Intraocular lens dislocation: manifestation, ocular and systemic risk factors.

PURPOSE: The aim of this study was to evaluate ocular and systemic risk factors for posterior chamber intraocular lens dislocation, as well as forms of manifestation. METHODS: A retrospective case-control study were all patients presented in the period 2012-2016 having intraocular lens dislocation and being treated with implantation of an iris-fixated intraocular lens was conducted at the University Hospital Mainz. As controls, pseudophakic patients presenting for other reasons were included. RESULTS: 150 eyes of 150 patients (mean age 72.7 ± 12.4 years, range 24-93 years) with IOL dislocation and 150 eyes of 103 controls were included in this study. The average time between primary implantation and IOL luxation was 86 months (iQR: 39.25-127 months) for all dislocations. Previous pars plana vitrectomy (PPV) (crudeOR = 2.14 (95% CI 1.23, 3.72), p = 0.011) and PEX (crudeOR = 11.6 (4.79, 28.12), p < 0.001) was linked with a higher risk of IOL luxation. Luxation occurs also earlier in patients with previous PPV and PEX than in eyes with neither PEX nor previous PPV (82.2 vs. 127 months). Rhegmatogenous retinal detachment was the major pathology that required a previous PPV for eyes with an IOL dislocation (57%). The average time between PPV and IOL dislocation was 74.67 months (range 0-186 months). CONCLUSION: Patients with a coexistence of both: PEX and a previous PPV had an elevated risk of IOL dislocation, and also had a shorter time interval between primary IOL implantation and IOL dislocation followed by eyes with PEX only and eyes with only a previous PPV.

Ionising radiation and lens opacities in interventional physicians: results of a German pilot study.

We assessed the feasibility of an epidemiological study on the risk of radiation-related lens opacities among interventional physicians in Germany. In a regional multi-centre pilot study associated with a European project, we tested the recruitment strategy, a European questionnaire on work history for the latter dosimetry calculation and the endpoint assessment. 263 interventional physicians and 129 non-exposed colleagues were invited. Questionnaires assessed eligibility criteria, risk factors for cataract, and work history relating to occupational exposure to ionising radiation, including details on type and amount of procedures performed, radiation sources, and use of protective equipment. Eye examinations included regular inspection by an ophthalmologist, digital slit lamp images graded according to the lens opacities classification system, and Scheimpflug camera measurements. 46 interventional (17.5%) and 30 non-exposed physicians (23.3%) agreed to participate, of which 42 and 19, respectively, met the inclusion criteria. Table shields and ceiling suspended shields were used as protective equipment by 85% and 78% of the interventional cardiologists, respectively. However, 68% of them never used lead glasses. More, although minor, opacifications were diagnosed among the 17 interventional cardiologists participating in the eye examinations than among the 18 non-exposed (59% versus 28%), mainly nuclear cataracts in interventional cardiologists and cortical cataracts in the non-exposed. Opacification scores calculated from Scheimpflug measurements were higher among the interventional cardiologists, especially in the left eye (56% versus 28%). Challenges of the approach studied include the dissuading time investment related to pupil dilatation for the eye examinations, the reliance on a retrospective work history questionnaire to gather exposure-relevant information for dose reconstructions and its length, resulting in a low participation rate. Dosimetry data are bound to get better when the prospective lens dose monitoring as foreseen by 2013 European Directives is implemented and doses are recorded.

Determinants of peripapillary retinal nerve fiber layer thickness regarding ocular and systemic parameters - the MIPH Eye&Health Study.

BACKGROUND: Optical coherence tomography (OCT) allows quantitative image analysis of retinal tissue in vivo. Peripapillary retinal nerve fiber layer (pRNFL) thickness is widely used for evaluation of retinal nerve fiber rarefaction in several optic neuropathies. This study evaluates associations of pRNFL thickness in healthy adult subjects in order to evaluate influencing factors. METHODS: A cross-sectional study was performed in a working-age population. Only eyes without detectable ocular pathologies were included in the analysis. Among analyzed systemic cardiovascular parameters were age, gender, body-mass index, mean arterial blood pressure, HbA1c, high- and low-density-lipoproteins, and triglycerides. A comprehensive ophthalmological examination including refraction, tonometry, keratometry, and central corneal thickness measurmentwas performed. In addition, pRNFL thickness was imaged by spectral-domain OCT. Univariable and multivariable associations of pRNFL thickness in all four quadrants and on average with systemic and ocular parameters were calculated using a generalized estimating equation model. RESULTS: Three hundred and six subjects were included. pRNFL thickness measurements showed a significant association with spherical equivalent: pRNFL thickness decreased with increasing myopia in all quadrants (multivariable regression coefficients Beta: superior: 1.16, 95 % CI [0.62;1.71], p < 0.001; temporal: 0.87, [0.33;1.41], p = 0.001; inferior: 1.80, [1.18;2.42], p < 0.001; nasal: 2.60, [2.01;3.20], p < 0.001) and on average (1.51, [1.20;1.82], p < 0.001). A thicker central cornea thickness was related to lower pRNFL in the superior (-0.05, [-0.10; -0.01], p = 0.01), the inferior quadrant (-0.05, [-0.10;0.00], p = 0.03) and on average (-0.04, [-0.07; -0.01], p = 0.02). All other parameters were not  associated. CONCLUSION: Our findings highlight the importance of refraction when evaluating pRNFL thickness and its independence from other systemic parameters.

Associations of macular thickness in spectral-domain OCT with ocular and systemic cardiovascular parameters - the MIPH Eye & Health Study.

PURPOSE: Beyond in-vivo histological analysis of retinal tissue, optical coherence tomography (OCT) allows quantitative image analysis. This study evaluates associations of macular retinal thickness measured with spectral-domain OCT (SD-OCT) and ocular and systemic cardiovascular parameters in adult subjects. METHODS: An epidemiological cross-sectional study was performed in the staff of a European high-tech company. Examination of known cardiovascular risk factors including biochemical blood analysis was performed, and ocular parameters such as refraction, tonometry, SD-OCT imaging of the macula and cornea, and fundus photography were evaluated. Retinal thickness measurements were evaluated according to the ETDRS grid. Associations of macular retinal thickness and systemic cardiovascular and ocular parameters were calculated by multivariate analysis using SPSS software. RESULTS: Four hundred and twenty-four probands were included. Macular thickness measurement were significantly associated with gender and refraction. Female persons had thinner retinal thickness in all zones. Macular thickness decreased with increasing myopia in all perifoveal measurements. Outer perifoveal measurements were associated with keratometry; a flatter corneal radius was linked to a thinner retina. Tonometry and systemic cardiovascular risk factors were not associated with macular retinal thickness in multivariate analysis (p > 0.05). CONCLUSIONS: Macular retinal thickness is associated with refraction and gender; cardiovascular risk factors or tonometry do not influence macular retinal thickness measurements. Keratometry might influence outer zone measurements. Our findings provide a dataset for quantitative evaluation of SD-OCT, and evaluate influencing factors.

The impact on vision of aspheric to spherical monofocal intraocular lenses in cataract surgery: a systematic review with meta-analysis.

PURPOSE: To provide a summary of the impact on vision of an aspheric intraocular lens (IOL) compared with a spherical IOL in cataract surgery. DESIGN: Systematic review with meta-analysis. PARTICIPANTS: Patients from published randomized controlled trials (RCTs) of cataract surgery with aspheric compared with spherical monofocal IOL implantation. METHODS: We systematically searched the peer-reviewed literature in MEDLINE, EMBASE, Web of Science, BIOSIS, and the Cochrane Library according to the Cochrane Collaboration method to identify relevant RCTs. The inclusion criteria were RCTs on cataract surgery comparing the use of aspheric versus spherical IOL implantation that assessed visual acuity, contrast sensitivity, or quality of vision. The effects were calculated as mean differences or standardized mean differences (Hedges' g) and pooled using random-effect models. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), contrast sensitivity, and subjective perception of the quality of vision. RESULTS: Forty-three studies provided data and were included, comprising 2076 eyes implanted with aspheric IOLs and 2034 eyes implanted with spherical IOLs. The BCVA showed a significant difference for aspheric IOLs (-0.01 logarithm of the minimum angle of resolution; 95% confidence interval [CI], -0.02 to -0.00). For contrast sensitivity, a significant advantage for aspheric IOLs was found under photopic and mesopic light conditions (photopic: Hedges' g 0.42, 95% CI 0.24-0.61 (3 cycles per degree [cpd]) to 0.53, 95% CI 0.33-0.73 (12 cpd); mesopic: Hedges' g 0.49, 95% CI 0.23-0.75 (1.5 cpd) to 0.76, 95% CI 0.52-1.00 (18 cpd)). Questionnaires targeting the subjective perception of quality of vision yielded less conclusive results. CONCLUSIONS: Overall, a patient may achieve better contrast sensitivity with an aspheric IOL than with a spherical IOL, especially under dim light. There was no clinically relevant difference in BCVA between aspheric and spherical IOL implantation. The findings on the subjective perception of visual quality were heterogeneous with no clear result favoring either option.

Width of anterior chamber angle determined by OCT, and correlation to refraction and age in a German working population: the MIPH Eye&Health Study.

BACKGROUND: Optical coherence tomography (OCT) of the anterior segment allows quantitative analysis of the geometry of the chamber angle. We performed bilateral spectral-domain OCT measurements in healthy, emmetropic, hyperopic, and myopic subjects to establish correlations between the width of the angle, the refraction, and intraocular pressure of the test persons. METHODS: Out of 4,617 eyes (2,309 subjects), those with refractive errors of < -4 or > +3 diopters were identified by objective refraction measurement (KR-8800 Kerato-Refractometer, Topcon Inc., Japan) and examined using the anterior segment mode of a spectral-domain 3D OCT-2000 (Topcon Inc., Japan). Non-contact tonometry was performed (CT-80, Topcon Inc., Japan). One hundred and eight eyes of 54 emmetropic subjects (± 0.5 dpt) served as reference group. Previous ocular surgery was exclusion criterion in all groups. Width of the chamber angle was determined using semi-automated software tools and statistical analysis of the data (Pearson correlation, ANOVA with post-hoc test and Bonferroni correction, regression analysis) was performed using SPSS software (SPSS 19.0, Chicago, IL, USA). RESULTS: Six hundred and sixty-eight eyes of 398 persons (292 male, 96 female) were included in the study. Mean hyperopic refraction was +4.24 (+3 to +7.75) dpt, mean myopic refraction was -5.86 (-4 to -11.75) dpt. Valid chamber angle OCT measurements could be obtained from 50 (69.4 %) hyperopic and 400 (71.4 %) myopic eyes meeting the inclusion criteria. The mean width of the chamber angle was determined as 31.8° (range: 13.5 to 45.6, SD 7.49) in the hyperopic group, 40.8° (range: 19.3 to 66.0, SD 8.1) in the myopic group, and 36.3° (range: 21.1 to 51.8, SD 6.8) in the emmetropic reference group. Correlation was highly significant (p > 0.001) between refractive error and the aperture of the chamber angle as measured from OCT. The association of the intraocular pressure and the refraction was also highly significant (p > 0.001) for the three groups. CONCLUSION: The spectral-domain OCT yielded measurements that could be used for digital analysis of the chamber angle geometry. Our results highlight the correlation between refraction and aperture of the angle in hyperopia and myopia as determined by the 3D OCT-2000: hyperopia is associated with a narrower chamber angle, myopia with a wider aperture of the angle.

Postoperative results after iris reconstruction with an Artificialiris® implant with consideration of the cause of the iris defects.

PURPOSE: To test the hypothesis that severely damaged eyes are more likely to experience postoperative complications after an ArtificialIris® (AI) implantation than other iris defects. METHODS: Patients after iris reconstruction with an AI were included in this consecutive case series of the Department of Ophthalmology, University of Mainz, Germany. Best-corrected visual acuity (BCVA), objective refraction (KR 8900 Topcon, Tokyo, Japan) and Scheimpflug imaging of the anterior segment with Pentacam® (Oculus, Wetzlar, Germany)and postoperative complications were evaluated. RESULTS: Thirty-two eyes of 32 patients after AI implantation were included, separated in partial or total aniridia in a closed globe (group 1, n = 16) and after perforating globe injury (group 2, n = 16). Two or more previous surgeries in the corresponding eye were found in two patients (12.5%) in group 1 and eleven patients (69%) in group 2 (p = 0.001). The time span between initial trauma or iris defect and AI implantation was not significantly related to the occurrence and severity of postoperative complications (p = 0.89). Postoperative complications were classified into mild and severe and showed no differences between group 1 and group 2 (mild: 1 vs. 0; p = 0.52; severe: 5 vs. 6 p = 0.8). CONCLUSION: AI implantation is a treatment option for various iris defects. An individual, case-based decision should be made with strict indication also considering other possible methods for pupil reconstruction. The postoperative outcome is not affected by the time point of AI implantation. So, an implantation is already possible as early as six weeks after the previous trauma.

Irregularity of the posterior corneal surface during applanation using a curved femtosecond laser interface and microkeratome cutting head.

PURPOSE: To evaluate the irregularity of the posterior corneal surface and intrastromal dissection during the preparation of donor tissue for Descemet stripping automated endothelial keratoplasty (DSAEK) using a curved interface femtosecond laser and microkeratome. METHODS: Sixteen human donor corneas unsuitable for transplantation were divided into two groups: a femtosecond (FS) laser group (n=7) using the VisuMax femtosecond laser (Carl Zeiss Meditec) and a microkeratome group (n=9) using the Amadeus II microkeratome (Ziemer Ophthalmic Group). The corneas were fixed on artificial anterior chambers. Horizontal cross-sections were obtained using spectral-domain optical coherence tomography prior to applanation, during applanation, as well as during and after intrastromal dissection at 450-µm corneal depth. The posterior surface and the dissection line were evaluated for irregularity by fitting a second-order polynomial curve using regression analysis and obtaining the root-mean-square error (RMSE). Groups were compared using analysis of variance. RESULTS: The RMSE of the posterior surface prior to applanation was 9.7 ± 3.1 µm in the FS laser group and 10.2 ± 2.3 µm in the microkeratome group. The RMSE increased to 50.7 ± 9.4 µm and 20.9 ± 6.1 µm during applanation and decreased again to 10.6 ± 1.4 µm and 8.1 ± 1.8 µm after applanation in the FS laser and microkeratome groups, respectively. The RMSE of the intrastromal cut was 19.5 ± 5.7 µm in the FS laser group and 7.7 ± 3.0 µm in the microkeratome group (P<.001). CONCLUSIONS: Our results show significantly greater irregularity with the curved interface femtosecond laser-assisted cleavage compared to microkeratome-assisted corneal dissection, possibly due to applanation-derived deformation of the posterior cornea.

Five Years Follow-Up of Acrysof Cachet® Angle-Supported Phakic Intraocular Lens Implantation for Myopia Correction.

Purpose: The Acrysof Cachet® angle-supported phakic intraocular lens (pIOL) (Alcon Laboratories, Inc., Fort Worth, TX) is designed to correct high refractive errors in human eyes. The aim of this study was to evaluate the outcome of AcrySof Cachet® angle-supported pIOL implantation with particular regard to efficacy and safety of the implant over a 60-month follow-up period. Design: Retrospective consecutive clinical case study. Methods: Prior to pIOL implantation, patients had a complete ophthalmologic examination including objective and subjective refraction, uncorrected visual acuity (UCVA) and corrected distance visual acuity (CDVA), endothelial cells density (ECD), slit lamp photography, optical coherence tomography (OCT), Scheimpflug digital videokeratoscopy, optical biometry, slit lamp examination, intraocular pressure (IOP) measurement, and pupillometry. Postoperatively, patients received yearly a complete eye examination. Results: Thirty-one eyes of 16 patients were included in this study. The mean age was 36.2 ± 8.1 years. UCVA (logMAR) improved from 1.33 ± 0.20 before surgery to 0.08 ± 0.14 one year after surgery and was 0.20 ± 0.20 five years after surgery. CDVA (logMAR) improved from 0.10 ± 0.10 before surgery to 0.05 ± 0.13 one year after surgery and was 0.04 ± 0.14 five years postoperatively. The mean percentage of endothelial cells loss (ECL) was 11.51% over the first year and 15.95% five years after surgery. There were no intraoperative complications in any of the eyes. Conclusions: Our results up to five years after implantation of the AcrySof Cachet® angle-supported pIOL demonstrated very good outcomes in all above shown measurements, including CDVA, UCVA, and ECD. However, since major endothelial cell loss may occur in some patients with this type of pIOL, regular follow-up visits are required.

Optical Coherence Tomography Position Analysis of Retropupillary Iris-Fixated Intraocular Lens in Iris Tissue.

Purpose: The aim of this study was to evaluate a micrometer-accurate analysis of the retropupillary Verisyse® intraocular lens (IOL) (Ophtec, Groningen NL; Santa Ana, USA) enclavation in the iris tissue. Methods: A retrospective consecutive case series was conducted at the Department of Ophthalmology, University Hospital Mainz. Patients with an optical coherence tomography (Spectralis®, Heidelberg Engineering®; Heidelberg, Germany) examination after retropupillary Verisyse® IOL implantation were included retrospectively. The enclavation geometry was measured using the Eye-Explorer® from Heidelberg Engineering® (Heidelberg, Germany). Seventeen measuring positions were determined nasally and temporally at the corresponding enclavation points. Results: 72 eyes of 67 patients after implantation of a retropupillary Verisyse® IOL were analyzed. The average age was 68 ± 17.2 years (63% female; 38% male). The analysis of the position of the Verisyse® IOL showed highly homogeneous data in all measured points. The depth of the anterior chamber showed a positive correlation with width of the posterior deflection of the iris tissue behind the enclavation (Pearson r: 0.321, p=0.041). The offset of the haptics showed greater deviations, and the lens diopter implanted was higher (r = 0.337, p=0.007). Conclusion: This is the first study that analysis the exact enclavation of retropupillary implanted Verisyse® IOL. It provides new information about the intrastromal course of the haptics in the iris tissue. It could be shown that the haptics do not run parallel in the iris tissue, but are anchored in the iris tissue with an average offset of 95 µm. This rebuts previous assumptions about the intrastromal course and provides new information.

Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty.

PURPOSE: Posterior lamellar keratoplasty is increasingly applied in patients with endothelial decompensation after penetrating keratoplasty (PK). The aim of this study was to compare the results of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) after PK. METHODS: In this retrospective study, clinical data of 30 patients who received DMEK (n = 19) or DSAEK (n = 11) for endothelial decompensation after PK were evaluated. All lamellar keratoplasties were performed at the Department of Ophthalmology at University Hospital Mainz, Germany. Primary end point included best-corrected visual acuity, and secondary end points included endothelial cell density, rebubbling, and rejection rates, all at 6 and 12 months. RESULTS: After 6 months and 12 months, 89% of DMEK and 73% of DSAEK grafts and 63% of DMEK and 64% of DSAEK grafts provided sufficient corneal deturgescence, respectively, represented by improvement in best-corrected visual acuity. DMEK group median preoperative Logarithm of the Minimum Angle of Resolution visual acuity of 1 increased to 0.5 after 6 and 12 months. DSAEK group median Logarithm of the Minimum Angle of Resolution visual acuity increased from 3 to 2 and 1.3 after 6 and 12 months. After 12 months, graft endothelial cell density had decreased by 58% in the DMEK group and by 59% in the DSAEK group. The proportion of patients requiring a rebubbling were 63% in the DMEK and 64% in the DSAEK group. No lamellar graft rejection occurred in either trial arm. CONCLUSIONS: Both DMEK and DSAEK significantly improved visual acuity in patients after PK. Lamellar graft survival, loss of endothelial cells, and mean rebubbling rates were similar in both groups.

Corneal opacity and copper levels of the Lewis syndrome after systemic chemotherapy.

PURPOSE: To report a female patient of biclonal Lewis syndrome which consists of a trias: biclonal gammopathy of undetermined significance, paraproteinemic keratopathy in form of a brownish discoid opacification at the level of Descemet's membrane and hypercupremia. After several years there was a conversion to multiple myeloma. Systemic chemotherapy led to a complete remission of multiple myeloma and to a normalization of the copper level in the blood that lasted five years. The corneal opacification remained unchanged. OBSERVATIONS: A currently 66-year-old woman suffered from biclonal Lewis syndrome. On both eyes there is a central discoid yellow-brownish discoloration in the Pre-Descemet's layer. The corneal findings were unchanged after a follow up of eight years. However, there was a conversion to multiple myeloma (MM) type IgG with progressive anemia and suspicious bone lesions. A multiple systemic myeloma-therapy was indicated. Chemotherapy with subsequent tandem autologous-stem cell therapy (auto-SCT) was performed. The blood examination after this therapy showed a complete remission of multiple myeloma, and it was also very surprising that the serum copper level was within normal range. This finding remained unchanged over a period of five years. The bilateral corneal opacification was identical to that before chemotherapy. To the best of our knowledge, this represents the first observation of a normalization of copper levels in Lewis syndrome after chemotherapy. CONCLUSIONS AND IMPORTANCE: The Lewis syndrome represents a very rare disorder. The first case reported in Europe (Lisch et al., 2016)1 showed a conversion from biclonal gammopathy of undetermined significance to MM after a follow-up of 17 years. Subjectively, the patient was in excellent health. The typical corneal, discoid brownish opacification at the level of Descemet's membrane is a suspicious hint of a copper disturbance for the ophthalmologist. The copper level of our patient was extremely elevated. The corneal opacification however, remained unchanged throughout the repeated ophthalmological examinations. In 2015, the conversion of our case with Lewis syndrome to MM performing chemotherapy in different steps and a twice auto-SCT resulted in a complete remission of MM and a normal range of the serum copper. The bilateral corneal opacification remained unchanged during an observation period of five years after chemotherapy.

[Indications and surgical techniques for implantation of the Artificial Iris®]. / Indikationen und Operationsmethoden für die Implantation der Artificial Iris®.

BACKGROUND: The implantation of the Artificial Iris® (Human Optics AG, Erlangen, Germany) is used for pupil and iris reconstruction in patients with partial or complete aniridia. So far, only a few case reports and short-term results are available in the literature. OBJECTIVE: The aim of this analysis is to present the various indications as well as the functional result. MATERIAL AND METHOD: This retrospective consecutive case study included 51 eyes of 50 patients with implantation of an Artificial Iris® for pupillary reconstruction. All operations were performed by the same ophthalmic surgeon (UV) at the University Eye Clinic Mainz. The initial findings were placed in relation to the indications and the functional results were investigated. RESULTS: In this study 51 eyes of 50 patients with a mean age of 57 ± 16.5 years (16 women and 34 men) were analyzed. While the majority of the patients suffered from a traumatic partial or complete aniridia, the minority showed congenital defects. The visual acuity could be improved in 53% of the patients (p = 0.0001) postoperatively. CONCLUSION: This analysis highlights the various and diverse indications for implanting the Artificial Iris®. Hereby, a gain in visual acuity is not invariably the primary objective but more often reduction of glare as well as cosmetic rehabilitation, as the eyes are severely damaged in many cases. The long-term results are currently being analyzed in a study and will soon be published.

Retinal pigment epithelial phenotype induced in human adipose tissue-derived mesenchymal stromal cells.

BACKGROUND AIMS: The non-exudative form of age-related macular degeneration (ARMD) is characterized by a progressive decay of retinal pigment epithelium cells at the posterior pole of the eye. As mesenchymal stromal cells (MSC) have been shown to differentiate into various cell types from the mesodermal and ectodermal lineages, we investigated whether we can induce a phenotype displaying retinal pigment epithelium (RPE) characteristics. METHODS: The differentiation of human lipo-aspirate-derived MSC toward the RPE lineage was triggered by exposure to conditioned medium from either human or porcine RPE cells. In a second approach we tested whether adding vasoactive intestinal peptide (VIP) is capable of further modifying differentiation processes. Resulting cell populations were assessed for expression of RPE-specific markers by immunofluorescence, quantitative real time (RT)-polymerase chain reaction (PCR) and Western blotting. The potential for pigment synthesis was assessed by the response to melanocyte-stimulating hormone (MSH). RESULTS: Following culture of undifferentiated MSC with RPE-conditioned medium and/or VIP, expression of typical RPE markers bestrophin, cytokeratins 8 and 18 and RPE 65 was induced. MSH induced the formation of pigmented granula in differentiated MSC. CONCLUSIONS: MSC are shown to express RPE markers upon induction with either RPE-conditioned medium and/or VIP. The gain of basic functional features of RPE cells was indicated by melanin synthesis. This alludes to a differentiation potential of MSC into the neuroectodermal lineage, yielding cells with phenotypic characteristics of RPE cells.

Intravitreal bevacizumab versus triamcinolone acetonide for exudative age-related macular degeneration.

BACKGROUND: To compare an intravitreal high-dose injection of triamcinolone acetonide with an intravitreal injection of bevacizumab for the treatment of progressive exudative age-related macular degeneration (AMD). METHOD: The comparative nonrandomized retrospective clinical interventional study included 305 patients with progressive AMD, divided into a bevacizumab group of 36 patients (1.5 mg bevacizumab) and a triamcinolone group of 269 patients (about 20 mg triamcinolone). All patients were consecutively included, in the first phase of the study for triamcinolone, and in the second phase of the study for bevacizumab. The mean follow-up was 8.5+/-6.8 months (2-35.7 months). RESULTS: In the bevacizumab group, best visual acuity increased significantly (p<0.001) by 3.2+/-3.4 Snellen lines, with 25 (69%) eyes and 21 (58%) eyes, improving by at least 2 and 3 Snellen lines, respectively. In the triamcinolone group, the visual acuity change was not statistically significant for any specific follow-up examination within the first 3 months. The maximal increase in visual acuity, the visual acuity change at 2 months after injection and the percentage of patients with an improvement by at least 2 and 3 Snellen lines were significantly (p<0.001) higher in the bevacizumab group than in the triamcinolone group. Intraocular pressure increased significantly (p<0.001) in the triamcinolone group and did not change significantly (p=0.47) in the bevacizumab group. CONCLUSION: In exudative AMD, intravitreal bevacizumab (1.5 mg) compared with intravitreal triamcinolone acetonide (about 20 mg) results in a higher improvement of visual acuity and does not markedly influence intraocular pressure within 2 months after injection.

Comparison of flap adhesion strength using the Amadeus microkeratome and the IntraLase iFS femtosecond laser in rabbits.

PURPOSE: To compare adhesion strength of flaps created with a mechanical microkeratome and the IntraLase femtosecond laser as well as to analyze the effect of different side-cut configurations. METHODS: A flap was created in four groups of New Zealand white rabbits--microkeratome group (Amadeus II microkeratome, Ziemer Group AG [5 eyes; 9-mm suction ring and 140-microm head]), and three IntraLase groups (IntraLase iFS 150 kHz femtosecond laser, AMO Inc [9-mm diameter and 120-microm flap each]): normal energy side-cut (4 eyes; side-cut angle 70 degrees, side-cut energy 0.8 microJ); high energy side-cut (4 eyes; side-cut angle 70 degrees, side-cut energy 1.6 microJ); and inverted side-cut (4 eyes; side-cut angle 140 degrees, side-cut energy 0.8 microJ). Flap adhesion strength was measured 75 days after surgery using a tension meter to dehisce the flaps. RESULTS: In the microkeratome group, mean force was 210+/-89 g (range: 151 to 360 g); 492+/-46 g (range: 439 to 540 g) in the normal energy side-cut group; 444+/-13 g (range: 426 to 455 g) in the high energy side-cut group; and 687+/-105 g (range: 552 to 797 g) in the inverted side-cut group. Differences between the microkeratome and all IntraLase groups were highly significant (P=.001), and differences between the inverted side-cut group and the standard 70 degrees side-cut groups were statistically significant (P=.01). CONCLUSIONS: Flap adhesion is significantly stronger with the IntraLase femtosecond laser than with the Amadeus mechanical microkeratome, and an inverted side-cut increases flap adhesion significantly compared with a standard side-cut.

Cultivation and differentiation characteristics of human limbal progenitor cells.

BACKGROUND: The aim of this study was to investigate whether limbal progenitor cells can be cultured, expanded and differentiated in vitro not only to enter corneal differentiation but also towards RPE (retinal pigment epithelium) characteristics. METHODS: A 3mm broad strip of human corneoscleral limbal tissue was digested enzymatically and cells were set into cell culture. Differentiation status and characteristics, proliferation and phagocytotic activity were assessed by immunocytochemical staining in combination with digital and confocal microscopy. RESULTS: Immunocytological analysis revealed expression of Nestin and p63 marker suggesting progenitor cell properties. Mitotic activity was demonstrated by BrdU (bromodesoxyuridine) uptake. Upon consecutive passages, corneal differentiation markers were predominantly expressed. Phagocytotic activity was demonstrated via uptake of FITC (fluorescein isothiocyanate) labelled latex beads. RPE markers Bestrophin and Cytokeratin 8/18 as well as glial marker GFAP and neuronal marker MAP with respective controls were negative indicating no differentiation towards characteristics of retinal pigment epithelium or neural and glial lineage. CONCLUSIONS: The results suggest that isolation and cultivation of proliferating and phagocytotic cells from the human corneal limbus was achieved which showed characteristics of both progenitor and differentiated corneal cells. No evidence was found for the hypothesis of spontaneous differentiation potential towards RPE lineage or neuronal characteristics, providing evidence of the inherent directional capacity of limbal progenitor cells.

Intravitreal bevacizumab for myopic choroidal neovascularization.

BACKGROUND AND OBJECTIVE: To evaluate the effect of intravitreal bevacizumab on visual acuity in patients with myopic choroidal neovascularization. PATIENTS AND METHODS: The retrospective case series study included 13 patients with myopic choroidal neovascularization who received three intravitreal injections of 1.5 mg of bevacizumab. RESULTS: At 1, 3, and 6 months after the first injection, mean visual acuity improved significantly from 0.63 +/- 0.41 logarithm of the minimum angle of resolution units (LogMAR) to 0.39 +/- 0.22 (P< .001), 0.47 +/- 0.49 (P= .002), and 0.52 +/- 0.49 LogMAR (P = 0.009), respectively. The increase in visual acuity was correlated with a significant decrease in central retinal thickness (P = .003) as measured by optical coherence tomography. Mean intraocular pressure did not change significantly (P> .05) during follow-up. CONCLUSION: Intravitreal injections of bevacizumab may be a therapeutic option for exudative myopic macular degeneration.

Induction of retinal pigment epithelium properties in ciliary margin progenitor cells.

PURPOSE: Degenerative processes in the retinal pigment epithelium (RPE) are known to play a pivotal role in the development of age-related maculopathy. Substitute RPE analogue cells could be used to preserve visual function. In this paper we investigate methods for the isolation, cultivation and RPE differentiation of undifferentiated cells from the ciliary marginal zone (CMZ) of rat eyes. METHODS: The CMZ was isolated from enucleated rat eyes, cell spheres formed in serum-free suspension culture, Bromodeoxyuridine (BrdU) incorporation indicated mitotic activity. Following baseline differentiation status assessment, directional differentiation was induced by cultivating cells in RPE-conditioned medium and vasoactive intestinal peptide (VIP). The differentiation status was analysed by immunocytochemistry. Fluorescein isothiocyanate (FITC)-labelled latex beads were used for functional evaluation. RESULTS: CMZ-derived cells were expanded for 6-12 months. Formation of spherical cellular conglomerates, subsphere formation and expression of nestin indicated progenitor cells. Baseline levels of markers MAP-2 for neuronal and GFAP for glial properties and baseline levels of bestrophin, cytokeratins 8 and 18 and RPE 65 for RPE properties were induced by serum culture, respectively. Culture in conditioned medium with addition of VIP significantly increased RPE marker expression and reduced neuronal features, uptake of latex beads indicated phagocytosis. CONCLUSIONS: We succeeded in isolating and cultivating cells from rodent CMZ with progenitor cell characteristics. Subsequently, these cells tested positive for neuronal, glial and RPE markers. Appropriate conditions significantly increased RPE marker expression. Unidirectional induction of differentiation makes the CMZ eligible as a source of regenerative ocular tissue for RPE-reconditioning therapy.

Visualization of corneal vascularization in peripheral hypertrophic subepithelial corneal opacification with OCT angiography.

PURPOSE: The major goal of this study was to test the hypothesis that in patients with peripheral hypertrophic subepithelial corneal opacification (PHSCO), visualization of corneal vessels is better with optical coherence tomography angiography (OCTA) than with conventional slit lamp microphotography. METHODS: Patients with PHSCO were included in this prospective study. The corneal findings were photographed using a slit lamp camera (Haag Streit BM 900® ) and visualized with anterior-segment OCT (Optovue XR Avanti, Fremont, California, USA). Additionally, OCTA with the Angiovue Imaging™ System was performed in the area of PHSCO. RESULTS: Thirty-four eyes of 19 patients (26% male and 74% female) with PHSCO were included in this study. In 21 eyes, vascularization in the area of PHSCO was visualized with the Angiovue-OCT, whereas only 10 eyes presented vessels in slit lamp photographs. CONCLUSION: Optical coherence tomography angiography allows better visualization of corneal neovascularization than slit lamp photography in patients with PHSCO. Corneal opacifications were found predominantly nasally, which was reflected by a local enlargement of corneal thickness.