Digital Fundus Photography Research Articles

Quantitative analysis of myopic chorioretinal degeneration using a novel computer software program

To quantify the fundus color on digital color fundus photographs as a surrogate of myopic chorioretinal degeneration in myopic subjects using a novel computer software program. In this cross-sectional study, the following details were recorded in 152 eyes of 78 myopic subjects: Snellen visual acuity, refractive status, ocular biometric parameters, intraocular pressure, color fundus photography, and myopic chorioretinal degeneration index (MCDI) using an automated computer program. The mean age of the subjects was 32.58 ± 11.12 years (range, 21-62 years). Subjects with aged ≥40 years had a significantly higher MCDI when compared with subjects with aged <40 years (MCDI: age ≥ 40 = 0.519; age < 40 = 0.462, P = 0.000). The MCDI demonstrated a statistically significant and positive relationship with axial length (r = 0.47, P = 0.000) and lens thickness (r = 0.26, P = 0.023). A significant positive relationship was observed between the MCDI and visual acuity (r = 0.30, P = 0.007). The MCDI represents an objective technique for quantitative assessment of chorioretinal degenerative changes in myopic subjects. Older myopic subjects with a relatively higher MCDI and longer axial length may represent a high-risk population who have an increased likelihood of developing visually consequential complications of myopia.

Screening For Diabetic Retinopathy: Review of Current Methods

Objective: To review the current screening methods for diabetic retinopathy, with a focus on nonmydriatic digital fundus photography. Methods: Articles from Medline were reviewed from 1976 to November 2011 for different combinations of the words “diabetic retinopathy,” “screening,” “fundus photography,” and “nonmydriasis.” Results: Because of its ease of use and cost-effectiveness, digital fundus photography is becoming the preferred method for diagnosing diabetic retinopathy. Current research has proven that pupillary dilation is not a necessary step in the fundus examination, although it reduces the number of unnecessary referrals to ophthalmologists. Automated grading systems, while saving time and reducing human error, still need refinement before they can replace manual grading by trained ophthalmologists. Conclusion: Nonmydriatic digital fundus photography with manual grading by a trained technician is an acceptable method of screening for diabetic retinopathy.

Transition from film to digital fundus photography in the Longitudinal Studies of the Ocular Complications of AIDS.

To describe the transition to digital imaging and assess any impact on ocular disease classification. Film and digital images, acquired by certified photographers, were evaluated independently according to standard procedures for the following: image quality, presence of cytomegalovirus retinitis lesions, and their extent and proximity from disk and macula. Intergrader agreement within the digital medium was also assessed. Among the 15 eyes with cytomegalovirus retinitis, the mean difference between film and digital images for linear distance of lesion edge to disk was 0.02 disk diameters, for distance to center of macula was -0.04 disk diameters, and area covered by cytomegalovirus retinitis was 0.95 disk area. There was no statistically significant difference in distance and area measurements between media. Intergrader agreement in measurements of digital images was excellent for distance and area estimated. Our results suggest that digital grading of cytomegalovirus retinitis in Longitudinal Studies of the Ocular Complications of AIDS is comparable with that from film regarding disease classification, measurements, and reproducibility. These findings provide support for continuity of grading data, despite the necessary transition in imaging media.

Prevalence and Risk Factors of Epiretinal Membrane in Asian Indians

To describe the prevalence of epiretinal membrane (ERM) and its risk factors in an Indian population and compare the findings with other populations. The Singapore Indian Eye Study is a population-based survey of 3400 Asian Indians aged between 40 and 80 years. A comprehensive ophthalmic examination, standardized interviews, and laboratory blood tests were performed. Digital retinal fundus photographs were assessed for the presence of ERM following the definitions used in the Blue Mountains Eye Study (BMES). ERM was classified into a less severe form termed "cellophane macular reflex" (CMR) and a more severe form termed "preretinal macular fibrosis" (PMF) and also as primary and secondary (if it was associated with retinal pathology or cataract surgery). A total of 3328 persons (mean age 57.8 ± [SD] 10.1 years, and 50.2% male) provided data in this study. The age-standardized prevalence of ERM was 7.6% (95% confidence interval [CI], 6.8-8.6), CMR 4.1% (95% CI, 3.5-4.9), and PMF 3.5% (95% CI, 2.9-4.2). Older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11, per year increase), increasing myopic refraction (OR, 1.14; 95% CI, 1.07-1.22, per diopter decrease), and narrower retinal arteriolar diameter (OR, 1.02; 95% CI, 1.00-1.03, per μm decrease) were significantly associated with primary ERM. The age-standardized prevalence of ERM in the Indian population in Singapore was 7.6%. This is similar to Malays in Singapore (8.0%) and higher than the prevalence in whites in Australia (4.7%). Significant factors associated with primary ERM were older age, myopia, and narrower retinal arteriolar diameter.

Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy in Chiapas, Mexico

To estimate the prevalence and causes of blindness in Chiapas, Mexico, and to assess the feasibility of using the Rapid Assessment of Avoidable Blindness framework to estimate diabetic retinopathy (DR) prevalence. A cross-sectional population-based survey. Sixty-six clusters of 50 people 50 years of age or older were selected by probability proportionate to size sampling. Households within clusters were selected through compact segment sampling. Participants underwent visual acuity (VA) screening and diagnosis of cause of visual impairment by an ophthalmologist. Participants were classed as having diabetes if they had a previous diagnosis of diabetes, were receiving treatment for glucose control, or had a random blood glucose level of more than 200 mg/dl. Participants with diabetes were assessed for DR using dilated clinical examination (direct and indirect ophthalmoscope) and 1 dilated digital fundus photograph per eye (graded by an ophthalmologist during the survey and regraded by a retinal specialist-"reference standard") following the Scottish DR grading protocol. Prevalence of blindness (VA <20/400 in the best eye with available correction) and DR. Three thousand three hundred subjects were selected, of whom 2864 (87%) were examined. The estimated prevalence of bilateral blindness was 2.3% (95% confidence interval [CI], 1.7%-2.9%). Cataract was the leading cause of bilateral blindness (63%), followed by posterior segment diseases (24%), which included DR (8% of blindness). The prevalence of diabetes was 21% (19.5%-23.1%). Among participants with diabetes, the prevalence of DR (in at least 1 eye) was 38.9% (95% CI, 33.7%-44.1%). The prevalence of sight-threatening DR (STDR; defined as proliferative DR, referable maculopathy, or both) was 21.0% (95% CI, 16.7%-25.3%). Agreement with the reference standard was good for any retinopathy and STDR for the clinical examination (κ = 0.80 and 0.79, respectively) and the photograph graded during the survey (κ = 0.80 and 0.82, respectively). The prevalence of diabetes and DR in Chiapas was high. Including the DR component was possible, but added considerably to the cost and complexity of the survey, and so would be warranted only if a high prevalence of diabetes is expected and if resources and time permit.

Detection of New-Onset Choroidal Neovascularization Using Optical Coherence Tomography: The AMD DOC Study

To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. Prospective, multicenter, observational study. Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39-0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV.

Quality of Nonmydriatic Digital Fundus Photography Obtained by Nurse Practitioners in the Emergency Department: The FOTO-ED Study

Nonmydriatic fundus photography by non-ophthalmic-trained personnel has recently been shown to be a potential alternative to direct ophthalmoscopy in the emergency department (ED). We evaluated the reliability of a novel quality rating scale and applied this scale to nonmydriatic fundus photographs taken during routine ED patient encounters to determine factors associated with diminished photograph quality. Prospective, cross-sectional study. We included 350 patients enrolled in the Fundus photography versus Ophthalmoscopy Trials Outcomes in the Emergency Department study who were photographed by nurse practitioners after <30 minutes of training followed by supervision. Photographs of both eyes were graded for quality on 2 occasions by 2 neuro-ophthalmologists. Four regions were independently evaluated for quality: Optic disc, macula, and superior and inferior vascular arcades. Quality as a function of the number of photographs taken was evaluated by Kaplan-Meier analysis. Mixed effects ordinal logistic regression was used to evaluate for predictors of image quality while accounting for the repeated measures design. Overall photographic quality (1-5 scale; 5 best). We evaluated 1734 photographs. Inter- and intraobserver agreements between neuro-ophthalmologists were very good (weighted kappa, 0.84-0.87). Quality of the optic disc area was better than those of other retinal areas (P<0.002). Kaplan-Meier analysis showed that if a high-quality photograph of an eye was not obtained by the third attempt, it was unlikely that one would be obtained at all. A 10-second increase in the interphotograph interval before a total of 40 seconds increased the odds of a 1-unit higher quality rating by 1.81 times (95% confidence interval [CI], 1.68-1.98), and a 10-year increase in age decreased the odds by 0.76 times (95% CI, 0.69-0.85). Black patients had 0.42 times (95% CI, 0.28-0.63) the odds of a 1-unit higher quality rating compared with whites. Our 5-point scale is a reliable measure of nonmydriatic photograph quality. The region of interest, interphotograph interval, and patient age and race are significant predictors of image quality for nonmydriatic photographs taken by nurse practitioners in the ED. Addressing these factors may have a direct impact on the successful implementation of nonmydriatic fundus photography into the ED.

Retinal Venular Caliber Predicts Visual Outcome after Intravitreal Ranibizumab Injection Treatments for Neovascular AMD

To examine whether baseline retinal vascular caliber predicts visual response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration (AMD). In this prospective cohort study, patients with neovascular AMD received three monthly intravitreal injections of ranibizumab, followed by as needed dosing up to 1 year. Retinal vascular caliber was measured from digital fundus photographs at baseline and summarized as central retinal artery equivalent (CRAE) and venular equivalent (CRVE), representing average caliber of arterioles and venules, respectively. Visual outcome at 12 months was assessed and the relation to baseline retinal vascular caliber was determined. A total of 88 eyes were analyzed at baseline. After accounting for age, sex, size of choroidal neovascularization, and number of injections, patients who deteriorated in visual acuity at 12 months had significantly larger baseline CRVE, 243.10 μm (95% confidence interval [CI], 227.01-259.19), compared with those who were stable, 214.30 μm (95% CI, 205.79-222.81) and those who improved, 215.26 μm (95% CI, 204.69-225.84; P = 0.007). Baseline CRAE did not differ significantly from eyes whose vision deteriorated, 150.12 μm (95% CI, 140.67-159.57), compared with those remaining stable, 143.64 μm (95% CI, 138.64-148.63), or gaining vision 142.92 μm (95% CI, 136.71-149.13; P = 0.69). In eyes with neovascular AMD treated with intravitreal ranibizumab, larger baseline retinal venular caliber was significantly associated with a poorer response to treatment, possibly reflecting increased disease severity.

Comparison of Autophotomontage Software Programs in Eyes with CMV Retinitis

Automated mosaic software programs are used to stitch together overlapping retinal fundus photographs. The performance of these programs in eyes with retinal diseases has not been independently evaluated. This study compares the quality of the mosaic products of three autophotomontage software programs, using digital fundus photographs of eyes with cytomegalovirus (CMV) retinitis. Photographs of 99 eyes with CMV retinitis of 94 patients with HIV were taken at Maharaj Nakorn Chiang Mai Hospital in Chiang Mai, Thailand. Automated mosaic images were created for each of the 99 eyes by three different commercially available programs: IMAGEnet (Topcon, Oakland, NJ), i2k Retina (DualAlign LLC, Clifton Park, NY), and AutoMontage (OIS, Sacramento, CA). Three masked graders ranked each set of mosaics for each eye. The graders also assessed the overall image quality and documented mosaic artifacts in each image. i2k Retina was ranked as the best program (70%-88%) more often than AutoMontage (10%-33%, P < 0.001) or IMAGEnet (0%-4%, P < 0.001) for creating automontages from digital fundus photographs of eyes with CMV retinitis. Acceptable quality mosaic images were reported most commonly for i2k Retina (93%-94%) and AutoMontage (91%-95%), followed by IMAGEnet (27%-56%, P < 0.001). IMAGEnet had a significantly higher percentage of mosaic errors than did either i2k Retina or AutoMontage (P < 0.001). In eyes with CMV retinitis, both the i2k Retina and AutoMontage software packages appear to create higher quality mosaics than does IMAGEnet. Automated retinal mosaic imaging may be valuable in diagnosing CMV retinitis and observing disease progression.

The Ringlike Structure of Macular Pigment in Age-Related Maculopathy: Results from the Muenster Aging and Retina Study (MARS)

The role of macular pigment (MP) in age-related maculopathy (ARM) is still not clearly understood. Recent studies have reported on variations in the spatial distribution of MP optical density (MPOD) including a secondary peak ("ring") in the slope of the MPOD profile. The authors investigated in a cross-sectional manner the presence of ringlike structures, their determinants, and their relationship with ARM. In all, 369 participants of the Muenster Aging and Retina Study were examined using dual-wavelength analysis of autofluorescence images. ARM was graded using digital fundus photographs according to the International Classification System. A ringlike structure was observed in 73 (19.8%) study participants. The MP maximum of the ring was located on average at 0.85° and the minimum at 0.48° from the center of the fovea. Their concordance between pairs of eyes was highly significant. MPOD measured at eccentricities of 0°, 0.25°, and 0.5° from the fovea was significantly lower in eyes with ringlike structure, whereas it was significantly higher at 1.0° and 2.0° than that in eyes without the ring. Ringlike structures were significantly more common in females and never smokers and were found significantly less often in eyes with ARM than in healthy eyes, even after adjustment for influential factors (adjusted odds ratio, 0.347; 95% confidence interval, 0.196-0.617). Ringlike structures in the MP spatial profile are fairly common, show a high degree of bilaterality, and appeared inversely related with ARM.

Automated Analysis of Optic Nerve Images for Detection and Staging of Papilledema

To develop an automated system that analyzes digital fundus images for staging and monitoring of optic disc edema (i.e., papilledema), due to raised intracranial pressure. A total of 294 retrospective, digital photographs of the right and left eyes of 39 subjects with papilledema acquired over the span of 2 years were used. Software tools were developed to analyze three features of papilledema from digital fundus photographs: (1) sharpness of the optic disc border, (2) discontinuity along major vessels overlying the optic nerve, and (3) texture properties of the peripapillary retinal nerve fiber layer (RNFL). A classifier used these features to assign a grade of papilledema according to a standard protocol used by an expert neuro-ophthalmologist (RK). The algorithm showed substantial agreement (κ = 0.71, P < 0.001) with the neuro-ophthalmologist when grading papilledema per patient. Vessel features showed statistical significance (P < 0.05) in differentiating grades 0, 1, and 2 from grades 3 and 4, whereas disc obscuration differentiated grades 0 or 1 from the rest (P < 0.05). These results show that this algorithm can be used to automatically grade papilledema. The algorithm provides objective and quantitative assessment of the stage of papilledema with accuracy that is comparable to grading by a neuro-ophthalmologist. One application is in rapid assessment of digital optic nerve photographs acquired in clinical, intensive care, and emergency response settings by nonophthalmologists to evaluate for the presence and severity of papilledema, due to intracranial hypertension.

Photographic Diabetic Retinopathy Screening in an Urban Family Practice Clinic: Effect on Compliance to Eye Examination

This study assessed the effect of introduction of diabetic retinopathy screening using non-mydriatic digital fundus photography (nDFP) in an urban academic family practice clinic on patient compliance to recommended dilated eye examination (REE). Two hundred four patients with diabetes mellitis who were noncompliant to annual REE were screened for diabetic retinopathy using nDFP. The images were electronically transmitted to the retinal specialist to triage them for follow-up REE based on the photographic findings. Retrospective review of their medical records compared the compliance to REE before and after nDFP screening. Compliance to REE increased from 9% before screening to 66.5% after screening (P < .0001). Good quality fundus images were obtained in 93% of the eyes. Introduction of nDFP for diabetic retinopathy screening in the family practice clinic can result in a dramatic increase in compliance to REE among patients with diabetes mellitis previously poorly compliant to REE.

Retinal venular calibre dilatation after intravitreal ranibizumab treatment for neovascular age‐related macular degeneration

To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration. Prospective interventional case series. Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period. Each patient received three monthly intravitreal injections according to a 'loading dose'. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (-0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.

A portable, contact animal fundus imaging system based on Rol’s GRIN lenses

To demonstrate a cost-effective, portable, and simple-to-use fundus imaging system for laboratory animals. Albino rats, pigmented mice, albino guinea pigs, and New Zealand white rabbits. A contact fundus imaging system was designed and constructed using standard optical and mechanical components: a digital camera, an otoscope, a fiber optic light source, and standard optical lenses and mounts. Digital fundus video and photography of two albino rats, two pigmented mice, two New Zealand white rabbits, and two albino guinea pigs were obtained. For all animals examined, pupils were dilated and local anesthetic was administered. Digital images of the fundus were obtained in all animals. Contrast of retinal vasculature and overall image quality varied from one species to another, as the axial length, ocular optics, and retinal reflectance varied significantly across species. Light intensity and focus were optimized via the light source and lens focusing mount to produce high-quality images for each animal. The portable, cost-effective contact fundus imaging system was easy to use for fundus examination of laboratory animals.

Comparison of Film and Digital Fundus Photographs in Eyes of Individuals with Diabetes Mellitus

To compare grading of diabetic retinopathy (DR) and diabetic macular edema (DME) from stereoscopic film versus stereoscopic digital photographs obtained from a subset of Diabetic Retinopathy Clinical Research Network (DRCR.net) participants. In this photographic media comparison study, digital and film images were obtained at a single study visit from some of the subjects enrolled in active DRCR.net clinical study protocols. Digital camera systems and digital and film photographers were certified to obtain images according to standard procedures. Images were graded for DR severity and DME in a masked fashion by Fundus Photograph Reading Center (Madison, WI) graders. Agreement between gradings was assessed by calculating the percentage of agreement and κ statistics. Images obtained with both film and digital media were submitted for 155 eyes of 96 study participants. On a nine-step Early Treatment Diabetic Retinopathy study DR severity scale, grading agreed exactly in 74%, and was within one step of agreement in 93%, with a weighted κ statistic of 0.82 (95% confidence interval [CI], 0.71-0.92). On a nine-step DME severity scale and three-step clinically significant macular edema (CSME) scale, grading agreed exactly in 39% and 88%, respectively, and within one step in 70% and 92% (weighted κ statistic, 0.44 [95% Cl, 0.34-0.54] and 0.72 [95% Cl, 0.55-0.90], respectively). Among clinical sites participating in the DRCR.net, agreement between film and digital images was substantial to almost perfect for DR severity level and moderate to substantial for DME and CSME severity levels, respectively. Replacement of film fundus images with digital images for DR severity level should not adversely affect clinical trial quality. (ClinicalTrials.gov numbers, NCT00367133, NCT00369486, NCT00444600, NCT00445003, NCT00709319.)

The types and severity of high myopic maculopathy in Chinese patients

To describe the severity and morphological features of high myopic maculopathy in Chinese patients and to evaluate their association with age, refractive error and visual acuity. Six hundred and four eyes of 337 patients (ages 8-88 years) with high myopia (refractive error ≤ -6.0 D) presenting to the Zhongshan Ophthalmic Center were studied retrospectively. All patients underwent an ophthalmological examination including digital colour fundus photography. Fundus fluorescein angiography was performed in 251 patients (443 eyes) and indocyanine green angiography was performed in 35 patients (63 eyes). The type and severity of myopic degeneration were categorized in each eye. Risk factors associated with high myopic maculopathy were evaluated using General Estimating Equation models. Two hundred and fifty-one patients (443 eyes) presented with maculopathy in this study. The most common subtype of high myopic maculopathy was lacquer cracks (prevalence 29.1%). The most commonly observed degree was M(3) (choroidal pallor and tessellation, with posterior staphyloma and lacquer cracks). Older age was significantly associated with diffuse chorioretinal atrophy (p = 0.024), patchy chorioretinal atrophy (p < 0.001), choroidal neovascularisation (CNV, p < 0.001) and macular atrophy (p = 0.002). Younger age was associated with lacquer cracks (p < 0.001). A higher degree of myopia was a risk factor for almost all kinds of maculopathy: tessellated fundus (p = 0.001), lacquer cracks (p < 0.001), diffuse chorioretinal atrophy (p < 0.001), patchy chorioretinal atrophy (p = 0.025) and macular atrophy p < 0.001), whereas a lower degree of myopia was associated with CNV (p = 0.001). A worse visual acuity was associated with lacquer cracks (p = 0.001), macular atrophy (p < 0.001) and CNV p < 0.001), while better visual acuity was associated with tessellated fundus (p < 0.001) and diffuse atrophy (p = 0.002). Older age (p < 0.001), more myopic refractive error (p < 0.001) and worse visual acuity (p < 0.001) were significantly associated with a greater severity of maculopathy. There was no gender difference in the type and severity of myopic maculopathy. Age and refractive error are important risk factors playing different roles in the development of distinct subtypes and varying severities of high myopic maculopathy. Visual acuity is significantly associated with various subtypes and the severity of high myopic maculopathy.

LONG-TERM EFFECTIVENESS OF INTRAVITREAL BEVACIZUMAB FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO ANGIOID STREAKS IN PSEUDOXANTHOMA ELASTICUM

To investigate the long-term effectiveness of intravitreal bevacizumab for treating active choroidal neovascularizations in pseudoxanthoma elasticum (PXE). Fourteen patients (16 eyes) received intravitreal bevacizumab (1.5 mg) and were investigated monthly. Further treatments were administered depending on disease activity. Examinations included best-corrected visual acuity, biomicroscopy, optical coherence tomography, fluorescein angiography and indocyanine green angiography, fundus autofluorescence, and digital fundus photography. Areas of atrophy of the retinal pigment epithelium and retinal fibrosis were quantified using semiautomated detection on fundus autofluorescence images. Mean age of the cohort was 55 ± 13 years, and mean best-corrected visual acuity at baseline was 20/80 (logarithm of the minimum angle of resolution, 0.56, SD, 0.51). At last follow-up, after an average of 6.5 ± 5.7 injections over 28 months, best-corrected visual acuity was 20/40 (logarithm of the minimum angle of resolution, 0.31, SD, 0.32; P = 0.04). Central retinal thickness was reduced from 254 ± 45 μm to 214 ± 40 μm (P = 0.035). The size of retinal pigment epithelial atrophy and retinal fibrosis measured on fundus autofluorescence images increased in both the treated eye and the fellow eye (P < 0.05). Best-corrected visual acuity of patients with early disease compared with that of those with advanced disease improved significantly more over the treatment course (20/25 vs. 20/63; P = 0.008). Intravitreal bevacizumab therapy demonstrates long-term effectiveness by preserving function in advanced disease and improving function in early disease. Best results of treating active choroidal neovascularizations in PXE are achieved when treatment starts the earliest possible.

Evaluation of a Computer-Aided Diagnosis System for Diabetic Retinopathy Screening on Public Data

To evaluate the performance of a comprehensive computer-aided diagnosis (CAD) system for diabetic retinopathy (DR) screening, using a publicly available database of retinal images, and to compare its performance with that of human experts. A previously developed, comprehensive DR CAD system was applied to 1200 digital color fundus photographs (nonmydriatic camera, single field) of 1200 eyes in the publicly available Messidor dataset (Methods to Evaluate Segmentation and Indexing Techniques in the Field of Retinal Ophthalmology (http://messidor.crihan.fr). The ability of the system to distinguish normal images from those with DR was determined by using receiver operator characteristic (ROC) analysis. Two experts also determined the presence of DR in each of the images. The system achieved an area under the ROC curve of 0.876 for successfully distinguishing normal images from those with DR with a sensitivity of 92.2% at a specificity of 50%. These compare favorably with the two experts, who achieved sensitivities of 94.5% and 91.2% at a specificity of 50%. This study shows, for the first time, the performance of a comprehensive DR screening system on an independent, publicly available dataset. The performance of the system on this dataset is comparable with that of human experts.

Proliferative retinopathy predicts nephropathy: a 25-year follow-up study of type 1 diabetic patients

We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same cohort. All type 1 diabetic patients from Fyn County, Denmark, were identified as of 1 July 1973. One hundred and eighty four patients were examined in 1981-1982 (baseline) and in 2007-2008 (follow-up). The level of retinopathy was graded by ophthalmoscopy at baseline and nine-field digital colour fundus photographs at follow-up. Single spot urine was used to evaluate nephropathy at both examinations. Proliferative retinopathy was present in 29 patients (15.8%) at baseline. At follow-up, these patients were more likely to macroalbuminuria (20.7% vs. 6.5%) than patients without proliferative retinopathy at baseline. In a multivariate logistic regression adjusted for baseline age, sex, duration of diabetes, smoking, HbA(1,) systolic and diastolic blood pressure, odds ratio of nephropathy (micro- and macroalbuminuria combined) was 2.98 (95% confidence interval 1.18-7.51, p = 0.02) for patients with proliferative retinopathy at baseline as compared to those without. At follow-up, there was a close relation between retinopathy and nephropathy. The level of macroalbuminuria was 4.3, 4.6 and 13.0% for patients with no or mild non-proliferative retinopathy, moderate non-proliferative retinopathy and proliferative retinopathy, respectively. In conclusion, proliferative retinopathy is an independent marker of long-term nephropathy in type 1 diabetes. Upcoming studies should examine whether these microvascular complications are also causally linked in type 1 diabetes.

Automated Measurement of the Arteriolar-to-Venular Width Ratio in Digital Color Fundus Photographs

A decreased ratio of the width of retinal arteries to veins [arteriolar-to-venular diameter ratio (AVR)], is well established as predictive of cerebral atrophy, stroke and other cardiovascular events in adults. Tortuous and dilated arteries and veins, as well as decreased AVR are also markers for plus disease in retinopathy of prematurity. This work presents an automated method to estimate the AVR in retinal color images by detecting the location of the optic disc, determining an appropriate region of interest (ROI), classifying vessels as arteries or veins, estimating vessel widths, and calculating the AVR. After vessel segmentation and vessel width determination, the optic disc is located and the system eliminates all vessels outside the AVR measurement ROI. A skeletonization operation is applied to the remaining vessels after which vessel crossings and bifurcation points are removed, leaving a set of vessel segments consisting of only vessel centerline pixels. Features are extracted from each centerline pixel in order to assign these a soft label indicating the likelihood that the pixel is part of a vein. As all centerline pixels in a connected vessel segment should be the same type, the median soft label is assigned to each centerline pixel in the segment. Next, artery vein pairs are matched using an iterative algorithm, and the widths of the vessels are used to calculate the AVR. We trained and tested the algorithm on a set of 65 high resolution digital color fundus photographs using a reference standard that indicates for each major vessel in the image whether it is an artery or vein. We compared the AVR values produced by our system with those determined by a semi-automated reference system. We obtained a mean unsigned error of 0.06 (SD 0.04) in 40 images with a mean AVR of 0.67. A second observer using the semi-automated system obtained the same mean unsigned error of 0.06 (SD 0.05) on the set of images with a mean AVR of 0.66. The testing data and reference standard used in this study has been made publicly available.