Biomedical subjects

J Leonard

Publications and source records attributed to J Leonard.

At least 55 records · Page 3Linked to original sources

PubMed1998

Safety, immunogenicity, and efficacy of an inactivated avian polyomavirus vaccine.

OBJECTIVE: To determine safety, immunogenicity, and efficacy of an inactivated avian polyomavirus vaccine in nonbudgerigar psittacine birds that varied in age, species, and immunologic status. ANIMALS: Safety of the vaccine was evaluated in 1,823 psittacines representing more than 80 species. Immunogenicity was evaluated in 285 birds (260 of various Psittaciformes species, 25 chickens). Efficacy was evaluated in 104 birds (78 of various Psittaciformes species, 26 chickens). PROCEDURES: Safety was evaluated by vaccinating birds that were determined to be seronegative or seropositive (titer > 1:10) prior to vaccination. Birds were then evaluated for clinically detectable systemic or local reactions for 2 months to 2 years. Immunogenicity was evaluated by testing for virus-neutralizing antibodies, vaccinating each bird twice, and then testing for a significant change in antibody titer. Efficacy was evaluated by vaccinating birds, followed in 2 to 4 weeks by intramuscular or intravenous challenge exposure. After challenge exposure, protection was evaluated by attempting to recover virus from tissues or by observing birds for clinical signs of disease and testing for a significant change in titer. CONCLUSIONS: Avian polyomavirus vaccine is safe, immunogenic, and efficacious for use in multiple species of mature and immature psittacines. CLINICAL RELEVANCE: Until now, prevention of polyomavirus infection in psittacine birds could only be accomplished through strict isolation to reduce potential exposure to the virus. The USDA-registered inactivated avian polyomavirus vaccine can safely be used to protect vaccinates from infection and control spread of this virus in flocks.

Animals↗

PubMed1997

A primatized MAb to human CD4 causes receptor modulation, without marked reduction in CD4+ T cells in chimpanzees: in vitro and in vivo characterization of a MAb (IDEC-CE9.1) to human CD4.

A Primatized anti-CD4 monoclonal antibody (MAb), CE9.1, with V-domain from cynomolgus macaque (showing 92% homology with human consensus sequence V-domains), and a human IgG1 constant region, was characterized in vitro and in vivo in chimpanzees. This MAb binds human CD4 with Kd of 1.0 nM and was also able to bind to human IgG Fc receptors (Fc gamma R). However, despite being of the IgG1 subclass, CE9.1 did not bind to complement component C1q, nor did it mediate complement-dependent cytotoxicity. Examination of T cells from a number of species showed restricted reactivity for CE9.1, recognizing only human and chimpanzee CD4. In both human and chimpanzee MLRs, it had an IC50 of about 10.0 ng/mL. Therefore, a chimpanzee in vivo model was used to characterize CE9.1, CE9.1 caused transient decrease in the number of lymphocytes bearing the CD4 receptor starting at doses of 0.3 mg/kg in an in vivo dose ranging study in one chimpanzee. This effect was reversed within approximately 7 days. In a multiple high-dose study in which 10.0 mg/kg of CE9.1 was administered at intervals of 1-3 months, there was a dramatic loss of CD4 marker with a reciprocal increase in the number of CD3+ CD8- CD4- cells. The CD4 receptor was totally undetectable on these lymphocytes for 1-2 weeks, with a gradual, but complete, reversal within 4 weeks. We interpret these observations as receptor modulation because, although there was apparent loss of CD4+ lymphocytes, an equivalent number of CD3+CD8- T lymphocytes were present in circulation in all four chimpanzees treated with 10.0 mg/kg CE9.1. Even at this high dose, only limited reduction of CD4+ T lymphocytes was observed in these animals. These observations are in sharp contrast to what has been reported in rodents or in human clinical studies using other IgG1 mAbs to human CD4. CD8 counts, although variable, remained unaffected by CE9.1 treatment. No adverse events were observed following administration of CE9.1 to chimpanzees, and there was no detectable host immune responses to the Primatized MAb.

Animals↗

PubMed1997

Immune enhancing effects of dehydroepiandrosterone and dehydroepiandrosterone sulphate and the role of steroid sulphatase.

Steroid hormones, such as glucocorticoids (GC), influence immune and inflammatory responses through their suppressive actions. Recent evidence suggests that another steroid hormone, dehydroepiandrosterone (DHEA), provides an immunostimulatory influence opposing the effect of GC. DHEA circulates in its inactive sulphated form, DHEAS, requiring conversion to DHEA by a steroid sulphatase (SS) enzyme for biological activity. Therefore, inhibition of SS activity may affect immune responses, allowing endogenous GC effects to predominate. We have shown that administration of DHEA and DHEAS in contact sensitization (CS) augments ear swelling by 39 and 46% respectively (P < 0.001). DHEAS at doses of 0.5, 5 and 50 mg/kg reverses the inhibitory effect of corticosterone (5 mg/kg) (P < 0.01). In CS, CT2251 (SS inhibitor) at 10 and 0.1 mg/kg inhibited ear swelling by 61 and 38% (P < 0.05) respectively. In addition, it inhibited DHEAS-augmented responses by 49 and 35% respectively (P < 0.05), with no effect on DHEA-augmented responses. DHEAS reversed CT2251 inhibition of the CS response with complete reversal at 50 mg/kg (P < 0.05). DHEAS and CT2251 appear to affect cellular infiltration into the ear, since DHEAS increased the number of lymphocytes by 63.8% and macrophages by 107% (P < 0.001), whereas CT2251 at 0.1 mg/kg decreased the number of lymphocytes by 65% (P < 0.001) and macrophages by 80% (P < 0.001). DHEAS, CT2251 and dexamethasone had no effect on oedema in the ear. From our data we have shown that steroid hormones, such as DHEA, have the potential to act as immunostimulatory factors in vivo. Inhibiting the conversion of DHEAS to DHEA by SS enzyme leads to an anti-inflammatory effect.

Adjuvants, Immunologic↗

PubMed1997

Population-based research data as a means to address health outcomes.

Health care restructuring efforts have been influenced by changes in public policy, payment mechanisms, and societal values. In today's environment, leading issues focus on quality and cost-effective care. Health care systems are moving from a concentration on structures and processes of care to an expanded view that encompasses the exploration, documentation, and improvement of patient outcomes. This article presents an overview of the domains of health outcomes, widely used surveys in the measurement of outcomes, methodological issues related to interpreting outcome measures, and trends for clinical practice and future research.

Community Health Planning↗

PubMed1997

Hormonal regulation of an islet-specific enhancer in the pancreatic homeobox gene STF-1.

The homeobox protein STF-1 appears to function as a master control switch for expression of the pancreatic program during development. Here we characterize a composite enhancer which directs STF-1 expression to pancreatic islet cells via two functional elements that recognize the nuclear factors HNF-3beta and BETA-2. In keeping with their inhibitory effects on islet cell maturation, glucocorticoids were found to repress STF-1 gene expression by interfering with HNF-3beta activity on the islet-specific enhancer. Overexpression of HNF-3beta suppressed glucocorticoid receptor-mediated inhibition of the STF-1 gene, and our results suggest that the expansion of pancreatic islet precursor cells during development may be restricted by hormonal cues which regulate STF-1 gene expression.

Animals↗

PubMed1997

Cerebrospinal fluid and plasma total homocysteine and related metabolites in children with cystathionine beta-synthase deficiency: the effect of treatment.

The neurologic complications of cystathionine beta-synthase deficiency are thought to be secondary to accumulation of homocyst(e)ine in the CNS. Treatment of this disorder with betaine has been shown to improve the behavior of individuals, to reduce plasma total homocysteine, and to correct secondary abnormalities of serine. To test the hypothesis that homocyst(e)ine accumulates within the CNS and that this can be reduced by treatment with betaine, we measured total homocysteine and related metabolites in the plasma of 10 children with cystathionine beta-synthase deficiency and cerebrospinal fluid of five children before and during betaine therapy. In plasma, betaine significantly lowered total homocysteine (but not to the normal range) and had a variable effect on methionine. In the cerebrospinal fluid, total homocysteine was raised before treatment (mean 1.2 microM) and was significantly reduced by betaine (mean 0.32 microM) but not to the normal range (<0.10 microM). Cerebrospinal fluid methionine was raised before and during treatment, but betaine did not cause a significant further increase. Cerebrospinal fluid serine was significantly reduced before treatment and rose to the normal range with betaine. Cerebrospinal fluid S-adenosylmethionine was normal before treatment and rose significantly with treatment; there were no significant changes in cerebrospinal fluid 5-methyltetrahydrofolate. The demonstration of accumulation of homocysteine within the CNS lends support to the hypothesis that this may be one cause of the neurologic complications of cystathionine beta-synthase deficiency. Betaine is effective in reducing cerebrospinal fluid homocysteine, but concentrations are still significantly raised during treatment.

Adolescent↗

PubMed1997

Evaluation of the effect of fluconazole on the pharmacokinetics of ritonavir.

The effects of fluconazole on the pharmacokinetics of the HIV protease inhibitor ritonavir were investigated after multiple dosing in an open-label study. In this randomized, two-period crossover study, eight healthy subjects received ritonavir alone (200 mg every 6 hr for 4 days) and ritonavir with fluconazole (400 mg on day 1, 200 mg every day on days 2-5) with a 2-week washout period. Ritonavir plasma concentrations were measured during the final four ritonavir dosing intervals (24 hr) and a 12-hr washout period. There were statistically significant increases in ritonavir C(max) and AUC0-24 (p < 0.02), with concurrent administration of fluconazole compared with administration of ritonavir alone. The difference between regimens in C(min) was marginally statistically significant (p = 0.089), and t(max) and beta were not statistically significantly different. Although some ritonavir parameters were affected by fluconazole, mean increases in C(max) and AUC were < or = 15% for the 24-hr period, and only 7-19% for individual dose intervals. Thus, the pharmacokinetics of ritonavir may be influenced only to a small extent when administered with fluconazole. These changes are probably of limited clinical significance and do not necessitate dosage adjustment of ritonavir when fluconazole is added to the regimen.

Adult↗

PubMed1997

Use of fluconazole in the treatment of non-AIDS cryptococcal meningitis.

The treatment of non-acquired immunodeficiency syndrome (AIDS) cryptococcal meningitis has not been well defined as yet. The current recommendation is amphotericin B with or without flucytosine. However, due to the many side effects of these drugs, fluconazole is becoming an attractive alternative in patients who cannot tolerate amphotericin B and flucytosine. This case study demonstrates the successful use of fluconazole in a patient with underlying diabetes mellitus and cryptococcal meningitis.

Aged↗

PubMed1997

Cellular retinaldehyde-binding protein is expressed by oligodendrocytes in optic nerve and brain.

Cellular retinaldehyde-binding protein (CRALBP) is abundant in the retinal pigment epithelium and Müller glial cells of the retina, where it forms complexes with endogenous 11-cis-retinoids. We examined the distribution of CRALBP in extraretinal tissues using polyclonal antibodies (pAb) and monoclonal antibodies (mAb). A protein was detected by immunoblot analysis in extracts of bovine and rat brain and optic nerve but not in several other tissues. This protein had electrophoretic, chromatographic, and retinoid-binding properties identical to those of CRALBP from bovine retina. Comparison of the masses of tryptic peptides and of partial amino acid sequences derived from brain and retinal CRALBP indicated that the two proteins are probably identical. Immunoperoxidase cytochemistry and double labeling immunofluorescence revealed CRALBP(+) cells in brain that resembled oligondendrocytes and not astrocytes, microglial cells, or pinealocytes. In 11-day-old rat brain, approximately 11% of the CRALBP(+) cells were labeled with the Rip antibody, a marker for oligodendroglia. In developing rat optic nerve, the temporal appearance of CRALBP(+) cells corresponded to that of oligodendrocytes and not that of astrocytes. In adult rat and mouse optic nerves, the CRALBP(+) somata showed the same distribution as oligodendrocytes. No endogenous retinoids were associated with CRALBP isolated from dark-dissected adult bovine brain. The results suggest that CRALBP has functions in addition to retinoid metabolism and visual pigment regeneration.

Amino Acid Sequence↗

PubMed1997

The cognitive, subjective, and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints.

We evaluated the effects of a Ginkgo biloba/ginseng combination on cognitive function in this 90-day, double-blind, placebo-controlled, parallel-group study. Sixty-four healthy volunteers (aged 40 to 65 years), selected on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia, were assigned randomly to four equal dosing groups, receiving 80, 160, or 320 mg of the combination b.i.d. or placebo. Assessments were performed on the day before dosing, and again at Days 1, 30, and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose. The assessments included the Cognitive Drug Research (CDR) computerized assessment system, the Vienna Determination Unit, cycle ergometry, and various questionnaires. The treatments were well tolerated by all volunteers. On Day 90 at 1 hour post morning dosing, dose-related improvements were seen on the CDR tests, the 320 mg dose being significantly superior to placebo. These effects, however, were reversed 1 hour after the afternoon dose, possibly suggesting that a longer inter-dosing interval would be preferable. The 80-mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load. There were also several supporting changes from other assessments, including an advantage of 320 mg over placebo on the global score from the Symptom Checklist-90-revised (SCL-90-R) at Day 90.

Adult↗

PubMed1997

Optimal scheduling of interleukin 12 and chemotherapy in the murine MB-49 bladder carcinoma and B16 melanoma.

The antitumor activity of interleukin (IL)-12, a naturally occurring cytokine, has been demonstrated in several murine solid tumors. Animals bearing established B16 melanoma or MB-49 bladder carcinoma were used to study the most effective scheduling of recombinant murine IL-12 (rmIL-12), along with systemic chemotherapy. rmIL-12 (0. 45, 4.5, or 45 microgram/kg) was more effective as a single agent when administered to mice bearing the MB-49 bladder carcinoma at the highest dose for 11 doses rather than for 5 doses. In combination with chemotherapy (Adriamycin, cyclophosphamide, or 5-fluorouracil), rmIL-12 administration did not increase the toxicity of the chemotherapy, and there was increased antitumor activity with each rmIL-12-drug combination. Administering rmIL-12 (45 microgram/kg) on days 4-14, along with Adriamycin, cyclophosphamide, or 5-fluorouracil on days 7-11, resulted in 2.2-2.7-fold increases in tumor growth delay, compared with the chemotherapy alone against the primary tumor, and a marked decrease in the number of lung metastases on day 20. Because the B16 melanoma grows more slowly than the MB-49 bladder carcinoma, allowing multiple courses of chemotherapy, cyclophosphamide could be administered. The rmIL-12 (45 microgram/kg)-cyclophosphamide combination regimen that was most effective overlapped 2 days with the terminal portion of the chemotherapy treatment. There was a parallel increase in the response of the primary tumor and metastatic disease to the lungs. Administration of rmIL-12 to animals bearing the MB-49 bladder carcinoma or the B16 melanoma was compatible with coadministration of chemotherapy at full dose without additional toxicity.

Animals↗

PubMed1996

Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif that binds USF.

The commitment of cells to specific lineages during development is determined in large part by the relative expression of various homeodomain (HOX) selector proteins, which mediate the activation of distinct genetic programs. But the mechanisms by which individual HOX genes are themselves targeted for expression in different cell types remain largely uncharacterized. Here, we demonstrate that STF-1, a homeodomain protein that functions in pancreatic morphogenesis and in glucose homeostasis is encoded by an "orphan" homeobox gene on mouse chromosome 5. When fused to a beta-galactosidase reporter gene, a 6.5-kilobase genomic fragment of 5'-flanking sequence from the STF-1 gene shows pancreatic islet specific activity in transgenic mice. Two distinct elements within the STF-1 promoter are required for islet-restricted expression: a distal enhancer sequence located between -3 and -6.5 kilobases and a proximal E-box sequence located at -104, which is recognized primarily by the helix loop helix/leucine zipper nuclear factor USF. As point mutation within the -104 E-box that disrupt USF binding correspondingly impair STF-1 promoter activity, our results demonstrate that USF is an important component of the regulatory apparatus which directs STF-1 expression to pancreatic islet cells.

Animals↗

PubMed1996

Vestibular compensation: role of visual motion cues in the recovery of posturo-kinetic functions in the cat.

Vision has long been recognized as a sensorimotor system which plays a major role in substitution for functional deficits induced by unilateral or bilateral exclusion of primary vestibular afferents. Little is known, however, about the post-lesion influence of visual inputs on the recovery of posturo-kinetic balance in a situation where fine, well-coordinated locomotor adjustments are required. The present study was carried out in order to gain some insight into the role played by motion vision in the restoration of fine posturo-kinetic balance in adult cats subjected to unilateral vestibular neurectomy. Prior to the lesion, 15 adult animals were trained to cross a beam rotating at various speeds. Their best global balance performance (highest beam rotation speed that did not provoke falling) and their average locomotion speed were evaluated. After the lesion, the cats were separated into three groups: (1) five animals were placed in a normal environment (animal house) (NV cats); (2) four animals were exposed to stroboscopic illumination which eliminated visual motion cues (SV cats) for 2 weeks following the lesion; and (3) three animals were placed in a normal environment and their training was interrupted for the same period as in the SV cats (NVI cats). The possible influence of the 2-week deprivation of visual motion cues on posturo-kinetic balance was also examined in three intact cats. The present behavioral study showed that: (1) early sensory deprivation caused suspension of the posturo-kinetic balance recovery process as long as it was maintained; (2) complete restoration of global balance capacities developed following the vestibular neurectomy after a significant delay in half of the SV cats; (3) the lack of motion cues resulted in severe alterations of fine posturo-kinetic balance (inappropriate dynamic motor adjustments and irregular locomotion speed regulation) in all SV cats; and (4) the visual deprivation induced a 2-week delay in the restoration of fine locomotor balance. These findings provide evidence for a defect in the visual sensory substitution processes that normally take place within the first few weeks following exclusion of primary vestibular afferents.

Animals↗

PubMed1996

Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538).

OBJECTIVE: To define genotypic and phenotypic resistance patterns following prolonged therapy with the protease inhibitor ritonavir (ABT-538). DESIGN: Seven HIV-1-infected patients, all but one previously treated with dideoxynucleoside analogues (zidovudine, didanosine, zalcitabine), were treated for 1 year with ritonavir. METHODS: Direct solid-phase sequencing of the protease gene starting from plasma derived viral RNA followed by comparison to phenotypic drug resistance data. RESULTS: The most frequent amino-acid substitutions occurring upon administration of the protease inhibitor were V82A/F (substrate binding site), I54V (flap region), A71V and L10I. Additional mutations found in more than one patient were I15V, M36I, I84V and I93L. Mutation L63P was found both in pre- and post-ritonavir samples. Phenotypic drug resistance assays confirmed resistance to ritonavir in post-treatment samples (approximately 170-fold) and showed cross-resistance to indinavir (approximately 30-fold) and partially to saquinavir (approximately fivefold). At 1 year of treatment, one patient without known resistance-associated mutations in the protease gene still showed a substantial rise in CD4 cell count accompanied by a more than 2.4 log decrease in RNA viral load. However, at week 78, mutations R8Q, E34K, R57K, L63P and I84V were detected and the treatment benefit was partially lost. CONCLUSIONS: Long-term treatment with ritonavir is associated with the emergence of multiple mutations in the HIV-1 protease gene. The mutations L10I, I54V, L63P, A71V, V82A/F and I84V correspond to known drug-resistance mutations for ritonavir and other protease inhibitors. Phenotypic resistance to ritonavir was detected in a majority of ritonavir-treated patients at 1 year of treatment. In addition, long-term ritonavir treatment selects for cross-resistance to the protease inhibitors indinavir and saquinavir. This argues against sequential therapy with several protease inhibitors. Delayed resistance in one patient was accompanied with a prolonged increase in CD4 cell count and decrease in viral load suggesting a temporary benefit of treatment.

Amino Acid Sequence↗

PubMed1996

Clinical and health service research needs in the group practice organization.

Clinical and health services research will play a more important role in group practice organizations because it provides a vehicle to identify and answer critical questions. Study initiatives can identify, describe, quantify, and help predict trends in clinical practice. Systematic investigation is a means to link structure and processes of care to clinical parameters, patient outcomes, and cost variables. Findings can be used to support sound clinical, quality of care, and educational decision making. The ultimate goal of research is to promote the appropriate access and delivery of quality care in a cost-effective manner.

Costs and Cost Analysis↗

PubMed1996

Use of the polymeric matrix as internal standard for quantitation of in vivo delivery of tetracycline HCl from Actisite tetracycline fiber during periodontal treatment.

Actisite (tetracycline hydrochloride) periodontal fiber is a 23 cm monofilament containing 12.7 mg tetracycline HCl homogeneously dispersed in a polymer. This product is indicated as an adjunct to scaling and root planing to reduce pocket depth and bleeding on probing in patients with adult periodontitis. The sustained-release system, placed in the periodontal pocket for 10 d, releases the antibiotic through mechanisms of diffusion and osmosis. A study was conducted in 13 patients with moderate to severe adult periodontitis to evaluate the amount of tetracycline HCl released during therapy (based on residual drug content). Fibers placed in the pocket remained in place for an average of 9 d. Each patient had 1-4 teeth treated with fiber therapy. At the termination of therapy samples from 29 teeth were retrieved and analyzed. The amount of matrix polymer was used as an internal standard for the quantitation of tetracycline, eliminating any uncertainties with respect to recovery or contamination. An average of 31% (SD 9%) of the tetracycline HCl content was released from the fiber during the treatment period. No single fiber had less than 50% of the original drug remaining. The study demonstrated that a substantial amount of the tetracycline remains in the Actisite fiber at removal (about 70%), which indicates that substantial drug concentrations are maintained in the pocket for the duration of treatment.

Administration, Topical↗

PubMed1996

Human serum alpha 1 acid glycoprotein reduces uptake, intracellular concentration, and antiviral activity of A-80987, an inhibitor of the human immunodeficiency virus type 1 protease.

The therapeutic utility of a human immunodeficiency virus type 1 (HIV-1) protease inhibitor may depend on its intracellular concentration, which is a property of its uptake, metabolism, and/or efflux. Previous studies in our laboratory indicated that the addition of alpha 1 acid glycoprotein (alpha 1 AGP) to the medium markedly increased the amount of the drug required to limit infection in vitro. In this study, physiologically relevant concentrations of alpha 1 AGP and a radiolabeled inhibitor, A-80987, were used to determine both the uptake and activity of the agent in HIV-1-infected human peripheral blood mononuclear cells and cell lines. Both the uptake and efflux of 14C-labeled A-80987 were rapid (t1/2, < 5 min). Uptake of the drug was linearly dependent on the concentration but insensitive to the metabolic inhibitors KF, sodium cyanide, or CCCP (carbonyl cyanide m-chlorophenyl hydrazone). The amount of A-80987 which entered the cells was inversely proportional to the concentration of alpha 1 AGP (r2, 0.99) and directly proportional to the amount of extracellular non-protein-bound drug (r2, 0.99). Most importantly, the antiviral activity of the drug in HIV-1-infected peripheral blood mononuclear cells and MT-2 cells was directly related to the amount of intracellular A-80987. This study demonstrates that A-80987 binds to alpha 1 AGP, resulting in a free fraction below 10%. Cellular uptake of A-80987 is proportionally decreased in the presence of alpha 1 AGP, which results in less-than-expected antiviral activity. Importantly, we demonstrate for the first time that the inhibition of HIV protease is highly correlated with the amount of intracellular inhibitor.

Cell Line↗

PubMed1996

Progression of disease in ocular cicatricial pemphigoid.

BACKGROUND: Ocular cicatricial pemphigoid (OCP) is a sight threatening autoimmune disease that can lead to severe conjunctival cicatrisation and keratopathy. It has a variable course and little is known about the factors that determine disease progression. This study analysed the factors that have prognostic significance regarding disease outcome, progression, and keratopathy. METHODS: Sixty six patients with OCP were monitored prospectively at Moorfields Eye Hospital. The influence of ocular features, the systemic disease, and the management were analysed to identify factors that influence the outcomes and disease progression. RESULTS: The mean age at presentation was 67 years; 56% were men. The binocular visual acuities were 6/24 or worse in 25%. Extensive cicatrisation at presentation was common but correlated only weakly with the visual prognosis. Systemic manifestations included lesions of the mouth in 44%, pharynx in 30%, oesophagus in 27%, nose/sinus in 18%, and skin in 17%. There was no association between the ocular and systemic manifestations. Persistent corneal epithelial defects and limbitis occurred in 18% and 32%, respectively, and both were associated with a worse visual prognosis. Systemic immunosuppression was ultimately prescribed in 74%, mainly in patients with advanced stages of conjunctival cicatrisation. Of patients with more than 24 months follow up, progression of cicatrisation occurred in 35% of eyes (16/46) all but one of which were associated with episodes of conjunctival inflammation. CONCLUSIONS: Persistent epithelial defects, limbal inflammation, and ongoing conjunctival inflammation are important factors that lead to keratopathy and visual handicap. These require aggressive management, often with systemic immunosuppressive treatment. Close follow up is required in cases with extensive cicatrisation.

Adult↗