Visual Electrodiagnostic Testing in Birdshot Chorioretinopathy

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune posterior uveitis that can affect the visual function and, if left untreated, can lead to sight-threatening complications and loss of central vision. We performed a systematic search of the literature focused on visual electrophysiology studies, including electroretinography (ERG), electrooculography (EOG), and visual evoked potentials (VEP), used to monitor the progression of BSCR and estimate treatment efficacy. Many reports were identified, including using a variety of methodologies and patient populations, which makes a direct comparison of the results difficult, especially with some of the earlier studies using nonstandardized methodology. Several different electrophysiological parameters, like EOG Arden’s ratio and the multifocal ERG response densities, are reported to be widely affected. However, informal consensus emerged in the past decade that the full-field ERG light-adapted 30 Hz flicker peak time is one of the most sensitive electrophysiological parameters. As such, it has been used widely in clinical trials to evaluate drug safety and efficacy and to guide therapeutic decisions in clinical practice. Despite its wide use, a well-designed longitudinal multicenter study to systematically evaluate and compare different electrophysiological methods or parameters in BSCR is still lacking but would benefit both diagnostic and therapeutic decisions

Visual Electrodiagnostic Testing in Birdshot Chorioretinopathy

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune posterior uveitis that can affect the visual function and, if left untreated, can lead to sight-threatening complications and loss of central vision. We performed a systematic search of the literature focused on visual electrophysiology studies, including electroretinography (ERG), electrooculography (EOG), and visual evoked potentials (VEP), used to monitor the progression of BSCR and estimate treatment efficacy. Many reports were identified, including using a variety of methodologies and patient populations, which makes a direct comparison of the results difficult, especially with some of the earlier studies using nonstandardized methodology. Several different electrophysiological parameters, like EOG Arden’s ratio and the multifocal ERG response densities, are reported to be widely affected. However, informal consensus emerged in the past decade that the full-field ERG light-adapted 30 Hz flicker peak time is one of the most sensitive electrophysiological parameters. As such, it has been used widely in clinical trials to evaluate drug safety and efficacy and to guide therapeutic decisions in clinical practice. Despite its wide use, a well-designed longitudinal multicenter study to systematically evaluate and compare different electrophysiological methods or parameters in BSCR is still lacking but would benefit both diagnostic and therapeutic decisions

Automated Method of Grading Vitreous Haze in Patients With Uveitis for Clinical Trials

Purpose: Uveitis is associated with accumulation of exudate in the vitreous, which reduces fundus visibility. The condition is assessed in patients by subjectively matching fundus photographs to a six-level (NIH) or nine-level (Miami) haze scale. This study aimed to develop an objective method of assessing vitreous haze. Methods: An image-processing algorithm was designed that quantifies vitreous haze via high-pass filtering, entropy analysis, and power spectrum integration. The algorithm was refined using nine published photographs that represent incremental levels of fundus blur and applied without further refinement to 120 random fundus photographs from a uveitis image library. Computed scores were compared against the grades of two trained readers of vitreous haze and against acutance, a generic measure of image clarity, using Cohen\u27s κ and Gwet\u27s AC statistics. Results: Exact agreement between algorithm scores and reader grades was substantial for both NIH and Miami scales (κ = 0.61 and 0.67, AC = 0.82 and 0.92). Within-one (κ = 0.78 and 0.82) and within-two (κ = 0.80 and 0.84) levels of agreement were almost perfect. The correspondence was comparable to that between readers. Whereas, exact (κ = 0.45 and 0.44, AC = 0.73 and 0.75), within-one (κ = 0.69 and 0.68), and within-two (κ = 0.73 and 0.72) levels of agreement for the two scales were moderate to substantial for acutance calculations. Conclusions: The computer algorithm produces a quantitative measure of vitreous haze that correlates strongly with the perception of expert graders. Translational Relevance: The work offers a rapid, unbiased, standardized means of assessing vitreous haze for clinical and telemedical monitoring of uveitis patients

Quantitative image analysis applied to the grading of vitreous haze

The present invention includes an automated method for grading the blurring of ocular fundus images to permit automated grading of severity of vitritis. Standard fundoscopic images are converted to gray-scale images. The gray-scale images are processed through a low-pass filter to eliminate high frequency components. The low pass image is subtracted from the corresponding original image, producing the difference image. The difference image is converted to the final entropy image. The entropy image is processed using Fast Fourier Transform to calculate its power. The final blur score is calculated

Automated Method of Grading Vitreous Haze in Patients With Uveitis for Clinical Trials

Purpose: Uveitis is associated with accumulation of exudate in the vitreous, which reduces fundus visibility. The condition is assessed in patients by subjectively matching fundus photographs to a six-level (NIH) or nine-level (Miami) haze scale. This study aimed to develop an objective method of assessing vitreous haze. Methods: An image-processing algorithm was designed that quantifies vitreous haze via high-pass filtering, entropy analysis, and power spectrum integration. The algorithm was refined using nine published photographs that represent incremental levels of fundus blur and applied without further refinement to 120 random fundus photographs from a uveitis image library. Computed scores were compared against the grades of two trained readers of vitreous haze and against acutance, a generic measure of image clarity, using Cohen\u27s κ and Gwet\u27s AC statistics. Results: Exact agreement between algorithm scores and reader grades was substantial for both NIH and Miami scales (κ = 0.61 and 0.67, AC = 0.82 and 0.92). Within-one (κ = 0.78 and 0.82) and within-two (κ = 0.80 and 0.84) levels of agreement were almost perfect. The correspondence was comparable to that between readers. Whereas, exact (κ = 0.45 and 0.44, AC = 0.73 and 0.75), within-one (κ = 0.69 and 0.68), and within-two (κ = 0.73 and 0.72) levels of agreement for the two scales were moderate to substantial for acutance calculations. Conclusions: The computer algorithm produces a quantitative measure of vitreous haze that correlates strongly with the perception of expert graders. Translational Relevance: The work offers a rapid, unbiased, standardized means of assessing vitreous haze for clinical and telemedical monitoring of uveitis patients

Validation of a Photographic Vitreous Haze Grading Technique for Clinical Trials in Uveitis

To validate a photographic vitreous haze grading technique using a 9-step logarithmic scale in patients enrolled in a randomized, controlled clinical trial in uveitis. Retrospective study of clinical trials methodology. Setting: University-based department of ophthalmology. Study population: Baseline fundus photographs of patients with intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. Observational procedure: Grading of vitreous haze using a previously described photographic scale. Regrading of a subset of photographs to assess intraobserver agreement. Main outcome measures: Interobserver and intraobserver intraclass correlation for photographic haze grading, and correlation between photographic and clinical vitreous haze scores, assessment of the clinical findings that significantly affect the photographic haze score. Vitreous haze was graded in 271 eyes (142 patients) by 3 postgraduate ophthalmologists. The interobserver and intraobserver intraclass correlations were excellent, with correlation coefficients between 0.84 and 0.93. There was moderately strong correlation between the photographic and clinical vitreous haze scores ( r = 0.51; P < .001), with significant differences among the mean and median photographic haze scores for the 3 lowest clinical grades of haze, 0, 1+, and 2+. Other parameters that correlated with photographic vitreous haze score included visual acuity of 20/50 or worse ( P = .003), degrees of posterior synechiae ( P < .001), lens abnormality ( P = .023) or posterior capsule obscuration ( P = .001), and amount of anterior vitreous cell ( P = .002). Photographic grading of vitreous haze with a 9-step logarithmic scale is a highly reproducible methodology that may be adaptable to use in future clinical trials

Aflibercept Nanoformulation Inhibits VEGF Expression in Ocular In Vitro Model: A Preliminary Report

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the United States, affecting approximately 11 million patients. AMD is caused primarily by an upregulation of vascular endothelial growth factor (VEGF). In recent years, aflibercept injections have been used to combat VEGF. However, this treatment requires frequent intravitreal injections, leading to low patient compliance and several adverse side effects including scarring, increased intraocular pressure, and retinal detachment. Polymeric nanoparticles have demonstrated the ability to deliver a sustained release of drug, thereby reducing the necessary injection frequency. Aflibercept (AFL) was encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) via double emulsion diffusion. Scanning electron microscopy showed the NPs were spherical and dynamic light scattering demonstrated that they were uniformly distributed (PDI \u3c 1). The encapsulation efficiency and drug loading were 75.76% and 7.76% respectively. In vitro release studies showed a sustained release of drug; 75% of drug was released by the NPs in seven days compared to the full payload released in 24 h by the AFL solution. Future ocular in vivo studies are needed to confirm the biological effects of the NPs. Preliminary studies of the proposed aflibercept NPs demonstrated high encapsulation efficiency, a sustained drug release profile, and ideal physical characteristics for AMD treatment. This drug delivery system is an excellent candidate for further characterization using an ocular neovascularization in vivo model

Validation of a Photographic Vitreous Haze Grading Technique for Clinical Trials in Uveitis

PURPOSE: To validate a photographic vitreous haze grading technique using a 9-step logarithmic scale in patients enrolled in a randomized, controlled clinical trial in uveitis. DESIGN: Retrospective study of clinical trials methodology. METHODS: SETTING: University-based department of ophthalmology. STUDY POPULATION: Baseline fundus photographs of patients with intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. OBSERVATIONAL PROCEDURE: Grading of vitreous haze using a previously described photographic scale. Regrading of a subset of photographs to assess intraobserver agreement. MAIN OUTCOME MEASURES: Interobserver and intraobserver intraclass correlation for photographic haze grading, and correlation between photographic and clinical vitreous haze scores, assessment of the clinical findings that significantly affect the photographic haze score. RESULTS: Vitreous haze was graded in 271 eyes (142 patients) by 3 postgraduate ophthalmologists. The interobserver and intraobserver intraclass correlations were excellent, with correlation coefficients between 0.84 and 0.93. There was moderately strong correlation between the photographic and clinical vitreous haze scores (r = 0.51; P < .001), with significant differences among the mean and median photographic haze scores for the 3 lowest clinical grades of haze, 0, 1+, and 2+. Other parameters that correlated with photographic vitreous haze score included visual acuity of 20/50 or worse (P = .003), degrees of posterior synechiae (P < .001), lens abnormality (P = .023) or posterior capsule obscuration (P = .001), and amount of anterior vitreous cell (P = .002). CONCLUSIONS: Photographic grading of vitreous haze with a 9-step logarithmic scale is a highly reproducible methodology that may be adaptable to use in future clinical trials

Scale for Photographic Grading of Vitreous Haze in Uveitis

PURPOSE: To validate a scale for grading vitreous haze in uveitis using digitized photographs and standardized scoring. DESIGN: Evaluation of clinical research methodology. METHODS: Calibrated Bangerter diffusion filters inducing incremental decrements of spatial contrast were placed in front of the camera lens while photographing a normal eye to simulate vitreous haze. The photographs were digitized and an ordinal scale was created from 0 (none) to 8 (highest level of opacification at which fundus details could be seen). The scale steps correspond approximately to decimal Snellen visual acuities of 1.0, 0.8, 0.4, 0.2, 0.1, 0.04, 0.02, 0.01, and 0.002, with approximately 0.3 log step between each step. For validation, digitized fundus photographs of uveitis patients were displayed on a computer monitor for comparison with the standard photos. Three observers graded the test set twice under standard conditions. Interobserver and intraobserver variability and κ values for agreement greater than chance were calculated. RESULTS: Variance component analysis determined that 87.7% of the variance in grades was attributable to the test item rather than to grader or session. The intraclass correlation between graders and grading sessions varied from 0.84 to 0.91. Simple agreement within 1 grade between graders and sessions occurred in 90 ± 5.5% of gradings. κ values averaged 0.91, which is considered near perfect. CONCLUSIONS: A 9-step photographic scale was designed to standardize the grading of vitreous haze in uveitis patients using fundus photographs. The scale is potentially adaptable to clinical trials in uveitis