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Purpose To quantify the presence of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) in allergic conjunctivitis. Materials and Methods Tears and peripheral blood samples were collected from patients with seasonal allergic conjunctivitis (SAC, n=6), vernal keratoconjunctivitis (VKC, n=12), and normal subjects (CT, n=12). From an additional six nonactive allergic patients, tears were collected before and after specific conjunctival allergen challenge (CAC). Upper tarsal conjunctival biopsies were obtained from five CT and five VKC patients. TNF-α in tears was measured by enzyme-linked immunoassay and identified in tissues by immunohistochemistry. Results Tear TNF-α levels in VKC patients were significantly increased compared to CT (p=0.03), and were significantly correlated with the severity of the disease. No differences were found between SAC and CT tear samples. TNF-α serum levels were higher in VKC than CT; however, this difference was not statistically significant. After CAC, tear TNF-a levels were found increased in only one of six patients. In VKC tissues, TNF-α positive cells were significantly increased compared to CT (p=0.03). Conclusions TNF-α may have a significant role in severe forms of allergic conjunctivitis.

Purpose To compare the inhibitory effects of a topical combination product, cromolyn sodium (DSCG) 4% with the antihistamine, chlorpheniramine, with those of topical ketotifen 0.05% on the clinical allergic reaction induced by the conjunctival allergen challenge (CAC). Methods Ten allergic but non-active patients were challenged in both eyes with increasing doses of specific allergen to obtain a positive bilateral reaction (visit 1). They were then rechallenged after 1 week to confirm the allergic threshold dose response (visit 2). After 2 weeks, a third CAC was performed bilaterally 30 minutes after topical application of DSCG-chlorpheniramine in one eye and ketotifen in the contralateral eye in a double-masked fashion (visit 3). Clinical signs and symptoms were registered 5, 10, 15, and 20 minutes after challenge using the standard scoring system. Tear cytology was performed 30 minutes after challenge. Results Comparing the two drug effects at visit 3, DSCG-chlorpheniramine was shown to be superior to ketotifen at all time points for itching (pConclusions DSCG-chlorpheniramine was found to be more effective than ketotifen at preventing itching and redness in the CAC model.

The objectives of this study were two-fold: to identify tear histamine content and its relationship to changes in tear histaminase activity during the early (EPR) and late phases (LPR) of the allergic reaction induced by a conjunctival provocation test (CPT) and to evaluate the effects of lodoxamide on histamine release and allergic signs and symptoms during EPR and LPR. A baseline CPT was administered to 20 allergic patients with no baseline signs or symptoms of allergy. Clinical signs and symptoms were evaluated after 20 minutes and 6 hours. Tear samples were taken after 5-10 minutes and after 6 hours for subsequent analyses of cytology and histamine content (ELISA). Patients were then randomly assigned to receive lodoxamide or placebo four times daily for one week in a double-masked fashion. A second CPT was done after this therapy and the same parameters were re-evaluated. During EPR, tear histamine increased significantly with respect to baseline values (p0.05). During LPR, tear histamine increased significantly (p0.05) only in histamine inactivated samples. Histaminase enzymes were also significantly less active during the EPR (5.5 +/- 0.7) than the LPR (9.9 +/- 2.3) and at baseline. Histamine levels significantly correlated with allergic signs and symptoms (p0.05) only during the EPR. Lodoxamide significantly reduced histamine release during EPR (p0.05), allergic signs and symptoms during both EPR (p0.001) and LPR (p0.005), and tear cytology counts during LPR. In conclusion, greater histaminase activity may account for the smaller amount of tear histamine generally found during LPR, while these enzymes seem to play less of a role during the surge of histamine release and activity in the EPR. Lodoxamide was shown to ideally inhibit various aspects of the allergic reaction: clinical signs and symptoms in both the early and late phases, the primarily EPR-related peak of histamine release, and the primarily LPR-related changes in tear cytology.

Rheumatoid arthritis presents with different clinical manifestations according to the age of onset. The authors have studied the involvement of the lacrimal function in two different cohorts of patients, 70 adult-onset (onset of the disease between 15 and 60 years of age) and 30 old-onset (60-79 years), as compared to two groups of normal controls of the same age. Schirmer I, Break-Up Time (BUT), and Bengal rose were tested. Senile rheumatoid arthritis (SRA) not only did not show more severe lacrimal changes when compared to adult rheumatoid arthritis (ARA) of the same duration, but failed to show statistical differences in tear secretion when compared to a healthy population of the same age. ARA patients showed a significant tear deficiency when compared to a healthy population of the same age. Within this cohort of patients, 'long-lasting' ARA showed more severe changes when compared to 'short-lasting' ARA. These results would suggest that the involvement of the lacrimal system is more important when rheumatoid arthritis develops in adult rather than in old age, being a function of the duration rather than of the severity of the disease.

To evaluate the frequency and epidemiological features of vernal keratoconjunctivitis (VKC) in Italy.a specific electronic clinical chart for vernal keratoconjunctivitis was created to standardize: 1) medical history; 2) diagnostic criteria; 3) signs and symptoms; and 4) treatments. This study involved 6 Italian referral centers for ocular surface diseases: between March 2005 and March 2006, all referred patients were included, clinical data collected and statistically examined.The mean age of the vernal keratoconjunctivitis population (n = 156) was 13.8 +/- 8.8 with 64.1% of subjects under 14 years of age and a male/female ratio of 3.5:1. Among VKC patients, 48.7% showed associated systemic allergic diseases. Only 32.1% of patients were positive for RAST and/or prick test. The limbal form (53.8%) was the most frequent subtype of vernal keratoconjunctivitis. Approximately 9% of patients showed a severe form of vernal keratoconjunctivitis. At the first visit patients were treated with: multiple action or mast cell stabilizer eye drops (58.1% and 41.3% of cases, respectively), topical corticosteroids alone (0.6%) or in association (26.8% of cases). All patients used topical steroids at least once in the studied year. Systemic antihistamine therapy was used by 25.6% of patients. In this cohort, 32.7% of patients required two or more examinations per year for exacerbations of their symptoms.Vernal keratoconjunctivitis is a severe ocular condition that mainly affects young males. Vernal keratoconjunctivitis is characterized by different clinical features and therapeutic responses, suggesting the need for a standardized therapeutic approach on the basis of a grading of disease severity.

PurposeCataract surgery in exudative uveitis is often followed by severe complications (pupillary seclusion/occlusion, dense posterior capsule/anterior vitreous opacification, cystoid macular edema following repeat YAG laser procedures) which often drastically limit functional recovery Total removal of cataract, anterior vitrectomy, and scleral fixation of a posterior chamber (PC) intraocular lens (IOL) has been tried as a surgical alternative, searching for lessened postsurgical complications and a better outcome.MethodsGroup A was a cohort of 12 patients with cataract after exudative (mostly sarcoidosis and Vogt-Koyanagi-Harada) uveitis, subjected to intracapsular cataract extraction, anterior vitrectomy, and scleral fixation of PC IOLs. Group B was the control group, including 12 patients with a similar clinical condition subjected to phacoemulsification or extracapsular cataract extraction plus in-the-bag or in-the-sulcus IOL implantation. Follow-up time for both groups was at least 7 years.ResultsPostoperative inflammatory signs were substantially less in Group A patients, from 2 days up to >7 years postsurgery Group A patients showed no cells/exudates adhering to the IOL surfaces, no synechiae, minimal (as compared to Group B) vitreous opacifications, and significantly higher visual acuity (p=0.024 at the seventh year control). Group A patients reported less frequent relapses of uveitis postsurgery, but the relevant clinical data did not allow statistical evaluations.ConclusionsTotal removal of cataract in highly exudative uveitic eyes, plus anterior vitrectomy and scleral fixation of PC IOLs, although technically a more demanding surgical procedure, proved to be safe and more effective than classical procedures.

A major cause of implant failure in skeletal tissues is failure of osseointegration, often due to lack of adhesion of cells to the titanium (Ti) alloy interface. Since arginine-glycine-aspartic acid (RGD)-containing peptides have been shown to regulate osteoblast adhesion, we tested the hypothesis that, bound to a Ti surface, these peptides would promote osteoblasts differentiation, while at the same time inhibit apoptosis. RGDS and RGES (control) peptides were covalently linked to Ti discs using an APTS linker. While the grafting of both RGDS and RGES significantly increased Ti surface roughness, contact angle analysis showed that APTS significantly increased the surface hydrophobicity; when the peptides were tethered to Ti, this was reduced. To evaluate attachment, MC3T3-E1 osteoblast cells were grown on these discs. Significantly more cells attached to the Ti-grafted RGDS then the Ti-grafted RGES control. Furthermore, expression of the osteoblasts phenotype was significantly enhanced on the Ti-grafted RGDS surface. When cells attached to the Ti-grafted RGDS were challenged with staurosporine, an apoptogen, there was significant inhibition of apoptosis; in contrast, osteoblasts adherent to the Ti-grafted RGES were killed. It is concluded that RGD-containing peptides covalently bonded to Ti promotes osteoblasts attachment and survival with minimal changes to the surface of the alloy. Therefore, such modifications to Ti would have the potential to promote osseointegration in vivo.

To quantify the presence of inflammatory/fibrogenic cytokines and procollagens type I (PICP) and III (PIIIP) in active and non-active tarsal and limbal forms of vernal keratoconjunctivitis (VKC), tear and blood samples were collected from 27 VKC patients (20 active and 7 non-active) and 15 normal subjects. Upper tarsal conjunctival biopses were obtained from 8 controls and 8 tarsal VKC patients. From biopses of 4 tarsal VKC, fibroblasts were cultured in F12 medium with 10% FCS. TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, PICP and PIIIP were measured in: (1) tears, (2) homogenized conjunctival tissues, (3) serum, (4) supernatants of tissue cultures at 24 hr, and fibroblast primary passage cultures. Results showed: (1) in tears, TGF-beta 1 and TNF were identified in several active VKC patients without significant differences between the tarsal and the limbal forms. IL-1 beta (27 +/- 51 pg ml-1, P = 0.03) and IL-6 (28 +/- 43 pg ml-1, P = 0.006) were significantly increased in tarsal VKC compared to controls. Both control and non-active VKC tear samples had undetectable levels of all of the above cytokines. PICP and PIIIP were significantly increased in tarsal VKC compared to both limbal VKC and controls. Non-active VKC levels were similar to controls. (2) In homogenized VKC tissues, TGF-beta 1 and IL-6 were both significantly increased compared to controls (P0.01) while no increases were observed in IL-1 and TNF-alpha. (3) In serum, IL-1 alpha, IL-1 beta and TNF-alpha were higher in VKC patients compared to controls. (4) In vitro fibroblasts from VKC patients showed an increased production of TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, PICP, and PIIIP over time. Increased levels of TGF-beta 1, IL-1 and IL-6 in VKC tissues and tears indicate a local production of these cytokines in active VKC. Collagen hyperproduction occurs only in active tarsal VKC and may be related to high levels of TGF-beta 1, IL-1 and IL-6. Increased serum levels of IL-1 and TNF-alpha suggests that systemic immunological changes occur in VKC. Cell culture can be used as a model to further study the pathogenesis of VKC and its characteristic local fibroblast activation.

Cytomegalovirus retinitis is the most frequent ocular opportunistic infection in AIDS patients. Untreated, it is always a progressive and destructive disease of the retina that results in blindness. Specific treatment is therefore mandatory to halt the progression of the retinal lesions. The authors report their experience in the treatment of CMV retinitis with foscarnet in 25 AIDS patients; the drug is an analog of pyrophosphate, virostatic against all herpes-class viruses including CMV. Foscarnet was successful in halting the progression of CMV retinitis during induction treatment (180 mg/kg/day) by either a TID (three times a day) or a BID (twice a day) regimen, and in healing retinal lesions during maintenance (90 mg/kg/day) in 14 out of 19 patients. Five patients had a relapse of retinitis during maintenance. In these patients a brief course of intravitreal foscarnet, in association with the lowest dosage of the drug administered systematically (90 mg/kg/day), was effective in healing the retinal lesions. The main systemic side effects, such as renal impairment and electrolytic disturbances, were observed only during the induction treatment, and only in one case was it necessary to stop the therapy.

The objectives of this study were to determine: 1) levels of tear eosinophil cationic protein (ECP) in patients with vernal keratoconjunctivitis (VKC); 2) the effect of pharmacologic therapy on ECP release; and 3) the correlation of this mediator with the severity of the disease. Tears were collected from 10 controls and 20 VKC patients before and after therapy for cytologic analysis and ECP measurement by radioimmunoassay. Ocular signs and symptoms were evaluated before tear collection. Mean ECP levels in controls were 7.5 +/- 0.4 microgram/l, and in VKC patients, 988.3 +/- 128 micrograms/l before therapy (P < 0.001) and 566.3 +/- 121 micrograms/l after therapy (P < 0.005). In dexamethasone (Dex) 0.1% or cyclosporin A (CsA) 2% patients (five per group), tear ECP decreased significantly after 7-14 days of treatment. Disodium cromoglycate (DSCG) 4% (five patients) for 14 days did not significantly affect ECP levels. ECP levels were significantly correlated with allergic signs (P < 0.001), symptoms (P < 0.001), and the number of eosinophils in tears (P < 0.005). The results of this study suggest that tear ECP levels accurately reflect the clinical status of VKC patients. The measurement of ECP may prove useful not only in the diagnosis and monitoring of allergic disease, but also as an objective parameter for the evaluation of new antiallergic therapies.

The efficacy, tolerability and safety of low doses (5-7 mg/kg/day) of oral ciclosporin (CS) for treatment of endogenous uveitis resistant to conventional therapy were studied in an open, noncontrolled, multicenter long-term trial. CS was shown to be effective for patients with posterior or intermediate noninfectious uveitis; it limited the progression of the disease, decreased the number and severity of inflammatory relapses, and improved visual acuity while reducing signs of intraocular inflammation. Moreover, in corticodependent patients, a steroid-sparing effect was also obtained. At low doses and by means of the careful monitoring of safety parameters, the side effects (especially renal function impairment) were well controlled. Efficacy was maintained during long-term treatment.

Normal rabbit lenses exposed in vitro to heterologous antibody (Ab)--antigen (Ag) interactions lose control of the intracellular 86Rb; this membrane damage, which seems to be related to the quantitative ratio Ab/Ag, is relatively complement independent and is followed by a subsequent leakage of lenticular proteins. A possible implication of these findings in the development of complicated cataracts in uveitis (as 'permeability cataracts') and in the self-maintenance of recurrent uveal inflammation is shortly discussed.

Normal rabbit lenses exposed in vitro to heterologous antilens and antiuveoretina antibodies lose control of the intracellular 86Rb and this effect is followed by a late leakage of lenticular proteins; both phenomena take place only in the presence of complement. This antibody-induced complement-dependent membrane damage might be involved in the pathogenesis of complicated cataracts in uveitis and in the self-maintenance of recurrent uveal inflammations.

We examined 60 patients affected by idiopathic recurrent anterior uveitis and studied the relevance of stressful life events and psychological distress in relation to relapses of the disease. The results were statistically insignificant when compared to the control groups. We found that neither life events nor psychological distress played a contributory role in this disease.

1. The utilization of respiratory substrates in calf-retina mitochondria has been studied. Calf-retina mitochondria oxidize pyruvate (+malate), α-oxoglutarate, succinate and glutamate at rates comparable to those reported for mitochondria from other mammalian tissues and with good P O ratios and respiratory control. Added isocitrate is not oxidized. Glutamate is oxidized through the transaminase pathway. 2. In the absence of inorganic phosphate, succinate oxidation shows an initial inhibited phase followed by a progressive activation. Evidence is given that oxaloacetate is responsible for the inhibition of succinate oxidation and that the activation requires ATP formation. It is suggested that ATP removes inhibitory oxaloacetate. 3. Retina mitochondria do not oxidize added NADH, NADPH or β-hydroxybutyrate. α-Glycerophosphate is very slowly oxidized and only in the presence of added Mg2+. These mitochondria are thus unable to oxidize extramitochondrial NADH directly, or through the β-hydroxybutyrate or the α-glycerophosphate cycles.