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PURPOSE: To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software "ACCMetrics," and to further investigate its diagnostic performance in discriminating DED patients. METHODS: IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann-Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls. RESULTS: Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p

Purpose: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings. Methods: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with “ACCMetrics;” neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty. Results: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings. Conclusions: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

Purpose: To compare the efficacy and tolerability of diclofenac and bromfenac ophthalmic solutions as adjunctive therapy after cataract surgery. Materials and Methods: This prospective randomized controlled study included 130 patients who underwent cataract surgery. One hundred patients were randomized to receive postoperatively diclofenac 0.1% (four times daily for 28 days, Group 1) or bromfenac 0.09% (twice daily for 14 days, Group 2) ophthalmic solutions in addition to steroid-antibiotic combination. Thirty patients instilled only steroid-antibiotic combination (Control Group 3). Laser flare-cell photometry and optical coherence tomography scans with central foveal thickness (CFT) measurement were performed before (V0) and 7 (V1), 14 (V2) and 28 days (V3) after surgery. Treatment tolerability was scored using the Ocular Comfort Grading Assessment. Results: Laser flare-cell photometry values were significantly higher at V1, V2 and V3 compared to V0 in all the groups (respectively 13.3 +/- 1.0, 12.7 +/- 0.9 and 9.6 +/- 0.9 vs 8.4 +/- 0.6 ph/ms for Group 1; 13.4 +/- 1.0, 12.7 +/- 0.9 and 12.7 +/- 1.0 vs 8.1 +/- 0.6 for Group 2; 15.9 +/- 0.8, 15.4 +/- 0.7 and 14.5 +/- 0.7 vs 7.5 +/- 0.5 for Group 3) (p < 0.001); flare increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.001). CFT values were higher after surgery in all the three groups; the increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.0002). The percentage of symptoms-free patients after study treatment was significantly higher in Group 2 compared to Group 1 (respectively 74% vs 14% of the total; p < 0.001). Conclusion: The addition of diclofenac or bromfenac ophthalmic solutions contributed to further reduce both inflammation and cystoid macular edema after cataract surgery compared to steroid-antibiotic combination alone. Diclofenac appeared to be more effective in reducing postoperative intraocular inflammation with a more intense and prolonged regimen, while bromfenac more tolerated with lower daily dose and treatment duration.

Purpose: To investigate the comparative effect of allogeneic peripheral blood serum (allo-PBS) and cord blood serum (CBS) eye drops on the status of the corneal subbasal nerve plexus in patients with dry eye disease by using an automated analysis system of in vivo confocal microscopy images. Methods: This prospective, randomized, double-blind study included 30 patients with severe dry eye disease assigned to receive allo-PBS (group 1) or CBS (group 2) eye drops 8 times a day for 30 days. The following in vivo confocal microscopy parameters were calculated with ACCMetrics before (visit 1 [V1]) and after treatment (visit 2 [V2]): corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fractal dimension (CNFrD). Results: In overall patients, the values of corneal nerve fiber density, corneal nerve fiber length, and CNFrD significantly increased, whereas the value of corneal nerve fiber width signif- icantly decreased at V2 compared with V1 (respectively, 20.4 6 7.9 vs. 17.4 6 10.1 n/mm2; 13.5 6 4.0 vs. 12.0 6 5.1 mm/mm2; 1.466 6 0.046 vs. 1.475 6 0.033; and 0.022 6 0.002 vs. 0.023 6 0.002; all P , 0.05). In the subanalysis according to the treatment type, the increase of CNFrD value from V1 to V2 was higher in group 2 compared with group 1 (respectively, from 1.455 6 0.041 to 1.471 6 0.030 and from 1.479 6 0.050 to 1.481 6 0.035; P = 0.030). Conclusions: Overall, both treatments significantly improved corneal subbasal nerve plexus parameters, and in particular, nerve density, length, width, and fractal dimension. Treatment with CBS eye drops was associated with a higher increase of CNFrD compared with allo-PBS.

PurposeTo compare corneal biomechanics between patients with ocular graft versus-host disease (oGVHD) and healthy subjects (controls), and to further correlate these values with ocular and hematological characteristics.Materials and MethodsThe following procedures were performed in oGVHD patients and controls: Schirmer test (ST), break-up time (BUT), corneal and conjunctival staining, tear matrix metalloproteinase-9 (MMP-9) assay (InflammaDry test, Rapid Pathogen Screening, Inc, Sarasota, FL). Corneal biomechanics were calculated by using ocular response analyzer (ORA, Reichert Instruments, Depew, New York, USA). The Mann-Whitney U test was used to compare continuous variables between oGVHD patients and controls. Correlations of corneal biomechanics with ocular and hematological parameters were examined using Spearman’s correlation.ResultsA total of 45 oGVHD patients (mean age ± SD, 51.5 ± 7.1 years) and 34 controls (47.8 ± 6.1 years) were included. Patients with oGVHD showed significantly lower values of corneal hysteresis (CH) and corneal resistance factor (CRF) compared to controls (respectively, 9.4 ± 1.8 mmHg vs 11.6 ± 1.6 and 9.7 ± 1.4 mmHg vs 12.3 ± 1.3; always p<0.001). Twenty-nine of the oGVHD eyes (64.4%) were strong-positive for MMP-9, while 16 (35.6%) were weak-positive. Conversely, only 4 of the control eyes (11.8%) were weak-positive for MMP-9. In patients with oGVHD, CH was significantly correlated with corneal staining (Rs = −0.316, p = 0.035), conjunctival staining (Rs = −0.437, p = 0.003), ST (Rs = 0.390, p = 0.008), BUT (Rs = 0.423, p = 0.004), oGVHD severity grade (Rs = −0.383, p = 0.009), and MMP-9 positivity grade (Rs = −0.429, p = 0.003), while CRF was correlated only with corneal staining (Rs = −0.317, p = 0.034).ConclusionsCorneal biomechanics are reduced in patients with oGVHD, and CH is negatively correlated with disease severity grade and MMP-9 tear levels.

Purpose: The aim of this study was to evaluate the safety and efficacy of ultrasound cyclo-plasty (UCP) for reducing intraocular pressure (IOP) in patients with glaucoma. Methods: This is a multicentre prospective study conducted in 3 Italian glaucoma centres. UCP was performed by EyeOP1, which delivers ultrasound beams using 6 piezoelectric transducers activated for 4/6 s (first generation) or 8 s (second generation). Primary outcomes were the mean IOP reduction and the rates of success after 1 year. Secondary outcomes were the mean IOP reduction at each follow-up, and the reduction of the number of hypotensive medications. Results: In total, 49 eyes from 47 patients were treated. One year postoperatively, the mean IOP had decreased from 27.7 ± 9.2 to 19.8 ± 6.9 mm Hg (p < 0.001), and the mean number of hypotensive drops and tablets had decreased from 3.2 and 0.5 to 2.3 and 0.2, respectively (p < 0.05). Postoperative IOP reduction was significantly related to preoperative IOP (r2 = 0.5034; p < 0.0001). Second-generation probes determined a significantly higher IOP reduction (p < 0.05). Qualified success was achieved in 25 eyes (51.1%) and complete success in 21 (42.9%), while failure was recorded in 12 (24.5%). Conclusions: UCP is safe and effective for reducing IOP. The procedure determines a greater IOP reduction in patients with higher preoperative IOP. Second-generation probes improve outcomes without detrimental effects on safety.

PURPOSE: To compare the proportion and the agreement rate in the diagnosis of chronic ocular graft-versus-host disease (GVHD) among three criteria applied with and without ophthalmological examination before hematopoietic stem cell transplantation (HSCT). METHODS: National Institutes of Health (NIH), International Consensus Criteria on ocular GVHD (ICCGVHD) and TFOS Dry Eye Workshop (DEWS) II criteria were used for the diagnosis of ocular GVHD according to two protocols: ophthalmological examination after HSCT (Protocol A), or before and after HSCT (Protocol B). Proportion of GVHD diagnosis and inter-rate agreement coefficient Kappa (K) among the criteria were calculated. RESULTS: One hundred nine patients undergone HSCT were included. NIH, ICCGVHD and DEWS II criteria diagnosed ocular GVHD in 14.7%, 17.4% and 59.6% of the patients (Protocol A), whereas in 11.9%, 15.6% and 33.0% of the HSCT patients (Protocol B). The coefficient K for the proportion of patients diagnosed with ocular GVHD by NIH and ICCGVHD criteria was K = 0.626 (Protocol A) and K = 0.615 (Protocol B). The K coefficient by NIH and DEWS II criteria was K = 0.144 (Protocol A), and K = 0.233 (Protocol B). The K coefficient by ICCGVHD and DEWS II criteria was K = 0.250 (Protocol A) and K = 0.499 (Protocol B). The K coefficient for ocular GVHD diagnosis applying Protocol A and B was K = 0.881 if NIH criteria were used, K = 0.933 if ICCGVHD criteria were used and K = 0.501 if DEWS II criteria were used. CONCLUSIONS: The diagnosis of ocular GVHD varied significantly in our cohort of hematological patients according to both the diagnostic criteria used and the visit protocols applied.

PURPOSE: To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease. METHODS: We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity. RESULTS: Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554-1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043-0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India. CONCLUSIONS: This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.

This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty (UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes (Eye OP1). After treatment, the mean intraocular pressure (IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6 (all P0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth (R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.

Objectives: To investigate longitudinally corneal sub-basal nerve plexus (SNP) by means of in vivo confocal microscopy (IVCM) in the contralateral eye (CE) of patients with unilateral neurotrophic keratitis (NK) secondary to central nervous system (CNS) diseases who underwent different treatments. Methods: Ten patients with NK and 10 matched controls were included. In 7 NK patients, conservative treatment maintained unchanged the clinical picture over the 1-year follow-up (Group 1), while NK progressed in 3 patients who underwent direct corneal neurotization (Group 2). IVCM scans of SNP of NK patients were acquired in CE at baseline (V0) ad after 1-year follow-up (V1). All images were analyzed with the automated software "ACCMetrics" and compared with controls. The following IVCM corneal nerve parameters were calculated at V0 and V1 with ACCMetrics: fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). Results: At V0, significantly lower mean values of CNFD and CNBD, and higher values of CNFW were detected in CE of NK patients compared to controls (respectively, 16.9 ± 8.7 vs 25.0 ± 8.3 n/mm2, P= .029; 19.3 ± 13.8 vs 33.8 ± 18.9 n/mm2, P= .023; 0.022 ± 0.002 vs 0.020 ± 0.001 mm/mm2, P< .001). From V0 to V1, all IVCM metrics of CE remained unchanged in Group 1, while they improved in Group 2. Conclusions: Contralateral eye of patients with unilateral NK secondary to CNS disease showed lower CNFD and CNBD and higher CNFW compared to controls. Unlike conservative treatment, direct corneal neurotization was able to improve SNP metrics also in CE.

Glaucoma is a chronic disease caused by the progressive degeneration of the optical nerve fibers, resulting in decreased visual field that can lead to severe visual impairment, and eventually blindness. This manuscript describes a simple, surgeon-friendly, non-incisional technique, named Ultrasound Cyclo Plasty (UCP), for reducing intraocular pressure (IOP) in glaucoma patients. The technique determines a selective coagulation necrosis of the ciliary body; in addition, the stimulation of supra-choroidal and trans-scleral portions of the uveo-scleral outflow pathway has been recently proposed. UCP shows several technical improvements in ultrasound technology compared to previous techniques, providing more precise focusing on the target zone. The procedure is performed in the operating room under peribulbar anesthesia. Briefly, the coupling cone is put in contact with the eye and the ring probe, that contains six piezoelectric transducers which produce the ultrasound beams, is inserted inside it. Their proper centering over the ocular surface represents a crucial step for the correct targeting of the ciliary body. Sterile balanced salt solution is used to fill the empty spaces to ensure ultrasound acoustic propagation. Surgical treatment consists in the sequential automatic activation of each of the six transducers, for a total duration of less than 3 min. The patient leaves the hospital 1 h after the procedure with the treated eye patched. In the present study, 10 patients with open-angle glaucoma were followed-up during at least 12 months after the procedure. IOP was reduced at each interval compared to pre-operative, as well as the number of hypotensive medications. Twenty percent of patients did not respond to the treatment, and needed subsequent surgery to better control IOP. Treatment tolerability was good, with no cases of hypotony or phthisis. The UCP procedure is simpler, faster, safer, and less invasive than traditional cyclodestructive procedures with similar results in reducing IOP.

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

Purpose To evaluate the rate and outcomes of immunologic stromal rejection occurring after large deep anterior lamellar keratoplasty (DALK) and the effect of the underlying disease on the cumulative probability of rejection. Methods This was a retrospective chart review of all eyes that underwent a 9-mm DALK at Ospedali Privati Forli (Forli, Italy). On the basis of preoperative diagnosis, eyes were assigned to group 1: keratoconus, group 2: stromal disease with a low risk for rejection, or group 3: stromal disease with a high risk for rejection. The cumulative probability of experiencing a rejection episode over time was assessed by Kaplan-Meier analysis and was compared among the 3 groups using the log-rank test. Values of corrected distance visual acuity, central corneal thickness, and endothelial cell density before and 6 months after rejection were compared. Results Twenty of 377 eyes (5.3%) experienced an episode of stromal rejection [17/265 (6.4%) in group 1, 2/71 (2.8%) in group 2, and 1/41 (2.4%) in group 3]. The mean time interval between DALK and the rejection onset was 11.8 months (range 1-24). The cumulative probability of rejection episodes did not differ significantly among the 3 groups. All episodes resolved within 6 months after the onset, with no significant differences between prerejection and 6-month postrejection values of corrected distance visual acuity, central corneal thickness, and endothelial cell density. Conclusions The rate of immunologic stromal rejection after large 9-mm DALK is within the range reported in the literature for conventional DALK, regardless of the indication for surgery.

PURPOSE: To 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). METHODS: A 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. RESULTS: The 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

PURPOSE: We standardized quality-controlled cord blood serum (CBS)-based eye drops and evaluated the efficacy of 1-month CBS treatment in the healing of diseased corneal epithelium in severe dry eye (DE) patients. METHODS: Seventeen graft-versus-host disease (GVHD) and 13 Sjogren syndrome patients with severe persistent corneal defects were enrolled in the framework of a registered clinical trial (ClinicalTrials.gov NCT01234623). Sterile CBS eye drops were prepared to supply 0.15 ng per eye per day epithelial growth factor and administered for 1 month in a 1-day dose dispensing. The extent of epithelial defect was evaluated in square millimeters area, and subjective symptom score (Ocular Surface Disease Index score), Schirmer test I, break-up time, tear osmolarity, corneal esthesiometry (Cochet-Bonnet esthesiometer), conjunctival scraping, and imprint cytology with goblet cell count were performed at baseline (V0) and after 15 (V1) and 30 (V2, endpoint) days of treatment. Satisfaction and tolerability questionnaires were evaluated at V1 and V2. RESULTS: A significant reduction was shown at the endpoint versus baseline in corneal epithelial damage (mean ± SD, 16.1 ± 13.7 vs. 40.9 ± 30 mm²/area, respectively), discomfort symptoms (Ocular Surface Disease Index score, 22.3 ± 10.3 vs. 39.3 ± 16.9), scraping cytology score (3.8 ± 1.2 vs. 6.6 ± 2.1), and tear osmolarity (312.5 ± 7 vs. 322 ± 9.1 mOsm/L), whereas a significant improvement was shown in corneal esthesiometry (48.2 ± 2.1 vs. 49.7 ± 2.1 nylon/mm/length, P < 0.05). All patients reported a high degree of satisfaction upon drop instillation. CONCLUSIONS: Heterologous CBS-based eye drops represent a promising therapeutic approach in the healing of severely injured corneal epithelium and in subjective symptom relief. These drops can be obtained as readily available and quality-controlled blood derivative from cord blood banks on a routine basis.

Purpose To evaluate Artelac Rebalance® eyedrops’ efficacy in symptoms reduction, ocular surface parameters recovery, and tolerability in the treatment of mild to moderate dry eye. Methods Fifteen patients were enrolled. Inclusion criteria were Ocular Surface Disease Index (OSDI) score >16, tear film break-up time (TFBUT) 10 mm/5 min, and mild ocular surface damage (Oxford grading) ≤3. Artelac Rebalance® eyedrops were administered 3 times daily for 2 months. Patients were evaluated at enrollment, after 2 days of washout (baseline), and after 1 and 2 months of treatment. Parameters for ocular discomfort (OSDI score), tear film quality (Schirmer test I, TFBUT, tear osmolarity), ocular surface damage (fluorescein staining, conjunctival imprint cytology), and inflammation (scraping cytology and exuded serum albumin) were measured. Tolerability and satisfaction were assessed by validated questionnaires. Results At endpoint versus baseline, all variables showed a statistically significant improvement (paired Student t test, p2 (140.8 ± 43.3 cells/mm2 vs 115.1 ± 15.8 cells/mm2), scraping cytology score (2.9 ± 1.0 vs 4.2 ± 1.3), and percentage of serum albumin in tears (9.2% ± 4.8% vs 24.1% ± 10.8%). Tolerability and satisfaction were scored high, with no adverse events reported. Conclusions Application of Artelac Rebalance® eyedrops for 2 months in mild to moderate dry eye resulted in a reduction of ocular inflammation parameters, ocular surface damage, and subjective discomfort symptoms, with a parallel improvement in tear film quality (measured by TFBUT and osmolarity).

Dry eye (DE) disease is an impairment of the lachrymal unit function and one the most frequent eye problems. A major challenge is to find accurate diagnostic criteria to be able to define DE severity, as symptoms poorly correlate with clinical signs. Tear osmolarity is considered a key factor in DE onset and perpetuation; its measurement is now possible in clinical setting by an innovative electrical impedance-based lab-on-a-chip technology. This article outlines the features of DE disease and the limitations of current clinical tests. The role of tear osmolarity in DE etiopathogenesis is surveyed, and the pitfalls in measurement are discussed. Diagnostic performance, accuracy and clinical applications of the technology in focus are critically reviewed. The instrument offers the possibility to measure tear osmolarity in a rapid and reliable way in daily practice. As scientific evidence grows, it is expected in the future that it will represent an objective indicator of ocular surface health in the management of DE disease and in clinical trials.

Purpose To try to explain the long-term stability of bilateral medial rectus botulinum toxin (botox) chemo-denervation in essential infantile esotropia; to evaluate divergent fusion amplitude in accommodative esotropia and acute comitant esotropia of emmetropes; to look for accommodation anomalies in high AC/A ratio accommodative esotropia and acute comitant esotropia of myopes; and to discuss characteristics of microstrabismus. Methods Retrospective analysis of 61 essential infantile esotropia patients with early treatment with one botox injection in both medial rectus; measurement of divergent fusion amplitude in accommodative esotropia and acute comitant esotropia; measurement of Near point of accommodation in high AC/A ratio accommodative esotropia and acute comitant esotropia of myopes. Results Stable results were found in 85.24% of essential infantile esotropia treated patients; reduced divergent fusion amplitude was detected in accommodative esotropia and acute comitant esotropia; hypo-accommodation was found in some patients with high AC/A ratio accommodative esotropia and a convergence spasm in acute comitant esotropia of myopes. Conclusions Very early botox treatment probably eradicates the effect of an excessive convergence tonus in essential infantile esotropia. A prevention of accommodative esotropia with full retinoscopic correction is only mandatory with a significantly reduced amplitude of fusional divergence. A deficit in accommodation should be looked for in high AC/A ratio accommodative esotropia, before bifocal lenses prescription. Early diagnosed acute comitant esotropia of myopic patients can be treated as a convergence spasm. Only surgery treats acute comitant esotropia, in patients with emmetropia or moderate hypermetropia.

PURPOSE: The aim of this study was to assess corneal hysteresis (CH) and corneal resistance factor (CRF) in healthy subjects, to evaluate the relationship with age, and to investigate possible associations with other ocular factors. METHODS: Four hundred Italian subjects (male-to-female ratio, 168:232; mean age, 58.8 ± 17.2 years) were included and divided into 5 subgroups based on age. CH, CRF, and central corneal thickness (CCT) were measured by using the Ocular Response Analyzer and the integrated handheld pachymeter, and their relationship with gender, age, and ocular factors was evaluated. RESULTS: The mean CH, CRF, and CCT values were 10 ± 1.6 mm Hg, 10.5 ± 1.7 mm Hg, and 532.2 μm, respectively. Women had a lower mean CH (9.9 vs. 10.2 mm Hg; P = 0.04) and CRF (10.3 vs. 10.8 mm Hg; P = 0.03) than did men. The youngest subjects had the highest CH (11.2 ± 1.5 mm Hg), whereas the oldest patients had the lowest CH values (9 ± 1.1 mm Hg). No significant differences in CRF were observed between age groups. CH and CRF showed a positive correlation (r = 0.58; P < 0.001), and both had a positive association with CCT (r = 0.27; P < 0.001 and r = 0.57; P < 0.001, respectively). The strongest correlations were observed between Goldmann-correlated intraocular pressure (IOP) and corneal-compensated IOP (r = 0.68; P < 0.001) and between Goldmann-correlated IOP and Goldmann applanation tonometry (r = 0.88; P < 0.001). CONCLUSIONS: Gender and advancing age may influence corneal biomechanical properties. In our population, CH decreased with aging, and men demonstrated a higher CH and CRF than women did. Further, CH, CRF, and CCT were significantly related.

PURPOSE: To evaluate the association between astigmatism and idiopathic congenital nystagmus (ICN) in infantile nystagmus syndrome (INS). MATERIALS AND METHODS: We analysed refractive errors in a cohort of 488 consecutive patients with ICN (group A) and further compared the results obtained with those of 488 age-matched controls with no nystagmus (group B). Only the worst eye was considered for statistical analysis. All patients were stratified into the following age groups: 1 to 4 years (age group 1); 5 to 12 years (age group 2); and 13 years to 57 years (age group 3) (mean age: 29). RESULTS: Three hundred and seventy patients (69.7 %) in group A and 269 patients (55,12 %) in group B had refractive errors. The types of refractive errors observed were: myopia, hyperopia (>0.50 dioptres) and astigmatism (>1.25 dioptres). Results in group A were as follows: 319 patients (65.37 %) were astigmatic, 34 (6.97 %) were hyperopic, and 17 (3.48 %) were myopic. Mean right-eye astigmatism was 2.72 dioptres, and mean left-eye astigmatism was 2.69 dioptres. Results in group B were as follows: 56 (11.47 %) were astigmatic, 165 (33.81) were hyperopic, and 48 (9.84) were myopic. Mean right-eye astigmatism was 2.05 dioptres, and mean left-eye astigmatism was 2.37 dioptres. The prevalence of astigmatism is greater, in the entire sample, for subjects from age groups 2 and 3 (p

PURPOSE: To assess subfoveal choroidal blood flow (ChBF) in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of central retinal integrity, standard automated perimetry (SAP) and pattern electroretinogram (PERG). METHODS: Subfoveal ChBF was determined by confocal, real-time laser Doppler flowmetry in 24 patients with EMG [>-6 dB mean deviation (MD), age range: 29-77 years, visual acuity: 20/25-20/20] and 23 age-matched control subjects. All patients had a therapeutically (topical beta-blockers with or without prostaglandin analogues) controlled intraocular pressure (IOP < 20 mmHg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and ChBF were determined as the average of three 60 second recordings. In all patients and controls, the PERG and SAP (Humphrey 30-2), following standardized protocols, were also recorded. RESULTS: In patients with EMG, reductions in average ChBVel and ChBF were roughly equal, respectively, by 30% and 33.4% (p < 0.01), when compared to control subjects, so that there was no significant difference in ChBVol between the two groups. Pattern electroretinogram amplitudes were reduced by 46% (p < 0.01) in patients compared to controls. No correlation was found between any of the ChBF parameters and PERG amplitude, or Humphrey 30-2 MD and pattern standard deviation. CONCLUSION: The results suggest a significant alteration of both ChBVel and ChBF in EMG, which does not appear to be associated with the severity of central retinal dysfunction. These findings may contribute to a better understanding of the pathophysiology of early glaucomatous damage in EMG and have implications for the treatment of this pathologic condition.

AIMS: To assess the relationship between endothelial dysfunction, endothelin 1 (ET-1) plasma levels and subclinical inflammation in primary open angle glaucoma (POAG) patients. MAIN METHODS: We enrolled 40 POAG patients with progressive visual field damage, although well controlled intraocular pressure (IOP) and compared to age and sex matched healthxy subjects. Each patient underwent an ophthalmological examination, a standard achromatic perimetry (SAP), blood sampling to assess ET-1 plasma levels, an objective assessment of cellularity within the anterior chamber (FLARE) and measurement of flow mediated dilation (FMD) with high resolution 2-dimensional ultrasonographic imaging of the brachial artery. KEY FINDINGS: At baseline, POAG patients, compared to healthy controls, showed an increase of ET-1 plasma levels: 2.83 ± 0.28 pg/ml vs. 1.75 ± 0.25 pg/ml (p0.001). SIGNIFICANCE: The increase of ET-1 in POAG patients is related to vascular dysfunction (r=0.942; p=0.001) and vascular dysfunction is related to sub-clinical intraocular inflammation (r=0.968; p=0.001). Thus ET-1 and vascular dysfunction related to sub-clinical inflammation may play a key role in determining a progressive visual field damage in POAG patients who present a well-controlled IOP.

Background To assess which of three methods, namely, optical coherence tomography (OCT), pattern electroretinogram (PERG) or frequency-doubling technology (FDT), is the most sensitive and specific for detecting early glaucomatous damage in ocular hypertension (OH). Methods Fifty-two patients with OH (24 men and 28 women, mean age of 56 ± 9.6 years) with an intraocular pressure (IOP) > 21 mmHg and fifty-two control patients (25 men and 27 women, mean age of 54.8 ± 10.4 years) with IOP All subjects underwent OCT, FDT and PERG. Data were analyzed with unpaired t-tests, Chi-square test and Receiver Operating Characteristic (ROC) curve analyses. Results In patients with OH, OCT showed retinal nerve fiber layer (RNFL) thinner than in control group in the superior quadrant (130.16 ± 10.02 vs 135.18 ± 9.27 μm, respectively; p Conclusions FDT is the most sensitive and specific method for detecting early glaucomatous damage in eyes with OH, and together with OCT, can be useful in identifying those patients who may develop glaucoma. Trial registration ISRCT number: ISRCTN70295497

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 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

PURPOSE: We propose a conjunctival Scraping Cytology Scoring System (SCSS) as a reliable method to diagnose and score ocular surface inflammation in dry eye. METHODS: Twenty normal subjects and 46 patients with dry eye of various severities were included in the study. Clinical signs were scored 1-4; an Ocular Surface Disease Index (OSDI) questionnaire was used to grade subjective symptoms. Concentrations of serum albumin and interleukin-6 (IL-6) in tears were evaluated. Scraped conjunctival cytology samples were processed and examined with light microscopy. The number of inflammatory cells was staged and sub-scores were assigned. SCSS resulted from their sum and ranged from 0-12. Statistical evaluation was performed by applying the unpaired Student's t-test and the Spearman's correlation test (significance p < 0.05). SCSS was also analyzed for sensitivity, specificity, ROC curves, likelihood ratio LR+, positive (PPV) predictive value. RESULTS: SCSS was positively correlated to clinical sign score, OSDI score, exudated serum albumin, and IL-6 in either control (Spearman's correlation test always p < 0.05) and in dry eye patients (respectively, p < 0.0001, p < 0.01, p < 0.05, and p < 0.0001). SCSS >or= 4 was selected as the cut-off value for moderate dry eye (LR+ 10,9; PPV 22,5), SCSS >or= 9 was selected as the cut-off value for severe dry eye (LR+ 15,6; PPV 26,2). CONCLUSIONS: SCSS can be applied in any trained laboratory. It is correlated with clinical signs and symptoms, and it shows a diagnostic performance to grade inflammation in dry eye, comparable to more expensive cytokine assay.

PURPOSE: We assessed the effect of palmitoylethanolamide (PEA) on systemic endothelial function in ocular hypertensive patients (OH). METHODS: We enrolled in this randomized, double-blind, placebo-controlled, crossover single-center study 40 never-treated OH patients and 40 healthy age-matched controls. At baseline, each participant underwent endothelium-dependent flow-mediated vasodilation (FMD) measurement using a noninvasive high-resolution 2-dimensional ultrasonographic imaging of the brachial artery. OH patients were assigned randomly to receive either 300 mg PEA (Group A) or a matching placebo (Group B), twice a day for three months (T1). The first medication period was followed by a two-month washout period (T2), and then patients switched to PEA or placebo (depending on the first drug received) for another three months (T3). FMD evaluations were repeated at T1, T2, and T3. RESULTS: At baseline FMD values in OH patients and controls were 6.06 ± 0.60% vs. 10.85 ± 1.80%, respectively (P < 0.001). At T1, FMD and IOP of Group A were, respectively, 8.46 ± 1.09% vs. 6.08 ± 0.62% (P < 0.001, r = 0.96) and 22.18 ± 1.26 vs. 23.03 ± 0.88 mm Hg (P < 0.001). At T2, Group A had better FMD values than at baseline (6.59 ± 0.33% vs. 6.08 ± 0.62%, P < 0.05). At T3, subjects in Group B showed better FMD and IOP than at T2 (8.52 ± 1.07% vs. 6.05 ± 0.68%, P < 0.001, r = 0.97; and 22.43 ± 1.17 vs. 23.03 ± 0.83 mm Hg, P < 0.01, respectively). No side effects were observed. CONCLUSIONS: Three-month PEA intake reduced IOP and led to significantly improved FMD values in OH patients compared to placebo, by ameliorating peripheral endothelial function, and its positive effect lasted longer than the period of PEA consumption. No adverse events were recorded. (Controlled-trials.com number, ISRCTN72647928.).

BACKGROUND: To report the effect of subtenon injections of natural leukocyte interferon α-2a (IFNα) on best corrected visual acuity (BCVA) and central macular thickness (CMT) in a patient with diabetic macular edema (DME). CASE PRESENTATION: A 66-year-old man affected by DME, with glycated hemoglobin (HbA1c) at 6.9%, refractory to laser grid treatment and intravitreal injections of triamcinolone, was selected to receive a cycle of three subtenon injections/week of IFNα (1×106 IU/ml). BCVA and CMT, using spectral domain ocular coherence tomography (SD-OCT), were evaluated preoperatively and at 1 week, 1 month, 4 months, and 1 year postoperatively. BCVA and CMT were significantly improved at 1 week after the three injections (20/200 vs. 20/40 and 498 μm vs. 237 μm, respectively). BCVA remained stable during the 1-year follow-up. CMT was slightly increased, but was still lower than the baseline value (215 μm, 255 μm, and 299 μm during the follow-up visits). No adverse events were recorded, with the exception of mild subconjunctival hemorrhage at the injection site. CONCLUSIONS: IFNα, with its immunomodulatory, anti-proliferative and anti-angiogenic actions, was effective in improving BCVA and reducing CMT in refractory DME. Further randomized controlled studies are required to assess the effect of IFNα alone or in combination with other therapies for DME treatment.