the pathogenetic understanding, diagnosis, prognosis, and therapy for malignant cutaneous melanoma. However, the scientific investigations on this matter should not overlook their still well-presented dual and contradictory role. The aim of our critical analysis is to provide an up-to-date overview of the emerging evidence concerning the dichotomous role of alarmins in the aforementioned clinical settings. Our literature revision was based on the extensive body of both preclinical and clinical findings published on the PubMed database over the past 5 years. In addition to this, we offer a special focus on potentially revolutionary new therapeutic frontiers, which, on the strength of their earliest successes in other clinical areas, could inaugurate a new era of personalized and precision medicine in the field of dermato-oncology.

Artificial Intelligence: A Snapshot of Its Application in Chronic Inflammatory and Autoimmune Skin Diseases.

Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

"Mens Sana in Cute Sana"-A State of the Art of Mutual Etiopathogenetic Influence and Relevant Pathophysiological Pathways between Skin and Mental Disorders: An Integrated Approach to Contemporary Psychopathological Scenarios.

The negative socioeconomic impact of mental health disorders and skin diseases has increased in part due to the conflict between Russia and Ukraine, which has been a fertile ground for the emergence of psychopathologies. It is firmly established that there is a direct thread of etiopathogenetic communication between skin diseases and neuropsychiatric disorders, and the literature has tried to reveal the pathophysiological mechanisms governing such bidirectionality. This paper discusses this complex network of molecular pathways that are targeted by conventional and biological pharmacological agents that appear to impact two pathological spheres that previously seemed to have little connection. This molecular discussion is supplemented with a literature review, from a clinical viewpoint, regarding skin-brain etiopathogenetic bidirectionality. We focus on post-traumatic stress disorder (PTSD), which can be considered for all intents and purposes a systemic inflammatory disease that also affects the skin. A brief overview is also provided on the diagnostic-therapeutic and follow-up potential of oxidative and inflammatory markers potentially involved in the pathophysiological mechanisms treated. The aim is to clarify how these mechanisms may be useful in defining different stress-coping strategies and thus individual phenotypes of stress sensitivity/resistance in order to promote personalized medicine in the field of psychodermatology.

Rosmarinus officinalis and Skin: Antioxidant Activity and Possible Therapeutical Role in Cutaneous Diseases.

The rosemary plant, Rosmarinus officinalis L., one of the main members of the Lamiaceae family, is currently one of the most promising herbal medicines due to its pharmaceutical properties. This research aimed to evaluate the antioxidant role of Rosmarinus officinalis and its bioactive compounds on the skin, with a focus on the newly emerging molecular mechanisms involved, providing extensive scientific evidence of its anti-inflammatory, antimicrobial, wound-healing and anticancer activity in dermatological practice. The search was conducted on articles concerning in vitro and in vivo studies in both animals and humans. The results obtained confirm the antioxidant role of R. officinalis. This assumption derives the possibility of using R. officinalis or its bioactive elements for the treatment of inflammatory and infectious skin pathologies. However, although the use of rosemary in the treatment of skin diseases represents a fascinating line of research, future perspectives still require large and controlled clinical trials in order to definitively elucidate the real impact of this plant and its components in clinical practice.

Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives.

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.

Effects of Benzene: Hematological and Hypersensitivity Manifestations in Resident Living in Oil Refinery Areas.

Literature is teeming with publications on industrial pollution. Over the decades, the main industrial pollutants and their effects on human health have been widely framed. Among the various compounds involved, benzene plays a leading role in the onset of specific diseases. Two systems are mainly affected by the adverse health effects of benzene exposure, both acute and chronic: the respiratory and hematopoietic systems. The most suitable population targets for a proper damage assessment on these systems are oil refinery workers and residents near refining plants. Our work fits into this area of interest with the aim of reviewing the most relevant cases published in the literature related to the impairment of the aforementioned systems following benzene exposure. We perform an initial debate between the two clinical branches that see a high epidemiological expression in this slice of the population examined: residents near petroleum refinery areas worldwide. In addition, the discussion expands on highlighting the main immunological implications of benzene exposure, finding a common pathophysiological denominator in inflammation, oxidative stress, and DNA damage, thus helping to set the basis for an increasingly detailed characterization aimed at identifying common molecular patterns between the two clinical fields discussed.

Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers.

BACKGROUND AND AIMS: Polyhexamethyl biguanide (PHMB), a widely used topical treatment for Acanthamoeba keratitis (AK), is unlicensed with no formal safety assessment. This study evaluated its safety and tolerability. METHODS: A prospective, randomised, double-masked controlled trial in 90 healthy volunteers. Subjects were treated with topical 0.04%, 0.06%, 0.08% PHMB or placebo (vehicle) 12× daily for 7 days, then 6× daily for 7 days. The rates of dose-limiting adverse events (DLAEs) leading to interruption of dosing, mild adverse events (AEs) (not dose limiting) and incidental AEs (unrelated to treatment) were compared. The primary outcome was the difference between treatments for DLAE rates. RESULTS: 5/90 subjects developed DLAE within <1-4 days of starting treatment; 2/5 using PHMB 0.06% and 3/5 PHMB 0.08%. These resolved within 1-15 days. There were no significant differences in DLAE between treatment groups. Mild AEs occurred in 48/90 subjects (including placebo). There was no trend for an increased incidence of any AE with increasing concentrations of PHMB, except for corneal punctate keratopathy with PHMB 0.08%, which fully resolved within 7-14 days. CONCLUSION: These findings are reassuring for PHMB 0.02% users. They also suggest that higher PHMB concentrations may show acceptable levels of tolerance and toxicity in AK subjects, whose susceptibility to AE may be greater than for the normal eyes in this study. Given the potential benefits of higher PHMB concentrations for treating deep stromal invasion in AK, we think that the use of PHMB 0.08% is justified in treatment trials. TRIAL REGISTRATION NUMBER: NCT02506257.

Short-Term Use of Dexamethasone/Netilmicin Fixed Combination in Controlling Ocular Inflammation After Uncomplicated Cataract Surgery.

PURPOSE: To evaluate the short-term anti-inflammatory effect of dexamethasone/netilmicin fixed combination in the management of ocular inflammation after cataract surgery. PATIENTS AND METHODS: Open-label, randomized, active-controlled, clinical study conducted in 6 sites in Italy; 238 patients were randomized 2:1 to dexamethasone/netilmicin (dexa/net, n=158) or betamethasone/chloramphenicol (beta/chl, n=80). Treatment started the day of surgery and continued 4 times daily for 7 days. The primary efficacy parameter was the anterior chamber (AC) flare. The percentage of patients displaying none or mild (ie, only barely detectable) AC flare was defined as "efficacy rate", whereas the percentage of patients showing a decrease of AC flare score from baseline was defined as "percentage of responders". Additional parameters evaluated were AC cells, conjunctival hyperaemia, corneal and lid oedema, symptoms of ocular discomfort, visual acuity, and intraocular pressure. Dexa/net was considered effective if the efficacy rate was not inferior (by means of 97.5% confidence interval) to that of beta/chl. RESULTS: After 7 days of treatment, no AC flare was observed in 92.8% (dexa/net) and 92.3% (beta/chl) of patients, whereas no AC cells were observed in 91.5% (dexa/net) and 93.6% (beta/chl) of patients, respectively. The "efficacy rate" was 100% in both groups, whereas the "percentage of responders" was 94.1% in the dexa/net and 93.6% in the beta/chl group. The p-value to reject the null hypothesis of inferiority was <0.001. Other efficacy parameters confirmed both treatments as highly effective, despite their difference in steroid content (2 mg/mL for beta/chl vs 1 mg/mL for dexa/net). IOP and visual acuity at the end of the study were comparable. Two cases of allergic conjunctivitis were considered adverse events and were both related to dexa/net. CONCLUSION: Short-term use of dexa/net fixed combination is safe and effective in the control of post-operative inflammation following uncomplicated cataract surgery.

Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases.

AIMS: To test the hypothesis that Acanthamoeba keratitis (AK) outcomes differ for different topical antiamoebic therapies (AAT) and to provide the detailed patient outcome data. METHODS: A retrospective cohort study of 227 patients developing AK between 25 July 1991 and 10 August 2012. Inclusion criteria required a complete record of AAT treatment for both the primary outcome of a medical cure rate at 12 months and the secondary outcome of Snellen visual acuity ≤6/24 and/or surgical intervention. Analysis used multivariable regression to control for differences in baseline disease characteristics for both primary and secondary outcomes with unadjusted analyses for other outcomes. Subjects were categorised for analysis both by the AAT used at baseline and also by mutually exclusive AAT (patients exposed to all the drugs in each group, and no others, for some period). AAT categories were PHMB monotherapy, PHMB+diamidine, PHMB+chlorhexidine+diamidine, diamidine monotherapy and other AAT. RESULTS: Analysis by baseline AAT showed no notable difference between treatments for both a medical cure at 12 months in 60.79% (138/227) or for a poor outcome in 49.34% (112/227). When AATs were analysed by mutually exclusive groups, PHMB monotherapy provided the best outcomes. These findings are subject to bias requiring careful interpretation. Overall cure rates for the 214 subjects with resolved outcomes were 94.27% (214/227), median time to cure 5 months (IQR 3.25-9.00 months) and range 1-26.24 months. CONCLUSION: PHMB 0.02% monotherapy for the initial treatment of AK is as effective as biguanide+diamidine combination therapy. Chlorhexidine monotherapy was too infrequent for comparison. The outcome data are the most detailed available.

Dexamethasone/Netilmicin Eye Drops and Eye Gel for the Treatment of Ocular Inflammation After Micro-Incisional Vitreoretinal Surgery.

PURPOSE: To evaluate the effect of dexamethasone/netilmicin (dexa/net) fixed combination in the treatment of ocular inflammation after sutureless micro-incisional vitreoretinal surgery (MIVS). PATIENTS AND METHODS: This multicenter, open, randomized, active-controlled, parallel-group, clinical trial was run in 6 sites in Italy. Treatment started the day of surgery and continued 4 times daily for 14 days. Patients were 1:1 randomized to dexa/net (eyedrops solution and eye gel) or dexamethasone/tobramycin (dexa/tobra) eyedrops suspension and ointment. Viscous formulations (gel or ointment) were used alone during the early post-operative phase; afterwards, a combination of eye drops during daytime and viscous formulations at bedtime was adopted. The primary efficacy parameter evaluated was bulbar conjunctival hyperemia. Additional efficacy and safety parameters (palpebral conjunctival hyperemia, anterior chamber flare and cells, symptoms of ocular discomfort and ocular tolerance, adverse events and intraocular pressure) were also evaluated. Control visits were performed at day 1, day 4 and day 14 after surgery; the endpoint of the study was set at 14±2 days after surgery. RESULTS: A complete resolution of bulbar conjunctiva hyperaemia at the study end point was reached in 92.9% of patients treated with dexa/net and 75.0% of those treated with dexa/tobra (p=0.02, Fisher's exact test). No differences were observed between treatments for other efficacy parameters. Statistically significant differences in favour of dexa/net (p< 0.0001, ANOVA) were observed for most of subjective tolerance variables examined (blurred vision, foreign body sensation, stickiness, burning) starting day 1 after surgery when only the viscous formulations were used. No increase in intraocular pressure or adverse events was observed during the study. CONCLUSION: The combination dexa/net is safe and effective in the treatment of post-operative inflammation following sutureless MIVS. In particular, the use of eye gel formulation is characterized by a great tolerability.

Changes in conjunctival epithelial cells after treatment with 0.2% xanthan gum eye drops in mild-moderate dry eye.

PURPOSE: To study the effects of xanthan gum eye drops on the ocular surface and conjunctival cytology of patients with mild-moderate dry eye. METHODS: This prospective, double-masked, controlled trial included 30 patients (age > 60 and Ocular Surface Disease Index score >12 and <33), divided into two groups of 15 subjects and treated with 0.2% xanthan gum eye drops (group 1) or 0.5% carboxymethylcellulose (group 2) qid. After a run-in period with saline qid, patients were evaluated by Ocular Surface Disease Index questionnaire, clinical assessment, and impression cytology at baseline (T0) and after 1 month (T1). For impression cytology, cellularity, cell-to-cell contacts, nucleus/cytoplasm ratio, chromatin aspect, goblet cells distribution, keratinization, and the presence of inflammatory cells were considered. Parameters were scored from 0 (no alterations) to 3 (evident alterations). For statistical analysis, Student's t-test, Wilcoxon rank-sum test, and Mann-Whitney U-test were used. RESULTS: Clinically, after 1 month of treatment, group 1 showed an improvement of corneal stain (T0 = 1.1 ± 1.4; T1 = 0.5 ± 0.7; p = 0.03) and a reduction of Schirmer I test (T0 = 9.8 ± 6.1; T1 = 5.9 ± 4.1; p = 0.001). In group 2, no differences were found between T0 and T1 for all the clinical tests. For impression cytology, in group 1 cellularity (T0 = 0.6 ± 0.5; T1 = 0.3 ± 0.5; p = 0.05), chromatin aspect (T0 = 1.2 ± 0.4; T1 = 0.8 ± 0.5; p = 0.01), keratinization (T0 = 1 ± 0.7; T1 = 0.5 ± 0.5; p = 0.03), and total score (T0 = 5.8 ± 1.3; T1 = 3.6 ± 1.7; p = 0.003) were significantly ameliorated, while in group 2 only total score improved significantly (T0 = 5 ± 1.4; T1 = 4.3 ± 1.5; p = 0.01). The comparison between groups showed significant amelioration for keratinization in group 1 at T1 (p = 0.02). CONCLUSION: The treatment with xanthan gum, a molecule with anti-oxidant and mucoadhesive properties, ameliorated conjunctival epithelium of mild-moderate dry eye patients better than carboxymethylcellulose.

Measurement of the Retention Time of Different Ophthalmic Formulations with Ultrahigh-Resolution Optical Coherence Tomography.

Purpose/aim of the study: The purpose of this study was to measure the pre-corneal retention time of two marketed formulations (eye drops and eye gel) of a steroid-antibiotic fixed combination (FC) containing 0.1% dexamethasone and 0.3% netilmicin. MATERIALS AND METHODS: Pre-corneal retention time was evaluated in 16 healthy subjects using an ultrahigh-resolution anterior segment spectral domain optical coherence tomography (OCT). All subjects randomly received both formulations of the FC (Netildex, SIFI, Italy). Central tear film thickness (CTFT) was measured before instillation (time 0) and then after 1, 10, 20, 30, 40 50, 60 and 120 min. The pre-corneal retention time was calculated by plotting CTFT as a function of time. Differences between time points and groups were analyzed by Student's t-test. RESULTS: CTFT increased significantly after the instillation of the eye gel formulation (p < 0.001). CTFT reached its maximum value 1 min after instillation and returned to baseline after 60 min. No effect on CTFT was observed after the instillation of eye drops. The difference between the two formulations was statistically significant at time 1 min (p < 0.0001), 10 min (p < 0.001) and 20 min (p < 0.01). CONCLUSIONS: The FC formulated as eye gel was retained on the ocular surface longer than the corresponding eye drop solution. Consequently, the use of the eye gel might extend the interval between instillations and decrease the frequency of administration.

In vitro effects of fluoroquinolone and aminoglycoside antibiotics on human keratocytes.

PURPOSE: The purpose of this study was to assess the cytotoxic effects of the fluoquinolone ofloxacin and the aminoglycoside netilmicin on stromal human keratocytes in vitro. METHODS: Cultured human keratocytes were exposed to various concentrations of ofloxacin or netilmicin (0.16-5.0 mg/mL). Both cell proliferation (MTT assay) and cell morphology (phase-contrast microscopy) were evaluated after 1, 4, 12, and 24 hours of incubation. Measurement of annexin V binding performed in association with the dye exclusion test using propidium iodide (PI) was also performed by FACS analysis after 4 hours of exposure. RESULTS: Both antimicrobials induced dose- and time-dependent morphologic changes in keratocytes, yet the effects of netilmicin were minimal. After 24 hours of exposure, both drugs induced a dose-dependent inhibition of cell proliferation; however, ofloxacin demonstrated significantly more toxic effects than netilmicin (t test for ED50 values, P < 0.0001). Statistical differences between 2 antibiotics start at concentrations above 1.25 mg/mL (ANOVA with post-hoc test, P < 0.01). Expression of the apoptotic marker annexin V was unaffected by antibiotic exposure, whereas the uptake of the necrotic marker PI was increased by ofloxacin (5 mg/mL) but not by netilmicin (ofloxacin versus netilmicin, ANOVA, P < 0.05). CONCLUSIONS: Relative effects of aminoglycosides and fluoroquinolones on stromal keratocytes appear to be different: netilmicin was shown to be significantly less toxic than ofloxacin. This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is absent or compromised, as after photorefractive keratectomy, alkali burns, or ulcerative keratitis.

Ocular flora and their antibiotic susceptibility in patients having cataract surgery in Italy.

PURPOSE: To characterize the ocular flora in a consecutive group of patients having cataract surgery and to determine the antibiotic susceptibility profile of isolates to several ophthalmic antibiotics. SETTING: Hospital Di Stefano, Catania, Italy. DESIGN: Observational case series. METHODS: Conjunctival and eyelid cultures from patients were obtained 14 days before surgery and, if positive, repeated the day of the surgery. Antimicrobial susceptibility for aminoglycosides (netilmicin and tobramycin), fluoroquinolones (ofloxacin, levofloxacin, and moxifloxacin), chloramphenicol, and azithromycin was tested using the Kirby-Bauer disk diffusion method. Susceptibility was also tested for oxacillin, cefuroxime, and vancomycin. All positive patients received a 2-day preoperative course of 3 mg/mL netilmicin ophthalmic solution 4 times a day. The recovery rate of microorganisms after antibiotic treatment compared with baseline was calculated. RESULTS: One hundred twenty consecutive patients were included in the study. Cultures were positive in 72.5% of patients; 131 isolates, mainly gram-positive, were identified. Staphylococcus epidermidis (58.0%) and Staphylococcus aureus (15.3%) were the most frequently isolated microorganisms. Methicillin-resistant staphylococci accounted for 3.8% of S epidermidis and 20.0% of S aureus. A high in vitro susceptibility (>90%) for all isolates, including multiresistant coagulase-negative Staphylococcus, was obtained for netilmicin, vancomycin, and cefuroxime. The recovery rate of isolates before surgery was reduced by 93.9% (P < .001). CONCLUSIONS: Conjunctival and lid margin isolates were sensitive to netilmicin, vancomycin, and cefuroxime. Microorganisms were less susceptible to other ophthalmic antibiotics, with the exception of moxifloxacin. A 2-day preoperative course with topical netilmicin reduced most bacteria identified on the conjunctiva and eyelids. FINANCIAL DISCLOSURE: Dr. Papa and Ms. Blanco are employees of Società Industria Farmaceutica Italiana SpA. Dr. Santocono has no financial or proprietary interest in any material or method mentioned.

Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye.

BACKGROUND/AIMS: Several studies have reported that sodium hyaluronate is able to improve both symptoms and signs in patients with dry eye but none have demonstrated an improvement of conjunctival epithelial cell abnormalities of the ocular surface. The aim of this study was to explore the effect of sodium hyaluronate-containing eye drops on the ocular surface of patients with dry eye during long term treatment. METHODS: A randomised double blind study was undertaken in 86 patients with medium to severe dry eye (that is, rose bengal and/or fluorescein test score of at least 3, tear film break up time <10 seconds, or Schirmer's test <5.5 mm). Patients were treated with either preservative-free sodium hyaluronate or saline for 3 months at a dose of one drop 4-8 times a day. Bulbar impression cytology, slit lamp examinations, and subjective symptoms were evaluated after 1, 2, and 3 months. Impression cytology was considered the primary efficacy parameter of the study. RESULTS: The efficacy analysis was performed on a total of 44 patients who were able to fully adhere to the protocol. After 3 months of treatment sodium hyaluronate improved impression cytology score (p = 0.024 v baseline). At the same time also the difference with respect to placebo was statistically significant (p = 0.036). Study medication was well tolerated and no treatment related adverse events occurred during the study. CONCLUSIONS: Sodium hyaluronate may effectively improve ocular surface damage associated with dry eye syndrome.

Efficacy and safety of desonide phosphate for the treatment of allergic conjunctivitis.

PURPOSE: To study the safety and efficacy of the topical corticosteroid, desonide 0.25% ophthalmic solution, for inhibition of the clinical allergic reaction induced by conjunctival provocation (CPT) and for the treatment of seasonal allergic conjunctivitis (SAC). METHODS: For the CPT study, 12 allergic but inactive patients were exposed in both eyes to increasing doses of a specific allergen until a positive bilateral, symmetrical early- and late-phase reaction was obtained. After 2 weeks the last positive dose was readministrated and their positive response confirmed. After an additional 2 weeks, CPT was performed 30 minutes after topical administration of desonide in one eye and placebo in the contralateral eye (Group A) or after topical desonide or placebo four times a day for 2 days (Group B). Clinical signs and symptoms were recorded after 15, 30, and 60 minutes, and after 6 hours. Regarding the seasonal study, 96 patients with active SAC were treated bilaterally with either desonide or fluorometholone for 3 weeks, and allergic signs and symptoms evaluated at regular intervals. The safety of the drugs was assessed by identification of any side effects or adverse events of any kind. RESULTS: For the CPT study: individual itching and redness, and the sum score for signs and symptoms were all statistically (p < 0.05) and clinically (greater than 1 change between treated eyes) significantly lower in desonide versus placebo eyes. Both early- and late-phase reactions were reduced by desonide pretreatment. Seasonal study: desonide and fluorometholone were both highly effective in reducing itching, tearing, and conjunctival hyperemia over time (p < 0.0001). Both drugs appeared safe, with no statistically significant changes in IOP observed with either treatment. CONCLUSIONS: Desonide has a significant therapeutic effect on both the induced conjunctival early- and late-allergic reaction and in active SAC. It was also safe, with no side effects such as increases in intraocular pressure observed by physician or patient.