Clinical Efficacy, Tolerability and Safety of a New Multiple-Action Eyedrop in Subjects with Moderate to Severe Dry Eye.

Background: To assess the clinical efficacy, tolerability and safety of a new-generation ophthalmic solution containing cross-linked hyaluronic acid 0.15% trehalose 3%, liposomes 1% and sterylamine 0.25% (Trimix® Off Health Italia, Firenze, Italy) (CXHAL) versus trehalose 3% (Thealoz®, Thea Pharmaceuticals, Clermont-Ferrand, France) (TRS) in subjects with moderate to severe dry eye disease (DED). Patients and methods: In this prospective, observational cohort study, 41 subjects with moderate to severe dry eye were enrolled and divided into two age- and sex-matched groups. Group 1 was treated with CXHA eye drops, and group 2 was treated with TRS eye drops four times daily for 2 months. All subjects were evaluated at baseline (V0) and at day 60 ± 3 (V1). The examination comprised Best Corrected Visual Acuity (BCVA) and Symptom Assessment in Dry Eye (SANDE). Tear osmolarity was evaluated using the TearLab Osmolarity System®; Keratograph 5M (Oculus, Wetzlar, Germany) was performed to assess tear meniscus height (TMH), fluorescein tear break-up time (TBUT) and corneal and conjunctival fluorescein staining and meibography; furthermore, slit lamp evaluation was performed for eyelid erythema and edema, conjunctival chemosis and hyperemia and Meibomian gland secretion quality. Results: All patients completed the treatment. BCVA remained stable in both groups, and no adverse events were reported. After 2 months, both groups showed statistically significant improvements for SANDE (p = 0.001 and p = 0.012, respectively), TBUT values (p < 0.001 and p < 0.001, respectively) and staining (p = 0.004 and p = 0.001, respectively) as compared to baseline values. Group 1 showed a statistically significant improvement in SANDE frequency and tear osmolarity (p = 0.02 and p = 0.001, respectively), whereas chemosis was significantly reduced in group 2. The amount of TBUT improvement was statistically higher in group 1 compared to that in group 2 (p = 0.041). Conclusion: A new-generation multiple-action ophthalmic solution was safe and clinically effective in the treatment of moderate and severe dry eye, with significant improvements in the main ocular surface parameters.

Effects of the Topical Use of the Natural Antioxidant Alpha-Lipoic Acid on the Ocular Surface of Diabetic Patients with Dry Eye Symptoms.

PURPOSE: The purpose of this study is to investigate the effects of the treatment with eye-drops based on a combination of antioxidant and mucomimetic molecules, namely 0.1% alpha-lipoic acid (ALA) and 0.3% hydroxy-propyl-methylcellulose (HPMC) on the ocular surface of diabetic patients with dry eye symptoms. METHODS: Seventy patients, 42 M and 28 F, aged from 50 to79 years (mean 62.1 ± 10.5), affected by type II diabetes mellitus, were enrolled and divided in two groups treated for 2 months as follows: Group 1 (35 patients), received topical ALA/HPMC three times a day, Group 2 (35 patients) received topical HPMC (0.3%) alone, three times a day. The main outcome measures were: Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), corneal fluorescein staining, Schirmer I test, corneal sensitivity. An examination of tear film morphology with confocal microscopy was carried out in a subset of patients of each group at baseline and after two months. Statistical analysis was performed with t-test for the parametric data and Mann-Whitney U-test or chi-squared test for the nonparametric data. RESULTS: Both treatments resulted in significant improvements of BUT, OSDI and tear film morphology, although the improvements observed in group 1 showed a higher trend than what observed for group 2. Moreover, only in group 1 a significant improvement was visible for corneal staining, and no significant improvements were observed in any group for Schirmer I and sensitivity. CONCLUSIONS: These results confirmed the efficacy of HPMC in the treatment of diabetic dry eye and indicated that the addition of a strong self-regenerating antioxidant like ALA may give a distinctive advantage for the healing of corneal defects (as evidenced by corneal staining), beside improving HPMC efficacy on three other parameters (BUT, OSDI score, tear morphology). Therefore, the addition of a strong antioxidant like ALA can be helpful in preventing or treating ocular surface defects in diabetic patients, in which the oxidative damage is predominant.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

PURPOSE: To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). METHODS: Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. RESULTS: The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. CONCLUSIONS: The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

The Role of Hi-Tech Devices in Assessment of Corneal Healing in Patients with Neurotrophic Keratopathy.

To prove the role of high-tech investigation in monitoring corneal morphological changes in patients with neurotrophic keratopathy (NK) using Keratograph 5M (K5M) and anterior segment OCT (AS-OCT), corneal healing was monitored with Keratograph 5M (Oculus, Wetzlar, Germany) and AS-OCT (DRI, Triton, Topcon, Tokyo, Japan) in 13 patients (8F and 5M), aged from 24 to 93 years (67.8 ± 19) with severe NK, who were treated with Cenegermin 0.002% (20 µg/mL) (Oxervate®, Dompè, Farmaceutici Spa, Milan, Italy). The surface defects were evaluated on Keratograph 5M with ImageJ software and the corneal thickness variations were measured using DRI-Triton OCT software. Instrumental procedures were performed at baseline, and after 4 and 8 weeks of the treatment, respectively. The main outcome measures were reduction of the ulcers' area and corneal thickness recovery. The mean area of the corneal ulcers was reduced between baseline and 4 weeks examination in all patients, and at 8 weeks all ulcers were completely healed. An increase of the corneal thickness was evidenced between the baseline visit and after the 4- and 8-week follow-up, respectively. Additionally, only in collaborating subjects the In Vivo Confocal Microscopy (IVCM) was performed with HRT Rostock Cornea Module (Heidelberg Eng GmbH) to study the corneal nerves fibres. High-tech diagnostics with K5M, AS-OCT and IVCM proved useful in the assessment of corneal morphology and the healing process in patients with NK and could be extended to assess other corneal pathologies.

Combined Phialemonium curvatum and Acanthamoeba Keratitis: The Importance of Early Diagnosis and Specific Therapy.

PURPOSE: To report the clinical and confocal findings of a unique case of combined Phialemonium curvatum and Acanthamoeba keratitis and to highlight the role of the prompt diagnosis and specific medical treatment in preserving visual function. METHODS: A case report and literature review. RESULTS: A 54-year-old woman presented with a 3-day history of visual impairment, photophobia, and ocular pain in her right eye. Her best corrected visual acuity was 0.4 Logarithm of the Minimum Angle of Resolution scale, and the slit-lamp examination showed whitish corneal stromal infiltrate with satellite lesions. In vivo confocal microscopy evidenced Acanthamoeba cysts and fungal hyphae that resulted P. curvatum in the culture examination. The intensive medical treatment was started with topical 0.02% polyhexamethylene biguanide, voriconazole 1%, and moxifloxacin hydrochloride 0.5%. Progressive improvement of clinical and confocal pictures was registered with a complete recovery of visual function after 1 month. CONCLUSIONS: This is the first case report of combined P. curvatum and Acanthamoeba keratitis. The fast diagnosis with in vivo confocal microscopy allowed early and intensive specific treatment with recovery of corneal infection.

Ophthalmologic Manifestations of Primary Sjögren's Syndrome.

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.

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

Purpose: 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. Methods: 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 I-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 T-test and Wilcoxon test were used as appropriate. Results: 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 P < 0.03) were observed; corneal-conjunctival staining improved at T28 (T0 vs. T28 P < 0.0001), and TBUT improved already at T7 (T0 vs. T7 P = 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. Conclusions: The treatment with 0.6% PVI was safe and well tolerated in a group of patients with a damaged ocular surface.

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

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.

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.

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.

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

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.

Secukinumab for plaque psoriasis with ocular comorbidity: a clinical experience.

Psoriasis is a systemic inflammatory disorder associated with many other chronic and progressive diseases. Ocular comorbidity has been reported in 10-15% of patients with plaque psoriasis, but the real incidence is still underestimated. This paper reports successful treatment with secukinumab of a patient with plaque psoriasis and dry eye syndrome. Secukinumab treatment was rapidly effective on skin psoriasis and this result was in agreement with observations reported in the literature. Interestingly, both the skin condition and the ocular disease improved after treatment. Our experience suggests that this drug should be used in patients with plaque psoriasis and ophthalmologic manifestations.

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

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.

Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.

PURPOSE: Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). METHODS: Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. RESULTS: At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. CONCLUSIONS: The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

Tear film and ocular surface assessment in psoriasis.

BACKGROUND: Psoriasis is a skin disease with also systemic involvement: its impact on the eye is not well established and often clinically underestimated. Aim of this study was to investigate the presence of ocular discomfort symptoms and of ocular surface changes in a population of patients with psoriasis. METHODS: For this cross-sectional, comparative study, 66 patients with psoriasis were subdivided according to the presence of arthritis and to the use of biological therapy. All patients underwent clinical evaluation with the following tests: Ocular Surface Disease Index Questionnaire, Tearscope examination, meibometry, tear film breakup time, corneal and conjunctival fluorescein staining, Schirmer I test, corneal aesthesiometry, meibomian gland dysfunction (MGD) assessment and conjunctival impression cytology. 28 healthy subjects were also enrolled and treated with the same clinical tests. A statistical analysis of the results was performed. RESULTS: Patients with psoriasis showed a significant deterioration of the ocular surface tests, if compared with healthy subjects, demonstrated by tear film lipid layer alteration, tear film instability, corneal and conjunctival epithelial suffering and mild squamous metaplasia at impression cytology. No differences were found in ocular surface test results of the psoriatic group when patients were divided according to the presence of arthritis, whereas the anti-inflammatory treatment with biological drugs demonstrated a significant improvement of corneal stain and MGD. CONCLUSIONS: Our findings suggest that the ocular surface involvement in patients with psoriasis indicates the need of periodic ophthalmological examinations to diagnose the condition and allow a proper treatment, so contributing to the amelioration of patients' quality of life.

Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.

Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes (P < .05). Moreover, the chiasmatic area and volume were significantly reduced (P < .05). Conclusion The findings show that visual system alterations can be detected in early stages of Parkinson disease and that the entire intracranial visual system can be involved. © RSNA, 2017 Online supplemental material is available for this article.

Comparative Confocal and Histopathological Study of Corneal Changes in Multiple Myeloma.

PURPOSE: Corneal opacities rarely occur in multiple myeloma (MM). Our study correlates the findings of in vivo confocal microscopy (IVCM), a useful diagnostic tool, with histopathological features of corneal opacities appearing in a patient with MM. METHODS: Case report. RESULTS: A 53-year-old man developed corneal opacities in both eyes, more pronounced in the left eye. After IVCM examination, he underwent penetrating keratoplasty in the left eye, and the button was processed for light and electron microscopy and immunohistochemistry. The diagnosis of MM was made, as confirmed by the elevation of IgGk light chains. IVCM demonstrated hyperreflective areas at the epithelial level, hyperreflective keratocytes of dendritic and lamellar morphology in whole stroma, and hyperreflective endothelial cells. Histopathological examination disclosed many vacuoles in the epithelial cell cytoplasm and a homogenous granular material in the Bowman layer. In stroma, keratocytes of different shape and size, with vesicles laden with an abnormal material, were evident. In Descemet membrane, the posterior nonbanded zone had a honeycomb appearance because of the presence of many roundish spaces among wide-spaced collagen fibers. Endothelial cells demonstrated vesicles filled with a material of uneven electron density. Immunohistochemical analysis showed strong positivity for IgGk light chains in keratocytes and among stromal lamellae. CONCLUSIONS: This is the first study describing a correspondence between IVCM features and histopathological alterations observed in corneal opacities in MM. The results of this study improve the current understanding of the pictures obtained by IVCM studies.

Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies.

PURPOSE: To investigate corneal confocal microscopic changes in nonneoplastic and neoplastic monoclonal gammopathies. METHODS: Three groups of subjects were considered: group 1, twenty normal subjects; group 2, fifteen patients with monoclonal gammopathy of undetermined significance (MGUS); group 3, eight patients with smoldering multiple myeloma and eight patients with untreated multiple myeloma. After hematologic diagnosis, patients underwent ophthalmologic exam and in vivo confocal microscopic study. The statistical analysis was performed using ANOVA and Student-Newman-Keuls tests and receiver operating characteristic (ROC) curve analysis. RESULTS: Epithelial cells of gammopathic patients showed significantly higher reflectivity than controls, demonstrated by optical density (P < 0.001). Subbasal nerve density, branching, and beading were significantly altered in gammopathic patients (P = 0.01, P = 0.02, P = 0.02, respectively). The number of keratocytes was significantly reduced in neoplastic patients (P < 0.001 versus both normal and MGUS) in the anterior, medium, and posterior stroma. The ROC curve analysis showed good sensitivity and specificity for this parameter. Group 2 and 3 keratocytes showed higher nuclear and cytoplasmatic reflectivity in the medium and posterior stroma. Endothelial cells were not affected. CONCLUSIONS: Patients with neoplastic gammopathies showed peculiar alterations of the keratocyte number, which appeared significantly reduced. A follow-up with corneal confocal microscopy of patients with MGUS is suggested as a useful tool to identify peripheral tissue alterations linked to possible neoplastic disease development.

Matrix metalloproteinase 9 and transglutaminase 2 expression at the ocular surface in patients with different forms of dry eye disease.

OBJECTIVE: To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye. DESIGN: Case control study. PARTICIPANTS: Seventy-five female subjects divided into 3 groups: group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD). METHODS: A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann-Whitney U test, and Spearman's correlation coefficient were used as appropriate. MAIN OUTCOME MEASURES: Conjunctival expression of MMP9 and TG2. RESULTS: MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS. CONCLUSIONS: The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation.

Effects of amino acids enriched tears substitutes on the cornea of patients with dysfunctional tear syndrome.

PURPOSE: To evaluate the effect of aminoacid enriched artificial tears on the ocular surface of patients with dysfunctional tear syndrome (DTS). METHODS: Forty patients were divided into two groups: group 1 treated for 90 days with sodium hyaluronate (SH) 0.15% 1 drop × 5 times/day; group 2 treated for 90 days with SH 0.15% + aminoacids mixture 1 drop × 5 times/day. Symptom score questionnaire, tear break-up time (TBUT), corneal fluorescein stain, Shirmer's I test and confocal microscopy were performed at baseline and after 30 and 90 days. Confocal images underwent morphometric analysis. RESULTS: Both treatments improved symptoms after 1 month. Group 2 patients showed at 1 month an improvement of TBUT and corneal stain, maintained throughout the study. Also Shirmer's I test improved after 3 months. In group 1, an improvement of TBUT and corneal stain was observed after 3 months. The morphometric analysis of confocal images demonstrated at month 1 an improvement of nerve tortuosity in group 2; after 3 months both groups showed a significant improvement versus baseline. The epithelium showed, in both groups, a reduction in hyperreflective large cells starting from 1 month; the area of the cells was significantly reduced after 3 months, with a significant higher reduction in group 2. The perineural stromal opacity was significantly increased after 3 months, particularly in group 2. CONCLUSION: This is the first study addressing corneal changes after amino acids administration in a DTS population. The treatment with amino acids enriched SH can be considered a useful tool in the treatment of DTS.

Safety and efficacy of 0.1% clobetasone butyrate eyedrops in the treatment of dry eye in Sjögren syndrome.

PURPOSE: To study the effects of a low administration rate and low concentration (0.1%) of clobetasone butyrate eyedrops in patients with Sjögren syndrome (SS).
 METHODS: This prospective, double-masked, randomized, placebo-controlled study included 40 subjects divided into 2 treatment groups: group 1 (2% polyvinylpyrrolidone eyedrops and placebo) and group 2 (2% polyvinylpyrrolidone and 0.1% clobetasone butyrate, 1 drop BID). The treatment lasted for 30 days, with visits at enrollment, baseline, day 15, day 30, and after 15 days of treatment discontinuation. At each visit, symptoms questionnaire, tear film break-up time, corneal fluorescein stain, lissamine green stain, conjunctival impression cytology for human leukocyte antigen-DR (HLA-DR) expression, intraocular pressure (IOP) measurement, and fundus examination were performed. 
 RESULTS: No changes in IOP or fundus examination were observed in either group at each time point. Group 1 patients showed at day 30 a statistically significant amelioration of symptoms and reduction of HLA-DR expression. No changes in other parameters were detected. Group 2 patients showed at day 15 a statistically significant improvement of corneal and conjunctival stain versus baseline values and group 1 at the same time; after 30 days the symptoms score was statistically significantly better than baseline values and group 1 at the same time. The HLA-DR expression and the epithelial cells area were statistically significantly reduced versus baseline and group 1 at the same time. 
 CONCLUSIONS: Anti-inflammatory therapy is critical for the treatment of SS dry eye. Clobetasone butyrate, at low dosage, proved to be safe and effective in treating this condition.