Effectiveness of Biofeedback in Individuals with Awake Bruxism Compared to Other Types of Treatment: A Systematic Review.

Excessive masticatory muscle activity is generally present in awake bruxism, which is related to increased anxiety and stress. It has been hypothesized that biofeedback could potentially manage awake bruxism, however, its effectiveness has not been empirically analyzed in a systematic manner. Therefore, this systematic review was designed to determine the effectiveness of biofeedback compared to other therapies in adults with awake bruxism. Extensive searches in five databases looking for randomized controlled trials (RCTs) that included biofeedback to manage awake bruxism were targeted. The risk of bias (RoB) assessment was conducted using the Cochrane RoB-2 tool. Overall, four studies were included in this systematic review, all of which used the electromyographic activity of the masticatory muscles during the day and night as the main endpoint. Auditory and visual biofeedback could reduce the excessive level of masticatory muscle activity in a few days of intervention. The majority of the included studies had a high RoB and only one study had a low RoB. The standardization of the biofeedback protocols was also inconsistent, which makes it difficult to establish the ideal protocol for the use of biofeedback in awake bruxism. Thus, it is proposed that future studies seek to reduce methodological risks and obtain more robust samples.

Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy.

PURPOSE: Biallelic variants in UCHL1 have been associated with a progressive early-onset neurodegenerative disorder, autosomal recessive spastic paraplegia type 79. In this study, we investigated heterozygous UCHL1 variants on the basis of results from cohort-based burden analyses. METHODS: Gene-burden analyses were performed on exome and genome data of independent cohorts of patients with hereditary ataxia and spastic paraplegia from Germany and the United Kingdom in a total of 3169 patients and 33,141 controls. Clinical data of affected individuals and additional independent families were collected and evaluated. Patients' fibroblasts were used to perform mass spectrometry-based proteomics. RESULTS: UCHL1 was prioritized in both independent cohorts as a candidate gene for an autosomal dominant disorder. We identified a total of 34 cases from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17). The mass spectrometry-based proteomics showed approximately 50% reduction of UCHL1 expression in patients' fibroblasts. CONCLUSION: Our bioinformatic analysis, in-depth clinical and genetic workup, and functional studies established haploinsufficiency of UCHL1 as a novel disease mechanism in spastic ataxia.

Full-field electroretinography, visual acuity and visual fields in Usher syndrome: a multicentre European study.

PURPOSE: Usher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TREATRUSH). METHODS: A total of 268 genetically confirmed USH patients underwent electrophysiological examinations in the context of multimodal ophthalmological examination in the study (75 USH1, 189 USH2 and four USH3). Full-field electroretinography (ERG) was performed according to ISCEV standards, visual field determination was carried out with either the Octopus or Goldmann perimeters and visual acuity was examined with either ETDRS or Snellen charts. The data were compared between USH subtypes (USH1/USH2/USH3) and correlated with age. RESULTS: Visual acuity decreases significantly with age for both USH1 and USH2 (p < 0.001), without a difference between the two cohorts. When corrected for age, the preserved kinetic visual field was significantly larger in USH2 than in USH1 (p = 0.04). Furthermore, the preserved kinetic visual field area showed a significant decrease with age (based on an exponential fit) in both USH1 and USH2 (p < 0.001). In USH1 patients, however, the visual field was already vastly reduced at an early age. The ERG results were abnormal in all patients. Detectable data for scotopic ERG were obtained from nine patients, and data of photopic ERG were obtained from 24 patients, without a difference between USH1 and USH2 subtypes. CONCLUSIONS: There are differences in the phenotypes of RP in USH subtypes, most visible in the progression of visual fields between USH1 and USH2. The perimetric reduction occurs earlier in USH1 than in USH2. In both subtypes, visual acuity decreases significantly with age and the ERG is not detectable already at early ages.

Accessory heterozygous mutations in cone photoreceptor CNGA3 exacerbate CNG channel-associated retinopathy.

Mutations in CNGA3 and CNGB3, the genes encoding the subunits of the tetrameric cone photoreceptor cyclic nucleotide-gated ion channel, cause achromatopsia, a congenital retinal disorder characterized by loss of cone function. However, a small number of patients carrying the CNGB3/c.1208G>A;p.R403Q mutation present with a variable retinal phenotype ranging from complete and incomplete achromatopsia to moderate cone dysfunction or progressive cone dystrophy. By exploring a large patient cohort and published cases, we identified 16 unrelated individuals who were homozygous or (compound-)heterozygous for the CNGB3/c.1208G>A;p.R403Q mutation. In-depth genetic and clinical analysis revealed a co-occurrence of a mutant CNGA3 allele in a high proportion of these patients (10 of 16), likely contributing to the disease phenotype. To verify these findings, we generated a Cngb3R403Q/R403Q mouse model, which was crossbred with Cnga3-deficient (Cnga3-/-) mice to obtain triallelic Cnga3+/- Cngb3R403Q/R403Q mutants. As in human subjects, there was a striking genotype-phenotype correlation, since the presence of 1 Cnga3-null allele exacerbated the cone dystrophy phenotype in Cngb3R403Q/R403Q mice. These findings strongly suggest a digenic and triallelic inheritance pattern in a subset of patients with achromatopsia/severe cone dystrophy linked to the CNGB3/p.R403Q mutation, with important implications for diagnosis, prognosis, and genetic counseling.

Usher Syndrome and Color Vision.

PURPOSE: The aim of this study is to report on the results of color vision testing in a European cohort of patients with Usher syndrome (USH). We describe the results in relation to Usher type (USH1 and USH2), age and visual acuity. METHODS AND METHODS: The color vision of 220 genetically confirmed adult USH patients, aged 18-70 years, was analyzed with one of three methods: the Farnsworth D-15 Dichotomous test (D-15) along with the Lanthony desaturated 15 Hue tests (D-15d), the Roth 28-Hue test, or the Ishihara 14-plate test. Visual acuity was measured with either the ETDRS or the SNELLEN charts. The Confusion index, the Selectivity index and the Confusion angle were calculated for the panel tests and used for analysis. The numbers of plates that could not be read were analyzed for the Ishihara test. RESULTS: For the panel tests, the degree of color loss (Confusion index) is similar in both subtypes of USH, but the polarization of error scores (Selectivity index) is significantly lower in USH1 than USH2, showing more diffuse errors than those found in USH2. There is no significant correlation between logMAR visual acuity and the Confusion or the Selectivity indices. Additionally, we find a significant correlation between patient age and the degree and the polarity of the loss only in USH2. There was no difference between USH1 and USH2 in the results of the Ishihara test. CONCLUSIONS: The examination of color vision in patients with USH shows a significant difference in the pattern of color vision loss in USH1 and USH2 patients, but not in the severity of the loss. In USH2, we find a correlation between patient age and the degree and the polarity of the loss. These results may be due to differences in the pathogenesis of retinal dystrophy in USH1 and USH2.

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12.

PURPOSE: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. DESIGN: Multicenter, international, prospective cohort study. METHODS: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. RESULTS: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was -0.0014 degrees (95% confidence interval [CI], -0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, -1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. CONCLUSIONS: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 7.

Importance: New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity. Objective: To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry). Design, Setting, and Participants: This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as "normal," "relative," or "deep" scotoma. Main Outcomes and Measures: Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas. Results: Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, -0.13 to -0.041; P < .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, -0.28 to -0.14; P < .001). Longer duration of STGD1 was associated with worse MS (ß = -0.18; P < .001), with a lower number of normal test points (ß = -0.71; P < .001), and with a higher number of deep scotoma points (ß = -0.70; P < .001). We found 11 eyes with low MS (<6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent). Conclusions and Relevance: We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.

Fixation Location and Stability Using the MP-1 Microperimeter in Stargardt Disease: ProgStar Report No. 3.

PURPOSE: To determine fixation location and fixation stability in Stargardt disease (STGD1) and their association with best-corrected visual acuity (BCVA). DESIGN: Cross-sectional analysis within the multicenter, prospective ProgStar study. PARTICIPANTS: A total of 238 patients and 440 eyes with ABCA4-related STGD1. METHODS: Patients underwent testing with the Nidek MP-1 microperimeter (Nidek Technologies Inc., Gamagori, Japan). Fixation location was expressed as the eccentricity of the preferred retinal locus (PRL) from the anatomic fovea, fixation stability was expressed as the bivariate contour ellipse area (BCEA), and BCVA was expressed as Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Linear models with generalized estimating equations were used for statistical analysis while accounting for between-eye correlations. MAIN OUTCOME MEASURES: Fixation location and fixation stability. RESULTS: Median PRL eccentricity from the fovea was 6° (mean, 6.3°; range, 0°-25°) and median BCEA was 6.31°2 (mean, 12.31°2; range, 0.03°2-365.63°2). Each year of later onset of symptoms of STGD1 was associated with 0.14° more central fixation location (P < 0.0001), but not with fixation stability (P = 0.53). A single linear model best described the relationship between fixation location and BCVA: 1° farther PRL eccentricity was associated with a 2.3-letter loss of BCVA (P < 0.0001). A piecewise linear model best described the relationship between fixation stability and BCVA: for a BCEA less than 2.8°2, an increase in BCEA by 1°2 was associated with a 10.5-letter (ETDRS) lower BCVA (P < 0.0001). For a BCEA 2.8°2 or more, an increase in BCEA by 1°2 was associated with a 0.036-letter (ETDRS) lower BCVA (P = 0.0234). Pearson correlation coefficients between patients' right and left eyes were 0.89 (P < 0.0001) for fixation location and 0.25 (P = 0.0006) for fixation stability. After 10 years of disease duration, 82% of patients had eccentric PRLs in both eyes. CONCLUSIONS: We provide the first extensive database of continuous fixation parameters in STGD1 and demonstrate their association with vision. These measures allow for a more comprehensive assessment of retinal function and may serve as potential secondary outcome measures for future treatment trials for STGD1 and other macular diseases.

Training to improve reading speed in patients with juvenile macular dystrophy: a randomized study comparing two training methods.

PURPOSE: In this study, we examined the clinical application of two training methods for optimizing reading ability in patients with juvenile macular dystrophy with established eccentric preferred retinal locus and optimal use of low-vision aids. METHOD: This randomized study included 36 patients with juvenile macular dystrophy (35 with Stargardt's disease and one with Best's disease). All patients have been using individually optimized low-vision aids. After careful ophthalmological examination, patients were randomized into two groups: Group 1: Training to read during rapid serial visual presentation (RSVP) with elimination of eye movements as far as possible (n = 20); Group 2: Training to optimize reading eye movements (SM, sensomotoric training) (n = 16). Only patients with magnification requirement up to sixfold were included in the study. Training was performed for 4 weeks with an intensity of ½ hr per day and 5 days a week. Reading speed during page reading was measured before and after training. Eye movements during silent reading were recorded before and after training using a video eye tracker in 11 patients (five patients of SM and six of RSVP training group) and using an infrared reflection system in five patients (three patients from the SM and two patients of RSVP training group). RESULTS: Age, visual acuity and magnification requirement did not differ significantly between the two groups. The median reading speed was 83 words per minute (wpm) (interquartile range 74-105 wpm) in the RSVP training group and 102 (interquartile range 63-126 wpm) in the SM group before training and increased significantly to 104 (interquartile range 81-124 wpm) and 122, respectively (interquartile range 102-137 wpm; p = 0.01 and 0.006) after training, i.e. patients with RSVP training increased their reading speed by a median of 21 wpm, while it was 20 wpm in the SM group. There were individual patients, who benefited strongly from the training. Eye movement recordings before and after training showed that in the RSVP group, increasing reading speed correlated with decreasing fixation duration (r = -0.75, p = 0.03), whereas in the SM group, increasing reading speed correlated with a decreasing number of forward saccades (r = -0.9, p = 0.01). CONCLUSION: Although the median effect of both training methods was limited, individual patients benefited well. Our results may indicate a difference in the training effect between both methods on the reading strategy: the RSVP method reduces fixation duration, the SM method decreases the number of forward saccades. Patients can apply their newly learned reading strategy in the natural reading situation, e.g. in page reading without special presentation of the text. These results can be used as a basis for further improvement in training methods for optimizing reading performance in patients with a central scotoma.

Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD.

BACKGROUND: Patients with early age-related maculopathy (ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD). METHODS: Testing of the central visual field (8 degrees radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years (CTRL). In addition, 39 eyes (minimum visual acuity of 0.63;20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n = 12), or early signs of ARM (eARM; n = 27) were examined. Performance was expressed summarily as a "field score" (FS). RESULTS: Performance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and CTRLs was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the CTRL group in at least one of the lower contrast levels. CONCLUSION: Using parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.

Assessment of parafoveal function in maculopathy: a comparison between the Macular Mapping Test and kinetic Manual Perimetry.

BACKGROUND: Parafoveal function is crucial for patients with maculopathies, because they have to use the parafoveal retina for reading after foveal vision loss. Manual perimetry is a reliable but lengthy method for assessing macular function. The Macular Mapping Test (MMTest) was therefore designed as a quick and easy test. In this study both methods were compared in patients with central scotoma. METHODS: In 50 patients with maculopathy (22 Stargardt's, 20 age-related, 5 diabetic, 3 other macular dystrophies), 30 degrees Tuebingen Manual Perimetry was performed kinetically. The MMTest assesses local responses to brief displays of letters in the central visual field (8 degrees radius) on a computer screen. A "wagon-wheel" pattern is used to stabilize gaze in the center. Comparison of the methods was based on the correspondence of field defects in each sector. RESULTS: The overall correspondence was 87.5%. The results could be divided into three groups, depending on fixation behavior: group 1 ( n=27): central fixation in both methods, median correspondence 87.5%, best in Stargardt's disease (95.3%), lowest in diabetic maculopathy (71.8%); group 2 ( n=21): eccentric fixation in both methods (84.3%); group 3 ( n=2): eccentric in TMP, central in MMTest (65.6% and 81.2%). CONCLUSION: Provided that the fixation locus is known, the MMTest is a quick and easy screening method, which shows a high correspondence with the results of manual perimetry.

Support for patients loosing sight.

This overview on support of patients loosing sight is based on a literature survey regarding reading disabilities and orientation and on results of experience trials performed at the University Eye Clinic Tübingen. In reading disorders, the main goal of rehabilitation is to regain or maintain the ability to read newspaper print. The fundament of rehabilitation is the use of optical and electronical devices and the application of specially designed training programs. The ability of a person with low vision to achieve successful orientation and mobility rehabilitation depends on residual vision, posture and balance, body image, auditory and tactile abilities, intelligence and personality. Rehabilitation efforts focus on the enhancement of residual vision applying magnifying contrast-enhancing and photomultiplying devices. The main pillar of orientation and mobility rehabilitation is a training especially designed for the patient's needs. Rehabilitation efforts must be tailored to the type of vision loss and to specific functional implications--the success rate is high. An optimal fitting of the required spectrum of low vision aids should be provided to the patient and importantly, professional teaching and training is recommended. Activities of daily living, orientation and mobility, and psychological concerns must be addressed. Close cooperation with other branches of rehabilitation is essential.

[Measurement of intraocular pressure using the Tono-Pen in comparison with Goldmann applanation tonometry - a clinical study in 100 eyes]. / Messung des Augeninnendrucks mit dem Tono-Pen im Vergleich zum Applanationstonometer nach Goldmann - eine klinische Studie an 100 Augen.

BACKGROUND: In clinical practice ophthalmologists often need a tonometer which is independent of a slit lamp. Such a hand-held device is the Tono-Pen. We compared the precision of two equal Tono-Pens with Goldmann applanation tonometry. MATERIAL AND METHODS: Measurement of intraocular pressure (IOP) was done in 100 eyes of 51 patients (mean age 63 +/- 15 years) suffering from ocular hypertension or glaucoma. According to a random table either the right or left eye was measured using Goldmann tonometer first and the Tono-Pen second. For the other eye the measurement was reversed. One of the two equal Tono-Pens (Solan/USA) was used according to a second random table. Three measurements were obtained with each instrument on both eyes within 15 minutes subsequently. Patients were placed in an upright position for all measurements. RESULTS: Even for well-trained ophthalmologists a learning curve of approximately 10 measurements was observed using the Tono-Pen. The Tono-Pen measured an average IOP of 16.9 mm Hg in all 100 eyes. The Goldmann tonometer measured an average IOP of 17.7 mm Hg. The difference was not statistically significant. The standard deviation for all measurements was better for the Tono-Pen (4.7 mm Hg vs 5.8 mm Hg for Goldmann tonometer). No reduction of the IOP after Tono-Pen measurement was observed (in contrast to the Goldmann tonometer). The reproducibility of the Tono-Pen on the same eye was inferior to the Goldmann tonometer by a factor of 2. There was an almost significant difference in reproducibility between two equal Tono-Pens. CONCLUSIONS: Measurement of IOP with the Tono-Pen is comparable to Goldmann applanation tonometry if an average of 3 measurements is used. The difference between two equal Tono-Pens indicates the need for improvement of the quality check during production.