Alberto Neri

Molecular and Clinical Characterization of Albinism in a Large Cohort of Italian Patients

PURPOSE The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations. METHODS DNA samples from 45 patients with ocular manifestations of albinism were analyzed by direct sequencing analysis of five genes responsible for albinism: TYR, P, TYRP1, SLC45A2 (MATP), and OA1. All patients studied showed a variable degree of skin and hair hypopigmentation. Eighteen patients with distinct mutations in each gene associated with OCA were evaluated by detailed ophthalmic analysis, optical coherence tomography (OCT), and fundus autofluorescence. RESULTS Disease-causing mutations were identified in more than 95% of analyzed patients with OCA (28/45 [62.2%] cases with two or more mutations; 15/45 [33.3%] cases with one mutation). Thirty-five different mutant alleles were identified of which 15 were novel. Mutations in TYR were the most frequent (73.3%), whereas mutations in P occurred more rarely (13.3%) than previously reported. Novel mutations were also identified in rare loci such as TYRP1 and MATP. Mutations in the OA1 gene were not detected. Clinical assessment revealed that patients with iris and macular pigmentation had significantly higher visual acuity than did severe hypopigmented phenotypes. CONCLUSIONS TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation.

Ophthalmologic and Systemic Features in Möbius Syndrome: An Italian Case Series

PURPOSE To describe clinical features in a large series of Möbius syndrome (MBS) cases, investigating whether specific neuro-ophthalmologic patterns of disease may provide further insight into MBS pathogenesis. DESIGN Observational, prospective study. PARTICIPANTS Fifty-five affected subjects. METHODS To make an MBS diagnosis, the criteria recommended in the First Scientific Conference on Möbius Syndrome were followed. Patients who did not meet the minimal criteria were classified as Möbius-like cases and were considered separately. Complete ophthalmologic evaluation, eyelid measurements, presence of abnormal tearing, and ocular motility also were assessed. MAIN OUTCOME MEASURES Pattern of ocular motility alteration, visual function disturbances, and eyelid and tearing defect. RESULTS Forty-six sporadic cases of true MBS were identified, with 3 specific patterns of ocular motility alterations. Pattern A, consisting of orthotopia in primary position with a complete defect in both abduction and adduction ocular movements, was found in 41% of cases. Pattern B, with large-angle esotropia, crossed fixation, and a relative sparing of convergence and adduction, was documented in 50% of cases. Pattern C, characterized by a large-angle exotropia in primary position with torticollis, absence of convergence, and vertical eye misalignment, was present in the minority of the patients (9%). Bilateral complete facial nerve palsy with lagophthalmos was present in 83% of patients; lacrimation showed abnormalities in 33% of cases. Visual acuity was good or impaired only moderately in all tested patients. Binocular function was testable in 31 of 46 patients, and all of them showed a complete absence of stereopsis with suppressive scotoma. CONCLUSIONS Based on the observed 3 different ocular motility defect patterns, the most compatible site and extension of the brainstem damage was inferred. Each pattern may reflect a different type of injury likely occurred during embryogenesis. The comparison of the characteristics of this series with those reported in different geographic areas supports the evidence that MBS does not differ phenotypically worldwide. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Dynamic imaging of accommodation by swept-source anterior segment optical coherence tomography

Purpose To study the accommodation process in normal eyes using a commercially available clinical system based on swept‐source anterior segment optical coherence tomography (AS‐OCT). Setting Ophthalmology Department, University of Parma, Italy. Design Evaluation of diagnostic technology. Methods Right eyes were analyzed using swept‐source AS‐OCT (Casia SS‐1000). The optical vergence of the internal coaxial fixation target was adjusted during imaging to obtain monocular accommodation stimuli with different amplitudes (0, 3.0, 6.0, and 9.0 diopters [D]). Overlapping of real and conjugate OCT images enabled imaging of all the anterior segment optical surfaces in a single frame. Central corneal thickness (CCT), anterior chamber depth (ACD), and lens thickness were extracted from the OCT scans acquired at different static accommodation stimulus amplitudes. The crystalline lens was analyzed dynamically during accommodation and disaccommodation by acquiring sequential OCT images of the anterior segment at a rate of 8 frames per second. The lens thickness was extracted from the temporal sequence of OCT images and plotted as a function of time. Results The study analyzed 14 eyes of 14 subjects aged 18 to 46 years. During accommodation, the decrease in the ACD was statistically significant (P < .05), as were the increase in the lens thickness (P < .001) and the slight movement forward of the lens central point (P < .01). The CCT and anterior chamber width measurements did not change statistically significantly during accommodation. The lens thickness at 0 D was positively correlated with age (P < .01). Conclusion High‐resolution real‐time imaging and biometry of the accommodating anterior segment can be effectively performed using a commercially available swept‐source AS‐OCT clinical device. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Corneal thickness mapping by 3D swept-source anterior segment optical coherence tomography

Purpose:  To assess accuracy and repeatability of central corneal thickness (CCT) measurements obtained by swept‐source anterior segment optical coherence tomography (AS‐OCT), spectral‐domain retinal OCT with corneal module and ultrasound pachymetry (USP), and to assess repeatability of pachymetric mapping with AS‐OCT.

Swept-source anterior segment optical coherence tomography in late-onset capsular block syndrome: High-resolution imaging and morphometric modifications after posterior capsulotomy

Purpose To study the characteristics of late‐onset capsular block syndrome (CBS) using swept‐source anterior segment optical coherence tomography (AS‐OCT) and assess morphometric variations after treatment with neodymium:YAG (Nd:YAG) laser posterior capsulotomy. Setting Ophthalmology, University of Parma, Parma, Italy. Design Case series. Methods Patients with late‐onset CBS had an ophthalmology evaluation, including slitlamp photography and AS‐OCT, before and 1 month after ND:YAG laser posterior capsulotomy. The diameter of the anterior capsulorhexis, the posterior displacement of the posterior capsule, and the anterior chamber depth (ACD) were measured using AS‐OCT. Measurements before and after Nd:YAG laser posterior capsulotomy were compared using the paired t test. Results The study evaluated 6 patients. Slitlamp examination showed accumulation between the intraocular lens (IOL) and the posterior capsule of milky‐white or particulate liquefied material that appeared hyperreflective on AS‐OCT and caused posterior displacement of the posterior capsule (mean 1.38 mm). The diameter of the anterior capsulorhexis (mean 4.5 mm) was smaller than the IOL optic in all cases. After uneventful Nd:YAG laser posterior capsulotomy, the corrected distance visual acuity improved in all patients (P<.01). The ACD (IOL position) and refraction did not change significantly after the capsulotomy (P=.15 and P=.36, respectively). Conclusions Anterior segment OCT allowed accurate imaging and measurement of anterior segment parameters in late‐onset CBS. No displacement of the IOL was found after treatment with Nd:YAG laser posterior capsulotomy. Neodymium:YAG laser posterior capsulotomy was an effective and safe therapy in the 6 late‐onset CBS cases. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Femtosecond laser assisted design of sutureless intrastromal graft as an alternative to partial thickness keratoplasty

Minimally invasive laser assisted surgery in ophthalmology is continuously developing in order to find new surgical approaches, preserve patient tissue and improve surgical results in terms of cut precision, restoration of visual acuity, and invasiveness. In order to achieve these goals, the current approach in corneal transplant is lamellar keratoplasty, where only the anterior or posterior part of the patient’s cornea is substituted depending on the lesion or pathology. In this work, we present a novel alternative approach: a case study of intrastromal sutureless transplant, where a portion of the anterior stroma of a donor cornea was inserted into the stroma of the recipient cornea, aiming to restore the correct thickness of the patient’s cornea. The patient cornea was paracentrally thin, as the result of a trophic ulcer due to ocular pemphigoid. A discoid corneal graft from the anterior stroma of a donor eye was prepared: a femtosecond laser cut with a trapezoidal profile (thickness was 300 μm, minor and major basis were 3.00 and 3.50 mm, respectively). In the recipient eye, an intrastromal cut was also performed with the femtosecond laser using a specifically designed mask; the cut position was 275 μm in depth. The graft was loaded into an injector and inserted as an intrastromal presbyopic implant. The postoperative analysis evidenced a clear and stable graft that selectively restored corneal thickness in the thinned area. Intrastromal corneal transplant surgery is a minimally invasive alternative to anterior or posterior lamellar keratoplasty in select cases. We believe that Sutureless Intrastromal Laser Keratoplasty (SILK) could open up new avenues in the field of corneal transplantation by fully utilizing the potential and precision of existing lasers.

Advanced adenoid cystic carcinoma of the conjunctiva: total upper eyelid and medial canthal region reconstruction with three local flaps plus auricular cartilage graft

Adenoid cystic carcinoma (ACC) of the eyelid is a rare malignant tumor which originates primarily from the conjunctiva or from the skin [1]. We report an advanced case of ACC involving the entire upper eyelid and the medial canthal region. This condition was treated by radical surgical resection and reconstruction using three local flaps plus an auricular cartilage graft. This obtained satisfactory functional and aesthetical results. To our knowledge only five cases of primary conjunctival ACC [1] and four cases of primary cutaneous ACC [2] of the eyelids have been described to date, and the case herein reported is the first involving the entire upper eyelid together with the medial canthal region.