Aloisa Librando

Biomolecular modulation of neurodegenerative events during ageing

The objective is to assess the modulation of retinal and optic nerve degenerative events induced by the combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) in an animal model of ageing. For this study, 24 male Wistar-Harlan strain rats were left to age for up to 24 months. One group of rats was subjected to a diet supplemented with ALA and SOD for 8 weeks, while another group was used as a positive control and not subjected to any dietary treatment. To assess the cytoprotective effects of the antioxidants, a morphological analysis was carried out on sections of retina and optic nerve head, stained with haematoxylin-eosin, followed by an analysis of the modifications to nuclear DNA detected by the TUNEL technique. The lipid peroxidation assay was used to assess the damage induced by oxidative stress at cell membrane level. The molecules involved in apoptosis mediated by oxidative stress, such as caspase-3 and inducible nitric oxide synthase, were also assayed by immunolocalization and western blot. ALA and SOD are able to counteract senile neurodegenerative deterioration to the retina and optic nerve. Indeed, the combination of these antioxidant molecules can reduce oxidative stress levels and thus prevent both nuclear degradation and subsequent cell death.

Juxtafoveal choroidal neovascularization associated with retinitis pigmentosa treated with intravitreal bevacizumab.

PURPOSE To describe a case of juxtafoveal choroidal neovascularization (CNV) occurring in a patient affected by retinitis pigmentosa (RP), treated with intravitreal bevacizumab over a 12-month follow-up. METHODS A 66 year-old woman referred to our center for visual acuity deterioration was diagnosed as having classic juxtafoveal CNV associated with RP. The patient was treated with intravitreal bevacizumab, and was regularly monitored every month. RESULTS At the end of the 12-month follow-up, best corrected visual acuity changed from 20/200 to 20/100 in the affected eye. Five intravitreal bevacizumab injections were required to obtain the stabilization of the CNV. CONCLUSIONS Intravitreal bevacizumab is effective in producing juxtafoveal CNV stabilization and visual acuity improvement in a patient affected by RP, over a 12-month follow-up. Future studies are required to ascertain the best therapeutic approach for CNV complicating RP.

Palmitoylethanolamide Effects on Intraocular Pressure After Nd:YAG Laser Iridotomy: An Experimental Clinical Study

PURPOSE The purpose of this article was to evaluate whether the anti-inflammatory agent palmitoylethanolamide (PEA) can counteract the increase of intraocular pressure (IOP) that may occur after neodymium-doped: yttrium aluminum garnet (Nd:YAG) laser iridotomy. METHODS Fifteen patients underwent bilateral laser iridotomy (Visulas YAG III Laser; Zeiss) for the prevention of primary closed-angle glaucoma. The IOP was measured at the beginning of the study (t-1), after 15 days of pretreatment with placebo or PEA (t0), and at 15, 30, and 120 min after the iridotomy (t1, t2, t3). The pretreatment consisted of 2 tablets of placebo or PEA per day for 15 days. RESULTS The t-test did not show a significant difference between the preoperative mean values of IOP t-1 and t0 in both the pretreatments. Analysis of variance/Tukeys test pointed out a significant increase of the postoperative IOP values in placebo pretreated patients (P≤0.05), but not in those who were pretreated with PEA. The trend analysis confirmed the significant positive trend in placebo pretreatment. The parallelism test between the 2 regressions showed a significant difference for the slopes (P=0.022) and not for the intercepts (P=0.520). CONCLUSIONS PEA can counteract the increase of IOP that occurs after iridotomy. It is likely that PEA controls the inflammatory process after iridotomy.

Fixed topical combinations in glaucomatous patients and ocular discomfort

Objective: The purpose of this study was to verify the ocular comfort of a fixed topical combination of brinzolamide 1% plus timolol 0.5% suspension vs. dorzolamide 2% plus timolol 0.5% solution, both preserved with benzalkonium chloride (BAK), in patients with primary open-angle glaucoma (POAG) through subjective and objective methods. BAK is the most commonly used preservative in topical glaucoma medications. Methods: 62 subjects were examined and included in the analysis. Each patient was asked to complete a questionnaire on symptoms (Ocular Surface Disease Index) and then underwent a series of examinations. The Ocular Protection Index evaluated the risk of damage to the ocular surface, and was expressed as the ratio between fluorescein breakup time and blinking interval. These and other analyses were repeated 30 days after instillation of the new eye drop treatment. Results: The results demonstrated that patients enrolled with the preserved fixed combination of dorzolamide or brinzolamide represented a subgroup of patients in which the discomfort symptoms were supposedly justified by the presence of BAK used chronically in antihypertensive drops. Ocular discomfort scores were significantly higher with dorzolamide/timolol than brinzolamide/timolol (p < 0.0001). Conclusions: This work shows the better tolerability of brinzolamide 1% plus timolol 0.5% suspension, compared with dorzolamide 2% plus timolol 0.5% solution. Fortunately, some of the adverse reactions induced by preserved eye drop glaucoma medication are reversible after removing the preservatives. Both the potential for added benefit and patient compliance should be considered when selecting ocular hypotensive therapy.

Iatrogenic dry eye disease: An eledoisin/carnitine and osmolyte drops study

BACKGROUND To evaluate the effects of an eye drop containing eledoisin and carnitine in patients suffering from primary open-angle glaucoma (POAG) and ocular discomfort syndrome secondary to a chronically treated with eye drops containing benzalkonium chloride (BAK) as preservative. The dry eye disease was defined as a multifactorial drop disease concerning tears and ocular surface, which brings to discomfort symptoms and visual disorders with potential damage to the ocular surface. Several studies underlined the beneficial effects of secretagogues drugs, such as eledoisin. It is a neuro-peptide extracted from the salivary glands of some shellfishes. Recently, it has been also showed the protective role of carnitine in respect of the ocular surface exposed to the tear film hyperosmolarity. MATERIALS AND METHODS This randomized double-blind pilot study has been evaluated by lubricant eye drop solutions containing eledoisin and carnitine in 40 patients with ocular discomfort syndrome secondary to POAG, since that the patients were chronically treated with eye drops which decrease eye pressure and contain BAK as preservative. The subjects filled out a questions form concerning the severity of the symptoms and their impact on daily activities. Subsequently Fluorescein Breakup Time (FBUT), Schirmer Test 1 (ST), and Ocular Protection Index (OPI) were measured at baseline and after 15days of treatment. RESULTS At the end of therapy it was possible to match the beneficial effects of eye drops with carnitin, taurine, sodium hyaluronate and eledoisin. In fact, after 15days of treatment, patients of group 1 showed a decrease of approximately 50% concerning the severity of symptoms and a significant improvement of the tests valued. CONCLUSION In summary, lubricant eye drops that restore physiological hosmolarity and stimulate tear production represent a promising strategy for dry eye syndrome.

Irritable eye syndrome: neuroimmune mechanisms and benefits of selected nutrients.

Previous studies showed comorbidity of some ocular, enteral, and affective symptoms comprising irritable eye syndrome. Aims of the present study were to learn more about the pathogenic mechanisms of this syndrome and to evaluate benefits of food supplements on these disorders. In in vitro assay, Lactobacillus acidophilus lysate inhibited interleukin (IL)-1β and tumor necrosis factor (TNF)-α generation of lipopolysaccharide (LPS)-stimulated macrophages in dose- and size-dependent manner. For a prospective, open-label phase I/II controlled clinical trial, 40 subjects affected by ocular dysesthesia and hyperesthesia and comorbid enteral and anxiety-depression symptoms were randomly assigned either into the treated group, which received a composition containing probiotic lysate, vitamins A, B, and D and omega 3 fatty acids, or into the control group, which received vitamins and omega 3 fatty acids. For reference, 20 age- and sex-matched healthy subjects were also selected. White blood count (WBC) and lymphocyte and monocyte counts, as well as IL-6 and TNF-α levels, were significantly above the reference levels in both treated and control groups. After 8 weeks, WBC and lymphocyte and monocyte counts, and cytokine levels significantly decreased, and ocular, enteral, and anxiety-depression symptoms significantly improved in the treated group as compared to the control group. This proof-of-concept study suggested that subclinical inflammation may be a common mechanism connecting ocular, enteral, and anxiety/depression symptoms, and supplements affecting dysbiosis may be a new approach to treating this syndrome.

Sturge-Weber Syndrome Associated with Monolateral Ocular Melanocytosis, Iris Mammillations, and Diffuse Choroidal Haemangioma

We present the case of a 12-year-old boy with Sturge-Weber syndrome and ocular melanocytosis who presented with bilateral naevus flammeus of the face and hyperpigmentation of the right iris associated with ipsilateral iris mammillations. The patient had glaucoma and a diffuse choroidal haemangioma of the right eye. Optical coherence tomography of the anterior segment confirmed iris hyper-pigmentation and did not show abnormalities of the chamber angle structures. B-scan ultrasonography and enhanced depth imaging optical coherence tomography were performed and showed a marked difference in thickness and reflectance between the right and left choroid. Visual field examinations with perimetry showed early defects in the right eye. Peripapillary optical coherence imaging showed borderline values of retinal nerve fibre layer thickness reduction in the right eye. Sturge-Weber syndrome associated with ocular melanocytosis and iris mammillations is an extremely rare condition. This paper highlights the role of multi-imaging methods in the enhanced evaluation of rare diseases towards choosing the most appropriate management strategies and improving the follow-up of patients over time.

Neuroprotection in Glaucoma: Old and New Promising Treatments

Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra- and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.