ABO-adjusted cPRA metric for kidney allocation in an Asian-predominant population.

Recent studies showed that ABO-adjusted calculated panel reactive antibody (ABO-cPRA) may better reflect the histocompatibility level in a multi-ethnic population, but such data in Asians is not available. We developed an ABO-adjusted cPRA metric on a cohort of waitlist kidney transplant patients (n = 647, 99% Chinese) in Hong Kong, based on HLA alleles and ABO frequencies of local donors. The concordance between the web-based ABO-cPRA calculator and the impact on kidney allocation were evaluated. The blood group distribution for A, B, O and AB among waitlist kidney candidates were 26.2%, 27.5%, 40.1%, and 6.1%, and their chances of encountering incompatible blood group donors were 32.6%, 32.4%, 57.6%, and 0%, respectively. There is poor agreement between web-based ABO-cPRA calculator and our locally developed metrics. Over 90% of patients showed an increase in cPRA after ABO adjustment, most notably in those with cPRA between 70% and 79%. Blood group O patients had a much greater increase in cPRA scores after adjustment while patients of blood group A and B had similar increment. 10.6% of non-AB blood group waitlist patients had ABO-cPRA elevated to ≥80%. A local ABO-adjusted cPRA metric is required for Asian populations and may improve equity in kidney distribution for patients with disadvantageous blood groups. The result from the current study potentially helps other countries/localities in establishing their own unified ABO-cPRA metrics and predict the impact on kidney allocation.

[Clinical efficacy of combined therapy in children with stage 4 neuroblastoma]. / 儿童4期神经母细胞瘤联合治疗的临床疗效观察.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS: Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong.

The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screening (NBS) programs for Severe Combined Immunodeficiency. The potential applications of combined TREC and KREC assay in PIDD diagnosis and immune reconstitution monitoring in non-neonatal patients have been suggested. Given that ethnicity, gender, and age can contribute to variations in immunity, defining the reference intervals of TREC and KREC levels in the local population is crucial for setting up cut-offs for PIDD diagnosis. In this retrospective study, 479 healthy Chinese sibling donors (240 males and 239 females; age range: 1 month-74 years) from Hong Kong were tested for TREC and KREC levels using a simultaneous quantitative real-time PCR assay. Age-specific 5th-95th percentile reference intervals of TREC and KREC levels (expressed in copies per µL blood and copies per 106 cells) were established in both pediatric and adult age groups. Significant inverse correlations between age and both TREC and KREC levels were observed in the pediatric age group. A significant higher KREC level was observed in females than males after 9-12 years of age but not for TREC. Low TREC or KREC levels were detected in patients diagnosed with mild or severe PIDD. This assay with the established local reference intervals would allow accurate diagnosis of PIDD, and potentially monitoring immune reconstitution following haematopoietic stem cell transplantation or highly active anti-retroviral therapy in the future.

Role of Regulatory T Cells in Noninherited Maternal Antigen-Related Tolerance in Cord Blood: An in Vitro Study.

Cord blood (CB) is an alternative stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT). The unique advantages of using CB as a stem cell source are a degree of permissibility for HLA mismatch, rapid availability, and relatively risk-free cell collection. Because HLA is highly polymorphic and population-specific, optimal HLA-matched unrelated donors or cord blood units (CBUs) might not be available. In view of the possibility that matched CBUs that include noninherited maternal antigens (NIMAs) might contain acceptable HLA mismatches, we attempted to determine the degree of alloreactivity of CB mononuclear cells (MNCs) on stimulation by the maternal, paternal, and unrelated stimulator cells. Suppression of T cell proliferation, cytotoxicity, and a cytokine profile indicating suppressed Th1 and elevated IL-10 and TGF-ß1 responses were observed in the mixed lymphocyte reaction in response to NIMAs. The increases in IL-10 and TGF-ß1 production may be due to the Th2 response and/or regulatory T cells (Tregs). The reduced IL-10 and TGF-ß1 production after CD25 depletion could have been due to removal of Tregs from the CB cells. Thus, Tregs appear to play an important role in the CB MNC response to NIMAs, possibly due to the induction of IL-10 and TGF-ß1. We hope that our work can provide some evidence of the beneficial effect of NIMAs.

Comparing Eye-tracking Data of Children with High-functioning ASD, Comorbid ADHD, and of a Control Watching Social Videos.

Children with autism spectrum disorders (ASD) are known to have sensory-perceptual processing deficits that weaken their abilities to attend and perceive social stimuli in daily living contexts. Since daily social episodes consist of subtle dynamic changes in social information, any failure to attend to or process subtle human nonverbal cues, such as facial expression, postures, and gestures, might lead to inappropriate social interaction. Traditional behavioral rating scales or assessment tools based on static social scenes have limitations in capturing the moment-to-moment changes in social scenarios. An eye-tracking assessment, which can be administered in a video-based mode, is therefore preferred, to augment clinical observation. In this study, using the single-case comparison design, the eye-tracking data of three participants, a child with autism spectrum disorder (ASD), another with comorbid attention deficit-hyperactive disorder (ADHD), and a neurotypical control, are captured while they view a video of social scenarios. The eye-tracking experiment has helped answer the research question: How does social attention differ between the three participants? By predefining areas of interest (AOIs), their visual attention on relevant or irrelevant social stimuli, how fast each participant attends to the first social stimuli appearing in the videos, for how long each participant continues to attend to those stimuli within the AOIs, and the gaze shifts between multiple social stimuli appearing concurrently in the same social scene are captured, compared, and analyzed in a video-based eye-tracking experiment.

Conflict monitoring in multi-sensory flanker tasks: Effects of cross-modal distractors on the N2 component.

The N2 component is a well-known neural correlate of conflict monitoring (CM), being more negative in the presence of conflicting information in visual conflict tasks. However, whether to-be-ignored auditory distractors can introduce additional conflict remains unknown. In the present work, subjects performed a visual (V) and audiovisual (AV) version of a Go/NoGo flanker task, and responded only if the target arrow pointed toward a pre-specified direction (e.g., left). In the AV task, in which to-be-ignored auditory distractors that were semantically associated with the flankers were concurrently presented, the congruency effect on both RT and N2 amplitude was enhanced, confirming that additional conflict can be brought about by cross-modal distractors at both behavioural and neural levels. Consistent with the hypothesis that N2 amplitude reflects response conflict in visual conflict tasks, within-subject correlation between N2 amplitude and RT was significant in the Go conditions for the V task (congruent/incongruent). However, for the AV task, the correlation was significant only in the congruent condition. These findings suggest that while the cross-modal conflict is registered by the CM process, only part of this conflict could effectively induce response conflict.

The impact of fertilization on the chicken egg yolk plasma and granule proteome 24 hours post-lay at room temperature: capitalizing on high-pH/low-pH reverse phase chromatography in conjunction with tandem mass tag (TMT) technology.

Chicken egg yolk is a rich source of nutrients providing high quality proteins, vitamins, minerals, carotenoids and antioxidants. Chicken egg yolk, recovered from whole egg within 24 hours post-lay has been utilized as a starting material in the preparation of a dietary supplement that has been demonstrated to lead to gains in muscle mass in a human clinical study. Further, an oil derived from chicken egg yolk has been utilized as a topical agent to treat third degree burn injury. The molecular changes that take place in fertilized, chicken egg yolk during the first 24 hours post-lay are not well understood. By studying how the protein composition of egg yolk varies with fertility status, one can utilize this knowledge to develop egg yolk-based products that have been optimized for specific applications. In this study, a direct quantitative comparison was made between the proteome of fertilized chicken egg yolk and the proteome of unfertilized chicken egg yolk, both maintained at 20 °C and analyzed within 24 hours post-lay. Egg yolk proteins from each fertility state were digested with trypsin, labeled with distinct chemical labels (tandem mass tag reagents) and then combined in a 1 : 1 ratio. A TMT-labeled tryptic digest derived from chicken egg yolk proteins (fertilized and unfertilized) was separated using high-pH/low-pH reverse-phase chromatography and analyzed using mass spectrometry. 225 protein identifications were made from this TMT-labeled tryptic digest based on a minimum of 2 unique peptides observed per protein. 9 proteins increased in abundance in fertilized egg yolk relative to unfertilized egg yolk and 9 proteins decreased in abundance in fertilized egg yolk relative to unfertilized egg yolk. Some proteins that increased in abundance in fertilized egg yolk play an important role in angiogenesis (pleiotrophin, histidine rich glycoprotein) and defense against pathogens (mannose-binding lectin, ß-defensin 11, serum amyloid P-component, ovostatin). Based on this study, fertilized chicken egg yolk may be more useful as a starting material relative to unfertilized chicken egg yolk for the purpose of enriching or isolating proteins with pro-angiogenic and anti-microbial properties.

Human electroretinal responses to grating patterns and defocus changes by global flash multifocal electroretinogram.

The electrical response of the retina was examined as a function of retinal region, using stimuli of various spatial frequencies in the first experiment. In the second experiment, the regional response of the retina to defocus at high and low spatial frequencies was investigated. Twenty three subjects were recruited for global flash multifocal electroretinogram (mfERG) in experiment 1. Black and white gratings (printed on plastic transparent sheets) of four spatial frequencies (SF), 0.24, 1.2, 2.4 and 4.8 cycle per degree were presented in front of the mfERG stimulation. The amplitudes and implicit times of the direct (DC) and induced (IC) components of mfERG responses were pooled into six concentric rings for analysis. There was low amplitude DC at low SF, which increased with increasing SF, and which decreased with increasing eccentricity. The IC was high in amplitude at all SF and reduced in amplitude with increasing eccentricity. Our findings suggested that outer and inner retina had different characteristics in processing spatial details. In experiment 2, Twenty-three young adults were recruited for mfERG measurement. The retinal electrical responses for low (0.24cpd) and high (4.8cpd) SF under fully corrected conditions of short-term negative defocus (-2D) and short term positive defocus (+2D) conditions were measured. There was a sign-dependent response to defocus in the DC response, mainly in peripheral regions. The sign dependent response at low SF was more obvious than that at high SF, and was located more peripherally. The IC response showed no clear trends for either defocus condition. The human retina seems to have a decoding system for optical defocus, which was tuned for low spatial frequency, and was located in the retinal near periphery.

A new great wall: commissioning a new hospital in China.

A nationwide healthcare reform in China began in 2009, when the government injected GBP 85 billion to improve the healthcare coverage for its 1.3 billion population. Healthcare in China is primarily a market-based system, driven principally by demand, but the necessary supervision is relatively ineffective. There is a lack of trust between patients, who act as paying clients, and doctors, who often put the institution first, leading to frequent medical disputes. The University of Hong Kong Shenzhen Hospital is a joint venture between the city of Shenzhen and the University, with the mission to provide a new healthcare model in China. A clear process is in place to improve the clinical standard while a clean governance structure is set up. The hospital has ushered in many new initiatives. It is hoped that these will serve as a model for healthcare reform in China.

Effect of lycium barbarum (wolfberry) polysaccharides on preserving retinal function after partial optic nerve transection.

Lycium Barbarum Polysaccharides (LBP) are the active components of Wolfberry (a traditional Chinese medicine) which has long been used for improving visual function. This study aims to investigate localized changes of retinal function in a partial optic nerve transection (PONT) model, and effects of LBP on visual function. The multifocal electroretinograms (mfERG) were obtained from 30 eyes of 30 Sprague-Dawley rats. The rats were divided into 6 groups (five treatment groups and one control group). Starting from the first day of the experiment, the rats in the (PONT+LBP) group and the (LBP) group were dosed with LBP; rats in the (PONT+PBS (phosphate buffered saline)) group and the (PBS) group were dosed with PBS via nasogastric tube every day until euthanized. The dorsal part of the optic nerve was transected in the (PONT), (PONT+LBP) and (PONT+PBS) groups at the end of week 1 (day 7 after LBP or PBS feeding began). The mfERG was measured at three time points: week 2, week 3 and week 5. Significant reduction of P1 and PhNR amplitudes of the mfERG were observed in all retinal regions a week after PONT. Feeding with LBP prior to PONT preserved retinal function. All mfERG responses returned to the normal range in the superior retina, which corresponds to the transected dorsal region of the optic nerve, while most of the inferior retinal responses were significantly increased at week 4 after PONT. The ventral part of the retina had secondary degeneration which was not only limited to the ganglion cell layer, but is a widespread effect affecting the outer retina. LBP altered the functional reduction caused by PONT by regulating the signal from the outer retina.

Rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p < 0.0001). Statistically significant differences in favour of RTX were also reported for a range of secondary endpoints. Assessment of overall survival benefit could be not made due to insufficient events. The ERG's main concern with the clinical-effectiveness data presented was their lack of maturity. The submitted incremental cost-effectiveness ratio was within the NICE threshold. The ERG questioned the model on a number of grounds, particularly the use of Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.

A novel missense mutation in the NYX gene associated with high myopia.

PURPOSE: Myopia is a complex eye disorder. The X-linked form of complete congenital stationary night blindness (CSNB1A) is usually associated with moderate to high myopia, and is caused by mutations in the NYX gene. We explored if NYX mutations could be associated with high myopia, but not CSNB1A. METHODS: The coding regions of the NYX gene were sequenced for 204 Chinese males with high myopia (-8.00 dioptres or worse for both eyes). The frequencies of any sequence variations identified were determined in 200 Chinese males without myopia. Electro-oculography, electroretinography and standard cone function tests were performed on a male high myope carrying a mutation. RESULTS: A missense mutation (c.529_530GC>AT or p.Ala177Met) was identified in one male subject with high myopia, but not in 200 male emmetropes. Neither was this variant found in any of the 529 male and 567 female subjects of various ethnic backgrounds whose genome sequences are documented in the 1000 Genomes Project database. The mutation was predicted to affect the protein function. From ocular electrophysiological tests, the proband was found to have normal rod function, but mildly abnormal cone function and inner retina function. He did not seem to suffer from CSNB1A. CONCLUSIONS: One novel missense NYX mutation was identified in an adult male presented with high myopia, but without the major electrophysiological features normally associated with CSNB1A. NYX gene mutations may be considered as one of the rare genetic risk factors for high myopia without key features of CSNB1A.

Porto-pulmonary hypertension exacerbated by platelet transfusion in a patient with ADAMTS13 deficiency.

We propose that porto-pulmonary hypertension (PPH) may arise as a consequence of deficiency of ADAMTS13 (a plasma metalloprotease that regulates von Willebrand factor size and reduces its platelet adhesive activity) and provide a clinical case history to support our hypothesis. A patient with non-cirrhotic intrahepatic portal hypertension (NCIPH), ulcerative colitis and celiac disease developed symptoms of PPH, which had advanced beyond levels which would have made her an eligible candidate for liver transplantation (mean pulmonary artery pressure (PAP) 49 mm Hg). She was known to have severe ADAMTS13 deficiency, which we considered to be causative of, or contributory to her NCIPH. We postulated that increasing porto-systemic shunting associated with advancing portal hypertension would make the next encountered vascular bed, the lung, susceptible to the pathogenic process that was previously confined to the portal system, with pulmonary hypertension as its consequence. Her pulmonary artery pressures fell significantly during the next year on weekly replacement of plasma ADAMTS13 by infusions of fresh frozen plasma and conventional drug treatment of her pulmonary hypertension. Her pulmonary artery pressures had fallen to acceptable levels when, in response to platelet infusion, it rose precipitously and dangerously. The sequence strongly supports our hypothesis that PPH is a consequence of ADAMTS13 deficiency and is caused by platelet deposition in afferent pulmonary vessels.

Temporal interactive response is resistant to cloudy ocular media in the slow double-stimulation multifocal electroretinogram.

AIM: To examine the influence of cloudy media on the slow double-stimulation multifocal electroretinogram (mfERG). METHODS: Slow double-stimulation mfERG responses were measured from 26 subjects with normal ocular health under normal and light scattering conditions (induced using acrylic sheets) (Experiment 1) and another nine cataract patients before and after cataract surgery (Experiment 2). The amplitudes and implicit times of the first (M(1)) and second (M(2)) stimulation were compared under normal and light scattering conditions in Experiment 1 and they were compared under precataract and postcataract surgery in Experiment 2. RESULTS: Compared with control conditions (normal and postcataract surgery), the M(1) amplitude in the central region was significantly reduced in light scattering conditions (acrylic sheets and precataract surgery); the M(2) amplitude and both M(1) and M(2) implicit times of all regions examined were moderately affected in precataract surgery. The M(1):M(2) amplitude ratio and implicit time ratio were virtually unaffected in cloudy media for either central or mid-peripheral regions. CONCLUSION: Cloudy media affects the mfERG amplitude and implicit time in the slow double-stimulation, but does not affect the response ratio (ie, M(1):M(2) amplitude ratio and implicit time ratio) between the two stimulations. This suggests that the ratio analysis can be applied in patients with mild to moderately cloudy ocular media to evaluate the functional integrity of the retina.

Luminance-modulated adaptation in the global flash mfERG: a preliminary study of early retinal functional changes in high-risk glaucoma patients.

PURPOSE: To investigate the association of the luminance-modulation global flash multifocal electroretinogram (mfERG) and other clinical assessments of vision in subsets of subjects at high risk of developing glaucomatous damage. METHODS: Eighteen subjects (28 eyes) with asymmetric glaucoma and ocular hypertension were measured in this longitudinal study of visual field, OCT, and multifocal electroretinogram (mfERG). Five ophthalmic examinations were scheduled, once every 12 months over a 4-year period. The mfERG was assessed using a luminance-modulated global flash stimulation paradigm. The adaptive index which we have reported previously was calculated. RESULTS: There was a significant thinning of the peripapillary retinal nerve fiber layer over the course of the study for eyes with ocular hypertension, or for fellow eyes with asymmetric glaucoma which initially had an abnormal adaptive index; such eyes showed a thinning rate of -3.59 and -3.69 µm/year, respectively. However, no significant thinning was found for eyes which initially had a normal adaptive index. Two subjects were shown to have glaucomatous damage, confirmed by abnormal thinning of the retinal nerve fiber layer and visual field loss respectively at the last visit. However, these patients had shown an abnormal adaptive index in the mfERG measurement at the first visit. CONCLUSIONS: The adaptive index calculated from the measurement of luminance-modulated global flash mfERG is useful for predicting progression of signs related to glaucoma, especially in high-risk groups. The abnormal adaptive index reflects the change in fast-adaptive mechanisms in the retina and indicates the risk of developing glaucoma.

EGFR nuclear import in gallbladder carcinoma: nuclear phosphorylated EGFR upregulates iNOS expression and confers independent prognostic impact.

BACKGROUND: The understanding of epidermal growth factor receptor (EGFR) deregulation in carcinogenesis remains incomplete. We investigated the implications of EGFR gene status and EGFR nuclear translocation in gallbladder carcinoma (GBCA). METHODS: Subcellular localization of EGFR and phosphorylated EGFR (pEGFR) was analyzed by fractional immunoblotting and confocal immunofluorescence in GBCA cell lines. pEGFR binding to iNOS promoter was assessed by chromatin immunoprecipitation with iNOS promoter activity evaluated by luciferase assay. EGFR, pEGFR, and iNOS were immunohistochemically assessable for localization and level in the training set of 104 GBCAs on tissue microarrays, with 76 cases analyzed for EGFR gene by chromogenic in situ hybridization (CISH) and mutant-enriched PCR targeting exons 19 and 21. The prognostic impact of nuclear pEGFR (N-pEGFR) immunoexpression was reaffirmed on whole sections of 58 GBCAs in the test set. RESULTS: Nuclear expression of EGFR and pEGFR was substantiated in vitro with augmented activity of iNOS promoter elicited by pEGFR binding upon EGF treatment. Despite no mutation, EGFR amplification, identified in 11 cases (15%) by CISH, strongly correlated with cytoplasmic EGFR expression (P < 0.001) but not with disease-specific survival (DSS). Immunoexpression of nuclear EGFR (N-EGFR), cytoplasmic pEGFR, and N-pEGFR was strongly related to that of iNOS (all ≤0.005). N-pEGFR independently predicted worse DSS in both training (P = 0.0468, HR = 2.024) and test sets (P = 0.0223, HR = 5.573). CONCLUSIONS: N-EGFR and N-pEGFR express in GBCA, conferring clinical aggressiveness partly through iNOS transactivation. Lacking response-predicting mutation, EGFR gene status, albeit amplified in 15% of GBCA, is neither related to nuclear EGFR translocation nor prognostically useful.

Effect of inner retinal dysfunction on slow double-stimulation multifocal electroretinogram.

PURPOSE: This study investigated the retinal adaptive mechanism in inner retinal dysfunction using the slow double-stimulation multifocal electroretinogram (mfERG) paradigm. METHODS: Slow double-stimulation mfERG responses were recorded from 15 eyes of 15 4-month-old Mongolian gerbils in control conditions and after suppression of inner retinal responses with injections of tetrodotoxin (TTX) and N-methyl-d-aspartic acid (NMDA). The stimulation consisted of five video frames: the two initial frames with multifocal flashes were triggered by two independent m-sequences, followed by three dark video frames. The results were compared with findings in humans: 7 subjects with glaucoma and 31 age-matched normal subjects were measured using the same mfERG protocol. RESULTS: The stimulation generates two responses (M(1) and M(2)) from the two independent multifocal frames. The M(1):M(2) ratio showed a significant reduction after administration of TTX+NMDA in the animal study. This matched with the human glaucoma findings. Glaucoma subjects generally have a reduced M(1):M(2) ratio; this ratio showed a sensitivity of 86%, with a specificity of 84% for differentiating normal eyes from glaucomatous eyes. CONCLUSION: This stimulation paradigm provides a method of measuring temporal visual characteristics. The M(1):M(2) ratio acts as an indirect functional indicator of retinal adaptation, which may be abnormal in the diseased retina. Further development of this method may help to describe the functional variation in the diseased retina and to predict the occurrence of a range of retinopathies.

Forward and backward adaptive effects in global flash multifocal electroretinogram stimulation.

PURPOSE: The present study investigated retinal adaptive responses in concert with the modulation of forward and backward adaptation induced by periodic global flashes using the global flash multifocal electroretinogram (mfERG). METHODS: Six normal subjects were recruited for global flash mfERG measurements, which consisted of 103 scaled hexagonal elements followed by a global flash frame. In experiments I and II, with constant luminance maintained in both local and global flash frames, the number of dark frames was independently varied and these frames were either inserted prior to or following the global flash frame to investigate the forward or backward adaptive effect of the global flash on the mfERG. In experiment III, the number of dark frames was fixed but the luminance of the global flash frame was varied with constant luminance of the focal flash. This was used to demonstrate that the adaptive effect related not to time but to variation of luminance. RESULTS: All the central, para-central and peripheral direct component amplitudes were found to be significantly influenced by variation of the number of dark frames (p < 0.01). Reducing the forward adaptive effect of the global flash enhanced the direct component response and it became steady after five dark frames were inserted following the global flash. Reducing the backward adaptive effect of the global flash also enhanced the direct component response but it started reducing after four dark frames were inserted prior to the global flash frame. These changes were different with luminance modulation of the global flash intensity with fixed dark frames, while the direct component amplitude grew approximately linearly with decreasing mean luminance of the global flash stimulation. CONCLUSION: The retina plays a major role in visual adaptation. Both forward and backward adaptive effects of the global flash on the direct component have been illustrated in this study. The results show that the forward and backward adaptive phenomena in the global flash mfERG are different and demonstrate that backward adaptation is found at the retinal level.

Applications of the multifocal electroretinogram in the detection of glaucoma.

Glaucoma is one of the most important eye diseases resulting in blindness worldwide. It affects the inner retina and is without signs and symptoms in the early stages, making early detection of glaucoma important for eye care professionals. Electroretinography (ERG) is an objective technique used to measure retinal electrical responses, which directly reflect retinal function. The multifocal electroretinogram (mfERG) is a relatively new tool in this area. Various modifications of the mfERG stimulation paradigms such as fast flicker, low contrast, slow sequence, global flash and luminance-modulation have been developed in recent years. Using these techniques and a better understanding of the mfERG characteristics has resulted in greater effectiveness of the mfERG in the diagnosis of glaucoma. It is likely that sensitive clinical mfERG measurement protocols for early detection of glaucomatous damage will be possible in the near future.