Ocular Vascular Changes in Mild Alzheimer's Disease Patients: Foveal Avascular Zone, Choroidal Thickness, and ONH Hemoglobin Analysis.

In Alzheimer's disease (AD), vascular changes could be caused by amyloid beta (Aß) aggregates replacing the contractile smooth musculature of the arteriole walls. These changes happen in the brain vascular network, but also in the eye, and are related to decreased vascular density and low blood flow. In patients with Alzheimer's disease, thinning of the choroid and the retina has been shown. The aim of this prospective study was to assess the retinal and choroidal vascular systems, analyzing the choroidal thickness with optical coherence tomography (OCT), the foveal avascular zone (FAZ) with OCT-angiography (OCTA), and the optic nerve head (ONH) hemoglobin with the Laguna ONhE program, to evaluate which of the two ocular vascular systems shows earlier changes in mild AD patients. These patients, compared to controls, showed a significantly thinner choroid at all the analyzed points, with the exception of the temporal macula (at 1000 and 1500 µm from the fovea). On the other hand, the FAZ and ONH hemoglobin did not show significant differences. In conclusion, a thinner choroid was the main ocular vascular change observed in mild AD patients, while the retinal vessels were not yet affected. Therefore, choroidal thickness could be used an early biomarker in AD.

Microglial changes in the early aging stage in a healthy retina and an experimental glaucoma model.

Glaucoma is an age-related neurodegenerative disease that begins at the onset of aging. In this disease, there is an involvement of the immune system and therefore of the microglia. The purpose of this study is to evaluate the microglial activation using a mouse model of ocular hypertension (OHT) at the onset of aging. For this purpose, we used both naive and ocular hypertensives of 15-month-old mice (early stage of aging). In the latter, we analyzed the OHT eyes and the eyes contralateral to them to compare them with their aged controls. In the eyes of aged naive, aged OHT and aged contralateral eyes, microglial changes were observed compared to the young mice, including: (i) aged naive vs young naive: An increased soma size and vertical processes; (ii) aged OHT eyes vs young OHT eyes: A decrease in the area of the retina occupied by Iba-1 cells and in vertical processes; and (iii) aged contralateral vs young contralateral: A decrease in the soma size and arbor area and an increase in the number of microglia in the outer segment layer. Aged OHT eyes and the eyes contralateral to them showed an up-regulation of the CD68 expression in the branched microglia and a down-regulation in the MHCII and P2RY12 expression with respect to the eyes of young OHT mice. Conclusion: in the early phase of aging, morphological microglial changes along with changes in the expression of MHCII, CD68 and P2RY12, in both naive and OHT mice. These changes appear in aged OHT eyes and the eyes contralateral to them eyes.

Macular Thickness Decrease in Asymptomatic Subjects at High Genetic Risk of Developing Alzheimer's Disease: An OCT Study.

In this case control study, we examined the retinal thickness of the different layers in the macular region and peripapillary retinal nerve fiber layer (RNFL) with optical coherence tomography (OCT) in healthy cognitive subjects (from 51 to 74 years old) at high genetic risk for developing Alzheimer's disease (AD). Thirty-five subjects with a family history of Alzheimer disease (AD) (FH+) and ApoE ɛ4 carriers and 29 age-matched control subjects without a family history of AD (FH-) and ApoE ɛ4 non-carriers were included. Compared to FH- ApoE ɛ4 non-carriers, in FH+ ApoE ɛ4 carriers, there were statistically significant decreases (p < 0.05) in (i) the foveal area of mRNFL; (ii) the inferior and nasal sectors in the outer and inner macular ring in the inner plexiform layer (IPL); (iii) the foveal area and the inferior sector in the outer macular ring in the inner nuclear layer (INL); and (iv) the inferior sector of the outer macular ring in the outer plexiform layer (OPL). However, no statistically significant differences were found in the peripapillary thickness of RNFL between both study groups. In subjects with cognitive health and high genetic risk for the development of AD, initial changes appeared in the macular area. OCT could be a promising, cost-effective and non-invasive test useful in early AD, before the onset of clinical symptoms.

Ocular Involvement in Friedreich Ataxia Patients and its Relationship with Neurological Disability, a Follow-up Study.

: Background: This study compared functional and structural visual changes in Friedreich ataxia (FRDA) patients with healthy controls (HC) and correlated these changes with neurological disability. METHODS: Eight FRDA Spanish patients and eight HC were selected from 2014 to 2018. Best corrected visual acuity (BCVA), visual field (VF), optic coherence tomography (OCT), and neurological disability measured by "scale for the assessment and rating of ataxia" (SARA) were taken in a basal exploration and repeated after 6 months. A linear mixed analysis and Bonferroni p-value correction were performed. RESULTS: FRDA baseline and follow-up patients showed statistically significant decreases in BCVA, VF, and OCT parameters compared with the HC. Some of the VF measurements and most of the OCT parameters had an inverse mild-to-strong correlation with SARA. Moreover, the analysis of the ROC curve demonstrated that the peripapillary retinal nerve fiber layer (pRNFL) average thickness was the best parameter to discriminate between FRDA patients and HC. CONCLUSIONS: The follow-up study showed a progression in OCT parameters. Findings showed a sequential effect in pRNFL, ganglion cell complex (GCC), and macula. The VF and the OCT could be useful biomarkers in FRDA, both for their correlation with neurological disease as well as for their ability to evaluate disease progression.

Situs inversus del nervio óptico. A propósito de un caso / Situs inversus of the optic nerve. A case report

Introducción. El situs inversus del nervio óptico es una anomalía congénita caracterizada por la emergencia de los vasos de la retina en dirección nasal en lugar de temporal. Es causado por una anómala inserción del tallo óptico en la vesícula óptica que da lugar a la variación de disposición de la cabeza del nervio óptico. No es una condición aislada y suele aparecer junto con el síndrome del disco inclinado y en pacientes con miopía. Se caracteriza por la presencia de un cono de atrofia inferior, defectos en el campo visual temporal, defectos de refracción y ambliopía. Caso clínico. Mujer de 22 años, que acude a revisión oftalmológica por presentar fuertes cefaleas frontales acompañadas de halos y pérdida de nitidez en la visión. Tras un examen optométrico y oftalmológico se llega al juicio clínico de que padece un cuadro compatible con esta anomalía anatómica congénita. Conclusiones. El situs inversus del nervio óptico es una condición rara que puede aparecer aislada o acompañada de otras patologías. La aplicación de la campimetría y de nuevas técnicas diagnósticas, como la tomografía de coherencia óptica, facilita el diagnóstico diferencial de esta situación. No se conoce su prevalencia, pues no se encuentra en el registro de las enfermedades raras. Además, el escaso número de pacientes estudiados y la exigua bibliografía existente sobre esta anomalía no permiten conocer si los defectos causados progresan en el tiempo, por lo que sería importante realizar un seguimiento oftalmológico de los pacientes con situs inversus del nervio óptico (AU)

Introduction. Situs inversus of the optic nerve is a congenital anomaly characterised by the emergence of the vessels in the retina towards the nose rather than in a temporal direction. It is caused by an anomalous insertion of the optic stalks into the optic vesicle that gives rise to dysversion of the head of the optic nerve. It is not an isolated condition and usually appears jointly with tilted disc syndrome and in patients with myopia. It is characterised by the presence of inferior conus atrophy, deficiencies in the temporal visual field, refraction defects and ambliopy. Case report. A 22 years-old female who attended an ophthalmological examination due to severe frontal headaches accompanied by halos and loss of sharpness in her sight. From the results of the ophthalmetric and ophthalmological examination she was diagnosed as suffering from a condition consistent with this congenital anatomical anomaly. Conclusions. Situs inversus of the optic nerve is a rare condition that may appear in isolation or accompanied by other pathologies. Application of the visual field test and new diagnostic techniques, such as optical coherence tomography, facilitates the differential diagnosis of this situation. Its prevalence remains unknown, as it is not included in the register of rare diseases. Moreover, the scant number of patients studied and the scarce literature on this anomaly do not allow us to know whether the defects it causes develop over time. It would therefore be important to perform an ophthalmological follow-up of patients with situs inversus of the optic nerve (AU)

El tratamiento con estatinas mejora las alteraciones ultraestructurales de los vasos oculares en el conejo hipercolesterolémico / Treatment with statins improves the ultrastructural changes of the ocular vessels in hypercholesterolemic rabbits

Introducción Evaluar los cambios ultraestructurales de los vasos coriorretinianos en conejos hipercolesterolémicos tratados con estatinas. Métodos Se utilizaron conejos New Zealand que fueron divididos en 4 grupos: control (G0; n=10), conejos alimentados con una dieta estándar durante 8 meses. Grupo hipercolesterolémico (G1, n=8), conejos alimentados con una dieta enriquecida con 0,5% de colesterol durante 8 meses. Grupo hipercolesterolémico más Fluvastatina sódica (G2A, n=4). Grupo hipercolesterolémico más Pravastatina sódica (G2B, n=4).Métodos Grupo estatinas (G2A y B, n=8), conejos alimentados con una dieta enriquecida con 0,5% de colesterol durante 8 meses más la administración de fluvastatina sódica o pravastatina sódica a una dosis de 2mg/kg/d. Los ojos fueron procesados para microscopía electrónica de trasmisión. Resultados G 1 tenía una gran cantidad de lípidos en la supracoroides que comprimían las capas vasculares coroideas. En G2 las células espumosas y los lípidos de la supracoroides y de las capas vasculares coroideas habían disminuido de forma considerable, aunque había más fibras de colágeno. Las luces de los vasos coroideos estaban más abiertas en G2 que en G1, estando en estos últimos casi colapsadas debido a la compresión y a la hipertrofia de las células musculares lisas y de las células endoteliales. La apariencia normal del endotelio vascular en G2 contrastaba con la necrosis observada en G1. En G2 el espesor de la membrana de Bruch y de las membranas basales de los vasos retinianos y coroideos estaba reducido en comparación con G1. Conclusiones El tratamiento con estatinas reduce la cantidad de lípidos y de macrófagos de la coroides. Además, protege a las células endoteliales y mantiene abiertas las luces de los vasos coroideos (AU)

Introduction To evaluate the ultrastructural changes of the chorioretinal vessels in hypercholesterolemic rabbits after treatment with statins. Methods New Zealand rabbits were divided into four groups: Control (G0; n=10), and fed a standard diet for 8 months; Hypercholesterolemic (G1, n=8), were fed a 0.5% cholesterol-enriched diet for 8 months. Statins group (G2A y B, n=8), were each fed a 0.5% cholesterol-enriched diet for 8 months plus administration of fluvastatin sodium (G2A) or pravastatin sodium (G2B) at a dose of 2mg/Kg/day. Eyes were processed by transmission electron microscopy. Results G1 had a buildup of lipids at the suprachoroidea that compressed the vascular layers. G2 had a substantial decrease in the number of foam cells and lipids but more collagen fibres in the suprachoroidea and vascular layers. The lumen of the choroidal vessels was opened more in G2 in comparison with G1, which had a reduction in the capillary lumen to the point of collapse due to compression and hypertrophy of endothelial and vascular smooth muscle cells. The normal appearance of endothelial cells in G2 was in contrast with the endothelial necrosis observed in G1. In G2, the thickness of the Bruch membrane and the basal membrane of the choroidal and retinal vessels were reduced in comparison with G1. Conclusions Treatment with statins reduces the build up of lipids and the number of macrophages in the choroid. Additionally, they preserve the endothelial cells and open the vascular lumens of choroidal vessels (AU)

Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats. METHODS: Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections. RESULTS: Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats. CONCLUSIONS: We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats.