Incidence, progression and risk factors of age-related macular degeneration in 35-95-year-old individuals from three jointly designed German cohort studies.

OBJECTIVE: To estimate age-related macular degeneration (AMD) incidence/progression across a wide age range. METHODS AND ANALYSIS: AMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification, CC) was assessed for 1513 individuals aged 35-95 years at baseline from three jointly designed population-based cohorts in Germany: Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Fit, KORA-FF4) and Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg (AugUR) with 18-year, 14-year or 3-year follow-up, respectively. Baseline assessment included lifestyle, metabolic and genetic markers. We derived cumulative estimates, rates and risk factor association for: (1) incident early AMD, (2) incident late AMD among no AMD at baseline (definition 1), (3) incident late AMD among no/early AMD at baseline (definition 2), (4) progression from early to late AMD. RESULTS: Incidence/progression increased by age, except progression in 70+-year old. We observed 35-55-year-old with 3CACSS-based early AMD who progressed to late AMD. Predominant risk factor for incident late AMD definition 2 was early AMD followed by genetics and smoking. When separating incident late AMD definition 1 from progression (instead of combined as incident late AMD definition 2), estimates help judge an individual's risk based on age and (3CACSS) early AMD status: for example, for a 65-year old, 3-year late AMD risk with no or early AMD is 0.5% or 7%, 3-year early AMD risk is 3%; for an 85-year old, these numbers are 0.5%, 21%, 12%, respectively. For CC-based 'early/intermediate' AMD, incidence was higher, but progression was lower. CONCLUSION: We provide a practical guide for AMD risk for ophthalmology practice and healthcare management and document a late AMD risk for individuals aged <55 years.

SLO-Microperimetry in Wet Age-Related Macular Degeneration During Anti-VEGF Therapy.

BACKGROUND AND OBJECTIVE: To evaluate the morphological and functional outcome of wet age-related macular degeneration (AMD) during antivascular endothelial growth factor therapy with bevacizumab using SLO microperimetry (SLO-MP) with eye tracking. PATIENTS AND METHODS: First, reproducibility was tested over the choroidal neovascularization (CNV) in 21 eyes of 19 patients with wet AMD. Second, 21 eyes of 19 patients with active CNV were studied longitudinally during bevacizumab therapy. Best-corrected visual acuity, SLO-MP, spectral-domain optical coherence tomography and fluorescein angiography were performed. RESULTS: There was good reproducibility with a concordance correlation coefficient of 0.85. In the longitudinal study, eyes with anatomical response demonstrated a significant increase of retinal sensitivity. Non-responders showed no change in SLO-MP. Retinal sensitivity at baseline had a significant predictive value for the change in retinal sensitivity during therapy with bevacizumab (P=.032). CONCLUSION: SLO-MP is able to analyze retinal function overlying lesions in wet AMD and can be a useful tool to monitor therapy in patients with macular diseases.

Restoration of retinal layers after epiretinal membrane peeling.

PURPOSE: To evaluate the morphologic restoration of retinal anatomy after surgery for epiretinal membrane (ERM) peeling using spectral domain optical coherence tomography. Correlation of retinal structure with visual outcome. DESIGN: Retrospective consecutive case series. METHODS: Thirty-four consecutive eyes with ERM underwent surgery with 1 year follow-up examination. Spectral domain optical coherence tomography scans were analyzed preoperatively and 1, 3, 6, 9, and 12 months postoperative. Best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts was measured at each visit. RESULTS: All eyes showed a significant improvement of BCVA after ERM peeling (P = 0.002). The time point of BCVA and retinal restoration seen on spectral domain optical coherence tomography occurred simultaneously and varied between individuals (occurrence of BCVA: mean, 4.82 months; retinal restoration: mean, 4.24 months). At 3 months, the retinal anatomical restoration rate was 70% and 88% at 6 months. CONCLUSION: Restoration of the retinal anatomical structure predominantly occurs within the first 3 months post-ERM peeling. An improvement of BCVA and anatomical retinal restoration after ERM removal varies in individuals. If retinal layers fully restore in their anatomical structure, BCVA improves at the same time point.

Accuracy of the Heidelberg Spectralis in the alignment between near-infrared image and tomographic scan in a model eye: a multicenter study.

PURPOSE: To evaluate temporal changes and predictors of accuracy in the alignment between simultaneous near-infrared image and optical coherence tomography (OCT) scan on the Heidelberg Spectralis using a model eye. DESIGN: Laboratory investigation. METHODS: After calibrating the device, 6 sites performed weekly testing of the alignment for 12 weeks using a model eye. The maximum error was compared with multiple variables to evaluate predictors of inaccurate alignment. Variables included the number of weekly scanned patients, total number of OCT scans and B-scans performed, room temperature and its variation, and working time of the scanning laser. A 4-week extension study was subsequently performed to analyze short-term changes in the alignment. RESULTS: The average maximum error in the alignment was 15 ± 6 µm; the greatest error was 35 µm. The error increased significantly at week 1 (P = .01), specifically after the second imaging study (P < .05); reached a maximum after the eighth patient (P < .001); and then varied randomly over time. Predictors for inaccurate alignment were temperature variation and scans per patient (P < .001). For each 1 unit of increase in temperature variation, the estimated increase in maximum error was 1.26 µm. For the average number of scans per patient, each increase of 1 unit increased the error by 0.34 µm. CONCLUSION: Overall, the accuracy of the Heidelberg Spectralis was excellent. The greatest error happened in the first week after calibration, and specifically after the second imaging study. To improve the accuracy, room temperature should be kept stable and unnecessary scans should be avoided. The alignment of the device does not need to be checked on a regular basis in the clinical setting, but it should be checked after every other patient for more precise research purposes.

Hydrosilylated porous silicon particles function as an intravitreal drug delivery system for daunorubicin.

PURPOSE: To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). METHODS: pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography-electrospray ionization-multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. RESULTS: The mean pSi particle size was 30×46×15 µm with an average pore size of 15 nm. Drug loading was determined as 22 µg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. CONCLUSIONS: Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected.

Effect of change in drusen evolution on photoreceptor inner segment/outer segment junction.

PURPOSE: To evaluate the integrity of photoreceptor inner segment/outer segment (IS/OS) junction after change of drusen size in age-related macular degeneration using spectral-domain optical coherence tomography. METHODS: Drusen volume raster scans were performed with the Spectralis spectral-domain optical coherence tomography (Heidelberg Engineering) through 2,624 drusen in 14 eyes with clinically dry age-related macular degeneration, which had been longitudinally followed-up between 23 and 28 months without intervention (mean, 26.3 months). All eyes had Early Treatment Diabetic Retinopathy Study visual acuity. A total of 416 of 2,624 drusen were analyzed. RESULTS: Of 416 drusen, 83 (20%) were found to have regressed spontaneously (Group A), 212 (51%) showed no change in size (Group B), and 121 (29%) progressed (Group C). Mean drusen size of all drusen was 63.7 ± 25.7 µm. Cross-sectional analysis of drusen morphology showed a correlation between drusen size and disrupted IS/OS junction/photoreceptor integrity (r = -0.48, P < 0.001). Of the drusen that regressed over time, there was intact IS/OS junction integrity. Even drusen that caused a major disruption showed IS/OS restoration in 74% of the drusen (P < 0.001). CONCLUSION: Progression of drusen shows structural disruption of the IS/OS junction. After drusen regression, the IS/OS junction is either able to restore as drusen regress or was artifactitiously compressed and not initially visible because of the initial drusen compression of the IS/OS junctional line. Therefore, drusen evolution may play an important role in affecting the photoreceptor IS/OS junction integrity.

Primary intraocular lymphoma: a review.

Primary intraocular lymphoma (PIOL) is a rare, non-Hodgkin lymphoma considered to be a subtype of primary central nervous system lymphoma. We describe a 65-year-old woman who presented to the Hematology/Oncology Clinic at Scripps Clinic, La Jolla, California, who was diagnosed with bilateral PIOL without systemic disease. She enjoyed a 16-month remission but ultimately recurred in the brain. We reviewed the literature and present a discussion of the diagnostic criteria for PIOL and current strategies for treating PIOL in immunocompetent patients.

Scanning laser ophthalmoscope imaging stabilized microperimetry in dry age-related macular degeneration.

PURPOSE: To determine the effect of drusen and geographic atrophy (GA) in dry age-related macular degeneration on retinal sensitivity using an eye tracking scanning laser ophthalmoscope microperimetry. METHODS: A total of 44 eyes from 22 patients with dry age-related macular degeneration and drusen and 11 patients with GA were imaged with scanning laser ophthalmoscope microperimetry (OPKO Health, Miami, FL). A custom microperimetry pattern was used to evaluate retinal sensitivity to a Goldmann III size target (108 µm on the retina). The perimetry used a 4-2 stepladder algorithm to determine maximal sensitivity. Microperimetry and optical coherence tomography were performed using a standardized protocol. Twenty-eight eyes with drusen and 16 eyes with GA were analyzed. RESULTS: Retinal sensitivity overlying drusen was significantly reduced compared with the adjacent uninvolved retina. There was a significant correlation between retinal sensitivity and drusen volume, as well as the grading of the photoreceptor inner segment/outer segment junction score. In patients with GA, an absolute scotoma was confirmed. Retinal sensitivity at the margin of GA was significantly decreased compared with the adjacent uninvolved retina. CONCLUSION: Scanning laser ophthalmoscope microperimetry is able to detect changes in retinal sensitivity in AMD patients overlying drusen and at the margin of GA. It is a useful device to grade focal retinal sensitivity in patients with dry age-related macular degeneration.