Keratoconus International Consortium (KIC)- advancing keratoconus research.

CLINICAL RELEVANCE: The Keratoconus International Consortium (KIC) will allow better understanding of keratoconus. BACKGROUND: Keratoconus is a disorder characterised by corneal elevation and thinning, leading to reduced vision. The current gaps in understanding of this disease will be discussed and the need for a multi-pronged and multi-centre engagement to enhance our understanding of keratoconus will be highlighted. DESIGN: KIC has been established to address the gaps in our understanding of keratoconus with the aim of collecting baseline as well as longitudinal data on several fields. PARTICIPANTS: Keratoconus and control (no corneal condition) subjects from different sites globally will be recruited in the study. METHODS: KIC collects data using an online, secure database, which enables standardised data collection at member sites. Data fields collected include medical history, clinical features, quality of life and economic burden questionnaires and possible genetic sample collection from patients of different ethnicities across different geographical locations. RESULTS: There are currently 40 Australian and international clinics or hospital departments who have joined the KIC. Baseline data has so far been collected on 1130 keratoconus patients and indicates a median age of 29.70 years with 61% being male. A total of 15.3% report a positive family history of keratoconus and 57.7% self-report a history of frequent eye rubbing. CONCLUSION: The strength of this consortium is its international, collaborative design and use of a common data collection tool. Inclusion and analyses of cross-sectional and longitudinal data will help answer many questions that remain in keratoconus, including factors affecting progression and treatment outcomes.

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

BACKGROUND/OBJECTIVES: Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. METHODS: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options. RESULTS: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6-22.1% (clinical trials programme), 0.5-70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. CONCLUSIONS: Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate-severe DAOSD and high-risk patients.

Clinical outcomes of herpes simplex keratitis: Two-year experience from a quaternary eye care centre in Sydney, Australia.

PURPOSE: To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia. METHODS: A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis. RESULTS: Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500 mg to 1 g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n = 114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8 days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n = 8) and secondary bacterial keratitis (n = 6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6 months. CONCLUSIONS: Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes.

Patterns in refractive error and treatment delay in keratoconus-An Australian study.

Keratoconus is the most common primary corneal ectasia and is associated with significant morbidity. In its early stages, keratoconus is often asymptomatic, making the identification of subclinical disease challenging. Refractive error is a parameter that is documented at most routine optometry visits, yet interestingly, changes in refraction of keratoconic patients over time have not yet been studied and compared with the general population. Early diagnosis of keratoconus facilitates timely referral for treatments such as corneal collagen cross-linking, which has been shown to slow disease progression. In this context, documenting delays between initial presentation to the optometrist and referral for collagen-cross-linking as well as comparing the trends in visual acuity and refractive error between keratoconic and non-keratoconic patients over time are particularly relevant.

Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry.

OBJECTIVE: To compare long-term effectiveness of Standard (UV intensity: 3 mW/cm2, duration: 30 min) vs Accelerated (UV intensity: 9 mW/cm2, duration: 10 min) corneal cross-linking (CXL) for stabilising keratoconus. METHODS: Data for this observational study were captured through a web-based registry system from the routine clinical practice (15 sites across Australia, New Zealand and Italy). The outcomes were compared using mixed-effects regression models. A total of 100 eyes (75 patients) who had standard CXL and 76 eyes (66 patients) who had accelerated CXL, with a follow-up visit at five-year post-CXL were included. RESULTS: Both CXL protocols were effective and safe in stabilising keratoconus and improving outcomes. The adjusted mean changes (95% CI) in outcomes were better in standard CXL than in accelerated CXL [visual acuity gain, 10.2 (7.9-12.5) vs 4.9 (1.6-8.2) logMAR letters; pinhole visual acuity 5.7 (3.5-7.8) vs 0.2 (-2.2 to 2.5) logMAR letters; Kmax -1.8 (-4.3 to 0.6) vs 1.2 (-1.5 to 3.9)D; K2 -0.9 (-2.2 to 0.3) vs 0.1 (-1.3 to 1.6)D; MCT -3.0 (-13.7 to 7.7) vs -11.8 (-23.9 to 0.4) µm (p values for visual acuity, pinhole visual acuity, Kmax: <0.05; for K2 and MCT: >0.05)]. The frequency of adverse events at the 5-year follow-up visit was low in both groups [standard, 5 (5%; haze 3; scarring 1, epithelial defect 1) and accelerated 3 (3.9%; haze 2, scarring 1)]. CONCLUSIONS: Both standard and accelerated CXL were safe and effective procedures for stabilising keratoconus in the long term. The standard CXL resulted in greater improvements in visual acuity and keratometry.

Development, Implementation, and Evaluation of Treatment Guidelines for Herpes Simplex Keratitis in Sydney, Australia.

PURPOSE: To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia. METHODS: The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline. RESULTS: Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources. CONCLUSIONS: Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

Euphorbia lactea sap keratouveitis: case report and review of the literature.

PURPOSE: To describe a case of Euphorbia lactea sap keratouveitis and to review all reported cases of ocular toxicity caused by Euphorbia species. METHODS: Case report and review of literature. RESULTS: A 79-year-old woman presented 34 hours after she felt some sap of an E. lactea plant spray into her right eye. Visual acuity was counting fingers at 1 m. Examination revealed ciliary injection, 90% corneal epithelial defect, marked stromal edema with Descemet folds, and anterior-chamber flare with a 1-mm hypopyon. There was no vitreitis, and funduscopy was unremarkable. No foreign body was seen on B scan ultrasound or computed tomography scan of the orbits. Corneal scraping excluded bacterial and herpetic keratitis. Intensive topical antibiotic therapy was started with cephalothin 5% and gentamicin 0.9%, and the pupil was dilated with atropine. Topical steroids were started once the epithelial defect had healed. Examination 11 weeks after the injury revealed minimal subepithelial corneal haze and marked improvement in visual acuity. CONCLUSIONS: To the best of our knowledge, this is only the third reported case of E. lactea sap keratouveitis. The clinical course of E. lactea sap keratouveitis is compared with that reported for other Euphorbia species.

Descemetorhexis Without Grafting for Fuchs Endothelial Dystrophy-Supplementation With Topical Ripasudil.

PURPOSE: To report the safety and efficacy of descemetorhexis without grafting as a primary intervention in Fuchs dystrophy, and the use of a ROCK inhibitor, ripasudil as a salvage agent in failing cases. METHODS: Twelve eyes of 11 patients underwent central descemetorhexis not exceeding 4 mm. All had Fuchs dystrophy-producing visual symptoms, requesting intervention. Exclusion criteria were a peripheral endothelial cell count <1000 and central edema. Corneal clearance and visual parameters were recorded monthly until corneal clearance was observed, then at intervals of 6 months. Cases failing to clear by month 2 were considered for salvage treatment. This consisted of treatment with 1 of 2 formulations of Rho-associated kinase inhibitor eye drops. Endothelial keratoplasty was planned as the final salvage procedure in unsuccessful cases. RESULTS: Nine of 12 eyes cleared spontaneously between 2 and 6 months. One eye failed to clear by month 5 and topical Y-27632 was administered, without success. Endothelial keratoplasty was performed. In 2 eyes, healing stalled at 3 and 2 months. In both cases, topical ripasudil administered 6 times a day for 2 weeks resulted in complete corneal clearance. In cases achieving corneal clearance, best spectacle corrected visual acuity improved from a mean of 0.26 to 0.125 (logMAR) with subjective improvement in quality of vision. CONCLUSIONS: In Fuchs dystrophy with visual degradation due to central guttae, descemetorhexis without grafting is a viable procedure for visual rehabilitation. Careful patient selection is required, but the advent of topical ripasudil as a salvage agent suggests that a broader application of the surgery may be possible. Further study into the use of this agent is now needed.

Ketamine-associated corneal edema.

PURPOSE: To report a case of ketamine-associated corneal edema. METHODS: Case report. RESULTS: A 61-year-old man prescribed oral ketamine for refractory depression developed bilateral corneal edema. This immediately resolved off ketamine and recurred with rechallenge. Rapid corneal endothelial cell loss occurred during this period. CONCLUSIONS: Ketamine may induce potentially reversible corneal edema with endothelial cell loss. A thorough medication history of this and other drugs should be sought in patients with an otherwise unexplained corneal endothelial failure.

Combined wedge resection and beveled penetrating relaxing incisions for the treatment of pellucid marginal corneal degeneration.

PURPOSE: To evaluate a new surgical approach for the treatment of pellucid marginal corneal degeneration (PMCD). METHODS: Prospective, noncomparative, interventional case series. Ten eyes of 10 consecutive patients were included in the series. Inclusion criteria were a clinical diagnosis of PMCD, topographic astigmatism >10 D, and contact lens intolerance. The patients underwent an inferior arcuate wedge resection of the thinned cornea (0.5 mm wide, 6.0 mm long) combined with 2 penetrating, sutureless, clear corneal tunnel relaxing incisions (3.2 mm wide) at the steep meridians. RESULTS: Visual acuity, refraction, and corneal topography were assessed preoperatively and at 1, 3, 6, 12, and 24 months postoperatively. Suture removal was complete in all patients by 4 months. Spectacle-corrected visual acuity was 20/40 or better in 8 of 10 patients at 6 months, with no substantial change at later examinations. Mean keratometric astigmatism was reduced from 15.1 D preoperatively to 4.6 D at 6 months postoperatively and was stable at further follow-ups. CONCLUSIONS: Corneal wedge resection combined with paired, opposed clear corneal penetrating relaxing incisions is a suitable surgical option for the treatment of PMCD, providing early adequate astigmatic control with long-term stability.

Development and surgical implantation of a vision prosthesis model into the ovine eye.

PURPOSE: A surgical technique was designed and tested to enable the implantation of an intraocular electrical retinal stimulator. METHOD: An inoperative perspex and silicone model was constructed to closely resemble the anticipated properties of the proposed visual prosthesis. The animal model chosen for these experiments was the sheep, because the dimensions of its ocular anatomy are approximately 30% larger than the human's, being otherwise grossly similar. The surgical method involved transplanar port-hole lensectomy and vitrectomy, insertion of the model implant through a limbal incision, and fixation of the perspex subunit close to the location of the native crystalline lens, by way of trans-pars plana fixation sutures. Adequate pre-retinal positioning of the implant's silicone extension was obtained by way of its inherent elastic recoil. RESULTS: The procedure was performed without macroscopic evidence of undue surgical trauma. CONCLUSION: Although further long-term experiments are required to fully assess the surgical procedure and biocompatibility of the implant, intraoperative assessment and postmortem computed tomographic imaging of the globe has confirmed the successful intraocular positioning and fixation of the implant.