Cataract surgery in exudative uveitis: effectiveness of total lens removal, anterior vitrectomy, and scleral fixation of PC IOLs.

PURPOSE: Cataract 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. METHODS: Group 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. RESULTS: Postoperative 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. CONCLUSIONS: Total 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.

RGDS peptides immobilized on titanium alloy stimulate bone cell attachment, differentiation and confer resistance to apoptosis.

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.

Identification of local Th2 and Th0 lymphocytes in vernal conjunctivitis by cytokine flow cytometry.

PURPOSE: Th2 lymphocytes may play a key role in the development of allergic diseases such as vernal keratoconjunctivitis (VKC). Cytokine flow cytometry of tear samples was used to identify the phenotypical and functional properties of lymphocytes at the actual site of the allergic reaction. METHODS: Tear and blood samples were obtained from patients affected by active VKC (n = 12) and from normal control subjects (n = 10). Tears were obtained after gentle scraping of the tarsal and bulbar conjunctiva. Tear and blood samples were placed in a solution of brefeldin-A, phorbol myristate acetate (PMA), ionomycin, and RPMI for 4 hours and then processed for flow cytometry. Lymphocytes were marked with the monoclonal antibodies, anti-IFN-gamma and anti-interleukin (IL)-4. Levels of IL-4, IL-2, IFN-gamma, IL-2R, total IgE, eosinophil cationic protein (ECP), eosinophil protein X/neurotoxin (EPX), and myeloperoxidase (MPO) were also evaluated in serum. RESULTS: Expression of IL-4 was observed in 9.2%+/-9.5% of lymphocytes in tears of patients with VKC. Of the 12 patients with VKC, 8 (67%) had tear lymphocytes positive for IL-4 (Th2). Two patients (17%) had a double population of lymphocytes: One was positive for Th2, and the other was positive for both IL-4 and IFN-gamma (Th0). One patient (8%) was positive for IFN-gamma (Th1) only, and one patient was negative for both ILs. No differences in the percentage of Th2 lymphocytes were found between tarsal and limbal patients. The percentage of Th2 lymphocytes was significantly correlated with the severity of the disease. No positive lymphocytes were found in tears of control subjects. Eosinophils, serum IgE, ECP, and EPX were all significantly higher in VKC than in control subjects. CONCLUSIONS: In ocular allergic diseases, local lymphocytes expressed the Th2 phenotype and, to a lesser degree, the Th0 phenotype. Although results of systemic allergic markers can be inconclusive in patients with VKC, flow cytometry demonstrated a local lymphocyte phenotype that can account for the clinical and histologic abnormalities of VKC.

Growth factors and collagen distribution in vernal keratoconjunctivitis.

PURPOSE: To study the extracellular composition of giant papillae in vernal keratoconjunctivitis (VKC) and the expression of growth factors that may stimulate fibrosis. METHODS: Upper conjunctival specimens were obtained by biopsy in 9 patients affected by active tarsal VKC (14 eyes) and 10 normal control subjects. Immunohistochemistry was performed on tissue sections using monoclonal antibodies (mAbs) for collagens I, III, and VII; tumor necrosis factor (TNF)-alpha; transforming growth factor (TGF)-ss1; basic fibroblast growth factor (bFGF); and platelet-derived growth factor (PDGF). The mAbs anti-tryptase, anti-CD4, anti-CD68, and anti-EG2 were used as markers for mast cells, T-helper lymphocytes, macrophages, and eosinophils, respectively. Immunofluorescent double-staining for growth factors and cell markers was performed in VKC tissues. RESULTS: Immunostaining was highly positive for collagens I, III, and VII in the subepithelium of VKC conjunctiva. Image analysis showed a significant increase of staining per tissue area for both collagens I and VII and increased basal membrane length. The number of cells positive for TNF-alpha, TGF-ss, bFGF, or PDGF was significantly higher in VKC tissue than in control samples. Double staining showed that eosinophils and macrophages were the main sources of PDGF and that FGF was expressed by 46% of mast cells. Significant PDGF and FGF staining was observed in the conjunctival epithelium and vascular endothelium of all VKC tissues. CONCLUSIONS: In giant papillae of VKC, the extracellular matrix is characterized by overproduction of collagens. Expression of growth factors in the conjunctiva by resident cells (mast cells, epithelial cells, endothelial cells) and inflammatory cells (macrophages, eosinophils) may contribute to papillae formation and fibrosis evolution in chronic ocular allergic diseases.

Effects of cyclosporin A on human conjunctival fibroblasts.

OBJECTIVE: To evaluate the effects of cyclosporin A (CsA) on cytokine and/or collagen production, cell growth, and apoptosis in conjunctival fibroblast cultures. METHODS: Fibroblast cultures derived from normal subjects and patients with vernal keratoconjunctivitis and pemphigoid were exposed to different concentrations of CsA for either 24 hours or 30 days. The effects were evaluated by the colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) test to assess cell proliferation, and by the measurement of procollagen I (PIP) and procollagen III (PIIIP) cytokines and total protein in culture medium. CsA-induced apoptosis was assessed by fluorescence-activated cell sorter analysis. RESULTS: After 24 hours of exposure to doses of CsA of more than 10 microg/mL, cell proliferation and migration were significantly reduced. Cyclosporin A reduced PIP and interleukin 1 (IL-1) production in a dose-dependent manner. Interleukin 6 and IL-8 were increased by 10 microg/mL of CsA, whereas transforming growth factor beta, PIIIP, and total protein were unaffected. Cyclosporin A exposure induced apoptosis in a time- and dose-dependent manner. Long-term exposure to CsA reduced IL-6 but did not modify PIIIP production. CONCLUSION: Exposure to CsA directly modified fibroblast behavior. CLINICAL RELEVANCE: Cyclosporin A ability to accelerate apoptosis in clinically fibrotic tissues may prove to be therapeutic and useful in hyperproliferative conjunctival disorders.

Intraoperative mitomycin C in the treatment of cicatricial obliterations of conjunctival fornices.

PURPOSE: To investigate whether the intraoperative use of topical mitomycin C improved the postoperative outcome in cases of cicatricial obliteration of conjunctival fornices. METHODS: Ten eyes of five patients were subjected to surgical lysis of the synechiae followed by intraoperative application of 0.4 mg mitomycin C per milliliter of saline for 3 to 5 minutes. RESULTS: After a follow-up period of 12 to 19 months, no recurrence of synechiae was observed, the conjunctival fornices remained open, and conjunctival overgrowths on the cornea did not recur. No adverse effect was observed. CONCLUSION: Intraoperative application of mitomycin C proved useful in the surgical treatment of cicatricial shrinkage of conjunctival fornices.

Topical use of cyclosporine in the treatment of vernal keratoconjunctivitis.

We treated 11 patients with vernal keratoconjunctivitis for four to nine months with topical cyclosporine as a 2% dilution in castor oil. No significant side effects occurred, except for mild and transient burning upon administration. Within the first 15 days, both symptoms and signs of the condition improved significantly, and these results were maintained throughout the entire treatment. Relapses of the disease occurred two to four months after the end of the therapy. A double-masked clinical trial of nine patients (2% cyclosporine in castor oil vs castor oil alone) confirmed the results. Treated eyes improved significantly for both signs and symptoms as compared to control eyes. Topical cyclosporine may, therefore, be considered an effective substitute for corticosteroids, with an excellent anti-inflammatory activity in patients with both corticosteroid-dependent and corticosteroid-resistant vernal keratoconjunctivitis.

Tear and serum soluble leukocyte activation markers in conjunctival allergic diseases.

PURPOSE: To measure markers of leukocyte activation in patients with an exclusively ocular inflammatory or bacterial disease. METHODS: Neutrophil myeloperoxidase, eosinophil cationic protein, eosinophil neurotoxin, and soluble interleukin-2 receptor were measured in serum and tears of 17 patients with allergic vernal keratoconjunctivitis, seven with atopic keratoconjunctivitis, 11 with seasonal allergic conjunctivitis, seven with giant papillary conjunctivitis, 13 with rosacea blepharokeratoconjunctivitis, seven with bacterial conjunctivitis, and 13 normal subjects as controls. RESULTS: In serum of patients with vernal and atopic keratoconjunctivitis, levels of eosinophil cationic protein, eosinophil neurotoxin, and interleukin-2 receptor were significantly increased compared with control subjects but were not correlated with the severity of ocular symptoms. In tears of patients with vernal and atopic keratoconjunctivitis and seasonal allergic conjunctivitis, as well as in the nonallergic diseases, rosacea blepharokeratoconjunctivitis and bacterial conjunctivitis, levels of eosinophil cationic protein, neurotoxin, and interleukin-2 receptor were significantly increased compared with control subjects. The highest values of these markers were found in vernal keratoconjunctivitis samples. Neutrophil myeloperoxidase was significantly increased in vernal and atopic keratoconjunctivitis, rosacea blepharokeratoconjunctivitis, and bacterial conjunctivitis. In vernal keratoconjunctivitis, tear markers were correlated to the clinical score of the disease, but not with cytology. CONCLUSIONS: Tear histamine was measured in 10 allergic patients after allergen challenge. Although none of the above markers can be considered specific to a single disease, their measurement may still be useful for the quantification of local cell activation in ocular inflammatory diseases.

A psychosomatic approach to idiopathic recurrences of anterior uveitis.

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.

Lysophosphatidyl choline in the aqueous humour during ocular inflammation.

Phospholipase A and lysophosphatidyl choline (LPC) have been shown to induce significant changes in the lens permeability in vitro to cations and soluble proteins. During uveal inflammation, in various experimental models and in man as well, the levels of LPC in the aqueous humour have been shown to reach values which are harmful to the lens in vitro. In addition, a phospholipase is thought to be activated during the antigen + antibody + complement sequence. The possible significance of these findings is discussed in relation to the pathogenesis of complicated cataracts in uveitis and the possible role of the lens as a source of autoantigens in recurrent uveitis.

Collagen types I and III in giant papillae of vernal keratoconjunctivitis.

AIMS: The objective of this study was to investigate alterations in conjunctival collagen and proteoglycans in the conjunctival giant papillae of patients with vernal keratoconjunctivitis (VKC). METHODS: Tissue samples from tarsal giant papillae of seven eyes from five patients with VKC, and five tarsal conjunctival samples from five normal patients were obtained. Tissues were processed and stained with haematoxylin and eosin, Van Gieson, trichromic Mallory, toluidine blue, Alcian blue, and alkaline Giemsa. Collagen extraction was performed in acetic acid and pepsin, total collagen was quantified using hydroxy-proline levels, and collagen types I and III were analysed by gel electrophoresis (SDS-PAGE). Proteoglycans were quantified using uronic acid levels. RESULTS: Histological evaluation showed a significant increase of mast cells in the epithelium (0/mm2 v 147/mm2, p < 0.01) and in the stroma (5.1/mm2 v 80/mm2, p < 0.01) of VKC patients. Collagen fibres were thicker and arranged irregularly, with the total amount significantly increased. Owing to an increased percentage of type III collagen, the ratio of collagen types I to III was decreased. Proteoglycans were also reduced in VKC samples. CONCLUSION: The well known morphological abnormalities observed in VKC correspond to alterations in the ratio between collagens and proteoglycans, and between different types of collagen. The greatly increased number of mast cells found in these tissues suggests an active role for these cells in the abnormal connective tissue metabolism observed in VKC.

Effect of lodoxamide and disodium cromoglycate on tear eosinophil cationic protein in vernal keratoconjunctivitis.

AIM: To validate the use of tear eosinophil cationic protein (ECP) as a marker for eosinophil activation, and its pharmacological modulation, in addition to evaluating the efficacy of lodoxamide and sodium cromoglycate in the treatment of vernal keratoconjunctivitis (VKC). METHODS: Tears were collected from 30 patients affected by active mild to moderate VKC before and after therapy with disodium cromoglycate 4% (DSCG) (n = 15) or lodoxamide 0.1% (n = 15) for 10 days. Tear cytology and ECP measurement were performed, and ocular signs and symptoms evaluated. RESULTS: While statistically significant changes did not occur after DSCG therapy, mean tear ECP increased from 343 (SD 363) micrograms/l to 571 (777) micrograms/l due to marked elevation in six eyes. The clinical score in DSCG eyes did not improve. After lodoxamide therapy, both clinical signs and symptoms, and tear ECP levels (560 (756) micrograms/l to 241 (376) micrograms/l) decreased significantly (p < 0.0001 and p < 0.01, respectively). Compared with DSCG treatment, lodoxamide was more effective in reducing signs and symptoms (p < 0.005). ECP levels were significantly correlated with signs, symptoms, corneal involvement, and number of eosinophils in tears (p < 0.0001). CONCLUSIONS: In patients with VKC, lodoxamide significantly reduced ECP tear levels, and thus, eosinophil activation, and was more effective than DSCG in reducing clinical signs and symptoms.

Anti-inflammatory and antiallergic effects of ketorolac tromethamine in the conjunctival provocation model.

AIM: To study the effect of the topical anti-inflammatory drug, ketorolac, on (1) the clinical allergic reaction induced by the conjunctival provocation test (CPT); (2) the release of tryptase in tears; and (3) the expression of adhesion molecules on the conjunctival epithelium. METHODS: 10 allergic but non-active patients were challenged in both eyes with increasing doses of specific allergen to obtain a positive bilateral reaction and rechallenged, after 1 week, to confirm the allergic threshold dose response. After 2 weeks, a third CPT was then performed bilaterally 30 minutes after topical application of ketorolac in one eye and placebo in the contralateral eye in a double blind fashion. Clinical symptoms and signs were registered 5, 10, 15, and 20 minutes after challenge. The following objective tests were performed: tear tryptase measurement; tear cytology; and conjunctival impression cytology for immunohistochemical expression of ICAM-1 on epithelial cells. RESULTS: Compared with placebo, ketorolac significantly reduced the total clinical score and the itching score in the 20 minutes after challenge (p<0.0005). Tear levels of tryptase were significantly reduced in the ketorolac pretreated eyes compared with placebo (p<0.03). Eosinophils, neutrophils, and lymphocytes in tear cytology were significantly lower in ketorolac treated eyes compared with placebo. A significant difference in the epithelial expression of ICAM-1 was observed between placebo and ketorolac treated eyes (p<0.05). CONCLUSION: Ketorolac proved to be effective in reducing mast cell degranulation, as indicated by significantly decreased tryptase tear levels, as well as the clinical and cytological allergic reaction.

Nedocromil sodium and astemizole, alone or combined, for treatment of seasonal allergic conjunctivitis (SAC).

SAC is caused by allergen interaction with IgE antibody on conjunctival mast cells, leading to local release of vasoactive inflammatory mediators such as histamine. Nedocromil sodium both stabilizes mast cells and has antiinflammatory activity against other cells involved in allergic inflammation. Astemizole is a second generation orally-active H(1)-receptor antagonist with reduced CNS effects such as drowsiness. This multicentre, double blind, double dummy trial compared efficacy and safety of qid 2% nedocromil sodium eye drops with once daily 10 mg oral astemizole, placebo, and combined active treatments for a four-week period. SAC patients (n=207, aged 6-70 years) recorded their symptoms each day on diary cards. Signs and symptoms were also evaluated by clinicians after one, two and four weeks and overall opinions were recorded at the end of treatment. Nedocromil sodium eye drops and astemizole, alone or combined, significantly reduced ocular symptoms compared to placebo (for diary card total symptom score and patients' opinion). Clinicians' opinion showed significantly decreased symptoms with nedocromil sodium, alone or combined, but not with astemizole alone. All treatments were well tolerated, with drowsiness the most frequent side effect observed in patients treated with astemizole. These results demonstrate the effectiveness of nedocromil sodium eye drops in the treatment of SAC.

Histopathology and ultrastructure of rabbit lenses exposed 'in vitro' to lysophosphatidylcholine (LPC).

Permeability changes which take place in the lens in the course of uveitis are probably due to 'Lens Permeability Factors' present in the inflammatory aqueous. One of these 'factors', lysophosphatidyl-choline (LPC), has been shown to damage the lens in vitro: a leakage of Rb(86) and proteins, and an increase of Na(+) and water content indicate a dose-related membrane lytic effect. Damaging levels of LPC (up to 10µg/ml of aqueous humor) were found in the anterior chamber of inflamed eyes in the course of experimental uveitis in rabbits, and also in humans during uveitis. This report deals with an ultrastructural investigation on the damaging effect of different concentrations of LPC on rabbit lenses in culture. Concentrations of LPC higher than 12µg/ml caused signs of degeneration immediately below the capsule. Scanning electron microscopy revealed grossly enlarged lens fibers, globular structures of different size and widespread water vacuoles. Transmission electron microscopy showed inter- and intracellular changes in the epithelium and the outer cortex, swollen lens epithelial cells, fiber cells separation, vacuoles, and areas of decreased electron density. The overall structure of the lens fibers in the inner cortex and in the nucleus was always intact.

Lacrimal defects in adult and senile rheumatoid arthritis.

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.

The anti-allergic effects of a cromolyn sodium-chlorpheniramine combination compared to ketotifen in the conjunctival allergen challenge model.

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 (p < 0.01) and at 5 minutes for redness (p < 0.01). For the total signs score, DSCG-chlorpheniramine was shown to be superior to ketotifen at all time points (p < 0.01), and at 10 and 15 minutes for the total symptoms score (p < 0.05). Compared to visit 2, DSCG-chlorpheniramine significantly lowered itching (p < 0.001) and redness (p < 0.05) at 5, 10, 15, and 20 minutes after challenge. Ketotifen significantly lowered itching at 5 and 10 minutes (p < 0.001) and redness at 5, 10, and 15 minutes (p < 0.05). Both drugs reduced the total number of cells evaluated by tear cytology during the early-phase reaction (p < 0.05). CONCLUSIONS: DSCG-chlorpheniramine was found to be more effective than ketotifen at preventing itching and redness in the CAC model.

Tumor necrosis factor-alpha (TNF-alpha) in seasonal allergic conjunctivitis and vernal keratoconjunctivitis.

PURPOSE: To quantify the presence of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 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-alpha in tears was measured by enzyme-linked immunoassay and identified in tissues by immunohistochemistry. RESULTS: Tear TNF-alpha 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-alpha serum levels were higher in VKC than CT, however, this difference was not statistically significant. After CAC, tear TNF-alpha levels were found increased in only one of six patients. In VKC tissues, TNF-alpha positive cells were significantly increased compared to CT (p=0.03). CONCLUSIONS: TNF-alpha may have a significant role in severe forms of allergic conjunctivitis.

Tear histamine and histaminase during the early (EPR) and late (LPR) phases of the allergic reaction and the effects of lodoxamide.

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 (p < 0.05). During LPR, tear histamine increased significantly (p < 0.05) 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 (p < 0.05) only during the EPR. Lodoxamide significantly reduced histamine release during EPR (p < 0.05), allergic signs and symptoms during both EPR (p < 0.001) and LPR (p < 0.005), 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.

Intravitreal and systemic foscarnet in the treatment of AIDS-related CMV retinitis.

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.