Vikram S Brar

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.

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.

Acute bilateral simultaneous angle closure glaucoma after topiramate administration: a case report

IntroductionA case of severe acute bilateral angle closure glaucoma with complete visual loss after oral topiramate therapy.Case presentationA 34 year-old woman developed bilateral severe visual loss 2 days after doubling the dosage of topiramate. Her best-corrected visual acuity (BCVA) was counting fingers in both eyes (OU). Intraocular pressures were 49 mm and 51 mm of Hg in right and left eyes respectively, with conjunctival chemosis, corneal edema, shallow anterior chamber and closed angles on gonioscopy. B-scan ultrasound revealed annular peripheral choroidal effusions in both eyes.ConclusionIntraocular pressures and anterior chamber depth were normalized after discontinuation of topiramate and initiation of antiglaucoma therapy. Two weeks later, visual acuities improved to 20/25 in the right eye and 20/40 in the left eye. B-scan ultrasound showed resolution of choroidal effusion. Topiramate, an oral sulpha-derivative medication is known to cause ciliochoroidal effusions, which lead to forward rotation of the ciliary body and displacement of the lens-iris diaphragm, with resultant acute angle closure glaucoma and myopic shift.

Intracameral bevacizumab effectively reduces aqueous vascular endothelial growth factor concentrations in neovascular glaucoma

Vascular endothelial growth factor (VEGF) concentrations in both the aqueous and vitreous are raised in ocular ischaemia secondary to exudative age-related macular degeneration, diabetes mellitus and other retinal vascular diseases.1 2 Retinal ischaemia upregulates VEGF production, resulting in neovascularisation of the retina and the iris (NVI). VEGF is significantly increased in neovascular glaucoma (NVG).3 In the following case series, we show increased aqueous VEGF concentrations in two patients with NVI, which significantly declined, with concurrent resolution of NVI, after off-label intracameral injections of bevacizumab. Two patients with NVI secondary to proliferative diabetic retinopathy were included in the study. After informed consent had been obtained, according to a protocol approved by the University of Florida Institutional Review Board, aqueous was collected before the injection of 0.05 ml intracameral bevacizumab (25 mg/ml) and …

Foveal structure defined by spectral domain optical coherence tomography correlates with visual function after macular hole surgery

Purpose. To study the correlation between final visual acuity after successful anatomic macular hole repair and features on spectral domain optical coherence tomography (SD-OCT). Methods. Retrospective review of charts of patients who underwent macular hole surgery. Data collection included pre- and postoperative best-corrected visual acuity (BCVA), central subfield foveal thickness (CSFT), and presence or absence of inner segment-outer segment (IS-OS) line changes on SD-OCT. Data collected from SD-OCT were correlated with Snellen BCVA, which was converted to logMAR score. Subjects were divided into 2 groups: group I had improvement in BCVA of 2 lines or more and group II improved less than 2 lines or had worsening of BCVA. Results. A total of 35 eyes of 32 patients had successful anatomic closure, which was documented both clinically and on SD-OCT. Mean age of the patients was 74.1 years and 71.2% (23/32) of patients were female. Overall, the mean BCVA changed from 1.01±0.38 preoperatively to 0.89±0.48 postoperatively (p=0.33). Based on the postoperative visual outcome, 16 eyes belonged to group I and 19 eyes belonged to group II. On the SD-OCT, the mean CSFT was 252.7±69.1 μm. No correlation was found between the mean CSFT and BCVA in either group. All the 16 patients in group I had a continuous IS-OS line on SD-OCT at the fovea in contrast to 26.3 % (5/19) of patients in group II (p=0.03). Conclusions. Establishment of continuity of IS-OS line is an important indicator of visual recovery in eyes with successful anatomic closure of macular hole.

Evaluation of cytotoxic effects of bevacizumab on human corneal cells.

Purpose: Corneal neovascularization contributes to corneal opacification in inflammatory conditions of the cornea and severely compromises the success of corneal transplantation. Vascular endothelial growth factor (VEGF) plays an important role in stimulating and maintaining corneal neovascularization. Anti-VEGF therapy, especially the use of anti-VEGF antibody bevacizumab, has gained popularity in the management of retinal neovascularization and is being used topically for corneal neovascularization. The aim of this study was to investigate the safety profile of bevacizumab on human corneal cell lines. Methods: Human corneal epithelial and fibroblast cell lines and an umbilical vascular endothelial cell line were treated with increasing doses of bevacizumab. The effect of this treatment on cell viability was assessed by WST-1 and crystal violet staining assays. Cytotoxicity was also assessed by fluorescent microscopy and flow cytometric evaluation of propidium iodide-stained cells. Results: In the cytotoxicity experiments, there was no difference in cell numbers after 24-hour exposure compared with control in any of the cell lines at the concentrations tested (P > 0.05 to 0.98). Conclusion: Bevacizumab was nontoxic to human corneal epithelial and fibroblast cells at 3 different concentrations.

Evaluation of ultraviolet light toxicity on cultured retinal pigment epithelial and retinal ganglion cells

Purpose: Our study is aimed at evaluating the role of UVB light in inducing cytotoxicity in an in vitro model. Methods: RGC-5 and ARPE-19 cells were exposed to different time periods of UVB light: 0, 15, 30, and 45 min. They were subsequently examined for changes in cell morphology, cell viability (neutral red uptake assay), generation of reactive oxygen species (ROS), expression of bax, bcl-2 and cytochome C by reverse transcriptase polymerase chain reaction and western blot, respectively. Results: Dose-dependent reduction in cell viability to UVB light was demonstrated with parallel increase in ROS. Increased duration of exposure (>15 minutes), was associated with increased expression of bax and cytochrome C, and absence of bcl-2 expression. Conclusion: UVB light exposure results in cell cytotoxicity. The concomitant generation of ROS and expression of apoptotic markers suggests the role of oxidative stress in UVB-mediated apoptosis in an in vitro model of retinal ganglion and pigment epithelial cells.

Evaluation of Differential Toxicity of Varying Doses of Bevacizumab on Retinal Ganglion Cells, Retinal Pigment Epithelial Cells, and Vascular Endothelial Growth Factor–Enriched Choroidal Endothelial Cells

PURPOSE To evaluate in vitro the effects of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, on retinal pigment epithelial cells (RPE) and retinal ganglion cells (RGC), at doses that were inhibitory to VEGF-enriched choroidal endothelial cells (CEC). METHODS Monkey CEC (RF6A), human RPE cells (ARPE-19), and rat RGC (RGC-5) were exposed for 24 h to increasing doses of bevacizumab. Cell numbers were quantified with WST-1 assay. Cell death was assessed using propidium iodide (PI) staining via flow cytometry and fluorescent microscopy. RESULTS Bevacizumab was inhibitory to RF6A at 2.0 mg/mL (P < 0.005). No effect on cell viability was noted on ARPE-19 and RGC-5 cell lines at this particular dose of bevacizumab. These results were supported by fluorescent microscopy of PI-stained cells. CONCLUSIONS VEGF-stimulated proliferation of CEC was inhibited by bevacizumab. Bevacizumab was not cytotoxic to human RPE and rat RGC in vitro at a dose that is inhibitory to monkey CEC.

Human Ciliary Epithelium as a Source of Synthesis and Secretion of Vascular Endothelial Growth Factor in Neovascular Glaucoma

IMPORTANCE Retinal ischemia-induced upregulation of vascular endothelial growth factor (VEGF) leads to endothelial proliferation of the anterior segment, resulting in neovascular glaucoma. OBJECTIVE To investigate the ciliary epithelium as a possible source of VEGF in human eyes enucleated for intractable neovascular glaucoma. DESIGN, SETTING, AND PARTICIPANTS In this proof-of-concept, laboratory-based study, 16 human enucleated eyes (8 with neovascular glaucoma and 8 as controls) were investigated. MAIN OUTCOMES AND MEASURES Presence of VEGF by immunohistochemical analysis (VEGF protein) and in situ hybridization (VEGF messenger RNA). RESULTS In eyes with neovascular glaucoma, strong VEGF immunoreaction in the nonpigmented epithelial cells of the ciliary processes and in the retina was noted. In situ hybridization for VEGF messenger RNA revealed a similar pattern, with positive stain results only in eyes with neovascular glaucoma. A minimal amount of VEGF immunostaining was seen in control eyes. CONCLUSIONS AND RELEVANCE The nonpigmented ciliary epithelium is an important site of VEGF synthesis in patients with neovascular glaucoma. The ciliary epithelium may represent an additional focus of treatment in the management of neovascular glaucoma, especially in eyes that are nonresponsive to panretinal photocoagulation.