Psychophysical, electrofunctional, and morphological evaluation in naïve neovascular AMD patients treated with intravitreal anti-VEGF.

Objectives: The aim of this study was to investigate the retinal morpho-functional characteristics of patients with neovascular wet age-related macular degeneration (nAMD) treated with intravitreal injection (IV) of aflibercept (AFL). Methods: The study was conducted on 35 patients previously diagnosed with type 1 nAMD who received a fixed-dosing regimen of aflibercept injections over 12 months. The goal was to assess trends in visual abilities over time by measuring visual acuity (VA), contrast sensitivity (CS), visual evoked potentials (VEPs), and spectral domain-optical coherence tomography (SD-OCT). The same psychophysical, electro-functional, and morphological tests administered at baseline (T0) were repeated 4 to 8 weeks after the last aflibercept injection (Tn), resulting in a total of six examinations. Results: At Tn, all subjects exhibited improved VA for both far and near distances compared to values detected at T0. Similarly, VEP amplitude and latency values at Tn showed a greater P100 improvement than those observed at T0. Additionally, the CS examination at Tn demonstrated improvement, particularly at high spatial stimulation frequencies. The Tn SD-OCT results highlighted a reduction in macular thickness compared to T0 values. Conclusions: This exploratory research indicates that intravitreal injections of AFL, following a fixed-dosing regimen, represent a valuable therapeutic approach for enhancing visual performance. This conclusion is supported by comprehensive statistical analysis of psychophysical, electro-functional, and morphological examinations within the same group of patients with nAMD, as demonstrated for the first time.

Insights into Novel Choroidal and Retinal Clinical Signs in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of this disease include iris Lisch nodules, ocular and eyelid neurofibromas, eyelid café-au-lait spots and optic pathway gliomas (OPGs). In the last years, new manifestations have been identified in the ocular district in NF1 including choroidal abnormalities (CAs), hyperpigmented spots (HSs) and retinal vascular abnormalities (RVAs). Recent advances in multi-modality imaging in ophthalmology have allowed for the improved characterization of these clinical signs. Accordingly, CAs, easily detectable as bright patchy nodules on near-infrared imaging, have recently been added to the revised diagnostic criteria for NF1 due to their high specificity and sensitivity. Furthermore, subclinical alterations of the visual pathways, regardless of the presence of OPGs, have been recently described in NF1, with a primary role of neurofibromin in the myelination process. In this paper, we reviewed the latest progress in the understanding of choroidal and retinal abnormalities in NF1 patients. The clinical significance of the recently revised diagnostic criteria for NF1 is discussed along with new updates in molecular diagnosis. New insights into NF1-related neuro-ophthalmic manifestations are also provided based on electrophysiological and optical coherence tomography (OCT) studies.

Anti-vascular endothelial growth factor monotherapy or combined with verteporfin photodynamic therapy for retinal angiomatous proliferation: a systematic review with meta-analysis.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP). Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes. Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes. Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy.

The Spectrum of Neurological and Sensory Abnormalities in Gaucher Disease Patients: A Multidisciplinary Study (SENOPRO).

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient's initial classification.

Oxidative Stress Implication in Retinal Diseases-A Review.

Oxidative stress (OS) refers to an imbalance between free radicals (FRs), namely highly reactive molecules normally generated in our body by several pathways, and intrinsic antioxidant capacity. When FR levels overwhelm intrinsic antioxidant defenses, OS occurs, inducing a series of downstream chemical reactions. Both reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced by numerous chemical reactions that take place in tissues and organs and are then eliminated by antioxidant molecules. In particular, the scientific literature focuses more on ROS participation in the pathogenesis of diseases than on the role played by RNS. By its very nature, the eye is highly exposed to ultraviolet radiation (UVR), which is directly responsible for increased OS. In this review, we aimed to focus on the retinal damage caused by ROS/RNS and the related retinal pathologies. A deeper understanding of the role of oxidative and nitrosative stress in retinal damage is needed in order to develop targeted therapeutic interventions to slow these pathologies.

Oxidative stress and visual system: a review.

Different types of tissues respond differently to the action of oxidative stress. The visual system is very sensitive to oxidative action due to continuous exposure to light. In consideration of the growing interest of scientific studies towards various compounds endowed with antioxidant and anti-inflammatory properties, we performed a review of the literature focusing on the use of some antioxidant molecules for the treatment of conditions affecting the visual system. In this study, we focused on the ability of two antioxidant agents, the small molecule α-lipoic acid (ALA) and the enzyme superoxide dismutase (SOD), to influence the neurodegenerative physiological processes related to aging and oxidative stress affecting the ocular segment. The literature data report that ALA and SOD can protect against neurodegenerative effects both the optic nerve and retina and, if administered together, they are able to lower the levels of oxidative stress, thus preventing neurodegeneration and reducing the apoptotic process.

Impact of screen exposure on pediatric vernal Keratoconjunctivitis: a survey during the COVID-19 pandemic in Italy.

BACKGROUND: The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown. METHODS: We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children's University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure. RESULTS: Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure. CONCLUSION: During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions.

Neuroretinal dysfunction in patients affected by neurofibromatosis type 1.

AIM: To examine neuroretinal function by using the multifocal electroretinography (mfERG) test in patients with neurofibromatosis type 1 (NF1) without optic pathway gliomas (OPGs). METHODS: This study was conducted on 35 patients (35 eyes) with NF1 and 30 healthy subjects (30 eyes) for the control group. Each subject underwent a complete ophthalmological examination including spectral domain-optical coherence tomography (SD-OCT) and mfERG. The 1.5-Tesla magnetic resonance imaging (MRI) scan of the brain was performed in NF1 patients to assess the presence of OPGs. All participants were recruited having a best corrected visual acuity (BCVA) of no less than 20/20 in each eye. The amplitude and implicit time of the P1 wave (first-order Kernel component) were evaluated on mfERG. Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field. RESULTS: Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy controls, while the reduction was not significant in the 2 central degrees between the groups. A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group, with lower amplitudes detected in the nasal quadrants. No differences in the implicit times were recorded in the 2 central degrees and in the 4 quadrants as compared between NF1 patients and controls. CONCLUSION: Impaired neuroretinal function in NF1 patients is expressed in a decreased amplitude of the P1-wave between 2 and 25 central retinal degrees on mfERG. Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate (cAMP) generation, can be involved. The possible use of mfERG as subclinical retinal damage indicator has a potential utility in clinical practice for the follow-up of NF1 patients.

Complement Mediators in Development to Treat Age-Related Macular Degeneration.

Over recent years, great attention has been paid to the role of the complement system in the pathogenesis of age-related macular degeneration (AMD). In particular, several studies have highlighted a link between AMD development and complement dysregulation, which can probably be explained as a complement cascade hyperactivation resulting from the presence of a series of risk factors such as aging; smoking; obesity; alcohol consumption; exposure to pesticides, industrial chemicals, or pollution; and other causes of oxidative stress. This hypothesis has been mainly supported by the presence of complement mediators as constituents of drusen, representing one of the earliest and most characteristic signs of retinal damage in AMD. Additionally, activated complement mediators and some complement regulators, such as vitronectin, have been found not only in the drusen and adjacent retinal areas but also in the peripheral blood of patients with AMD. Therefore, we aim to provide a review of recently studied complement factors to highlight their role in the pathogenesis of AMD and to evaluate new potential therapeutic strategies.

Diabetic retinopathy, oxidative stress, and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons.

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegeneration, and metabolic diseases. In DR sirtuins 1,3,5, and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g., antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focus on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR.

Vernal keratoconjunctivitis activity induces decrease of ocular surface CD14, TLR-4 and TLR-9 expression.

PURPOSE: CD14 is involved in the modulation of immune reaction via toll-like receptors (TLR) and may influence the development of allergic diseases. The role of CD14 in vernal keratoconjunctivitis (VKC) has not yet been investigated. The aim of this study is to evaluate changes of tear soluble sCD14 and conjunctival CD14, TLR-4 and 9 expression in patients with VKC in the active and quiescent phases. METHODS: Eighteen patients with VKC during active inflammation (group A, N = 9), in the quiescent phase (group Q, N = 5) and after recovery (group R, N = 4) and 10 healthy subjects were included. Expression of sCD14 in tears and of CD14, TLR-4, and TLR-9 by conjunctival epithelium were evaluated by Western Blot in all groups. RESULTS: Expression of tear sCD14 and of conjunctival CD14, TLR-4, and TLR-9 was significantly decreased in group A when compared with healthy subjects and with VKC group Q and R. Lower expression of sCD14, CD14, TLR-4, and TLR-9 were significantly correlated with the severity of papillary reaction, while the lower sCD14 was correlated with severity of conjunctival hyperemia. CONCLUSIONS: Tear sCD14, and conjunctival CD14, TLR4, and TLR-9 decreased during ocular surface inflammatory reaction in patients with VKC. CD14 and TLRs ocular surface evaluation may represent biomarkers of VKC activity and novel therapeutic target.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF PERIPAPILLARY MICROVASCULAR CHANGES AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To evaluate the radial peripapillary capillary plexus (RPCP) vessel density (VD) and the retinal nerve fiber layer (RNFL) thickness in eyes successfully treated with pars plana vitrectomy for primary rhegmatogenous retinal detachment. METHODS: In this cross-sectional multicenter clinical study, eyes with a minimum 12-month follow-up were reexamined. The RPCP VD and RNFL thickness in the rhegmatogenous retinal detachment subfields of the affected eye (study group) were compared with the corresponding areas of the healthy fellow eyes (control group). RESULTS: Fifty-three eyes were included in the study. A significantly lower RPCP VD and RNFL thickness were observed in those subfields affected by rhegmatogenous retinal detachment compared with those of the control group (P < 0.001). No statistically significant differences were observed between undetached subfields in the study group and their corresponding images in the control group. In the study group, a significant correlation was found between RPCP VD and RNFL thickness in subfields with detached retina (r = 0.393, P < 0.001) and undetached retina (r = 0.321, P < 0.001). CONCLUSION: Radial peripapillary capillary plexus VD changes were found in the subfields of detached retina successfully treated with pars plana vitrectomy and they correlated with RNFL thinning. These data suggest a coexistence of neuronal and microvascular damage in patients affected by rhegmatogenous retinal detachment.

Vernal keratoconjunctivitis: state of art and update on treatment.

Vernal keratocongiuntivitis (VKC) is a chronic inflammatory disease affecting the ocular conjunctiva and cornea. It is a rare and underestimated pathology, whose missed or delayed diagnosis can lead to the development of serious ocular complications. Moreover, despite VKC symptoms are well known, they can overlap and be mistaken with allergic conjunctivitis. In fact, diagnostic criteria and severity grading are not standardized yet. The pathogenesis of VKC is still controversial and it is difficult to identify a single mechanism underlying the chronic ocular inflammation. Different studies hypothesized both allergies and autoimmune diseases and also oxidative stress contribute significantly to the origin of the disease. However, the unclear pathogenesis and the lack of specific disease biomarkers make treatment a challenge. The standard therapy includes antihistamines, anti-inflammatory and immunosuppressant drugs and novel therapies are currently under investigation. However, considering treatment guidelines and recommendations are not well defined yet, therapy should be personalized on the clinical features of the patient. This paper provides an overview of the VKC and updates on the challenges that need to be addressed in the future to improve the management of the patient with this disease and improve his quality of life.

Ten-Year Outcomes of Intravitreal Bevacizumab for Myopic Choroidal Neovascularization: Analysis of Prognostic Factors.

The current standard treatment of myopic choroidal neovascularisation (mCNV) is intravitreal injection of VEGF antagonists. This study was proposed to assess efficacy and safety of intravitreal bevacizumab (IVB) for the treatment of mCNV across a 10-year follow-up. Thirty eyes of thirty patients with treatment-naïve mCNV who underwent IVB and were followed up with for a minimum of ten years were recruited for the present retrospective cohort study. All participants were treated with three monthly IVB at baseline and then evaluated and treated under pro re nata (PRN) schedule. Outcome measures were to determine BCVA changes over years and identify the predictive factors of both final visual outcome and need for retreatment. Analysis of the main involved prognostic factors with correlations among variables is reported. Visual acuity remained stable at 10-year follow-up (p = 0.001) with the greatest improvement at 2 years (p < 0.0001) in all CNV locations. Baseline BCVA correlated positively with final BCVA (ß = 0.88, p < 0.0001, R2: 0.75). No predictive factors for the need of additional injections were identified. Retinal and choroidal thickness significantly reduced over time but without correlation with the number of injections. CNV max height and area significantly decreased at 10 years (p < 0.0001 and p = 0.003, respectively), with complete regression of mCNV lesion in 40% of subjects. Intravitreal bevacizumab resulted as long-term effective and safe therapy for mCNV with sustained results at 10 years.

Recent Advances and Disputes About Curcumin in Retinal Diseases.

Curcumin belongs to the group of so-called phytocompounds, biologically active molecules produced by plants exerting a beneficial effect on health. Curcumin shows a wide spectrum of different properties, being an anti-inflammatory, antioxidant, antimicrobial and antimutagenic molecule. The purpose of the review is to examine what literature reported on the characteristics of curcumin, particularly, on the beneficial and controversial aspects of this molecule, aiming for a better therapeutic management of retinal diseases. The retina is a constant target of oxidative stress, this tissue being characterized by cells rich in mitochondria and by vessels and being, obviously, continuously reached from photons affecting its layers. Particularly, the retinal ganglion cells and the photoreceptors are extremely sensitive to oxidative stress damage and it is well known that an imbalance in reactive oxygen species is often involved in several retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, central serous chorioretinopathy, macular edema, retinal ischemia-reperfusion injury, proliferative vitreoretinopathy, hereditary tapeto-retinal degenerations, and retinal and choroidal tumors. To date, several studies suggest that oral treatment with curcumin is generally well tolerated in humans and, in addition, it seems to have no negative effects: therefore, curcumin is a promising candidate as a retinal disease therapy. Unfortunately, the primary limitation of curcumin is represented by its poor bioavailability, in fact only a minimal fraction of this substance can reach the blood stream in the form of a biologically active compound. However, many steps have been made in several fields. In the future, it is expected that the strategies developed until now to allow curcumin to reach the target tissues in adequate concentrations could be ameliorated and, above all, large in vivo studies on humans are needed to demonstrate the total safety of these compounds and their effectiveness in different eye diseases.

Anti-inflammatory role of curcumin in retinal disorders (Review).

Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione], the main component of turmeric (Curcuma longa, a flowering plant of the ginger family, Zingiberaceae), is known to possess different pharmacological activities, particularly anti-inflammatory and antioxidant properties. Since an underlying inflammatory process exists in several ocular conditions, such as anterior uveitis, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), the aim of the present review was to summarize the pleiotropic effects exerted by this molecule, focusing in particular on its beneficial role in retinal diseases. The anti-inflammatory activity of curcumin has also been described in numerous systemic inflammatory pathologies and tumors. Specifically, the biological, pharmaceutical and nutraceutical properties of curcumin are associated with its ability to downregulate the expression of the following genes: IκBα, cyclooxygenase 2, prostaglandin E2, interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor-α. According to this finding, curcumin may be useful in the treatment of some retinal disorders. In DR, proliferative vitreoretinopathy and AMD, beneficial effects have been observed following treatment with curcumin, including slowing down of the inflammatory process. Despite the aforementioned evidence, the main disadvantage of this substance is that it possesses a low solubility, as well as poor oral bioavailability due to its reduced absorption, rapid metabolism and rapid elimination. Therefore, several curcumin analogues have been synthesized and tested over the years, in order to improve the possible obtainable therapeutic effects. The purpose of the present review was to identify new aspects that could guide future research on this important traditional medicine, which is a well-tolerated natural product, and is widely considered safe and economical.

Mesenchymal stem and non-stem cell surgery, rescue, and regeneration in glaucomatous optic neuropathy.

BACKGROUND: Glaucomatous optic neuropathy (GON) is an anatomofunctional impairment of the optic nerve triggered by glaucoma. Recently, growth factors (GFs) have been shown to produce retinal neuroenhancement. The suprachoroidal autograft of mesenchymal stem cells (MSCs) by the Limoli retinal restoration technique (LRRT) has proven to achieve retinal neuroenhancement by producing GF directly into the choroidal space. This retrospectively registered clinical study investigated the visual function changes in patients with GON treated with LRRT. METHODS: Twenty-five patients (35 eyes) with GON in progressive disease conditions were included in the study. Each patient underwent a comprehensive ocular examination, including the analysis of best corrected visual acuity (BCVA) for far and near visus, sensitivity by Maia microperimetry, and the study of the spectral domain-optical coherence tomography (SD-OCT). The patients were divided into two groups: a control group, consisting of 21 eyes (average age 72.2 years, range 50-83), and an LRRT group, consisting of 14 eyes (average age 67.4, range 50-84). RESULTS: After 6 months, the BCVA, close-up visus, and microperimetric sensitivity significantly improved in the LRRT-treated group (p<0.05), whereas the mean increases were not statistically significant in controls (p>0.5). CONCLUSIONS: Patients with GON treated with LRRT showed a significant increase in visual performance (VP) both in BCVA and sensitivity and an improvement of residual close-up visus, in the comparison between the LRRT results and the control group. Further studies will be needed to establish the actual significance of the reported findings.

Electrophysiological Study of Visual Pathways in Nevoid Basal Cell Carcinoma Syndrome Patients.

INTRODUCTION: Gorlin-Goltz syndrome (GGS) also known as nevoid basal cell carcinoma syndrome (NBCCS) is a complex rare genetic disorder characterized by a wide range of clinical and radiological manifestations. Ophthalmological alterations have always been reported, but no study on the eventual pattern visual evoked potentials (pVEPs) abnormalities has yet been published. PURPOSE: The purpose of the study was to evaluate the functionality of the optic pathways in a group of NBCCS patients through pattern reversal VEPs, after a thorough exclusion of subjects with preexisting ocular and optic pathways pathologies. METHODS: Nineteen NBCCS patients (31 eyes) and 20 healthy controls (40 eyes) have been recruited for this study. All subjects underwent an evaluation of the functionality of the optic pathways through pVEPs with small (120'), medium (60'), and large (15') check size stimulation. RESULTS: NBCCS patients showed a statistically significant alteration in the transmission of the macular pathway function when compared to controls. PVEPs analysis confirmed a reduced amplitude and an increased latency of the P100 component, suggesting an involvement of the visual pathway even in the absence of ocular clinical manifestations. CONCLUSION: Visual pathways may have been affected both by a subclinical myelination deficit, determined directly by the genetic alteration, as well as by neurological abnormalities typical of this syndrome. Further studies are warranted.