Changes in reticular pseudodrusen area in eyes that progressed from early to late age-related macular degeneration.

OBJECTIVE: This retrospective cohort study utilized 3 imaging modalities to analyze quantitatively reticular pseudodrusen (RPD) area changes in eyes that progressed from early to late age-related macular degeneration (AMD). METHODS: Subjects with AMD, unilateral choroidal neovascularization (CNV), and early AMD with RPD in the fellow eye (the study eye) were included. The study eyes underwent indocyanine green angiography (ICGA), near-infrared reflectance (NIR-R), and short-wavelength autofluorescence (AF) imaging of the macula at baseline and at follow-up. Study eyes were analyzed for RPD and for the development of late AMD-CNV and/or geographic atrophy (GA). RPD area was measured at baseline and at follow-up as a percentage of the 30-degree field. RESULTS: During the study period (mean follow-up time 23.5 ± 5.0 months), 12/31 study eyes developed CNV and 4/31 developed GA. In the eyes that developed CNV, there was a statistically significant decrease in mean RPD area over the follow-up period as seen on AF (P < 0.01) and NIR-R (P = 0.01), and the decrease in mean RPD area approached statistical significance on ICGA (P = 0.08). CONCLUSION: Using 3 en face imaging techniques, we demonstrate that RPD undergo dynamic spatiotemporal changes in eyes that progress from early AMD to CNV, namely a decrease in the area of lesions detected.

Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review.

Geographic atrophy (GA) and choroidal neovascularization (CNV), the two late forms of age-related macular degeneration, are generally considered two distinct entities. However, GA and CNV can occur simultaneously in the same eye, with GA usually occurring first. The prevalence of this combined entity is higher in histological studies than in clinical studies. No distinct systemic or genetic risk characteristics are associated with the combined GA/CNV entity, although on clinical examination and retinal imaging it can feature drusen or subretinal drusenoid deposits. GA and CNV may exist within the spectrum of a single disease, or they may be two very different diseases. Therapy with antivascular endothelial growth factor (anti-VEGF) is often successful for CNV, but some evidence suggests increased rates of GA development in eyes treated with anti-VEGF. In this article, we review the current literature regarding the epidemiology, clinical presentation, and treatment options for patients with the combined GA/CNV entity.

Reticular macular lesions: a review of the phenotypic hallmarks and their clinical significance.

Reticular macular lesions, also known as 'reticular macular disease', 'reticular drusen', 'reticular pseudodrusen', or 'subretinal drusenoid deposits', are a pattern of lesions commonly found in age-related macular degeneration and best visualized using at least two imaging techniques in combination. Reticular lesions have four stages of progression observable on spectral domain optical coherence tomography, but they do not show the usual signs of regression of soft drusen (calcification and pigment changes). Furthermore, reticular lesions correlate histologically with subretinal drusenoid deposits localized between the retinal pigment epithelium and the inner segment ellipsoid band. Reticular lesions are most commonly seen in older age groups of female patients with age-related macular degeneration and are usually bilateral. They are not clearly associated with known age-related macular degeneration genes and are highly associated with late-stage age-related macular degeneration and an increased mortality rate. They are also associated with alterations in the neural retina and choroid.

Osteoporosis, Fractures, and Blindness Due to a Missense Mutation in the LRP5 Receptor.

Familial exudative vitreoretinopathy (FEVR) is a genetic disorder whose presentation can include osteoporosis, multiple fractures, and incomplete retinal angiogenesis leading to retinal detachment and blindness if left untreated. Discussed herein are the cases of two pediatric siblings who presented to the orthopedic service with multiple fractures and, through interdisciplinary management, were diagnosed with FEVR and treated appropriately before permanent visual impairment. The skeletal manifestations of FEVR, which have not been explored in depth in prior literature, are described. One sibling presented to orthopedic services for evaluation of a closed distal radius fracture sustained while playing sports. A comprehensive history revealed he had suffered at least four appendicular fractures in his lifetime, and dual-energy x-ray absorptiometry (DEXA) scan revealed his bone density to be in the first percentile for his age. Concurrent evaluation of his younger sibling revealed a similar history of multiple fractures and low bone density. Referral to genetic services and ensuing whole-exome sequencing revealed a likely pathogenic variant in both siblings' LRP5 gene, the only known causative mutation for FEVR that leads to skeletal manifestations. While FEVR is well known in genetic and ophthalmologic settings, greater awareness of FEVR and other genetic disorders that predispose to fractures in pediatric populations is warranted in orthopedic settings. This will lead to reduced sequelae in pediatric patients with genetic disorders and improved interdisciplinary expertise. The story of these siblings illustrates that a high index of suspicion for genetic diseases is essential when treating children with osteoporosis and growth delays.

Pediatric Central Retinal Vein Occlusion Secondary to Concurrent Mechanisms of Optic Neuritis and Antiphospholipid Syndrome.

Purpose: To report a pediatric case of optic neuritis with subsequent development of central retinal vein occlusion (CRVO). Methods: A case and its findings were analyzed. Results: A 16-year-old boy presented with painful vision loss in the left eye, an afferent pupillary defect, and optic disc edema. Magnetic resonance imaging showed optic nerve enhancement and contrast-enhancing cerebral white-matter lesions, consistent with optic neuritis and demyelinating disease. He received intravenous methylprednisolone followed by a prednisone taper. At the 3-week follow-up, the visual acuity (VA) in the left eye had worsened and fundoscopic examination showed a new CRVO. A hypercoagulable workup showed antiphospholipid syndrome, which was treated with warfarin. He received intravitreal antivascular endothelial growth factor treatment with subsequent improvement in VA and resolution of the macular edema. Conclusions: This case describes an unusual mechanism for CRVO via a combination of optic disc edema from optic neuritis and hypercoagulability from antiphospholipid syndrome. It is important to recognize this complication of optic disc edema and the necessary workup for a pediatric CRVO.

The Relationship Between Reticular Macular Disease and Choroidal Thickness.

PURPOSE: Subretinal drusenoid deposits (SDD) are the main structural lesion of reticular macular disease (RMD), a phenotype of age-related macular degeneration (AMD). We aim to demonstrate spatiotemporal relationships between SDD and choroidal thickness (CTh) alterations in RMD+ and RMD- eyes. METHODS: Thirty-three eyes (26 subjects) with early AMD/no SDD (RMD-) and 18 eyes (16 subjects) with early AMD/SDD (RMD+) underwent enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) for CTh measurements at 11 points per scan, in 5 horizontal B scans, creating a grid of 55 points/eye. The 55 points were treated as a cluster, controlling within-subject correlation. Marginal generalized estimating equation modeling was used to estimate the association between CTh and RMD status. All eyes were divided by their median age (≤82 and >82 years) for stratified analyses. RESULTS: CTh was not significantly reduced in RMD+ eyes compared with RMD- eyes (mean difference [MD] -16.84 µm, P = 0.24). Among younger subjects, mean CTh was significantly reduced in RMD+ versus RMD- eyes (MD -53.72 µm, P = 0.01). Conversely, among older subjects, there was no significant difference in CTh between RMD+ and RMD-. CONCLUSIONS: In RMD, the association of SDD and CTh alterations varies with age but not by macular region. Among younger subjects (<82 years old), CTh was significantly thinner in RMD+ versus RMD- eyes.

Topical glaucoma therapy and ocular surface disease: a prospective, controlled cohort study.

OBJECTIVE: To evaluate the association between the intensity and duration of glaucoma topical therapy and severity of signs and symptoms of ocular surface disease (OSD). DESIGN: Single-site, prospective, controlled, cross-sectional study. PARTICIPANTS: Sixty-one patients with no diagnosis of or previous treatment for OSD were identified. METHODS: Patients were assigned to 2 groups: the glaucoma group with 31 patients diagnosed with primary open-angle glaucoma and using at least 1 topical intraocular pressure (IOP)-lowering medication and the control group including 30 patients with no diagnosis of glaucoma or history of topical therapy usage. The right eye of each patient was arbitrarily chosen. Each patient completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent evaluation of the ocular surface by conjunctival and corneal lissamine green (LG) staining and tear breakup time (TBUT). The intensity index (drops/wk × therapy duration in years) was calculated to quantify the topical therapy. RESULTS: OSDI scores of the glaucoma group correlated to the intensity index (r = 0.46, CI 0.13-0.69). The glaucoma group had a higher mean OSDI score than the control group (18.97 ± 9.5 versus 6.25 ± 5.7, p = 5.85E-08). Abnormal TBUT and LG staining scores were prevalent in the glaucoma group compared with the control group (68% vs 17%, p = 0.000078; 65% vs 3%, p = 2.9E-07). CONCLUSIONS: Patients on glaucoma therapy have a greater prevalence of OSD symptoms, and their intensity index correlates to the OSDI score. The intensity index reflects quantitatively the amount of treatment and can be further validated in future studies as a predicting tool for OSD development.

9.1 cm abdominal aortic aneurysm in a 69-year-old male patient.

We are presenting a case of one of the largest un-ruptured abdominal aortic aneurysm ever reported. Presented here is a rare case of a 69-year-old active smoker male with history of hypertension and incidental diagnosis of abdominal aortic aneurysm of 6.2 cm in 2003, who refused surgical intervention at the time of diagnosis with continued smoking habit and was managed medically. Patient was subsequently admitted in 2012 to the hospital due to unresponsiveness secondary to hypoglycemia along with diagnosis of massive symptomatic pulmonary embolism and non-ST elevation myocardial infarction. With the further inpatient workup along with known history of abdominal aortic aneurysm, subsequent computed tomography scan of abdomen pelvis revealed increased in size of infrarenal abdominal aortic aneurysm to 9.1 cm of without any signs of rupture. Patient was unable to undergo any surgical intervention this time because of his medical instability and was eventually passed away under hospice care.

Risk characteristics of the combined geographic atrophy and choroidal neovascularisation phenotype in age-related macular degeneration.

AIM: To investigate the risk characteristics of the combined geographic atrophy (GA) and choroidal neovascularisation (CNV) phenotype of age-related macular degeneration (AMD) compared to GA or CNV. METHODS: Patients with advanced AMD were identified and divided into three groups using multimodal imaging: patients with GA in at least one eye, patients with CNV in at least one eye, and patients with simultaneous GA and CNV in at least one eye. Epidemiologic and clinical factors were gathered from patient questionnaires. Genotypes for age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) were determined. RESULTS: 42 patients with GA or CNV, and 16 patients with combined GA/CNV were identified. Patients with the combined phenotype were older (86.4 vs 81.8 years, p=0.049), and had a higher prevalence of advanced AMD in the fellow eye (81.3% vs 31.0%, p<0.001). CFH and ARMS2 risk alleles were not associated with the combined phenotype. CONCLUSIONS: The combined GA/CNV phenotype has similar epidemiologic, clinical, and genetic features as GA and CNV, but occurs at an older age and is more associated with advanced AMD in the fellow eye, suggesting that all these phenotypes are part of the same spectrum of disease and that the combined phenotype represents an even more advanced form of AMD than either GA or CNV.