Allergic conjunctivitis: current concepts on pathogenesis and management.

Allergic conjunctivitis (AC) includes a wide spectrum of clinical entities characterized by different incidence, age of onset, natural course, clinical outcome and response to treatment. Taken together, they represent one of the most frequent ocular surface diseases affecting more than 30% of the young-adult population and show an increasing incidence over the years. Moreover, comorbidities with other systemic atopic conditions such as asthma, atopic dermatitis and rhinitis require a multidisciplinary approach. Recent advances in the knowledge of the pathogenic mechanism overcome the classic role of type I hyper-sensitivity and mast cells’ activation, demonstrating an involvement of innate immunity and neuroinflammation in the pathogenesis of the most severe forms such as atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). Ocular itching, swelling and tearing are the most frequent symptoms complained by patients with all forms of AC, while photophobia and pain are typical of the most severe forms, such as VKC and AKC, due to the frequent corneal involvement. Upper tarsal papillary reaction represents the main clinical sign of AC associated with conjunctival hyperemia and mucous secretion. Diagnosis is based on clinical history and eye evaluation and can be confirmed through allergological tests. Additional ocular exams include specific allergen conjunctival provocation tests and the presence of eosinophils in the conjunctival scraping. Current treatments of AC include the use of antiallergic eye drops for mild forms, while recurrences of ocular surface inflammations with corneal involvement in severe forms require the use of topical steroids to avoid visual impairment. Novel steroid sparing therapies such as Cyclosporine A eye drops or topical Tacrolimus have been proposed to improve VKC and AKC management.

Degenerative events in retina and optic nerve induced by inhibition of carnitine transport.

Biochemical and pharmacological evidence supports the hypothesis that the mechanism of action of mildronate [3-(2,2,2-trimethylhydrazinium)propionate dihydrate] is based on its regulatory effect on carnitine concentration. The present study demonstrates that carnitine acts as a neuroprotective agent both in optic nerve head and in retinal ganglion cell (RGC) by means of antioxidant and antiradical activities. In fact, carnitine normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and inducible nitric oxide synthase (iNOS) expression by stabilizing mitochondrial membranes, as assessed by quantitative and qualitative analysis. This research shows that the neuroprotective effects of carnitine result, at least partially, from anti-neurodegenerative (anti-apoptotic) and anti-inflammatory mechanisms. It is suggested that the molecular conformation of carnitine can facilitate its easy binding to mitochondria, and regulate the expression of different signal molecules, hence maintaining normal cellular signaling and survival by modulating caspase-3 activity.

Mechanisms of ocular neuroprotection by antioxidant molecules in animal models.

This work was conducted to evaluate the efficacy of a treatment on retinal ganglion cells (RGC) and on astrocytes of the optic nerve of glaucomatous eyes, using a combination of alpha-lipoic acid (ALA) and superoxide dismutase (SOD). Thirty-two male Wistar rats were fed with a diet supplemented with ALA, SOD, ALA and SOD or with no product for 8 weeks. Ocular hypertension was induced with 2% methylcellulose (MTC) and then rats were sacrificed. TUNEL assay showed a marked fluorescence in the ganglion cells and astrocytes of MTC-treated rats evidencing induction of apoptosis. In contrast, sections of eyes pretreated with ALA and SOD showed a lack of fluorescence quite similar to that of the controls. Similarly, eyes sections from rats pre-treated with ALA and SOD showed reduced differential expression of inducible nitric oxide synthase (iNOS) and of caspase-3 in compared to normally-fed/MTC-inoculated cases. An increase of ALA and SOD exerts an antiapoptotic effect and protects against oxidative stress and hence against the structural remodelling of the RGCs and astrocytes of the optic nerve in the presence of an ischemic and pressure stress.

Influence of age and physical exercise on sirtuin activity in humans.

Sirtuins are NAD+-dependent lysine deacetylases. Sirtuins acquired worldwide attention because of their ability to increase yeast, flies, worms and mice lifespan. Recently, this assumption has been challenged. However, their beneficial role on the quality of ageing is widely accepted. In this work we aimed to study how and if sirtuins expression and activity levels varies in function of age and, in the case of young subjects, of exercise. Fifteen blood donors of different ages and fifteen athletes of the Italian rowing male team were enrolled and peripheral blood mononuclear cells (PBMCs) isolated from blood samples. Our results show that sirtuins deacetylases activity measured in PBMCs increases from 18 to 40 years of age and then decreases during the following 20 years. Moreover, physical exercise in professional athletes can upregulate sirtuin activity. Thus, for the first time in humans, we demonstrate that sirtuin activity is a function of age and can be altered through physical exercise.

Botulinum toxin treatment in glaucomatous patients: a pilot study.

PURPOSE: The purpose was to evaluate the efficacy of the treatment of iatrogenic entropion (IE), in patients affected by primary open angle glaucoma (POAG), by botulinum toxin injections (BTI). PATIENTS AND METHODS: 20 patients of the "Glaucoma Center" of the Hospital "Umberto I" (Rome) were examined. These patients had POAG and used prostaglandin analogues (PA). Mean age was 75.5 years old (range 68-83); they had been suffering from PAOG since 10 years and were not affected by other relevant systemic diseases. One to three BTI were made into the lower orbicularis muscle using a 0.3 G needle (0.025 to 0.05 units for each injection site). RESULTS: The results were particularly significant in 18 out of 20 patients. Two patients showed slight improvements. A rating scale ranging from 0 to 6 points (0 corresponded to 'no effect' and 6 to the 'complete' resolution of the entropion) was used to evaluate the goals of the treatment. The average rating was 5.37 points. CONCLUSIONS: The entropion due to glaucoma therapy with PA can be successfully treated with BTI in the orbicularis muscle, despite offering temporary therapeutic effects.

Treatment of glaucomatous patients by means of food supplement to reduce the ocular discomfort: a double blind randomized trial.

BACKGROUND AND AIM: Chronic use of multi-dose eye drops containing preservatives, such as it may happen in patients affected by primary open angle glaucoma, often results in a damage of the ocular surface due to the inherent toxicity of preservatives, that with time may lead to a lacrimal dysfunction syndrome and eye dryness. PATIENTS AND METHODS: This double blind, randomized, pilot study was conducted on 38 glaucomatous patients suffering from dry eye induced by long-term use of eye drops preserved with BAK. RESULTS: Treatment of these patients with a food supplement containing an association of forskolin, rutin and vitamins B1 and B2 for 30 days increased significantly their OPI values and improved the symptoms of dry eye with respect to a placebo-treated control group. CONCLUSIONS: The association of forskolin, rutin and vitamins B1 and B2 appears to be protective for the ocular surface, contributing to restore a normal equilibrium of the tear film in those subjects in which toxic agents such as BAK had determined alterations of its homeostasis.

Vernal keratoconjunctivitis: atopy and autoimmunity.

BACKGROUND: Vernal Keratoconjunctivitis (VKC) is a rare chronic ocular inflammatory disease and it mainly affects boys in the first decade of life. Although it is a self-limiting disease, patients may present many phases characterized by an exacerbation of inflammatory symptoms with a consequent decline of the quality of life. PURPOSE: define the clinical and immunological profile of patients affected by VKC and investigate their familiar history of autoimmune disorders and their autoimmunity pattern. PATIENTS AND METHODS: 28 children were enrolled (20 males, 71%) aged between 4 and 14 years of life affected by VKC. Family history of allergic and immunological diseases was collected for each patient. In particular, it was asked whether some components of their families were affected by Hashimoto's thyroiditis, type I diabetes, psoriasis or rheumatoid arthritis and Systemic Lupus Erythematosus (SLE). All VKC children underwent a serological evaluation of anti-nuclear antibodies (ANA). RESULTS: A family history of immunological disorders was found in 46% of patients, 28% of Hashimoto's thyroiditis, 14% of type I diabetes, 14% of psoriasis, and 1 of Systemic Lupus Erythematosus. Furthermore, 35% of patients was ANA positive and they corresponded to patients with a higher ocular score and with the most important clinical symptoms. CONCLUSIONS: the detection of ANA positivity and of a familiar history of autoimmune disorders in a high percentage of children with VKC may help us to better understand the association of this ocular inflammatory disease with systemic autoimmune disorders and atopic condition.

Serum levels of IL-17 in patients with vernal keratoconjunctivitis: a preliminary report.

BACKGROUND AND AIM: Vernal Keratoconjunctivitis (VKC) is a chronic and often severe form of bilateral tarsal and/or bulbar conjunctivitis. The purpose of the present study is to measure the Interleukin-17 (IL-17) serum levels in children with VKC evaluating the role of the systemic inflammation in patients affected by VKC. PATIENTS AND METHODS: Fifteen patients were enrolled with VKC aged between 6 and 10 years of life. Serum were obtained from the peripheral blood samples collected from all the children included in the study to evaluate serum level of IL-17. RESULTS: Serum levels of IL-17 were significantly higher in patients with VKC than in healthy controls (10.3 ± 9.36 pg/ml vs. 3.3 ± 6.20 pg/ml respectively; p < 0.04). CONCLUSIONS: The presence of a significantly higher level of IL-17 in patients with VKC suggests a possible role of this cytokine in the pathogenesis of VKC. Further studies on larger samples of patients are warranted to confirm These findings in order to identify new possible therapeutic targets.

The effect of latanoprost and influence of changes in body position on patients with glaucoma and ocular hypertension.

BACKGROUND AND OBJECTIVES: Some patients have an elevation of intraocular pressure (IOP) in the supine position (IOPSP). It has been suggested that topical latanoprost 0.005% (LP) has an attenuating effect on these IOP elevations. The Authors report a simple procedure to evaluate the change in the IOPSP. This paper presents the results of the change in the IOPSP in normals, in patients with ocular hypertension (OH) and in patients with primary open angle glaucoma (POAG). The study also evaluates the effect of the addition of topical LP on those patients with an elevation of their IOPSP. PATIENTS AND METHODS: Part 1 evaluated the change in the IOPSP in the morning in 40 eyes of normals, 82 eyes in patients with OH and 77 eyes in patients with POAG. The IOP was measured before and after lying in the supine position (SP) for 90 minutes. In part 2 the patients with OH or POAG with an increase in their IOPSP were selected and the test was repeated again after the addition of topical LP. RESULTS: When compared with normals, the patients with OH and POAG had significantly greater IOPSP increases. The patients with POAG had significantly greater IOPSP increases than did those with OH. The addition of LP partially decreased but did not eliminate the IOP increases in the SP. CONCLUSIONS: Patients with OH and POAG have a larger increase in their IOPSP than do normals. The addition of topical LP partially decreased but did not totally eliminate these pressure increases.

Oxidative stress in the closed-eyelid test: management of glaucoma.

BACKGROUND AND OBJECTIVES: To evaluate the role of antioxidant drugs in the tonometric increase that follows the closed eyelid test (CET), a predicitive test for glaucoma, after administration of antioxidant substances was observed. MATERIALS AND METHODS: 30 subjects of 54.57+/=5.62 years, 13 males and 17 females, were examined by measuring the ocular pressure after 1 hour from the CET, both in normal conditions and after the administration of antioxidants such as: vitamin A (50,000 IU/die), vitamin E (600 mg/die), and vitamin C (1000 mg/die). The increases in temperature of the iridocorneal angle and of the iris were also measured in the same conditions with an infrared Thermo-Precision tonometer (Sola Electro-Optics, China) both before and after CET. RESULTS: The results showed increased pressure after CET and decreased pressure after the administration of each antioxidant substance, although vitamin A was found to be more effective and with statistically significant values compared to vitamins E and C. CONCLUSIONS: Considering the responses obtained after administration of antioxidant drugs, the ocular hypertension induced after CET could be a response to mixed stress, oxidative and thermic, with degenerative effects on the trabecular meshwork (TM). Besides, in light of these considerations the research results underline that the open angle glaucoma (OAG) should be considered a multifactorial degenerative disease.

Keratoconus: the possible involvement of inflammatory cytokines in its pathogenesis. An experimental study and review of the literature.

OBJECTIVE: Keratoconus (KC) is generally described as a non-inflammatory disease, characterized by thinning in the central region of the cornea with consequent tissue degradation producing impaired visual acuity. MATERIALS AND METHODS: In our experimental study, we analyzed the presence and implications of several inflammatory cytokines in the corneal tissues of patients suffering from keratoconus by immunohistochemical analysis. RESULTS: The analysis showed increased levels of inflammatory factors in the pathological tissues compared to controls, confirming that KC cannot be considered an entirely non-inflammatory pathology and that its etiopathogenesis includes several chronic inflammatory events. CONCLUSIONS: In the light of these results, the classification of KC as an inflammatory pathology or as a pathology related to inflammation might be useful in directing future research aimed at developing effective anti-inflammatory therapies to pharmacologically target the inflammatory mediators which contribute to the development and progression of the disease.

The role of inflammation in diabetic retinopathy: a review.

OBJECTIVE: Diabetic retinopathy and diabetes represent serious health conditions, being considered among the main causes of blindness. In recent years, anti-VEGF therapies have been of great help in the treatment of retinal pathology and, until now, they represent the primary choice therapy for diabetic retinopathy. Nevertheless, many patients do not experience significant benefits of vision after an anti-VEGF monotherapy. For this reason, several researchers recently focused their attention on the mechanisms that play a central role in the development and progression of diabetic retinopathy. RESULTS: Available scientific evidence confirms that diabetic retinopathy requires other molecules capable of modifying the mechanisms that, together with angiogenesis, contribute to the development of the condition, such as vascular and neuroinflammation. CONCLUSIONS: This review summarizes the current knowledge of the pathological changes that occur in diabetic retinopathy and that might contribute to identify possible new strategies for the treatment of this condition.

Vernal Keratoconjunctivitis: an update focused on clinical grading system.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a severe disease with a prevalence of < 1 case out of 10,000 in Europe, which occurs mainly in pediatric age and is characterized by a severe and often bilateral chronic inflammation of the ocular surface. The diagnosis is generally confirmed by the finding at the ocular examination of conjunctival hyperemia, papillary hypertrophy in the tarsal conjunctiva, giant papillae, papillae in the limbus region. OBJECTIVE: Aim of this review is to provide an updated overview on the disease focused on clinical grading system, searching papers published in the last decade on VKC in scientific databases. RESULTS: Currently there are no standardized criteria for diagnosis of VKC and there is no uniformity to define disease severity, which makes difficult to diagnose and treat the disease. CONCLUSIONS: Given the wide overlap of the symptoms of VKC with the allergic conjunctivitis, criteria of probable, possible or improbable diagnosis are needed, providing pediatricians with parameters useful for deciding whether to drive the patient to the ophthalmologist for diagnostic confirmation.

Macular hole in retinitis pigmentosa patients: microincision vitrectomy with polydimethylsiloxane as possible treatment.

PURPOSE: To investigate long-term retinal changes after microincision pars plana vitrectomy surgery (MIVS) for macular hole (MH) in retinitis pigmentosa (RP) patients-retrospective and observational study. METHODS: Three RP patients suffering from MH were evaluated by means of best corrected visual acuity, anterior and posterior binocular examination, spectralis high-resolution optical coherence tomography, MP-1 microperimetry (MP-1), and full-field electroretinogram (ERG), before MIVS and during the 36-month follow-up. Patients underwent simultaneous MIVS and microincision cataract surgery; IOL was positioned in capsular bag. Patients were hospitalised for 2 days after the surgery. Surgical procedure was performed according the following schedule: surgical removal of crystalline lens, MIVS with 23-gauge sutureless system trocars, core vitreous body removal, peeling of the inner limiting membrane, and balanced sterile saline solution-air-micro-structured polydimethylsiloxane (PDMS) exchange. PDMS tamponade, after 6 months starting from MIVS, was removed. RESULTS: In all patients visual acuity increased after vitrectomy as a consequence of complete MH closure and restoration of retinal architecture. None of the patients developed ocular hypertension, or re-opening of MH during the 3-year follow-up. MP-1 bivariate contour ellipse area was reduced in its dimensions and improved in all patients demonstrating a better fixation. CONCLUSIONS: MIVS could be an effective treatment in RP patients with MH if medical therapy is not applicable or not sufficient. Finally more studies will be needed to improve knowledge about this genetic disease.

Posterior capsule opacity in Retinitis Pigmentosa according to different biomaterials of intraocular lenses: Our clinical experience.

BACKGROUND AND AIM: Complicated Cataract is frequently associated with Retinitis Pigmentosa (RP). This retinopathy is a great cause of visual impairment, and cataract surgery may resolve partially the situation and restore sight. Unfortunately, in this case there is a very high incidence of Posterior Capsule Opacity (PCO) ranging in several studies a percentage of 100% at six months. Our goal was to evaluate whether the high incidence of PCO is associated to specific type of Intraocular Lens (IOL) biomaterials. MATERIALS AND METHODS: This observational retrospective study deals with 75 eyes of 43 patients affected with RP who underwent to cataract surgery with posterior chamber IOL implants (40% ECCE and 60% Phaco). Selected biomaterials were: 30 Poly (methyl methacrylate) (PMMA), 11 silicone, 34 acrylic. Observations were performed with retro-illumination camera and when recorded capsular fibrosis a PCO YAG laser capsulotomy was made. The patients were controlled at 3-6-12 months after the initial surgical treatment. RESULTS: At three months of follow up, 80% of patients with PMMA, 81.8% silicone implants underwent to YAG capsulotomy while only 44% of acrylic type. At six months of follow-up 83.3% of patients with PMMA and 81.8% silicone implants underwent to YAG capsulotomy while only 49.88% of acrylic type. At 12 months of follow up 89.9% of patients with PMMA and 90.95 silicone implants underwent to YAG capsulotomy while only 52.82% of acrylic type. CONCLUSIONS: We could not be able to differentiate incidence between different brand type of lens in PMMA. For Acrylic lens instead we noted an incidence of PCO of 41.38% with hydrophobic material and 60.0% of hydrophilic material. In conclusion to avoid massive PCO in RP, our experience is statistically significant, in fact the protective action of smooth material hydrophobic lens avoids the epithelial growth and fibrosis towards the center of visual axis.

Degenerative effects in rat eyes after experimental ocular hypertension.

This study was used to evaluate the degenerative effects on the retina and eye-cup sections after experimental induction of acute ocular hypertension on animal models. In particular, vascular events were directly focused in this research in order to assess the vascular remodeling after transient ocular hypertension on rat models. After local anaesthesia by administration of eye drops of 0.4% oxibuprocaine, 16 male adult Wistar rats were injected in the anterior chamber of the right eye with 15 µL of methylcellulose (MTC) 2% in physiological solution. The morphology and the vessels of the retina and eye-cup sections were examined in animals sacrificed 72 h after induction of ocular hypertension. In retinal fluorescein angiographies (FAGs), by means of fluorescein isothiocyanate-coniugated dextran (FITC), the radial venules showed enlargements and increased branching, while the arterioles appeared focally thickened. The length and size of actually perfused vessels appeared increased in the whole superficial plexus. In eye-cup sections of MTC-injected animals, in deep plexus and connecting layer there was a bigger increase of vessels than in controls. Moreover, the immunolocalization of astrocytic marker glial fibrillary acidic protein (GFAP) revealed its increased expression in internal limiting membrane and ganglion cell layer, as well as its presence in Müller cells. Finally, the pro-angiogenic factor vascular endothelial growth factor (VEGF) was found to be especially expressed by neurones of ganglion cell layer, both in control and in MTC-injected eyes. The data obtained in this experimental model on the interactions among glia, vessels and neurons should be useful to evaluate if also in glaucomatous patients the activation of vessel-adjacent glial cells might play key roles in following neuronal dysfunction.

Preliminary study on combined pharmacological and laser treatment in optic pit serous maculopathy after literature review.

The pit of the optic nerve head (ON) is a rare congenital defect that sometimes presents itself with a maculopathy of various neuroretinal layers for unknown reason. This study was focused, before and after pharmacological and parasurgical treatment, on the structural and functional visual assessment in a patient with optic pit maculopathy (OPM). In order to achieve this the latest generation of hi-tech diagnostic tests were used, such as Spectral-Domain Optical Coherence Tomography (SD-OCT), Visual Evoked Potentials (VEP), full-field Electroretinography (ERG), multifocal ERG (mfERG), Microperimetry (MP-1), Standard Automated Perimetry (SAP), Fluorescein Angiography (FA) and Indocyanine Green Angiography (ICG). The research was conducted through a review of past and recent literature.

Keratoconjunctivitis by confocal microscopy after topical cyclosporine.

AIM: To describe the observations obtained by confocal microscopy concerning corneal stromal structure in the process of adenoviral epidemic keratoconjunctivitis, from the onset of the disease up to 20 weeks of follow-up, after topical cyclosporine. METHODS: A 16-years-old boy has developed subepithelial infiltrates and an epidemic keratoconjunctivitis from adenovirus in both eyes. Clinical case was analyzed by confocal microscopy (40x mode, Nidek ConfoScan 4) before and after administration of topical cyclosporine. RESULTS: Two weeks after the onset of the symptoms, corneal stroma showed the presence of cells with highly reflective area. These cells, comparable to keratocytes, had a typical fusiform shape and assumed a particular rosette disposition, never highlighted in the literature. Hyperreflective areas disappeared in both eyes after administration of topical cyclosporine 1% for 30 days. This outcome was also confirmed after five months. CONCLUSION: The confocal microscopy performed on the surface of the stroma before and after treatment with cyclosporine suggests the presence of a localized immune activation in subepithelial layer.

Corneal haze in course of Fuchs' endothelial dystrophy.

This article describes the observations obtained with confocal microscopy (CM) on the corneal structure in course of corneal edema in a patient with Fuchs endothelial corneal dystrophy (FD). The patient was a 40 year old male, suffering from second stage FD, in course of corneal edema and bullous keratopathy. The tissue structure was analyzed with CM confoscan CS4 (Nidek Technologies(®), Birmingham, UK) using the 40x mode. The CM has shown the presence of gaps due to corneal edema and a diffuse stromal hyper reflectivity related to the alteration of the extracellular matrix. It has also showed the presence of binucleate cells, assimilable to keratocytes, in cytokinesis which presented a typical fusiform aspect with two highly reflective nuclei awaiting cell division. The total number of cells was much lower than that of healthy control subjects of similar age, sex and race. The CM in this case suggests a significantly lower number of cells, presumably keratocytes, compared to normal range, but mostly it shows the presence of cells undergoing cytokinesis, which witnesses the active processes of collagenogenesis and possible vasculogenesis that represent early stages of loss of the normal corneal transparency.

Forskolin and rutin prevent intraocular pressure spikes after Nd:YAG laser iridotomy.

AIM: the purpose of this research was to evaluate whether an oral treatment with an association of forskolin and rutin can blunt the intraocular pressure (IOP) spikes and avoid the damage that may occur after laser iridotomy. METHODS: Ten patients underwent bilateral Neodymium:YAG (Nd:YAG) laser iridotomy (Visulas YAG III Laser, Zeiss), for the prevention of primary closed-angle glaucoma. IOP was measured in subjects before and after 7 days of pretreatment with placebo or forskolin and rutin by Goldman applanation tonometry. The IOP was measured before surgery and after surgery at 30-60-120 minutes, and 4-7 days. RESULTS: Analysis of variance indicated a significant increase of the postoperative values in patients receiving treatment with placebo (p < 0.001), but not in those who received treatment with the forskolin and rutin association. T test analysis confirmed that IOP still remained significantly elevated 7 days after laser intervention in placebo treated patients, whereas it stayed within normal values in forskolin/rutin treated patients. CONCLUSION: Forskolin and rutin can blunt the increase of IOP that occurs after Nd-YAG laser iridotomy. This can avoid serious risk to the optic nerve of the patients under laser treatment for iridotomy.