Epithelial ingrowth following laser in situ keratomileusis (LASIK): prevalence, risk factors, management and visual outcomes

The number of laser in situ keratomileusis (LASIK) procedures is continuing to rise. Since its first application for correcting simple refractive errors over 25 years ago, the role of LASIK has extended to treat other conditions, including postkeratoplasty astigmatism/ametropia, postcataract surgery refractive error and presbyopia, among others. The long-term effectiveness, predictability and safety have been well established by many large studies. However, due to the creation of a potential interface between the flap and the underlying stroma, interface complications such as infectious keratitis, diffuse lamellar keratitis and epithelial ingrowth may occur. Post-LASIK epithelial ingrowth (PLEI) is an uncommon complication that usually arises during the early postoperative period. The reported incidence of PLEI ranged from 0%–3.9% in primary treatment to 10%–20% in retreatment cases. It can cause a wide spectrum of clinical presentations, ranging from asymptomatic interface changes to severe visual impairment and flap melt requiring keratoplasty. PLEI can usually be treated with mechanical debridement of the affected interface; however, additional interventions, such as alcohol, mitomycin C, fibrin glue, ocular hydrogel sealant, neodymium:yttriumaluminum garnet laser and amniotic membrane graft, may be required for recurrent or refractory cases. The aims of this review are to determine the prevalence and risk factors of PLEI; to describe its pathogenesis and clinical features and to summarise the therapeutic armamentarium and the visual outcome of PLEI

Current and emerging therapies for corneal infection: a clinical and laboratory study

Corneal infection or infectious keratitis (IK) is a major cause for corneal blindness worldwide. Broad-spectrum antimicrobial therapy is currently the mainstay of treatment for IK, but the efficacy is being challenged by the emergence of antimicrobial resistance. Host defense peptides (HDPs), also known as antimicrobial peptides (AMPs), are evolutionarily conserved molecules of innate immune system that are found in all kingdoms of life. HDPs have shown promise as a novel class of antimicrobial therapeutics due to their broad-spectrum and rapid antimicrobial activity against a wide array of infection with minimal risk of developing resistance. At the ocular surface, HDPs, particularly human cathelicidin (LL-37) and human beta-defensins (HBDs), have been shown to play a vital role during IK. The first part of this work (Chapter 2 to Chapter 4) consisted of a body of work examining the epidemiology, causes, clinical characteristics, outcomes, and prognostic factors of IK in Nottingham, UK. IK was shown to be a persistent burden in Nottingham over the past decade, with ocular surface diseases, contact lens wear and systemic immunosuppression being the most common risk factors. More than 50% of the patients with IK required hospitalisation for intensive treatment, highlighting the burden of the disease on the patients and the healthcare system. Poor clinical outcome was significantly affected by older age, large infiltrate size and poor presenting vision. The second part (Chapter 5 and Chapter 6) systematically examined the effectiveness and safety of adjuvant therapeutic corneal collagen cross-linking (PACK-CXL) and amniotic membrane transplant for treating IK, in addition to standard antimicrobial therapy. The meta-analyses demonstrated that both interventions significantly expedited the healing of IK, though the overall quality of evidence was low, highlighting the need for further high-quality randomised controlled trials. The third part (Chapter 7 and Chapter 8) highlighted a body of work in developing a new class of HDP-based antimicrobial therapy for IK based on hybrid derivatives of human cathelicidin (LL-37) and human beta-defensins-1 to -3. CaD23, derived from LL-37 and HBD-2, exhibited good in vitro efficacy against Gram-positive bacteria and moderate efficacy against Gram-negative bacteria. It demonstrated a rapid antimicrobial activity, which was likely attributed to its membrane-permeabilising activity, supported by SYTOX green dye uptake assay and molecular dynamics simulation study. CaD23 was also shown to exhibit a strong additive effect when used in combination with conventional antibiotics against Gram-positive bacteria. Finally, CaD23 exhibited good antimicrobial efficacy against Gram-positive bacteria (1.2 logCFU or 94% reduction in the bioburden) in a murine bacterial keratitis model. The discovery of CaD23 has provided a new scaffold for future development of newer generations of hybrid peptides

Spontaneous Pupillary Recovery of Urrets-Zavalia Syndrome Following Descemet’s Membrane Endothelial Keratoplasty

To report a case of Urrets-Zavalia syndrome (UZS) with spontaneous pupillary recovery following Descemet's membrane endothelial keratoplasty (DMEK). This was an interventional case report with literature review. A 37-year-old female phakic patient presented to our clinic with bilateral decreased vision secondary to worsening Fuch’s endothelial dystrophy. She underwent bilateral inferior peripheral iridotomies prior to undergoing left DMEK surgery under general anaesthesia. The DMEK surgery was uncomplicated but she had a large fixed and dilated left pupil on the following day despite a normal examination with a normal intraocular pressure. A diagnosis of UZS was made. The pupil remained fixed and dilated until 4 months postoperatively, which anisocoria started to improve by time. At 6 months postoperative, anisocoria had fully resolved with normal pupillary reactions and complete resolution of photopic symptoms. UZS is a rare complication of DMEK surgery and, to our best knowledge, only one case has been reported in the literature. Surgeons and patients should be aware of this potential phenomenon following uneventful DMEK surgery. Conservative measures should be considered for initial management of UZS in young patients as spontaneous recovery may sometimes ensue, as occurred in our case

Effect of high-vacuum setting on phacoemulsification efficiency

Purpose To evaluate the effect of a high-vacuum setting versus a low-vacuum setting on the efficiency of phacoemulsification. Setting Sunderland Eye Infirmary, Sunderland, United Kingdom. Design Prospective clinical trial. Methods Consecutive patients having cataract surgery in 2014 were recruited. Cataract surgery was performed by 2 experienced surgeons using a phacoemulsification machine with monitored forced infusion. The cataractous lens was split into 2 heminuclei using the stop-and-chop technique; in 1 heminucleus, phacoemulsification and aspiration used a high-vacuum setting (600 mm Hg; treatment group) and in the other heminucleus, a low-vacuum setting (350 mm Hg; control group). The high and low settings were alternated by case per the operating list to reduce surgeon bias. The main outcome measures were cumulative dissipated energy (CDE) and active heminucleus removal time. Results One hundred sixty patients (160 eyes) were enrolled in the study, and 158 were included in the analysis. The CDE per heminucleus was significantly lower with the high-vacuum setting than with the low-vacuum setting (mean 2.81 percent-seconds; 95% confidence interval (CI), 2.44-3.21 versus 3.81 percent-seconds; 95% CI, 3.38-4.20; P < .001). The active heminucleus removal time was significantly shorter in the high-vacuum group than the low-vacuum group (mean 27.77 seconds; 95% CI, 25.26-30.19 versus 33.59 seconds; 95% CI, 31.07-35.92; P < .001). The observed differences were independent of the surgeon, patient age and sex, incision size, and nucleus density. No intraoperative complications were observed in either group. Conclusion A high-vacuum setting improved phacoemulsification efficiency using an active fluidics system and torsional phacoemulsificatio

Strategies in Translating the Therapeutic Potentials of Host Defense Peptides

The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties. However, the mission of translating novel HDP-derived molecules from bench to bedside has yet to be fully accomplished, primarily attributed to their intricate structure-activity relationship, toxicity, instability in host and microbial environment, lack of correlation between in vitro and in vivo efficacies, and dwindling interest from large pharmaceutical companies. Based on our previous experience and the expanding knowledge gleaned from the literature, this review aims to summarize the novel strategies that have been employed to enhance the antimicrobial efficacy, proteolytic stability, and cell selectivity, which are all crucial factors for bench-to-bedside translation of HDP-based treatment. Strategies such as residues substitution with natural and/or unnatural amino acids, hybridization, L-to-D heterochiral isomerization, C- and N-terminal modification, cyclization, incorporation with nanoparticles, and “smart design” using artificial intelligence technology, will be discussed. We also provide an overview of HDP-based treatment that are currently in the development pipeline

Photoactivated chromophore for infectious keratitis – Corneal cross-linking (PACK-CXL): A systematic review and meta-analysis

Purpose: To examine the efficacy of adjuvant photoactivated chromophore for infectious keratitis–corneal cross-linking (PACK-CXL) for the treatment of infectious keratitis (IK). / Methods: Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for articles related to PACK-CXL. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies, case series and case reports, were included. A meta-analysis was further performed when there were sufficient similarities in the included RCTs. Primary outcome measure was time to complete corneal healing and secondary outcome measures included size of epithelial defect and infiltrate, corrected-distance-visual-acuity (CDVA), and adverse events. / Results: Forty-six eligible studies (including four RCTs) with 435 patients were included. When compared to standard antimicrobial treatment (SAT) alone, adjuvant PACK-CXL resulted in shorter mean time to complete corneal healing (−7.44 days; 95% CI, −10.71 to −4.16) and quicker resolution of the infiltrate at 7 days (−5.49 mm2; 95% CI, −7.44 to −3.54) and at 14–30 days (−5.27 mm2; 95% CI, −9.12 to −1.41). There was no significant difference in the size of epithelial defect, CDVA and risk of adverse events. Evidence on the use of PACK-CXL in acanthamoeba and mixed IK was insufficient. / Conclusions: Our study demonstrates that adjuvant PACK-CXL expedites the healing of IK when compared to SAT alone (low-quality evidence). Further adequately powered, high-quality RCTs are required to fully ascertain the therapeutic effect of PACK-CXL

Amniotic Membrane Transplantation for Infectious Keratitis: A Systematic Review and Meta-Analysis

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n>5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment (SAT) alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (-4.08 days; 95% CI, -6.27 to -1.88;

Real-world experience of using ciclosporin-A 0.1% (Ikervis) in the management of ocular surface inflammatory diseases

Purpose: To report the real-world experience of using topical ciclosporin, Ikervis, in the management of ocular surface inflammatory diseases (OSIDs).Methods: This was a retrospective study of patients treated with Ikervis for OSIDs at the Queen’s Medical Centre, Nottingham, between 2016 and 2019. Relevant data, including demographics, indications, clinical parameters, outcomes and adverse events, were collected and analysed for patients who had completed at least 6 months follow-up. For analytic purpose, clinical outcome was categorised as ‘successful’ (resolved or stable disease), ‘active disease’ and ‘drug intolerance’.Results: 463 patients were included; mean age was 51.1±21.6 years, with a 59.0% female predominance. Mean follow-up was 14.6±9.2 months. The most common diagnosis was dry eye disease (DED; 322, 69.5%), followed by allergic eye disease (AED; 53, 11.4%) and ocular mucous membrane pemphigoid/Steven-Johnson syndrome (OMMP/SJS; 38, 8.2%). Successful treatment was achieved in 343 (74.1%) patients, with 44 (9.5%) requiring additional treatment and 76 (16.4%) reporting drug intolerance. The efficacy of Ikervis was highest in DED (264, 82.0%), followed by OMMP/SJS (25, 65.8%) and post-keratoplasty (7, 50.0%;

Clinical Characteristics and Outcomes of Fungal Keratitis in the United Kingdom 2011–2020: A 10-Year Study

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen’s Medical Centre, Nottingham, and the Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. We included 117 patients (n = 117 eyes) with FK in this study. The mean age was 59.0 ± 19.6 years (range, 4–92 years) and 51.3% of patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9 ± 16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67 ± 1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3 mm), and poor presenting CDVA (60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p < 0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcomes, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need

12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study

Background/aims: To examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK.Methods: A retrospective study of all patients who were diagnosed with IK and underwent corneal scraping between July 2007 and October 2019 (a 12-year period) at a UK tertiary referral centre. Relevant data, including demographic factors, microbiological profiles and in vitro antibiotic susceptibility of IK, were analysed.Results: The estimated incidence of IK was 34.7 per 100 000 people/year. Of the 1333 corneal scrapes, 502 (37.7%) were culture-positive and 572 causative microorganisms were identified. Sixty (4.5%) cases were of polymicrobial origin (caused by ≥2 different microorganisms). Gram-positive bacteria (308, 53.8%) were most commonly isolated, followed by Gram-negative bacteria (223, 39.0%), acanthamoeba (24, 4.2%) and fungi (17, 3.0%). Pseudomonas aeruginosa (135, 23.6%) was the single most common organism isolated. There was a significant increase in Moraxella spp (