Laser-assisted subepithelial keratomileusis with mitomycin C for myopic astigmatism ≥2.00 diopters using a Zeiss MEL 80 Excimer.

To examine the refractive and visual outcome of laser-assisted subepithelial keratomileusis (LASEK) with mitomycin C(MMC) in eyes with myopic astigmatism ≥2.00 diopters (D). This study comprised 82 eyes of 82 consecutive patients (37 male, 45 female; mean age at surgery 34.7 ± 9.0 years) with preoperative topographic astigmatism ≥2.00 D and mean preoperative spherical equivalent (SE) -4.50 ± 1.13 D. To assess whether the refractive results differed with the amount of corrected sphere, the data were separated by preoperative SE thereby defining two groups with SE < -5.00 D (-2.00 to -4.75 D) and ≥-5.00 D (-5.00 to -7.75 D). Mean manifest refraction spherical equivalent (MRSE) of -0.39 ± 0.52 D was obtained at the 6-months (5.4 ± 1.6 months) follow-up. The results were within ±1.00 D of the attempted correction in 89 % of patients. The mean postoperative corrected distant visual acuity was -0.02 ± 0.065 logMAR (range -0.10 to 0.15 logMAR). Sixty-seven (81.7 %) of all eyes did not change lines in safety. There was no statistically significant difference (P = 0.262) in safety between the SE groups. Mean efficacy was 0.89 ± 0.27. There was a statistically significant difference in efficacy (P = 0.024) between the preoperative SE groups. Larger ablation zones were associated with better visual outcome, confirmed by safety, efficacy and predictability. The data reported here demonstrated that LASEK using a Zeiss MEL 80 excimer laser with an additional application of MMC is a safe and efficient technique with predictable results for the correction of eyes with myopic astigmatism ≥2.00 D.

[Refractive predictability and stability of three-piece versus single-piece intraocular lenses in patients with high axial myopia]. / Refraktive Vorhersagbarkeit und Stabilität von 3-teiligen vs. 1-teiligen Intraokularlinsen bei hoher Achsenmyopie.

BACKGROUND: Based on previous data on single-piece and three-piece intraocular lenses (IOLs) there is no evidence for significant differences in decentration, tilt and refractive shift. The purpose of the current study was to compare single-piece and three-piece IOLs in patients with high axial myopia. MATERIAL AND METHODS: A total of 68 eyes of 50 patients with high axial myopia (axis length ≥ 28.00 mm) with and without cataract who underwent complication-free phacoemulsification and IOL implantation were retrospectively examined. To compare single-piece and three-piece IOLs, the patients were retrospectively grouped depending on IOL type: group 1 acrylic single-piece IOL (n = 37; ACR6D SE, Corneal, France) and group 2 acrylic three-piece IOL with fixed haptic frame (n = 31; AF-1 UY, Hoya, Japan). Patient files were analyzed regarding best spectacle-corrected visual acuity (BSCVA), refractive predictability and stability. RESULTS: In this study the mean BSCVA was determined as 0.22 ± 0.12 logMAR and 0.13 ± 0.11 logMAR 6 months postoperatively for the ACR6D SE group and the AF-1 UV group, respectively (p = 0.09). Refractive predictability was less accurate in the ACR6D SE (+ 1.75 ± 2.2 dpt) compared to the AF-1 UV (- 0.37 ± 1.1) treated eyes (p = 0.001). Refractive stability, defined as the difference in diopters between the first week and the sixth month after surgery, resulted in + 0.40 ± 1.7 dpt and -0.16 ± 1.2 dpt for the ACR6D SE and the AF-1 UV, respectively (p = 0.022). CONCLUSIONS: The three-piece AF-1 UV showed satisfactory refractive predictability and stability in patients with high axial myopia. The ACR6D SE has a high refractive unpredictability and should not be used in eyes with high axial myopia.

Near-infrared autofluorescence and indocyanine green angiography in central serous chorioretinopathy.

PURPOSE: To evaluate the diagnostic potential of near-infrared (NIR) autofluorescence (AF) in central serous chorioretinopathy (CSC) and to present a method to analyze NIR-AF findings quantitatively. PROCEDURES: NIR-AF images, indocyanine green (ICG) angiograms, blue-light autofluorescence (BL-AF) images and fluorescein angiograms were recorded with the use of a confocal scanning laser ophthalmoscope in 19 eyes of 17 patients with CSC. Gray-value ratios were calculated to compare the methods. RESULTS: Using NIR-AF, hypofluorescent spots were observed at the leakage site in 18 of 19 eyes (94.7%). The mean gray-value ratio (±SD) was 0.55 ± 0.22 for the site of the leakage point with NIR-AF and 0.65 ± 0.35 with BL-AF. ICG angiography showed a gray-value ratio of 2.37 ± 2.07. Fluorescein angiography had the best contrast, with a gray-value ratio of 13.44 ± 15.02. CONCLUSION: NIR-AF demonstrated CSC in 94.7% of the cases. NIR-AF may be a noninvasive alternative to detect CSC.

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

PURPOSE: Clinical 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. METHODS: Intravitreal 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. RESULTS: Mean 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. CONCLUSIONS: Our 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.

[Visual function with blue light filter IOLs]. / Visuelle Funktion mit Blaulichtfilter-IOL.

BACKGROUND: Recently, intraocular lenses (IOLs) with a blue light filter have been introduced to protect the retina from age-related macular degeneration (AMD) after cataract extraction. A reduction of longitudinal chromatic aberration by filtering blue light may enhance patient's visual function. In this study we compared subjective and objective parameters of visual function following implantation of blue light filter (yellow) IOLs and IOLs of the same design without filter. PATIENTS AND METHODS: 21 patients (21 eyes) underwent implantation of an IOL with a blue light filter (AF-1 UY, Hoya, Japan), 22 patients (22 eyes) received an IOL without blue light filter (AF-1 UV, Hoya, Japan). Patients were examined three months postoperatively for uncorrected and best corrected spectacle visual acuity, mesopic and photopic contrast sensitivity, colour vision and subjective quality of vision by a standard questionnaire. RESULTS: Eyes with blue light filter IOLs did not show any significant difference in any parameter analysed when compared to eyes without the blue light filter IOL. Subjective quality of vision was considered to be high by all patients and no significant difference was observed between the two IOL groups. CONCLUSION: The visual function of patients with blue filter IOLs is not significantly different to those without blue light filter IOLs. Since blue light filter IOLs did not show any functional disadvantage, but potentially protect the macula from AMD, blue light filter IOLs may be considered as a reasonable alternative to traditional IOLs, especially in eyes with a high risk for the development of macular degeneration.

Lamellar corneal dissection for visualization of the anterior chamber before triple procedure.

PURPOSE: Open-sky cataract extraction during triple procedure can be associated with higher risk of complications owing to the missing counterbalance by the cornea. Herein, we present a fast and easy technique for visualization of the anterior chamber and the lens in eyes with opaque corneas planed for triple procedure. MATERIALS AND METHODS: Four patients with corneal oedema due to Fuchs' endothelial dystrophy and cataract underwent triple procedure. As the anterior chamber view was limited, the central 7.0 mm of the cornea was marked. Then, 60-80% of the corneal thickness was removed by lamellar dissection and filled with hydroxypropylmethylcellulose. Continuous curvilinear capsulorhexis (CCC) and phacoemulsification with intraocular lens implantation through a corneoscleral tunnel were then performed and at the end the remaining corneal tissue was excised and the donor tissue fixed with a single running continuous suture. RESULTS: Lamellar corneal dissection enhances the anterior chamber view and CCC can be performed under stable anterior chamber condition. Phacoemulsification via sclerocorneal tunnel could be easily performed under good anterior chamber view in all cases. The operation time was 60-75 min in all cases. CONCLUSION: Lamellar corneal dissection in opaque corneas before cataract extraction is a useful technique for enhancing anterior chamber view in cases of triple procedure.

Adverse skin reactions to infliximab in the treatment of intraocular inflammation.

TNFalpha 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.

TNF-alpha promoter polymorphisms and primary open-angle glaucoma.

PURPOSE: Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-alpha(TNF-alpha) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-alpha-308G>A and -238G>A gene polymorphisms and the presence of POAG in a Caucasian population. METHODS: The present case-control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-alpha-308G>A and -238G>A polymorphisms was performed using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distributions of both the TNF-alpha-308G>A and -238G>A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-alpha-308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-alpha-238A-allele. CONCLUSION: Our data suggest that none of the investigated TNF-alphagene polymorphisms is a major risk factor among Caucasian patients with POAG.

[ABO blood group expression in corneal allograft failures]. / ABO-Blutgruppenexpression in Hornhäuten mit Transplantatversagen.

BACKGROUND: ABO blood group antigens are only expressed by the epithelial cells of normal human corneas. Since AB0 blood group antigens are also known to be expressed on stromal and endothelial cells of inflamed corneas, this study aimed to investigate the extend of ABO blood group antigen expression in corneal allograft failures. MATERIAL AND METHODS: Twenty-two failed corneal allografts of 22 patients were examined. In 12 cases the patients had clinically proven corneal allograft rejection. In 10 cases there was no evident history of allograft rejection and the diagnosis graft failure due to chronic endothelial cell loss was made. Immunohistochemical staining of paraffin embedded sections was performed with monoclonal mouse antibodies to human blood group antigen A or B using the streptavidin-biotin-peroxidase complex technique. RESULTS: Blood group antigens A or B were expressed by stromal keratocytes in 5 out of 12 and by endothelial cells in 7 out of 12 corneas with clinically proven immunologic graft rejection. Corneal transplants with chronic endothelial cell loss expressed blood group antigens A and/or B on the endothelial cells in three out of ten cases. CONCLUSION: The results of this study show that ABO blood group antigens can be up-regulated in cases of corneal allograft failure, especially in cases of immune mediated graft rejection. This phenomenon might play a role in corneal allograft rejection.

[Optic nerve involvement in syphilis in 4 patients]. / Optikusbeteiligung bei Lues bei 4 Patienten1.

BACKGROUND: Due to increasing numbers of cases syphilis again becomes more important in ophthalmology. Syphilitic ocular manifestations do not show any typical characteristics and therefore are often not diagnosed although a correct and early diagnosis with adequate therapy is very important for the visual outcome. PATIENTS: We report on four patients with luetic ocular fundus manifestations, who were referred to our clinic with unspecific ocular complaints. Funduscopic examination revealed in all patients a papilledema, which was bilateral in three patients and unilateral in one patient. Additional findings were a non-granulomatous uveitis anterior and a chorioretinitis in both eyes of a 61-year-old HIV positive patient with retinal scars from a bilateral acute retinal necrosis syndrome (ARN), a mild non granulomatous iridocyclitis in a 53-year-old patient and a bilateral chorioretinitis and a cystoid macular edema in a 37-year-old patient. A 54-year-old patient showed a vein branch occlusion. Serological analysis demonstrated active syphilis in all cases and an EBV-infection in two patients. After penicillin therapy the ocular findings resolved. CONCLUSION: In all cases of inflammatory fundus manifestations syphilis should be taken into consideration and serological lues tests should be performed routinely.

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.

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 micrograms/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 micrograms/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 no change 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.

Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1b, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis.

PURPOSE: Matrix metalloproteinases have been shown to play a role in active uveitis. Transcription of MMPs is induced by a number of growth factors and cytokines. This study investigates the role of MMPs in chronic uveitis and correlates the amounts of MMP-2 and -9 in intraocular samples to the intraocular levels of proinflammatory cytokines (Interleukin-1 [IL-1], Interleukin-12 [IL-12] and Interleukin-1 receptor antagonist [IL-1ra]). METHODS: Aqueous humor of 16 patients was collected during surgical or diagnostic procedures (control group: cataract patients). MMP-2 and -9 were measured using zymography. IL-1beta, IL-12 and IL-1ra were evaluated by ELISA. RESULTS: We found MMP-2 and -9 in all of our uveitis patients. In the control group only MMP-2 was seen. Higher levels of MMP-2 and -9 were found in patients with higher activity of uveitis (p < 0.014 for MMP-2, p < 0.0054 for MMP-9). The amounts of IL-1beta, IL-12 and IL-1ra detected in our uveitis patients correlated with levels of MMP-2 (p < 0.07, p < 0.0004, p < 0.03) and MMP-9 (p < 0. 003, p < 0.0001, p < 0.002), and IL-12 (p < 0.004, p < 0.0001). Patients with moderately active uveitis presented with twice the level of MMP-2 as the control group; MMP-9 levels reached up to 92% of the amounts found in patients with active uveitis. Two patients in remission for almost one year still had detectable intraocular MMP-9 levels. CONCLUSION: Our data suggests that the high levels of MMPs found in patients with chronic uveitis might contribute to the damage often seen in these eyes. Since MMPs are capable of releasing proinflammatory cytokines bound to components of the extracellular matrix, and facilitate the secretion of active TNF-alpha by cleavage of the membrane bound form, it is conceivable that MMPs contribute to the chronicity of some uveitis cases.