Longitudinal evaluation of morphological, functional and vascular alterations in a rat model of experimental glaucoma.

Glaucoma, the leading cause of irreversible blindness worldwide, is a neurodegenerative disease characterized by chronic axonal damages and progressive loss of retinal ganglion cells, with increased intraocular pressure (IOP) as the primary risk factor. While current treatments focus solely on reducing IOP, understanding glaucoma through experimental models is essential for developing new therapeutic strategies and biomarkers for early diagnosis. Our research group developed an ocular hypertension rat model based on limbal plexus cautery, which provides significant glaucomatous neurodegeneration up to four weeks after injury. We evaluated long-term morphological, functional, and vascular alterations in this model. Our results showed that transient ocular hypertension, lasting approximately one week, can lead to progressive increase in optic nerve cupping and retinal ganglion cells loss. Remarkably, the pressure insult caused several vascular changes, such as arteriolar and venular thinning, and permanent choroidal vascular swelling. This study provides evidence of the longitudinal effects of a pressure insult on retinal structure and function using clinical modalities and techniques. The multifactorial changes reported in this model resemble the complex retinal ganglion cell degeneration found in glaucoma patients, and therefore may also provide a unique tool for the development of novel interventions to either halt or slow down disease progression.

Compensatory contribution of retinal larger vessels to perfusion density in diabetics without retinopathy.

Vessel and perfusion densities may decrease before diabetic retinopathy appears; it is unknown whether these changes affect the contribution of vessel density to perfusion density. This was a non-experimental, comparative, prospective, cross-sectional study in non-diabetic subjects (group 1) and diabetics without retinopathy (group 2). Vessel and perfusion densities in the superficial capillary plexus were compared between groups at the center, inner, and full regions and by field (superior, temporal, inferior, nasal) using optical coherence tomography angiography. Coefficients of determination (R2) between vessel and perfusion densities were calculated to find the contribution of larger retinal vessels to perfusion density. Percent differences were used to evaluate the contribution of these vessels to perfusion density in a regression model. There were 62 participants, 31 eyes by group; vessel and perfusion densities as well as the coefficients of determination between them were lower in group 2, especially in the nasal field (R2 0.85 vs. 0.71), which showed a higher contribution of larger retinal vessels to perfusion density. The regression model adjusted to a quadratic equation. In diabetics without retinopathy the contribution of vessel density to perfusion density may decrease; a low vessel density may increase the contribution of larger retinal vessels to perfusion density.

Pre-ischemic enriched environment increases retinal resilience to acute ischemic damage in adult rats.

Retinal ischemia is a condition associated with several degenerative diseases leading to visual impairment and blindness worldwide. Currently, there is no highly effective therapy for ischemic retinopathies. This study was designed to determine possible benefits of pre-exposure to enriched environment against retinal damage induced by acute ischemia. For this purpose, adult male Wistar rats were randomly assigned to a pre-ischemic standard environment or a pre-ischemic enriched environment for 3 weeks, followed by unilateral ischemia induced by increasing intraocular pressure above 120 mm Hg for 40 min and reperfusion for 1 or 2 weeks in standard environment. Animals were subjected to electroretinography and histological analysis. Pre-ischemic enriched environment afforded significant functional protection in eyes exposed to ischemia/reperfusion injury. A marked reduction in retinal layer thickness, reduced synaptophysin-immunoreactivity and retinal ganglion cell (RGC) number, and increased microglia/macrophage reactivity were observed in ischemic retinas from animals submitted to pre-ischemic standard environment, which were prevented by pre-ischemic enriched environment. A deficit in anterograde transport from the retina to the superior colliculus and the lateral geniculate nucleus was observed in animals exposed to pre-ischemic standard environment, which was lower in animals previously exposed to enriched environment. The exposure to enriched environment before ischemia increased retinal brain derived neurotrophic factor (BDNF) protein levels in ischemic retinas and the administration of ANA-12 (a TrkB antagonist) abolished the protective effect of enriched environment on retinal function and retinal ganglion cell number. These results indicate that pre-ischemic enriched environment increases retinal resilience to acute ischemic damage, possibly through a BDNF/TrkB mediated pathway.

Fenómenos vasculares retinianos en esclerosis múltiple. Reporte de caso y revisión narrativa de la literatura / Retinal vascular phenomena in multiple sclerosis. Case report and narrative review of the literatura

Introducción: La esclerosis múltiple (EM) es la enfermedad inflamatoria desmielinizante del sistema nervioso central (SNC) más prevalente en el mundo. Puede presentar afectación a nivel ocular a través del compromiso inflamatorio de distinto tejidos. Objetivo: Dar a conocer la importancia del enfoque temprano de la esclerosis múltiple por parte del médico oftalmólogo. Diseño del estudio: Reporte de caso y revisión narrativa de la literatura. Resumen del caso: Se reporta el caso de una paciente joven con signos de vasculitis retiniana (VR) asociada a neuritis óptica bilateral y uveítis anterior como debut de inusual de la EM. Para la revisión narrativa se llevó a cabo la búsqueda avanzada en tres bases de datos electrónicas: PUBMED, LILACS y OVID. Por medio del gestor de referencias Zotero se realizó la eliminación de duplicados y lectura crítica de título y resumen de 162 artículos por parte de dos investigadores. Conclusión: La EM es una enfermedad crónica inflamatoria del SNC. Puede afectar las estructuras oculares de distintas maneras, una de ellas es la VR, que aunque se caracteriza por el compromiso de vasos venosos, hay que tener en cuenta presentaciones atípicas como hemorragias periarteriolares, aneurismas de grandes vasos, cierre capilar periférico, oclusión de arterial central de la retina, neovascularización del nervio óptico o aparición en etapas tempranas de la enfermedad. La fuerte asociación entre la VR y la actividad de la EM destaca la importancia del reconocimiento de patrones atípicos de una enfermedad que requiere del manejo y seguimiento oportuno por parte de neurología y oftalmología.

Background: Multiple sclerosis (MS) is the most prevalent infl ammatory demyelinating disease of the central nervous system (CNS) in the world. It may present involvement at the ocular level through the inflammatory compromise of different tissues. Objective: To provide knowledge on the importance of the early approach of multiple sclerosis by the ophthalmologist. Study design: Case report and narrative review of the literature. Case summary: We report the case of a young patient with signs of retinal vasculitis (RV) associated with bilateral optic neuritis and anterior uveitis as an unusual debut of MS. For the narrative review, the advanced search was carried out in three electronic databases: PUBMED, LILACS and OVID. Through the Zotero reference manager, the elimination of duplicates and critical reading of the title and summary of 162 articles by two researchers was carried out. Conclusion: MS is a chronic inflammatory disease of the CNS. It can affect the ocular structures in different ways, one of them is RV, which although it is characterized by the involvement of venous vessels, we must take into account atypical presentations such as periarteriolar hemorrhages, large vessel aneurysms,peripheral capillary closure, retinal artery occlusion, neovascularization of the optic nerve or appearance in the early stages of the disease. The strong association between RV and MS activity highlights the importance of recognizing atypical patterns of a disease that requires early management and follow-up by neurology and ophthalmology.

Optical Coherence Tomography Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND: Optical coherence tomography angiography (OCTA) has demonstrated good utility in qualitative analysis of retinal and choroidal vasculature and therefore may be relevant in the diagnostic and treatment efforts surrounding nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: Retrospective, cross-sectional study of 10 eyes of 9 patients with a previous or new diagnosis of NAION that received imaging with OCTA between November 2015 and February 2016. Two independent readers qualitatively analyzed the retinal peripapillary capillaries (RPC) and peripapillary choriocapillaris (PCC) for flow impairment. Findings were compared with automated visual field and structural optical coherence tomography (OCT) studies. RESULTS: Flow impairment seen on OCTA in the RPC corresponded to structural OCT deficits of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) in 80% and 100% of eyes, respectively, and to automated visual field deficits in 90% of eyes. Flow impairment seen on OCTA in the PCC corresponded to structural OCT deficits of the RNFL and GCC in 70% and 80% of eyes, respectively, and to visual field deficits in 60%-80% of eyes. CONCLUSIONS: OCTA can noninvasively visualize microvascular flow impairment in patients with NAION.

Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes.

Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brain's microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type-2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.

Effect of bacterial lipopolysaccharide on ischemic damage in the rat retina.

PURPOSE: The purpose of this study was to investigate whether bacterial lipopolysaccharide (LPS) induces ischemic preconditioning in the rat retina, and, if so, whether nitric oxide (NO) is involved in this process. METHODS: Rats were intravitreously injected with different doses of LPS (0.1, 1, or 5 microg) in one eye and vehicle in the contralateral eye 24 hours before retinal ischemia induced by increasing intraocular pressure to 120 mm Hg for 40 or 60 minutes. Subsequently, 7 or 14 days after ischemia, the rats were subjected to electroretinography and histologic analysis. One group of animals received intraperitoneal injections of NOS inhibitors, N-nitro-L-arginine methyl ester (L-NAME) aminoguanidine or N-(3-(aminomethyl)benzyl)acetamidine (W1400) before the injection of LPS or vehicle. Retinal nitric oxide synthase (NOS) activity was assessed through the conversion of (3)H-L-arginine to (3)H-L-citrulline. RESULTS: One microgram (but not 0.1 or 5 microg) LPS afforded significant morphologic and functional protection in eyes exposed to ischemia-reperfusion injury. The beneficial effect of LPS was reversed by treatment with L-NAME, aminoguanidine, or W1400. LPS (1 and 5 microg, but not 0.1 microg) significantly increased retinal NOS activity. CONCLUSIONS: These results indicate that LPS provides retinal protection against ischemia-reperfusion injury in a dose-dependent manner, probably through an inducible NOS-dependent mechanism.

[Ophthalmologic findings in cardiac transplant recipients]. / Achados oftalmológicos em pacientes que receberam transplante cardíaco.

PURPOSE: To evaluate findings of ophthalmologic examinations in cardiac transplant recipients, searching especially for changes in the retinal nerve fiber layer by means of Scanning Laser Polarimetry. METHODS: Fifteen cardiac transplant recipients were examined from September 2003 to July 2004. All of them underwent ophthalmologic examination, which consisted of visual acuity (VA), biomicroscopy, tonometry and fundoscopy. Fiber layer analyzer-GDx-examination was performed in eleven patients. Twelve patients were men. The mean age was 55.0+/-13.5 years. The follow-up since transplantation lasted from 3 to 74 months; mean value 29.7+/-20.8 months. RESULTS: VA with best correction in all patients attained at least 20/40. Subcapsular posterior cataract was seen in one patient; another presented corneal nubeculae secondary to herpes zoster. In one case a scar suggesting retinocoroiditis was seen at fundoscopy. Biomicroscopic and the fundoscopic findings were expected because of immunosuppressive treatment, following transplantation. GDx examination disclosed loss of fibers in the superior retinal fiber layer in 12 of the 22 examined eyes. CONCLUSION: These results support the hypothesis that reduction of oxygen inflow in retinal circulation before or during heart transplantation could lead to loss of fibers in the retinal nerve fiber layer.

Achados oftalmológicos em pacientes que receberam transplante cardíaco / Ophthalmologic findings in cardiac transplant recipients

OBJETIVO: Avaliar os achados oculares, pelo exame oftalmológico, em indivíduos que receberam transplante cardíaco, buscando especialmente investigar possíveis alterações na camada de fibras nervosas da retina com polarímetro de varredura a laser. MÉTODOS: Foram estudados 15 indivíduos que receberam transplante cardíaco no período de setembro de 2003 a julho de 2004. Todos foram submetidos a exame que constava de acuidade visual para longe (AVL), biomicroscopia, tonometria e fundoscopia. Onze pacientes foram submetidos ao analisador de fibras nervosas GDx. Doze eram do sexo masculino e a média da idade foi de 55,0 ± 13,5 anos. O tempo decorrido desde o transplante variou de 3 a 74 meses, com média de 29,7 ± 20,8 meses. RESULTADOS: A AVL com melhor correção foi igual ou melhor do que 20/40 em todos os pacientes. Em um deles observou-se a presença de catarata subcapsular posterior; em outro, nubéculas na córnea secundárias a quadro de herpes zoster. À fundoscopia pôde-se observar lesão cicatrizada sugestiva de retinocoroidite em um paciente. As alterações observadas à biomicroscopia e à fundoscopia eram esperadas devido à imunossupressão subseqüente ao transplante. Ao GDx observou-se perda de fibras da camada de fibras nervosas da retina superior em 12 dos 22 olhos avaliados. CONCLUSÃO: Os resultados apóiam a suposição de que antes ou durante o transplante cardíaco tenha havido diminuição no aporte de oxigênio à circulação retiniana, levando a perda parcial de fibras da retina.

PURPOSE: To evaluate findings of ophthalmologic examinations in cardiac transplant recipients, searching especially for changes in the retinal nerve fiber layer by means of Scanning Laser Polarimetry. METHODS: Fifteen cardiac transplant recipients were examined from September 2003 to July 2004. All of them underwent ophthalmologic examination, which consisted of visual acuity (VA), biomicroscopy, tonometry and fundoscopy. Fiber layer analyzer - GDx - examination was performed in eleven patients. Twelve patients were men. The mean age was 55.0 ± 13.5 years. The follow-up since transplantation lasted from 3 to 74 months; mean value 29.7 ± 20.8 months. RESULTS: VA with best correction in all patients attained at least 20/40. Subcapsular posterior cataract was seen in one patient; another presented corneal nubeculae secondary to herpes zoster. In one case a scar suggesting retinocoroiditis was seen at fundoscopy. Biomicroscopic and the fundoscopic findings were expected because of immunosuppressive treatment, following transplantation. GDx examination disclosed loss of fibers in the superior retinal fiber layer in 12 of the 22 examined eyes. CONCLUSION: These results support the hypothesis that reduction of oxygen inflow in retinal circulation before or during heart transplantation could lead to loss of fibers in the retinal nerve fiber layer.

Systemic high blood pressure and inner ear dysfunction: a preliminary study.

OBJECTIVE: To assess the association between inner ear dysfunction and retinal vascular changes related to systemic arterial hypertension. DESIGN: A comparative, cross-sectional and observational study. SETTING: Primary care. MAIN OUTCOMES MEASURES: Hearing and vestibular symptoms evaluated by a standardized questionnaire; cochlear function evaluated by audiometry and distortion product otoacoustic emissions; vestibular function evaluated by oculomotor and bithermal caloric tests and vascular retinal compromise evaluated by ophthalmoscopy (according to the modified Scheie classification). RESULTS: Forty-two subjects participated in the study, 21 with and 21 without arterial hypertension, age and sex matched; with no history of diabetes mellitus and with normal glucose levels and normal blood lipids. Although patients with hypertension reported vertigo more frequently than control subjects, conventional oculomotor and bithermal caloric tests showed no difference between the two groups. Patients with hypertension showed deterioration of hearing thresholds at 8 kHz and, compared with normotensive subjects, a higher frequency of abnormal otoacoustic emissions (P = 0.01). According to Scheie classification, 43% (95% CI: 33-53%) of the patients showed second degree retinal vascular compromise and 24% (95% CI: 15-33%) of them showed first degree compromise. The degree of the vascular retinal compromise was significantly correlated with the hearing thresholds at 8 kHz (Spearman's correlation coefficient 0.45, P = 0.002) and it was also consistent with the absence of otoacoustic emissions at frequencies between 4 and 8 kHz. CONCLUSION: The results of this preliminary study suggest that patients with systemic arterial hypertension may have cochlear dysfunction associated with the vascular disease because of hypertension, which could be silent and without clear evidence of vestibular dysfunction.

Risk factors for conjunctival and retinal vessel alterations in sickle cell disease.

PURPOSE: The aim of this study was to clarify whether the clinical, laboratory and genetic aspects of sickle cell disease (SCD) influence the occurrence of vessel alterations in the conjunctiva and retina. METHODS: A total of 102 SCD patients underwent biomicroscopical and retinal examination, in addition to evaluations of haemoglobin (Hb) and haematocrit (Ht) levels, fetal haemoglobin (HbF) estimations, serum creatinine and albuminuria levels, glomerular filtration rate (GFR) values, phenotypes, beta-globin gene haplotypes and alpha-thalassaemia. The relationship between ocular vessel alterations and clinical, laboratory and genetic features were evaluated using chi-squared or Fisher tests and logistic regression analysis. In 13 patients on enalapril treatment, a second ophthalmological evaluation was performed after a 12-month period to evaluate the longitudinal effect of the drug on ocular vessels. RESULTS: Conjunctival vessel alteration (CVA) was not influenced by age, gender, HbF estimation, serum creatinine and albuminuria levels, GFR values, beta-globin gene haplotypes or alpha-thalassaemia. However, increased frequencies of CVA were found in patients with Hb

Retinal fluorescein contrast arrival time of young patients with the hepatosplenic form of the Schistosomiasis mansoni.

Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage.

Estudio de las alteraciones oftalmoscópicas en la hipertención arterial / Ophtalmoscopic features studied by opthalmoscopy in arterial hypertension

La oftalmoscopía puede proporcionar información del grado de actividad y antigüedad de la hipertensión arterial sistémica. Con el advenimiento de la terapia antihipertensiva, la historia natural de la retinopatía hipertensiva se ha modificado, así como los cuadros oftalmoscópicos que se obserban en la antigüedad (exceptuando las manifestaciones oftalmoscópicas secundarias a hipertensión maligna). Trataremos de correlacionar las variables de edad, sexo y factores causales de hipertensión arterial tales como nefropatía, uropatía. etc., con el grado de actividad y antigüedad de la hipertensión, demostrable en las alteraciones oftalmoscópicas

Amaurosis fugax / Amaurosis fugax

La amaurosis fugax es considerada una ceguera monocular transitoria secundaria a isquemia por embolización o insuficiencia vascular que representa un síntoma de enfermedades sistémicas cuyos mecanismos fisiopatológicos incluyen además trombosis, inflamación vascular, hipotensión o vasoespasmo. Su diagnóstico requiere de estudio de laboratorio e imagen para conocer la causa y algunas veces poder ofrecer tratamiento oportuno a los individuos que presentan estos episodios

Microangiopatía retiniana en el síndrome de anticuerpos antifosfolípido primario. Reporte de un caso / Primary antiphospholipid syndrome and microangiopathy. A case report

Se presenta un caso clínico de una paciente del sexo femenino de 35 años de edad con pérdida brusca de la visión de ojo derecho, sin antecedentes de colangenopatías y clínicamente sana hasta el inicio de su padecimiento. La pérdida de la visión se asoció con una hemorragia en la arteria retiniana de la región temporal, con edema papilar discreto. La fluorangiografía correlacionó con el examen del fondo del ojo. Los estudios de laboratorio mostraron títulos altos de anticuerpos antifosfolípido de clase IgG. Los anticuerpos antinucleares y los estudios de inmunoespecificidad resultaron negativos, al igual que la serología para padecimientos infecciosos. La paciente recibió esteroides y aspirina y progresivamente mejoró el cuadro y los títulos de anticuerpos antifosfolípidos decrecieron después de 45 días de tratamiento. Se presenta este caso como una manifestación del síndrome de antifosfolípido primario

El ojo y la hipertensión arterial / The eye and high-blood pressure

En el presenta trabajo se describen las alteraciones que ocurren en algunas estructuras del órgano de la visión como consecuencia de la hipertensión arterial. No se detalla la correspondencia entre la alteración y tipo de hipertensión. Sólo se expone la descripción de cambios que ocurren en el paciente hipertenso. Las alteraciones de la retina y sus vasos vistas por oftalmoscopia ocupan el centro de esta revisión donde también se aportan algunas experiencias en el campo de la electrofisiología, así como las modificaciones encontradas en la microcirculación de la conjuntiva. Los cambios ocurridos en la retina se separan en 2 grupos y se señala la importancia de estos hallazgos en relación con el diagnóstico precoz, pronóstico y evolución de la hipertensión. Se describen las alteraciones electrofisiológicas en los capilares así como otros cambios menos frecuentes (la reducción del campo visual, la asociación glaucoma: hipertensión arterial y la disminución del sentido cromático) (AU)

El ojo y la hipertensión arterial / The eye and high-blood pressure

En el presenta trabajo se describen las alteraciones que ocurren en algunas estructuras del órgano de la visión como consecuencia de la hipertensión arterial. No se detalla la correspondencia entre la alteración y tipo de hipertensión. Sólo se expone la descripción de cambios que ocurren en el paciente hipertenso. Las alteraciones de la retina y sus vasos vistas por oftalmoscopia ocupan el centro de esta revisión donde también se aportan algunas experiencias en el campo de la electrofisiología, así como las modificaciones encontradas en la microcirculación de la conjuntiva. Los cambios ocurridos en la retina se separan en 2 grupos y se señala la importancia de estos hallazgos en relación con el diagnóstico precoz, pronóstico y evolución de la hipertensión. Se describen las alteraciones electrofisiológicas en los capilares así como otros cambios menos frecuentes (la reducción del campo visual, la asociación glaucoma: hipertensión arterial y la disminución del sentido cromático)

Significado del pulso venoso espontaneo en la retina / Heaning of the spontaneous venous pulsation in the retina

El hallazgo del pulso venoso espontáneo en una o varias venas retinianas en un porcentaje apreciable de la población mundial, ha sido un fenómeno que se viene estudiando desde finales del siglo pasado. Su etiología ha sido explicada mediante diversas teorías. Con el estudio de la incidencia del pulso venoso espontáneo en pacientes y en la población general, se llegó a comprender su mecanismo de producción, y ha llegado a ser un instrumento clínico de despistaje en el campo de la neuroftalmología. Antes de entrar es su importancia clínica se deben considerar algunos aspectos