Kakarla V. Chalam

Normative Data for Macular Thickness by High-Definition Spectral-Domain Optical Coherence Tomography (Spectralis)

PURPOSE To establish normative data for the macular thickness by spectral-domain optical coherence tomography (SD-OCT) in subjects with no known retinal disease. DESIGN Prospective, observational study in an academic institutional setting. METHODS Fifty subjects (age range, 20 to 84 years) with no known retinal disease, best-corrected visual acuity 20/20, and normal intraocular pressure were enrolled. The subjects were divided into 3 age groups: group 1 included subjects 20 to 40 years of age; group 2 included subjects 41 to 60 years of age; and group 3 included subjects 61 years of age and older. All subjects underwent a complete ophthalmologic examination to rule out any retinal diseases or glaucoma. All the OCT scans were performed by a single operator, and data obtained from the right eyes were analyzed by default, unless the right eye did not meet the inclusion criteria, and then data from left eyes were analyzed (n = 4). Central point thickness (CPT) and retinal thickness (RT) in 9 Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, including central subfield (CSF), were analyzed. Statistical analyses were carried out using the analysis of variance. RESULTS Overall, the mean CPT was 227.3 +/- 23.2 microm, and mean CSF was 270.2 +/- 22.5 microm. Among the ETDRS subfields, the outer nasal quadrant had the maximum thickness (mean +/- standard deviation, 339.5 +/- 16.9 microm). The RT did not show significant difference with age (P = .62) or with gender (P = .1). However, there was a suggestion of significant difference in RT of Black subjects as compared with White subjects (P = .007) in the present study. CONCLUSIONS Normative values for macular thickness in otherwise healthy eyes were measured to be 227.3 microm (CPT) and 270.2 microm (CSF) using commercially available Spectralis SD-OCT. Based on the data, the present study proposes the guidelines for normal CSF thickness to be 315 microm for future studies using macular thickness measurements with Spectralis SD-OCT (Heidelberg Engineering, Vista, California, USA).

Comparison of Retinal Thickness in Normal Eyes Using Stratus and Spectralis Optical Coherence Tomography

PURPOSE Spectral-domain optical coherence tomography (SD-OCT) is an advancement over time-domain OCT (TD-OCT) in the imaging of retinal disorders. Retinal thickness measured by SD-OCT differs from that measured by TD-OCT because the delineation of the outer boundary of the retina differs in the two instruments. The present study aims to evaluate this difference by comparing macular thickness, as obtained by Stratus and Spectralis OCT, in subjects without any known retinal disease. METHODS Thirty-six subjects with no history of retinal disease and with normal vision and normal intraocular pressure were enrolled in the study. Both Stratus and Spectralis OCT scanning were performed by the same operator on all subjects in one eye. Central point thickness (CPT) and retinal thickness in nine ETDRS subfields, including central subfield (CSF), were measured. Students t-test was used to determine statistical significance. RESULTS Mean CPT, as measured by the Stratus and Spectralis OCT, was 166.9 +/- 20.9 microm and 225.1 +/- 17.1 microm (P < 0.0001), and mean CSF was 202.3 +/- 19.6 microm and 271.4 +/- 19.6 microm (P < 0.0001), respectively. Although the mean difference in CSF thickness was 69.1 microm, it ranged from 61.9 to 74 microm in the other eight ETDRS subfields. CONCLUSIONS An increased measurement in retinal thickness of approximately 65 to 70 microm, as measured by Spectralis OCT compared with Stratus OCT, is consistent with the extent of axial retinal thickness measured by the two instruments. This increased measurement corresponds to the inclusion of the outer segment-RPE-Bruchs membrane complex by Spectralis OCT, which is relevant to studies using the newer SD-OCT for assessment of retinal thickness.

Optical coherence tomography angiography in retinal diseases

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTAs utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases.

Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.

OBJECTIVE To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. DESIGN Discussion of treatment protocol for DME. PARTICIPANTS Subjects with vision loss resulting from DME involving the center of the macula. METHODS The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithms underlying rationale. MAIN OUTCOME MEASURES Clinical guidelines based on a DRCR.net protocol. RESULTS The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. CONCLUSIONS Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Intracameral Avastin dramatically resolves iris neovascularization and reverses neovascular glaucoma.

Purpose To report the biologic effect of intracameral bevacizumab in patients with iris neovascularization secondary to proliferative retinal vasculopathies. Methods Sixteen eyes of 15 patients with iris neovascularization associated with or without neovascular glaucoma secondary to proliferative retinal vasculopathies received intracameral bevacizumab (1.25 mg). Ophthalmic evaluations included Snellen visual acuity (VA), complete ophthalmic examination, fluorescein iris angiography, and slit lamp photography Main outcome measure was change in degree of iris neovascularization. Secondary outcomes included fluorescein iris angiographic leakage, control of intraocular pressure, and changes in VA. Results All patients with neovascularization demonstrated by slit lamp photography and fluorescein angiography (16/16 eyes) had complete (or at least partial) reduction in leakage of the neovascularization within 3 weeks after the injection. Leakage from iris neovascularization resolved in 12 of 16 (75%) eyes. In two cases recurrent leakage was seen as early as 4 weeks necessitating repeat injection. Intraocular pressure was controlled with maximum medical therapy in eight of nine eyes reducing the need for glaucoma surgery. Visual acuity improved from a median of hand motions to 20/200. Conclusions In summary, intracameral bevacizumab was effective in reversing iris neovascularization in the majority of patients. It also facilitated intraocular pressure control in patients with associated glaucoma.

Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography.

PURPOSE To evaluate macular thickness in people with diabetes but minimal or no retinopathy using Heidelberg Spectralis optical coherence tomography (OCT). METHODS In a multicenter, cross-sectional study of mean retinal thickness, on Spectralis OCT in the nine standard OCT subfields, spanning a zone with 6-mm diameter, center point, and total retinal volume were evaluated. Central subfield (CSF) thickness was evaluated for association with demographic and clinical factors. Stratus OCT scans also were performed on each participant. RESULTS The analysis included 122 eyes (122 participants) with diabetes and no (n = 103) or minimal diabetic retinopathy (n = 19) and no macular retinal thickening on clinical exam. Average CSF thickness was 270 ± 24 μm. Central subfield thickness was significantly greater in males relative to females (mean 278 ± 23 μm vs. 262 ± 22 μm, P < 0.001). After adjusting for gender, no additional factors were found to be significantly associated with CSF thickness (P > 0.10). Mean Stratus OCT CSF thickness was 199 ± 24 μm. CONCLUSIONS Mean CSF thickness is approximately 70 μm thicker when measured with Heidelberg Spectralis OCT as compared with Stratus OCT among individuals with diabetes in the absence of retinopathy or with minimal nonproliferative retinopathy and a normal macular architecture. CSF thickness values ≥ 320 μm for males and 305 μm for females (~2 SDs above the average for this normative cohort) are proposed as gender-specific thickness levels to have reasonable certainty that diabetic macular edema involving the CSF is present using Spectralis measurements.

A review: role of ultraviolet radiation in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the western world. The retina is highly susceptible to photochemical damage from continuous exposure of light and oxygen. The cornea and the lens block a major portion of the ultraviolet (UV) radiation from reaching the retina (<295 nm). The relationship between UV light exposure and AMD is unclear, although short wavelength radiation and the blue light induce significant oxidative stress to the retinal pigment epithelium. Epidemiologic evidence indicates a trend toward association between severity of light exposure and AMD. In this review, we discuss type 1 and type 2 photochemical damage that occurs in response to UV exposure. We examine the impact of different doses of exposure to UV radiation and the subsequent production of oxidative stress in AMD. Local and systemic protective mechanisms of the retina including antioxidant enzymes and macular pigments are reviewed. This article provides a review of possible cellular and molecular effects of UV radiation exposure in AMD and potential therapies that may prevent blindness resulting from this disease.

The Role of Lutein in Eye-Related Disease

The lens and retina of the human eye are exposed constantly to light and oxygen. In situ phototransduction and oxidative phosphorylation within photoreceptors produces a high level of phototoxic and oxidative related stress. Within the eye, the carotenoids lutein and zeaxanthin are present in high concentrations in contrast to other human tissues. We discuss the role of lutein and zeaxanthin in ameliorating light and oxygen damage, and preventing age-related cellular and tissue deterioration in the eye. Epidemiologic research shows an inverse association between levels of lutein and zeaxanthin in eye tissues and age related degenerative diseases such as macular degeneration (AMD) and cataracts. We examine the role of these carotenoids as blockers of blue-light damage and quenchers of oxygen free radicals. This article provides a review of possible mechanisms of lutein action at a cellular and molecular level. Our review offers insight into current clinical trials and experimental animal studies involving lutein, and possible role of nutritional intervention in common ocular diseases that cause blindness.

Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life. DOI: http://dx.doi.org/10.7554/eLife.00324.001

Differential Effects of TGFβ and Vitreous on the Transformation of Retinal Pigment Epithelial Cells

PURPOSE In proliferative vitreoretinopathy retinal pigment epithelial (RPE) cells undergo epithelial-mesenchymal transformation (EMT). Vitreous and transforming growth factor-beta (TGFbeta) have been implicated in this EMT. The role of TGFbeta in the vitreous-mediated transformation of low-passage human RPE cells was investigated. METHODS Cells were treated with vitreous or TGFbeta2. SB431542 was used to inhibit TGFbeta signaling. Morphology was investigated using phase-contrast or confocal microscopy. Motility was measured using a monolayer-wounding assay. Invasion was determined using basement membrane matrix-based assays. Gene expression was measured by quantitative PCR, immunohistochemistry, or immunoblotting. RESULTS Changes in phosphorylation or cellular localization of Smad -2, -3, or -4 indicated a TGFbeta-like activity in vitreous. Cortical actin filaments in untreated cells were replaced by stress fibers after TGFbeta treatment, but peripheral actin aggregates were seen in vitreous-treated cells. SB431542 did not block the morphologic change induced by vitreous. Vitreous-treated cells exhibited increased motility and invasion, whereas TGFbeta-treated cells did not. However, SB431542 decreased vitreous-meditated changes in motility and invasion. The levels of mRNA for genes indicative of myofibroblast differentiation (alpha-SMA and CTGF) were increased by treatment with TGFbeta but suppressed by vitreous. TGFbeta or vitreous caused increased expression of Snail1. CONCLUSIONS Vitreous or TGFbeta caused a fibroblast-like morphology and induced Snail1, a marker of EMT. TGFbeta activity in vitreous was necessary but not sufficient for the vitreous-induced motile, invasive phenotype. However, differences in the cytoskeletal organization and in the expression of CTGF and alpha-SMA suggested that TGFbeta-treatment caused differentiation along a myofibroblast pathway, whereas vitreous treatment suppressed myofibroblast formation.