Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration.

PurposeIntravitreal murine lineage-negative bone marrow (BM) hematopoietic cells slow down retinal degeneration. Because human BM CD34+ hematopoietic cells are not precisely comparable to murine cells, this study examined the effect of intravitreal human BM CD34+ cells on the degenerating retina using a murine model.MethodsC3H/HeJrd1/rd1 mice, immunosuppressed systemically with tacrolimus and rapamycin, were injected intravitreally with PBS (n = 16) or CD34+ cells (n = 16) isolated from human BM using a magnetic cell sorter and labeled with enhanced green fluorescent protein (EGFP). After 1 and 4 weeks, the injected eyes were imaged with scanning laser ophthalmoscopy (SLO)/optical coherence tomography (OCT) and tested with electroretinography (ERG). Eyes were harvested after euthanasia for immunohistochemical and microarray analysis of the retina.ResultsIn vivo SLO fundus imaging visualized EGFP-labeled cells within the eyes following intravitreal injection. Simultaneous OCT analysis localized the EGFP-labeled cells on the retinal surface resulting in a saw-toothed appearance. Immunohistochemical analysis of the retina identified EGFP-labeled cells on the retinal surface and adjacent to ganglion cells. Electroretinography testing showed a flat signal both at 1 and 4 weeks following injection in all eyes. Microarray analysis of the retina following cell injection showed altered expression of more than 300 mouse genes, predominantly those regulating photoreceptor function and maintenance and apoptosis.ConclusionsIntravitreal human BM CD34+ cells rapidly home to the degenerating retinal surface. Although a functional benefit of this cell therapy was not seen on ERG in this rapidly progressive retinal degeneration model, molecular changes in the retina associated with CD34+ cell therapy suggest potential trophic regenerative effects that warrant further exploration

Increased choroidal thickness in adults with Down syndrome.

INTRODUCTION: People with Down syndrome (DS) are particularly susceptible to Alzheimer's disease (AD) due to the triplication of the amyloid precursor protein (APP) gene. In this cross-sectional study, we hypothesized that choroidal thinning reported in sporadic AD (sAD) is mirrored in adults with DS. METHODS: The posterior pole of the eye for 24 adults with DS and 16 age-matched controls (Ctrl) were imaged with optical coherence tomography. Choroidal thickness (ChT) was measured and analyzed in relation to cognitive status and cerebral amyloid beta (Aβ) load. RESULTS: ChT was increased in people with DS (pwDS) compared to Ctrl. This increase was associated with gender differences and positively correlated with cerebral Aβ load in a small subset. There was no significant correlation detected between ChT and age or cognitive status. DISCUSSION: In contrast to sAD this study found a significantly thicker choroid in pwDS. Whether these changes are related to Aβ pathology in DS needs further investigation

Psychological impact of anti-VEGF treatments for wet macular degeneration-a review.

To review the current literature on the psychological impact of anti-VEGF treatments for wet age-related macular degeneration (wAMD), in terms of patients' experiences of receiving these treatments, and the impact of these treatments for patients' mental health and quality of life.We critically analyzed current literature evaluating psychological impact of anti-VEGF treatments for wAMD. Primary searches of PubMed, Science Direct, and Web of Science were conducted in July and August of 2015. We reviewed all papers on the topic published until August 5, 2015.Our literature search found 14 papers addressing the psychological impact of anti-VEGF treatments for wAMD. Results highlighted potential anxieties and experiences of pain caused by receiving regular intravitreal injections. A positive visual outcome of anti-VEGF therapy is associated with positive vision-related QOL outcomes, although such association seems to be dependent on improvements on visual acuity. In the literature reviewed, patients receiving anti-VEGF treatments showed a prevalence rate of depression between 20 and 26 %.Although anti-VEGF treatments can cause some anxiety and being experienced as a stressful event, especially in the beginning of the treatment, preliminary findings suggest a potential benefit for long-term vision-related quality of life. Further longitudinal and qualitative research should bring more evidence on the positive and negative effects of these treatments on patients' long-term mental health

Benefit of an electronic head‐mounted low vision aid

Purpose: To evaluate the efficacy of electronic head-mounted low vision aid (e-LVA) SightPlus (GiveVision, UK, givevision.net) and to determine which people with low vision would see themselves likely using an e-LVA like this. Methods: Sixty participants with low vision aged 18 to 93 used SightPlus during an in-clinic study session based on a mixed methods design. Visual acuity (ETDRS), contrast sensitivity (Pelli-Robson) and reading performance (MNREAD) were measured binocularly at baseline (no device), with the device in ‘normal’ mode (zoom only), and with preferred enhanced mode (zoom and one of four digital image enhancements). At the end of the session, a short questionnaire recorded willingness to use an e-LVA like SightPlus, potential use cases, positive/negative comments and adverse effects. Results: Binocular distance visual acuity improved significantly by 0.63 logMAR on average (p < 0.0001) to 0.20 logMAR. Contrast sensitivity improved significantly by 0.22 log units (p < 0.0001) to 1.21 log units with zoom only and by 0.40 log units to 1.37 log units with zoom and preferred image enhancement. Reading performance improved significantly for near visual acuity and critical print size (p < 0.015), although reading speed significantly decreased (p < 0.0001). Nearly half (47%) of the participants indicated they would use an e-LVA like SightPlus, especially for television, reading and entertainment (e.g. theatre). Multivariate logistic regression showed that proportion of lifetime affected by sight loss, baseline contrast sensitivity and use of electronic LVAs explained 41% of the variation in willingness to use. Conclusions: SightPlus improves visual function in people with low vision and would be used in its current form by one half of the people who tried it. Adverse effects were infrequent and resolved when the device was removed. Future work should focus on comparing e-LVAs through repeatable real-world tasks and impact on quality of life

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

Management of persistent loculated subretinal fluid after pneumatic retinopexy

AIM—To report on the incidence and management of a unique and troublesome complication of pneumatic retinopexy—localised, delayed subretinal fluid absorption (DSRFA).
METHODS—A retrospective chart review was done for all patients who underwent pneumatic retinopexy for retinal detachment over a 5( )year period to identify the patients with DSRFA.
RESULTS—Seven phakic patients (five females, two males, age range 26-87 years) were identified with the phenomenon of delayed resolution of subretinal fluid after pneumatic retinopexy and cryotherapy. In four patients the subretinal fluid involved the macula. Time taken to complete absorption of the subretinal fluid ranged from 10 to 26 months. In one patient there was still residual fluid inferiorly at 18 months of follow up. During the follow up period additional procedures were performed—scleral buckling (five eyes), pars plana vitrectomy (one eye), and mild laser scatter to extramacular areas of shallow subretinal fluid (four eyes). None of these procedures appeared to influence the rate of fluid absorption.
CONCLUSIONS—Loculated subretinal fluid following pneumatic retinopexy may persist for very long periods, extending up to more than 2 years. Additional surgical procedures or laser photocoagulation do not affect the rate of subretinal fluid absorption. Spontaneous reattachment eventually occurs in most eyes, and conservative management is indicated.