The Effect of Blindness on Biological Rhythms and the Consequences of Circadian Rhythm Disorder.

Various physiological systems and behaviors such as the sleep-wake cycle, vigilance, body temperature, and the secretion of certain hormones are governed by a 24-hour cycle called the circadian system. While there are many external stimuli involved the regulation of circadian rhythm, the most powerful environmental stimulus is the daily light-dark cycle. Blind individuals with no light perception develop circadian desynchrony. This leads to non-24-hour sleep-wake rhythm disorder, which is associated with sleep-wake disorders, as well as mood disorders and loss of appetite and gastrointestinal disturbances due to disrupted circadian hormone regulation. As the diagnosis is often delayed because of under-recognition in clinical practice, patients must cope with varying degrees of social and academic dysfunction. Most blind individuals report that non-24-hour sleep-wake rhythm disorder affects them more than blindness. In the treatment of totally blind patients suffering from non-24-hour sleep-wake rhythm disorder, the first-line management is behavioral approaches. Drug therapy includes melatonin and the melatonin agonist tasimelteon. Diagnosing blind individuals' sleep disorders is also relevant to treatment because they can be improved with the use of melatonin and its analogues or by phototherapy if they have residual vision. Therefore, assessing sleep problems and planning treatment accordingly for individuals presenting with blindness is an important issue for ophthalmologists to keep in mind.

Unexpected amaurosis occurring after peribulbar anesthesia: Exploring the causes in two cases.

Peribulbar anesthesia (PB) is known to be safer than retrobulbar (RB) anesthesia. To our knowledge, no amaurosis has been described after PB. We report here the cases of two patients who underwent PB before membrane peeling. The injections were administered with a 25-gauge, 22-mm bevel disposable needle. The anesthetic used was ropivacaine 1% with a volume of 8 ml and 75 µg of clonidine as an adjuvant (7.5 µg/ml). Given that complete akinesia was not achieved, a second injection of 2 ml was administered in the supero-medial injection site. Thirty minutes after the PB, the first patient experienced amaurosis with no light perception (LP). The ophthalmic examination was normal. Visual acuity recovered after 1 day. Regarding the second patient, the loss of VA was observed 20 min after the PB. IOP was 20 mmHg. The anterior segment and fundus exam were normal. Rubin found the PB technique to be as effective and safer than RB injection, as the needles are not supposed to enter the RB space and Davis and Mandel found no amaurosis after PB. PB is administered via the extraconal injection of an anesthetic agent. These amaurosis might be explained by the fact that some anesthetic may have penetrated the RB space. In cases where two PB injections are administered, the anatomy is expected to change due to the volume effect of the first injection. The second injection is higher risk as it is administered closer to the optic nerve.

Alternativas terapéuticas de la úlcera corneal infecciosa / Therapeutic alternativesfor the infectious corneal ulcer

Introducción: La úlcera corneal infecciosa es una afección frecuente en la consulta de oftalmología. Su resolución es un problema de salud a resolver, pues los tratamientos convencionales no siempre garantizan una evolución favorable de los casos diagnosticados debido a la resistencia microbiana, por lo que se siguen buscando alternativas terapéuticas. Objetivo: Describir las alternativas de tratamiento en la úlcera corneal infecciosa para minimizar sus secuelas y disminuir la ceguera por esta enfermedad. Desarrollo: La administración tópica de antibióticos de amplio espectro sigue siendo el método preferido para el tratamiento farmacológico de las úlceras corneales infecciosas, a pesar de los informes de fracasos clínicos por la resistencia a los antibióticos, por lo que se investiga acerca del uso de nuevas alternativas terapéuticas que minimicen las secuelas de esta enfermedad.Se realizó una revisión sistemática de la evidencia científica en los últimos diez años en diversos artículos, en los que se constató la aplicación de diferentes sustancias como tratamiento alternativo. Conclusiones: En la úlcera corneal infecciosa el tratamiento protocolizado combinado con sustancias alternativas, que tienen en común una actividad de amplio espectro, resultaría ser ventajoso por ser productos económicos y seguros, que han demostrado un gran poder bactericida. Se propone generalizar el uso de estos compuestos, dada la resistencia de los microorganismos al tratamiento convencional; lo que hace que la úlcera corneal sea un problema de salud a resolver.

Introduction: The infectious corneal ulcer is a frequent disorder in the ophthalmology outpatient department, its solution is a health problem to be solved, as the conventional treatments don't always guarantee a favorable clinical course of the diagnosed cases. Because of the microbial resistance, so that therapeutic alternatives are still looked for. Objective: To describe the treatment alternatives in the infectious corneal ulcer for minimizing their sequelae and to decrease blindness due to this disease. Development: The topical administration of wide spectrum antibiotics continues being the favorite method for the pharmacological treatment of the infectious corneal ulcers, in spite of the clinical failures reports caused by the resistance to antibiotics, that is why the use of new therapeutic alternatives minimizing the sequels of this disease is investigated. Method: A systematic review of the scientific evidence in the last ten years was carried out on several works, in which it was evidenced the use of different substances as alternative treatment. Conclusions: In the infectious corneal ulcer the protocolized treatment combined with alternative substances which have in common a wide spectrum activity would turn out to be advantageous as they are economic and sure products which have demonstrated a great power against bacteria. The use of these compounds could be generalized, given the resistance of organisms to the conventional treatment; what makes the corneal ulcer a health problem to be solved.

Complete unilateral vision loss and optic nerve cupping from metastatic prostate cancer to the optic canal.

A 71-year-old man, living with metastatic castrate-resistant prostate cancer to the lymph nodes, spine and skull, presented with acute on chronic left eye vision loss. Examination revealed no-light-perception vision, a relative afferent pupillary defect and optic disc cupping. MRI brain revealed optic canal narrowing from metastatic sphenoid bone expansion and extraosseous tumour compressing the intracanalicular optic nerve. The optic disc cupping and excavation without significant pallor of the remaining neuroretinal rim was likely secondary to chronic compression of the optic nerve. The patient was treated with radiation therapy, but did not regain vision and was referred to palliative care as his condition continued to worsen. As patients live longer with advanced cancer, there is a greater risk of metastasis to atypical areas of the body including the optic nerve. This case demonstrates the unique combination of optic disc cupping from optic canal metastasis due to prostate cancer.

Light Perception Vision Recovery After Treatment for Calcium Hydroxylapatite Cosmetic Filler-Induced Blindness.

A 51-year-old woman presented with no light perception vision of the right eye 12 hours after another provider injected calcium hydroxylapatite into the glabella and dorsum of the nose. Exam and fluorescein angiography demonstrated optic nerve edema and choroidal hypoperfusion consistent with ischemia of the posterior ciliary circulation. The central retinal circulation appeared intact. One thousand two hundred units of retrobulbar hyaluronidase were injected urgently in several boluses. Oral prednisone and aspirin also were administered. Ocular massage was also initiated. One day later, visual acuity improved to light perception that remained stable at 3 months. Retrobulbar hyaluronidase injection, ocular massage, prednisone, and aspirin were correlated to recovery of light perception vision in this case of calcium hydroxylapatite filler embolization to the choroidal circulation. The mechanism for the recovery of some vision and the role of hyaluronidase and other medications remain uncertain. Further research in treatments for ophthalmic complications of facial fillers is warranted.

Severe vision loss caused by cosmetic filler augmentation: Case series with review of cause and therapy.

Hyaluronic acid (HA) injection is a popular nonsurgical, facial rejuvenating procedure. Due to the rapidly expanding use of HA injections, significant potential complications have also increased in frequency. Among these complications, the rare but most devastating one is arterial occlusion, which can result in skin necrosis or blindness. To describe the mechanisms behind vision loss secondary to hyaluronic acid injection and the efficacy of treatments to restore vision and associated ocular functionality. We reviewed six cases of patients from October 2011 to December 2017 who experienced vision loss after receiving facial HA injections and the subsequent treatments undertaken to attempt to reverse the vision loss and additional eye complications. Of the six patients, four received nose, one received forehead, and another one received temple injections. All six patients developed vision loss secondary to hyaluronic acid embolization in retinal or ophthalmic arteries. Additional complications included severe periorbital pain, ptosis, impairment of extraocular muscle functionality. Recovery of vision was dependent on the type, frequency, and duration of subsequent treatment. Vision loss is a rare but catastrophic complication caused by hyaluronic injection that occurs secondary to hyaluronic acid embolization in retinal or ophthalmic arteries due to retrograde flow from facial vascular anastomoses. We suggest the early supratrochlear/supraorbital hyaluronidase injection, ocular massage, and re-breathing into a plastic bag as safe, uncomplicated and effective methods to restore the retinal circulation and reverse vision loss.

Subconjunctival hemorrhage and vision loss after regional ocular anesthesia.

PURPOSE: To report two cases of retinal vascular occlusion and associated subconjunctival hemorrhage in needle optic nerve injury during local bulbar anesthesia. METHODS: Surgical records of these two subjects who presented with acute vision loss after cataract extraction were studied, and systemic workup and ocular imaging were carried out to establish the cause. RESULTS: Computerized tomography showed evidence of optic nerve injury. CONCLUSION: Subconjunctival hemorrhage could be an associated clinical finding in hypodermic needle injury-related retinal vascular occlusion during ocular anesthesia.

[Ophthalmological rehabilitation of visually impaired children]. / Ophthalmologische Rehabilitation sehbehinderter Kinder.

BACKGROUND: There are very few studies on visually impaired children in Germany; therefore, the aim of this study was to investigate the current spectrum of diseases of visually impaired children and the care of these children in schools and kindergartens with aids and integrative support. PATIENTS AND METHODS: In a retrospective study all children (n =303) who attended the outpatient department for the visually impaired of the University Eye Hospital Tübingen in 2013 and 2014 were evaluated. The target values were ophthalmological diagnosis, best corrected visual acuity, needs for magnification, prescribed aids, measures for early support and integrative care and inclusion during schooltime. RESULTS: The most frequent diagnosis in this collective which led to visual impairment in children was optic atrophy (22.4%) followed by hereditary retinal dystrophy (18.5%), congenital nystagmus (9.9%), albinism (8.6%), retinopathy of prematurity (ROP, 7.9%), aniridia (4.6%), cerebral visual impairment (CVI, 4.3%) and severe myopia (3%). Of the children 21% suffered from multiple disabilities, 66% were visually impaired (visual acuity ≤0.3 and >0.05), 9% were severely visually impaired (visual acuity ≤0.05) and 6% were legally defined as blind (visual acuity ≤0.02). Of the schoolchildren 52% (n = 241) were able to visit a mainstream school within the framework of integrative care. For 77% of these schoolchildren integrative care was already provided by a special pedagogic institution at the time of presentation for school entry and 73% of all the schoolchildren needed magnifying aids at school: 20% used optical magnifying aids (e.g. reading stones) and 53% needed electronic magnifying aids, such as screen magnifiers or camera reading systems. CONCLUSION: Particularly for children, the use of magnifying aids for reading is essential for education in schools and 73% of the children used optical or electronic devices for reading. Of the children 52% attended a mainstream school and were additionally supported by special pedagogic counseling services.

[Clinical Results after Implantation of Epiretinal Visual Prostheses]. / Klinische Ergebnisse epiretinaler Sehprothesen.

Epiretinal visual prostheses have already been implanted in blind retinitis pigmentosa (RP) patients. Here we report on clinical experience with the Argus® II device and the EPIRET 3 device, on the basis of data from patients operated in Germany. Twenty-eight patients were implanted with the Argus II device and followed for up to three years. EPIRET 3 was implanted in six patients for a period of four weeks. With Argus II, an improvement in visual performance was achieved in the majority of cases, as demonstrated by improved localisation of a light spot and a better perception of moving targets. Mobility and self-confidence improved. The main complications were conjunctival erosion due to the combined extra- and intraocular concept of the device. Among the 28 implanted systems, two needed to be removed because complications refractive to treatment. In contrast, EPIRET 3 is a fully intraocular epiretinal system. During a four week implantation, period thresholds were recorded and exhibited high variability between subjects. However, patients were able to recognise simple patterns. Epiretinal implants for electrical stimulation of the retina should be considered to treat advanced photoreceptor degeneration, and thus to restore basic visual functions at an acceptable rate of complications.

Vision Loss in Older Adults.

Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

IMPORTANCE: Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. OBJECTIVE: To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. MAIN OUTCOMES AND MEASURES: Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). RESULTS: A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. CONCLUSIONS AND RELEVANCE: The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

The Effect of Early Visual Deprivation on the Neural Bases of Auditory Processing.

Transient congenital visual deprivation affects visual and multisensory processing. In contrast, the extent to which it affects auditory processing has not been investigated systematically. Research in permanently blind individuals has revealed brain reorganization during auditory processing, involving both intramodal and crossmodal plasticity. The present study investigated the effect of transient congenital visual deprivation on the neural bases of auditory processing in humans. Cataract-reversal individuals and normally sighted controls performed a speech-in-noise task while undergoing functional magnetic resonance imaging. Although there were no behavioral group differences, groups differed in auditory cortical responses: in the normally sighted group, auditory cortex activation increased with increasing noise level, whereas in the cataract-reversal group, no activation difference was observed across noise levels. An auditory activation of visual cortex was not observed at the group level in cataract-reversal individuals. The present data suggest prevailing auditory processing advantages after transient congenital visual deprivation, even many years after sight restoration. SIGNIFICANCE STATEMENT: The present study demonstrates that people whose sight was restored after a transient period of congenital blindness show more efficient cortical processing of auditory stimuli (here speech), similarly to what has been observed in congenitally permanently blind individuals. These results underscore the importance of early sensory experience in permanently shaping brain function.

Diabetic Retinopathy Screening and Monitoring of Early Stage Disease in Australian General Practice: Tackling Preventable Blindness within a Chronic Care Model.

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of preventable blindness in Australia. Up to 50% of people with proliferative DR who do not receive timely treatment will become legally blind within five years. Innovative and accessible screening, involving a variety of primary care providers, will become increasingly important if patients with diabetes are to receive optimal eye care. METHOD: An open controlled trial design was used. Five intervention practices in urban, regional, and rural Australia partnered with ophthalmologists via telehealth undertook DR screening and monitoring of type 2 diabetes patients and were compared with control practices undertaking usual care 2011-2014. RESULTS: Recorded screening rates were 100% across intervention practices, compared with 22-53% in control practices. 31/577 (5%) of patients in the control practices were diagnosed with mild-moderate DR, of whom 9 (29%) had appropriate follow-up recorded. This was compared with 39/447 (9%) of patients in the intervention group, of whom 37 (95%) had appropriate follow-up recorded. DISCUSSION AND CONCLUSION: General practice-based DR screening via Annual Cycle of Care arrangements is effective across differing practice locations. It offers improved recording of screening outcomes for Australians with type 2 diabetes and better follow-up of those with screen abnormalities.

Blind people are more sensitive than sighted people to binaural sound-location cues, particularly inter-aural level differences.

Blind people use auditory information to locate sound sources and sound-reflecting objects (echolocation). Sound source localization benefits from the hearing system's ability to suppress distracting sound reflections, whereas echolocation would benefit from "unsuppressing" these reflections. To clarify how these potentially conflicting aspects of spatial hearing interact in blind versus sighted listeners, we measured discrimination thresholds for two binaural location cues: inter-aural level differences (ILDs) and inter-aural time differences (ITDs). The ILDs or ITDs were present in single clicks, in the leading component of click pairs, or in the lagging component of click pairs, exploiting processes related to both sound source localization and echolocation. We tested 23 blind (mean age = 54 y), 23 sighted-age-matched (mean age = 54 y), and 42 sighted-young (mean age = 26 y) listeners. The results suggested greater ILD sensitivity for blind than for sighted listeners. The blind group's superiority was particularly evident for ILD-lag-click discrimination, suggesting not only enhanced ILD sensitivity in general but also increased ability to unsuppress lagging clicks. This may be related to the blind person's experience of localizing reflected sounds, for which ILDs may be more efficient than ITDs. On the ITD-discrimination tasks, the blind listeners performed better than the sighted age-matched listeners, but not better than the sighted young listeners. ITD sensitivity declines with age, and the equal performance of the blind listeners compared to a group of substantially younger listeners is consistent with the notion that blind people's experience may offset age-related decline in ITD sensitivity.

Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2).

Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21-p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown-Vialleto-Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation.

Neural Correlates of Human Echolocation of Path Direction During Walking.

Echolocation can be used by blind and sighted humans to navigate their environment. The current study investigated the neural activity underlying processing of path direction during walking. Brain activity was measured with fMRI in three blind echolocation experts, and three blind and three sighted novices. During scanning, participants listened to binaural recordings that had been made prior to scanning while echolocation experts had echolocated during walking along a corridor which could continue to the left, right, or straight ahead. Participants also listened to control sounds that contained ambient sounds and clicks, but no echoes. The task was to decide if the corridor in the recording continued to the left, right, or straight ahead, or if they were listening to a control sound. All participants successfully dissociated echo from no echo sounds, however, echolocation experts were superior at direction detection. We found brain activations associated with processing of path direction (contrast: echo vs. no echo) in superior parietal lobule (SPL) and inferior frontal cortex in each group. In sighted novices, additional activation occurred in the inferior parietal lobule (IPL) and middle and superior frontal areas. Within the framework of the dorso-dorsal and ventro-dorsal pathway proposed by Rizzolatti and Matelli (2003), our results suggest that blind participants may automatically assign directional meaning to the echoes, while sighted participants may apply more conscious, high-level spatial processes. High similarity of SPL and IFC activations across all three groups, in combination with previous research, also suggest that all participants recruited a multimodal spatial processing system for action (here: locomotion).

An experimental treatment of ocular quinine toxicity with high-dose 9-cis Beta-carotene.

PURPOSE: To report a case of severe ocular quinine toxicity after a suicide attempt and an experimental treatment with high-dose 9-cis beta-carotene. METHODS: Interventional case report. RESULTS: A 59-year-old woman presented with acute bilateral blindness after ingesting high dose (12 g) of quinine sulphate. Her vision was no light perception in either eye, and her pupils were fixed and middilated. Because of limited vision and poor prognosis, she was treated with an experimental rescue therapy of high-dose 9-cis beta-carotene Dunaliella bardawil powder for 3 months, starting 10 days postingestion. Electroretinography measurements showed transient improvement in a-wave amplitudes. The electroretinography b-wave showed only partial transient improvement in the left eye. Overall, the patient's visual acuity improved to 20/33 in the right eye and 20/40 in the left eye, but with extremely constricted visual fields. CONCLUSION: Transient improvement in electroretinography measurements was observed under treatment with high-dose 9-cis beta-carotene in ocular quinine toxicity, although no clinical benefit was documented. More research is needed to determine its effect in patients with toxic retinal damage.

Mid-latency auditory evoked potential response revealed as an evidence of neural plasticity in blinnd individuals.

There is a general impression that visually blind individuals show an exceptionally better perception of other sensory modalities such as hearing, touch and smell sensations. In this study, we intended to compare the mid-latency auditory evoked potential response (MLAEP) or Middle latency Response (MLR) to get an idea of the activity pattern of auditory thalamus and cortex between 30 visually handicapped subjects and 30 normal sighted subjects. The results showed a decrease in many of the MLR wave latencies, but highly significant for the wave Pa (P value <0.002). This fact can be reflected as an evidence of existence of cross-modal neuroplasticity. We also inferred that there are significant gender differences with latencies shorter in males than females (P value <0.02) in the blind subjects group which could be attributed to their rehabilitation training.