Clinically significant macular edema in an underserved population: Association with demographic factors and hemoglobin A1c.

SIGNIFICANCE: Suspected clinically significant macular edema (SCSME) from exudates differed among ethnic groups in our underserved population. African American and Asian subjects had higher prevalence than Hispanics and non-Hispanic Caucasians, from the same clinics. Men had higher prevalence than women. Highly elevated blood glucose was frequent and associated with SCSME. PURPOSE: We investigated the association between the presence of SCSME from exudates and hemoglobin A1c (HbA1c), as well as demographic factors such as age, sex, and ethnic group. Our population was underserved diabetic patients from the same geographic locations. Ethnic groups were White Hispanic, non-Hispanic Caucasian, African American, and Asian, with a high proportion of underrepresented minorities. METHODS: In a diabetic retinopathy screening study at four community clinics in Alameda County, California, nonmydriatic 45° color fundus images were collected from underserved diabetic subjects following the EyePACS imaging protocol. Images were analyzed for SCSME from exudates by two certified graders. Logistic regression assessed the association between SCSME from exudates and age, sex, ethnic group, and HbA1c. RESULTS: Of 1997 subjects, 147 (7.36%) had SCSME from exudates. The mean ± standard deviation age was 53.4 ± 10.5 years. The mean ± standard deviation HbA1c level was 8.26 ± 2.04. Logistic regression analysis indicated a significant association between presence of SCSME from exudates and HbA1c levels (p<0.001), sex (p=0.027), and ethnicity (p=0.030). African Americans (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.06 to 2.50; p=0.025) and Asians (OR, 1.63; 95% CI, 1.05 to 2.54; p=0.029) had a higher risk than Hispanics. After adjusting for ethnicity, sex, and age, the odds of developing SCSME from exudates increased by 26.5% with every 1% increase in HbA1c level (OR, 1.26; 95% CI, 1.18 to 1.36; p<0.001). CONCLUSIONS: In our underserved population, many diabetic patients had very high HbA1c values. Ethnic background (African American > Asians > Hispanics), sex (male > female), and HbA1c level were strong indicators for identifying who is at increased risk of developing SCSME from exudates.

2022 Prentice Award Lecture: Advancing Retinal Imaging and Visual Function in Patient Management and Disease Mechanisms.

SIGNIFICANCE: Patient-based research plays a key role in probing basic visual mechanisms. Less-well recognized is the role of patient-based retinal imaging and visual function studies in elucidating disease mechanisms, which are accelerated by advances in imaging and function techniques and are most powerful when combined with the results from histology and animal models.A patient's visual complaints can be one key to patient management, but human data are also key to understanding disease mechanisms. Unfortunately, pathological changes can be difficult to detect. Before advanced retinal imaging, the measurement of visual function indicated the presence of pathological changes that were undetectable with existing clinical examination. Over the past few decades, advances in retinal imaging have increasingly revealed the unseen. This has led to great strides in the management of many diseases, particularly diabetic retinopathy and macular edema, and age-related macular degeneration. It is likely widely accepted that patient-based research, as in clinical trials, led to such positive outcomes. Both visual function measures and advanced retinal imaging have clearly demonstrated differences among retinal diseases. Contrary to initial thinking, sight-threatening damage in diabetes occurs to the outer retina and not only to the inner retina. This has been clearly indicated in patient results but has only gradually entered the clinical classifications and understanding of disease etiology. There is strikingly different pathophysiology for age-related macular degeneration compared with photoreceptor and retinal pigment epithelial genetic defects, yet research models and even some treatments confuse these. It is important to recognize the role that patient-based research plays in probing basic visual mechanisms and elucidating disease mechanisms, combining these findings with the concepts from histology and animal models. Thus, this article combines sample instrumentation from my laboratory and progress in the fields of retinal imaging and visual function.

Quantifying frequency content in cross-sectional retinal scans of diabetics vs. controls.

PURPOSE: To examine subtle differences in the structure of diabetic vs. control retinas. METHODS: Spectral-domain optical coherence tomography (SD-OCT) images were compared for the retinas of 33 diabetic subjects who did not have clinical evidence of diabetic macular edema and age-matched controls, with central macular thicknesses of 275 and 276 microns, respectively. Cross-sectional retinal images through the fovea, called B-scans, were analyzed for spatial frequency content. The B-scans were processed to remove and smooth the portions of the retinal image not within regions of interest in the retina. The remaining retinal images were then quantified using a Fast Fourier Transform (FFT) approach that provided amplitude as a function of spatial frequency. RESULTS: The FFT analysis showed that diabetic retinas had spatial frequency content with significantly higher power compared to control retinas particularly for a deeper fundus layer at mid-range spatial frequencies, ranging from p = 0.0030 to 0.0497 at 16.8 to 18.2 microns/cycle. There was lower power at higher spatial frequencies, ranging from p = 0.0296 and 0.0482 at 27.4 and 29.0 microns/cycle. The range of mid-range frequencies corresponds to the sizes of small blood vessel abnormalities and hard exudates. Retinal thickness did not differ between the two groups. CONCLUSIONS: Diabetic retinas, although not thicker than controls, had subtle but quantifiable pattern changes in SD-OCT images particularly in deeper fundus layers. The size range and distribution of this pattern in diabetic eyes were consistent with small blood vessel abnormalities and leakage of lipid and fluid. Feature-based biomarkers may augment retinal thickness criteria for management of diabetic eye complications, and may detect early changes.

Central Macular Thickness in Diabetic Patients: A Sex-based Analysis.

SIGNIFICANCE: The pathological changes in clinically significant diabetic macular edema lead to greater retinal thickening in men than in women. Therefore, male sex should be considered a potential risk factor for identifying individuals with the most severe pathological changes. Understanding this excessive retinal thickening in men may help preserve vision. PURPOSE: The purpose of this study was to investigate the sex differences in retinal thickness in diabetic patients. We tested whether men with clinically significant macular edema had even greater central macular thickness than expected from sex differences without significant pathological changes. This study also aimed to determine which retinal layers contribute to abnormal retinal thickness. METHODS: From 2047 underserved adult diabetic patients from Alameda County, CA, 142 patients with clinically significant macular edema were identified by EyePACS-certified graders using color fundus images (Canon CR6-45NM). First, central macular thickness from spectral domain optical coherence tomography (iVue; Optovue Inc.) was compared in 21 men versus 21 women without clinically significant macular edema. Then, a planned comparison contrasted the greater values of central macular thickness in men versus women with clinically significant macular edema as compared with those without. Mean retinal thickness and variability of central macular layers were compared in men versus women. RESULTS: Men without clinically significant macular edema had a 12-µm greater central macular thickness than did women (245 ± 21.3 and 233 ± 13.4 µm, respectively; t40 = -2.18, P = .04). Men with clinically significant macular edema had a 67-µm greater central macular thickness than did women (383 ± 48.7 and 316 ± 60.4 µm, P < .001); that is, men had 55 µm or more than five times more (t20 = 2.35, P = .02). In men, the outer-nuclear-layer thickness was more variable, F10,10 = 9.34. CONCLUSIONS: Underserved diabetic men had thicker retinas than did women, exacerbated by clinically significant macular edema.

Evaluation of intraretinal migration of retinal pigment epithelial cells in age-related macular degeneration using polarimetric imaging.

The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF). Intraretinal RPE migration was defined by the presence of depolarization at intraretinal hyperreflective foci on PS-SLO and PS-OCT images, and by the presence of hyper-AF on both NIR-AF and SW-AF images. RPE migration was detected in 52 of 155 eyes (33.5%) and was observed in drusenoid pigment epithelial detachment (PED) and serous PED with significantly higher frequencies than in other groups (P = 0.015). The volume of the migrated RPE cluster in serous PED was significantly correlated with the volume of the PED (R2 = 0.26; P = 0.011). Overall, our results showed that intraretinal RPE migrations occurred in various AMD stages, and that they occurred more commonly in eyes with serous and drusenoid PED.

Comparison of Cysts in Red and Green Images for Diabetic Macular Edema.

PURPOSE: To investigate whether cysts in diabetic macular edema are better visualized in the red channel of color fundus camera images, as compared with the green channel, because color fundus camera screening methods that emphasize short-wavelength light may miss cysts in patients with dark fundi or changes to outer blood retinal barrier. METHODS: Fundus images for diabetic retinopathy photoscreening were acquired for a study with Aeon Imaging, EyePACS, University of California Berkeley, and Indiana University. There were 2047 underserved, adult diabetic patients, of whom over 90% self-identified as a racial/ethnic identify other than non-Hispanic white. Color fundus images at nominally 45 degrees were acquired with a Canon Cr-DGi non-mydriatic camera (Tokyo, Japan) then graded by an EyePACS certified grader. From the 148 patients graded to have clinically significant macular edema by the presence of hard exudates in the central 1500 µm of the fovea, we evaluated macular cysts in 13 patients with cystoid macular edema. Age ranged from 33 to 68 years. Color fundus images were split into red, green, and blue channels with custom Matlab software (Mathworks, Natick, MA). The diameter of a cyst or confluent cysts was quantified in the red-channel and green-channel images separately. RESULTS: Cyst identification gave complete agreement between red-channel images and the standard full-color images. This was not the case for green-channel images, which did not expose cysts visible with standard full-color images in five cases, who had dark fundi. Cysts appeared more numerous and covered a larger area in the red channel (733 ± 604 µm) than in the green channel (349 ± 433 µm, P < .006). CONCLUSIONS: Cysts may be underdetected with the present fundus camera methods, particularly when short-wavelength light is emphasized or in patients with dark fundi. Longer wavelength techniques may improve the detection of cysts and provide more information concerning the early stages of diabetic macular edema or the outer blood retinal barrier.

Utility of hard exudates for the screening of macular edema.

PURPOSE: The purpose of this study was to determine whether hard exudates (HEs) within one disc diameter of the foveola is an acceptable criterion for the referral of diabetic patients suspected of clinically significant macular edema (CSME) in a screening setting. METHODS: One hundred forty-three adults diagnosed as having diabetes mellitus were imaged using a nonmydriatic digital fundus camera at the Alameda County Medical Center in Oakland, CA. Nonstereo fundus images were graded independently for the presence of HE near the center of the macula by two graders according to the EyePACS grading protocol. The patients also received a dilated fundus examination on a separate visit. Clinically significant macular edema was determined during the dilated fundus examination using the criteria set forth by the Early Treatment Diabetic Retinopathy Study. Subsequently, the sensitivity and specificity of HEs within one disc diameter of the foveola in nonstereo digital images used as a surrogate for the detection of CSME diagnosed by live fundus examination were calculated. RESULTS: The mean (±SD) age of 103 patients included in the analysis was 56 ± 17 years. Clinically significant macular edema was diagnosed in 15.5% of eyes during the dilated examination. For the right eyes, the sensitivity of HEs within one disc diameter from the foveola as a surrogate for detecting CSME was 93.8% for each of the graders; the specificity values were 88.5 and 85.1%. For the left eyes, the sensitivity values were 93.8 and 75% for each of the two graders, respectively; the specificity was 87.4% for both graders. CONCLUSIONS: This study supports the use of HE within a disc diameter of the center of the macula in nonstereo digital images for CSME detection in a screening setting.

Avaliação da perimetria macular em pacientes com degeneração macular relacionada à idade por meio do oftalmoscópio de rastreamento a laser / Evaluation of macular perimetry in patients with age-related macular degeneration using the scanning laser ophthalmoscope

OBJETIVOS: Verificar a relação entre alterações anatômicas (drusas duras, drusas moles, hiperpigmentação, neovasos, descolamento do epitélio pigmentado da retina, hipopigmentação e atrofia coriorretiniana) e a sensibilidade à luz em pacientes com degeneração macular relacionada à idade (DMRI); analisar a sensibilidade macular em áreas com ausência de lesões anatômicas nos pacientes com DMRI comparando-as ao grupo de controles, para avaliar a existência ou não de lesão funcional em área sem lesão anatômica. MÉTODOS: Estudo comparativo, descritivo e analítico, de corte transversal. O grupo de casos foi formado por 31 indivíduos portadores de DMRI com idade entre 51 e 88 anos. O grupo de controles ficou composto por 31 indivíduos considerados "sadios", não portadores de DMRI com idade entre 61 e 80 anos. Os grupos foram pareados por sexo e idade. Realizou-se a perimetria macular estática, vermelho-vermelho, com o oftalmoscópio de rastreamento a laser (ORL). Os resultados da perimetria macular foram correlacionados à lesão anatômica identificada no local correspondente pelo laser infravermelho e fotografias coloridas. RESULTADOS: As áreas com neovasos ou atrofia apresentaram sensibilidade significantemente diferente em relação às áreas com ausência de lesões anatômicas nos pacientes com DMRI. Houve perda funcional significativa em áreas com ausência de lesões anatômicas nos pacientes com DMRI em relação ao grupo de controles. CONCLUSÕES: Áreas com neovasos ou atrofia podem ser fatores individuais de piora da sensibilidade macular localizada. Pode ocorrer perda funcional mesmo sem lesão anatômica aparente nos pacientes com DMRI.

PURPOSES: To evaluate the correlation between anatomical changes (hard druses, soft druses, hyperpigmentation, new vessels, detachment of retinal pigment epithelium, hypopigmentation and chorioretinal atrophy) and light sensitivity in patients with age-related macular degeneration (ARMD); analyze macular sensitivity in areas with no anatomical lesions in patients with ARMD and compared them to the control group in order to detect if there was any functional lesion in areas with no anatomical changes. METHODS: A cross-sectional, comparative, descriptive and analytic study was performed. The case group consisted of 31 subjects with ARMD aged between 51 and 88 years. The control group consisted of 31 "healthy" subjects, without ARMD aged between 61 and 80 years. The groups were matched for gender and age. We performed static macular perimetry, red-red, using a scanning laser ophthalmoscope (SLO). Results of macular perimetry were correlated with the anatomic lesion identified in the same site by infrared laser and color photographs. RESULTS: Areas with new vessels or atrophy showed a significantly different sensitivity in relation to areas without anatomical lesions in patients with ARMD. There was significant functional loss in areas with no anatomical lesions in patients with ARMD in relation to the control group. CONCLUSIONS: Areas with new vessels or atrophy could be distinct factors for worsening of the localized macular sensitivity. There might be functional loss even in areas with no apparent anatomical changes in ARMD patients.

Birefringence of intraocular lenses.

PURPOSE: To determine the polarization properties of intraocular lenses (IOLs) in vitro and whether these properties contribute to significant intraindividual differences in the optical performance of the eye, including retinal imaging. SETTING: Tokyo Medical University, Shinjuku, Tokyo, Japan. METHODS: The single-pass linear birefringence was evaluated at 546.5 nm for the central 1.5 mm of the following IOLs: poly(methyl methacrylate) (MZ30BD, EZE55, UV-60SB, 824C, LS-106S), acrylic (MA60BM, VA-60CB, AR40e), and silicone (SI-40NB). To evaluate the influence of folding, models MA60BM, VA-60CB, AR40e, and SI-40NB were folded, unfolded, and measured for retardation values. To evaluate glistenings in vitro, experimental manipulation using the MA60BM was done to produce regions of glistenings. Retardation values were measured at the center of the micro-opacities and the adjacent clear areas. RESULTS: Striking polarization patterns were seen only in the compression-molded IOL, model 824C. Its retardation values ranged from 2.8 to 41.0 nm in the 30.0 diopter model. In other IOLs, the in vitro retardation values were minimal, even with folding, and barely nonuniform with glistening formation. CONCLUSIONS: The birefringence of the 824C IOL could be a source of error during polarization measurements of the fundus or with instruments that transmit polarized light through the IOL.

Imaging and visualization of pathology beneath the retinal surface.

Pathology beneath the highly reflective surface, such as the human retina, is key in the detection and management of disease. Advanced imaging techniques can help reveal these. Visualization and guiding the imaging to the appropriate area still remain as problems, in part due to the small scale of the pathology with respect to the potential area to be covered.