Brain structure in children with congenital visual disorders and visual impairment.

AIM: To examine if congenital visual impairment is associated with differences in brain anatomy in children. METHOD: Ten children (8-12y) with congenital disorders of the peripheral visual system with severe visual impairment (SVI; >0.8 logMAR) or mild-to-moderate visual impairment (MVI; 0.6-0.8 logMAR) were compared to 21 typically sighted comparison (TSC) children. Thalamus volume, grey matter density, white matter microstructure, and integrity of visual tracts were investigated in SVI, MVI, and TSC groups with anatomical and diffusion-weighted magnetic resonance imaging. RESULTS: Compared to the TSC group, the SVI group had lower white matter integrity in tracts of the visual system (optic radiations: SVI 0.35±0.015, TSC 0.39±0.007 [p=0.022]; posterior corpus callosum: SVI 0.37±0.019; TSC 0.42±0.009 [p=0.033]) and lower left thalamus volume (SVI 4.37±0.087; TSC 4.99±0.339 [p=0.015]). Neuroanatomical differences were greater in the SVI group, while no consistent differences between the MVI and TSC group were observed. INTERPRETATION: Posterior tracts of the visual system are compromised in children with congenital visual impairment versus those who are typically sighted. The severity of visual input appears to have affected neuroanatomical development as significant reductions were only found in the SVI group. WHAT THIS PAPER ADDS: Severe visual impairment in mid-childhood is associated with reduced integrity of visual pathways and reduced thalamus volume.

Lutein and Zeaxanthin Isomers in Eye Health and Disease.

Current evidence suggests lutein and its isomers play important roles in ocular development in utero and throughout the life span, in vision performance in young and later adulthood, and in lowering risk for the development of common age-related eye diseases in older age. These xanthophyll (oxygen-containing) carotenoids are found in a wide variety of vegetables and fruits, and they are present in especially high concentrations in leafy green vegetables. Additionally, egg yolks and human milk appear to be bioavailable sources. The prevalence of lutein, zeaxanthin, and meso-zeaxanthin in supplements is increasing. Setting optimal and safe ranges of intake requires additional research, particularly in pregnant and lactating women. Accumulating evidence about variable interindividual response to dietary intake of these carotenoids, based on genetic or metabolic influences, suggests that there may be subgroups that benefit from higher levels of intake and/or alternate strategies to improve lutein and zeaxanthin status.

Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review.

PURPOSE: Hypothalamic-pituitary (HP) neurosarcoidosis (NS) accounts for 0.5 % cases of sarcoidosis and 1 % of HP masses. Correlative data on endocrine and neurological outcomes is lacking. METHODS: Retrospective case series and literature review of presentation, treatment and outcome of HP NS. RESULTS: Our series includes 4 men, ages 34-59, followed for a median of 7.3 years (range 1.5-17). All had optic neuropathy, multiple pituitary hormone abnormalities (PHAs) and other organ involvement by sarcoidosis (lung, sino-nasal, brain/spine and facial nerve). Two patients had central diabetes insipidus and one impaired thirst with polydipsia. After treatment with high-dose glucocorticoids, optic neuropathy improved in one case and stabilized in the others. After treatment, HP lesions improved radiologically, but PHAs persisted in all cases. Review of four published series on HP NS in addition to ours yielded 46 patients, age 37 ± 11.8 years, 65 % male. PHAs consisted of anterior hypopituitarism (LH/FSH 88.8 %, TSH 67.4 %, GH 50.0 %, ACTH 48.8 %), hyperprolactinemia (48.8 %) and diabetes insipidus (65.2 %). PHAs were the first sign of disease in 54.3 % patients. Vision problems occurred in 28.3 % patients, but optic neuropathy was not well documented in previous series. Most patients (93.5 %) received high-dose glucocorticoids followed by taper; 50 % also received other immunomodulators, including methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, infliximab and hydrochloroquine. Only 13 % patients showed improvement in PHAs. All-cause mortality was 8.7 %. CONCLUSION: HP NS is a serious disease requiring multidisciplinary treatment and lifelong follow-up. Prospective multicentric studies are needed to determine a more standardized approach to HP NS and outline predictors of disease outcome.

QLT091001, a 9-cis-retinal analog, is well-tolerated by retinas of mice with impaired visual cycles.

PURPOSE: Investigate whether retinas of mice with impaired retinal cycles exposed to light or kept in the dark tolerate prolonged high-dose administration of QLT091001, which contains as an active ingredient, the 9-cis-retinal precursor, 9-cis-retinyl acetate. METHODS: Four- to six-week-old Lrat(-/-) and Rpe65(-/-) mice (n = 126) as well as crossbred Gnat1(-/-) mice lacking rod phototransduction (n = 110) were gavaged weekly for 6 months with 50 mg/kg QLT091001, either after being kept in the dark or after light bleaching for 30 min/wk followed by maintenance in a 12-hour light ≤ 10 lux)/12-hour dark cycle. Retinal health was monitored by spectral-domain optical coherent tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) every other month and histological, biochemical, and visual functional analyses were performed at the end of the experiment. Two-photon microscopy (TPM) was used to observe retinoid-containing retinosome structures in the RPE. RESULTS: Retinal thickness and morphology examined by SD-OCT were well maintained in all strains treated with QLT091001. No significant increases of fundus autofluorescence were detected by SLO imaging of any strain. Accumulation of all-trans-retinyl esters varied with genetic background, types of administered compounds and lighting conditions but retinal health was not compromised. TPM imaging clearly revealed maintenance of retinosomes in the RPE of all mouse strains tested. CONCLUSIONS: Retinas of Lrat(-/-), Rpe65(-/-), and crossbred Gnat1(-/-) mice tolerated prolonged high-dose QLT091001 treatment well.

Current concepts for diagnosis and treatment of retinoblastoma in Germany: aiming for safe tumor control and vision preservation.

Retinoblastoma affects approximately 40 children in Germany per year. Most children are diagnosed early with localized intraocular disease, and the overall survival rate exceeds 95%. However, the prognosis of metastasized retinoblastoma remains poor. In 40% of the patients, retinoblastoma occurs bilaterally and, especially for these children, the salvage of the eye and visual function is of major importance. The variety of conservative treatment options for localized retinoblastoma includes laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. While systemic chemotherapy has nearly completely replaced external beam radiotherapy in the primary treatment of intraocular retinoblastoma, intra-arterial, intravitreal and periocular application of chemotherapy was also shown to be effective in treating intraocular retinoblastoma in case series. Genetic testing is an integral part of the routine diagnostics of all patients. Available tumor material should be analyzed to detect mutational mosaicism, that affects >10% of children with unilateral retinoblastoma. Genetic testing also identifies children with heritable (50% of patients) retinoblastoma. These children have a genetic predisposition for second malignancies. For this reason, late effects are an increasing concern and the care of patients with retinoblastoma requires a multidisciplinary approach to tailor therapy and long-term follow-up. Multicenter clinical trials are being developed to evaluate evidence-based treatment concepts for localized and metastasized retinoblastoma to improve survival rates and quality of life of children with retinoblastoma.

Alzheimer's disease in the retina: imaging retinal aß plaques for early diagnosis and therapy assessment.

BACKGROUND: Definite Alzheimer's disease (AD) diagnosis at early stages is vital for targeting intervention, yet currently unavailable. Noninvasive detection of the pathological hallmark, amyloid-ß protein (Aß) plaques, is limited in the brain. However, the existence of Aß plaques in the retina, possibly at presymptomatic stages, may improve early detection of AD. OBJECTIVE: To summarize clinical and preclinical evidence showing that the retina, an accessible part of the central nervous system, displays abnormalities in AD, especially Aß plaque pathology. The ability to monitor in vivo retinal plaque dynamics in response to immunotherapy is also assessed. METHODS: Literature analysis of retinal AD pathology and imaging is provided. In our studies, systemic curcumin is administered to enable monitoring of retinal Aß plaques in live APP(SWE)/PS1(Δ)(E9) transgenic mice by optical imaging. RESULTS: Visual and retinal abnormalities, including early manifestation of retinal Aß plaque pathology, have been documented in AD patients and animal models. In mouse models, retinal Aß plaques accumulate with age and decrease in response to immunotherapy, consistent with brain pathology. Here, we demonstrate that retinal plaques can be individually monitored in real time following glatiramer acetate immunization. CONCLUSION: Translation of noninvasive retinal-plaque imaging to humans could eventually facilitate early and accurate AD diagnosis and therapy assessment.

Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices.

Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models.

Retinal spectral domain optical coherence tomography in early atrophic age-related macular degeneration (AMD) and a new metric for objective evaluation of the efficacy of ocular nutrition.

PURPOSE: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). METHODS: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. RESULTS: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: -5.5 µm/decade thinning vs. Non-AMD: -1.1 µm/decade, P < 0.02; nasal quad: -5.0 µm/decade thinning vs. Non-AMD: -1.0 µm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = -0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82-91) is needed to fully substantiate the model. CONCLUSION: A simple new SD OCT clinical metric called "% extra-foveal RT" correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the effect of repleting ocular nutrients, such as zinc, antioxidants, carotenoids, n-3 essential fats, resveratrol and vitamin D.

Optic neuropathy and a reversible splenial lesion after gastric bypass: shared pathophysiology?

A 22-year-old female presented 2months after a laparascopic gastic bypass with 3weeks of progressive painless visual loss. Ophthalmologic exam revealed severely reduced visual acuity, central scotomas, and optic nerve edema bilaterally. She was noted to have a mild encephalopathy. MRI of the brain revealed restricted diffusion in the splenium of the corpus callosum. The patient was treated with 3days of intravenous methylprednisolone, intravenous fluids, and re-institution of vitamin supplementation. Four weeks later, she had significant improvement in her visual acuity and marked reduction in central scotomas. Her encephalopathy resolved and the splenial abnormality disappeared on repeat brain MRI. This is the first reported case of a bilateral optic neuropathy and a reversible splenial lesion syndrome after gastric bypass. The presentation of both conditions in our patient may suggest a shared pathophysiology.

Low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular diseases: a pilot study.

Macular disease is one of the main causes of visual impairment. We studied the efficacy of low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular disease. Five patients were enrolled (3 female and 2 male, mean age 53.8 years) and a total of 9 eyes was examined: 2 eyes with vitelliform dystrophy, 1 with a post-traumatic macular scar, 2 with Stargardt disease, 2 with myopic macular degeneration, 2 with cone dystrophy. All the patients underwent the following tests: visual acuity, reading speed, fixation test, MP-1 microperimetry. Low-vision rehabilitation, which lasted 10 weeks, consisted of 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student's t-test. p values less than 0.05 were considered statistically significant. After training all patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity and reading speed. Fixation behaviour within the 2 degrees diameter circle improved and was statistically significant for reading speed (p = 0.01). Reading speed improved from a mean value of 64.3 to 92 words/min. Our results show that audio feedback can, by increasing attentional modulation, help the brain to fix the final preferred retinal locus. Audio feedback facilitates stimuli transmission between intraretinal neurons as well as between the retina and brain, which is where the highest level of stimuli processing occurs, thereby probably supporting a "remapping phenomenon".

Inverse stimuli in perimetric performance reveal larger visual field defects: implications for vision restoration.

PURPOSE: When studying the efficacy of vision restoration training (VRT), near-threshold and super-threshold perimetry revealed visual field enlargements whereas the Scanning Laser Ophthalmoscope (SLO) did not. Because the SLO procedure differs in many parameters from the other perimetric tests (task difficulty, inability to reveal relative defects, inverse stimulus presentation, bright red background) the question arises which of these parameters might be responsible for such discrepancies in outcome. We have therefore simulated with a computer-based campimetry test some of the SLO parameters and compared performance with that in standard perimetry. METHODS: A 46-year old female patient was evaluated with computer-based high resolution perimetry (HRP) using detection tasks of "positive" (bright) stimuli on grey background. Performance was compared with an SLO-like task using "inverse" black target stimuli on red background. RESULTS: Detection rate was 89% when the stimuli were positive (HRP) but dropped to 79.6% and 80.4% in the SLO-like "inverse" stimulation mode with red background, and striped red background, respectively. The number of false positives increased from 8.5 when a grey background was used, to 9.8 and 9.5 for plain red and striped red background, respectively. Reaction times were prolonged from 384 ms using a grey background to 412 ms and 391 ms using a plain red and striped red background, respectively. Thus, visual fields tested with SLO-like "inverse" stimuli showed larger scotomata and prolonged reaction time. CONCLUSIONS: Inverse stimulus detection on red background is apparently a more difficult task for hemianopic patients than standard perimetric protocols (such as those used in Tuebinger Automatic Perimetry or HRP). The difference in stimulus features might explain why VRT-induced visual field enlargements could not be observed with the SLO. Our findings also suggest that vision restoration training does not improve all aspects of vision, such as inverse, chromatic stimulus detection.

Effects of peripheral and central visual impairment on mental imagery capacity.

This paper reviews a number of behavioral, neuropsychological and neuroimaging studies that bear on the question of whether and how visual disorders of peripheral or central origin lead to disorders of mental imagery capacity. The review of the literature suggests that in cases of blindness of peripheral origin lack of vision can progressively lead to representational disorders. However, in patients suffering from peripheral visual deficits, representational disorders can partially or completely be compensated by other sensory modalities as well as by cortical reorganization. Interestingly, in brain-damaged patients, neurovisual disorders following occipital or parietal lesions are not systematically associated with representational deficits, thus demonstrating that visual perception and visual imagery may not rely on the same cortical structures as previously hypothesized. Impairments seen on mental imagery tasks among brain-damaged patients with visual and/or spatial deficits might be due to an often co-existing attentional deficit. We discuss this possible dissociation between visual perception and visual mental imagery and its implications for theoretical models of mental representation.

Corneal tattoo with tea infusion.

Except in animal models of cataractogenesis, the literature on the effects of tea infusion on ocular tissue is scant. In our patient, prolonged exposure to tea infusion may have led to a hypesthetic cornea with secondary limbal stem cell loss. In turn, the eye developed keratinization and corneal neovascularization.

Parkinson's disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process.

For more than 50 years, Parkinson's disease (PD) has been conceptualized as a product of nigro-striatal dopamine (NSD) system degeneration. In spite of a growing body of evidence depicting the mammalian brain as an interrelated complexity of circuitous systems, dopamine (DA) deficiency of the NSD is still regarded as the main problem, with DA replacement being the purpose of therapeutic intervention. For at least 191 years circadian involvement in various aspects of PD, including depression and insomnia, has been recognized as an integral part of the symptom matrix of PD and yet attempts to elucidate the involvement of this system is uncharted territory. The present review attempts a major reorganization of mammalian brain into a coordinated complex involving the NSD and the retinal hypothalamic tract (RHT) as the primary systems involved in the retino-diencephalic/mesencephalic-pineal (RDMP) axis. Secondary systems including the lateral hypothalamus (LH), the area postraema (AP) and the subthalamic nucleus (STN) also form an integral part of this system as they have been shown to be either intimately related to the primary systems of the RDMP axis or have been shown to be significantly involved in the expression and treatment of PD. A large volume of evidence suggests that the RDMP axis is activated during the course of PD and during therapeutic intervention. Four types of neurotoxicity associated with melatonin are identified and the susceptibility of various parts of the RDMP axis to undergo neuropathological change, the tendency for melatonin to induce PD-like behavioural toxicity, and the relationship of this to PD symptomotology are described. This includes adverse effects of melatonin on motor function, hypotension, the adjuvant use of benzodiazepines, depression, insomnia, body weight regulation and various biochemical effects of melatonin administration: all problems currently facing the proposal to introduce melatonin as an adjuvant. It is suggested further that traditional DA replacement may well work by exerting its effect upon the circadian system, rather than simply replacing deficient DA. Activation of the circadian function by antagonizing melatonin with bright light not only has therapeutic value in treating the primary symptoms of PD but it shares a common mechanism with L-dopa in reducing the occurrence of seborrheic dermatitis. Concepts at the centre of understanding pineal function in PD, including pineal calcification, melatonin deficiency, symptomatic versus protective features of melatonin and antioxidative effects, are explained in a counterintuitive context. Intriguing propositions including the role of the retina in the aetiology of PD and that the nigra functions as a retina in this disorder are presented with the intention to provide a new understanding of the underlying compromised function in PD and to provide new treatment strategies. For the first time, abundant evidence is presented describing PD as an endocrine disorder of melatonin hyperplasia. The role of circadian interventive therapies and internal desynchrony in the aetiology and progression of PD provides a new direction for understanding the underlying physiology of a disease which is currently in a state of impasse and provides new hope for those who suffer from its debilitating effects.

Thalamic atrophy in infants with PVL and cerebral visual impairment.

The aim of this retrospective study was to establish the presence and severity of cerebral visual impairment in preterm infants with PVL. We also wished to establish whether abnormalities of visual function are related to brain MRI findings and more specifically not only to the involvement of optic radiations and occipital cortex but also to changes in the thalami, that are often affected in infants with PVL. Twelve infants with cystic PVL were assessed at 1 year (+2) corrected age with a battery of tests specifically designed to assess various aspects of visual function in infancy, such as ocular movements, visual acuity, visual fields and fixation shift. All infants also had a brain MRI. Eleven of the 12 had involvement of the optic radiations: all had some abnormalities of visual function and visual impairment was more severe in infants with more extensive involvement of the optic radiations. The child with normal optic radiations had normal visual function. Six of the 12 infants also had obvious signs of atrophy of the thalami and all had severe and wide-ranging abnormalities of visual function in all testing domains. Two children had equivocal atrophy of the thalami, both had some abnormalities of visual function. Four children had normal thalami and had normal visual function or only minor abnormalities on one of the visual tests. Our results suggest that the atrophy of the thalami may play an additional role in the abnormal development of visual function in infants with PVL and abnormal optic radiations.

Hyperbaric oxygen therapy reduces visual field defect after macular hole surgery.

BACKGROUND AND OBJECTIVE: One of the serious complications that may arise after macular hole (MH) surgery is a temporal visual fields (TVF) defect. We hypothesized that hyperbaric oxygen (HBO) therapy improves the visual field (VF) in these patients. MATERIALS AND METHODS: Vitrectomy for MH was performed on 73 eyes from 1994 to 1997. TVF defect was detected in 19 eyes and, of that 19, 12 patients were followed. Seven patients were treated with HBO therapy and 5 were controls. HBO was performed for approximately 110 minutes a day with 100% oxygen inhalation and a maximum of 2.8 atmospheric pressure. This continued for 20 days. The preoperative VF determined by kinetic perimetry was considered to be 100%, and the VF following HBO therapy was compared with that standard. RESULTS: We detected VF defect (postoperative VF area average 71.9+/-12.8% of the preoperative VF). In all 5 patients who had no HBO therapy, TVF defects remained, while the TVF recovered remarkably in all patients treated with HBO therapy. The VF recovered to 81.7+/-16.7% of the preoperative VF after 3 days of HBO, and to 91.6+/-15.8% months after HBO therapy. CONCLUSION: We speculated that the cause of TVF defect is likely to be chorioretinal circulation disturbance during surgery, and that HBO activates the retinal cells and improves VF. We conclude that HBO is useful in the treatment of TVF defect after macular hole surgery.

Neglect in vision and visual imagery: a double dissociation.

We report two patients with right hemisphere lesions who demonstrate a double dissociation on visual imagery and visual perceptual tasks. One (M.N.) performed normally on a variety of standard tests for neglects as well as on measures of visual attention known to be sensitive to the presence of neglect, yet failed to report items from the left side of an imagined scene. In contrast, the other (C.I.) performed normally on tests of visual imagery but demonstrated substantial neglect on visual perceptual and visual attentional tasks. These data are not readily accommodated by accounts which attribute neglect to a single processing deficit, but suggest that the disorder is a heterogeneous syndrome attributable to disruptions of different aspects of spatial cognition.

Visual function in patients undergoing long-term total parenteral nutrition.

To evaluate the effects of long-term total parenteral nutrition (TPN) on eye function, 27 adults and 12 children in the UCLA Home TPN Clinic underwent ophthalmoscopic examination and visual-function testing. Direct inspection of the fundus showed a marked granularity of the retinal pigmented epithelium in some patients. About one-half of the children and one-third of the adults tested had at least one and usually two abnormalities in their electroretinogram. Determination of blood nutrients thought to affect vision revealed that zinc and vitamin E were within normal range. Vitamin A concentrations were above normal in 10 of 19 adults and selenium concentrations were below normal in 10 of 10 children and 17 of 21 adults tested. Linoleic and linolenic acid concentrations were low; plasma, platelet, and urine taurine concentrations were significantly lower than normal. Despite these diffuse nutrient abnormalities, only zinc and vitamin E concentrations correlated significantly with any index of visual function.

Optic pit versus glaucomatous cupping in a myopic patient.

A myopic patient with bilaterally deep cupping of her optic discs and an arcuate scotoma in the bjerrum area in the right eye and borderline IOP is presented. The problem of diagnosing a glaucomatous process in this patient is discussed.