Advances in Retinal Tissue Engineering

Retinal degenerations cause permanent visual loss and affect millions world-wide. Current treatment strategies, such as gene therapy and anti-angiogenic drugs, merely delay disease progression. Research is underway which aims to regenerate the diseased retina by transplanting a variety of cell types, including embryonic stem cells, fetal cells, progenitor cells and induced pluripotent stem cells. Initial retinal transplantation studies injected stem and progenitor cells into the vitreous or subretinal space with the hope that these donor cells would migrate to the site of retinal degeneration, integrate within the host retina and restore functional vision. Despite promising outcomes, these studies showed that the bolus injection technique gave rise to poorly localized tissue grafts. Subsequently, retinal tissue engineers have drawn upon the success of bone, cartilage and vasculature tissue engineering by employing a polymeric tissue engineering approach. This review will describe the evolution of retinal tissue engineering to date, with particular emphasis on the types of polymers that have routinely been used in recent investigations. Further, this review will show that the field of retinal tissue engineering will require new types of materials and fabrication techniques that optimize the survival, differentiation and delivery of retinal transplant cells.Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USABoston Univ, Dept Grad Med Sci, Boston, MA 02215 USAUniversidade Federal de São Paulo, Dept Ophthalmol, BR-09210170 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, BR-09210170 São Paulo, BrazilWeb of Scienc

Choroidal Imaging Using Spectral-Domain Optical Coherence Tomography

Author Manuscript received 2012 June 22.Background: A structurally and functionally normal choroidal vasculature is essential for retinal function. Therefore, a precise clinical understanding of choroidal morphology should be important for understanding many retinal and choroidal diseases. Methods: PUBMED ( http://www.ncbi.nlm.nih.gov/site...) was used for most of the literature search for this article. The criterion for inclusion of an article in the references for this review was that it included materials about both the clinical and the basic properties of choroidal imaging using spectral-domain optical coherence tomography. Results: Recent reports show successful examination and accurate measurement of choroidal thickness in normal and pathologic states using spectral-domain optical coherence tomography systems. This review focuses on the principles of the new technology that make choroidal imaging using optical coherence tomography possible and on the changes that subsequently have been documented to occur in the choroid in various diseases. Additionally, it outlines future directions in choroidal imaging. Conclusion: Optical coherence tomography is now proven to be an effective noninvasive tool to evaluate the choroid and to detect choroidal changes in pathologic states. Additionally, choroidal evaluation using optical coherence tomography can be used as a parameter for diagnosis and follow-up.Research to Prevent Blindness, Inc. (United States) (Unrestricted Grant)National Institutes of Health (U.S.) (Contract RO1-EY11289-25)National Institutes of Health (U.S.) (Contract R01-EY13178-10)National Institutes of Health (U.S.) (Contract R01-EY013516-07)National Institutes of Health (U.S.) (Contract R01-EY019029-02)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-10-1-0063

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT

ABSTRACT Purpose: To evaluate choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT) imaging at baseline and 6 months after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). Methods: A retrospective chart review was performed to identify patients with DME who underwent intravitreal injection of anti-VEGF (bevacizumab or ranibizumab) in a pro re nata (PRN) regimen. Subfoveal choroidal thickness was compared between values obtained at baseline and at 6-month follow-up visits. Results: Thirty-nine eyes (15 females, 24 males) from 39 patients were enrolled (mean age, 62.43 ± 8.7 years; range, 44-79 years). Twenty-three and 16 eyes were treated with ranibizumab and bevacizumab respectively. The mean number of anti-VEGF injections was 2.28 ± 1.27 (range, 1-5). Mean nasal, subfoveal, and temporal choroidal thickness (CT) measurements at baseline were 234.10 ± 8.63 µm, 246.89 ± 8.94 µm, and 238.12 ± 8.20 µm, respectively, and those at 6 months post-treatment were 210.46 ± 8.00 µm, 215.66 ± 8.29 µm, and 212.43 ± 8.14 µm, respectively. Significant differences in CT were observed between baseline and the 6-month follow-up at all measured points (p=0.0327). Conclusions: Over a 6-month period, the use of intravitreal anti-VEGF was associated with significant thinning of the choroid in patients with DME. The clinical significance of a thinner choroid in DME is currently unknown; however, it may contribute to long-term adverse effects on choroidal and retinal function, representing an area requiring future investigation

CHOROIDAL THICKNESS in PATIENTS WITH DIABETIC RETINOPATHY ANALYZED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY

Purpose: This study was designed to examine choroidal thickness in patients with diabetes using spectral-domain optical coherence tomography.Methods: Forty-nine patients (49 eyes) with diabetes and 24 age-matched normal subjects underwent high-definition raster scanning using spectral-domain optical coherence tomography with frame enhancement software. Patients with diabetes were classified into 3 groups: 11 patients with mild or moderate nonproliferative diabetic retinopathy and no macular edema, 18 patients with nonproliferative diabetic retinopathy and diabetic macular edema, and 20 patients with treated proliferative diabetic retinopathy and no diabetic macular edema (treated proliferative diabetic retinopathy). Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-mu m intervals up to 2,500 mu m temporal and nasal to the fovea.Results: Reliable measurements of choroidal thickness were obtainable in 75.3% of eyes examined. Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and thinning again temporally in normal subjects and patients with diabetes. Mean subfoveal choroidal thickness was thinner in patients with diabetic macular edema (63.3 mu m, 27.2%, P < 0.05) or treated proliferative diabetic retinopathy (69.6 mu m, 30.0%, P < 0.01), compared with normal subjects. There was no difference between nonproliferative diabetic retinopathy and normal subjects.Conclusion: Choroidal thickness is altered in diabetes and may be related to the severity of retinopathy. Presence of diabetic macular edema is associated with a significant decrease in the choroidal thickness. RETINA 32: 563-568, 2012Research to Prevent BlindnessNational Institutes of HealthAir Force Office of Scientific ResearchCarl Zeiss Meditech, IncOptovue, IncTopcon Medical Systems, Inc.Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilBoston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USAMIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilNational Institutes of Health: RO1-EY11289-23National Institutes of Health: R01-EY13178-07National Institutes of Health: R01-EY013516-07Air Force Office of Scientific Research: FA9550-07-1-0101Air Force Office of Scientific Research: FA9550-07-1-0014Web of Scienc

Choroidal thickness in retinal pigment epithelial tear as measured by spectral domain optical coherence tomography

Purpose: To evaluate the choroidal thickness with spectral domain optical coherence tomography in subjects with retinal pigment epithelial (RPE) tear compared with the choroidal thickness of their fellow eye.Methods: For this cross-sectional investigation, seven eyes of seven patients with neovascular age-related macular degeneration and RPE tear in one eye imaged with spectral domain optical coherence tomography were identified. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500 mu m intervals up to 2,500 mu m temporal and nasal to the fovea in both the eye with the RPE tear and the eye with intact RPE. All measurements were performed by two independent observers and averaged for the purpose of the analysis. Measurements were compared using paired t-test.Results: The average age of patients was 79 years (range, 66-88 years). All subjects had dome-shaped pigment epithelial detachments before RPE tear and no dome-shaped pigment epithelial detachments in the unaffected eye. Average subfoveal choroidal thickness in the eye with the RPE tear was 154.9 +/- 10.1 mu m. Average subfoveal choroidal thickness in the eye with intact RPE was 212.9 +/- 10.6 mu m (P = 0.035).Conclusion: There is a significant decrease in subfoveal choroidal thickness in the subjects with RPE tear compared with their fellow eye with intact RPE. It is unclear if this thinning is a consequence of or precedes the RPE tear. Further studies are necessary to prospectively follow choroidal thickness in subjects with dome-shaped pigment epithelial detachments.Research to Prevent BlindnessTufts University School of Medicine, National Institutes of HealthMassachusetts Lions Eye Research FundCarl Zeiss Meditech, IncOptovue, Inc.Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USAUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilTufts University School of Medicine, National Institutes of Health: RO1-EY11289-23Tufts University School of Medicine, National Institutes of Health: R01-EY13178-07Tufts University School of Medicine, National Institutes of Health: R01-EY013516-07Web of Scienc

Reproducibility of Choroidal Thickness Measurements Across Three Spectral Domain Optical Coherence Tomography Systems

Purpose: To investigate the reproducibility of choroidal thickness measurements in normal subjects on 3 spectral domain optical coherence tomography (SD-OCT) instruments: Zeiss Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA), Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany), and Optovue RTVue (Optovue Inc., Fremont, CA).Design: Cross-sectional non-interventional study.Participants: Images were obtained in 28 eyes of 28 healthy undilated volunteers without ocular pathology in a clinical setting.Methods: All subjects were imaged on the fovea using Cirrus HD 1-line raster, Spectralis enhanced depth imaging (EDI), and RTVue retina-cross.Main Outcome Measures: the choroid was measured subfoveally, 750 mu m temporal, and 750 mu m nasal to the fovea. All measurements were performed by 2 independent observers. Two-way analysis of variance (ANOVA) with Bonferroni's post-test, Pearson correlation, and Bland-Altman analysis were used to compare measurements.Results: the group of 28 subjects consisted of 7 men and 21 women, with an average age of 35.2 years (range, 23-64 years). A 2-way ANOVA with Bonferroni's post-test revealed no significant difference in the average subfoveal choroidal thickness (P > 0.05) among systems for any location: subfoveally, 750 mu m temporal, and 750 mu m nasal to the fovea. the measurements of choroidal thickness from any pair of 3 instruments (Cirrus vs. Spectralis, Cirrus vs. RTVue, Spectralis vs. RTVue) were also strongly correlated. the Pearson correlation among all 2 system pairs of the 3 systems was greater than 0.9 (P < 0.0001). the 95% limits of agreement among 4 choroidal thickness measurements were +11.21% to -13.57% (bias -1.17) between Cirrus and RTVue, +10.85% to -12.45% (bias -0.80) between Spectralis and RTVue, and +12.81% to -13.33% (bias -0.25) between Cirrus and Spectralis.Conclusions: in our population of young healthy adults with normal vision, there was good reproducibility among choroidal thickness measurements of images acquired with Cirrus, Spectralis, and RTVue.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 119-123 (C) 2012 by the American Academy of Ophthalmology.Research to Prevent BlindnessNational Institutes of HealthAir Force Office of Scientific ResearchTufts Univ New England Med Ctr, Tufts Med Ctr, Boston, MA 02111 USABoston Univ, Sch Med, Boston, MA 02118 USAUniversidade Federal de São Paulo, São Paulo, BrazilUniv Hosp Albacete, Albacete, SpainMIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USAUniversidade Federal de São Paulo, São Paulo, BrazilNational Institutes of Health: RO1-EY11289-25National Institutes of Health: R01-EY13178-10National Institutes of Health: R01-EY013516-07National Institutes of Health: R01-EY019029-02Air Force Office of Scientific Research: FA9550-10-1-0551Air Force Office of Scientific Research: FA9550-10-1-0063Web of Scienc