Digital Fundus Photography Research Articles

Genotype-phenotype correlations seen in a cohort of British patients with Leber’s congenital amaurosis

Introduction: The purpose of this study was to investigate the relationship between genotype and phenotype in a large cohort of patients with Leber’s Congenital Amaurosis (LCA). A trial of gene therapy in a subset of patients with LCA due to mutations in the RPE65 gene is planned and it is essential that patients with mutations in this gene and others are identified and the phenotypes are carefully refined. Methods: Patients were recruited from two main centers (Moorfields Eye Hospital and Great Ormond Street Hospital, London, UK). Where possible, all patients underwent a full ophthalmic examination including refraction, Goldman visual fields, optical coherence tomography, fundus autofluorescence, and digital fundus photography. DNA aliquots were sent for analysis using the LCA chip (Asper Bio), which identifies previously published mutations in eight known genes. Direct sequencing of three genes, RPE65, RDH12 and CRB1, was carried out. Results: Eighty-six probands from 75 families were recruited. Phenotypic information was obtained in 70 subjects. A definitive molecular genetic diagnosis was obtained in 16/62 (26%) families: 9 patients were identified with mutations in RPE65; 2 in RPGRIP1, 2 in GUCY2D; 1 in AIPL1; and 9 with mutations in CRB1; no patients with LCA were found to have mutations in RDH12. There is a characteristic phenotype recognizable in both RPE65 and CRB1 patients. Conclusions: Identification of causative mutations remains a challenge but use of the LCA chip and careful assessment of the phenotype can improve the efficiency of genotyping strategies. RDH12 is not a cause of LCA in our cohort of patients.

Diabetic Retinopathy and IGF-1 Gene Polymorphic Cytosine-Adenine Repeats in a Southern Indian Cohort

Background/Aims: Growth factors have been implicated in the pathogenesis of diabetic retinopathy (DR). IGF-1 is known to trigger a critical cascade of molecular events that initiate retinal angiogenesis. Increased vitreous IGF-1 levels have been correlated with the severity of ischemia-associated diabetic retinal neovascularization. In the present study, a cytosine-adenine (CA)_n repeat in the promoter of the IGF-1 gene is studied for association with DR. Methods: A total of 127 patients with retinopathy (cases: DR+) and 81 patients without retinopathy (controls: DR–) who had type 2 diabetes were recruited for the study. Patients underwent detailed clinical examination and DR was graded based on stereoscopic digital fundus photographs. Frequencies of alleles and genotypes between the two groups were analyzed for significance using relevant statistical tests. (CA)₁₇ and (CA)₁₈ repeats were the more frequent alleles. Results: The frequency of the 18-repeat genotype was significantly higher in DR+ patients when compared to DR– patients and found to confer a 2.4 times (95% CI: 1.2–5.0) and 2.8 times (95% CI: 1.1–7.5) higher risk for developing DR and proliferative DR, respectively, when compared to <18-repeat genotypes. Conclusions: Our study suggests that the 18-repeat genotype is a susceptibility genotype for DR and its clinical severity in a Southern Indian cohort.

Maculopathy Due to the R345W Substitution in Fibulin-3: Distinct Clinical Features, Disease Variability, and Extent of Retinal Dysfunction

To determine (1) clinical features that distinguish maculopathy due to the R345W substitution in fibulin-3 from other forms of inherited or early-onset drusen, (2) the phenotypic variability, and (3) the extent of retinal disease in those with a positive molecular diagnosis. Affected individuals underwent ophthalmic examination, digital color fundus photography, fundus autofluorescence (AF) imaging, and psychophysical testing with automated photopic and dark-adapted perimetry and fine matrix mapping. Blood samples were taken for DNA extraction and screening for the R345W mutation in fibulin-3. Patients were subsequently divided into mutation-positive and -negative groups, to compare the identified phenotypic findings in these two sets of subjects. Twenty-nine subjects from 19 families were ascertained with inherited or early-onset drusen. Twenty-four (83%) subjects from 15 families were found to harbor the R345W fibulin-3 mutation. Peripapillary deposition and a radial distribution of macular drusen were consistent, distinguishing signs in the mutation-positive group. Subretinal neovascular membrane (SRNVM) was a rare occurrence, affecting only 1 of 48 eyes, whereas hyperpigmentation and atrophy of the retinal pigment epithelium (RPE) were common in older mutation-positive patients. Increased AF corresponding to the drusen was detected in both the mutation-positive and -negative groups. The phenotype in the group of patients positive for the R345W mutation was extremely variable, with evidence of interocular, intrafamilial, and interfamilial variability in visual loss, natural history, ophthalmoscopic findings, autofluorescence imaging, and psychophysical data. The novel finding of nonpenetrance was observed in a 62-year-old asymptomatic, mutation-positive man. The findings from detailed perimetry performed on a subset of subjects were consistent with the presence of widespread retinal dysfunction not isolated to the macula. Marked inter- and intrafamilial variation associated with the fibulin-3 R345W mutation in terms of retinal appearance, severity, progression, and nonpenetrance were identified. It was noted that SRNVM is a rare occurrence in R345W fibulin-3 maculopathy. These findings are helpful for advice regarding prognosis and for genetic counseling. The findings established that the presence of peripapillary deposit is highly likely to indicate that a patient carries the R345W mutation.

The Retinal Vasculature and Function of the Neural Retina in a Rat Model of Retinopathy of Prematurity

In a rat model of retinopathy of prematurity (ROP), the retinal vasculature and function of the neural retina were studied longitudinally. Vascular and neural parameters were evaluated for significant relationships. Retinopathy was induced by exposing newborn rats to alternating 50% and 10% oxygen until age 14 days. To evaluate the function of the neural retina, electroretinographic (ERG) responses to full-field stimuli were recorded from dark-adapted rats at ages 18 and 31 days. Sensitivity and saturated amplitude of photoreceptor and postreceptor activity were derived from ERG a- and b- waves. To evaluate the retinal vasculature, digital fundus photographs were obtained at the same ages, and the tortuosity indices of the arterioles (TIA) and venules (TIV) were calculated. ROP rats and room-air-raised control animals were compared. Vascular and response parameters were evaluated for significant relationships. In ROP rats, TIA was high at 18 days and decreased in every rat to nearly normal levels by 31 days. TIV was less affected by ROP or age. Deficits in all receptor and post-receptor response parameters were present in 18-day-old ROP rats. Post-receptor sensitivity recovered completely by 31 days. Deficits in other response parameters persisted. No significant correlations between vascular and ERG parameters were found in 18-day-old ROP rats. Noninvasive, longitudinal measures in this model of ROP showed significant abnormalities in both the retinal vasculature and function of the neural retina that were most marked at age 18 days. However, vascular and neural abnormalities did not correlate.

A Web-based Telemedicine System for Diabetic Retinopathy Screening Using Digital Fundus Photography

The purpose was to design and implement a Web-based telemedicine system for diabetic retinopathy screening using digital fundus cameras and to make the software publicly available through Open Source release. The process of retinal imaging and case reviewing was modeled to optimize workflow and implement use of computer system. The Web-based system was built on Java Servlet and Java Server Pages (JSP) technologies. Apache Tomcat was chosen as the JSP engine, while MySQL was used as the main database and Laboratory of Neuro Imaging (LONI) Image Storage Architecture, from the LONI-UCLA, as the platform for image storage. For security, all data transmissions were carried over encrypted Internet connections such as Secure Socket Layer (SSL) and HyperText Transfer Protocol over SSL (HTTPS). User logins were required and access to patient data was logged for auditing. The system was deployed at Hubert H. Humphrey Comprehensive Health Center and Martin Luther King/Drew Medical Center of Los Angeles County Department of Health Services. Within 4 months, 1500 images of more than 650 patients were taken at Humphrey's Eye Clinic and successfully transferred to King/Drew's Department of Ophthalmology. This study demonstrates an effective architecture for remote diabetic retinopathy screening.

Association between systemic arterial stiffness and age-related macular degeneration

A number of epidemiological studies suggest that age-related macular degeneration (AMD) and cardiovascular disease share the same risk factors. Systemic arterial stiffness is a clear indicator of cardiovascular disease. We investigated whether there is an association between directly measured systemic arterial stiffness and the presence of AMD. We used a SphygmoCor 2000 system to noninvasively measure two indicators of the systemic arterial stiffness, the arterial pulse wave velocity (PWV) and the central aortic blood pressure waveform, from which the augmentation pressure is determined. We studied 50 patients with AMD (12 men, 38 women, aged 60 to 91 years, mean 77 years) and 11 age-matched control subjects (3 men, 8 women, aged 66 to 92 years, mean 75 years). All study subjects received a complete ophthalmic examination including digital fundus photography. All of the patients with AMD were classified as stage 3 or worse in at least one eye according to the AREDS system. Pulse wave velocity was significantly higher in the patients with AMD (8.2+/-1.1 m/s, mean +/- SD) compared with controls (7.1+/-0.8 m/s, p=0.0025), indicating increased arterial stiffness. There was no significant difference in PWV in AMD patients with and without choroidal neovascularization. There was no association between PWV and the presence of hypertension in either the patients or the controls. The central aortic augmentation pressure was significantly higher in the AMD patients than in the controls (p=0.040), also indicating increased arterial stiffness. Patients with AMD have increased systemic arterial stiffness compared with age-matched controls. Treatments aimed at preventing or reversing systemic arterial stiffness may also be effective in preventing the onset or slowing the progression of AMD.

Digital fundusphotography in equine ophthalmology

Digital fundusphotography in equine ophthalmology

Comparison of optical coherence tomography and fundus photography for measuring the optic disc size

To assess the agreement and repeatability of optic nerve head (ONH) size measurements by optical coherence tomography (OCT) as compared to conventional planimetry of fundus photographs in normal eyes. For comparison with planimetry the absolute size of the ONH of 25 eyes from 25 normal subjects were measured by both OCT and digital fundus photography (Zeiss FF camera 450). Repeatability of automated Stratus OCT measurements were investigated by repeatedly measuring the optic disc in five normal subjects. Mean disc size was 1763 +/- 186 vertically and 1632 +/- 160 microm horizontally on planimetry. On OCT, values of 1772 +/- 317 microm vertically (p = 0.82) and a significantly smaller horizontal diameter of 1492 +/- 302 microm (p = 0.04) were obtained. The 95% limits of agreement were (-546 microm; +527 microm) for vertical and (-502 microm; +782 microm) for horizontal planimetric compared to OCT measurements. In some cases large discrepancies existed. Repeatability of automatic measurements of the optic disc by OCT was moderately good with intra-class correlation coefficients (ICC) of 0.78 horizontally and 0.83 vertically. The coefficient of repeatability indicating instrument precision was 80 microm for horizontal and 168 microm for vertical measurements. OCT can be used to determine optic disc margins in moderate agreement with planimetry in normal subjects. However, in some cases significant disagreement with photographic assessment may occur making manual inspection advisable. Automatic disc detection by OCT is moderately repeatable.

Heritability of Cilioretinal Arteries: A Twin Study

To determine whether the presence of one or more cilioretinal arteries, a distinct element of the pattern of fundus vessels, is genetically programmed, influenced by environmental factors, or the result of random mechanisms of vascular development. The fundi of 112 pairs of healthy monozygotic and dizygotic twins were examined using digital fundus photography and visual assessment of grayscale fundus photographs and color transparencies to detect the presence of cilioretinal arteries. Cilioretinal arteries were present in 45.1% of participants and 28.8% of eyes. The majority of cilioretinal arteries, 88.2%, were located temporally, and 11.8% were located nasally. Monozygotic twins had higher concordance rates for cilioretinal arteries than dizygotic twins. Tetrachoric correlations and Mantel-Haenszel odds ratios demonstrated statistically significant evidence of a genetic effect underlying the presence of cilioretinal arteries (P < 0.01). Statistical analysis supported the hypothesis that additive genetic factors influenced the presence of cilioretinal arteries with a heritability of 71.4%, the remaining variance being attributable to nonshared or random environmental factors. The presence or absence of one or more cilioretinal arteries in healthy persons is markedly influenced by genetic factors.

Screening for Diabetic Retinopathy by One-Field, Non-Mydriatic, 45° Digital Photography Is Inadequate

Purpose: To evaluate the sensitivity and specificity of one-field, non-mydriatic, 45° digital photography for screening for diabetic retinopathy compared to indirect ophthalmoscopy using a slit-lamp, the reference standard. Methods: A total of 100 consecutive diabetic patients (200 eyes) who underwent digital fundus photography and ocular examinations from June 2002 to November 2002 were included in this retrospective study. The patients, recruited from a hospital-based, retina referral practice, underwent 45°, non-mydriatic, digital fundus photography using a non-mydriatic fundus camera. One image was obtained focusing the mid fundus between the optic disc and the macula. The fundus images were printed and graded by endocrinologists and a retinal specialist separately. The patients also underwent complete standard ocular examinations as the reference method for determining diabetic retinopathy, including dilation of their pupils and slit-lamp biomicroscopy done by ophthalmologists. The sensitivity and specificity of the digital photographic method were calculated by comparison to the reference method. Results: The sensitivity and specificity of the retinal specialist’s diabetic retinopathy grades were 53.8 and 89.0%, respectively. The sensitivity and specificity of the endocrinologists’ grades were 45 and 75.3%, respectively. The false negative rates were 22 and 21.5% for endocrinologists and the retinal specialist, respectively. Conclusions: Screening for diabetic retinopathy using one-field, non-mydriatic, 45° digital photography is inadequate.

Assessment of Optic Disc Cupping With Digital Fundus Photographs

To determine the agreement between the assessment of retinal digital images by using an overlay transparency sheet and the Heidelberg retinal tomograph (HRT) in determining cup-disk ratios greater than 0.6. Diagnostic test comparison. Computerized topographic and monoscopic digital images of the optic disk of 628 people aged 70 to 79 years were assessed. A grader (M.C.) defined the disk margin on HRT images, and the operation software computed the area cup-disk ratio. The same grader also determined whether the vertical cup-disk ratio on retinal images was greater than 0.6 by superimposing a transparency overlay sheet over the images. Findings of a second grader (J.G.F.) were used to establish reliability measures. The intragrader reliability for the overlay method and HRT was almost perfect (intraclass correlation coefficient [ICC] = 0.96 and 0.99, respectively), whereas the intergrader reliability was good (ICC = 0.77 and 0.92, respectively). A perfect agreement was found on 28 (85%) of 33 eyes between the overlay and HRT methods in determining cup-disk ratios greater than 0.6. The overlay transparency method appears to be a reliable and promising alternative in determining cup-disk ratios greater than 0.6 in a community screening setting.

Complications of Type 2 Diabetes Among Aboriginal Canadians

Despite a dramatically increasing burden of type 2 diabetes in Aboriginal Canadian communities (1–5), relatively little information is available regarding the prevalence of, and risk factors for, the complications of type 2 diabetes in this population (6). Although previous studies have documented micro- and macrovascular disease in Aboriginal Canadians with diabetes, the majority of these reports have relied heavily on hospital records, chart reviews, and disease registries (6). These approaches may underestimate the magnitude of the complications burden because only those with the severest disease are included, and standardized methods are infrequently used to document complications. The objective of the present research project was to systematically determine, using validated methods, the prevalence of micro- and macrovascular complications among Aboriginal Canadians who have type 2 diabetes and to identify risk factors that are associated with these conditions. The Sandy Lake Diabetes Complications Study has been presented in detail previously (6). Briefly, all community members known to have type 2 diabetes were invited to participate; 189 of 250 (76%) eligible subjects were enrolled, although the sample size varies given time-limited access to certain equipment. Participants were older than nonparticipants and more likely to be male but did not differ in diabetes treatment. Signed informed consent was obtained from all participants, and the study was approved by the Sandy Lake First Nation Band Council and the Mount Sinai Hospital Ethics Review Committee. We used validated measures to assess retinopathy, neuropathy, nephropathy, and cardiovascular disease risk factors, as described previously (6). Digital fundus photography was performed using a nonmydriatic retinal camera, with …

Screening for age-related macular degeneration using nonstereo digital fundus photographs

Age-related macular degeneration (AMD) is a disease with significant visual morbidity and accounts for the majority of blind registrations in the developed world including the UK. Certain forms of neovascular AMD are amenable to treatment but require expeditious referral to a retinal specialist. To evaluate the possibility of using nonstereo fundus photographs as a low-cost screening tool for neovascular AMD. Retrospective review of patients referred to the macular clinic of a teaching hospital in London. A total of 198 randomised digital fundus photographs, without any other clinical information, were presented to two independent ophthalmic interns who graded them into one of the three categories: normal, age-related maculopathy (ARM), or neovascular age-related macular degeneration (AMD) to determine the urgency of referral to clinic. The results were compared with the known diagnosis for each patient and sensitivities and specificities for each diagnostic category calculated. The intraobserver Kappa statistic was 0.75 and 0.91 for grader 1 and 2, respectively. The interobserver Kappa was 0.54. The mean sensitivity and specificity for the identification of ARM was 60.5 and 76.3%, respectively The mean sensitivity and specificity for the identification of AMD was 85.7 and 78.8%, respectively. Nonstereo digital fundus photograph is a reasonable screening tool for CNV and may aid in decreasing the visual morbidity it causes by enabling timely referrals and treatment.

Automatic detection of red lesions in digital color fundus photographs

The robust detection of red lesions in digital color fundus photographs is a critical step in the development of automated screening systems for diabetic retinopathy. In this paper, a novel red lesion detection method is presented based on a hybrid approach, combining prior works by Spencer et al. (1996) and Frame et al. (1998) with two important new contributions. The first contribution is a new red lesion candidate detection system based on pixel classification. Using this technique, vasculature and red lesions are separated from the background of the image. After removal of the connected vasculature the remaining objects are considered possible red lesions. Second, an extensive number of new features are added to those proposed by Spencer-Frame. The detected candidate objects are classified using all features and a k-nearest neighbor classifier. An extensive evaluation was performed on a test set composed of images representative of those normally found in a screening set. When determining whether an image contains red lesions the system achieves a sensitivity of 100% at a specificity of 87%. The method is compared with several different automatic systems and is shown to outperform them all. Performance is close to that of a human expert examining the images for the presence of red lesions.

Visual acuity and structural findings in old age-related macular degeneration

Although exudative age-related macular degeneration (AMD) leads to a substantial visual loss in most patients there is still significant variation in the end- stage visual acuity level. We analysed lesions in eyes with long-standing AMD in order to find contributing factors for this variation. Sixty-one out of 121 patients examined for exudative AMD and still alive 4.8-9.2 (mean 6.8) years after the acute phase were re-examined. The lesion size, area of subretinal fibrosis, geographic atrophy, presence of a persistent exudative process, and shortest distance to normal looking retina were measured from digital fundus photographs taken at the re-examination and correlated with visual acuity. Lesion size, the presence of a continuing exudative process, or subretinal fibrosis were independent predictors for poor vision. Better vision in the other eye was connected with poor vision in the affected study eye. In addition to lesion size, the presence of a continuing exudative process and subretinal fibrosis also have deleterious effects on long-term visual acuity after exudative AMD.

Prospective evaluation of digital non-stereo color fundus photography as a screening tool in age-related macular degeneration

To evaluate mydriatic, non-stereo digital color fundus photographs as a screening tool for identifying and classifying exudative age-related macular degeneration (AMD). Prospective case series. Digital color fundus photographs were obtained from patients seen in the AMD screening clinic over a 9-month period at the Ivey Eye Institute in London, Ontario. Photographs for eligible patients were separated by eye, cataloged, blinded, and randomly labeled before interpretation by an experienced vitreoretinal surgeon. Exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of the fundus photographs in diagnosing, classifying, and managing cases of suspected exudative AMD were then calculated against gold standard clinical examination and fluorescein angiography. A total of 223 images were used from 118 eligible patients. Exact agreement between photographic evaluation and gold standard ranged from 89.2% (presence of pigment epithelial detachment (PED)) to 82.5% (evidence of retinal pigment epithelium geographic atrophy). Sensitivities ranged from 89.2% (presence of choroidal neovascular membrane (CNVM)) to 40.0% (presence of PED). Specificities ranged from 94.1% (presence of PED) to 86.8% (presence of retinal pigment epithelium geographic atrophy). Positive predictive value ranged from 86.1% (presence of CNVM) to 40.0% (presence of PED). Negative predictive value ranged from 94.1% (presence of PED) to 88.9% (presence of CNVM). As a screening tool for high-risk dry changes and active exudative changes, overall sensitivity specificity, positive predictive value, and negative predictive value were 82.1%, 79.1%, 70.4%, and 88.0%, respectively. Digital, non-stereo color fundus photographs are highly sensitive and have high negative predictive value as a screening tool. Very few treatable lesions are missed using telemedicine in age-related macular degeneration.

Automated Detection of Macular Drusen Using Geometric Background Leveling and Threshold Selection

Age-related macular degeneration (ARMD) is the most prevalent cause of visual loss in patients older than 60 years in the United States. Observation of drusen is the hallmark finding in the clinical evaluation of ARMD. To segment and quantify drusen found in patients with ARMD using image analysis and to compare the efficacy of image analysis segmentation with that of stereoscopic manual grading of drusen. Retrospective study. University referral center.Patients Photographs were randomly selected from an available database of patients with known ARMD in the ongoing Columbia University Macular Genetics Study. All patients were white and older than 60 years. Twenty images from 17 patients were selected as representative of common manifestations of drusen. Image preprocessing included automated color balancing and, where necessary, manual segmentation of confounding lesions such as geographic atrophy (3 images). The operator then chose among 3 automated processing options suggested by predominant drusen type. Automated processing consisted of elimination of background variability by a mathematical model and subsequent histogram-based threshold selection. A retinal specialist using a graphic tablet while viewing stereo pairs constructed digital drusen drawings for each image. The sensitivity and specificity of drusen segmentation using the automated method with respect to manual stereoscopic drusen drawings were calculated on a rigorous pixel-by-pixel basis. The median sensitivity and specificity of automated segmentation were 70% and 81%, respectively. After preprocessing and option choice, reproducibility of automated drusen segmentation was necessarily 100%. Automated drusen segmentation can be reliably performed on digital fundus photographs and result in successful quantification of drusen in a more precise manner than is traditionally possible with manual stereoscopic grading of drusen. With only minor preprocessing requirements, this automated detection technique may dramatically improve our ability to monitor drusen in ARMD.

Tratamiento digital de retinografías para detectar automáticamente lesiones asociadas con la retinopatía diabética

Diabetic retinopathy is a leading cause of vision loss in developed countries. Regular diabetic retinal eye screenings are needed to detect early signs of retinopathy, so that appropriate treatments can be rendered to prevent blindness. Digital imaging is becoming available as a means of screening for diabetic retinopathy. However, with the large number of patients undergoing screenings, medical professionals require a tremendous amount of time and effort in order to analyse and diagnose the fundus photographs. Our aim is to develop an automatic algorithm using digital image analysis for detecting these early lesions from retinal images. An automatic method to detect hard exudates, a lesion associated with diabetic retinopathy, is proposed. The algorithm is based on their colour, using a statistical classification, and their sharp edges, applying an edge detector, to localise them. A sensitivity of 79.62% with a mean number of 3 false positives per image is obtained in a database of 20 retinal images with variable colour, brightness and quality. It can also be seen that the number of the false negative cases increases when the hard exudates were very close to the vessel tree. The long term goal of the project is to automate the screening for diabetic retinopathy with retinal images. We have described the preliminary development of a tool to provide automatic analysis of digital fundus photographs to localise hard exudates. Future work will address the issue of improving the obtained results and also will focus on detecting other lesions.

Evaluation of a mobile diabetes care telemedicine clinic serving Aboriginal communities in northern British Columbia, Canada

Introduction. In British Columbia, Aboriginal diabetes prevalence, hospitalization and mortality rates are all more than twice as high as in the rest of the population. We describe and evaluate a program to improve access to diabetes care for Aboriginal people in northern communities. Study design. Cost-effectiveness evaluation. Methods. A diabetes nurse educator and an ophthalmic technician travel to Aboriginal reserves, offering people with diabetes services recommended in current clinical practice guidelines: retinopathy screening by digital retinal fundus photography, glaucoma screening by tonometry, point-of-care urine and blood testing to detect microalbuminuria and dyslipidemia and to measure glycated hemoglobin, foot examinations and foot care advice, blood pressure and height and weight measurement and diabetes care advice. Via electronic communication, an ophthalmologist and an endocrinologist in Vancouver review the findings and supervise the mobile clinic staff. Results. During the first year, 25 clinics were held at 22 sites, examining 339 clients with diabetes. Exit surveys showed high levels of client satisfaction. Mean cost per client (Cdn$1,231) was less than for the alternative, transporting clients to care in the nearest cities (Cdn$1,437). Conclusions. The mobile clinic is cost-ef-fective and improves access to the recommended standard of diabetes care.

Computer-assisted measurement of retinal vessel diameters in the Beaver Dam Eye Study: methodology, correlation between eyes, and effect of refractive errors

Objective Narrowed retinal arterioles may independently predict cardiovascular disease. We describe a computer-assisted method to measure retinal vessel diameters from digitized fundus photographs in a large population, and examine the correlation of retinal vessel diameters between eyes and whether refractive errors affect these measurements. Design and population Population-based, cross-sectional study in Beaver Dam, Wisconsin (n = 4926; age, 43–84 years). Methods Retinal photographs were digitized, and all arterioles and venules located in an area 0.5 to 1 disc diameter from the optic disc were measured with the aid of computer software. Main outcome measures Summary of retinal arteriolar and venular diameters, and the ratio of their diameters (arteriole:venule ratio [AVR]). Results Correlation between right and left eyes was substantial for retinal arteriolar diameters (Pearson correlation coefficient, ρ = 0.71) and venular diameters (ρ = 0.74), and moderate for the AVR (ρ = 0.49). The inverse association of higher blood pressure and smaller retinal arteriolar diameters was similar using data from either one eye or two eyes; arteriolar diameters decreased by 4.1 μm (right eyes), 4.0 μm (left eyes), and 4.0 μm (mean of both eyes) with each 10-mmHg increase in mean arterial blood pressure. A myopic refraction was associated with smaller retinal vessel diameters; arteriolar diameters decreased by 2.8 μm and venular diameters by 3.3 μm with each −1.0-diopter shift towards myopia. However, the pattern and strength of the association of blood pressure and retinal vessel diameters were not altered by variations in refractive errors. Conclusions There is good correlation of retinal vessel diameters between eyes. A myopic refraction is associated with smaller retinal vessel diameters. The association of retinal arteriolar diameters and blood pressure seems similar using data from either one eye or two eyes, and is minimally affected by refraction. These data suggest that measurement of retinal vessel diameters from one eye without regard to its refractive status may provide adequate information indicative of a person's retinal vessel caliber if information from two eyes and refraction is unavailable.