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.

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.

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.

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.

Steeper Iris Conicity Is Related to a Shallower Anterior Chamber: The Gutenberg Health Study.

PURPOSE: To report the distribution of iris conicity (steepness of the iris cone), investigate associated factors, and test whether pseudophakia allows the iris to sink back. METHODS: A population-based cross-sectional study was carried out. Ophthalmological examination including objective refraction, biometry, noncontact tonometry, and Scheimpflug imaging (Pentacam®, Oculus) was performed including automated measurement of iris conicity. 3708 phakic subjects, 144 subjects with bilateral and 39 subjects with unilateral pseudophakia were included. Multivariable analyses were carried out to determine independently associated systemic and ocular factors for iris conicity in phakic eyes. RESULTS: Mean iris conicity was 8.28° ± 3.29° (right eyes). Statistical analysis revealed associations between steeper iris conicity and shallower anterior chamber depth, thicker human lens and higher corneal power in multivariable analysis, while older age was related to a flatter iris conicity. Refraction, axial length, central corneal thickness, pupil diameter, and intraocular pressure were not associated with iris conicity. Pseudophakia resulted in a 5.82° flatter iris conicity than in the fellow phakic eyes. CONCLUSIONS: Associations indicate a correlation between iris conicity with risk factors for angle-closure, namely, shallower anterior chamber depth and thicker human lens. In pseudophakic eyes, iris conicity is significantly lower, indicating that cataract surgery flattens the iris.

Suprachoroidal Bleeding After XEN Gel Implantation.

PURPOSE: To report for the first time a clinical case of suprachoroidal bleeding after XEN45 gel implantation. OBSERVATIONS: A 84-year old female patient with pseudoexfoliation glaucoma with intraocular pressure (IOP) (20 mm Hg) above target despite maximal IOP-lowering therapy was scheduled for XEN45 gel implantation. The XEN45 gel implantation went without complications and was properly placed in the anterior chamber and beneath the conjunctiva. On the first postoperative day, the patient presented with an IOP of 4 mm Hg, a functioning bleb and a deep anterior chamber. On the second day she developed suprachoroidal bleeding. A wait and see strategy was followed and the patient monitored steadily. The bleeding resolved spontaneously after 6 weeks. CONCLUSIONS AND IMPORTANCE: Minimally invasive glaucoma surgery is developed to provide a safer and less-invasive option to reduce IOP in glaucoma patients compared with trabeculectomy. Although the concept of the XEN45 gel stent seems to be a favorable to reach IOP-lowering results similar to those of trabeculectomy, complications may be similar, too. We have to keep this in mind when informing patients about surgical options.

The impact of pseudophakia on vision-related quality of life in the general population - The Gutenberg Health Study.

Cataract surgery is the most frequently performed surgical procedure worldwide. We aim to determine the prevalence of having implanted an artificial lens (pseudophakia) and of no lens (aphakia) and to compare visual function.As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in Germany. An ophthalmological examination including slit-lamp examination was conducted. Prevalence including 95% confidential intervals were calculated and analyses were conducted for systemic and ocular associated factors with pseudophakia using multivariable logistic regression models. Vision-related quality of life was assessed using a standardized questionnaire and Rasch transformation.14,696 people were included. Of these, 1.55% [1.36%-1.77%] had unilateral pseudophakia and 3.08% [2.81%-3.37%] had bilateral pseudophakia. Unilateral aphakia was present in 21 people and bilateral aphakia in 2 people. Pseudophakia was independently associated with age, higher body weight and lower body height, diabetes and smoking. Vision-related quality of life values were similar for those with bilateral phakia and pseudophakia but were lower for those with unilateral pseudophakia.The pseudophakia status is related to several cardiovascular risk factors, indicating a relationship to an aging effect that causes premature lens opacification. Bilateral pseudophakia can almost imitate the physiological condition of phakia except for the need to use glasses.

Curvature of iris profile in spectral domain optical coherence tomography and dependency to refraction, age and pupil size - the MIPH Eye&Health Study.

PURPOSE: Optical coherence tomography (OCT) of the anterior segment allows quantitative analysis of the geometry of the iris. We performed spectral domain OCT examinations in healthy emmetropic, hyperopic and myopic subjects to investigate iris curvature and its associations. METHODS: In a cross-sectional study, out of 4617 eyes (2309 subjects) those with refractive errors of <-4 or >+3 dioptres were identified by objective refraction. The iris was examined using the anterior segment mode of a spectral domain 3D OCT-2000 (Topcon Inc., Japan) in the temporal meridian, and OCT scans were investigated with respect to presence and amount of convex and concave iris configuration. Ninety-three eyes of 50 subjects served as emmetropic group (-0.5 ≤ x ≤+0.5 dioptres). Previous ocular surgery was exclusion criterion. RESULTS: Six hundred and sixty-eight eyes of 398 persons [292 male (76%); age range; 18-66 years] were included in the study. In the myopic group, 105 eyes had a concave iris configuration (26%), while in the hyperopic group, no eye had this configuration (0%) and in the emmetropic group five eyes (5%). Convex iris configuration was found in 96% of hyperopic, in 85% of the emmetropic and in 67% of the myopic eyes. There was an association between concave iris configuration and myopia, younger age and male gender, and with anterior chamber angle width. CONCLUSION: Spectral domain OCT images can be used for analysis of the iris structure and geometry. Our results are limited to the properties of the study population having an age range from 18 to 66 years and consisting mainly of men.

Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma.

BACKGROUND: Primary congenital glaucoma (PCG) and early onset glaucomas are one of the major causes of children and young adult blindness worldwide. Both autosomal recessive and dominant inheritance have been described with involvement of several genes including CYP1B1, FOXC1, PITX2, MYOC and PAX6. However, mutations in these genes explain only a small fraction of cases suggesting the presence of further candidate genes. METHODS: To elucidate further genetic causes of these conditions whole exome sequencing (WES) was performed in an Italian patient, diagnosed with PCG and retinal detachment, and his unaffected parents. Sanger sequencing of the complete coding region of COL1A1 was performed in a total of 26 further patients diagnosed with PCG or early onset glaucoma. Exclusion of pathogenic variations in known glaucoma genes as CYP1B1, MYOC, FOXC1, PITX2 and PAX6 was additionally done per Sanger sequencing and Multiple Ligation-dependent Probe Amplification (MLPA) analysis. RESULTS: In the patient diagnosed with PCG and retinal detachment, analysis of WES data identified compound heterozygous variants in COL1A1 (p.Met264Leu; p.Ala1083Thr). Targeted COL1A1 screening of 26 additional patients detected three further heterozygous variants (p.Arg253*, p.Gly767Ser and p.Gly154Val) in three distinct subjects: two of them diagnosed with early onset glaucoma and mild form of osteogenesis imperfecta (OI), one patient with a diagnosis of PCG at age 4 years. All five variants affected evolutionary, highly conserved amino acids indicating important functional restrictions. Molecular modeling predicted that the heterozygous variants are dominant in effect and affect protein stability and thus the amount of available protein, while the compound heterozygous variants act as recessive alleles and impair binding affinity to two main COL1A1 binding proteins: Hsp47 and fibronectin. CONCLUSIONS: Dominant inherited mutations in COL1A1 are known causes of connective tissues disorders such as OI. These disorders are also associated with different ocular abnormalities, although recognition of the common pathology for both features is seldom being recognized. Our results expand the role of COL1A1 mutations in different forms of early-onset glaucoma with and without signs of OI. Thus, we suggest including COL1A1 mutation screening in the genetic work-up of glaucoma cases and detailed ophthalmic examinations with fundus analysis in patients with OI.

Distribution of Anterior Chamber Angle Width and Correlation With Age, Refraction, and Anterior Chamber Depth-The Gutenberg Health Study.

PURPOSE: Scheimpflug imaging allows quantitative analysis of the width of the anterior chamber angle. We report the population-based distribution of the anterior chamber angle width using this noncontact imaging technique and investigate associated factors. METHODS: A population-based cross-sectional study was carried out in Germany. A comprehensive ophthalmologic examination including refraction, biometry, and Scheimpflug imaging was performed. Automated measurement of the anterior chamber angle was performed in each anterior chamber quadrant. Exclusion criteria were previous ocular surgery or inadequate image quality. Association analyses were carried out to determine independently associated systemic and ocular factors for anterior chamber angle width using a generalized estimating equation model. RESULTS: A total of 3014 subjects (48% female) with a mean age of 58.6 ± 10.4 years were included in this study. The mean anterior chamber angle width was 32.6° ± 5.5°. Statistical analysis revealed an independent association between a smaller anterior chamber angle and female sex, higher age, and more hyperopic refraction. When including biometric parameters, shallow anterior chamber depth, shorter axial length, higher central corneal thickness, and lower corneal power were independently associated with a narrower mean anterior chamber angle width. CONCLUSIONS: These parameters are considered risk factors for angle-closure glaucoma.

Ocular wavefront analysis of aspheric compared with spherical monofocal intraocular lenses in cataract surgery: Systematic review with metaanalysis.

This review was conducted to compare the physical effect of aspheric IOL implantation on wavefront properties with that of spherical IOL implantation. The peer-reviewed literature was systematically searched in Medline, Embase, Web of Science, Biosis, and the Cochrane Library according to the Cochrane Collaboration method. Inclusion criteria were randomized controlled trials comparing the use of aspheric versus spherical monofocal IOL implantation that assessed visual acuity, contrast sensitivity, or quality of vision. A secondary outcome was ocular wavefront analysis; spherical aberration, higher-order aberrations (HOAs), coma, and trefoil were evaluated. Effects were calculated as standardized mean differences (Hedges g) and were pooled using random-effect models. Thirty-four of 43 studies provided data for wavefront analysis. Aspheric monofocal IOL implantation resulted in less ocular spherical aberration and fewer ocular HOAs than spherical IOLs. This might explain the better contrast sensitivity in patients with aspheric IOLs.

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.

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.

KLEIP deficiency in mice causes progressive corneal neovascular dystrophy.

PURPOSE: The BTB-kelch protein KLEIP/KLHL20 is an actin binding protein that regulates cell-cell contact formation and cell migration. The aim of our study was to characterize KLEIP's function in ocular health and disease in mice. METHODS: KLEIP(-/-) mice were generated, and corneas were examined histologically and stained for keratin-1, loricrin, keratin-12, keratin-14, CD31, LYVE-1, F4/80, E-cadherin, and Ki67. Corneal abrasions were performed after eyelid opening. RESULTS: Corneas of KLEIP(+/+) and KLEIP(-/-) mice were indistinguishable at birth. After eyelid opening corneal epithelial hyperplasia started to manifest in KLEIP(-/-) mice, showing a progressive epithelial metaplasia leading to total corneal opacity. In KLEIP(-/-) mice the initial stratified squamous corneal epithelium was altered to an epidermal histo-architecture showing several superficial keratinized cells, cell infiltrations into the stroma, and several apoptotic cells. Skin markers keratin 1 and loricrin were positive, and surface disease was accompanied by deep stromal vascularization. Expression analysis for E-cadherin in KLEIP(-/-) corneas showed acellular areas in the squamous epithelium, indicating a progressive fragile corneal integrity. Removal of the virgin epithelium accelerated strongly development of the epithelial and stromal alterations, identifying mechanical injuries as the major trigger for corneal dystrophy formation and scarification in KLEIP(-/-) mice. CONCLUSIONS: The data identify KLEIP as an important molecule regulating corneal epithelial integrity.

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.

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.

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.