Preparing for success in final summative medical specialist examinations: The case for RACE.

BACKGROUND: Failure rates on medical specialist final summative examinations in Australia are high, regardless of speciality. Examination failure can have detrimental psycho-social, financial and job security effects on the trainee, while delays in completion of training adversely impacts workforce growth and health outcomes for the community. The study aimed to explore the preparation factors that contribute to ophthalmology trainee success in their final summative examination. METHODS: Semi-structured in-depth interviews were conducted with 29 participants via telephone or Zoom with ophthalmology trainees and Fellows. To be eligible, interviewees had to have sat the Royal Australian and New Zealand College of Ophthalmologists Advanced Clinical Examination (RACE) within the past five years or were providing supervision to trainees preparing for RACE. Interviews were audio-recorded, transcribed and thematically analysed. RESULTS: Examination success was underpinned by six themes relating to preparation: (i) 'Those who fail to plan, plan to fail', which related to development and adherence to a study plan; (ii) 'It takes a village' encompassed trainees establishing and activating personal and professional supports; (iii) 'Get to know your opponent', which encompassed developing an understanding of the examination construct, format and requirements; (iv) 'There is no substitute for hard work', which related to intensive study over a period of 12-18 months; (v) 'Keep pace with the herd', which referred to benchmarking preparation efforts and progress against peers; and (vi) 'Don't jump the gun', which related to ensuring readiness to sit. CONCLUSIONS: Maximising medical specialist examination pass rates is in the best interest of trainees, training Colleges, health care systems and communities. Recognising and facilitating preparation approaches that foster success in final summative examinations are the collective responsibility of trainees, specialist training Colleges, training networks and health systems. Trainees need to plan for examination success, be self-determined to commit to intensive study over an extended time period and be realistic about their readiness to sit.

Estimating Phosphene Locations Using Eye Movements of Suprachoroidal Retinal Prosthesis Users.

Purpose: Accurate mapping of phosphene locations from visual prostheses is vital to encode spatial information. This process may involve the subject pointing to evoked phosphene locations with their finger. Here, we demonstrate phosphene mapping for a retinal implant using eye movements and compare it with retinotopic electrode positions and previous results using conventional finger-based mapping. Methods: Three suprachoroidal retinal implant recipients (NCT03406416) indicated the spatial position of phosphenes. Electrodes were stimulated individually, and the subjects moved their finger (finger based) or their eyes (gaze based) to the perceived phosphene location. The distortion of the measured phosphene locations from the expected locations (retinotopic electrode locations) was characterized with Procrustes analysis. Results: The finger-based phosphene locations were compressed spatially relative to the expected locations all three subjects, but preserved the general retinotopic arrangement (scale factors ranged from 0.37 to 0.83). In two subjects, the gaze-based phosphene locations were similar to the expected locations (scale factors of 0.72 and 0.99). For the third subject, there was no apparent relationship between gaze-based phosphene locations and electrode locations (scale factor of 0.07). Conclusions: Gaze-based phosphene mapping was achievable in two of three tested retinal prosthesis subjects and their derived phosphene maps correlated well with the retinotopic electrode layout. A third subject could not produce a coherent gaze-based phosphene map, but this may have revealed that their phosphenes were indistinct spatially. Translational Relevance: Gaze-based phosphene mapping is a viable alternative to conventional finger-based mapping, but may not be suitable for all subjects.

Endophthalmitis: Microbiology and Organism Identification Using Current and Emerging Techniques.

Endophthalmitis is an ophthalmological emergency requiring timely and appropriate diagnosis and treatment. Microbiological methods of microscopy (Gram's staining) and culture are the current gold standard for organism identification. However, a significant proportion of endophthalmitis remains culture-negative-perhaps the inflammation is non-infectious in origin, results from a novel organism are unidentifiable or because the causative organism is non-culturable often due to pre-treatment with antibiotics. This review outlines the microbiological profile of endophthalmitis, current clinically used methods for organism identification, and the newer molecular techniques of polymerase chain reaction (PCR) and next-generation sequencing (NGS) technology as diagnostic tools for endophthalmitis. They offer the potential to improve organism identification rates and clinical outcomes in infectious diseases, representing an exciting future direction for organism identification in endophthalmitis. Based on the largest ophthalmic hospital in Australia, we highlight the key practical challenges faced by Australian diagnostic laboratories for their use in a clinical setting.

Interobserver Agreement of Electrode to Retina Distance Measurements in a Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis.

Purpose: The electrode to retina (ER) distance is an important contributory factor to the safety and efficacy of a suprachoroidal retinal prosthesis. Measuring ER distance may be performed by different observers during multisite studies. The aim of this study was to assess the interobserver agreement in measuring ER distance. Methods: Three independent, trained observers measured ER distance from the center of each suprachoroidal electrode to the inner retinal pigment epithelium in spectral-domain optical coherence tomography (SD-OCT) B-scans. A total of 121 ER distance measurements from 77 B-scans collected over 5 months from one subject implanted with a second-generation 44-channel suprachoroidal retinal prosthesis (NCT03406416) were made by each observer. Results: ER distance ranged from 208 to 509 µm. Pearson's correlation coefficient (ρ) showed agreement of 0.99 (95% confidence interval [CI] = 0.98-0.99) in measuring ER for each pairwise comparison. The mean difference in ER distance between observers ranged from 2.4 to 6.4 µm with pairwise limits of agreement (95% CI) of ±20 µm (5.5% of mean). Intraclass correlation coefficient (ICC) showed agreement of 0.98 (95% CI = 0.97-0.99) between observers. Conclusions: There is high agreement in measuring ER distances for suprachoroidal retinal prostheses using our systematic approach between multiple, trained observers, supporting the use of a single observer for each image. Translational Relevance: High interobserver agreement outcomes indicate that multiple, trained observers can be used to take ER measurements across different images in suprachoroidal retinal prosthesis studies. This improves multisite study efficiency and gives confidence in interpreting results relating to the safety and efficacy of suprachoroidal retinal prostheses.

Cytokine Expression in Staphylococcal and Streptococcal Endophthalmitis.

Background: Endophthalmitis is an infection of ocular tissues, often with devastating outcomes for vision. Immunomodulation is an emerging avenue for therapeutic intervention in endophthalmitis, with the expression of cytokines central to potential mechanisms. This literature review with a systematic approach characterizes the cytokine expression in both animal and human staphylococcal and streptococcal endophthalmitis. Method and Results: Four online databases were searched for studies profiling cytokine levels in animal models or human populations with staphylococcal and/or streptococcal endophthalmitis. Of the 1,060 articles identified, 14 studies were included in this review comprising eight animal models and six human populations. Mouse, rat, and rabbit models of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae endophthalmitis had elevated levels of IL-1ß, IL-6, IFN-γ, TNF-α, and IL-8, with earlier peaks observed in S. epidermidis infection. Human endophthalmitis demonstrated significantly increased mediator levels compared to controls for a range of pro-inflammatory and anti-inflammatory cytokines, chemokines, and growth factors. Several associations were established between cytokine concentrations and both initial visual acuity and visual prognosis, with no consistent correlations across trials. Conclusions: It may be that virulence factors and the combinations of toll-like receptors activated influence the pathogen-specific visual outcomes observed in endophthalmitis. Furthermore, disease severity and potential therapeutic targets may be dependent on synergistic and compensatory cytokine pathways and the expression of anti-inflammatory mediators. Future research should aim to better characterize the roles of inflammatory mediators and solidify associations between pathogens, inflammation, and endophthalmitis outcomes. This has exciting implications for the prevention and treatment of endophthalmitis in clinical settings.

A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Long-Term Observation of the Electrode-Tissue Interface.

Purpose: To report the long-term observations of the electrode-tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant. Methods: Four subjects (S1-4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode-retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase. Results: Electrode impedances were stable longitudinally. The electrode-retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode-retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode-retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02). Conclusions: Chronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode-retina distances after a period of settling after surgery. Translational Relevance: Chronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.

Inflammatory complications of CGRP monoclonal antibodies: a case series.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. CASES: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. CONCLUSION: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Interim Clinical Trial Results.

Purpose: To report the initial safety and efficacy results of a second-generation (44-channel) suprachoroidal retinal prosthesis at 56 weeks after device activation. Methods: Four subjects, with advanced retinitis pigmentosa and bare-light perception only, enrolled in a phase II trial (NCT03406416). A 44-channel electrode array was implanted in a suprachoroidal pocket. Device stability, efficacy, and adverse events were investigated at 12-week intervals. Results: All four subjects were implanted successfully and there were no device-related serious adverse events. Color fundus photography indicated a mild postoperative subretinal hemorrhage in two recipients, which cleared spontaneously within 2 weeks. Optical coherence tomography confirmed device stability and position under the macula. Screen-based localization accuracy was significantly better for all subjects with device on versus device off. Two subjects were significantly better with the device on in a motion discrimination task at 7, 15, and 30°/s and in a spatial discrimination task at 0.033 cycles per degree. All subjects were more accurate with the device on than device off at walking toward a target on a modified door task, localizing and touching tabletop objects, and detecting obstacles in an obstacle avoidance task. A positive effect of the implant on subjects' daily lives was confirmed by an orientation and mobility assessor and subject self-report. Conclusions: These interim study data demonstrate that the suprachoroidal prosthesis is safe and provides significant improvements in functional vision, activities of daily living, and observer-rated quality of life. Translational Relevance: A suprachoroidal prosthesis can provide clinically useful artificial vision while maintaining a safe surgical profile.

Functional Vision in the Real-World Environment With a Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis.

Purpose: In a clinical trial (NCT03406416) of a second-generation (44-channel) suprachoroidal retinal prosthesis implanted in subjects with late-stage retinitis pigmentosa (RP), we assessed performance in real-world functional visual tasks and emotional well-being. Methods: The Functional Low-Vision Observer Rated Assessment (FLORA) and Impact of Vision Impairment-Very Low Vision (IVI-VLV) instruments were administered to four subjects before implantation and after device fitting. The FLORA contains 13 self-reported and 35 observer-reported items ranked for ease of conducting task (impossible-easy, central tendency given as mode). The IVI-VLV instrument quantified the impact of low vision on daily activities and emotional well-being. Results: Three subjects completed the FLORA for two years after device fitting; the fourth subject ceased participation in the FLORA after fitting for reasons unrelated to the device. For all subjects at each post-fitting visit, the mode ease of task with device ON was better or equal to device OFF. Ease of task improved over the first six months with device ON, then remained stable. Subjects reported improvements in mobility, functional vision, and quality of life with device ON. The IVI-VLV suggested self-assessed vision-related quality of life was not impacted by device implantation or usage. Conclusions: Subjects demonstrated sustained improved ease of task scores with device ON compared to OFF, indicating the device has a positive impact in the real-world setting. Translational Relevance: Our suprachoroidal retinal prosthesis shows potential utility in everyday life, by enabling an increased environmental awareness and improving access to sensory information for people with end-stage RP.

Retinal prostheses: Where to from here?

Researchers have been working towards the development of retinal prostheses, so called "bionic eyes" since the 1960s in an effort to restore functional vision to severely visually impaired patients. Groups from all around the world are involved in this research but in particular, groups from the United States, Germany, France, Japan and Australia have conducted clinical trials of these devices and three of these devices have achieved either FDA HDE (U.S. Food and Drug Administration Humanitarian Device Exception) or CE mark approval for commercial production. Despite this, all three of these devices are now not in commercial production. There are many challenges to overcome to develop devices suitable to implant in human patients and then reach commercial distribution. This is an exacting process and many hurdles need to be overcome to reach this point so that leaving the market after achieving this goal is a significant decision. Ongoing research is exploring the possibility of less complicated surgery with better visual processing algorithms to provide more useful visual information for our patients to provide a commercial alternative.

Comparison of the Icare ic100 Rebound Tonometer and the Goldmann Applanation Tonometer in 1,000 Eyes.

BACKGROUND: Measurement of intraocular pressure (IOP) forms a crucial component in the diagnosis and management of glaucoma. Many devices have been developed to measure IOP with Goldmann applanation tonometry (GAT) considered the gold standard for IOP measurement. OBJECTIVES: The objective was to compare the IOP measured using Icare ic100 and GAT. METHODS: This cross-sectional study measured IOP in 1,000 eyes (500 left and 500 right) using the Icare ic100 and GAT. Central corneal thickness (CCT) was measured using a hand-held pachymeter. IOP measurements were investigated in all eyes, by IOP substrata, by CCT group, by number of topical glaucoma medications, and diagnosis. RESULTS: There was moderate agreement between ic100 and GAT IOP measurements (intraclass correlation coefficient 0.73). Mean IOP was significantly lower when measured by ic100 than by GAT (12.1 vs. 16.2 mm Hg, p < 0.0001). Mean ic100 IOPs were also significantly lower than mean GAT IOPs within each IOP strata ≤12 (7.9 vs. 9.7 mm Hg, p < 0.0001), 13-21 (12.1 vs. 16.6 mm Hg, p < 0.0001), and ≥22 (18.4 vs. 25.2 mm Hg, p < 0.0001) and within each subanalysis. CONCLUSIONS: The Icare tonometer consistently under estimated IOP compared to GAT, irrespective of CCT ranges and other subgroup analyses. The mean difference of 4.2 mm Hg can have significant clinical implications, particularly in the management of glaucoma patients.

Fungal endophthalmitis: A 20-year experience at a tertiary referral centre.

IMPORTANCE: Fungal endophthalmitis is an uncommon and serious intraocular infection, often with poor outcomes. This study examines the trend in this disease over 20 years, to inform clinician decision-making and optimize patient outcomes. BACKGROUND: Due to infrequent presentation of fungal endophthalmitis, there is limited understanding to formulate a standardized approach to management. DESIGN: A prospective case series over the period January 1, 1999 to December 31, 2018. PARTICIPANTS: Patients with clinically diagnosed fungal endophthalmitis managed at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. METHODS: Review of the Victorian Endophthalmitis Registry for endophthalmitis episode of each patient. MAIN OUTCOME MEASURES: Patient demographics, co-morbidities, visual acuity (VA) at presentation, aetiology, treatment, microbiology results and final VA outcome. RESULTS: Eighty-four cases of fungal endophthalmitis were identified over the study period with a median age of 43.5 years [IQR 30.8-63.0]. Then, 65.5% (n = 55) of patients were male; 81.0% (n = 68) of these cases were secondary to endogenous causes, of which 55.9% were associated with intravenous drug use (IVDU). Among the exogenous causes, penetrating eye injury (56.3%) was the most common aetiological factor. Thirty-nine patients (46.4%) grew Candida species from ocular fluid specimens, all of which were sensitive to fluconazole. CONCLUSION AND RELEVANCE: Our case series provides important insights into fungal endophthalmitis-a high degree of suspicion for fungal endophthalmitis in patients with history of IVDU, and relatively good outlook for vision when Candida is the causative organism. This should allow institutions to implement a standardized management strategy based on evidence.