Publications by authors named "Pasquale Aragona"

88 Publications

Transepithelial photorefractive keratectomy for the management of hyperopic regression after conductive keratoplasty.

BMJ Case Rep 2021 Apr 28;14(4). Epub 2021 Apr 28.

Ophthalmology Unit, Department of Biomedical Sciences, University Hospital of Messina, Messina, ME, Italy.

Several refractive techniques are available for the treatment of hyperopia. Conductive keratoplasty (CK) is a safe and non-ablative procedure suitable for the treatment of low hyperopia and presbyopia. Due to the high rate of regression, it is not a commonly used technique. There is minimal literature about the use of refractive procedures for the treatment of hyperopic regression after CK. We report a case of a 49-year-old man who had undergone bilateral CK 15 years before for the correction of his hyperopia. He experienced a regression, with sph +2.75 cyl -0.50(20) in the right eye and sph +2.50 cyl -0.75(170) in the left eye. Transepithelial photorefractive keratectomy (tPRK) was performed with Schwind Amaris 750 s. After 12 months, his best-corrected visual acuity was 20/20, with -0.25 sph in both eyes. To the best of our knowledge, this is the first reported case of tPRK performed after CK.
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http://dx.doi.org/10.1136/bcr-2020-241144DOI Listing
April 2021

The Ocular Microbiome and Microbiota and their Effects on Ocular Surface Pathophysiology and Disorders.

Surv Ophthalmol 2021 Apr 2. Epub 2021 Apr 2.

Ophthalmology Départment, Hôpitaux Universitaires Paris-Sud, APHP, Université Paris-Saclay; IDMIT infrastructure, CEA, Inserm U1184, 18 route du Panorama, 92265, Fontenay-aux-Roses Cedex, France.

The ocular surface flora performs an important role in the defense mechanisms of the ocular surface system. Its regulation of the immunological activity and the barrier effect against pathogen invasion are remarkable. Composition of the flora differs according to the methods of investigation, because the microbiome, composed of the genetic material of bacteria, fungi, viruses, protozoa, and eukaryotes on the ocular surface, differs from the microbiota, which is the community of microorganisms that colonize the ocular surface. The observed composition of the ocular surface flora depends on harvesting and examining methods, whether with traditional culture or with more refined genetic analysis, based on rRNA and DNA sequencing. Environment, diet, sex, and age influence the microbial flora composition, thus complicating the analysis of the baseline status. Moreover, potentially pathogenic organisms can affect its composition like also various disorders, including chronic inflammation, and therapies applied to the ocular surface. A better understanding of the composition and function of microbial communities at the ocular surface could bring new insights and clarify the epidemiology and pathology of ocular surface dynamics in health and disease. The purpose of this review is to provide an up-to-date overview of knowledge about this topic.
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http://dx.doi.org/10.1016/j.survophthal.2021.03.010DOI Listing
April 2021

Ophthalmologic Manifestations of Primary Sjögren's Syndrome.

Genes (Basel) 2021 Mar 4;12(3). Epub 2021 Mar 4.

Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy.

Sjögren's syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with different types of severity, e.g., dry eye and dry mouth symptoms, due to early involvement of the lacrimal and salivary glands, which may be associated with parotid enlargement and dry eye; keratoconjunctivitis sicca (KCS) is its most common ocular manifestation. It is still doubtful if the extent ocular surface manifestations are secondary to lacrimal or meibomian gland involvement or to the targeting of corneal and conjunctival autoantigens. SS is the most representative cause of aqueous deficient dry eye, and the primary role of the inflammatory process was evidenced. Recent scientific progress in understanding the numerous factors involved in the pathogenesis of pSS was registered, but the exact mechanisms involved still need to be clarified. The unquestionable role of both the innate and adaptive immune system, participating actively in the induction and evolution of the disease, was recognized. The ocular surface inflammation is a central mechanism in pSS leading to the decrease of lacrimal secretion and keratoconjunctival alterations. However, there are controversies about whether the ocular surface involvement is a direct autoimmune target or secondary to the inflammatory process in the lacrimal gland. In this review, we aimed to present actual knowledge relative to the pathogenesis of the pSS, considering the role of innate immunity, adaptive immunity, and genetics.
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http://dx.doi.org/10.3390/genes12030365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998625PMC
March 2021

Impact of corneal parameters, refractive error and age on density and morphology of the subbasal nerve plexus fibers in healthy adults.

Sci Rep 2021 Mar 16;11(1):6076. Epub 2021 Mar 16.

Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital of Messina, Via Consolare Valeria, 98100, Messina, Italy.

The purpose of this study was to analyze corneal sub-basal nerve plexus (SBNP) density and morphology and their relationships with corneal parameters and refractive status. In this single center study, in vivo confocal microscopy (IVCM) was performed in 76 eyes of 38 healthy subjects aged 19-87 (mean age 34.987 ± 1.148). Nerve fiber analysis was performed using Confoscan 4 microscope with semi-automated software (Nidek Technologies, Italy) The nerve fiber length (NFL) µm/mm, nerve fiber density (NFD) no./mm, tortuosity coefficient (TC), and nerve beadings density (NBD) no./mm were considered. Relationship between SBNP parameters and corneal curvature, thickness, diameter, and refraction were analyzed. Additionally, the association with gender, laterality and age were determined. NFL was inversely correlated with age (r = - 0.528, p < 0.001), myopic refractive error (spherical value) (r = - 0.423, p < 0.001), and cylindrical power (r = - 0.340, p = 0.003). NFD was inversely correlated with age (r = - 0.420, p < 0.001) and myopic refractive error (r = - 0.341, p = 0.003). NBD showed a low inverse correlation with cylindrical power (r = - 0.287, p = 0.012) and a slight positive correlation with K (r = 0.230, p = 0.047). TC showed a significant negative correlation between age (r = - 0.500, p < 0.001) and myopic refractive error (r = - 0.351, p = 0.002). Additionally, there were strong positive correlations between NFL and NFD (r = 0.523, p < 0.001), NFL and TI (r = 0.603, p < 0.001), and NFD and TC (r = 0.758, p < 0.001). Multiple regression analysis revealed age to be the most significant factor affecting SBNP density (B = - 0.467, p = 0.013) and length (B = - 61.446, p < 0.001); myopic refractive error reduced both SBNP density (B = - 2.119, p = 0.011) and length (B = - 158.433, p = 0.016), while gender and laterality had no significant effects (p > 0.005). SBNP fiber length decreases with age, myopic refractive error and cylindrical power. SBNP fiber density reduces with age and myopic refractive error. Corneal nerve parameters are not influenced by gender or laterality.
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http://dx.doi.org/10.1038/s41598-021-85597-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966734PMC
March 2021

Iatrogenic Dry Eye Disease: Dealing with the Conundrum of Post-Cataract Discomfort. A P.I.C.A.S.S.O. Board Narrative Review.

Ophthalmol Ther 2021 Jun 8;10(2):211-223. Epub 2021 Feb 8.

Ocular Surface Unit, ISPRE, Genoa, Italy.

The incidence and prevalence of dry eye disease (DED) after cataract surgery is greatly underestimated. The severity of dry eye symptoms has been reported to peak 7 days after cataract surgery and may persist for months, significantly affecting patients' quality of life (QoL). The importance of considering surgical outcomes not only in terms of visual acuity, but also in terms of the patients' QoL, necessitates the assessment and evaluation of the ocular surface by the cataract surgeon prior to the procedure. This narrative review, drafted by the P.I.C.A.S.S.O. (Italian Partners for the Correction of Ocular Surface Alterations) board, analyses the physiopathology of post-cataract surgery DED and highlights the pre-, intra- and postoperative risk factors that may alter ocular surface homeostasis; it proposes a practical comprehensive algorithm for the prevention, treatment and management of DED associated with cataract surgery. Particular attention needs to be paid to the pre- and intraoperative risk factors to reduce the incidence of postoperative dry eye and to improve cataract surgery outcome.
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http://dx.doi.org/10.1007/s40123-021-00332-7DOI Listing
June 2021

Safety and Tolerability of an Eye Drop Based on 0.6% Povidone-Iodine Nanoemulsion in Dry Eye Patients.

J Ocul Pharmacol Ther 2021 Mar 23;37(2):90-96. Epub 2020 Dec 23.

Department of Biomedical Sciences, Ophthalmology Clinic, University of Messina, Messina, Italy.

To evaluate safety and tolerability on the ocular surface of an anti-septic formulation containing 0.6% povidone-iodine (0.6% PVI) for a 4 week period. An observational, prospective study included 20 mild-moderate dry eye disease (DED) patients who enrolled at the Ocular Surface Disease Unit of the University of Messina, receiving 0.6% PVI eye drops for 28 days, 2 drops twice daily (BID). The assessment included the Ocular Surface Disease Index questionnaire; symptoms score (0 = absent to 3 = severe) for burning, ocular dryness, foreign body sensation, watery eyes, tearing, photophobia, and ocular pain; fluorescein tear break-up time (TBUT); and corneal-conjunctival staining, performed at baseline (T0), after 7 (T7) and 28 (T28). Schirmer -test, corneal endothelial cell count, intraocular pressure, and fundus examination were performed at T0 and T28. The main outcome measures were TBUT and corneal-conjunctival staining as markers of ocular surface homeostasis. For statistical analysis, Student's -test and Wilcoxon test were used as appropriate. No significant alterations of the safety parameters were found throughout the study. Further, at T28 a significant improvement of burning, ocular dryness, foreign body sensation, and watery eyes (T0 vs. T28  < 0.03) were observed; corneal-conjunctival staining improved at T28 (T0 vs. T28  < 0.0001), and TBUT improved already at T7 (T0 vs. T7  = 0.0008) lasting so till the end of the study. The only adverse event was mild burning at instillation for the first 3 days of treatment in most of the patients. The treatment with 0.6% PVI was safe and well tolerated in a group of patients with a damaged ocular surface.
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http://dx.doi.org/10.1089/jop.2020.0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984652PMC
March 2021

Ocular surface manifestation of COVID-19 and tear film analysis.

Sci Rep 2020 11 19;10(1):20178. Epub 2020 Nov 19.

Biomedical Science Department, Institute of Ophthalmology, University of Messina, Via Consolare Valeria, 1, Messina, Italy.

To evaluate the ocular manifestation in patients hospitalized with coronavirus disease 2019 (COVID-19) and to search for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears. This study was conducted in 29 hospitalized patients who were admitted to the COVID center at the Policlinic Hospital of the University of Messina, Italy. All patients underwent an ophthalmologic assessment comprising a Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire, anterior segment, and the ocular surface examination of both eyes using a portable slit lamp. The Schirmer I test was performed, and the filter paper strip was used to search for the presence of SARS-CoV-2 on the ocular surface by real-time quantitative polymerase chain reaction (RT-qPCR). A total of 10 patients reported ocular symptoms; in particular, four reported eye burning, three reported foreign body sensation, and three reported tearing. Moreover, seven patients presented conjunctival hyperemia and/or chemosis, eleven patients presented blepharitis signs such as lid margin hyperemia and/or telangiectasia, crusted eyelashes, and meibomian orifices alterations. Tear analysis did not reveal the presence of SARS-CoV-2. Ocular symptoms are common in patients with COVID-19; although, tear analysis did not reveal the presence of SARS-CoV-2.
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http://dx.doi.org/10.1038/s41598-020-77194-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677531PMC
November 2020

Post-surgical management of cataract: Light and dark in the 2020s.

Eur J Ophthalmol 2020 Oct 20:1120672120963458. Epub 2020 Oct 20.

Department of Ophthalmology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Cataract surgery is the most frequently performed elective surgery worldwide. Although considered a safe procedure, potentially sight-threatening adverse events are possible. Among these, post-surgical inflammation and infections are the most relevant. Anti-inflammatory drugs, such as corticosteroids, and topical antibiotics are the pillars for the treatment of inflammation and for the prevention of infections. However, uncertainties remain regarding the duration of both topical antibiotic prophylaxis and corticosteroid treatment. LEADER7, a recent international clinical study conducted with the new fixed combination of levofloxacin and dexamethasone eye drops in patients undergoing uncomplicated cataract surgery, found that 1-week topical antibiotic prophylaxis is just as effective as the 2-week course commonly used in clinical practice. The study also showed that treatment for 1 week with dexamethasone results in complete resolution of inflammatory signs and symptoms in over 85% of patients, for whom further prolongation of corticosteroid treatment is, therefore, not necessary. This new treatment strategy can represent a significant step forward to reduce the unjustified use of prophylactic antibiotics after cataract surgery, limiting the emergence of bacterial resistance, as well as representing an opportunity to optimize the use and safety of the corticosteroid treatment.
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http://dx.doi.org/10.1177/1120672120963458DOI Listing
October 2020

Safety and Efficacy of a Preservative-Free Artificial Tear Containing Carboxymethylcellulose and Hyaluronic Acid for Dry Eye Disease: A Randomized, Controlled, Multicenter 3-Month Study.

Clin Ophthalmol 2020 1;14:2951-2963. Epub 2020 Oct 1.

Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia.

Purpose: To compare the efficacy and safety of an artificial tear combining the polymers carboxymethylcellulose (CMC) and hyaluronic acid (HA), to a formulation of CMC alone in subjects with dry eye.

Methods: A preservative-free artificial tear (CMC-HA) was compared with an existing artificial tear (CMC). Subjects with mild-to-severe signs and symptoms of dry eye were enrolled in this double-masked, randomized, multicenter trial, and dosed at least twice daily for 90 days, with follow-up visits at Days 7, 30, 60, and 90. Ocular Surface Disease Index (OSDI) was the primary outcome measure. Secondary outcome measures were tear break-up time (TBUT), ocular surface staining, Schirmer test with anesthesia, and visual analog scale (VAS) scores of dry eye symptom severity and formulation acceptability. Safety measures included adverse events, biomicroscopy, and visual acuity.

Results: A total of 460 subjects were enrolled across 45 sites (38 in Europe; 7 in Australia), of whom 454 were randomized to receive treatment. The per-protocol (PP) population consisted of 394 subjects, 364 (92.4%) of whom completed the study. In the PP population, the mean ± SD change from baseline in OSDI score at the primary timepoint, Day 90, was -16.9±17.5 for CMC-HA and -16.0±16.1 for CMC. CMC-HA was non-inferior to CMC based upon a confidence interval method. Both treatments significantly improved (<0.001) OSDI, symptom VAS scores, TBUT, and ocular surface staining from baseline at all follow-up visits, with minimal differences between groups. Greater reduction of overall ocular pain/discomfort was reported in subjects using CMC-HA versus CMC (=0.048). Approximately 10% of subjects in each group reported treatment-related adverse events of generally mild to moderate severity.

Conclusion: The new CMC-HA formulation was effective and well tolerated, and demonstrates a greater potential for symptom relief compared with CMC. These data support implementation of this formula for the management of dry eye patients.
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http://dx.doi.org/10.2147/OPTH.S256480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534849PMC
October 2020

Updated definition and classification of dry eye disease: Renewed proposals using the nominal group and Delphi techniques.

Eur J Ophthalmol 2021 Jan 2;31(1):42-48. Epub 2020 Oct 2.

Centro Occhio Secco, IS.PRE Oftalmica, Genova, Italy.

The aim of our research was to obtain expert consensus for updated definition and classification of dry eye disease using formal methodology. The nominal group technique (NGT) involved a steering committee of four ophthalmologists began with collection of ideas followed by group discussion. The ideas were collated, refined, and voted upon. The main characteristics considered, each with different degrees of severity in types I, II, and III, were the ability or not of the ocular surface to re-equilibrate itself, frequency of symptoms, presence of inflammation, epithelial alterations, and possible alterations in the quality of vision. This was followed by three rounds of a "mini-Delphi" involving an expert panel of 13 ophthalmologists, with the last round including all 17 ophthalmologists. Consensus in the final round of voting (⩾75% of votes) was reached on the definition of dry eye disease and on criteria for its classification in three forms. Type I is a transient and reversible form with subclinical inflammation, possible epithelial alterations, and occasional alterations in vision. Type II is a recurrent form characterized by a reduced ability to re-equilibrate the ocular surface, frequent symptoms and alterations in vision with clinically-evident inflammation, and clear evidence of epithelial alterations. Type III is a chronic form with inability to re-equilibrate the ocular surface and accompanied by clinically-evident and chronic inflammation, persistent epithelial alterations, and frequent alterations in quality of vision. The vast majority of patients with dry eye disease can be easily classified into one of these three forms. Dry eye disease definition was updated accordingly.
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http://dx.doi.org/10.1177/1120672120960586DOI Listing
January 2021

Corneal nerves in diabetes-The role of the in vivo corneal confocal microscopy of the subbasal nerve plexus in the assessment of peripheral small fiber neuropathy.

Surv Ophthalmol 2021 May-Jun;66(3):493-513. Epub 2020 Sep 19.

Ophthalmology Clinic, Department of Biomedical Sciences, University of Messina, Messina, Italy.

The cornea's intense innervation is responsible for corneal trophism and ocular surface hemostasis maintenance. Corneal diabetic neuropathy affects subbasal nerve plexus, with progressive alteration of nerves' morphology and density. The quantitative analysis of nerve fibers can be performed with in vivo corneal confocal microscopy considering the main parameters such as corneal nerve fibers length, corneal nerve fibers density, corneal nerve branching density, tortuosity coefficient, and beadings frequency. As the nerve examination permits the detection of early changes occurring in diabetes, the invivo corneal confocal microscopy becomes, over time, an important tool for diabetic polyneuropathy assessment and follow-up. In this review, we summarize the actual evidence about corneal nerve changes in diabetes and the relationship between the grade of alterations and the duration and severity of the disease. We aim at understanding how diabetes impacts corneal nerves and how it correlates with sensorimotor peripheral polyneuropathy and retinal complications. We also attempt to analyze the safety of the most common surgical procedures such as cataract and refractive surgery in diabetic patients and to highlight the specific risk factors. We believe that information about the corneal nerve fibers' condition obtained from the in vivo subbasal nerve plexus investigation may be crucial in monitoring peripheral small fiber polyneuropathy and that it will help with decision-making in ophthalmic surgery in diabetic patients.
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http://dx.doi.org/10.1016/j.survophthal.2020.09.003DOI Listing
September 2020

Ocular morphology development and function in children with congenital hypothyroidism diagnosed by neonatal screening.

Endocrine 2020 Aug 27. Epub 2020 Aug 27.

Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, Messina, Italy.

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http://dx.doi.org/10.1007/s12020-020-02457-4DOI Listing
August 2020

Modern approach to the treatment of dry eye, a complex multifactorial disease: a P.I.C.A.S.S.O. board review.

Br J Ophthalmol 2021 Apr 23;105(4):446-453. Epub 2020 Jul 23.

Ocular Surface Unit, ISPRE, Genoa, Italy

Dry eye disease (DED) is a growing public health concern affecting quality of life and visual function, with a significant socio-economic impact. It is characterised by the loss of homoeostasis, resulting in tear film instability, hyperosmolarity and inflammation of the ocular surface. If the innate immune response is unable to cope with internal bodily or environmental adverse conditions, the persistent, self-maintaining vicious circle of inflammation leads to the chronic form of the disease. Treatment of DED should be aimed at the restoration of the homoeostasis of the ocular surface system. A proper diagnostic approach is fundamental to define the relevance and importance of each of the DED main pathogenic factors, namely tear film instability, epithelial damage and inflammation. Consideration also needs to be given concerning two other pathogenic elements: lid margin changes and nerve damage. All the factors that maintain the vicious circle of DED in the patient's clinical presentation have to be considered and possibly treated simultaneously. The treatment should be long-lasting and personalised since it has to be adapted to the different clinical conditions observed along the course of the disease. Since DED treatment is frequently unable to provide fast and complete relief from symptoms, empathy with patients and willingness to explain to them the natural history of the disease are mandatory to improve patients' compliance. Furthermore, patients should be instructed about the possible need to increase the frequency and/or change the type of treatment according to the fluctuation of symptoms, following a preplanned rescue regimen.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005804PMC
April 2021

Symptomatology in head and neck district in coronavirus disease (COVID-19): A possible neuroinvasive action of SARS-CoV-2.

Am J Otolaryngol 2020 Sep - Oct;41(5):102612. Epub 2020 Jun 18.

Department of Adult and Development Age Human Pathology "Gaetano Barresi", Unit of Otorhinolaryngology, University of Messina, Via Consolare Valeria 1, 98125 Messina, ME, Italy. Electronic address:

Objective: The aim of this manuscript is to investigate transversally Ear Nose Throat (ENT) symptoms COVID-19 infection correlated and to study the neurotropism and neuroinvasiveness of the virus in the head-neck district through the investigation of the sense of smell, taste, tearing, salivation and hearing.

Methods: A total of 50 patients with laboratory-confirmed COVID-19 infection were included in our study. For each patient we evaluated the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS), the Summated Xerostomia Inventory-Dutch Version (SXI-DV), The Standardized Patient Evaluation of Eye Dryness (SPEED), Schirmer test I, the Hearing Handicap Inventory For Adults (HHIA) and the Tinnitus Handicap Inventory (THI). All the tests we carried out were performed during the active phase of the symptomatology from COVID-19 (Condition A) and 15 after SARS-COV-2 RT-PCR test negative (Condition B).

Results: A total of 46 patients (92%) had olfactory dysfunction related to the infection. The 70% of patients reported gustatory disorders. Cough, fever, headache and asthenia were the most prevalent symptoms. There was a statistically significant difference (p < 0,001) in sQOD-NS, SXI-DV, SPEED, Schirmer test, HHIA and THI between Condition A and Condition B.

Conclusions: In our population there was an alteration of the sense of taste, of the sense of smell, dry eyes and of the oral cavity and an auditory discomfort, symptoms probably linked to the neurotropism of the virus. Furthermore, anosmia, dysgeusia and xerostomia are early symptoms of COVID-19, which can be exploited for an early quarantine and a limitation of viral contagion.
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http://dx.doi.org/10.1016/j.amjoto.2020.102612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301823PMC
September 2020

The Application of a Venous Catheter for the Surgical Treatment of Punctal Occlusion.

J Craniofac Surg 2020 Sep;31(6):1829-1830

Department of Biomedical Sciences, Eye Clinic.

Purpose: Presentation about advantages of a new surgical technique in 20 patients with punctal occlusion with a venous catheter during punctoplasty.

Methods: The arrangement of a 30-mm venous catheter used during puncoplasty surgery was performed in 10 patients with punctal occlusion. The venous catheter was removed after 15 to 45 days after surgery.

Results: The use of the venous catheter supports the recanalization of the lacrimal drainage system 15 days after surgery. The venous catheter is easy to find, not expensive, and easy to use.

Conclusion: The technique is performed under regional anesthesia. Furthermore, after surgery, the recanalization of the lacrimal drainage system was observed with a significant reduction of the epiphora in 6 months after surgery.
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http://dx.doi.org/10.1097/SCS.0000000000006536DOI Listing
September 2020

Oral l-Cysteine Supplementation Enhances the Long Term-Effect of Topical Basic Fibroblast Growth Factor (bFGF) in Reducing the Corneal Haze after Photorefractive Keratectomy in Myopic Patients.

Pharmaceuticals (Basel) 2020 Apr 15;13(4). Epub 2020 Apr 15.

Biomedical, Dental and Morphological and Functional Images Sciences, Department, University of Messina, 98122 Messina, Italy.

We aimed at evaluating the long-term effects of l-cysteine oral supplementation to basic fibroblast growth factor (bFGF) eye-drops on corneal re-epithelization and transparency in myopic patients subjected to photorefractive keratectomy (PRK). Forty patients subjected to bilateral PRK for myopia were enrolled and randomly divided into two groups receiving an additional therapy together with the standard postoperative treatment consisting in local tobramycin 0.3%, dexamethasone 0.1%, diclofenac 0.1%, and 0.2% hyaluronate. Group 1 included 20 patients (11 males and 9 females; 34.09 ± 8 years of age) receiving only bFGF eye-drops (10 μg/10 μL) four times a day for 7 days starting from the day of surgery; Group 2 included 20 patients (12 males and 8 females; 37.35 ± 11.5 years of age) who were postoperatively administered with topical basic fibroblast growth factor (bFGF; 10 μg/10 μL) four times a day for 7 days plus oral l-cysteine supplementation (500 mg/capsule) once a day for 15 days, starting 7 days before PRK. Patients were followed-up for 12 months. Clinical ophthalmologic parameters were recorded for all the 80 examined eyes. The corneal transparency was evaluated in vivo by slit lamp and confocal microscopy. The data showed that: (a) the corneal haze occurred in a smaller percentage of the patients who were postoperatively administered with topical bFGF plus oral l-cysteine supplementation (Group 2) compared to patients who received only bFGF (Group 1); (b) at 6 months of follow-up, the stromal mean image brightness of the patients belonging to Group 2 was significantly lower than that of the Group 1 ( < 0.03), and, interestingly, the difference was even more evident at 12 month from the treatment ( < 0.001). Moreover, the final mean of the spherical equivalent refraction was -0.06 ± 0.2 D in Group 1 and -0.08 ± 0.3 D in Group 2, whereas the final uncorrected distance visual acuity (UDVA) was equal or superior to 20/25 in 100% of eyes in both Group 1 and 2. Post refractive patients can benefit from the administration of l-cysteine before the surgery and in association with bFGF in the early postoperative period, showing a faster corneal re-epithelization able to prevent corneal haze in the long-term recovery.
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http://dx.doi.org/10.3390/ph13040067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243117PMC
April 2020

Surgical Treatment of Dacryocystitis by Using a Venous Catheter.

J Craniofac Surg 2020 Jun;31(4):1120-1121

Department of Biomedical Sciences, Eye Clinic.

Purpose: Aim of this work is to highlight the advantages of a new surgical technique performed over 15 patients affected dacryocystitis and treated by using a venous catheter.The arrangement of a 30 mm venous catheter used at the end of a dacryocystectomy (DCT) was performed in 15 patients with dacryocystitis. The venous catheter was removed at 30 days after the surgery.The use of the venous catheter allows washing the lacrimal drainage system, reducing the risk of postoperative infections and supports the recanalization of the lacrimal drainage system 30 days after surgery.The presented cases demonstrated how the technique is easy and it reduces the possibility of the post-operative infection. It could be performed under regional anesthesia. Furthermore, after the surgery the recanalization of the lacrimal drainage system with a significant reduction of the epiphora in 6 months after surgery has been observed.
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http://dx.doi.org/10.1097/SCS.0000000000006237DOI Listing
June 2020

Rhino-Orbito-Cerebral Mucormycosis in Diabetic Disease Mucormycosis in Diabetic Disease.

J Craniofac Surg 2020 Jun;31(4):e321-e324

Department of Adult and Development Age Human Pathology "Gaetano Barresi", Unit of Otorhinolaryngology.

The authors present their experience about clinical evidences that include patients with an untreated diabetes who developed rhino-orbito-cerebral mucormycosis (ROCM). They were treated with endoscopic sinus surgery and medical treatment with intravenous, intradural therapy, and sinus washes with amphotericin B. The ROCM is a disease with a rapid evolution and an increase in mortality rate, especially if the fungus enters the cranial cavity. Therefore, it would be necessary in all diabetic patients with sinus symptoms, headaches, visual changes, suspect a mucormycosis, and perform a careful radiology assessment and a nasal endoscopy. Often, despite an early diagnosis and rapid treatment for ROCM, it is not possible to stem the disease, which ends with the patient's death.
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http://dx.doi.org/10.1097/SCS.0000000000006191DOI Listing
June 2020

Infectious conjunctivitis caused by in infected and extrused scleral buckles.

BMJ Case Rep 2020 Jan 8;13(1). Epub 2020 Jan 8.

U.O.C. Ophthalmology, Università degli Studi di Messina Facolta di Medicina e Chirurgia, Messina, Italy.

Extrusion of the scleral buckle is one of the complications patients may encounter undergoing the surgical treatment for retinal detachment. We present two cases of persistent -related conjunctivitis which infected the silicone explant after retinal surgery. One of them is a 73-year-old Caucasian female patient with hyperaemia, intense pain and mucopurulent discharge. After the conjunctival swabs detected a infection, she started both topical and systemic treatment without any results; for this reason we opted for the buckle removal always under systemic therapy. The second case is an 84-year-old Caucasian female patient with fever, periorbital oedema, chronic ocular pain, hyperaemia and purulent discharge. has also been detected in this case. No improvement with topical and systemic treatment, so this convinced us to remove patient's buckles and to continue systemic therapy. Both cases had the complete resolution after surgery. It is important to quickly recognise exposed scleral buckles because they can be a source of infections and a rare but threatening cause of endophthalmitis.
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http://dx.doi.org/10.1136/bcr-2019-232296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954750PMC
January 2020

Twelve-Month Results of Cyclosporine A Cationic Emulsion in a Randomized Study in Patients With Pediatric Vernal Keratoconjunctivitis.

Am J Ophthalmol 2020 04 23;212:116-126. Epub 2019 Nov 23.

Department of Neuroscience, Ophthalmology Unit, University of Padua, Padua, Italy. Electronic address:

Purpose: To assess the safety and efficacy of cyclosporine A cationic emulsion (CsA CE) 0.1% eye drops in pediatric patients with severe active vernal keratoconjunctivitis (VKC).

Design: Multicenter, double-masked, randomized controlled trial 8-month safety analysis.

Methods: Of 169 patients (age range, 4-17 years) initially randomized in the 4-month VErnal KeratoconjunctiviTIs Study (VEKTIS), 142 entered the 8-month follow-up period during which CsA CE patients remained on their original regimen (CsA CE 4 times daily [QID, high-dose] or CsA CE twice daily [BID, low-dose] + vehicle BID) and vehicle patients were allocated to one of these 2 active regimens. Main outcome measures were safety, including treatment-emergent adverse events, and efficacy, including corneal fluorescein staining (CFS) score.

Results: Improvements in CFS score, rescue medication use, key VKC symptoms (photophobia, tearing, itching, and mucous discharge), and quality of life (QoL) assessed by QUICK questionnaire observed with CsA CE compared with vehicle during the 4-month evaluation period remained stable during the 8-month follow-up period, with the high-dose regimen continuing to provide greater benefits in most efficacy measures. CsA CE was well tolerated. Treatment-related treatment-emergent adverse events during the 12-month study were reported in 15 (20.8%) and 11 (15.7%) of the CsA CE high-dose and low-dose patients, respectively, most commonly instillation site pain (13.9% and 7.1%, respectively). Laboratory data, vital signs, slit lamp examination, best-corrected distance visual acuity, and intraocular pressure raised no safety concerns.

Conclusions: Improvements in keratitis, symptoms, and QoL achieved after CsA CE treatment for 4 months remained stable over the 8-month follow-up period. CsA continued to maintain a favorable safety profile.
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http://dx.doi.org/10.1016/j.ajo.2019.11.020DOI Listing
April 2020

Physicochemical Properties of Hyaluronic Acid-Based Lubricant Eye Drops.

Transl Vis Sci Technol 2019 Nov 1;8(6). Epub 2019 Nov 1.

Allergan plc, Irvine, CA, USA.

Purpose: To assess the physicochemical properties of hyaluronic acid (HA)-based artificial tears.

Methods: The average molecular weight (MW) and polydispersion index (PDI) of HA in 18 commercially available artificial tears were determined by light scattering/high-performance liquid chromatography. Osmolality, pH, viscosity, and sodium concentration were determined using an osmometer, pH meter, rheometer, and inductively coupled plasma mass spectrometer, respectively.

Results: The MW of HA varied considerably between formulations. The PDI was >2.0 in two formulations (2.28 and 4.94), suggesting the presence of a copolymer and/or HA size variability. Three formulations exhibited viscosity exceeding the blur threshold at different shear rates. Viscosity at low shear rates was generally highest in formulations containing high-MW HA. Correlations were found between observed viscosity and a predictive/calculated value, except for four copolymer-containing formulations, and osmolality (range, 154-335 mOsm/kg) and sodium concentration (range, 22-183 mM), with two exceptions. Compared with organic osmolytes, adding sodium decreased viscosity, particularly at lower shear rates.

Conclusions: In the context of the literature, our findings suggest that for most patients with dry eye disease, the ideal HA-based artificial tear should include high-MW HA with a low PDI and exhibit enhanced viscosity at low shear rate (without exceeding the blur threshold). The inclusion of synergistic copolymers and a low sodium concentration may increase viscosity, but whether any of these physicochemical properties or correlations can predict clinical efficacy will require further investigation.

Translational Relevance: Understanding the properties of HA-based artificial tears will support the development of unique formulations that target specific ocular surface conditions.
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http://dx.doi.org/10.1167/tvst.8.6.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827422PMC
November 2019

Scleral pockets for an innovative technique of intrascleral fixation of intraocular lens.

Eur J Ophthalmol 2020 Sep 29;30(5):985-990. Epub 2019 Jul 29.

Department of Biomedical Sciences, Eye Clinic, University of Messina, Messina, Italy.

The aim of this article is to report the results of an innovative technique for a scleral fixation of a posterior chamber intraocular lens using our new modified technique. We retrospectively reviewed the medical records of 15 eyes of 15 patients who underwent sutureless intrascleral intraocular lens fixation using our modified technique. We used a 23-gauge knife to perform sclerotomy and create two parallel scleral pockets for the haptics. The mean follow-up period was 3 years (3 ± 1). No complications were detected during the follow-up period. The creation of two parallel scleral pockets, parallel to the limbus, greatly simplifies the introduction of intraocular lens haptics.
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http://dx.doi.org/10.1177/1120672119866018DOI Listing
September 2020

The Use of a Venous Catheter as a Stent for Treatment of Acquired Punctal and Canalicular Stenosis.

J Craniofac Surg 2019 Nov-Dec;30(8):2544-2545

Department of Biomedical Sciences, Eye Clinic, University of Messina, Messina.

Purpose: The aim of this study was to describe a simple technique to insert a venous catheter as a stent for the treatment of acquired punctal and canalicular stenosis.

Methods: We performed this technique using a central venous catheter as a stent for the treatment of acquired punctal and canalicular stenosis.

Results: The results show the easy availability of the material used for the intervention, its easy execution, and the low costs of materials. The goal of this technique is to have a lacrimal dot dilated and canalicular duct easy to irrigate.

Conclusion: The use of a venous catheter as a stent for treatment of acquired punctal and canalicular stenosis seems to be simple, safe, repeatable, and noninvasive.
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http://dx.doi.org/10.1097/SCS.0000000000005743DOI Listing
January 2020

Changes in conjunctival epithelial cells after treatment with 0.2% xanthan gum eye drops in mild-moderate dry eye.

Eur J Ophthalmol 2020 May 11;30(3):439-445. Epub 2019 Mar 11.

SIFI SpA, Catania, Italy.

Purpose: To study the effects of xanthan gum eye drops on the ocular surface and conjunctival cytology of patients with mild-moderate dry eye.

Methods: This prospective, double-masked, controlled trial included 30 patients (age > 60 and Ocular Surface Disease Index score >12 and <33), divided into two groups of 15 subjects and treated with 0.2% xanthan gum eye drops (group 1) or 0.5% carboxymethylcellulose (group 2) qid. After a run-in period with saline qid, patients were evaluated by Ocular Surface Disease Index questionnaire, clinical assessment, and impression cytology at baseline (T0) and after 1 month (T1). For impression cytology, cellularity, cell-to-cell contacts, nucleus/cytoplasm ratio, chromatin aspect, goblet cells distribution, keratinization, and the presence of inflammatory cells were considered. Parameters were scored from 0 (no alterations) to 3 (evident alterations). For statistical analysis, Student's t-test, Wilcoxon rank-sum test, and Mann-Whitney U-test were used.

Results: Clinically, after 1 month of treatment, group 1 showed an improvement of corneal stain (T0 = 1.1 ± 1.4; T1 = 0.5 ± 0.7; p = 0.03) and a reduction of Schirmer I test (T0 = 9.8 ± 6.1; T1 = 5.9 ± 4.1; p = 0.001). In group 2, no differences were found between T0 and T1 for all the clinical tests. For impression cytology, in group 1 cellularity (T0 = 0.6 ± 0.5; T1 = 0.3 ± 0.5; p = 0.05), chromatin aspect (T0 = 1.2 ± 0.4; T1 = 0.8 ± 0.5; p = 0.01), keratinization (T0 = 1 ± 0.7; T1 = 0.5 ± 0.5; p = 0.03), and total score (T0 = 5.8 ± 1.3; T1 = 3.6 ± 1.7; p = 0.003) were significantly ameliorated, while in group 2 only total score improved significantly (T0 = 5 ± 1.4; T1 = 4.3 ± 1.5; p = 0.01). The comparison between groups showed significant amelioration for keratinization in group 1 at T1 (p = 0.02).

Conclusion: The treatment with xanthan gum, a molecule with anti-oxidant and mucoadhesive properties, ameliorated conjunctival epithelium of mild-moderate dry eye patients better than carboxymethylcellulose.
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http://dx.doi.org/10.1177/1120672119833278DOI Listing
May 2020

A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study.

Ophthalmology 2019 05 27;126(5):671-681. Epub 2018 Dec 27.

University Hospital Necker Enfants Malades, APHP, and Rare Eye Disease Center OPHTARA, CNRS Unit FR3636, Paris Descartes University, Paris, France. Electronic address:

Purpose: Vernal keratoconjunctivitis (VKC) is a chronic, allergic, and potentially severe ocular disease affecting children and adolescents that can lead to impaired quality of life (QoL) and loss of vision. This study evaluated the efficacy and safety of an investigational therapy for severe VKC, cyclosporine A (CsA) cationic emulsion (CE), an oil-in-water emulsion with increased bioavailability versus conventional CsA formulations.

Design: The VErnal KeratoconjunctiviTIs Study (VEKTIS) is a phase 3, multicenter, double-masked, vehicle-controlled trial.

Participants: Pediatric patients (4 to younger than 18 years) with active severe VKC (grade of 3 or 4 on the Bonini severity scale) and severe keratitis (corneal fluorescein staining [CFS] score of 4 or 5 on the modified Oxford scale).

Methods: One hundred sixty-nine patients were randomized to CsA CE 0.1% (1 mg/ml) eye drops 4 times daily (high dose), CsA CE twice daily (low dose) plus vehicle twice daily, or vehicle 4 times daily for 4 months.

Main Outcome Measures: The primary end point was a mean composite score that reflected CFS, rescue medication use (dexamethasone 0.1% 4 times daily), and corneal ulceration over the 4 months.

Results: Differences in least-squares means versus vehicle for the primary end point were statistically significant for both the high-dose (0.76; P = 0.007) and the low-dose (0.67; P = 0.010) groups, with treatment effect mainly driven by CFS score. Significant differences were found between both active treatment groups and vehicle for use of rescue medication. Vernal keratoconjunctivitis symptoms and patient QoL (assessed by visual analog scale and the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire) improved in all 3 groups, with significant improvements for high-dose CsA CE versus vehicle.

Conclusions: The efficacy of high-dose CsA CE in improving keratitis, symptoms, and QoL for those with severe VKC was demonstrated in these study patients. In addition, in this study cohort, CsA CE was well tolerated.
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http://dx.doi.org/10.1016/j.ophtha.2018.12.027DOI Listing
May 2019

The Use of a Double Suture and Conjunctival Cuts in the Lateral Tarsal Strip: A New Approach to Involutional Ectropion.

J Craniofac Surg 2018 Nov;29(8):2312-2315

Department of Biomedical Sciences, Eye Clinic, University of Messina, Messina.

Purpose: To describe the use of a double suture and conjunctival cuts in the lateral tarsal strip (LTS) and to evaluate postsurgical outcome in patients with severe involutional ectropion.

Methods: A prospective randomized study was conducted on 16 eyelids of 8 patients with symptomatic severe involutional ectropion. The 8 patients were between 62 and 79 years. They were distributed into 2 groups consisting of 4 patients each. The control group was treated with a conventional lateral tarsal strip (C-LTS), the second group underwent a modified lateral tarsal strip (M-LTS). The mean follow-up was 18 months. Success was defined as relief in lid laxity. The recurrence rate was also evaluated.

Results: Patients treated with M-LTS showed lower horizontal laxity (3.5 ± 0.2) than patients treated with C-LTS (5.7 ± 0.2). During the 18-month follow-up, a statistically significant difference was found between the 2 groups with P value <0.05.

Conclusions: The use of a double suture and conjunctival cuts in the lateral tarsal strip proposed by Meduri showed a reduction of postsurgical ectropion's grade and postsurgical recurrences. This technique could be used for the treatment of patients with a severe ectropion.
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http://dx.doi.org/10.1097/SCS.0000000000004838DOI Listing
November 2018

Role of corneal nerves in ocular surface homeostasis and disease.

Acta Ophthalmol 2019 Mar 17;97(2):137-145. Epub 2018 Sep 17.

Complutense University, Madrid, Spain.

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.
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http://dx.doi.org/10.1111/aos.13844DOI Listing
March 2019

Photorefractive keratectomy after cataract surgery in uncommon cases: long-term results.

Int J Ophthalmol 2018 18;11(4):612-615. Epub 2018 Apr 18.

Department of Surgery, Ophthalmology Clinic, University Hospital of Messina, Messina 98124, Italy.

Aim: To evaluate the efficacy and safety of the excimer laser correction of the residual refractive errors after cataract extraction with intraocular lens (IOL) implantation in uncommon cases.

Methods: Totally 24 patients with high residual refractive error after cataract surgery with IOL implantation were examined. Twenty-two patients had a history of phacoemulsification and IOL implantation, and two had extra-capsular cataract extraction with IOL implantation. Detailed examination of preoperative medical records was done to explain the origin of the post-cataract refractive errors. All patients underwent photorefractire keratectomy (PRK) enhancement. The mean outcome measures were refraction, uncorretted visual acuity (UCVA), best corrected visual acuity (BCVA) and corneal transparency and follow up ranged from 1 to 8y.

Results: The principal causes of residual ametropia was inexact IOL calculation in abnormal eyes with high myopia and congenital lens abnormalities, followed by corneal astigmatism both suture induced and preexisting. After cataract surgery and before the laser enhancement the mean spherical equivalent (SE) was -0.56±3 D ranging from -4.62 to +2.25 D in high myopic patients, instead it was -1±1.73 D ranging from -3.25 to +3.75 D in the astigmatic eyes, with a mean cylinder of -3.75±0 ranging from -3 to +5.50 D. After laser refractive surgery the mean SE was 0.1±0.73, ranging from -0.50 to +1.50 in the myopic group, and it was -0.50±0.57 ranging from -1.25 to +0.50 in astigmatic patients, with a mean cylinder of -0.25±0.75. In myopic patients the mean UCVA and BCVA were 0.038±0.072 logMAR and 0.018±0.04 respectively, both ranging from 0.10 to 0.0. In astigmatic patients, the mean UCVA and BCVA were 0.213±0.132 and 0.00±0.0 respectively, UCVA ranging from 0.50 to 0.22 and BCVA was 0.00. All patients presented normal corneal transparency. No ocular hypertension was detected and no corneal haze was observed. All registered values remained stable also at the end line evaluation.

Conclusion: The excimer laser treatment of residual refractive errors after cataract surgery with IOL implantation in abnormal eyes resulted in satisfactory and stable visual outcome with good safety and efficacy.
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http://dx.doi.org/10.18240/ijo.2018.04.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902365PMC
April 2018

Stargardt Phenotype Associated With Two ELOVL4 Promoter Variants and ELOVL4 Downregulation: New Possible Perspective to Etiopathogenesis?

Invest Ophthalmol Vis Sci 2018 02;59(2):843-857

Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Neuroscience-Applied Molecular Genetics and Predictive Medicine, Istituto Euro Mediterraneo di Scienza e Tecnologia (I.E.ME.S.T.), Palermo, Italy.

Purpose: Stargardt disease (STGD) is the most common form of inherited juvenile macular degeneration. It is inherited as autosomal recessive trait (STGD1), although STGD3 and STGD4 are inherited as autosomal dominant inheritance pattern. STGD3 is caused by mutations in the elongation of very long-chain fatty acids-like 4 (ELOVL4) gene encoding for a very long-chain fatty acid elongase. Mutations lead to a truncated Elovl4, lacking of a dilysine motif necessary for retention of transmembrane proteins in the endoplasmic reticulum. STGD occurs due to altered synthesis of very long-chain polyunsaturated fatty acids (VLC-PUFA). Our work investigates the role of two variants in the ELOVL4 gene promoter region, c.-236 C>T (rs240307) and c.-90 G>C (rs62407622), identified in a patient with STGD in transconfiguration.

Methods: Their effects on ELOVL4 expression were examined by Dual-Luciferase Reporter assay.

Results: rs62407622 and rs240307 variants caused 14% and 18% of expression reduction, respectively, compared with wild-type promoter. A very strong decreased gene expression was caused by coexistence of both variants.

Conclusions: A highly reduced activity of the ELOVL4 promoter was registered due to combination of two variants. Decrease of ELOVL4 enzymatic activity could lead to a deficiency of VLC-PUFA, essential components for rods function and longevity, which are among the parameters involved in the etiopathogenesis of STGD.
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http://dx.doi.org/10.1167/iovs.17-22962DOI Listing
February 2018

Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

Cornea 2018 Apr;37(4):448-454

Department of Biomedical Sciences, Regional Referral Center for the Ocular Surface Diseases, University of Messina, Messina, Italy.

Purpose: To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD).

Methods: A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls.

Results: Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106).

Conclusions: Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.
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http://dx.doi.org/10.1097/ICO.0000000000001517DOI Listing
April 2018