Optical Coherence Tomography Findings in Glaucoma With Coexisting Vitamin A Deficiency.

This case study reports on the presence of vitamin A deficiency in an adult with asymmetric normal tension glaucoma. The retinal OCT findings demonstrated not only expected loss of the outer retinal layers, typically seen in vitamin A deficiency, but also severe and bilateral loss of the inner retinal layers. After vitamin A supplementation, visual acuity, dark adaptation, and color vision normalized. The outer retinal layers had a restoration of thickness after vitamin A supplementation, but the inner layers did not change. This case is unique because it may give us an insight into the role of vitamin A on the inner retina and demonstrate the recovery of the outer retinal layers with vitamin A supplementation.

Visual Dysfunction and Structural Correlates in Sorsby Fundus Dystrophy.

PURPOSE: To elucidate morphological determinants of rod and cone dysfunction in Sorsby fundus dystrophy (SFD), and to systematically compare visual function tests for interventional trials. DESIGN: Prospective cross-sectional study. METHODS: Patients with SFD (n = 16) and controls (n = 20) underwent visual function testing (best-corrected visual acuity [BCVA] and low luminance visual acuity [LLVA], contrast sensitivity, mesopic and dark-adapted (DA) fundus-controlled perimetry [FCP], rod-mediated dark adaptation [RMDA]), and multimodal imaging. Vision-related quality of life was evaluated. FCP and RMDA thresholds were analyzed using mixed models and structure-function correlation using machine learning (ML). Longitudinal data of 1 patient with high-dose vitamin A supplementation were available. RESULTS: Although photopic BCVA was normative in SFD, LLVA was impaired (0.30 LogMAR [0.20; 0.45] vs 0.20 LogMAR [0.03; 0.28], P < .05). Scotopic visual function exhibited a delayed rod-intercept time (21 minutes [12.15; 21] vs 4.05 minutes [3.22; 5.36], P < .001), and marked DA cyan mean sensitivity loss (-11.80 dB [-3.47; -19.85]), paralleled by a reduced vision-related quality of life. ML-based structure-function correlation allowed prediction of mesopic, DA cyan, and red sensitivity with high accuracy (cross-validated mean absolute error: 4.36, 7.77, and 5.31 dB, respectively), whereas RMDA could be slowed even in the absence of fundus alterations on multimodal imaging. After high-dose vitamin A supplementation, RMDA and DA thresholds improved markedly. CONCLUSIONS: Patients with SFD exhibit severely impaired scotopic visual function even in the absence of funduscopic alterations on multimodal imaging. In contrast to BCVA, scotopic visual function tests are suitable to quantify dysfunction in the early stages. Improvement of scotopic dysfunction after (off-label) high-dose vitamin A intake, as observed in one patient in our study, is compatible with the hypothesized local deficiency of vitamin A secondary to Bruch's membrane alterations.

IMPAIRED DARK ADAPTATION ASSOCIATED WITH A DISEASED BRUCH MEMBRANE IN PSEUDOXANTHOMA ELASTICUM.

PURPOSE: To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane. METHODS: In this prospective case-control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life. RESULTS: Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation. CONCLUSION: Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.

Lipopolysaccharide (LPS) induced sickness in early adolescence alters the behavioral effects of the short-chain fatty acid, propionic acid, in late adolescence and adulthood: Examining anxiety and startle reactivity.

Early life immune challenges are risk factors for neurodevelopmental disorders. In adolescence, they elicit behavioral symptoms that resemble clinical disorders. Stressors during this time may alter signaling from the gut microbiome, which increases the risk for psychiatric disorders. It was hypothesized that adolescent immune challenges may interact with a gut bacterial product, the short-chain fatty acid, propionic acid (PPA), to potentiate symptoms of anxiety and sensory abnormality. The present study investigated the effects of repeated lipopolysaccharide (LPS) exposure during early adolescence, on the behavioral effects of PPA in late adolescence and adulthood. Male adolescent rats were injected with LPS (0.2 mg/kg i.p.) or the vehicle on postnatal days (P) 28, P30, P32, and P34. They were later administered either PPA (500 mg/kg i.p.) or the vehicle during late adolescence on P40 and P43, and were subsequently tested on the light-dark anxiety test and acoustic startle response, respectively. In adulthood, the rats were again injected with PPA or the vehicle and tested on the light-dark and acoustic startle tasks on P74 and P77. The results of this study showed that LPS and PPA both decreased locomotor activity. PPA reduced vertical activity, percent prepulse inhibition, and acoustic startle response magnitude. LPS increased anxiogenic behaviors and induced a delayed increase in acoustic startle response magnitude in adulthood. Although no LPS and PPA interactions were found, the results of this study suggest that early adolescent immune activation can induce long-term behavioral changes that resemble the complex phenotypes of clinical disorders.

Blast-induced brain injury in rats leads to transient vestibulomotor deficits and persistent orofacial pain.

Blast-induced traumatic brain injury (blast-TBI) is associated with vestibulomotor dysfunction, persistent post-traumatic headaches and post-traumatic stress disorder, requiring extensive treatments and reducing quality-of-life. Treatment and prevention of these devastating outcomes require an understanding of their underlying pathophysiology through studies that take advantage of animal models. Here, we report that cranium-directed blast-TBI in rats results in signs of pain that last at least 8 weeks after injury. These occur without significantly elevated behavioural markers of anxiety-like conditions and are not associated with glial up-regulation in sensory thalamic nuclei. These injuries also produce transient vestibulomotor abnormalities that resolve within 3 weeks of injury. Thus, blast-TBI in rats recapitulates aspects of the human condition.

Low-Level Nighttime Light Therapy for Age-Related Macular Degeneration: A Randomized Clinical Trial.

Purpose: To investigate the safety, acceptability, and effectiveness of light therapy on the progression of AMD over 12 months. Methods: This was a phase I/IIa, prospective, proof-of-concept, single-center, unmasked randomized controlled trial. Sixty participants (55 to 88 years) with early AMD in the study eye and neovascular AMD (nAMD) in the fellow eye were recruited from a hospital nAMD clinic. Eligible participants were randomized (ratio 1:1) to receive light therapy or to an untreated control group. Light therapy was delivered via a light-emitting mask (peak 505 nm, 23 scotopic Td), which was worn each night for 12 months. Co-primary outcome measures were disease progression (onset of nAMD or increased drusen volume beyond test-retest limits) and change in time constant of cone dark adaptation. Other main outcomes included adverse events, compliance, and subjective sleep quality data. Results: Disease progression over 12 months was seen in 38.1% (18.1%-61.6% confidence interval [CI]) of intervention participants and 48.3% (29.4%-67.5% CI) of controls (Mantel-Haenszel test, common odds ratio = 0.763, P = 0.495). A significantly larger delay in cone adaptation was observed in the intervention group (1.66 ± 0.61 minutes) than in the control group (0.66 ± 0.49 minutes) over the follow-up period. No reported adverse events were deemed to be associated with the intervention. Conclusions: Although acceptable to the patients, light therapy did not have a substantial effect on the progression of early AMD over 12 months. Further investigation is necessary to discover the permanency and cause of the adverse effect of light therapy on dark adaptation.

Ocular Topical Anesthesia Does Not Attenuate Light-Induced Discomfort Using Blue and Red Light Stimuli.

Purpose: To investigate whether melanopsin-containing ophthalmic trigeminal ganglion cells provide significant input to mediate light-induced discomfort. This is done by studying the effect of ocular topical anesthesia on light-induced discomfort threshold to blue light and red light stimuli using a psychophysical approach. Method: Ten visually normal participants completed the experiment consisting of two trials: an anesthesia trial in which light stimuli were presented to both eyes following 0.5% proparacaine eye drops administration, and a placebo trial in which normal saline drops were used. In each trial, a randomized series of 280 blue and red light flashes were presented over seven intensity steps with 20 repetitions for each color and light intensity. Participants were instructed to report whether they perceived each stimulus as either "uncomfortably bright" or "not uncomfortably bright" by pressing a button. The proportion of "uncomfortable" responses was pooled to generate individual psychometric functions, from which 50% discomfort thresholds (defined as the light intensity at which the individuals perceived the stimulus to be uncomfortably bright/unpleasant 50% of the time) were calculated. Results: When blue light was presented, there was no significant difference in the light-induced discomfort thresholds between anesthesia and placebo trials (P = 0.44). Similarly, when red light was used, no significant difference in threshold values was found between the anesthesia and placebo trials (P = 0.28). Conclusions: Ocular topical anesthesia does not alter the light-induced discomfort thresholds to either blue or red light, suggesting that the melanopsin-containing ophthalmic trigeminal ganglion cells provide little or no significant input in mediating light-induced discomfort under normal physiologic conditions.

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial.

BACKGROUND: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. METHODS: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. FINDINGS: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change -9·2 µm [SE 2·5] for the light mask vs -12·9 µm [SE 2·9] for the sham mask; adjusted mean difference -0·65 µm, 95% CI -6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9-51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). INTERPRETATION: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. FUNDING: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PURPOSE: To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). METHODS: Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. RESULTS: Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; ß = 0.30, P = 0.045), taking AREDS vitamins (ß = 5.51, P < 0.001), and family history of AMD (ß = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (ß = 1.84, P = 0.006), taking AREDS supplements (ß = 1.67, P = 0.021) and alcohol intake (ß = 0.07, P = 0.017). CONCLUSION: Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.

Purpose: Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively. Methods: RBP4-Tg mice reared on normal mouse chow in normal cyclic light conditions were directly compared to RBP4-Tg mice exposed to chow supplemented with the RBP4-lowering compound A1120 or dark-rearing conditions. Quantitative retinal histological analysis was conducted to assess retinal degeneration, and electroretinography (ERG) and optokinetic tracking (OKT) tests were performed to assess retinal and visual function. Ocular retinoids and bis-retinoid A2E were quantified. Results: Dark-rearing RBP4-Tg mice effectively reduced ocular bis-retinoid A2E levels, but had no significant effect on retinal degeneration or dysfunction in RBP4-Tg mice, demonstrating that retinal degeneration is light-independent. A1120 treatment lowered serum RBP4 levels similar to wild-type mice, and prevented structural retinal degeneration. However, A1120 treatment did not prevent retinal dysfunction in RBP4-Tg mice. Moreover, RBP4-Tg mice on A1120 diet had significant worsening of OKT response and loss of cone photoreceptors compared to RBP4-Tg mice on normal chow. This may be related to the very significant reduction in retinyl ester levels in the retina of mice on A1120-supplemented diet. Conclusions: Retinal degeneration in RBP4-Tg mice is RBP4-dependent and light-independent.

Verso e avesso da sombra: tessitura de profanação sensível (pensartecorpo na experiência de bioética e aionética)

Tratou-se de um experimento Mítico-Erótiko no suporte da BioÉtica-AionÉtica-Éticada-Vidapor meio de uma cultura da Skótos (Sombra) em solução abstrato-teóricofilosófica(vide procedimentos em Giorgio Agamben) onde se desenvolveram cepashíbridas de idiopaticidade e de criptogenicidade que foram inoculadas no galo-deSócrates-para-Asclépioem vias de administração da oralidade, do rito, daespiritualidade, da filosofia, das humanidades e das artes (dança-Butô, teatro,performance, música, cinema, pintura, fotografia, literatura epistolar, poética,biográfica) com o propósito de observar uma sintomatologia do Contemporâneo e seuspossíveis efeitos adversos (Contra-Temporâneos) nos corpos da potência, diferença,sensações e afetos. Ao descrever os processos de mutações que se efetivaram nesseprotocolo, constatou-se que o próprio campo da Linguagem empreendeu uma curvaendógena (experiência sobre si mesmo), em dobraduras que resistiram às configuraçõesfixadas para um uso da gramática e/ou da finalidade identitária. Nessa zona limítrofelaboratorialdas variáveis no Pensamento e na Linguagem (Fora), enquanto aSubjetividade e os Saberes dos Modernos espargiram-se nas intensidades da imanência,persistiu uma estrutura expelida da Pólis arcana, uma arké da feiticeira no Sertão,outrora marginal ao tratamento que o Discurso-Verdade recebe na poesia (das Musas) ena filosofia (do Lógos), nos termos da Lei (Nómos) e da Ordem (Kósmos). A análisepara a coleta dos dados restritos ao presente sugere a multiplicidade de novos estudos apartir da intersecção de metodologias de conhecimento tácito em camadas distintas davirtualidade. Por fim, esse trabalho declara conflito de interesses às problemáticas dasua época, atinente às influências dos Pós-Modernos, dos Pós-Estruturalistas e dosContemporâneos no pensamento da Saúde e do Cuidado.

A Mythical-Erotic experiment in BioEthics-AionEthics-Life Ethics as substantiated by aculture of Skotos (Darkness) in an abstract-theoretical-philosophical solution (seeprocedures in Giorgio Agamben) within which hybrid strains of idiopathy andcryptogenicity were developed and inoculated in Socrates‘s Cock-for-Asclepius duringthe process of administration, of orality, of the rite, of spirituality, of philosophy, of thehumanities and of the arts (Butoh dance, theater, performance, music, cinema, painting,photography, epistolary literature, poetics, biography), with the aim of observing asymptomatology of the Contemporary and its possible adverse affects (CounterTemporaries)upon the bodies of potency, difference, sensations and facts. In describingthe processes of mutations that took place within that protocol, it became clear that thefield of Language itself had performedan endogenous curve (experience of oneself) infolds that resisted fixed configurations for grammar and/or identity purposes. Whereas,in this coterminous laboratorial zone of variables in Thought and Language (Outside),Subjectivity and the Knowledge of the Moderns spread throughout the intensities ofimmanence, one structure that had been expelled from the arcane Polis lives on – anarche of witchcraft in the Sertão, once marginal to the treatment that Truth-Discoursegiven to poetry (by the Muses) and to philosophy (by the Logos), in terms of Law(Nomos) and Order (Kósmos). The analysis of data collection restricted to the presentsuggests the multiplicity of new studies based on the intersection of methodologies oftacit knowledge in distinct layers of virtuality. Finally, this thesis declares a conflict ofinterests with the problems of its age, pertaining to the influence of the Postmoderns,the Poststructuralists and the Contemporaries upon Health and Care thinking.

Light-Dark Adaptation of Channelrhodopsin Involves Photoconversion between the all-trans and 13-cis Retinal Isomers.

Channelrhodopsins (ChR) are light-gated ion channels of green algae that are widely used to probe the function of neuronal cells with light. Most ChRs show a substantial reduction in photocurrents during illumination, a process named "light adaptation". The main objective of this spectroscopic study was to elucidate the molecular processes associated with light-dark adaptation. Here we show by liquid and solid-state nuclear magnetic resonance spectroscopy that the retinal chromophore of fully dark-adapted ChR is exclusively in an all-trans configuration. Resonance Raman (RR) spectroscopy, however, revealed that already low light intensities establish a photostationary equilibrium between all-trans,15-anti and 13-cis,15-syn configurations at a ratio of 3:1. The underlying photoreactions involve simultaneous isomerization of the C(13)═C(14) and C(15)═N bonds. Both isomers of this DAapp state may run through photoinduced reaction cycles initiated by photoisomerization of only the C(13)═C(14) bond. RR spectroscopic experiments further demonstrated that photoinduced conversion of the apparent dark-adapted (DAapp) state to the photocycle intermediates P500 and P390 is distinctly more efficient for the all-trans isomer than for the 13-cis isomer, possibly because of different chromophore-water interactions. Our data demonstrating two complementary photocycles of the DAapp isomers are fully consistent with the existence of two conducting states that vary in quantitative relation during light-dark adaptation, as suggested previously by electrical measurements.

Manganese-Enhanced MRI for Preclinical Evaluation of Retinal Degeneration Treatments.

PURPOSE: Apply manganese-enhanced magnetic resonance imaging (MEMRI) to assess ion channel activity and structure of retinas from mice subject to light-induced retinal degeneration treated with prophylactic agents. METHODS: Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated with strong light. Manganese-enhanced MRI was used to image the retina 2 hours after intravitreous injection of MnCl2 into one eye. Contrast-enhanced MRIs of the retina and vitreous humor in each experimental group were assessed and correlated with the treatment. Findings were compared with standard structural and functional assessments of the retina by optical coherence tomography (OCT), histology, and electroretinography (ERG). RESULTS: Manganese-enhanced MRI contrast in the retina was high in nonilluminated and illuminated Ret-NH2-treated mice, whereas no enhancement was evident in the retina of the light-illuminated mice without Ret-NH2 treatment (P < 0.0005). A relatively high signal enhancement was also observed in the vitreous humor of mice treated with Ret-NH2. Strong MEMRI signal enhancement in the retinas of mice treated with retinylamine was correlated with their structural integrity and function evidenced by OCT, histology, and a strong ERG light response. CONCLUSIONS: Manganese-enhanced MRI has the potential to assess the response of the retina to prophylactic treatment based on the measurement of ion channel activity. This approach could be used as a complementary tool in preclinical development of new prophylactic therapies for retinopathies.

Using Flickering Light to Enhance Nonimage-Forming Visual Stimulation in Humans.

PURPOSE: Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate nonimage-forming visual functions such as pupillary constriction and circadian photoentrainment. Optimizing daytime nonimage-forming photostimulation has health benefits. We aimed to enhance ipRGC excitation using flickering instead of steady light. METHODS: Human subjects were tested with a three-dimensional matrix of flickering 463-nm stimuli: three photon counts (13.7, 14.7 and 15.7 log photons cm(-2)), three duty cycles (12%, 47%, and 93%) and seven flicker frequencies (0.1, 0.25, 0.5, 1, 2, 4, and 7 Hz). Steady-state pupil constrictions were measured. RESULTS: Among stimuli containing 13.7 log photons cm-2, the one flickering at 2 Hz with a 12% duty cycle evoked the greatest pupil constriction of 48% ± 4%, 71% greater than that evoked by an equal-intensity (12.3 log photons cm(-2) s(-1)) continuous light. This frequency and duty cycle were also best for 14.7 log photons cm-2 stimuli, inducing a 58% ± 4% constriction which was 38% more than that caused by an equal-intensity (13.3 log photons cm(-2) s(-1)) constant light. For 15.7 log photons cm-2 stimuli, the 1-Hz, 47% duty cycle flicker was optimal although it evoked the same constriction as the best 14.7 log photons cm(-2) flicker. CONCLUSIONS: Pupillary constriction depends on flicker frequency and duty cycle besides intensity. Among the stimuli tested, the one with the lowest photon count inducing a maximal response is 13.3 log photons cm(-2) s(-1) flickering at 2 Hz with 12% duty cycle. Our data could guide the design of healthier architectural lighting and better phototherapy devices for treating seasonal affective disorder and jet lag.

A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial.

BACKGROUND: This study will evaluate hypoxia, as a novel concept in the pathogenesis of diabetic macular oedema (DMO). As the oxygen demand of the eye is maximum during dark-adaptation, we hypothesize that wearing light-masks during sleep will cause regression and prevent the development and progression of DMO. The study protocol comprises both an efficacy and mechanistic evaluation to test this hypothesis. METHOD/DESIGN: This is a phase III randomised controlled single-masked multicentre clinical trial to test the clinical efficacy of light-masks at preventing dark-adaptation in the treatment of non-central DMO. Three hundred patients with non-centre-involving DMO in at least one eye will be randomised 1:1 to light-masks and control masks (with no light) to be used during sleep at night for a period of 24 months. The primary outcome is regression of non-central oedema by assessing change in the zone of maximal retinal thickness at baseline on optical coherence tomography (SD-OCT). Secondary outcomes will evaluate the prevention of development and progression of DMO by assessing changes in retinal thickness in different regions of the macula, macular volume, refracted visual acuity and level of retinopathy. Safety parameters will include sleep disturbance. Adverse events and measures of compliance will be assessed over 24 months. Participants recruited to the mechanistic sub-study will have additional retinal oximetry, multifocal electroretinography (ERG) and microperimetry to evaluate the role of hypoxia by assessing and comparing changes induced by supplemental oxygen and the light-masks at 12 months. DISCUSSION: The outcomes of this study will provide insight into the pathogenesis of DMO and provide evidence on whether a simple, non-invasive device in the form of a light-mask can help prevent the progression to centre-involving DMO and visual impairment in people with diabetes.

myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses.

Mutations in myosin VIIa (MYO7A) cause Usher Syndrome 1B (USH1B), a disease characterized by the combination of sensorineural hearing loss and visual impairment termed retinitis pigmentosa (RP). Although the shaker-1 mouse model of USH1B exists, only minor defects in the retina have been observed during its lifespan. Previous studies of the zebrafish mariner mutant, which also carries a mutation in myo7aa, revealed balance and hearing defects in the mutants but the retinal phenotype has not been described. We found elevated cell death in the outer nuclear layer (ONL) of myo7aa(-/-) mutants. While myo7aa(-/-) mutants retained visual behaviors in the optokinetic reflex (OKR) assay, electroretinogram (ERG) recordings revealed a significant decrease in both a- and b-wave amplitudes in mutant animals, but not a change in ERG threshold sensitivity. Immunohistochemistry showed mislocalization of rod and blue cone opsins and reduced expression of rod-specific markers in the myo7aa(-/-) ONL, providing further evidence that the photoreceptor degeneration observed represents the initial stages of the RP. Further, constant light exposure resulted in widespread photoreceptor degeneration and the appearance of large holes in the retinal pigment epithelium (RPE). No differences were observed in the retinomotor movements of the photoreceptors or in melanosome migration within the RPE, suggesting that myo7aa(-/-) does not function in these processes in teleosts. These results indicate that the zebrafish myo7aa(-/-) mutant is a useful animal model for the RP seen in humans with USH1B.

A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients.

BACKGROUND: Patients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self-reports support the hypothesis that acupuncture may improve visual function. METHODS: A prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half-hour sessions over two weeks. Pre- and post-treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli-Robson contrast sensitivity (CS), Goldmann visual fields, and dark-adapted full-field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester-1 (SST-1) dark-adaptometry was performed on the last two subjects. RESULTS: Six of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5 dB (that is, 13- to 53-fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test-retest variability (95% CI: 3-3.5 dB) previously found in retinitis pigmentosa. SST-1 dark-adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30 dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was completed and well tolerated by all, without adverse events or visual loss. CONCLUSIONS: Acupuncture entails minimal risk, if administered by a well-trained acupuncturist and may have significant, measurable benefits on residual visual function in patients with retinitis pigmentosa, in particular scotopic sensitivity, which had not previously been studied. These preliminary findings support the need for future controlled studies of potential mechanisms.