Visual acuity of 20/32, 13.5 years after a retinal pigment epithelium and choroid graft transplantation

Purpose: To present the 13.5-year-survival of an autologous retinal pigment epithelium (RPE) and choroid graft transplantation with good visual acuity results. Observations: A 72-year old patient presented with a 5-weeks-old visual acuity deterioration to excentric finger counting at half a meter. Fundoscopy showed a fibrotic macular scar, a large subretinal hemorrhage, partly recent, combined with intraretinal fluid, blood, and hard exudates. RPE-choroid graft surgery was performed, and visual acuity improved to 20/32, and maintained up until 13.5 years postoperative. Microperimetry performed at the same time revealed a 3.4 dB sensitivity, with fixation on the graft. During the postoperative years glaucoma developed, an uveitis anterior was treated, and to treat a small Coats' like lesion; one bevacizumab injection was administered. Conclusions and importance: A best corrected visual acuity of 20/32 could be achieved and maintained up to 13.5 years after an RPE-choroid graft transplantation, despite an unfavorable preoperative presentation and some early and late complications. This case is a proof of principle that an RPE-choroid graft harvested from the midperiphery can support the macular metabolism up to 13.5 after surgery in a patient with severe exudative AMD. It also represents a rationale for pursuing stem cell derived RPE replacement. Anti-vascular endothelial growth factor injections are nowadays the mainstay of therapy for choroidal neovascularization and/or small hemorrhages and offer good results. Nevertheless, selected patients that cannot benefit from this therapy may profit from an autologous RPE-choroid graft transplantation

PROPHYLACTIC LASER TREATMENT TO DECREASE THE INCIDENCE OF RETINAL DETACHMENT IN FELLOW EYES OF IDIOPATHIC GIANT RETINAL TEARS

Purpose: To evaluate the effectiveness of prophylactic 360° laser treatment in the fellow eye of patients with unilateral idiopathic giant retinal tear (GRT) to prevent the occurrence of a (macula-off) retinal detachment. Methods: We conducted a retrospective, nonrandomized case–control study. Clinical data of consecutive patients, undergoing surgery for idiopathic GRT, between 2003 and 2015 were analyzed. The data c

Thrombin Generation in Vitreous and Subretinal Fluid of Patients with Retinal Detachment

Purpose: To measure prothrombin fragments (F1+2) and thrombin-antithrombin complex (TAT) in vitreous and subretinal fluid (SRF) of rhegmatogenous retinal detachment (RRD) patients and to validate and further specify our earlier finding of increased thrombin activity in patients with proliferative vitreoretinopathy (PVR). Methods: F1+2 and TAT were measured in 31 vitreous and 16 SRF samples using the Enzygnost® immunoassays. Results: We found significant levels of F1+2 and TAT in the vitreous of all patients with RRD compared to patients with macular hole or macular pucker. However, there was no significant difference between patients who would develop PVR in the future, had established PVR, and patients with uncomplicated RRD both in vitreous concentrations of F1+2 (Kruskal-Wallis p = 0.963) and TAT (p = 0.516). Conclusion: The analysis of F1+2 and TAT confirmed significant thrombin generation in both vitreous and SRF of patients with RRD. An imbalance between the thrombin regulation mechanisms TAT and α2-macroglobulin possibly explains the difference from our previous findings

The effect of a preoperative subconjuntival injection of dexamethasone on blood-retinal barrier breakdown following scleral buckling retinal detachment surgery: a prospective randomized placebo-controlled double blind clinical trial

Background: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively. Methods: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement. Results: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit. Conclusion: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR

Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes

AIM: To evaluate the possibility of translocating autologous peripheral retinal pigment epithelial (RPE) cells and enhance their adhesion to improve functional outcome after choroidal neovascular membrane extracti

Smaller Foveal Avascular Zone in Deep Capillary Plexus Is Associated with Better Visual Acuity in Patients after Macula-off Retinal Detachment Surgery

Purpose: To associate the change in the foveal avascular zone (FAZ) and vessel density (VD) with final best corrected visual acuity (BCVA) in eyes after macula-off rhegmatogenous retinal detachment surgery, and to investigate the evolution of FAZ and VD during 12 months of follow-up. Methods: We prospectively evaluated 47 patients with macula-off rhegmatogenous retinal detachment and healthy fellow eyes. At 1.5, 3.0, 6.0, and 12.0 months postoperatively, optical coherence tomography angiography scans were obtained from both eyes on a 3.0 × 3.0 mm macula-centered grid. En face images of the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were used to quantify FAZ and VD. BCVA was assessed with ETDRS-charts (logarithm of the minimal angle of resolution). At 12 months postoperatively, the association between the change in optical coherence tomography angiography parameters and visual function in study eyes was evaluated using the Spearman correlation coefficient. We calculated the BCVA difference and the percentage difference of FAZ and VD between the study and control eye. The evolution of FAZ and VD was investigated with linear mixed-effects models with nested random effects (eyes nested within patients). Results: At 12 months postoperatively, FAZ difference of the deep capillary plexus and BCVA difference were correlated (P = 0.0004, rs = 0.5). Furthermore, there was no evidence that FAZ and VD changed during follow-up. Conclusions: Although FAZ and VD remained stable during 12 months after surgery for macula-off rhegmatogenous retinal detachment, a smaller FAZ in the deep capillary plexus is associated with better BCVA. Translational relevance: Reduction in FAZ area may be caused by angiogenesis to counteract ischemia, therefore therapeutic stimulation of angiogenesis could be beneficial to visual recovery

Preoperative Posturing of Patients with Macula-On Retinal Detachment Reduces Progression Toward the Fovea

Purpose: Traditionally, preoperative posturing consisting of bed rest and positioning is prescribed to patients with macula-on retinal detachment (RD) to prevent RD progression and detachment of the fovea. Execution of such advice can be cumbersome and expensive. This study aimed to investigate if preoperative posturing affects the progression of RD. Design: Prospective cohort study. Participants: Ninety-eight patients with macula-on RD were included. Inclusion criteria were volume optical coherence tomography (OCT) scans could be obtained with sufficient quality; and the smallest distance from the fovea to the detachment border was 1.25 mm or more. Methods: Patients were admitted to the ward for bed rest in anticipation of surgery and were positioned on the side where the RD was mainly located. At baseline and before and after each interruption for meals or toilet visits, a 37°×45° OCT volume scan was performed using a wide-angle Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The distance between the nearest point of the RD border and fovea was measured using a custom-built measuring tool. Main Outcome Measures: The RD border displacement and the average RD border displacement velocity moving toward (negative) or away (positive) from the fovea were determined for intervals of posturing and interruptions. Results: The median duration of intervals of posturing was 3.0 hours (interquartile range [IQR], 1.8-14.0 hours; n = 202) and of interruptions 0.37 hours (IQR, 0.26-0.50 hours; n = 197). The median RD border displacement was 2 μm (IQR, -65 to +251 μm) during posturing and -61 μm (IQR, -140 to 0 μm) during interruptions, a statistically significant difference (P < 0.001, Mann-Whitney U test). The median RD border displacement velocity was +1 μm/hour (IQR, -21 to +49 μm/hour) during posturing and -149 μm/hour (IQR, -406 to +1 μm/hour) during interruptions, a statistically significant difference (P < 0.001). Conclusions: By making use of usual interruptions of preoperative posturing we were able to show, in a prospective and ethically acceptable manner, that RD stabilizes during posturing and progresses during interruptions in patients with macula-on RD. Preoperative posturing is effective in reducing progression of RD

Retinal oximetry and fractal analysis of capillary maps in sickle cell disease patients and matched

Purpose: Fractal analysis can be used to quantitatively analyze the retinal microvasculature and might be a suitable method to quantify retinal capillary changes in sickle cell disease (SCD) patients. Retinal oximetry measurements might function as a proxy for the pathophysiology of cerebrovascular diseases. Moreover, hypoxia has an important role in the pathophysiology of diabetic and other retinopathies. However, little is known about the oximetry around the macula in SCD patients. With this study, we explored the feasibility to perform these quantified measurements in SCD patients. Methods: Retinal microvascular and oximetry measurements were performed in eight SCD patients and eight healthy matched controls. Oximetry pictures and non-invasive capillary perfusion maps (nCPM) were obtained by the retinal function imager. Measurements were conducted twice on two different study days. Measured variables included monofractal dimension (Dbox), relative saturation, deoxygenated hemoglobin (deoxyHb), and oxygenated hemoglobin (oxyHb) concentration. Results: No statistically significant differences in vessel density were found in the different annular zones (large vessels, p = 0.66; small vessels, p = 0.66) and anatomical quadrants (large vessels, p = 0.74; small vessels, p = 0.72). Furthermore, no significant between-group differences were found in the other different anatomical quadrants and annular zones around the fovea for relative saturation levels and deoxygenated Hb. However, the oxyHb levels were significantly lower in SCD patients, compared with those in matched controls in the temporal quadrants (p = 0.04; p = 0.02) and the superior nasal quadrant (p = 0.05). Conclusions: Our study demonstrated the feasibility of multispectral imaging to measure retinal changes in oxygenation in both SCD patients and matched volunteers. The results suggest that in SCD patients before any structural microvascular changes in the central retina are present, functional abnormalities can be observed with abnormal oximetry measurements

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models

Purpose To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. Methods Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. Results The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. Conclusions We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials

A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation

Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined= 3.4 × 10-9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2= 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined= 2.1 × 10-7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height