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To analyze the urinary metabolomic profile of central serous chorioretinopathy (CSC) cases.In a cross-sectional study, 80 participants with CSC were compared with 80 age- and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4TM platform.Of 1031 metabolites total that were measured in urine samples, 53 were up-regulated and 27 down-regulated in CSC participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid sub-pathway. The down-regulated metabolites are unrelated to the identified corticosteroid sub-pathway.The upregulation of urinary tetrahydrocortisol sulfate in CSC cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

Purpose: To evaluate medium and large choroidal vessel layer thickness (MCVT and LCVT, respectively) in eyes with acute and chronic central serous chorioretinopathy (CSC) in comparison with age-matched controls. Methods: The study included 96 eyes of 96 patients with CSC, including 53 eyes with acute CSC, 43 eyes with chronic CSC, and 30 eyes of 30 age-matched normal subjects. Manual measurements of subfoveal choroidal thickness (SFCT), MCVT, and LCVT at subfoveal and 750 μm nasal and temporal to the fovea locations were made on enhanced depth imaging optical coherence tomography (EDI-OCT) of the macula in all subjects using ImageJ software (National Institutes of Health, Bethesda, MD, USA). Results: SFCT in acute CSC was significantly larger than that in healthy eyes (P = 0.0001). SFCT in acute CSC did not differ significantly from that in chronic CSC eyes. Subfoveal LCVT and MCVT in acute CSC eyes were greater than those in healthy eyes (P = 0.02 and P = 0.03, respectively). Mean SFCT and MCVT in chronic CSC eyes were significantly larger than those in control eyes (P = 0.01 and P = 0.04, respectively). No significant difference in LCVT was observed between chronic and control eyes. Conclusion: Choroidal vasculature is altered in both acute and chronic CSC. SFCT, MCVT, and LCVT are higher in eyes with acute CSC. The thickening of medium choroidal vessels is still detectable in chronic CSC compared to control eyes.

BACKGROUND: Comparison of presentation and outcomes of central serous chorioretinopathy (CSC) between male and female subjects in different ethnic populations. METHODS: Retrospective comparison between male and female subjects with CSC was completed. Demographic details, clinical presentations, imaging features and treatment outcomes were compared at baseline and at last follow-up. RESULTS: This study included 155 male and 155 female subjects with a mean (CSD) age of 43.8 ± 10.3 and 57.0 ± 12.1 years, respectively, and a mean duration of follow-up of 8.49 ± 12.6 months. At presentation, there was no difference in visual acuity; however, visual acuity was significantly higher for female subjects at last follow-up (p = 0.02). Optical coherence tomography (OCT) analysis showed that subretinal deposits (p

Purpose To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCHs) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti–vascular endothelial growth factor and anti–platelet-derived growth factor signaling. Design Observational case review. Participants Three patients with advanced VHL-related juxtapapillary RCHs treated with systemic sunitinib malate. Methods Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCHs, and degree of exudation were recorded at each visit. Optical coherence tomography and fluorescein angiography were also obtained at some visits. Main Outcome Measures Visual acuity, size of RCHs, and degree of exudation. Results Three patients with advanced VHL-associated juxtapapillary RCHs were treated with systemic sunitinib malate. Although none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCHs. Improvements in RCH-associated retinal edema were observed in 2 patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the 3 patients had to discontinue treatment prematurely and the third required dose reduction. Conclusions Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCHs. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCHs when used at the doses described in this report. Further studies are required to determine if this medication, used at lower doses with different treatment strategies; other medications in the same class; or drugs directed at multiple targets in the tumor may be safer and more effective for the treatment of advanced VHL-associated RCHs.

Background Ehlers‒Danlos Syndrome (EDS) is a rare disease affecting approximately 1 in 5,000 people. Although ophthalmic conditions associated with EDS have been described, little data exist concerning ophthalmic surgical outcomes experienced by EDS patients. Methods Patients with EDS were surveyed via the EDS Society and asked about their ophthalmic surgical experiences including procedure, complications, and the timing with respect to receiving the EDS diagnosis. Complications were confirmed as such by subspecialists. Results Of 579 respondents, 467 reported confirmed EDS, and 112 of those had an ophthalmic procedure, including refractive surgery, cataract/lens surgery, retinal surgery, strabismus surgery, oculoplastic surgery, corneal surgery, and laser surgery for glaucoma. The rate of confirmed complications was: 23%‐refractive, 33%‐lens/cataract, 33%‐retina, 59%‐strabismus, 23%‐ oculoplastics, 0%‐cornea, and 25%‐glaucoma laser. In addition, 76% of patients underwent surgery prior to the EDS diagnosis. Conclusions Patients with EDS may have elevated risk of postoperative ophthalmic surgical complications. It would seem reasonable to systemically and prospectively explore how patients with EDS respond to ophthalmic surgery. Furthermore, it would seem circumspect to ask surgical candidates patients about whether they carry a diagnosis of EDS or have signs and symptoms of EDS prior to surgery., Eye surgery on patients with Ehlers‒Danlos may have a higher complication rate than seen in the general population. Surgeons should be cognizant that the diagnosis of Ehlers‒Danlos might not be made in patients suffering this condition.

Purpose To evaluate long-term visual and anatomic outcomes in patients with retinal vein occlusion (RVO) treated with anti–vascular endothelial growth factor (VEGF) agents. Design Prospective, interventional case series. Participants Patients with central RVO (CRVO) or branch RVO (BRVO). Methods Number of anti-VEGF injections and improvement from baseline best-corrected visual acuity (BCVA) and central subfield thickness (CST) were prospectively recorded in 40 eyes of 39 CRVO patients and 50 eyes of 47 BRVO patients. Results Mean follow-up was 58 months for BRVO and 78 months for CRVO. Within 6 months of last follow-up, 58% of BRVO patients and 75% of CRVO patients required anti-VEGF injections to control edema. Analysis of the course of each patient over time showed that for BRVO patients, BCVA letter score increased by a mean of 24, from baseline of 52 (20/100) to peak of 76 (20/32), and subsequently decreased by 13, to 63 (20/50), at final visit; and for CRVO patients, BCVA letter score increased by a mean of 26, from baseline of 48 (20/100) to peak of 74 (20/32), and subsequently decreased by 18, to 56 (20/80), at last follow-up. Loss from peak BCVA occurred primarily owing to persistent/recurrent edema and related foveal damage. Conclusions Patients with RVO showed large improvements in BCVA after initiation of anti-VEGF injections, but in many patients some visual gains were lost over time owing to bouts of recurrent edema. Sustained suppression of VEGF may help to provide optimal outcomes in RVO and reduce treatment burden.

Purpose To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Design Post hoc analysis of a prospective clinical study. Participants There were 69 participants with nAMD in ≥1 eye. Methods Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square root transformed areas. Main Outcome Measures Development of new-onset GA and rate of GA area growth measured on ocular imaging, including fundus autofluorescence images of the study eyes. Results Sixty-nine participants (mean age, 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of the 69 study eyes (32%) were treatment naive. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had preexisting GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared with those who did not develop new GA. Of the 12 treatment-naive study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/y, compared with 0.19±0.12 mm/y in eyes developing new-onset GA (5/21). Conclusions Although 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development of GA is unclear. Further prospective longitudinal studies are required to determine the eyes most at risk of developing GA in the setting of anti–vascular endothelial growth factor treatment.

Purpose The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro-permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME. Design Prospective, randomized crossover clinical trial. Methods Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral-domain optical coherence tomography (SDOCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Crossover at week 16 provided changes in protein levels after each intervention in all 20 patients. Results After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including 3 known PPFs: angiopoietin-2 (r = 0.40, P = .001), hepatocyte growth factor (HGF; r = 0.31, P = .02), and endocrine gland-VEGF (EG-VEGF, r = 0.43, P Conclusions Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multifactorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factors to chronic DME.

Purpose To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Design Randomized, double-masked, 36-week, 3-period crossover clinical trial. Participants Fifty-six subjects with DME involving the center of the macula in one or both eyes. Methods Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Main Outcome Measures Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Results Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was −89 μm for bevacizumab and −137 μm for ranibizumab (difference, 48 μm; P Conclusions This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti–vascular endothelial growth factor drugs for DME.

To report clinical characteristics and treatment outcomes from the largest case series of choroidal neovascularization secondary to central serous chorioretinopathy.Retrospective analysis of 46 eyes of 43 consecutive subjects. Collected data included demographic details, history of presenting illness, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were the proportion of eyes that had improved (3 or more lines), stable (within ±1 line), or decreased (3 or more lines) vision at the final visit as compared with baseline examination. Secondary efficacy outcomes included change in visual acuity at final follow-up, number of injections, treatment-free interval, and adverse events.Mean age was 57.56 years (range 29-79 years). Mean follow-up duration was 38.3 months ± 58.9 months. More than 3 lines of improvement in 12 eyes (26%), vision was stable (within ±1 line) in 19 eyes (41.3%), and3 lines of loss was noted in 6 eyes (13%). Mean change in the number of lines was 1.16 ± 3.74. Mean number of anti-vascular endothelial growth factor injections during the follow-up was 4.45 ± 4.1. The longest treatment-free interval was 8.9 months ± 7.5 months. There were no adverse events noted.Anti-vascular endothelial growth factor therapy as a primary therapy for choroidal neovascularization secondary to central serous chorioretinopathy is safe and efficacious, without any serious adverse events.

Purpose The purpose of this 1-year prospective study was to investigate how induction/pro re nata ranibizumab intravitreal treatment of eyes with neovascular age-related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. Methods High-speed indocyanine green (HS-ICG) angiography measurements provided quantification of the CNV size in 60 patients followed for 1 year. Minimum intensity projection optical coherence tomography (MinIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography was also assessed to evaluate late retinal leakage. Results After 1 year, the mean area of CNV measured with indocyanine green angiography decreased by 5.8%. The mean area of MinIP OCT of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of fluorescein angiography leakage decreased by 6.3%. Both the area of outer retinal disruption measured with MinIP OCT and the area of leakage on fluorescein angiography typically exceeded the area of CNV on indocyanine green angiography at baseline and 1 year. Conclusion Choroidal neovascularization treated with induction/pro re nata intravitreal ranibizumab for 1 year essentially remained static. Minimum intensity projection optical coherence tomography suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on indocyanine green angiography and MinIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.

Objective To evaluate the frequency of central serous chorioretinopathy (CSC) in African Americans/blacks within an academic center in a predominantly African American city, as the current belief is that CSC is rare in this population. Methods A retrospective review of all patients' charts diagnosed with CSC at Wilmer Eye Institute/Johns Hopkins University from August 2009–August 2015 was conducted via an electronic health record search (EPIC). The charts were categorized by self-reported race and gender. The diagnosis was confirmed by multiple physician consensus through chart and imaging review. Fluorescein angiograms were classified as single versus multiple point leakage. OCTs were evaluated for subfoveal thickness, location of fluid, presence or absence of pigment epithelial detachment. Color photos were categorized as to the extent of retinal pigment epithelial changes. Results Of the 590 charts identified via EPIC as CSC patients, 407 were confirmed as CSC through chart and imaging review. 45 patients (11.1%) were African Americans and 298 patients (73.2%) were Caucasians. Of all patients seen during the study period, 0.09% of African Americans at Wilmer had CSC and 0.18% of Caucasians had CSC. While three fold more Caucasians were seen during the study period as compared to African Americans, this study's prevalence rate in African Americans/blacks at Wilmer Eye Institute was half of that in Caucasian/whites. Conclusions CSC has been reported as exceedingly rare in African Americans, but our study suggests that CSC may be underestimated in this population. A large nationally representative population based study is needed to determine true racial prevalence to ensure that the diagnosis of CSC is not overlooked in African Americans.

Recent evidence suggests that neovascular age-related macular degeneration (AMD) may have an immune mediated component. Palomid 529, an investigational medication involving the immune Akt/mTOR pathway, is unique in dissociating both targets of rapamycin complexes TORC1 and TORC2. This small short-term pilot study assesses the safety of subconjunctival Palomid 529 in the treatment of neovascular AMD, with some limited efficacy information.In this 12-week phase I open-label prospective pilot study, five participants with neovascular age-related macular degeneration that were refractory to intravitreal anti-vascular endothelial growth factor (VEGF) received three serial monthly subconjunctival doses of 1.9 mg Palomid 529. All participants were also offered concomitant monthly intravitreal anti-VEGF injections. Safety was monitored via adverse events recording. Additional outcome measures included visual acuity, optical coherence tomography, fluorescein angiography, indocyanine green angiography and fundus photography.The study drug was well-tolerated by all participants. There were no drug-related adverse events and no serious adverse events. A depot formed at the injection site, which persisted at the end of the study. In these anti-VEGF refractory patients, no clinically important changes in best-corrected visual acuity, fluorescein leakage pattern, choroidal neovascularization size on indocyanine green angiography, or autofluorescence pattern on fundus autofluorescence were observed compared to baseline. The fluid status, assessed with optical coherence tomography showed that central retinal thickness and macular volume remained stable in three participants, while the other two participants clinically progressed.Serial subconjunctival injections of Palomid 529 were well-tolerated and resulted in depot formation. There were no concerns for any ocular or systemic toxicity during this small short-term study. Larger randomized studies are required to determine efficacy.

Purpose Central serous chorioretinopathy (CSC) management lacks well-defined guidelines given the variable natural history of this disease and the lack of prospective trials. We conducted an online preferred physician practice survey to track international trends and variations in the management of CSC data. Methods We designed and distributed an online 27-item questionnaire with secure confidential access to retina specialists with a publication record in CSC. Physicians with at least one publication as first or corresponding author in any national or international peer reviewed journal in the English language on CSC within the last 2 years on PubMed were included. Participants were masked to the responses from other participants. Results The response rate was 82.3% (107 out of 130). 79.1% physicians preferred to observe cases of acute CSC. For chronic cases, 66.7% offered photodynamic therapy (PDT) as first line treatment. The most commonly used PDT protocol was full dose and half-fluence (60.6%). For chronic cases with intraretinal cystic changes, 43.1% opted for observation. Enhanced depth imaging, optical tomography was a common diagnostic tool for 59.8%, while indocyanine green angiography was only used by 37.8%. One regional difference was a preference for focal laser in Asia for initial treatment. Conclusions While there are some common practice patterns for of CSC, there are still variations in regional and individual practice patterns indicating the need to establish more definitive practice guidelines. This survey data could be useful to plan a prospective study to address many unanswered questions.

Summary Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. Although recent studies have demonstrated strong genetic associations between AMD and SNPs in a number of genes, other modes of regulation are also likely to play a role in the etiology of this disease. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Furthermore, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and messenger RNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis.

The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity.Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity.Mean retinal thickness and PROS length were 298 mum to 381 microm and 30 microm to 32 mum, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81.Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that the PROS measures may be more directly related to visual function. Photoreceptor outer segment length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects.

To determine whether optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD). Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus OCT system and the spectral-domain Cirrus OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analysed. Cirrus OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients for all parameters analysed. A pair-wise comparison of Cirrus OCT with Stratus OCT systems revealed that Cirrus-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (P

To compare noninvasive autofluorescence (AF) photography with conventional fundus photography and fluorescein angiography (FA) in the detection of basal laminar drusen (BLD).A retrospective case review of 20 patients with BLD studied with AF and conventional imaging was performed. Three selected patients with different degrees of BLD are presented. AF imaging employed an excitation filter at 580 nm and a barrier filter at 695 nm with acquisition by a Topcon 50X fundus camera. Corresponding detail regions in each image were enlarged for comparison. The AF detail image was registered by a projective transformation in Matlab (Mathworks 7.0, Natick, MA) with the color photograph/red free photograph (RF) and/or FA image detail for exact superimposition in Photoshop and lesion comparison.Each visible drusen in the color or RF photograph corresponded when superimposed to a focal hypoautofluorescent lesion in the AF image. However, similar to the starry sky pattern in FA, the AF lesions significantly outnumbered the clinically evident drusen. When BLD lesions were not advanced enough to show the classic starry sky fluorescein hyperfluorescence, the BLD were detectable with AF.In our case series, AF imaging demonstrated a higher level of sensitivity when compared with conventional fundus photography and is less invasive than FA for the detection of BLD. Fundus AF, therefore, is valuable for diagnosing and following BLD, particularly since these patients are at risk for development of pseudovitelliform detachment which may simulate CNV.

Purpose To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab. Design Secondary outcome measure in randomized double-masked controlled clinical trial. Participants Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). Methods Subjects were randomized to 0.5 or 2.0 mg ranibizumab every month for 6 months and then were re-randomized to pro re nata (PRN) groups receiving either ranibizumab plus scatter laser photocoagulation or ranibizumab alone for an additional 30 months. Main Outcome Measures Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5 versus 2.0 mg ranibizumab, during monthly injections versus ranibizumab PRN, and in patients treated with ranibizumab PRN versus ranibizumab PRN plus laser. Results In RVO patients given monthly injections of 0.5 or 2.0 mg ranibizumab for 6 months, there was no significant difference in the percentage who showed reduction or increase in the area of RNP. However, regardless of dose, during the 6-month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared with subsequent periods of ranibizumab PRN treatment. After the 6-month period of monthly injections, BRVO patients, but not CRVO patients, randomized to ranibizumab PRN plus laser showed significantly less progression of RNP compared with patients treated with ranibizumab PRN. Conclusions Regardless of dose (0.5 or 2.0 mg), monthly ranibizumab injections promote improvement and reduce progression of RNP compared with PRN injections. The addition of scatter photocoagulation to ranibizumab PRN may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

To describe the short-term anatomical and visual acuity responses after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).We conducted a retrospective study of patients with CNV secondary to AMD who were treated with intravitreal injection of bevacizumab (1.25 mg) during a 3-month period. Patients underwent best-corrected Snellen visual acuity testing, optical coherence tomography, and ophthalmoscopic examination at baseline and follow-up visits.There were 266 consecutive eyes of 266 patients who received injections, and follow-up information was available for 251 (94.4%). The mean age of the patients was 80.3 years, the mean baseline visual acuity was 20/184, and 175 (69.7%) had inadequate response to alternate methods of treatment. At the 1-month follow-up (data available for 244 patients), the mean visual acuity was 20/137 (P0.001 as compared with baseline), and 74 (30.3%) of patients had improvement in visual acuity as defined by a halving of the visual angle. At the 2-month follow-up (data available for 222 patients), the mean visual acuity was 20/122 (P0.001), and 78 (31.1%) of patients had visual improvement. At the 3-month follow-up (data available for 141 patients), the mean visual acuity was 20/109 (P0.001), and 54 (38.3%) of patients had visual acuity improvement. The mean central macular thickness at baseline was 340 mum and decreased to a mean of 247 microm at month 1 (P0.001) and 213 microm at month 3 (P0.001). At 1 month, two patients had mild vitritis, as did one patient at 2 months, who had a history of recurrent uveitis. No endophthalmitis, increased intraocular pressure, retinal tear, or retinal detachment occurred. The risk for thromboembolic disorders did not seem to be different than reported previously in studies concerning macular degeneration.There were no apparent short-term safety concerns for intravitreal bevacizumab injection for CNV. Treated eyes had a significant decrease in macular thickness and improvement in visual acuity. The follow-up was too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Importance Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies. Objectives To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews. Design, Setting, and Participants This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease. Main Outcomes and Measures Proportion of review outcomes also reported in trials and vice versa. Results This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews. Conclusions and Relevance Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

To describe a case of acute idiopathic maculopathy (AIM) with positive antibody titers indicative of acute infection with coxsackievirus, the suspected etiology of this disorder.A 15-year-old boy presented with acute severe central visual loss in the left eye after a sore throat with pustular lesions. Visual acuity was 20/200, and fundus examination revealed a pigmented plaque at the level of the retinal pigment epithelium with an overlying neurosensory detachment.Titers of antibody to coxsackievirus, measured by complement fixation testing, were positive for acute infection with coxsackievirus B1. Our treatment recommendation was observation. In a few weeks, visual acuity spontaneously returned to 20/20 as the exudative changes resolved leaving only a bull's eye-type lesion.Determination of titers of antibody to coxsackievirus, as shown by our case, is a useful laboratory test along with careful fundus biomicroscopy and history taking to confirm a clinical suspicion for AIM.

The contribution of DNA damage to the pathogenesis of age-related macular degeneration (AMD) has been reported. Recently, a genomewide association study detected the association of a single-nucleotide polymorphism (SNP) in RAD51B (rs8017304 A>G) with AMD. RAD51B is involved in recombinational repair of DNA double-strand breaks. We analyzed RAD51B influence on AMD using two cohorts from Caucasian and Han Chinese populations. The Caucasian set replicated the rs8017304 A>G association and revealed two novel AMD-associated SNPs in RAD51B, rs17105278 T>C and rs4902566 C>T. Under the dominant model, these two SNPs exhibit highly significant disease risk. SNP–SNP interaction analysis on rs17105278 T>C and rs4902566 C>T homozygous demonstrated a synergistic effect on AMD risk, reaching an odds ratio multifold higher than well-established AMD susceptibility loci in genes such as CFH, HTRA1, and ARMS2. Functional study revealed lower RAD51B mRNA expression in cultured primary human fetal retinal pigment epithelium (hfRPE) carrying rs17105278 T>C variants than in hfRPE carrying rs17105278 wild type. We concluded that the risk of developing AMD exhibits dose dependency as well as an epistatic combined effect in rs17105278 T>C and rs4902566 C>T carriers and that the elevated risk for rs17105278 T>C carriers may be due to decreased transcription of RAD51B. This study further confirms the role of DNA damage/DNA repair in AMD pathogenesis.

Pseudoxanthoma elasticum (PXE) is a systemic disease with characteristic findings on fundus examination. The fundus findings may be difficult to detect with ophthalmoscopy. A case report is described as follows. A PXE patient had subtle retinal findings on fundoscopy that were more prominently seen using a combination of both fundus autofluorescence (FAF) imaging and indocyanine green (ICG) angiography. The fundus features visualized using each of these two modalities appeared different from each other. FAF imaging and ICG angiography may be able to more prominently detect pathology at the level of the retinal pigment epithelium and Bruch's membrane, respectively. The use of these imaging modalities together may be complementary and useful in the evaluation of patients with PXE.

An 83-year-old man presented with a retinal arterial macroaneurysm complicated by vitreous hemorrhage, hyphema and ghost cell glaucoma requiring surgical intervention. After pars plana vitrectomy, anterior chamber wash-out and laser photocoagulation, the retinal arterial macroaneurysm closed but blood-staining of the optic nerve, internal limiting membrane and peripapillary vessels persisted. The rare sequela of blood-staining, which in this case did not adversely affect the final visual outcome, further contributes to our understanding of the wide ranging clinical spectrum of retinal arterial macroaneurysms.

PURPOSE To describe the fundus autofluorescence photographic pattern in a case of deferoxamine retinopathy. METHODS Observational case report. RESULTS A 91-year-old woman receiving intravenous deferoxamine treatment presented with a history of deteriorating vision in both eyes. Autofluorescence photography revealed well circumscribed areas of hyperautofluorescence that correlated with areas of pigmentation shown by color photography. Deferoxamine retinopathy was diagnosed. CONCLUSION Fundus autofluorescence photography is a noninvasive imaging method for early detection of deferoxamine retinopathy and can be used to monitor the status of the macula in patients at risk for this toxicity.

Recent technological advances--new pathophysiological insights, new imaging techniques for diagnosis and management, and new treatments--have led to an improved understanding of central serous chorioretinopathy (CSC). The primary role of the choroid has become more widely accepted with widespread use of indocyanine green angiography. Optical coherence tomography (OCT), and particularly enhanced depth imaging OCT, demonstrate a thickened and engorged choroid. Adaptive optics, fundus autofluorescence, multifocal electroretinography, microperimetry, and contrast sensitivity testing reveal that patients with even a mild course suffer previously undetected anatomic and functional loss. Although focal laser and photodynamic therapy are the current standard of care for persistent subretinal fluid in CSC, they are not appropriate in all cases, and the optimal timing of intervention remains unclear.

While cataract and glaucoma are the most common causes of blindness among blacks, age-related macular degeneration (AMD) is the leading cause in whites in the USA. Although no evidence-based nutritional recommendations exist in the management of glaucoma or age-related cataracts research has supported nutritional treatment strategies for AMD. This chapter will focus on nutritional therapy for AMD.

Purpose To evaluate the prevalence of large drusen in a uveitis clinic population. Design Retrospective, cohort study. Methods Patients with primary, non-infectious uveitis 55 years or older who were seen at the National Eye Institute of the National Institutes of Health from 2004 through August 2013 were reviewed using electronic medical records and photographic databases. Patients were classified as having age-related macular degeneration (AMD) if either eye had large drusen, geographic atrophy or neovascular AMD according to definitions used by the Eye Diseases Prevalence Research Group (EDPRG). The expected number of cases and standardised mortality ratio (SMR) for large drusen were estimated based on EDPRG estimates. Results We identified 177 patients aged ≥55 years as having primary non-infectious uveitis; 170 (96.0%) had gradable fundus photos. Average age was 65.0±7.5 years (range 55–87), and 87 were non-Hispanic white, 66 non-Hispanic black, 6 Hispanic white and 11 of other race/ethnicity. Large drusen were identified in four patients (2.4%; 95% CI 0.6 to 6.0). No patients were identified to have late AMD. In the uveitis cohort, the SMR for cases of large drusen, which was adjusted for age, was calculated to be 0.32 (95% CI 0.12 to 0.70) for the whole cohort, 0.28 (95% CI 0.09 to 0.79) for non-Hispanic whites and 0.46 (95% CI 0.14 to 1.29) for non-Hispanic blacks. Conclusions Large drusen prevalence among patients with uveitis ≥55 years of age appears less than the prevalence in the general US population after accounting for differences in age distribution, especially for non-Hispanic whites. Although the racial and gender distribution in this study population is not directly representative of the general US population, results of this study suggest possible sparing of patients with uveitis from AMD. A larger systematic study with greater power would be needed to confirm these findings.

Age-related macular degeneration (AMD) is a leading cause of irreversible central visual loss in the elderly. A recent genome-wide association studies (GWAS) reported that rs9621532 near the tissue inhibitor of metalloproteinase 3 (TIMP3)/synapsin III (SYN3) region of 22q12.3 is associated with AMD. In this study, we characterize its phenotypic influence on AMD using three independent study cohorts: case–control studies from the National Eye Institute Clinical Center (NEI, n=397) and the Age-Related Eye Disease Study (n=523) as well as a nested case–control study from Blue Mountains Eye Study (BMES, n=852). Comparisons between cases and controls show no association between rs9621532 and AMD in the three sample sets. However, stratifying NEI cases uncovers a moderate protective role of rs9621532 in neovascular AMD (nAMD) and the association adhered to a dominant model (odds ratios=0.32; 95% CI: 0.11–0.89; P=0.02). The BMES data followed the same pattern of association with nAMD as that seen in the NEI sample but did not reach statistical significance. Polychotomous logistic regression showed a trend that rs9621532 correlates with less severe disease, for example, with the majority of carriers having intermediate AMD rather than nAMD/geographic atrophy AMD. Functionally, rs9621532 influences TIMP3 mRNA expression in cultured primary human fetal retinal pigment epithelium (hfRPE) cells. In hfRPE donors carrying the protective rs9625132 allele, we measured a reduction in TIMP3 mRNA by quantitative RT-PCR. Our data suggest that rs9621532 carriers have a lower risk of developing nAMD, potentially because of decreased transcription of TIMP3.

Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME.A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA).Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors.In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data. In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 μl (440 μg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes. Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar. Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial.

Purpose To evaluate the safety and efficacy of finasteride, an inhibitor of dihydrotestosterone synthesis, in the treatment of chronic central serous chorioretinopathy. Methods Five patients with chronic central serous chorioretinopathy were prospectively enrolled in this pilot study. Patients were administered finasteride (5 mg) daily for 3 months, after which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity, central subfield macular thickness, and subretinal fluid volume as assessed by optical coherence tomography. Serum dihydrotestosterone, serum testosterone, and urinary cortisol were also measured. Results There was no change in mean best-corrected visual acuity. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months and rose to levels that were below baseline by 6 months. The changes in both optical coherence tomography parameters paralleled those in serum dihydrotestosterone level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased after discontinuation of finasteride. In the remaining patient, both optical coherence tomography parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion Finasteride may represent a novel medical treatment for chronic central serous chorioretinopathy. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of central serous chorioretinopathy.

Multiple evanescent white dot syndrome (MEWDS) is part of a spectrum of disease entities known as acute zonal occult outer retinopathy-complex that share photoreceptor disruption as a cardinal feature. Optical coherence tomography (OCT) allows for qualitative assessment of the integrity of the photoreceptor layer via examination of the junction between the photoreceptor inner and outer segments. A patient with atypical MEWDS who demonstrated disruption of the inner segment/outer segment junction during the acute phase of the disease is described. The change in photoreceptor architecture and abnormalities on fundus autofluorescence imaging and microperimetry were restored to normal following resolution of the disease. Using a novel OCT-based method of quantitatively measuring photoreceptor outer segment length, the authors show that photoreceptor outer segment length appears decreased acutely with restoration to normal following disease resolution. OCT can assess photoreceptor recovery, both qualitatively and quantitatively, in patients with MEWDS features.

Geographic atrophy (GA) is the advanced atrophic form of age-related macular degeneration (AMD) that increases in prevalence with age1–3 and results in progressive moderate and severe visual loss over time.4 GA is characterized anatomically by the development and progressive enlargement of areas of retinal atrophy that extend through the outer neuroretina, retinal pigment epithelium (RPE), and choroid,5,6 effectively depriving affected areas of light sensitivity.7 There is currently no treatment that has been demonstrated to effectively prevent the onset of GA8 or to retard lesion enlargement and/or vision loss.9,10 Given the size and significance of this unmet need, clinical trials that further our knowledge of investigational methods and therapeutic strategies are of public health significance. Although the pathogenic mechanisms underlying GA are largely unknown, oxidative stress, associated also with aging11 and smoking,12 has been implicated as a potential etiologic factor.13,14 In this purported mechanism, reactive oxygen species in the retina exert cumulative cellular damage, leading to eventual retinal and retinal pigment epithelial cell atrophy and death. The presence of oxidized lipids in drusen15,16 and the deleterious effects associated with oxidized derivatives of retinal molecules17,18 suggest the etiologic relevance of oxidative stress and indicate a possible benefit in reducing free radicals in the AMD retina.13 Piperidine nitroxides, exemplified by compounds such as Tempol, are capable of reacting directly with free radicals and exert potential antioxidant effects.19–21 This information provided a scientific rationale to investigate the therapeutic significance of OT-551, a disubstituted hydroxylamine compound that is converted to the piperidine Tempol-H, for the treatment of GA. Tempol-H has been reported to protect RPE cells from oxidative damage in vitro22 and photoreceptors from acute light-induced damage in experimental animals.23 The main objective of the present pilot study was to determine the safety and efficacy of topical OT-551 in the treatment of bilateral GA. Other objectives of the study were to develop and evaluate anatomic and functional outcome measures for the interventional studies of GA, in a unilateral treatment study design.24

To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD).We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval.Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments).Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

Optical coherence tomography (OCT) evaluation of macular structure is important in the diagnosis and monitoring of patients with diabetic macular edema (DME). Automated measurements of retinal thickness and volume in the macula from retinal tomograms using image-processing software have been useful in observing patients longitudinally in clinical practice and making comparisons in clinical trials. To date, time domain OCT using the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) has been the most widely used technique for obtaining macular measurements1-5 and has been shown in previous studies to generate measurements with high repeatability.6-9 This instrument acquires images at a rate of 400 axial scans per second, with an axial resolution of 10 μm. Recently, a new class of OCT instruments employing spectral (Fourier) domain technology has been developed. One such instrument that is currently commercially available is the Cirrus HD-OCT (Carl Zeiss Meditec, Inc.). Although both time domain and spectral domain OCT use the same basic working principles, the scan rate of spectral domain OCT is at least 20,000 axial scans per second, with an improved axial resolution of 5 μm. Both the Stratus OCT and the Cirrus HD-OCT systems employ intrinsic software algorithms to calculate retinal thicknesses averaged across standardized subfields in the macula. Data for thickness calculations are collected from an array of A-scans distributed across the macula. This array differs between the Stratus OCT and Cirrus HD-OCT systems. In the Cirrus HD-OCT system, significantly more A-scans are used, and these are evenly distributed over the scanned area. The Stratus OCT employs fewer A-scans, and these are more heavily weighted toward the center of the scan. The Stratus OCT system corrects for this effect by extrapolating across areas not sampled; but, depending on the nature of the macular anatomy in those areas, quantitative differences in macular thickness computations may arise between the OCT systems. Also, although both OCT software systems perform automated delineations of retinal boundaries, each system uses different anatomic landmarks in the specification of the outer retinal boundary (information from the manufacturer, Carl Zeiss Meditec, Inc.). These differences may contribute to a different absolute value for thickness measurements, and may also affect how retinal boundaries are reliably delineated between the two OCT systems. For both clinical practice and in the conduct of clinical trials, the repeatability of OCT measurements has an important impact on how the data may be interpreted. The multiple differences between the time domain Stratus OCT and the spectral domain Cirrus HD-OCT systems may influence how repeatable macular measurements are in the context of DME where there may be considerable deviation from normal anatomy. Spectral domain OCT has been demonstrated to improve visualization of retinal structures in various macular diseases.10-12 The reliability of macular measurements obtained by using spectral domain OCT, however, has not been determined. Furthermore, a comparison of the reliability of these two OCT technologies in the determination of macular measurements has not been performed. The purpose of this study was to evaluate and compare the reliability of macular measurements obtained using time domain versus spectral domain OCT in patients with DME. The results of this study will provide information on how OCT macular measurements using both time domain and spectral domain technology can be compared and will further our understanding of how different modes of data capture and analysis in OCT systems can influence the measurements.

Nonproliferative diabetic retinopathy (NPDR) is a microvascular complication of diabetes mellitus that can lead to irreversible visual loss. Intraretinal microvascular changes, such as altered retinal vascular permeability and eventual retinal vessel and capillary closure, characterize NPDR. Macular edema, the most frequent cause of visual loss in NPDR, may result from increased vascular leakage. Retinal hypoxia, secondary to chronic hyperglycemia, triggers the pathologic processes of NPDR. Additionally, there is increasing evidence that inflammatory mechanisms may play a role in the pathogenesis. Systemic factors such as glycemic control, hypertension, and serum lipid level also contribute to the development and progression of NPDR. Prompt and appropriate initiation of laser photocoagulation for macular edema or severe retinal nonperfusion, along with optimal control of systemic factors, can prevent visual loss.