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1.  Nutritional Risk Factors for Age-Related Macular Degeneration 
BioMed Research International  2014;2014:413150.
Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10−6; 2–6x/week: OR: 1.67, P = 7.98 × 10−5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD.
doi:10.1155/2014/413150
PMCID: PMC4101976  PMID: 25101280
2.  Impact of the Common Genetic Associations of Age-Related Macular Degeneration upon Systemic Complement Component C3d Levels 
PLoS ONE  2014;9(3):e93459.
Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002), higher age (p = 1.56×10−7), AMD phenotype (p = 1.15×10−11) and the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower C3d/C3 ratios were found for diabetes (p = 2.87×10−6), higher body mass index (p = 1.00×10−13), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003), rs12144939 (p = 4.60×10−6) in CFH, rs4151667 (p = 1.01×10−5) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.
doi:10.1371/journal.pone.0093459
PMCID: PMC3968152  PMID: 24675670
3.  SDOCT Thickness Measurements of Various Retinal Layers in Patients with Autosomal Dominant Optic Atrophy due to OPA1 Mutations 
BioMed Research International  2013;2013:121398.
Purpose. To specify thickness values of various retinal layers on macular spectral domain Optical Coherence Tomography (SDOCT) scans in patients with autosomal dominant optic atrophy (ADOA) compared to healthy controls. Methods. SDOCT volume scans of 7 patients with ADOA (OPA-1 mutation) and 14 healthy controls were quantitatively analyzed using manual grading software. Mean thickness values for the ETDRS grid subfields 5–8 were calculated for the spaces neurosensory retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), a combined space of inner plexiform layer/outer plexiform layer/inner nuclear layer (IPL+INL+OPL), and a combined space of outer nuclear layer/photoreceptor layers (ONL+PL). Results. ADOA patients showed statistically significant lower retinal thickness values than controls (P < 0.01). RNFL (P < 0.001) and GCL thicknesses (P < 0.001) were significantly lower in ADOA patients. There was no difference in IPL+INL+OPL and in ONL+PL thickness. Conclusion. Manual subanalysis of macular SDOCT volume scans allowed detailed subanalysis of various retinal layers. Not only RNFL but also GCL thicknesses are reduced in the macular area of ADOA patients whereas subjacent layers are not involved. Together with clinical findings, macular SDOCT helps to identify patients with suspicion for hereditary optic neuropathy before genetic analysis confirms the diagnosis.
doi:10.1155/2013/121398
PMCID: PMC3760180  PMID: 24024178
4.  Grading of Age-Related Macular Degeneration: Comparison between Color Fundus Photography, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography 
Journal of Ophthalmology  2013;2013:385915.
Purpose. To compare color fundus photography (FP), fluorescein angiography (FA), and spectral domain optical coherence tomography (SDOCT) for the detection of age-related macular degeneration (AMD), choroidal neovascularisation (CNV), and CNV activity. Methods. FPs, FAs, and SDOCT volume scans from 120 eyes of 66 AMD and control patients were randomly collected. Control eyes were required to show no AMD, but other retinal pathology was allowed. The presence of drusen, pigmentary changes, CNV, and signs for CNV activity was independently analyzed for all imaging modalities. Results. AMD was diagnosed based on FP in 75 eyes. SDOCT and FA showed sensitivity (specificity) of 89% (76%) and 92% (82%), respectively. CNV was present on FA in 68 eyes. Sensitivity (specificity) was 78% (100%) for FP and 94% (98%) for SDOCT. CNV activity was detected by SDOCT or FA in 60 eyes with an agreement in 46 eyes. Sensitivity was 88% for SDOCT and 88% for FA. FP showed sensitivity of 38% and specificity of 98%. Conclusions. CNV lesions and activity may be missed by FP alone, but FP may help identifying drusen and pigmentary changes. SDOCT is highly sensitive for the detection of AMD, CNV, and CNV activity; however, it cannot fully replace FA.
doi:10.1155/2013/385915
PMCID: PMC3665260  PMID: 23762528
5.  Cost-effectiveness of autologous retinal pigment epithelium and choroid translocation in neovascular AMD 
AIM
To assess the cost-effectiveness of autologous retinal pigment epithelium and choroid translocation (PATCH) in neovascular age-related macular degeneration (AMD).
METHODS
Visual acuity and complication rates of published patient series were used to determine the incremental utility of treatment for the patient. The utility data applied assume that the better eye was affected. Comparator was a meta-analysis of recent control groups, in which patients received best supportive care. To assess cost-effectiveness, costs per quality adjusted life years (QALYs) and costs of avoiding low vision (“legal blindness”, i.e. ≤20/200) were calculated. Costs were based on a German sick fund perspective and in a scenario on US costs. Robustness of the model was investigated by univariate and probabilistic multivariate sensitivity analysis (PSA).
RESULTS
Cost-utility analysis showed surgery to be the dominant (“cost-saving”) strategy for Germany and for the US in both, cost-effectiveness and cost-utility analysis (costs per QALY). In the sensitivity analysis the intervention remained dominant or cost-effective in all scenarios investigated. Clinical outcomes and duration of modeling were the most influential factors in the sensitivity analyses.
CONCLUSION
Therapy of neovascular AMD by PATCH is a cost-effective treatment option for selected patients, who are not well suitable for other current treatment options.
doi:10.3980/j.issn.2222-3959.2010.03.11
PMCID: PMC3340621  PMID: 22553560
age-related macular degeneration; choroidal neovascularization; cost-utility analysis; macular surgery; QALY
6.  Histological evidence for revascularisation of an autologous retinal pigment epithelium–choroid graft in the pig 
Background
Translocation of a free autologous graft consisting of retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in patients with exudative age‐related macular degeneration is currently being evaluated in clinical practice. Angiographic studies in these patients suggest that their grafts become revascularised.
Aim
To investigate the histological evidence of revascularisation of the graft in a porcine model.
Methods
In 11 pigs (11 eyes), an RPE–choroid graft was translocated from the mid‐periphery to an intact or an intentionally damaged RPE and Bruch's membrane at the recipient site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections were evaluated using immunohistochemistry.
Results
Bridging vessels between recipient layer and graft were identified from 1 week to 3 months after surgery. This reconnection occurred regardless of whether the Bruch's membrane of the recipient site was left intact or intentionally damaged at the time of transplantation. The vasculature of the graft appeared open and perfused. Vessels with transcapillary pillars and conglomerates of small new vessels were present in the graft.
Conclusions
This study showed histological evidence for revascularisation by angiogenesis of a free autologous RPE–choroid graft.
doi:10.1136/bjo.2006.103259
PMCID: PMC1994759  PMID: 16987900
7.  In vitro emulsification assessment of new silicone oils 
Aim
To investigate whether the emulsification of conventional silicone oils can be reduced by adding small amounts of silicone molecules of a very long chain length.
Methods
Siluron 1000, Siluron 2000, Siluron 5000, Acri.Sil-Ol 5000, Oxane 5700, Densiron 68 LV, Densiron 68 and Densiron 68 HV (0.5 ml) were each tested along with either plasma or serum (0.5 ml) in a glass cuvette. Emulsification was induced by sonication and documented by photography. The total area of emulsified oil was assessed using the ImageJ software.
Results
The addition of small amounts of very-long-chain silicone molecules significantly reduced the emulsification for 1000 cSt silicone oil (Siluron 2000) and for 1000 cSt silicone oil with an admixture of F6H8 (Densiron 68 HV).
Conclusion
New low-viscosity silicone oils show a reduced emulsification similar to that of 5000 cSt oils. In future, it may be possible to avoid using 5000 cSt oils. The findings may foster silicone oil surgery in general, and in particular the application of small-incision techniques.
doi:10.1136/bjo.2009.170852
PMCID: PMC2976467  PMID: 19955199
Silicone oil; polydimethylsiloxane; emulsification; vitreous; treatment surgery
8.  Autologous translocation of choroid and retinal pigment epithelium in geographic atrophy: long-term functional and anatomical outcome 
The British Journal of Ophthalmology  2009;94(8):1040-1044.
Purpose
To evaluate the long-term outcome of autologous graft of retinal pigment epithelium (RPE) in patients with geographic atrophy.
Methods
Ten patients with progressive geographic atrophy underwent translocation of an autologous graft of RPE, Bruch membrane and choroid. The visual acuity (VA), reading performance, microperimetry, optical coherence tomography (OCT), fundus autofluorescence, fluorescein angiography and indocyanine green angiography were assessed.
Results
No recurrence of RPE atrophy was seen. All but one transplant were revascularised. Vascularisation persisted throughout the 3 years' follow-up. Spectral-domain OCT in some cases showed intact photoreceptors or intact outer nuclear and outer plexiform layer overlying the graft. In three cases, the grafts were positioned eccentrically; these patients did not benefit from surgery. The mean VA decreased from 20/80 (range: 20/800 to 20/40) at baseline to 20/200 (range: perception of hand movements to 20/32) at last follow-up. In two patients, VA were stable from 20/50 to 20/32 and 20/40 at the last follow-up, respectively. Postoperative complications included retinal detachment due to proliferative vitreoretinopathy, macular pucker, iritis, branch retinal vein occlusion and secondary ocular hypertension.
Conclusions
Some patients benefit for at least 3 years from a functioning RPE-choroid graft. Functional outcome in most patients, however, was limited due to complications and unfavourable patient selection.
doi:10.1136/bjo.2009.161299
PMCID: PMC2976216  PMID: 19692368
Age-related macular degeneration; geographic atrophy; retinal pigment epithelium; treatment surgery; retina; macula; choroid
9.  Fundus autofluorescence and spectral-domain optical coherence tomography findings suggesting tissue remodelling in retinal pigment epithelium tear 
The British Journal of Ophthalmology  2012;96(9):1211-1216.
Aim
To study tissue remodelling and wound healing after retinal pigment epithelium (RPE) tears due to age-related macular degeneration.
Methods
Retrospective longitudinal study of 36 eyes (33 patients) with RPE tears. Imaging was performed using fundus autofluorescence (FAF) (λ=488 nm) and spectral-domain optical coherence tomography (SD-OCT). Presence of intraretinal hyper-reflective dots in SD-OCT, which correlated with hyperfluorescent dots in FAF, indicating RPE migration was studied. Morphology of subretinal mass and RPE layer integrity in the RPE denuded area over time were examined.
Results
7 of 36 eyes (19.4%) showed patchy or hazy hyperfluorescent areas in FAF, and the majority of eyes (83.3%) showed hyper-reflective dots, which possibly represent intraretinal RPE migration and hard exudates. Homogenous subretinal mass was encountered in about half of all cases. In one case (2.8%), the RPE layer proliferated and covered the defect.
Conclusions
SD-OCT and FAF showed a considerable amount of RPE proliferation, migration and repopulation. Intraretinal RPE migration did not form a functional RPE layer. A small defect might be repaired by cell proliferation. But this RPE proliferation is not sufficient to cover large defects.
doi:10.1136/bjophthalmol-2012-301750
PMCID: PMC3432490  PMID: 22826551
Retinal pigment epithelium tear; pigment migration; spectral-domain optical coherence tomography; fundus autofluorescence; macula; pharmacology; neovascularisation; drugs; clinical trial; treatment surgery
10.  Spectral-domain optical coherence tomography in subjects over 60 years of age, and its implications for designing clinical trials 
The British Journal of Ophthalmology  2012;96(10):1325-1330.
Aims
To study the variability of central retinal thickness (CRT), its concordance to the fellow eye, and the implications for designing future clinical trials using spectral-domain optical coherence tomography (SD-OCT).
Methods
Cross-sectional retrospective analysis of European Genetic Database. 632 eyes of 316 subjects over 60 years of age without macular pathology were examined using SD-OCT.
Results
Mean CRT was 280.22 µm and 281.02 µm for the right and left eyes, respectively. There was a strong concordance for all measured values between right and left eyes. Men had significantly thicker CRT than women. Variation up to 23 µm difference between both eyes was seen. To detect a change of at least 30 µm in CRT, a sample size of 90 or 176 per group is needed for a single-arm or double-arm study, respectively (α=0.05, power=0.80, no loss to follow up, assuming SD in future studies=100 µm).
Conclusions
Clinical trials using CRT as an endpoint are feasible in terms of sample size needed.
doi:10.1136/bjophthalmol-2012-301885
PMCID: PMC3595499  PMID: 22863948
Imaging; Macula; Retina
11.  Retinal layers measurements in healthy eyes and in eyes receiving silicone oil-based endotamponade 
Acta Ophthalmologica  2013;92(4):e292-e297.
Purpose
To characterize the concordance/symmetry of each retinal layers in individuals without macular pathology and to further characterize the localization of inner retinal thinning in eyes receiving silicone oil-based endotamponade.
Methods
Retinal layers of one hundred eyes of 50 individuals without macular pathology were imaged using spectral domain optical coherence tomography (SD-OCT) and manually segmented using ImageJ software (developed by Wayne Rasband, NIH, Bethesda, MD, USA). In the second part of the study, retrospective analysis of 3028 cases of pars plana vitrectomy in University Eye Hospital Cologne, Germany, was conducted, retrieving nine patients with silicone oil-based endotamponade with no macular condition interfering retinal layers measurements. These patients had retinal detachment not involving the macula due to various conditions. In these patients, retinal layer segmentation was performed and compared with the fellow eye.
Results
There is a moderate-to-high concordance for all retinal layers between the right and the left eye of the same individual. In eyes receiving silicone oil-based endotamponade, the inner retinal layers become subsequently thinner. Ganglion cell and inner plexiform layers contribute most to this thinning, that is, 0.537 ± 0.096 mm3 compared with 0.742 ± 0.117 mm3; p = 0.006. Outer retinal layers were not affected by silicone oil-based endotamponade (p = 0.439 for the differences of calculated outer retinal layers).
Conclusion
Ganglion cell and inner retinal layers become subsequently thinner after the use of silicone oil-based endotamponade. This study advocates the use of spectral domain optical coherence tomography for patient management with silicone oil endotamponade to early detect subsequent retinal thinning.
doi:10.1111/aos.12307
PMCID: PMC4153956  PMID: 24238324
retinal thickness; silicone oil; spectral domain optical coherence tomography

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