Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson's disease.

Retinal thickness may serve as a biomarker in Parkinson's disease (PD). In this prospective longitudinal study, we aimed to determine if PD patients present accelerated thinning rate in the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) compared to controls. Additionally, we evaluated the relationship between retinal neurodegeneration and clinical progression in PD. A cohort of 156 PD patients and 72 controls underwent retinal optical coherence tomography, visual, and cognitive assessments between February 2015 and December 2021 in two Spanish tertiary hospitals. The pfGCIPL thinning rate was twice as high in PD (ß [SE] = -0.58 [0.06]) than in controls (ß [SE] = -0.29 [0.06], p < 0.001). In PD, the progression pattern of pfGCIPL atrophy depended on baseline thickness, with slower thinning rates observed in PD patients with pfGCIPL below 89.8 µm. This result was validated with an external dataset from Moorfields Eye Hospital NHS Foundation Trust (AlzEye study). Slow pfGCIPL progressors, characterized by older at baseline, longer disease duration, and worse cognitive and disease stage scores, showed a threefold increase in the rate of cognitive decline (ß [SE] = -0.45 [0.19] points/year, p = 0.021) compared to faster progressors. Furthermore, temporal sector pRNFL thinning was accelerated in PD (ßtime x group [SE] = -0.67 [0.26] µm/year, p = 0.009), demonstrating a close association with cognitive score changes (ß [SE] = 0.11 [0.05], p = 0.052). This study suggests that a slower pattern of pfGCIPL tissue loss in PD is linked to more rapid cognitive decline, whereas changes in temporal pRNFL could track cognitive deterioration.

Differential Distribution of RBPMS in Pig, Rat, and Human Retina after Damage.

RNA binding protein with multiple splicing (RBPMS) is expressed exclusively in retinal ganglion cells (RGCs) in the retina and can label all RGCs in normal retinas of mice, rats, guinea pigs, rabbits, cats, and monkeys, but its function in these cells is not known. As a result of the limited knowledge regarding RBPMS, we analyzed the expression of RBPMS in the retina of different mammalian species (humans, pigs, and rats), in various stages of development (neonatal and adult) and with different levels of injury (control, hypoxia, and organotypic culture or explants). In control conditions, RBPMS was localized in the RGCs somas in the ganglion cell layer, whereas in hypoxic conditions, it was localized in the RGCs dendrites in the inner plexiform layer. Such differential distributions of RBPMS occurred in all analyzed species, and in adult and neonatal retinas. Furthermore, we demonstrate RBPMS localization in the degenerating RGCs axons in the nerve fiber layer of retinal explants. This is the first evidence regarding the possible transport of RBPMS in response to physiological damage in a mammalian retina. Therefore, RBPMS should be further investigated in relation to its role in axonal and dendritic degeneration.

Actualización de la utilidad de la tomografía de coherencia óptica para el estudio del ángulo iridocorneal / Update on the usefulness of optical coherence tomography in assessing the iridocorneal angle

El ángulo iridocorneal por sus implicaciones en la fisiopatología del drenaje del humor acuoso es una estructura fundamental de la cámara anterior. La tomografía de coherencia óptica de segmento anterior es una técnica rápida y no invasiva que obtiene imágenes de los tejidos vivos con una alta resolución permitiendo conocer la anatomía normal del ángulo, sus alteraciones y los cambios que se producen en el mismo tras diferentes intervenciones terapéuticas. La tecnología de la tomografía de coherencia óptica de segmento anterior ha ido evolucionando hasta ofrecer imágenes que permiten identificar y cuantificar estructuras angulares claves en sujetos sanos y en pacientes con glaucoma, especialmente la malla trabecular y el canal de Schlemm, lo que puede contribuir a ampliar el conocimiento de la fisiopatología del glaucoma. Además, permite cuantificar la abertura angular con unos parámetros objetivos descritos en los últimos años, entre los que destacan el ángulo iridotrabecular, la distancia de abertura angular y el área iridotrabecular. La tomografía de coherencia óptica de segmento anterior presenta múltiples utilidades en el estudio de los distintos mecanismos del cierre angular, la evaluación de los cambios angulares tras la realización de una iridotomía láser o iridoplastia, cirugía de la catarata o el implante de lentes fáquicas

The iridocorneal angle, due to its implications in the physiopathology of aqueous humour drainage, is a fundamental structure of the anterior chamber. Anterior segment optical coherence tomography is a rapid and non-invasive technique that obtains images in vivo. The high resolution allows it to analyse the normal anatomy of the angle, any alterations, and the changes that occur after different therapeutic interventions. Anterior segment optical coherence tomography technology has evolved to provide images that allow the identification and quantification of the angular structures in healthy subjects and in glaucoma patients, and especially the trabecular meshwork and the Schlemm's canal. It also enables the angle width to be quantified, with some objective parameters that have been standardised in recent years, such as the trabecular-iris angle, the angle opening distance, and the trabecular-iris area. This technique has multiple uses in the study of the different mechanisms of angle closure, the evaluation of changes after a laser peripheral iridotomy or iridoplasty after cataract surgery, as well as after the implantation of phakic lenses

Update on the usefulness of optical coherence tomography in assessing the iridocorneal angle. / Actualización de la utilidad de la tomografía de coherencia óptica para el estudio del ángulo iridocorneal.

The iridocorneal angle, due to its implications in the physiopathology of aqueous humour drainage, is a fundamental structure of the anterior chamber. Anterior segment optical coherence tomography is a rapid and non-invasive technique that obtains images in vivo. The high resolution allows it to analyse the normal anatomy of the angle, any alterations, and the changes that occur after different therapeutic interventions. Anterior segment optical coherence tomography technology has evolved to provide images that allow the identification and quantification of the angular structures in healthy subjects and in glaucoma patients, and especially the trabecular meshwork and the Schlemm's canal. It also enables the angle width to be quantified, with some objective parameters that have been standardised in recent years, such as the trabecular-iris angle, the angle opening distance, and the trabecular-iris area. This technique has multiple uses in the study of the different mechanisms of angle closure, the evaluation of changes after a laser peripheral iridotomy or iridoplasty after cataract surgery, as well as after the implantation of phakic lenses.

Diagnostic ability of Humphrey perimetry, Octopus perimetry, and optical coherence tomography for glaucomatous optic neuropathy.

PurposeTo evaluate and compare the diagnostic accuracy of the Humphrey Field Analyzer (HFA), Octopus perimetry, and Cirrus OCT for glaucomatous optic neuropathy.MethodsEighty-eight healthy individuals and 150 open-angle glaucoma patients were consecutive and prospectively selected. Eligibility criteria for the glaucoma group were intraocular pressure ≥21 mm Hg and glaucomatous optic nerve head morphology. All subjects underwent a reliable standard automated perimetry with the HFA and Octopus perimeter, and were imaged with the Cirrus OCT. Receiver-operating characteristic (ROC) curves were plotted for the threshold values and main indices of the HFA and Octopus, the peripapillary retinal nerve fiber layer thicknesses, and the optic nerve head parameters. Sensitivities at 85 and 95% fixed-specificities were also calculated. The best areas under the ROC curves (AUCs) were compared using the DeLong method.ResultsIn the glaucoma group, mean deviation (MD) was -5.42±4.6 dB for HFA and 3.90±3.6 dB for Octopus. The MD of the HFA (0.966; P<0.001), mean sensitivity of the Octopus (0.941; P<0.001), and average cup-to-disc (C/D) ratio measured by the Cirrus OCT (0.958; P<0.001) had the largest AUCs for each test studied. There were no significant differences among them. Sensitivities at 95% fixed-specificity were 82% for pattern standard deviation of the HFA, 81.3% for average C/D ratio of OCT, and 80% for the MD of the Octopus.ConclusionsHFA, Octopus, and Cirrus OCT demonstrated similar diagnostic accuracies for glaucomatous optic neuropathy. Visual field and OCT provide supplementary information and thus these tests are not interchangeable.

Changes in Surface Tension of Aqueous Humor in Anterior Segment Ocular Pathologies.

The aim of this study was to identify and determine differences in surface tension (ST) of aqueous humor (AH) in patients with cataract, glaucoma and Fuchs endothelial dystrophy (FED). Two hundred and two samples of AH were analyzed (control n = 22; cataract n = 56; glaucoma n = 81; and n = FED 43). Patients with previous history of anterior segment surgery, anterior segment pathology or intraocular injections were excluded from the study. Different types of glaucoma were identified, cataracts were graded using total phaco time data during surgery and clinical severity of FED was assessed by clinical examination. Around 150 microliters AH were obtained during the first step of a surgical procedure, lensectomy, phacoemulsification, nonpenetrating deep sclerotomy (NPDE) and Descemet membrane endothelial keratoplasty (DMEK). A pendant drop-based optical goniometer OCA-15 (Dataphysics, Filderstadt, Germany) was used to measure surface tension. Mean ST was 65.74 ± 3.76 mN/m, 63.59 ± 5.50 mN/m, 64.35 ± 6.99 mN/m, and 60.89 ± 3.73 mN/m in control, cataract, glaucoma and FED patients respectively. Statistically significant differences between FED and control group were found (p < 0.001). Lens condition, cataract maturity, age, and gender did not show influence in ST. ST of AH is significantly decreased in FED patients independently from age and lens condition. These findings may aid to the understanding of the physiopathology of the disease.

Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments.

The aim of the present study is to evaluate the neuroprotective effect of two antiglaucomatous substances, regardless of their hypotensive effect in the eye. Brimonidine, which does not reduce IOP when administered intraperitoneally, and latanoprost, which has a renowned hypotensive effect topically. We examined rat retinal ganglion cell (RGC) survival and size distribution in experimental glaucoma in response to different glaucomatous agents. IOP was elevated by episcleral vein cauterization (EVC) prior to the application of different treatments: (I) PBS application (control group), (II) intraperitoneal administration of brimonidine (a general hypotensive agent), (III) topical application of latanoprost (an ocular hypotensive agent), and (IV) latanoprost combined with brimonidine. After 12 weeks, RGCs were retrogradely labeled with fluorogold and RGC density was analyzed. EVC caused a significant increase (42%) in IOP in each group before drug treatment. After 12weeks of EVC, RGC survival in control vs. EVC rats was 78.9+/-3.2%. No IOP reduction was observed in brimonidine injected rats, but RGC survival at 12 weeks was total (103.7+/-2.7%). In latanoprost treated rats, IOP dropped by around 22% and 94.7+/-3.7% of the RGC population survived. Finally in the latanoprost+brimonidine combined group, IOP was significantly reduced by 25% and 94.4+/-2.2% of RGCs survived. Surprisingly, whereas EVC led to a 6% increase in RGC soma size, brimonidine treatment was associated with a 9% reduction in the soma size of RGCs at 12 weeks. We conclude that brimonidine exerts a neuroprotective effect via a mechanism which is independent of IOP reduction. These findings indicate that cell survival in glaucoma may be enhanced by neuroprotective strategies which are independent of IOP reduction. No synergistic neuroprotective effect was observed when both treatments were applied simultaneously.

Three experimental glaucoma models in rats: comparison of the effects of intraocular pressure elevation on retinal ganglion cell size and death.

Glaucoma is a chronic and progressive optic nerve neuropathy involving the death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is considered to be the major risk factor associated with the development of this neuropathy. The objective of the present study was to compare the effects on RGC survival of three different experimental methods to induce chronic elevation of IOP in rats. These methods were: (i) injections of latex microspheres into the eye anterior chamber; (ii) injections into the anterior chamber of a mixture of microspheres plus hydroxypropylmethylcellulose (HPM) and (iii) cauterization of three episcleral veins. The IOP of right (control) and left (glaucomatous) eyes was measured with an applanation tonometer in awake animals. Thirteen to 30 weeks later, RGCs were retrogradely labeled with 3% fluorogold. Subsequently, we analyzed the density of RGCs, as well as the major axis length and area of RGC soma resulting from the application of each method. A significant increase in IOP was found following application of each of the three methods. Cell death was evident in the glaucomatous eyes as compared to controls. However, no statistical differences were found between the extent of cell death associated with each of the three methods. IOP increase also induced a significant increase in the size of the soma of the remaining RGCs. In conclusion, the three methods used to increase IOP induce a similar degree of RGC death. Moreover, the extent of cell death was similar when the retinas were maintained under conditions of elevated IOP for 24 weeks in comparison to 13 weeks.

[Retinal ganglion cell neuroprotection in culture]. / Neuroprotección de las células ganglionares de la retina.

PURPOSE: To study the pig retinal ganglion cell (RGC) survival in culture, analysing the possible neuroprotective effect of retinal Müller glia (RMG) and brain-derived neurotrophic factor (BDNF). METHODS: Adult pig retina were dissociated and cultured under different conditions: 1) on laminin/poly-D-lysine-coated coverslips in chemically defined medium (CDM); 2) on laminin/poly-D-lysine-coated coverslips in CMD supplemented with BDNF; 3) on confluent monolayer cultures of RMG in CDM; 4) on laminin/poly-D-lysine substrate in conditioned medium obtained from RMG. RGCs were identified by immunocytochemistry using antibody against 68 kDa neurofilament and observed under an fluorescent microscope. RGCs were classified on the basis of the size, number and length of neurites, and their survival was assayed for each treatment. RESULTS: Confluent RMG substrates and RMG conditioned medium significantly increased the survival of cultured pig RGC. Moreover these two conditions increased the mean area of RGCs and enhanced neurite growth and elongation. Addition of BDNF to culture medium did not modify survival but increased RGC size, neurite number and neurite length. CONCLUSIONS: These findings demonstrate that factor(s) secreted by RMG exert beneficial effects on adult RGC survival and neurite regeneration in vitro, and might constitute important agent(s) for RGC neuroprotection. BDNF also increases the mean area of RGCs and enhances neurite growth but it does not increase the survival of RGCs.

Síndrome de Lyell asociado a lamotrigina / Lyell's syndrome associated with lamotrigine

Introducción. La lamotrigina (LTG) es un nuevo antiepiléptico de uso habitual en monoterapia tanto en epilepsias parciales como en generalizadas, que presenta entre otros efectos adversos la aparición de erupciones cutáneas leves y, con menos frecuencia, graves como el síndrome de Stevens-Johnson y el síndrome de Lyell o necrólisis epidérmica tóxica, sobre todo en combinación con valproato (VPA). Caso clínico. Mujer de 44 años en tratamiento por epilepsia toxicoalcohólica con VPA. Presenta neutropenia, probablemente secundaria, por lo que se intentó cambiar a LTG, siguiendo una pauta ascendente de LTG y descendente de VPA. En la sexta semana de tratamiento desarrolló una erupción cutánea eritematosa que, tras exposición solar, una semana después, se agravó con fiebre y malestar general, presentando en cabeza, región torácica anterior y posterior, abdomen, extremidades superiores e inferiores lesiones eritematosas con áreas costrosas, áreas de despegamiento de epidermis con signo de Nikolsky positivo y afectación severa de mucosas, siendo diagnosticada de síndrome de Lyell. Las lesiones mejoraron lentamente con sueroterapia, antibioterapia, corticosteroides parenterales y tratamientos tópicos. Conclusiones. Hay una probabilidad de erupción cutánea grave asociada a LTG que se debe tener en cuenta, se aconseja por lo tanto a los pacientes la suspensión de la medicación ante la mínima erupción cutánea (AU)

[Lyell syndrome associated with lamotrigine]. / Síndrome de Lyell asociado a lamotrigina.

INTRODUCTION: Lamotrigine (LTG) is a new antiepileptic of habitual use in monotherapy as much in partial epileptic as in generalised, which presents among other adverse effects: slight rashes and less frequently severe rashes such as Stevens-Johnson syndrome and Lyell syndrome or toxic epidermal necrolysis, above all in combination with valproate (VPA). CLINICAL CASE: A 44-yr-old woman in toxico-alcoholic epileptic treatment with VPA, showed a neutropenia possibly of secondary type which it was intended to change to LTG, following an ascending dose of LTG joined to a descending dose of VPA. In the sixth treatment week, the patient developed an erythematous rash which after a week of solar exposure, presented temperature, general discomfort, and in the head, on the front and back part of the thoracic and upper and lower limbs, erythematous lesions with scabbed areas, loosening epidermis areas with a positive Nikolsky sign and severe mucous membrane involvement, being diagnostic of Lyell syndrome. The lesions got slowly better with serum therapy, antibiotherapy, parenteral corticoids and topical treatments. CONCLUSIONS: There is a probability of severe rash associated with lamotrigine which has to be taken into account, and we advise patients to suppress the medication when they present a minimum rash.

[Evaluation of the Mullan's technique in the treatment of trigeminal neuralgia]. / Valoración de la técnica de Mullan en el tratamiento de la neuralgia del trigémino.

OBJECTIVE: The aim of the present study is to examine the operative technique and results of the treatment of trigeminal neuralgia (TN) by percutaneous microcompression of the trigeminal ganglion (Mullan's technique) in 20 consecutive patients over 3 years. PATIENTS AND METHODS: The average age of the patients was 63 years. There were 8 men and 12 women. The operative technique is similar to Mullan and Lichtor's original description with some modifications. RESULTS: On average it takes 30 minutes to complete the procedure. On 2 occasions the catheter had to be replaced as the balloon burst without clinical repercussions. Detectable changes were noted in systemic blood pressure and cardiac rhythm in 10 cases. On 17 occasions the radiographic appearance of the balloon was pear-shaped and in the remaining cases it was oval or irregular. Follow-up ranged from 6 months to 3 years. All but 1 patient were initially relieved of pain and it was progressively possible to suspend treatment with carbamazepine. The recurrence rate was 25%. Mean time until recurrence was 18 months. There was no relation between pain location and recurrence. Morbidity: some degree of transient cheek discomfort, herpes simplex perioralis, hypesthesia and masseter weakness were the rule. Meningitis in one case. CONCLUSIONS: Early results indicate that Mullan's technique provides a reliable, safe, cheap and effective, with low morbidity and no mortality.