Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation

The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings

Investigation of pepsin in tears of children with laryngopharyngeal reflux disease

Objectives: Numerous investigations postulated that Laryngopharyngeal reflux (LPR) is implicated in the pathogenesis of various upper airway inflammatory diseases as sinusitis or dacryostenosis. The presence of pepsin in tears might be confirmed the presuntive hypothesis of the arrival in the nasolacrimal ducts and precorneal tears film through the laryngopharyngeal reflux of either gastric acid or stomach secretions (pepsin) with inflammatory potentialities. The aim of this preliminary study was to identify the presence or absence of pepsin in the tears collected from children with a high suspicion of LPR who underwent 24-h pH (MII-pH) monitoring to confirm the disease. Methods: This study enrolled twenty patients suffering from symptoms of laryngopharyngeal reflux that underwent 24-h multichannel intraluminal impedance (MII)-pH monitoring to confirm the disease. The findings of the study group were compared with those of a control group of patients with negative pH monitoring. The quantitative analysis of human pepsin concentration in the tear samples was performed by ELISA method in both groups. Results: Four children (20%) of the study group showed pepsin in the tears. All of the subjects belonging to the control group were negative for its presence. No difference differences in the total number of reflux episodes and the number of weakly basic reflux in the pepsin positive patients vs pepsin negative children were present. Conclusions: 20% of the children with diagnosed LPR showed pepsin in the tears. Our specific investigation might provide information regarding sinusitis or dacryostenosis

Age and diabetes related changes of the retinal capillaries: an ultrastructural and immunohistochemical study

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes

Gastroesophageal reflux disease and the presence of pepsin in the tears.

The nasolacrimal duct in association with the lacrimal puncta, lacrimal canaliculi and lacrimal sac functions to collect and drain the tear film into the nasal cavity at the inferior nasal meatus where a fold of nasal mucosa, the so-called valve of Hasner, prevents mucous from entering the nose. High-resolution computed tomography demonstrated air inside the sac and nasolacrimal duct in approximately 29.3% of healthy patients suggesting that the system is not completely competent and that air and secretions might reach the precorneal film. Gastroesophageal reflux disease may contribute to dacryostenosis and subsequent primary acquired nasolacrimal duct obstruction. However a cause-effect relationship is unclear and only presumptive unless the presence of pepsin in tears can be demonstrated. Gastroesophageal and extra-esophageal reflux could reach the tear film via the nasolacrimal duct in a retrograde fashion and the middle ear via the Eustachian tube. We postulated that the ascending products of gastroesophageal reflux could cause edema of the nasolacrimal duct mucosa, which might progress to fibrosis and chronic inflammation and, ultimately, complete obstruction of the duct with epiphora. The role of reflux in the initial phase of this pathophysiological mechanisms could be demonstrated indirectly by pepsin. By contrast, the development of dacryostenosis blocking the passage of the nasolacrimal duct and thereby preventing pepsin from reaching the lacrimal film failed to explain the influence of gastroesophageal reflux disease with certainty

Histological findings in a failed corneal riboflavin-UVA collagen cross-linking performed for progressive keratoconus

Purpose: To report the histological and immunohistochemical findings in a cornea removed from a patient who had undergone collagen cross-linking (CXL) with riboflavin and ultraviolet-A for progressive keratoconus. CXL was performed following the Siena protocol. Two years post-CXL, a visual acuity impairment in the treated eye secondary to corneal stromal opacity had occurred, together with corneal thinning and flattening. Methods: The excised cornea was formalin-fixed, paraffin-embedded, and examined microscopically. Deparaffinized 4-mu m sections were stained with hematoxylin-eosin and Masson trichrome. Further tissue sections were subjected to immunohistochemical evaluation of CD34 and Ki-67 antigens. Results: Histologically, there was no scar tissue in the failed cornea. The biomicroscopic stromal opacity corresponded microscopically to an acellular area, devoid of keratocytes, and to compaction of the lamellar collagen. Amorphous, weakly eosinophilic interlamellar deposits, extending from the anterior to the posterior two thirds of the stroma, were noted. Conclusions: CXL is a promising procedure for the treatment of progressive keratoconus with minimal reported side effects. In the present case, we speculate that the short corneal soaking time (15 minutes according to the Siena protocol) may have resulted in inefficient ultraviolet-A blocking, thermal injury, and deeper keratocyte death. Inadequate keratocyte stem cells reservoir could also play a role in individual cases

Late corneal decompensation after obstetrical forceps ocular trauma at birth

A 51-year-old woman presented with recurrent painful ulcers in her left cornea over a period of six months. She had a history of a birth that required obstetrical forceps delivery and poor vision in the left eye since childhood, resulting in deep amblyopia. At the level of Desçemet’s membrane, confocal microscopy demonstrated cicatricial highly reflective scroll-structures above the endothelial cell layer. Penetrating keratoplasty and cataract phacoemulsification with intraocular lens implantation were performed in the left eye. The indications for penetrating keratoplasty were related to the painful corneal ulcers, as there was little prospect of visual improvement. The histological findings were consistent with corneal endothelial decompensation and associated old ruptures in Desçemet’s membrane and posterior stroma scarring

An update on oculodermal melanocytosis and rare associated conditions

Oculodermal melanocytosis (ODM) is a rare disease, which is characterized by hyperpigmentation of facial skin and several parts of the eye, such as the sclera, conjunctiva, cornea, iris, ciliary body, and choroid. The condition usually affects the Asian female population. The most typical presenting ocular sign is iris heterocromia. Iris hyperpigmentation may be associated with iris mammillations, which are dome-shaped protuberations of the iris surface. They are linked to a higher risk of malignant transformation when present in patients with ODM. Glaucoma is a complication of ODM and is caused by angle abnormalities or mechanical occlusion by melanocytes in an open irido-corneal angle. Choroidal and ciliary body melanoma have a higher incidence in this condition characterized by melanocytosis. Patients presenting ODM should undergo routine ophthalmological examination in order to carefully monitor for glaucoma and melanoma

Un caso anomalo di sindrome di Posner – Schlossman

Gli autori hanno riportato un caso anomalo di Posner-Schlossman in una giovane paziente di 46 anni. Tale sindrome, come è noto, è caratterizzata da episodi acuti e recidivanti di ipertensione oculare, associata a segni modesti di flogosi uveale anteriore che colpisce essenzialmente soggetti giovani di età compresa tra 20 e 50 anni. Ciò che ha interessato particolarmente nello studio di questo caso clinico è la particolare insorgenza, la brevissima durata (qualche ora) e la monolateralità degli episodi ipertensivi affiancati da una negatività dell’esame obiettivo e di quelli diagnostici svolti