Brooke Nesmith

Poor responders to bevacizumab pharmacotherapy in age-related macular degeneration and in diabetic macular edema demonstrate increased risk for obstructive sleep apnea.

Purpose: To investigate the risk for obstructive sleep apnea (OSA) in patients with exudative age-related macular degeneration (AMD) or diabetic macular edema with poor response to anti-vascular endothelial growth factor therapy with bevacizumab (Avastin). Methods: Age-related macular degeneration group was categorized into nonexudative, exudative, or poor response exudative. Diabetic macular edema group included patients with nonproliferative diabetic retinopathy and cystoid macular edema. Patients were categorized based on the number of intravitreal injections of bevacizumab received. Both groups were compared with age-matched controls. Patients completed a screening questionnaire to assess the risk for OSA, the main outcome measure. Results: Of 103 patients with AMD, 56 (54.37%) had nonexudative AMD and 47 (45.63%) had exudative AMD, of which 14 (29.79%) had poor response exudative AMD and were at a significantly higher risk of OSA (P < 0.05). Of 30 diabetic macular edema patients with cystoid macular edema, 4 (19%) received 1 injection, 18 (81.82%) received 2 or more consecutive injections, and 16 (72.73%) received 3 or more consecutive injections. Risk for OSA increased significantly with increasing number of injections (P < 0.05). Conclusion: Patients with exudative AMD and diabetic macular edema with poor response to anti-vascular endothelial growth factor therapy have a significantly higher risk of OSA compared with age-matched controls and should be screened to assess the risk of OSA.

Choroidal Hyperreflective Foci in Stargardt Disease Shown by Spectral-Domain Optical Coherence Tomography Imaging: Correlation With Disease Severity

IMPORTANCE The presence of choroidal hyperreflective foci in Stargardt disease is, to our knowledge, a potentially new finding. Evaluation of these foci may aid in better understanding of the disease process. OBJECTIVES To report the presence of choroidal hyperreflective foci in spectral-domain optical coherence tomography (SD-OCT) images from eyes with Stargardt disease and investigate the relationship between the number of hyperreflective foci and disease severity. DESIGN, SETTING, AND PARTICIPANTS Twenty-six eyes of 13 patients with a clinical diagnosis of Stargardt disease were evaluated in a retrospective case series. Patient data were collected between January 1, 2009, and August 31, 2014. MAIN OUTCOMES AND MEASURES The number of choroidal hyperreflective foci in Stargardt disease as well as correlation with visual acuity, central macular thickness (CMT), and disease duration were the main outcomes. A total of 707 macular SD-OCT scans of 13 patients with Stargardt disease were reviewed and evaluated for the presence and number of retinal/choroidal hyperreflective foci, central macular thickness, visual acuity, and disease duration. Enhanced depth imaging with OCT (EDI-OCT) scans available for 2 patients were compared with SD-OCT scans. A PubMed/Google search was performed to identify SD-OCT images in Stargardt disease; these findings were reviewed for the presence of choroidal hyperreflective foci. RESULTS The mean (SD) numbers of hyperreflective foci in each retinal/choroidal layer in decreasing frequency were as follows: Bruch membrane/retinal pigment epithelial (RPE) complex, 78.22 (24.39); choriocapillaris, 25.77 (17.57); Sattler layer, 18.59 (12.89); outer retina, 16.64 (6.96); inner retina, 0.95 (1.58); and Haller layer, 0.73 (0.87). The number of hyperreflective foci in the Bruch membrane/RPE complex increased exponentially with decreasing CMT (R2 = 0.99; P = .008). The number of hyperreflective foci in the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer increased proportionally with decreasing visual acuity (R2 = 0.97, R2 = 0.95, and R2 = 0.99, respectively; and P = .007, P = .006, and P = .008, respectively). Direct correlation existed between the number of hyperreflective foci in the choriocapillaris and the Sattler layer and disease duration (R2 = 0.98 and R2 = 0.99, respectively; and P = .006 and P =.009, respectively). In the 10 studies on Stargardt disease, choroidal hyperreflective foci were present in 51 of 54 SD-OCT images (94%). CONCLUSIONS AND RELEVANCE Based on the findings of the present study, choroidal hyperreflective foci in Stargardt disease, prominent at the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer, correlate with disease severity in terms of retinal atrophy, decline in vision, and disease duration. Further studies are necessary to assess whether these findings are unique to Stargardt disease.

Mathematical Analysis of the Normal Anatomy of the Aging Fovea

PURPOSE To mathematically analyze anatomical changes that occur in the normal fovea during aging. METHODS A total of 2912 spectral-domain optical coherence tomography (SD-OCT) normal foveal scans were analyzed. Subjects were healthy individuals, aged 13 to 97 years, with visual acuity ≥20/40 and without evidence of foveal pathology. Using automated symbolic regression software Eureqa (version 0.98), foveal thickness maps of 390 eyes were analyzed using several measurements: parafoveal retinal thickness at 50 μm consecutive intervals, parafoveal maximum retinal thickness at two points lateral to central foveal depression, distance between two points of maximum retinal thickness, maximal foveal slope at two intervals lateral to central foveal depression, and central length of foveal depression. A unique mathematical equation representing the mathematical analog of foveal anatomy was derived for every decade, between 10 and 100 years. RESULTS The mathematical regression function for normal fovea followed first order sine curve of level 10 complexity for the second decade of life. The mathematical regression function became more complex with normal aging, up to level 43 complexity (0.085 fit; P < 0.05). Young foveas had higher symmetry (0.92 ± 0.10) along midline, whereas aged foveas had significantly less symmetry (0.76 ± 0.27, P < 0.01) along midline and steeper maximal slopes (29 ± 32°, P < 0.01). CONCLUSIONS Normal foveal anatomical configuration changes with age. Normal aged foveas are less symmetric along midline with steeper slopes. Differentiating between normal aging and pathologic changes using SD-OCT scans may allow early diagnosis, follow-up, and better management of the aging population.

UNTREATED OBSTRUCTIVE SLEEP APNEA HINDERS RESPONSE TO BEVACIZUMAB IN AGE-RELATED MACULAR DEGENERATION.

Purpose: To compare functional and anatomical responses to intravitreal bevacizumab in patients with exudative age-related macular degeneration (AMD) between two groups of patients with obstructive sleep apnea (OSA) with and without treatment with continuous positive airway pressure therapy. Methods: Patients with OSA were categorized into 2 groups: 18 untreated and 20 treated with continuous positive airway pressure therapy. All patients had exudative AMD and received treatment with intravitreal bevacizumab. Central retinal thickness was plotted against time to assess anatomical response. Logarithm of the minimum angle of resolution visual acuity changes determined functional effect. Total number of intravitreal injections administered was assessed. Results: Treated OSA group received 8 ± 7 total injections; untreated OSA group received 16 ± 4 injections (P < 0.05). Treated OSA group achieved statistically significant better visual acuity (logarithm of the minimum angle of resolution, 0.3 ± 0.24, 20/40), as opposed to the untreated group (logarithm of the minimum angle of resolution, 0.7 ± 0.41; P < 0.05). Central retinal thickness improved in the treated OSA group compared with the untreated group: 358 ± 95 &mgr;m to 254 ± 45 &mgr;m and 350 ± 75 &mgr;m to 322 ± 105 &mgr;m, respectively (P < 0.05, 20/100). Conclusion: Untreated OSA hinders the response of exudative AMD to intravitreal bevacizumab. Treatment of OSA with continuous positive airway pressure therapy yields a subsequent anatomical response and functional improvement while requiring significantly less injections. Identifying and treating underlying OSA earlier in patients with exudative AMD may yield better functional outcomes.

VITREOMACULAR ADHESION EVOLUTION WITH AGE IN HEALTHY HUMAN EYES.

Purpose: To quantify the changes in vitreomacular interactions that occur with normal aging in normal eyes. Methods: Spectral domain optical coherence tomography (SD-OCT, Spectralis; Heidelberg Engineering, Heidelberg, Germany) foveal scans of subjects with best corrected visual acuity better than 20/40 and no ocular pathology were included in the study. Each scan was analyzed to determine the status of vitreoretinal interface: complete vitreous adhesion, partial posterior vitreous detachment (PVD) with persistent vitreomacular adhesion (VMA), or complete PVD. Area of VMA was delineated using the Spectralis drawing tool and calculated in mm2 for each scan. Subjects, aged 10 years to 97 years, were divided into 9 age groups according to decade of life. Results: Five hundred and sixty-six SD-OCT scans were analyzed. Area of VMA (mm2) decreased sigmoidally (R2 = 0.99) with each decade of life. With aging, percentage of PVD increased while percentage of complete adhesion decreased. Males were found to have significantly larger area of VMA (mm2) compared with females in the fifth through eighth decades of life, P < 0.05. Conclusion: Vitreomacular interface interactions throughout life are age and gender dependent. This adds to our current understanding of the normal aging process undergone by the vitreous, thereby providing assistance in the clinical differentiation between normal and pathologic vitreomacular interactions.

DIABETES ALTERS THE MAGNITUDE OF VITREOMACULAR ADHESION.

Purpose: To quantify the changes in vitreomacular interactions that occur with aging in diabetic eyes in comparison with age-matched control eyes. Methods: Spectral-domain optical coherence tomography (Spectralis; Heidelberg Engineering) foveal scans of diabetic patients, without evidence of cystoid macular edema, were included. Twenty-five raster foveal scans were performed on every subject. Area of vitreomacular adhesion was delineated using the Spectralis drawing tool and calculated in square millimeter. Data collected included gender, race, best-corrected visual acuity, and posterior vitreous detachment status. Subjects were divided into age groups according to decade of life. Results: Spectral-domain optical coherence tomography scans from 141 diabetic patients were analyzed. Area of vitreomacular adhesion (mm2) showed a hyperbolic decline in diabetic patients (35.5 ± 0, 35.0 ± 3, 34.0 ± 3, 33.9 ± 5, 33.7 ± 6, 29.0 ± 11, 23 ± 15, 13 ± 15). With aging, incidence of posterior vitreous detachment increased and incidence of complete attachment decreased. Conclusion: Diabetes affects the magnitude of attachment of the vitreous gel to the macula that results in stronger and longer lasting attachment of the gel throughout life. Gender differences were not noticed in diabetic patients, suggesting that vitreomacular adhesion remains robust in both genders in diabetes despite aging.