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.

Contact Lens Use Advice-Risks and Outcomes: Are Patients Drowning in Information but Starved for Knowledge?

Objectives: Microbial keratitis can cause significant visual morbidity and is a common reason for presentation to eye casualty clinics. Contact lens wear and poor contact lens hygiene significantly increase the risk of corneal infection. This study aimed to determine the level of contact lens hygiene awareness amongst contact lens wearers attending our service and determining whether contact lens type and hygiene attitude are related to severity of disease. Materials and Methods: This prospective questionnaire-based study included 50 consecutive patients attending the eye casualty clinic of a tertiary referral center. Visual acuity was assessed at presentation and 2 weeks after diagnosis. Patients were divided into subgroups according to contact lens type (monthly, bi-weekly, daily, and extended day and night wear) and risk group (low, medium, and high) depending on their contact lens hygiene practices. Results: Thirty-four women and 16 men were included in this study. Twenty-four patients used monthly disposable contact lenses, 16 used daily disposable contact lenses, 6 were using bi-weekly replacement lenses, and 4 patients were using extended wear (day and night) contact lenses. Twenty-five patients were diagnosed with corneal ulcer, 23 of which had some degree of poor contact lens hygiene. Best corrected visual acuity (BCVA) significantly improved after treatment. Mean BCVA was 0.24 LogMAR before treatment and 0.09 LogMAR after treatment (p<0.05). Conclusion: Our study highlights the need to improve contact lens hygiene awareness and influence hygiene practices. Patients with the poorest contact lens hygiene had slower visual recovery and a higher prevalence of corneal ulcer. Contact lens hygiene advice needs to be clear and reinforced over time.

Blink Reflex in Neurotrophic Keratopathy: An Electrophysiological Evaluation.

PURPOSE: Neurotrophic keratitis (NK) is a rare condition which may result in visual loss. This case review investigates if there may be an association between NK and the blink reflex in the absence of facial nerve palsy and lagophthalmos. METHODS: This is a retrospective case review of 5 patients with trigeminal nerve damage referred to the oculoplastic department with suspected anesthetic corneae. Information on etiology, symptoms, duration, associated medical conditions, medications, examination findings including Mackie stage of keratopathy, management of keratopathy, and blink electrophysiology results was obtained. RESULTS: All 5 patients demonstrated absence of corneal sensation. All patients had preserved facial nerve function with no evidence of lagophthalmos. Keratopathy ranged from Mackie stage 0-2. Management ranged from ocular lubricants to Botulinum-toxin-induced ptosis. Blink studies demonstrated reduction in amplitude as well as increased latency in 2 patients, conferring reduced blink strength. Two patients demonstrated an absent blink reflex on the affected side. One patient had blink latency within the normative range; this patient recovered corneal sensation and was discharged. CONCLUSIONS: Our finding of reduced amplitude in blink studies offers both a factor in pathogenesis of NK and a potential therapeutic target. Additionally, blink studies may provide prognostic information for recovery and therefore guide management. We suggest performing blink electrophysiology in patients with trigeminal nerve damage to assess nerve function.

1 year posterior corneal changes after Bowman Layer Transplant for keratoconus.

INTRODUCTION: To report the posterior corneal changes after Bowman Layer Transplant for keratoconus in a tertiary hospital in the UK. METHODS: 5 eyes of 5 patients receiving Bowman Layer Transplant for advanced keratoconus in Royal Gwent Hospital (Newport, UK) were included. Pre and postoperative posterior corneal astigmatism, posterior Kmean, and back surface elevation were analysed. RESULTS: No significant changes were seen in the posterior corneal astigmatism, posterior Kmean, or back surface elevation between the pre- and postoperative period. CONCLUSION: This results would support the idea that the corneal changes seen after Bowman Layer Transplant are mainly in the anterior corneal surface.

Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey.

OBJECTIVES: To compare sociodemographics and vision-related quality of life (QoL) of individuals with or without dry eye disease (DED); and to explore the impact of DED symptom severity on visual function, activity limitations and work productivity. DESIGN: Cross-sectional web-based survey. SETTING: General UK population. PARTICIPANTS: Adults ≥18 years with (N=1002) or without (N=1003) self-reported DED recruited through email and screened. MAIN OUTCOME MEASURES: All participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), with six additional questions (items A3-A8), and the EuroQol 5 dimensions 5 levels. DED participants also completed Impact of Dry Eye on Everyday Life questionnaire, 5-item Dry Eye Questionnaire and the Standardised Patient Evaluation of Eye Dryness questionnaire along with the Ocular Comfort Index, Work Productivity and Activity Impairment and the Eye Dryness Score (EDS), a Visual Analogue Scale. RESULTS: Baseline demographic and clinical characteristics were similar in participants with versus without DED (mean age, 55.2 vs 55.0 years; 61.8% vs 61.0% women, respectively) based on recruitment targets. Scores were derived from NEI VFQ-25 using the new 28-item revised VFQ (VFQ-28R) scoring. Mean (SD) VFQ-28R scores were lower in participants with versus without DED, indicating worse functioning (activity limitations, 73.3 (12.3) vs 84.4 (12.3); socioemotional functioning, 75.3 (21.5) vs 90.3 (16.2); total score, 71.6 (12.8) vs 83.6 (12.6)). Higher percentages of problems/inability to do activities were observed among those with versus without DED. The impact of DED on visual function was worse for participants with more severe DED symptoms, as assessed by EDS. In addition, a higher EDS was associated with worse symptoms on common DED scales and a worse impact on work productivity. CONCLUSIONS: DED symptoms were associated with negative effects on visual function, activities and work productivity, whereas worse DED symptoms had a greater impact on vision-related QoL and work productivity.

Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae.

OBJECTIVES: To determine the presenting features of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To establish the need for treatment of dupilumab-associated ocular surface disease and report any long-term effects on the ocular surface. METHODS: A retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken. Data were collected on demographics, incidence and type of ocular disease features, natural history and treatment. RESULTS: A total of 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (±6.1) weeks from starting dupilumab. Of these, 69% (9/13) were diagnosed with conjunctivitis associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. In all, 67% (6/9) patients went on to have on-going ocular inflammation requiring maintenance drops at a mean of 16 (±6.9) months of follow-up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects. CONCLUSION: The rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed on-going treatment. Close liaison with an ophthalmologist should be considered in those patients who develop conjunctivitis or have a past history of severe ocular surface disease.

Ocular manifestations of emerging viral diseases.

Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.

Morphological and cytokine profiles as key parameters to distinguish between Gram-negative and Gram-positive bacterial keratitis.

Bacterial keratitis (BK) is an ocular disorder associated with poor visual prognosis. Quantification of the associated inflammatory response may provide insight into the pathogenesis of BK and guide treatment options. In this exploratory study, we evaluated 45 BK patients and 20 healthy controls by optical coherence tomography and pro-inflammatory tear cytokine analysis. The aim was to quantify the differential morphological and cytokine inflammatory response between Gram-negative and Gram-positive BK and to determine the diagnostic value of corneal thickness (CT) and infiltrate thickness (IT) in distinguishing Gram-ve BK in a clinical cohort. Greater CT and IT, at clinical presentation, were indicative of Gram-ve infection with values detected of ≥ 950 µm and ≥ 450 µm, respectively. Combination of these CT and IT values had a 100% sensitivity and 83.3% specificity as a diagnostic indicator of Gram-ve infection. Similarly, there were higher levels of IL-1ß, IL-6 and IL-8 cytokines were quantified in keratitis caused by Gram-negative bacteria. Among the different tear cytokines analysed, a significant reduction after three days of treatment was detected for pro-inflammatory cytokines IL-1ß, IL-2, IL-6, IL-8 and TNF-α, prior to starting with the administration of steroid drops. Overall, this study shows the potential value of serial OCT and tear cytokine measurements in the management of BK.

Tectonic Descemet Stripping Endothelial Keratoplasty for the Management of Corneal Perforation: A Case Series.

PURPOSE: Corneal perforations pose a considerable challenge for ophthalmic surgeons. The aim remains restoring the anatomical integrity of eye while attempting to preserve as much visual function as possible. To our knowledge, we report the first case series of 4 successful tectonic Descemet stripping endothelial keratoplasty (DSEK) grafts completed for acute corneal perforation. In all cases, restoration of globe integrity was achieved. In cases where visual potential remained, deep anterior lamellar keratoplasty over DSEK was offered. METHODS: Four patients presenting to Royal Gwent Hospital (Newport, Wales) with corneal perforation were included. Etiological origins included exposure keratopathy, corneal hydrops secondary to pellucid marginal degeneration with fistulization-associated aqueous leak, and herpetic keratitis. Patients were treated with initial temporary therapies, including glue patch, the use of bandage contact lenses, amniotic membrane transplant, and antibiotic cover, depending on the size and location of the perforation. Subsequent DSEK was subsequently performed under local anesthesia. RESULTS: All patients had successful tectonic grafts (3 DSEKs and 1 hemi-DSEK) up to 4 months postoperatively. In the case involving a hemi-DSEK, the patient underwent 2 refloating attempts of the graft before anchoring suture placement because of repeated graft detachment. Successful graft placement and tectonic globe restoration was confirmed by anterior segment imaging. CONCLUSIONS: Tectonic DSEK provides corneal surgeons with a new modality of treating corneal perforations. It provides clinicians an additional tool in their armamentarium in complex cases where anterior lamellar or penetrating keratoplasty may be contraindicated or deemed high risk of complications.

Personal hygiene risk factors for contact lens-related microbial keratitis.

OBJECTIVE: Microbial keratitis is a sight-threatening complication of contact lens wear, which affects thousands of patients and causes a significant burden on healthcare services. This study aims to identify compliance with contact lens care recommendations and identify personal hygiene risk factors in patients who develop contact lens-related microbial keratitis. METHODS AND ANALYSIS: A case-control study was conducted at the University Hospital Southampton Eye Casualty from October to December 2015. Two participant groups were recruited: cases were contact lens wearers presenting with microbial keratitis and controls were contact lens wearers without infection. Participants underwent face-to-face interviews to identify lens wear practices, including lens type, hours of wear, personal hygiene and sleeping and showering in lenses. Univariate and multivariate regression models were used to compare groups. RESULTS: 37 cases and 41 controls were identified. Showering in contact lenses was identified as the greatest risk factor (OR, 3.1; 95% CI, 1.2 to 8.5; p=0.03), with showering daily in lenses compared with never, increasing the risk of microbial keratitis by over seven times (OR, 7.1; 95% CI, 2.1 to 24.6; p=0.002). Other risks included sleeping in lenses (OR, 3.1; 95% CI, 1.1 to 8.6; p=0.026), and being aged 25-39 (OR, 6.38; 95% CI, 1.56 to 26.10; p=0.010) and 40-54 (OR, 4.00; 95% CI 0.96 to 16.61; p=0.056). CONCLUSION: The greatest personal hygiene risk factor for contact lens-related microbial keratitis was showering while wearing lenses, with an OR of 3.1, which increased to 7.1 if patients showered daily in lenses. The OR for sleeping in lenses was 3.1, and the most at-risk age group was 25-54.

Modified thin manual Descemet stripping endothelial keratoplasty with air-guided, non-pachymetric donor lenticule dissection: outcomes of graft thickness and complication rate.

AIM: To describe a modified technique of donor lenticule dissection for thin manual Descemet stripping endothelial keratoplasty (TM-DSEK). METHODS: Donor material was soaked in balanced salt solution (BSS) for 30min, before being mounted on an artificial anterior chamber (AAC). Rather than BSS, the AAC was filled with filtered air, resulting in a visible reflection at the corneal endothelium-air interface. This reflection served as a landmark for the depth of the dissection, facilitating the creation of a thin lenticule with low risk of perforation. Dissection was commenced at a standardized depth of 500 microns, with no initial pachymetry necessary. Totally 29 donor corneas were dissected by a novice TM-DSEK surgeon. Dissection time, central graft thickness at 2mo and complications were analysed. RESULTS: Results were similar to other endothelial keratoplasty techniques, despite the cases being performed by a novice DSEK surgeon. Mean dissection time was 7min (range 6-10). One graft perforation occurred (3.45%), but the air tamponaded the break and enabled dissection to be restarted and completed from a different location. Mean central graft thickness after at least two months follow-up was 106 microns (range 25-170). CONCLUSION: A problem with manual DSEK is the risk of graft perforation by attempting to dissect too thin a lenticule, or creating a thick graft due to fear of perforating. This modified air-guided technique addresses this problem, and is recommended for surgeons either embarking on the learning curve, or who wish to achieve more consistently thin grafts while reducing perforation rates.

Neurotrophic keratopathy.

Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK.