Progressive Loss Of Visual Function Research Articles

Resilience and neuroprotection: The efficacy of saffron Repron® in counteracting the progression of inherited retinal degeneration

E‐mail: ilaria.piano@unipi.it.Retinal diseases can be induced by several factors, including genetic mutations, environmental stresses, and dysmetabolic processes. The result is a progressive loss of visual function, that can leading to total blindness. Among the diseases still orphaned of an effective therapy for slowing retinal degeneration is Retinitis Pigmentosa (RP). RP is one of the inherited retinal degenerative diseases (IRDs) whose cause is attributed to genetic mutations mainly at the level of rod‐specific genes. To date, about 150 mutations out of 60 different genes have been identified.Several therapeutic strategies are being investigated, although the results are still mostly unsatisfactory and limited to specific diseases, particularly in the case of gene therapy, which is applicable only to specific mutations and therefore not applicable on a large scale. Most of the proposed treatments have been tested in animal models, but few have progressed to human clinical trials. An important approach is to identify targets at the level of those mechanisms that are in common in all forms of RP and that drive disease progression, such as stress‐oxidative and inflammation that all together are known as oxinflammation. Here we provide data showing that in RP natural compounds are effective in slowing down the progression of the disease mainly counteracting oxinflammation. Specifically, saffron “Repron” was proved to be effective in AMD and Stargardt patients as well as in pre‐clinical models both “in vitro” and “in vivo.” We tested this treatment in a IRD model. Preliminary obtained in an animal model of RP (rd10 mice) where saffron treatment was able to slow down even the degeneration of rod due to a genetic mutation. In this study, the treatment began in rd10 pregnant females and continued throughout the weaning phase and then in pups that had become autonomous. Functional, immunohistochemical, molecular biology and biochemical analyses were performed at multiple time points from P20 to P120. The results obtained show a protective effect of saffron on both retinal function and morphology, opening a prospect of preventive treatment for those inherited diseases whose progression is known.

METABOLIC SYNDROME AND THE AGING RETINA: A SYSTEMATIC REVIEW

As we get older, we experience a progressive loss of visual function in our eyes. Changes in the structures of the ocular tissues, specifically the cornea, lens, retina, retinal pigment epithelium (RPE), choroid, and optic nerve, are the root cause of age-related macular degeneration, which leads to a loss of vision. Aging is linked to a wide variety of eye conditions, including Fuch's dystrophy, dry eye syndrome, cataracts, presbyopia, age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, amongst others. Vision can be impaired as a result of these conditions in between 4 and 20 percent of people over the age of 65. The term "metabolic syndrome" (MetS) refers to a cluster of cardiometabolic components, some of which include abdominal obesity, hypertension, elevated glucose levels, and dyslipidemia. These components are highly predictive of type 2 diabetes mellitus and cardiovascular diseases (CVD), which eventually cause morbidity and mortality. The retinal age difference has proven itself as an innovative and reliable screening technique for metabolic syndrome and inflammation. When compared to earlier screening methods that were based on blood tests or anthropometric measurements, the retinal age gap is calculated using a deep learning model that automatically integrates all of the information from fundus images. This reduces the likelihood of making an error during manual assessment and eliminates the requirement for invasive testing. We discovered that there was a strong association between MetS and age gaps in the retina, as well as inflammation.

Genetic, environmental and other risk factors for progression of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.

Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by a progressive loss of visual function that primarily affect photoreceptors, resulting in the complete disorganization and remodeling of the retina. Progression of the disease is enhanced by increased oxidative stress in the retina, aqueous humor, plasma, and liver of RP animal models and patients. Melatonin has beneficial effects against age-related macular degeneration, glaucoma, and diabetic retinopathy, in which oxidative stress plays a key role. In the present study, we used the P23HxLE rat as an animal model of RP. Melatonin treatment (10 mg/kg b.w. daily in drinking water for 6 months) improved the parameters of visual function and decreased the rate of desynchronization of the circadian rhythm, both in P23HxLE and wild-type rats. Melatonin reduced oxidative stress and increased antioxidant defenses in P23HxLE animals. In wild-type animals, melatonin did not modify any of the oxidative stress markers analyzed and reduced the levels of total antioxidant defenses. Treatment with melatonin improved visual function, circadian synchronization, and hepatic oxidative stress in P23HxLE rats, an RP model, and had beneficial effects against age-related visual damage in wild-type rats.

Effect of Hemodialysis on Diabetic Retinopathy

Diabetes mellitus is a serious health problem in both developed and developing countries. It is expected that by 2040 the incidence of diabetes mellitus in the world will increase to 642 million people. With the increase in the incidence of diabetes mellitus, the incidence of diabetic vascular complications increases, which worsen the quality of life of patients and triple the risk of death. Diabetic retinopathy is one of the most common microvascular complications of diabetes mellitus, leading to progressive loss of visual function. Diabetic retinopathy occurs in conjunction with diabetic nephropathy. This fact is associated with the anatomical similarity of the blood-retinal barrier and the glomerular filtration barrier, as well as with the general pathogenetic mechanisms of the effect of hyperglycemia on peripheral microcirculation. On average, after 10–15 years, patients with decompensated diabetes mellitus develop end-stage renal failure, requiring renal replacement therapy, such as peritoneal dialysis, programmed hemodialysis, and kidney transplantation. This article highlights the latest data on the effect of programmed hemodialysis on the morphofunctional state of the retina in patients with diabetes mellitus.

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells.

To create new immunodeficient Royal College of Surgeons (RCS) rats by introducing the defective MerTK gene into athymic nude rats. Female homozygous RCS (RCS-p+/RCS-p+) and male nude rats (Hsd:RH-Foxn1mu, mutation in the foxn1 gene; no T cells) were crossed to produce heterozygous F1 progeny. Double homozygous F2 progeny obtained by crossing the F1 heterozygotes was identified phenotypically (hair loss) and genotypically (RCS-p+ gene determined by PCR). Retinal degenerative status was confirmed by optical coherence tomography (OCT) imaging, electroretinography (ERG), optokinetic (OKN) testing, superior colliculus (SC) electrophysiology, and by histology. The effect of xenografts was assessed by transplantation of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) and human-induced pluripotent stem cell-derived RPE (iPS-RPE) into the eye. Morphological analysis was conducted based on hematoxylin and eosin (H&E) and immunostaining. Age-matched pigmented athymic nude rats were used as control. Approximately 6% of the F2 pups (11/172) were homozygous for RCS-p+ gene and Foxn1mu gene. Homozygous males crossed with heterozygous females resulted in 50% homozygous progeny for experimentation. OCT imaging demonstrated significant loss of retinal thickness in homozygous rats. H&E staining showed photoreceptor thickness reduced to 1-3 layers at 12weeks of age. Progressive loss of visual function was evidenced by OKN testing, ERG, and SC electrophysiology. Transplantation experiments demonstrated survival of human-derived cells and absence of apparent immune rejection. This new rat animal model developed by crossing RCS rats and athymic nude rats is suitable for conducting retinal transplantation experiments involving xenografts.

Transcriptional Changes in the Mouse Retina after Ocular Blast Injury: A Role for the Immune System.

Ocular blast injury is a major medical concern for soldiers and explosion victims due to poor visual outcomes. To define the changes in gene expression following a blast injury to the eye, we examined retinal ribonucleic acid (RNA) expression in 54 mouse strains 5 days after a single 50-psi overpressure air wave blast injury. We observe that almost 40% of genes are differentially expressed with a false discovery rate (FDR) of <0.001, even though the nominal changes in RNA expression are rather small. Moreover, we find through machine learning approaches that genetic networks related to the innate and acquired immune system are activated. Accompanied by lymphocyte invasion into the inner retina, blast injury also results in progressive loss of visual function and retinal ganglion cells (RGCs). Collectively, these data demonstrate how systems genetics can be used to put meaning to the transcriptome changes following ocular blast injury that eventually lead to blindness.

Prescribing pattern and adverse events of drugs used in patients with primary open-angle glaucoma (POAG) attending a tertiary care hospital: Retrospective study

Background: Primary open-angle glaucoma (POAG) is the most prevalent type of glaucoma leading to progressive loss of visual function in adults. Aims and Objectives: This study was conducted to determine the prescribing pattern and to assess the associated adverse reactions of drugs used in the treatment of POAG in a tertiary care teaching hospital. Materials and Methods: This was a retrospective, case-record-based study conducted on patients attending the department of ophthalmology for treatment of POAG at Srinivas Hospital, Mukka, from October 2014 to December 2015. The study was initiated after obtaining approval from the Institutional Ethics Committee. Data were analyzed using statistical package for social sciences version 17 and presented as percentages and frequency. Results: Out of 74 prescriptions analyzed, 48 (64.86%) patients were treated with monotherapy and 26 patients with combination therapy of drugs. The majority of patients were on timolol as monotherapy with prescription rate of 29.16% followed by bimatoprost 20.83%. Combination therapy was prescribed to 35.14% of the patients; the commonly used regimen was timolol + brimonidine (30.76% patients). 16 patients reported adverse effects such as blurred vision, ocular irritation, and foreign body sensation; however, the most of the patients tolerated the prescribed drugs well. Conclusion: The present study results help to know the different treatment strategies employed in the management of POAG, and reasons for the preference of prescribed drugs. Most of the patients tolerated the antiglaucoma medications well and had a few side effects which did not warrant discontinuation of treatment.

Factors Associated with Loss of Visual Function in Medically Treated Advanced Normal Tension Glaucoma

ABSTRACTPurpose: To investigate the risk factors associated with a progressive loss of visual function (LV) in medically treated advanced normal tension glaucoma (NTG).Methods: In this retrospective observational study, a total of 87 eyes of the 87 NTG patients with a baseline visual field (VF) mean deviation (MD) of worse than –10 decibel (dB) (average follow-up period: 5.3 years) were included. All the participants were categorized into two groups according to the baseline VF MD [group 1 (≥−16 dB) and group 2 (<−16 dB), respectively]. The participants were also divided into older (≥64 years) and younger (<64 years) groups according to the median split of baseline age. Hazard ratios (HRs) for the association between potential risk factors and LV were obtained using the Cox proportional hazards models.Results: Fifty-one eyes were classified as group 1 (VF MD; −13.5 ± 1.8 dB), and 36 eyes as group 2 (−21.0 ± 4.1 dB). LV occurred in 33 eyes (64.7%) in group 1 and in 29 eyes (80.6%) in group 2 during the follow-up period. In total participants, younger age (HR; 0.971, p = 0.008) and lower initial best-corrected visual acuity (BCVA) (HR; 18.4, p = 0.007) were found to be significant risk factors for LV. In group 1, younger age and lower baseline BCVA were associated with LV; whereas, no significant risk factor was found in group 2. In the younger group, myopia and disc hemorrhage were found to be the risk factors.Conclusion: The risk factors associated with progressive LV differed according to the baseline VF stages or the age among advanced medically treated NTG patients.

Deimination restores inner retinal visual function in murine demyelinating disease

Progressive loss of visual function frequently accompanies demyelinating diseases such as multiple sclerosis (MS) and is hypothesized to be the result of damage to the axons and soma of neurons. Here, we show that dendritic impairment is also involved in these diseases. Deimination, a posttranslational modification, was reduced in the retinal ganglion cell layer of MS patients and in a transgenic mouse model of MS (ND4 mice). Reduced deimination accompanied a decrease in inner retinal function in ND4 mice, indicating loss of vision. Local restoration of deimination dramatically improved retinal function and elongation of neurites in isolated neurons. Further, neurite length was decreased by downregulation of deimination or siRNA knockdown of the export-binding protein REF, a primary target for deimination in these cells. REF localized to dendrites and bound selective mRNAs and translation machinery to promote protein synthesis. Thus, protein deimination and dendritic outgrowth play key roles in visual function and may be a general feature of demyelinating diseases.

Clinical Phenotypes and Prognostic Full-Field Electroretinographic Findings in Stargardt Disease

To investigate the relationships between clinical and full-field electroretinographic (ERG) findings and progressive loss of visual function in Stargardt disease. Retrospective cohort study. We performed a retrospective review of data from 198 patients with Stargardt disease. Measures of visual function over time, including visual acuity, quantified Goldmann visual fields, and full-field ERG data were recorded. Data were analyzed using SAS statistical software. Subgroup analyses were performed on 148 patients with ERG phenotypic data, 46 patients with longitudinal visual field data, and 92 patients with identified ABCA4 mutations (46 with 1 mutation, and 47 with 2 or more mutations). Of 46 patients with longitudinal visual field data, 8 patients with faster central scotoma progression rates had significantly worse scotopic B-wave amplitudes at their initial assessment than 20 patients with stable scotomata (P = .014) and were more likely to have atrophy beyond the arcades (P = .047). Overall, 47.3% of patients exhibited abnormal ERG results, with rod-cone dysfunction in 14.2% of patients, cone-rod dysfunction in 17.6% of patients, and isolated cone dysfunction in 15.5% of patients. Abnormal values in certain ERG parameters were associated significantly with (maximum-stimulation A- and B-wave amplitudes) or tended toward (photopic and scotopic B-wave amplitudes) a higher mean rate of central scotoma progression compared with those patients with normal ERG values. Scotoma size and ERG parameters differed significantly between those with a single mutation versus those with multiple mutations. Full-field ERG examination provides clinically relevant information regarding the severity of Stargardt disease, likelihood of central scotoma expansion, and visual acuity deterioration. Patients also may exhibit an isolated cone dystrophy on ERG examination.

The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with "L/M interchange" mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy.

Myelin Sheath Decompaction, Axon Swelling, and Functional Loss during Chronic Secondary Degeneration in Rat Optic Nerve

To examine chronic changes occurring at 6 months following partial optic nerve (ON) transection, assessing optic axons, myelin, and visual function. Dorsal ON axons were transected, leaving ventral optic axons vulnerable to secondary degeneration. At 3 and 6 months following partial transection, toluidine-blue stained sections were used to assess dimensions of the ON injury site. Transmission electron microscopy (TEM) images of ventral ON were used to quantify numbers, diameter, area, and myelin thickness of optic axons. Immunohistochemistry and fluoromyelin staining were used to assess semiquantitatively myelin protein, lipids in ventral ON, and retinal ganglion cells (RGCs) in midventral retina. Visuomotor function was assessed using optokinetic nystagmus. Following partial ON transection, optic axons and function remained disrupted at 6 months. Although ventral ON swelling observed at 3 months (P ≤ 0.05) receded to normal by 6 months, ultrastructurally, myelinated axons remained swollen (P ≥ 0.05), and myelin thickness increased (P ≤ 0.05) due to loosening of lamellae and an increase in the number of intraperiodic lines. Axons with decompacted myelin persisted and were distinguished as having large axonal calibers and thicker myelin sheaths. Nevertheless, progressive loss of myelin lipid staining with fluoromyelin was seen at 6 months. Despite no further loss of ventral optic axons between 3 and 6 months (P ≥ 0.05), visuomotor function progressively declined at 6 months following partial transection (P ≤ 0.05). Continued decompaction of myelin, altered myelin structure, and swelling of myelinated axons are persistent features of the chronic phases of secondary degeneration and likely contribute to progressive loss of visual function.

Longitudinal Measures of Visual Function, Tumor Volume, and Prediction of Visual Outcomes after Treatment of Optic Pathway Gliomas

To examine longitudinal changes in visual acuity, tumor volume, and visual evoked potentials (VEP) before and after treatment in children with optic pathway gliomas. Retrospective cohort study. Twenty-one patients (0.7-9 years of age). Patients initially were treated either by chemotherapy (n = 18) or radiotherapy (n = 3). Patients were followed up with serial magnetic resonance imaging, age-corrected visual acuity measurements in logarithm of the minimum angle of resolution (logMAR) units, and pattern VEP. Longitudinal visual outcome data were obtained on average for 9 years (range, 4-16 years). Tumor volumes before and after treatment were estimated in 15 patients. Multivariate regression was used to predict visual outcomes. Visual acuity, relative tumor volumes, and VEP. Before treatment, 81% of patients had reduced visual acuity and 81% had optic nerve pallor, whereas all had a reduced VEP in 1 or both eyes. After initial treatment, tumor volume decreased in 53%, stabilized in 27%, and progressively increased in 20%. Treatment arrested the rapid decline in visual acuity loss and stabilized visual acuity for 4 to 5 years. The rate of visual acuity decline was not correlated with tumor shrinkage. Sixty-two percent of patients required additional treatment with either chemotherapy or radiation because of tumor growth or progressive loss of visual function. Visual acuity at last examination was stable or improved in 33% of patients, but on average declined 0.4 logMAR units. Visual acuity was 20/200 or better in 1 eye of 62% of patients. The rate of visual acuity decline was predicted weakly by tumor volume at presentation (R(2) = 0.19; P<0.009). Visual acuity at last examination was predicted best by visual acuity and tumor volume at presentation (R(2) = 0.66; P<0.001). Systemic chemotherapy arrested the decline in visual acuity and stabilized vision on average for 5 years. At presentation, VEPs were a more sensitive indicator of optic pathway damage than visual acuity or optic nerve appearance. Although tumor reduction or stabilization was achieved in 80% of patients, pre-existing visual damage, indexed by objective measures of tumor volume and visual function, limited visual outcomes. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Molecular genetic cause of X-linked retinitis pigmentosa in a Czech family

Editor, A branch of a large eight generation Caucasian Czech family diagnosed with presumable X-linked retinitis pigmentosa (XLRP) was investigated (Fig. 1). This study adhered to the tenets of the Declaration of Helsinki. Men were severely affected in this family with early onset of night blindness and myopia, usually at the beginning of the second decade, and progressive loss of visual function resulting in blindness in the fourth decade. Women were either asymptomatic or developed symptoms with later onset (Otradovec et al. 1979). There is no evidence of male to male transmission. After obtaining informed consent, blood samples were drawn and DNA extracted. Polymorphic microsatellite markers located on the X chromosome (Table 1) were amplified using fluorescently labelled oligonucleotides and analysed on an ABI-377 DNA sequencer (Applied Biosystems, Darmstadt, Germany) using GeneScan software (Applied Biosystems). Haplotype analysis indicated that the disease segregates with markers encompassing both the RPGR and RP2 genes as RPGR lies between markers DXS1214 and DXS1068 and RP2 between DXS1055 and DXS991 (Fig. 1). The chromosomal region between the most proximal and most distal marker used in this study encompassed approximately 200 known protein-coding genes (http://www.ensembl.org). Investigated branch of an eight generation Czech family with X-linked retinitis pigmentosa. The affected haplotype is shown as a black bar and encompasses the RPGR and RP2 genes located between DXS1214–DXS1068 and DXS1055–DXS991, respectively. Sequencing of the RP2 gene, as previously described (Hardcastle et al. 1999), did not reveal any pathogenic changes. ORF15 of the RPGR gene (Vervoort et al. 2000) was then amplified and bidirectionally sequenced in four overlapping fragments using the ABI Prism® BigDye™ dGTP Terminator Ready Reaction Cycle Sequencing Kit (Applied Biosystems). A pathogenic mutation, c.2426_2427 delAG (g.ORF15+673_674delAG), leading to p.Glu809fs (ORF15Glu224fs) was identified in all affected males and three female obligate carriers (Fig. 2). The change was also detected in one other female family member (individual IV:6) and was absent in females IV:2 and IV:4 (1, 2). This mutation has been observed previously in different XLRP patient populations (http://rpgr.hgu.mrc.ac.uk), including one Japanese XLRP families (Jin et al. 2006). Interestingly, no other sequence variants were identified in the highly polymorphic RPGR ORF15 in our family. Sequence chromatogram showing the c.2426_2427delAG mutation in ORF15 of the RPGR gene in an obligate carrier III:1 (A) and an affected male IV:5 (B). The mutation was not detected in an unaffected female IV:4 (C). Reference sequence NM_001034853 was used. All three affected men were documented to have bone spicules on fundus examination. There were marked interindividual differences between IV:1 and IV:5 despite similar age; IV:5 was much more severely affected with night blindness, whereas IV:1 reported no symptoms. II:3 was registered blind in the fourth decade. Examined female carriers (III:1, III:5, IV:6) had some peripheral pigmentary changes but not classic bone spicules. RPRG mutations are the most frequent cause of XLRP (Vervoort et al. 2000; http://rpgr.hgu.mrc.ac.uk). The pedigree we have investigated here represents the first Czech family with an identified molecular genetic cause of RP. Although in Western European countries the prevalence and mutational spectrum of various RP types has been extensively studied, little is known about this heterogeneous group of disorders and their molecular genetic cause in the restructured countries of Central and Eastern Europe. To the best of our knowledge, prior to this study, only one other report describes a pathogenic mutation causing XLRP in a family of Bulgarian Gypsy origin (Chakarova et al. 2006). Here, we would like to propose the necessity for service offering molecular genetic testing for RP patients, and also for patients with other inherited ocular disorders, in all European countries. This should be supported by continuous education in the field of ophthalmic genetics among medical practitioners which would lead to improved counselling. However, as it is technically challenging to establish mutation analysis for every gene causing inherited ocular disorders in every country, we suggest that where X-linked inheritance cannot be excluded, the RPGR gene is screened for mutations using already established diagnostic services. This work was in part supported by the Czech Ministry of Education, Youth and Sports research project 0021620806/20610011.

Management of sight‐threatening optic nerve sheath meningioma with fractionated stereotactic radiotherapy

Previous management of optic nerve sheath meningioma included conservative observation, surgery, radiosurgery and conventional radiotherapy. All carried significant risk, either of visual loss or damage to adjacent structures. Fractionated stereotactic radiotherapy appears to have few side-effects and may preserve or improve vision. To date only three groups have published their experience with this modality. A retrospective review of patients with optic nerve sheath meningioma treated with stereotactic radiotherapy in an academic complex was conducted. Patients with greater than 18 months follow up and no previous related surgery were eligible for inclusion. Patients received an average of 43.5 Gy to the tumour in 26 fractions. Case records from the treating institutions as well as those of the referring ophthalmologist were analysed. The limited literature on the subject was reviewed in order to draw conclusions relevant to contemporary patient management. Four patients had undergone follow up for over 18 months. Prior to treatment all had exhibited progressive loss of visual function. In all cases visual function remained stable or improved at the last assessment. Side-effects included radiologically detected cerebral changes in one patient and transient hair loss in one patient. This treatment modality represents a promising refinement of previous treatment options. It may be offered to patients who demonstrate progressive loss of visual function caused by optic nerve sheath meningioma. It offers significant advantages over other currently available therapeutic options but its use should be tempered by the knowledge that long-term side-effects are yet to be determined.

Erdheim-Chester disease: A case report

Erdheim-Chester disease (ECD) is a rare histiocytosis, histologically characterized by xanthogranulomatous inflammation. It may affect the bones, heart, lung, liver, kidneys, retroperitoneum, brain, and, rarely, the orbit. In the majority of patients, orbital infiltration is bilateral. A 61-year-old man presented with bilateral exophthalmos and progressive loss of visual function caused by chorioretinal folds and papillary swelling due to retrobulbar pseudotumor. The computed tomogram of the abdomen showed retroperitoneal thickening, leading to the interpretation of multifocal fibrosclerosis. This was further substantiated by an orbital biopsy revealing chronic fibrosing inflammation. Retrobulbar radiotherapy (20 Gy) and long-term systemic corticosteroid treatment followed. Although the retroperitoneal involvement decreased, no significant effect on orbital involvement was achieved. A second review of the orbital biopsy revealed foamy cell infiltration and the presence of a sclerotic process. Immunohistochemical examination demonstrated positive CD 68 stains, whereas S-100 and CD 1a were negative, thus confirming ECD. The histologic finding was comparable to a biopsy of the retroperitoneum. Endonasal decompression was performed but visual acuity (VA) decreased to 20/250 in the right eye and on finger counting in the left eye. The patient continues to be under therapy with prednisolone 20 mg/day and methotrexate 25 mg/week. The clinical orbital manifestation of ECD occurs in two different forms: one presenting as a mild impairment of visual function, while the second, clinical form, observed in our patient, is characterized by a progressive loss of VA despite therapeutic efforts such as immunosuppressive systemic therapy, radiation, and surgery. The described case illustrates that clinical findings in multifocal fibrosclerosis overlap with those observed in ECD.

Síndrome de Bardet-Biedl: relato de dois casos

A síndrome de Bardet-Biedl é doença de herança autossômica recessiva caracterizada por distrofia retiniana, polidactilia, obesidade, retardo mental e hipogenitalismo. Um ou mais dos achados acima que caracterizam a síndrome podem estar ausentes, mas a distrofia retiniana é achado consistente. Esta se manifesta clinicamente na infância com progressiva perda visual, causando grave dificuldade visual na adolescência. Os autores descrevem dois casos de síndrome de Bardet-Biedl, os resultados da acuidade visual, biomicroscopia, oftalmoscopia, angiografia, campo visual e eletrorretinograma. Foi realizada revisão bibliográfica com ênfase na identificação dos sinais sistêmicos, envolvimento ocular, testes eletrofisiológicos e avaliação genética.

Pseudotumour cerebri and optic hydrops—magnetic resonance imaging diagnostic and therapeutical considerations in a paediatric case

We report the case of a 4-year-old girl with progressive visual loss. Magnetic resonance imaging (MRI) demonstrated a perioptic subarachnoidal space dilatation. In this case, a clear differentiation between pseudotumour cerebri and optic hydrops was not possible. Administration of acetazolamid, furosemid and corticosteroids did not show any success. Progressive loss of visual function was halted with ventriculo-peritoneal shunting. We discuss MRI findings, aetiology and course of the disease, and its literature.

High Dosage Corticosteroids in the Treatment of Optic Neuritis and Prophylaxis of Multiple Sclerosis

Optic neuritis is regarded as an immune-mediated inflammatory disorder affecting any portion of the optic nerve. It most commonly begins with pain in the ipsilateral orbit followed by rapidly progressive loss of visual function over several days. The vision begins to improve within 2 to 4 weeks, and recovery is fairly rapid over another 2 to 3 weeks followed by slow further improvement up to 1 year. The pain typically resolves ahead of visual dysfunction — usually within the first 2 weeks.