The use of rh-NGF in the management of neurotrophic keratopathy.

Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively.

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.

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.

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

The purpose of this study was to analyze corneal sub-basal nerve plexus (SBNP) density and morphology and their relationships with corneal parameters and refractive status. In this single center study, in vivo confocal microscopy (IVCM) was performed in 76 eyes of 38 healthy subjects aged 19-87 (mean age 34.987 ± 1.148). Nerve fiber analysis was performed using Confoscan 4 microscope with semi-automated software (Nidek Technologies, Italy) The nerve fiber length (NFL) µm/mm2, nerve fiber density (NFD) no./mm2, tortuosity coefficient (TC), and nerve beadings density (NBD) no./mm were considered. Relationship between SBNP parameters and corneal curvature, thickness, diameter, and refraction were analyzed. Additionally, the association with gender, laterality and age were determined. NFL was inversely correlated with age (r = - 0.528, p < 0.001), myopic refractive error (spherical value) (r = - 0.423, p < 0.001), and cylindrical power (r = - 0.340, p = 0.003). NFD was inversely correlated with age (r = - 0.420, p < 0.001) and myopic refractive error (r = - 0.341, p = 0.003). NBD showed a low inverse correlation with cylindrical power (r = - 0.287, p = 0.012) and a slight positive correlation with K (r = 0.230, p = 0.047). TC showed a significant negative correlation between age (r = - 0.500, p < 0.001) and myopic refractive error (r = - 0.351, p = 0.002). Additionally, there were strong positive correlations between NFL and NFD (r = 0.523, p < 0.001), NFL and TI (r = 0.603, p < 0.001), and NFD and TC (r = 0.758, p < 0.001). Multiple regression analysis revealed age to be the most significant factor affecting SBNP density (B = - 0.467, p = 0.013) and length (B = - 61.446, p < 0.001); myopic refractive error reduced both SBNP density (B = - 2.119, p = 0.011) and length (B = - 158.433, p = 0.016), while gender and laterality had no significant effects (p > 0.005). SBNP fiber length decreases with age, myopic refractive error and cylindrical power. SBNP fiber density reduces with age and myopic refractive error. Corneal nerve parameters are not influenced by gender or laterality.

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.

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.

A combination of different diagnostic tools allows identification of inactive hepatitis B virus carriers at a single time point evaluation.

BACKGROUND & AIMS: Serial evaluation of hepatitis B virus (HBV) DNA and aminotransferase values is required for identification of inactive HBV carriers (ICs). Recently, HBV surface antigen quantification (qHBsAg) and liver stiffness measurement (LSM) have been proposed as diagnostic tools in chronic HBV infection. The aim of this study was to evaluate the efficacy of HBV DNA quantification, qHBsAg and LSM in diagnosing ICs at a single time point. METHODS: Fifty-seven previously characterized ICs and 90 untreated HBsAg-/anti-HBe-positive patients [49 chronic hepatitis (CH), 41 cirrhosis] were enrolled. HBV DNA ≤2000 IU/mL, LSM ≤6.2 kPa and qHBsAg ≤1000 IU/mL were used as cut-offs to evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA). RESULTS: Combined HBV DNA quantification and qHBsAg correctly identified 30/57 (52.6%) ICs showing 94% sensitivity, 96% specificity, 98% PPV, 87% NPV and 95% DA. HBV DNA coupled with LSM identified 40/57 (70.2%) ICs showing 97% sensitivity, 97% specificity, 98% PPV, 95% NPV and 97% DA. Combined LSM and qHBsAg identified 33/57 (57.9%) ICs showing 95% sensitivity, 78% specificity, 89% PPV, 89% NPV and 89% DA. The evaluation of the three parameters altogether allowed the identification of 23/57 (40.3%) ICs showing 100% specificity, 96% sensitivity, 100% PPV, 92% NPV and 97% DA. Similar results were obtained when either CH or cirrhotic patients were excluded from the analysis. CONCLUSIONS: Combined evaluation of HBV DNA amount with LSM and/or qHBsAg is a highly reliable tool allowing the identification of a considerable number of HBV ICs at a single time point evaluation.

Albumin in chronic liver disease: structure, functions and therapeutic implications.

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

Atrial fibrillation in patients with cirrhosis.

BACKGROUND & AIMS: Few information is available regarding atrial fibrillation in cirrhotic patients. The aim of this study was to investigate the occurrence and clinical impact of atrial fibrillation in these patients. METHODS: Three hundred and thirty-five cirrhotic patients (219 males; mean age 65 ± 10.85 years; 196 Child-Pugh class A, 104 class B and 35 class C) were consecutively analysed and followed up for 24 months. Electrocardiograms were available for all patients before starting the study, at basaltime and during the follow-up. Echocardiography was performed in individuals with atrial fibrillation and in 100 randomly chosen patients without it. RESULTS: Atrial fibrillation was observed in 21/335 cirrhotics (mean age 75 ± 7 years, 13 male), six of whom had permanent and 15 had paroxysmal atrial fibrillation. At univariate analysis, atrial fibrillation significantly correlated with older age, history of coronary heart disease, Child-Pugh score, serum albumin, hepatic encephalopathy, treatment with furosemide, QTc prolongation, atrial section areas, increased PAPs and thickness of interventricular septum. Age [odd ratio 1.12, 95% CI (1.05-1.2), P = 0.001], history of coronary heart disease [odd ratio 4.93, 95% CI (1.04-23.54), P = 0.04] and PAPs [odd ratio 1.12, 95% CI (1.02-1.2), P = 0.01] maintained statistical significance at multivariate analysis. Fifty-one of the 335 patients died during the follow-up. At Cox regression analysis, advanced Child-Pugh score [hazard ratio 1.546, 95% CI (1.357-1.762), P = 0.037] and increased heart rate [hazard ratio 1.117, 95% CI (1.021-1.223), P = 0.016] were significantly associated with mortality which was independent of atrial fibrillation occurrence. CONCLUSIONS: Cirrhosis is not a predisposing factor of atrial fibrillation, which in turn has no impact on mortality in cirrhotic patients.

The clinical significance of occult HBV infection.

The presence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg)-negative individuals is defined as occult HBV infection (OBI). OBI is related in some cases to infection with variant viruses (S-escape mutants) undetectable by HBsAg commercial kits. More frequently, however, it is due to infection with wild-type viruses that are strongly suppressed in their replication activity. OBI may be involved in different clinical contexts, including the transmission of the infection by blood transfusion or liver transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it may contribute to the development of cirrhosis and may have an important role in hepatocarcinogenesis.

Comparison of ocular surface disease index and tear osmolarity as markers of ocular surface dysfunction in video terminal display workers.

PURPOSE: To compare the Ocular Surface Disease Index (OSDI) questionnaire and tear osmolarity, to screen ocular surface alterations in video display terminal (VDT) users. DESIGN: Cross-sectional study. METHODS: Sixty-four VDT workers were screened for ocular surface alterations using OSDI and tear osmolarity. Furthermore, tear film break-up time (TBUT), fluorescein corneal stain, and assessment for meibomian glands dysfunction (MGD) were carried out. The alteration of 2 or more among these parameters was considered a sign of ocular surface dysfunction. Data for the statistical analysis were obtained from the eyes with the worst tear osmolarity score. Main outcome measures were OSDI and tear osmolarity. For the statistical analysis the receiver operating characteristic (ROC) curves and Spearman correlation coefficient were used. A P < .05 was considered statistically significant. RESULTS: The area under the ROC curve (AUC) for tear osmolarity (ranging from 0.71 to 0.86) showed, for all the classification variables considered, statistically significantly higher values than those obtained with OSDI (ranging from 0.51 to 0.58) (P < .01). Furthermore, tear osmolarity showed a direct correlation with corneal stain and ocular surface dysfunction and an inverse correlation for TBUT. No correlation was found between OSDI and the parameters considered. CONCLUSIONS: Tear osmolarity can be considered a more reliable test than OSDI, when screening VDT users for possible ocular surface alterations.

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.

Recurrence of Salzmann nodular degeneration of the cornea in a Crohn's disease patient.

The purpose of this study is to describe a recurrence of Salzmann nodular degeneration (SND) concurrent with the clinical onset of severe Crohn's disease. The method used in this study is single observational case report. A 43-year-old male was treated for bilateral advanced SND by manual asportation of the corneal nodules. Two years after the treatment Crohn's disease was diagnosed and during the following year a rapid bilateral and symmetric recurrence of the nodules was observed with progressive visual impairment. In conclusion, the timing of the recurrence of Salzmann nodules and the clinical manifestations of severe Crohn's disease might suggest a link between the diseases.

Morphological and morphometric study of the pecten oculi in the budgerigar (Melopsittacus undulatus).

The pecten oculi is a highly vascular and pigmented organ placed in the vitreous body of the avian eye. As no data are currently available on the morphological organization of the pecten in the Psittaciformes, the pecten oculi of the budgerigar (Melopsittacus undulatus) was studied. The eyes from adult male budgerigars were examined by light, transmission, and scanning electron microscopy and a morphometric study on both light and transmission electron microscopy specimens was also performed in the different parts of the organ. In the budgerigar, the type of the pecten oculi was pleated. Its basal part had a cranio-caudal and postero-anterior course; its body consisted of 10-12-folds joined apically by a densely pigmented bridge. The pecten showed many capillaries, whose wall was thick and formed by pericytes and endothelial cells. These latter had a large number of microfolds, rectilinear on their luminal surface and tortuous on their abluminal surface. Interstitial pigment cells were placed among the capillaries, filled with melanin granules and showed many cytoplasmic processes. The morphometric analysis demonstrated significant differences among the three parts of the organ relative to the length of the endothelial processes and to the number and size of the pigment granules. The morphological and morphometric analysis showed that the bridge of the budgerigar, different from the other birds, had a large number of capillaries, so that this part of the organ could also play a trophic role for the retina in addition to the choriocapillaris.

Morphologic and confocal investigation on Salzmann nodular degeneration of the cornea.

PURPOSE: To investigate the ultrastructure of advanced Salzmann nodular degeneration (SND) and to correlate it to confocal in vivo findings. METHODS: The corneal degenerative nodules from four patients with SND were examined with confocal microscopy and then removed and processed for light microscopy (LM) and transmission electron microscopy (TEM). RESULTS: The confocal examination revealed elongated basal epithelial cells and activated keratocytes in the anterior stroma near the nodules. Occasional subbasal nerves and tortuous stromal nerve bundles were observed. With LM and TEM, five zones were described: one internodular and four pertaining the nodule, each characterized by peculiar aspects of the epithelium and stroma. As also confirmed by the morphometry, in the zones corresponding to the nodules, the epithelium was lower and with fewer cell layers than the peripheral zones. Over the nodules, the basement membrane was discontinuous or absent and the Bowman's layer, when present, had a granular-filamentous appearance. The nodular stroma was formed by many activated keratocytes and irregular lamellae. Subbasal nerves were always isolated and had degenerative changes in the center of the nodule. CONCLUSIONS: This work illustrates the confocal microscopic findings associated with LM and TEM observations in patients with advanced SND. Our data revealed milder changes of the epithelium together with more pronounced changes of the basement membrane and Bowman's layer, which are aspects of increased keratocyte activity and an altered nerve pattern. All of these structures seem to contribute to the characteristic corneal disorganization of SND.

Systemic omega-6 essential fatty acid treatment and pge1 tear content in Sjögren's syndrome patients.

PURPOSE: To determine the effect of oral omega-6 essential fatty acids on PGE(1) tear content and signs and symptoms of ocular discomfort in patients with Sjögren's syndrome (SS). METHODS: This randomized, double-masked, controlled, clinical trial involved 40 patients with primary SS, divided into two groups: group 1: 20 patients (18 women, 2 men; mean age, 36.9 +/- 7.9 years [SD]) treated for 1 month with linoleic acid (LA; 112 mg), and gamma-linolenic acid (GLA; 15 mg) administered twice daily; group 2: 20 patients (19 women, 1 man; mean age, 36.3 +/- 5.5 years) treated twice daily with placebo. Patients underwent three examinations: at baseline (T0), after 1 month of treatment (T1), and 15 days after suspension of treatment (T2). At each examination, the following tests were performed: tear sampling (2 microL) from the inferior meniscus, tear break-up time (BUT), fluorescein stain of the ocular surface, and tear basal secretion. A symptom score was also obtained at each examination. PGE1 was evaluated by enzyme immunoassay. The primary efficacy variable was PGE1 content of tears. RESULTS: The tear PGE1 levels were significantly increased in group 1 at T1 versus T0 (PGE1 level: T0, 44 +/- 5.4 ng/mL; T1, 58.3 +/- 5.5 ng/mL; P < 0.01 versus T0 and group 2 at T1). At examination T2, a statistically significant reduction of PGE1 levels toward baseline was observed (45.7 +/- 5.2 ng/mL; P < 0.01 versus T1). A statistically significant reduction of symptom score was observed in group 1 at examination T1 (P < 0.01 versus T0 and group 2 score). At examination T2, the symptom score was significantly higher than T1 but remained lower than T0. The corneal fluorescein stain in group 1 showed a statistically significant improvement at examination T1 versus T0 and group 2 (P < 0.01). This improvement was also present at T2 (P < 0.02). No statistically significant differences were found for the other tests. No statistically significant changes were observed in the patients in group 2 at all examination time points. CONCLUSIONS: Omega-6 administration increases the PGE1 levels in tears of patients with SS and improves ocular surface signs and symptoms of ocular discomfort.