Prognostic factors and epidemiology of adult open globe injuries from Western Sydney: a twelve-year review.

BACKGROUND: To identify prognostic factors determining final visual outcome following open globe injuries. METHODS: Retrospective case series of patients presenting to Westmead Hospital, Sydney, Australia with open globe injuries from 1st January 2005 to 31st December 2017. Data collected included demographic information, ocular injury details, management and initial and final visual acuities. RESULTS: A total of 104 cases were identified. Predictors of poor final visual outcomes included poor presenting visual acuity (p < 0.001), globe rupture (p < 0.001), retinal detachment (p < 0.001), Zone III wounds (p < 0.001), hyphema (p = 0.003), lens expulsion (p = 0.003) and vitreous hemorrhage (p < 0.001). Multivariate analysis demonstrated presenting visual acuity (p < 0.001), globe rupture (p = 0.013) and retinal detachment (p = 0.011) as being statistically significant for predicting poor visual outcomes. The presence of lid laceration (p = 0.197) and uveal prolapse (p = 0.667) were not significantly associated with the final visual acuity. CONCLUSIONS: Poor presenting visual acuity, globe rupture and retinal detachment are the most important prognostic factors determining final visual acuity following open globe injury.

Isolated painful trigeminal neuropathy as an unusual presentation of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids: A case report.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory central nervous system disorder, typically presenting with subacute symptoms referable to brainstem and cerebellar pathology. This is the first report of CLIPPERS presenting with a painful trigeminal neuropathy. CASE REPORT: We report an unusual case of CLIPPERS presenting with facial pain and sensory symptoms, in the absence of other brainstem or cerebellar signs. Perivascular enhancement of peri-pontine structures on neuroimaging, lymphocytic infiltrate on histopathology and rapid clinical and radiological responsiveness to glucocorticosteroids were key to diagnosis. Extensive investigations excluded various differential aetiologies. CONCLUSION: The pathogenesis of CLIPPERS is poorly understood, and the diagnostic criteria are yet to be validated. In this case, facial pain was not associated with other brainstem or cerebellar signs, broadening current understanding of how CLIPPERS may present. This has clinical implications in guiding future investigations for patients presenting with painful trigeminal neuropathy.

Intracranial Arterial Compression of the Anterior Visual Pathway.

Compression of anterior visual pathway (AVP) structures by intracranial arteries is observed not infrequently on neuroimaging. Whether or not such compression results in damage to these structures, however, remains unclear. This information is important to define as AVP compression by intracranial arteries may be a causative factor in patients with otherwise unexplained visual dysfunction. In a single centre, 37 patients with evidence of intracranial artery AVP compression demonstrated on magnetic resonance imaging were identified by retrospective review of case records over the period 2011-2017. Variables were collected, including patient demographics, visual acuity, visual fields, pupillary reactions and optic disc appearance for patients in the case series. Visual field deficits correlated with compression sites in the 37 patients examined. Internal carotid artery-optic nerve compression was the most frequent (unilateral compression n = 9, bilateral compression n = 14), followed by chiasmal compression by the anterior cerebral artery (n = 8) and a combination of optic nerve and chiasmal compression (n = 5). Visual acuity and visual fields were stable on follow-up (mean 4 years) in 24 of 26 cases (93%). We conclude that AVP compression by intracranial arteries may be a causative factor in unexplained visual dysfunction. The visual defects are largely non-progressive.

The current state of stem cell therapy for ocular disease.

Herein, we review the safety, efficacy, regulatory standards and ethical implications of the use of stem cells in ocular disease. A literature review was conducted, registered clinical trials reviewed, and expert opinions sought. Guidelines and codes of conduct from international societies and professional bodies were also reviewed. Collated data is presented on current progress in the field of ocular regenerative medicine, future challenges, the clinical trial process and ethical considerations in stem cell therapy. A greater understanding of the function and location of ocular stem cells has led to rapid advances in possible therapeutic applications. However, in the context of significant technical challenges and potential long-term complications, it is imperative that stem cell practices operate within formal clinical trial frameworks. While there remains broad scope for innovation, ongoing evidence-based review of potential interventions and the development of standardized protocols are necessary to ensure patient safety and best practice in ophthalmic care.

Simulated patient and role play methodologies for communication skills training in an undergraduate medical program: Randomized, crossover trial.

Background: Educators utilize real patients, simulated patients (SP), and student role play (RP) in communication skills training (CST) in medical curricula. The chosen modality may depend more on resource availability than educational stage and student needs. In this study, we set out to determine whether an inexpensive volunteer SP program offered an educational advantage compared to RP for CST in preclinical medical students. Methods: Students and volunteer SPs participated in interactions across two courses. Students allocated to SP interactions in one course participated in RP in the other course and vice versa. Audio recordings of interactions were made, and these were rated against criterion descriptors in a modified Calgary-Cambridge Referenced Observation Guide. Results: Independent t-test scores comparing ratings of RP and SP groups revealed no significant differences between methodologies. Discussion: This study demonstrates that volunteer SPs are not superior to RP, when used in CST targeted at preclinical students. This finding is consistent with existing literature, yet we suggest that it is imperative to consider the broader purpose of CST and the needs of stakeholders. Consequently, it may be beneficial to use mixed methods of CST in medical programs.

Nature and incidence of severe limbal stem cell deficiency in Australia and New Zealand.

BACKGROUND: This study aimed to determine the nature and incidence of severe limbal stem cell deficiency (LSCD) in Australia and New Zealand. DESIGN: A 1-year pilot surveillance study with a 1-year follow-up period was conducted in association with the Australian and New Zealand Ophthalmic Surveillance Unit. PARTICIPANTS: The study included patients reported by practising ophthalmologists on the Surveillance Unit's database. METHODS: Ophthalmologists were provided with a definition of severe limbal stem cell deficiency, contacted on a monthly basis by the Unit and asked to report newly diagnosed cases. MAIN OUTCOME MEASURES: Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium and superficial corneal neovascularization or conjunctivalization. RESULTS: On average, 286 report cards were sent by the Surveillance Unit to practising ophthalmologists each month (total 3429 over 12 months) and the Unit received an average of 176 responses per month (total 2111; 62% response rate). During the 1-year study period from April 2013 to March 2014, 14 positive cases were reported to the Unit. A range of underlying aetiologies were implicated, with contact lens over-wear and cicatrizing conjunctivitis being the most common (n = 3). CONCLUSIONS: This surveillance study is the first worldwide to document the incidence of limbal stem cell deficiency; however, because of study design limitations, it is likely to have been under-reported. It provides novel data on the demographics, clinical conditions and management of patients with limbal stem cell deficiency as reported by treating ophthalmologists.

Contact Lenses: A Delivery Device for Stem Cells to Treat Corneal Blindness.

: Worldwide, 45 million people are blind. Corneal blindness is a major cause of visual loss, estimated to affect 10 million. For the most difficult to treat patients, including those with a disease called limbal stem cell deficiency, a donor corneal graft is not a viable option; thus, patients are treated with specialized stem cell grafts, which fail in a significant proportion (30 to 50%) of subjects. This unacceptable failure rate means there is a pressing need to develop minimally invasive, long-lasting, cost-effective therapies to improve patient quality of life and lessen the economic burden. Restoring vision in patients with severe corneal disease is the main focus of our research program; however, to achieve our goals and deliver the best quality stem cell therapy, we must first understand the basic biology of these cells, including their residence, the factors that support their long-term existence, markers to identify and isolate them, and carriers that facilitate expansion, delivery, and protection during engraftment. We recently achieved some of these goals through the discovery of stem cell markers and the development of a novel and innovative contact lens-based cell transfer technique that has been successfully trialed on patients with corneal blindness. Although several popular methodologies are currently available to nurture and transfer stem cells to the patients' ocular surface, contact lenses provide many advantages that will be discussed in this review article. The job for clinician-researchers will be to map precisely how these cells contribute to restoring ocular health and whether improvements in the quality of cells and the cell delivery system can be developed to reduce disease burden.

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.

Ethics of medical research in Aboriginal and Torres Strait Islander populations.

Conducting ethical health research in Aboriginal and Torres Strait Islander populations requires an understanding of their unique cultural values and the historical context. The assimilation of Indigenous people with the broader community through colonial policies such as the dispossession of land and forcible removal of children from their families in the Stolen Generation, deprived entire communities of their liberty. Poorly designed research protocols can perpetuate discriminatory values, reinforce negative stereotypes and stigmas and lead to further mistrust between the Indigenous community and healthcare professionals. The manuscript offers a fresh perspective and an up-to-date literature review on the ethical implications of conducting health research in Aboriginal and Torres Strait Islander communities.

An Unusual Presentation of Pediatric Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma.

Ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma is uncommon in the pediatric population. Initial misdiagnosis is common and there is lacking consensus regarding the optimal approach to treatment. Herein, we report an atypical presentation of pediatric conjunctival MALT lymphoma and review the presentation and management of this rare condition.

Native and synthetic scaffolds for limbal epithelial stem cell transplantation.

Limbal stem cell deficiency (LSCD) is a complex blinding disease of the cornea, which cannot be treated with conventional corneal transplants. Instead, a stem cell (SC) graft is required to replenish the limbal epithelial stem cell (LESC) reservoir, which is ultimately responsible for regenerating the corneal epithelium. Current therapies utilize limbal tissue biopsies that harbor LESCs as well as tissue culture expanded cells. Typically, this tissue is placed on a scaffold that supports the formation of corneal epithelial cell sheets, which are then transferred to diseased eyes. A wide range of biological and synthetic materials have been identified as carrier substrates for LESC, some of which have been used in the clinic, including amniotic membrane, fibrin, and silicon hydrogel contact lenses, each with their own advantages and limitations. This review will provide a brief background of LSCD, focusing on bio-scaffolds that have been utilized in limbal stem cell transplantation (LSCT) and materials that are being developed as potentially novel therapeutics for patients with this disease. STATEMENT OF SIGNIFICANCE: The outcome of patients with corneal blindness that receive stem cell grafts to restore eye health and correct vision varies considerably and may be due to the different biological and synthetic scaffolds used to deliver these cells to the ocular surface. This review will highlight the positive attributes and limitations of the myriad of carriers developed for clinical use as well as those that are being trialled in pre-clinical models. The overall focus is on developing a standardized therapy for patients, however due to the multiple causes of corneal blindness, a personal regenerative medicine approach may be the best option.

Incidence, clinical features and diagnosis of cicatrising conjunctivitis in Australia and New Zealand.

AIMS: This study aimed to determine the incidence, clinical features and management of cicatrising conjunctivitis in Australia and New Zealand, also enabling comparison with data from the United Kingdom. METHODS: A prospective surveillance study was conducted over 17 months via the Australian and New Zealand Ophthalmic Surveillance Unit with a one-year follow-up period. Practicing ophthalmologists on the Surveillance Unit's database were asked to report recently diagnosed cases of cicatrising conjunctivitis on a monthly basis. Initial and follow-up questionnaires were sent to ophthalmologists who had reported positive cases to obtain demographic and clinical data. The minimum incidence of cicatrising conjunctivitis was calculated based on cases reported during the study period and from population data. RESULTS: During the 17-month study period (December 2011-April 2013), 56 cases of cicatrising conjunctivitis were reported. Data was obtained for 35 cases (62%) with a mean age of 74 years (range, 28-94 years). The most common aetiologies were ocular mucus membrane pemphigoid (n = 18 cases, 51.4%), Stevens-Johnson Syndrome (n = 3, 8.6%) and graft versus host disease (n = 3, 8.6%). The minimum incidence of cicatrising conjunctivitis in Australia and New Zealand was 1.5 per million, comparable to incidence data from the United Kingdom. CONCLUSIONS: This study is the first to prospectively record the incidence of cicatrising conjunctivitis in Australia and New Zealand and the second worldwide. It provides novel data on demographics and management of cicatrising conjunctivitis, as reported by treating ophthalmologists.

Clinical outcomes of xeno-free expansion and transplantation of autologous ocular surface epithelial stem cells via contact lens delivery: a prospective case series.

INTRODUCTION: Depletion of limbal stem cells leads to a debilitating condition known as limbal stem cell deficiency, characterised by impaired corneal wound healing and poor vision. The aim of this study was to determine whether delivering progenitor cells on a contact lens is a viable and effective alternative to current transplantation techniques, which are complicated by biological and xenogeneic materials. METHODS: Sixteen eyes of 16 patients who had total (n=14) and partial (n=2) limbal stem cell deficiency (chemical burns, five eyes; iatrogenic causes, four eyes; aniridia, three eyes; trachoma-induced, two eyes; contact lens over-wear, one eye; and cicatrising conjunctivitis, one eye) and who had failed prior therapy were recruited prospectively into the study. Autologous limbal (n=7) or conjunctival epithelial (n=9) biopsies were harvested from patients and placed on the concave surface of silicone hydrogel contact lenses. Cells were expanded in culture with autologous serum and transplanted onto the ocular surface. RESULTS: Restoration of a transparent avascular and clinically stable corneal epithelium was attained in 10 of 16 eyes (63%) at a median follow-up time of 2.5 years (range of 0.8 to 5.8 years). Although minor complications occurred in two eyes of two patients because of contact lens insertion or removal, these were not associated with long-term sequelae. CONCLUSIONS: This is the first and largest study to evaluate the mid-term outcomes of autologous limbal/conjunctival stem cell transplantation via a US Food and Drug Administration-approved contact lens, demonstrating that delivery of ocular progenitor cells via this procedure offers a viable, effective, and xeno-free alternative to current transplantation methodologies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN012607000211460. Registered 17 April 2007.