Search

Chiara Fariselli, Giuseppe Giannaccare, Michela Fresina, Piera Versura Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine (DIMES), Alma Mater Studiorum University of Bologna and St Orsola-Malpighi Teaching Hospital, Bologna, Italy Aim: To assess the ocular surface parameters, inflammatory marker level in tears, and mucin expression in conjunctival epithelium before and after treatment with trehalose/hyaluronate tear substitute in dry eye (DE) patients.Patients and methods: Fifteen DE patients were evaluated in an open-label, pilot study at enrollment, after 2 days of washout (baseline) and after 1 and 2 months (endpoint) of treatment with a trehalose/hyaluronate tear substitute (one drop/eye/three times daily). Data for symptoms of discomfort (Ocular Surface Disease Index and Visual Analogue Scale pain score), tear film (Schirmer test I, tear film breakup time), ocular surface damage (corneal National Eye Institute) and conjunctival van Bijsterveld scores, impression cytology scored by Nelson’s grade and goblet cells (GCs) number/mm2 analysis, and MUC4 immunostaining, and inflammation (interleukin [IL]-1β, IL-6, and IL-8 levels) were measured.Results: Significant changes at endpoint as compared to baseline were found for Ocular Surface Disease Index score (respectively, mean±SD, 22.2±2.9 vs 38.7±12.7), Visual Analogue Scale score (3.4±1.3 vs 6.6±1.4), tear film breakup time (8.6±1.28 vs 6.17±1.9 seconds), corneal staining (National Eye Institute grade 1.23±0.64 vs 3.37±0.49), conjunctival staining (1.73±1.14 vs 4.17±0.91), impression cytology (Nelson grade 1.10±0.20 vs 1.63±0.54), and GC density (139.9±22.0 vs 107.8±16.2 GC/mm2). IL-1β, IL-6, and IL-8 tear levels showed a significant decrease at endpoint as compared to baseline (respectively, pg/mL tears: 12.3±6.9, 26.6±25.2, 743.5±477.7 vs 33.6±17.3, 112.0±24.3, 1,139.2±671.7).Conclusions: A decrease in ocular discomfort symptoms, surface damage, and tear cytokine levels was shown after 2 months’ treatment with trehalose/hyaluronate tear substitute in DE patients, along with a significant GC density recovery. These results may be associated with the synergic action of both trehalose and hyaluronic acid in targeting different entries of the DE vicious loop. Keywords: dry eye, trehalose, hyaluronic acid, tear substitute, inflammation

Piera Versura, Giuseppe Giannaccare, Marco Pellegrini, Stefano Sebastiani, Emilio C Campos Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Sant’Orsola-Malpighi Teaching Hospital, Bologna, Italy Abstract: Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described. Keywords: neurotrophic keratitis, neurotrophic corneal ulcer, corneal nerves

Giuseppe Giannaccare, Michela Fresina, Alberto Pazzaglia, Piera Versura Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Sant’Orsola‑Malpighi Teaching Hospital, Bologna, Italy Abstract: Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional treatment. In addition, it could be especially useful in diabetic patients unable to receive systemic steroids. Keywords: keratoplasty, corneal graft rejection, dexamethasone intravitreal implant, confocal microscopy, keratoconus

Giuseppe Giannaccare,1 Michela Fresina,1 Aldo Vagge,2 Piera Versura1 1Ophthalmology Unit, DIMES, S Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy; 2Eye Clinic, DiNOGMI, University of Genoa, Genoa, Italy Abstract: This report describes a case of a 72-year-old Caucasian woman presenting with a large neurotrophic keratitis with a large persistent epithelial defect, with a longest linear diameter of 7 mm and greatest perpendicular width of 5 mm, affecting epithelium, Bowman membrane, and anterior stroma. Corneal disease was resistant to conventional treatment and classified as stage 2 according to Mackie classification. Patient was instructed to instill regenerating agent (RGTA) eye drops in the morning, as the first eye drop, once every 5 days in combination with daily cord blood serum (CBS) eye drops 6 times/day. The patient was asked to visit after 1 week (V1), 2 weeks (V2), 3 weeks (V3), and 4 weeks (V4) of study treatment. In V4 treatment, corneal sensitivity improved, and keratitis healed with resolution of stromal inflammation. Global treatment tolerance was very satisfactory. Patient continued the therapy for a further month after complete healing. Currently, the patient has been followed up for 3 months without any sign of keratitis recurrence. To the best of our knowledge, this case report describes for the first time the successful combined use of RGTA and CBS eye drops for the treatment of neurotrophic keratitis resistant to conventional treatment. We hypothesize that RGTA eye drops could provide an optimal migration substrate and that growth factors supplied by CBS eye drops could strengthen the repair process by promoting cell growth over the matrix. Combined RGTA and CBS eye drop therapy could be a new potential option for the successful treatment of resistant neurotrophic keratitis, particularly when each drug alone is not effective. Keywords: neurotrophic keratitis, regenerating agent, cord blood serum eye drops, penetrating keratoplasty, in vivo confocal microscopy

Introduction: Dry eye disease is a multifactorial disease which affects the ocular surface system, and determines ocular discomfort symptoms and visual disturbance. Various types of ocular surgery, including strabismus one, represents a recognized cause for iatrogenic dry eye. However, it is not uncommon that strabismus patients, even not undergone to surgery, report symptoms of ocular discomfort and dryness. Hypothesis We hypothesize that two possible mechanisms may determine dry eye in strabismus patients by setting up a specific vicious circle: firstly, the increased exposure of the area of the bulbar conjunctiva located on the opposite side compared to the deviation may cause the thinning of the tear film lipid layer, with increased tear film instability; secondly, the dysfunctional lubricity secondary to the altered relationship between the eyelids and the deviated globe may cause blinking-related microtrauma, and thus inflammation and tear hyperosmolarity. These two entry points into the vicious circle of dry eye may determine a cascade of detrimental mechanisms, leading to further damage of the tear film, thus closing the disease circle.Discussion: Strabismus patients may be affected by signs and symptoms of dry eye syndrome. The increased exposure of the bulbar conjunctival area along with the dysfunctional lubricity between the eyelids and the deviated eye could be the main underlying pathophysiological mechanisms acting as entry points into the vicious circle of dry eye disease. If our hypothesis was to be confirmed, ocular surface parameters should be routinely investigated in strabismus patients, whilethe use of tear substitutes with the aim of moistening and nourishing the ocular surface could help in reducing dry eye signs and symptoms. [ABSTRACT FROM AUTHOR]

PurposeTo describe the results achieved using muscle belly union associated with the recession of the ipsilateral medial rectus muscle to treat myopic myopathy and restore the normal anatomical relationship of superior and lateral rectus (LR).MethodsA retrospective, nonrandomized study performed on 33 eyes of 26 patients who underwent muscle belly union between January 2004 and October 2012. We preoperatively and postoperatively recorded: best-corrected visual acuity; refraction; intraocular pressure; complete orthoptic assessment, including the angle of deviation and maximal abduction measured using the Goldmann perimeter. Pictures of the eyes in all gaze directions were taken before and after the surgical treatment. Anatomical relationships between muscle cone and eye globe were preoperatively analyzed using magnetic resonance imaging (MRI). Surgical complications were noted.ResultsThe follow-up period was 6 months. Preoperative mean BVCA was 0.97±0.96 logMAR (ranging from 0.1 to 3 logMAR) and no changes were detected during postoperative controls. Preoperative mean hypotropia and esotropia were, respectively, 10.2±3.9 prism diopters (PD) and 46.2±15.5 PD. Postoperative mean hypotropia was 2.48±2.00 PD (P<0.001) and mean esotropia was 7.36±9.09 PD (P<0.001). A statistical incrementation of mean maximal abduction (P<0.001) was also noticed.ConclusionsMuscle belly union-coupled with the recession of the ipsilateral medial rectus muscle when considered convenient-is the elective surgical technique in myopic myopathy, when a downward displacement of LR muscle is shown on MRI with coronal sections. [ABSTRACT FROM AUTHOR]

Purpose:To analyze tear protein variations in patients suffering from dry eye symptoms in the presence of tear film instability but without epithelial defects.Methods:Five microlitres of non-stimulated tears from 60 patients, suffering from evaporative dry eye (EDE) with a break-up time (BUT) <10 s, and from 30 healthy subjects as control (no symptoms, BUT >10 s) were collected. Tear proteins were separated by mono and bi-dimensional SDS-PAGE electrophoresis and characterized by immunoblotting and enzymatic digestion. Digested peptides were analyzed by liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry followed by comparative data analysis into Swiss-Prot human protein database using Mascot. Statistical analysis were performed by applying a t-test for independent data and a Mann–Whitney test for unpaired data (P<0.05).Results:In EDE patients vscontrols, a significant decrease in levels of lactoferrin (data in %±SD): 20.15±2.64 vs24.56±3.46 (P=0.001), lipocalin-1: 14.98±2.70 vs17.73±2.96 (P=0.0001), and lipophilin A–C: 2.89±1.06 vs3.63±1.37 (P=0.006) was revealed, while a significant increase was observed for serum albumin: 9.45±1.87 vs3.46±1.87 (P=0.0001). No changes for lysozyme and zinc α-2 glycoprotein (P=0.07 and 0.7, respectively) were shown. Proteomic analysis showed a downregulation of lipophilin A and C and lipocalin-1 in patients, which is suggested to be associated with post-translational modifications.Conclusions:Data show that tear protein changes anticipate the onset of more extensive clinical signs in early stage dry eye disease. [ABSTRACT FROM AUTHOR]

Purpose: Tear osmolarity is considered a key point in dry eye disease (DED) and its measurement is the gold standard in dry eye diagnosis. Tear osmolarity was evaluated in dry eye (DE) patients vs. a control group to assess its diagnostic performance compared to clinical and laboratory tests performed in either clinical or research settings. Methods: Tear osmolarity was measured with the TearLab Osmolarity System (OcuSense) in 25 normal subjects and 105 DE patients (severity score 1–4, Dry Eye Workshop (DEWS)). The following tests were also performed: Ocular Surface Disease Index (OSDI) symptoms questionnaire, Schirmer I test, Tear Film Break Up Time (TFBUT), ferning test, lissamine green staining, tear clearance, corneal esthesiometry, and conjunctival cytology by scraping and imprint. Statistical evaluation was performed by unpaired Student’s t and Mann-Whitney tests, the Spearman’s ρ and the Pearson’s r correlation coefficients (significance p < 0.05); all variables were also analyzed for sensitivity, specificity, Receiver Operating Characteristics (ROC) curves, likelihood ratio LR+, and positive predictive value (PPV). Results: Tear osmolarity normal values were 296.5 ± 9.8 mOsm/L, increasing values were shown stepwise DE severity (mild to moderate to severe dry eye, respectively: 298.1 ± 10.6 vs. 306.7 ± 9.5 vs. 314.4 ± 10.1, p < 0.05). A progressive worsening occurred in all the parameters with DED severity increase. Tear osmolarity exhibited the larger correlation strength vs. tear clearance, TFBUT and clinical score, strength increased with DED severity, mainly to inflammatory score and corneal sensitivity. Tear osmolarity 305 mOsm/L was selected as cut-off value for dry eye, 309 mOsm/L for moderate dry eye, 318 mOsm/L for severe dry eye (Area-Under-the-Curve was 0.737, 0.759, and 0.711, respectively). Conclusions: Tear osmolarity can now be considered a test suitable to be performed in a clinical setting. It showed a good performance in dry eye diagnosis, higher than the other tests considered, mainly in severe dry eye. Tear osmolarity values should be interpreted as an indicator of DED evolutionary process to severity. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the diagnostic performance of the tests included in primary Sjogren's syndrome (SS-I) diagnostic criteria (Schirmer I, break-up time, vital dye staining) and to compare them with other examinations related to the ocular surface status.MethodsClinical and cytological data were collected from 177 patients (62 SS-1, 56 non-SS autoimmune diseases, 59 Sicca syndrome). Tear tests included: a validated questionnaire on symptoms, Schirmer I, Jones test, Ferning test, BUT, corneal aesthesiometry, tear clearance test, lissamine green staining, impression conjunctival cytology. Data were statistically evaluated and sensitivity, specificity, likelihood ratio (LR+), receiver-operating characteristics (ROC) curves were calculated for each test.ResultsData showed a poor diagnostic performance of Schirmer test I (sensitivity 0.42; specificity 0.76; LR+1.75) and BUT (sensitivity 0.92; specificity 0.17; LR+1.11) (area under the curve in ROC analysis <0.58). Validated subjective symptoms questionnaire (sensitivity 0.89; specificity 0.72; LR+3.18), Jones test (sensitivity 0.60; specificity 0.88; LR+5), corneal aesthesiometry (sensitivity 0.80; specificity 0.67; LR+2.42), and tear clearance test (sensitivity 0.63; specificity 0.84; LR+3.93), all exhibited a high diagnostic performance (area under the curve in the ROC analysis always >0.70). Lissamine green staining exhibited the best performance (sensitivity 0.63; specificity 0.89; LR+5.72) but the result could be distorted by an incorporation bias.ConclusionsOur data suggest to implement the items for ocular signs and symptoms contained in many SS-I diagnostic criteria with the use of a validated questionnaire, performance of Jones test, corneal aesthesiometry measurement, and tear clearance rate evaluation.Eye (2007) 21, 229–237. doi:10.1038/sj.eye.6702204; published online 6 January 2006 [ABSTRACT FROM AUTHOR]

Introduction: Acute acquired distance esotropia (AADE) is a poorly understood moderate-angle strabismus, affecting young adult myopes and determining bothersome diplopia. Symptoms can be intermittent in the early stages, becoming constant in long-lasting disease. Symptomatic therapy includes prism correction, while surgery is the only curative treatment. However, the latter is affected by high rate of symptoms recurrence with the frequent need for reoperation.Hypothesis: We hypothesize that AADE could be caused by the increase of the accommodative demand, often secondary to a myopic overcorrection. This condition could determine an increase in induced hyperopia at near, dominated by an excess of accommodation and therefore of convergence. The latter cannot be relaxed at distance and diplopia develops. We speculate that early-stage AADE could be successfully treated by cycloplegic eye drops slowly tapered within three months. On the other hand, surgery remains the only option in long-lasting AADE. In these cases, we propose a new pre-operative assessment of esotropia by asking the patient to fix alternatively a stimulus at near and at distance in order to stimulate the accommodative convergence. This technique allows to unmask the total amount of the angle of deviation and to plan a wider bilateral medial rectus muscle recession avoiding long-term residual esotropia.Discussion: Currently, AADE curative therapy is surgical regardless of onset time but it is usually affected by poor outcomes. If our hypothesis was to be confirmed, pharmacological treatment could solve early-stage AADE, avoiding any surgery. Furthermore, a wide bilateral medial rectus muscle recession, quantified on the basis of the above mentioned test for measuring the total amount of the strabismus angle, could improve outcomes eliminating the need for reoperation in long-lasting AADE. [ABSTRACT FROM AUTHOR]

Purpose Dry eye disease (DED), the result of an insufficient tear film, is manifest by symptoms of ocular discomfort and ocular surface damage. An ideal DED therapy would regenerate each deficient tear film layer. Cationorm®, a preservative‐free cationic emulsion, augments the aqueous‐mucous and lipid layers of the tear film and reduces evaporation. The efficacy of Cationorm® was evaluated. Methods Adults with moderate DED defined by at least 1 symptom >3 cm on a visual analog scale (VAS) and total corneal fluorescein score ≥3 and tear film break up time (BUT) <7 seconds were enrolled in a 3 month, controlled, randomized, single‐masked study. Randomization to qid treatment with Cationorm® (Novagali), Optive® (Allergan) or Emustil® (SIFI) followed a washout period. Efficacy assessments were evaluated at 1 and 3 months. Results Of 71 patients, 8 (44%) Emustil treated patients discontinued prior to month 3. At month 1, the VAS score in Optive® and Cationorm® patients revealed a statistically significant improvement evident by month 3 for all treatments. Improvements in BUT and reduced fluorescein staining at month 3 were statistically significant for Cationorm® and Optive® but not Emustil®. While Cationorm® and Optive® significantly reduced tear film osmolarity only Cationorm® showed a statistically significant difference compared to Emustil®. Conclusion In moderate DED patients, Cationorm® was more effective than Emustil®. Although not statistically different, overall improvements were greater in patients treated with Cationorm® than Optive®. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the diagnostic performance of meibometry in classifying and quantifying Meibomian gland dysfunction(MGD) Methods Ninety‐six patients with MGD (138 eyes, 62 women, 34 men) and 30 normal control subjects(55 eyes)were enrolled. Eighty six eyes were classified as high delivery (HD)‐MGD (meibomian seborrhea/hypersecretory MGD), 52 as low delivery (LD)‐MGD on the basis of expression quality scores and morphological signs. Direct Meibometry (DM) measurements were made with an MB550 Meibometer (Courage‐Khazaka GmbH). Standard curves were constructed relating arbitrary Meibometer optical density units (AU). Integrated Meibometry (IM) was performed on scanned images of the lipid blots. Symptoms were scored by OSDI,Schirmer test I, Break Up Time (BUT), tear osmolarity (Tearlab, Ocusense), conjunctival scraping cytology were performed. Statistical analysis used SPSS 14.0 and MedCalc 5.0 Results AU values plotted on a log scale correlated highly with the lipid equivalent values (R2= 0.913). Significant differences were found between control subjects vs all MGD patients and between HD vs LD‐MGD patients for all the parameters evaluated. In particular: controls: 300+/‐121 AU (0.04+/‐0.015 microliter), LD‐MGD: 218+/‐122 AU (0.03+/‐0.015) and HD‐MGD: 564+/‐115 AU (0.07+0.015) (median+/‐SD). Significant correlation was found DM vs IM (r=0.691,p<0.0001) and DM was shown to be correlated with BUT, OSDI score, scraping score and tear osmolarity, especially in LD‐MGD patients. The selected DM diagnostic cut off for LD‐MGD was <275 AU (sens 73, spec 60, PPV 63) and for HD‐MGD was >450 AU; (sens 86, spec 87, PPV 91) Conclusion Meibometry is confirmed to be a reliable method to distinguish normal subjects from MGD subgroups with a good degree of accuracy [ABSTRACT FROM AUTHOR]

Purpose To assess the expressibility of the meibomian gland we proposed a new diagnostic tool. We evaluated the use of the instrument by assessing the time of the meibomian gland expressibility and the intraocular pressure change in two groups of healthy patients. Methods We selected two groups of patients divided according to age. The first group consisted of 45 subjects aged between 20 and 30 years (mean 28 ±4.5 yrs) and a second group (group B) of 45 subjects aged between 40 and 50 years (mean 46±3.8 yrs). Meibomian gland evaluations were performed using a standardized technique with an evolved new diagnostic instrument patented in Italy. The instrument has a rectangular contact surface area of 40.57 mm2. The head surface is covered with a plastic film that is changed at each examination. The instrument exerts a constant pressure of 1.2 gr/mm2 under piezoelectric control. We evaluated the time to onset of fluid at the orifices of the meibomian glands and changes of intraocular pressure (IOP) after compression of the lower eyelid with applanation tonometry. Results In the group A and in group B the time to onset the fluid was 3.69±1.22 vs. 6.62±1.39 sec. (p<0.001). The IOP before and after compression of the eyelid was 14±1.13 vs. 23.4±2.0 mm/Hg (p<0.001). The mean number of meibomian gland secretion in each third of the lower eyelid were significantly different (p<0.001). Temporal: 1.29±0.13, central: 2.72±0.11, nasal: 3.51±0.14. Conclusion Our custom diagnostic meibomian gland expression instrument that is an evolution of other proposed devices has proved effective in evaluating the expressibility of the meibomian gland with a small increase of the intraocular pressure. [ABSTRACT FROM AUTHOR]