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.

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.

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.

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.

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.

Assessment of the Electronic Retinal Implant Alpha AMS in Restoring Vision to Blind Patients with End-Stage Retinitis Pigmentosa.

PURPOSE: To report the initial efficacy results of the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for partial restoration of vision in end-stage retinitis pigmentosa (RP). DESIGN: Prospective, single-arm, investigator-sponsored interventional clinical trial. Within-participant control comprising residual vision with the retinal implant switched ON versus OFF in the implanted eye. PARTICIPANTS: The Retina Implant Alpha AMS was implanted into the worse-seeing eye of 6 participants with end-stage RP and no useful perception of light vision. Eligibility criteria included previous normal vision for ≥12 years and no significant ocular or systemic comorbidity. METHODS: Vision assessments were scheduled at 1, 2, 3, 6, 9, and 12 months postimplantation. They comprised tabletop object recognition tasks, a self-assessment mobility questionnaire, and screen-based tests including Basic Light and Motion (BaLM), grating acuity, and greyscale contrast discrimination. A full-field stimulus test (FST) was also performed. MAIN OUTCOME MEASURES: Improvement in activities of daily living, recognition tasks, and assessments of light perception with the implant ON compared with OFF. RESULTS: All 6 participants underwent successful implantation. Light perception and temporal resolution with the implant ON were achieved in all participants. Light localization was achieved with the implant ON in all but 1 participant (P4) in whom the chip was not functioning optimally because of a combination of iatrogenic intraoperative implant damage and incorrect implantation. Implant ON correct grating detections (which were at chance level with implant OFF) were recorded in the other 5 participants, ranging from 0.1 to 3.33 cycles/degree on 1 occasion. The ability to locate high-contrast tabletop objects not seen with the implant OFF was partially restored with the implant ON in all but 1 participant (P4). There were 2 incidents of conjunctival erosion and 1 inferotemporal macula-on retinal detachment, which were successfully repaired, and 2 incidents of inadvertent damage to the implant during surgery (P3 and P4). CONCLUSIONS: The Alpha AMS subretinal implant improved visual performance in 5 of 6 participants and has exhibited ongoing function for up to 24 months. Although implantation surgery remains challenging, new developments such as OCT microscope guidance added refinements to the surgical technique.

Colour discrimination ellipses in choroideremia.

PURPOSE: The purpose of this study was to characterise alterations in colour discrimination in a cohort of patients with choroideremia prior to gene therapy, using a test previously validated for use in patients with retinal dystrophies. METHODS: We tested 20 eyes of 10 patients with a diagnosis of choroideremia and an age-matched cohort of 10 eyes of 10 normal controls using the "Cambridge Colour Test" (CCT), in which subjects are required to distinguish the gap in a C presented in one of 4 orientations in a Stilling-type array. Colour discrimination was probed along eight axes in the CIE L*u*v* colour space, and the resulting data were plotted in the CIE 1976 chromaticity diagram and fitted with least-squares ellipses. Subsequently, we estimated the achromatic area for each subject by calculating the area of the resultant discrimination ellipse and calculated sensitivity thresholds along relevant colour confusion axes. RESULTS: Colour discrimination-as quantified by log10 of the ellipse area expressed in square 1/1000th2 units in CIE 1976-was 2.26 (range 1.82 to 2.67) for normal subjects and 3.85 (range 2.35 to 5.41) for choroideremia patients. There was a statistically significant correlation between both achromatic area and red-green colour discrimination at the CCT and BCVA, and to a lesser degree between blue colour discrimination at the CCT and BCVA. The majority of ellipses in choroideremia were aligned close to the tritan axis, and loss of sensitivity was significantly larger in the tritan direction than in the red-green. CONCLUSIONS: The majority of our patients demonstrated greater loss in tritan discrimination than in red-green colour discrimination using the CCT. There was a significant correlation between achromatic area and BCVA. In keeping with our current understanding of the machinery of colour vision, there was a significant correlation between BCVA and colour discrimination thresholds, which was stronger for red-green colour discrimination, than for tritan colour discrimination. We propose that this and similar tests of colour discrimination may prove to be suitable tools for assessing functional outcomes in gene therapy trials for choroideremia.

METAMORPHOPSIA AND ITS QUANTIFICATION.

PURPOSE: To discuss and analyze the pathophysiologic mechanisms underlying metamorphopsia, the nature of adaptational mechanisms to this symptom, the development and clinical utility of tests of metamorphopsia, and to discuss the cost-effectiveness of screening populations at risk of exudative age-related macular degeneration using such tests. METHODS: A primary literature search of PubMed and Web of Science was conducted for articles covering the mechanisms and/or tests of metamorphopsia. RESULTS: A number of possible mechanisms of metamorphopsia were identified in addition to lateral photoreceptor displacement. These included disorders of image formation, changes in effective axial length, and pathology of the visual pathways and centers. The simplest tests of metamorphopsia rely on highly subjective assessments of regular patterns, as exemplified by Amsler grids. Such tests seem to offer poor sensitivity when used in real-life home-monitoring situations. Newer tests such as so-called preferential hyperacuity perimetry may offer more robust paradigms to assess the perception of distortion but suffer from an inherent disadvantage of being unable to precisely correlate function to structure. The recently published findings of the AREDS2-HOME trial suggest that formalized monitoring of visual function using a preferential hyperacuity perimetry task results in detection of exudative age-related macular degeneration when vision is better-preserved. A cost-benefit analysis using the data from the AREDS2-HOME trial suggests that the calculated cost of screening per letter gained/saved is $3,351 per year. CONCLUSION: Metamorphopsia is an important symptom in retinal disease and may occur through a variety of mechanisms. Although the human visual system is exquisitely sensitive to metamorphopsia, commonly used tests of this symptom may be unreliable in real-life conditions. Newer tests of metamorphopsia such as preferential hyperacuity perimetry may improve early detection rates of exudative age-related macular degeneration in at-risk populations.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR PROLIFERATIVE DIABETIC RETINOPATHY: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review and perform meta-analysis on the available randomized controlled trial data for anti-vascular endothelial growth factor (anti-VEGF) agents in the management of proliferative diabetic retinopathy and its complications. METHODS: The authors identified randomized controlled trials using anti-VEGF agents, either as stand-alone therapy or combined with other interventions, in the management of proliferative diabetic retinopathy. The primary outcome measures were change in best-corrected visual acuity and (in the context of vitrectomy) duration of surgery and postoperative vitreous hemorrhage. Secondary outcomes were change in central retinal thickness and (in the context of vitrectomy) intraoperative variables suggestive of complex surgery (retinal breaks, intraoperative bleeding, and endodiathermy applications). The quality of evidence for all outcomes was appraised using the GRADE criteria. RESULTS: Twenty-two studies involving 1,397 subjects met the criteria for inclusion in this study. One study compared intravitreal ranibizumab with saline, one compared intravitreal pegaptanib to pan-retinal photocoagulation (PRP), one compared intravitreal bevacizumab to PRP, 3 compared combined intravitreal ranibizumab/PRP to PRP, 5 compared combined intravitreal bevacizumab/PRP to PRP alone, and 11 compared combined intravitreal bevacizumab/PPV to PPV alone. When used in conjunction with PRP, there is a high-quality evidence to suggest that intravitreal ranibizumab is associated with superior visual acuity and central retinal thickness outcomes at 3 months to 4 months. In the context of PPV, there is moderate quality evidence to suggest that preoperative intravitreal bevacizumab results in a significant reduction in the duration of surgery, fewer retinal breaks, less intraoperative bleeding, and fewer endodiathermy applications. Although there is evidence to suggest occurrence of early postoperative vitreous hemorrhage is reduced, the quality of evidence in support of this finding is low. CONCLUSION: The use of anti-VEGF agents before PRP results in superior functional and structural outcomes at 3 months to 4 months. The use of anti-VEGF agents before PPV results in decreased duration of surgery, fewer breaks, and less intra-operative bleeding. Although there is evidence for a decreased incidence of early postoperative vitreous hemorrhage, the quality of evidence is low. The available data therefore support the use of anti-VEGF agents as adjuncts to PRP and PPV in patients with complicated proliferative diabetic retinopathy primarily as a means of facilitating, and potentially minimizing the iatrogenic damage resulting from, these procedures.

Postoperative macular hole formation after vitrectomy with internal limiting membrane peeling for the treatment of epiretinal membrane.

PURPOSE: To evaluate the incidence, clinical features, and outcomes of macular hole formation after pars plana vitrectomy with internal limiting membrane peeling for the management of epiretinal membrane. METHODS: Retrospective consecutive chart review of 423 cases. RESULTS: Eleven subjects developed postoperative macular holes (incidence 2.6%; 95% confidence interval, 1.5-4.6%). Two of the 11 subjects developed central macular holes (incidence 0.5%; 95% confidence interval, 0.1-1.7%) while 9 had eccentric (nonfoveal) macular holes (incidence 2.1%; 95% confidence interval, 1.1-4.0%). Seven of the 9 eccentric macular holes were <115 µm in diameter, 7 were determined to be along the margin of the internal limiting membrane peel, and 8 were either in the superior or temporal macula. The two central macular holes were closed with subsequent pars plana vitrectomy and gas tamponade. There was no association between macular hole formation and age, gender, preoperative visual acuity, axial length, and preoperative central macular thickness. Overall, a 0.2 or more improvement in logMAR was associated with pseudophakia and poorer preoperative acuity on univariate and multivariate analysis, whereas increased preoperative central macular thickness was associated with improved outcomes on univariate but not multivariate analysis. CONCLUSION: Postoperative macular hole formation is an infrequent sequela to pars plana vitrectomy with internal limiting membrane peeling for epiretinal membrane. In our cohort, eccentric macular holes tended to be small, located along the edge of the internal limiting membrane peel, and were not visually significant.

Treat-and-extend bevacizumab for neovascular age-related macular degeneration: the importance of baseline characteristics.

PURPOSE: To evaluate the factors affecting visual and anatomical outcomes and the number of intravitreal bevacizumab injections required in the treatment of neovascular age-related macular degeneration using a treat-and-extend regimen. METHODS: Retrospective consecutive case series. The charts of subjects treated with intravitreal bevacizumab for neovascular age-related macular degeneration using a treat-and-extend regimen over a 12-month period were reviewed. The key variables explored were patient age, phakic status, posterior vitreous detachment status, baseline best-corrected visual acuity (BCVA), baseline central macular thickness (CMT), and type of chorodial neovascularization. The primary outcome measures were improvement in BCVA of 3 logMAR lines or more, maintenance of BCVA within 3 logMAR lines of baseline, number of intravitreal injections delivered over a 12-month period, and final CMT on optical coherence tomography. RESULTS: A total of 230 eyes met the criteria. Mean presenting BCVA was Snellen 20/55 (0.44 logMAR) and mean final BCVA was Snellen 20/44 (0.35 logMAR) (P < 0.001). A total of 23.5% (95% confidence interval [CI], 18.5-29.4%) of the subjects demonstrated an improvement in BCVA of 3 or more logMAR lines, whereas 96.5% (95% CI, 93.3-98.2%) of the subjects lost fewer than 3 logMAR lines. Mean CMT on optical coherence tomography changed from a baseline average of 373.1 µm (95%CI, 360.3-386.1 µm) to a final average of 305.5 µm (95% CI, 290.0-316.0 µm). The average number of injections during the 12-month period was 9.2 (95% CI, 9.0-9.4). Posterior vitreous detachment was associated with fewer injections on univariate and multivariate analysis (8.7 injections in the posterior vitreous detachment group versus 9.8 in the non-posterior vitreous detachment group, P < 0.001). Patients with poorer presenting BCVA and greater baseline CMTs were more likely to demonstrate a 3 or more logMAR line improvement in BCVA. Thinner final CMTs were independently associated with thinner presenting CMTs and fewer injections. CONCLUSION: Favorable visual and anatomical outcomes may be achieved with intravitreal bevacizumab in the treatment of neovascular age-related macular degeneration using a treat-and-extend regimen. Our study suggests that posterior vitreous detachment may play a role in the efficacy of intravitreal bevacizumab during the treatment of neovascular age-related macular degeneration.

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.

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.

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.

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.