Albert Caramoy

Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study

Aims To evaluate the outcome after two types of retinal pigment epithelium (RPE) transplantation techniques. Methods Fourteen consecutive patients with advanced exudative age-related macular degeneration (AMD) were randomly assigned to RPE-choroid sheet transplantation (group 1) or RPE cell-suspension transplantation (group 2). Outcome measures included best corrected distance and near visual acuity (BCVA), complication and recurrence rates, autofluorescence (AF), angiography, and time-domain and spectral-domain optical coherence tomography (TD- and SD-OCT). Results A gain of three or more lines in BCVA at 24 months was found in two patients in group 1 and in one patient in group 2, whereas a loss of vision of three or more lines occurred in one patient in each group. Revision surgery for proliferative vitreoretinopathy was required in one patient in group 1. Epiretinal membranes developed in two patients in group 1 and in one patient in group 2. No recurrence occurred in this series. AF showed hyperfluorescence coincident with the graft in group 1, and hyper- and hypofluorescence in irregular patterns in group 2. Revascularisation of the graft was present in all patients in group 1, and a normal choroidal vasculature in the area of RPE atrophy in all patients in group 2. OCT showed a decrease in retinal thickness in all patients, with an improved visualisation of inter- and intralaminar structures with SD-OCT. Conclusion The anatomical and functional outcome after both RPE transplantation techniques was comparable. Intrastructural irregularities of the sheet assessed using SD-OCT might explain the rather limited visual gain in otherwise successful sheet transplants. Clinical Trial Registration NCT00401713

Evaluation of Serum Lipid Concentrations and Genetic Variants at High-Density Lipoprotein Metabolism Loci and TIMP3 in Age-Related Macular Degeneration

PURPOSE To analyze the association between polymorphisms in the TIMP3 gene and genes of the high-density lipoprotein (HDL) metabolism and age-related macular degeneration (AMD), and evaluate serum lipid and lipoprotein levels in AMD patients compared with control individuals. METHODS Single nucleotide polymorphisms in or near the TIMP3, ABCA1, FADS1-3, CETP, LIPC, and LPL genes were genotyped. Serum levels of apolipoprotein B (ApoB), apolipoprotein A1, lipoprotein a, cholesterol, triglycerides, and HDL-cholesterol were determined. RESULTS Significant associations were found between AMD and variants in ABCA1 and FADS1-3, and a nearly significant association in TIMP3. No significant associations were observed for variants in LPL, LIPC, and CETP. We also observed a significant elevation of ApoB levels in serum of AMD patients. Other lipids and lipoproteins were not significantly altered. CONCLUSIONS These results confirm associations of AMD with variants near the TIMP3 gene and at loci involved in HDL metabolism. They further highlight a role of the extracellular matrix and the HDL metabolism in the pathogenesis of AMD. This study identified increased ApoB levels as a possible new serum biomarker for AMD.

Fundus autofluorescence and spectral-domain optical coherence tomography findings suggesting tissue remodelling in retinal pigment epithelium tear

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.

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.

Spectrum of Uveitis in A German Tertiary Center: Review of 474 Consecutive Patients

Abstract Purpose: To analyze the spectrum of uveitis at a German tertiary center. Patients and methods: A total of 474 consecutive patients with uveitis were classified according to the primary anatomic site of inflammation, examined for laterality of disease, and screened for etiologies. Results: Out of the total, 253 patients (53%) had anterior uveitis, 90 patients (19%) had intermediate uveitis, 100 patients (21%) had posterior uveitis, and 31 patients (7%) had panuveitis. Fifty-six percent of the patients had bilateral involvement, predominantly in intermediate uveitis (ratio 4:1) and panuveitis (ratio 3.4:1). Regarding the etiology of all uveitis cases we found 17% infectious, 23% specific clinical entities, 20% associated with systemic disease (most commonly sarcoidosis with 11%), and 41% idiopathic uveitis. Conclusions: Anterior uveitis was the most common anatomic site of intraocular inflammation. Using a tailored approach, screening for systemic etiologies is recommended, since 20% of all patients had associated systemic diseases.

Disruption of the retinitis pigmentosa 28 gene Fam161a in mice affects photoreceptor ciliary structure and leads to progressive retinal degeneration

Mutations in the FAM161A gene were previously identified as the cause for autosomal-recessive retinitis pigmentosa 28. To study the effects of Fam161a dysfunction in vivo, we generated gene-trapped Fam161a(GT/GT) mice with a disruption of its C-terminal domain essential for protein-protein interactions. We confirmed the absence of the full-length Fam161a protein in the retina of Fam161a(GT/GT) mice using western blots and showed weak expression of a truncated Fam161a protein by immunohistochemistry. Histological analyses demonstrated that photoreceptor segments were disorganized in young Fam161a(GT/GT) mice and that the outer retina was completely lost at 6 months of age. Reactive microglia appeared in the outer retina and electroretinography showed an early loss of photoreceptor function in 4-month-old Fam161a(GT/GT) animals. Light and electron microscopy revealed a remarkable phenotype of a significantly shortened connecting cilium, spread ciliary microtubule doublets and disturbed disk organization in Fam161a(GT/GT) photoreceptor cells. Co-immunolabeling experiments demonstrated reduced expression and mislocalization of centrin 3 and disturbed targeting of the Fam161a interactors lebercilin and Cep290, which were restricted to the basal body and proximal connecting cilium in Fam161a(GT/GT) retinas. Moreover, we identified misrouting of the outer segment cargo proteins opsin and rds/peripherin 2 in Fam161a(GT/GT) mice. In conclusion, our results suggest a critical role for the C-terminal domain of Fam161a for molecular interactions and integrity of the connecting cilium. Fam161a is required for the molecular delivery into the outer segment cilium, a function which is essential for outer segment disk formation and ultimately visual function.

Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization

Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar1−/− mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD.

Retinal layers measurements in healthy eyes and in eyes receiving silicone oil-based endotamponade.

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.

Aqueous flare is increased in patients with clinically significant cystoid macular oedema after cataract surgery

Background To analyse the relationship of clinically significant cystoid macular oedema (CME after phacoemulsification to blood–aqueous barrier breakdown as determined by aqueous flare, visual acuity and retinal thickness in optical coherence tomography (OCT). Materials and methods 30 eyes of 30 consecutive patients with clinically significant CME and vision loss were included. 46 pseudophakic and 45 phakic eyes without CME served as controls. Clinical data included age, gender, best-corrected visual acuity (BCVA) and spectral domain OCT volume scans. Retinal thickness measuring of the foveal central subfield was determined. Aqueous flare was measured quantitatively with the Kowa FM-500 Laser Flare-Cell Meter. Results Patients with CME had significantly higher flare values compared with pseudophakic patients (p<0.0001). For patients with CME, aqueous flare values correlated significantly with BCVA (Spearman rs=0.4, p=0.041), while there was no correlation with retinal thickness. Using flare values to predict CME, receiver operating characteristic analysis returned an area under the curve of 0.976. Conclusions Aqueous flare as a marker for inflammation and breakdown of the blood–retinal barrier is increased in patients with CME after cataract surgery.

Anterior chamber aqueous flare is a strong predictor for proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment.

Purpose: To investigate preoperative aqueous flare as a predictive factor for proliferative vitreoretinopathy (PVR) redetachment in patients with rhegmatogenous retinal detachment. Methods: Preoperatively, the aqueous flare of 116 consecutive patients with retinal detachment was measured quantitatively with a laser flare-cell meter (Kowa FM-500; Kowa Company, Ltd, Tokyo, Japan). Seventy-four healthy partner eyes and 41 eyes of healthy age-matched patients served as controls. At least 6 months after surgery, patients were reevaluated, whether surgery was performed again because of PVR redetachment. Results: Eyes with retinal detachment that developed PVR redetachment later on (n = 12) had higher flare values than eyes with uncomplicated retinal detachment (n = 104) (median, 27.63 vs. 8.83 photon counts per millisecond; P < 0.0001). No eye with PVR redetachment had a flare value <10.8 photon counts per millisecond. In eyes with flare values exceeding 15 photon counts per millisecond, the odds of PVR redetachment development increases 16-fold. Conclusion: Our study shows that the breakdown of the blood–ocular barrier as determined by aqueous flare is a major risk factor for PVR redetachment. The laser flare-cell meter is a fast, noninvasive, and safe tool that allows predicting the PVR redetachment risk preoperatively. It provides the surgeon with an estimate to choose those patients who could benefit from intravitreal drugs to prevent PVR.