The Michigan Vision-Related Anxiety Questionnaire: A Psychosocial Outcomes Measure for Inherited Retinal Degenerations.

OBJECTIVE: We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations. DESIGN: Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback. METHODS: Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of "worry" and "anxiety." The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis-Hastings Robbins-Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test-retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later. RESULTS: The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test-retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety). CONCLUSIONS: The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.

Inherited retinal degeneration current genetics practices - a needs assessment.

BACKGROUND: Clinical assessment of patients with IRD often includes thorough documentation of medical and ocular history in addition to genetics related practices like assessing the family history and genetic testing. Previous studies have demonstrated the genetic counseling needs of IRD patients are not being fully met, but there is a lack of literature showing the current genetics practices of ophthalmologists and optometrists in the U.S. The goal of this study is to assess the current genetics related practices being provided to patients with IRD. METHODS: Data from 51 survey participants were included in the analysis. The survey assessed their current practices of risk counseling to patients with IRD, their confidence level of ocular genetics, and resources they may utilize in the future. Descriptive statistics were used to summarize quantitative data while data from open ended responses were coded using thematic analysis generated through grounded theory. RESULTS: Responses suggest some discussion of genetics is occurring with IRD patients. However, there are limitations to these discussions given time constraints and lack of understanding of the genetics of IRDs and available testing. The study also revealed that there are minimal referrals to genetic counseling being made at this time, though there is interest in working with genetic counselors. Additionally, there is a need for continued education regarding the genetics related to IRDs. CONCLUSION: Future larger-scale studies are warranted to provide additional insight into these genetics related practices and where genetic counselors are needed in this field.

Psychosocial assessment of potential retinal prosthesis trial participants.

BACKGROUND: As the field of retinal prostheses advances, volunteers are required for device trials, and optimal participant recruitment is vital for intervention success. The aims of this study were: (i) to select tests that assess the psychosocial aspects of visual impairment and develop a psychosocial assessment protocol for persons who may be eligible for participation in retinal prostheses trials; (ii) to investigate correlations between these tests; and (iii) to determine associations between psychosocial factors and a person's interest in participating in a retinal prosthesis (bionic eye) trial. METHODS: Cross-sectional study of 72 adults with advanced retinal degeneration. Questionnaire assessments included personality, cognitive ability, social-support, self-efficacy, coping, optimism, depression, and quality of life (Impact of Vision Impairment Profile ([IVI], and Vision and Quality of Life Index [VisQoL]). Level of interest in a retinal prosthesis was also evaluated. RESULTS: All questionnaires were completed without floor or ceiling effects and with minimal respondent burden. Depression correlated with decreased quality of life (rho = -0.37 and 0.40, p < 0.001 for IVI and VisQoL, respectively). Together, depression, gender and vision-specific coping explained 35.2 per cent of variance in IVI quality of life (p < 0.001). Forty-nine per cent of participants were interested in a retinal prosthesis now and 77 per cent in the future. Although the personality trait of 'openness' was somewhat predictive of interest in retinal prostheses (odds ratio 0.78, 95% CI 0.62-0.97), neither severity of vision impairment nor any of the psychosocial measures were strong predictors. CONCLUSIONS: Several existing psychosocial questionnaires can be used for patients with advanced retinal degeneration and may be useful in exploring suitability for a retinal prosthesis or evaluating outcomes. However, the questionnaires used in this study were not good predictors of whether or not a person might be interested in a retinal prosthesis.

Optical coherence tomography findings in patients with bipolar disorder.

BACKGROUND: Research in bipolar disorder suggests the presence of structural brain abnormalities. It is not clear whether these findings are trait markers or operate with the onset and progress with disease severity and duration. Optical coherence tomography (OCT) is a non-invasive technique that detects degenerative changes in the retina reflecting brain degeneration. This study aimed at detecting these changes and relating them to disease severity and clinical characteristics. METHODS: A case-control study conducted in Psychiatry and Addiction Medicine hospital, Faculty of Medicine at Cairo University. Forty inpatients with bipolar disorder -according to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) - were compared to forty matched healthy controls. Patients were subjected to the Structured Clinical Interview of DSM-IV (SCID-I), Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). Both patients and controls were subjected to OCT. RESULTS: Patients showed thinning of Retinal Nerve Fiber Layer (RNFL) relative to control subjects in most of the OCT parameters including Right average (p<.001 and 95% CI [14.39, 19.84]), Lt average (p<.001 and 95% CI [13.03, 19.42]). Patients also showed decreased Ganglionic Cell Complex (GCC) significantly in Rt average (p=.002 and 95% CI [2.33, 9.78]), Lt average (p<.001) and 95% CI [4.47, 11.63]. Age at onset, number of episodes, and severity did not significantly correlate with OCT parameters. LIMITATIONS: The small sample and absence of follow-up. CONCLUSIONS: Patients with bipolar disorder show degenerative changes detected by OCT in relation to healthy controls.

Relación entre autoconcepto y nivel de depresión en personas con retinosis pigmentaria / Relationship between self-concept and depression level in people with retinitis pigmentosa

Investigaciones previas han resaltado dificultades en autoconcepto y presencia de depresión en personas con una patología degenerativa visual (retinosis pigmentaria), pero no se conoce si existe relación entre estas variables, la estimación del número de personas de apoyo en caso de necesidad y la edad; siendo éste el primer objetivo del estudio, realizado con 51 personas (36.5% hombres y 63.5% mujeres) (M edad = 41.85) que padecen esta problemática; y determinar, en segundo lugar, si el nivel de depresión influye en el autoconcepto. Se utilizó la Escala de Autoconcepto Tennesse (Fitts, 1965), el Inventario de Depresión de Beck (Beck, Rush, Shaw, y Emery, 1979) y un documento sociodemográfico. La correlación de Pearson revela que el número de personas de apoyo correlaciona con los factores de autoconcepto físico y personal, la edad con puntuaciones más altas en depresión, asociándose ésta a menores puntuaciones justo en los dos factores mencionados. El MANCOVA efectuado confirma que las personas con depresión se percibían más negativamente en todos los factores de autoconcepto. Se concluye recomendando prevenir la depresión y favorecer la mejora del autoconcepto con el fin de potenciar la competencia personal, calidad de vida y funcionamiento visual de esta población

Previous studies have highlighted difficulties in self-concept and the presence of depression in people with a degenerative visual pathology visual (Retinitis Pigmentosa), but it is not known if there is a relationship between these variables, the estimate of the number of support people in case of need and age; this being the first objective of the study, carried out with 51 people affected (36.5% men and 63.5% women) (M age = 41.85); and secondly, to analyze if depression level could influence some selfconcept factors. Instruments such as the Tennessee Self-Concept Scale (Fitts, 1965), the Beck Depression Inventory (Beck, Rush, Shaw, & Emery, 1979) and a sociodemographic questionnaire were used. A Pearson's correlation analysis revealed that the number of support people correlates with the factors of physical and personal self-concept, age is associated with higher scores on depression, associating this to lower scores in the two factors above-mentioned. The MANCOVA made confirms that people with higher level of depression were perceived more negatively in all selfconcept factors. It concludes recommending to prevent depression and to promote the improvement of the self-concept, in order to enhance the personal competence, the quality of life and visual functioning of this people

Red-Tinted Contact Lenses May Improve Quality of Life in Retinal Diseases.

Supplemental digital content is available in the text. ABSTRACT: To determine the benefits provided by centrally red-tinted contact lenses on visual acuity, contrast sensitivity (CS), photophobia, and quality of life in patients with degenerative retinal diseases.We evaluated the impact of centrally red-tinted hydrogel contact lenses on nine patients (aged 15 to 22 years) with severe photophobia and poor visual acuity. Each patient underwent a full eye examination with and without contact lenses, including visual acuity at distance and near, CS, eye movement recording for nystagmus, refraction, and a fundus examination. All patients completed a low vision-adapted VFQ 25-Version 2000 quality-of-life questionnaire.Seven of nine patients demonstrated improvement in binocular visual acuity as well as improvement in CS with the tinted contact lenses. Subjectively, all patients described a major improvement in their photophobia both outdoors and indoors, as well as a marked improvement in quality of life.Red-tinted contact lenses may dramatically improve visual functions, outdoor performance, and quality of life of patients suffering from retinal diseases. These lenses should be a part of the regular assessment in specialty clinics treating patients with low vision, glare, and photophobia.

The role of whiskers in compensation of visual deficit in a mouse model of retinal degeneration.

Sensory deprivation in one modality can enhance the development of the remaining modalities via mechanisms of synaptic plasticity. Mice of the C3H strain suffer from RD1 retinal degeneration that leads to visual impairment at weaning age. We examined a role of whiskers in compensation of the visual deficit. In order to differentiate the contribution of the whiskers from other mechanisms that can take part in the compensation, we investigated the effect of both chronic and acute tactile deprivation. Three-month-old mice were used. We examined motor skills (rotarod, beam walking test), gait control (CatWalk system), spontaneous motor activity (open field) and CNS excitability to an acoustic stimulus for assessment of compensatory changes in auditory system (audiogenic epilepsy). In the sighted mice, the only effect was a decline in their rotarod test performance after acute whisker removal. In the blind animals, chronic tactile deprivation caused changes in their gait and impaired the performance in motor tests. Some other compensatory mechanisms were involved but the whiskers are essential for the compensation as it emerged from more marked change of gait and the worsening of the motor performance after the acute whisker removal. Both chronic and acute tactile deprivation induced anxiety-like behaviour. Only a combination of blindness and chronic tactile deprivation led to an increased sense of hearing.

Emotional state of family members of adults with retinal degeneration / Estado emocional de familiares de adultos con degeneración retiniana

Various studies have documented the emotional changes that accompany the loss of vision in people with retinal degeneration (such as Retinitis Pigmentosa), but the emotional state of family members who live with them has not been extensively studied. However it is known that chronic diseases have repercussions not only on the well-being and quality of life of those affected, but also on their families, possibly making them more susceptible to depression and/or anxiety. Results from 37 family members tested against a control group (38 people) partially supported our hypothesis and revealed that the family members showed higher levels of anxiety, especially the women, whereas partners showed higher scores in depression. The findings indicated that the family members should be receiving some kind of support to help them to resolve problems associated with the progression of the visual pathology (AU)

Distintos estudios han documentado los cambios emocionales que acompañan a la pérdida de visión en personas con degeneración retiniana (como la retinosis pigmentaria), pero el estado emocional de miembros de la familia que conviven con ellas, no ha sido muy estudiado. Sin embargo, es conocido que la presencia de enfermedades crónicas no sólo repercute en el bienestar y calidad de vida de los afectados, sino también en el de sus familiares, haciéndoles posiblemente más vulnerables a la depresión y o la ansiedad. Los resultados obtenidos de 37 miembros de familias de personas afectadas, frente a un grupo control (38 personas), apoya parcialmente nuestra hipótesis y revela que los primeros mostraban niveles más altos de ansiedad, principalmente las mujeres; mientras las parejas de afectados presentaban puntuaciones más altas en depresión. Los hallazgos indicaban que los miembros de familias de personas afectadas deberían recibir algún tipo de apoyo para ayudarles a resolver problemas asociados al avance de la patología visual (AU)

Pain perception at laser treatment of peripheral retinal degenerations with green and infrared wavelengths.

PURPOSE: To compare the pain perception at laser treatment of peripheral retinal degenerations with green (532-nm) and infrared (810-nm) wavelengths. DESIGN: Prospective randomized clinical trial. METHODS: Sequential patients with indications for photocoagulation of bilateral peripheral retinal degenerations were invited to participate in the study. Thirty patients (60 eyes) were enrolled in the study. Each patient had 1 eye treated with infrared laser (diode, 810-nm wavelength) and the other eye treated with green laser (frequency-doubled solid-state laser, diode-pumped, with 532-nm wavelength). The eyes were randomized to infrared or green wavelengths. The right eye was the first treated in all cases regardless of the wavelength arrangement. Immediately after photocoagulation of each eye, the patient was asked to grade pain perception according to an 11-point (ie, 0-10) numerical rating scale (NRS), with 0 meaning "No pain" and 10 meaning "Pain as bad as you can imagine." The primary outcome was the assessment of pain. RESULTS: The mean grading of pain perception was 2.80 (SD 1.27; mode and median = 2) to green wavelengths and 5.07 (SD 1.36; mode = 4 and median = 5) to infrared wavelengths (P < .001). CONCLUSIONS: The results showed a statistically and clinically significant difference of pain perception between the 2 groups, with advantage to the green laser group.

Negative and positive masking responses to light in retinal degenerate slow (rds/rds) mice during aging.

Bright light suppresses locomotor activity in mice (negative masking) but dim light augments activity (positive masking). Retinal degeneration slow mice (rds/rds) were tested for responses to light at 3 months, 1 and 2 years old. The suppressive effect of light increased between 1 and 2 years, but the positive response to dim lights was severely reduced at 1 year. No such effects occurred in aging wildtypes. The results indicate that enhancement of negative masking depends on the degree of degeneration of the classical photoreceptors, and that residual function in photoreceptors lacking outer segments is initially sufficient for positive masking.

A computational model of perceptual fill-in following retinal degeneration.

The ablation of afferent input results in the reorganization of sensory and motor cortices. In the primary visual cortex (V1), binocular retinal lesions deprive a corresponding cortical region [lesion projection zone (LPZ)] of visual input. Nevertheless, neurons in the LPZ regain responsiveness by shifting their receptive fields (RFs) outside the retinal lesions; this re-emergence of neural activity is paralleled by the perceptual completion of disrupted visual input in human subjects with retinal damage. To determine whether V1 reorganization can account for perceptual fill-in, we developed a neural network model that simulates the cortical remapping in V1. The model shows that RF shifts mediated by the plexus of spatial- and orientation-dependent horizontal connections in V1 can engender filling-in that is both robust and consistent with psychophysical reports of perceptual completion. Our model suggests that V1 reorganization may underlie perceptual fill-in, and it predicts spatial relationships between the original and remapped RFs that can be tested experimentally. More generally, it provides a general explanation for adaptive functional changes following CNS lesions, based on the recruitment of existing cortical connections that are involved in normal integrative mechanisms.

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: improved restoration of visual function.

The aim of this study was to evaluate the functional efficacy of retinal progenitor cell (RPC) containing sheets with BDNF microspheres following subretinal transplantation in a rat model of retinal degeneration. Sheets of E19 RPCs derived from human placental alkaline phosphatase (hPAP) expressing transgenic rats were coated with poly-lactide-co-glycolide (PLGA) microspheres containing brain-derived neurotrophic factor (BDNF) and transplanted into the subretinal space of S334ter line 3 rhodopsin retinal degenerate rats. Controls received transplants without BDNF or BDNF microspheres alone. Visual function was monitored using optokinetic head-tracking behavior. Visually evoked responses to varying light intensities were recorded from the superior colliculus (SC) by electrophysiology at 60days after surgery. Frozen sections were studied by immunohistochemistry for photoreceptor and synaptic markers. Visual head tracking was significantly improved in rats that received BDNF-coated RPC sheets. Relatively more BDNF-treated transplanted rats (80%) compared to non-BDNF transplants (57%) responded to a "low light" intensity of 1cd/m2 in a confined SC area. With bright light, the onset latency of SC responses was restored to a nearly normal level in BDNF-treated transplants. No significant improvement was observed in the BDNF-only and no surgery transgenic control rats. The bipolar synaptic markers mGluR6 and PSD-95 showed normal distribution in transplants and abnormal distribution of the host retina, both with or without BDNF treatment. Red-green cones were significantly reduced in the host retina overlying the transplant in the BDNF-treated group. In summary, BDNF coating improved the functional efficacy of RPC grafts. The mechanism of the BDNF effects--either promoting functional integration between the transplant and the host retina and/or synergistic action with other putative humoral factors released by the RPCs--still needs to be elucidated.

Behavioral and anatomical abnormalities in a sodium iodate-induced model of retinal pigment epithelium degeneration.

We characterized changes in the visual behavior of mice in which a loss of the retinal pigment epithelium (RPE) was experimentally induced with intravenous (i.v.) administration of sodium iodate (NaIO3). We compared and correlated these changes with alterations in neural retinal structure and function. RPE loss was induced in 4-6 week old male C57BL/6 mice with an i.v. injection of 1% NaIO3 at three concentrations: 35, 50, or 70 mg/kg. At 1, 3, 7, 14, 21, and 28 days (d) as well as 6 months post injection (PI) a behavioral test was performed in previously trained mice to evaluate visual function. Eye morphology was then assessed for changes in both the RPE and neural retina. NaIO3-induced RPE degeneration was both dose and PI time dependent. Our low dose showed no effects, while our high dose caused the most damage, as did longer PI times at our intermediate dose. Using the intermediate dose, no changes were detectable in either visual behavior or retinal morphology at 1 d PI. However, at 3 d PI visual behavior became abnormal and patchy RPE cell loss was observed. From 7 d PI onward, changes in retinal morphology and visual behavior became more severe. At 6 months PI, no recovery was seen in any of these measures in mice administered the intermediate dose. These results show that NaIO3 dosage and/or time PI can be varied to produce different, yet permanent deficits in retinal morphology and visual function. Thus, this approach should provide a unique system in which the onset and severity of RPE damage, and its consequences can be manipulated. As such, it should be useful in the assessment of rescue or mitigating effects of retinal or stem cell transplantation on visual function.

ENU-induced late-onset night blindness associated with rod photoreceptor cell degeneration in zebrafish.

We describe a dominant mutation, night blindness d (nbd), that causes late-onset rod photoreceptor cell degeneration in zebrafish. The mutation was induced by treating male zebrafish with N-ethyl-N-nitrosourea (ENU). Visual sensitivity was tested using a behavioral assay based on a visually mediated escape response. At a young age, the heterozygous (nbd+/-) fish did not show any signs of night blindness or retinal degeneration. At 2 years, their behaviorally assessed visual sensitivity was decreased, albeit no alterations in the electroretinogram (ERG) were detected. Histology revealed that in the mutant retinas the rod photoreceptor cell outer segments (ROS) were thinned out. In homozygous larvae (nbd-/-), mass neural degeneration was detectable at about 2 days post fertilization (dpf). They died at an early age, usually no later than 8 dpf. In conclusion, nbd is a dominant mutation that causes late-onset night blindness with slow progression. However, nbd is not photoreceptor cell-specific, as becomes clear from the systemic dysfunctions of the homozygous larvae.

[Retinopathia centralis serosa--stomach ulcer of ophthalmology?]. / Retinopathia centralis serosa--Magengeschwür der Augenheilkunde?

Centralis serosa retinopathy is regarded in ophthalmology as a psychosomatic disease, although this assumption has not been satisfactorily proven so far. With the use of the Freiburg Personality Inventory (FIP, [4]), the questionnaire for the evaluation of psychosomatic pathological processes [10], and by recording the affliction undergone by stressful events in the patients' lives, the question as to whether a psychogenic contributory cause existed was examined with a control group study (n = 11), parallelised according to age and sex. The results proved significantly that there was a psychosomatic connection, specifically a tendency to somatisation in patients with centralis serosa retinopathy. However, it was not possible to compile a typical personality profile, although it was possible to describe some conspicuous personality features. As a conclusion, the consequences for a subsequent study are being discussed.

Thresholds for masking responses to light in three strains of retinally degenerate mice.

Mutant mice with retinal degeneration (rd/rd) were given 1-h pulses of light of varying brightness at times of the night when they would normally be active. The mutant mice showed a significantly greater inhibition of locomotor activity to light (negative masking) than wildtype controls. Lack of impairment, or even enhancement of negative masking suggests that this response may depend on sparing in retinally degenerate mice of the same receptor type that mediates clock resetting, because synchronization of the circadian system is known to be unimpaired in these mutants. With very dim light pulses, mutants did not change their activity, but wildtypes actually became more active (positive masking). Positive and negative masking appear to depend on different sensory and central processes.

Spatial responses to light in mice with severe retinal degeneration.

It is known that mice homozygous for the retinal degeneration (rd) mutation are able to synchronize their circadian rhythms to light-dark cycles. In the present experiments mice were given a choice of a dark or an illuminated living and nesting area. C3H, CBA and C57 rd/rd mice spent more time in the dark than in the illuminated area. Also, they spent as much time in the dark area as did wildtype controls. This shows that, despite advanced retinal degeneration, light can be used to control behaviour in space as well as in time. This was true of mutant mice over a year old, when retinal degeneration is very severe, and also of a transgenic strain of mice whose rods are destroyed as they begin to develop in the first few weeks after birth.

Congenital retinal dystrophies: a study of early cognitive and visual development.

The reported incidence of mental retardation in Leber's congenital amaurosis has varied from 10% to 87%. There has been no review of the estimate since it became possible to delineate an increasing number of diagnostic subcategories. In this study, the visual and cognitive development of 38 children with congenital retinal dystrophies has been followed up prospectively. Children with associated disorders in other systems and those with central nervous system malformations or degenerations were significantly more likely to have learning disability than those without additional medical problems. Most subgroups made little or no visual progress with the exception of the group with associated hypoplasia of the cerebellar vermis. The study highlights the importance of using the specialised techniques now available to delineate fully the visual diagnosis and paediatric perspective because of their relevance to cognitive and visual prognosis.

[The psychophysiological basis of the compensatory development of visual perception in vision disorders]. / Psikhofiziologicheskoe obosnovanie kompensatornogo razvitiia zritel'nogo vospriiatiia pri narusheniiakh zreniia.

At comparison of the data obtained in psychophysical and electrophysiological studies, disturbances were revealed of neurophysiological mechanisms of visual perception in children with the diseases of retinocortical tract. For compensation of the disturbances and development of perception a method is suggested of specific activation of neuronal formations based on their fundamental property--plasticity. The method consists in using rhythmical repeated stimulation of eyes with images which widely vary by the brightness, contrast, colour, form, orientation and spatial position in the visual field. Experimental verification of the method was conducted by a special program of correction studies with children having weak and residual sight. After 2-3 years of studies a significant increase was observed of probability of correct recognition of images by one parameter or combination of two parameters, increase of perception volume and improvement of its other properties. It is supposed that activation of sensory information processes lowers the level of deprivation and mobilizes reserve mechanisms of compensation in the projection and associative areas of the cerebral cortex.