Navid Ardjomand

Intravitreal VEGF levels in uveitis patients and treatment of uveitic macular oedema with intravitreal bevacizumab

PurposeClinical data suggest a role for VEGF in uveitic cystoid macular oedema (CME), even though the data on intravitreal VEGF levels in these eyes is still inconclusive. We determined intravitreal VEGF levels and treated uveitis patients with intravitreal bevacizumab.MethodsIntravitreal VEGF levels were measured in eight uveitis patients and 10 controls using cytometric bead array technology. In 11 eyes of a second group of uveitis patients, CME was treated using 1.25 mg bevacizumab intravitreally. Re-injections of bevacizumab were given in patients showing a transient positive effect, defined as an increase of the best-corrected vision of at least two lines on a snellen chart. Alternatively, triamcinolone was given in patients, not responding to bevacizumab.ResultsMean intravitreal VEGF concentration was 82.75±171.71 pg/ml (±SD) (range, 0.0–502.1 pg/ml), and below the detection levels in controls. A significant reduction of retinal thickness was seen at weeks 2 (P=0.001) and 4 (P=0.007). A significant improvement in VA was seen at week 2 (P=0.02). Patients presenting with a CME in baseline fluorescein-angiogram responded well towards bevacizumab treatment, unless an extensive leakage from the choroid or a leakage of the optic disk was detectable. In these patients, only intravitreally administered triamcinolone led to a reduction of the CME.ConclusionsOur data suggest that patients presenting with a diffuse leakage from the choroid in the fluorescein angiogram or an extensive leakage of the optic disk should be treated with intravitreal triamcinolone, whereas in patients presenting only a cystoid macular oedema bevacizumab treatment seems like a good choice.

Synthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human explant organ cultures after treatment with latanoprost and dexamethasone.

Purpose: To determine changes in production of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the ciliary body, the trabecular meshwork and the retinal pigment epithelium induced by both prostaglandins and corticosteroids.Methods: Explant organ cultures were removed by a scleral incision 3 mm posterior to the limbus. Retinal pigment epithelium was grown to confluence. Organ and cell cultures were treated with latanoprost and/or dexamethasone for 72 h. The activity of MMP- 2, -3 and -9 was assessed using zymography. The synthesis pattern of MMPs and TIMP-1 and -2 was identified using immunostaining.Results: Treatment of explant organ cultures with 10 μg/ml of latanoprost induced a mean upregulation of MMP-2 by 36%, MMP-3 by 112% and MMP-9 by 156% as seen by zymography. Dexamethasone 500 nm reduced the amounts of secreted MMP-2 by 13%, MMP-3 by 69%. MMP-9 was not detectable in the media of corticosteroid-treated explant organ cultures. The addition of 10 fLg/ml of latanoprost to dexamethasone-treated cultures increased MMP-2 by 14%, MMP-3 by 43% and MMP-9 by 49%. Using immunohistochemistry we found staining with antibodies against MMP-2, -3, -9 and TIMP-1 and -2 within the ciliary body, and only to a lesser degree in the trabecular meshwork. Latanoprost treatment caused an increase of 29% in MMP-2 (p < 0.0001), 98% in MMP-3 (p < 0.0001) and 108% in MMP-9 (p < 0.0001). Dexamethasone reduced the staining for MMP-2 by 32% (p < 0.0001), for MMP-3 by 33% (p < 0.0001) and for MMP-9 by 83% (p < 0.0001). Almost nochange in staining for MMPs was detectable in the trabecular meshwork. Neither latanoprost treatment nor dexamethasone induced significant changes (p < 0.93) in the secretion of TIMPs. In the media of non-treated retinal pigment epithelium (RPE) cells the only MMP detected was MMP-2. RPE cells in culture did not respond to either treatment with a change in their MMP secretion. Conclusion We detected a profound upregulation of both MMP-3 and MMP-9 and a mild induction of MMP-2 through latanoprost in the ciliary body, but not the trabecular meshwork or RPE cells. Corticosteroids, on the other hand, downregulated MMP expression in both tissues. This inhibiting effect of corticosteroids on MMP production was reversed by latanoprost.

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.

MMP-9 is predominantly expressed in epithelioid and not spindle cell uveal melanoma

Extracellular matrix‐degrading enzymes are crucial for cancer metastases. One group of enzymes that has been increasingly implicated in the breakdown of the extracellular matrix, and hence the intravasation and dissemination of tumour cells, is the family of metalloproteinases. In the recent past, increasing efforts have led to the development of more or less specific matrix metalloproteinase (MMP) inhibitors. Data concerning the molecular nature and timing of the contribution of MMPs to tumour spread is of paramount importance in clarifying which MMP is an appropriate target for more selective MMP inhibition in future tumour therapy. This study immunohistochemically characterized the expression pattern of MMP‐2, ‐3, and ‐9 in 26 uveal melanomas. Forty‐six per cent of the uveal melanomas expressed MMP‐2 and/or MMP‐9. MMP‐3 expression was seen in 17 out of 26 uveal melanomas. MMP‐9, previously shown to play an important part in tumour dissemination, was predominantly present in epithelioid melanomas (71.4%) or the epithelioid portion of mixed cell uveal melanomas (67%), whereas only one out of ten spindle cell melanomas showed MMP‐9 expression (10%). MMP‐2 and MMP‐9 expression was associated with a significantly higher incidence of metastatic disease. The survival rate of patients with MMP‐2‐positive melanomas was 31% vs. 85% for patients with MMP‐2‐negative (p<0.05); for MMP‐9‐positive uveal melanomas the survival rate was 27% vs. 85% with MMP‐9‐negative uveal melanomas (p<0.04). The fact that patients suffering from TIMP‐1‐ as well as TIMP‐2‐positive uveal melanomas tended to show a better survival rate (72% vs. 45% for TIMP‐1; 88% vs. 37% for TIMP‐2) supports the view that proteolytic enzymes are of importance in tumour spread. Copyright

Loss of corneal Langerhans cells during storage in organ culture medium, optisol and McCarey-Kaufman medium

Purpose This study compares the influence of different corneal preservation media on HLA-DR positive corneal Langerhans cells (LCs).Methods Using fluorescence-associated immunohistochemistry, corneal sections were stained for HLA-DR antigens after preserving corneal-scleral discs in three different storage media: organ culture medium, Optisol and McCarey-Kaufman medium. HLA-DR positive LCs were present in corneal epithelium and upper stroma of fresh corneas.Results A storage period of even 3 days had a significant influence on the number of HLA-DR positive corneal LCs. The number of LCs decreased at the limbus from 15.3 ± 4.1 LCs/0.25 mm2 to 11.8 ± 1.2 LCs/0.25 mm2 (p<0.01) during preservation in McCarey-Kaufman medium, to 11.2 ± 1.9 LCs/0.25mm2 (p<0.01) during preservation in organ culture medium and to 12.7 ± 3.4 LCs/0.25 mm2 (p<0.01) during preservation in Optisol. A greater loss was detected after 7 days and we found a cell number of 1.6 ± 1.1 LCs/0.25 mm2 (p<0.001) after storage in organ culture medium and of 1.4 ± 1.5 LCs/0.25 mm2 (p<0.001) after storage in Optisol. The donor tissues entirely lacked HLA-DR positive LCs, regardless of the preservation medium used, when stored for up to 14 days.Conclusion These results demonstrate that loss of HLA-DR antigens is mainly related to storage period and is independent of the type of preservation medium and preservation temperature.

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.

Long-term follow-up with I-care phakic IOLs

Aim To evaluate visual quality and postoperative results as well adverse events in myopic patients undergoing I-CARE anterior-chamber angle-supported phakic intraocular lens (IOL) implantation. Design A retrospective, non-randomised, case series. Participants Data on 29 eyes (16 patients) receiving I-CARE phakic IOL for high myopia (–11.66±3.3) were analysed. Methods The IOLs were implanted between 2003 and 2006 at the Department of Ophthalmology, Medical University, Graz, Austria. The mean follow-up was 51.7±16 months (17–78 months). Main outcome measures The authors measured uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA); patients underwent slit-lamp examination, corneal topography, Scheimpflug imaging and measurement of endothelial cells (EC). Results The mean UCVA and BCSVA were 0.63 and 0.94 decimal after 1 year. Endothelial cell loss was the most serious adverse event observed. The mean EC loss was 2%, 9%, 17%, 21%, 33% and 47% after 1 year (n=17), 2 years (n=20), 3 years (n=17), 4 years (n=17), 5 years (n=12) and 6 years (n=3), respectively. Eight IOL explantations were made due to severe EC loss 3–6 years after implantation. Other serious complications included one patient with Urrets–Zavalia Syndrome (one eye). Conclusion Implantation of the I-CARE phakic-IOL is not a safe method for the correction of high myopia due to serious endothelial cell loss that might occur in a high number of patients. Patients with these IOLs should be followed up at least every 6 months, and the IOL should be explanted, once the EC count drops to less than 2000 cells/mm2.

Bedeutung der Gewebslagerzeit für den Erfolg nach kornealer Transplantation

Hintergrund: Das HLA-DR-Antigen nimmt in der Transplantationsimmunologie eine Schlüsselrolle ein. Die Organkulturlagerung führt zum Verlust HLA-DR-positiver kornealer Langerhans-Zellen. Die voriegende Arbeit untersucht die Bedeutung einer verlängerten kornealen Lagerzeit für den Erfolg einer perforierenden Keratoplastik.Patienten und Material: 84 Patienten mit 99 perforierenden kornealen Transplantationen wurden retrospektiv untersucht. Wir unterteilten das Patientenkollektiv in 2 Gruppen: Die Patienten aus der Gruppe 1 erhielten Spendermaterial mit einer durchschnittlichen Hornhautlagerzeit von 1,9 Tagen (±1,4), die Lagerzeit in Gruppe 2 betrug 9,8 Tage (±4,7).Ergebnisse: Nach 18 Monaten waren bei den Hochrisikopatienten in der Gruppe 1 34,4% (±8,7), in der Gruppe 2 69,2% (±12) (p<0,01) der Transplantation erfolgreich. Bei den Niedrigrisikopatienten war die Erfolgsrate 72,7% (±8,2) in Gruppe 1 und 91% (±6,1) in Gruppe 2 (p<0,01).Schlußfolgerung: Wir hatten signifikant bessere Ergebnisse bei Patienten mit einer längeren Gewebslagerzeit (9,8 Tage) verglichen mit denen der Gruppe 1 (1,9 Tage). Diese Resultate dürften auf den Verlust HLA-DR-positiver Zellen während der verlängerten Hornhautkonservierungszeit zurückzuführen sein.Background: HLA-DR antigen plays a key role in transplantation immunology. Organ culture storage leads to loss of HLA-DR-positive corneal Langerhans cells. This study investigates the importance of prolonged storage period for the success rate after penetrating keratoplasty.Patients and material: Eighty-four patients with 99 penetrating corneal transplantations were examined retrospectively. Group 1 represented keratoplasty patients with an average corneal storage period of 1.9 days (±1.4) and in group 2 the patients received tissues stored for 9.8 days (±4.7).Results: The success rate of high-risk patients was 34.4% (±8.7) in group 1 and 69.2% (±12) in group 2 after 18 months (p<0.01). In non-risk patients we had a success quota of 72.7% (±8.2) in group 1 and 91% (±6.1) in group 2 (p<0.01).Conclusion: We found significantly better results in patients receiving tissues stored for an average time of 9.8 days than in those receiving corneas preserved for 1.9 days. The results are thought to be based on the loss of HLA-DR-positive cells during prolonged organ culture preservation.

IL2RA gene polymorphism rs2104286 A>G seen in multiple sclerosis is associated with intermediate uveitis: possible parallel pathways?

PURPOSE Uveitis is a major cause for visual impairment. Inflammation-related gene polymorphisms have previously been shown to confer susceptibility to different types of uveitis. Recently, IL-2 receptor alpha (IL2RA, also called CD25) and IL-7 receptor alpha (IL7RA) gene variants (rs2104286, rs12722489, and rs6897932) have been identified to play an essential role in the pathogenesis of immune-mediated diseases. Their role in uveitis, however, has not yet been studied. The present study was set to investigate a hypothesized association of these gene polymorphisms and the presence of either intermediate or HLA-B27-associated acute anterior uveitis. METHODS One hundred forty-five patients with HLA-B27-associated acute anterior uveitis (AAU), 84 patients with intermediate uveitis, 132 HLA-B27-negative controls, and 61 HLA-B27-positive controls were enrolled. Determination of genotypes was done by polymerase chain reaction. RESULTS The frequency of carriers of the minor allele for rs2104286 was significantly lower in patients with intermediate uveitis compared with HLA-B27 positive and negative controls combined (P = 0.006). Frequencies of the minor allele for rs2104286 did not differ significantly in patients with HLA-B27-associated uveitis (28.3%) when compared with HLA-B27-negative controls (24.2%; P = 0.29) and HLA-B27-positive controls (30.3%; P = 0.72). The rs12722489 and rs6897932 polymorphisms were not significantly associated with either investigated uveitis entity (P > 0.005). CONCLUSIONS These findings suggest an association of the rs2104286 polymorphism with intermediate uveitis, but not with HLA-B27-associated acute anterior uveitis. Because this polymorphism was associated with multiple sclerosis in previous studies, the authors suggest possible parallel pathways between multiple sclerosis and intermediate uveitis but not HLA-B27-associated uveitis.

Adverse skin reactions to infliximab in the treatment of intraocular inflammation

TNFα inhibitors are more widely used in the treatment of intraocular inflammation, thus ophthalmologists should become aware of possible adverse events, associated with this form of treatment. Herein we report two cases of cutaneous adverse events in uveitis patients treated with infliximab. In one patient, the primary outbreak of pustular psoriasis was observed after her third infusion. A second patient developed impetigo contagiosa induced by Staphylococcus aureus. Thus patients undergoing treatment with infliximab should be monitored carefully since dermal infections and pustular psoriasis, which may be triggered by streptococcal infection, may occur under this regime.