Mechanisms of cone sensitivity loss in retinitis pigmentosa.

PURPOSE: To explore the mechanisms of cone sensitivity loss in retinitis pigmentosa by combining two-colour perimetry with threshold versus intensity (tvi) testing. METHODS: Seven subjects with autosomal recessive retinitis pigmentosa and 10 normal subjects were recruited and underwent perimetric testing of one eye using 480- and 640-nm Goldman size V targets presented under scotopic conditions (no background illumination) and against a white background ranging in luminance from -1.5 to 2 log cd m-2 in 0.5 log cd m-2 steps. Data were fitted with tvi functions of the form logT = logT0 + log ((A + A0)/A0)n, where T is the threshold, T0 is the absolute threshold, A is the background intensity, A0 is the 'dark-light' constant and n is a gain constant. RESULTS: Reliable tvi functions could not be obtained within the region of the visual field corresponding to loss of the ellipsoid zone on optical coherence tomography. At fixation, changes in both T0 and A0 were observed, consistent with a d1 mechanism loss, which resulted in an upwards and rightwards shift of the tvi function. Losses at [±3°, ±3°] demonstrated changes in T0, consistent with a d3 mechanism loss, resulting in an upwards translation of the tvi curve. CONCLUSIONS: Although the absolute cone threshold was elevated at each location, shifts in the tvi function (so-called d1 mechanism loss) at fixation minimise threshold elevation in the presence of white adapting backgrounds, such as those typically employed in standard two-colour perimetry. At more peripheral testing locations, changes in threshold occurred independent of background luminance (so-called d3 mechanism loss). These findings suggest that backgrounds which selectively adapt rods while maintaining cones at, or near, absolute threshold may be preferable to conventional two-colour perimetry for assessing loss of cone sensitivity, especially at the point of fixation.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Consensus and controversies in the science of endophthalmitis management: Basic research and clinical perspectives.

Infectious endophthalmitis is a severe intraocular infection caused by bacteria, or less commonly by fungi. It can occur after penetrating eye procedures, trauma, or the spread of infection from contiguous structures or via emboli from distant organs. Because of the time-critical nature of the treatment, endophthalmitis is treated with the clinical diagnosis and modified by the microbiological report of the intraocular contents. The current strategy for managing endophthalmitis relies on pre-clinical literature, case series, and one large multi-center randomized clinical trial on post-cataract surgery endophthalmitis. Culture-susceptibility of the microorganisms from undiluted vitreous guides the definitive treatment in non-responsive cases. Strategies to reduce the incidence of endophthalmitis after penetrating eye procedures have been developed concurrently with refined means of treatment. Despite these advances, outcomes remain poor for many patients. Although consensus articles have been published on managing endophthalmitis, treatment patterns vary, and controversies remain. These include (1) the use of newer methods for early and precise microbiological diagnosis; (2) the choice of intravitreal antibiotics; (3) the need for systemic therapy; (4) early and complete vitrectomy. Here, we review the current consensus and address controversies in diagnosing and managing endophthalmitis. This review is intended to familiarize physicians and ophthalmologists with different aspects of endophthalmitis management to make informed decisions.

Sodium Fluorescein as an Optical Label to Evaluate Subretinal Injection.

PURPOSE: There is renewed interest in subretinal drug delivery as the result of novel and emerging treatments for retinal diseases, including retinal gene therapy. However, our knowledge of the distribution of subretinally delivered drugs is incomplete; herein, we describe a qualitative and quantitative means of surveying the early intraocular distribution of subretinally delivered drugs using dilute sodium fluorescein (NaFl). METHODS: Sodium fluorescein 10% was serially diluted and mixed with a solution containing tissue plasminogen activator (tPA) at a final concentration of 0.1 mg/mL NaFl and 0.5 mg/mL of tPA. Because this solution was to be used in the context of subretinal tPA injection in the treatment of subretinal hemorrhage, fluorophotometry with, and without, the presence of human whole blood was performed to derive a formula to calculate the concentration of NaFl based on the fluorescence of aspirated intraocular fluid. Videos of subretinal tissue plasminogen activator surgery in a case are presented as a qualitative demonstration of the technique and vitreous cavity fluid collected at case completion underwent fluorophotometry to estimate the loss of therapeutic solution. RESULTS: Although the presence of hemoglobin in blood suppresses fluorescence of NaFl, we demonstrate that centrifuging admixtures of blood with NaFl negates the optical effects of blood and yields identical fluorescence versus concentration plots to those of NaFl solution alone. We also demonstrate that NaFl at 0.1 mg/mL can be readily used to qualitatively assess drug losses before, during, and after subretinal injection. Furthermore, we describe how it may be used to quantitatively estimate the total loss of therapeutic solution during subretinal injection using fluorophotometry on aspirated fluid from the vitreous cavity (loss estimated as 4% in the case presented). CONCLUSION: Sodium fluorescein at a concentration of 0.1 mg/mL can be used to quantitatively and qualitatively assess the fate of subretinally injected drugs during subretinal injection surgery.

Optogenetic restoration of high sensitivity vision with bReaChES, a red-shifted channelrhodopsin.

The common final pathway to blindness in many forms of retinal degeneration is the death of the light-sensitive primary retinal neurons. However, the normally light-insensitive second- and third-order neurons persist optogenetic gene therapy aims to restore sight by rendering such neurons light-sensitive. Here, we investigate whether bReaChES, a newly described high sensitivity Type I opsin with peak sensitivity to long-wavelength visible light, can restore vision in a murine model of severe early-onset retinal degeneration. Intravitreal injection of an adeno-associated viral vector carrying the sequence for bReaChES downstream of the calcium calmodulin kinase IIα promoter resulted in sustained retinal expression of bReaChES. Retinal ganglion cells (RGCs) expressing bReaChES generated action potentials at light levels consistent with bright indoor lighting (from 13.6 log photons cm-2 s-1). They could also detect flicker at up to 50 Hz, which approaches the upper temporal limit of human photopic vision. Topological response maps of bReaChES-expressing RGCs suggest that optogenetically activated RGCs may demonstrate similar topographical responses to RGCs stimulated by photoreceptor activation. Furthermore, treated dystrophic mice displayed restored cortical neuronal activity in response to light and rescued behavioral responses to a looming stimulus that simulated an aerial predator. Finally, human surgical retinal explants exposed to the bReaChES treatment vector demonstrated transduction. Together, these findings suggest that intravitreal gene therapy to deliver bReaChES to the retina may restore vision in human retinal degeneration in vivo at ecologically relevant light levels with spectral and temporal response characteristics approaching those of normal human photopic vision.

Glaucoma diagnosis using multi-feature analysis and a deep learning technique.

In this study, we aimed to facilitate the current diagnostic assessment of glaucoma by analyzing multiple features and introducing a new cross-sectional optic nerve head (ONH) feature from optical coherence tomography (OCT) images. The data (n = 100 for both glaucoma and control) were collected based on structural, functional, demographic and risk factors. The features were statistically analyzed, and the most significant four features were used to train machine learning (ML) algorithms. Two ML algorithms: deep learning (DL) and logistic regression (LR) were compared in terms of the classification accuracy for automated glaucoma detection. The performance of the ML models was evaluated on unseen test data, n = 55. An image segmentation pilot study was then performed on cross-sectional OCT scans. The ONH cup area was extracted, analyzed, and a new DL model was trained for glaucoma prediction. The DL model was estimated using five-fold cross-validation and compared with two pre-trained models. The DL model trained from the optimal features achieved significantly higher diagnostic performance (area under the receiver operating characteristic curve (AUC) 0.98 and accuracy of 97% on validation data and 96% on test data) compared to previous studies for automated glaucoma detection. The second DL model used in the pilot study also showed promising outcomes (AUC 0.99 and accuracy of 98.6%) to detect glaucoma compared to two pre-trained models. In combination, the result of the two studies strongly suggests the four features and the cross-sectional ONH cup area trained using deep learning have a great potential for use as an initial screening tool for glaucoma which will assist clinicians in making a precise decision.

IMPAIRMENTS IN CONE PIGMENT REGENERATION AND ABSOLUTE THRESHOLD IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To test the hypothesis that Müller cell dysfunction in macular telangiectasia type 2 (MacTel) results in delayed cone adaptation kinetics and to assess absolute cone and rod thresholds in this condition. METHODS: Adaptation after an approximate 63.5% full-field cone photopigment bleach was assessed for Goldmann size V (1.7° diameter) 640 nm (red) and 480 nm (blue) targets presented at a retinal locus corresponding to 2° temporal to fixation. The cone time constant of adaptation and absolute cone and rod thresholds were calculated from exponential functions fitted to the resultant dark adaptation curves. RESULTS: Eighteen eyes with MacTel (from 11 patients) were compared with 19 control eyes (from 16 normal subjects). Cone adaptation kinetics were significantly impaired in MacTel, as was the absolute cone threshold. Final thresholds for blue targets were also significantly elevated in MacTel, consistent with impaired rod absolute threshold. Losses in sensitivity observed in MacTel were consistent with a so-called d1/2 mechanism (i.e., receptoral) site of sensitivity loss. CONCLUSION: In addition to previously documented impairments in rod dark adaptation, MacTel results in a significant elevation in cone thresholds because of pathology at the level of the photoreceptors. The delays in cone adaptation that we found in eyes with MacTel may reflect impairment of the Müller cell-mediated cone-specific visual cycle.

IMPAIRMENTS OF L-CONE/M-CONE AND S-CONE-MEDIATED COLOR DISCRIMINATION IN MACULAR TELANGIECTASIA TYPE II.

PURPOSE: To characterize red-green and tritan color discrimination in eyes with macular telangiectasia Type II (MacTel). METHODS: Color discrimination was assessed by metameric matching methods using an Oculus MR Anomaloscope. Red-green color discrimination was assessed using the Rayleigh equation, and tritan color discrimination was assessed using the Moreland equation. Results were expressed as anomalquotient (AQ) and tritanomalquotient (TAQ) units, respectively. RESULTS: Seventeen eyes with MacTel were compared with 16 control eyes with normal vision. Twelve eyes with MacTel demonstrated abnormal color matches; except for two eyes with red-shifted Rayleigh matches, the primary abnormality evident was reduced color discrimination. On average, Rayleigh matching ranges were significantly widened in MacTel (0.518 ± 0.066 AQ units) compared with normal (0.14 ± 0.03 AQ units; P < 0.0001). Similarly, Moreland matching ranges were significantly wider (0.794 ± 0.109 TAQ units) than normal control subjects (0.204 ± 0.070 TAQ units; P < 0.0001). Losses in color discrimination did not correlate significantly with the best-corrected visual acuity, although Moreland matching ranges were significantly correlated to Rayleigh matching ranges. CONCLUSION: MacTel results in a combined acquired red-green and tritan color vision deficiency. A minority of eyes demonstrated red-shifted Rayleigh matches, consistent with decreases in cone photopigment optical density.

Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials.

The study of individual differences in perception at absolute threshold has a rich history, with much of the seminal work being driven by the need to identify those with superior abilities in times of war. Although the popularity of such testing waned in the latter half of the 20th century, interest in measures of visual function at the absolute limit of vision is increasing, partly in response to emerging treatments for retinal diseases, such as gene therapy and cellular therapies, that demand "new" functional measures to assess treatment outcomes. Conventional clinical, or clinical research, testing approaches generally assess rod sensitivity at or near absolute threshold; however, cone sensitivity is typically assayed in the presence of adapting backgrounds. This asymmetry may artifactually favor the detection of rod abnormalities in patients with outer retinal disease. The past decade has seen the commercialization of devices capable of assessing absolute threshold and dark adaptation, including specialized perimeters and instruments capable of assessing "full-field sensitivity threshold" that seek to integrate responses over time and space in those with unstable fixation and/or limited visual fields. Finally, there has also been a recent recapitulation of tests that seek to assess the subject's ability to interpret the visual scene at or near absolute threshold. In addition to assessing vision, such tests simultaneously place cognitive and motor demands on patients in line with the activities of daily living they seek to replicate. We describe the physical and physiological basis of absolute threshold and dark adaptation. Furthermore, we discuss experimental psychophysical and electrophysiological approaches to studying vision at absolute threshold and provide a brief overview of clinical tests of vision at absolute threshold.

Scotopic microperimetry: evolution, applications and future directions.

For many inherited and acquired retinal diseases, reduced night vision is a primary symptom. Despite this, the clinical testing options for spatially resolved scotopic vision have until recently been limited. Scotopic microperimetry is a relatively new visual function test that combines two-colour perimetry with fundus-controlled perimetry performed in scotopic luminance conditions. The technique enables spatially resolved mapping of central retinal sensitivity alongside the ability to distinguish between rod and cone photoreceptor sensitivities. Two companies produce commercially available scotopic microperimeters - Nidek (Nidek Technologies Srl, Padova, Italy) and CenterVue (CenterVue S.p.A., Padova, Italy). Scotopic microperimetry is a promising technology capable of detecting changes in retinal sensitivity before changes in other measures of visual function. Scotopic microperimetry is a promising functional biomarker that has the potential as a useful clinical trial outcome measure. This review summarises the evolution and applications of scotopic microperimetry, and discusses testing options, including testing grid selection, dark-adaptation time and threshold sensitivity analyses.

Two-step versus 1-step subretinal injection to compare subretinal drug delivery: a randomised study protocol.

INTRODUCTION: There is increasing interest in subretinal injections as a surgical procedure, largely as a result of emerging treatments for ocular diseases which necessitate this manoeuvre. However, surgical variables in the efficacy of such treatments have to date been largely overlooked and the proportion of drug which reaches the intended compartment of the subretinal space remains unknown. Our aims are twofold: first, to determine the proportion of subretinally injected medication retained following surgical delivery and second, to compare two different techniques of injection ('1-step' vs '2-step'). METHODS: We outline a randomised controlled trial of subretinal injection of alteplase following vitrectomy for the management of submacular haemorrhage secondary to age-related macular degeneration. Patients will be randomised to receive either 1-step injection, where the therapeutic solution simultaneously defines the surgical plane or 2-step injection, where the surgical plane is first identified with balanced salt solution prior to injection of subretinal alteplase, as outlined below. Sodium fluorescein will be used as an optical label to track drug reflux into the vitreous cavity using quantitative protocols established in our laboratory. All patients will undergo fluid air exchange at the completion of surgery, with injection of bevacizumab 1.25 mg and 20% sulfahexafluoride gas as the vitreous substitute (both of which may help improve outcomes). Alteplase, sodium fluorescein and bevacizumab will all be used for off-label indications in the trial. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South Eastern Sydney Local Health District's Human Research Ethics Committee (HREC 17/092). The results of this trial will be disseminated in peer-reviewed proceedings (associated with conference presentation) and in scholarly journals. TRIAL REGISTRATION NUMBER: ACTRN12619001121156.

Endophthalmitis: Changes in Presentation, Management and the Role of Early Vitrectomy.

Endophthalmitis is a sight-threatening condition, and its timely and appropriate management is essential in preventing permanent vision loss. Recent changes in clinical practice in endophthalmitis and advances in modern vitreoretinal surgery may limit the applicability of established randomised clinical trial evidence to current management. This review discusses the epidemiology, pathophysiology, changing patient presentation, diagnosis and advances in the management of endophthalmitis, presenting the existing literature on this topic and results from Sydney Eye Hospital.

Retinal Stem/Progenitor Cells Derived From Adult Müller Glia for the Treatment of Retinal Degeneration.

Over the past two decades, progress in our understanding of glial function has been revolutionary. Within the retina, a subset of glial cells termed the "Müller glia (MG)," have been demonstrated to play key roles in retinal homeostasis, structure and metabolism. Additionally, MG have also been shown to possess the regenerative capacity that varies across species. In teleost fish, MG respond to injury by reprogramming into stem-like cells capable of regenerating lost tissue. The expression of stem/progenitor cell markers has been demonstrated broadly in mammalian MG, including human MG, but their in vivo regenerative capacity appears evolutionarily limited. Advances in stem cell therapy have progressively elucidated critical mechanisms underlying innate MG reprogramming in teleost fish, which have shown promising results when applied to rodents. Furthermore, when cultured ex vivo, MG from mammals can differentiate into several retina cell types. In this review, we will explore the reparative and regenerative potential of MG in cellular therapy approaches, and outline our current understanding of embryonic retinal development, the stem-cell potential of MG in adult vertebrate retina (including human), and microenvironmental cues that guide MG reprogramming.

Structural and Functional Characteristics of Color Vision Changes in Choroideremia.

Color vision is considered a marker of cone function and its assessment in patients with retinal pathology is complementary to the assessments of spatial vision [best-corrected visual acuity (BCVA)] and contrast detection (perimetry). Rod-cone and chorioretinal dystrophies-such as choroideremia-typically cause alterations to color vision, making its assessment a potential outcome measure in clinical trials. However, clinical evaluation of color vision may be compromised by pathological changes to spatial vision and the visual field. The low vision Cambridge Color Test (lvCCT) was developed specifically to address these latter issues. We used the trivector version of the lvCCT to quantify color discrimination in a cohort of 53 patients with choroideremia. This test enables rapid and precise characterization of color discrimination along protan, deutan, and tritan axes more reliably than the historically preferred test for clinical trials, namely the Farnsworth Munsell 100 Hue test. The lvCCT demonstrates that color vision defects-particularly along the tritan axis-are seen early in choroideremia, and that this occurs independent of changes in visual acuity, pattern electroretinography and ellipsoid zone area on optical coherence tomography (OCT). We argue that the selective loss of tritan color discrimination can be explained by our current understanding of the machinery of color vision and the pathophysiology of choroideremia.

The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration.

Age-related neurodegenerative diseases, such as Alzheimer disease (AD) and age-related macular degeneration (AMD), are multifactorial and have diverse genetic and environmental risk factors. Despite the complex nature of the diseases, there is long-standing, and growing, evidence linking microbial infection to the development of AD dementia, which we summarize in this article. Also, we highlight emerging research findings that support a role for parainfection in the pathophysiology of AMD, a disease of the neurosensory retina that has been shown to share risk factors and pathological features with AD. Acute neurological infections, such as Bacterial Meningitis (BM), trigger inflammatory events that permanently change how the brain functions, leading to lasting cognitive impairment. Neuroinflammation likewise is a known pathological event that occurs in the early stages of chronic age-related neurodegenerative diseases AD and AMD and might be triggered as a parainfectious event. To date, at least 16 microbial pathogens have been linked to the development of AD; on the other hand, investigation of a microbe-AMD relationship is in its infancy. This mini-review article provides a synthesis of existing evidence indicating a contribution of parainfection in the aetiology of AD and of emerging findings that support a similar process in AMD. Subsequently, it describes the major immunopathological mechanisms that are common to BM and AD/AMD. Together, this evidence leads to our proposal that both AD and AMD may have an infectious aetiology that operates through a dysregulated inflammatory response, leading to deleterious outcomes. Last, it draws fresh insights from the existing literature about potential therapeutic options for BM that might alleviate neurological disruption associated with infections, and which could, by extension, be explored in the context of AD and AMD.

SURGICAL RETINAL EXPLANTS AS A SOURCE OF RETINAL PROGENITOR CELLS.

PURPOSE: To describe the novel observation of spontaneously migrating retinal cells from living donor surgical retinal explants that express progenitor cell markers in the absence of exogenous growth factors. METHODS: Surgical retinal explants were harvested from 5 consecutive patients undergoing 23 G pars plana vitrectomy for the management of rhegmatogenous detachment. During surgery, equatorial flap tears were trimmed with the vitreous cutter and aspirated. Excised tissue was then regurgitated into a syringe containing balanced salt solution and immediately transferred to tissue culture. Migrating cells subsequently underwent immunohistochemical staining and their characteristics were compared with those of a spontaneously immortalized Müller stem cell line. RESULTS: Spontaneously migrating cells were observed from samples taken from all 5 patients from Day 2 to 10 after transfer to culture. These cells were found to express embryonic cell markers, including paired box 6 (Pax6), sex-determining region Y-box 2 (Sox-2), nestin, cone-rod homeobox, and cyclin-dependent kinase inhibitor 1B (p27Kip1) as well as proteins consistent with early or retained differentiation down the Müller cell lineage, including glial fibrillary acidic protein and glutamine synthetase. CONCLUSION: After injury, the human equatorial retina is capable of spontaneously producing cells that demonstrate migration and that express progenitor cell markers. In addition, these cells express proteins consistent with Müller cell lineage. These initial observations support the assertion that the human retina may possess the potential for regeneration and that surgical retinal explants could also act as a ready source of retinal progenitor cells.

Intravitreal anti-vascular endothelial growth factor versus panretinal LASER photocoagulation for proliferative diabetic retinopathy: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and perform a meta-analysis on the available evidence for anti-vascular endothelial growth factor (anti-VEGF) monotherapy versus panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR). DESIGN: Systematic review and meta-analysis PARTICIPANTS: Randomized clinical trials included participants ≥18 years old with clinical or angiographic evidence of PDR. Interventions included were anti-VEGF monotherapy and PRP. Excluded studies were those with potentially biased treatment allocation and those offering combination therapies. METHODS: The primary outcome was mean change in best-corrected visual acuity. Secondary outcomes were the proportion of patients developing severe (<6/60) or moderate (6/24-6/60) vision loss, rates of vitrectomy or vitreous hemorrhage, worsening macula edema, and reduced visual field indices. RESULTS: Five studies of varying quality met the inclusion criteria (n = 632). The anti-VEGF intervention arm had a mean difference of -0.08 logMAR or 4 Early Treatment Diabetic Retinopathy Study (EDTRS) letters gained (p = 0.02) when compared with PRP at 12 months. The difference in rates of vitrectomy and vitreous hemorrhage favoured anti-VEGF over PRP (risk difference [RD] -0.10, p = < 0.001 and RD -0.10, p = 0.003 respectively). CONCLUSIONS: This meta-analysis of the available evidence in patients with early PDR demonstrates a potential benefit for anti-VEGF over PRP alone. However, these benefits must be weighed against the relative costs of treatment and the potential risks of loss to follow-up.

Threshold versus intensity functions in two-colour automated perimetry.

PURPOSE: Two-colour computerised perimetry is a technique developed for assessing cone- and rod-function at fixed background luminances in retinal disease. However, the state of adaptation during testing is unknown but crucial in the interpretation of results. We therefore aimed to determine the adaptational state of rod- and cone-mechanisms in two-colour perimetry. METHODS: Sensitivity to 480 nm (blue) and 640 nm (red) Goldmann size V targets was determined for 10 normal subjects aged 16 to 46 years at 17 locations in the central 60 degrees of the visual field under scotopic conditions and then from -1.5 log cd m-2 to 2 log cd m-2 (white background) in 0.5 log unit steps. Data were fitted with threshold versus intensity (tvi) functions of the form logT = logT0 + log ((A + A0 )/A0 )n . RESULTS: No clear rod-cone break was observed for 640 nm stimuli. For 480 nm stimuli, transition from rod-detection to cone-detection occurred at mesopic illumination levels, where rod adaptation approached Weber behaviour. Cone detection mechanisms did not display Weber-like adaptation until the background luminance approached 1 log cd.m-2 . Diseases resulting in a "filter effect" - including disorders of the photoreceptors - are therefore predicted to affect sensitivity when rod function is probed with short-wavelength targets under scotopic conditions, but less so under mesopic conditions. Filter effects are similarly anticipated to affect cone function measured using long-wavelength targets under mesopic conditions (e.g., during microperimetry), but less so under photopic conditions. CONCLUSIONS: Asymmetries in adaptation in automated two-colour perimetry are predicted to artefactually favour the detection of losses in rod sensitivity under scotopic conditions and cones under mesopic conditions.

Ab-externo drainage with continuous anterior chamber infusion for non-resolving exudative retinal detachment: a case report.

BACKGROUND: Drainage of exudative retinal detachment may be necessary for either therapeutic or diagnostic purposes (or both). Here, we describe an external drainage technique for non-resolving vision-threatening exudative retinal detachment which combines the advantages of internal drainage (widefield viewing and intraocular pressure control using continuous anterior chamber infusion) with those of external drainage (drainage of sub-retinal fluid without vitrectomy). CASE PRESENTATION: To illustrate this technique, we present a 13-year-old girl with macula-off exudative retinal detachment secondary to Vogt-Koyanagi-Harada syndrome, which was unresponsive to aggressive medical management. External drainage was undertaken using widefield viewing and chandelier illumination. Intraocular pressure was maintained with an anterior chamber infusion. Near-complete drainage of sub-retinal fluid was achieved, and retinal reattachment was maintained at 6 months postoperatively, with a corresponding improvement in visual acuity from 20/63 to 20/40. CONCLUSIONS: External drainage under chandelier-assisted viewing at the surgical microscope with anterior chamber infusion offers the ergonomic and optical advantages of the surgical microscope and widefield visualisation, continuous IOP control and drainage of sub-retinal fluid without the need for pars plana vitrectomy.

Post-surgical versus post-intravitreal injection endophthalmitis: changing patterns in causative flora.

IMPORTANCE: Endophthalmitis is a serious complication of intraocular procedures: knowledge of its causative organisms and outcomes may guide prevention and treatment. BACKGROUND: To determine the outcomes and spectrum of causative organisms in acute post-procedural endophthalmitis. DESIGN: A retrospective observational case series performed at a tertiary referral hospital during the period 1 July 2012 to 31 July 2017. PARTICIPANTS: Two hundred and forty-eight patients diagnosed with acute (≤ 6 weeks post-inciting event) endophthalmitis. METHODS: Chart review of microbiological and clinical data. MAIN OUTCOME MEASURES: The main outcome measure was odds of any improvement in visual acuity (3 months versus presentation). Secondary outcomes included causative organism, likelihood of vitrectomy and likelihood of evisceration. RESULTS: One hundred and ninty cases were post-cataract surgery or post-intravitreal injection (49 and 141, respectively). Causative organisms were identified in 45% of post-cataract surgery and 54% of post-injection cases (OR = 0.69; P = 0.61). Staphylococcus epidermidis was the most frequent causative organism. Streptococcus species accounted for 32% of post-surgical and 7% of culture-positive post-injection cases (OR = 6.63; P = 0.02). At 3 months, 81% of post-surgical and 84% of post-injection cases had improved BCVA over presentation (OR 0.59; P = 0.61). CONCLUSIONS AND RELEVANCE: S. epidermidis is the most common causative organism. In contrast to other studies, we did not find evidence for an increased odds of Streptococcus spp. endophthalmitis following intravitreal injection. This may in turn reflect guideline-driven changes in practice.