Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode.

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. METHODS: Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. RESULTS: Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). CONCLUSION: First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.

Evolution of MRI Findings in Patients with Idiopathic Intracranial Hypertension after Venous Sinus Stenting.

BACKGROUND AND PURPOSE: The correlation between imaging findings and clinical status in patients with idiopathic intracranial hypertension is unclear. We aimed to examine the evolution of idiopathic intracranial hypertension-related MR imaging findings in patients treated with venous sinus stent placement. MATERIALS AND METHODS: Thirteen patients with idiopathic intracranial hypertension (median age, 26.9 years) were assessed for changes in the CSF opening pressure, transstenotic pressure gradient, and symptoms after venous sinus stent placement. Optic nerve sheath diameter, posterior globe flattening and/or optic nerve protrusion, empty sella, the Meckel cave, tonsillar ectopia, the ventricles, the occipital emissary vein, and subcutaneous fat were evaluated on MR imaging before and 6 months after venous sinus stent placement. Data are expressed as percentages, medians, or correlation coefficients (r) with P values. RESULTS: Although all patients showed significant reductions of the CSF opening pressure (31 versus 21 cm H2O; P = .005) and transstenotic pressure gradient (22.5 versus 1.5 mm Hg; P = .002) and substantial improvement of clinical symptoms 6 months after venous sinus stent placement, a concomitant reduction was observed only for posterior globe involvement (61.5% versus 15.4%; P = .001), optic nerve sheath diameter (6.8 versus 6.1 mm; P < .001), and subcutaneous neck fat (8.9 versus 7.4 mm; P = .001). Strong correlations were observed between decreasing optic nerve sheath diameters and improving nausea/emesis (right optic nerve sheath diameter, r = 0.592, P = .033; left optic nerve sheath diameter, r = 0.718, P = .006), improvement of posterior globe involvement and decreasing papilledema (r = 0.775, P = .003), and decreasing occipital emissary vein diameter and decreasing headache frequency (r = 0.74, P = .035). Decreasing transstenotic pressure gradient at 6 months strongly correlated with decreasing empty sella (r = 0.625, P = .022) and regressing cerebellar ectopia (r = 0.662, P = .019). CONCLUSIONS: Most imaging findings persist long after normalization of intracranial pressure and clinical improvement. However, MR imaging findings related to the optic nerve may reflect treatment success.

Prediction of cortical theta oscillations in humans for phase-locked visual stimulation.

BACKGROUND: The timing of an event within an oscillatory phase is considered to be one of the key strategies used by the brain to code and process neural information. Whereas existing methods of studying this phenomenon are chiefly based on retrospective analysis of electroencephalography (EEG) data, we now present a method to study it prospectively. New method: We present a system that allows for the delivery of visual stimuli at a specific phase of the cortical theta oscillation by fitting a sine to raw surface EEG data to estimate and predict the phase. One noteworthy feature of the method is that it can minimize potentially confounding effects of previous trials by using only a short sequence of past data. RESULTS: In a trial with 10 human participants we achieved a significant phase locking with an inter-trial phase coherence of 0.39. We demonstrated successful phase locking on synthetic signals with a signal-to-noise ratio of less than - 20 dB. Comparison with existing method(s): We compared the new method to an autoregressive method published in the literature and found the new method was superior in mean phase offset, circular standard deviation, and prediction latency. CONCLUSIONS: By fitting sine waves to raw EEG traces, we locked visual stimuli to arbitrary phases within the theta oscillatory cycle of healthy humans.

8-Hydroxyquinoline-5-sulfonamides are promising antifungal candidates for the topical treatment of dermatomycosis.

AIM: The purpose of this study was to uncover insights into the mechanism of action of the 8-hydroxyquinoline derivatives PH151 and PH153. In addition, with the future perspective of developing a topical drug for the treatment of candidiasis and dermatophytosis, the antifungal activity of a nanoemulsion formulation containing the most active compound (PH151) is also presented here. METHODS AND RESULTS: Sorbitol protection assay and scanning electron microscopy indicate that the 8-hydroxyquinoline derivatives act on the cell wall of Candida sp. and dermatophytes and they inhibit the pseudohyphae formation of C. albicans. These findings demonstrate a strong effect of these compounds on C. albicans morphogenesis, which can be considered a potential mode of action for this molecule. Besides, the nanoemulsion formulation MIC values ranged from 0·5 to 4 µg ml-1 demonstrating the significant antifungal activity when incorporated into a pharmaceutical formulation. CONCLUSIONS: Taken together, the results support the potential of these molecules as promising antifungal candidates for the treatment of candidiasis and dermatophytosis. SIGNIFICANCE AND IMPACT OF THE STUDY: There is an emerging need to fill the pipeline with new antifungal drugs due to the limitations presented by the currently used drugs. In this study, we have described a novel formulation with a 8-hydroxyquinoline-5-sulfonamide derivative which has presented a great potency in providing a finished product. Furthermore, the derivative has shown a selective mechanism of action confirming its potential to be developed into a new drug candidate.

Close-range laser scanning in forests: towards physically based semantics across scales.

Laser scanning with its unique measurement concept holds the potential to revolutionize the way we assess and quantify three-dimensional vegetation structure. Modern laser systems used at close range, be it on terrestrial, mobile or unmanned aerial platforms, provide dense and accurate three-dimensional data whose information just waits to be harvested. However, the transformation of such data to information is not as straightforward as for airborne and space-borne approaches, where typically empirical models are built using ground truth of target variables. Simpler variables, such as diameter at breast height, can be readily derived and validated. More complex variables, e.g. leaf area index, need a thorough understanding and consideration of the physical particularities of the measurement process and semantic labelling of the point cloud. Quantified structural models provide a framework for such labelling by deriving stem and branch architecture, a basis for many of the more complex structural variables. The physical information of the laser scanning process is still underused and we show how it could play a vital role in conjunction with three-dimensional radiative transfer models to shape the information retrieval methods of the future. Using such a combined forward and physically based approach will make methods robust and transferable. In addition, it avoids replacing observer bias from field inventories with instrument bias from different laser instruments. Still, an intensive dialogue with the users of the derived information is mandatory to potentially re-design structural concepts and variables so that they profit most of the rich data that close-range laser scanning provides.

Long-term immunosuppression after solitary islet transplantation is associated with preserved C-peptide secretion for more than a decade.

We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid-sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42-year-old female with a 12-year history of T1D, received two islet infusions; patient B, a 53-year-old female with a 40-year T1D history, received one islet infusion. Pretransplant, both had undetectable C-peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33 units/kg/day, respectively. Posttransplant, C-peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re-started 2 years posttransplant in both patients. Since patient A's glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C-peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30 000 measurements per patient) and ß cell function based on C-peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.

Assessment of a new Goldmann applanation tonometer.

BACKGROUND/AIMS: The classic Goldmann applanation tonometer (GAT) has been further developed by Haag-Streit International. The applanation principle has been retained, while the internal force transmission and the pressure gauging have been optimised, the display of results digitised. The authors compared the GAT standard with the new GAT digital. METHODS: Four fixed tonometer pairs were used. The protocol included: non-contact pachymetry, slit-lamp examination, three consecutive measurements with each tonometer with a 5 min interval in between, check for side effects in 15 min. Three groups (intraocular pressure (IOP) levels) were defined: (1) IOP ≤ 16; (2) IOP>16 and <23; (3) IOP ≥ 23 mm Hg. RESULTS: 125 Patients (250 eyes) were evaluated. IOP (mm Hg), GAT standard versus GAT digital, for the rights eyes was: Group 1: 12.94 ± 0.55 versus 13.11 ± 0.53, p=0.71. Group 2: 18.26 ± 0.59 versus 18.03 ± 0.52, p=0.53; Group 3: 30.28 ± 0.48 versus 30.42 ± 0.41, p=0.97; all right eyes: 17.48 ± 7.48 versus 17.73 ± 7.4, p=0.99. For the left eyes, there was no significant difference, either. The correlation was very good and was not influenced by the IOP level. The Pearson coefficient for the right eye was 0.985, and for the left eye 0.994. In the Bland-Altman analysis, although there were two single readings that differed by as much as 5 mm Hg, GAT digital measures showed almost no skew, and the mean difference was 0.03 ± 1.23 mm Hg (n=250). A multiple regression analysis showed no influence of order of measurement, eyeside or pachymetry. CONCLUSIONS: The new GAT digital is as reliable and safe as GAT standard. IOP values correlate well. It offers a digitised display and a wireless transfer of data. The display of values up to the first decimal digit is not necessarily associated with a more precise measurement, but may offer an additional comfort compared with the 2 mm Hg scale of the classic GAT.

Anomalous global effects induced by 'blind' distractors in visual hemifield defects.

Previous research has revealed that a stimulus presented in the blind visual field of participants with visual hemifield defects can evoke oculomotor competition, in the absence of awareness. Here we studied three cases to determine whether a distractor in a blind hemifield would be capable of inducing a global effect, a shift of saccade endpoint when target and distractor are close to each other, in participants with lesions of the optic radiations or striate cortex. We found that blind field distractors significantly shifted saccadic endpoints in two of three participants with lesions of either the striate cortex or distal optic radiations. The direction of the effect was paradoxical, however, in that saccadic endpoints shifted away from blind field distractors, whereas endpoints shifted towards distractors in the visible hemifields, which is the normal global effect. These results provide further evidence that elements presented in the blind visual field can generate modulatory interactions in the oculomotor system, which may differ from interactions in normal vision.

Abuse of vasoconstrictive eyedrops mimicking an ocular pemphigoid.

PURPOSE: To describe conjunctival histopathologic alterations induced by excessive chronic astringent use. METHODS: Report of a case with clinical picture, epicutane test results, histologic workup of conjunctival biopsy using conventional staining, and immunohistochemical markers. RESULTS: A 45-year-old man using a phenylephrine preparation hourly for years presented with grotesque eye redness, fornix shortening, and scarring of puncta lacrimalia. Direct and indirect immunofluorescence were negative for ocular pemphigoid. Histology revealed signs of chronic inflammation and neovascularization in the conjunctiva. Symptoms resolved after cessation of therapy. CONCLUSIONS: Chronic abuse of decongestant eyedrops can produce a clinical picture resembling an ocular pemphigoid. Histology suggests that late onset immunoreaction and chronic vasoconstriction cause chronic inflammation and neovascularization, respectively.

Unilateral papilledema after trabeculectomy in a patient with intracranial hypertension.

BACKGROUND: Increased intracranial pressure usually leads to bilateral disc swelling. HISTORY AND SIGNS: A patient presented with recurrent visual disturbances following trabeculectomy in the right eye. Intraocular pressure in the right and left eye were 11 and 24 mmHg, respectively. The optic nerve head was swollen in the right, but not in the left eye. Lumbar puncture showed an opening pressure of 32 cmH (2)O. Magnetic resonance imaging, neurological examination and composition of cerebrospinal fluid were normal. According to the modified Dandy criteria, an idiopathic intracranial hypertension was diagnosed. THERAPY AND OUTCOME: Treatment with acetazolamide led to resolution of papilledema in the right eye within six months. CONCLUSION: The intracranial-intraocular pressure gradient in the right eye was markedly higher as compared to that of the left eye. We suggest that this pressure gradient induced the collapse of axoplasmatic transport at the lamina cribrosa with subsequent disc swelling. As no significant pressure gradient was present in the left eye, the optic disc remained normal. Based on analogous calculations in three additional published cases of unilateral papilledema we thus suggest that intraocular pressure should be taken into account when evaluating patients with papilledema.

Retinal detachment in patients with acute retinal necrosis: a case series.

BACKGROUND: Acute retinal necrosis is a rare and severe infectious ocular disease frequently complicated by retinal detachment. PATIENTS AND METHODS: Records of six consecutive eyes from five patients with acute retinal necrosis were reviewed. RESULTS: PCR analysis of intraocular fluids was positive for Varizella zoster virus, Herpes virus 1 or 2. Treatment consisted of systemic acyclovir, systemic and local corticosteroids as well as aspirin. Progression of the necrosis could be effectively controlled, however all eyes developed retinal detachment within 55 +/- 24 days. Retinal surgery including pars plana vitrectomy, encircling scleral buckling, liquid silicone or gas filling led to retinal reattachment in all patients during the follow-up time (590 +/- 242 days). The mean visual acuity at the end of the follow-up time was 0.4 +/- 0.3. CONCLUSIONS: The diagnosis of acute retinal necrosis is reliably confirmed using PCR analysis of intraocular fluids. Currently available treatments are effective in stopping progression of the necrosis. There is, however, a high risk of retinal detachment, which can be successfully treated with vitreoretinal surgery.

[Therapeutic strategies in RP (retinitis pigmentosa): light at the end of the tunnel?]. / Therapieversuche bei RP: Licht am Ende des Tunnels?

Retinitis pigmentosa (RP) is a hereditary retinal dystrophy which leads to severe visual impairment or blindness and affects about 3.5/1000 of individuals in the industrial world. During the past decades, numerous animal models carrying mutations analogous to mutations in human RP have been studied to elucidate the molecular mechanisms leading to apoptotic photoreceptor cell death in this disease. Up to date, there is no effective treatment to influence the fatal outcome of RP. Recent progress in basic research promotes the development of new therapeutic strategies. In order to restore visual function in blind individuals, the development of electronic photoreceptor prosthesis is being investigated by several researchgroups. Other promising approaches are somatic gene therapy, the application of growth factors and/or pharmacological agents and the inhibition of photoreceptor cell death by interfering with the apoptotic pathway. However, a better understanding of the molecular events leading to cell loss due to photoreceptor apoptosis will be essential for the development of effective treatment.

Retinal degeneration in the rd mouse in the absence of c-fos.

PURPOSE: Apoptosis is the final common death pathway of photoreceptors in light-induced retinal degeneration and in several animal models for retinal dystrophy. To date, little is known about gene regulation of apoptosis in the retina. The expression of the immediate early gene c-fos is upregulated concomitant with apoptosis in light-induced photoreceptor degeneration and in the rd mouse, an animal model for inherited retinal degeneration. In a recent study it was shown that c-Fos is essential for light-induced apoptosis of photoreceptors in vivo. To determine whether c-Fos is also involved in the apoptotic pathway of inherited retinal degeneration, rd/rd, c-fos -/- double-mutant mice have been generated. METHODS: Double-mutant mice (rd/rd, c-fos -/-) were crossbred from c-fos+/- mice and rd/rd mice. Their genotype was determined by polymerase chain reaction analysis of genomic DNA. Wild-type control mice and homozygous rd mice were killed at 2-day intervals from postnatal day (P)9 through P21. Double-mutant mice were killed at postnatal days P9, P11, P13, P15, and P21. To determine levels of apoptosis in the retina, eyes were enucleated and processed for light microscopy and in situ nick-end labeling. Total retinal DNA was extracted from isolated retinas for DNA fragmentation analysis. RESULTS: Morphologic, histochemical, and biochemical analyses showed that the time course of apoptosis and the outcome of photoreceptor degeneration in rd/rd, c-fos-/- double-mutant mice was indistinguishable from that in rd mice carrying functional c-fos. CONCLUSIONS: These data suggest that in contrast to its role in light-induced photoreceptor degeneration, c-Fos is not essential for apoptosis in the rd mouse.