Ongoing reserach projects
1. Neuronal damage in diabetic eyes as a cause for blindness
Peripheral neuropathy is one of the commonest and most serious chronic complications caused by diabetes mellitus, with a prevalence of about 50%. At the ocular level, it manifests itself as corneal and retinal neuropathy. As far as the cornea is concerned - along with the well-documented reduction in corneal sensibility and reduced secretions from the tear glands leading to increased eye dryness – recent scientific studies have evidenced an increasing interest in the corneal structure and morphology, with particular reference to quantitative and qualitative alterations of the sub-basal and stromal nerve plexus and the morphology of individual corneal cells. At the retinal level, the involvement of ganglion cells (highlighted by the increase in cell deaths) has been documented; a consequence of this is a reduction in the number of ganglion cells leading to a thinning of the inner nuclear layer. The glial cells of the retina and the muller cells are also involved; these cells play a key role in the functional links between retinal vessels and neuronal cells, as well as in retinal glucose metabolism and the preservation of the hemato-retinal barrier. The goal of this study is the in vivo assessment of corneal neuropathies through the use of confocal microscopy.
2. In vivo cytogenetic classification of uveal melanoma: assessment of the risk of metastasis on the basis of stem-cell-like/non-stem-cell-like expression profile.
Half of patients affected by choroidal melanoma dies within ten years of diagnosis due to the onset of metastasis, in spite of local control of the neoplasm. Currently, there are no known therapies that can stop clinically evident metastasis. The genetic classification of choroidal melanoma is currently considered to be more reliable in identifying patients at high risk of metastasis compared to those at low risk. The existence of a sub-class of uveal melanomas with an aggressive phenotype, whose expression profile can be classified as stem-cell like, has been suggested by several authors. The goal of this study is to achieve the in vivo cytogenetic classification of uveal melanoma through an assessment of the risk of metastasis on the basis of stem-cell-like/non-stem-cell-like expression profile.
3. Topical antimetabolites: monitoring of therapeutic applications in ophthalmology
Antimetabolites are molecules that are actively being used in ophthalmology, including surgery. The two most commonly used molecules in ophthalmology are Mitomicyn C (MMC) and 5-Fluoruracil (5-FU). 5-FU is a cycle-specific pyrimidine analog, with selective activity on cells in the active replication phase, and with side effects that are clinically classifiable as limited and transient. The 5-FU molecule is not very sensitive to inactivation on the part of UV rays, and is quite resistant in preparations for topical use. MMC is a non-cycle-specific antimetabolite, active both on actively proliferating cells and cells in the G0 phase, with side effects that are more frequent and significant compared to those of 5-FU, albeit often transient. Both substances are used in surgery as scarring modulators in light of their pharmacological properties, or as topical therapies in the treatment of corneo-conjuctival neoplasms. The goal of this study is the monitoring of the side effects of the therapeutic application of topical antimetabolites in ophthalmology, principally through the use of confocal in-vivo microscopy.
4. Advanced diagnostic methodologies in ocular toxicology
Chronic infections with the hepatitis C and B viruses (HCV and HBV, respectively) are the leading causes of hepatopathy, cirrhosis, and hepatocarcinoma in the world. Hepatitis caused by HBV remains a health problem of global relevance, since 350 million people are chronically infected, and annual mortality attributed to HBV ranges between 500,000 and over one million deaths. Antiviral therapy with pegylated interferon and ribavirin is the “gold standard” for the treatment of chronic hepatitis caused by HCV. With regards to chronic hepatitis caused by HBV, peginterferon alfa-2° is used in monotherapy for 48 weeks, preferably in young patients in which the disease is at a minor or moderate stage. The aim of this study is to define the prevalence, type, and possible effect of antiviral therapy with interferon and ribavirin (for hepatitis C) and antiviral therapy with interferon (for hepatitis B) at the ocular level with the aim of documenting local neurovascular toxicity and to use this model for a broader in vivo study.
5. Prevention of complications from brachytherapy in the treatment of uveal melanoma
Radiotherapy is currently the standard conservative treatment for choroidal melanoma. Nevertheless, regardless of the type of radiation used (brachytherapy, protons), this therapeutic approach is often associated with complications caused directly by the radiations themselves (retinopathy and/or opticopathy, neovascular glaucoma, serous retinal detachment) – in 30% to 60% of all cases – which inevitably leads to a gradual and significant loss of visual acuity and, in advanced cases, to the anatomical loss of the eye, making enucleation necessary (12% of cases).
Triamcinolone acetonide is a synthetic corticosteroid and is used in light of its strong anti-inflammatory properties. Its intravitreous use has been reported to be efficient in treating diabetic macular edema and cystoid macular edema. Triamcinolone acetonide persists for long periods in the site of injection; low concentrations have been found in samples of aqueous humour up to 1.5 years after intravitreous injection. Triamcinolone has also proved efficient in preventing cystoid macular edema and in reducing tumour volume after brachytherapy in patients affected by choroidal melanoma. The goal of this study is to assess the safety and efficacy of the use of triamcinolone acetonide through intravitreous injection in the integrated treatment of complications from brachytherapy.
6. The eye as a model in the evaluation of iatrogenitic damage to the central and peripheral nervous system
Chemotherapy-induced peripheral neuropathy (CIPN) is a clinically significant problem whose severity in terms of the functional limitations it imposes on the lives of affected subjects has often been underestimated. Current treatments are rather inefficient, in part because there have not yet been any national or international clinical trials of sufficient magnitude for identifying an adequate therapy. Not all chemotherapy patients develop CIPN. Aside from the role played – for some drugs – by cumulative doses, no other risk factors have been identified so far, and early or subclinical diagnosis is not currently possible. The goal of this study is to assess the presence of iatrogenic damage to the central and peripheral nervous system caused by chemotherapy and visible at the ocular level, through the use of non-invasive diagnostic technique such as OCT and confocal microscopy.
7. Neuronal and vascular retinal and choroidal damage in dystmetabolic pathologies
Thanks to the development of new diagnostic techniques, it is now possible to evaluate the posterior segment of the eye in vivo and in a non-invasive manner. In particular, the introduction of clinical activities in Spectral –Domain OCT (SD-OCT) has made it possible to obtain detailed information on the various layers of the retina, and to assess the thickness of the choroid. Automatic studies, made possible by the “layering” function of SD-OCT instruments, evaluates in a selective and reliable manner the individual retinal layers. Histological studies have shown that inner retinal layers (the nerve fibre layer, the ganglion cell layer, the inner plexiform layer, and the inner nuclear layer) are prematurely altered in dysmetabolic pathologies (such as diabetic retinopathy). This is an early sign of retinal neuropathology and is present in various pathologies. Being able to prove the presence of these alterations in vivo and in real time would make it possible to document and achieve the early diagnosis of retinal neuronal alterations in order to better orient the choice of treatment.
Additionally, the clinical study of the choroid, which until recently was only possible using indocyanine green and B-scan, can now be carried out thanks to the specific characteristics of SD-OCT and the use of certain image acquisition techniques. The main goal of this study is to assess neuronal and vascular retinal and choroidal damage in dysmetabolic pathologies. In particular, with regards to diabetic retinopathy, the study will examine periparillary and macular choroidal thickness and correlate it with the degree of diabetic retinopathy and the presence of macular edema.
8. Methodology of screening for vision loss
Senile macular degeneration is the main cause of legal blindness in industrialized countries for people over the age of 65. This is a chronic and progressive disease with various phenotypic manifestations and different stages of evolution and progression. Reduced visual acuity occurs only during the advanced phases of the disease; by then, functional damage is difficult to reverse. Often, in the early and intermediate stages of the disease (characterized by the presence of macular drusen and pigmentary alterations of the pigmented retinal epithelium), visual acuity remains normal. For this reason, measuring visual acuity does not seem to be the best functional parameter for evaluating this disorder. Alterations in sensitivity to contrast, adaptation to darkness, and the sensitivity of the macular retina have been recorded in the early stages of senile macular degeneration. A simple, early diagnosis of functional damage could help prevent irreversible vision loss and be used as a screening method for this disorder. To this end, this study will assess the use of a new instrument for determining macular retinal sensitivity and fixation stability in a large number of subjects affected by senile macular degeneration in its early and intermediate phases.