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Biomedical subjects

Navid Ardjomand

Publications and source records attributed to Navid Ardjomand.

17 recordsLinked to original sources

Keratitis after intracorneal ring segment insertion for keratoconus.

We report a case of sterile keratitis after Ferrara intracorneal ring (Ferrara Ophthalmics) implantation into the right cornea of a keratoconus patient who also suffered from atopic blepharoconjunctivitis. The keratitis resolved within a few days after removal of the Ferrara rings. Ocular atopy with sterile keratitis should be considered in the differential diagnosis of keratitis after the insertion of intracorneal ring segments, which can be easily treated by ring removal.

Adult↗

Polymorphisms within the tumor necrosis factor-alpha promoter region in patients with HLA-B27-associated uveitis: association with susceptibility and clinical manifestations.

PURPOSE: The existence of genetic variations in a number of cytokines has been considered to influence susceptibility or relate to disease severity in various autoimmune diseases. Among these, single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor alpha (TNF-alpha) promoter at nucleotides -308 and -238 are considered to be protective against inflammation in HLA-B27-positive individuals, whereas the SNP at position -857 has been associated with disease development in anterior uveitis. We investigate a hypothesized association between the TNF-alpha -857 C-to-T, -308 G-to-A, and the TNF-alpha -238 G-to-A SNPs and the presence of HLA-B27-associated uveitis. DESIGN: Retrospective case-control study. PARTICIPANTS: One hundred fourteen Caucasian patients with HLA-B27-associated uveitis were studied. Mean age of patients was 44.9+/-14 years (range, 16-81), and mean duration of HLA-B27-associated uveitis was 115.6+/-104 months (range, 6 months-51 years). Eighty-six patients (75.4%) suffered from an additional systemic manifestation of the disease. Sixty-three unrelated healthy HLA-B27-positive blood donors and 88 unrelated healthy HLA-B27-negative individuals served as controls. METHODS: Genotypes were determined by polymerase chain reaction. MAIN OUTCOME PARAMETERS: Association of genotypes at positions -857, -308, and -238 of the TNF-alpha gene with disease development. RESULTS: Frequencies of the TNF-alpha -308GA and TNF-alpha -238GA genotypes were significantly lower in patients with HLA-B27-associated uveitis (6.1% and 0%, respectively) when compared with the HLA-B27-negative control group, 23% at -308 (P = 0.003), and 7.9% at -238 (P = 0.0003). When compared with healthy HLA-B27-positive controls, a significantly lower frequency of the TNF-alpha -238GA genotype was found among patients (6.3%, P = 0.015). The frequency of the TNF-alpha -308GA genotype was also found to be lower in patients than among HLA-B27-positive control subjects, without, however, reaching statistical significance (6.1%, P = 0.07). No difference in frequencies was seen among the different groups for the SNPs at position -857. CONCLUSION: Our data suggest that HLA-B27-positive individuals show a higher susceptibility towards development of an intraocular inflammation in the presence of an A allele at nucleotide -238 and, to a lesser degree, at nucleotide -308 of the TNF-alpha gene promoter.

Adolescent↗

Role of the CCL2/MCP-1 -2518A>G gene polymorphism in HLA-B27 associated uveitis.

PURPOSE: Acute anterior uveitis (AAU) is the most common form of uveitis. Up to 50% of patients with AAU are HLA-B27 positive. Since HLA B27 itself plays only a minor role in the overall genetic background, other genetic variants are likely to contribute to the susceptibility to AAU. The chemokine (C-C motif) ligand 2 (CCL2) gene, coding for monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine, is involved in the induction of uveitis. A CCL2 gene polymorphism, which is characterized by an A>G substitution at nucleotide -2518 in the promoter region of CCL2 has been previously shown to affect MCP-1 synthesis. The purpose of the present study was to investigate a hypothesized association between this genetic variant and the presence of HLA-B27 associated AAU. METHODS: The study group comprised 114 patients with HLA-B27 associated AAU. One hundred and eleven healthy HLA-B27 positive individuals served as the HLA-B27 positive control group, whereas 81 healthy HLA-B27 negative individuals served as a HLA-B27 negative control group. Genotyping for the CCL2 -2518A>G polymorphism was performed by polymerase chain reaction. RESULTS: Carriers of a CCL2 -2518G allele were found significantly more often in patients with HLA-B27 associated AAU than among HLA-B27 positive controls (49.2% and 31.5%, respectively; odds ratio 2.1; 95% confidence interval 1.2-3.6; p=0.007). CONCLUSIONS: Our data suggest that the CCL2 -2518A>G polymorphism may play a role in HLA-B27 associated acute anterior uveitis.

Acute Disease↗

Comparison of HIV-1 and EIAV-based lentiviral vectors in corneal transduction.

In this study we compare the ability of self-inactivating Human Immunodeficiency Virus 1 (HIV-1) and Equine Infectious Anaemia Virus (EIAV)-based vectors to mediate gene transfer to rabbit and human corneas and to a murine corneal endothelial cell line. Both vectors were pseudotyped with vesicular stomatitis virus-G (VSV-G) envelope and contained marker transgenes under the control of an internal CMV promoter. For specificity of action, the heterologous promoter in the EIAV-vector was exchanged for an inducible E-Selectin promoter, previously shown to regulate gene-expression in a plasmid system. We show that EIAV is more efficient than HIV in transducing human and rabbit corneal endothelial cells. Rabbit corneal endothelial cells are transduced in higher quantity than human corneal endothelial cells. In the inducible system, however, we detected impairment between the vector and its internal E-Selectin promoter. Instead of controlled transgene expression or silencing of promoter activity, the U3-modified long-terminal-repeats (LTR) impaired the conditional activity of the E-Selectin promoter. Significant transgene expression was seen without stimulation of the inducible promoter. We show efficient transduction by lentiviruses of a corneal endothelial cell line and of full thickness corneas from different species, confirming that those vectors would be appropriate tools for gene therapy of selected corneal diseases. However, the modification within the U3-LTR did not adequately allow regulated transgene expression. These findings have important implications for vector design for diagnostic or therapeutic opportunities.

Animals↗

Pupil ovalization after phakic intraocular lens implantation is associated with sectorial iris hypoperfusion.

OBJECTIVE: To investigate iris perfusion in patients with and without pupil ovalization after phakic intraocular lens implantation. METHODS: Comparative retrospective randomized case series of 6 participants, each with a regular pupil, and 6 participants with pupil ovalization after phakic intraocular lens implantation for high myopia were included in the study. Indocyanine green angiography was performed between 20 and 40 months (mean +/- SD, 26 +/- 6.1 months) after lens implantation. RESULTS: Iris perfusion defects were found in 5 of 6 patients with pupil ovalization. No perfusion deficits were noted in patients with round pupils. CONCLUSION: Iris ovalization after phakic intraocular lens implantation may be associated with a lack of iris perfusion and with secondary ischemia. Patients with these lenses and pupil ovalization should be followed regularly.

Adult↗

Lymph node metastases arising from uveal melanoma.

Since the eye lacks lymphatic vessels, uveal melanomas primarily metastasize hematogenously. Here we report the case of a patient with ciliary body ring melanoma who developed lymph node metastases after a fistulating glaucoma operation. A 40-year-old female Caucasian patient presented with unilateral pigment dispersion. Pigment dispersion glaucoma was diagnosed and since the intraocular pressure could not be managed with topical medication, transscleral cyclophotocoagulation and two trabeculectomies had to be performed. Due to enlargement of the pigmented iris mass and cell deposits in the chamber angle, a ciliary body ring melanoma was presumed and the eye enucleated. Histology confirmed the diagnosis of "ciliary body ring melanoma". Six months after enucleation the patient presented multiple metastases including ipsilateral preauricular and submandibular lymph node metastases. The patient died two months later. Lymph node metastases arising from ciliary body melanomas are very rare. Tumor seeding through the trabeculectomy site into the bleb and then via conjunctival lymphatic vessels might be the crucial factor for this pathway of metastases. Therefore, in cases of unilateral pigment dispersion, malignancy should be excluded before fistulating operations are performed.

Adult↗

Keratopathy after ultraviolet B phototherapy.

Atopic dermatitis is the most common chronic inflammatory skin disease among children in industrialized countries. The prevalence is recorded to be up to 20% in children. Phototherapy with ultraviolet B (UVB) is an effective form of treatment with a low complication rate. Here we report on a patient with atopic dermatitis who underwent UVB treatment to the facial area including the eyelids and who developed severe keratitis with facial erythema. The symptoms diminished within a few days under topical steroid treatment. Although phototherapy seems to be a safe treatment procedure for atopic dermatitis, patients undergoing UVB treatment should be informed about possible side effects if the eyes are not fully closed during treatment. The use of protective eye shields should be considered, since UVB might induce long-term corneal damage and early onset of cataract.

Anti-Bacterial Agents↗

Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients.

Tyrosinase-based reverse transcriptase-polymerase chain reaction (RT-PCR) is a method for the detection of circulating melanoma cells in peripheral blood. To our knowledge, no long-term studies on the prognostic impact of tyrosinase PCR in uveal melanoma have yet been reported. In this prospective, non-randomized, observational cohort study, we included 41 patients with uveal malignant melanoma. RT-PCR for tyrosinase was performed in each patient before and after treatment. A clinical follow-up was performed for each patient for at least 5 years, including chest X-ray, serum liver enzyme determination, ultrasound of the liver and bone scintigraphy. The PCR results, age of the patients, tumour size, tumour location, tumour therapy, internal reflectivity, histology, development of distant metastasis and survival rate during follow-up were analysed. At the time of diagnosis, tyrosinase messenger RNA (mRNA) in peripheral blood, suggesting the presence of circulating melanoma cells, was detected in 16 of the 41 patients. Sixty-nine percent of the PCR samples with a positive result prior to therapy revealed a negative result after therapy. The internal reflectivity of the tumour (P=0.021) and the 5-year survival (P=0.023) showed a statistically significant association with positive PCR. It can be concluded that tyrosinase RT-PCR is a sensitive method for the detection of melanoma cells in peripheral blood. This study indicates that the presence of tumour cells in peripheral blood correlates with 5-year survival. Our results suggest a prognostic value of this method. Nevertheless, prospective analysis of a larger cohort is needed to determine the ultimate value of RT-PCR for tyrosinase in blood testing.

Adult↗

Phototherapeutic keratectomy with an epithelial flap for recurrent erosion syndrome.

Phototherapeutic keratectomy (PTK) is an acceptable technique to treat recurrent erosion syndrome. Its disadvantage is postoperative pain. We present a modified technique to reduce the immediate pain from removal of the epithelium after PTK. Nine patients with recurrent erosion syndrome had PTK with epithelial reflap (similar to laser-assisted subepithelial keratectomy) and contact lens application. The follow-up was 6 months. No patient reported severe postoperative pain. Three of 9 patients reported mild pain during the first 24 hours postoperatively. The best spectacle-corrected visual acuity was 0.40 to 0.63 logMAR on the first postoperative day and 0.80 to 1.00 logMAR after a week. No patient developed recurrent erosion.

Adult↗

Influence of donor storage time on corneal allograft survival.

PURPOSE: To investigate the influence of graft storage time on corneal allograft survival in high-risk and low-risk patients. DESIGN: Comparative retrospective nonrandomized clinical trial. PARTICIPANTS: Overall, 193 patients with 210 corneal allografts were classified as high risk or low risk for corneal allograft rejection on the basis of recipient corneal neovascularization and number of ipsilateral transplants. METHODS: Data from 3 groups were evaluated. The first group received fresh (no storage in culture medium) corneas, the second received corneas of donor storage time less than 7 days in minimum essential medium (MEM) at 37 degrees C, and the final group received corneas stored in MEM longer than 7 days. Recipients were analyzed for development of immune rejection according to storage time of the corneal tissue. Corneal allograft survival rate was determined with Kaplan-Meier survival analysis. The log-rank test was used to determine statistical significance. MAIN OUTCOME MEASURES: Risk of reversible and irreversible allograft rejection in corneas stored at various intervals in high-corneal and low-corneal transplant patients. RESULTS: High-risk corneal allograft recipients had a significantly prolonged allograft survival when the tissue was stored for 7 days or greater, compared with recipients receiving fresh tissues. Patients at low risk of corneal allograft rejection also showed a tendency for prolonged survival, although not statistically significant (P = 0.06). CONCLUSIONS: Storage of corneal tissue may reduce the frequency of allograft rejection, especially in high-risk patients.

Adolescent↗

Expression of somatostatin receptors in uveal melanomas.

PURPOSE: To investigate the distribution of somatostatin receptor (SSR) subtypes 2, 3, and 5 in uveal melanomas and their diagnostic and possible therapeutic value. METHODS: SSRs were investigated in 25 paraffin-embedded eyes with uveal melanomas and in 6 normal eyes without any disease, by using polyclonal antiserum directed to SSR2A, -2B, -3, and -5. Antigen expression was evaluated by a semiquantitative method. The expression pattern of SSR was correlated with the patients' ad vitam prognosis by use of the Kaplan-Meier survival curve. Six different human melanoma cell lines were incubated with octreotide and vapreotide, and a proliferation assay was performed by determining [(3)H]-TdR uptake. [111-Indium-DTPA-D-Phe1]-octreotide scintigraphy was performed in the eyes of four patients with known uveal melanomas. RESULTS: All uveal melanomas were positive for SSR2. SSR2A was expressed in 15 of 25, SSR2B in 23 of 25, SSR3 in 7 of 25, and SSR5 in 13 of 25 uveal melanomas. A Kaplan-Meier survival curve showed a significantly better ad vitam prognosis for patients with tumors expressing high levels of SSR2. Cell proliferation was inhibited up to 36% +/- 6% in three of six melanoma cell lines at a concentration of 10(-4) M octreotide or vapreotide. Eyes of two patients with uveal melanomas showed positive uptake of [111-Indium-DTPA-D-Phe1]-octreotide. CONCLUSIONS: SSR2, -3, and -5 are expressed in human uveal melanomas and patients with a high amount of SSR2 in the melanoma tissue have a better ad vitam prognosis. Because a melanoma cell proliferation assay showed an inhibitory effect of up to 36% +/- 6% using octreotide or vapreotide, somatostatin analogues may be beneficial in the treatment of patients with ocular melanomas.

Aged↗

Modulation of costimulation by CD28 and CD154 alters the kinetics and cellular characteristics of corneal allograft rejection.

PURPOSE: To examine the effect of modulating the lymphocyte costimulation pathways through CD28 and CD154 (CD40 ligand) in a model of corneal allograft rejection, with particular interest in changes in the observed features of rejection. METHODS: CD28 knock-out (CD28KO) and wild-type BALB/c control mice received corneal grafts from fully major histocompatibility complex (MHC)-mismatched C3H donors and were treated with CTLA4-Ig and/or anti-CD154 Ab on days 0, 2, and 4 after transplantation. Proliferation of BALB/c and CD28KO T cells in response to C3H stimulators was examined in a mixed lymphocyte reaction (MLR) in the presence of CTLA4-Ig or anti-CD154 Ab. RESULTS: Corneal allograft survival in wild-type BALB/c mice (median survival time [MST] 14 days) was significantly prolonged by blockade of the costimulatory pathways with CTLA4-Ig or anti-CD154 Ab (MST 21 days and 25 days respectively). MST in recipients treated with CTLA4-Ig and anti-CD154 Ab in combination was 29 days, not significantly longer than graft survival in single-treatment groups. MST in CD28KO recipients was 46 days and was not prolonged after treatment with anti-CD154 Ab (MST, 43 days). A similar result was found in the MLR, in which anti-CD154 Ab had no effect on proliferation of CD28KO compared with wild-type T cells. In CTLA4-Ig-treated CD28KO, grafts were rejected at an accelerated tempo, similar to that in wild-type BALB/c recipients (MST 16 days). More severe graft injury after the onset of rejection in untreated allograft recipients was accompanied by a higher number of graft-infiltrating CD45(+) cells, but similar proportions of CD4(+) and CD8(+) cells. CONCLUSIONS: CD28- and CD154-mediated costimulation have significant functional roles in corneal allograft rejection. Agents that modulate CD28 and CD154 pathways delay onset and reduce the severity of observed allograft rejection. However, their use in combination did not have an additive effect, MLR data indicating that the CD40-CD154 system depends on a functioning CD28 costimulatory pathway.

Abatacept↗

Coinfection of the retina by Epstein-Barr virus and cytomegalovirus in an AIDS patient.

PURPOSE: To report an immunohistochemically proven case of a coinfection of the retina by Epstein-Barr virus and cytomegalovirus in a patient with acquired immunodeficiency syndrome (AIDS). DESIGN: Interventional case report. METHODS: Postmortem evaluation of retinal tissue of a 45-year-old female AIDS patient with atypical fibrinous iridocyclitis and vitritis in course of a cytomegalovirus retinitis in the left eye was performed for evidence of dual infection with cytomegalovirus and other herpes group viruses. Immunohistochemical examination with double-staining techniques and antibodies against Epstein-Barr virus and cytomegalovirus was used. RESULTS: In the retina of the left eye, cells reacting with antibodies against cytomegalovirus and cells stained with antibodies against Epstein-Barr virus were detected in the layer of ganglionic cells and the inner granular cell layer. CONCLUSION: Epstein-Barr virus coinfection should be taken into consideration in unusual cases of necrotizing cytomegalovirus retinitis in AIDS patients.

AIDS-Related Opportunistic Infections↗

Pupillary block after phakic anterior chamber intraocular lens implantation.

A 49-year-old patient developed pupillary block glaucoma with an intraocular pressure (IOP) of 29 mm hg after implantation of a phakic intraocular lens (IOL) (NuVita, Bausch & Lomb) in the left eye. the anterior chamber deepened again, and the iop decreased to 16 mm hg after a neodymium: YAG iridotomy. Pupillary block glaucoma may occur after phakic IOL implantation without iridotomy, and we advocate that routine iridotomy be performed during phakic IOL surgeries.

Anterior Chamber↗

Effect of administration of CTLA4-Ig as protein or cDNA on corneal allograft survival.

PURPOSE: To examine the role of the CD28-CD80-CD86 pathway of T-lymphocyte costimulation in corneal allograft rejection and the effect of blockade of that pathway on graft survival. METHODS: Kinetics of CD80 and CD86 expression in the cornea and draining lymph nodes were examined by RT-PCR and immunohistochemistry in untreated allograft recipients in a high-responder rat model. The effect of blockade of CD28-mediated costimulation was first examined by ex vivo incubation of excised Brown Norway rat donor cornea with the inhibitory protein CTLA4-Ig or an adenovirus vector (AdCTLA) expressing CTLA4-Ig, before grafting into Lewis rat recipients. A second group of graft recipients received systemic posttransplantation treatment with either CTLA4-Ig or AdCTLA. RESULTS: Expression of CD80 mRNA was increased in both donor and recipient cornea 16 hours after transplantation, whereas CD86 was detected constitutively, with no significant early increase. Immunohistochemistry on day 5 after transplantation demonstrated major histocompatibility complex (MHC) class II expression, no CD80, and only a trace of CD86 in corneal allografts. In lymph nodes strong MHC class II, weak CD80, and moderate CD86 expression was noted. Both donor cornea and recipient treatment with CTLA4-Ig resulted in prolonged allograft survival. AdCTLA was found to induce sustained secretion of bioactive CTLA4-Ig from corneas infected ex vivo. Survival of corneal allografts incubated with AdCTLA was marginally prolonged, and systemic treatment with AdCTLA significantly prolonged survival. CONCLUSIONS: Protein- or gene-based administration of CTLA4-Ig prolongs allograft survival by treatment of either the recipient or the donor tissue ex vivo before grafting.

Abatacept↗